CN119455135A - A porous microsphere composite sodium hyaluronate gel and preparation method thereof - Google Patents
A porous microsphere composite sodium hyaluronate gel and preparation method thereof Download PDFInfo
- Publication number
- CN119455135A CN119455135A CN202411677443.4A CN202411677443A CN119455135A CN 119455135 A CN119455135 A CN 119455135A CN 202411677443 A CN202411677443 A CN 202411677443A CN 119455135 A CN119455135 A CN 119455135A
- Authority
- CN
- China
- Prior art keywords
- sodium hyaluronate
- porous
- microsphere composite
- gel
- porous microsphere
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229920002385 Sodium hyaluronate Polymers 0.000 title claims abstract description 45
- 229940010747 sodium hyaluronate Drugs 0.000 title claims abstract description 45
- 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 title claims abstract description 45
- 239000004005 microsphere Substances 0.000 title claims abstract description 40
- 239000002131 composite material Substances 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 238000001879 gelation Methods 0.000 title description 2
- CGMRCMMOCQYHAD-UHFFFAOYSA-J dicalcium hydroxide phosphate Chemical compound [OH-].[Ca++].[Ca++].[O-]P([O-])([O-])=O CGMRCMMOCQYHAD-UHFFFAOYSA-J 0.000 claims abstract description 18
- 150000004676 glycans Chemical class 0.000 claims abstract description 18
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 18
- 239000005017 polysaccharide Substances 0.000 claims abstract description 18
- 229920000642 polymer Polymers 0.000 claims abstract description 17
- 238000011049 filling Methods 0.000 claims abstract description 15
- 229940071643 prefilled syringe Drugs 0.000 claims abstract description 5
- 238000001694 spray drying Methods 0.000 claims abstract description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 12
- 238000002347 injection Methods 0.000 claims description 10
- 239000007924 injection Substances 0.000 claims description 10
- 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 description 9
- 229930195725 Mannitol Natural products 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 239000000594 mannitol Substances 0.000 claims description 9
- 235000010355 mannitol Nutrition 0.000 claims description 9
- 210000004623 platelet-rich plasma Anatomy 0.000 claims description 9
- 108010087806 Carnosine Proteins 0.000 claims description 8
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 claims description 8
- 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 8
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 8
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 claims description 8
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 8
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 6
- 230000003444 anaesthetic effect Effects 0.000 claims description 6
- 235000011187 glycerol Nutrition 0.000 claims description 6
- 229960004194 lidocaine Drugs 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 230000001954 sterilising effect Effects 0.000 claims description 4
- 230000008961 swelling Effects 0.000 claims description 4
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- ZKMNUMMKYBVTFN-HNNXBMFYSA-N (S)-ropivacaine Chemical compound CCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C ZKMNUMMKYBVTFN-HNNXBMFYSA-N 0.000 claims description 2
- LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 229960003150 bupivacaine Drugs 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 229960004919 procaine Drugs 0.000 claims description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 2
- 229960001549 ropivacaine Drugs 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 102000008186 Collagen Human genes 0.000 abstract description 6
- 108010035532 Collagen Proteins 0.000 abstract description 6
- 229920001436 collagen Polymers 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 239000003431 cross linking reagent Substances 0.000 abstract description 4
- 238000010382 chemical cross-linking Methods 0.000 abstract description 3
- 230000008929 regeneration Effects 0.000 abstract description 3
- 238000011069 regeneration method Methods 0.000 abstract description 3
- 239000011149 active material Substances 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 19
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 19
- 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 description 9
- 229920002674 hyaluronan Polymers 0.000 description 9
- 229960003160 hyaluronic acid Drugs 0.000 description 9
- 230000015556 catabolic process Effects 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000001815 facial effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 238000000498 ball milling Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 238000001354 calcination Methods 0.000 description 2
- 230000002439 hemostatic effect Effects 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010024604 Lipoatrophy Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010040830 Skin discomfort Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/48—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers
-
- 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
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/3616—Blood, e.g. platelet-rich plasma
-
- 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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
- A61L27/425—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of phosphorus containing material, e.g. apatite
-
- 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
- A61L27/52—Hydrogels or hydrocolloids
-
- 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
