CN118161456A - Microsphere as well as preparation method and application thereof - Google Patents
Microsphere as well as preparation method and application thereof Download PDFInfo
- Publication number
- CN118161456A CN118161456A CN202410313095.6A CN202410313095A CN118161456A CN 118161456 A CN118161456 A CN 118161456A CN 202410313095 A CN202410313095 A CN 202410313095A CN 118161456 A CN118161456 A CN 118161456A
- Authority
- CN
- China
- Prior art keywords
- microsphere
- parts
- glucose
- beta
- sodium alginate
- 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
- 239000004005 microsphere Substances 0.000 title claims abstract description 93
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 238000001694 spray drying Methods 0.000 claims abstract description 28
- 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 abstract description 23
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims abstract description 23
- 239000000661 sodium alginate Substances 0.000 claims abstract description 23
- 235000010413 sodium alginate Nutrition 0.000 claims abstract description 23
- 229940005550 sodium alginate Drugs 0.000 claims abstract description 23
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims abstract description 22
- 108010022355 Fibroins Proteins 0.000 claims abstract description 22
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 22
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims abstract description 22
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims abstract description 22
- 239000002994 raw material Substances 0.000 claims abstract description 17
- 238000002347 injection Methods 0.000 claims abstract description 15
- 239000007924 injection Substances 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 12
- 239000002861 polymer material Substances 0.000 claims abstract description 10
- 229920000728 polyester Polymers 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 40
- 238000002156 mixing Methods 0.000 claims description 28
- 238000004945 emulsification Methods 0.000 claims description 11
- 230000001804 emulsifying effect Effects 0.000 claims description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 239000002537 cosmetic Substances 0.000 claims description 3
- 238000013268 sustained release Methods 0.000 claims description 3
- 239000012730 sustained-release form Substances 0.000 claims description 3
- 230000015556 catabolic process Effects 0.000 abstract description 11
- 238000006731 degradation reaction Methods 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- 230000001681 protective effect Effects 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 12
- 229920000747 poly(lactic acid) Polymers 0.000 description 9
- 238000001035 drying Methods 0.000 description 8
- 239000011259 mixed solution Substances 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 208000034530 PLAA-associated neurodevelopmental disease Diseases 0.000 description 7
- 238000000265 homogenisation Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 229960002117 triamcinolone acetonide Drugs 0.000 description 4
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 4
- 108010046377 Whey Proteins Proteins 0.000 description 3
- 102000007544 Whey Proteins Human genes 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 235000021119 whey protein Nutrition 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000003796 beauty Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229920001610 polycaprolactone Polymers 0.000 description 2
- 239000004632 polycaprolactone Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 229960002372 tetracaine Drugs 0.000 description 1
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1658—Proteins, e.g. albumin, gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
-
- 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
-
- 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
- A61L27/227—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
- A61L27/50—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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of biological medicines, and discloses a microsphere and a preparation method and application thereof. The microsphere of the invention comprises the following raw materials: polyester high polymer material, carboxymethyl cellulose, sodium alginate, beta-glucose, silk fibroin and solvent. The raw materials of the invention contain carboxymethyl cellulose, sodium alginate, beta-glucose and silk fibroin, and through reasonable collocation and combined action of the raw materials, a protective film can be formed on the surface of the microsphere, so that the microsphere is prevented from softening and deforming in the spray drying process, and the microsphere can keep a stable degradation rate, thereby meeting the injection requirement.
Description
Technical Field
The invention belongs to the technical field of biological medicine, and particularly relates to a microsphere and a preparation method and application thereof.
Background
The injection beauty technology is a beauty technology for carrying out local modification on a human body in an injection mode so as to achieve exquisite local morphology and coordinated overall morphology. The injection type cosmetic products in the current market are various, and the common products are degradable injection filling microspheres, and the main preparation method of the microspheres comprises a spray drying method and the like.
