CN115501390A - Skin beautifying compound injection and preparation method thereof - Google Patents

Skin beautifying compound injection and preparation method thereof Download PDF

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Publication number
CN115501390A
CN115501390A CN202211275825.5A CN202211275825A CN115501390A CN 115501390 A CN115501390 A CN 115501390A CN 202211275825 A CN202211275825 A CN 202211275825A CN 115501390 A CN115501390 A CN 115501390A
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China
Prior art keywords
injection
polysaccharide
polylactic acid
percent
graft copolymer
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CN202211275825.5A
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Chinese (zh)
Inventor
孟昭旭
廉鹤
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Shenyang Pharmaceutical University
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Shenyang Pharmaceutical University
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Priority to CN202211275825.5A priority Critical patent/CN115501390A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/20Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23Carbohydrates
    • A61L2300/232Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/62Encapsulated active agents, e.g. emulsified droplets
    • A61L2300/626Liposomes, micelles, vesicles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/06Flowable or injectable implant compositions

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to a skin beautifying composite injection and a preparation method thereof, belonging to the technical field of beauty. The skin beautifying composite injection consists of the following components in percentage by mass: 0 to 25 percent of hyaluronic acid, 1 to 25 percent of polysaccharide-polylactic acid graft copolymer, 0 to 5 percent of mannitol and 45 to 99 percent of water solution for injection. The skin beautifying composite injection disclosed by the invention is prepared by adding the polysaccharide-polylactic acid graft copolymer serving as a component into the hyaluronic acid injection, wherein the polysaccharide-polylactic acid graft copolymer exists in a sol or micelle form, and can stimulate cells to generate collagen by using a degradation product lactic acid while keeping the needle penetration property, so that the long-acting wrinkle removing function is realized, and the skin beautifying composite injection is an iteration of the existing hyaluronic acid injection beautifying product.

Description

Skin beautifying compound injection and preparation method thereof
Technical Field
The invention relates to a skin beautifying composite injection and a preparation method thereof, belonging to the technical field of beauty.
Background
With age, human skin undergoes collagen loss and cell aging, resulting in the production of wrinkles. Subcutaneous injection of hyaluronic acid and its salts can engorge skin tissue, remove wrinkles and fill skin contours. However, hyaluronic acid and its salts do not stimulate collagen production by skin cells and have a limited duration of action, requiring repeated injections.
In recent years, graft copolymers have been developed rapidly, and natural polysaccharides such as dextran, chitosan, hyaluronic acid, etc. can be formed into graft copolymers with polylactic acid by various chemical synthesis methods. The polysaccharide-polylactic acid graft copolymer has good biocompatibility, can be degraded in a human body, and degradation products are non-toxic, and in addition, as an amphiphilic polymer, the polysaccharide-polylactic acid graft copolymer can form micelles or hydrogel, so that the polysaccharide-polylactic acid graft copolymer can be widely applied to the field of biological medicines as a drug delivery carrier. At present, the application of the polysaccharide-polylactic acid graft copolymer in the aspect of beautifying and wrinkle removal is not found.
Disclosure of Invention
The invention aims to provide a skin beautifying compound injection capable of stimulating cells to produce collagen.
The skin beautifying composite injection consists of the following components in percentage by mass:
0 to 25 percent of hyaluronic acid, 1 to 25 percent of polysaccharide-polylactic acid graft copolymer, 0 to 5 percent of mannitol and 45 to 99 percent of water solution for injection.
The sum of the mass percentages of the components is 100 percent.
Preferably, the injection consists of the following components in percentage by mass: 1 to 20 percent of hyaluronic acid, 10 to 25 percent of polysaccharide-polylactic acid graft copolymer, 0.1 to 5 percent of mannitol and 55 to 88.9 percent of water solution for injection.
In the skin beautifying composite injection, the polysaccharide-polylactic acid graft copolymer exists in the form of sol or micelle in the injection.
Preferably, the polysaccharide in the polysaccharide-polylactic acid graft copolymer is glucan, chitosan or hyaluronic acid, and the molecular weight of a polysaccharide chain segment is any value between 1 and 100 kDa.
Preferably, the polylactic acid segment in the polysaccharide-polylactic acid graft copolymer is PLLA or PDLLA, and the molecular weight of the polylactic acid segment is any value between 1 and 50 kDa.
In the skin beautifying composite injection, the polysaccharide-polylactic acid graft copolymer can be synthesized by various methods disclosed by the prior art, for example, direct polymerization of lactic acid directly initiated by polysaccharide (Wu Jingmei and the like, preparation and characterization of chitosan-polylactic acid graft copolymer, novel chemical materials, 2012.40), lactide ring-opening grafting (Cai Qing and the like, research on synthesis and in-vitro degradation behaviors of polylactic acid graft glucan copolymer, published by high molecular report, 2004.5), end group reaction grafting (Yuan Hua and the like, preparation and characterization of chitosan-polylactic acid graft copolymer, high molecular material science and engineering, 2009.25) and the like.
Preferably, the molecular weight of the hyaluronic acid is any value between 10 and 100 kDa.
Preferably, the aqueous solution for injection is physiological saline or phosphate buffer
The invention also aims to provide a preparation method of the skin beautifying compound injection.
A skin caring compound injection is prepared by stirring hyaluronic acid, polysaccharide-polylactic acid graft copolymer, mannitol, and injectable water solution to obtain uniform mixed solution; subpackaging the mixed solution, and performing radiation sterilization to obtain the skin beautifying compound injection.
Preferably, the radiation sterilization mode is Co 60 Sterilizing by radiation, wherein the radiation dose is any value of 7-10 kGy.
The beneficial effects of the invention are as follows: the skin beautifying composite injection disclosed by the invention is prepared by adding the polysaccharide-polylactic acid graft copolymer serving as a component into the hyaluronic acid injection, wherein the polysaccharide-polylactic acid graft copolymer exists in a sol or micelle form, and can stimulate cells to generate collagen by using a degradation product lactic acid while keeping the needle penetration property, so that the long-acting wrinkle removing function is realized, and the skin beautifying composite injection is an iteration of the existing hyaluronic acid injection beautifying product.
Drawings
Fig. 1 shows the appearance of the skin beautifying compound injection prepared in example 1 of the present invention.
Detailed Description
The following non-limiting examples are presented to enable those of ordinary skill in the art to more fully understand the present invention and are not intended to limit the invention in any way.
The test methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.
One of the specific implementation modes is as follows:
a skin caring compound injection comprises hyaluronic acid, polysaccharide-polylactic acid graft copolymer, mannitol, and injectable aqueous solution.
The molecular weight of the hyaluronic acid is any value between 10 and 100 kDa. The mass percentage of the hyaluronic acid is any value in the range of 0-25%.
The polysaccharide-polylactic acid graft copolymer comprises, but is not limited to, dextran, chitosan, hyaluronic acid and the like. The polysaccharide-polylactic acid graft copolymer has a polysaccharide chain segment with a molecular weight of 1-100 kDa. The polysaccharide-polylactic acid graft copolymer has any value in the range of 1-25% by mass.
The polylactic acid chain segment of the polysaccharide-polylactic acid graft copolymer comprises PLLA and PDLLA. The polysaccharide-polylactic acid graft copolymer has a polylactic acid chain segment with a molecular weight of 1-50 kDa. The polysaccharide-polylactic acid graft copolymer has any value in the range of 1-25% by mass.
The mannitol is in any value within the range of 0-5% by mass.
The water solution for injection is normal saline or phosphate buffer solution, and the mass percentage content of the water solution for injection is any value in the range of 45-99%.
The invention provides a preparation method of a skin beautifying compound injection capable of stimulating cells to produce collagen, which comprises the following steps: hyaluronic acid, polysaccharide-polylactic acid graft copolymer, mannitol and water solution for injection are fully stirred to obtain uniform mixed solution. Subpackaging the mixed solution, and performing radiation sterilization to obtain the skin beautifying composite injection.
The polysaccharide-polylactic acid graft copolymer exists in the form of sol or micelle in injection.
The radiation sterilization adopts Co 60 Radiation of radiationSterilizing, and irradiating with any value of 7-10 kGy.
In the following examples, the polysaccharide-polylactic acid graft copolymer was prepared as follows:
adding primary hydroxyl polylactic acid (PLLA-OH) and N, N-dicyclohexylcarbodiimide with specific molecular weight into dimethyl sulfoxide (DMSO) according to a molar ratio of 1:1 at room temperature, precipitating the solution with absolute ethyl alcohol after 20h, centrifugally separating the obtained precipitate, and carrying out vacuum drying after decompression and suction filtration of the precipitate part to obtain a white powdery solid product. Dispersing a certain amount of polysaccharide in DMSO, adding PLLA-CHO (the molar ratio of the polysaccharide to the polysaccharide is 1.
Example 1
A method for preparing skin beauty compound injection capable of stimulating cells to produce collagen comprises the following steps:
1.0g of dextran-polylactic acid graft copolymer (Dex) 6000 -PLLA 4000 ) 0.2g of hyaluronic acid (molecular weight: 100000), 0.25g of mannitol and 10mL of physiological saline for injection were thoroughly mixed. After completely dissolving uniformly, co is adopted 60 Radiation sterilization is carried out, and the radiation dose is 7kGy. And sterilizing to obtain the skin beautifying composite injection.
Example 2
A method for preparing skin beauty compound injection capable of stimulating cells to produce collagen comprises the following steps:
0.1g of hyaluronic acid-polylactic acid graft copolymer (HA) 40000 -PLLA 10000 ) 0.5g of hyaluronic acid (molecular weight: 100000) was thoroughly mixed with 9.5mL of physiological saline for injection. After completely dissolving uniformly, co is adopted 60 Radiation sterilization is carried out, and the radiation dose is 7kGy. And sterilizing to obtain the skin beautifying composite injection.
Example 3
A method for preparing skin beauty compound injection capable of stimulating cells to produce collagen comprises the following steps:
1.0gChitosan-polylactic acid graft Copolymer (CS) 6500 -PDLLA 6000 ) 0.1g hyaluronic acid (molecular weight 200000), 0.1g mannitol and 10mL injection physiological saline fully mixed. After completely dissolving uniformly, co is adopted 60 Sterilizing by radiation, and the radiation dose is 10kGy. Sterilizing to obtain the skin beautifying compound injection.
Example 4
A method for preparing skin beauty compound injection capable of stimulating cells to produce collagen comprises the following steps:
2.0g of chitosan-polylactic acid graft Copolymer (CS) 10000 -PDLLA 50000 ) Mixed well with 8mL of physiological saline for injection. After the mixture is completely and uniformly dissolved, co is adopted 60 Sterilizing by radiation, and the radiation dose is 10kGy. Sterilizing to obtain the skin beautifying compound injection.
Cytotoxicity was measured by MTT assay for examples 1 to 4.
Cytotoxicity reference GB/T16886.5-2017 medical device biology evaluation part 5: in vitro cytotoxicity test examine the survival of cells after different groups of cosmetic injections are added. And (3) converting the relative cell proliferation rate into 5-grade reaction to evaluate the toxicity of the sample, wherein the negative control is PBS, and the positive control is zinc diethyldithiocarbamate.
TABLE 1 cytotoxicity test results
Group of Increment rate Toxicity rating
Negative control 100% Level 0
Example 1 96.5% Level 1
Example 2 95.7% Level 1
Example 3 97.3% Level 1
Example 4 95.2% Level 1
Positive control 18.7% 4 stage

