WO2022142350A1 - Matériau de remplissage par injection et procédé de préparation - Google Patents
Matériau de remplissage par injection et procédé de préparation Download PDFInfo
- Publication number
- WO2022142350A1 WO2022142350A1 PCT/CN2021/111380 CN2021111380W WO2022142350A1 WO 2022142350 A1 WO2022142350 A1 WO 2022142350A1 CN 2021111380 W CN2021111380 W CN 2021111380W WO 2022142350 A1 WO2022142350 A1 WO 2022142350A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- filling material
- sodium hyaluronate
- injection
- polyester
- injection filling
- Prior art date
Links
- 239000000463 material Substances 0.000 title claims abstract description 43
- 238000011049 filling Methods 0.000 title claims abstract description 34
- 239000007924 injection Substances 0.000 title claims abstract description 22
- 238000002347 injection Methods 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 229920000728 polyester Polymers 0.000 claims abstract description 24
- 239000006185 dispersion Substances 0.000 claims abstract description 21
- 229920002385 Sodium hyaluronate Polymers 0.000 claims abstract description 20
- 229940010747 sodium hyaluronate Drugs 0.000 claims abstract description 20
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims abstract description 20
- 239000004005 microsphere Substances 0.000 claims abstract description 18
- 108010022355 Fibroins Proteins 0.000 claims abstract description 12
- 102000001187 Collagen Type III Human genes 0.000 claims abstract description 9
- 108010069502 Collagen Type III Proteins 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 9
- 239000007788 liquid Substances 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 4
- 239000000872 buffer Substances 0.000 claims description 3
- 238000004945 emulsification Methods 0.000 claims description 3
- 229940071643 prefilled syringe Drugs 0.000 claims description 3
- 229920001577 copolymer Polymers 0.000 claims description 2
- 229920001519 homopolymer Polymers 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000002504 physiological saline solution Substances 0.000 claims description 2
- 238000010008 shearing Methods 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000008215 water for injection Substances 0.000 claims description 2
- 239000007853 buffer solution Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 abstract description 5
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 abstract description 5
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 abstract description 5
- 229920002674 hyaluronan Polymers 0.000 abstract description 5
- 229960003160 hyaluronic acid Drugs 0.000 abstract description 5
- 241001465754 Metazoa Species 0.000 abstract description 4
- 239000011159 matrix material Substances 0.000 abstract description 4
- 102000008186 Collagen Human genes 0.000 abstract description 3
- 108010035532 Collagen Proteins 0.000 abstract description 3
- 229920001436 collagen Polymers 0.000 abstract description 3
- 241000255789 Bombyx mori Species 0.000 abstract description 2
- 102000012422 Collagen Type I Human genes 0.000 abstract description 2
- 108010022452 Collagen Type I Proteins 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 238000000855 fermentation Methods 0.000 abstract description 2
- 230000004151 fermentation Effects 0.000 abstract description 2
- 235000015097 nutrients Nutrition 0.000 abstract description 2
- 230000028327 secretion Effects 0.000 abstract description 2
- 150000001720 carbohydrates Chemical class 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 238000013268 sustained release Methods 0.000 abstract 1
- 239000012730 sustained-release form Substances 0.000 abstract 1
- 210000001519 tissue Anatomy 0.000 description 7
- 230000006870 function Effects 0.000 description 4
- 210000004872 soft tissue Anatomy 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 229940077731 carbohydrate nutrients Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 230000003863 physical function Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/622—Microcapsules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Definitions
- the invention relates to the technical field of biotechnology, in particular to an injection filling material and a preparation process.
- the materials used for the repair and reconstruction of human tissue functions include hyaluronic acid, collagen, acellular matrix, etc.
- Hyaluronic acid and collagen have a single function, and acellular matrix can provide most of the nutrients and growth factors required by the tissue. , but its production process introduces a variety of toxic substances, and the current production process is difficult to ensure that the impurities or fragments containing immunogenicity can be removed on the premise of retaining functional components, so as to bring security risks.