In the spray drying method, a material solution to be dried, or a suspension or emulsion in which a biodegradable polymer and a drug are uniformly dissolved, is supplied to a nozzle, sprayed through the nozzle, and exposed to hot air to evaporate the solvent used. Unlike other methods of preparing slow release microspheres, the spray drying method is advantageous because it provides a continuous process that facilitates the production of microspheres and thus facilitates the conversion of small scale production to large scale production. Although the spray drying method has the advantage of allowing the large-scale production of the microspheres, in order to sufficiently remove the used solvent, the spray drying temperature is usually set to be higher, the softening point of the degradable synthetic polymer material is lower, deformation, adhesion and the like are easy to occur at the temperature of more than 120 ℃, the microsphere state is influenced, and the traditional microspheres have the problems of unstable degradation rate and uncontrollable degradation rate.
Thus, there is still room for improvement in the current degradable injection-filled microspheres.
Disclosure of Invention
The present invention aims to solve at least one of the technical problems in the prior art described above. Therefore, the invention provides the microsphere, the preparation method and the application thereof, and the microsphere is uniform and complete in shape, controllable in particle size specification, good in biocompatibility and stable and controllable in degradation rate.
In a first aspect of the present invention, there is provided a microsphere comprising the following raw materials: polyester high polymer material, carboxymethyl cellulose, sodium alginate, beta-glucose, silk fibroin and solvent.
In some embodiments of the present invention, the microsphere comprises the following raw materials in parts by mass: 25-50 parts of polyester high polymer material, 8-15 parts of carboxymethyl cellulose, 5-10 parts of sodium alginate, 4-8 parts of beta-glucose, 1-3 parts of silk fibroin and 20-80 parts of solvent.
In some embodiments of the present invention, the polyester-based polymer material includes at least one of PCL (polycaprolactone), PLA (polylactide), PLA-PEG (polylactic acid-polyethylene glycol block copolymer), PGA (polyglycolide), and PVA (polyhydroxyvaleric acid).
In some embodiments of the invention, the solvent comprises an organic solvent and water; the organic solvent comprises one of dichloromethane, chloroform or ethyl acetate.
In a second aspect, the present invention provides a method for preparing the microsphere according to the first aspect, comprising the following steps:
mixing a polyester polymer material with an organic solvent to obtain an oil phase;
mixing carboxymethyl cellulose, sodium alginate, beta-glucose, silk fibroin and water to obtain a water phase;
Mixing the oil phase and the water phase, homogenizing, emulsifying, and spray drying to obtain the microsphere.
In some embodiments of the invention, the temperature of the homogeneous emulsification is 60-80 ℃; and/or the rotational speed of the homogenizing emulsification is 3500-4500 rpm; and/or the homogenizing and emulsifying time is 10-15min.
In some embodiments of the invention, the spray-dried inlet air temperature is 150-200 ℃; and/or the air outlet temperature of the spray drying is 80-100 ℃.
In some embodiments of the invention, the spray drying conditions further comprise: the input speed of the oil phase and water phase mixed solution is 10-15mL/min, and the pressure of compressed air is 0.3-0.5MPa.
In a third aspect, the invention provides the use of the microsphere according to the first aspect of the invention for the preparation of a drug sustained release product.
In a fourth aspect, the present invention provides the use of a microsphere according to the first aspect of the present invention for the preparation of an injection cosmetic product.
In a fifth aspect, the present invention provides a microsphere composition for injection comprising the microsphere according to the first aspect of the present invention.
In some embodiments of the invention, in the injectable microsphere composition, the microspheres are loaded with a cosmetically and/or pharmaceutically active ingredient.
In some embodiments of the invention, the active ingredient comprises at least one of triamcinolone acetonide or a pharmaceutically acceptable salt thereof, hydrocortisone or a pharmaceutically acceptable salt thereof, dexamethasone or a pharmaceutically acceptable salt thereof, prednisone or a pharmaceutically acceptable salt thereof, cortisone or a pharmaceutically acceptable salt thereof, lidocaine or a pharmaceutically acceptable salt thereof, tetracaine or a pharmaceutically acceptable salt thereof, tranexamic acid or a pharmaceutically acceptable salt thereof, vitamin C, vitamin E.