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- 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
- A61L27/56—Porous materials, e.g. foams or sponges
-
- 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
- A61L27/58—Materials at least partially resorbable by the body
-
- 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
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
-
- 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
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
-
- 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
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/30—Compounds of undetermined constitution extracted from natural sources, e.g. Aloe Vera
-
- 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
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
-
- 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
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- 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
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
-
- 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
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/418—Agents promoting blood coagulation, blood-clotting agents, embolising agents
-
- 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
- A61L2300/604—Biodegradation
-
- 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
-
- 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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/04—Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Transplantation (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Composite Materials (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Botany (AREA)
- Zoology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及生物医药技术领域，尤其涉及一种多孔微球复合透明质酸钠凝胶及其制备方法。本发明通过用喷雾干燥法制备多孔羟基磷灰石微球，将多孔羟基磷灰石微球与透明质酸钠溶液物理混合，再将其加入多糖聚合物凝胶中，使多孔微球均匀分散在凝胶中，真空灌装在预灌封注射器中，高压蒸汽灭菌，得到含多孔微球复合透明质酸钠凝胶。本发明的透明质酸钠为非交联型，避免了化学交联剂的残留导致的安全性问题，并通过引入活性材料多孔微球，起到即时填充，促进胶原蛋白再生的作用。本发明所制备的凝胶填充效果可持续12～18个月，并能够安全降解，还能大批量制备，适于工业化生产。
The present invention relates to the field of biomedicine technology, and in particular to a porous microsphere composite sodium hyaluronate gel and a preparation method thereof. The present invention prepares porous hydroxyapatite microspheres by spray drying, physically mixes the porous hydroxyapatite microspheres with a sodium hyaluronate solution, and then adds the porous hydroxyapatite microspheres to a polysaccharide polymer gel, so that the porous microspheres are evenly dispersed in the gel, vacuum-filled in a prefilled syringe, and sterilized by high-pressure steam to obtain a porous microsphere composite sodium hyaluronate gel. The sodium hyaluronate of the present invention is non-cross-linked, which avoids the safety problems caused by the residue of chemical cross-linking agents, and by introducing active material porous microspheres, it plays an instant filling role and promotes collagen regeneration. The gel filling effect prepared by the present invention can last for 12 to 18 months, can be safely degraded, and can also be prepared in large quantities, which is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of biological medicine, in particular to porous microsphere composite sodium hyaluronate gel and a preparation method thereof.
Background
Hyaluronic acid is a natural linear polysaccharide existing in human and animal tissues, and is mainly distributed in the parts of eye vitreous body, joints, umbilical cord, skin, etc. Hyaluronic acid has good physical and chemical properties and bioactivity such as water retention, lubricity, viscoelasticity, biodegradability and biocompatibility, and the hyaluronic acid is a mainstream material instead of collagen at present due to the problems of cost, safety and the like. However, hyaluronic acid products have the following defects of 1, high cost and one needle spending thousands of yuan to tens of thousands of yuan. 2. The maintenance time is short, degradation and absorption are basically completed within about 6 months in the body, and the consumer needs to re-inject, so that the burden and pain of the consumer are increased. 3. The facial mask has the effects of filling and tissue compatibilization only on the face, can not promote the synthesis of self collagen and can not remove oxygen free radicals in subcutaneous tissue of the face. 4. The condition that the injection product bleeds at the skin injection point is not considered, and particularly for hemophilia users, the bleeding problem can seriously endanger life if the product has no hemostatic function. 5. The cross-linking agent in hyaluronic acid causes inflammation, skin allergy, and the like.
Hydroxyapatite is used as a main component of human bones, has excellent biocompatibility and is a commonly used bone tissue engineering material. The hydroxyapatite microsphere can be used as a human body filling material, and is commonly used for facial filling, lipoatrophy filling and the like. After the hydroxyapatite is injected into a human body, a human body cell growth bracket can be formed in the human body, a platform is provided for cell growth, and the human body can be stimulated to accelerate the generation of filling cells, so that a long-term filling effect is formed.
In chinese patent CN117323471a, hydroxyapatite is used to prolong the action of hyaluronic acid, and in order to overcome the problem of rapid degradation of hyaluronic acid, components such as hydroxyapatite are added to prolong the action of hyaluronic acid, but the residue of chemical crosslinking agent used causes adverse reactions such as inflammation and allergy.
