CN101791285B - Clausenamide composite nanometer emulsion for clearing facial age pigment (lipofuscin) and preparation method thereof - Google Patents

Abstract

The invention relates to the field of cosmetic preparations, and discloses a clausenamide composite nanometer emulsion for clearing facial age pigment (lipofuscin) and a preparation method thereof. The composite nanometer emulsion micro-particles are ovate and have small grain sizes and very uniform distribution, thereby having fast osmosis function on skin and being well absorbed by skin. In addition, the invention provides a nanometer emulsion compound external preparation for clearing the facial age pigment, which has high safety and convenient administration, and can be used without medical supervision. The preparation process of the clausenamide composite nanometer emulsion is concise, the technical operation is simple, and special instruments and equipment are not needed in the whole preparation process. The nanometer emulsion can spontaneously generate a nanometer emulsion system under the condition of normal temperature so that the energy source and the cost can be saved, the environment is not polluted, and the nanometer emulsion is suitable for scale production.

Description

A kind of clausenamide composite nano-emulsion that is used to remove facial senile plaque and preparation method thereof

Technical field

The present invention relates to a kind of novel external preparation that is used to remove facial senile plaque, be specifically related to a kind of clausenamide composite nano-emulsion preparation capable of permeating skin that is used to remove facial senile plaque and preparation method thereof.

Background technology

The preparation capable of permeating skin technical background

Preparation capable of permeating skin at present field of medicaments use more and more widely because preparation capable of permeating skin has the advantage that general dosage form does not possess.Preparation capable of permeating skin does not receive the influence of complicated factors such as pH value, food, medicine in the digestive tract, can avoid the first pass effect of functional component at liver, can control dosage, speed; Preparation capable of permeating skin gives at body surface in addition; Easy to use, and in case go wrong, interruption of the administration at any time.

But because the characteristics of skin barrier; Can strictly limit exogenous material; Comprise that protein, water, sugar, lipid, vitamin, inorganic ions or cosmetic industry any material that becomes to grade passes through, comprise that the senile plaque transdermal functional component of dispelling etc. all can't or be difficult to bring into play due biological action through complete keratodermatitis barrier.

In fact, in horny layer of epidermis, exist potential two passages: the one, between every 3-10 horn cell bundle, there is the crack (width＞0.1 μ m) of broad; The 2nd, the passage (average pore size 30nm) that the even narrow permeability that between each horn cell, exists is relatively poor.Therefore, make functional component can bring into play its effect and advantage, must make them can see through this road barrier of epidermis effectively; And to make these functional components see through epidermal barrier its biological agent of performance and advantage; Break through following approach only if adopt some effective ways: promptly reversibility ground changes flat Keratinocytic folded in order collection arrangement architecture in the keratodermatitis; Increase the epidermis cell gap, and make the complete fluidisation of its lipoids; The binding ability of nitrogen substance and water improves cuticular hydration in the enhancing skin surface keratin; Effectively sebum property noble cells on interior sebum of dissolving skin sebaceous gland duct or the lumen of gland wall reduces hydrophobicity in the sebaceous gland duct; Through expansion and soften cuticle, thereby make the opening of sweat gland, hair follicle become the big functional component Transdermal absorption that promotes; When promoting its transdermal, suppress velocity of blood flow, it is increased in local skin concentration.

In order to realize this goal; A large amount of research staff are not only carrying out deep discussion and well-designed aspect the prescription of external product and the technological process; And in the kind of solvent, the allotment of substrate, short functional component transdermal; A large amount of scientific researches have been carried out in aspects such as adjusting percutaneous mechanism of absorption, and attempt or developed the targeting vector and the movement system of a series of skin functional components.For example, in preparation capable of permeating skin, be added with the natural medicine that is beneficial to short skin functional component Transdermal absorption, as adding terpenoid: comprise monoterpene, sesquiterpene, triterpenoid compound; Quintessence oil: comprise Oleum menthae, Oleum Caryophylli, oil of rosemary, Oleum Rosae Rugosae, Jasmin oil, Essential lavender oil, Laurel wet goods; Alkaloid; Lactone; Other: is like menthol and Borneolum Syntheticum etc.Add the synthesising preparation that some help the functional component Transdermal absorption in addition, like organic acid and esters thereof: comprise fatty acid, fatty acid ester, amino-acid ester, lactams ester, cholinester etc.; Pyrrolidinone compounds; Phospholipid and phosphoric acid salt; Amide-type; Enzyme etc.Wherein pass by the most frequently used have dimethyl sulfoxide, sodium tetradecyl sulfate, laurocapram, lauric acid, cocoa butter, Oleum Terebinthinae, shark alkane etc., and laurocapram has become the object of reference of some new short transdermal agents.The possible mechanism of these short Transdermal absorption synthesising preparations is through the lipid of dissolving skin surface, makes epidermal protein qualitative change property, simultaneously; Through to modes such as functional component solubilising or hydrotropies; Increasing its permeability that passes the keratodermatitis barrier and their diffusion and distributions in each layer of epidermis, thereby reach the purpose that promotes the functional component Transdermal absorption.

Yet, although above-mentioned short skin penetrant is promoting to have brought into play certain function aspect the skin functional component Transdermal absorption, because the source of functional component is different in the transdermal mechanism; Its physicochemical property also has nothing in common with each other, and some is a water solublity, and some is fat-soluble; Some is pure dissolubility; Also some is that water oil is two molten or two insoluble, and therefore, the dissolubility and the stability that solve between above-mentioned short skin penetrant and the functional component are all very difficult; And; The molecular weight of some functional component is little; The molecular weight of some functional component is big, and molecular structure and form be obvious difference also, depends merely on the passive transdermal effect of above-mentioned short skin penetrant; Still be not enough to make functional component Transdermal absorption and the maximum biological action of performance smoothly, some functional component even still can't Transdermal absorption and its due biological action of performance.Particularly along with above-mentioned short skin penetrant great majority are chemosynthesis or semi-synthetic preparation; Increasing or use like working concentration are too frequent, and the cost of product is increased, and; The irritated rate and the zest of skin are strengthened, and toxic and side effects is more obvious; Some effect materials are to warm, to pH value, to illumination, responsive to oxidation reaction in addition; Therefore; Even above-mentioned short skin penetrant can promote the functional component Transdermal absorption; But because the unstability of functional component, in the implementation process of concrete formulated product, make these functional component inactivations again easily and can't bring into play its corresponding effect.

In order to overcome above-mentioned shortcoming and defect, there is the scholar to propose liposome (Liposome) technology is applied in cosmetics in recent years.Liposome is a kind of carrier of short functional component Transdermal absorption preferably; It is to seal the hollow spheres body that forms by bimolecular lamellar lipid membrane; Diameter is between 100-1000nm; Because of its constituent and structure and biomembrane and cell membrane fairly similar, be prone to make functional component to see through the keratodermatitis barrier and get into subcutaneous.Though liposome truly has as the functional component carrier system and is beneficial to its biological effect of performance, and externally applied product preparation aspect performance application promise in clinical practice; But it is as carrier formulation, remains to still have to be overcome and solution in some problems: liposome is in the preparation process, and is with an organic solvent too much; Particularly organic solvents such as chloroform (chloroform), methanol use too much; Not only cause cost to raise, and very big to preparation person's health effect, cause serious environmental pollution etc. simultaneously; The preparation of liposome is main with phospholipid (soybean phospholipid and lecithin) and cholesterol; Phospholipid (soybean phospholipid and lecithin) costs an arm and a leg, and not only increases product cost greatly, makes the product cost price higher; And; Its dissolving in the preparation process is difficulty very, time-consuming, bothersome, effort, and very trouble operates also; Although functional component is good by liposome, the surface has been completed into a kind of lipoids structure, therefore, when preparation water solublity functional component, but be difficult to mix, and, also there is certain problem with the intermiscibility of other preparation; In addition, when practical application, the long-term stability of liposome is preserved certain difficulty, and after placing a period of time, and by the transdermal functional component of liposome seepage and overflowing automatically still, less stable loses the parcel meaning; The preparation of functional component liposome is influenced by several factors and disturbs, and the operating technology of liposome still can not make liposome very high to the envelop rate of functional component especially at present, and in fact the envelop rate of the functional component liposome of preparation is lower; Because of the physicochemical property of liposome itself adds the problem of technological operation itself, comparatively speaking, the particle diameter of liposome is still bigger, and skewness, and this has also influenced the performance of its effect; Liposome still belongs to passive carrier, and its targeting is still limited, and therefore, action effect also receives certain influence.

A kind of new carrier formulation-nano-emulsion (nanoemulsion) has been born again in the recent period.Nano-emulsion is begun one's study from the forties in 20th century by Schulman, just has medicinal nano breast to come out up to late 1990s, and nano-emulsion is just really used also thing in recent years in pharmaceutical formulation.Nano-emulsion is celebrated with atomic grain, and the emulsion droplet particle diameter that it is made up of oil phase, water, emulsifying agent and co-emulsifier is about the transparent or semitransparent liquid between the 10-100nm, and its emulsion droplet is dispersed in the another kind of liquid and forms dispersion system of colloid; Has certain opalescence; Its emulsion droplet is spherical mostly, and size is more even, good fluidity; Can not make it layering through heating or autoclaving or centrifugalize yet, belong to the thermodynamically metastable fixed system usually.Two fundamental differences of nano-emulsion and common emulsion are: at first, the formation of ordinary emulsion generally needs the external world that energy is provided, and the formation of nano-emulsion is spontaneous; Secondly, ordinary emulsion is a thermodynamic unstable system, in depositing process will coalescence take place and finally be divided into oil, water is biphase.And nano-emulsion is a thermodynamic stable system, coalescence can not take place.

