CN102617596B - The black amber terpene of sesterterpene compounds I and its production and use - Google Patents

Abstract

The present invention relates to medical technical field, be specifically related to a kind of black amber terpene of sesterterpene compounds I being separated to and its production and use from marine animal sponge. With ethanol diacolation extraction sponge routinely, concentrating and separating purifying is get Hei Po terpene I, and its molecular formula is C₂₄H₃₅NO₂; Preparation technology is simple, yield is high, and stable in properties is used the quality of the pharmaceutical preparations of preparation stable, convenient quality control, and production cost is lower, is convenient to suitability for industrialized production; This compound pharmacological action is stronger; can be used for antitumor, anti-diabetic and anti-obesity; and evident in efficacy; safety and low toxicity; easy to use; one-object-many-purposes, its raw material sources are abundant, inexpensive, for prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-diabetic and anti-obesity and directly related disease thereof provide a kind of new medicament sources and safe raw material.

Description

The black amber terpene of sesterterpene compounds I and its production and use

Technical field

The present invention relates to medical technical field, specifically relate to derive from a kind of compound of marine animal and carryGet the technical fields such as separation, use, more particularly relate to a kind of compound being separated to from marine animal sponge andPreparation method and purposes, more specifically relate to a kind of sesterterpene compounds black amber terpene I (HippolideI) and system thereofPreparation Method and purposes.

Background technology

(1) research overview of sponge

1, general introduction

Sponge (English name: SpongiatiaorSponge, Latin name: PhylumPorifera) for porous movingThe common name of thing, belongs to animal kingdom paleontology invertebrate paleontology Poritera (Porifera). Poritera is largeThe general designation of approximately 5,000 kinds of original multicellular aquatic animals. Be fresh water production except spongilla sp belongs to (Spongilla) approximately 20 kinds, divide equallyCloth is in the intertidal zone to 8 of ocean, and 500 meters of (more than 28,000 feet) depths, seek set life.

Sponge just lived in ocean before 200,000,000 years, of a great variety, widely distributed, had developed into so far kind more than 10,000,Accounting for 1/15 of marine animal kind, is one huge " family ", wherein nearly 1/3 lives near the marine site of Australia, isIn ocean except coral the second a large amount of marine animal. , all there is the figure of sponge in ocean everywhere, from intertidal zone to deep-sea, fromTropical Ocean has distribution to Antarctic Ice sea. Sponge not only can live in ocean, can also live in river and lake. PerhapsBeing that sponge health is soft mostly lives in ocean like continuous, and the name of " sponge " is come therefrom.

Because sponge is often branch shape, and can not move, be regarded plant by people in the past. Within 1755, just someone describes itThere is the feature of animal. Within 1765, observe by the keying of current and the blasthole of sponge, confirmation sponge is animal. SpongeStructure, function and growth are different from other animals. Spongia does not have mouth, there is no gastrovascular cavity, there is no central nervous system, its yetIn body wall, having countless apertures is its filter food and passage of breathing, is the many cells such as low the most ancient, the simplest and the most originalAnimal.

By to sponge genetic test and with the gene comparisons of other animals (fly, fish, the frog and people), scientist thinks,Animal ancestors were the earliest sponges, and they have been survived at least 5.6 hundred million years on earth, apart from the spongeization of modern about approximately 500,000,000 yearsStone is also found, but complete cavernous body bone is very rare in fossil record. Cavernous body be by calcareous or siliceous spur andThe sponge support of cutin forms. If sponge is fished for up from water, dig pit and bury by the sea, wait to wait the meat that rots, surplusThe lower fibrous bone interweaving, then pass through rinsing, be only our daily being seen sponge.

Sponge secondary metabolite is rich and varied, wherein contains and has in a large number antitumor, antiviral, antibacterial, anti-inflammatory and exempt fromThe different bioactive compounds such as epidemic disease adjusting are the focuses of marine nature products chemistry research always.

2, form and structure

Sponge is the simplest multicellular animals of structure in the world. Saying that it is simple, is because it had not both had head, does not also haveTail, does not have trunk and four limbs, more there is no nerve and organ. Spongia originates in seawater mostly, and minority is lived in fresh water, because ofHealth is soft and gain the name.

The sponge overwhelming majority inhabits benthos, anchors at different waters. Although sponge belongs to animal, it can notOneself walking, can not move about, can only be attached to fixed on the rock in seabed and coral reef and grow, even near submarine volcano mouth,As plant, anchor at as you were, the seabed that reposes throughout the year, from flow through seawater at one's side, obtain food. Take a fancy to from appearanceGo, sponge extraordinary image plant, for this reason, in long time sponge to be mistaken as be a Plants of living in water always,Even some biologists also think like this. Because sponge can not be walked about, can not drift with the tide, or be fixed on rock in water,On shell, water plant or other object. Before 18th century, sponge is treated as plant always, afterwards due to microscopicalInvention, and animal embryology progress of research, people are familiar with the true features of sponge, have finally determined the real genus of spongeProperty: 1765 one make the biologist of Ai Lesi for the first time sponge be belonged to animal.

Sponge color is dazzled beautiful colorful, has cerise, silver gray, white etc., but lives in the sponge in seawater, and majority is ashThe block of yellow, brown or black. So, although sponge is called as " marine flower and fruit ", look general like plant,Be actually a kind of animal. So that sponge seems more to seem a feast for the eyes: under the searchlighting of light, some pictures are a stringLarge red lantern, more as unsurpassed in exquisiteness vase and cup small cup. This feature of sponge makes people's difficulty distinguish true features especially. UntilIn modern age, microscopical appearance, has just opened the mystery of the ownership of the sponge of arguement whole 2,000 years.

The Morphological Features of sponge has three:

(1) build is asymmetric

The build of sponge is varied, and little only several grams, large but has 45 kilograms. Spongia mostly is colony, monomerLess. Monomer health is radiation symmetric or asymmetric, generally makes pyramid, dish type, goblet shape, spherical etc. The profile of colonyAlter a great deal, shape and size differences are large, and shape is peculiar, in different poses and with different expressions, extraordinary-looking, cover shape to barrel-shaped and flower by very thin tableDoleiform not etc., does not have sheet, irregular bulk, ampuliform, tubulose, spherical shape, gyalectiform, fan-shaped and dendroid etc., numerous. ExampleAs Leucosolenia is the colony of flat tube shape, loquat sponge is as a round loquat, and short cypress sponge is like the lantern of a string exquisiteness, BuddhistSon is situated between as same glass fibre ball stands on handle, and hermit crab suberite is flat as thin paper, venu's-flower-baskets and is called as " dimensionReceive this gaily decorated basket ".

Due to environment difference of living in, condition is changeable, and the matrix type adhering to is different, and current power differs, and has therefore formedThe form that sponge is colourful. Most sponges live on the substrate of solid rock. The waters that ocean current is strong, the height of sponge is generalLess than 2.5 centimetres, and the surface of sponge forms many fairshaped lines, and this evolution can be avoided being rolled over by wave and ocean currentDisconnected. Some sponges are liked living in caves, and they get into the cave everywhere on the shell of abalone and oyster, under then living away from home on their shell.What is interesting is, the shape of sponge is normal similar with the set thing of sponge, is fixed on the sponge of coral or crust, and shape is just as coralOr crust. Conventionally the size of flow rate of water flow, the power of wave activity, the hard soft degree of substrate, also often makes the sea of same speciesSilk floss has different formalnesses, for example offshore surf zone life conventionally like wrapping on rock, like thin eggplant skin orGinger peel; Live in anxious environment at stream again mostly as knoll, have good streamlined build; And at unhurried current or right up and downPerch in environment, the bodily form again more is towering chimney-like.

The color of sponge is rich and varied equally. Their color is mainly in body, to have different types of marine alga symbiosis,Make them present different colors. The appearance of tubulose sponge resembles the chimney of setting very much, so be called again chimney sponge. Tubulose spongeHealth in have a lot of apertures. Water constantly flows through from aperture, and nutriment is wherein just by tubulose spongy absorbing. WithTime, the refuse that tubulose sponge produces also can be along with seawater flows away. Seawater flows in the body of sponge from the aperture that spreads all over sponge whole body.Each aperture leads to a cubicle, is called filter chamber. All filter chambers all lead in a chamber as bottle, this chamberBe called hole ante-chamber. The upper end in chamber is a very large apopore. The passage that the aperture of sponge enters as oxygen had both played breathingEffect, can absorb again the nutriment in water, and excretion refuse, can also discharge sperm and ovum, completes reproductive function.

(2) there is no clear and definite tissue and organ

Spongia is organized original, without real gastrovascular cavity and nervous system. Unique is simply the internal structure of sponge:Sponge is a kind of two germinal layers (not growing completely) animals, and whole health is made up of inside and outside two-layer cell, there is no the group of differentiation in bodyKnit, only some cell has difference in structure and function, and outer (cortex) is made up of flat cell and porocyte; Mesoglea is not haveThe cell of stratification, comprising calcareous, siliceous or keratose; Internal layer is made up of choana, is mainly trophic function, plays cellInterior digestion.

On sponge body wall, there are many apertures (claiming " blasthole "), therefore also claim " porifera ". Individual body image bottle, kettle, mortar etc., haveShi Liancheng colony. Most marine products, set life. There is macropore opening (claiming " delivery port ") free one end. Body wall is by inside and outside two-layerCellularity, okioplast is flat, the thin brain flaggellation of internal layer, most tool plasm necks, therefore claim " choana ", main row is ingestedEffect with intracellular digestion. Blasthole passes into the raceway groove in body, complicated with flagellated chamber and the delivery port composition of choana compositionChannel system. The seawater that contains bait, due to the continuous vibration of interior confluent monolayer cells flagellum, flows in body from blasthole, indigestibleThing flows out external with seawater from the delivery port on top. At inside and outside two-layer iuntercellular, also have one deck mesoglea, wherein resemble changeThe free cell of shape worm, reproduction cell, osteoblast, spongioblast etc. The needle-like that in spongia body wall, many tools are supportedSkeleton, claims spicule. In this animal, there is a few species can be for swabbing machine, firearms and press and shower; Some kind energyDestroying shell, is the harmful animal of shellfish culture.

Sponge can not be recognized from photograph, size, shape, distribution and arrangement that its main characteristic of division is that spiculeDeng. Between sponge two confluent monolayer cells, also has some special structures---spicule, just because of had structure like steelframe, just guarantorHold sponge and there are various forms. The textural very ingenious exquisiteness of spicule of sponge, meet the principle of mechanics, but this must pass throughElectron microscope just can be seen.

Bone has three kinds, the mineral matter of spicule (spicule), bone silk (spongin) and non-spicule type, and spicule can divide by sizeFor macrosclere and spiculum. Spicule composition is calcareous (calcite, aragonite) or siliceous (opal), and the composition of spongin is cutinOrganic compound, be thread, branch or handing-over together. Spicule and spongin: have archaeocyte, become sclerblast and Cheng HaiContinuous silk cell. Spongin is perishable, is difficult for forming fossil.

Though poriferous cell has the division of labor, cooperate with one another very micro-, as sponge is ground and sieved, what wherein separated is thinBorn of the same parents still can be survived a couple of days (being equivalent to protozoan). If but no longer combination each other just can not survive down, spongia thisPlant the i.e. independent feature of cooperating again, show that its organism structure still belongs to cell grade, has shown original metazoan feature.

(3) there is ditch property

The basic structure of spongia health is made up of around a cavity of central authorities two confluent monolayer cells. Free one endThere is a large delivery port (Osculum) that central chamber (CentralCavity) is communicated with the external world. Form spongia body wallTwo confluent monolayer cells in the different ditch of different species composition complexities system, according to ditch, system can be by poriferous body structureBe divided into three types.

1. ascon (AsconType) is the most original, is also the simplest body wall structure, and kind is little, and Leucosolenia justBelong to this class.

Ascon sponge is monomer or colony, and length is generally no more than 10cm, and the individual profile in colony is obvious, often each and every oneBody is all little tubulose, and delivery port has spicule to surround around, and central chamber is broad, and body wall has middle colloid by two confluent monolayer cells therebetween(Mesoglea) form, okioplast claims cortex (DermalEpithelium), is mainly by one deck pinacocyte(Pinacocytes) composition, it is different from the epidermal layer cells of other animals, because their source and other multicellular animalsEpidermal area difference, and this pinacocyte do not have basement membrane, the edge of cell can shrink. Many pinacocytes shrink simultaneouslyCan make health diminish. Some pinacocyte specializations forms tubulose, is called porocyte (Porocyte), intert pinacocyte itBetween. The outer end of porocyte communicates with the external world, and the inner communicates with central chamber, and the aperture of porocyte outer end is exactly ascon spongiaThe water inlet aperture (Ostia) of body surface or title ostium (IncurrentPore), so it is cell endoporus, water is entered by ostiumEnter central chamber. The contraction of porocyte and diastole can be controlled the influx of water. The internal layer of body wall also claims gastral layer (GastralEpithelium), be made up of neck flagellated cell (being also called for short choana), the choana of ascon sponge is round whole central authoritiesChamber. Choana is oval, and what its base portion was loose is seated in mesoglea, and free-end stretches out a flagellum, around the base of flagellumThere is a telescopic plasm neck in portion, is made up of the microvillus (Microvilli) of many separation. Sponge passes through asconThe swing of choana flagellum makes water be flowed into by porocyte (or claiming ostium incurrens), is flowed out through central chamber by delivery port again. ChoanaIn form, be very similar to the neck flagellate of protozoa, therefore someone thinks that spongia is by the evolution of neck flagellateCome. Between the cortex of body wall and gastral layer, be mesoglea, it is a kind of gluey residuite that contains protein, comprising there being tripFrom ameboid cell (Amoebocyte) and disperse spicule (Spicule). Ameboid cell can be divided into different forms, exampleIf any the elongated branch of ameboid cell pseudopodium, formation connected with each other is netted, is called asterism cell (Collencyte), someone thinksIt is the most original a kind of cell with nervous function. Another kind of cell is larger, and its nucleus is also larger, has lobopodia,Claim archaeocyte (Archeocyte), this is a kind of undifferentiated cell, engulfs and the function of digest food except itself havingOutward, it can also change into tool reproductive function reproduction cell (GenerativeCell), can secrete the osteoblast of bone(Scleroblast), the storage cell (Thesocyte) of stored nutrient material, the muciparous gland cell (Gland of energyCell) etc. The maximum feature of ascon spongia is that body wall structure is simple as can be seen from the above, the bag that its two confluent monolayer cells is straightEnclose central chamber. Because central chamber is broad, moving by the flagellum of choana the water velocity that makes to flow through health is slowly, and metabolismLow, so ascon spongia is all generally small-sized. Spongia has increased by the inverted pleat of body wall during evolutionThe quantity of choana and the surface area of distribution have reduced the volume of central chamber simultaneously, have consequently formed sycon or multiple ditchThe body wall of type, has so just accelerated water and has flow through the speed of health, has improved the ability of metabolism, makes the animal also increase volume.

2. sycon (SyconType) is the preliminary form of one of body wall inverted pleat, for example cup sponge (Scypha), sycon(Grantia) etc. The pinacocyte pleat of sycon spongy cortex, to mesoglea, forms multiple blind pipes that are arranged in parallel, and is called streamEnter pipe (incurrentcanal), the perforate ostium (incurrentpore) by name of inflow pipe outer end. The choana of gastral layerAlso form multiple blind pipes that are interspersed between inflow pipe by central chamber is outstanding outward, be called flagellum pipe (flagellatedOr flagellated chamber canal), also referred to as banj (radialcanal), its inner perforate is called apopyle (apopyle),Result inflow pipe and flagellum pipe have formed the body wall of sycon alternately. Between adjacent inflow pipe and flagellum pipe, also there is apertureTwo pipes are communicated, and this aperture claims prosopyle (prosopyle). Due to the appearance of pipeline, the body wall of sycon has been thickeied, alsoBecause choana pleat enters in flagellum pipe, on central chamber wall, no longer include choana, but surrounded by pinacocyte. Sycon spongeCurrent approach be: water → ostium → inflow pipe → prosopyle → flagellum pipe → apopyle → central chamber → delivery port →External. Sycon sponge has increased the area of choanosome, and the dwindling of the increase of pipeline and central chamber also accelerated current and passed throughThe speed of health. In sycon sponge, its cortical cell of some kind and mesoglea are more flourishing, so that have hidden whole body surface,Having formed the crust (cortex) that one deck or thin and thick differ, there is more ostium in result, can increase like this in body wallHydraulic pressure, accelerate water in vivo flow.

3. the complicated rhagon that just formed of the further inverted pleat of rhagon (leucontype) body wall, most seaContinuous animal belongs to this type, for example fresh water sponges. The change list of rhagon structure is following four aspects now:

(i) flagellum pipe continues to enter to mesoglea invaginate, so that has formed the flagellated chamber of multiple circles, for example thin bud sponge(Microciona) body wall of every square millimeter, flagellated chamber can reach 1,000;

(ii) mesoglea is more flourishing, and has formed numerous cortex hole (Dermalpore) or skin together with epidermal cellCavity of resorption (Subdermalspace);

(iii) inflow pipe is divided into many sprigs, and then enters flagellated chamber;

(iv) central chamber dwindles further, is finally replaced by the outlet pipe of branch (ExcurrentCanal). Multiple ditchThe current approach of type sponge is: water → cortex hole → cavus subdermalis → inflow pipe → prosopyle → flagellated chamber → apopyle → streamGo out pipe → delivery port → external. In some rhagon sponge, its forward and backward pylorus hole has extended to form forward and backward pyloric canal(Prosodus, Aphodus), structure is more complicated. Therefore rhagon spongia has larger choana surface area, in body, hasThe pipeline communicating in length and breadth, central chamber also further dwindles and has become tubulose, and the discharge of therefore flowing through in body increases, water flow velocityDegree is accelerated. The volume of rhagon sponge is all also relatively large, particularly in the large-scale sponge of colony, we only can from many go outForm and the size of sponge individuality judged at the mouth of a river, for example rock sponge (Reniera). The colony of fresh water sponges becomes bulk, veryDifficulty has been judged individual form.

3, classification

The kind of sponge is numerous, and modern sponge a few types in Demospongia belongs to fresh water sponges, most seasSilk floss is marine animal, lives in seabed always. Scientist estimates, approximately has 15,000 kinds of sponges to be distributed in each waters, the world, from shallowThe trace of the extra large sponge that grows on trees to the deep-sea of 8,000 meters: the tender calcisponge of modern rock-block field is distributed in sublittoral more, but glassGlass sponge can reach in the deep-sea of 6,000m deeply in perch, and fossil sponge also requires the similar depth of water substantially. Sponge is on different groundThe matter epoch often form reefs with stromatoporoids, bryozoan together with algae. Although found again so far kind more than 1,000 from 1994New sponge kind, but great majority do not confirm in detail and describe, and still have many new kinds also undiscovered, as for Hong KongSponge is seldom as research.

Each difference of poriferous color and luster, has the shades of colours such as bright red, bud green, brown Huang, milky white, purple, as flower oneSample beauty. Therefore, people believe that it is plant always, until 1825, along with leaning on microscopical invention and use, and physiologyThe work of and embryology aspects, scientist just determines that it is animal. In fact, poriferous color derives from phycobiontOr inactive storage pigment, for example green is because of the viridescent zoochlorellae of its parachorium, and redness, yellow, orange colour etc.That its existence can be produced shades of colour because cell contains fat-soluble carotene. On body wall due to it, there is many titleFor the aperture of " blasthole ", foamed plastics seemingly, so cry again porifera, be a class of minimum grade in multicellular animalsGroup.

Biology classification is upper, and spongia belongs to the primitive invertebrate of the animal kingdom, and whole health is by inside and outside two-layer thinBorn of the same parents' composition, the interior tissue that there is no differentiation of body, only some cell has difference in structure and function, and body surface has 4,000 hundred million aperturesCommunicating with body cavity, and supported by the contact of chiltern fibrous skeleton, just looks like the densely covered canalizations in thousands upon thousands networks of rivers.

Poritera (Porifera) is the general designation of about 5,000 kinds of original multicellular aquatic animals. Sponge is porousThe general designation of animal pupil thing, Poritera is divided: Calcispongea (Calcispongea), Hexactinellida, DemospongiaeAnd four outlines such as os osseum sponge guiding principle.

Be fresh water production except spongilla sp belongs to (Spongilla) approximately 20 kinds, be distributed in the intertidal zone to 8 of ocean, 500 meters(more than 28,000 feet) depths, battalion's set life. As a very original animal monoid, its embryonic development and other are multipleAnimal difference has reverse phenomenon in primitive gut forming process, thinks that according to the most scholar of these features spongia existsPosition in the animal kingdom isolates, and is that a metazoan side is propped up, and therefore also someone is referred to as Parazoa suberathem(Parazoa)。

Spongia is the minimum grade person in metazoa. The needle-like skeleton of many tools supporting function in spongia body wall,Claim spicule. According to the character of spicule, can divide calcisponge and the large class of non-calcisponge (Incalcarea) two.

In Porifera (Spongia) animal, there is a few species can be for swabbing machine, firearms and press and shower;Some kind can be destroyed shell, is the harmful animal of shellfish culture. Porifera comprises as follows:

1. Calcispongea (Calcarea), a guiding principle for Poritera, the spicule forming taking tool calcium carbonate is as main specialLevy. The whole marine products of calcisponge, live in littoral shallow sea mostly. Build is generally very little, is often lead or grey. Spicule topOutside normal excrescence, cause sponge to be thorn-like; Typical calcisponge is radiosymmetric ampuliform, and top is delivery port, is often erectedVertical long monaxon is around, title delivery port Tassel. Spicule is not of uniform size, but all can be regarded as macrosclere on taxology, has 3 kinds substantiallyType: monaxon, triactine and tetractine, shape is varied. Calcispongea is divided into Calcaronea and limeSponge subclass.

Calcispongea kind is many, has monomer, as sycon (Grantia); There is branch to become colony, as Leucosolenia(Leucosolenia) calcareous spicule has spicule, triradiata etc. The appearance of calcisponge in stratum is later than ordinary spongeAnd hexactinellid.

2. Hexactinellida (Hexactinellida), a guiding principle for Poritera. Major comonomer. Skeleton is all six to putTrichite (three axles respectively meet at a bit mutually with right angle) formed, i.e. the siliceous hexactine (being triaxon) of tool, sixSpoke is orthogonal to intersect at a point. The spicule of hexactinellid can be divided into macrosclere and spiculum. The hexactine of some kind is mutualHealing, forms fixing body wall bone mutually.

Originate in deep-sea, major part lives in 200～8, the seabed of 500 meters. Foremost as " venu's-flower-basketing "(Euplectella), for upper end is large, the slightly thin oval cage shape in lower end; Often there is paired shrimp (pari shrimp) to live wherein, " live together to a ripe old ageSame cave " one come therefrom. " stroking son is situated between " (Hyalonema) is and has the gaily decorated basket of lid shape, and lower end has a branch of elephant to stroke sub lengthGlass fiber, in order to be inserted in the silt of seabed.

In bone without spongioplasm. Cavernous body is often radiosymmetric ampuliform, column, gyalectiform or funnel-form; Tissue looseness, structureMake exquisiteness, have numerous species base portion to there is the spicule (claiming base palpus) of fibrous root shape, be directly inserted in globigerina. Hexactinellida dividesSix Astraeospongia orders and double plate sponge order. Hexactinellid, particularly six Astraeospongia orders are most important classes in fossil sponge. ?Early come across in Cambrian rock stratum, peak to the Cretaceous period and Jurassic Period.

3. Demospongiae (Demospongiae), a guiding principle of maximum in Poritera. Bone is siliceous and spongioplasm,In trichite, there is no 6 spoke spicules, but have dividing of size. Normal and the trichite of spongioplasm bone exists simultaneously.

Kind is a lot, and Gai Xi colony is block. Spicule is siliceous, borrows spongioplasm (a kind of thing of similar silk between pin and pinMatter) adhesion mutually; The spicule of some kind is wrapped in spongioplasm, and the spicule of other kinds all disappears, and only has spongeThe webbed skeleton of the crisscross intersection structure of fiber of matter. For example bath sponge (Euspongiaofficinalis) and horse sponge(Hippospongiaequina), bath sponge originates in Mediterranean, and the southern Chinese island of Hainan also produces. Mesh is thin, resilient beam, technique, doctorLearning and using all day needs.

This guiding principle kind accounts for the over half of sponge kind. Most marine products, are distributed in intertidal zone, shallow sea to deeply reaching 5000mSeabed; Also have a class to live in fresh water. The ditch system of ordinary sponge all belongs to rhagon, and cavernous body does not have central chamber. Lai WeiThis guiding principle is divided into 3 subclasses: Tetractinomorpha, horny sponge subclass and with bone sponge subclass. The bone that Spongiidae is various types ofFor pure spongioplasm structure, quality softness, is used to water suction, shampooing etc. for a long time. Mainly be distributed in Perenniporia martius shallow sea.

Fresh water sponges (Spongilla) massive colony, is yellow, brown, green isochrome. Spicule is little shaft-like. Except gemmation,Winter, some soma was concentrated a place, external double-layer films, and intermembranous respectively have the spicule of a shallow bid to support by two ends, formsSo-called " gemmule ", grows for ordinary colony spring again. Move in fresh water, be common on water plant branches and leaves and stone. KindClass is many.

Fine hair horse sponge (Hippospongialachne) belongs to Demospongiae (Demospongiae) net Keratosa(Dictyoceratida) angle bone Spongiidae (Spongiidae) sponge, is distributed in the regions such as marine site, South China Sea Xisha. FromIn this genus sponge, separate and obtain the multiple terpenoids such as terpenes quinones, furans terpenes, triterpene olefin(e) acid, but so far for seeing from thisBelong to the report that is separated to sesterterpenoids compound H ippolideI in sponge.

4. os osseum sponge guiding principle (Sclerespongiae) a: guiding principle for Poritera. Mere formality stone matter or calcite matter spicule,The fibrous inner skeleton of trichite and spongioplasm. The cavernous body bulk of os osseum sponge, base portion has one deck to be slightly honeycombCalcareous (aragonite matter) bone, the size and shape of each chamber is slightly different. Above base portion bone, there is one layer of cells tissue, in tissueThere are siliceous needle and organic fiber shape bone; There is many volcanoes shape protuberance on sponge surface, and its top is circular delivery port, goes outWater pipe radially distributes in cell tissue from delivery port. Lower point of two orders of this guiding principle: star thorn sponge order and tabulare sponge order.

4, existence and breeding

The spongia a corner of always staying alone, just seldom there is other animal in the place of every spongia perch extremely lonelylyBefore go live. Scientist analyze reason that this phenomenon forms be first spongia to those voracious animals without any suctionGravitation, its spicule and fiber from head to foot makes other animal be difficult to swallow, and therefore poriferous natural enemy is few. Secondly, sponge is movingThing is perched mostly the mobile seabed of ocean current, and a lot of animal is all difficult to live in such environment. Because there, itLarva or washed away by current, or by spongia filter food. In addition, spongia has one unpleasant evil with it conventionallySmelly, this is also possible be that other animals are reluctant one of reason of associating with it.

The Individual Size of sponge differs greatly, little several millimeters, greatly tens meters. In the one of An Liesi archipelago lifeSpongia, shape is as a hollow vase, and 106 centimetres of heights are wide 91.5 centimetres; Neptune sponge is also the kind that the bodily form is largerClass, long 120 centimetres of section, but not too wide. The spongia of bodily form maximum is once to drag for one that obtains in Bahamas Islands in 1909,Enclosing length is 183 centimetres, and just water outlet weighs 40 kilograms, and the weight after drying is more than 5,000 gram. The heaviest sponge is as a large ball, the insideCan contain 100 premium on currency, the weight of these water is at least the more than 30 times of sponge. So sponge is just individual ghost in fact. Minimum kindClass is Leucosolenia, only 3 millimeters of heights, and body weight only has several grams, equally little with a sesame.

Little sponge approximately can live 1 year, and the large life-span is longer, and some kinds allegedly can be lived the centuries. Marine sponge 7 yearsHou just reaches size for commodity, and the life-span may reach 20 years.

(1) predation and symbiosis

How does spongia obtain food? its predation method is very peculiar, is by a kind of filter food mode. MonomerSponge is the spitting image of a vase, and each aperture on bottle wall is one " face ". Spongia passes through constantly vibration body wallFlagellum, makes the seawater that contains bait constantly infiltrate bottle chamber from these apertures, enters in body. There is countless neck flagellums at " bottle " inwallCell, is fluctuateed to top spirally by base portion, thereby produces unidirectional gravitation, plays the pump of similar water pumper and inhales workWith. In the time that seawater infiltrates from bottle wall, the nutriment in water, as animals and plants chip, algae, bacterium etc., just by neck flagellated cellAfter seizure, engulf. Through digesting and assimilating, those indigestible things flow out external with seawater from delivery port. If graphite powder orSeveral melted inks drop in the poriferous side of work of raising in aquarium, do not cross how long bottleneck (apopore) is located to flow outThe thread of black. Along with current endlessly, bacterium, diatom, protozoan or organic debris are also brought in body as neck is thinBorn of the same parents capture and are made for nutrition. This foraging pattern has fully proved that it belongs to the heterotrophism animal of filter food.

Most of sponges are all attached to his thing, as rock face, or on a solid object in silt, anchor at other biologicalTime, make sometimes these biologies (as barnacle) death. Sometimes the biology of sponge and institute's set is mutuality of interest, on hermit crab shellSuberite (Suberitesdomuncula) by hermit crab with mobile, and the smell of sponge is kept out of the way fish and other animals.In the surface of sponge or water pipe and chamber, also have various animals and plants life work, that sometimes in a sponge, lives has several thousand lifesThing. Sponge is liked and other biocenosis commensalism. Some animal and sponge are set up extraordinary symbiosis or parasitism, haveSponge just becomes the inhabitation place of hermit crab, and some algae is long makes its whole body become green on the body of sponge, at first glanceIt similarly is a beautiful algae. Some ghost crab is liked that sponge is torn into fragment and is attached on leg or shell, allows sponge on their bodyGrowth is got up, and like putting on the thick armor of one deck, ghost crab is defendd harmful animal with this. Sponge is often fixed wtih at whelk or oyster shellUpper, oyster and whelk are willing, because sponge can secrete niff with it, help them to draw back harmful animal with fear. This is also seaOcean biologist can be in can the move about reason of sponge of seabed discovery.

In the commensal of porifera, the most important thing is unicellular or many cells algae. Sponge provides protection and generation to algaeThank to refuse, and algae is supplied with sponge oxygen, the dead Hou of algae also can be used as the food of sponge. Some animals colonize in sponge body surface orIn body, if cyclops is the most important parasite of marine products sponge. Wheel animalcule colonize in fresh water sponges body ， Shui ?lay eggs therein,Shui Ling section (Sisyridae) larva lives in fresh water sponges body and taking sponge as food. In general, carnivore does not eat seaSilk floss because sponge the smell is awful, have os osseum pin. But some shellfishes (chiton, limpet), shell-fish and fish are taking sponge as food.

The young that pari shrimp belongs to (Spongicola) can enter in some sponge, and growth Hou is lived and wherein can not be swum in couplesGo out the symbol that Japanese is considered as these shrimps to live a long life together. Why Here it is finds sometimes a pair of work in the body of spongeThe reason of shrimp. This is some paired male and female shrimps, and they creep in the body of sponge and live, grow up and just can't get out," be stranded " inside, until old dead. Their nutriment of sponge supply, shrimp is cleared up the dirt in duct in cavernous body, twoSide's mutual reciprocity and mutual benefit, harmonious coexistence. This phenomenon is biologically referred to as " venu's-flower-basketing " (Venus ' sflowerbasket). AndPaired shrimp in cavernous body, this owing to living " cage " life, lives a long life together, and will never change until death, and becomes resembling of loyal and steadfast loveLevy. Japanese often gives married couple them as wedding present, and shrimp is beautiful its " pari shrimp " by name also.

(2) filter food is with energy-conservation

The swing of flagellum will be consumed energy. Concerning the spongia of battalion's set life, from food, obtain chemical energyBeing difficult for. Therefore, spongia always lives in the seabed of ocean current process, in the evolutionary process of millions upon millions of years, perfectA set of ability of utilizing the natural fluid energy of flow, thus valuable food chemistry energy saved. One high 10 centimetres, 1 li of diameterThe sponge of rice, can take out 22.5 liters, seawater in one day, the water velocity of water outlet can reach 5 meter per seconds. The current that this high speed is left awayEnsure no longer " to melt down " from waste from bodies of animals. Spongia has had filter food and energy-conservation ability just, could lackIn the tropical coral reef of nutrition and shelf area, polar region is procreation from generation to generation. Sponge is the filter feeder of set. One end when sponge lifeSet, the other end is free, i.e. numerous projections of sponge body surface, there are many apertures (blasthole) on the side of projection, common projectionThere is a macropore (apopore) on top. Sponge is covered with the ring of having many flagellums and a sieve-like in the aperture of whole body,Seawater is taken in the swing of available whip, and seawater is brought oxygen, bacterium, small algae and other organic debris into, and seawater just flows from apertureEnter, to the pipeline that is abound with tail cell (being choana) in body; Along with the rhythmical swing of choana afterbody, seawater is again through ringShape thing filters, and flows out again from macropore; Water ceaselessly flows in cavernous body from the hole of flat cell, then flows out from apopore,Take a fancy to just as a water pump, had no life. Meanwhile, those small biologies are along with current enter in cavernous body, in seaFood particle and oxygen in water can be filtered out, and remaining part can be discharged from apopore, finally become sponge dimension meterThe food of existence " hauling oneself willingly into the net ".

