CN117402206A - 一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法 - Google Patents
一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法 Download PDFInfo
- Publication number
- CN117402206A CN117402206A CN202311351237.XA CN202311351237A CN117402206A CN 117402206 A CN117402206 A CN 117402206A CN 202311351237 A CN202311351237 A CN 202311351237A CN 117402206 A CN117402206 A CN 117402206A
- Authority
- CN
- China
- Prior art keywords
- proteins
- preserving
- pharmaceutical
- development
- protein
- 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
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 47
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 47
- 238000000034 method Methods 0.000 title claims abstract description 31
- 239000002537 cosmetic Substances 0.000 title claims abstract description 15
- 230000000087 stabilizing effect Effects 0.000 title claims abstract description 13
- 238000011161 development Methods 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000003102 growth factor Substances 0.000 claims abstract description 11
- 230000003993 interaction Effects 0.000 claims abstract description 8
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims abstract description 8
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000008169 grapeseed oil Substances 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims abstract description 4
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims abstract description 4
- 230000010261 cell growth Effects 0.000 claims abstract description 4
- 238000009472 formulation Methods 0.000 claims abstract description 4
- 229940126864 fibroblast growth factor Drugs 0.000 claims abstract description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- 101800003838 Epidermal growth factor Proteins 0.000 claims description 7
- 229940116977 epidermal growth factor Drugs 0.000 claims description 6
- 239000006185 dispersion Substances 0.000 claims description 4
- 239000004615 ingredient Substances 0.000 claims description 4
- SLINHMUFWFWBMU-UHFFFAOYSA-N Triisopropanolamine Chemical compound CC(O)CN(CC(C)O)CC(C)O SLINHMUFWFWBMU-UHFFFAOYSA-N 0.000 claims description 3
- 239000004359 castor oil Substances 0.000 claims description 3
- 235000019438 castor oil Nutrition 0.000 claims description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 3
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 3
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 claims description 3
- 229960001295 tocopherol Drugs 0.000 claims description 3
- 229930003799 tocopherol Natural products 0.000 claims description 3
- 235000010384 tocopherol Nutrition 0.000 claims description 3
- 239000011732 tocopherol Substances 0.000 claims description 3
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 claims description 3
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 3
- 102000009024 Epidermal Growth Factor Human genes 0.000 claims 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 abstract description 4
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 abstract description 4
- 239000002609 medium Substances 0.000 description 8
- 102400001368 Epidermal growth factor Human genes 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 4
- 230000006641 stabilisation Effects 0.000 description 4
- 238000011105 stabilization Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000002144 chemical decomposition reaction Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000033115 angiogenesis Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000002906 microbiologic effect Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010040925 Skin striae Diseases 0.000 description 1
- 208000031439 Striae Distensae Diseases 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000006318 protein oxidation Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000000275 quality assurance Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000037394 skin elasticity Effects 0.000 description 1
- 230000037393 skin firmness Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1808—Epidermal growth factor [EGF] urogastrone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/02—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length in solution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1825—Fibroblast growth factor [FGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1841—Transforming growth factor [TGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K9/10—Dispersions; Emulsions
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法，尤其是细胞生长因子和/或蛋白质，如表皮生长因子(EGF)与成纤维生长因子(bFGF)。本方法包括以下步骤：提供分散相，在常温常压下，蛋白质在所述分散相中并入无水介质中，所述无水介质由油性成分形成，所述油性成分具有亲水性残基，可确保与蛋白质的相互作用，同时保持蛋白质的天然构象，所述油性成分为葡萄籽油、由不同成分组成的基底和丁基羟基甲苯。
Description
相关申请
本申请是申请号为201480028046.2，发明名称为“一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法”的中国申请的分案申请，该申请是PCT发明专利申请PCT/ES2014/000151进入中国国家阶段的申请，申请日为2014年9月23日，其要求了P201331394的优先权，2013年9月25日为优先权日。
发明目的
如题所述，本发明涉及一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法。
本发明的目的在于提供一种方法，该方法设想建立一种分散系统，该分散系统作为蛋白质在常温常压下、在油相中的保存、稳定和贮藏手段。具体地，本发明提出的方法基于蛋白质掺入由各成分组成的介质中，例如细胞生长因子(如表皮生长因子EGF和成纤维细胞生长因子bFGF)，但不限于此，所述各成分组成的介质如葡萄籽油、由多种化合物组成的基底(所述多种化合物在本说明书下文中会详细说明)和丁基羟基甲苯(BHT)，形成所述油相。具体地，本发明所提出的方法利用油相成分的某些化学基团促进蛋白质残基的物理-化学作用，使蛋白质天然分子结构维持更长一段时间。因此，本方法简单、经济、具有普适性，对取代通常用于保存蛋白质的复杂保存技术和/或采用水的方法具有潜在的能力。
技术领域
本发明可用于工业化学领域，特别是致力于制造药剂及化妆品的工业，尤其是意在保存生长因子的工业。
背景技术
目前，蛋白质稳定性在化学、药剂和化妆品领域备受关注。蛋白质在许多疾病治疗中作为活性物质，例如糖尿病、癌症、血友病、心肌梗塞等(Krishnamurthy和Manning，2002)。值得注意的是，近年来，利用蛋白质结构已引起化妆品工业的极大兴趣，例如生长因子、表皮生长因子(EGF)。如果蛋白质不能得到恰当的稳定化，会失去其天然结构，以致丧失其生物活性(Krishnamurthy和Manning，2002)。