Nano-emulsion shows tempting prospect as the carrier of preparation capable of permeating skin, and main cause is: 1. compare with submicron emulsion, nano-emulsion more helps bioactive substance and functional component uniform distribution; 2. compare with microemulsion, nano-emulsion only needs the surfactant of conventional amount used; 3. other is compared with liposome etc., and nano-emulsion is more stable, and preparation more is prone to industrialization or industrialization.4. blank nano-emulsion outward appearance is light blue opalescence, and molecular weight is little, is easy to absorb, and uses comfortable etc.

The senile plaque notion

Senile plaque (Senile Speckle; Be called for short SS) or (senile plaques; Be called for short SP) be aging the most outstanding, typical case, one of characteristic the most intuitively the most of application on human skin, be the lipofuscin that produced by aging constantly is deposited in Skin Cell, the sweat gland cells and is formed at skin surface gradually, occur at most with old people's skin surface especially; Occurrence rate on the human body skin surface accounts for old people's about 30% greatly, and the person can reach hundred places at most.Senile plaque is the common optimum epidermis verrucous hyperplasia of middle-aged and elderly people, is verruca senilis again; Motherland's medical science is referred to as it " senile plagues " or " senile plaques "; Biologically, be " seborrheic keratosis " or " basal cell papilloma " on the clinical medicine with its called after " lipofuscin " or " lipofuscin ".Have the scholar will be deposited on old and feeble skin surface high-visible, develop the brown plaque form by " lipofuscin " or " lipofuscin ", abbreviate the skin senile plaque as.Specifically; The skin senile plaque is that a kind of a kind of quantity that is grown in old and feeble human body face, the back of the hand, arm even body surface does not wait, size is uneven, brownish black or sepia or the flat speckle of pitchy or the speckle of likeness in form oval, Semen Glycines size; Being main with scalp and facial temporo, cheekbone wherein, secondly is that the back of the hand, cervical region, chest, back and extremity etc. are located to see more.Senile plaque is from the beginning of being pore syringe needle size on every side, and it is faint yellow, filbert that outward appearance is, and is clear-cut flat maculopapule; And enlarged is 2 centimetres or bigger circle, oval patch gradually, and the quality of touching is soft, rough surface; Often be coated with one deck greasy scales; Be prone to divest, but can regenerate, the speckle of dark brown or black is deepened, is to later color gradually.Senile plaque does not generally influence healthyly except influencing appearance, and malignant change also seldom takes place the skin verrucous hyperplasia.

The Pathophysiology characteristics and the clinical meaning of senile plaque

(1) the pathophysiology characteristics of senile plaque: along with the age that increases of human body; Body is day by day old and feeble; Lipofuscin is accelerated to produce, content also increases gradually; Particularly owing to old people's histiocyte functional deterioration, to decomposition and the decreased excretory function even the disappearance of lipofuscin, the result makes its bulk deposition in the skin basal layer.Lipofuscin can make the pigment of epidermis increase, and stimulates epidermis to produce the change of verrucous hyperplasia sexually transmitted disease (STD), has formed senile plaque.Senile plaque mainly is made up of three types cell: basal cell, spine cell and melanocyte.

(2) clinical meaning of senile plaque: senile plaque not only only appears at old people's skin surface, also can extensively be present in some organ and tissue, in cells of tissues such as brain, spinal cord, neuroganglion, heart, blood vessel and gonad.After lipofuscin in the cell runs up to a certain degree, can occupy the locus of cell, change the space structure of cell, make cellular atrophy, metabolism disorder etc.When it is deposited on people's body surface, just produce the skin senile plaque; When it is deposited on the blood vessel wall, will make blood vessel wall generation fibrous lesions, cause cardiovascular diseases such as arteriosclerosis, hypertension, myocardial infarction; When it accumulates on the brain cell in a large number, will cause old people nervous organ functional disorder, cause hypomnesis, dysnoesia, depression or dementia etc. appear.Therefore, the skin senile plaque forms the clinical meaning that also has particular importance.We can say, when senile plaque occurring on the skin, deposited a large amount of lipofuscins in fact in its neurocyte and the cardiovascular cell, prompting can take place in the body or occur and the relevant various diseases of lipofuscin damage.

The cause of disease of senile plaque and mechanism

(1) formation of old and feeble (senescence) and skin senile plaque: human ageing process is greatly about beginning in 25 years old; Age pigment can build up in human body cell later on; More intracellular submicroscopic structures have been tied up; Thereby upset the locus of cell, influenced the normal function of cell.When biomembrane (cell membrane, mitochondrial membrane, microsomal membrane, lysosome membrane etc.) impaired (impaired like mitochondrial membrane, cell descends to the utilization rate of oxygen, and reducing substances increases), harmful substance generates and increases in the body.Cause age pigment generation and deposition to increase, can cause slowly death by suffocation of cell in the course of time.Lipofuscin forms the relation of mechanism and cell ageing and the biochemical process of lipofuscin formation has certain scientific basis.It has been generally acknowledged that the skin senile plaque is old and feeble tendency and performance of inside of human body histoorgan.With advancing age, spent 45 years old or 50 years old after, the physiological function of each histoorgan of whole body promptly begins to take place gradually degeneration; Metabolic processes, blood circulation speed slows down, and removes the harmful substance ability and weakens; Old people's food-intake reduces or reasons such as partial eclipse in addition; Just form a kind of old and feeble material--lipofuscin that promotes in the blood gradually, this insoluble brown lipofuscin granule constantly is deposited on skin surface and can forms the skin senile plaque.

(2) formation of gene genetic factors such as (genes genetic) and skin senile plaque: from the Alzheimer disease is claimed the up-to-date research of senile dementia disease (AD) incidence inheritance factor again, find; (Presenilin, PS) gene mutation is relevant with the formation of senile plaque for presenilin.Found that therewith sick relevant genetic locus has the p amyloid precursor protein Gene A PP on the chromosome No. 21, PSI gene on the ApoE4 allele on No. 19 chromosomes, No. 14 chromosomes and the PS2 gene on the I chromosome etc.Common trait after these PS gene mutation is the secretion that has increased brain inner cell A β (1-42), quickens the deposition of A β at senile plaque, and A β (1-42) is the main protein composition of senile plaque.Show that on evidence PS1 can directly influence the zymolysis of the not clear gamma secretase in source, this zymolysis can make APP albumen discharge a composition.

(3) free radical (FreeRadical, the formation of chemical factor and skin senile plaque such as FR): biology relevant lipofuscin the existing certain experiment confirm of formation, promptly mitochondrion and lysosome are two important sources of lipofuscin formation.Because mitochondrial DNA exposes, and lacks the protection of histone,, can make DNA take place crosslinked or the fracture inactivation, and become lipofuscin class deposit through the powerful cross-linking agent malonaldehyde that lipid peroxidation generates.Free radical is many to be produced in mitochondrion, can with generation lipid peroxidation such as the phospholipid of cell and protein, damaged tissue cell; Form lipid peroxide and catabolite malonaldehyde (MDA) thereof; Produce macromolecules cross-linking with the amino radical reaction of proteinic one-level, form fluorescence-causing substance schiff bases (lipofuscin fluorescent material), and the difficult amino with protein, peptide class or lipid of the dialdehyde base of malonaldehyde forms Schiff alkali; Make between the film adipose membrane albumen or be cross-linked with each other between itself; Become water-fast macromolecule polyalcohol, after lysosome is engulfed, be not hydrolyzed mould type of digestion and progressively accumulate the formation lipofuscin than original big several times even tens times.Medically also to tend to the generation of lipofuscin be relevant with free radical to Most scholars.With advancing age; The free radical that metabolic process produced in the human body cell increases gradually; When body is removed the function reduction of free radical; Effect rapidly and strong damage will take place with body in the active free radical of these chemical property, and wherein oxygen-derived free radicals the relation maximum occurs to biomembranous attack of lipid and senile plaque.It can make unsaturated fatty acid be oxidized to peroxide, and this peroxide can further decompose, and produces a large amount of aldehydes, alcohols and hydro carbons.Wherein malonaldehyde (MDA) has very strong bio-toxicity, very easily reacts with phospholipoprotein matter etc., and forming age pigment is lipofuscin.

(4) formation of physical factor such as ultraviolet (ultraviolet radiation) irradiation and skin senile plaque: long-term, a large amount of, ultraviolet radiation can make epidermis cell produce singlet oxygen (1Q) and superoxide radical, hydroxy radical isoreactivity oxygen continuously; They can not only make the 8-hydroxyl bird glycoside (8-OhdG) of DNA impaired and cause hereditary variation; And; They can produce or accelerate the epidermis lipid peroxidation, form lipofuscin or senile plaque.Except that sun exposure, air pollutant, radiation, ozone or the like all can be facilitated the formation of free radical, and make skin accelerate to form senile plaque.Theoretically, along with increasing of height above sea level, partial pressure of oxygen reduces gradually; Compare low 7.89kpa with the sea level, and the ultraviolet in the solar radiation is along with the every rising 100m of height above sea level, place, strength ratio sea level increases by 3～4%; Because anoxia can cause the skin microcirculation obstacle, end blood Oxygen cycle slightly changes.Sunshine-duration is long, and solar radiation is strong, and arid is short of rain; Air drying, wind day is long, and strong wind is many; These climatic characteristics can make the moisture of skin evaporation, make it be in the mild dehydration state, have also aggravated the generation of senile plaque and skin aging; But with advancing age, the natural aging of skin also is a factor.Senile plaque, skin aging are a kind of common skin diseases of high altitude localities, and men and women, old and young all can be ill, but the male sees more, have research worker to study living in height above sea level 2260m area 1000 application on human skin senile plaques, skin aging a situation arises.The result shows, the highest age bracket of male's skin senile plaque incidence rate is 50～59 years old, 60～69 years old, and incidence rate is respectively 63%, 79%; The highest age bracket of the aged incidence rate of female skin is 50～59 years old; Incidence rate is 38%, senile plaque then be 40～49 years old, incidence rate is 44%.