- the present invention provides a formula without adding harmful ingredients, which aims to provide a new type of implant that has no rejection reaction, excellent biocompatibility, is similar to human soft tissue in terms of physical and biological functions, and can promote tissue function repair. It can improve the living environment of soft tissue cells in the most gentle way, so as to protect and repair the function of soft tissue cells.
- the purpose of the present invention is to provide an injection filling material and a preparation process.
- an injection filling material comprises the following raw materials in a mass ratio of more than 100%: sodium hyaluronate 0.1-2%, polyester microspheres 1-30%, silk fibroin 0.1-5% , Recombinant type III collagen 0.01-1%, and the balance is dispersion liquid.
- the injection filling material comprises the following raw materials in a mass ratio of more than 100%: sodium hyaluronate 1.2%, polyester microspheres 15%, silk fibroin 2%, recombinant type III collagen 0.05%, and the balance is dispersion liquid .
- the polyester microspheres are homopolymers or copolymers of PLA, PCL, PGA, and PDO absorbable synthetic polyester materials, and the diameter of the polyester microspheres ranges from 100 nm to 100 ⁇ m.
- the particle size range of the polyester microspheres is 5 ⁇ m-75 ⁇ m, and the optimum is 15-50 ⁇ m;
- the sodium hyaluronate is cross-linked or uncross-linked high-molecular-weight sodium hyaluronate, with a molecular weight of ⁇ 1.2 million;
- the sodium hyaluronate is uncross-linked sodium hyaluronate, and the molecular weight is 1.8-2.6 million, and the most optimal is 2.0-2.4 million.
- the dispersion is buffer, physiological saline or water for injection.
- the dispersion liquid is a PBS buffer, which provides the product with an osmotic pressure close to the cell liquid phase and a pH close to the tissue liquid phase.
- a preparation process of an injection filling material S1.
- the polyester material is prepared into polyester microspheres with a corresponding particle size range by an emulsification volatilization method or an electrostatic spray method or a microfluidic method;
- the polyester material in the filling material is artificially synthesized, and sodium hyaluronate and recombinant protein are made by fermentation.
- the silk fibroin is extracted from the secretions of silkworms instead of animal tissues.
- Cell matrix has better biosafety;
- polyester microspheres added to the filling material can form a slow-release effect on the system and prolong the effective time of the filling material, which is longer than that of the single-component material;
- the filler material contains type I collagen (silk fibroin), type III collagen (recombinant protein), and carbohydrate nutrients (hyaluronic acid) required for tissue production, and can provide a complete external environment for tissue production.
- Example 1-3 The injection filling materials are proportioned according to the mass ratio of raw materials in Table 1.