At present, the disclosed technical information related to facial filling for injection type cosmetic and plastic uses all technical problems of prolonging the degradation time of hyaluronic acid, promoting the synthesis of collagen and the like, and the invention is novel injection gel integrating antibacterial, anti-inflammatory, antioxidant and hemostatic functions and lasting effects.
Disclosure of Invention
In order to achieve the above purpose, the present invention provides the following technical solutions:
The invention provides a porous microsphere composite sodium hyaluronate gel, which comprises, by mass, 1-30% of porous hydroxyapatite microspheres, 1-3% of sodium hyaluronate solution, 0.5-4% of polysaccharide polymer, 0.5-1.5% of glycerol, 1-5% of mannitol, 0.1-0.2% of L-carnosine, 0.01-0.05% of platelet-rich plasma, 0-0.4% of anesthetic and the balance of injection water solution.
Further, the particle size of the porous hydroxyapatite microsphere is in the range of 5-50 μm.
Still further, the porous hydroxyapatite microsphere has a particle size ranging from 10 μm to 30 μm.
Further, the concentration of the sodium hyaluronate solution is 10-30mg/ml, and the molecular weight is 1-300 ten thousand Da.
Further, the concentration of the sodium hyaluronate solution is 10mg/ml, and the molecular weight is 20-100 ten thousand Da.
Further, the polysaccharide polymer is one of sodium alginate, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl cellulose and hydroxypropyl methyl cellulose.
Still further, the polysaccharide polymer is sodium carboxymethyl cellulose.
Further, the anesthetic is one of lidocaine, procaine, bupivacaine and ropivacaine.
Still further, the anesthetic is lidocaine.
The second aspect of the invention provides a preparation method of the porous microsphere composite sodium hyaluronate gel, which comprises the following steps:
S1, preparing porous hydroxyapatite microspheres by using a spray drying method;
s2, physically mixing the porous hydroxyapatite microspheres prepared in the step S1 with a sodium hyaluronate solution to obtain a mixture;
S3, adding the mixture obtained in the step S2 into a polysaccharide polymer gel which is swelled uniformly, wherein the polysaccharide polymer gel is obtained by fully and uniformly swelling sodium carboxymethyl cellulose, glycerol, mannitol, L-carnosine, platelet-rich plasma and an aqueous solution for injection in a constant temperature oscillator, so that porous hydroxyapatite microspheres are uniformly dispersed in the polysaccharide polymer gel, filling in a prefilled syringe in vacuum, and sterilizing by high-pressure steam to obtain the porous microsphere-containing composite sodium hyaluronate gel.
The invention has the beneficial effects that:
The porous microsphere composite sodium hyaluronate gel provided by the invention has the advantages that the L-carnosine in the porous microsphere composite sodium hyaluronate gel plays an antioxidant role, the degradation of free radicals on non-crosslinked sodium hyaluronate is inhibited, the degradation time is prolonged, the growth of cells and the production of structural substances are ensured after the porous microsphere composite sodium hyaluronate gel is injected into skin tissues, the effects of filling, shaping and the like are achieved, the porous microsphere composite sodium hyaluronate gel can be maintained for a longer time in vivo and can be safely degraded, and mannitol in the porous microsphere composite sodium hyaluronate gel component is used as a polyalcohol compound, so that the porous microsphere composite sodium hyaluronate gel has the characteristics of excellent moisturizing, anti-inflammatory, antibacterial, permeability and the like, and the mannitol also has remarkable anti-inflammatory and antibacterial effects. When the skin is damaged or stimulated by the outside, mannitol can quickly respond, inhibit inflammatory reaction, lighten skin discomfort, resist invasion of harmful microorganisms, protect the skin from infection, and the porous microsphere composite sodium hyaluronate gel component is added with Platelet Rich Plasma (PRP) which is rich in various growth factors and cytokines, thereby being beneficial to tissue repair, blood vessel regeneration, anti-inflammatory, collagen synthesis promotion and other functions.