The prevention of skin senile plaque

Senile plaque can prevent and delay to take place.Prevention to the skin senile plaque.Its basic measures are exactly slow down aging.And the influence factor of slow down aging is numerous, and the item that should be noted that is also a lot, and wherein, important comprises: (1) logical diet: at first be to make the food variation, the meat and vegetables thickness will be arranged in pairs or groups as far as possible; Next is to make eating patterns reasonable, and it is sufficient that vegetable is wanted, and fruit is indispensable, and wherein Fructus Benincasae, Semen Sesami Nigrum, Semen Nelumbinis, Semen Juglandis etc. all are anti-aging beauty-care food preferably.Oil will be limited the quantity of, and sweet food will be eaten less, drinks and will control; (2) adhere to good living habit: keep good hours, go to bed early and get up early.And guarantee the sleep of 7--8 hour every day; Simultaneously, firmly overcome bad habit (smoking and excessive drinking) etc. and be unfavorable for healthy custom; (3) appropriate exercise is taken exercises: motion can increase man's lifespan, and the hormone secretion in the hormonal system is increased, and can promote that the body each several part is harmonious, reduces disease.The skin motion and the motion of preserving moisture can make skin pore enlarge, and sweat gland is active, promotes the blood circulation in the skin histology effectively, accelerate body intracellular metabolite waste discharge.In addition, strengthen skin movements and can strengthen the moistening of skin.Motion washes one's face with warm water after finishing immediately, removes through the excretory refuse of skin, and avoids the salinity in the sweat stain to be trapped in chafe on the face after for a long time; (4) mental status and the psychology prevention of keeping fit: keeping young phychology, healthy psychology, happy spirit etc. also is the good method of slow down aging; (5) adopt suitable skin nursing: after giving the skin exfoliation, be stained with the moisturizing essence or the moisturizing that contain the macromole or the micromolecular Natural antioxidant with gauze and grow face dew, apply at face quiet lying several minutes.Be 2--3 time weekly, can not only prevent the skin senile plaque, can also replenish physiological water to skin, also of great advantage to skin nursing; (6) note sun-proof: sun-proofly not only can alleviate the coup injury of ultraviolet, and can control free radical and generate and increase,, prevent or delay the generation and the development of chloasma and senile plaque for reducing melanin and lipofuscin formation to skin; (7) often massage is facial: the massage face can promote facial blood circulation, improves the metabolism ability of skin.Delay skin aging, prevention or delaying skin senile plaque form. (8) keep clean and tidy pure and fresh environment: warm comfortable room makes people's mood happy, and the room keeps suitably ventilating, and has sufficient sunlight and fresh air, enjoys the vital principle that the Nature is granted; (9) self health care: under physician guidance, can suitably take some antioxidants, like vitamin C, vitamin E, beta-carotene etc.

The treatment of skin senile plaque

Though senile plaque can prevent or delay, as the facial senile plaque that has occurred, and area is bigger; In particular for preventing that senile plaque from cancerating, when promptly pathological changes begins irregular pigmented spots, then gradually to enlarging all around; Diameter number centimetre, the edge is irregular, while and occur expanding disappearing; Skin color after disappearing shoals, and is in exposure portion again, particularly facial person; Irregular lump appears in diseased region, develops into tuberosity afterwards, and the surface person of festering all should in time arrive examination in hospital, diagnosis and treatment, does not incur loss through delay.

(1) way of dining treatment: senile plaque forms and adds that weight average damages with the body free-radical oxidation or the oxidation resistance deficiency is relevant.And contain abundant antioxidant and free radical scavenger in vegetable and the fruit; They all can remove free radical, and the oxidation or the peroxidating process of blocking-up free radical suppress the formation and the accumulation of free radical and metabolite thereof; Blood circulation promoting and metabolism; Regulate hormone secretion, strengthen the Skin Cell vigor, control skin lipofuscin forms with old.Free radical scavenger in vegetable and the fruit mainly contains carotene, plain, the chemical compound of rope C, E and flavone compound and phenol hydroxyl class formation etc. of supporting one's family of sarranine.Therefore, can from some foods, obtain enough free radical scavengers, to remove owing to crossing lipofuscin and the senile plaque that the polyradical effect forms through diet.The free radical scavenger that comprises in the orange plants such as Radix Dauci Sativae, Fructus Cucurbitae moschatae, peach, Fructus Pruni, Fructus Citri tangerinae mainly is β-Radix Dauci Sativae rope.Beta-carotene can interrupt the lipid peroxidation chain reaction with lipid peroxidation attitude combined with radical, also can stop simultaneously absorb that oxygen receives illumination and the Oxidation that becomes excited oxygen.Beta-carotene and radical reaction produce epoxies carotene, and then split into stable aldehydes and ketone; The free radical scavenger that comprises in the yellow plants such as grapefruit, Fructus Citri Limoniae, Semen Fagopyri Esculenti mainly is a flavone compound.Flavone compound can be used as chain rupture antioxidant blocking-up free chain reaction.Also can chelating some as the heavy metal of prooxidant or suppress the activity of lipid oxidation enzyme.The free radical scavenger that comprises in the green plantss such as Herba Spinaciae, Folium Allii tuberosi, Brassica oleracea var. acephala dish, water spinach, LVHUA Broccoli, cabbage mustard dish, Fructus Hippophae, Fructus actinidiae chinensis mainly is support one's family rope C and vitamin E.Vitamin C can react with peroxide and the hydroxy radical in the cell, and the oxidation chain reaction is ended and then the protection cell integrity.In addition, vitamin C also can be given the vitamin E free radical with hydrogen atom, and to recover and to protect the function of vitamin E, the effect of free radical is removed in performance indirectly.Vitamin E is strong effectively free radical scavenger, and it can suppress the peroxidation of lipid effectively.Vitamin E also can prevent the generation of Oxidation of Fat and Oils and blocking nitrosamine formation.The antioxidant that comprises in the red plants such as Fructus Lycopersici esculenti (being the abundantest food of content of lycopene), grapefruit (red meat), Citrullus vulgaris mainly is a lycopene.Lycopene is effective biological anti-oxidant.Its cancellation singlet oxygen is very capable with removing peroxy free radical.The free radical scavenger that comprises in the plants such as Bulbus Allii, cabbage, Bulbus Allii Cepae, Folium Allii tuberosi and Herba Alii fistulosi mainly is an acrylic sulfide.All these not only can protect body to avoid ultraviolet infringement, can also stop the deposition of lipofuscin and the formation of senile plaque.Contain gingerol in the Rhizoma Zingiberis Recens, very strong free radical scavenging effect is arranged; Report is arranged, and some people drank the Rhizoma Zingiberis Recens hydromel 1 year, and senile plaque facial and the back of the hand obviously alleviates or disappears.Also have report, eat that the Fructus Solani melongenae senile plaque reduces and can be thin out more; Simultaneously.Someone makes speckle removing diet therapy soup (Retinervus Luffae Fructus, Bombyx Batryticatus, Poria, Flos Chrysanthemi, Fructus Jujubae, Flos Rosae Rugosae add the water Baoshang) by oneself and five elements' vegetable soup (Fructus Vins, Radix seu Herba Tetrastigmatis Hypoglauci, Lentinus Edodes, white turnip, Fructus Arctii Baoshang) treatment senile plaque is also achieved tangible results.

(2) physical method treatment: (1) is fulgerized to rule by law and is treated senile plaque: utilize acusector moment heat production, make senile plaque solidify degeneration, gasification, carbonization, disappearance.The degree of depth of fulgerizing is at epidermis and high dermis intersection.Postoperative is coated with skim antimicrobial ointment protection wound surface, exposes naturally.Can there be slight redness the part, 2～4d .7～14d decrustation of forming a scab, and pinkiness after the decrustation, beginning after 1 month has pigmentation, can return to the normal colour of skin after 6～12 months, no cicatrization.The great advantage of the method for fulgerizing be easy to operate, the focus of fulgerizing accurately but regulated at will voltage, consumptive material are few, be applicable to the various skin treatment of diseases, little as long as operation appropriately also has a damage, recover fast, no cicatrix does not influence the advantage of work; (2) laser method treatment senile plaque: laser significantly reduces the hot injury of laser heat energy to biological tissue through selective light heat damage principle, can be under the situation that does not influence the normal structure structure, and autotelic destruction pathological tissues, thus avoid postoperative scar to form.Adopting the laser therapy senile plaque is a kind of effective, safe, feasible, painful little, no cicatrix in treatment back, post-operative complication method few, simple to operate.Certainly; The curative effect height of this method treatment senile plaque except that with the course of disease length of senile plaque, weight, the depth etc., also relevant with treatment number of times, wavelength, pulsewidth, energy density, spot size and hot spot coverage density, treatment length blanking time, skin type, overall health of patients, environment (ultraviolet), medicine and food factors such as (photosensitive); (3) other: can adopt methods such as ultrahigh-frequency current effect, freezing, cutting, skin grinding.Particularly produce the hyperpyrexia gasification through the ultrahigh-frequency current effect, directly strip off the shallow tissue of skin senile plaque table, it is comparatively meticulous thoroughly to dispel senile plaque; The damage normal structure is few, and the normal structure regenerative healing is fast, and pigmentation is light; Time is short, recovery is fast, simultaneously, merges the preparations that use some to promote planing surface to heal and reduce other pigment regeneration; And avoid sun exposure, therapeutic effect will be more remarkable.The somebody uses three scorching hot treatment senile plaque 437 examples of fiery pin, cures 426 examples 1 time as a result, 2 healing 11 examples, all effectively. and non-evident effect.