- polyester microspheres in proportion, add them to a certain amount of dispersion, stir mechanically for 30 minutes, and stir at a rate of 500 rpm;
- the cross-linked sodium hyaluronate gel was used as the control group, the normal saline was used as the blank control group, and the three groups of examples were used as the test group. Animal experiments were carried out with rabbits using different lesion modeling. , get the following data:
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Public Health (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
L'invention concerne un matériau de remplissage par injection et un procédé de préparation. Le matériau de remplissage comprend les matières premières suivantes, en pourcentage en masse : 0,1-2 % d'hyaluronate de sodium, 1-30 % de microsphères de polyester, 0,1-5 % de fibroïne de soie, 0,01-1 % de collagène de type III recombinant, le reste étant un liquide de dispersion. Le matériau polyester est synthétisé artificiellement ; l'hyaluronate de sodium et la protéine recombinante sont préparés au moyen d'un procédé de fermentation ; la fibroïne de soie est extraite de sécrétions de ver à soie de mûrier au lieu de tissus animaux et, par rapport au collagène extrait de tissus animaux, une matrice décellularisée est biologiquement plus sûre ; et les microsphères de polyester ajoutées peuvent produire un effet de libération prolongée sur un système, prolonger la durée de validité du matériau de remplissage et le matériau de remplissage dure plus longtemps par rapport à un matériau à un seul constituant. Le matériau de remplissage comprend du collagène de type I (fibroïne de soie), du collagène de type III (protéine recombinante) et une substance nutritive glucidique (acide hyaluronique), qui sont nécessaires pour la production de tissu et peut fournir un environnement externe complet pour la production de tissu.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011610786.0 | 2020-12-30 | ||
| CN202011610786.0A CN112587721A (zh) | 2020-12-30 | 2020-12-30 | 一种注射填充材料及制备工艺 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022142350A1 true WO2022142350A1 (fr) | 2022-07-07 |
Family
ID=75206270
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2021/111380 WO2022142350A1 (fr) | 2020-12-30 | 2021-08-09 | Matériau de remplissage par injection et procédé de préparation |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN112587721A (fr) |
| WO (1) | WO2022142350A1 (fr) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114917410A (zh) * | 2022-07-19 | 2022-08-19 | 媄典(北京)生物科技有限公司 | 石榴式凝胶球及其制备方法 |
| CN116271224A (zh) * | 2023-05-06 | 2023-06-23 | 南京思元医疗技术有限公司 | 一种软组织再生填充剂及其制备方法 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112587721A (zh) * | 2020-12-30 | 2021-04-02 | 广州益诚生物科技有限公司 | 一种注射填充材料及制备工艺 |
| CN113877001A (zh) * | 2021-09-27 | 2022-01-04 | 广州益诚生物科技有限公司 | 一种注射用丝素蛋白复合凝胶 |
| CN115887760A (zh) * | 2022-11-21 | 2023-04-04 | 娜罗曼苏(杭州)医疗生物科技有限公司 | 一种注射用左旋聚乳酸制备工艺 |
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| US20140308362A1 (en) * | 2011-11-09 | 2014-10-16 | University of Pittsburgh of the Commonweathl Syste | Injectable silk fibroin particles and uses thereof |
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2020
- 2020-12-30 CN CN202011610786.0A patent/CN112587721A/zh active Pending
-
2021
- 2021-08-09 WO PCT/CN2021/111380 patent/WO2022142350A1/fr active Application Filing
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| US20140308362A1 (en) * | 2011-11-09 | 2014-10-16 | University of Pittsburgh of the Commonweathl Syste | Injectable silk fibroin particles and uses thereof |
| CN104258470A (zh) * | 2014-05-13 | 2015-01-07 | 山东省医疗器械研究所 | 注射用聚乳酸微球和交联透明质酸混合凝胶及其制备方法 |
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| CN109621003A (zh) * | 2018-12-07 | 2019-04-16 | 长春杭盖生物科技有限公司 | 一种含有微球的可注射透明质酸钠凝胶的制备方法 |
| CN111184909A (zh) * | 2019-10-21 | 2020-05-22 | 湖北翎美生物科技有限公司 | 一种透明质酸缓释填充物及制备方法 |
| CN110787319A (zh) * | 2019-11-19 | 2020-02-14 | 上海摩漾生物科技有限公司 | 用于面部美容提拉的植入物及其应用 |
| CN112587721A (zh) * | 2020-12-30 | 2021-04-02 | 广州益诚生物科技有限公司 | 一种注射填充材料及制备工艺 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114917410A (zh) * | 2022-07-19 | 2022-08-19 | 媄典(北京)生物科技有限公司 | 石榴式凝胶球及其制备方法 |
| CN114917410B (zh) * | 2022-07-19 | 2022-09-30 | 媄典(北京)生物科技有限公司 | 石榴式凝胶球及其制备方法 |
| CN116271224A (zh) * | 2023-05-06 | 2023-06-23 | 南京思元医疗技术有限公司 | 一种软组织再生填充剂及其制备方法 |
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