CN101757031A - Cartialgenous all-component uniform freeze-dried preparation and production method thereof - Google Patents
Cartialgenous all-component uniform freeze-dried preparation and production method thereof Download PDFInfo
- Publication number
- CN101757031A CN101757031A CN201010127734A CN201010127734A CN101757031A CN 101757031 A CN101757031 A CN 101757031A CN 201010127734 A CN201010127734 A CN 201010127734A CN 201010127734 A CN201010127734 A CN 201010127734A CN 101757031 A CN101757031 A CN 101757031A
- Authority
- CN
- China
- Prior art keywords
- cartialgenous
- preparation
- cornu cervi
- cervi pantotrichum
- freeze
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention aims to provide a uniform preparation which contains all components of cartialgenous. Compared with the conventional cartialgenous decoction tablets which are graded into various specifications such as leucogen tablets, wax tablets, sand tablets, sclerites and the like, the uniform preparation contains the all components, of the cartialgenous, existing in a uniform state, provides a medicinal material or a medicament with uniform quality for a doctor or a sufferer to cure diseases with the cartialgenous, and provides a material base for ensuring a curative effect and preventing the fluctuation of a drug effect. Compared with the modern novel processing technology of crashing the cartialgenous into dry powder after the cartialgenous is freeze-dried, the whole process has no high-temperature process, which effectively protects the activity of components of biological factors, and provides a preparation form which can rapidly absorb micromolecular active substances and peptide components through oral mucosa at the same time. Through the technical means of flavor-correction and taste-masking, the mouthfeel of the decoction tablets and the preparation is good and the use compliance is improved.
Description
Technical field
The present invention relates to a kind of lyophilizing figuration preparation and production method thereof that contains active ingredient of Chinese herbs, particularly relate to a kind of Cartialgenous all-component uniform freeze-dried preparation and production method thereof.
Background technology
The medicinal Shennong's Herbal in ancient times that sees the earliest of Cornu Cervi Pantotrichum, Li Shizhen (1518-1593 A.D.) has more at large been introduced the concocting method and the medicinal efficacy of Cornu Cervi Pantotrichum in Compendium of Material Medica.
Cornu Cervi Pantotrichum is the still unossified young tender antler of stag.The fine and soft beginning for the treatment of the preponderant disease instead of the secondary disease is answered in Cornu Cervi Pantotrichum processing.Getting fine and soft method has two kinds substantially, and the one, paste the scalp saw down with saw, claim saw fine and soft; The 2nd, connect skull band young pilose antler and cut down, claim to cut young pilose antler.The Cornu Cervi Pantotrichum that takes off will wash earlier, extracts fine and soft interior hematocele out.Cut young pilose antler and also will repair the bone shaping, make shape attractive in appearance.The Cornu Cervi Pantotrichum of pharmacopeia regulation is: the sika deer velvet antler medical material is divided into two thick sticks, three troubles.The cervus elaphus linnaeus medical material is divided into three trouble and Flos Nelumbinis.
Commercially available Cornu Cervi Pantotrichum section generally is divided into level Four, and it is that Cornu Cervi Pantotrichum is cut into for vertical one section that first-class is spent fine and soft sheet, is called the blood sheet; Second grade is level and smooth owing to tangent plane, no sponge sample hole, and color such as wax sample are bright and clean, practise claiming wax disk(-sc); C grade is because of surperficial heterogeneity, and no wax sample gloss is practised title sand sheet, and the fourth class is practised the title osteocomma because there is sponge sample hole on the surface.
Cornu Cervi Pantotrichum " is reported the matter of pure sun, is contained the gas of hair growth promoting ", is classified as the drug of first choice of high benefit " Yuanyang " by the traditional Chinese medical science.From the modern medicine viewpoint, " Yuanyang " has comprised basic human body physiological functions such as reproduction, growth metabolism.Cornu Cervi Pantotrichum has spermatogenesis benefit marrow, beneficial blood is supporing yang, the function of strengthening the tendons and bones, cures mainly diseases such as all are deficient, dizzy, deaf, order dark, sexual impotence, spermatorrhea, weakness of the waist and knees, deficiency and coldness leukorrhagia, metrorrhagia.Clinical usual amounts is 1.5～3g, general maximum 6g that are no more than.Modern pharmacology discovers that Cornu Cervi Pantotrichum has heart tonifying, human body immunity improving function, promotes wound healing, and gonadotropic Effect.Cornu Cervi Pantotrichum also is common in nourishing class health product, for example pantocrine, deer antler wine, antler gelatin or the like except that using in tcm prescription.
The main purpose of Cornu Cervi Pantotrichum processing is dehydration, dry, anticorrosion, sterilization, conformal, guarantor's color, improves the quality, and is beneficial to preservation.For a long time, the processing of China's Cornu Cervi Pantotrichum adopts boiling water to boil fried and high-temperature baking technology always.But there is very big defective in this processing method.This is because the basis of the pharmacological activity of Cornu Cervi Pantotrichum is mainly a large amount of protein-based bioactie agent that wherein contains, even also can make protein denaturation and add Chinese liquor, therefore traditional Cornu Cervi Pantotrichum processing method cause fine and soft in the effective ingredient active substance suffer in various degree loss and destruction.