Body surface and inner-walls of duct in sponge have pinacocyte. Also fenestrated cell of the appearance of calcisponge class, above has into waterAperture, when environment is bad, porocyte shrinks and closes aperture. In mesoglea, also has collencyte, in order to eccrine fiber. Hat is thinOne end of born of the same parents has a microscler cytoplasm prominent, thereby is similar to comet outward, can secrete the skeletogenous spongioplasm of shape. Osteocyte produces boneMatter, forms spicule, can be divided into again calcareous osteocyte and silicon matter osteocyte. Myocyte is microscler, can shrink, at most other at delivery port,Can control its switching. Bone is the important evidence of sponge classification, has plenty of inanimate matter, as calcareous and silicon matter spicule, have byProtein becomes to be grouped into other, as spongin. Spicule scatters in vivo or is linked to be fiber, rises and supports and protective effect. PorousAnimal is filtered and takes food, and seizes the food grain in water in suspension by choana, is mainly bacterium, organic debris, also may absorb dissolvingOrganic matter. In ocean, have hundreds of thousands kind sponge all day water inspiration to be gone to spue again and come, they extract food from water with this. ByOn choana, the swing of flagellum, causes current. Direct exchanging gas between tissue and water. Refuse is through delivery port and body surface rowLet out. The sponge seawater that filters its volume three to four-fold per minute, every day is quite surprising by the water yield of its health, and one is straightThe sponge that footpath is only 1 centimetre, high 10 centimetres approximately has 2,250,000 flagellated chambers, within one day, can filter 20 kilograms of seawater; Large sponge can reachTon water, sponge but only can therefrom absorb pitiably little food.

(3) reproduction and growth

Poriferous reproduction is asexual reproduction and two kinds of modes of zoogamy.

1. asexual reproduction

Asexual reproduction is taking gemmation as main, mostly occurs in marine products kind. When environment is around not suitable for sponge lifeWhile depositing, sponge will produce gemma, because gemma outside has thick film can resist the impact of external environment condition, makes them passableSurvival for a long time, after surrounding environment is improved, gemma develops into little sponge again.

Parent's ameboid cell while sprouting, the top end surface that particularly some archaeocytes move to parent by mesoglea is assembledAgglomerating, then develop into little sprout, be shed to subsequently bottom and develop into new sponge, or be connected to form colony with parent. Fresh waterSponge and minority marine products kind can form gemmule (gemmule) under certain condition, are also considered to a kind of asexual reproduction, individualArchaeocyte in body ingested assemble after a large amount of materials agglomerating, surrounded one deck osteoblast. Outside original cell pelletSecrete voluntarily layer protecting film, its constituent class is similar to spongin, to protect inner gemmule cell, and osteoblast secretion afterwardsThe spicule of layer double plate shape or needle-like, makes gemmule have the ability of very strong opposing adverse circumstances. A spongia can formMany gemmules. In the time that external condition is suitable, the cell in gemmule discharges by micropore (micropyle), then shape laterBecome a new individuality. The gemmule outside of marine products kind is surrounded by spongin, has or do not have spicule. Not tool of the gemmule of a few speciesThere is spongin.

Poriferous regeneration is also considered to a kind of asexual reproduction, and the sponge of numerous species has very strong Regenerated energyPower, for example Leucosolenia, its health fragment is only greater than 0.4mm, and with some choanas, just one new of energy regenerationBody, this is because poriferous cell has stronger polymerizing power and recognition capability. Also there is people by poriferous healthWith mechanical means crushing, by cell separation, then use filtered through gauze, the cell dispersion in its filtrate is put into seawater again and is cultivated, knotThe cell polymerization again that fruit separates, and move to respectively on correct position, one or several new individuality finally formed. AlsoHaving a classical experiment is to be undertaken by Galtsoff (1925), and he tests with two kinds of sponges that do not belong to together, a kind ofThin bud sponge (Microciona), its cell tool haematochrome; Another kind is Haliclona, tool uranidin in its cell, and he willTwo kinds of sponge mixing with cells that are separated in advance suspension together, originally two kinds of random polymerizations of cell, but very fast two kinds of cells are pressedPlant and be separated from each other, form respectively red cell mass and chloragogen cell group, the cell masses different with latter two break up separately, last shapeBecome two kinds of thin bud sponge (erythrocyte) and Haliclona (xantholeucophore) new individual. Also find many fresh water sea laterThe sponge of silk floss and marine products has this characteristic. There is afterwards people to confirm the sugared egg of a kind of macromolecule of sponge cell surface with experimentBe the identification molecule of sponge cell in vain, it has the specificity of planting, so cell energy polymerization of the same race, cell not of the same race divides mutuallyFrom. Homocellular polymerizing power makes it can regenerate and form new individuality.

Why sponge has huge and prosperous family, should give the credit to that peculiar and extremely strong power of regeneration, can not onlyRecover part impaired or that lose, and can be from an even neosome of individual cells formation of fragment. The regeneration of starfish and sea cucumberAbility is very strong, but compared with sponge, can be exactly to have felt dwarfed. In the time that environment is unfavorable, sponge becomes fractionlet, byArchaeocyte of pinacocyte outsourcing forms; When condition takes a turn for the better, then grow up to sponge. Because not having central authorities, sponge regulates organ(brain), cells in vivo can move again, so be difficult to discriminate individuals and colony, can only say every by a common ectoderm wrappingIt is exactly body one by one.

Someone tears sponge to throw in the sea of faces to bits, sponge can also one piece independently grow up to complete newly individual one by oneBody. Orange sponge is smashed into pieces to cell suspension with Huanghai Sea brocade and mix, can find that two kinds of sponges are by kind weight separatelyNew arrangement and polymerization, forms new orange sponge and Huanghai Sea silk floss. If the sponge of smashing to pieces is put and examined under a microscope, can seeThree or five, sponge cell bunches up, and just becomes soon new cavernous body one by one.

Compared with other invertebrates, the structure of sponge is simpler, there is no the organs such as heart, brain, head, mouth, only by manyPlant cell aggregation and formed together inside and outside two layers of body wall. Outer layer body parietal cell is divided two kinds, flat cell and garland cells. Ring is thinBorn of the same parents one end have a circle tiny, be bar-shaped cilium, wherein long have one long like the same flagellum of whip, cell can be ceaselesslyBrandish flagellum, by constantly inspiration of water with eject, the bacterium in water, tiny organism are bonded on flagellum as oneself simultaneouslyFood. Flat cell has many holes, and water flows in cavernous body by hole, and therefore sponge is also referred to as " porous " animal. SpongeInterior confluent monolayer cells can be out of shape and migration everywhere in cavernous body, can also become the cell of other kinds, as outer field garland cells, flatThe reproduction cell of flat-shaped cell and generation sperm and ovum. Express one's surprise, wonder, etc most, interior confluent monolayer cells becomes after other cells, can also become againReturn, this cell is called " totipotent cell " by scientist, and this is also why sponge can also grow newly after broken againThe reason place of sponge.

The gemmule of a kind of fresh water sponges that Spongia belongs to has diaphragm outward, and has spicule to reinforce. When environment takes a turn for the better, former thinBorn of the same parents overflow from aperture, are divided into different cells and grow up to new individuality. Other asexual reproduction are as formed stolon or individual fracture.In order to resist natural enemy, not by the animal predation such as fish, green turtle, sponge also has the safeguard measure of oneself, and some sponges can produce veryNiff, shies away other biological; Some meetings are outside exposed by spicule, and predator dare not be acted rashly; HaveA kind of material that is similar to venom of meeting secretion, this is the mean of defense of sponge, in order to strike back harmful animal, or kills around in seawaterPoisonous microorganism, make surrounding's seawater of sponge life become cleaner.

2. generative propagation

Except tetractinellia (Tetractinellida), spongia all can be manageed it zoogamy. Most of kinds areHermaphroditic (hermaphordite), but sperm and ovum are often in the same period ripe, can be in same internal fertilization, butAlso can between allosome, carry out mating. Embryonated egg first develops into larva in cavernous body, then leaves parent floating with currentDevelop into little sponge to surrounding. A few species is gonochorism (dioecism). Reproduction cell is by the archaeocyte shape in mesogleaOne-tenth, choana also can lose flagellum and plasm neck and become spermatogonium (spermatogonia) sometimes, then division formsSperm. After spermioteleosis, excrete with current, and enter other individual flagellated chambers with current. It was observed some torrid zoneThe paroxysmal release sperm of sponge energy in area, in seawater, forms a milky nebulous sperm band, and its length canReach 2～3 meters. A sponge has discharged sperm and often can also discharge sperm by inducing peripheral sponge. The sperm discharging enters with currentAfter other individual flagellated chambers, then enter choana. At this moment choana loses neck and flagellum, carrying sperm to mesoglea andOvum fusion forms embryonated egg. Most of poriferous embryonated eggs are to grow in vivo. Some poriferous embryonic developments byIn the reverse of germinal layer and there is very large particularity, the sponge embryo development procedure of different guiding principles is also not quite similar, and this is mainly manifested inSpongia can form two kinds of dissimilar larvas. In calcisponge, form the amphiblastula of hollow(amphiblastula), in Demospongiae, form solid parenchymula larva (parenchymula).

Calcisponge, the embryonated egg of for example Leucosolenia or sycon is grown in the mesoglea of parent, when embryonated egg is through thinBorn of the same parents divide while forming 16 cells, and what form animal pole is 8 cellules, and what form plant pole is 8 maxicells. Animal poleCellule division is rapider, after splitting into the cell of some, has formed one and has had blastocelic blastaea, celluleAll grow a flagellum towards blastocelic one end, the outward opening of later cellule through between maxicell routed up, result celluleFlagellum move on to surface, formed one end amphitrichous, the atrichous amphiblastula in one end. Amphiblastula leaves mother with currentBody, swims in the water after a period of time through the caving in or Magnocellular outsourcing of cellule, or the associating of two kinds of methods and shapeBecome the primitive gut shape of two confluent monolayer cells, and anchored at bottom. Originally the flagellatus cellule of animal pole has formed the stomach of adultLayer (choanosome), originally the maxicell of plant pole has formed the cortex (pinacocyte layer) of adult, more common by two confluent monolayer cellsForm mesoglea and ameboid cell. Poriferous this Cell Differentiation and layering, with every other metazoan germinal layerDifferentiation is different. In other metazoas except spongia, animal pole cellule develops into skin (the i.e. outer embryo of adultLayer), plant pole maxicell develops into internal layer (being entoderm). This animal pole of calcisponge animal is contrary with plant pole cellDifferentiating phenomenon be called reverse phenomenon (inversion), therefore its two confluent monolayer cells are not called ectoderm and entoderm, and distinguishBe called cortex and gastral layer. Developmental reverse phenomenon is one of reason of spongia being classified as Parazoa.

Particularly rhagon sponge also recurrence through a primitive stage in growth in calcisponge, warp in growingSpend olynthus (Olynthus) stage of an ascon, then after stage of development through a sycon, finally just formThe adult of one rhagon. During most of hexactinellids and ordinary sponge grow through a parenchymula larva, the appearance of parenchymula larvaFace is flagellatus cellule except rear end, and later flagellatus okioplast moves into inner, forms gastral layer, inner distortionCell moves on to outside and forms cortex. In Demospongiae, many rhagon kinds, when growth directly from a rhagon larva(rhagon), this larva has broad base portion, narrow and small top, very large spongocoel, very little flagellated chamber, through body wallAfter inverted pleat, develop into rhagon adult.

Sponge does not possess the organ of carrying out various functions. Its most important structure is hydraulic pipeline, mainly by blasthole, neck carefullyBorn of the same parents and delivery port composition. According to the development degree of the arrangement mode of choana and water pipe, ditch is from simple to complexity, can be divided intoAscon, sycon and 3 basic models of rhagon. Without significantly organizing, body surface and inner chamber respectively have one layer of cells; Centre is middle glueLayer, is gluey, inside has other cells and fiber. Single ditch is the internal layer of sponge, is made up of choana amphitrichous, flagellum choanaThe neck that has a circle to be formed by cytoplasm around. The major function of choana is to cause current, and catches food grain. In mesogleaArchaeocyte, claims again ameboid cell, contains a large amount of ribonucleic acid in cytoplasm; The food of choana picked-up can be delivered to health eachPortion; Can develop into again various kinds of cell, in regeneration, work; Can generate if desired female, male sex-cell. But Calcispongea(Calcispongiae) reproduction cell (especially male sex-cell) is become by choana.

, sometimes on same individuality, there is sex reversal in the general hermaphroditic of sponge. Fertilization mode is special, sperm disengage Hou withWater flows in another sponge, is seized by choana, and choana becomes ameboid cell, and sperm is delivered to ovum place. Embryonic development hasDifferent approach, the pattern of result larva is incessantly a kind of. Calcispongea and some Demospongiae (Demospongiae)Larva claims amphiblastula. Demospongiae accounts for 80% of whole sponge kinds, and common larva is middle real larva. Larva swimmingA few hours, to a couple of days Hou, are found suitable place set, grow up to new individuality through metamorphosis. Asexual reproduction mode has several, gemmuleReproduction, is gathered and is formed gemmule by cell (being mainly archaeocyte). In some marine products kind, this is a kind of normal reproduction sideFormula, sometimes as spending a kind of means of poor environment.

5, research and development

1. Evolution History

The ancestors of the mankind and all animals are the sponges that lived at least on earth 500,000,000 years, and the ancestors of sponge unexpectedlyIt is fungi!

Today, most of biologists believe that tellurian life originates from the very simple biology of one the earliest, stillWhat does is this simple ancient biology on earth? there is there what relation with the human and animal of today? but do not find for a long timeAnswer. But, under the subsidy of NIH and Nasa, U.S.'s microbial evolution is learned expert meter QieEr Suojin (MichellSogin) uses automated DNA permutation technology and computer program, is finding recently this problemAn answer: the ancestors of the mankind and all animals are the sponges that lived at least on earth 500,000,000 years, and the ancestors of sponge are fungies!Suo Jin says, understands animal and how to evolve, highly significant---not only can help us to understand future of life and will occur assortedChange, even can help us to understand the possibility that other life exist in universe.

Violent, susceptible, active---not " silk floss " of personality of sponge

Suo Jin had first understood sponge before understanding fungi.

In ocean on earth, have 9,000 kinds of sponges at least. Some sponges even live in fresh water. They are by bodyOn aperture, from tons of seawater, be filled into several grams of meagre nutriments and sustain life. Sponge is many cells(multicellular) biology, although some sponge has the bone that glass is the same. But on the whole, sponge is not organized, fleshMeat, organ, nerve, these important documents of brain.

The main component of sponge cell is calcium carbonate or carbonic acid silicon and a large amount of collagens. On the tube wall of sponge, longHave the long palpus (cilia) of swing, long palpus can filter refuse from seawater, leaves nutrition. No matter the volume of sponge is much, requiredAs long as food to meet each cell just much of that, not greedy. Certainly, in sponge, also there is " ferociousness " person. Raw in HawaiiLong sea of fire silk floss can be secreted venom, causes severe pain to other animal; Be grown in Mediterranean a kind of sponge, possess trick littleThe ability of shellfish, can stretch out sharp thorn they are surrounded completely, makes a hearty meal.

Sponge is also generative propagation biology the earliest, and most sponge is all hermaphroditic, can produce ovum simultaneouslySon and sperm also enter in water. Sperm can be roamed always in seawater, until find the reception entrance of another sponge pipeline.

The susceptible of sponge also shows: if it also has another mode of reproduction---a sponge suffers external force brokenBad, the cell of having been broken can be found companion in seawater, then again gets together, copy out one with their father and mother generation phasesSame sponge. After sponge is injured, can not replace the mode healing of wound of old cell with new cell, arrive but transfer old cellSite of injury, stops wound further to spread.

Like this, sponge very chicly lives under water, and provides sanctuary for thousands of kind biologies around. In addition,Sponge is in fact fine moving. Biologist Ka Er sweat Bond (CalhounBond) of North Carolina university in 1986Just find, sponge is not actionless, and he observes by precision instrument, and the edge of sponge can help certainly as limbsOneself is mobile, and what have can move 4 millimeters for one day, and what have can climb up glass container wall unexpectedly.

From 1,500,000/probability, look for answer---gene divides exploring to look for a needle in a haystack

In the past, scientist judged that the contact between animal mainly depends on observation animal appearance, comprised that fossil judges. AsTwo kinds of biologies of fruit have common feature, such as claw, will be considered to have certain kinship. Along with dashing forward of gene technologyFly, utilize genetic analysis to find biological origin and started practical application. The seventies in last century, the tutor Ka Erwu of Suo JinYi Si (CarlWoese) has just started the research of this respect. Within 1989, Suo Jin has set up laboratory, and the problem of taking over tutor continuesContinuous research. Suo Jin concentrates on research direction evolution and the parasite aspect of gene, and he wishes that answer is led by these researchThe problem that teacher proposes: the most important unit of life, how cell forms.

Genetic analysis is not that some biological full gene of comparison forms, but by comparing some biological total baseBecause of section, analyze difference wherein and judge relation between the two, if both have similar sequence in the gene, and with equallyGene expression characteristics, so just can there are same ancestors by two kinds of biologies of inference. If gene order is very different, just canKnow they a long time ago with regard to bifurcated, evolved towards different directions.

Suo Jin wishes under this theoretical direction, adopts rRNA means, sets up an objective zoogeny structureEquation, he starts with from the gene order of very rare ancient bacterium (archaea), from planktonic organism, fungi, sponge, jellyfish, seaIn certain herbaceous plants with big flowers, mollusk, extract DNA, relatively their sequence in the gene order, relatively rRNA, and application decade countMethod, calculates the relation between they and insect, fish, birds, mammal.

Before two more than ten years, gene technology is also at the early-stage, and such planning is very farsighted at that time. In 20 generationDiscipline early eighties, scientist determines that a gene of tedemia ignis will consume year, all work are allManual operations. After several years, they can be in 10～15 factors of 1 year inner analysis. Today, Suo Jin can do overnight1,000 factorial analysis. Even if but today, it is right that one section of specific genome also may comprise 3,000,000,000 pairs of bases,Find out the relation of 2,000 pairs, probability is 1,500,000/, therefore, find answer similarly is still to look for a needle in a haystack.

2. previous and present life

Suo Jin has looked through the most ancient all biology, after the gene of jellyfish, sea anemone, sponge, mollusk, starfish etc.,Finally reach a conclusion: sponge is certainly the most direct ancestors of all animals today. Before Suo Jin, some biologist bosomsDoubtful sponge is actually a Plants, and other biologists suspect that sponge is the one life being independent of outside zoogeny chainThing, and the evolution result of today does not contact.

His discovery also shows, " younger generation " after sponge is trichocyst animal (cnidarians) class, such as jellyfish,Sea anemone, coral etc., they are the same with sponge has the bag-shaped bodily form, and they all have feeler, and have at the end of feelerThe mouth opening as face. But the cell shape of sponge has the feature of annular cell, it with very little long must, thisA littlely surrounded by less (hair shape) microvillus of a group again. Thousands of must ceaselessly brandishing in water, by freshSeawater is sent into " in mouthful ".

Suo Jin believes that the most direct ancestors of sponge are choanoflagellates, and choanoflagellate is also the biology of individual cells, has long whip oneThe palpus of sample, and surround must be a series of microvillus. Some in the middle of them are even leaned on to such an extent that very closely formed group, almost fastDevelop into animal.

Although what the sponge being unable to find out today is the earliest, at least still possesses some of sea todayContinuous feature, today, we can find that diatom, these animals of horse crab are all about the same with their evolution appearance before.

All animals are all from fungi

The prior discovery of Suo Jin is that, on evolution coordinate, the ancestors more Zao than choanoflagellate are fungies, sponge and allAnimal comprises that the mankind are from fungi. Before this, a lot of scientists range plant mistakenly by fungi. But Suo Jin'sResearch discovery, plant and fungi are diverse two class biologies. Fungi and animal are the earliest from same family, and this point is notOnly understanding life source is had to meaning, understanding fungi is had more to realistic meaning to the invasion of human body.

Suo Jin says, the disease that fungi causes comprises ringworm, athlete's foot, myocarditis. Why difficult the disease that fungi causes isControlling is because fungi and the mankind have a lot of common ground, only has two kinds of biologies of working as to have different features, same what treat in other wordsWhen time does not injure main body, it is just easier to treat, this point, and believing can be to biomedical research enlightenment in the future. In addition, annualThousands of AIDS patients is died from cassette pneumocystis carinii pneumonia. Up to date, a lot of people also believe that this is one and malariaRelevant parasitic protozoa causes, but the recent findings of Suo Jin research group, and it is a kind of that cassette pneumocystis carinii pneumonia is actuallyThe biology close with fungi cast, uses and just can effectively suppress cassette pneumocystis carinii pneumonia to antimycotic medicine.

Suo Jin says, after sponge and trichocyst animal, has just occurred the biology of this both sides of insect symmetry, after this, rawThere is once volatile evolution revolution in thing, from then on, biological autotelic mobility is strengthened greatly, has possessed in the past anyBiological unexistent superiority.

3. purposes

Greeks, roman and ancient Chinese working people are familiar with and the animal that sponges very early, particularly batheWith sponge, mesh is thin, resilient beam, good water absorption, can be for operated bathing body cleaning, wash the dishes etc., afterwards again in technique, medical science and dailyLife aspect has represented increasing extensive use, as does paint brush, as liner and other mats of steel helmet, incineratesCan treat pin pain etc. In Mediterranean, Red sea and the ground such as America is coastal, the animal industry that carries the artificial cultivation of sponges is very flourishing, people are by seaSilk floss cuts into piece, ties up on frame with rope, drops into marinely, within 2～3 years, just can gather in the crops large quantities of sponges. But, along with artificial sponge's industryDevelopment, made spongia aquaculture decline increasingly. But along with scientific and technical development, people have found againThe value that spongia is new, for example, have people studying to use sponge purifying sea water, maintains the marine environment ecological balance to reachObject.

At present, sponge is to find the abundantest marine organisms of marine active substance, has become the weight of marine drug exploitationWant resource. In addition, American scientist represents recently, and they have confirmed a kind of dark abyssal cavernous body that is grown inCan produce fine glass fibre, this fiber can at least transmit luminous energy as the fiber optic cables of communication industry use.The glass fibre of this natural generation also more has pliability than made fiber optic cables. This cavernous body is grown in the torrid zoneDepths, seabed, it is high approximately 1 foot half, with a complicated silicon web frame, glass fibre forms one in the bottom of cavernous bodyIndividual crown. About 2～7 inches long of fiber, every almost thick with human hair.

Because sponge has the ability of degraded seawater pollution thing, also show the using value at marine pollution aspect. CloselyNian Lai, has had scientist to propose the concept of " spongy biological technology ". Can predict, sponge is at marine drug, marine organisms materialIn material, marine environmental protection, will bring into play significant role.

4. raise

Raise difficulty: because of after seizure and fishmonger's deal with improperly, or do not have enough food to provide, thus raise difficult,In cylinder, be difficult to permanent raising.

Temperature: 22～28 DEG C

Current: in to slightly strong current

Luminosity: most sponge does not have phycobiont, does not require (but to be placed on high light place, likely to cause that tongue is raw to illuminationBe longer than on sponge, be applicable to so be placed on dark bit comparison. )

Food: must feed and raise. Can feed the food that swims.

Remarks: process when sponge, sponge can not leaving water, otherwise the pipeline of feed in sponge can be hindered by airPlug, causes the sponge phytoplankton of can not taking food, then just can be slowly dead.

5. exploitation

It is not only the most original ancestors of animal because of them that scientist makes earnest efforts the research of sponge, and wishes by themEcology to whole ocean is studied. Since the middle of last century scientific research personnel finds there are many active biomass in sponge, can killAfter dead various harmful bacteria and virus, the people who is engaged in the world sponge research is more and more. But, Chinese Academy of Sciences's ocean researchThe people who does ocean means of taxonomic research in the scientific research institutions of Suo Deng ocean is almost the old scientist that whole-colored silver hair is grey, and youngResearcher but can not see, especially spongia means of taxonomic research leaves no successor especially.

Spongia is the most original, minimum etc. a kind of multicellular animals, not only extraordinary-looking, and has extraordinary regenerationAbility. Sponge can not only be used for daily life, and because it contains natural antibiotics, can kill tubercle bacillus, can be peopleTreatment rheumatism and the nervous system disease. In addition, sponge can secrete a kind of material that is similar to venom, in order to strike back harmful animal or to killThe poisonous microorganism in seawater around, scientist also finds that this toxin in cavernous body can be used for pharmacy, treatment tumour, the heartThe disease such as blood vessel and respiratory system. More make people joyful, have multiple cancer-resisting substance in cavernous body, some is extracted, just wideGeneral be applied to clinical.

Before three more than ten years, it is found that in cavernous body and have many special chemical substances, can be used as the raw material of medicine, cureSome difficult diseases, up to the present, people have found various active material in sponge kind animal body, can kill multiple thinBacterium with virus, so it attracts much attention again in recent years, will for people roughly the same disease, especially wage a struggle and do with cancerGo out contribution.

There is recently report, in the sponge of deep-sea, find anti-malarial material (Chinese golden medicine net). France developmental research scienceFamily announces recently, has found antimalarial material in the natural sponge at deep-sea, New Caledonia. In addition, according to French developmental researchResearch report, in wide vast living marine resources, deeply hiding in a large number virus, bacterium or cancer cell has inhibition meritNatural materials and the cell protein of energy. And at present the mankind are not for understanding, research and the chemical analysis of these natural precious deposits alsoTo 1%.

(2) extraction separation method of conventional Chinese medicine active ingredient

1, solvent extraction method

(1) principle: solvent extraction method is that it is right to select according to the dissolution properties of various chemical compositions in solvent in Chinese herbal medicineActive component solubility is large, to not needing the little solvent of composition solubility of stripping, active ingredient is dissolved in medicinal material tissueMethod out. In the time that solvent is added in herbal raw material (need suitably pulverize), solvent is because diffusion, osmosis are passed through graduallyCell membrane penetrates in cell, has dissolved solable matter, and causes the concentration difference inside and outside cell, so intracellular concentrated solutionConstantly, to external diffusion, solvent constantly enters again in medicinal material histocyte, so repeatedly comes and goes, until the inside and outside solution concentration of cell reachesDuring to dynamic equilibrium, this saturated solution is leached, continue repeatedly to add novel solvent, just needed composition can be bordering on completelyStripping or the stripping of large portion. The solubility of medicinal herb components in solvent is directly relevant with solvent property. Solvent can be divided into hydrophilyOrganic solvent and lipophilicity organic solvent, dissolved material also has hydrophily and lipophilic difference. Organic compound molecule knotIn structure, hydrophilic radical is many, and its polarity is negligent of greatly oil; Some hydrophilic radicals are few, and its polarity is little and be negligent of water. Each kind solventCharacter, equally also relevant with its molecular structure. Like this, inventor just can, by medicinal herb components structural analysis, go to estimateCount their this type of character and the solvent of selecting. Generally speaking, as long as the hydrophily of medicinal herb components and lipophilicity and solventThis character is suitable, will have therein larger solubility, i.e. the rule of so-called " similar mixing ". This is to select appropriate solventIn Chinese herbal medicine, extract required composition according to one of.

(2) selection of solvent: using the key of solvent extraction method, is to select suitable solvent. Solvent is selected suitably, just canMore successfully the composition of needs is extracted. Selective solvent will be noted following 3 points: 1. solvent dissolves active ingredientDegree is large, little to impurity solubility; 2. solvent can not play chemical change with the composition of Chinese medicine; 3. solvent is wanted economical, is easy to get, uses peaceCongruence. Common extraction solvent can be divided into following three classes:

1. water: water is a kind of strong polar solvent. Hydrophilic composition in Chinese herbal medicine, as inorganic salts, carbohydrate, molecule not tooLarge polysaccharide, tannin, amino acid, protein, acylate, alkaloid salt and glycoside etc. can by water-soluble go out. In order to increaseThe solubility of some composition, also often adopts sour water and buck as extracting solvent.

2. hydrophilic organic solvent: namely general said and the miscible organic solvent of water, as ethanol (claim again:Alcohol), methyl alcohol (claim again: another name for), acetone etc., the most frequently used with ethanol. The solubility property of ethanol is relatively good, to Chinese herbal medicine cellPenetration capacity is stronger. Outside hydrophilic composition isolating protein, mucilaginous substance, pectin, starch and part polysaccharide etc., large multipotency is at ethanolMiddle dissolving. Be insoluble in the lipophilic composition of water, the solubility in ethanol is also larger. Can also be according to the property that is extracted materialMatter, adopts the ethanol of variable concentrations to extract. More less than water consumption with alcohol extract, extraction time is short, dissolves water-solubleProperty impurity also few. Ethanol is organic solvent, though inflammable, toxicity is little, low price, and convenient sources, has a locking equipment to returnReceive Reusability, and the extract of ethanol is difficult for moldy metamorphism. Due to these reasons, with the method for alcohol extract be alwaysOne of conventional method. The character of methyl alcohol is similar with ethanol, boiling point lower (64 DEG C), but toxic, when use, should note.

3. lipophilic organic solvent: namely general said and the not miscible organic solvent of water, as benzinum,Benzene, chloroform, ether, ethyl acetate, dichloroethanes etc. The selectivity of these solvents is strong, can not or be not easy to propose hydrophilyImpurity. But this kind solvent volatility is large, how inflammable (except chloroform), generally poisonous, price is more expensive, and equipment requirement is higher, and itPenetrate plant tissue ability a little less than, often need repeatedly to extract for a long time and could extract completely. If contained in medicinal materialMany moisture, is just difficult to leach its active ingredient with this kind solvent, therefore, while extracting herbal raw material in a large number, directly applies thisKind solvent has certain limitation.

(3) extracting method: use solvent extraction medicinal herb components, conventional infusion process, percolation, decocting method, reflux extractionAnd continuous circumfluence extraction method etc. Meanwhile, the factor such as the degree of grinding of raw material, extraction time, extraction temperature, appointed condition also can shadowRing extraction efficiency, must take in.

1. flood extraction method (being called for short: infusion process): the dipping genealogy of law packs herbal powder or fragment in suitable container into,Add suitable solvent (as ethanol, rare alcohol or water), dipping medicinal material is with the wherein method of composition of stripping. This law is fairly simple easilyOK, but leaching rate is poor, and as water be solvent, the easy moldy metamorphism of its extract, must note adding suitable anticorrisive agent.

2. permeating extraction (being called for short: percolation): percolation is that herbal powder is contained in percolator, constantly adds newSolvent, makes it penetrate medicinal material, flows out a kind of leaching method of leachate from top to bottom from percolator bottom. When solvent infilters medicinePowder, dissolved element proportion strengthen and while moving down, its position is just replaced in the solution on upper strata or rare immersion liquid, causes good concentrationPoor, diffusion energy is carried out preferably, therefore leaching effect is better than infusion process. But answer coutroi velocity, oozing in transient at any time from medicineOn face, supplement novel solvent, make in medicinal material till active ingredient fully leaches. Maybe ought ooze dropping liquid color extremely shallow or ooze the volume that gushes liquidWhile being equivalent to heavy 10 times of crude drug, just can thinking and substantially extract completely. Normal by rare leaching of collecting in a large amount of productionLiquid is as the use of the solvent of another batch of new raw material.

3. decoct extraction method (being called for short: decocting method): decocting method is traditional leaching method that China is used the earliest. Appearance usedDevice is generally pottery, sand tank or copper, enamel ware, should not use iron pan, in order to avoid liquid variable color. When straight fire heating, preferably often stirMix, in order to avoid that local medicinal material is heated is too high, be easily charred. Have the pharmaceutical factory of steam-heating apparatus, adopt more large reaction pot, large copper pot,Barrel, or pass into Steam Heating in the pond of cement block. Also several decocting devices can be connected to each other by pipeline, carry out continuouslyDecoct and soak.

4. heating and refluxing extraction method: the heating of application organic solvent is extracted, and needs to adopt reflux heating device, in order to avoid solvent evaporatesLoss. While operation in a small amount, can on round-bottomed flask, connect reflux condenser. The in-built medicinal material of bottle is about 20%～60% of capacity,Solvent soaked approximately 1～2cm of medicinal material surface. In water-bath, add hot reflux, general maintenance, seethes with excitement 3～6 hours, lets cool filtration, thenSolubilizer in the dregs of a decoction, does second and third time and adds hot reflux about half an hour respectively, or to till substantially putting forward most active ingredient. This method is carriedGet efficiency high compared with cold-maceration, the continuous extractions that adopt in a large amount of production more.

5. continuous circumfluence extraction method: application volatile organic solvent extract Chinese herbal medicine effective ingredients, no matter small test orLarge-scale production, all with continuous extraction for well, and need by quantity of solvent lessly, extract composition also more complete. Fat is commonly used in laboratoryFat extractor or title apparatus,Soxhlet's. Continuous extraction, generally needs a few hours could extract completely. Extract composition heated timeLonger, the labile composition of case of thermal instability should not adopt this method.

2, Isolation and purification method

Extracts of Chinese herbal medicine or extract that said extracted method obtains remain mixture, need further remove impurity,Separate and refine.

(1) solvent segregation: be generally by above-mentioned total extract, select three, the solvent of four kind of opposed polarity, by low polarityExtract separation to high polarity substep. Aqueous extract or ethanol extract are often jelly, are difficult to be dispersed in low polar solventIn, therefore can not extract completely, can admix appropriate inert filler, as diatomite or fiber powder etc., then low temperature or natural drying,After pulverizing, then to select solvent to extract successively, make each constituent in total extract, according to its solubility in opposed polarity solventDifference and separated. Utilize Chemical Constituents of Chinese Traditional And Folk Medicine, the solubility in opposed polarity solvent is carried out separation and purification, isConventional method.

(2) solvent extraction:

1. extraction: solvent extraction extraction is called for short again extraction is to utilize in mixture each composition two kinds of phases not mutuallyThe difference of distribution coefficient in molten solvent and reach the method for separation. If each composition distribution coefficient in solvent differs when extractionLarger, separative efficiency is higher; If the active ingredient in aqueous extract is lipophilic material, general multiplex lipophilicity hasMachine solvent, as benzene, chloroform or ether extract, if active ingredient is to be partial to hydrophilic material, in lipophilic solventIndissoluble solution, just need to use weak lipophilic solvent, such as ethyl acetate, butanols etc. instead. Can also in chloroform, ether, add suitableAmount ethanol or methyl alcohol are to increase its hydrophily. While extracting flavones ingredient, multiplex ethyl acetate and water extraction. Extraction hydrophily is strongSaponin(e for multiselect n-butanol, isoamyl alcohol and water extract. But, common organic solvents hydrophily is larger, extracts with waterEffect just more bad because can make more hydrophilic impurities follow, on active ingredient, further refining impact is very large.

2. counter current continuous extraction method: be a kind of continuous solvent extraction. Its device can have one, several or moreExtracting tube. In pipe with little porcelain circle or the filling of little stainless steel wire ring, the contact-making surface when increasing solvent extraction. If a kind of medium-height grassThe infusion of medicine need to extract with benzene, the ethyl acetate etc. lighter than water, needs water extracting liquid to be contained in extracting tube, andBenzene, ethyl acetate are stored in high-level container. Extract whether complete, desirable for sample thin-layer chromatography, paper chromatography and chromogenic reaction orPrecipitation reaction checks.

3. counter-current distribution method: counter-current distribution method claims again CCD method, counter-current distribution or countercurrent distribution. Adverse current is distributedMethod is consistent with solvent counter-current extraction principle, but application of sample amount is certain, and continuous in the solvent of certain capacity, extracts through multi-shiftGet and distribute and reach the separation of mixture.

4. drop counter-current distribution method: drop counter-current distribution method claims again droplet countercurrent chromatography method. For distributing in adverse current in recent yearsImproved solvent extraction on method basis. To the substantially same counter-current distribution method of the selection of solvent system, but requirement can be at short noticeBe separated into, and can generate effective drop. Form mutually drop due to mobile, in thin distribution extracting tube with fixing phase effectivelyContact, friction constantly form new surface, promote the distribution of solute in solvent, therefore its separating effect often distributes than adverse currentMethod is good.

(3) Flavonoids by Macroporous Adsorption Resin: macroporous absorbent resin is the class organic polymer growing up the sixties in 20th centuryAdsorbent, has good absorption property, be applied to gradually in the recent decade Chemical Constituents of Chinese Traditional And Folk Medicine extraction separate and inDeveloping of medicine new drug.

Macroporous absorbent resin is the parting material that absorption and screening principle combine. Its adsorptivity is because Van der Waals drawsThe result of power or generation hydrogen bond. Screening principle is because itself cellular structure determines. Due to absorption and screening principle, haveOrganic compounds, according to the size of the difference of absorption affinity and molecular weight, divides through certain solvent elution on macroporous absorbent resinOpen. This make organic compound especially the purification of water soluble compound greatly simplified. The skeleton of macroporous absorbent resin byStyrene and divinylbenzene polycondensation and generate, due to adding of modifier, the polarity of macroporous absorbent resin changes, according to treeThe surface nature of fat, that polymeric adsorbent is generally divided into is nonpolar, Semi-polarity and polarity three classes.

Nonpolar adsorption resin is not setting with the absorption of any function base of being made by the very little monomer-polymer of dipole momentFat. Typical example is the polymeric adsorbent of styrene-divinylbenzene system, as D101, XAD-1, DiaionHP-10 macroporous absorptionResin.

Semi-polarity polymeric adsorbent refers to the polymeric adsorbent containing ester group, as acrylate or methacrylate and two metering systemThe analog copolymer that acid esters etc. are crosslinked. It is on the basis of nonpolar macroporous adsorption resin, adds methyl acrylate or propyleneNitrile polycondensation forms, as the often AB-8 macroporous absorbent resin of use of China.

Polar Adsorbent Resin refers to that amide-containing, itrile group, phenolic hydroxyl group etc. are nitrogenous, the polymeric adsorbent of oxygen, sulphur polar functionalities base.In addition, sometimes the ion exchange resin of the ligand groups such as nitrogenous, oxygen, sulphur is called to strong Polar Adsorbent Resin, strong polarity absorption treeThe boundary of fat and ion exchange resin is difficult to difference. Polar macroporous adsorption resin can be by methyl methacrylate, acrylamideOr sulfoxide type polycondensation forms, as the XAD-10 of the DiaionHP2MG of Mitsubishi chemical industry, Rohm-hass company of the U.S., XAD-9 macroporous absorbent resins.

Compare with other adsorbent with active carbon, macroporous absorbent resin has advantages of a lot, as the suction to certain materialAttached selectively higher; Physical and chemical stability and mechanical strength are better; Description is more, can change as required resin physicsOr chemical constitution; Polymeric adsorbent is generally spherical particle, and fluid resistance is less etc. Thereby be widely used in chemical industry, medicineIn field, about macroporous absorbent resin, the report of the application study in natural product extraction separates is more and more in recent years. MacroporePolymeric adsorbent has certain to Chemical Constituents of Chinese Traditional And Folk Medicine as alkaloid, flavones, saponin(e, cumarin and some other methods of glycosidesSuction-operated. Very poor to sugared adsorption capacity, stronger to the adsorption capacity of pigment.

(4) precipitation method: be to add some reagent to make to produce precipitation in extracts of Chinese herbal medicine, to obtain active ingredient or to removeThe method of decontamination. As lead salt precipitation: lead salt precipitation is one of classical way separating some medicinal herb components. Due to vinegarLead plumbate and basic lead acetate, in water and alcoholic solution, can generate with multiple medicinal herb components lead salt or the complex salt precipitation of indissoluble, thereforeCan utilize this character that active ingredient is separated with impurity. Then lead salt precipitation is suspended in novel solvent, passes to stink dampBody, makes to decompose and to transfer insoluble sulfuration to plumbous and precipitate.

(5) salting out method: salting out method is in the water extraction liquid of Chinese herbal medicine, adds inorganic salts to finite concentration, or reaches capacityState, can make the solubility of some composition in water reduce Precipitation, and separate with water-soluble large impurity. Be commonly used for and saltoutInorganic salts have sodium chloride, sodium sulphate, magnesium sulfate, ammonium sulfate etc.

(6) dialysis: dialysis is to utilize small-molecule substance can pass through pellicle in solution, and macromolecular substances can notBy the character of pellicle, reach the method for separation. Otherwise also macromolecular impurity can be stayed in pellicle, and by little moleculeMaterial enter in the outer solution of film by pellicle, and separation and purification in addition.

(7) crystallization, recrystallization and Steppecd crystallization: qualification Chemical Constituents of Chinese Traditional And Folk Medicine, study its chemical constitution, first must beMedicinal herb components is prepared into monomer sterling. At normal temperatures, material nature is the compound of liquid, can use respectively fractionating processOr chromatography is carried out separation and purification. In general, Chemical Constituents of Chinese Traditional And Folk Medicine is the material of solid at normal temperatures mostly, all has knotThe general character of crystal, can reach according to the difference of solubility the object of separation and purification with crystallisation.

3, conventional drying method

(1) vacuum drying: be the general principle based on such: water saturation vapour pressure and temperature are closely related, in vacuumUnder state, the boiling point of water reduces, i.e. namely operation at low temperatures of operation under vacuum, can avoid at high temperature nutritional labeling asThe destruction of vitamin etc. has been improved rate of drying simultaneously. Vacuum drying is widely used in industries such as food, pharmacy, chemical industry,China also develops and has introduced various vacuum dryers, and its version is varied. Conventional form mainly contains box trueEmpty drier, double-cone type vacuum desiccator, belt vacuum desiccator etc. These traditional Minton dryers mainly adopt heatWind, the heating such as steam or electricity, utilize hot conduction, convection current or radiation theory heat to be passed to material inside from outside. Vacuum dryingHave baking temperature low, relatively hypoxia in hothouse, can avoid fat oxidation, and the series of advantages such as pigment brown stain, are suitable for heatSensitiveness food material dry, equipment cost, dry expense are also relatively low in addition.

(2) spraying is dry: be that fluidization technique is for a kind of dry method of liquid material. Because being wink-dry, suitable especiallyFor heat sensitive material, therefore products obtained therefrom quality is good, keep original color, smell and taste, and soluble. Utilize spraying to be dried to prepareThe research of micro-capsule is carried out, and it is that heart material is suspended in the solution of dress material, sprayed in thermal current through centrifugal atomizer,The product of gained is the micro-capsule that dress material bag heart material forms, and this micro-capsule powder can be used in direct tablet compressing, also can prepare capsule,Syrup or supensoid agent.

(3) freeze drying: be that dry liquid material is frozen into solid, utilize the sublimability of ice under low-temperature reduced-pressure conditionCan, low-temperature material is dewatered and reach a kind of dry method. Because material is dry under high vacuum and cryogenic conditions, therefore rightThe dry of some extremely thermo-labile article is well suited for. Wang great Lin has reported a kind of spraying ventilation freeze-drying new technology, is to utilize cold skyGas or nitrogen are as medium, and the scars of flowing through rapidly make water sublimate, and the product particulate that makes of spraying freeze-drying is little, fast drying, timeShort, even, good fluidity, and the good instant capacity of tool. In recent years, plaster material and the dry research of sticky material have been obtainedGreater advance, fluidization technology, spraying technique, inert carrier technology grow up on this Research foundation. Rotation is dodgedSteam drying machine, thermojet pneumatic drier, inert carrier drying machine and be all applicable to the dry of heat sensitive material and plaster material. ThisA little new achievements in research are produced for Chinese medicine preparation, by greatly improving the technical merit of Chinese medicine processing, enhance productivity.

(4) far infrared heating drying method: be a new dry technology, its drying principles is to change electric energy into far infraredRadiation, thus by the molecule absorption of medicinal material, produce resonance, cause vibration and the rotation of molecule and atom, cause object heating, warpCross thermal diffusion, evaporation and chemical change, finally reach dry object. Far-infrared ray drying can be saved electric energy 20%～50%, effectFruit better.

(5) micro-wave drying method: be the new technology developing rapidly a sixties in 20th century, microwave drying is actuallyBy eddy-current heating and dielectric heating, the moisture and the fat microwave energy absorbing to some extent that make to be dried in thing, and itThereby change heat into and reach dry object. Microwave drying can killing microorganisms and mould, and has disinfective action. At presentThe microwave heating installation that state produces has 915mhz and two frequencies of 2450mhz.

4, supercritical CO₂Extracting process

(1) about the extracting method of animal and plant fatty oil component has: water-boiling method, hydrophily partition method, molecular clock and decompressionThat the way of distillation, metal add is legal, extractive crystallization process, point freezing milling process of dish and organic solvent method etc.

Adopt hot water bath method, because the heat time is long, temperature is high, easily make heat-labile volatile ingredient change,As the oxidation of some unrighted acids. Hydrophily partition method, the obvious advantage of this partition method is to have eliminated organic solvent method to causeHigh cost and public hazards, but the shortcoming of this technology is the saturated fatty acid that obtains and purity or the rank of unrighted acidBe not so good as Batteries by Organic Solvent Partition Process high. Molecular clock and distillation under vacuum, for reducing thermal denaturation, need come by methods such as urea adductsRemove most of saturated fatty acid, in the product obtaining, must be removed; Although can obtain purer aliphatic acid, need severalStep just can reach target, and more time-consuming, effort, has increased production cost. Metal adds the lower K cryogenic treatment of legal separation needs,After also to manage to remove metal ion, remove and not to the utmost also can cause metal ion pollution. Extractive crystallization process obtains aliphatic acid purityHigher, at lower temperature, carry out, can prevent the oxidation of aliphatic acid, but the time is longer, be not too applicable to large-scale industryChange and produce. Divide the freezing milling process shortcoming of dish to be, the refrigerating chamber of laying plate rail and hydraulic press needs area and the Pang of thousands of square metresLarge cooling system, large facility needs many people's operations, and labour intensity is high, and separating rate is slow, and efficiency is low, can not grasp continuouslyDo. Organic solvent method is to adopt benzinum or ether organic solvent under heating state, to carry out reflux cycle extraction in water-bath; ByIn adopted organic solvent as benzinum or ether etc. are a kind of low-boiling point material, inflammable and explosive, meanwhile, organic solventUse and pollute the environment on the one hand, organic solvent likely has residually in extract on the other hand, can affect extract doctorFurther application on medicine.

(2) about the supercritical CO of animal and plant fatty oil component₂Extracting process: a kind of fluid is when being in its critical-temperatureDuring with pressure state, be called as supercritical fluid. Because the density of supercritical fluid is close to liquid, have and liquid flux phaseWhen extracting power. There is again the low viscosity suitable with gas, large 100 times than liquid of diffusivities, thereby have higherMass transfer performances. When adopting supercritical extract, utilize these character of supercritical fluid, make it to contact with material to be separatedPenetrate matrix, therefrom extract target substance. Then utilize the way of step-down and/or intensification to reduce its density, thereby reduce moltenMatter solubility therein, makes extract and separated from solvent. Because different materials is solubility under identical extraction conditionsBe different, thereby likely by this species diversity, they further separated. Supercritical fluid extraction is usually selected CO₂Deng facingTemperature low and chemically inert material in boundary's is extractant, and it is specially adapted to separating of heat-sensitive materials and readily oxidizable substance, thereforeBe highly suitable for separating for the extraction of animal fat. Therefore, the present invention takes the method, can prepare highly purified being extractedThe fat oil of thing.

Supercritical CO₂Extracting process is to extract like this: the meal of dry extract is placed on to supercritical extract and establishesIn standby, use CO₂Extract, after decompression, obtain the fat oil of extract, under room temperature condition, be light yellow transparent oily; ExtractThe fat oil of extract in the purity of TFA more than 40, be better than other extracting methods; TFA generally comprisesOther components of oleic acid, linoleic acid, palmitic acid and surplus etc.

Supercritical CO₂The method of the fat oil of extraction extract comprises the steps:

(1) dry extract is crushed to after 10～30 orders, is placed in supercritical extraction reactor, pass into continuously super facingCO under boundary's state₂Extract, preferably condition generally: CO₂Flow 10～55kg/hkg raw material, pressure 5～50Mpa,15～75 DEG C of temperature, time 0.5～6h; Further preferred condition generally: CO₂Flow 45kg/hkg raw material, pressure35Mpa, temperature 50 C, time 1h;

(2) CO of fat oil of extract will have been extracted₂Be decompressed to 1～12MPa, can obtain at ambient temperature byThe fat oil of extract, in the fat oil of extract the purity of TFA more than 40%, the physicochemical character of extract andAliphatic acid purity is all better than other extracting methods.

The selection of extraction conditions realizes by following way: first selected four factors, three levels, and according to orthogonal designMethod, by L9 (3⁴) (orthogonal arrangement is with reference to Guo Zuchao chief editor " Medical Statistics ", people to hand over design table experiment arrangementPeople's militia cures publishing house, the first edition in 1999). From Orthogonal experiment results, analyze and be extracted process conditions.

To supercritical CO₂The fat oil of the extract of extraction carries out, after methyl esterification of fatty acid, carrying out gas-chromatography～matterAnalysis of spectrum.

Supercritical CO₂The preparation method of the fat oil of extraction extract does not with an organic solvent wait material, can not pollute, there is not the problems such as harmful dissolvent residual in environment yet, and easy and simple to handle, extraction time is short, product purity is high, the CO of use₂Cheap and can repetitive cycling use, industrial production is with low cost.

(3) research overview of antineoplastic

Malignant tumour serious harm people's health, according to RST statistics, in the whole world 50 the more in hundred million populations every year on averageDie from malignant tumour person and reach 6,900,000 people, new cases are 8,700,000 examples, and numeral is also increasing year by year. Therefore, national governments, grindStudy carefully mechanism and drugmaker and tumor research and antineoplastic are paid much attention to for a long time always, at antineoplasticIn research, obtain at present major progress. The development of molecular weight tumor in recent years,, molecular pharmacology makes tumour essenceProgressively illustrate; The invention of the advanced technologies such as extensive rapid screening, combinatorial chemistry, genetic engineering and application acceleration drug developmentProcess; The research and development of antineoplastic have entered brand-new epoch. Antineoplastic is just from traditional cytotoxicityMedicine, to the new type antineoplastic medicine development of the too many levels effect for machine-processed.

Therefore, research and develop novel antineoplastic and become exigence. The large drug market table in the world seven in 2000Bright, the drug market of antineoplastic has increased nearly one times from more than 400,000,000 dollar of the mid-90 in 20th century, calendar year 2001 the whole worldNearly 1,200,000,000 dollars of market value; External analyst's prediction patient within Future Ten year will be increased to 20% left and right, medicine cityThe growth rate of field is by the rising having by a relatively large margin. Due to being on the increase of patient, the market sales revenue of medicine also alwaysIn steady-state growth. The nineties in 20th century, such medicine became situation of selling well medicine, nineteen ninety-five world's sales volume reached 5,000,000,000 dollars. 21Beginning of the century, the sales volume of such medicine has exceeded the treatment cardiovascular disease treating medicine, the treatment gastrointestinal disease medicine that are arranged in first threeWith the share in anti-infectives market, its growth momentum is good.

At present, such disease is more and more subject to China national and social great attention, and due to such disease classBe similar to the rich man's diseases such as diabetes, equally need long-term taking medicine, therefore its medication market along with aging population byFlaring is large, and market prospects are good. Based on this, for understanding in time the market situation of Chinese medicine, China national food and medicineSurveillance Authority south information centre of medication economics research institute choose six main medication cities of China (Beijing, Shanghai, Guangzhou,Nanjing, Hangzhou, Chengdu) various schools of thinkers sampling hospital, 60 doctor experts and 120 consumers, to China medication market(1999 and 2000) and mainly compete kind and carried out comprehensive market survey activity.

Medicine sell data show, global pharmacy corporation the last 50 is 2.8% at the prescription medicine sale growth of 2007,And wherein antitumor class medicine growth is the fastest, reach 14%. 2006 annual datas show equally, the pin of antineoplastic in 10 class medicinesSell growth and rank first, reach 20.5%. This has reflected the continuing of antineoplastic, the market demand of rapid growth. China is in systemOn the basis of fixed medium-term and long-term scientific development planning, propose to set up a collection of great special project. " great new drug initiative " is from Eleventh Five-Year PlanTo one of national major project of supporting between the year two thousand twenty. This project will be for the multiple serious harm people such as tumour, cardiovascular diseaseMajor disease, development original new drug. Clearly, the research and development of anti-cancer agent, are control serious harm people diseasesSick needs are also the vital tasks of Chinese sustainable development and construction innovation-oriented country. What " great new drug initiative " was special sets up,To the process of Chinese anti-cancer agent research and development be produced to active influence.

Treatment of cancer is the great difficult problem of Med Biol. Development can be effected a radical cure the medicine of tumour, still " shoulders heavy responsibilities ".Compared with advanced international standard, China is still having big gap aspect anti-cancer agent research. The research of anti-cancer agent with openSending out is a difficult task, is long-term, a complicated process, needs scientific and technical personnel to work without single devotion for a long time with long-pendingTired. Therefore, need to provide stable working environment and condition for researcher; Need each side professional and associated mechanisms concerted effortCooperation; Need to be conducive to promote Guaranteeing measures of policy and the organizational coordination mechanism of cooperation; Need to have larger amt funds to comprise facesThe support energetically of the funds of research and clinical research before bed.

Current, anti-cancer agent research and development are faced with good opportunity. Chinese Medicine the reach of science, various novel for developingAntineoplastic provides important theoretical foundation and new technical support. The development of Health Care in China cause, to comprising cancerDisease is had higher requirement at interior therapy of serious disease medicine, and the great demand of Chinese market and world market can be given research and developmentUnit brings considerable economic benefit. China sets up " great new drug initiative " great special project, will greatly promote that Chinese new drug comprisesThe research and development of anti-cancer agent.

Treatment of cancer medicine accounts for the 7th of world's drug market, is worth 6,100,000,000 dollars to the end of the year 2005. And it is anticancer at presentDisease drug is mainly relief of symptoms, does not contain the development of the state of an illness. Therefore,, in conjunction with Chinese Chinese traditional herbs, therefrom excavate and haveThe medicine of effect, low toxicity, inexpensive treatment cancer, seeking a kind of effective methods for the treatment of, to stop potential pathogenic process be very mustWant, so it is considered herein that development is for preventing, diagnose, detect, protect and the particularly medicine tool of product of the aspect such as treatmentThere is very important meaning, also can produce significant Social benefit and economic benefit.

The cancer research of several important kind that just wherein the present invention pays close attention to is below summarized.

(4) progress of lung cancer

1, general introduction

Primary bronchogenic carcinoma of lung (abbreviation lung cancer), is modal malignant tumour in the world at present, has every year 102100000 newly-increased cases, wherein non-small cell lung cancer accounts for 80%. Lung cancer is China's the first lethal cancer especially, has every year 600000 patientsDie from lung cancer.

The incidence of disease and the fatal rate of lung cancer rank first, account for 16% of whole malignant tumours, all cancer mortality number28%, the serious harm mankind's health. Although operation, radiotherapy, chemotherapy become three large sharp weapons for the treatment of lung cancer, ChineseThe incidence of disease of lung cancer is always in rising trend, increases progressively every year on average 11.9%, expects 2025, the annual new pulmonary carcinosis of ChinaNumber can reach 1,000,000 people, becomes first lung cancer big country. Chinese Medicine is also being brought into play in the lung cancer control of countries in the world can notAlternative effect, has obtained the achievement attracting people's attention, and has been subject to paying close attention to widely.

2, pulmonary carcinosis because of research

Pulmonary carcinosis is because of 1. smoking; 2. physical chemistry carcinogen; 3. atmosphere pollution; 4. chronic Pulmonary Diseases and body are exempted fromEpidemic disease hypofunction; 5. endocrinopathy and 6. Family genetic factors etc.

American scholar Minna in 1998 by perspective to lung cancer occur, molecular pathology research in evolution, carryGo out the genetic mutation pattern of lung carcinoma cell: 3P gene loss → 9P gene loss and ras gene mutation → carcinoma in situ (p53,17p13.3 gene mutation) → invasion of lung cancer or transfer (p15, p16, C-myc, c-erB2, EGFR gene mutation). No. 10 dyeingThe phosphatase that body is lost and tensin homologue (be called for short: PTEN) gene is a tumor suppressor gene with phosphatase activity,PTEN positive expression is starkly lower than normal lung tissue in cancerous lung tissue, and it may participate in development and the infiltration of lung cancer and turnMove.

In lung cancer all there is the abnormal of 26S Proteasome Structure and Function in p16 gene, proved the generation phase of p16 gene inactivation with lung cancerClose. P15 gene is newfound CDKN2, and its product p15 albumen cell growth plays down regulation, vascular endothelial growthThe factor (is called for short: VEGF) be one of angiogenic factors, tumour cell produces VEGF, has important in tumor vessel generatesMeaning. P15 gene is by regulating VEGF to control the generation of blood vessel, and this contributes to find the development mechanism of tumour.Survivin is that a kind of human body cell IAP of recent findings (is called for short: hIAP), be minimum hIAP albumen.Survivin gene may be by suppressing Increase Apoptosis of Lung Cancer Cells, and generation, development to lung cancer play an important role.

3, lung cancer parting and epidemiology survey

(1) lung cancer somatotype substantially

1. position somatotype

Centre type: the bronchus that the tumour section of occurring in is above;

Peripheral: the bronchus that the tumour section of occurring in is following;

Diffuse type: at bronchiole or alveolar, fill the air and be distributed in two lungs.

2. Type of injury

Intracanalicular type, tube wall infiltrative type, nodular type, block type, Differentiation of Diffuse Invasive.

(2) the clinical common histological classification of lung cancer

Lung cancer from can be divided into substantially ED-SCLC (be called for short: SCLC) and non-small cell lung cancer (abbreviation: NSCLC). ItsMiddle major part is non-small cell lung cancer, accounts for 80%, and ED-SCLC accounts for 20%. Approximately 65%～70% non-small cell lung cancerWhen medical just in late period.

1. non-small cell lung cancer

Phosphorus cancer: tend to, to bronchial wall growth, also send out to central authorities, form central authorities' property downright bad and empty. And easily blockTube chamber causes obstructive pneumonia. And easily invade blood vessel lymphatic vessel and backward DISTANT METASTASES IN.

Gland cancer: mostly be peripheral pulmonary parenchyma lump. Can invade in early days blood vessel, lymphatic vessel, the primary tumor of being everlasting causes symptomBefore shift.

Maxicell lung cancer: this class tumor growth is rapid, often invades lymph node, blood vessel and distant place organ.

2. ED-SCLC: often occur in large bronchus, how to have transferred to hilus pulumonis and mediastinal lymph nodes in early days, owing to easily invadingViolate blood vessel, in the time of diagnosis, the existing lung of great majority shifts outward.

Lung cancer metastasis and recurrence: lung carcinoma cell often follows lymphatic dissemination to hilus pulumonis, mediastinum, clavicle and axillary lymph knotDeng, it can directly invade blood vessel, and cancer embolus occurs, and causes DISTANT METASTASES IN. Liver, brain, adrenal gland, bone, hypodermis etc. are the most commonMetastasis site, lung cancer likely forms extensive lymphatic channel and Blood route metastasis in early days.

Lymph Node Metastasis: head is shown in bronchopulmonary lymph nodes, paratracheal lymph nodes, lymphonodi cervicales, hilar lymph node, mediastinal lymphKnot.

Hematogenous metastasis: be common in brain, adrenal gland and kidney.

Causes of recurrence: postoperative not complex treatment, uncertain its check.

The incidence of disease of lung cancer present with the industrial area in city taper off to surrounding rural area distribute trend. The morbidity of lung cancerRate increases with age growth, within 40 years old, rises rapidly later, within 50～60 years old, rises remarkable especially, within 70 years old, slightly decline later, and manProperty is higher than women, and men and women's ratio is 3～7.1: 1.

4, the progress of pulmonary cancer diagnosis

The early diagnosis of lung cancer is the effective way that improves result for the treatment of, is also the key factor that determines patient's prognosis, butLack at present effective early diagnosis means. Molecular biology research result contributes to the early diagnosis of lung cancer, iconography and phlegmThe progress of liquid exfoliative cytology is also for the early diagnosis of lung cancer provides advantage.

(1) lung cancer clinical manifestation

Lung cancer symptom is divided lung cancer early symptom and advanced lung cancer symptom, in early days how not obvious, middle and advanced stage expectoration, hemoptysis, pressureCompel symptom typical case. Obviously whether the symptom of lung cancer, is the signal of interest of the diagnosis early stage of lung cancer, and advanced lung cancer easily occurs to shift as brainTransfer, Lymph Node Metastasis, bone shift, hepatic metastases.

1. lung cancer early symptom: the most common cough, spitting of blood, pectoralgia and heating.

Lung cancer early symptom: excitant dry cough, white mucus spume sample phlegm, blood-stained sputum silk or hemoptysis, or pectoralgia, chestDiscomfort, expiratory dyspnea and fever etc.

2. lung cancer middle and advanced stage symptom:

Bronchial obstruction: make gas be difficult for discharging, form obstructive emphysema. When lump is grown up, even atelectasis.

Infect: occur obstructive pneumonia, when serious, can form pulmonary abscess.

Compressing and metastasis symptom: compressing brachial plexus nerve causes brachialgia, paralysis, amyotrophia, sensorimotor function obstacle etc.; FoodRoad is invaded or can be produced to swallow when pressurized to be blocked; Nervus phrenicus is invaded generation phrenoparalysis; Recurrent nerve is invaded, trachyphonia; Compressing is invadedThe vena cave of going against one's superiors, causes superior vena cava syndrome, has giddy, dim eyesight, Head And Face and upper limbs swelling, front venous engorgement; InvadeWhen pleura, there is hydrothorax, when pericardium is invaded, can occur hydropericardium.

Other symptoms: the joint symmetry enlargement pain of long bone, acropachia (toe) etc., the skins such as itch all over and nettle rashSymptom.

(2) lung cancer sign

Localized wheezing sound, hoarseness, superior vena cava syndrome, shoulder arm pain, diaphragmatic paralysis, dysphagia, the heartBag is invaded, pleura shifts, lung shifts outward.

(3) pulmonary cancer diagnosis main points

1. x-ray rabat is found Solitary pulmonary nodule or lump, or has bronchial obstruction sign through CT examination, should doubt as lungCancer.

2. the long-term smoking male sex is more than 40 years old, and irritable cough, accompanies spitting of blood on a small quantity, and rabat is found limitation focus, anti-inflammatoryTreating tuberculosis (2～4 weeks) is invalid or focus counter become increase.

3. obviously out of breath, cough, x-ray rabat both sides are millet appearance or dispersivity focus, should get rid of miliarytuberculosis, lung turnsMove the pathology person such as cancer, pneumomycosis.

4. find in the heart lung's piece shape, with hilus pulumonis or (with) mediastinal lymph node enlargement, and occur superior vena cava block, larynxThe neural blood vessel pressure symptoms such as nervus recurrens paralysis, or with distant place lymphatic metastasis person.

5. cytolgical examination or the biopsy person of clarifying a diagnosis.

(4) other auxiliary diagnosises

(be called for short: TTF-1) be a new tumor markers of recent findings, main and first shape the Thyroid metastasis factor-1Adenoncus knurl is relevant with lung neoplasm. Detect the diagnosis that TTF-1 can effectively improve lung cancer. The sun of TTF-1 in ED-SCLCProperty rate is 81%～100%. 1996, Byrd-Gloster differentiated adenocarcinoma of lung and the outer gland cancer of lung with TTF-1, in result adenocarcinoma of lungTTF-1 positive rate is 76%, and the outer gland cancer positive rate of lung is 0, shows that TTF-1 is for differentiating that the outer gland cancer of adenocarcinoma of lung and lung has importantMeaning.

Specific neuronal anti Hu antibody is to come across paraneoplastic neurologic syndromes (to be called for short: one spy PNSNS)The opposite sex, sensitiveness antibody, PNSNS is mainly seen in ED-SCLC, and anti-Hu antibody is 20% left and right at the positive rate of SCLC, and thisTime tumour in the early stage radical cure stage, therefore, significant to early diagnosis ED-SCLC.

Telomerase is the tumor markers of generally acknowledging at present known wide spectrum the most. The hand of Kumaki to 115 routine patients with lung cancerArt sample detects, and positive rate of telomerase is 93%. Wherein the telomerase activation of ED-SCLC is significantly than other typeCancer telomerase activation is high. Telomerase activation detect conjunctive tissue and cytolgical examination can improve pulmonary cancer diagnosis rate be 90% withOn.

Iconography is irreplaceable in the effect of diagnosing. The disease of 2～3mm can be accurately found in spiral CT inspection at presentKitchen range. And positive electron fluorescent scanning (is called for short: PET) can be used for discriminating good before performing the operation, malignant tumour. In conjunction with fine needle aspiration biopsy orThoracoscope biopsy can draw reliable diagnosis. In recent years Imaging Technology is constantly progressive, and new technology is examined as Virtual bronchoscopeLook into, low-dose spiral CT inspection hinders diagnostic method in conjunction with Wicresoft, can obviously improve the early diagnosis of lung cancer.

The fluorescence bronchoscope developed the nineties in 20th century (be called for short: LIFE), its operation principle be with wavelength be 400The blue light illumination bronchial tree of～440nm, bronchoscope connects high-resolution camera, and the image of look-out station is passed through to dataConverter input computer, is finally reflected into the image of look-out station on fluorescent screen. Normal structure is sent green glow, and precancerosisChange, carcinoma in situ and early invasive carcinoma are sent different ruddiness, LIFE to the diagnosis of precancerous lesion and carcinoma in situ than common Bronchofiberscope1.5～6.3 times are improved. Also high than the common Bronchofiberscope degree of accuracy to infiltrating carcinoma. Another kind of fluorescence Bronchofiberscope is Storz bronchusMirror, it only with white light by blue filter as exciting light, and without laser and high-resolution camera, patient need first take 5-Aminolaevalinicacid (is called for short: ALA), to strengthen the autofluorescence intensity of pathological tissues, can make like this precancerous lesion portionStronger ruddiness is sent in position, strengthens the colour contrast of diseased region and normal structure, is conducive to find precancerous lesion, improves early stageDiagnosis. But fluorescence Bronchofiberscope is mainly used in central type carcinoma of lung, and specificity is lower, approximately 33%.

Mediastinoscopy and thoracoscopy can be understood accurately to thoracic cavity endolymph knot transfer case, are convenient to accuratelyLung cancer is carried out by stages, the prognosis of lung cancer is judged. Its degree of accuracy reaches 93%～100%, and effect is as open chest surgery.

Clinically by the pathological examination of imaging examination and operation find no shift be diagnosed as early stage non-little, also may there is invisible transfer in the patient of cell lung cancer, be called micrometastasis (Micromestasis). How to find micrometastasisIt is the hot issue of studying at present. Current research mainly concentrates on lymph node, marrow and peripheral blood aspect. Molecular biologyLearning a skill with molecular immune is the Main Means that detects micrometastasis.

5, the progress of lung cancer therapy

The treatment of lung cancer is taking multidisciplinary synthesis treatment as principle, as operation, radiotherapy, chemotherapy, physical treatment, immunization therapy,Biological therapy, targeted therapy, traditional Chinese medical herbal treatment. The Chinese medicine two of the main point lung cancer Western medicine of lung-cancer medicament classification and treatment lung cancerLarge class, although treatment lung cancer does not have specific drug, along with lung cancer therapy progress, anti-lung cancer medication is imitated significant medicine as easilyAuspicious sand, Erlotinib, chloroxoquinoline, clearing lung-heat Sanjie Pill, Jin Fukang, the evergreen capsule of compound, cantharides capsule, purple Long Jin etc., warpClinical verification is evident in efficacy and be widely used in the treatment of lung cancer.

(1) therapeutic purposes

Suppress to greatest extent or tumors destroyed. Whole body therapeutic and topical therapeutic; There is operation idicatio person, first-selected operation.Intra-operative or (with) operation after, no matter whether chemoradiotherapy all should coordinate traditional Chinese medicine, for complex treatment, (targeted therapy, biology are controlledTreatment, PCI, etc.) create conditions, reduce tumour diffusion transfer, improve symptom, extend life cycle, improve life quality.

(2) lung cancer therapy principle

1. therapy for small cell lung cancer principle: general not first-selected operative treatment in principle, taking chemotherapy and radiation as main, in cooperationDoctor's Chinese medicine.

2. Treatment for Non-small Cell Lung principle: Lymph Node Metastasis is remarkable, in preoperative auxiliary taking operation as main to I, II, IIIA phaseWith chemoradiotherapy. The IV phase, (having transfer far away) person cannot perform the operation, and can consider to accept chemoradiotherapy, extended life cycle, improved life quality, to the greatest extentAmount strives for being with knurl long term survival.

Anti-non-small cell lung cancer new approaches: " recognizing " accurate cell is treated again

Under normal circumstances, accepting after the treatment of various chemotherapy regimens, the gross tumor volume of Patients with Non-small-cell Lung can be byStep is dwindled, but still has part cancer cell " to flee from " drug effect, occurs diffusion, and continued growth. A few days ago, U.S. Dana-Farber ICR and Massachusetts Quan Ke hospital (are called for short: MGH) researcher of Cancer center delivers on " cancer cell " magazineArticle, thinks if can confirm the patient that this part occurs cancer cell diffusion, and with the pharmaceutical admixtures that initial stage is used combine intoRow treatment, can make patient's the state of an illness paracmasis continue the longer time.

Research has been chosen Patients with Non-small-cell Lung with EGFR gene mutation (with the patient of EGFR gene mutation approximatelyAccount for U.S.'s Patients with Non-small-cell Lung 12%), conventionally, this part patient is at the protein-tyrosine of accepting taking EGFR as target cellInhibitors of kinases class medicine, after the treatment of Erlotinib (Tarceva) or Iressa (Gefitinib), tumour there will be volumeThe reaction such as obviously dwindle.

Research group has found a kind of phenomenon several years ago, originally at Erlotinib (Tarceva) or Iressa (Ji FeiFor Buddhist nun) Chemotherapy under dormant non-small cell lung cancer cell, can reenter another one growth cycle, for this reason,Researcher thinks that these cells have produced drug resistance to medicine. And these cells all contain a large amount of MET gene magnification conventionallyThing. In this research, researcher has found again a kind of new phenomenon: even press down not yet starting to accept protein tyrosine kinaseBefore preparation for treating, in the Patients with Non-small-cell Lung body of part with EGFR gene mutation, just occur what fraction increasedMET cell. Researcher also finds, this sub-fraction cell can be (to be called for short: HGF) excite tumour by HGFCell produces drug resistance.

Researcher represents, HGF plays a role by diverse two approach, and produces drug resistance. First, it canProduce Growth of Cells signal by GAB1 albumen. Secondly, it is by promoting the generation of MET propagation cancer cell, to guarantee that they becomeTopmost cell type in tumour cell. Research shows, although non-small cell lung cancer tumour cell contains few before treatmentThe MET proliferative cell of amount, if but by special medicine and tyrosine kinase inhibitor use in conjunction for this class cell, curative effectCan be more remarkable.

Researcher sums up and thinks: " our research provides a kind of brand-new thinking, at the treatment initial stage, part is suffered fromPerson carries out the therapeutic scheme of Drug combination, is especially proved to be at the very start and in body, exists MET amplified matter for thosePatient, more should be like this. Before treatment, patient's tumor cell type is carried out to a multianalysis, will contribute to determineThe response situation of patient's later stage to therapeutic scheme, thus make clinician can more accurately formulate therapeutic scheme, withAvoid to large degree the generation of drug resistance. "

(3) methods for the treatment of

1. operative treatment: operation excision is the most effective means for the treatment of at present lung cancer, as much as possible removal of lesions was andThe lymph node shifting is the precondition that improves patients with lung cancer survival rate. Minimally invasive surgery is the new technology of in recent years carrying out, as chestEndoscope-assistant surgery, little to patient trauma, but can not pursue Wicresoft wound and abandon Operative Range. The standard procedures mode of lung cancerFor lobectomy of lungs.

2. chemotherapy: chemotherapy brings up to current approximately 70 to the remission rate of ED-SCLC from 40% of early 1980s～80%, and the remission rate of non-small cell lung cancer brings up to 35～45% from 15%, due to the research and development of medicine, has alleviated malicious secondary workWith, increase curative effect.

Current lung cancer chemotherapy scheme is mainly platinum containing regimens, NACT and full dose band knurl chemotherapy after can performing an operation. 20Having 70～eighties of century scholar to think can, by chemotherapy by the reduction by stages of lung cancer, improve Resection Rate, but disputeLarger. Because ED-SCLC is comparatively responsive to chemotherapy, curative effect is better, no matter local lesion is dwindled or to control micrometastasis kitchen range equalBeneficial, thought in the past that ED-SCLC was not suitable for operation, the excision of can performing the operation again after chemotherapy, is therefore again preoperative auxiliaryizationTreat, on therapy for small cell lung cancer, have certain status, simultaneously also for the development of non-small cell lung cancer induction chemotherapy has established oneFixed basis. Preoperative chemotherapy cycles number is generally advisable with 2～3 cycles, exceedes for 3 cycles above can cause pleaural adhesion, fiberChange and cause operating difficulty increase, increase complication. Be reported in one group of 484 routine statistics, think induction chemotherapy after remission rateReach 65%, the mean treatment death rate is 7%, and survival rate is longer, has statistical significance. The effect of preoperative new adjuvant chemotherapy in recent yearsBe under suspicion, no matter think from Resection Rate, median survival interval, 5 years survival rates, whether do Neoadjuvant chemotherapy withoutNotable difference.

Also there is dispute in postoperative chemotherapy, whether postoperative chemotherapy useful arguement always, until 2003 at U.S. ASCO(Americansocietyofclinicaloncology), in meeting, LeChevalier etc. have reported that 1867 examples are postoperative3～4 cycle random research of chemotherapy two generations platinum containing regimens, chemotherapy group is compared 5 years survival rates with chemotherapy group not and is respectively 44.5%Be respectively 39.4% and 34.3% with 40.5%, 5 year Progression free survival rate, median survival interval is respectively 50.8 months and 44.4Month, be better than not chemotherapy group, there is statistical significance. And chemotherapy group 23% (neutrophil leucocyte toxicity) has >=and the IV level toxicity of 1, deadAccount for 0.8% in chemotherapy person, scholars think that above-mentioned study on large sample can illustrate the effect of postoperative chemotherapy at non-small cell lung cancer,But to the effect of asynchronous non-small cell lung cancer, if first phase non-small cell lung cancer is because pathology is limited to, whether NACT to be,Need further to be studied.

The method of administration of chemotherapy also has multiple, except conventional systemic vein administration, also has Catheterization of Bronchial Artery perfusionChemotherapeutics, Bronchial Arterial Chemotherapy drug infusion add the method such as arterial embolism, tumor by local puncture administration.

The medicament selection of chemotherapy: through a large amount of clinical analysis, tumour association of the U.S. (is called for short: ASCO) think and select at presentBest as basic combined treatment curative effect taking platinum class, First-line chemotherapy medicine is recommended two regimens, to not using platinum class medicineThe patient of thing, the non-platinum class scheme for combining of two new drugs of recommendation. The chemotherapy new drug for the treatment of lung cancer mainly contains taxol (Thailand at presentElement), gemcitabine (gemzar), vinorelbine (NVB). And the up-to-date medicine using in China is Alimta.

Does is best chemotherapy cycles how many for suitable? thought in the past, chemotherapy should be with 2～8 cycles for well, recently BritainA result of study demonstration, continuously uninterrupted chemotherapy is not tolerant to most patients, and only can increase toxic action, alsoDo not have evidence prompting to increase result for the treatment of, show, after 3～4 cycle chemotherapy, the remission rate of most patients no longer improves,Extend chemotherapy cycles and only can increase toxicity, therefore, the optimal period of chemotherapy is to be suitable in 3～4 cycles.

3. radiotherapy: radiotherapy is one of primary treatment means for the treatment of lung cancer, but little alone radiotherapy is as unique treatmentMeans. There are chemotherapy and companion's row Radiotherapy chemotherapy after chemotherapy before preoperation radiotherapy, postoperation radiotherapy, radiotherapy, radiotherapy the opportunity of radiotherapy. RadiotherapyDosage has half amount radiotherapy and curative radiotherapy. Various radiotherapy patterns all have relevant bibliographical information above, generally speaking, and preoperation radiotherapyCan only reduce local relapse, without benefit, can only increase operating difficulty to lymphatic metastasis and DISTANT METASTASES IN, can not extend existenceTime. And the prolongation in various degree of other radiotherapy pattern patient's life span. Companion's row Radiotherapy chemotherapy increase cytotoxicity andDigestive tract reaction, increases complication rate, and therefore application is restricted.

4. immunization therapy: patients with lung cancer often presents immunologic function and suppresses, and immunologic function is lower, and prognosis is poorer. At presentImmunization therapy is mainly divided into active immunotherapy, passive immunization therapy and gene therapy. Active immunotherapy is divided into again non-specificProperty active immunotherapy and specificity active immunotherapy. Non-specific active immunotherapy application has immunoregulation effectStimulating factor, by the immune system of nonspecific effect excitating organism, strengthens anti-tumor immune response, as BCG vaccine, short and smallCorynebacteria etc., but its poor specificity, DeGrain. The difficult point of specificity active immunotherapy is escaping of tumour antigenEase, some common tumour antigens are used for making anti-tumor vaccine as CEA, MUC1, GD2, HuD etc. And dendritic cells (letterClaim: DC) cell vaccine is current focus. Experiment shows, the dendritic cells of derived from peripheral blood, when itself and the gland cancer of processingThe non-small cell lung cancer cell co-incubation that clone or operation are taken out, can be clear and definite under Electronic Speculum or flow cytometerLower discovery dendritic cells picked-up tumour cell, the more important thing is, the gland cell system of dendritic cells delivery can be effectively byTumour antigen absorbs and is passs T cell, thereby excites corresponding immune response. There is at present multinomial lung cancer associated antigen researchUnderway, some has entered the III phase clinical trial stage, and the progress of lung cancer vaccine is fast, desirable. PassiveImmunity is divided into again adoptive immunotherapy and antibody therapy, and adoptive immunotherapy is the antitumor activity that has self or allosomeIn immune serum or immunocyte input patient body, reach antineoplastic object, but result of use is not good separately. Antibody therapyJust becoming another study hotspot of lung cancer, the acceptor of growth factor, cell factor, protease C, cyclooxygenase 2 is that lung cancer is controlledThe targeting site for the treatment of, uses corresponding monoclonal antibody to be combined with the oncogene of unconventionality expression and can block the abnormal of cancer cellSignal transduction pathway, thereby the development of prevention cancer. Gene therapy is inseparable with immunization therapy, intersects each other, divides in recent yearsSub-biology techniques and recombinant DNA technology fast development, for the monoclonal antibody of oncogene as HER-2 monoclonal antibody,For complementary lung cancer therapy. Gene therapy key is Gene transfer techniques, and current most of carrier is virus. Controlling of geneTreating strategy is (to be called for short: TAAs) in the gene of coded sequence importing human body, excite corresponding anti-containing specific tumour necrosis factorFormer passing held cell and passed and hold to T cell (being mainly tumor-specific cytotoxicity T lymphocyte CTL cell), thereby producesImmune response killing tumor cell.

The lung cancer secret of falling ill has in early days been local late period when most of non-small cell Finding case disease or shift,Miss surgical engine meeting. The appearance of targeted drug, brings the hope of existence to the patient of chemotherapy failure.

5. physical treatment: utilize heat, cold physical means to treat tumour, thermotherapy aspect, adopts ultrasonic wave to tumour office morePortion is heated to 40～45 DEG C, continues 30～40 minutes, reaches the object of killing off tumor cells, and cold therapy is also basic identical, profitTo-180 DEG C～-190 DEG C, continue 10～30 minutes by cooled with liquid nitrogen tumour, make tumour cell intercrystalline, break, kill tumourCell. Physical treatment is used when patient is without too many treatment means late, and its effect is also limited, only have dwindle swollenThe effect of knurl focus.

6. traditional Chinese medical herbal treatment: traditional Chinese medicine is mainly to treat the lung of late period without special treatment in the application for the treatment of lung cancerCancer patient, improves symptom with Chinese medicine, improves the quality of living, and extends life span; Reduce the toxic and side effect of chemotherapy radiotherapy, improve and treatEffect. Strengthening vital QI to eliminate pathogenic factors, to treat both principal and secondary aspect of disease be the basic principle of Chinese traditional treatment lung cancer. Lung cancer is divided into four types by the traditional Chinese medical science: qi-deficiency type, the deficiency of YinType, type of deficiency of both QI and YIN, the malicious type of phlegm heat silt. According to diagnosis and treatment based on an overall analysis of the illness and the patient's condition, therapy of combing traditional Chinese and Western medicine, has obtained certain curative effect, but always reportsRoad number of cases is few, and repeatability is not strong. In addition, the traditional Chinese medical science is emphasized dietetic treatment, thinks the anti-lung cancer soup of yellow croaker (root of large-flowered skullcap, sealwort, fish raw meatGrass, PERICARPIUM TRICHOSANTHIS, fritillaria thunbergii etc.), david lily pig lung decoction, fig cordate houttuynia soup etc. have certain help to patients with lung cancer.

(5) progress of official's neck cancer

1, general introduction

Cervical carcinoma (cervicalcancer, be called for short: CC) be one of modal malignant tumour in global women, only inferiorOccupy second in breast cancer, particularly common in developing country, be one of gynaecology's three large malignant tumours. According to uniting in world wideMeter, the annual cervical carcinoma new cases that approximately have 500,000 left and right, account for 5% of all cancer new cases; The World Health Organization points out,New cases 90% are from developing country, just have a women to lose because of cervix cancer every two minutes.

2, the cause of disease

Cervical carcinoma is to cause the principal element of global women because of cancer mortality. Along with going deep into of medical research, find a lotHazards are all closely related with the generation of cervical carcinoma, and it is summarised as to virulence factor, host, ring by epidemilogic triangle patternThree, border key element. HPV virus (people's papilloma sample virus, English in more than 90% Cervix Squamous Cell cancerous tissue, are detectedLiterary composition: existence humanpapillomaviru); 40 years old following adenocarcinoma of the uterine cervix women, 89% infects HPV virus, and more than 60 years oldIn female population, its infection rate is only 40%.

HPV virus infections is the major reason of cervical carcinoma, but is not unique factor. No matter smoking is active or quiltMoving smoking can cause cervical carcinoma. Oral contraceptive is also one of key factor, and the more than 5 years women's illness rate of taking medicine increases by fourDoubly. The factors such as other morning and evenings that start as socioeconomic status, schooling, marriage or sexual behaviour, fecund, nutrition have necessarilyEffect. In the situation of HPV virus sustainable existence, many factors acting in conjunction has damaged the immunologic mechanism of cervical epithelial cells.The generation of cervical carcinoma and sexual's number and the age of sexual behaviour are for the first time in close relations. Cervix Squamous Cell cancer and fecundClose relation, the childbearing age is early all close with SCC, gland cancer relation.

HPV virus 16 types and 18 types in cervical cancer tissues, detected from application nucleic acid hybridization techniques such as Durst in 1999Since DNA, Zhang etc. (2002) carry out the correlation of HPV and cervical carcinoma to different aspects such as molecular biology from clinicalLarge quantity research, thinking that the morbidity of cervical carcinoma is main infects and causes that body endogenous factor exerts an influence with HPV, as the cancer base of being correlated withBecause of activation, tumor suppressor gene inactivation, telomerase activation high expressed and a series of pathological changes such as Organism immunoregulation mechanism is unbalance, drawPlay Cell apoptosis and proliferation dysregulation, cause tissue canceration.

Prevent early screening and effectively control for these hazards, for reversing precancerous lesions of uterine cervix, blocking-upThe development of its pernicious behavior has great significance.

3, symptom

Colporrhagia: young patient often shows as contact bleeding, occurs in sexual life, gynecologial examination and hemorrhage after an action of the bowels.Amount of bleeding is the amount doesn't matter, generally according to size of tumor, invade and interstitial in the situation of blood vessel determine. Early stage amount of bleeding is few, late period diseaseKitchen range shows as and bleeds profusely more greatly, may cause mortality massive haemorrhage once corrode compared with trunk. Young patient also can show asMenostaxis, cycle shortening, menorrhagia etc. Irregular colporrhagia after the normal main suit of gerontal patient menopause.

Neoplasm: patient often tells neoplasm and increases, white or courageous and upright, thin in water sample or thin rice gruel sample, there is stench taste.Because of cancerous tissue ulceration, necrosis, scabies secondary infection etc., have a large amount of purulences or thin rice gruel sample fetor ex vagina to discharge late period.

The symptom of late cancer: occur Secondary Symptom according to focus infringement scope. Focus involves pelvic cavity connective tissue, pelvisWhen wall, compressing ureter or rectum, sciatic nerve, often tell frequent micturition, urgent urination, rectal tenesmus, constipation, tenesmus, lower limbSwell and ache etc., when serious, cause ureteral obstruction, nephredema, finally cause uremia. Arrived disease latter stage, disappearing can appear in patientThin, anaemia, heating and cachexia.

4, check and diagnose

(1) inspection of cervical carcinoma

Comprise general physical checkup and gynecologial examination. When gynecologial examination, can find that cervical carcinoma position is harder, easily hemorrhage, and should noteThere is absence of vagina to shift, answer lay special stress on to do three to close and examine (in abdominal touch, vagina, examine with anus in examine), understand rear, uterus and palaceSide has or not metastasis of cancer, uses definite extent of disease, carries out clinical stages.

Cervical carcinoma symptom after Ib phase and II phase is obvious, makes diagnosis by gynecologial examination and cervical biopsy.

0 phase and Ia phase symptom and sign are often not obvious, easy to cause missed diagnosis.

The prognosis of 0 phase and Ia phase taking the latter as good, should be paid attention to its early diagnosis far beyond the Ib phase.

(2) method of early diagnosis of cervical carcinoma

The all chance doubtful cases of cytolgical examination, as uterine neck contact bleeding or rotten to the corn heavier, obstinate person, should make uterine neckScraping blade is looked into oncocyte. As find further row cervical biopsy of cancer cell or dyskaryotic cell. When cervical cancer screening, adopt this moreMethod is screened cervical biopsy.

Iodine test is drawn materials in the district of being unstained, and can improve accuracy, while drawing materials, should comprise outside uterine neck squama post epithelium boundary, andFortunately do 4 biopsies at 3,6,9,12, in case fail to pinpoint a disease in diagnosis.

Vaginoscopy gynecatoptron can amplify uterine neck 16～40 times, can more carefully observe the change of epithelium of cervix uteri, andCan see squama post epithelium intersection. Under gynecatoptron instructs, do biopsy, can improve accuracy. Can't see squama post epithelium intersectionTime, should scratch and scrape as cervical canal, will scrape thing and send disease inspection.

Uterine neck is made excisional cone by uterine neck cone biopsy. Preoperatively should first determine diseased region as gynecatoptron, also can do iodine examinationTest. Excision sample should do serial sectioning with except infiltrating carcinoma.

(3) antidiastole

Be not difficult with other tumours in uterus as the discriminating such as fibroid, carcinoma of uterine body according to every symptom and sign.

Fibroid:

1. menorrhalgia and intermenstrual flow: cervix tumor under mucous membrane particularly occurs.

2. pain: general pain is indistinct pain, unless fibroid under mucous membrane will be discharged in uterus itself, andCause uterine contractile.

3. pressure symptom: fibroid can be urged to bladder, ureter, blood vessel, nerve and intestines, and produces various shadowsRing the operation of these organs.

4. infertile: fibroid can have influence on structure and the endometrial operation of uterine cavity, implantation is difficult for. But alsoThere is the patient of fibroid, equally can become pregnant normally, produce normally.

Carcinoma of uterine body:

1. after colporrhagia menopause, there is vagina continuation or irregular bleeding; Not yet menopause person can have menorrhalgia or notRule is hemorrhage.

2. neoplasm a few patients has water sample or courageous and upright discharge opeing to increase in pathology in early days, when late period, concurrent necrosis was infected,Can there is ichor blood system secretion.

3. pain generally occurs over just late period, in the time that canal of uterine cervix is caused hematocele in uterine cavity or empyema by interstitial laser photocoagulation obstruction,Can occur inferior belly gas pain or cancer knurl to stimulate uterine contraction and cause pain, when late cancer infiltrates tub wall, can occur pain in waist and lower extremities.

5, prevention and treatment

At present after world's treatment of human cervical cancer, total five-year survival rate is 55.5%, wherein I phase 80.04%, II phase 58.9%,III phase 32.8%, IV phase 7.1%.

Recurrence in 1 year after the patient treatment of about half, 25% in Second Year recurrence, 5% recurrence afterwards in 5 years. Therefore, suffer fromPerson monthly checks once in latter 1 year planted agent for the treatment of, and every 2 months of Second Year checks once. Within every 6 months later, check once. At every turnAll should make detailed pelvioscopy and vaginal smear.

SL checks to early cervical carcinoma effective and low wound: a perspective multicenter study prompting, sentinel lymph node (letterClaim: SL) check and can show the extraordinary lymphatic drainage path of early cervical carcinoma or detect metastasis of cancer, and avoid SL negative patient to enterThe unnecessary lymph node of row is removed.

128 routine IA1～IB1 phase Patients with Cervical Cancers are included in this research in. Extraordinary position SL refers to the pouring beyond sacroiliac region territoryFawn on. ITC), micrometastasis and the definition obviously shifted be respectively focus < 0.2mm, 0.2～2mm monoma cell (is called for short:With > 2mm.

Result shows, in 98.4% patient, SL detected. Extraordinary position 37.5% patient detects at least oneIndividual SL. In 16.4% patient, detect 26 positive SL, wherein 38% is obviously to shift, and 33% is micrometastasis, and 29% isITC; 27% can only detect by Immunohistochemical Method. In the patient's (81.2%) who shifts without SL, do not find false negative result.

(1) principle of reatment

The processing of cervix cancer divides atypical hyperplasia, early invasive carcinoma under carcinoma in situ, mirror, the processing method of infiltrating carcinoma.

1. atypical hyperplasia: biopsy, as being slight atypical hyperplasia person, by inflammation processing, is followed up a case by regular visits to scraping blade and necessity half a year temporarilyShi Zaizuo biopsy. Pathology continues constant person and can continue to observe. Be diagnosed as moderate atypical hyperplasia person, should be suitable for laser, freezing, electricPress. To severe atypical hyperplasia, the general row complete hysterectomies of advocating more. As an urgent demand fertility, also can be after excisional coneRegularly closely follow up a case by regular visits to.

2. carcinoma in situ: the general row complete hysterectomies of advocating, retain bilateral ovaries more; Also there is opinion to excise vagina 1 simultaneously～2cm person. The useful laser therapy of recent domestic, but must closely follow up a case by regular visits to after treatment.

3. early invasive carcinoma under mirror: general many opinions are done to expand complete hysterectomy, and the vagina tissue of 1～2cm. Because of mirrorThe possibility of lower early invasive carcinoma Lymph Node Metastasis is minimum, does not need to eliminate pelvic cavity lymphoid tissue.

4. infiltrating carcinoma: methods for the treatment of should be other according to the clinical phase, age and systemic conditions, and appointed condition. Conventional controlsTreatment method has radiation, operation and chemotherapy. Generally speaking, radiotherapy is applicable to each phase patient; The operation of Ib to IIa phaseCurative effect and radiotherapy are close; Adenocarcinoma of the uterine cervix is slightly poor to radiotherapy susceptibility, should take the complex treatment of operation excision plus radiotherapy.

(2) operative treatment

Adopt radical hysterectomy and pelvic lymph node to eliminate. Excision extension comprises full uterus, bilateral annex, vaginaStandby group lymph node in epimere and paracolpium and pelvic cavity (by cervix, in closed pore, ilium, outer, the total hypomere lymph node of ilium of ilium).Requirements of operation thoroughly, safety, strictly grasp indication, prevent complication.

(3) postoperative complication and processing

1. postoperative complication has that intraoperative hemorrhage, postoperative pelvic infection, lymphocyst, pool the Lushui River stay, urinary system infection contamination and defeatedUrethrovaginal fistula etc.

2. the processing of postoperative complication, in recent years, due to the improvement of operation method and anaesthesia technology, PAApplication, and the measure such as the outer negative pressure drainage of postoperative employing peritonaeum, the incidence of above-mentioned complication significantly reduces.

(4) radiotherapy

For the first-selected therapy of cervical carcinoma, can be applicable to each phase cervical carcinoma, radiation scope comprise cervix and the vagina of getting involved,Corpus uteri, the other tissue in palace and pelvic lymph node. Illuminating method is generally all taked with interior external exposure combination, and internal radiation is mainly for palaceNeck primary tumor and contiguous position thereof, comprise corpus uteri, portio supravaginalis and contiguous palace other tissue (" A ") point thereof. External exposure is mainRegion (" the B ") point that will distribute for pelvic lymph node. Internal source adopt radium in chamber (be called for short: Ra) or 137 caesiums (abbreviation:137Cs), mainly for uterine neck primary lesion. Outer radioactive source employing 60 brills (be called for short: 60Co), beyond primary lesionMET, comprise pelvic lymph node drainage district. Dosage is generally 60Gy. At present to the many opinions of early cervical carcinoma interior photograph in advancePenetrate. And to late cancer, particularly local Voluminously, hemorrhage active, or companion the infected is advisable with external exposure in advance.

III phase Randomized multicentre trial of the U.S. shows, with standard care (cisplatin chemotherapy add synchronize external exposure radiotherapy)Compare, gemcitabine+cis-platinum add synchronous external exposure radiotherapy (be called for short: XRT) sequential brachytherapy, be aided with gemcitabine again and add suitablePlatinum chemotherapy, can significantly improve the Clinical Outcome of local Advanced Cervical Carcinoma, but toxic and side effect also significantly increases.

This research is included 515 examples in and is not received chemotherapy and IIB～IVA phase cervical cancer patient of radiotherapy, and it is divided at randomTwo groups. A group: the sequential gemcitabine of cis-platinum 1 time weekly, continuous 6 weeks, the simultaneously sequential brachytherapy of row XRT (50.4Gy/28f)(30～35Gy), then be aided with gemcitabine and add cisplatin chemotherapy, 3 weeks × 2; B group: cis-platinum 1 time weekly, be used in conjunction 6 weeks, row XRT simultaneouslySequential brachytherapy (with A group).

Result demonstration, 3 years PFS of A group lead and are significantly higher than B group (74% pair 65%, P=0.029), OS (P=0.0224), extremelyThe tumour progression time (P=0.0008) also obtains significantly improves. But 3 grades of A groups or 4 grades of toxic reaction incidences are significantly higher than B group(86.5% pair 46.3%, P < 0.001).

(5) chemotherapy

Up to the present cervix cancer is insensitive to most of cancer therapy drugs, and the efficient of chemotherapy is no more than 15%, late periodPatient can adopt the complex treatment such as chemotherapy, radiotherapy. Chemotherapeutics can adopt 5-fluor-uracil, and adriamycin etc. carry out vein or partInjection.

(6) progress of colon cancer

1, general introduction

Colon cancer (ColonCancer) is the common malignant tumor of digestive tract that betides colon position, accounts for intestines and stomach swollenThe 3rd of knurl. Predilection site is rectum and rectum and sigmoid colon intersection, accounts for 65%. Morbidity is many after 40 years old, men and women itThan being 2～3: 1. The highest with 40 years old～50 years old age group incidence of disease. According to sick investigation, the incidence of disease of China and dead learned of world popRate is lower than common cancers such as cancer of the stomach, the cancer of the esophagus, lung cancer. Various places data shows, along with the raising of living standards of the people, drinksThe change of food structure, its incidence of disease is goes up each trend year by year.

2, the colon cancer cause of disease

Definite pathogenic factor and the mechanism of colon cancer, the same with other tumour, still imperfectly understand, from EPDMLViewpoint sees, the morbidity of colon cancer and environment, habits and customs, especially diet style are relevant.

(1) diet reason

The diet that studies show that saturated fatty acid can increase the concentration of bile acid and neutral sterol in colon, and changes large intestineThe composition of flora. Bile acid can generate the carcinogens such as 3-MECA through bacterial action, and sterol ring also can be through bacterial action quiltAromatization and form carcinogen. Food fiber comprises cellulose, pectin, hemicellulose, lignin etc., absorbs moisture, increasesIght soil amount, residue concentration in dilution intestines, can shorten that ight soil reduces carcinogen by the time of large intestine and intestinal mucosa connectsThe tactile time, if when dietary fiber is not enough, be one of pathogenic factors of colon cancer.

(2) inherent cause

Inherent cause is one of pathogenic factor of colon cancer. First degree relative must be crossed colorectal cancer, and its next generation is in all one's lifeThis disease of middle trouble is more than general population. About 1/4 new patient has the family history of colorectal cancer.

(3) IBD

It is much higher that the patient of trouble ulcerative colitis obtains colon cancer than ordinary people, is more common in Juvenile onset extent of disease wideThe patient that the course of disease is long, canceration often occurs in flat mucous membrane. In the evolution of the proliferative lesion of inflammation, often can be with polyp shapeBecome, be further development of intestinal cancer; Crohn (Crohn) disease has colon, rectum affected individual also can cause canceration. Clone disease or routedThe morbidity chance of ulcer colitis is 30 times of ordinary person.

(4) snail fever

The colon cancer incidence and mortality of He Fei Endemic Area, blood fluke Endemic Area has obvious difference, and chronic schistosomiasis is suffered fromPerson stimulates and can cause colorectal mucosa chronic ulcer because intestines wall schistosome ovum deposits with toxin, inflammatory polyp etc., and then cause canceration.Supposition schistosome ovum is deposited under mucous membrane of colon and causes chronic inflammation and polypoid proliferation, is that cancer is sent out inducement.

(5) polyp

Part colon cancer is to develop from little precancerous lesion, and the main inducing of morbidity is bad polyp. Its medium stapleThe easier canceration of galley proof adenomatoid polyp, it is 25% left and right that canceration obtains incidence; The tubular adenoma sample polyp rate of cancerating is 3%Left and right.

(6) postcholecystectomy

Due to the injection colon of bile continuation, secondary bile acid enters that enteric cavity stimulating mucosal causes inflammation, adenoma, increases knotThe incidence of disease of intestinal cancer.

3, colon cancer symptom

Whole colon, taking transverse colon middle part as boundary, is divided into two parts of right hemicolon and left hemicolon, these two cancerous swellingsClinical manifestation really respectively has its feature, and the symptom of different parts colon cancer is as follows:

(1) Right-sided Colon Cancer

Right hemicolon chamber is thick, and in intestines, ight soil is aqueous, and the cancerous swelling of this section of intestinal tube mostly is ulcer type or dashes forward to the dish of enteric cavityFlower-shaped cancer, seldom ring constriction, therefore seldom block. But the normal diabrosis of these cancerous swellings is hemorrhage, scabies secondary infection, inhales with toxinReceive, therefore it can have clinically stomachache discomfort, stool change, abdomen piece, anaemia, become thin or dyscrasia performance.

1. the patient of stomachache uncomfortable approximately 75% has abdominal discomfort or secret anguish, just be intermittence, after transfer continuation to, be often positioned atRight lower abdomen resembles chronic appendicitis outbreak very much. As tumour is positioned at hepatic flexure of colon place and ight soil when drier and harder, also can there is angina, shouldNote differentiating mutually with chronic cholecystitis. Approximately 50% patient has the phenomenons such as poor appetite, glutted belch, n and V.

2. the early stage ight soil of stool change is thin, has purulence blood, and defecation frequency increases, and forms relevant with cancerous swelling ulcer. Treat tumourVolume increases, and affects ight soil and passes through, and can alternately occur diarrhoea and constipation. Amount of bleeding is little, along with wriggling and the ight soil of colon are abundantMix, visually observe and be difficult for finding out, but OBT is often positive.

3. when abdomen piece is medical, patients more than half can find abdomen piece. This lump may be exactly cancerous swelling itself, may be alsoThe agglomerate that the outer infiltration of intestines and adhesion form. The former form is more regular, and profile is clear; The latter's form is very irregular. Lump is generalQuality is harder, mobile restricted once scabies secondary infection, and has tenderness.

4. there is anaemia because of cancerous swelling diabrosis continuous bleeding in the patient of anaemia and cachexia approximately 30%, and lose weight,Weakness of limbs, even whole body cachexia phenomenon.

(2) proportion of cancer of left side of colon

Left hemicolon enteric cavity is thinner, and in intestines, ight soil becomes stiff because moisture is absorbed. Proportion of cancer of left side of colon is most for infiltratingType, often causes ring constriction, therefore clinical manifestation is mainly acute and chronic intestinal obstruction. Lump small volume, both diabrosis was hemorrhage less, againAbsorb without toxin, therefore rare anaemia is become thin, the phenomenon such as dyscrasia, be also difficult for laying one's hand on and lump.

1. cramp is that the cancerous swelling ileac main manifestations that occurs together blocks and can happen suddenly, and occurs cramp, companion's abdominal distension, intestinesHyperperistalsis, constipation and exhaust are obstructed; When chronic obstruction, show as abdominal distension discomfort, paroxysmal stomachache, gurgling sound hyperfunction, justSecret, blood stool and mucus, partial intestinal obstruction sometimes continues the several months and is just transformed into complete intestinal obstruction.

2. difficult defecation half patient has this symptom, and along with the progress of the course of disease, constipation situation is more shown in seriously. As cancerous swelling positionLower, also can there is the not smooth and tenesmic sensation of defecation.

3. blood stool or mucus are because the ight soil in left hemicolon is gradually shaped, and blood is not mixed mutually with ight soil with mucus,In approximately 25% patient's ight soil, visually observe visible blood and mucus.

(3) carcinoma of the rectum

Main clinical manifestation is to have blood in stool and the change of bowl evacuation habit. Have blood in stool and be the modal symptom of rectal cancer patient, manyBe blood or kermesinus blood, do not obscure mutually with stool, the person of bleeding profusely is rare. Sometimes, contain clot in having blood in stool and come offSlough. Bowl evacuation habit changes, and is also one of main clinic symptoms of rectal cancer patient. Increasing of times of defecation, every dayFor several times to ten for several times, many persons even tens of times of every day, only arrange a small amount of blood and Mucous Stool at every turn, accompany continuation rectal tenesmus moreSense and defecation are felt not to the utmost. Stool often attenuates, is out of shape, and even has difficult defecation and just closes.

4, check and diagnose

Much lighter colon cancer early symptom is or not obvious, often ignored by patient, also easy to cause missed diagnosis. Therefore patient above middle age is hadWhen following performance, should enhance your vigilance, consider to have or not the possibility of colon cancer: 1. occur at no distant date that bowl evacuation habit changes (as constipation, abdomenRush down or defecation not smooth), continue abdominal discomfort, secret anguish or abdominal distension; 2. occult blood test lasting masculin; 3. ight soil is thinning, or bandThere are blood and mucus; 4. belly can be laid one's hand on and lump; 5. agnogenic anaemia, weak or lose weight etc.; Have above-mentioned suspicious existingWhile elephant, except doing further disease history inquire and physical examination, should carry out following systems inspection, to determining diagnosis.

(1) diagnostic method:

1. anal tube touch and microscopic examination of rectum inspection have or not rectal polyp, the carcinoma of the rectum, internal piles or other pathologies, as a means of discriminating.

Though 2. sigmoidoscope and the long 25cm of fibercolonscopy sigmoidoscope, 75% colorectal cancer is positioned at second shapeIn the scope that Sigmoidoscope can be spied on. When microscopy, not only can find cancerous swelling, go back its size of observable, position and local infiltrationScope. Can take tissue to make pathologic finding by sigmoidoscope. Fibercolonscopy can provide higher diagnosis, stateInside extensive use, skilled operation person can be inserted to fibro-colonoscope caecum and terminal ileum, also can take a picture, a kind of reallyDesirable inspection method.

3. x-ray inspection

Abdominal plain film examination be applicable to the to occur together case of acute ileus, the colon of visible region of obstruction top has inflation swollenLarge phenomenon.

The intestines rigid wall at the visible cancerous swelling of barium enema inspection position, dilatancy is poor, wriggles to affected area and weakens or disappear, knotIntestines bag form irregular or disappear, stenosis of bowel, altered distribution of mucosal folds, destruction or disappearance, filling defect etc. Barium agent air is dualContrast radiography more contributes to diagnose the tumour with the base of a fruit in colon.

4. carcinomebryonic antigen (is called for short: CEA) test is little to the diagnostic value of early-stage cases, but multiple to inferring prognosis and judgementSend out and have certain help.

Laparoscopic surgery, SLND, Molecular Prediction curative effect and PET inspection etc. are all in recent years occur newThe focus of technology new method or research. These technology are very careful in clinical application. Recently one, U.S. is to 872 nothingsLaparoscopic surgery and abdominal tumor recurrence rate base are thought in the comparative studies of shifting colon cancer laparoscopic surgery and abdominalThis is identical, and laparoscopic surgery has had more believable clinical testing support for colon cancer. But NCCN is still used for laparoscopic surgeryTreatment of colon cancer has proposed strict condition, comprise requirement patient there is abundant laparoscopic surgery experience, without rectum or far-endColon tumor, without DISTANT METASTASES IN, without block or bore a hole, without abdominal cavity adhesion with require patient to detect abdominal cavity comprehensively. Along with abdominal cavityThe raising of the universal and surgical technic of videoendoscopic surgery, laparoscopic surgery may increase gradually for treatment of colon cancer.

SLND is only still restricted to for clinical research, and Molecular Prediction curative effect continues this tableShow and do not support. PET is unconventional inspection item, and the Advanced Colon Cancer patient who has recurrence or shift in suspection, multi-detector CTUniversal chest abdomen pelvic cavity combined with CT be gradually scanned into and examine pushing away in inspection, relapse and metastasis inspection and follow-up examination for colon cancer headRecommend project. New edition guide clearly proposes the high-risk recidivist of colon cancer and after radical correction, in 3 years, carries out every year chest abdomen pelvic cavity connection one timeClose CT scan.

(2) antidiastole

1. the colon benign goitre course of disease is longer, and symptom is lighter, and x-ray shows as local filling defect, form rule, surface lightSliding, clear-cut margin, enteric cavity is narrowless, and uninvolved haustrum is complete.

2. colon inflammatory illness (comprising tuberculosis, snail fever granuloma, ulcerative colitis, dysentery etc.) intestinal inflammatoryRespectively there is its feature pathology medical history aspect, and stool microscopy all may have its special discovery, and as worm's ovum, phagocyte etc., dysentery can be trainedRaise pathogenic bacteria. X-ray checks that the pathology intestinal tube of getting involved is longer, exceedes 10 centimeters and cancerous swelling is general little. Enteroscopy and pathologic groupKnit and learn also difference of inspection, can further make a definite diagnosis.

3. spastic colon: x-ray inspection is segment stenosis of bowel is recoverability. Appendiceal abscess; There is abdominal mass, but x-ray inspectionLook into outside the caecum of enclosed mass position, patient has appendicitis medical history.

5, treatment of colon cancer development

The state-run comprehensive cancer network of the U.S. in 2010 (be called for short: the colon cancer practice guidelines of NCCN) announcing, colon cancer is dividedBecome colonic adenoma companion to invade profit cancer, invade profit cancer and transfer or the large group of recurrence colon cancer three without shifting, grouping embodies grade malignancy graduallyThe difference of the colon cancer raising aspect clinical means and clinical complexity. Treatment of colon cancer method is taking operation as leading and being aided withChemotherapy, the complex treatment of immunization therapy and other supportive treatment. Biological targeting medicine, tumour molecular labeling, laparoscopic surgery,SLND and PET check to be all focuses in tumor research in recent years.

(1) operative treatment

First the treatment of colon cancer emphasizes operation excision, and focuses on the complex treatments such as the preoperative chemotherapy of associating, radiotherapy to improveResection Rate, reduces recurrence after operation rate, improves survival rate. The principle of operative treatment is: radical cure as far as possible; Protect pelvic cavity as far as possibleVegetative nerve, preservation patient's sexual function, urinary function and bowel movement function, improve life quality.

Operation method:

1. right hemicolectomy is applicable to the cancerous swelling of caecum, the colon ascendens and hepatic flexure of colon portion. Excision extension: terminal ileumThe right side of 15～20 centimeters, caecum, the colon ascendens and transverse colon half, together with affiliated mesentery and lymph node. The excision of still needing of the cancerous swelling of hepatic flexure of colonThe lymph node of the large portion of transverse colon and right gastroepiploic artery group. After excision, do back, (seam closes colon for colon end to end anastomosis or end-to-side anastomosisThe broken ends of fractured bone). Right hemicolon carcinectomy Reservation of colon medium sized artery right hemicolon carcinectomy excision arteria colica media

2. left hemicolectomy is applicable to colon descendens, left flexure of colon portion cancerous swelling. Excision extension: transverse colon is left half, fall knotIntestines, part or all of sigmoid colon, together with affiliated mesentery and lymph node. Excision postcolon and colon or colon and rectum end end kissClose.

3. resection of transverse colon is applicable to transverse colon cancerous swelling. Excision extension: transverse colon and hepatic flexure of colon thereof, splenic flexure. After excision, doAscending, descending colon end to end anastomosis. If coincide overtension, can add and do right hemicolon excision, do back, Colonic anastomosis.

4. the radical resection of sigmoid colon cancerous swelling, according to the concrete position of cancerous swelling, except excision sigmoid colon, or does and falls knotIntestines excision or part rectum resection. Making colon colon or colorectum coincide.

5. after making enteron aisle and prepare with intestinal obstruction patient's operative Principle is preoperative as intestinal contents obviously reduces, patient's conditionAllow, can make One-stage Resection, but will take safeguard measure in art, reduce and pollute as far as possible. As full in enteron aisle, patient's conditionPoor, can first make the colostomy of tumour nearside, after taking a turn for the better, patient's condition goes again the second stage of radical operation.

Can not make the operative Principle tumor by local of radical correction and invade profit extensively, or fix and can not excise with surrounding tissue, internal organsTime, if intestinal tube has blocked or may block soon, the short circuit operation of available tumour distally and nearside, also can make colostomy.When if there are at a distance internal organs shift, local tumor still allows to excise, excision is appeased in available part, blocks, chronic mistake to removeBlood, infect the symptoms such as poisoning.

(2) chemotherapy

The about half patient of colon cancer occurs shifting and recurrence after surgery, except part early stage patient, and late period and operation excisionAfter patient all need to accept chemotherapy. Chemotherapy is except another critical treatment measure after surgical intervention in colon cancer complex treatment.

NCCN recommends have fluorouracil, capecitabine, oxaliplatin and Irinotecan four for the medicine of colon cancer chemotherapyPlant medicine. These ingredients various scheme for combining, comprise FOLFOX, IFL, FOLFIRI, CAPOX and classical 5-FU CFCoupling scheme, these schemes all can be used for the first-line treatment of colon cancer. For the selection of chemotherapy regimen, the common recognition of NCCN has:

1. recommendation 5-FU vein Continuous Perfusion, because it has less side effect than injecting, and curative effect does not reduceOr there is a lifting.

2. capecitabine be generally used for intravenous chemotherapy can not resistance to receptor, capecitabine list medication effect is equal to 5-FU/CF sideCase chemotherapy. CAPOX is that 2B recommends rank for First-line chemotherapy, and other scheme for combining of capecitabine waits assessment.

3. IFL is not used in the supplemental treatment of colon cancer, has larger toxicity containing Irinotecan scheme, and is unprofitable to existenceImprove, must be careful for supplemental treatment. Adopt containing Irinotecan scheme and second line treatment or relapse and metastasis person.

4. on 5-FU/CF basis, add and be obviously better than 5-FU/CF scheme with oxaliplatin (FOLFOX scheme).

The further lifting that chemotherapy acts in treatment of colon cancer shows the former II phase colon cancer NACT of being queriedThat can be benefited affirms, all II phase and above colon cancers with high-risk Recurrence all must give NACT. Turn at liver, lungMoving focus can make in NCCN recommendation that the tumour phase of falling excised by new adjuvant chemotherapy. Even if hepatic metastases person is by new auxiliaryizationTreatment is fallen after phase excision, must give after surgery the chemotherapy of short-term. And for the biological targeting medicine of colon cancer EGFR and VEGFRApply the more further raising of chemotherapeutic efficacy and brought hope and actual effect.

Biological therapy targeted drug have for the chimeric monoclonal antibody Cetuxmab of humanization of the Immunoglobulin IgG1 of EGFR andFor the anti-angiogenic generation monoclonal antibody Bevacizumab of VEGF. According to clinical test results, Cetuxmab only recommended withIrinotecan is combined for recurrence or is shifted colon cancer. Bevacizumab is extensively recommended to add for all kinds of colon cancer chemotherapiesScheme, even if NCCN thinks that Bevacizumab may be not remarkable on the impact of existence, but has at least and helps fall with chemotherapy couplingLow recurrence. But NCCN has also pointed out to use the danger of anti-angiogenic generation monoclonal antibody. For avoiding fatal hemorrhage in artDanger, is used the interval of Bevacizumab and operation at least should be more than 6 weeks for the last time, and old man is owing to easily increasing apoplexyOr the danger of arterial disease and must careful use. For recommendation no longer of the patient who once applied Bevacizumab,The mono-medicine of Bevacizumab application or there is no actual curative effect with failed chemotherapy combined application, therefore also recommendation not. ThoughThere are many problems in biological therapy targeted drug so in treatment of colon cancer, but targeted drug is the medicine treatment of colon cancer after allOpen a new direction, along with deepening continuously of colon cancer basic scientific research, may have in the near future better curative effectBiological therapy targeted drug occurs.

The method of administration of chemotherapy also has multiple, except conventional systemic vein administration, also has Intra-arterial chemotherapy medicineThing, arterial chemotherapy drug infusion add the method such as arterial embolism, tumor by local puncture administration.

1. systemic vein Combination chemotherapy

Colon cancer chemotherapy scheme mainly (is called for short: 5-FU), as basis, Calciumlevofolinate (is called for short: LV) conduct taking 5 FU 5 fluorouracilConditioning agent can enhancement effect agent 5-FU curative effect.

Its curative effect of 5-FU/LV drug combination is confirmed by most research institutes, is worldwide standard treatment of present stage.FOLFOX4 scheme is treatment Advanced Colon Cancer chemotherapy regimen the most safely and effectively, is auxiliaryization of III phase cancer patients simultaneouslyThe preferably selection for the treatment of. That Venous Chemotherapy can be used for is preoperative, in art and postoperative: preoperative chemotherapy claims again new adjuvant chemotherapy, its objectBe to prevent DISTANT METASTASES IN, dwindle knurl body and be beneficial to excision, but because the time is short, the chemosensitivity difference of different tumor patients,Therefore after operation, still need to give NACT; Postoperative chemotherapy, mainly adopts taking 5-FU/LV as basic Combination chemotherapy and (connectsWith 5 days, after 1 month, repeat at least 6 cycles), this has become III phase cancer patients standard treatment.

2. the oral chemotherapeutic of oral chemotherapy of colon cancer mainly refers to 5-FU class pro-drug, after absorbing by 1 time or repeatedlyMetabolism is transformed into 5 FU 5 fluorouracil, performance antitumaous effect. Oral chemotherapy curative effect in clinical practice is high, bad reaction is few, administrationConvenient, can treat-and-release, be suitable for Senile Tumor patient and family's chemotherapy, become a new trend of colon cancer supplemental treatment.

(3) radiotherapy

Although operation excision is the Main Means for the treatment of of colorectal cancer, but local relapse after surgery alone is higher,Most of local recurrence occur in pelvic cavity, and therefore the operation of tumour intrusion rectum surrounding soft tissue cannot thoroughly be excised. CauseThis pelvic irradiation is unique effective ways of Gong selecting of removing these cancer cell depositions. But colon cancer patient to preoperative andPostoperation radiotherapy is all without effective. Radiotherapy is only applicable to radiotherapy in the art of colon cancer patient.

1. the radiotherapy scheme of colon cancer

Radical radiation therapy: by the thorough killing off tumor cells of radiotherapy be only applicable to the early stage patient of minority and cell type specialResponsive patient;

Suiting the medicine to the illness property radiotherapy: taking mitigation symptoms as object. Be applicable to pain relieving, hemostasis, minimizing secretion, dwindle tumour, controlThe palliative therapies such as tumour;

2. the mode of colon cancer radiotherapy

Preoperation radiotherapy: can make the reduced activity of cancer cell, send out while making to perform the operation or the residual difficult survival of cancer cell; RightHuge and fixing, estimate the inconvenient cancerous swelling of excision, preoperation radiotherapy can make knurl body dwindle, thereby improves resection rate; Radiation biologicalLearn research show, blood for or oxygen supply reduce time, preoperative cancer cell is to the more postoperative height of the sensitiveness of radioactive ray. Preoperation radiotherapyShould strictly grasp dosage, be advisable with median dose (3500～4500cGY), neither increase postoperative complication, can improve again operationCurative effect.

Postoperation radiotherapy: find according to operation, after excision primary tumo(u)r, to position that may residual tumor carry out mark,Location, thus make the irradiated site may be more accurate, to irradiate and have selectively, effect is better; After primary tumo(u)r excision, tumor loadSignificantly reduce, be conducive to improve the effect of residual tumor to radioactive ray.

Radiotherapy in art: to being suspected to have residual tumor place and thoroughly excision place, carry out high-dose irradiation one time with β line in art.

(4) Chinese medicine

Chinese medicine can regulate immunity of organisms, the function of immune system of postoperative patient is restored, strengthens, and has association with chemotherapyWith synergy and attenuation, the digestive tract reaction, the hematopoietic function inhibition etc. that especially chemotherapy are caused have protective effect, therefore not only existDomestic, some developed countries also come into one's own day by day in the world. To cancer patients patient, the traditional Chinese medical science generally adopts beneficial gas strongSpleen, clearing heat and detoxicating therapy, according to dialectical result, also can be in conjunction with powdered medicine ' Tongluosan ' connection, concrete medication varies with each individual, according to different sickThe situations such as phase, different physique, different syndrome type, carry out individualized treatment. The traditional Chinese medical science is emphasized diagnosis and treatment based on an overall analysis of the illness and the patient's condition, is divided into damp-heat accumulation type; The stasis of bloodResistance type in poison; Insufficiency of the spleen Qi-stagnation type; Yang deficiency of spleen and stomache.

(5) immunization therapy

Tumor patient often presents immunologic function and suppresses, and immunologic function is lower, and prognosis is poorer. Immunization therapy is at present mainBe divided into active immunotherapy, passive immunization therapy and gene therapy. Active immunotherapy is divided into again non-specific active immunity and treatsMethod and specificity active immunotherapy. Immunotherapy can improve the antineoplastic ability of patient, and development in recent years is very fast, such as dryDisturb element, interleukins, transfer factor, TNF etc., extensive use gradually, not only can improve patient's immunityAbility and carrying out that can combined with chemotherapy.

(6) biological therapy

Colorectal cancer patients after being treated surgically, for prevent cancer cell not completely excision can accept serializationTreat, then prevent the secondary recurrence of cancer cell and shift. Biotherapy helps chemotherapy to complete smoothly, due to postoperative patient health ratioWeaker, add continuous chemotherapy, the toxic and side effect that medicine brings is larger to the destruction of physical function, and biotherapy can be timelyRepair, improve the normal physical function of patient, increase the sensitiveness of tumour to chemotherapeutics, lower toxic and side effect, makingTreatment can complete smoothly; Biological therapy can be removed the cancer cell that chemotherapeutics cannot be removed or left behind, and reaches more and removesThe object of cancer cell. The patient of postoperative and postoperative metastasis in chemotherapy process in conjunction with biological therapy technology, as biological cell therapeutical,Biological targeting treatments etc., can obtain better effect. So-called molecular targeted therapy, is on cellular and molecular level, forThrough clear and definite carcinogenic site, (this site can be a protein molecular of tumour cell inside, can be also a gene sheetSection), design corresponding medicine, medicine enters can be selected carcinogenic site to combine in body to have an effect, make specificallyTumor cell specific death, and can not involve the normal tissue cell around tumour, so molecular targeted therapy is otherwise known as" biological missile ". Different from the chemotherapeutics that only acts on tumor cell proliferation, by with VEGF specific binding, stop its withAcceptor interaction, brings into play tumor vascular multiple effect: existing tumor vessel is degenerated, thereby cut off tumour cellGrow required oxygen and other nutriments; Make the tumor vessel normalization of survival, reduce between tumor tissues and press, improve chemotherapeuticThing, to the transmission in tumor tissues, improves chemotherapy effect; Suppress tumor angiogenesis, thereby lasting inhibition tumor cellGrowth and transfer.

(7) progress of diabetes

1, general introduction

Diabetes (diabetes) are by inherent cause, immunologic function disorder, infected by microbes and toxin thereof, free radical poisonElement, the various virulence factors of mental element etc. act on body causes hypoinsulinism, insulin resistance etc. and cause sugar,A series of metabolic disorder syndromes such as protein, fat, power and water Xie Zhi, clinically taking hyperglycaemia as main feature, typical case is sickCan there is diuresis in example, the performance such as drink more, eat more, become thin, i.e. " three-many-one-little " symptom, and diabetes (blood sugar) are once control bad meetingCause complication, cause the exhaustion pathology at the positions such as kidney, eye, foot, and cannot cure.

2, the somatotype of diabetes and the research of the cause of disease

(1) diabetes somatotype

GDM), other specific types diabetes are mainly divided into type i diabetes, type ii diabetes, gestational diabetes mellitus and (are called for short:Diabetes (diabetes that β cytogene defect causes, diabetes, the exocrine pancreas that insulin action gene defect causesDiabetes, the medicine reason that gland disease causes brought out the diabetes or the chemical reason that cause and brought out the diabetes that cause).

(2) progress of the diabetes cause of disease

1. the factor relevant with type i diabetes is relevant:

Autoimmunity system defect: because can find various autoimmune antibody in type i diabetes patient's blood, asGlutamic acid decarboxylase antibody (being called for short: GAD antibody), ICA (being called for short: ICA antibody) etc. What these were abnormal self resistsBody can damage the B cell of human pancreatic islet excreting insulin, makes it normally excreting insulin.

2. the factor relevant with type ii diabetes

Quantity research shows greatly, and human body (is called for short: under stimulation FFA), free radical is large in hyperglycaemia and high free fatty acidAmount generates, and then starts oxidative stress. IR), pancreas islet the activation of oxidative stress signal path can cause insulin resistance (to be called for short:Impaired and the diabetic angiopathy of element secretion. As can be seen here, oxidative stress has not only participated in the pathogenic process of type ii diabetes, alsoForm the pathogenesis of diabetic complications. Oxidative stress and diabetes are mutually promoted, and form a monster that is difficult to breakCircle.

Insulin resistance can occur prior to diabetes, and under its effect, the early stage insulin compensatory secretion of disease increasesTo keep NGT. In the time that insulin resistance strengthens, insulin compensatory secretion reduces or the two jointly occurs, disease byGradually, to impaired glucose tolerance and diabetes progress, blood sugar starts to raise. Hyperglycaemia and high FFA cause a large amount of generations of ROS and oxygen jointlyChange stress, also activate stress sensitive signal pathway, from and increase the weight of insulin resistance, show as clinically diabetes continue progressWith deterioration. In vitro study demonstration, ROS and oxidative stress can cause the cascade reaction that multiple serine kinase activates. Nearest is anti-Oxidant improves glycemic control test and also confirms, ROS and oxidative stress can cause insulin resistance. β cell is also oxidative stressImportant target spot β cell in antioxidase level lower, therefore comparatively responsive to ROS. ROS can coup injury beta Cell of islet, promotesβ Apoptosis, also can suppress β cell function indirectly by affecting Insulin signaling pathway. β cell is impaired, and insulin dividesBleeding pancake is low, secretion peak postpones, and blood glucose fluctuation aggravates, thereby is difficult to control the rapid rising of postprandial blood sugar, and cell is madeBecome infringement more significantly. Within 2004, professor Ceriello proposes common soil theory, and oxidative stress is insulin resistance, sugarThe common pathogenesis basis of urine disease and angiocardiopathy, 2004 is theory, within 2009, has become undisputable fact.

Inherent cause: and type i diabetes is similar, the feature of type ii diabetes Ye You family morbidity. Therefore probably with baseBecause of heredity relevant. This hereditary capacity type ii diabetes is more more obvious than type i diabetes. For example: suffered from I for one in twinsType diabetes, another has 40% chance to suffer from this disease; But if type ii diabetes, another just has 70% chanceSuffer from type ii diabetes.

Fat: a key factor of type ii diabetes may be exactly obesity. Genetic cause can cause obesity, equally alsoCan cause type ii diabetes. The superabundant fats of body centre's type adiposis patient concentrates on belly, and they concentrate on than those fatMore easily there is type ii diabetes in the people on buttocks and thigh.

Age: the age is also the pathogenic factors of type ii diabetes. There is the II type glycosuria patient of half how after 55 years old, to send outSick. Elderly patient easily occurs that diabetes are also easily overweight relevant with auld people.

Life style: food and the momental minimizing of eating high heat also can cause diabetes, someone think this be also byCause in fat. Obesity is the same with type ii diabetes, in those diet and the activity habit American Asia of " westernization " allMore general in descendants and Latin US business people.

3. the factor relevant with pregnancy pattern diabetes

Hormone abnormality: when gestation, placenta can produce the multiple hormone for development of fetus growth, these hormones are strong to fetusKang Chengchang is extremely important, but can block the insulin action in mother's body, therefore causes diabetes. Pregnant the 24th week to 28Cycle is the peak time of these hormones, is also a normal time of pregnancy pattern diabetes.

Hereditary basis: the patient that gestational diabetes mellitus occurs occur in the future the danger of type ii diabetes very large (but with I type glycosuriaSick irrelevant). Therefore someone think the gene that causes gestational diabetes mellitus with cause that the gene of type ii diabetes may be relative to each other.

Obesity: obesity not only easily causes type ii diabetes, equally also can cause gestational diabetes mellitus.

3, clinical symptoms

Diabetic symptom can be summarized as " three-many-one-little ", and so-called " more than three " refer to " many foods, many drinks, diuresis ", and " one is few " refers to" lose weight ". Many foods, because a large amount of glucoses in urine are lost, more than losing sugared 500g every day, body is in semistarvation state, and energy lacksWeary needs supplement and cause bulimia, and appetite increases. While is again because hyperglycaemia stimulates insulin secretion, thereby patient easily produces famineStarve sense, bulimia, has on short commons sensation always, even eats meal every day five or six times, and staple food reaches 1～1.5kg, and non-staple foodstuff is also than normallyPeople's showed increased, can't meet appetite. Many drinks, due to diuresis, loss of moist is too much, and dehydration in cell occurs, and stimulates thirstyMaincenter, occurs that polydipsia drinks more, and amount of drinking water and drinking times all increase, and keep the skin wet with this. Urinate more, drink water also more, shapeProportional. Diuresis, hydrouria, every urinary volume for twenty four hours reaches 3,000～5,000ml, more than reaching as high as 10,000ml. UrinateNumber of times also increases, once, two hours may urine 1 time, some patients even often can reach more than 30 times round the clock.

Diabetes blood glucose's Enrichment, can not be fully utilized in body, and particularly glomerulus leaches and quilt completelyReabsorption, so that form osmotic diuresis, there is diuresis. Blood sugar is higher, and the glucose in urine of discharge is more, and urine amount is also more.Lose weight, due to insufficient insulin, body can not make full use of glucose, fat and protein is decomposed and accelerate to supplement energyAmount and heat. Its result is consumed carbohydrate, fat and protein in body in a large number, adds the loss of moisture, patientLose weight, body becomes thin, severe patient body weight tens of jin that can decline, so that fatigue and weak, lassitude. Equally, the course of disease timeLonger, blood sugar is higher; The state of an illness is heavier, becomes thin also just more obvious.

4, diagnostic criteria:

American diabetes association in 2010 (be called for short: ADA) 1. glycosated Hb A 1c >=6.5% of diabetes diagnosis standard,2. fasting blood-glucose FPG >=7.0mmol/l, is defined as on an empty stomach empty calory at least 8 hours and takes in, 3. oral glucose tolerance test (letterClaim: OGTT) 2h blood sugar >=11.1mmol/l, 4. the patient with typical hyperglycaemia or hyperglycaemia crisis symptom, random bloodSugar >=11.1mmol/l. When without clear and definite hyperglycaemia, should carry out confirmation standard 1～3 by duplicate detection.

People at highest risk's diagnostic criteria: 1. age >=40 year old; Overweight-obesity, body mass index (is called for short: BMI) >=24, the male sexWaistline > 90cm, women's waistline > 85cm; There were IGT or IFG person in the past; Or glycosated Hb A 1c be positioned at 5.7～6.5% itBetween, 2. there is diabetes family history person, 3. HDL-C (is called for short: HDL) low (< 0.9mmol/L) and/or glycerineThree esters (> 2.8mmol/L) person, 4. has hypertension (adult blood pressure >=140/90mmHg) and/or cardio cerebrovascular affection person, 5. yearThe gravid woman of age >=30 year old has glycosuria gravidarum medical history person; Once there is the large baby of childbirth (>=4kg); There is inexplicable bradytoia person;There is the women of Stein-Leventhal syndrome, 6. do not participate in physical exertion throughout the year, 7. use as glucocorticoid, diuretics etc. GlycosuriaAt least annual islet function (C peptide secretion test) of looking into for 2 times of sick people at highest risk, early examines and early controls, 8. long-term taking depression medicine.

5, the development of diabetes mellitus prevention and treatment

(1) prevention of diabetes

IGT), IFG (is called for short: IFG) or the trouble of A1C5.7%～6.4% (be called for short: for Impaired Glucose Tolerance TreatedPerson should carry out the intervening measure of continuous and effective to lose weight 5～10%, at least carries out weekly 150 minutes moderate strengths simultaneouslyPhysical exertion is as walking. The regular consulting of following up a case by regular visits to is very important for the successful implementation of plan. Except life style intervention,For those diabetes utmost point people at highest risk (be associated with additional other hazards of IFG and IGT simultaneously, as A1C > 6%, high bloodPress, low hdl (be called for short: HDL) cholesterol, high triglyceride, diabetes first degree relative) and fat 60 years old withUnder crowd, can consider to use melbine. Should carry out every year follow-up visit monitoring to determine it for prediabetes patientWhether develop into diabetes.

(2) progress for the treatment of diabetes

1. the assessment of glycemic control

Blood sugar monitoring Main Basis oneself blood sugar test (is called for short: SMBG) (be called for short: A1C) with glycosylated hemoglobin. GuideRecommend the blood sugar monitoring frequency of individuation. The patient of additional drawbacks injection every day or employing insulin pump in treatment, every dayShould carry out oneself detect blood sugar (be called for short: SMBG) 3 times or more than. Few or only adopt oral drugs for injection of insulin number of timesOr medical nutrient treatment (is called for short: patient MNT), SMBG is perhaps conducive to treat successfully. SMBG is perhaps conducive to after the meal after the mealGlycemic control is up to standard. After SMBG doctor's advice, should ensure that patient obtains initial guidance and the regular follow-up assessment of SMBG, and use SMBG numberAdjust treatment according to instructing. Carrying out Dynamic Blood Glucose Monitoring for age more than 25 years old type i diabetes patient (is called for short: CGM) associating pancreasIsland element intensive treatment is the useful tool that reduces A1C level. Although reduce the card of A1C children and adolescents and young patientAccording to not strong, but CGM is perhaps helpful to this crowd. Apply this instrument and treat and successfully there is correlation. CGM can be used asThe one of SMBG is supplemented, suitable especially hypoglycemia unawareness and/or the hypoglycemic patient that takes place frequently.

Glycosylated hemoglobin (is called for short: A1C) at least carry out twice every year for treatment (glycemic control is stable) up to standard patientA1C detects. Change therapeutic scheme or the below standard patient of glycemic control are carried out to an A1C detection per season. Determine to change at needsWhile becoming therapeutic scheme, can detect A1C in good time.

2. the glycemic control of being grown up target

Guideline recommendation, considers from prevention capilary and macrovascular complications, and non-pregnant maturity-onset diabetes patient A1C is controlledOverall goal to be decided to be < 7% be the selection of comparison rationality. For some patient, not there is not severe hypoglycemia or other treatmentIn the situation of side effect, can advise that it is also the selection of rationality that its A1C is reduced to the level lower than 7% general target.These patients comprise that those diabetes medical histories are shorter, and life expectancy is longer, and there is no the patient of obvious CVD complication. PhaseInstead, for have severe hypoglycemia medical history, life expectancy limited, with capilary or macrovascular complications, suffer from it simultaneouslyHis serious disease and have the patient of long-term diabetes medical history, although implemented diabetes self-management education, suitable blood sugarMonitor, applied the multiple hypoglycemic medicine including insulin of effective dose, but blood sugar is still difficult to person up to standard, not too strictA1C control target like more applicable.

3. nutrition treatment (is called for short: MNT)

Any diabetes and prediabetes patient need to accept according to therapeutic purpose the MNT of individuation, if can beUnder the registered dietitian who is familiar with diabetes content instructs, complete better. Owing to can saving cost, and can improve prognosis (B), say withMNT should be covered by relevant insurance company and other disbursers. Energy balance, overweight and fat, appropriate ameliorate body Beijing South Maxpower Technology Co. Ltd is effectiveAlleviate insulin resistance. Be the calculated important component part of fat-reducing to the change of physical exertion and behavior, have most simultaneouslyHelp keep loss of weight.

In the fat picked-up for the treatment of diabetes, saturated fat intake should not exceed 7% of total absorption energy. Few food is anti-Formula fat can reduce LDL-C and increase HDL cholesterol; So should reduce the absorption of trans fats.

Carbohydrate calculating for picked-up, food exchange part or the empirical estimating monitoring carbohydrate for the treatment of diabetes are taken the photographEnter amount and be still glycemic control key up to standard

4. bariatric surgery

For bariatric surgery, guideline recommendation is taked careful attitude. Guideline recommendation, for BMI >=35kg/m²Adult IIDiabetes mellitus type, especially treats by life style intervention and medicine but diabetes or related complication are still difficult to controlPerson, can consider to carry out bariatric surgery treatment. But the long-term benefit to bariatric surgery, the risk that cost benefit is when correlated with, also needDesigning good randomized control study compares with the medicine with optimizing and life style treatment. Implement the II of bariatric surgeryDiabetes mellitus type should be accepted long-term life style Management Advisory Services and medical monitoring. Although small research show BMI 30～35kg/m²Between type ii diabetes patient to accept bariatric surgery treatment be useful in glycemic control, but do not have at presentEnough evidence-based medicals prove can recommend BMI < 35kg/m except research²Type ii diabetes patient carries out diet handArt processing. The long-term benefit of type ii diabetes patient bariatric surgery, cost benefit when risk, should with optimize medicine and lifeMode is treated and is carried out randomized control study.

Conventional operation: Gastric bypass (Roux-en-ygastricbypass, be called for short: RYGB), your stomach and intestine short circuit art(minigastricbypass), and courage pancreas exclusion and duodenum version (be called for short: BPD&BPD-DS), the excision of sleeve shape stomachArt (is called for short: SLEEVE), adjustable gastric bandage art (is called for short: LAGB).

5. diabetes self-management education (is called for short: DSME)

Guide is paid much attention to the important value of DSME. Guideline recommendation, diabetic population one i.e. basis on demand after diagnosingNational standard is accepted DSME. Effectively self-management and quality of life are the key factors that determines DSME effect, should serve as glycosuriaThe part of sick management is assessed and is monitored. DSME should pay close attention to psychological problems.

6. physical training

Guideline recommendation diabetic carries out weekly the aerobic physical exertion of at least 150 minutes moderate strengths. In nothing tabooIn the situation of card, encourage type ii diabetes patient to carry out weekly 3 endurance trainings.

7. psychological assessment and management

Guide thinks to the assessment of patients ' psychological and social state it should is the important component of diabetic medicine management. PsychologyExamination and following up a case by regular visits at least comprise the attitude to disease, expectation to treatment and prognosis, emotion/emotional state, entirety andQuality of life, resource (economy, society and emotion) and the psychiatric history relevant to diabetes.

8. hypoglycemia

Aspect hypoglycemic processing, guideline recommendation, for conscious hypoglycemia patient, contains grape although anyThe carbohydrate of sugar all can be selected, but glucose (15～20g) is still first-selected. Once SMBG shows that blood sugar recovery is normal, buildsView patient takes in diet or dessert, to prevent hypoglycemic recurrence. Guideline recommendation prescription hyperglycemic factor is given all in seriouslyThe patient of hypoglycemia high-risk status. For occurring unaware hypoglycemia or occurring the diabetes of one or many severe hypoglycemiaPatient, should advise that it improves glycemic control desired value, strictly to avoid at least again occurring hypoglycemia and part in recent weeksReverse unaware hypoglycemia and reduce following risk of showing effect.

9. immunity inoculation

Guideline recommendation, the diabetic who should be institute has age >=6 month provides the inoculation of influenza vaccines every year. Should be instituteThere is 2 years old above diabetic to inoculate pneumococcal polysaccharide vaccine. For the age > 64 that accepted vaccine before 65 years oldThe patient in year, as vaccine inoculation time last time exceedes 5 years, need inoculate once again.

(3) prevention and treatment diabetic complication

1. angiocardiopathy

Coronary heart disease diabetic's systolic pressure should be controlled at < 130mmHg. Diabetic's diastolic pressure should be controlled at< 80mmHg. The treatment of hypertensive life style comprises when overweight and losing weight, and DASH type diet style comprises low salt diet, increasingAdd absorption, responsible drinking, the increase physical exertion of potassium. Therapeutic scheme should comprise ACEI (be called for short:ACEI) or angiotensin II receptor antagonists (be called for short: ARB). If one wherein can not tolerate, should be with another kindReplace. If blood pressure is still below standard, when patient's glomerular filtration rate(GFR (is called for short: GFR) >=30mlmin/1.73m², should addWith thiazide diuretic, as patient GFR < 30mlmin/1.73m², should add with medullary loop class diuretics. Usually need multipleTreated with combined medication (two kinds or more kinds of maximum dose) is to reach controlling of blood pressure target. Occur pregnant diabeticWhen CH, suggestion blood pressure desired value should be 110～129/65～79mmHg. Pregnancy duration, ACEI and ARB all belong to tabooAvoid.

Dyslipidemia and treating regardless of level should use statins on the basis of life style interventionThing, statins control LDL-C is up to standard is still primary selection. If it is up to standard that his spit of fland of maximum tolerated dose does not have, can consider connectionMake blood fat up to standard with Ta Ting and other fat-reducing medicaments, but not yet have the research of its CVD final result of assessment and security. Pregnancy duration is prohibitedUse statin treatment.

Antiplatelet therapy can be taked aspirin primary prevention treatment (dosage 75～162mg/day). There is CVD historyDiabetic uses aspirin (dosage 75～162mg/day) secondary prevention therapies. To the patient of diabetes of aspirin allergyPerson, should use clopidogrel (dosage 75mg/day). Diabetic occurs after acute coronary syndrome, can adoptAspirin (dosage 75～162mg/day) associating clopidogrel (dosage 75mg/day) treatment 1 year.

Smoking cessation guideline recommendation is advised all patient's smoking cessations. Smoking cessation consulting and other forms for the treatment of of smoking cessation should be considered as to glycosuriaThe part of sick conventional therapy.

2. the examination of ephrosis and treatment

Strengthen examination to diabetic nephropathy, for type i diabetes patient more than 5-year courses and all after diagnosingType ii diabetes patient, should detect assessment urinary albumin excretion ratio every year. For all maturity-onset diabetes patients, no matter its urineAER is how many, detects at least every year serum creatinine. Serum creatinine should be for assessment of glomerular filtration rate(GFR (letterClaim: GFR) and to chronic renal disease (be called for short: CKD) carry out by stages (if having CKD).

3. the examination of PVR and treatment

For reducing the occurrence risk of PVR or delaying its progress, blood sugar and controlling of blood pressure are optimized in suggestion. Guide is builtView is strengthened the examination to DRP. Guideline recommendation, adult and 10 years old and above type I diabetes of children patientIn 5 years after onset diabetes, should accept the first comprehensive eye being carried out by ophthalmologist, oculist or optist under mydriasis conditionSection checks. After making a definite diagnosis, type ii diabetes patient should accept as early as possible first being entered by ophthalmologist, oculist or optist under mydriasis conditionThe comprehensive eye examination of row.

4. sufficient diagnosis and treatment are carried out comprehensive foot inspection every year to all diabetics, to determine the danger of ulcer of foot and amputationDanger factor. Foot inspection should comprise that the loss of visual examination, pedal pulse, protectiveness sensation (is called for short: inspection (10g LOPS)Single nylon yarn+below any one: 128Hz tuning fork test seismesthesia, picotement, ankle jerk, seismesthesia threshold value).

5. DPN treatment

The all diabetics of guideline recommendation all should use simple Clinical detection at least every year in the time of diagnosis and after diagnosisMeans examination far-end symmetry polyneuropathy (is called for short: DPN). Generally do not need to carry out electrophysiological examination. II type glycosuriaPatient when diagnosis and type i diabetes patient after diagnosis 5 years, symptom and body that all should examination cardiovascular autonomic neuropathyLevy. Guideline recommendation drug application alleviates specific symptoms that DPN is relevant with autonomic neuropathy to improve patient's quality of life

6, treating diabetes development

Novel antidiabetic Dapagliflozin by A Sidikang and Shi Guibao company Joint Production has completedIII phase clinical verification work, is expected to recent listing. Dapagliflozin belongs to sodium-glucose transporter 2 inhibitor, Ke YitongCrossing inhibition kidney absorbs glucose again and reaches and fall hypoglycemic object. This medicine is taken once every day, and medication separately, more canFall hypoglycemic effect to combine use with other OHA, to play, and this class medicine can reduce body weight.

The oral administration system of novel development: particulate delivery system, lipoprotein emulsion, other (colon spacer, enteric coatings).Particle drug-loaded preparation comprises micro-capsule, microballoon, nanoparticle, nanocapsule, and protection insulin is not significantly improved insulin by stomach acids destroyBioavilability.

GLP-1 is a kind of incretin, can by dipeptidyl peptidase-4 (dipeptidylpeptidase4, be called for short:DDP-4) fast degradation, therefore its half-life in blood is only 1～2min, needs the effect of continuous infusion competence exertion. Grind(AC2993 is called for short: ByettaTM) as artificial synthetic Exendin-4, at body the Exendin-4Amylin&Lilly sending outThe interior half-life reached about 4 hours. LiraglutideNovoNordisk (is called for short: NN2211), be that a kind of amidatioon is repaiiedThe long-acting analog of GLP-1 of decorations, the half-life is 12 hours. CJC-1131 Canada Conjuchem, the L-Ala that its N end is the 2ndReplaced by D-Ala, and connect amides compound at C end, the half-life reaches 10～12 days. ZP-10 Denmark Zealand adoptsThe structure induction probe peptide patented technology of modifying, French Sanofi-Aventis company further develops.

Pancreatic islets transplantation comprises: heterograft, stem cell, genetic engineering modified insulin secretory cell. Stem-cell therapy sugarUrinate sick method as follows: transfer autologous bone marrow stem cells, autoblood stem cell transplantation, human embryo stem cell is transplanted, and bleeding of the umbilicus is dryCell transplantation, inductivity pluripotent stem cell (being called for short: iPS cell). Melton research group studies confirm that, 3 are transcribedFactor Ngn3, Pdx1 and Mafa import to after maturity-onset diabetes mice pancreatic, and it is celliform that Exocrine Pancreas In Rats can be converted into βEndocrine cell, this cell and natural beta Cell of islet are at size, form, ultra microstructure, function related gene expression etc.Aspect is all without obvious difference, and can eliminate by rebuilding Pancreas Islet Structure the hyperglycaemia of streptozotocin diabetic mice model.

(8) progress of obesity

1, general introduction

Obesity (obesity) refer to body fat overheap or (with) Fat Distribution is abnormal, normal and sugar tolerance is differentOften, insulin resistance, disorders of lipid metabolism and hypertension etc. merge existence, general designation metabolic syndrome. Asian tends to occur abdomenType obesity is not that whole body obesity but intra abdominal fat are assembled. Occur during lower than European obesity standard at body mass index withThe fat relevant metabolic disease such as danger-diabetes and disorders of lipid metabolism and the M & M of cardiovascular and cerebrovascular diseases are brightAobvious increasing. 15%～18% of the about percentage of liveweight of Normal Male Adults adipose tissue weight, women accounts for 20%～25%. With the ageIncrease the corresponding increase of body fat proportion. Because the increase of body fat makes body weight be above standard body weight 20% or body mass index [BMI=bodyHeavy (Kg)/height²(m²)], be greater than 23 and be called obesity. As can be the person of seeking claimed simple obesity without the obvious cause of disease; Have clear and definiteCause of disease person is called secondary obesity.

2, the somatotype of obesity and the cause of disease

(1) somatotype

Simple obesity: constitutional obesity is onset childhood, family history, obesity is whole body and distributes, insensitive to INS; ObtainObtaining property fat is the morbidity of growing up, and four limbs are fat, diet control.

Secondary Obesity: endocrine disturbance, dysbolism.

(2) cause of disease

1. obesity has obvious genetic predisposition, belongs to multiple-factor inheritance. In the report such as Mayer parents, a side is fat, itsChildren's obesity rates is about 50%; In parents, both sides are obesity, and its children's obesity rates rises to 80%. Human obesity be it is generally acknowledgedBelong to multiple-factor inheritance, heredity plays a part one in its morbidity easily to be sent out, fat formation still with living habits, ingestBehavior, hobby, insulin response and socio-psychological factor interact relevant.

2. neural mental element: in the hypothalamus of the known mankind and many animals, exist two pairs relevant with feeding behaviourNerve nucleus. A pair of is that abdomen offside core (is called for short: VMH), claim again satiety center; Another is to being ventral lateral nucleus of thalamus (abbreviation: LHA), claim again hungryMaincenter. Satiety center excitation time has full sense and food refusal, and when destruction, appetite increases; Honey stomach when hungry central excitation, when destructionApocleisis food refusal. In the time of hypothalamus generation pathology, and though belong to inflammation sequelae (after meningitis, encephalitis), wound, tumour andWhen his pathological change, as ventromedial nucleus destroys, relatively hyperfunction the and voracious nothing of ventral lateral nucleus of thalamus function is detested, and causes obesity. Otherwise, whenVentral lateral nucleus of thalamus destroys, and ventromedial nucleus function is relatively hyperfunction and apocleisis causes and becomes thin.

3. hyperinsulinemia: the effect of hyperinsulinemia in obesity morbidity is in recent years noticeable. Fat normal withHyperinsulinemia is also deposited, but it is generally acknowledged to be that hyperinsulinemia causes obesity. Hyperinsulinemia overweight people's pancreas isletElement burst size is about 3 times of normal person. Pancreas islet have the effect of significant promotion lipopexia, and someone thinks, insulin can be used asAn index of total BFM, and can be used as in a sense the fat monitoring factor. More someone thinks, plasma insulinConcentration is significant positive correlation with total BFM.

4. brown adipose tissue is abnormal: brown adipose tissue is found a kind of adipose tissue just in recent years, with masterBeing distributed in subcutaneous and internal organ white adipose around organizes corresponding. Brown adipose tissue has a very limited distribution, and is only distributed inBetween omoplate, around nape portion, axillary region, mediastinum and kidney, its tissue appearance is light brown, and cell volume changes relatively little. In vainLook adipose tissue is a kind of energy storage form, body is stored in superfluous energy with neutral fat form between, and when body needs energy, fatIn fat cell, neutral fat hydrolysis is employed. White adipose cell volume changes greatly with releasing energy and energy storage. Brown adipose tissue existsIn function, be a kind of heat production organ, in the time that body is ingested or be subject to cold stimulation, fat combustion in brown fat cell, thereby certainlyDetermine the energetic supersession level of body. Above two kinds of situations are referred to as respectively to call ingest induction heat production and cold coldinduced thermogenesis. Certainly, thisThe function of specific proteins is subject to again the impact of many factors. As can be seen here, this heat production tissue of brown adipose tissue is participated in directlyTotal adjusting of intimate heat, distributes waste heat in body to external, human body energy metabolism is tended to balance.

5. other: feed too much can by the stimulation of small intestine is produced too much gastrointestinal inhibitory peptide (be called for short: GIP), GIP stimulateBeta Cell of islet uelralante. Low in pituitary function, particularly growth hormone minimizing, short sexual gland and thyrotropic hormone subtractFew sexual gland causing, the obesity that specific type can occur hypothyroidism, may reduce with lipid mobilization, relatively syntheticIncrease relevant. Fat taking women as many clinically, particularly multipara or menopause or oral contraceptive for female person easily occur, and carryShow that estrogen is relevant with Fatty synthesis metabolism. When adrenal cortex function is hyperfunction, cortisol secretion increases, and promotes gluconeogenesis,Blood sugar increases, stimulate insulin secretion and increase, so Fatty synthesis increase, and cortisol promote lipolysis.

6. dietetic life mode is unreasonable, and the raising of economic level is fat important environmental factor. Physical exertion subtractsFew, dietary structure changes, and fat intake increases, and saturated fat and less fiber more in recipe all easily occur fat. ChinaObesity rates is more American-European low, and degree is also lighter, but along with the improving constantly of economic life, Overweight and obesity has becoming of increasing graduallyGesture. Chinese are also the group of people at high risks of abdominal obesity.

7. the fat variation to adipose tissue: as mentioned above, the adjusting of adipocyte size and number is to lean on from fatty groupThe nerve that hair-weaving goes out or hormone signal arrive brain, when adipocyte can not suitably send signal or brain can not enter this signalThere is obesity in row appropriate reaction.

Affect the enzyme of Fatty synthesis and decomposition in adipose tissue: lipoprotein lipase, due to this enzymatic activity in mesenterium fatStronger, be easy to occur abdominal obesity, and in subcutaneous fat, this enzymatic activity is lower; Hormone-sensitive lipase, overweight people's adipocyteLipolytic enzyme is resisted the stimulation of catecholamine, and overweight people often accompanies hyperinsulinemia all to make lipolysis subtract simultaneouslyFew. The anti-α of fat of male sex's belly₂The short fat decomposition of adrenergic receptor is more obvious than women stomach fat, the therefore male sexMore easily there is abdominal obesity.

8. external cause taking hyperphagia and Lack of Movement as the main same day calorie of taking food exceed while consuming required energy, divided byOutside the form storage of liver, muscle glycogen, be almost converted into fat completely, be stored in whole body fat storehouse. As too much in regular absorptionNeutral fat and carbohydrate, make Fatty synthesis accelerate, and becomes the external cause of obesity, often the in the situation that of Lack of Movement, as stopsOnly physical training, alleviate manual labor or Recovery Phase of diseases is lain up, recuperation in postpartum etc. occurs fat.

3, clinical symptoms

(1) the general body fat of simple obesity is uniformly distributed, but women obesity fat is easily gathered in stern hip position and thigh,Similar pyriform; Male overweight adipose tissue is assembled at belly and internal organ, outward appearance is apple shape, and the latter Geng Yi causes various metabolismComplication is as diabetes, hypertension, disorders of lipid metabolism, hyperuricemia etc.

(2) obesity causes heart burden, pulmonary hypertension, right heart failure: due to hypertension and high power capacity, left chamber increases, a left sideChamber end-diastolic presses liter, left chamber function occurs bad; Heart failure is the major reason of severe obesity death. Severe depletion of oxygen causes the rhythm of the heartNot normal outbreak increases by 10 times than the sudden death of regular severe one.

(3) to cause respiratory function bad for obesity: breathe hard, shortness of breath and respiratory function is bad, snoring, central nervous system be to CO₂Sensitiveness lowers, and sleep apnea is common, and abdominal obesity degree and neck length are short relevant with OA, and severe one canSudden death. Be severe obesity than ideal body weight high approximately 60% or overweight 45kg person. Now heart and breathing are seriously influenced, chronic lowVentilation, partial pressure of oxygen declines and partial pressure of carbon dioxide rising, causes hypercapnia; Due to the low ventilation of serious alveolar, high significantlyCarbonemia and respiratory acidosis, cause erythremia and cyanosis and claim Pickwick (Pickwickian) syndrome, and patient has a liking forSleep or go into a coma.

(4) daily work and the activity of the huge physical effects patient of spiritual mental handicape, comprises and purchases fit clothes, takes advantage ofCar, seize the opportunity the each side such as seat and all throw into question.

(5) bear a heavy burden in backbone, joint, and increase obesity makes backbone, articulation structure is loaded increases, common pain in back and loin and leg boneArthropathy.

4, diagnosis and antidiastole

(1) diagnosis

1. body mass index

Clinical the most frequently used body mass index BMI judges patient's Overweight and obesity [BMI=body weight/height²(kg/m²)]. BMI withFat is closely related, but muscular person BMI height is not necessarily fat; The people of little skeleton and few muscle obesity and BMI is low.

2. the relation of height and body weight

Clinical also to have fairly simple method be (kg) taking height cms～105 as SBW, exceedes 10% for superHeavy, exceed 20% for fat. CT examination, MRI and ultrasonic examination detect the also comparative maturity of method of overall and local fat. FertileThe definite of fat standard is reference groups statistics and the incidence of disease and the death of various relevant important diseases along with the increase of body fatThe boundary value that rate significantly rises is determined. The World Health Organization according to this principle determined European's body weight criteria for classification andDanger with relevant disease generation. Table 39 is listed European and Asian according to the weight sorting of BMI.

3. waistline

Can reflect the degree of abdominal obesity, closely related with fat complication, arm's length standard European is decided to be male <94cm, female < 80cm, the normal waistline of Asian is just decided to be man≤90cm, female≤80cm. Also useful waistline and hip circumference ratio (W/H)Judge abdominal obesity, but not as alone waistline more simple and reliable.

Measuring method: waistline: the Zhou Jing of the midpoint of anterior superior iliac spine and the 12nd rib lower edge line, when measurement, stand, both feetSeparately 25～30cm. Hip circumference: around the Zhou Jing of pelvis most salient point.

4. fat

How much fat also once used different parts skinfold (skinfoldthickness) judgement, electrical bio-impedanceAccording to the electric conductivity of adipose tissue and resistance degree measure body fat proportions different from its hetero-organization, the general fat of normal maleFat percentage of liveweight 15%～20%, women is 20%～25%.

Obesity often accompany blood sugar, blood fat and dysarteriotony and gonad development to fall behind and sexual function attenuating etc. with other in pointSecreting disease obscures. Come from endocrinopathic obesity generally very not serious, body weight is above standard the above person of body weight 30% less than 5%,And the obesity that endocrine system disease causes has special feature and laboratory examination is abnormal.

(2) antidiastole

1. blood_lipid

Normal companion's hypogonadism is frohlich syndrome (Frohlichsyndrome), be women obesity withAnd centrality fat accumulation, often because encephalic wound, tumour, encephalitis etc. cause, sexual gland agensis, lacks secondary sex characters. Can have and sleepThe dormancy time puts upside down, drowsiness, body temperature and perspiration abnormal etc.

2. hypercortisolism

Be central obesity, moon shaped face, abdomen is large but four limbs are relatively thin, sanguine temperament, skin has purple striae, blood cortisol and urine tripRaise from cortisol and 17-OHCS, CT or MRI check that hypophysis or adrenal gland can have tumour sign.

3. hypothyroidism

Be special myxedema face, be afraid of cold, lazy moving, dry skin is lossless, celostomia, and constipation, T3, T4 are low in blood chemical examination,And TSH rising helps discriminating.

4. insulinoma

Owing to repeatedly occurring hypoglycemia, the normal feed again and again of patient causes obesity, and hunger and hypoglycemia symptom are mainly in the morningOn an empty stomach or occur in while dining for a long time.

Accidental in the situation that, obesity may be a part for some genetic syndrome. As: Prader-willi is comprehensiveLevy, have many food obesities, diabetes and feeblemindedness; Laurence-Moon-Biedl syndrome, patient eats more, fat, intelligence is lowUnder, hypogonadism, pigment iritis and refer to (toe) deformity etc. more.

5, prophylactic treatment

Therapeutic purpose is alleviate 5～6 kilograms of unnecessary body weight or alleviate 10% of original body weight, strives that BMI maintains <23. Weight recovery is normally very difficult, and suitably loss of weight is certainly good for health.

(1) improve diet structure, adhere to suitable physical exertion, give up smoking and lack wine

Light physical exertion diet can calculate by (height cm-105) × 25kcal/ (kgd), general women every day 800～1200kcal, the male sex 1000～1400kcal, distributes one day total amount of heat, should not leak meal, does not eat sweet food and Sugared beverages, avoids mealBetween with dessert. The favourable loss of weight of raw fiber food, can lower appetite, and fat and oil account for total amount of heat < 20%～30%, in total amount of heatWhat provided by saturated fatty acid is no more than 10%, and the absorption of cholesterol should be reduced to and be less than 300mg every day; Carbohydrate accounts for always55%～65% of heat, protein accounts for total amount of heat should be less than 15%. Many food fresh fruit, vegetables and coarse food grains, limit wine, uses nothingThe sweetener of nutrition. Very low calorie diet can lose weight in a short time, and body weight can increase more, and inadvisable afterwards. For a long timeAdhere to that low-heat diet is more effective. Short-term very low calorie diet can be used for extremely fat.

Suddenly increasing amount of exercise has certain danger, and encouraging will have habitually regular daily work according to individual instancesMoving, increase amount of exercise every day, overweight people does not answer aggravating activities. Swimming, all useful by bike on foot. Motion reduces overweight peopleBody fat proportion. Diet and motion only can make adipocyte smaller volume, and adipocyte number does not generally subtract, and fat-reducing starts severalWhen week, rapid Body weight loss may be that water sodium is lost, and occurs slowly that catabolism of fat increases later, and this phase body may haveMetabolic rate declines, and loss of weight is more slow. The general first month Body weight loss 1.5 at loss of weight is to 2kg, and motion and limit are eaten 3 monthsCan make Body weight loss 4～5kg. Strict diet moves and can make Body weight loss 6kg in latter 1 year, but often in returning to again in 5 yearsWeight. It is very difficult above that simple diet motion control successfully reaches 12～18 months, and only approximately 20% patient can after fat-reducingKeep 5～15 years, must emphasize insistent changing lifestyles.

Though fat-reducing can not recover impaired islet cells but Body weight loss can improve insulin secretion delay phenomenon, increase weekEnclose the sensitiveness of tissue to insulin. The danger that diabetes occur Body weight loss 3kg can obviously decline. Women is in 10 yearsLose weight more than 5kg, more than there is the dangerous drop by half of diabetes.

Lose weight and also can improve disorders of lipid metabolism, make blood pressure drops. Moderate lose weight (reduce 5%) can make high bloodPressure patient has the blood pressure drops of clinical meaning, also can increase the effect of depressor.

(2) medicine treatment

Diet and approximately 3 to 6 months Body weight loss 6% of motion or BMI > 27 can add and use medicine supplemental treatment. Following situations alsoShould consider medicine treatment: 1. hunger or significantly bulimia; 2. have relevant disease accompanied as IGT, hypertension,Dyslipidemia; 3. there are other severe complications: severe bone arthropathy, obstructive sleep apnea, reflux esophagitis, positionProperty oedema etc.

1. act on central nervous system, lose weight by lowering appetite

By acting on 5-HT and norepinephrine bypass is worked: sibutramine (Sibutramine) suppresses 5-HTAnd norepinephrine reuptake, be wide spectrum monoamine uptake inhibitor, improve satiety, reduce caloric intake, also reduce α andThe regulating action of Beta-3 adrenergic receptor, increases themogenesis, to reduce body weight. Its side effect is dry, and heart rate is fast, nonreactiveThe side effect of cholinergic drug and the habituation of amphetamine, oxidation and demethylation metabolism in liver, metabolite is from urineDischarge, the half-life is 16 hours, and 10～15mg takes medicine one every day.

Work by norepinephrine bypass: ephedrine and caffeine etc. causes apocleisis, also have some calorigenic effects.Phentermine early takes 15mg before the meal, can increase to sooner or later each 15mg before the meal, and the diethylpropion morning of 75mg before the meal, is amphetamine derivativeThing, appetite-suppressing, amphetamine swashs effect to central nervous system spinosity, easily habituation. Only recommend short application use (< 3 months orBe interrupted and be applied in overweight more than 30% or BMI >=27).

Work by serotonin (5-HT) bypass: should not share with MAOI. Fenfluramine and the right sideRevolving fenfluramine does not apply because of the complication that causes former pulmonary hypertension and cardiac valves hypertrophy. Prozac is to act on 5-hydroxylThe antidepressants of tryptamines, especially for there being the voracious adiposis patient of depression, every day 20～40mg, can have nauseating, diarrhoea and headacheDeng side effect.

2. act on gastrointestinal drug

Orlistat (Orlistat, Xenical, Xenical) pancreatic lipase inhibitor, is dose dependent and reduces fatAbsorb. Reduce body weight and improve blood fat, suppressing triglycerides and convert FFA to. Oral 120mgtid when meal. Main side effectBe gastrointestinal reaction, oiliness just.

Melbine: can be so that overweight people's body weight when merging IGT person applies Or Metformin In Treating hyperglycaemiaAlleviate severe depletion of oxygen, the bad prevention lactic acidosis that should be noted of darling renal function.

Diuretics and laxative there is no obvious fat-reducing effect, and L-T4 also should not use, dangerous.

(3) operation

For the above person in BMI >=35～40. Operation reduces stomach volume, to impel satiety, reduces food and enters amount. Comprise stomachSeptation operation makes stomach proximal volume≤80ml; Stomach band or stitching operation, laparoscope is placed adjustable inflatable band and stomach jejunum dividesStream art etc. Perform the operation in latter 1 year and can reduce 40%～50% of overweight body weight, but the highly concentrated liquid of can not taking food, otherwise body weight is stillCan increase. Long-term safety and the validity of operation are still uncertain.

Small intestine changes its course operation because there being the long-range complication need not. Lipsuction is used for belly local fat accumulation person, but necessaryDetermine idicatio and operate by experienced doctor, to reduce the complication such as fat embolism.

(4) other

Many people follow obesity to have psychological abnormality to adjust, the various diseases of following of also answering active treatment to bring because of obesityDisease, abnormal as hypertension, hyperglycaemia and blood fat.

In a word, existing technical data analysis shows, sesterterpenoids compound H ippolideI is a new chemical combinationThing, researchs and develops the purposes of this sesterterpenoids compound H ippolideI, further studies sesterterpene compoundsThe preparation technique of HippolideI, improve the quality of products and clinical efficacy, can there is significant social benefit, economic benefit.

By literature search, up to the present, not yet find that there is the product of sesterterpenoids compound H ippolideI aspectReport.

Summary of the invention

The technical problem that will solve required for the present invention be disclose a kind of sesterterpene compounds and preparation method thereof andPurposes, a kind of new sesterterpenoids compound H ippolideI and its production and use, deposits to overcome prior artAbove-mentioned defect.

That is to say, the present invention is by the research such as zoopery, clinical testing and theory study, and one of object is intended to provideA kind of new sesterterpenoids compound H ippolideI.

Two of object of the present invention is to provide a kind of preparation method of this sesterterpenoids compound H ippolideI.

Another object of the present invention is that clear and definite sesterterpenoids compound H ippolideI is antitumor, anti-diabetic andThe activity of the application aspect such as anti-obesity, the pharmaceutical composition that contains above-mentioned sesterterpenoids compound H ippolideI is doneFor preparing the application of the aspects such as antitumor product, anti-diabetic product and anti-obesity product, namely sesterterpenoids chemical combinationThe purposes of thing HippolideI. In said composition, sesterterpenoids compound H ippolideI of the present invention accounts for 10%～90% (percentage by weight), preferably accounts for 50%～90% (percentage by weight).

(1) definition of the present invention

Antitumor product of the present invention refers to and is directly used in prevention, diagnosis, detection, protection, treatment and research tumourAnd one or more in the product of directly related disease, comprise that anti-lung cancer product, anti-cervical cancer product or inhibitor against colon carcinoma cells produceOne or more in product; Described tumour is to comprise one or more in lung cancer, cervical carcinoma or colon cancer.

Anti-lung cancer product of the present invention refers to and is directly used in prevention, diagnosis, detection, protection, treatment and research lung cancerAnd one or more in the product of directly related disease, described lung cancer refers in non-small cell lung cancer and ED-SCLCOne or more, described non-small cell lung cancer is to comprise one or more in phosphorus cancer, gland cancer or maxicell lung cancer.

Anti-cervical cancer product of the present invention refers to and is directly used in prevention, diagnosis, detection, protection, treatment and research palaceOne or more in the product of neck cancer and directly related disease thereof, described cervical carcinoma is under atypical hyperplasia, carcinoma in situ, mirrorOne or more in early invasive carcinoma or infiltrating carcinoma.

Inhibitor against colon carcinoma cells product of the present invention refers to and is directly used in prevention, diagnosis, detection, protection, treatment and research knotOne or more in the product of intestinal cancer and directly related disease thereof, described colon cancer refers to proportion of cancer of left side of colon, right hemicolonOne or more in cancer or the carcinoma of the rectum.

Anti-diabetic product of the present invention refers to and is directly used in prevention, diagnosis, detection, protection, treatment and research sugarOne or more in the product of urine disease and directly related disease thereof, described diabetes refer to type i diabetes, II type glycosuriaOne or more in the diabetes of disease, gestational diabetes mellitus or other specific types; The diabetes of other described specific typesTo comprise the diabetes that β cytogene defect causes, diabetes, the pancreatic exocrine gland disease that insulin action gene defect causesDiabetes, the medicine reason that disease causes brought out the diabetes that cause or chemical reason and brought out a kind of or many in the diabetes that causeKind.

Anti-obesity product of the present invention refers to and is directly used in prevention, diagnosis, detection, protection, treatment and research fertilizerOne or more in the product of fat disease and directly related disease thereof, described obesity refers to simple obesity, acquired fertilizerFat.

Antitumor product of the present invention, anti-diabetic product and anti-obesity product be all comprise medicine, food orOne or more in field of beverage product, a kind of in preferred agents, reagent, food, health food, additive or beverage orMultiple, further one or more in preferred agents, reagent, Foods or drinks etc., most preferably medicine.

The medicinal raw material that sesterterpenoids compound H ippolideI of the present invention uses refers to sponge or spongeCrude extract, preferred Demospongiae (Demospongiae) sponge or Demospongiae (Demospongiae) sponge crude extract,One or more in Calcispongea (Calcarea) sponge or Calcispongea (Calcarea) sponge crude extract etc., enter oneWalk preferred sycon (Grantia) or sycon (Grantia) crude extract, Leucosolenia (Leucosolenia) or Leucosolenia(Leucosolenia) crude extract, bath sponge (Euspongiaofficinalis) or bath sponge (EuspongiaOfficinalis) crude extract, fine hair horse sponge (Hippospongialachne) or fine hair horse sponge (HippospongiaLachne) one or more in crude extract, fresh water sponges (Spongilla) or fresh water sponges (Spongilla) crude extract etc.;Preferred fine hair horse sponge (Hippospongialachne) or fine hair horse sponge (Hippospongialachne) crude extract againDeng in one or more.

Sesterterpenoids compound H ippolideI is prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-The active component of diabetes and anti-obesity, its occupation mode is to comprise independent use or combine use etc. with other chemical substancesIn one, preferably separately use, all can be used in preparation antitumor product, anti-diabetic product and anti-obesity product.

Test sample is all to take conventional preparation method to obtain, the sesterterpenoids compound H ippolide obtainingThe general < 60% of I content, but by purifying, can obtain the pure of sesterterpenoids compound H ippolideI after purifyingDegree can be more than 95%, i.e. the defined sesterterpenoids compound H of the present invention ippolideI.

That is to say, adopting sesterterpenoids compound H ippolideI is raw material, or directly adopts and contain two timesThe sponge of half terpenoid HippolideI is raw material, or directly adopts and contain sesterterpenoids compound H ippolideThe sponge crude extract of I is raw material, can both be directly or indirectly for the preparation of antitumor product, anti-diabetic product and anti-obesityProduct. It is defined two sesquialters of the present invention that sesterterpenoids compound H ippolideI preferably uses with substantially pure formTerpenoid HippolideI, as purity >=95% of sesterterpenoids compound H ippolideI.

(2) technical conceive

Independent development original new drug is a current urgent task of China, and traditional Chinese medicine has a long history, and usesChemoprophylaxis and treatment disease aspect have also accumulated rich experience, therefore particularly find ocean and have from existing natural resourcesThe active component of effect or find that its new purposes is all effective quick approach is also that the advantage of Chinese original new drug development is with fastThe place of prompt approach.

Marine organisms are one of valuable sources of pharmaceuticals industry always, are also study hotspots in recent years. Ocean approximatelyTake up an area 71% of ball surface area, microbial resources are richly stored with. Along with continually developing of marine resources, find new oceanBiological or to screen the difficulty of new active component increasing, and resistance to the action of a drug problem is day by day serious, make marine organisms sourceNew drug development is faced with severe challenge. But increasing research shows in recent years, marine organisms---especially those are with seaThere is the biology of the relation such as symbiosis or parasitism in ocean microorganism---and can produce structure metabolism unique and the strong physiologically active of tool and produceThing, has broad application prospects. Scientists is estimated, is developed new marine drug and will place hope on this new neck of marine organismsTerritory. For example, sponge secondary metabolite is rich and varied, wherein contains and has in a large number antitumor, antiviral, antibacterial, anti-inflammatory and exempt fromThe different bioactive compounds such as epidemic disease adjusting are the focuses of marine nature products chemistry research always.

Inventor, by sponge extract being carried out to the chemical constitution study of system, screens and proves in this sponge extractNew sesterterpenoids compound H ippolideI and activity and purposes, thus inventor infers sesterterpene compoundsHippolideI lives at aspects such as prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-diabetic and anti-obesitiesThe clinical drug effect of property should be mainly also by particularly sesterterpene compounds of this sponge extract of active siteThe drug effect of HippolideI is brought into play, and result of study also proves and confirmed particularly sesterterpenoids of this sponge extractCompound H ippolideI has significant pharmacologically active.

Inventor through the latest find of research is: sesterterpenoids compound H ippolideI can antitumor, anti-sugarThe new role of urine disease and anti-obesity etc.

Tumour, diabetes etc. have a strong impact on health and the life quality of Chinese population, development prevention, diagnosis, detection, guarantorProtect, product, particularly medicine, diagnostic reagent and the health care for the treatment of and the aspect such as Effect of Anti tumour, anti-diabetic and anti-obesityProduct etc., have significant social benefit, economic benefit.

According to this idea and thinking, inventor, by experimental study and analysis repeatedly, successfully obtains sesterterpenoidsCompound H ippolideI and corresponding application product thereof.

(3) structure and properties of sesterterpenoids compound H ippolideI

The present invention to sesterterpenoids compound H ippolideI at prevention, diagnosis, detection, protection, treatment and Effect of AntiExperimental study and the theory study of multi-angle have been carried out in the aspects such as tumour, anti-diabetic and anti-obesity.

The invention provides a kind of new sesterterpenoids compound H ippolideI, its chemical structural formula is as follows:

Structural Identification is as follows:

Routinely through various modern spectral techniques such as NMR, HRESIMS, CD, IR, and the change such as recrystallization, Mosher reactionChemical constitution and the spatial configuration of method HippolideI, its absolute configuration is 4R, 24R.

Physicochemical data: colorless oil;

Infrared spectrum data: v_max3369，2926，1596，1448，1212，1067，840，673cm^-1；

High resolution mass spectrum provides molecular ion peak m/z392.2567[M+Na]⁺；

Molecular formula is C₂₄H₃₅NO₂；

¹HNMR(CDCl₃, 400MHz) and¹³CNMR(CDCl₃, 100MHz) and data are in table 1.

Table 1, HippolideI's¹H and¹³C nuclear magnetic resonance data table

(4) preparation method of sesterterpenoids compound H ippolideI

The present invention provides following technical scheme according to above-mentioned technical conceive and result of study:

The preparation method of the compounds of this invention HippolideI is as follows:

(1) prepare sponge extract medicinal extract

1. freezing sponge is chopped into fritter, with ethanol diacolation extraction routinely, obtains extract;

2. by extract reduced pressure concentration, obtain extract medicinal extract;

Described sponge is to comprise Demospongiae (Demospongiae) sponge, Calcispongea (Calcarea) spongeDeng in one or more, further preferably sycon (Grantia), Leucosolenia (Leucosolenia), bath sponge(Euspongiaofficinalis), fine hair horse sponge (Hippospongialachne), fresh water sponges (Spongilla) etc.In one or more; Preferred fine hair horse sponge (Hippospongialachne) again.

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate, concentrated extract obtains fat-solubleMedicinal extract; Fat-soluble medicinal extract is suspended in methanol solution, and with non-polar organic solvent extraction, concentrated extract obtains nonpolarly havingMachine solvent extraction medicinal extract; Add water the methanol concentration of suspension is adjusted to 60%, with dichloromethane extraction, concentrated extract obtainsCarrene extracts medicinal extract; By initial water extracting n-butyl alcohol, concentrated that n-butanol extracts medicinal extract;

Described methanol solution is 50%～95% methanol solution, preferably 80%～95% methanol solution, further90% methanol solution;

Described non-polar organic solvent is to comprise one or more in benzinum, ether or benzene etc., preferably benzinumOr one or more in ether etc., further preferred benzinum;

2. carrene is extracted to medicinal extract through decompression column chromatography, with carrene: methyl alcohol=100: 1,50: 1,30: 1,20:Be solvent gradient elution at 1,10: 1,5: 1,1: 1, and according to TLC, colour developing merges similar stream part, obtains 9 component Fr.1～Fr.9;

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50: 1,20: 1,10: 1,5: 1,1: 1 be solvent gradient elution at 3: 1, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainTo compound H ippolideI, through qualification, it is sesterterpenoids noval chemical compound.

(5) pharmacologically active of sesterterpenoids compound H ippolideI

1, anti tumor activity in vitro experiment

Compound H ippolideI of the present invention has been carried out to Cytostatic to tumor cell test, and test method adopts normalThe mtt assay of rule.

(1) tumor cell line: A549 (human lung carcinoma cell), HeLa (human cervical carcinoma cell), (human colon carcinoma is thin for HCT-116Born of the same parents), provided by the biological Co., Ltd of Shanghai Tian Jia;

(2) experiment reagent, consumptive material and instrument: DMSO and MTT (sigma company), culture dish, pipette and 96 orifice plates(Corning company);

(3) experimental drug: compound H ippolideI is prepared by embodiment;

(4) cell is cultivated

Respectively by the 3 strain cell A549, HCT-116, HeLa that grow in exponential phase routinely through 0.01% pancreatinDigestion, adjusts cell density to 2.0 × 10³Individual/hole, is inoculated in respectively 96 orifice plates with every hole 100 microlitres, and 4 96 orifice plates are putIn 5%CO₂37 DEG C of overnight incubation in incubator.

(5) cell viability test experience

Every 96 orifice plates are established 8 groups, i.e. positive controls, negative control group, 6 concentration groups of medicine. Positive control drug isAdriamycin, is mixed with the solution that concentration is 0.4 grams per milliliter with DMSO, by experimental drug thing plakortoneH orIt is 100,50,25,12.5 that plakortoneJ is mixed with respectively concentration with DMSO, and the medicine of 6.5,3.125 (ug/ml) is moltenLiquid, joins the drug solution of variable concentrations (20 microlitre) respectively in 96 orifice plate corresponding apertures, and negative control group adds equal-volumeDMSO, positive controls adds adriamycin solution 20 microlitres, and each concentration is established three multiple holes, at 5%CO₂Training in 37 DEG C of incubatorsSupport 72 hours, every hole adds the MTT of the 5mg/ml of 20 microlitres, continues at 37 DEG C and hatches 3 hours, sucks the solution in hole, more everyHole adds the DMSO of 100 microlitres to dissolve, and uses SpectraMAX340 ELIASA to detect absorbance value L1 in wavelength 550nm, inReference wavelength 690 nanometer detection absorbance value L2, map poor (L1-L2) of absorbance value to inhibitor variable concentrations, withSigmoidaldose-response (varibleslope) is models fitting, and application software GraphpadPrism4 calculatesIC₅₀, the results are shown in Table 2.

Table 2, the HippolideI half effective inhibition concentration (μ M) to tumour cell

Above-mentioned experimental result shows: compound H ippolideI all shows obviously and presses down three kinds of different tumor cell linesMake use, therefore can be for the preparation of antineoplastic.

2, Protein-tyrosine-phosphatase PTP1B active testing

Compound H ippolideI of the present invention has been carried out to Protein-tyrosine-phosphatase PTP1B inhibition test.

(1) enzyme: PTP1B, is provided by the biological Co., Ltd of Shanghai Tian Jia;

(2) substrate: pNPP;

(3) experiment reagent, consumptive material and instrument: DMSO and MTT (sigma company), culture dish, pipette and 96 orifice plates(Corning company), VERSAmax (MolecularDevices, USA);

(4) experimental drug: compound H ippolideI is prepared by embodiment;

(5) PTP1B suppresses active testing: sample dissolves with DMSO, and low temperature is preserved, the concentration control of DMSO in final systemWithin not affecting the scope of detection of active. Adopt light absorption detection method, in the flat transparent microwell plate in 96 holes or 384 holes, examineSurvey enzymatic activity. Substrate pNPP is hydrolyzed through PTP1B the free product obtaining has very strong light absorption at 405nm place. Pass through ELIASAThe variation of monitoring 405nm place optical absorption intensity, calculates initial velocity of reaction. The control compound adopting in experiment is Na₃VO₄。Taking sigmoidaldose-response (varibleslope) as models fitting, application software GraphpadPrism4 meterCalculate IC₅₀, the results are shown in Table 3.

Table 3, the HippolideI half effective inhibition concentration (μ M) to PTP1B

(6) purposes of sesterterpenoids compound H ippolideI

1, general introduction

The object of this invention is to provide a kind of for prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-glycosuriaThe product of sick and anti-obesity and directly related disease thereof, comprises one or more in medicine, reagent, food etc., preferred medicineThing.

Prove by Pharmacological Activity Screening, sesterterpenoids compound H ippolideI is its prevention, diagnosis, detection, guarantorProtect, the active site for the treatment of and Effect of Anti tumour, anti-diabetic and anti-obesity and directly related disease thereof.

Antitumor activity in vitro shows, compound H ippolideI is to human lung cancer cell A549, human cervical carcinoma cellHela, human colon cancer cell HCT-116 all shows that inhibition is active, therefore can be used for preparing antineoplastic.

Protein-tyrosine-phosphatase PTP1B active testing shows, compound H ippolideI is to protein-tyrosine-phosphatase 1Enzyme PTP1B shows that inhibition is active. PTP1B is first certified protein-tyrosine-phosphatase (proteintyrosinePhosphatase), the experiment on mice of rejecting by PTP1B shows, PTP1B is by the dephosphorization acidylate to insulin receptor, and thenIn adjusting insulin sensitivity and fat metabolism process, play very important effect. Thereby compound H ippolideI canFor the preparation of the medicine of diabetes and obesity.

The present invention, for development antitumor product, anti-diabetic product and anti-obesity product medicine, provides new guideCompound, provides scientific basis for developing Chinese Sea medicine resource.

Show through experimental study, sesterterpenoids compound H ippolideI is external can significantly delay relevant diseaseDevelopment. Completed acute toxicity testing proves, mouse stomach administration exceedes 1.0g/ to the maximal tolerance dose of this active siteKg, is equivalent to the more than 200 times of clinical recommended drug dosage, shows that this active component is safe and reliable, has solved in Chinese medicine compound prescriptionLow and the problem that contains toxic component of complicated component, active constituent content.

In sum, inventor has carried out theory study to sesterterpenoids compound H ippolideI, through a large amount ofParticularly long-term pharmacology test of experimental study, finds that the sesterterpenoids compound H ippolideI addressing has significantlyThe work of prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-diabetic and anti-obesity and directly related disease thereofProperty.

Therefore, sesterterpenoids compound H ippolideI and composition thereof can be used for preparing antitumor product, anti-glycosuriaSick product and anti-obesity product, be preferably prepared from taking sesterterpenoids compound H ippolideI of the present invention as raw materialMedicine.

2, the using method of sesterterpenoids compound H ippolideI and composition thereof and requirement

Sesterterpenoids compound H ippolideI of the present invention can combine use separately or with other active component, bagDraw together for the preparation of for prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-diabetic and anti-obesity and directlyThe product of relevant disease, comprises medicine, reagent or food etc., especially medicine.

In concrete use, sesterterpenoids compound H ippolideI of the present invention can use separately, exampleAs the form application with active site, its derivative or pharmaceutical salts, can also use together with other many chemical substances. No matterWhether these chemical substances have biologically active or have the function for the treatment of disease, comprise miscellaneous function as collaborative amplification,The side effects of antagonism or alleviation sesterterpenoids compound H ippolideI etc., these chemical substances are to comprise pharmaceutically canOne or more in carrier, food, natural products, chemical synthetic drug or the mankind's medication etc. of accepting; Preferably include medicineOne or more in acceptable carrier or food etc.; Further preferred pharmaceutically acceptable carrier.

" pharmaceutically acceptable carrier " used herein comprises the applicable solvent of any and all physiology, disperses to be situated betweenOne or more in matter, afterbirth, antiseptic and antifungal agent, isotonic agent or absorption delay agent etc. Pharmaceutically acceptable yearThe example of body comprises in one or more water, salt solution, PBS, glucose, glycerine or ethanol etc. and composition thereofOne or more. In many cases, in said composition, preferably include isotonic agent, for example, sugar, such as sweet mellow wine, sorbOne or more in polyalcohol or the sodium chloride etc. of alcohol, sorbierite. Pharmaceutically acceptable carrier can also comprise a small amount ofAuxiliary substance, such as, in wetting agent or emulsifying agent, anticorrisive agent or buffer solution etc. one or more, they have strengthened this two sesquialterThe term of validity of terpenoid HippolideI or effect.

From concrete classification, said pharmaceutically acceptable carrier refers to that the medicine of medicine and pharmacology field routine carriesBody, comprises lubricant, as one or more in talcum powder, polyethylene glycol or dolomol etc.; Disintegrant, as microcrystalline celluloseDeng; Filler, as one or more in starch, dextrin or lactose etc.; Adhesive, as pregelatinized starch, cellulose derivative,One or more in alginates, gelatin or polyvinylpyrrolidone etc.; Osmotic pressure regulator, as sodium chloride, glucose, sugarcaneOne or more in sugar, sorbierite or sweet mellow wine etc.; PH adjusting agent, a kind of in the acid such as example hydrochloric acid, NaOH or alkali orMultiple; Solvent, as in water, buffer solution, ethanol or propane diols etc. one or more etc.; Antioxidant and complexing agent, as sulfurous acidOne or more in sodium, EDTA etc.; Surfactant, as quaternary ammonium compound, hexadecanol etc.; Absorption carrier, as kaolinOr one or more in soap clay etc.; Macromolecular scaffold agent, as a kind of in cyclodextrin, polyethylene glycol, poloxamer etc. orMultiple; In addition, can also in composition, add other assistant agent, as the one in flavouring agent, anticorrisive agent or sweetener etc. or manyKind.

For example,, by active component sesterterpenoids compound H ippolideI dissolving, suspendible or be emulsifiable in suitable water-basedFor example, in (, one or more in distilled water, physiological saline or Green's solution etc.) or oil-based solvent (for example, plant in solventOne or more in oil such as olive oil, sesame oil, cottonseed oil, corn oil or propane diols etc.) in, can make injection systemAgent, wherein can contain solubilizer (for example, polyoxyethylene sorbitan monoleate, Crodaret, PVP, cyclodextrin, pool in solventOne or more in Luo Shamu, polyethylene glycol, phenmethylol, chlorobutanol or phenol etc.), osmotic pressure regulator (for example, chlorinationOne or more in sodium, glycerine, D9-mannose, D-glucitol or glucose etc.). In this case, if necessary, canAdd additive, for example stabilizing agent (for example, human serum albumins etc.), anodyne (for example, procaine hydrochloride or lidocaineDeng in one or more) etc.

Of the present invention and sesterterpenoids compound H ippolideI can also combine and make with the form of compositionWith, particularly with by other chemical substance animal especially mammal is comprised to people or other animals treat institute as medicineWith composition or similar composition. Described mammal, comprise people, mouse, rat, sheep, monkey, ox, pig, horse, rabbit,One or more in dog, chimpanzee, baboon, marmoset, macaque or rhesus macaque etc., preferably people, mouse, rat, monkey, pig, rabbit or dogDeng in one or more, further preferably one or more in people, rat or monkey etc. For example, can be by two times of the present inventionHalf terpenoid HippolideI add be suitable for to curee's Pharmaceutical composition in. Conventionally this Pharmaceutical composition bag,Containing sesterterpenoids compound H ippolideI of the present invention and pharmaceutically acceptable carrier.

The composition of sesterterpenoids compound H ippolideI particularly pharmaceutical composition can have various forms, bagDraw together one or more in the dosage forms such as such as liquid, semisolid and solid; Wherein said pharmaceutical composition comprises treatmentThe sesterterpenoids compound H ippolideI of effective dose is active component, and one or more are pharmaceutically acceptableCarrier.

Sesterterpenoids compound H ippolideI of the present invention or its pharmaceutical composition can adopt abilityThe known conventional production method in territory is made any formulation that is suitable for experiment, research or applies clinically, comprises solid systemAgent is as capsule, tablet, granular preparation etc., and liquid preparation is as oral liquid or injection etc.

For example make active component mix with one or more carriers, be then made into required formulation. Described formulationComprise one or more in tablet, capsule, granule, supensoid agent, emulsion, solution, syrup or injection etc., takeOral or injection (comprise in intravenous injection, drip-feed, intramuscular injection or hypodermic injection etc. one or more), mucous membrane dialysisDeng in one or more methods of administration carry out antitumor, anti-diabetic and anti-obesity and directly related disease thereof prevention,Diagnosis, detection, protection, treatment or scientific research.

It is 0.5%～99% active component sesterterpene compounds that pharmaceutical composition preferably contains weight ratioHippolideI, further preferably contains weight ratio and is 1%～95% active component sesterterpene compoundsHippolideI, most preferably contains weight ratio and is 5%～90% active component sesterterpenoids compound H ippolideI.

The pharmaceutical composition of sesterterpenoids compound H ippolideI generally must be aseptic and be being produced under condition of storageStable. Said composition can be mixed with to solution, microemulsion, dispersion liquid, liposome or other is suitable for having of high drug concentrationOrder structure. By by a kind of of this sesterterpenoids compound H ippolideI of aequum and required mentioned component or combinationAdd together in suitable solvent and then carry out aseptic filtration and prepare aseptic parenteral solution. Generally speaking, by by this two sesquialterTerpenoid HippolideI adds in the aseptic solvent that contains basic decentralized medium and required above-mentioned other composition and preparesDispersion liquid. In the case of the sterile powder for the preparation of aseptic parenteral solution, the preparation method of recommendation is vacuum drying and freezingDrier. For example, by the dressing such as lecithin, the dispersion liquid in the situation that by keeping required granular size and by makingWith surfactant, can keep the adequate liquidity of solution.

In said composition, can comprise the medicament that postpones absorption, for example Monostearate or gelatin, to reach injectable compositionProlongation absorb; Can comprise high molecular polymer carrier, as HPMC or polyoxyethylene, to reach Orally administered compositionProlongation discharge.

During for patient, sesterterpenoids compound H ippolideI dosage of the present invention is 10～40mg/kgD, can use one or more times, and this dosage or consumption are conventionally according to patient or user's age and body weight and health shapeThe situation of condition or patient's symptom decides.

Sesterterpenoids compound H ippolideI of the present invention and Pharmaceutical composition thereof can comprise " treatment effective dose " orThe sesterterpenoids compound H ippolideI of the present invention of " prevention effective dose ". " treatment effective dose " refers at necessary dosageWith the amount that effectively reaches required result for the treatment of under the time. The treatment effective dose of sesterterpenoids compound H ippolideI canDraw at this individuality according to the patient's condition such as individual, age, sex and body weight and this sesterterpenoids compound H ippolideIPlay the factor such as ability of required reaction and change. Treatment effective dose also refers to having of this sesterterpenoids compound H ippolideIBenefit result for the treatment of exceedes the amount of its any toxicity or harmful effect.

" prevention effective dose " refers to the amount that effectively reaches required preventive effect under necessary dosage and time. Because prophylacticAmount is for the ill front or early stage curee of disease, and prevention effective dose is less than treatment effective dose conventionally. Sesterterpene of the present inventionThe typical non-limiting scope of the treatment of compounds HippolideI or prevention effective dose is 10～40mg/kg, more preferablyBe 15～25mg/kg. It should be noted that dose value will change according to the disease type of wanting to alleviate and seriousness, that is to say for suffering fromWhen person, sesterterpenoids compound H ippolideI dosage of the present invention or consumption, conventionally according to patient or userThe situation of age and body weight and health or patient's symptom decides.

In addition, it should be understood that for any specific curee, should along with the time according to individual need and give with or supervision giveAdjust given dose system with the people's of described composition professional judgement, and the dosage range of setting is only illustrative herein, can't limit scope or the practice of claimed composition.

That is to say, need to, according to object, method of administration, disease and the situation etc. for the treatment of for the treatment of, change the present invention twoDosage or the consumption of the each and/or every day of sesquiterpenoids HippolideI. For example, give mammal through vein,Especially adult (as body weight 60kg), the single dose of described sesterterpenoids compound H ippolideI is about 80～1500mg, preferred about 120mg, preferably administration every day 1～3 time. Can adjust dosage unit, to put forward the best required reaction (example of archAs, treatment or prevention are replied).

For example, can single-bolus high-dose administration, can within a period of time, give several divided doses or according to treatment situationUrgency reduce in proportion or increase dosage. Preparation is easy to the non-enteron aisle combination of administration and the unified dosage unit form of dosageThing is especially favourable. Dosage unit form used herein, refers to be suitable for the dosage unit of the mammalian subject of wish treatmentPhysical separation unit; The calculating that each unit contains scheduled volume is for together producing required result for the treatment of with required pharmaceutical carrierActive matter sesterterpenoids compound H ippolideI. The specification of dosage unit form of the present invention, is determined by the following and directlyDepend on the specific characteristic of following (a) this sesterterpenoids compound H ippolideI and particular treatment or the prevention of wanting to reachEffect, and (b) mix in this technology that is used for the treatment of individual sensitivity sesterterpenoids compound H ippolideI inIn restriction.

3, the pharmaceutical dosage form of sesterterpenoids compound H ippolideI and composition thereof and method of administration

Sesterterpenoids compound H ippolideI of the present invention and composition thereof prepare for prevention, diagnosis,The product of detection, protection, treatment and Effect of Anti tumour, anti-diabetic and anti-obesity and directly related disease thereof, wherein according toThat product prepared by the requirement of beverage, food technology field can be used in prevention, protects and treats is antitumor, anti-diabetic and anti-fertilizerFat disease and directly related disease thereof; The product of preparing according to the requirement of medical technical field can be used in patient's treatment or guarantorStrong, can either to be directly used in separately preparation treatment or to keep healthy medicine, also can mix or group with many chemical substancesClose, directly or indirectly for the preparation of the medicine for the treatment of or keeping healthy. Above described phase of chemical substance described here and this sectionWith.

In the present invention, required material comprises raw material of the present invention, above-mentioned matching used chemical substance etc., all should basisActual conditions and needs, the material of employing food stage or pharmaceutical grade.

Sesterterpenoids compound H ippolideI of the present invention and composition thereof, can be with known in the artThe whole bag of tricks administration, although method of administration/administering mode of recommending in many therapeutical uses is spray or oral administration. ButThat technical staff will appreciate that method of administration/administering mode changes with required result. In some concrete enforcement, this activityCompound can with this compound of protection avoid the carrier that discharges fast together preparation example as empty release formulation, comprise that graft transmitsSystem, transdermal paste one or more in transmission system or micro-capsule transmission system etc. In addition, can also use biodegradable, biocompatible polymer, for example ethylene-ethyl acetate, polyanhydride, polyglycolic acid, collagen, polyorthoesters or PLADeng in one or more. Prepare the equal patent applied for of many methods of this preparation or generally known to those skilled in the art(for example SustainedandControlledReleaseDrugDeliverySystems, J.R.Robinson edits,MarcelDekker, Inc., New York, 1978).

In sesterterpenoids compound H ippolideI of the present invention or its pharmaceutical composition, can be containing capableThe known pharmaceutically acceptable carrier in territory and other optional member. Carrier comprises CMS, starch, cellulose, brightGlue, sodium acid carbonate, propane diols or Tween 80 etc. Optional member is for example colouring agent, sweetener, antioxidant etc.

Sesterterpenoids compound H ippolideI of the present invention and composition thereof, conventionally by oral, rectum orOne or more modes in parenteral etc., are applied to the patient who needs this treatment.

Sesterterpenoids compound H ippolideI of the present invention, its derivative or pharmaceutical salts, composition are particularlyPharmaceutical composition can be made any formulation that is suitable for applying clinically, comprises solid pharmaceutical preparation, as capsule, tablet,Grain preparation etc., semisolid preparation is as ointment etc., and liquid preparation is as oral liquid, supensoid agent, emulsion etc., or injection. Take mouthClothes or injection (comprise in intravenous injection, drip-feed, intramuscular injection or hypodermic injection etc. one or more), mucous membrane dialysis etc.In one or more methods of administration carry out antitumor, anti-diabetic and anti-obesity and directly related disease thereof prevention, examineDisconnected, detection, protection, treatment or scientific research.

When oral, can be made into conventional solid pharmaceutical preparation as a kind of in tablet, pulvis, granula or capsule etc. orMultiple. Implement time, sesterterpenoids compound H ippolideI of the present invention can with for example inert diluent or assimilableEdible carrier is together oral. This sesterterpenoids compound H ippolideI (with common its composition, if needed) can also be wrapped inHard or soft shell gelatin capsules, be pressed into tablet or directly add in curee's meals. About oral therapeutic administration, can be byDescribed sesterterpenoids compound H ippolideI adds and with edible tablet, buccal tablet agent, lozenge, glue together with excipientOne or more forms in capsule, suspension, syrup or wafer etc. are used.

For to give sesterterpenoids compound H ippolideI of the present invention outside parenterai administration, may need to useThe material that prevents its inactivation to this sesterterpenoids compound H ippolideI dressing or with this sesterterpene compoundsHippolideI together gives. Supplementary reactive compound can also be added in said composition. In the specific implementation, incite somebody to action thisInvention sesterterpenoids compound H ippolideI and one or more other medicines that can be used for the treatment of disease are joined altogetherMake and/or give altogether. Thisly combine use, can utilize primely this medicine giving compared with low dosage, therefore avoidPossible toxicity or the complication relevant to various monotherapies.

Make liquid preparation as one or more in aqua, oil-suspending agent or other liquid preparation, as syrup, tincture orOne or more in elixir etc.; During for parenteral, solution, aqua or the oiliness that can be made into injection suspendOne or more in agent etc.

Above medicine or pharmaceutical composition can use various approach, and in described type of service, preferred form isOral formulations (as one or more in tablet, coated tablet, capsule, solution or suspension etc.), non-enteron aisle give formulation (asOne or more in injection, ointment or patch etc.) etc. in one or more, further preferred tablet, capsule or injectionOne or more in agent etc., the particularly preferably one in tablet or injection.

In addition the medicinal raw material that, sesterterpenoids compound H ippolideI uses comprises sponge or sponge crude extractDeng also can be directly used in separately in some cases for the preparation of prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour,The product of anti-diabetic and anti-obesity and directly related disease thereof, also can mix or combine with many chemical substances,With the form of composition directly or indirectly for the preparation of for prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-sugarThe product of urine disease and anti-obesity and directly related disease thereof. Above described phase of chemical substance described here and this sectionWith.

For example, the medicinal raw material that sesterterpenoids compound H ippolideI uses comprises sponge or sponge crude extractDeng powder for the preparation of for antitumor, anti-diabetic and anti-obesity prevention, diagnosis, protection and particularly medicine for the treatment of productThe various formulations of thing, or the medicinal raw material that sesterterpenoids compound H ippolideI uses comprises sponge or spongeThe powder of crude extract etc. and relevant auxiliary material are for the preparation of for prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-The product of diabetes and anti-obesity and directly related disease thereof is the various formulations of medicine especially, or sesterterpenoidsThe powder that the medicinal raw material that compound HippolideI uses comprises sponge or sponge crude extract etc. with relevant for the preparation of in advanceThe product of anti-, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-diabetic and anti-obesity and directly related disease thereof asMedicine together for the preparation of for prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-diabetic and anti-obesity andThe product of its directly related disease is as the various formulations of medicine, or sesterterpenoids compound H ippolideI usesThe medicinal raw material powder that comprises sponge or sponge crude extract etc. and relevant ancillary drug together for the preparation of for prevention, examineThe product of disconnected, detection, protection, treatment and Effect of Anti tumour, anti-diabetic and anti-obesity and directly related disease thereof is as medicineVarious formulations, as one or more in tablet, capsule or supensoid agent etc., preferably capsule.

One of described method is that the medicinal raw material that sesterterpenoids compound H ippolideI is used comprises spongeOr the powder filling of sponge crude extract etc. is capsule, two of method is that sesterterpenoids compound H ippolideI is madeWith the medicinal raw material powder that comprises sponge or sponge crude extract etc. with relevant for the preparation of prevention, diagnosis, detect, protection,Treatment and the product of Effect of Anti tumour, anti-diabetic and anti-obesity and directly related disease thereof as filling together with medicine be glueWafer, three of method be medicinal raw material that sesterterpenoids compound H ippolideI is used comprise sponge or sponge thickThe powder of extract etc. is filling together with relevant ancillary drug is capsule; Four of method is by sesterterpene compoundsThe powder that the medicinal raw material that HippolideI uses comprises sponge or sponge crude extract etc. and relevant auxiliary material are together routinelyMethod is directly pressed as tablet, and five of method is that the medicinal raw material that sesterterpenoids compound H ippolideI is used comprisesThe powder of sponge or sponge crude extract etc., other relevant antitumor, anti-diabetic and anti-obesity and directly related diseases thereofParticularly medicine of product, directly press as tablet according to a conventional method with relevant auxiliary material together, six of method is by sesterterpeneThe medicinal raw material that compounds HippolideI uses comprises the powder of sponge or sponge crude extract etc., relevant adjuvantIt is tablet etc. that thing is directly pressed according to a conventional method with relevant auxiliary material together.

Except six kinds of above-mentioned basic skills, can also select sesterterpenoids compound H ippolideI to useMedicinal raw material comprises other forms of sponge or sponge crude extract etc. or sesterterpenoids compound H ippolideI is usedMedicinal raw material carry out after method processing well known in the art, for preparing various formulations contains sesterterpene compoundsThe product of the medicinal raw material that HippolideI uses is as medicine. But, it should be noted that two times of above-mentioned direct usesWhen the medicinal raw material that half terpenoid HippolideI uses comprises sponge or sponge crude extract etc., first basisThe dosage requirement of the sesterterpenoids compound H ippolideI using, converts and obtains the sesterterpenoids of required useThe medicinal raw material that compound H ippolideI uses comprises the consumption of sponge or sponge crude extract etc.

In sum, sesterterpenoids compound H ippolideI of the present invention and composition thereof can be used for prevention, diagnosis,The product of detection, protection, treatment and Effect of Anti tumour, anti-diabetic and anti-obesity and directly related disease thereof, preferred agentsAnd food, further preferred agents.

(7) technology speciality

The present invention provides for preventing, diagnose, detect, protect, treat and studying tumour, diabetes and the first-class disease of obesityA kind of new particularly medicine of product sesterterpenoids compound H ippolideI, thereby to existing antitumor, anti-glycosuriaSick and anti-obesity product has carried out improvement, has improved.

The present invention is safe and effective, and practicality is stronger, and its preparation technology is easy, inexpensive, and easily operation, convenient and swift, usesEasy, evident in efficacy, can be used for the diseases such as prevention, diagnosis, detection, protection, treatment and study of various tumour, diabetes and obesitySick treatment and supplemental treatment.

The present invention studies sponge targetedly, has found a kind of new sesterterpenoids compound H ippolideI, doesGone out beyond thought achievement, it uses safety, has brought into play to greatest extent effect; Product property is stable, is suitable for industrialization rawProduce; The result for the treatment of of prevention, diagnosis, detection, protection, treatment and study of various disease is obvious, and the scope of application is wide especially, thereforeEasily apply, can have a tremendous social and economic benefits in the short period of time.

In a word, active adaption of the present invention modern medical service and the need of work of scientific research field and the needs of human nature service,The present invention, for research and development radioresistance provides new preparation source, has important valency to improving existing medical levelValue.

The present invention has expanded new medical usage to sesterterpenoids compound H ippolideI, also for prevention, diagnosis,Detection, protection, treatment and Effect of Anti tumour, anti-diabetic and anti-obesity and directly related disease thereof provide a kind of new medicineThing source. Sesterterpenoids compound H ippolideI safety and low toxicity of the present invention, pharmacological action is stronger, and its raw material sources are richRich, inexpensive, preparation technology is simple, and yield is high, can be used for preparing prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-The product of diabetes and anti-obesity and directly related disease thereof.

The present invention studies sesterterpenoids compound H ippolideI targetedly, and its pharmacological action is stronger, its useSafety, one-object-many-purposes, has brought into play effect to greatest extent; Sesterterpenoids compound H ippolideI stable in properties, is used systemThe standby quality of the pharmaceutical preparations is stable, is more suitable for the suitability for industrialized production of antitumor, anti-diabetic and anti-obesity product; Prevention, diagnosis, inspectionThe successful of survey, protection, treatment and Effect of Anti tumour, anti-diabetic and anti-obesity and directly related disease thereof, and useScope is wide especially, therefore easily applies, and can have a tremendous social and economic benefits in the short period of time.

In a word, active adaption of the present invention modern medical service and the need of work of scientific research field and the needs of human nature service,The present invention provides new source for researching and developing new antitumor, anti-diabetic and anti-obesity product, in developingThe medicinal marine resources of state have important value, are for prevention, diagnosis, detection, protection, treatment and Effect of Anti tumour, anti-sugarThe safe raw material of the aspects such as urine disease and anti-obesity and directly related disease thereof.

Detailed description of the invention

The present invention has studied existing sesterterpenoids compound H ippolideI preparation, provides a kind of new two timesHalf terpenoid HippolideI, is convenient to the convenient of medical industry and safe handling.

Taking fine hair horse sponge as example, briefly set forth the preparation of sesterterpenoids compound H ippolideI of the present invention belowMethod.

(1) prepare sponge extract medicinal extract

1. prepare extract

Freezing sponge is chopped into fritter, and with 95% ethanol percolation extraction 6 times, each diacolation 3 days, merges extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains liposolubleProperty medicinal extract; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtains oilEther position medicinal extract; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extract obtainsCarrene position medicinal extract; By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract that to obtain;

2. carrene is extracted to medicinal extract through decompression column chromatography, with carrene: methyl alcohol=50: 1,25: 1,15: 1,5: 1,1: 1 be solvent gradient elution at 2: 1, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging.

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50: 1,20: 1,10: 1,5: 1,1: 1 be solvent gradient elution at 3: 1, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainTo compound H ippolideI.

Taking several typical formulations as example, elaborate the various formulations of sesterterpenoids compound H ippolideI belowConcrete preparation method.

The present invention prepares powder-injection and generally adopts conventional freeze-drying, using water as solvent, the steps include: to get two timesHalf terpenoid HippolideI, adds excipient, is dissolved in water, and adds active carbon, and filtration sterilization is filling, partly rolls plug,Freeze drying, lid is rolled in tamponade. Excipient used is selected from sweet mellow wine, gelatin hydrolysate, glucose, lactose or dextran etc.In one or more. Every bottle containing sesterterpenoids compound H ippolideI10～100mg.

By the sesterterpenoids compound H ippolideI water that obtains soluble in water sesterterpenoids compound H ippolideISolution, is dissolved in the tert-butyl alcohol obtaining phospholipid solution by phosphatide and Span80, then two solution is mixed to composition eutectic mixtures,Freeze drying, except desolventizing, obtains sesterterpenoids compound H ippolideI compound, by sesterterpene compoundsHippolideI fat complexes is dissolved in oil phase, if added with polyalcohol, is together dissolved in oil phase with phosphatide complexes, to obtain final productSesterterpenoids compound H ippolideI oil solution.

The present invention prepares powder-injection also can adopt spray drying process, using water as solvent, the steps include: to get sesterterpenoidsCompound H ippolideI, adds or does not add excipient (excipient is the same), is dissolved in water, and adds active carbon, filtration sterilization, sprayMist is dry, and aseptic subpackaged, lid is rolled in tamponade. Every bottle containing sesterterpenoids compound H ippolideI10～100mg.

When the present invention prepares small-volume injection, using water for injection as solvent, preparation, also can add appropriate amount of auxiliary materials, and auxiliary material is selected fromOne or more in ethanol, propane diols, glycerine, polyethylene glycol, Ergol or dimethylacetylamide etc. Every containing two timesHalf terpenoid HippolideI10～100mg.

The present invention prepares the transfusion of glucose infusion liquid or sodium chloride, using water for injection as solvent, add appropriate glucose orSodium chloride preparation, also can add appropriate amount of auxiliary materials, auxiliary material be selected from ethanol, propane diols, glycerine, polyethylene glycol, Ergol orOne or more in dimethylacetylamide etc. Every bottle containing sesterterpenoids compound H ippolideI10～100mg.

The present invention prepares the oral formulations such as tablet, capsule, granule, oral liquid, auxiliary material can be lactose, starch, dextrin,Stearate etc., technology preparation routinely.

The present invention is preferably prepared into sesterterpenoids compound H ippolideI and applies, and enumerates embodiment below and entersRow further illustrates.

In the present invention, the embodiment of above-described detailed description of the invention and the following stated is all in order to set forth betterThe present invention is not for limiting scope of invention. Below by embodiment, the present invention is described in detail.

Embodiment 1,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 1500mg phosphatide and be dissolved in 2mlIn the tert-butyl alcohol, mix and blend 30min, freeze drying, is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsCapmulMCM) in and get final product.

Embodiment 2,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsMigyol812) in and get final product.

Embodiment 3,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in the (choosing of 1ml medium-chain fatty glyceride by freeze dryingWith CapmulMCM) and the mixed solvent of propane diols in (5: 5) and get final product.

Embodiment 4,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsCapmulMCM) and in the mixed solvent of propane diols (7: 3) and get final product.

Embodiment 5,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsCapmulMCM) and in the mixed solvent of propane diols (9: 1) and get final product.

Embodiment 6,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsCapmulMCM) and in the mixed solvent of glycerine (5: 5) and get final product.

Embodiment 7,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsCapmulMCM) and in the mixed solvent of glycerine (7: 3) and get final product.

Embodiment 8,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsGTCC) in and get final product.

Embodiment 9,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in the (choosing of 1ml medium-chain fatty glyceride by freeze dryingWith GTCC) and the mixed solvent of propane diols in (5: 5) and get final product.

Embodiment 10,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsGTCC) and in the mixed solvent of propane diols (7: 3) and get final product.

Embodiment 11,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsGTCC) and in the mixed solvent of propane diols (9: 1) and get final product.

Embodiment 12,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsGTCC) and in the mixed solvent of glycerine (5: 5) and get final product.

Embodiment 13,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in 1ml medium-chain fatty glyceride and glycerine (choosing by freeze dryingWith GTCC) mixed solvent in (7: 3) and get final product.

Embodiment 14,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan85 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsCaptex300) in and get final product.

Embodiment 15,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan85 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsCaptex300) and in the mixed solvent of propane diols (5: 5) and get final product.

Embodiment 16,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and150mgSpan85 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in the (choosing of 1ml medium-chain fatty glyceride by freeze dryingWith Captex300) and the mixed solvent of propane diols in (7: 3) and get final product.

Embodiment 17,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan85 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsCaptex300) and in the mixed solvent of propane diols (9: 1) and get final product.

Embodiment 18,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan85 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsCaptex300) and in the mixed solvent of glycerine (5: 5) and get final product.

Embodiment 19,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan85 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml medium-chain fatty glyceride by freeze drying powder and (selectsCaptex300) and in the mixed solvent of glycerine (7: 3) and get final product.

Embodiment 20,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 1500mg phosphatide and be dissolved in 2mlIn the tert-butyl alcohol, mix and blend 30min, freeze drying, is dissolved in 1ml long-chain fat acid glyceride by freeze drying powder and (selects oilAcid glyceride) in and get final product.

Embodiment 21,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in the (choosing of 1ml long-chain fat acid glyceride by freeze dryingWith olive oil) in and get final product.

Embodiment 22,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in the (choosing of 1ml long-chain fat acid glyceride by freeze dryingWith olein) and the mixed solvent of propane diols in (5: 5) and get final product.

Embodiment 23,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in the (choosing of 1ml long-chain fat acid glyceride by freeze dryingWith olein) and the mixed solvent of propane diols in (7: 3) and get final product.

Embodiment 24,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml long-chain fat acid glyceride by freeze drying powder and (selects oleic acidGlyceride) and the mixed solvent of propane diols in (9: 1) and get final product.

Embodiment 25,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml long-chain fat acid glyceride by freeze drying powder and (selects oleic acidGlyceride) and the mixed solvent of glycerine in (5: 5) and get final product.

Embodiment 26,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan80 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml long-chain fat acid glyceride by freeze drying powder and (selects oleic acidGlyceride) and the mixed solvent of glycerine in (7: 3) and get final product.

Embodiment 27,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml long-chain fat acid glyceride by freeze drying powder and (selects bayAcid glyceride) in and get final product.

Embodiment 28,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml long-chain fat acid glyceride by freeze drying powder and (selects bayAcid glyceride) and the mixed solvent of propane diols in (5: 5) and get final product.

Embodiment 29,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mg

Span20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in 1ml long-chain fat acid glyceride by freeze dryingIn the mixed solvent of (selecting glyceryl laurate ester) and propane diols (7: 3) and get final product.

Embodiment 30,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in the (choosing of 1ml long-chain fat acid glyceride by freeze dryingWith glyceryl laurate ester) and the mixed solvent of propane diols in (9: 1) and get final product.

Embodiment 31,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml long-chain fat acid glyceride by freeze drying powder and (selects bayAcid glyceride) and the mixed solvent of glycerine in (5: 5) and get final product.

Embodiment 32,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml long-chain fat acid glyceride by freeze drying powder and (selects bayAcid glyceride) mixed solvent in (7: 3) and get final product.

Embodiment 33,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in the (choosing of 1ml long-chain fat acid glyceride by freeze dryingWith soybean oil) in and get final product.

Embodiment 34,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml long-chain fat acid glyceride by freeze drying powder and (selects soybeanOil) and the mixed solvent of propane diols in (5: 5) and get final product.

Embodiment 35,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and 150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying is dissolved in 1ml long-chain fat acid glyceride by freeze drying powder and (selects soybeanOil) and the mixed solvent of propane diols in (7: 3) and get final product.

Embodiment 36,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in the (choosing of 1ml long-chain fat acid glyceride by freeze dryingWith soybean oil) and the mixed solvent of propane diols in (9: 1) and get final product.

Embodiment 37,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in the (choosing of 1ml long-chain fat acid glyceride by freeze dryingWith soybean oil) and the mixed solvent of glycerine in (5: 5) and get final product.

Embodiment 38,

Take 100mg sesterterpenoids compound H ippolideI and be dissolved in 4ml water, take 300mg phosphatide and150mgSpan20 is dissolved in the 2ml tert-butyl alcohol, and freeze drying powder is dissolved in the (choosing of 1ml long-chain fat acid glyceride by freeze dryingWith soybean oil) in mixed solvent (7: 3) and get final product.

One of preparation method of embodiment 39, compound H ippolideI

(1) prepare fine hair horse sponge extract medicinal extract

1. prepare extract

By fine hair horse sponge (Hippospongialachne) 3.6kg (dry weight) in freezing marine site, South China Sea XishaBe chopped into fritter, with 95% ethanol 20L diacolation extraction 6 times, each diacolation 3 days, merges extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract 714g;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains liposolubleProperty medicinal extract 252g; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtainsPetroleum ether part medicinal extract 93g; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extractionLiquid obtains carrene position medicinal extract 124g. By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract that to obtain93g；

2. carrene is extracted to medicinal extract 93g through decompression column chromatography, with carrene: methyl alcohol=50: 1,25: 1,15: 1,5: be solvent gradient elution at 1,2: 1,1: 1, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging.

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50: 1,20: 1,10: 1,5: 1,1: 1 be solvent gradient elution at 3: 1, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainTo 7.1mg compound H ippolideI.

The preparation method's of embodiment 40, compound H ippolideI two

(1) prepare fresh water sponges extract medicinal extract

1. prepare extract

Freezing fresh water sponges (Spongilla) 3.6kg (dry weight) is chopped into fritter, carries with 95% ethanol 20L diacolationGet 6 times, each diacolation 3 days, merges extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract 733g;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains liposolubleProperty medicinal extract 267g; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtainsPetroleum ether part medicinal extract 105g; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extractionGet liquid and obtain carrene position medicinal extract 124g. By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract that to obtain79g；

2. carrene is extracted to medicinal extract 124g through decompression column chromatography, with carrene: methyl alcohol=50: 1,25: 1,15: 1,5: 1,1: 1 be solvent gradient elution at 2: 1, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging.

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50: 1,20: 1,10: 1,5: 1,1: 1 be solvent gradient elution at 3: 1, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainTo 6.4mg compound H ippolideI.

The preparation method's of embodiment 41, compound H ippolideI three

(1) prepare bath sponge extract medicinal extract

1. prepare extract

Freezing bath sponge (Euspongiaofficinalis) 3.6kg (dry weight) is chopped into fritter, uses 95% secondAlcohol 20L diacolation extracts 6 times, and each diacolation 3 days, merges extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract 757g;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains liposolubleProperty medicinal extract 276g; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtainsPetroleum ether part medicinal extract 113g; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extractionGet liquid and obtain carrene position medicinal extract 139g. By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract that to obtain98g；

2. carrene is extracted to medicinal extract 139g through decompression column chromatography, with carrene: methyl alcohol=50: 1,25: 1,15: 1,5: 1,1: 1 be solvent gradient elution at 2: 1, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging.

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50: 1,20: 1,10: 1,5: 1,1: 1 be solvent gradient elution at 3: 1, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainTo 7.6mg compound H ippolideI.

The preparation method's of embodiment 42, compound H ippolideI four

(1) prepare Leucosolenia extract medicinal extract

1. prepare extract

Freezing Leucosolenia (Leucosolenia) 3.6kg (dry weight) is chopped into fritter, with 95% ethanol 20L diacolationExtract 6 times, each diacolation 3 days, merges extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract 688g;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains liposolubleProperty medicinal extract 241g; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtainsPetroleum ether part medicinal extract 86g; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extractionLiquid obtains carrene position medicinal extract 110g. By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract that to obtain79g；

2. carrene is extracted to medicinal extract 110g through decompression column chromatography, with carrene: methyl alcohol=50: 1,25: 1,15: 1,5: 1,1: 1 be solvent gradient elution at 2: 1, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging.

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50: 1,20: 1,10: 1,5: 1,1: 1 be solvent gradient elution at 3: 1, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainTo 6.5mg compound H ippolideI.

Embodiment 43, accelerated test and long-term stable experiment research

The sesterterpenoids compound H ippolideI sample that utilizes the preferred embodiment of the invention to prepare, according to " changingLearn medicine stability investigative technique guideline " carry out accelerated test and long-term stable experiment research. Accelerated test and long-termStability test 12 months, measures the quality index such as its content, related substance, the results are shown in Table 4 and table 5 shown in.

Table 4, accelerated test result

Table 5, long-term test results

The preparation method's of embodiment 44, compound H ippolideI five

(1) prepare sycon (Grantia) extract medicinal extract

1. prepare extract

Freezing sycon (Grantia) 3.6kg (dry weight) is chopped into fritter, with 95% ethanol 20L diacolation extraction 6 times,Each diacolation 3 days, merges extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract 726g;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains liposolubleProperty medicinal extract 266g; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtainsPetroleum ether part medicinal extract 86g; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extractionLiquid obtains carrene position medicinal extract 112g. By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract that to obtain80g；

2. carrene is extracted to medicinal extract 112g through decompression column chromatography, with carrene: methyl alcohol=50: 1,25: 1,15: 1,5: 1,1: 1 be solvent gradient elution at 2: 1, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging.

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50: 1,20: 1,10: 1,5: 1,1: 1 be solvent gradient elution at 3: 1, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainTo 6.2mg compound H ippolideI.

Claims (25)

1. the black amber terpene of sesterterpene compounds I, is characterized in that, the described black amber terpene of sesterterpene compounds I molecular formulaFor C₂₄H₃₅NO₂, there is following chemical structural formula:

2. the preparation method of the black amber terpene of sesterterpene compounds according to claim 1 I, is characterized in that, describedThe preparation method of the black amber terpene of sesterterpene compounds I comprises the steps:

(1) prepare sponge extract medicinal extract

1. freezing sponge is chopped into fritter, with ethanol diacolation extraction routinely, obtains extract;

2. by extract reduced pressure concentration, obtain extract medicinal extract;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate, concentrated extract obtains fat-soluble medicinal extract;Fat-soluble medicinal extract is suspended in methanol solution, and with non-polar organic solvent extraction, concentrated extract obtains nonpolar organic moltenMedicinal extract is extracted in agent; Add water the methanol concentration of suspension is adjusted to 60%, with dichloromethane extraction, concentrated extract obtains dichloroMethane extracts medicinal extract; By initial water extracting n-butyl alcohol, concentrated that n-butanol extracts medicinal extract;

2. carrene is extracted to medicinal extract through decompression column chromatography, with carrene: methyl alcohol=100:1,50:1,30:1,20:1,10:1,5:1,1:1 is solvent gradient elution, according to TLC, colour developing merges similar stream part, obtains 9 component Fr.1～Fr.9;

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50:1,20:1,10:1,5:1,3:1,1:1 is solvent gradient elution, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtain twoThe black amber terpene of the noval chemical compound I of sesquiterpenoids;

Described sponge is sycon (Grantia), Leucosolenia (Leucosolenia), bath sponge (EuspongiaOfficinalis), the one in fine hair horse sponge (Hippospongialachne) or fresh water sponges (Spongilla) or manyKind.

3. the preparation method of the black amber terpene of sesterterpene compounds according to claim 2 I, is characterized in that, describedSponge is fine hair horse sponge (Hippospongialachne).

4. the preparation method of the black amber terpene of sesterterpene compounds according to claim 2 I, is characterized in that, describedMethanol solution is 60%～95% methanol solution.

5. the preparation method of the black amber terpene of sesterterpene compounds according to claim 4 I, is characterized in that, describedMethanol solution is 80%～95% methanol solution.

6. the preparation method of the black amber terpene of sesterterpene compounds according to claim 5 I, is characterized in that, describedMethanol solution is 90% methanol solution.

7. the preparation method of the black amber terpene of sesterterpene compounds according to claim 2 I, is characterized in that, describedNon-polar organic solvent is to comprise one or more in benzinum, ether or benzene.

8. the preparation method of the black amber terpene of sesterterpene compounds according to claim 7 I, is characterized in that, describedNon-polar organic solvent is to comprise one or more in benzinum or ether.

9. the preparation method of the black amber terpene of sesterterpene compounds according to claim 8 I, is characterized in that, describedNon-polar organic solvent is benzinum.

10. the preparation method of the black amber terpene of sesterterpene compounds according to claim 1 I, is characterized in that, describedThe preparation method of the black amber terpene of sesterterpene compounds I comprises the steps:

(1) prepare sponge extract medicinal extract

1. prepare extract

Freezing sponge is chopped into fritter, and with 95% ethanol percolation extraction 6 times, each diacolation 3 days, merges extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains fat-soluble soakingCream; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtains benzinum portionPosition medicinal extract; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extract obtains dichloroMethane position medicinal extract; By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract that to obtain;

2. carrene is extracted to medicinal extract through decompression column chromatography, with carrene: methyl alcohol=50:1,25:1,15:1,5:1,2:1,1:1 is solvent gradient elution, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging;

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50:1,20:1,10:1,5:1,3:1,1:1 is solvent gradient elution, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, changedThe black amber terpene of compound I.

The preparation method of the black amber terpene of 11. sesterterpene compounds according to claim 10 I, is characterized in that, described inThe preparation method of the black amber terpene of sesterterpene compounds I comprise the steps:

(1) prepare fine hair horse sponge extract medicinal extract

1. prepare extract

Fine hair horse sponge (Hippospongialachne) the dry weight 3.6kg in freezing marine site, South China Sea Xisha is chopped intoFritter, with 95% ethanol 20L diacolation extraction 6 times, each diacolation 3 days, merges extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract 714g;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains fat-soluble soakingCream 252g; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtains oilEther position medicinal extract 93g; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extract obtainsTo carrene position medicinal extract 124g; By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract 93g that to obtain;

2. carrene is extracted to medicinal extract 93g through decompression column chromatography, with carrene: methyl alcohol=50:1,25:1,15:1,5:1,2:1,1:1 is solvent gradient elution, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging;

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50:1,20:1,10:1,5:1,3:1,1:1 is solvent gradient elution, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainThe black amber terpene of 7.1mg compound I.

The preparation method of the black amber terpene of 12. sesterterpene compounds according to claim 10 I, is characterized in that, described inThe preparation method of the black amber terpene of sesterterpene compounds I comprise the steps:

(1) prepare fresh water sponges extract medicinal extract

1. prepare extract

Freezing fresh water sponges (Spongilla) dry weight 3.6kg is chopped into fritter, with 95% ethanol 20L diacolation extraction 6 times,Each diacolation 3 days, merges extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract 733g;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains fat-soluble soakingCream 267g; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtains oilEther position medicinal extract 105g; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extractObtain carrene position medicinal extract 124g; By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract 79g that to obtain;

2. carrene is extracted to medicinal extract 124g through decompression column chromatography, with carrene: methyl alcohol=50:1,25:1,15:1,5:1,2:1,1:1 is solvent gradient elution, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging;

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50:1,20:1,10:1,5:1,3:1,1:1 is solvent gradient elution, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainThe black amber terpene of 6.4mg compound I.

The preparation method of the black amber terpene of 13. sesterterpene compounds according to claim 10 I, is characterized in that, described inThe preparation method of the black amber terpene of sesterterpene compounds I comprise the steps:

(1) prepare bath sponge extract medicinal extract

1. prepare extract

Freezing bath sponge (Euspongiaofficinalis) dry weight 3.6kg is chopped into fritter, with 95% ethanol 20LDiacolation extracts 6 times, and each diacolation 3 days, merges extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract 757g;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains fat-soluble soakingCream 276g; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtains oilEther position medicinal extract 113g; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extractObtain carrene position medicinal extract 139g; By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract 98g that to obtain;

2. carrene is extracted to medicinal extract 139g through decompression column chromatography, with carrene: methyl alcohol=50:1,25:1,15:1,5:1,2:1,1:1 is solvent gradient elution, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging;

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50:1,20:1,10:1,5:1,3:1,1:1 is solvent gradient elution, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainThe black amber terpene of 7.6mg compound I.

The preparation method of the black amber terpene of 14. sesterterpene compounds according to claim 10 I, is characterized in that, described inThe preparation method of the black amber terpene of sesterterpene compounds I comprise the steps:

(1) prepare Leucosolenia extract medicinal extract

1. prepare extract

Freezing Leucosolenia (Leucosolenia) dry weight 3.6kg is chopped into fritter, with 95% ethanol 20L diacolation extraction 6Inferior, each diacolation 3 days, merges extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract 688g;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains fat-soluble soakingCream 241g; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtains oilEther position medicinal extract 86g; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extract obtainsTo carrene position medicinal extract 110g; By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract 79g that to obtain;

2. carrene is extracted to medicinal extract 110g through decompression column chromatography, with carrene: methyl alcohol=50:1,25:1,15:1,5:1,2:1,1:1 is solvent gradient elution, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging;

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50:1,20:1,10:1,5:1,3:1,1:1 is solvent gradient elution, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainThe black amber terpene of 6.5mg compound I.

The preparation method of the black amber terpene of 15. sesterterpene compounds according to claim 10 I, is characterized in that, described inThe preparation method of the black amber terpene of sesterterpene compounds I comprise the steps:

(1) prepare sycon (Grantia) extract medicinal extract

1. prepare extract

Freezing sycon (Grantia) dry weight 3.6kg is chopped into fritter, with 95% ethanol 20L diacolation extraction 6 times, oozes at every turnFilter 3 days, merge extract;

2. prepare extract medicinal extract

Reduced pressure concentration said extracted liquid, obtains extract medicinal extract 726g;

(2) separation and purification

1. said extracted thing medicinal extract suspendible is scattered in water, is extracted with ethyl acetate 4 times, concentrated extract obtains fat-soluble soakingCream 266g; Fat-soluble medicinal extract is suspended in 90% methanol solution, with petroleum ether extraction 3 times, concentrated extract obtains oilEther position medicinal extract 86g; Add water the methanol concentration of suspension is adjusted to 60%, use dichloromethane extraction 3 times, concentrated extract obtainsTo carrene position medicinal extract 112g; By extracting n-butyl alcohol 3 times of initial water, the concentrated n-butanol portion medicinal extract 80g that to obtain;

2. carrene is extracted to medicinal extract 112g through decompression column chromatography, with carrene: methyl alcohol=50:1,25:1,15:1,5:1,2:1,1:1 is solvent gradient elution, obtains 9 component Fr.1～Fr.9 according to the similar stream part of TLC colour developing merging;

3. to the component Fr.3 column chromatography that again reduces pressure, with benzinum: ethyl acetate=50:1,20:1,10:1,5:1,3:1,1:1 is solvent gradient elution, and according to TLC, colour developing merges similar flow point, obtains Fr.10～Fr.14 totally 5 components;

4. component Fr.11 is carried out to positive and negative phase silica gel column chromatography, gel column chromatography repeatedly, then purify with high efficiency liquid phase, obtainThe black amber terpene of 6.2mg compound I.

The black amber terpene of 16. sesterterpene compounds according to claim 10 I produces at the antitumor product of preparation, anti-diabeticApplication in product and anti-obesity product;

Described antitumor product refers to and is directly used in prevention, diagnosis, detection, protection, treatment and research tumour and direct phase thereofOne or more in the product of related disorders, comprise the one in anti-lung cancer product, anti-cervical cancer product or inhibitor against colon carcinoma cells productOr multiple; Described tumour is to comprise one or more in lung cancer, cervical carcinoma or colon cancer.

The application of the black amber terpene of 17. sesterterpene compounds according to claim 16 I, is characterized in that, described is anti-Lung cancer product refers to the product that is directly used in prevention, diagnosis, detection, protection, treatment and research lung cancer and directly related disease thereofIn one or more, described lung cancer refers to one or more in non-small cell lung cancer and ED-SCLC, described is non-ED-SCLC is to comprise one or more in phosphorus cancer, gland cancer or maxicell lung cancer.

The application of the black amber terpene of 18. sesterterpene compounds according to claim 16 I, is characterized in that, described is anti-Cervical carcinoma product refers to and is directly used in prevention, diagnosis, detection, protection, treatment and research cervical carcinoma and directly related disease thereofOne or more in product, described cervical carcinoma is under atypical hyperplasia, carcinoma in situ, mirror in early invasive carcinoma or infiltrating carcinomaOne or more.

The application of the black amber terpene of 19. sesterterpene compounds according to claim 16 I, is characterized in that, described is anti-Colon cancer product refers to and is directly used in prevention, diagnosis, detection, protection, treatment and research colon cancer and directly related disease thereofOne or more in product, described colon cancer refers to a kind of or many in proportion of cancer of left side of colon, Right-sided Colon Cancer or the carcinoma of the rectumKind.

The application of the black amber terpene of 20. sesterterpene compounds according to claim 16 I, is characterized in that, described is anti-Diabetes product refers to and is directly used in prevention, diagnosis, detection, protection, treatment and research diabetes and directly related disease thereofOne or more in product, described diabetes refer to type i diabetes, type ii diabetes, gestational diabetes mellitus or other are specialOne or more in the diabetes of type; The diabetes of other described specific types are to comprise that β cytogene defect causesDiabetes, the diabetes that insulin action gene defect causes, diabetes, the medicine reason that exocrine pancreas gland disease causesBring out the diabetes that cause or chemical reason and bring out one or more in the diabetes that cause.

The application of the black amber terpene of 21. sesterterpene compounds according to claim 16 I, is characterized in that, described is anti-Obesity product refers to and is directly used in prevention, diagnosis, detection, protection, treatment and research obesity and directly related disease thereofOne or more in product, described obesity refers to simple obesity, acquired obesity.

The application of the black amber terpene of 22. sesterterpene compounds according to claim 16 I, is characterized in that, described is anti-Tumour product, anti-diabetic product and anti-obesity product are the one comprising in medicine, reagent or food.

The application of the black amber terpene of 23. sesterterpene compounds according to claim 22 I, is characterized in that, described is anti-Tumour product, anti-diabetic product and anti-obesity product are medicines.

The application of the black amber terpene of 24. sesterterpene compounds according to claim 16 I, is characterized in that, described twoPurity >=95% of the black amber terpene of sesquiterpenoids I.

The application of the black amber terpene of 25. sesterterpene compounds according to claim 16 I, is characterized in that, described twoThe occupation mode of the black amber terpene of sesquiterpenoids I is to comprise independent use or combine one in use with other chemical substancesKind.