(3) chemical method treatment: mainly be chemical peeling.Chemical peeling is in the academic meeting of the plastic surgery of U.S. New Orleans, to put forward in 1962.It adopts chemical cracking-off agent that skin surface is destroyed, forms a scab, and makes it to come off, to reach therapeutic purposes.With chemical cracking-off agent the skin senile plaque being carried out beauty therapeutic also is a kind of method commonly used in the medical cosmetology.Before the treatment, according to the senile plaque of the different courses of disease, size and the depth and area, the kind of chemical cracking-off agent is selected in decision for use earlier.Diameter is selected 33% trichloroacetic acid solution for use less than the senile plaque of 3ram, and diameter is then selected painless phenol (prescription: carbolic acid 500g, dyclonine 10g, Camphora 1g, anhydrous smart 50ml, the glycerol 50ml of spilling) treatment for use greater than the senile plaque of 3mm.General treatment was formed a scab after 3 days, left and right sides decrustation in 14 days, and wound surface is pale pink after the decrustation, and smooth surface does not have cicatrization, the back further consultation of 2 weeks.Indivedual residual pigmented spots can be gone secondary treatment after 1 month, the dark person of skin lesion can treat 3--4 time repeatedly and disappear to skin lesion.Chemistry should strictly observe doctor's advice after stripping off the treatment senile plaque: 1. keep incrustation dry, 2 all backs come off naturally; 2. note sun-proof after the decrustation; 3. the pungent irritable food of fasting; 4. postoperative orally-ingestible VITAMIN C TABLET is to alleviate other chromogenesis.In addition, according to state's Extra Pharmacopoeia Martindale Synthetic 2,7-diformazan folder thioxanthene, and be that functional component is mixed with QUBAN SHUANG (contain 2, it is that 15% pair of age pigment dermatoses or senile plaque have certain effect that 7-diformazan folder thia is feared concentration with this chemical synthetic drug.

(4) biotechnology treatment: (1) SOD preparation and SOD-CCE system: superoxide dismutase (SOD) and SOD compound enzyme (SOD-CCE).Comprise SOD, peroxidating hydrogen enzyme (CAT), glutathion peroxidase compound systems such as (GSH-PX).Its mechanism of action to the skin senile plaque is: caused the interior free yl scavenging system to generate reducing when human senescence or skin aging produce polyradical or aging, free radical scavenging is ineffective and when causing free radical to increase; SOD is the catalysis ultra-oxygen anion free radical at first, makes it to change into H ₂O ₂And O ₂, and then by CAT catalysis H ₂O ₂Generate nontoxic color H ₂O water and O ₂, and the synergy of GSH-PX and SOD, CAT, thus peroxide injury such as radical pair albumen, nucleic acid, phospholipid and other unsaturated fatty acid eliminated and the lipofuscin or the senile plaque that form.That uses at present at most, uses most convenient still is mixed with external preparation and cosmetics with SOD and SOD-CCE.As prepare essence (the active 200U brush of SOD) or preparation cream (frost) agent (the active 100-200U/g of SOD), after skin senile plaque place firmly removed horny layer of epidermis, direct again, repeated multiple times was smeared every day 2～3 times.Got final product in continuous about 1～3 month.Certainly, also can use neozoic SOD derivant (like PEG-SOD, L-SOD, Ac-SOD, Ms-SOD, rh-SOD, Ge-SOD, Se-SOD etc.) and quasi-SOD active substance, can bring into play better action effect; (2) metallothionein (MT): be one type and be rich in cysteine residues and the very strong non-pheron of bivalent metal ion binding ability, to free radical particularly hydroxy radical scavenging action is preferably arranged, can also protect cell membrane to avoid the damage of free radical.At present, domestic existing people has succeeded in developing the MT cosmetics, like MT day cream and NT late frost and MT anti-aging beauty-care frost etc., nursing skin, delay skin aging and prevention skin senile plaque etc. is all had positive role; Have the scholar prolonging the MT half-life, eliminate macromole or researchs such as heterogenetic antigen allergy, transdermal, permeable membrane absorption and the interior effect of cell, some has obtained positive progress; (3) activates relay albumen: protected protein (PRP) is a kind of novel antioxidation albumen that Kim etc. at first extracted from beer yeast in 1988.PRP does not have SOD, and traditional Peroxidase activity such as GSH-Px also has no homology on DNA and aminoacid sequence.But its ability specificity prevents to be served as by sulfhydryl compound such as dithiothreitol, DTT (DTT), beta-mercaptoethanol etc. the multiple oxidative damage of mixed-function oxidation system (MFO) mediation of electron donor; Prevent the inactivation and the DNA of plurality of enzymes; The fracture of calf thymus DNA; At present they are classified as one type of novel antioxidation protein family, are referred to as also albumen (PRx) of peroxidating oxygen.Discover both at home and abroad, PRP external have remove hydroxyl radical free radical and H ₂O ₂Effect, scholar separation and purification PRP from the HRBC is arranged, and to lipofuscin or senile plaque effect.The result shows that protected protein is a kind of novel antioxidation albumen, wild type and recombinant type many through Cys-47 with Cys-170 formation disulfide bond and exist with dimeric forms.Its antioxidant activity of experiment proof relies on sulfydryl, and PRP destroys disulfide bond external through DTT Ah, exposes its reproducibility sulfydryl and has the hydroxyl radical free radical of removing and H ₂O ₂Effect.There is experimental result to show that PRP can prevent the active decline of SOD, lipid peroxidation and lipofuscin or senile plaque deposition.

(5) western medicine and medical practitioners treatment: see with meclofenoxane (Meclophcnoxate), beta-endorphin, chlorpromazine, taurine, estrogen, glutathion (GSH), cysteine, selenium and selenides, phosphatidylcholine, Magnesium Orotate, taurine, vitamin C, vitamin E, kawain, capsaicin etc. more.Also have the scholar to report, took Squalene or polyene unsaturated fatty acid (DHA and EPA) two months, senile plaque is disappeared gradually, hear when adhering to taking one section again, can make in the health with skin on sedimentary lipofuscin be eliminated.Experiment showed, vitamin E can with oxygen-derived free radicals active group direct reaction, and it can also form complex with polyunsaturated acid on the cell membrane, prevents that it from peroxidization taking place, and the formation of lipofuscin is had certain inhibitory action; In addition, vitamin C and capsaicin also can reduce the deposition of lipofuscin in soma.In addition; Amyloid beta is proved to be the main component of senile plaque; And amyloid beta be by β-with its precursor protein of gamma-secretase cracking (APP) and forming, therefore, the activity that suppresses beta-secretase can reduce the formation of amyloid-beta; At present the Okalahoma biomedical research foundation has found that under study for action two have better inhibiting chemical compound OM-991 and OM-992 to beta-secretase, are expected to the medicine as senile plaque.

(6) traditional Chinese medical herbal treatment: Chinese medicine is dispeled main at present employing of lipofuscin and is had obvious antioxidation, free radical and metabolite scavenging action thereof and improve macromolecular radical scavenger content and the active single medicinal material of SOD and herbal mixture or Chinese patent medicine.(1) single medicinal material and extracting solution thereof or fermentation liquid: mainly contain Radix Polygoni Multiflori, Fructus Lycii, Radix Ginseng, Radix Panacis Quinquefolii, Radix Salviae Miltiorrhizae, the Radix Astragali, Herb Gynostemmae Pentaphylli, Margarita powder, Radix Notoginseng, Radix Rhodiolae, Rhizoma Chuanxiong, Herba Cynomorii, Radix Rhapontici, Fructus Schisandrae Chinensis; Report is arranged, Fructus Lycii, Radix Rehmanniae grind into powder share the treatment senile plaque effective; (2) herbal mixture and Chinese patent medicine: at present many herbal mixtures and Chinese patent medicine antioxidation and free radical scavenging receive much concern with the lipofuscin effect of dispelling.Radix curcumae side, U.S. face ball, logical strongly fragrant soup, decoction of four noble drugs, Buddha's warrior attendant body-building liquor, world soup ultrasound wave water extract, world soup nanometer formulation, etc. also all to improve animal blood slurry SOD active and reduce LPO content.Some Chinese medicinal formulae such as BAINIANLE, GUILINGJI, ginseng Trionyx sinensis Wiegmann paste up, also Wheat Protein such as Fructus Schisandrae Chinensis Granulae, compound Salviae Miltiorrhizae mixture; (3) natural drug effective ingredient:, much also have the inhibitory action of the lipofuscin of dispelling by the effective ingredient that extracts in the natural drug except with single medicinal material and herbal mixture prescription and the effect of Chinese patent medicine to the lipofuscin of dispelling.Wherein, flavone compound, triterpenoid compound, Rhizoma Zingiberis Recens chlorins compound,, oside compound, fear research such as quinones and use at most.Other natural drug and preparation thereof that is used to suppress lipofuscin also has: antioxidant TA9901, spirulina, salvianolic acid A, TANSHINONES, danshensu, deoxyschizandrin, schisandrin B, SALLRSIPA SAL ADNF-9 schizronol schisanhenol, baicalin, Radix Glycyrrhizae flavone, Chinonin, arasaponin, ligustrazine, garlicin, Action of DNA from Carp Spermary, gingerol, crust halberd plain (glucoside monomer component, molecular weight 396), Ganoderma fermentation liquid, Herba Epimedii functional component (ESPS).