In sum, there are following 2 problems in traditional Cornu Cervi Pantotrichum concocting method and decoction pieces in actual applications:
(1) somatomedin class materials such as the nerve growth factor that contains in the Cornu Cervi Pantotrichum, epidermal growth factor, para-insulin like growth factor all are protein hormones or polypeptide hormone constituents, and the fried technology of elevated temperature heat makes these active ingredient loss totally;
(2) traditional Cornu Cervi Pantotrichum classification is the classification on appearance character, is qualitatively, but not quantitative, this has brought great puzzlement for doctor and patient's medication, do not have conversion relation between each classification pilose antler piece, when equivalent conversion meeting is switched, cause the greatest differences of drug effect between different decoction pieces.
In order to solve as above problem, the lyophilizing Cornu Cervi Pantotrichum arises at the historic moment, the concocting method of lyophilizing Cornu Cervi Pantotrichum is to adopt modern food and biological product freeze preservation and dry technology theory, organizational structure and biological characteristics in conjunction with Cornu Cervi Pantotrichum, manage to make fine and soft intravital free water and constitution water to be easy to separate out, make bright young pilose antler after quick-freezing, the dehydrate that directly distils under the cryogenic vacuum condition becomes the new technology of best buy young pilose antler.Avoided existing " decocting in water, baking " processing method to temperature-sensitive active component in the Cornu Cervi Pantotrichum as the destruction of enzyme, protein hormones and polypeptide hormone etc.; Can keep shape, color and luster, the taste of bright Cornu Cervi Pantotrichum constant substantially; And keep the nutritional labeling of Cornu Cervi Pantotrichum and physiologically active ingredient not to run off, do not destroy to greatest extent, improved the product quality and the appearance property of Cornu Cervi Pantotrichum.
Though solved the 1st problem of traditional process of preparing Chinese medicine decoction pieces with the Cornu Cervi Pantotrichum of this processing mode acquisition, it is the active difficult problem of preserving of active factors constituents and other thermally sensitive compositions, but same organizational structure and resemblance because of there being Cornu Cervi Pantotrichum, the 2nd problem exists equally.To the bottom, the difference of different parts decoction pieces is difficult to hold comparatively accurately to dosage in actual use from the Cornu Cervi Pantotrichum top, causes the difference of curative effect and the puzzlement in the use, does not also meet modern medicines to basic demand stable and controllable for quality.
In order to solve as above problem, attempt the lyophilizing Cornu Cervi Pantotrichum is passed through technologies such as pulverizing, mixing, attempt to obtain powder, perhaps it is inserted capsule, become a kind of whole part homogeneous decoction pieces or preparation.But mechanical force in the technical processs such as pulverizing at different levels and heat production meeting destroy the activity of active factors constituents and other thermally sensitive compositions greatly, anatomical structure because of Cornu Cervi Pantotrichum is divided into osseous part and skin zone simultaneously, osseous part is more easily pulverized after drying, and skin zone is after drying, just as tanned leather, be very difficult to pulverize, often cause such material to be heated excessively, and contain a large amount of effective ingredient in the fine and soft skin of Cornu Cervi Pantotrichum, loss is especially huge in crushing process, even the employing pulverize at low temperature also is difficult to the fine and soft skin of drying is crushed to suitable particle size.
Even in future, fresh-keeping Cornu Cervi Pantotrichum might be handled and obtain fresh-keeping fine and soft powder, the formed mode of taking of its preparation form also can cause active factors constituents and other thermally sensitive compositions to be difficult to play a role, the capsule that oral powder and powder are filled makes active factors constituents and other thermally sensitive compositions under the effect of gastrointestinal tract soda acid and various digestive enzyme, basic degraded, very difficult absorption plays a role.Simultaneously, the mouthfeel of oral powder it is also to be difficult to accept.
Lyophilizing figuration preparation is to adopt freeze-drying, in addition suitable adjuvant figuration and the preparation that obtains in technical process.Be used to prepare chemicals in early days, employing Freeze Drying Techniques such as Gregory have been made the pharmaceutical carrier of high porosity, the disintegrate after the oral cavity runs into saliva of this carrier, do not need water delivery service, take medicine to some function of deglutition patient bad and water intaking inconvenience convenience is provided, more and more be subjected to liking of patient with its unique advantages.
But traditional lyophilizing figuration preparation has strict requirement to adjuvant, must possess the carrier that a certain amount of binding agent and skeleton proppant could form high porosity, and drug loading is limited, and every milliliter of maximum drug loading is no more than 100 milligrams.Easily 1 to 2 restrain for the Cornu Cervi Pantotrichum dry product, even bigger dose, do not find a place where one uses one's talents.
Summary of the invention
The inventor of present patent application is at problems of the prior art, with keen determination, unexpectedly finding through research in depth can be to be divided into carrier material as one-tenth such as collagen protein, hyaluronic acids in the aquatic foods product Cornu Cervi Pantotrichum, further preserve the activity of active factors constituents and other thermally sensitive compositions by freeze-drying, obtain figuration simultaneously, become and a kind ofly contain various thermal sensitivity compositions at interior Cartialgenous all-component homogeneous preparation.The preparation that produces can by mucosa absorption, be brought into play various thermal sensitivity compositions at intraoral disintegration, the especially effect of biotic factor active component, thus finished the present invention.
The object of the invention is to provide a kind of Cartialgenous all-component uniform freeze-dried figuration preparation; Another purpose of the present invention is to provide the preparation method of this Cartialgenous all-component uniform freeze-dried figuration preparation.
The present invention also aims to provide a kind of with your fines medical material and the lyophilizing figuration preparation of whole part homogeneous Cornu Cervi Pantotrichum compatibility and the preparation methoies of described preparation thereof such as Radix Ginseng, Radix Notoginseng, clam scholar toad, Nidus collocaliae, Cordyceps, Rhizoma Gastrodiae, Fel Ursi, Ganodermas.
