CN116585205B - Freeze-dried powder preparation with relieving effect - Google Patents
Freeze-dried powder preparation with relieving effect Download PDFInfo
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- CN116585205B CN116585205B CN202310447454.2A CN202310447454A CN116585205B CN 116585205 B CN116585205 B CN 116585205B CN 202310447454 A CN202310447454 A CN 202310447454A CN 116585205 B CN116585205 B CN 116585205B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 55
- 230000000694 effects Effects 0.000 title claims abstract description 33
- 239000000843 powder Substances 0.000 title claims abstract description 33
- 229920001661 Chitosan Polymers 0.000 claims abstract description 67
- 230000006872 improvement Effects 0.000 claims abstract description 43
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 claims abstract description 27
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000002270 dispersing agent Substances 0.000 claims abstract description 24
- 239000000945 filler Substances 0.000 claims abstract description 24
- 239000008367 deionised water Substances 0.000 claims abstract description 22
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 22
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 21
- 239000002994 raw material Substances 0.000 claims abstract description 12
- 239000000853 adhesive Substances 0.000 claims abstract description 11
- 230000001070 adhesive effect Effects 0.000 claims abstract description 11
- 238000003756 stirring Methods 0.000 claims description 36
- 238000002156 mixing Methods 0.000 claims description 35
- 239000000243 solution Substances 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 24
- 238000000227 grinding Methods 0.000 claims description 22
- 230000004048 modification Effects 0.000 claims description 22
- 238000012986 modification Methods 0.000 claims description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 21
- 238000001035 drying Methods 0.000 claims description 21
- 238000001354 calcination Methods 0.000 claims description 19
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 18
- 239000007788 liquid Substances 0.000 claims description 17
- 239000000463 material Substances 0.000 claims description 17
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 14
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- 239000000661 sodium alginate Substances 0.000 claims description 14
- 235000010413 sodium alginate Nutrition 0.000 claims description 14
- 229940005550 sodium alginate Drugs 0.000 claims description 14
- 229910052901 montmorillonite Inorganic materials 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 12
- 239000006185 dispersion Substances 0.000 claims description 12
- 239000011230 binding agent Substances 0.000 claims description 11
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 11
- 238000005406 washing Methods 0.000 claims description 10
- 238000002715 modification method Methods 0.000 claims description 7
- -1 polyoxyethylene Polymers 0.000 claims description 7
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 6
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 6
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 6
- 239000001341 hydroxy propyl starch Substances 0.000 claims description 6
- 235000013828 hydroxypropyl starch Nutrition 0.000 claims description 6
- 229920000609 methyl cellulose Polymers 0.000 claims description 6
- 239000001923 methylcellulose Substances 0.000 claims description 6
- 230000001105 regulatory effect Effects 0.000 claims description 6
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 5
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 5
- 229960000913 crospovidone Drugs 0.000 claims description 5
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 5
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 5
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 5
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 239000007884 disintegrant Substances 0.000 claims description 3
- 239000012530 fluid Substances 0.000 claims description 3
- 238000013268 sustained release Methods 0.000 claims description 3
- 239000012730 sustained-release form Substances 0.000 claims description 3
- 239000002352 surface water Substances 0.000 claims description 2
- 239000008176 lyophilized powder Substances 0.000 claims 8
- 238000009472 formulation Methods 0.000 claims 7
- 238000004090 dissolution Methods 0.000 abstract description 11
- 230000001976 improved effect Effects 0.000 abstract description 8
- 230000032683 aging Effects 0.000 abstract description 2
- 230000002040 relaxant effect Effects 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 12
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 210000004927 skin cell Anatomy 0.000 description 3
- 101100120045 Bos taurus FGF1 gene Proteins 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000032677 cell aging Effects 0.000 description 2
- 230000019522 cellular metabolic process Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 208000028990 Skin injury Diseases 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
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- 238000011069 regeneration method Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0216—Solid or semisolid forms
- A61K8/022—Powders; Compacted Powders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/26—Aluminium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/736—Chitin; Chitosan; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/005—Preparations for sensitive skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Inorganic Chemistry (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to the technical field of freeze-dried powder preparations, and in particular discloses a freeze-dried powder preparation with a relieving effect, which comprises the following raw materials in parts by weight: 20-30 parts of aFGF, 5-10 parts of slow-release skeleton improvement body, 4-7 parts of modified chitosan, 3-7 parts of filler, 2-4 parts of disintegrating agent, 2-5 parts of adhesive, 15-25 parts of dispersing agent and 30-40 parts of deionized water. According to the freeze-dried powder preparation, aFGF is dispersed by a dispersing agent, and a disintegrating agent and a filling agent are added, so that the high-efficiency dissolution of aFGF can be promoted, a to-be-slowly-released body prepared firstly is matched with a slowly-released skeleton improvement body, the slowly-released dissolution efficiency of aFGF can be enhanced by the slowly-released skeleton improvement body, the dissolution efficiency of a product is further improved by the increase of modified chitosan, the problem of sudden release of the product is solved, the stability of the product is improved, the slowly-released efficiency of the product is improved, and thus the product has a relaxing effect and can resist aging effectively for a long time.