(7) cosmetics treatment: (1) Oleum concha Mactrae control senile plaque: Oleum concha Mactrae not only skin moisturizing is smooth, can also make senile plaque on the back of the hand also thin out gradually with disappear.Simple method is: use Oleum concha Mactrae to wipe hands in annual spring, autumn, 3 every days in season of winter and wipe face; (2) natural Chinese medicinal herb beauty cream control senile plaque:, and extract wherein that effective ingredient is mixed with cosmetics with multiple herbal prescription.Contain abundant bioactive ingredients in these natural Chinese herbal medicines, comprise plant free radical scavenging chaste tree and SOD, several amino acids and trace element etc., have skin moisturizing, preserve moisture, bright and clean, fine and smooth, soft, brighten, effect such as speckle dispelling, reduce wrinkle.Find that in clinical trial it also has good result to senile plaque; (3) Mus silver paste treatment skin senile plaque: utilize Armadillidium section animal armadillidum vulgare to grind into fine powder into powder with the Folium Ginkgo extract oven dry; And be mixed with the Mus silver paste according to conventional cream cream preparation technology; Directly be coated on the skin senile plaque every day twice at every turn, use one month continuously after; On the senile plaque of curing, continue to strengthen and used 10-15 days, total effective rate reaches 93%; (4) contain the cosmetics of antioxidant such as SOD: adhere to using the cosmetics that contain antioxidants such as SOD, can effectively remove the free radical in the skin, suppress lipofuscin and produce, prevent that senile plaque from forming.Usually, after giving the skin exfoliation, be stained with the essence or the moisturizing that contain SOD with gauze and grow face dew, apply at face, quiet lying several minutes, with a moment that gauze is taken off gently, you can feel immediately and bear a pretty, delicate skin clearly.If can make the facial film that contains SOD for 2～3 times weekly, can not only prevent and treat senile plaque, can also keep the skin wet to skin, also of great advantage to skin; (5) micromolecule Natural antioxidant cosmetics control skin senile plaque: micromolecule Natural antioxidant cosmetics are representative with vitamin E and vitamin C.Not long ago oily from the Aloe-VeraVitamin E skin oil and the Royal Jelly face of U.S. successor China market; Its main component is exactly a vitamin E; Theoretically, it can remove free radical as fat-soluble small molecule antioxidant, blocking-up lipid peroxidation chain reaction; Protection skin and cell membrane are avoided the free-radical oxidation damage, to the inhibitory action that is formed with of skin senile plaque.

The weak point of current production

The senile plaque that forms at skin surface is removed most of technical security, feasible, painful little, the no cicatrix in treatment back, post-operative complication method few, simple to operate through the physical technique means.But this method requires height to hospital and patient, and compliance is poor, and these class methods can only play temporary transient control action, can not fundamentally treat senile plaque, destroys horny layer, and improper use also might form permanent wound surface at skin surface.The chemical method treatment mainly is a chemical peeling.Chemical peeling is in the academic meeting of the plastic surgery of U.S. New Orleans, to put forward in 1962.It adopts chemical cracking-off agent that skin surface is destroyed, forms a scab, and makes it to come off, to reach therapeutic purposes.The method also is through chemical constituent keratodermatitis to be destroyed, and reaches the effect of removing surperficial senile plaque, the mechanism that does not the form senile plaque that disinthibites from senile plaque, and cause skin side-effects easily.

In addition, the patient must go to hospital could realize with relevant mechanism when using physical technique to dispel senile plaque with chemotherapy, and a lot of ordinary people patient Lai Shuoshi one are hindered greatly, and what they needed is a kind of easy to use, effective externally applied product.Use though general common externally applied transdermal product is convenient, a lot of products is because of the barrier action of skin, and functional component can only act on the local skin epidermal area, can't arrive skin corium at all.Therefore will deeply solve the skin splash problem, the senile plaque product efficacy of just need dispelling composition can see through keratodermatitis and reach deep skin, basal layer, could fundamentally suppress the formation of senile plaque like this, improves skin comprehensively.

Therefore, market is flat to press for a kind of dispel product of senile plaque of skin that is used for, and this product can use as cosmetics are convenient, need not spend hospital or the mechanism that improves looks, and need just not strip off through physical technique or chemistry not reach good effect.

Summary of the invention

The present invention is directed to the defective and the deficiency of prior art, a kind of clausenamide composite nano-emulsion that is used to remove facial senile plaque (lipofuscin) is provided, said preparation is a preparation capable of permeating skin, and Transdermal absorption is good, good stability, particle diameter is little, sense organ is good, convenient drug administration.The objective of the invention is to provide a kind of method for preparing that is used to remove the clausenamide composite nano-emulsion of facial senile plaque (lipofuscin).For solving the problems of the technologies described above, technical scheme provided by the present invention is following.

1. technical scheme of the present invention

(1) a kind of clausenamide composite nano-emulsion that is used to remove facial senile plaque (lipofuscin) of the present invention is made up of following raw materials by weight percent:

Clausenamide 1～5%

P-chlorophenoxyacetic acid dimethylamino second fat 0.700-0.950%

Superoxide dismutase 0.005-0.007%

Vitamin E 1.2～2.5%

Gingerol 1.0～1.5%

Oleum Hippophae 1.0～1.5%

Isopropyl myristate 12～16%

Coenzyme Q10 1.0～1.5%

Tri-distilled water 32～35%

Citric acid 0.1～0.2%

Sodium citrate 0.60～0.85%

Sad capric acid polyethyleneglycol glyceride 32～36%

Polyglyceryl fatty acid ester 10～12%

(2) a kind of clausenamide composite nano-emulsion that is used to remove facial senile plaque (lipofuscin) of the present invention, wherein the preferred weight percent of each raw material is:

Clausenamide 2%

P-chlorophenoxyacetic acid dimethylamino second fat 0.875%

Superoxide dismutase 0.006%

Vitamin E 2%

Gingerol 1%

Oleum Hippophae 1%

Isopropyl myristate 15%

Coenzyme Q10 1%

Tri-distilled water 31.146%

Citric acid 0.14%

Sodium citrate 0.833%

Sad capric acid polyethyleneglycol glyceride 33.75%

Polyglyceryl fatty acid ester 11.25%

(3) mechanism of action of functional component of the present invention and theoretical foundation thereof:

Be used to remove the clausenamide composite nano-emulsion of facial senile plaque (lipofuscin), adopt the functional component of multiple different mechanism to carry out composite forming, above functional component has antioxidation, removes free radical, promotes cellular metabolism, improves skin function.Above functional component is researched and developed through a kind of advanced skin-communication carrier-nano-emulsion.Nano-emulsion helps functional component to see through deep skin rapidly, plays a role.Below be the mechanism of action of each functional component:

Clausenamide is from Rutaceae clausena plant Folium clausenae lansii aqueous extract, to separate a kind of pyrrolidones that obtains.In addition, in exsiccant Semen clausenae lansii, also can detect certain concentration.Contain 4 asymmetric carbon atoms in its chemical constitution, its optical isomer has 16 in theory, can obtain 3S, 4R, 5R, 7S configuration through asymmetric synthesis and directed fractionation, is called left-handed clausenamide; 3R, 4S, 5S, 7S configuration are called the dextrorotation clausenamide.Research shows that the liver lipid peroxidation that clausenamide can obviously suppress to be brought out by alcoholism reacts, and this is favourable for stabilized cell membrane lipid, minimizing tissue injury, slow down aging.Because clausenamide can make the GSH-PX activity in the liver cerebral tissue endochylema liquid obviously increase, thereby plays the removing free radical, the effect that the protection cell is avoided damaging.It is a kind of alkaloid, can suppress the MC lipid peroxidation of rat brain, the heart, liver and testis that ferrum-the cysteine system causes.Research shows that clausenamide is one of mechanism of its lipoid peroxidization resistant to the direct seizure effect of oxygen-derived free radicals.

Clausenamide is dispeled the another one mechanism of senile plaque and is removed shallow lake β-powder appearance albumen, and β-powder appearance albumen is the nucleus of forming senile plaque.Amyloid is a kind of globulin and ateroid, because of its have similar starch chemical reaction (as with Iod R), so name is irrelevant with carbohydrate starch in fact.Groupization confirmation amyloid silk can be complete light chain, the also amino terminal of light chain segment, or both are its major protein composition.Under the Electronic Speculum, amyloid is made up of bifurcated directly and not, the silk of misfitting, irregular arrangement, and its diameter is 6～10nm, peripheral electron density central authorities is high, so be hollow cylindrical, length is uncertain.Immunochemistry finds that amyloid contains gamma Globulin, complement C1, C3 and C4, Fibrinogen, histone and alpha globulin etc.Claim when amyloid extensively is deposited on internal organs, muscle, mucosa and skin that general property or systemic amyloidosis are sick, further be divided into constitutional, Secondary cases, heritability and type such as senile.A lot of researchs confirm that compare with present β-powder appearance protein inhibitor, clausenamide can significantly reduce body β-proteic level of powder appearance, has the effect of remarkable anti-senile plaque.