A kind of Cartialgenous all-component uniform freeze-dried preparation of the present invention by complete Cornu Cervi Pantotrichum obtained by freeze drying, is characterized in that it has fixed form but not powder body, wherein contain Cartialgenous all-component, and the vitality index of described preparation can restrain the 10-1500IU/ gram for 10-1000IU/, the 10-1800IU/ gram, 10-2000IU/ gram, 10-2500IU/ gram, 10-3, the 000IU/ gram, 10-3,500IU/ gram, the 20-1000IU/ gram, the 20-1500IU/ gram, 20-1800IU/ gram, 20-2000IU/ gram, the 20-2500IU/ gram, the 20-3000IU/ gram, 20-3,500IU/ gram, the 30-1000IU/ gram, the 30-1500IU/ gram, 30-1800IU/ gram, 30-2000IU/ gram, the 30-2500IU/ gram, the 30-3000IU/ gram, 30-3500IU/ restrains (with version pharmacopeia appendix XH recombinant human epidermal growth factor Determination of biological activity method cell proliferation/MTT colorimetric method for determining in 2005), preferred 10-3, the 000IU/ gram, preferred especially 20-2500IU/ gram.
Described Cartialgenous all-component is the material that the complete Cornu Cervi Pantotrichum of Cervus nippon Temminck or Cervus elaphus linnaeus or other suitable deer obtains behind freezing, freezing and pulverizing, low-temperature homogenate.The content range of described Cartialgenous all-component in Cartialgenous all-component uniform freeze-dried preparation can be 1-100%, 1-99%, 2-99%, 5-99%, 10-99%, 20-99%, 30-99%, 1-95%, 2-95%, 5-95%, 10-95%, 20-95%, 30-95%, 1-90%, 2-90%, 5-90%, 10-90%, 20-90%, 30-90%, 1-80%, 2-80%, 5-80%, 10-80%, 20-80%, 30-80%, preferred 5-100% is more preferably 10-100%, preferred especially 20-100%, most preferably 30-100%.
In the Cartialgenous all-component uniform freeze-dried figuration preparation of the present invention except that the Cartialgenous all-component that contains homogeneous, can also contain other Chinese crude drug or Chinese crude drug extract and other adjuvants, for example various saccharides, aminoacid, long-chain is natural or synthesising macromolecule copolymer and essence or correctives.
Described other Chinese crude drug or Chinese crude drug extract can be bright medical material, as fresh ginseng, bright Radix Panacis Quinquefolii, bright Radix Notoginseng, bright clam scholar toad etc., or pharmaceutical decocting piece, as Radix Ginseng, sun-dried Radix Panacis Quinquefolii, Radix Ginseng Rubra, Korean Ginseng, Radix Ginseng (processed with sugar), Radix Notoginseng, clam scholar toad, or the extract of medical material, as Radix Ginseng extract, Radix Notoginseng extract, clam scholar toad extract, Radix Ginseng total saponins, American ginseng total saponins, Radix Notoginseng total arasaponins, Oviductus Ranae etc., can also be the active concentrate of Cornu Cervi Pantotrichum, the concentrate of the supernatant that obtains after promptly bright Cornu Cervi Pantotrichum homogenate is centrifugal.Described other Chinese crude drug preferably ginseng, Radix Notoginseng, clam scholar toad, Nidus collocaliae, Cordyceps, Rhizoma Gastrodiae, Fel Ursi, Ganoderma etc.It can join in the Cartialgenous all-component uniform freeze-dried preparation with single or compatibility form, and content range is 0-98%, and preferred 1-90 or 5-90% are more preferably 10-80%, preferred especially 20-70%, most preferably 30-60%.
Described saccharide is mannitol, sorbitol, maltose alcohol, xylitol, lactose, erythritol, hydroxyl isomaltulose, lactose, xylose, cottonseed sugar, maltose, glucose, galactose, trehalose, dextrin or hydroxypropyl cyclodextrin; The preferred mannitol of described saccharide, erythritol, maltose, trehalose, mannitol most preferably, described saccharide is 0-50% at the content range of Cartialgenous all-component uniform freeze-dried figuration preparation, preferred 0.2-40%, be more preferably 0.3-30%, preferred especially 0.5-30%, most preferably 1-30%
Described aminoacid is to have 2 amino acid whose one or more mixture to 12 carbon atoms; Described aminoacid is: glycine, arginine, serine, proline, alanine, aspartic acid, glutamic acid, hydroxyproline, isoleucine, leucine or phenylalanine.Be preferably glycine.The content range of described aminoacid in Cartialgenous all-component uniform freeze-dried figuration preparation is 0-50%, and preferred 2-40% is more preferably 3-30%, preferred especially 4-30%, most preferably 5-30%.
Natural or the synthesising macromolecule copolymer of described long-chain includes but not limited to any or several the mixture in natural origin glue classes such as Pullulan, gelatin, xanthan gum, Konjac glucomannan, dextran, alginate jelly, arabic gum, guar gum, agar, hydroxy methocel, carrageenin, pectin and synthetic macromolecular compound or polymer such as polyvinylpyrrolidone, carbomer, glucosan and other polypeptide or the polysaccharide; Described long-chain natural or the preferred Pullulan of synthesising macromolecule copolymer, gelatin and hydrolysate thereof.Natural or the content range of synthesising macromolecule copolymer in Cartialgenous all-component uniform freeze-dried figuration preparation of described long-chain is 0-50%, and preferred 2-40% is more preferably 3-30%, preferred especially 4-30%, most preferably 5-30%.