Description
Technical Field
The invention relates to the technical field of freeze-dried powder preparations, in particular to a freeze-dried powder preparation with a relieving effect.
Background
The freeze-dried powder preparation is prepared by freezing the liquid medicine in a sterile environment, mixing the raw material medicines in certain auxiliary materials or dissolving the raw material medicines in certain solvents, and preparing the preparation in different forms through certain processing treatment, namely the freeze-dried powder injection. AFGF can promote the growth and reproduction of skin tissues, regulate the division, reproduction and growth and differentiation of skin epithelium, endothelium and stroma cells by combining with cell surface specific receptors, promote cell metabolism and enhance oxidation; can promote rapid growth and reproduction of cells related to skin injury, and regulate synthesis, secretion and decomposition of intercellular matrix; can promote regeneration of horny layer cells, accelerate repair of horny layer and matrix layer of skin, and promote growth of skin cells of human body; can enhance protein synthesis and cellular metabolism of skin cells, and has effects in delaying skin cell aging, promoting epidermal cell repair and growth, and making skin smooth and plump.
The existing AFGF freeze-dried powder preparation has poor relieving effect, burst release is easy to occur in slow release, the product stability is poor, and further cell aging treatment and poor repairing efficiency are further treated.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a freeze-dried powder preparation with a relieving effect so as to solve the problems in the prior art.
The invention solves the technical problems by adopting the following technical scheme:
the invention also provides a freeze-dried powder preparation with a relieving effect, which comprises the following raw materials in parts by weight:
20-30 parts of aFGF, 5-10 parts of slow-release skeleton improvement body, 4-7 parts of modified chitosan, 3-7 parts of filler, 2-4 parts of disintegrating agent, 2-5 parts of adhesive, 15-25 parts of dispersing agent and 30-40 parts of deionized water;
the preparation method of the freeze-dried powder preparation comprises the following steps:
step one, preparation of a slow-release skeleton improvement body:
s101: grinding montmorillonite in a grinder with a speed of 1050-1150r/min for 20-30min to obtain grinding material;
s102: the grinding material is sent into 2-3 times of modification treatment liquid for modification stirring treatment, and after the treatment is finished, the grinding material is washed and dried;
s103: delivering the S102 product into a reactor at 145-155 ℃ for thermal calcination for 25-35min, and after the calcination is finished, washing and drying to obtain a slow-release skeleton improvement body;
stirring and mixing aFGF and a dispersing agent fully, adding a filling agent and a disintegrating agent, and stirring at the rotating speed of 450-550r/min for 15-25min, wherein the stirring is finished to obtain a sustained-release body;
step three, the body to be slowly released, the slow release skeleton improvement body and deionized water are preliminarily mixed fully to obtain a premix;
and step four, the premix in the step three and the modified chitosan are mixed for the second time until the mixture is fully mixed, and then frozen for 1 to 2 hours at the temperature of minus 5 ℃ to obtain the freeze-dried powder preparation.