Compared with the prior art, the invention has the following beneficial effects:
The raw materials of the invention contain carboxymethyl cellulose, sodium alginate, beta-glucose and silk fibroin, and through reasonable collocation and combined action of the raw materials, a protective film can be formed on the surface of the microsphere, so that the microsphere is prevented from softening and deforming in the spray drying process, and the microsphere can keep a stable degradation rate, thereby meeting the injection requirement.
Detailed Description
The present invention will be described in further detail with reference to specific examples. The starting materials, reagents or apparatus used in the examples are all commercially available from conventional sources or may be obtained by methods known in the art unless otherwise specified. Unless otherwise indicated, assays or testing methods are routine in the art.
Example 1
The microsphere consists of the following raw material components in parts by weight:
35 parts of PLA, 11 parts of carboxymethyl cellulose, 8 parts of sodium alginate, 6 parts of beta-glucose, 2 parts of silk fibroin, 40 parts of dichloromethane and 30 parts of water.
The preparation method of the microsphere comprises the following steps:
Mixing PLA and methylene dichloride to obtain an oil phase;
mixing carboxymethyl cellulose, sodium alginate, beta-glucose, silk fibroin and water to obtain a water phase;
mixing the oil phase and the water phase, homogenizing, emulsifying, spray drying, collecting microsphere from cyclone separator, and drying under reduced pressure at 50deg.C to obtain microsphere;
Wherein, the conditions of the homogenization and emulsification are as follows: the temperature is 70 ℃, the rotating speed is 4000 turns/min, and the time is 12min;
The spray drying conditions were as follows: the inlet air temperature is 160 ℃, the outlet air temperature is 90 ℃, the input speed of the oil phase and water phase mixed solution is 12mL/min, and the pressure of compressed air is 0.4MPa.
Example 2
The microsphere consists of the following raw material components in parts by weight:
25 parts of PLA, 8 parts of carboxymethyl cellulose, 5 parts of sodium alginate, 4 parts of beta-glucose, 1 part of silk fibroin, 35 parts of dichloromethane and 20 parts of water.
The preparation method of the microsphere comprises the following steps:
Mixing PLA and methylene dichloride to obtain an oil phase;
mixing carboxymethyl cellulose, sodium alginate, beta-glucose, silk fibroin and water to obtain a water phase;
mixing the oil phase and the water phase, homogenizing, emulsifying, spray drying, collecting microsphere from cyclone separator, and drying under reduced pressure at 50deg.C to obtain microsphere;
Wherein, the conditions of the homogenization and emulsification are as follows: the temperature is 70 ℃, the rotating speed is 4000 turns/min, and the time is 12min;
The spray drying conditions were as follows: the inlet air temperature is 160 ℃, the outlet air temperature is 90 ℃, the input speed of the oil phase and water phase mixed solution is 12mL/min, and the pressure of compressed air is 0.4MPa.
Example 3
The microsphere consists of the following raw material components in parts by weight:
50 parts of PLA, 15 parts of carboxymethyl cellulose, 10 parts of sodium alginate, 8 parts of beta-glucose, 3 parts of silk fibroin, 55 parts of dichloromethane and 25 parts of water.
The preparation method of the microsphere comprises the following steps:
Mixing PLA and methylene dichloride to obtain an oil phase;
mixing carboxymethyl cellulose, sodium alginate, beta-glucose, silk fibroin and water to obtain a water phase;
mixing the oil phase and the water phase, homogenizing, emulsifying, spray drying, collecting microsphere from cyclone separator, and drying under reduced pressure at 50deg.C to obtain microsphere;
Wherein, the conditions of the homogenization and emulsification are as follows: the temperature is 70 ℃, the rotating speed is 4000 turns/min, and the time is 12min;
The spray drying conditions were as follows: the inlet air temperature is 160 ℃, the outlet air temperature is 90 ℃, the input speed of the oil phase and water phase mixed solution is 12mL/min, and the pressure of compressed air is 0.4MPa.
Example 4
The microsphere consists of the following raw material components in parts by weight:
35 parts of PLA, 11 parts of carboxymethyl cellulose, 8 parts of sodium alginate, 6 parts of beta-glucose, 2 parts of silk fibroin, 40 parts of dichloromethane and 30 parts of water.