(meclofenoxate hydrochloride Meclofenoxate Hydrochlorid MH) is white powder, soluble in water, nontoxic to p-chlorophenoxyacetic acid dimethylamino second fat.It is the agent of cellular metabolism functional activation, has effects such as antioxidation, removing free radical.Report is arranged, and it can remove the lipofuscin in the animal's nerve cells, adds p-chlorophenoxyacetic acid dimethylamino second fat (meclofenoxate hydrochloride) back three days; The pigment of lipofuscin promptly dissolves in the neuron; Thereby make the lipofuscin color thin out gradually, some lipofuscin becomes cavity, and some is cracking then.This effect maybe be relevant with effects such as its antioxidation that is had, removing free radicals.Free radical superfluous in the body is very harmful active oxide material, can strong oxidation reaction take place with each tissue of body. destructive extremely strong, not only can bring out a series of chain reaction; Make polypeptide chain take place crosslinked or fracture, cause protein denaturation, make the amino-acid oxidase or the reduction of zymophore; Cause the change of enzyme molecule secondary structure and make enzyme deactivation; Make the unsaturated fatty acid on the cell membrane produce peroxidization, cause that the physicochemical property of film changes, cause that oxidation, chain break and the protein one of ribose and base is crosslinked etc.; And, can also cause forming lipid peroxidation and lipofuscin and senile plaque.Lipofuscin is a kind of lipid or proteinic polymer, is present in the lysosome of different tissues postmitotic cells, and it increases along with the increase at age, and " aged pigment " or " old and feeble sign " or " senile plaque " therefore are otherwise known as.Use p-chlorophenoxyacetic acid dimethylamino second fat (meclofenoxate hydrochloride); Can be in vivo with the Intradermal metabolism after generate to phenoxy acetic acid and DMAE etc., all have the ability of free radical resisting, and can influence biochemical metabolism with and the mitochondrion electron transport chain in some key enzymes; Influence tricarboxylic acid cycle; Suppress glucose zymolysis and aerobic metabolism approach, promote the pentose phosphate approach, thereby promote the skin histology energy metabolism; Simultaneously; Meclofenoxate hydrochloride can also obviously strengthen the activity of cytochrome C-reductase, glutathione dehydrogenase, promotes cellular metabolism, and particularly it can improve antioxidase in the body; The activity that comprises superoxide dismutase (SOD) and glutathion peroxidase (GSHPX); But the also oxygen radical removing ability of enhancing body, (meclofenoxate hydrochloride and cell membrane have certain affinity, can combine with membrane phospholipid owing to p-chlorophenoxyacetic acid dimethylamino second fat; Regulate membrane structure; Be increased under the quiescent condition cell membrane permeability of potassium ion kept the transmembrane potential of senile cell, and through it to through measured by esr technique participation protective cell membrane; Slow down because of the waste product that the cell intracellular metabolic caused due to the age growth too much produces etc., this has positive role to the formation that alleviates or suppress skin lipofuscin and senile plaque.

SOD (superoxide dismutase) is the antioxygen enzyme, can effectively prevent skin aging, speckle dispelling, crease-resistant.Anti-free radical theory according to aging; Wearing out is free-radical generating and the result who eliminates function generation obstacle, under normal circumstances produce to be in poised state with elimination, but along with the aging of body or the influence of some extraneous factor; This balance is often broken; Unnecessary free radical just can damage body through multiple channel, and SOD is ultra oxyradical scavenger, can effectively prevent or delay the generation of said process to the continuous supplemented with exogenous SOD of body through suitable approach.

Vitamin E is ideal oil-soluble wide spectrum antioxidant, can remove multiple oxygen-derived free radicals, and can stop peroxidization and unsaturated fatty acid to generate lipofuscin pigment.And vitamin C also is the water solublity wide spectrum antioxidant of comparatively generally acknowledging, both can directly remove free radical, brings into play good antioxidation, and can assist the vitamin E effect, and can bring into play collaborative each other and synergic biological action with vitamin.

(Seabuckthorn oil is the elite of from the Fructus Hippophae pit, extracting SO) to Oleum Hippophae, contains multiple bioactive ingredients.Fructus Hippophae total flavones content wherein is higher, and this type of bioactive ingredients not only has regulating power in various degree to the too many levels of body immune system, and has very strong antioxidation and remove the free radical function; Contain organic acid such as the malic acid that contains in the multiple bioactive ingredients such as a large amount of aminoacid, organic acid, particularly Fructus Hippophae, oxalic acid in the Fructus Hippophae and have direct or indirect removing lipofuscin and senile plaque effect.Phosphide compounds in the Fructus Hippophae also is the higher composition of a kind of biological activity, can promote cellular metabolism, improves skin function.And phospholipid, triterpenoid compound etc. suppress lipid through control lipid synzyme and form, and promote lipid transfer and removing.Natural bioactive ingredients such as the bioactive ingredients anthocyanidin in the Fructus Hippophae, guassin, coumarin have different physiological roles, have positive role for removing lipofuscin and senile plaque effect.And Oleum Hippophae contains abundant unsaturated fatty acid ability anticoagulant, prevents that lipofuscin and senile plaque from forming and gathering.Wherein oleic acid, linoleic acid, linolenic acid etc. can be partly dissolved and remove and be deposited on intracellular lipofuscin and senile plaque; Sterol in the Oleum Hippophae is one of composition that constitutes cell membrane, can promote cell metabolism, also can promote lipofuscin and senile plaque to remove metabolism.A kind of especially powerful antioxidant of the VE that is rich in the Oleum Hippophae can enhance metabolism, and prevents the incidence and development and the aggravation of peroxidization, suppresses the unsaturated fatty acids acid oxidase, thereby prevention and reduction skin lipofuscin and senile plaque form and assemble.

Gingerol is the main component in the oil of Rhizoma Zingiberis Recens, has blood circulation promoting and blood stasis dispelling, microcirculation improvement etc., and all these all deposit positive effect to prevention and treatment lipofuscin and senile plaque.

Coenzyme Q10 (Coenzyme Q10) is a kind of fat-soluble quinone lopps chemical compound.Coenzyme Q10 mainly contains two effects in vivo, and the one,, nutrient substance plays an important role in being converted into the process of energy in mitochondrion, and the 2nd, tangible lipoid peroxidization resistant is arranged.Free-radical oxidation damage biomacromolecule is the reason that causes body aging and multiple Senile disease to take place, and can remove free radical effectively with antioxidant, has the function of slow down aging.Sweden Emster discloses the antioxidation and the free radical scavenging effect of biostearin material coenzyme Q10.It is high 16 times to nuclear DNA to the degree of injury of mitochondrial DNA that the mitochondrion aging is considered to oxygen-derived free radicals in the effect of body aging process.Its reason maybe with the more accessible endogenous oxygen-derived free radicals of DNA in the mitochondrial matrix, and the Intramitochondrial DNA repair mechanism can not show a candle to nuclear DNA.So inference, subunit is increased by radical damage in the mitochondrial DNA with advancing age.Old and feeble experiment display line plastochondria coenzyme Q10 concentration reduction with mitochondrion coenzyme Q10 concentration relationship is an importance of the aging of skeletal muscle.The old and feeble experimentation of a rat shows that old and feeble rat heart mitochondrion coenzyme Q10 content reduces, and liver and skeletal muscle intensive amount are lower.Immunologic function degression with age growth is the result of free radical and radical reaction.Coenzyme Q10 is effective anti-oxidants and free radical scavenger; It is embedded in the mitochondrial inner membrane lipid bimolecular as the ingredient of mitochondrial respiratory chain; Behind 2 electronics of mitochondrion complex I or complex II acceptance, become pure formula, give complex III with electron transport again.The body coenzyme Q 10 is become pure formula by lot of consumption, and it is an effective anti-oxidants, also is the ELECTRON OF MOTION carrier simultaneously, and it is given to the lipid peroxidation free radical with hydrogen atom from its hydroxyl, thereby reduces the MDA reaction of mitochondrial inner membrane.In this process, generated and the out-of-proportion free radical ubisemiquinone of the pure formula of coenzyme Q10 and coenzyme Q10; Or with the oxygen formation superoxides that reacts; The free radical ubisemiquinone is transported free radical and is realized Detoxication under superoxide dismutase and catalatic effect; The respiratory chain that so moves in circles has been recovered its antioxidant activity effect with the continuous regeneration alcohol of coenzyme Q10 formula.Test and react through direct and peroxide radical after proof body coenzyme Q 10 becomes pure formula, and the VE that can regenerate, the effect of also collaborative by one's own efforts VE performance antioxidant.Immunologic function degression with age growth is the result of free radical and radical reaction; Coenzyme Q10 uses separately as a kind of powerful antioxidant or is used in combination the modification that can suppress the microtubule system that receptor is relevant with activity with cell differentiation on the radical pair immunocyte with vitamin B6 (pyridoxol); The enhance immunity system, slow down aging.Local experiment shows the ability drop of resisting oxidation stimulus object damages such as ultraviolet along with the increase skin collagen at age; And the life-time service coenzyme Q10 can prevent effectively that the skin light decay is old; Reduce the wrinkle of circumference of eyes; Because coenzyme Q10 penetrates into the oxidation reaction that the skin growth layer can weaken photon, under the assistance of fertility alcohol, can start specific phosphorylated tyrosine kinases, prevent the oxidative damage of DNA; Suppress the expression of application on human skin fibroblast Collagenase under the irradiation under ultraviolet ray, protection skin avoids damage.Extensive studies thinks that coenzyme Q10 suppresses lipid peroxidation; Reduce the generation of free radical; Protection SOD active center and structure thereof are avoided the free-radical oxidation damage; Enzymatic activitys such as SOD in vivo enhancement, the inductive apoptosis of inhibited oxidation stress has significant antioxidation, function in delaying senility.

Citric acid and two hydration trisodium citrates can be formed good buffer system, keep the relatively stable of nano-emulsion system pH value, thereby help effective performance of functional component.

(4) a kind of method for preparing that is used to remove the clausenamide composite nano-emulsion of facial senile plaque (lipofuscin) of the present invention

1. the preparation of water: in tri-distilled water, dissolve clausenamide, citric acid, sodium citrate, meclofenoxate hydrochloride and SOD successively, with this solution as water.