Wherein said essence or correctives include but not limited to mint flavored, the jasmine flavor, the Arillus Longan flavor, the Flos Chrysanthemi flavor, the Fructus Fragariae Ananssae flavor, the Fructus Musae flavor, chocolate flavoured, the Semen arachidis hypogaeae flavor, the Fructus Crataegi flavor, the Fructus Mangifera Indicae flavor, the Fructus Jujubae flavor, the Fructus Pruni flavor, the Flos Osmanthi Fragrantis flavor, the Fructus Ananadis comosi flavor, the Herba Passiflorae Caeruleae flavor, the Punica granatum L. flavor, the Fructus psidii guajavae immaturus flavor, the Fructus Fici flavor, the Semen Sesami flavor, egg yolk flavor, the Fructus Lycopersici esculenti flavor, the corn flavor, creamy taste, the black currant flavor, blue berry flavor, the Radix Glycyrrhizae flavor, the orange flavor, the Fructus Vitis viniferae flavor, lemon, the Fructus actinidiae chinensis flavor, caramel, vanilla flavored, cherry-flavored, the hami melon flavor, the Fructus Chaenomelis flavor, the Fructus Mali pumilae flavor, the Fructus Caricae flavor, the Fructus Litchi flavor, the pears flavor, the peach flavor, caf, tea flavour, the essence of milk flavor etc. or the mixture of above one or more fragrance; Its content can be 0.01-5%.
The preparation method of Cartialgenous all-component uniform freeze-dried preparation of the present invention may further comprise the steps (those skilled in the art can suitably add other step again under the prerequisite that does not deviate from essence of the present invention):
1. fresh Cornu Cervi Pantotrichum low temperature (below 0 ℃) is freezing;
2. refrigerated Cornu Cervi Pantotrichum is ground into refrigerated granule (about particle diameter 20 orders) below 40 ℃;
3. add in the purified water and contain medical material or its extracts such as Radix Ginseng, Radix Notoginseng, clam scholar toad, Nidus collocaliae, Cordyceps, Rhizoma Gastrodiae, Fel Ursi, Ganoderma in right amount, add or do not add various saccharides, aminoacid, long-chain is natural or synthesising macromolecule copolymer, add or do not add essence or correctives, mixed dissolution is reduced to low temperature below 40 ℃ after disperseing;
4. the 2nd go on foot frozen particle homogenizing below 40 ℃ or the homogenate formation suspendible preparation liquid that obtains, or the 2nd frozen particle that obtains of step is dispensed in solution, suspension or the emulsion that purified water or the 3rd step obtain, form suspendible preparation liquid with homogeneous emulsifying machine homogenizing or homogenate below 40 ℃;
5. the 4th go on foot the suspendible preparation liquid that obtains, divide the mould that is filled to suitable volumes, behind pre-freeze and two processing steps of lyophilization, obtain Cartialgenous all-component uniform freeze-dried figuration preparation.
The present invention is under the situation of prior art without any instruction, creatively propose to be divided into carrier material as one-tenth such as collagen protein, hyaluronic acids in the aquatic foods product Cornu Cervi Pantotrichum, further by the freeze-drying figuration, obtained a kind ofly have fixed form but not the Cartialgenous all-component homogeneous preparation of powder body, thereby finished the present invention.The formed brand-new Cartialgenous all-component homogeneous preparation of the present invention has effectively been preserved the temperature-sensitive in the Cornu Cervi Pantotrichum, high activity material; Its preparation form is achieved mucosa absorption, and effective absorption of assurance whole part also plays a role; Its homogeneity provides can be for adjusting and prescription use material base, and for solving Chinese medicine, especially decoction pieces, a quality homogeneous and a controlled difficult problem provide a kind of new settling mode simultaneously; Wherein can add your fines medical material and extract such as ginseng (Radix Ginseng, Korean Ginseng, Radix Panacis Quinquefolii), seven (Radix Notoginseng), Oviductus Ranae, Nidus collocaliae, Cordyceps, Rhizoma Gastrodiae, Fel Ursi, Ganoderma, make the compatibility of Chinese medicine use the higher level of bringing up to.And mouthfeel and compliance when having changed medication.
In addition, the vitality index of Cartialgenous all-component uniform freeze-dried preparation of the present invention is 10-3, the 500IU/ gram, and vigor is higher.Why adopting vitality index to characterize Cartialgenous all-component uniform freeze-dried figuration preparation of the present invention is because Cornu Cervi Pantotrichum processing is in the past concocted, if adopt cryodesiccated method to carry out processed to whole bright Cornu Cervi Pantotrichum, often find to have better pharmacological effect, but to the material of this biological effect characterize just with: " at certain molecular weight ranges place; finding has a large amount of albumen, or how many water miscible total protein concentration recruitments is." between material base and drug activity, do not set up necessary relation, for quality homogeneous and quality control, there is not the index of estimating and controlling yet.The present invention adopts active unit as the quality evaluation index to active hairy antler, organically the advantage of freeze drying process and the basis of material and drug effect is united, for optimization and process for stabilizing, product quality provides condition and guarantee continually and steadily.
In addition, bibliographical information, the short rat skeletonization like cell proliferation activity (mtt assay) of lyophilizing Cornu Cervi Pantotrichum water extract are 2.2 times of the fried Cornu Cervi Pantotrichum of traditional hot up to 245.25%; The IGF-I secretory volume is 1.2 times of the fried young pilose antler of heat also up to 66.3ng/ml; Suppressing the hepatoma carcinoma cell activity is 47.64%, is 1.4 times of the fried young pilose antler of heat.So a lot of methods all are to be used as medicine getting the alternative Cornu Cervi Pantotrichum of supernatant lyophilizing behind the bright Cornu Cervi Pantotrichum low-temperature homogenate.
But this innovation is not considered: low-temperature homogenate is got behind the supernatant also has a large amount of effective ingredient in the abandoned Cornu Cervi Pantotrichum, as: hypoxanthine, cerebrin, sialic acid, phospholipid etc. are in non-supernatant part distribution to be arranged also, abandon non-supernatant part a large amount of other loss of effective components are then arranged, and can not reflect the characteristics of whole part Cornu Cervi Pantotrichum, the Chinese medicine medication under instructing with traditional Chinese medicine theory has more significant gap.
So the present invention has not only preserved highly active sensitivity composition, has also kept the whole part of Cornu Cervi Pantotrichum, is to be body with the Chinese medical theory, with the modern science means the useful trial of the modernization of Chinese medicine of usefulness.It is controlled that this invention can also guarantee that the quality of the Cornu Cervi Pantotrichum product that obtains continues homogeneous, can industrialization, and satisfy of the requirement of Modern Law rules to medicine medical material and health product, Chinese medicine is gone to the world provides a kind of strong support pattern.
Simultaneously; the preparation taking convenience that is obtained; the oral cavity collapses molten; the raw material viscosity that excites in unique technology can promote the mucosa adhesion of Cornu Cervi Pantotrichum; compare as oral forms such as tablet, capsule, granule, soft capsules with other; can increase the absorption that produces by mucosa before the stomach, make the bioactie agent of technology protection and destruction that other heat-sensitive substances can not be subjected to gastrointestinal tract soda acid, multiple enzyme and inactivation, better bring into play the effect of bright Cornu Cervi Pantotrichum.Therefore the present invention has beneficial effect preferably with respect to prior art.Concrete experimental data is referring to embodiment.
The specific embodiment
The present invention is described by the following examples in further detail, but these embodiment are of the present invention giving an example, the present invention is not limited to this.
Prepare Cartialgenous all-component homogeneous preparation according to composition shown in the table 1 and quantity thereof, its concrete grammar is as follows:
1. fresh Cornu Cervi Pantotrichum low temperature (below 0 degree centigrade) is freezing;
2. refrigerated Cornu Cervi Pantotrichum is ground into refrigerated granule (about particle diameter 20 orders) below 40 degrees centigrade;
3. add in the purified water and contain medical material or its extracts such as Radix Ginseng, Radix Notoginseng, clam scholar toad, Nidus collocaliae, Cordyceps, Rhizoma Gastrodiae, Fel Ursi, Ganoderma in right amount, add or do not add various saccharides, aminoacid, long-chain is natural or artificial high molecular polymer, add or do not add essence or correctives, mixed dissolution is reduced to below 40 ℃ after disperseing;
4. the 2nd go on foot frozen particle homogenizing below 40 ℃ or the homogenate formation suspendible preparation liquid that obtains, or the 2nd frozen particle that obtains of step is dispensed in solution, suspension or the emulsion that purified water or the 3rd step obtain, homogenizing or homogenate below 40 ℃ form suspendible preparation liquid;
5. the 4th go on foot the suspendible preparation liquid that obtains, divide the mould that is filled to suitable volumes, behind pre-freeze and two processing steps of lyophilization, obtain Cartialgenous all-component uniform freeze-dried figuration preparation.
Table 1:
| Whole part homogeneous Cornu Cervi Pantotrichum | Expensive thin medical material | Saccharide | The long-chain high molecular polymer | Aminoacid | Purified water | Other adjuvants | |
| Embodiment 1 | The bright Cornu Cervi Pantotrichum of 200mg | ??—— | ??—— | ??—— | ??—— | ??—— | ??—— |
| Embodiment 2 | The bright Cornu Cervi Pantotrichum of 40mg | ??—— | ??—— | ??—— | ??—— | ??200mg | 0.1mg golden Supreme Being's chocolate essence, 0.1mg Herba Menthae essence |
| Whole part homogeneous Cornu Cervi Pantotrichum | Expensive thin medical material | Saccharide | The long-chain high molecular polymer | Aminoacid | Purified water | Other adjuvants | |
| Embodiment 3 | The bright Cornu Cervi Pantotrichum of 100mg | The bright Radix Panacis Quinquefolii of 200mg | —— | ??—— | ?—— | ??50mg | 0.05mg golden Supreme Being's chocolate essence, 0.05mg Herba Menthae essence |
| Embodiment 4 | The bright Cornu Cervi Pantotrichum of 12mg | The 50mg Korean ginseng extract | 4mg mannitol | ??—— | ?—— | ??100mg | 0.05mg ginseng essence |
| Embodiment 5 | The bright Cornu Cervi Pantotrichum of 150mg | The 200mg Oviductus Ranae | —— | The 10mg Pullulan | ?—— | ??100mg | 0.05mg Herba Menthae essence |
| Embodiment 6 | The bright Cornu Cervi Pantotrichum of 3mg | The 20mg Radix Notoginseng total arasaponins | —— | The 2mg gelatin hydrolysate | The 2mg glycine | ??100mg | ??—— |
| Embodiment 7 | The bright Cornu Cervi Pantotrichum of 300mg | 300mg Radix Ginseng total saponins, 200mg Oviductus Ranae | —— | The 40mg Pullulan | ??300mg | 1mg gold Supreme Being chocolate essence, 1mg Herba Menthae essence, 1mg acesulfame potassium |
Annotate: glycine: Beijing essence is asked chemical industry Co., Ltd,
Mannitol: Beijing essence is asked chemical industry Co., Ltd
Menthol: standing grain field, Suzhou spice company limited
Acesulfame potassium: Zhangjiagang Haobo Chemical Product Co., Ltd.