The preparation method of the microsphere comprises the following steps:
Mixing PLA and methylene dichloride to obtain an oil phase;
mixing carboxymethyl cellulose, sodium alginate, beta-glucose, silk fibroin and water to obtain a water phase;
mixing the oil phase and the water phase, homogenizing, emulsifying, spray drying, collecting microsphere from cyclone separator, and drying under reduced pressure at 50deg.C to obtain microsphere;
Wherein, the conditions of the homogenization and emulsification are as follows: the temperature is 60 ℃, the rotating speed is 3500 revolutions per minute, and the time is 10 minutes;
The spray drying conditions were as follows: the inlet air temperature is 150 ℃, the outlet air temperature is 80 ℃, the input speed of the oil phase and water phase mixed solution is 10mL/min, and the pressure of compressed air is 0.3MPa.
Example 5
The microsphere consists of the following raw material components in parts by weight:
35 parts of PLA, 11 parts of carboxymethyl cellulose, 8 parts of sodium alginate, 6 parts of beta-glucose, 2 parts of silk fibroin, 40 parts of dichloromethane and 30 parts of water.
The preparation method of the microsphere comprises the following steps:
Mixing PLA and methylene dichloride to obtain an oil phase;
mixing carboxymethyl cellulose, sodium alginate, beta-glucose, silk fibroin and water to obtain a water phase;
mixing the oil phase and the water phase, homogenizing, emulsifying, spray drying, collecting microsphere from cyclone separator, and drying under reduced pressure at 50deg.C to obtain microsphere;
Wherein, the conditions of the homogenization and emulsification are as follows: the temperature is 80 ℃, the rotating speed is 4500 revolutions per minute, and the time is 15 minutes;
the spray drying conditions were as follows: the air inlet temperature is 200 ℃, the air outlet temperature is 100 ℃, the input speed of the oil phase and water phase mixed solution is 15mL/min, and the pressure of compressed air is 0.5MPa.
Comparative example 1 (differing from example 1 in that carboxymethyl cellulose was replaced with tween 80)
The microsphere consists of the following raw material components in parts by weight:
35 parts of PLA, 11 parts of Tween 80, 8 parts of sodium alginate, 6 parts of beta-glucose, 2 parts of silk fibroin, 40 parts of dichloromethane and 30 parts of water.
The preparation method of the microsphere comprises the following steps:
Mixing PLA and methylene dichloride to obtain an oil phase;
Mixing Tween 80, sodium alginate, beta-glucose, silk fibroin and water to obtain a water phase;
mixing the oil phase and the water phase, homogenizing, emulsifying, spray drying, collecting microsphere from cyclone separator, and drying under reduced pressure at 50deg.C to obtain microsphere;
Wherein, the conditions of the homogenization and emulsification are as follows: the temperature is 70 ℃, the rotating speed is 4000 turns/min, and the time is 12min;
The spray drying conditions were as follows: the inlet air temperature is 160 ℃, the outlet air temperature is 90 ℃, the input speed of the oil phase and water phase mixed solution is 12mL/min, and the pressure of compressed air is 0.4MPa.
Comparative example 2 (differs from example 1 in that silk fibroin was replaced with whey protein)
The microsphere consists of the following raw material components in parts by weight:
35 parts of PLA, 11 parts of carboxymethyl cellulose, 8 parts of sodium alginate, 6 parts of beta-glucose, 2 parts of whey protein, 40 parts of methylene dichloride and 30 parts of water.
The preparation method of the microsphere comprises the following steps:
Mixing PLA and methylene dichloride to obtain an oil phase;
Mixing carboxymethyl cellulose, sodium alginate, beta-glucose, whey protein and water to obtain a water phase;
mixing the oil phase and the water phase, homogenizing, emulsifying, spray drying, collecting microsphere from cyclone separator, and drying under reduced pressure at 50deg.C to obtain microsphere;
Wherein, the conditions of the homogenization and emulsification are as follows: the temperature is 70 ℃, the rotating speed is 4000 turns/min, and the time is 12min;
The spray drying conditions were as follows: the inlet air temperature is 160 ℃, the outlet air temperature is 90 ℃, the input speed of the oil phase and water phase mixed solution is 12mL/min, and the pressure of compressed air is 0.4MPa.