Preferably, the freeze-dried powder preparation comprises the following raw materials in parts by weight:
25 parts of aFGF, 7.5 parts of slow-release skeleton improvement body, 5.5 parts of modified chitosan, 5 parts of filler, 3 parts of disintegrating agent, 3.5 parts of adhesive, 20 parts of dispersing agent and 35 parts of deionized water.
Preferably, the disintegrating agent is one of sodium carboxymethyl cellulose and crospovidone; the filler is hydroxypropyl starch.
Preferably, the dispersing agent is prepared by mixing polyoxyethylene and ethanol according to a weight ratio of 1:4; the binder is methylcellulose.
Preferably, the rotational speed of the modification stirring treatment is 450-550r/min, and the stirring time is 35-45min.
Preferably, the preparation method of the modified treatment fluid comprises the following steps:
s111: calcining 10-20 parts of talcum powder at 450-470 ℃ for 10-20min, and then cooling to room temperature at a speed of 1-4 ℃/s;
s112: adding into 35-45 parts of sodium alginate aqueous solution, then adding 2-5 parts of trehalose, fully mixing, then adding hydrochloric acid, and regulating the pH value to 5.0;
s113: and (3) standing the S111 product at 65-75 ℃ for 15-25min, and then dispersing at a high speed to obtain the modified treatment liquid.
The modified treatment fluid adopts talcum powder to disperse through calcination and sodium alginate solution, and then is compounded with montmorillonite to improve the montmorillonite, and the modified montmorillonite and talcum powder compound body is used as a framework of the freeze-dried powder to play a role in supporting the product, thereby providing a foundation for slow release dissolution.
The inventor of the invention finds that the product has burst release phenomenon in 2-6 hours without adding a slow release skeleton improving body, the aFGF release amount is faster and larger, the release of active ingredients is easy to cause too fast, and long-acting repairing effect is difficult to realize, while in the embodiment 3, the dissolution release efficiency of the product is slowly carried out until 24 hours reach the optimal state as seen from 2, 6, 12 and 24 hours, and the product has obvious release slow release improving effect;
the slow-release skeleton improvement body is replaced by montmorillonite, and in the preparation process, talcum powder is replaced by calcium carbonate, and the slow-release effect is not obvious as the improvement effect of the invention, and the slow-release effect of the invention is optimal;
after the chitosan is modified, the stability effect can be achieved in the early-stage slow release, the modification methods of the chitosan are different, the slow release stability is different, and the improvement effect is most obvious by adopting the method of the invention.
Preferably, the mass fraction of the sodium alginate aqueous solution is 0.5-2%.
Preferably, the rotating speed of the high-speed dispersion is 1200-1500r/min, and the dispersing time is 35-45min.
Preferably, the modification method of the modified chitosan comprises the following steps:
mixing citric acid and acetic acid according to a weight ratio of 3:1 to obtain mixed acid, and then adding deionized water with the total amount of 4-5 times of the mixed acid to obtain mixed acid solution;
adding chitosan into 3-4 times of mixed acid solution to prepare chitosan solution;
standing chitosan solution at 30-40deg.C for 15-25min, adding binder, mixing thoroughly, and drying to obtain modified chitosan.
Preferably, the drying condition is that the surface water content of the chitosan is lower than 5 percent after drying at 75-85 ℃.