2. the preparation of oil phase: accurately take by weighing isopropyl myristate with analytical balance, place another container through decontamination; Then, dissolving adds vitamin E, gingerol, Oleum Hippophae, coenzyme Q10 successively again, fully behind the mixed dissolution, with this solution as oil phase.

3. the preparation of emulsifying agent/co-emulsifier mixture: according to the sad capric acid polyethyleneglycol glyceride (S) that designed in the prescription: the ratio of polyglyceryl fatty acid ester (C)=3: 1; Accurately take by weighing sad capric acid polyethyleneglycol glyceride and polyglyceryl fatty acid ester respectively, and the two raw material is placed the 3rd suitable vessel; Add a cover, and this container is placed rapidly on the liquid flash mixer, fully mix homogeneously makes it to form emulsifying agent/co-emulsifier mixture.

4. according to oil phase: emulsifying agent/co-emulsifier: the ratio of water=20%: 45%: 35%, the phase of fetching water respectively earlier, S/C mixture place the 4th through among the 200mL clean container of decontamination.

5. after above-mentioned water, S/C mixture two liquid phases fully being mixed, in this container, directly add oil phase again, and with whole system in ultrasonator about ultrasonic 5min, after fully mixing.The system outward appearance is colourless in this way, fluidity and good dispersion, obviously visible opalescence person is arranged, and is a kind of clausenamide composite nano-emulsion that is used to remove facial senile plaque (lipofuscin).

6. this a kind of clausenamide composite nano-emulsion that is used to remove facial senile plaque (lipofuscin) is sub-packed in rapidly among the lucifuge glass container of different size, adds a cover rapidly, packing, and airtight preservation gets final product among placing the room temperature of drying, ventilation, cool place, lucifuge.

2. beneficial effect of the present invention

A kind of clausenamide composite Nano emulsion formulation that is used to remove facial senile plaque (lipofuscin) of the present invention, has certain fluidity at little faint yellow, transparent, the visible opalescence of outward appearance.Detect through transmission electron microscope, droplet diameter distribution is between 10～100nm.The employing staining identifies, the clausenamide composite Nano emulsion formulation that is used to remove facial senile plaque (lipofuscin) is the oil-in-water type nano-emulsion.

The present invention has the following advantages compared with prior art:

1. thermodynamic stability is high: nanoemulsions as two kinds of immiscible liquid according to a certain percentage; Under the combined effect of surfactant and cosurfactant, form thermodynamically stable dispersion naturally; The present invention prepares fairly simple, and not phase-splitting, bin stability improve.

2. functional component upgrades: the senile plaque functional component of dispelling that we select like clausenamide, gingerol, Oleum Hippophae, coenzyme Q10, p-chlorophenoxyacetic acid dimethylamino second fat, all is a determined curative effect, and side effect is little.Also be not applied at present dispel in the senile plaque field.Be used to remove the clausenamide composite nano-emulsion of facial senile plaque (lipofuscin) in addition; Adopt the functional component of multiple different mechanism to carry out composite forming; Suppress senile plaque from various angle, have antioxidation, remove free radical, promote cellular metabolism, improve skin function.Reach comprehensive effect.

3. carrier is novel: nanoemulsions belongs to the thermodynamically metastable fixed system as novel transdermal delivery drug-supplying system (TDDS); Dispel to use aspect the senile plaque at skin and still belong to initiative; Utilize best nano-emulsion system to contain and parcel has the collaborative skin with the synergy effect of the mutual aid senile plaque functional component of dispelling, make product use more safety with effectively.

4. sense organ property is better: the product of the present invention preparation be two kinds of immiscible liquid according to a certain percentage; That combined effect through surfactant and cosurfactant forms naturally is thermodynamically stable, isotropic, good fluidity, as clear as crystal, glittering and translucent, have trickle xanchromatic, have a little opalescent dispersion; Have good perception property, actual comfort is splendid.

5. bioavailability improves: common preparation capable of permeating skin needs some effective penetrating agent to assist; Just might see through epidermal barrier and get into their due biological actions of performance in the skin; And common penetrating agent not only skin is had must zest, make skin increase a kind of anaphylactogen.The clausenamide composite nano-emulsion particle diameter that is used to remove facial senile plaque (lipofuscin) of the present invention is little, and the functional component dispersion that is contained improves greatly, has improved insoluble drug dissolubility and unit volume functional component concentration, makes the drug potency increasing.Add the characteristics of nano-emulsion carrier, promote the Transdermal absorption of functional component, improved the bioavailability of functional component.

6. improved product antiseptical ability: nano-emulsion is a transparency liquid, can filter, and is easy to sterilization and handles, and certain antibacterial action is arranged itself, need not add chemical preservative and just can prevent product rotten, and skin irritation is reduced, and safety improves.

7. the method for the present invention's preparation at room temperature prepares; The activity of therefore thermo-labile for protection, high temperature functional component and content, particularly protected protein class, peptide class, enzyme, cell growth factor subclass isoreactivity material have important value; Improve the stability of protein and peptide drugs or functional component; Can keep its biological activity and biological action to greatest extent, the application in other field also provides a kind of good method for these functional components of protection.

8. this product preparation process is simple, is beneficial to environmental protection.Traditional emulsion cosmetic is owing to need to use plurality of raw materials; Its oil phase and water-phase component are complicated, and technological process is loaded down with trivial details, and the production cycle is longer; Particularly oil phase and water must could be accomplished emulsifying etc. under hot conditions; And this product preparation composition simplify, with low cost, preparation technology is simple, practical operation is easy, preparation efficiently fast, does not need special instruments and equipment, does not need the external world energy to be provided, not to need to heat, do not need electric power and other energy, but both energy savings and cost; Free from environmental pollution again, be fit to large-scale production.

4. preparation points for attention of the present invention

1. product used container of when preparation must strictly according to the rules clean and sterilization, and preferably adopt strong acid to soak back water and dash, clear water washes clean again, dry with distilled water immersion the back, places after the baking oven high-temperature sterilization drying subsequent use again; In addition, when carrying out the product preparation, used container all will be paid special attention to prevent to contain impurity or pollutions such as metal ion and microorganism, in order to avoid influence product quality and stability.

2. because of at present the quality standard that takes off senile plaque functional component and raw material of the same race is incomplete same, particularly there is some difference for content and purity, therefore, carrying out product when preparing, the quality and the source of the hig diligence raw material of being sure to.After in the end confirming formula material and method for preparing, do not change raw material sources and quality more in principle, in order to avoid influence product quality, stability and result of use.

3. prepare in strict accordance with above-mentioned dosage and method.When carrying out this product preparation; Should add according to above-mentioned flow sequence, its additive capacity must require accurate, and; In the interpolation of other raw material; Could add a kind of raw material down after must waiting a kind of raw material of adding fully to dissolve again,, influence the preparation of whole nano-emulsion system in order to avoid occur muddyly.

4., the preparation external need select and definite S/C mass ratio (km value) when taking off the senile plaque nano-emulsion; And definite S/C mass ratio (km value) 1,2,3,4; Be to confirm at last after carrying out the biphase binary liquid test of titration water oil and pass through pseudo-ternary phase diagram analyzing; Only, be only comparatively ideal km value confirming and calculating the km value that obtains maximum nano-emulsion zone.Above-mentioned method for preparing confirms that through testing Km value has been 3, but actual when carrying out the product preparation, surfactant (S) and cosurfactant in this ratio still must be after mixing also will be more abundant mixing, prepare effect and quality in order to avoid influence.

5. because the proportion or the density different relationships of liquid solution; When carrying out the product preparation, the capacity of selected preparation container must be a bit larger tham the product volume of actual preparation, like preparation 100g product; Need to select the preparation container of 150-200mL; So both be convenient to each composition and fully mixed and dissolve, and also be convenient to ultrasonic concussion or stirring and evenly mixing, and be unlikely to overflow outward.

Though 6. blank nano-emulsion itself has the characteristics of certain bacteria growing inhibiting; Other interpolation antiseptic is not arranged, so when carrying out the product preparation, except that the preparation container must carry out strictness cleaning and sterilization in this formula for a product; Also should be during concrete the preparation in strict accordance with rule of operation; Under aseptic condition and according to the sterile working, require to operate as far as possible, avoid this nano-emulsion sample to be polluted, influence product quality.

7. the sample of preparation completion must be packed with lucifuge, and places shady and cool dry ventilation lucifugal place to preserve as far as possible, keep fire away or thermal source.In addition, after product uses at ordinary times, need not place low temperature or refrigerator to preserve, but must seal tightly, be positioned over natural room temperature and keep in Dark Place and get final product.

8. these article possibly have zest to skin, please suspend use immediately as using the position significant reaction to occur; In actual use, be sure not these article are done ophthalmic; Skin is injured, have wound or redness must not use, use the back red and swollen if any continuing, and should stop using; Baby and child must not use; The skin sensitivity person should do the skin sensitivity property testing before using, and tests completely without irritative response and can use.

Description of drawings

Fig. 1. a kind of preparation technology's flow process and technology path that is used to remove the clausenamide composite nano-emulsion of facial senile plaque (lipofuscin).

The specific embodiment

The examples of implementation that embodiment provides through the inventor below 1. further specify a kind of concrete method for preparing that is used to remove the clausenamide composite nano-emulsion of facial senile plaque (lipofuscin).

A kind of preferred weight percent that is used to remove each raw material of clausenamide composite nano-emulsion of facial senile plaque (lipofuscin) is:

Isopropyl myristate 15%, sad capric acid polyethyleneglycol glyceride 33.75%, polyglyceryl fatty acid ester 11.25%, tri-distilled water 31.146%; Clausenamide 2%, vitamin E 2%, gingerol 1%; Oleum Hippophae 1%, coenzyme Q10 1%, p-chlorophenoxyacetic acid dimethylamino second fat 0.875%; Superoxide dismutase 0.006%, citric acid 0.14%, sodium citrate 0.833%.

A kind of concrete method for preparing (100g is an example with preparation) that is used to remove the clausenamide composite nano-emulsion of facial senile plaque (lipofuscin):

1. in 31.146g water, dissolve 0.14g citric acid, 0.833g sodium citrate, 2g clausenamide, 0.875g p-chlorophenoxyacetic acid dimethylamino second fat and 0.006g superoxide dismutase successively.With this solution as water (I) 35g.

2. accurately take by weighing the isopropyl myristate of 15g weight with analytical balance, place another through among the 50mL conical flask of decontamination; Then, dissolving adds 2g vitamin E, 1g gingerol, 1g Oleum Hippophae, 1g coenzyme Q10 successively again, behind the abundant mixed dissolution of ultrasonic 5min, with clear oil phase (II) 20g that is labeled as of marking pen.

3. according to the sad capric acid polyethyleneglycol glyceride (S) that has designed in advance: the ratio of polyglyceryl fatty acid ester (C)=3: 1; Accurately take by weighing sad capric acid polyethyleneglycol glyceride of 33.75g and 11.25g polyglyceryl fatty acid ester respectively, and the two raw material is placed among the clean conical flask of 100mL of the 3rd process decontamination; Add a cover, and this conical flask is placed rapidly on the liquid flash mixer, open the liquid flash mixer; And it is transferred to the II shelves, fully mix homogeneously makes it to form emulsifying agent/co-emulsifier (S/C) mixture; Behind the 3-5min; The closing liquid flash mixer takes off conical flask, and with clear S/C mixture (III) 45g that is labeled as of marking pen.

4. according to oil phase (II): S/C (III): the ratio of water (I)=20%: 45%: 35%, phase (I) 35g that fetches water respectively earlier, S/C mixture (III) 45g place among the 4th the clean conical flask of the 200mL through decontamination.

5. after above-mentioned water (I), S/C mixture (III) two liquid phases fully being mixed; Again under 25 ℃ of conditions of room temperature or in the natural room temperature; Put it into and shake in the ultrasonator also about ultrasonic 2min; Perhaps under 25 ℃ of conditions of room temperature or in the natural room temperature, start the time constant-temperature magnetic stirring apparatus, with 200rpmmin ^-1Rotating speed magnetic agitation 5min, then, in this container, directly add oil phase (II) 20g again; And with whole system in ultrasonator about ultrasonic 5min; Perhaps under 25 ℃ of conditions of room temperature or in the natural room temperature, start the time constant-temperature magnetic stirring apparatus, with 200rpmmin ^-1Rotating speed magnetic agitation 20min.

6. close ultrasonator or time constant-temperature magnetic stirring apparatus; Take off the 200mL conical flask; Observe its outward appearance orange in this way transparent, fluidity and good dispersion, obviously visible opalescence person is arranged, be the clausenamide composite nano-emulsion that 100g is used to remove facial senile plaque (lipofuscin) for a kind.

7. the clausenamide composite nano-emulsion that this 100g is used to remove facial senile plaque (lipofuscin) for a kind is sub-packed in rapidly among the lucifuge glass container of different size; Add a cover rapidly; Packing, and airtight preservation gets final product among placing the room temperature of drying, ventilation, cool place, lucifuge.

Embodiment 2.

The clausenamide composite nano-emulsion that the foregoing description 1 preparation a kind of is used to remove facial senile plaque (lipofuscin) carries out the study on the stability experiment.

1. strong illumination test: get the clausenamide composite nano-emulsion, place glass port grinding bottle, in the illumination held of 4000lx, measured in the 5th day, the tenth day, the result does not relatively have difference before placing.It is still transparent that the result finds originally to be used to remove the clausenamide composite nano-emulsion outward appearance of facial senile plaque (lipofuscin), finds muddy or deposition, and no layering and demulsifying phenomenon are explained good stability.

2. the room temperature investigation that keeps sample: with commercially available back room temperature (25 ℃ ± 2 ℃/RH75%) carry out under the condition, press certain hour (0,1,3,6,12,24,36 month) at interval, measure study on the stability project (having or not layering).It is still transparent that the result finds originally to be used to remove the clausenamide composite nano-emulsion outward appearance of facial senile plaque (lipofuscin), finds muddy or deposition, and good stability is described.

3. hot test is investigated: get the clausenamide composite nano-emulsion; Place airtight vessel to place respectively in 40 ℃, 60 ℃, 80 ℃; Measured in the 5th day, the tenth day; It is still transparent that the result finds originally to be used to remove the clausenamide composite nano-emulsion outward appearance of facial senile plaque (lipofuscin), finds muddy or deposition, and good stability is described.

4. the freeze proof investigation of low temperature: commercially available back is carried out under-4 ℃ of conditions in refrigerator, by certain hour at interval (0,1,3,6,12 month) take out and return to room temperature, measure study on the stability project (whether transparent, have or not layering).It is still transparent that the result finds originally to be used to remove the clausenamide composite nano-emulsion outward appearance of facial senile plaque (lipofuscin), finds muddy or deposition, explains that this product frost resistance is good, stable.

5. accelerated stability is investigated: take in the clausenamide composite nano-emulsion of removing facial senile plaque (lipofuscin), place high speed centrifuge supporting centrifuge tube, with 15000rpmmin ^-1The centrifugal 20min of speed, do not have layering, still transparent, explain that this product stability is good.

Experimental result shows the clausenamide composite nano-emulsion good stability that the present invention prepares, can long term store.

Embodiment 3.

The clausenamide composite nano-emulsion that the foregoing description 1 preparation a kind of is used to remove facial senile plaque (lipofuscin) carries out the experiment of transdermal penetration rate.

This tests main research contents contains the senile plaque functional component of dispelling among same concentrations the present invention for preparation Emulsion, gel and nano-emulsion; Through Franz transdermal test in vitro diffusion instrument the transdermal characteristic of three kinds of preparations is compared research, thereby the ability of estimating the transdermal test in vitro infiltration of nano-emulsion is studied.The result shows the clausenamide composite nano-emulsion, has better percutaneous permeability than general preparation capable of permeating skin, and the accumulative total Transdermal absorption amount (seeing table 1) (P＜0.01) of three kinds of different transdermal dosage forms has significant difference, nano-emulsion＞Emulsion＞gel.

The unit are accumulation Transdermal absorption amount Q (n=3) of table 1. clausenamide composite Nano emulsion formulation, Emulsion, gel preparation

Embodiment 4.

The clausenamide composite nano-emulsion that the foregoing description 1 preparation a kind of is used to remove facial senile plaque (lipofuscin) carries out skin irritation test.

8 of healthy new zealand white rabbits, male and female half and half are carried out skin irritation test, in administration preceding 24 hours, Na are used in animal spinal column both sides ₂The S depilation, depilation district area is 35cm ²Get final product.Rabbit one side is coated with the dressing of clausenamide composite nano-emulsion 1mL, and opposite side is coated with the dressing of clausenamide composite nano-emulsion 3mL, and administration was thrown off wound dressing after 24 hours, removes the skin left drug with warm water, observes obvious skin irritation all not occur.

Embodiment 5.

The clausenamide composite nano-emulsion that the foregoing description 1 preparation a kind of is used to remove facial senile plaque (lipofuscin) the senile plaque viewing test of dispelling.

Subjects is 30 routine senile plaque patients, and the men and women half and half.Sooner or later coat about the clausenamide composite nano-emulsion 1mL of inventor's prepared in laboratory after cleaning face every day, used continuously one month, experimental result is found.Have improvement in various degree among 30 patients, wherein 22 routine patient's effects are remarkable, and obvious effective rate reaches 73.3%.Observe the clausenamide composite nano-emulsion simultaneously after use, tangible zest all do not occur.Individual patient little red stain can occur after bringing into use, but behind the life-time service, this situation will disappear.Though this test does not compare with the relevant external senile plaque product of dispelling, this test has confirmed the effectiveness of clausenamide composite nano-emulsion.

Embodiment of the present invention only is the description that preferred implementation of the present invention is carried out; Be not that design of the present invention and scope are limited; Do not breaking away under the preceding topic of design philosophy of the present invention, engineers and technicians make technical scheme of the present invention in this area various modification and improvement all should fall into protection scope of the present invention; The technology contents that the present invention asks for protection all is documented in claims.

Claims (6)

1. clausenamide composite nano-emulsion preparation capable of permeating skin that is used to remove facial senile plaque is characterized in that it is made up of following weight percentages:

2. a kind of clausenamide composite nano-emulsion that is used to remove facial senile plaque according to claim 1, wherein the preferred weight percent of each raw material is:

3. a kind of clausenamide composite nano-emulsion that is used to remove facial senile plaque according to claim 1 is characterized in that it is made up of the raw material of following weight ratio: oil phase 20%, emulsifying agent and co-emulsifier 45%, water 35%.

4. a kind of clausenamide composite nano-emulsion that is used to remove facial senile plaque according to claim 3 is characterized in that described oil phase is isopropyl myristate, vitamin E, gingerol, Oleum Hippophae, coenzyme Q10.

5. a kind of clausenamide composite nano-emulsion that is used to remove facial senile plaque according to claim 3 is characterized in that described water is tri-distilled water, clausenamide, citric acid, sodium citrate, p-chlorophenoxyacetic acid dimethylaminoethyl, superoxide dismutase.

6. a kind of clausenamide composite nano-emulsion that is used to remove facial senile plaque according to claim 3 is characterized in that described emulsifying agent/co-emulsifier is the mixture of sad capric acid polyethyleneglycol glyceride, polyglyceryl fatty acid ester.

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