Test example 1 degradation Performance test
The microspheres prepared in examples 1-5 and comparative examples 1-2 were placed in buffer solutions having a pH of 7.4, subjected to degradation experiments in a shaking table at 37 ℃ and taken out at intervals, and the residual mass of the microspheres was weighed after centrifugation, washing and drying, and the test results are shown in table 1; the values in Table 1 are the percentages by mass of the microspheres remaining.
TABLE 1
As can be seen from the data in table 1, the microspheres prepared in examples 1 to 5 can maintain a relatively stable degradation rate, are used for preparing sustained-release microspheres of drugs, are beneficial to controlling the release amount of the drugs, and have a relatively long degradation time; whereas comparative example 1 and comparative example 2 were significantly different in degradation rate in the interval period due to the change of the preparation raw material system of the microspheres, it was possible that comparative example 1 and comparative example 2 were greatly affected by high temperature during spray drying, and some of them had undergone softening deformation, resulting in unstable degradation rate.
Test example 2 suction test
A needle with an inner diameter of 0.5mm and a length of 19.7mm (namely a common 1mL syringe gun head) is used as injection rate detection equipment for a disposable 1mL syringe sleeve, and 1mL microsphere dispersion (the dry weight of microspheres is 0.1g and is marked as M0) is used as an experimental sample. 0.1g of the microspheres prepared in examples 1 to 5 and comparative examples 1 to 2 were weighed, dispersed in 1mL of distilled water, and placed in a glass bottle. And after rapid mixing, microsphere dispersion liquid is formed. Sucking 1mL of the dispersion with a 1mL syringe, and freeze-drying the microspheres sucked in the syringe, respectively; the total mass (M0) of the microspheres was expressed as the percent of the mass (M1) of the microspheres sucked into the syringe (M1/M0). Times.100% of the total mass of the microspheres, and the test results are shown in Table 2.
TABLE 2
| Group of | Suction rate/% |
| Example 1 | 93 |
| Example 2 | 91 |
| Example 3 | 92 |
| Example 4 | 91 |
| Example 5 | 90 |
| Comparative example 1 | 72 |
| Comparative example 2 | 74 |
As can be seen from Table 2, the microspheres prepared in examples 1 to 5 have a higher extractability than 90%, which is significantly higher than those of comparative examples 1 and 2, because the microspheres of comparative examples 1 and 2 are greatly affected by high temperature during spray drying, and some of the microspheres have been softened, deformed and adhered, resulting in a decrease in the extractability.
Application example 1
A microsphere composition for injection comprising the microsphere prepared in example 1, the microsphere being loaded with triamcinolone acetonide. The load of triamcinolone acetonide is calculated according to the conventional dosage.
It is conceivable that the microsphere composition for injection provided in the above application example can effectively release triamcinolone acetonide due to the use of the microsphere of the present invention, and reduce the injection times and drug tolerance.
While the preferred embodiment of the present application has been described in detail, the application is not limited to the embodiments, and various equivalent modifications and substitutions can be made by those skilled in the art without departing from the spirit of the application, and these modifications and substitutions are intended to be included in the scope of the present application as defined in the appended claims.
Claims (10)
1. A microsphere, wherein the microsphere comprises the following raw materials: polyester high polymer material, carboxymethyl cellulose, sodium alginate, beta-glucose, silk fibroin and solvent.
2. The microsphere of claim 1, wherein the microsphere comprises the following raw materials in parts by mass: 25-50 parts of polyester high polymer material, 8-15 parts of carboxymethyl cellulose, 5-10 parts of sodium alginate, 4-8 parts of beta-glucose, 1-3 parts of silk fibroin and 20-80 parts of solvent.
3. The microsphere of claim 1 or 2, wherein the polyester-based polymer material comprises at least one of PCL, PLA, PLA-PEG, PGA, and PVA.