Compared with the prior art, the invention has the following beneficial effects:
according to the freeze-dried powder preparation, the aFGF is dispersed by the dispersing agent, the disintegrating agent and the filling agent are added, so that the high-efficiency dissolution of the aFGF can be promoted, the slow-release body to be slowly released is prepared by matching with the slow-release skeleton improvement body, the slow-release skeleton improvement body can enhance the slow-release dissolution efficiency of the aFGF, the improvement of the modified chitosan can further improve the dissolution efficiency of the product, the problem of sudden release of the product is solved, the stability of the product is improved, the slow-release efficiency of the product is improved, and thus the product has a relieving effect and can effectively resist aging for a long time.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The freeze-dried powder preparation with the relieving effect comprises the following raw materials in parts by weight:
20-30 parts of aFGF, 5-10 parts of slow-release skeleton improvement body, 4-7 parts of modified chitosan, 3-7 parts of filler, 2-4 parts of disintegrating agent, 2-5 parts of adhesive, 15-25 parts of dispersing agent and 30-40 parts of deionized water;
the preparation method of the freeze-dried powder preparation comprises the following steps:
step one, preparation of a slow-release skeleton improvement body:
s101: grinding montmorillonite in a grinder with a speed of 1050-1150r/min for 20-30min to obtain grinding material;
s102: the grinding material is sent into 2-3 times of modification treatment liquid for modification stirring treatment, and after the treatment is finished, the grinding material is washed and dried;
s103: delivering the S102 product into a reactor at 145-155 ℃ for thermal calcination for 25-35min, and after the calcination is finished, washing and drying to obtain a slow-release skeleton improvement body;
stirring and mixing aFGF and a dispersing agent fully, adding a filling agent and a disintegrating agent, and stirring at the rotating speed of 450-550r/min for 15-25min, wherein the stirring is finished to obtain a sustained-release body;
step three, the body to be slowly released, the slow release skeleton improvement body and deionized water are preliminarily mixed fully to obtain a premix;
and step four, the premix in the step three and the modified chitosan are mixed for the second time until the mixture is fully mixed, and then frozen for 1 to 2 hours at the temperature of minus 5 ℃ to obtain the freeze-dried powder preparation.
The freeze-dried powder preparation of the embodiment comprises the following raw materials in parts by weight:
25 parts of aFGF, 7.5 parts of slow-release skeleton improvement body, 5.5 parts of modified chitosan, 5 parts of filler, 3 parts of disintegrating agent, 3.5 parts of adhesive, 20 parts of dispersing agent and 35 parts of deionized water.
The disintegrating agent of the embodiment is one of sodium carboxymethyl cellulose and crospovidone; the filler is hydroxypropyl starch.
The dispersing agent of the embodiment is prepared by mixing polyoxyethylene and ethanol according to the weight ratio of 1:4; the binder is methylcellulose.
The rotational speed of the modification stirring treatment is 450-550r/min, and the stirring time is 35-45min.
The preparation method of the modified treatment liquid in the embodiment comprises the following steps:
s111: calcining 10-20 parts of talcum powder at 450-470 ℃ for 10-20min, and then cooling to room temperature at a speed of 1-4 ℃/s;
s112: adding into 35-45 parts of sodium alginate aqueous solution, then adding 2-5 parts of trehalose, fully mixing, then adding hydrochloric acid, and regulating the pH value to 5.0;
s113: and (3) standing the S111 product at 65-75 ℃ for 15-25min, and then dispersing at a high speed to obtain the modified treatment liquid.
The mass fraction of the sodium alginate aqueous solution of the embodiment is 0.5-2%.
The high-speed dispersion speed of the embodiment is 1200-1500r/min, and the dispersion time is 35-45min.
The modification method of the modified chitosan in the embodiment comprises the following steps:
mixing citric acid and acetic acid according to a weight ratio of 3:1 to obtain mixed acid, and then adding deionized water with the total amount of 4-5 times of the mixed acid to obtain mixed acid solution;
adding chitosan into 3-4 times of mixed acid solution to prepare chitosan solution;
standing chitosan solution at 30-40deg.C for 15-25min, adding binder, mixing thoroughly, and drying to obtain modified chitosan.
The drying conditions of this example were dried at 75-85 ℃ until the surface moisture content of the chitosan was below 5%.
Example 1.