(1) The sodium hyaluronate is non-crosslinked, so that the safety problem caused by the residue of a chemical crosslinking agent is avoided;
(2) By introducing active material porous microspheres, the instant filling is realized, and the collagen regeneration is promoted;
(3) The L-carnosine has an antioxidation effect, and can effectively inhibit the degradation of the sodium hyaluronate by free radicals;
(4) The gel prepared by the method can last for 12-18 months and can be safely degraded;
(5) The gel prepared by the invention has the functions of resisting bacteria, resisting inflammation, resisting oxidation and stopping bleeding, has simple process, can be prepared in large scale, and is suitable for industrial production.
Drawings
FIG. 1 is a scanning electron microscope SEM image of hydroxyapatite microspheres according to the invention.
Fig. 2 is an enlarged view of a portion of fig. 1.
FIG. 3 shows a porous microsphere composite sodium hyaluronate gel product prepared in example 1.
FIG. 4 is a porous microsphere composite sodium hyaluronate gel product made in example 2.
Detailed Description
The following description of the embodiments of the present invention is provided to facilitate understanding of the present invention by those skilled in the art, but it should be understood that the present invention is not limited to the scope of the embodiments, and all the inventions which make use of the inventive concept are protected by the spirit and scope of the present invention as defined and defined in the appended claims to those skilled in the art.
Example 1:
s1, preparation of porous hydroxyapatite microspheres
(1) Preparing a hydroxyapatite suspension, namely preparing a hydroxyapatite aqueous solution with the mass concentration of 30%, and placing the hydroxyapatite aqueous solution in a planetary ball mill for ball milling for 20min to obtain the hydroxyapatite suspension;
(2) Preparing NH 4HCO3 solution with the mass concentration of 7%;
(3) Adding the NH 4HCO3 solution in the step (2) into the hydroxyapatite suspension in the step (1) according to the mass ratio of 1:1, and stirring and mixing uniformly to obtain a mixed solution;
(4) Performing centrifugal spray drying and calcination treatment on the mixed solution obtained in the step (3) to obtain hydroxyapatite porous microspheres;
(5) And collecting the microspheres with the target particle size within the range of 10-30 mu m by adopting a machine sieving method.
S2, homogenizing 1g of porous hydroxyapatite microspheres and 1g of sodium hyaluronate solution for 1min in a high-speed homogenizing and dispersing machine, and obtaining a mixed system;
S3, fully and uniformly swelling 3g of sodium carboxymethyl cellulose, 0.5g of glycerol, 1.5g of mannitol, 0.2g L-carnosine, 0.03g of platelet-rich plasma, 0g of lidocaine and 92.77g of aqueous solution for injection in a constant-temperature oscillator to obtain polysaccharide polymer gel;
S4, adding the system obtained after mixing the S2 into the S3 polysaccharide polymer gel, and uniformly stirring under a vacuum condition to obtain a gel-like mixture;
S5, filling the gel-like mixture stirred uniformly in the step S4 into 1ml of a prefilled syringe, and sterilizing the gel-like mixture by high-pressure steam at 121 ℃ for 15-30min to obtain the porous microsphere composite sodium hyaluronate gel.
Example 2:
s1, preparation of porous hydroxyapatite microspheres
(1) Preparing a hydroxyapatite suspension, namely preparing a hydroxyapatite aqueous solution with the mass concentration of 30%, and placing the hydroxyapatite aqueous solution in a planetary ball mill for ball milling for 10min to obtain the hydroxyapatite suspension;
(2) Preparing NH 4HCO3 solution with the mass concentration of 7%;
(3) Adding the NH 4HCO3 solution in the step (2) into the hydroxyapatite suspension in the step (1) according to the mass ratio of 1:1, and stirring and mixing uniformly to obtain a mixed solution;
(4) Performing centrifugal spray drying and calcination treatment on the mixed solution obtained in the step (3) to obtain hydroxyapatite porous microspheres;
(5) And collecting the microspheres with the target particle size within 20-30 mu m by a machine sieving method.
S2, homogenizing 20g of porous hydroxyapatite microspheres and 3g of sodium hyaluronate solution for 2min in a high-speed homogenizing and dispersing machine, and obtaining a mixed system;
S3, fully and uniformly swelling 3.5g of sodium carboxymethyl cellulose, 0.5g of glycerol, 1.5g of mannitol, 0.2g L-carnosine, 0.03g of Platelet Rich Plasma (PRP), 0.03g of lidocaine and 71.24g of aqueous solution for injection in a constant temperature oscillator to obtain polysaccharide polymer gel;
S4, adding the system obtained after mixing the S2 into the S3 polysaccharide polymer gel, and uniformly stirring under a vacuum condition to obtain a gel-like mixture;
S5, filling the gel-like mixture stirred uniformly in the step S4 into 1ml of a prefilled syringe, and sterilizing the gel-like mixture by high-pressure steam at 121 ℃ for 15-30min to obtain the porous microsphere composite sodium hyaluronate gel.