Experimental example
The determination of activity of the Cartialgenous all-component homogeneous preparation of embodiment 1-8 preparation
Assay method adopts version Chinese Pharmacopoeia appendix XH recombinant human epidermal growth factor biologic activity in 2005
Algoscopy cell proliferation/MTT colorimetry
1 experiment material
1.1RPMI1640 culture fluid
Every 1000ml adds the 2.2g sodium bicarbonate, and 4 ℃ of preservations are stand-by.
1.2 complete culture solution
RPMI-1640 adds 10% (ml/ml) calf serum, and 4 ℃ of preservations are stand-by.
1.3 keep culture fluid
RPMI-1640 adds 4% (ml/ml) calf serum, and 4 ℃ of preservations are stand-by.
1.4PBS
Get 121 ℃ of solution, 15min sterilization that 8g sodium chloride, 0.2g potassium chloride, 1.44g sodium hydrogen phosphate, 0.24g potassium dihydrogen phosphate adding distil water are mixed with 1000ml.
1.5 Thiazolyl blue MTT solution
Be mixed with the solution of 5.0mg/ml with PBS, through 0.22 μ m membrane filtration degerming, place glass or plastic bottle, 4 ℃ keep in Dark Place.
1.6 lysate
Dimethyl sulfoxine (DMSO, analytical pure)
1.7BALB/c3T3 cell strain
The test that is used to tire in back 48 hours of going down to posterity.
1.8rh EGF determination of activity standard substance
2 test procedures
Below 2.1～2.9 steps all need under aseptic condition, to carry out.
2.1 test is prepared
To test the pre-temperature of used solution to 37 ± 1 ℃.
2.2 preparation cell stock solution
Get the BALB/c3T3 cell culture fluid of capacity, centrifugal collection BALB/c3T3 cell with complete culture solution washing three times, is resuspended in the cell stock solution that complete culture solution is mixed with 5.0 * 104 cell/ml then, place 37 ± 1 ℃ standby.
2.3 standard solution
Get standard substance and be mixed with 1000IU/ml, be diluted to 50IU/ml with complete culture solution with sterilized water.
2.4 sample solution
With the product of embodiment 1-7 preparation with the sterilized water dissolving after, to be measured.
2.5 dilution mensuration
In 96 porocyte culture plates, with 4 times of serial dilutions, reference material and sample are with doing 8 dilution factors to standard substance, sample solution, and each gradient is done 2 multiple holes.
2.6 add cell stock solution and cultivation
Get cell stock solution and be inoculated in the 96 porocyte culture plates, every hole 100 μ l.Place 37 ± 1 ℃, cultivate after 24 hours under the 5%CO2 condition, change into and keep culture fluid, continue to place 37 ± 1 ℃, cultivated 24 hours under the 5%CO2 condition.
2.7 adding sample and standard solution cultivates
The Tissue Culture Plate of preparation discards keeps liquid, adds standard substance and sample solution, every hole 100 μ l.Place 37 ± 1 ℃, cultivated under the 5%CO2 condition 66～72 hours.
2.8 add MTT solution and cultivation
Every hole adds 20 μ l MTT solution, puts 37 ℃, and 5%CO2 cultivates 4h-6h.
2.9 adding lysate
Discard the liquid in the culture plate, every hole adds 100 μ l lysates, the mixing dissolving.
2.10 mensuration absorbance
Colorimetric on microplate reader is measured wavelength 570nm, reference wavelength 630nm, record measurement result.
2.11 the result calculates
Handle with four parametric regression computing methods, calculate partly imitating extension rate (promptly from sample solution to be checked to the extension rate that is equivalent to reference material 50% ceiling effect point) and being calculated as follows the result of each product to be checked respectively.
In the formula: T1 ... sample is tired, IU
T0 ... standard substance are tired, IU
D1 ... the pre-extension rate of sample
D0 ... the pre-extension rate of standard substance
H1 ... sample is partly imitated extension rate
H0 ... standard substance are partly imitated extension rate
The determination of activity result:
| Embodiment 1 | The 2000IU/ gram |
| Embodiment 2 | The 350IU/ gram |
| Embodiment 3 | The 1000IU/ gram |
| Embodiment 4 | The 100IU/ gram |
| Embodiment 5 | The 1500IU/ gram |
| Embodiment 6 | The 30IU/ gram |
| Embodiment 7 | The 3000IU/ gram |
It should be noted that those skilled in the art can carry out various modifications for various details of the present invention, but undoubtedly, these modifications will fall within protection scope of the present invention all.
Claims (8)
1. Cartialgenous all-component uniform freeze-dried preparation, by complete Cornu Cervi Pantotrichum obtained by freeze drying, it is characterized in that it has fixed form but not powder body, wherein contain Cartialgenous all-component, the content range of described Cartialgenous all-component in Cartialgenous all-component uniform freeze-dried preparation is 1-100%, and the vitality index of described preparation is the 10-3500IU/ gram, and described vitality index is measured with version Chinese Pharmacopoeia appendix XH recombinant human epidermal growth factor Determination of biological activity method in 2005.
2. lyophilized formulations as claimed in claim 1 is characterized in that also containing other Chinese crude drug or Chinese crude drug extract.
3. lyophilized formulations as claimed in claim 2, it is characterized in that described other Chinese crude drug is one or more in Radix Ginseng, Radix Notoginseng, clam scholar toad, Nidus collocaliae, Cordyceps, Rhizoma Gastrodiae, Fel Ursi, the Ganoderma, described Chinese crude drug extract is one or more in the active concentrate of Radix Ginseng extract, Radix Notoginseng extract, clam scholar toad extract, Cornu Cervi Pantotrichum.
4. as each described lyophilized formulations of claim 1-3, it is characterized in that also containing various saccharides, aminoacid, long-chain is natural or synthesising macromolecule copolymer, essence and/or correctives.
5. lyophilizing sheet as claimed in claim 4 is characterized in that described saccharide is one or more in mannitol, sorbitol, maltose alcohol, xylitol, lactose, erythritol, hydroxyl isomaltulose, lactose, xylose, cottonseed sugar, maltose, glucose, galactose, trehalose, dextrin or the hydroxypropyl cyclodextrin.
6. as claim 4 or 5 described lyophilizing sheets, it is characterized in that described aminoacid is one or more in glycine, arginine, serine, proline, alanine, aspartic acid, glutamic acid, hydroxyproline, isoleucine, leucine or the phenylalanine.
7. as each described lyophilizing sheet of claim 4-6, it is characterized in that the natural or synthesising macromolecule copolymer of described long-chain be selected from Pullulan, gelatin, xanthan gum, Konjac glucomannan, dextran, alginate jelly, arabic gum, guar gum, agar, hydroxy methocel, carrageenin, the pectin one or more natural origin glue class and be selected from one or more synthesising macromolecule copolymer in polyvinylpyrrolidone, carbomer, the glucosan.
8. as the preparation method of any described lyophilizing sheet of claim 1-7, may further comprise the steps:
(1) fresh Cornu Cervi Pantotrichum is freezing below 0 degree centigrade;
(2) refrigerated Cornu Cervi Pantotrichum is ground into refrigerated granule below 40 degrees centigrade, about described particle grain size 20 orders;
(3) adding contains medical material or its extracts such as Radix Ginseng, Radix Notoginseng, clam scholar toad, Nidus collocaliae, Cordyceps, Rhizoma Gastrodiae, Fel Ursi, Ganoderma in right amount in the purified water, add or do not add various saccharides, aminoacid, long-chain is natural or artificial high molecular polymer, add or do not add essence or correctives, mixed dissolution is cooled to below 40 ℃ after disperseing;
Frozen particle homogenizing below 40 ℃ that (4) the 2nd steps obtained or homogenate form suspendible preparation liquid, or the 2nd frozen particle that obtains of step is dispensed in solution, suspension or the emulsion that purified water or the 3rd step obtain, homogenizing or homogenate below 40 ℃ form suspendible preparation liquid;
The suspendible preparation liquid that (5) the 4th steps obtained divides the mould that is filled to suitable volumes, obtains Cartialgenous all-component uniform freeze-dried figuration preparation behind pre-freeze and two processing steps of lyophilization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101277348A CN101757031B (en) | 2010-03-19 | 2010-03-19 | Cartialgenous all-component uniform freeze-dried preparation and production method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101277348A CN101757031B (en) | 2010-03-19 | 2010-03-19 | Cartialgenous all-component uniform freeze-dried preparation and production method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101757031A true CN101757031A (en) | 2010-06-30 |
| CN101757031B CN101757031B (en) | 2013-08-21 |
Family
ID=42488512
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101277348A Active CN101757031B (en) | 2010-03-19 | 2010-03-19 | Cartialgenous all-component uniform freeze-dried preparation and production method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101757031B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101757030A (en) * | 2010-03-19 | 2010-06-30 | 董玲 | Cartialgenous all-component uniform freeze-dried preparation and production method thereof |
| CN102440309A (en) * | 2010-10-12 | 2012-05-09 | 宜昌三峡玉泉寺茶叶有限公司 | Manufacturing process for antler organic tea and preparation thereof |
| WO2012122678A1 (en) * | 2011-03-16 | 2012-09-20 | Dong Ling | Uniform freeze-dried preparation containning all components of pilose antler and production method thereof |
| CN106619539A (en) * | 2015-11-02 | 2017-05-10 | 董玲 | Method for preparing freeze-dried excipient preparation in any shape and product of method |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU563146A1 (en) * | 1975-12-16 | 1977-06-30 | Marugin Igor A | Method of unossified antlers canning |
| CN1266895A (en) * | 2000-02-21 | 2000-09-20 | 郑刚 | Formulation of red deer's blood, antler and tail oral liquid and its preparing process |
| CN1401330A (en) * | 2002-09-05 | 2003-03-12 | 新疆香巴拉食品有限公司 | Buccal red deer horn tablet |
| CN1481816A (en) * | 2003-07-24 | 2004-03-17 | 白秀娟 | Method of extracting Water-soluble antler extract product |
| CN1686170A (en) * | 2005-04-08 | 2005-10-26 | 张海峰 | Velvel deerhorn extract freeze dried powder injection agent and its preparation method |
| CN101757030A (en) * | 2010-03-19 | 2010-06-30 | 董玲 | Cartialgenous all-component uniform freeze-dried preparation and production method thereof |