The freeze-dried powder preparation with the relieving effect comprises the following raw materials in parts by weight:
20 parts of aFGF, 5 parts of slow-release skeleton improvement body, 4 parts of modified chitosan, 3 parts of filler, 2 parts of disintegrating agent, 2 parts of adhesive, 15 parts of dispersing agent and 30 parts of deionized water;
the preparation method of the freeze-dried powder preparation comprises the following steps:
step one, preparation of a slow-release skeleton improvement body:
s101: grinding montmorillonite in 1050r/min grinder for 20min to obtain grinding material;
s102: the grinding material is sent into 2 times of modification treatment liquid for modification stirring treatment, and after the treatment is finished, the grinding material is washed and dried;
s103: delivering the S102 product into a reactor at 145 ℃ for thermal calcination for 25min, and after the calcination is finished, washing and drying to obtain a slow-release skeleton improvement body;
stirring and mixing aFGF and a dispersing agent fully, adding a filling agent and a disintegrating agent, and stirring at the rotating speed of 450r/min for 15min, wherein the stirring is finished to obtain a to-be-slowly-released body;
step three, the body to be slowly released, the slow release skeleton improvement body and deionized water are preliminarily mixed fully to obtain a premix;
and step four, the premix in the step three is mixed with the modified chitosan for the second time, and after the mixing is finished, the mixture is frozen for 1 hour at the temperature of minus 5 ℃ to obtain the freeze-dried powder preparation.
The disintegrant of this example is sodium carboxymethyl cellulose; the filler is hydroxypropyl starch.
The dispersing agent of the embodiment is prepared by mixing polyoxyethylene and ethanol according to the weight ratio of 1:4; the binder is methylcellulose.
The rotational speed of the modification stirring treatment in this example was 450r/min, and the stirring time was 35min.
The preparation method of the modified treatment liquid in the embodiment comprises the following steps:
s111: calcining 10 parts of talcum powder at 450 ℃ for 10min, and then, at a speed of 1 ℃/s, setting the room temperature;
s112: adding into 35 parts of sodium alginate aqueous solution, then adding 2 parts of trehalose, fully mixing, then adding hydrochloric acid, and regulating the pH value to 5.0;
s113: and (3) standing the S111 product at 65 ℃ for 15min, and then dispersing at a high speed to obtain the modified treatment liquid.
The mass fraction of the sodium alginate aqueous solution of this example was 0.5%.
The rotational speed of the high-speed dispersion in this example was 1200r/min, and the dispersion time was 35min.
The modification method of the modified chitosan in the embodiment comprises the following steps:
mixing citric acid and acetic acid according to a weight ratio of 3:1 to obtain mixed acid, and then adding deionized water with the total amount of 4 times of the mixed acid to obtain mixed acid solution;
adding chitosan into 3 times of mixed acid solution to prepare chitosan solution;
standing chitosan solution at 30deg.C for 15min, adding binder, mixing thoroughly, and drying to obtain modified chitosan.
The drying conditions of this example were dried at 75 ℃ until the surface moisture content of the chitosan was below 5%.
Example 2.
The freeze-dried powder preparation with the relieving effect comprises the following raw materials in parts by weight:
30 parts of aFGF, 10 parts of slow-release skeleton improvement body, 7 parts of modified chitosan, 7 parts of filling agent, 4 parts of disintegrating agent, 5 parts of adhesive, 25 parts of dispersing agent and 40 parts of deionized water;
the preparation method of the freeze-dried powder preparation comprises the following steps:
step one, preparation of a slow-release skeleton improvement body:
s101: grinding montmorillonite in 1150r/min grinder for 30min to obtain grinding material;
s102: the grinding material is sent into 3 times of modification treatment liquid for modification and stirring treatment, and the treatment is finished, washed and dried;
s103: delivering the S102 product into a furnace at 155 ℃ for thermal calcination for 35min, and after the calcination is finished, washing and drying to obtain a slow-release skeleton improvement body;
stirring and mixing aFGF and a dispersing agent fully, adding a filling agent and a disintegrating agent, and stirring at a rotating speed of 550r/min for 25min, wherein the stirring is finished to obtain a to-be-slowly-released body;
step three, the body to be slowly released, the slow release skeleton improvement body and deionized water are preliminarily mixed fully to obtain a premix;
and step four, the premix in the step three is mixed with the modified chitosan for the second time, and after the mixing is finished, the mixture is frozen for 2 hours at the temperature of minus 5 ℃ to obtain the freeze-dried powder preparation.