While the principles and embodiments of the present invention have been described in detail in the foregoing embodiments and are presented to facilitate understanding of the principles and concepts of the invention, those skilled in the art will readily appreciate that many modifications are possible in the scope of the present invention without materially departing from the novel teachings and this disclosure.
Claims (10)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411677443.4A CN119455135A (en) | 2024-11-22 | 2024-11-22 | A porous microsphere composite sodium hyaluronate gel and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411677443.4A CN119455135A (en) | 2024-11-22 | 2024-11-22 | A porous microsphere composite sodium hyaluronate gel and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN119455135A true CN119455135A (en) | 2025-02-18 |
Family
ID=94577615
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202411677443.4A Pending CN119455135A (en) | 2024-11-22 | 2024-11-22 | A porous microsphere composite sodium hyaluronate gel and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN119455135A (en) |
-
2024
- 2024-11-22 CN CN202411677443.4A patent/CN119455135A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10207024B2 (en) | Biodegradable single-phase cohesive hydrogels | |
| JP6660469B2 (en) | Hyaluronic acid injectable composition containing hyaluronic acid derivative and DNA fraction and use thereof | |
| KR101514831B1 (en) | Heat sterilised injectable composition of hyaluronic acid or one of the salts thereof, polyols and lidocaine | |
| Duranti et al. | Injectable hyaluronic acid gel for soft tissue augmentation: A clinical and histological study | |
| RU2648450C2 (en) | Acceptable for injections sterile water composition on the basis of stitched hyaluronic acid and hydroxyapatite for application in plastic surgery | |
| CN108478867A (en) | Injectable macromolecule hydrogel, preparation method based on acylhydrazone key and macromolecule hydrogel injection | |
| MXPA06011386A (en) | Particles for soft tissue augmentation. | |
| JP2015531280A (en) | Sterile aqueous formulations for injection based on crosslinked hyaluronic acid and hydroxyapatite for therapeutic use | |
| TW202041221A (en) | Modified hyaluronic acid derivative and method for preparing same, applications thereof, use thereof, crosslinked hydrogel and method for preparing same, kit for the in situ formation thereof | |
| CN115335414B (en) | High molecular weight cosmetic compositions | |
| CN113278170A (en) | Chemically crosslinked hyaluronic acid hydrogel and preparation method and application thereof | |
| CN115317665B (en) | Polyester particle composite temperature-sensitive instant gel subcutaneous implant | |
| CN116370707A (en) | A kind of injection filler and preparation method thereof | |
| Wollina et al. | Spontaneous and induced degradation of dermal fillers: A review | |
| CN115645613A (en) | Moulding material and preparation method and application thereof | |
| KR102070878B1 (en) | Method of preparing muk-gel for filler procedure by cross-linking hyaluronic acid using electron-beam without cross-linking agent | |
| CN115245597A (en) | Composition of cross-linked hyaluronic acid gel and acellular matrix microparticles | |
| CN119455135A (en) | A porous microsphere composite sodium hyaluronate gel and preparation method thereof | |
| KR102202188B1 (en) | Composition for improving the stability of high molecular weight hyaluronic acid and dermal filler comprising the same | |
| CN108853595A (en) | A kind of preparation method of the crosslinking sodium hyaluronate microballoon of calcium phosphate modification | |
| CN114641319A (en) | Dermal filler compositions | |
| US20200230289A1 (en) | Time-delayed cross-linking of tissue fillers and applications thereof | |
| EP3126008B1 (en) | In vivo degradation of polysaccharide-containing fillers | |
| KR102348467B1 (en) | A method for manufacturing a filler containing dna fraction and the filler prepared therefrom | |
| CN116370706B (en) | A regenerated silk fibroin solid microsphere scaffold and an injectable soft tissue regeneration filler |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |