CN114470171A - Collagen liposome freeze-dried milk and preparation method thereof - Google Patents
Collagen liposome freeze-dried milk and preparation method thereof Download PDFInfo
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- 102000008186 Collagen Human genes 0.000 title claims abstract description 81
- 108010035532 Collagen Proteins 0.000 title claims abstract description 81
- 229920001436 collagen Polymers 0.000 title claims abstract description 81
- 235000013336 milk Nutrition 0.000 title claims abstract description 14
- 239000008267 milk Substances 0.000 title claims abstract description 14
- 210000004080 milk Anatomy 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 239000011259 mixed solution Substances 0.000 claims abstract description 29
- 238000001035 drying Methods 0.000 claims abstract description 24
- 239000000243 solution Substances 0.000 claims abstract description 23
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 22
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 21
- 239000001116 FEMA 4028 Substances 0.000 claims abstract description 21
- 229930195725 Mannitol Natural products 0.000 claims abstract description 21
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims abstract description 21
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- 229960004853 betadex Drugs 0.000 claims abstract description 21
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000000839 emulsion Substances 0.000 claims abstract description 15
- 230000008014 freezing Effects 0.000 claims description 26
- 238000003756 stirring Methods 0.000 claims description 22
- 238000007710 freezing Methods 0.000 claims description 18
- 238000010438 heat treatment Methods 0.000 claims description 16
- 239000008213 purified water Substances 0.000 claims description 16
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- 241000235058 Komagataella pastoris Species 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- 238000004321 preservation Methods 0.000 claims description 2
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- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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Abstract
The invention discloses a collagen liposome freeze-dried emulsion and a preparation method thereof. According to the method, mannitol and beta-cyclodextrin are sequentially added into a collagen liposome solution according to a proportion to form a mixed solution, and then a freeze-drying process is adopted to extract solute of the solution to prepare the freeze-dried milk. The invention adopts the freeze-drying process to prepare the collagen liposome freeze-dried emulsion, can force the solution to be supercooled and crystallized, is favorable for improving the drying efficiency under the negative pressure condition, and the dried part forms a loose structure along with the gradual extraction of water in the solution, and the mannitol plays the role of a skeleton, and the beta-cyclodextrin can surround the bioactive material in the drying process, thereby improving the stability of the liposome structure. In a dry environment, the collagen can be effectively prevented from enzymolysis, the stability of the product is improved, and the long-term storage of the product is facilitated.
Description
Technical Field
The invention relates to the technical field of medical instruments, and relates to a collagen liposome freeze-dried emulsion and a preparation method thereof.
Background
Liposomes (Liposomes, Lips) are micro-vesicle bodies formed by encapsulating active substances in lipid bilayers, wherein the Liposomes can wrap water-soluble drugs in internal water-based vesicles or fat-soluble drugs in lipid bilayers and then directly act on the lipid bilayers of stratum corneum cells to improve the permeation of the active substances and promote the transdermal absorption of the active substances, and the Liposomes can completely permeate the stratum corneum through skin accessory organs or intercellular pathways to reach the dermis to form an active substance storage reservoir which slowly and permanently acts on an affected part. The phospholipid and cholesterol in the liposome are inherent components of human body, and have no irritation and toxicity to human body.
The collagen liposome is prepared by wrapping high-activity recombinant collagen (RHC) in liposome vesicle by liposome wrapping technology, so that the recombinant collagen can penetrate through the epidermis of skin in an accelerated manner and completely permeate to the basal layer of the skin, and the effects of resisting aging, repairing and the like can be rapidly exerted. However, liposomes are unstable in aqueous environments and are prone to leakage in solution and hydrolysis of phospholipids.
Disclosure of Invention
The invention aims to provide a collagen liposome freeze-dried emulsion and a preparation method thereof.
The technical scheme for realizing the purpose of the invention is as follows:
the collagen liposome freeze-dried milk comprises the following components in parts by weight of 100 parts: the collagen liposome preparation method comprises the following steps of 10 parts of collagen liposome, 5-10 parts of mannitol, 0.5-2 parts of beta-cyclodextrin and 78-84.5 parts of purified water, and is characterized by comprising the following steps:
(1) according to the proportion, firstly adding collagen liposome (LLA) into purified water, stirring and dissolving at normal temperature to obtain a collagen liposome solution, then sequentially adding mannitol and beta-cyclodextrin, and stirring and dissolving at normal temperature to obtain a mixed solution;
(2) placing the mixed solution in a freeze dryer, setting the cooling temperature to be 5 +/-1 ℃, pre-cooling for 20-30 min, starting a pre-freezing program, wherein the freezing temperature is-40 to-50 ℃, and the freezing time is 2-3 h;
(3) after pre-freezing, automatically entering a primary drying stage by a program, setting the vacuum degree to be 0.1-0.5 mbar, the temperature of the plate layer to be-25-20 ℃, keeping the temperature for 3-4 h, heating the plate layer to-15 ℃, keeping the temperature for 2-3 h, heating the temperature of the plate layer to 0 ℃, and keeping the temperature for 1-2 h;
(4) and (3) automatically entering a secondary drying stage after the primary drying, setting the temperature of the plate layer to be increased to 15 ℃, keeping the temperature for 1-1.5 hours, setting the vacuum degree to be 0.01mbar, and setting the temperature of the plate layer to be increased to 30 ℃, and keeping the temperature for 2-4 hours to obtain the collagen liposome freeze-dried emulsion.
The collagen in the collagen liposome is recombinant human collagen, is produced by fermenting Pichia pastoris with the preservation number of CGMCC No.5021, and has the molecular weight of 55 KDa.
The average particle size of the collagen liposome vesicle is 300-320 nm. Compared with the prior art, the invention has the following advantages:
(1) the invention takes collagen liposome (LLA), mannitol and beta-cyclodextrin as raw materials to prepare the collagen liposome freeze-dried emulsion, mannitol as a skeleton agent in the liposome freeze-drying process can surround the bioactive material in the drying process to form a porous network structure, so that the bioactive material is prevented from being directly exposed in the surrounding environment, and the beta-cyclodextrin can surround the bioactive material in the drying process, thereby improving the stability of the liposome vesicle structure and ensuring the encapsulation efficiency of the product.
(2) The freeze-dried emulsion of the collagen liposome is prepared by adopting a freeze-drying process, the solution can be forced to be supercooled and crystallized, the drying efficiency can be improved under the negative pressure condition, the dried part forms a loose structure along with the gradual extraction of water in the solution, and mannitol plays a role of a skeleton. In a dry environment, the collagen is effectively prevented from enzymolysis, the stability of the product is improved, and the long-term storage of the product is facilitated.
Drawings
FIG. 1 is a schematic diagram of a collagen liposome product prepared in example 1;
fig. 2 is a schematic diagram of a product of the collagen liposome prepared in comparative example 1.
Detailed Description
The present invention will be described in more detail with reference to the following examples and the accompanying drawings.
The collagen liposomes used in the following examples were purchased from Jiangsu Jiangshan Convergence Biotech, Inc.
Example 1
The freeze-dried collagen liposome milk of the present example was prepared by the following steps:
respectively weighing 10 parts of collagen liposome, 5 parts of mannitol, 0.5 part of beta-cyclodextrin and 84.5 parts of purified water according to parts by mass. Adding collagen liposome into purified water, stirring and dissolving at normal temperature to obtain a collagen liposome solution, adding mannitol into the collagen liposome solution, stirring and dissolving at normal temperature to obtain a mixed solution A, adding beta-cyclodextrin into the mixed solution A, and stirring and dissolving at normal temperature to obtain a final mixed solution. And (3) placing the final mixed solution in a freeze dryer, setting the temperature of the plate layer to be 5 ℃, pre-cooling for 30min, starting a pre-freezing program, setting the freezing temperature to be 40 ℃ below zero, freezing for 3h to obtain a frozen product, adjusting the temperature of the plate layer to be 20 ℃ below zero, setting the vacuum degree to be 0.5mbar, keeping the temperature for 4h, heating the plate layer to be 15 ℃ below zero, keeping the temperature for 3h, heating the temperature of the plate layer to be 0 ℃, and keeping the temperature for 2 h. And (3) automatically entering a secondary drying stage after the primary drying is finished, setting the temperature of the plate layer to be increased to 15 ℃, keeping the temperature for 1h, setting the vacuum degree to be 0.01mbar, increasing the temperature of the plate layer to be 30 ℃, keeping the temperature for 4h, and taking out of the box to obtain the collagen liposome freeze-dried emulsion.
Example 2
The freeze-dried collagen liposome milk of the present example was prepared by the following steps:
respectively weighing 10 parts of collagen liposome, 10 parts of mannitol, 2 parts of beta-cyclodextrin and 78 parts of purified water according to parts by mass. Adding collagen liposome into purified water, stirring and dissolving at normal temperature to obtain a collagen liposome solution, adding mannitol into the collagen liposome solution, stirring and dissolving at normal temperature to obtain a mixed solution A, adding beta-cyclodextrin into the mixed solution A, and stirring and dissolving at normal temperature to obtain a final mixed solution. And (3) placing the final mixed solution in a freeze dryer, setting the temperature of a plate layer to be 5 ℃, pre-cooling for 30min, starting a pre-freezing program, setting the freezing temperature to be-40 ℃, freezing for 2h to obtain a frozen product, adjusting the temperature of the plate layer to be-25 ℃, setting the vacuum degree to be 0.1mbar, keeping the temperature for 4h, heating the plate layer to be-15 ℃, keeping the temperature for 3h, heating the plate layer to be 0 ℃, and keeping the temperature for 2 h. And (3) automatically entering a secondary drying stage after the primary drying is finished, setting the temperature of the plate layer to be increased to 15 ℃, keeping the temperature for 1h, setting the vacuum degree to be 0.01mbar, increasing the temperature of the plate layer to be 30 ℃, keeping the temperature for 4h, and taking out of the box to obtain the collagen liposome freeze-dried emulsion.
Example 3
The freeze-dried collagen liposome milk of the present example was prepared by the following steps:
respectively weighing 10 parts of collagen liposome, 5 parts of mannitol, 0.5 part of beta-cyclodextrin and 84.5 parts of purified water according to parts by mass. Adding collagen liposome into purified water, stirring and dissolving at normal temperature to obtain a collagen liposome solution, adding mannitol into the collagen liposome solution, stirring and dissolving at normal temperature to obtain a mixed solution A, adding beta-cyclodextrin into the mixed solution A, and stirring and dissolving at normal temperature to obtain a final mixed solution. And (3) placing the final mixed solution in a freeze dryer, setting the temperature of a plate layer to be 5 ℃, pre-cooling for 30min, starting a pre-freezing program, setting the freezing temperature to be-40 ℃, freezing for 2h to obtain a frozen product, adjusting the temperature of the plate layer to be-25 ℃, setting the vacuum degree to be 0.1mbar, keeping the temperature for 4h, heating the plate layer to be-15 ℃, keeping the temperature for 3h, heating the plate layer to be 0 ℃, and keeping the temperature for 2 h. And (3) automatically entering a secondary drying stage after the primary drying is finished, setting the temperature of the plate layer to be increased to 15 ℃, keeping the temperature for 1h, setting the vacuum degree to be 0.01mbar, increasing the temperature of the plate layer to be 30 ℃, keeping the temperature for 4h, and taking out of the box to obtain the collagen liposome freeze-dried emulsion.
Comparative example 1
The collagen liposome freeze-dried milk of the comparative example was prepared by the following steps:
respectively weighing 10 parts of collagen liposome, 2 parts of mannitol, 0.5 part of beta-cyclodextrin and 87.5 parts of purified water according to parts by mass. Adding collagen liposome into purified water, stirring and dissolving at normal temperature to obtain a collagen liposome solution, adding mannitol into the collagen liposome solution, stirring and dissolving at normal temperature to obtain a mixed solution A, adding beta-cyclodextrin into the mixed solution A, and stirring and dissolving at normal temperature to obtain a final mixed solution. And (3) placing the final mixed solution in a freeze dryer, setting the temperature of a plate layer to be 5 ℃, precooling for 30min, starting a pre-freezing program, setting the freezing temperature to be-40 ℃, freezing for 2.5h to obtain a frozen product, adjusting the temperature of the plate layer to be-22.5 ℃, setting the vacuum degree to be 0.3mbar, keeping for 4h, heating the plate layer to be-15 ℃, keeping for 3h, heating the plate layer to be 0 ℃, and keeping for 2 h. And (3) automatically entering a secondary drying stage after the primary drying is finished, setting the temperature of the plate layer to be increased to 15 ℃, keeping the temperature for 1h, setting the vacuum degree to be 0.01mbar, increasing the temperature of the plate layer to be 30 ℃, keeping the temperature for 3h, and taking out of the box to obtain the collagen liposome freeze-dried emulsion.
Comparative example 2
The collagen liposome freeze-dried milk of the comparative example was prepared by the following steps:
respectively weighing 10 parts of collagen liposome, 7.5 parts of mannitol, 1.25 parts of beta-cyclodextrin and 81.25 parts of purified water according to parts by mass. Adding collagen liposome into purified water, stirring and dissolving at normal temperature to obtain a collagen liposome solution with the mass fraction of 10%, adding mannitol into the collagen liposome solution, stirring and dissolving at normal temperature to obtain a mixed solution A, adding beta-cyclodextrin into the mixed solution A, and stirring and dissolving at normal temperature to obtain a final mixed solution. And (3) placing the final mixed solution in a freeze dryer, setting the temperature of a plate layer to be 5 ℃, pre-cooling for 30min, starting a pre-freezing program, setting the freezing temperature to be-40 ℃, freezing for 1h to obtain a frozen product, adjusting the temperature of the plate layer to be-22.5 ℃, setting the vacuum degree to be 0.3mbar, keeping the temperature for 4h, heating the plate layer to be-15 ℃, keeping the temperature for 3h, heating the temperature of the plate layer to be 0 ℃, and keeping the temperature for 2 h. And (3) automatically entering a secondary drying stage after the primary drying is finished, setting the temperature of the plate layer to be increased to 15 ℃, keeping the temperature for 1h, setting the vacuum degree to be 0.01mbar, increasing the temperature of the plate layer to be 30 ℃, keeping the temperature for 3h, and taking out of the box to obtain the collagen liposome freeze-dried emulsion.
Comparative example 3
The collagen liposome freeze-dried milk of the comparative example was prepared by the following steps:
respectively weighing 10 parts of collagen liposome, 7.5 parts of mannitol, 1.25 parts of beta-cyclodextrin and 81.25 parts of purified water according to parts by mass. Adding collagen liposome into purified water, stirring and dissolving at normal temperature to obtain a collagen liposome solution with the mass fraction of 10%, adding mannitol into the collagen liposome solution, stirring and dissolving at normal temperature to obtain a mixed solution A, adding beta-cyclodextrin into the mixed solution A, and stirring and dissolving at normal temperature to obtain a final mixed solution. And (3) placing the final mixed solution in a freeze dryer, setting the temperature of a plate layer to be 5 ℃, precooling for 30min, starting a pre-freezing program, setting the freezing temperature to be-40 ℃, freezing for 3h to obtain a frozen product, adjusting the temperature of the plate layer to be-22.5 ℃, setting the vacuum degree to be 0.8mbar, keeping the temperature for 4h, heating the plate layer to be-15 ℃, keeping the temperature for 3h, heating the temperature of the plate layer to be 0 ℃, and keeping the temperature for 2 h. And (3) automatically entering a secondary drying stage after the primary drying is finished, setting the temperature of the plate layer to be increased to 15 ℃, keeping the temperature for 1h, setting the vacuum degree to be 0.01mbar, increasing the temperature of the plate layer to be 30 ℃, keeping the temperature for 3h, and taking out of the box to obtain the collagen liposome freeze-dried emulsion.
TABLE 1 Performance data of freeze-dried milk of collagen liposome prepared in each example and comparative example
Note: the reconstitution capacity index in the table: + indicates that the compound can be redissolved by slight shaking; + means that the re-dissolution can be carried out by shaking with force; meaning that reconstitution can also occur with vigorous shaking, but at a slower rate; - -indicates insolubility after vigorous shaking.
As can be seen from table 1, the freeze-dried collagen liposome emulsions prepared in examples 1 to 3 can form a loose and porous dried product by using a freeze-drying process in combination with a mannitol skeleton agent, thereby ensuring the stability of the product and solving the problems of instability of the liposome in an aqueous environment, leakage in a solution, hydrolysis of phospholipids, and the like. The beta-cyclodextrin surrounds the bioactive material in the drying process, so that the stability of the bioactive material structure is protected, the strength of the loose porous structure is improved, and the degradation of collagen is effectively prevented.
Various other modifications and changes may be made by those skilled in the art based on the above-described technical solutions and concepts, and all such modifications and changes should fall within the scope of the claims of the present invention.
Claims (4)
1. The collagen liposome freeze-dried milk is characterized by comprising the following components in parts by weight of 100 parts: the collagen liposome preparation method comprises the following steps of 10 parts of collagen liposome, 5-10 parts of mannitol, 0.5-2 parts of beta-cyclodextrin and 78-84.5 parts of purified water, and is characterized by comprising the following steps:
(1) according to the proportion, firstly adding the collagen liposome into purified water, stirring and dissolving at normal temperature to obtain a collagen liposome solution, then sequentially adding mannitol and beta-cyclodextrin, and stirring and dissolving at normal temperature to obtain a mixed solution;
(2) placing the mixed solution in a freeze dryer, setting the cooling temperature to be 5 +/-1 ℃, pre-cooling for 20-30 min, starting a pre-freezing program, wherein the freezing temperature is-40 to-50 ℃, and the freezing time is 2-3 h;
(3) after pre-freezing, automatically entering a primary drying stage by a program, setting the vacuum degree to be 0.1-0.5 mbar, the temperature of the plate layer to be-25-20 ℃, keeping the temperature for 3-4 h, heating the plate layer to-15 ℃, keeping the temperature for 2-3 h, heating the temperature of the plate layer to 0 ℃, and keeping the temperature for 1-2 h;
(4) and (3) automatically entering a secondary drying stage after the primary drying, setting the temperature of the plate layer to be increased to 15 ℃, keeping the temperature for 1-1.5 hours, setting the vacuum degree to be 0.01mbar, and setting the temperature of the plate layer to be increased to 30 ℃, and keeping the temperature for 2-4 hours to obtain the collagen liposome freeze-dried emulsion.
2. The lyophilized milk of collagen liposome according to claim 1, wherein the collagen in said collagen liposome is recombinant human collagen.
3. The freeze-dried liposome of collagen according to claim 1, wherein the recombinant human collagen is produced by fermentation of Pichia pastoris with preservation number CGMCC No. 5021.
4. The freeze-dried collagen liposome milk according to claim 1, wherein the average particle size of the collagen liposome vesicle is 300-320 nm.
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|---|---|---|---|
| CN202111677274.0A CN114470171B (en) | 2021-12-31 | 2021-12-31 | Collagen liposome freeze-dried emulsion and preparation method thereof |
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| CN202111677274.0A CN114470171B (en) | 2021-12-31 | 2021-12-31 | Collagen liposome freeze-dried emulsion and preparation method thereof |
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| CN114470171A true CN114470171A (en) | 2022-05-13 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115227597A (en) * | 2022-08-01 | 2022-10-25 | 斐缦(长春)医药生物科技有限责任公司 | Active collagen freeze-dried preparation and preparation method and application thereof |
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| CN102443057A (en) * | 2011-10-26 | 2012-05-09 | 南京理工大学 | Recombinant humanized collagen and its preparation method |
| CN103110935A (en) * | 2013-01-25 | 2013-05-22 | 江苏圣宝罗药业有限公司 | Hydrolyzed collagen liposome for local skin and preparation method thereof |
| CN103536452A (en) * | 2013-11-06 | 2014-01-29 | 四川大学 | Active collagen-beta-cyclodextrin facial mask and preparation method thereof |
| CN108785128A (en) * | 2018-07-04 | 2018-11-13 | 肇庆市创业帮信息技术有限公司 | A kind of Hydrolyzed Collagen liposome and preparation method thereof of polypropylene glycol modification |
| CN111854339A (en) * | 2020-07-03 | 2020-10-30 | 江苏聚源医疗技术有限公司 | Freeze-drying method of collagen-containing skin-whitening, anti-wrinkle and skin-care freeze-dried powder |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102443057A (en) * | 2011-10-26 | 2012-05-09 | 南京理工大学 | Recombinant humanized collagen and its preparation method |
| CN103110935A (en) * | 2013-01-25 | 2013-05-22 | 江苏圣宝罗药业有限公司 | Hydrolyzed collagen liposome for local skin and preparation method thereof |
| CN103536452A (en) * | 2013-11-06 | 2014-01-29 | 四川大学 | Active collagen-beta-cyclodextrin facial mask and preparation method thereof |
| CN108785128A (en) * | 2018-07-04 | 2018-11-13 | 肇庆市创业帮信息技术有限公司 | A kind of Hydrolyzed Collagen liposome and preparation method thereof of polypropylene glycol modification |
| CN111854339A (en) * | 2020-07-03 | 2020-10-30 | 江苏聚源医疗技术有限公司 | Freeze-drying method of collagen-containing skin-whitening, anti-wrinkle and skin-care freeze-dried powder |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115227597A (en) * | 2022-08-01 | 2022-10-25 | 斐缦(长春)医药生物科技有限责任公司 | Active collagen freeze-dried preparation and preparation method and application thereof |
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