Preferably, the disintegrant is one of crospovidone; the filler is hydroxypropyl starch.
Preferably, the dispersing agent is prepared by mixing polyoxyethylene and ethanol according to a weight ratio of 1:4; the binder is methylcellulose.
The rotational speed of the modification stirring treatment in this example was 550r/min, and the stirring time was 45min.
The preparation method of the modified treatment liquid in the embodiment comprises the following steps:
s111: calcining 20 parts of talcum powder at 470 ℃ for 20min, and then, cooling to room temperature at a speed of 4 ℃/s;
s112: adding into 45 parts of sodium alginate aqueous solution, then adding 5 parts of trehalose, fully mixing, then adding hydrochloric acid, and regulating the pH value to 5.0;
s113: and (3) standing the S111 product at 75 ℃ for 25min, and then dispersing at a high speed to obtain the modified treatment liquid.
The mass fraction of the sodium alginate aqueous solution of this example was 2%.
The rotational speed of the high-speed dispersion in this example was 1500r/min, and the dispersion time was 45min.
The modification method of the modified chitosan in the embodiment comprises the following steps:
mixing citric acid and acetic acid according to a weight ratio of 3:1 to obtain mixed acid, and then adding deionized water with the total amount of 5 times of the mixed acid to obtain mixed acid solution;
adding chitosan into 4 times of mixed acid solution to prepare chitosan solution;
standing chitosan solution at 40deg.C for 25min, adding binder, mixing thoroughly, and drying to obtain modified chitosan.
The drying conditions of this example were dried at 85 ℃ until the surface moisture content of the chitosan was below 5%.
Example 3.
The freeze-dried powder preparation with the relieving effect comprises the following raw materials in parts by weight:
25 parts of aFGF, 7.5 parts of slow-release skeleton improvement body, 5.5 parts of modified chitosan, 5 parts of filler, 3 parts of disintegrating agent, 3.5 parts of adhesive, 20 parts of dispersing agent and 35 parts of deionized water;
the preparation method of the freeze-dried powder preparation comprises the following steps:
step one, preparation of a slow-release skeleton improvement body:
s101: grinding montmorillonite in a grinder at 1100r/min for 25min to obtain grinding material;
s102: the grinding material is sent into 2.5 times of modification treatment liquid for modification stirring treatment, and the treatment is finished, washed and dried;
s103: delivering the S102 product into a furnace at 150 ℃ for thermal calcination for 30min, and after the calcination is finished, washing and drying to obtain a slow-release skeleton improvement body;
stirring and mixing aFGF and a dispersing agent fully, adding a filling agent and a disintegrating agent, and stirring at a rotating speed of 500r/min for 20min, wherein the stirring is finished to obtain a to-be-slowly-released body;
step three, the body to be slowly released, the slow release skeleton improvement body and deionized water are preliminarily mixed fully to obtain a premix;
and step four, the premix in the step three is mixed with the modified chitosan for the second time, and after the mixing is finished, the mixture is frozen for 1.5 hours at the temperature of minus 5 ℃ to obtain the freeze-dried powder preparation.
The disintegrating agent of the embodiment is one of sodium carboxymethyl cellulose and crospovidone; the filler is hydroxypropyl starch.
The dispersing agent of the embodiment is prepared by mixing polyoxyethylene and ethanol according to the weight ratio of 1:4; the binder is methylcellulose.
The rotational speed of the modification stirring treatment in this example was 500r/min, and the stirring time was 40min.
The preparation method of the modified treatment liquid in the embodiment comprises the following steps:
s111: 15 parts of talcum powder is calcined for 15min at 460 ℃ before the room temperature is reached at the speed of 2.5 ℃/s;
s112: adding into 40 parts of sodium alginate aqueous solution, then adding 3.5 parts of trehalose, fully mixing, then adding hydrochloric acid, and regulating the pH value to 5.0;
s113: and (3) standing the S111 product at 70 ℃ for 15-25min, and then dispersing at a high speed to obtain the modified treatment liquid.