4. Microspheres according to claim 1 or 2, wherein the solvent comprises an organic solvent and water; the organic solvent comprises one of dichloromethane, chloroform or ethyl acetate.
5. A method of preparing the microsphere according to any one of claims 1 to 4, comprising the steps of:
mixing a polyester polymer material with an organic solvent to obtain an oil phase;
mixing carboxymethyl cellulose, sodium alginate, beta-glucose, silk fibroin and water to obtain a water phase;
Mixing the oil phase and the water phase, homogenizing, emulsifying, and spray drying to obtain the microsphere.
6. The method of claim 5, wherein the temperature of the homogeneous emulsification is 60-80 ℃; and/or the rotational speed of the homogenizing emulsification is 3500-4500 rpm; and/or the homogenizing and emulsifying time is 10-15min.
7. The method of claim 5, wherein the spray-dried inlet air temperature is 150-200 ℃; and/or the air outlet temperature of the spray drying is 80-100 ℃.
8. Use of the microsphere according to any one of claims 1 to 4 for the preparation of a pharmaceutical sustained release product.
9. Use of the microspheres according to any one of claims 1 to 4 for the preparation of an injection cosmetic product.
10. Microsphere composition for injection, characterized in that it comprises microspheres according to any one of claims 1 to 4.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410313095.6A CN118161456A (en) | 2024-03-19 | 2024-03-19 | Microsphere as well as preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410313095.6A CN118161456A (en) | 2024-03-19 | 2024-03-19 | Microsphere as well as preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118161456A true CN118161456A (en) | 2024-06-11 |
Family
ID=91349984
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410313095.6A Pending CN118161456A (en) | 2024-03-19 | 2024-03-19 | Microsphere as well as preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118161456A (en) |
-
2024
- 2024-03-19 CN CN202410313095.6A patent/CN118161456A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0625069B1 (en) | Method of manufacturing microcapsules | |
| Bee et al. | Approaches to improve therapeutic efficacy of biodegradable PLA/PLGA microspheres: a review | |
| US4853226A (en) | Sustained-release particulate preparation and process for preparing the same | |
| US5288502A (en) | Preparation and uses of multi-phase microspheres | |
| KR19990064267A (en) | Sustained-release particles | |
| CN102198102B (en) | Preparation method of drug-carrying microspheres | |
| CN1330921A (en) | Method of mfg. slowly-released microball by combined milk process | |
| JPH04283510A (en) | Granular therapeutic composition suitable for adjustable release of pharmaceutically active substance and method for its preparation | |
| JP2002534372A (en) | Production of microparticles with selective release characteristics | |
| JP2003534268A (en) | Method for preparing microparticles with selected polymer molecular weight | |
| KR20030051687A (en) | Biodegradable microparticles for controlled release administration, with purified amylopectin-based starch of reduced molecular weight | |
| CN114634634B (en) | Biological function composite porous polyester microsphere and preparation method thereof | |
| JP2012515790A (en) | Continuous double emulsion process for fine particle production | |
| CN111875817A (en) | Preparation method and application of hollow microspheres | |
| CN105386155A (en) | Paclitaxel loaded catenulate nano fiber and preparation method thereof | |
| CN101797232A (en) | Method for preparing small-granularity recombination human vascular endothelium inhibin slowly-released particle for injection | |
| Guiziou et al. | Investigation of in-vitro release characteristics of NSAID-loaded polylactic acid microspheres | |
| JP6121006B2 (en) | Emulsions for microencapsulation containing biodegradable surface-active block copolymers as stabilizers | |
| CN1903939A (en) | Polysaccharide polymer having protein large molecule and its preparation method | |
| CN118161456A (en) | Microsphere as well as preparation method and application thereof | |
| CN101890008B (en) | Amoxicillin sodium/sulbactam sodium composition microsphere injection | |
| US9314503B2 (en) | Sustained release systems and preparation method thereof | |
| CN116473927B (en) | Preparation method and application of injectable PLA microspheres | |
| JP2837675B2 (en) | Sustained-release fine-particle preparation | |
| CN101816634A (en) | Technology for preparing bone growth factor carrying microsphere by using ultrasonic atomization method |
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 |