Claims (9)

1. The skin beautifying composite injection is characterized by comprising the following components in percentage by mass:
0 to 25 percent of hyaluronic acid, 1 to 25 percent of polysaccharide-polylactic acid graft copolymer, 0 to 5 percent of mannitol and 45 to 99 percent of water solution for injection.
2. The injection according to claim 1, which consists of the following components in percentage by mass: 1 to 20 percent of hyaluronic acid, 10 to 25 percent of polysaccharide-polylactic acid graft copolymer, 0.1 to 5 percent of mannitol and 55 to 88.9 percent of water solution for injection.
3. The injection according to claim 1, wherein the polysaccharide-polylactic acid graft copolymer exists in the form of sol or micelle in the injection.
4. The injection according to claim 1, wherein the polysaccharide in the polysaccharide-polylactic acid graft copolymer is dextran, chitosan or hyaluronic acid, and the molecular weight of the polysaccharide segment is any value between 1-100 kDa.
5. The injection according to claim 1, wherein the polylactic acid segment of the polysaccharide-polylactic acid graft copolymer is PLLA or PDLLA, and the molecular weight of the polylactic acid segment is any value between 1 and 50 kDa.
6. The injection according to claim 1, wherein the molecular weight of the hyaluronic acid is any value between 10 and 100 kDa.
7. The injection according to claim 1, wherein the aqueous solution for injection is physiological saline or phosphate buffer.
8. A method for preparing the skin beautifying compound injection as claimed in any one of claims 1 to 7, characterized by comprising the following steps: fully stirring hyaluronic acid, polysaccharide-polylactic acid graft copolymer, mannitol and water solution for injection to obtain uniform mixed solution; subpackaging the mixed solution, and performing radiation sterilization to obtain the skin beautifying compound injection.
9. The method of claim 8, wherein the radiation sterilization is performed by Co 60 Sterilizing by radiation, wherein the radiation dose is any value of 7-10 kGy.
CN202211275825.5A 2022-10-18 2022-10-18 Skin beautifying compound injection and preparation method thereof Pending CN115501390A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116832213A (en) * 2023-07-11 2023-10-03 杭州帕莱拉医疗科技有限公司 Preparation method of injectable dextran/poly-L-lactic acid interpenetrating network microsphere composite hydrogel filler

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KR102051467B1 (en) * 2019-06-12 2019-12-03 박상준 Skin filler composition and method for manufacturing the same
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CN111249172A (en) * 2020-01-15 2020-06-09 陈勇 Beauty injection gel and preparation method thereof
CN113663059A (en) * 2021-08-31 2021-11-19 苏州姑苏欣颜魅丽医疗美容诊所有限公司 Anti-aging beauty injection and preparation method thereof
CN113730652A (en) * 2021-09-01 2021-12-03 北京大清生物技术股份有限公司 Mixed gel for injection and preparation method and application thereof
CN114699554A (en) * 2021-12-20 2022-07-05 南京思元医疗技术有限公司 Injection for correcting skin wrinkles for medical cosmetology and preparation method thereof
CN114948790A (en) * 2021-04-06 2022-08-30 郑州欧华医疗美容医院有限公司 Rainbow water-light composite skin-beautifying formula

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US20160175342A1 (en) * 2013-08-09 2016-06-23 Genbiotech Continuous release compositions made from hyaluronic acid, and therapeutic applications of same
KR102051467B1 (en) * 2019-06-12 2019-12-03 박상준 Skin filler composition and method for manufacturing the same
CN110638676A (en) * 2019-09-30 2020-01-03 西安博和医疗科技有限公司 Hyaluronic acid injection and preparation method thereof
CN111249172A (en) * 2020-01-15 2020-06-09 陈勇 Beauty injection gel and preparation method thereof
CN114948790A (en) * 2021-04-06 2022-08-30 郑州欧华医疗美容医院有限公司 Rainbow water-light composite skin-beautifying formula
CN113663059A (en) * 2021-08-31 2021-11-19 苏州姑苏欣颜魅丽医疗美容诊所有限公司 Anti-aging beauty injection and preparation method thereof
CN113730652A (en) * 2021-09-01 2021-12-03 北京大清生物技术股份有限公司 Mixed gel for injection and preparation method and application thereof
CN114699554A (en) * 2021-12-20 2022-07-05 南京思元医疗技术有限公司 Injection for correcting skin wrinkles for medical cosmetology and preparation method thereof

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116832213A (en) * 2023-07-11 2023-10-03 杭州帕莱拉医疗科技有限公司 Preparation method of injectable dextran/poly-L-lactic acid interpenetrating network microsphere composite hydrogel filler

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