The mass fraction of the sodium alginate aqueous solution of this example was 1.25%.
The rotational speed of the high-speed dispersion in this example was 1350r/min, and the dispersion time was 40min.
The modification method of the modified chitosan in the embodiment comprises the following steps:
mixing citric acid and acetic acid according to a weight ratio of 3:1 to obtain mixed acid, and then adding deionized water with the total amount of 4-5 times of the mixed acid to obtain mixed acid solution;
adding chitosan into 3.5 times of mixed acid solution to prepare chitosan solution;
and standing the chitosan solution at 35 ℃ for 20min, then adding the adhesive, fully mixing, and drying to obtain the modified chitosan.
The drying conditions of this example were dried at 80 ℃ until the surface moisture content of the chitosan was below 5%.
Comparative example 1.
The difference from example 3 is that no slow-release matrix modification was added.
Comparative example 2.
The difference from example 3 is that the slow-release matrix modification is replaced by montmorillonite.
Comparative example 3.
The difference from example 3 is that the talc powder is replaced by calcium carbonate in the preparation of the slow-release matrix modification.
Comparative example 4.
The difference from example 3 is the method of preparing a slow release matrix modification;
mixing montmorillonite and talcum powder according to a weight ratio of 3:1, then sending the mixture into sodium alginate aqueous solution with a mass fraction of 2-3% which is 3 times of the total amount of the montmorillonite for dispersion, washing with water, drying, calcining at 125 ℃ for 10min, and obtaining the slow-release skeleton improvement body.
Comparative example 5.
The difference from example 3 is that no modified chitosan was added.
Comparative example 6.
The difference from example 3 is that the modified chitosan is replaced by chitosan.
Comparative example 7.
The difference from example 3 is the modification of chitosan:
adding chitosan into acetic acid solution with the concentration of 3.5 times to prepare chitosan solution, then washing with water to be neutral, and performing ion washing, water washing and drying to obtain the modified chitosan.
The dissolution performance of the aFGF products of examples 1-3 and comparative examples 1-7 were tested as follows:
as can be seen from comparative example 1 and example 3, the product has burst release phenomenon in 2-6 hours without adding a slow release skeleton improving body, the aFGF release amount is faster and larger, the release of active ingredients is easy to cause too fast, and long-acting repairing effect is difficult to realize, while in example 3, as can be seen from 2, 6, 12 and 24 hours, the dissolution release efficiency of the product is slowly carried out until 24 hours reaches the optimal state, and the slow release improving effect is obvious;
from comparative examples 2-4, the slow-release skeleton improvement body is replaced by montmorillonite, and talcum powder is replaced by calcium carbonate in the preparation process, the preparation method is different, the slow-release effect is not obvious as the improvement effect of the invention, and the slow-release effect of the invention is optimal;
from comparative examples 5 to 7, the modified chitosan can play a role in stability in the early-stage slow release, and the modified chitosan has different slow release stability, so that the improved effect is most obvious by adopting the method of the invention.
The product was subjected to stability testing:
after the product was stored at-10℃for 24 hours, performance tests were conducted using examples 1 to 3, comparative examples 1 to 7
After the product is stored for 24 hours at the temperature of minus 10 ℃, compared with examples 1 to 7, no slow-release skeleton improvement body is added, the product has obvious sudden release phenomenon in the early stage of 2 and 6 hours, the addition of the slow-release skeleton improvement body has obvious improvement on the stability of the product, and meanwhile, after the chitosan is modified, the chitosan also has the effect of synergistic improvement on the stability of the product, and the dissolution stability of the product is improved, so that the relief effect is improved, and the anti-aging is effectively carried out for a long time.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Furthermore, it should be understood that although the present disclosure describes embodiments, not every embodiment is provided with a separate embodiment, and that this description is provided for clarity only, and that the disclosure is not limited to the embodiments described in detail below, and that the embodiments described in the examples may be combined as appropriate to form other embodiments that will be apparent to those skilled in the art.