-
2010
- 2010-03-19 CN CN2010101277348A patent/CN101757031B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU563146A1 (en) * | 1975-12-16 | 1977-06-30 | Marugin Igor A | Method of unossified antlers canning |
| CN1266895A (en) * | 2000-02-21 | 2000-09-20 | 郑刚 | Formulation of red deer's blood, antler and tail oral liquid and its preparing process |
| CN1401330A (en) * | 2002-09-05 | 2003-03-12 | 新疆香巴拉食品有限公司 | Buccal red deer horn tablet |
| CN1481816A (en) * | 2003-07-24 | 2004-03-17 | 白秀娟 | Method of extracting Water-soluble antler extract product |
| CN1686170A (en) * | 2005-04-08 | 2005-10-26 | 张海峰 | Velvel deerhorn extract freeze dried powder injection agent and its preparation method |
| CN101757030A (en) * | 2010-03-19 | 2010-06-30 | 董玲 | Cartialgenous all-component uniform freeze-dried preparation and production method thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101757030A (en) * | 2010-03-19 | 2010-06-30 | 董玲 | Cartialgenous all-component uniform freeze-dried preparation and production method thereof |
| CN102440309A (en) * | 2010-10-12 | 2012-05-09 | 宜昌三峡玉泉寺茶叶有限公司 | Manufacturing process for antler organic tea and preparation thereof |
| WO2012122678A1 (en) * | 2011-03-16 | 2012-09-20 | Dong Ling | Uniform freeze-dried preparation containning all components of pilose antler and production method thereof |
| CN106619539A (en) * | 2015-11-02 | 2017-05-10 | 董玲 | Method for preparing freeze-dried excipient preparation in any shape and product of method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101757031B (en) | 2013-08-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101757030A (en) | Cartialgenous all-component uniform freeze-dried preparation and production method thereof | |
| CN105999159B (en) | Brown sugar and saussurea involucrata composition and preparation method thereof | |
| WO2012122678A1 (en) | Uniform freeze-dried preparation containning all components of pilose antler and production method thereof | |
| CN104873624B (en) | A kind of pharmaceutical composition for gouty arthritis | |
| CN103083642A (en) | Aloe preparation for skin enhancement | |
| CN105707875A (en) | Red and black fructus lycii lozenges and preparation method thereof | |
| CN101757031B (en) | Cartialgenous all-component uniform freeze-dried preparation and production method thereof | |
| CN101020715B (en) | Process of extracting and preparing deer nerve growth factor (DEER NGF) | |
| CN109222100A (en) | A kind of ginseng Cordyceps militaris composition, ginseng Cordyceps militaris pressed candy and preparation method thereof | |
| CN105999210A (en) | Lucid-ganoderma active lactobacillus preparation and preparing method | |
| CN102579501B (en) | A kind of Full-ingredient uniform freeze-drying preparation for royal and production method thereof | |
| WO2007007993A1 (en) | Pharmaceutical composition for the prevention and treatment of liver disease comprising a lonicera caerulea l. var. edulis extract | |
| CN101732347B (en) | Antler freeze-dried tablet and production method thereof | |
| CN114377105A (en) | Baoyuan effervescent tablet and preparation method and application thereof | |
| CN106174484A (en) | There is the enzyme composition of cough and asthma relieving efficacy, effervescent granule and preparation method | |
| KR101039110B1 (en) | A water composition comprising Broussonetia kazinoki Sieb. for immunopotentiating | |
| CN108813465A (en) | A kind of fig function chewable tablets and preparation method thereof | |
| CN101128210B (en) | A herbal mixture extract of rehmanniae radix preparata and acanthopanacis cortex and a composition comprising the same for prevention and treatment of osteoporosis | |
| CN103845722A (en) | Oligopeptide composition for control of radiation damage or chemotherapy damage and preparation method thereof | |
| CN105434738A (en) | Traditional Chinese medicine composition for treating ADHD (Attention Deficit Hyperactivity Disorder) and preparation method thereof | |
| US20100074975A1 (en) | Pharmaceutical composition for the prevention and treatment of liver disease comprising a lonicera caerulea L. Var. Edulis extract | |
| CN102302515A (en) | Hairy antler freeze-dried excipient and production method thereof | |
| CN103845450A (en) | Application of hawthorns in preparing medicine for treating hyperuricemia, gout and renal insufficiency | |
| CN107854609A (en) | Red ginseng, the tuber of dwarf lilyturf, fruit of Chinese magnoliavine composition are used for the purposes for preparing the medicine for the treatment of depression | |
| CN104622993B (en) | Chewable tablet with protective effect on alcoholic liver injuries and preparation method of chewable tablet |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee | ||
| CP02 | Change in the address of a patent holder |
Address after: 101312 1, 6 Anqing Avenue, Shunyi District airport industry zone, Beijing, Patentee after: Dong Ling Address before: 101100, No. 1204, building 131, Wangjing garden, Beijing, Chaoyang District Patentee before: Dong Ling |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20161018 Address after: 101312 1, 6 Anqing Avenue, Shunyi District airport industry zone, Beijing, Patentee after: Beijing Weibo Haitai Biotechnology Co. Ltd. Address before: 101312 1, 6 Anqing Avenue, Shunyi District airport industry zone, Beijing, Patentee before: Dong Ling |