Claims (8)
1. The freeze-dried powder preparation with the relieving effect is characterized by comprising the following raw materials in parts by weight:
20-30 parts of aFGF, 5-10 parts of slow-release skeleton improvement body, 4-7 parts of modified chitosan, 3-7 parts of filler, 2-4 parts of disintegrating agent, 2-5 parts of adhesive, 15-25 parts of dispersing agent and 30-40 parts of deionized water;
the preparation method of the freeze-dried powder preparation comprises the following steps:
step one, preparation of a slow-release skeleton improvement body:
s101: grinding montmorillonite in a grinder with a speed of 1050-1150r/min for 20-30min to obtain grinding material;
s102: the grinding material is sent into 2-3 times of modification treatment liquid for modification stirring treatment, and after the treatment is finished, the grinding material is washed and dried;
s103: delivering the S102 product into a reactor at 145-155 ℃ for thermal calcination for 25-35min, and after the calcination is finished, washing and drying to obtain a slow-release skeleton improvement body;
stirring and mixing aFGF and a dispersing agent fully, adding a filling agent and a disintegrating agent, and stirring at the rotating speed of 450-550r/min for 15-25min, wherein the stirring is finished to obtain a sustained-release body;
step three, the body to be slowly released, the slow release skeleton improvement body and deionized water are preliminarily mixed fully to obtain a premix;
step four, the premix in the step three and the modified chitosan are mixed for the second time until the mixture is fully mixed, and then frozen for 1 to 2 hours at the temperature of minus 5 ℃ to obtain a freeze-dried powder preparation; the preparation method of the modified treatment fluid comprises the following steps:
s111: calcining 10-20 parts of talcum powder at 450-470 ℃ for 10-20min, and then cooling to room temperature at a speed of 1-4 ℃/s;
s112: adding into 35-45 parts of sodium alginate aqueous solution, then adding 2-5 parts of trehalose, fully mixing, then adding hydrochloric acid, and regulating the pH value to 5.0;
s113: standing the S111 product at 65-75 ℃ for 15-25min, and then dispersing at a high speed to obtain a modified treatment liquid; the modification method of the modified chitosan comprises the following steps:
mixing citric acid and acetic acid according to a weight ratio of 3:1 to obtain mixed acid, and then adding deionized water with the total amount of 4-5 times of the mixed acid to obtain mixed acid solution;
adding chitosan into 3-4 times of mixed acid solution to prepare chitosan solution;
standing chitosan solution at 30-40deg.C for 15-25min, adding binder, mixing thoroughly, and drying to obtain modified chitosan.
2. The lyophilized powder formulation with soothing effect according to claim 1, wherein the lyophilized powder formulation comprises the following raw materials in parts by weight:
25 parts of aFGF, 7.5 parts of slow-release skeleton improvement body, 5.5 parts of modified chitosan, 5 parts of filler, 3 parts of disintegrating agent, 3.5 parts of adhesive, 20 parts of dispersing agent and 35 parts of deionized water.
3. The lyophilized powder formulation with soothing effect according to claim 1, wherein the disintegrant is one of sodium carboxymethylcellulose and crospovidone; the filler is hydroxypropyl starch.
4. The lyophilized powder preparation with relieving effect according to claim 1, wherein the dispersing agent is prepared by mixing polyoxyethylene and ethanol according to a weight ratio of 1:4; the binder is methylcellulose.
5. The lyophilized powder formulation with soothing function according to claim 1, wherein the rotational speed of the modified stirring treatment is 450-550r/min and the stirring time is 35-45min.
6. The lyophilized powder formulation with soothing function according to claim 1, wherein the mass fraction of the aqueous sodium alginate solution is 0.5-2%.
7. The lyophilized powder formulation with soothing effect according to claim 1, wherein the high-speed dispersion speed is 1200-1500r/min and the dispersion time is 35-45min.
8. The lyophilized powder formulation with soothing effect according to claim 1, wherein the drying condition is at 75-85 ℃ until the surface water content of chitosan is below 5%.
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