但问题是蛋白质的稳定化是特别困难的，因为蛋白质非常容易发生降解现象：物理降解、化学降解和酶降解。化学降解涉及脱氨、氧化、还原、水解过程和一些化学相互作用，如二硫键相互作用。物理降解包括表面吸附、聚集、解离、变性和光解过程。此外，还有一些影响与分散介质特性相关的蛋白质聚集的因素，如温度(与蛋白质构象改变的热力学和动力学有关)、pH值(与蛋白质残基与正/负电荷的相互作用有关)、离子强度(与与带电基团相互作用的盐、浓度有关)和表面活性剂(与构象热力学稳定性有关)(Chi等人，2003)。
现有技术工艺可确保蛋白质保持天然构象更长一段时间，这些工艺可以为物理方法，如冷冻(低于-10℃)或冷冻干燥(用于消除蛋白质水溶液的湿气)，但是，通过这些方法得到的产品也会降解；或通过添加共溶剂的化学方法(Chang和PIKAL，2009)。
EGF是首先被分离并被视为生长因子的多肽。EGF具有生物活性，能够刺激角化细胞和成纤维细胞的增殖(随后形成胶原蛋白)，促使血管再生(即，形成新的血管)，并且在它应用的区域形成后续血管，EGF这些生物活性与其天然结构有关。这些特性可促进具有一定厚度的新皮肤的生成，恢复皮肤弹性和紧实度，从而减少细胞氧化带来的影响，并消除皱纹(Tang等人，1994)。这种生长因子最近已开始用于一些制剂中，其中在有关组织再生、加速烧伤愈合、治疗瘢痕疙瘩、痤疮和妊娠纹方面已获得非常良好的效果，甚至可以改善一些治疗效果，如手术、合并植皮，以及剥落后的应用。然而，虽然在医药和化妆品行业正越来越多地使用该蛋白质，但由于其价格高和难以稳定，因此还没有被大量使用(Schouest等人，2012)。
成纤维细胞生长因子(bFGF)是一种生长因子，其作用是增加有丝分裂活性指数及DNA合成，促进各种前体细胞的增殖，如软骨细胞、纤维细胞和成骨细胞等，所述前体细胞形成主体的纤维、结缔组织和支持组织。成纤维细胞生长因子有助于伤口的愈合、造血、血管生成或胚胎发育，因此可表现出截然不同的作用：一)有利于受损组织愈合期间的上皮再形成；二)有血管形成诱导活性；三)参与血细胞系的分化过程；以及四)参与骨骼肌和心肌分化、肺部成熟和内胚层细胞的肝细胞特化。
因此，本发明的目的是提供一种保存和稳定蛋白质的新方法，该方法可用于卫生制剂、医药及化妆品工业发展，且不同于传统的方法。该方法在油相中进行，使得它更简单和经济。需要指出的是，申请人不知晓公开了与本申请提出的用于保存和稳定蛋白质的方法类似的技术特征的任何公开文件或类似发明。
发明内容
一种用于分散蛋白质的介质，所述介质的成分为所述介质提供油性特质。如上所述，EGF、bFGF和其它细胞生长因子和/或蛋白质为大分子，难以稳定化，因为目前多数的分散手段为水性特质，通过采用分散系统可获得短期的稳定，例如乳剂，或一些昂贵、特殊的方法，但是这些方法又不能确保蛋白质天然结构得以长期维持，例如冻干。
本发明中，EGF和其它生长因子和/或蛋白质保存在油性介质，可应用在一些特定的工业过程中，促进蛋白质的稳定性，在这种介质中保存非变性蛋白质是更有效的做法。
更具体地，根据本发明的方法，在制剂中，生长因子由无水介质包围，所述无水介质由其他成分组成，所述成分作为与蛋白质残基相互作用的助剂，包括葡萄籽油，所述葡萄籽油构建介质，保持蛋白质天然构象的同时减少蛋白质残基的静电作用；基底，所述基底由以下物质组成：辛酸/癸酸甘油三酯、PEG－18蓖麻油二油酸酯、丙二醇、季戊四醇四(双-t-苄基羟基氢化肉桂酸)酯、生育酚和三异丙醇胺，这些可促进蛋白质结构域的分子间作用力，使得结构的热力学稳定性更强；以及丁基羟基甲苯(BHT)，其作为一种抗氧化剂，很大程度上避免了蛋白质氧化的化学降解现象。
需要注意的是，蛋白质介入油相成分的过程中，应当有适当的质量保证。优选地，该过程在无尘室中、层流条件下进行，应保证对环境的质量控制与微生物控制，以确保产品的无菌性。
简而言之，本发明提出了一种保存、贮藏和稳定蛋白质的方法，采用具有环境和微生物质量的无水分散相(即，不存在水)，通过应用具有亲水性残基的油性物质，保证了与蛋白质的相互作用，保持其天然构象，因此构成了一种相对于需要使用设备的、复杂的和需要有资格的人员的其他方法来说，更简单、更经济、可重复的方法。
经过充分描述本发明的性质、实施方式后，本领域技术人员可理解其范围与有益效果，因此没有必要再作更广泛的解释。应当了解，本发明在实际应用的其他实施方式中，可能不同于本实施例列举的细节，但在不脱离本发明原理的前提下，这些实施方式也视为本发明的保护范围。
参考文献
Chang LL,Pikal MJ.Mechanisms of Protein Stabilization in the SolidState.J.Pharm.Sci.98；2009:2886-2908.
Chi EY,Krishnan S,Randolph TW,Carpenter JF.Physical stability ofproteins in aqueoussolution:mechanism and driving forces in nonnative proteinaggregation.Pharm Res.2003；20:1325-36.
Krishnamurthy R,Manning MC.The stability factor:importance informulation development.Curr Pharm Biotechnol.2002；3:361-71.
Schouest JM,Lun TK,Moy RL.Improved texture and appearance of barleyproduced,synthetic,human-like epidermal growth factor(EGF)serum.J.DrugsDermatol.2012；11(5):613-620.
Tang Z,Zhang Z,Zheng Y et al.Cell aging of human diploid fibroblastsis associated withchanges in responsiveness to epidermal growth factor andchanges in HER-2 expression.Mechanisms of Ageing and Development 1994；73(1):57-67.
Claims (5)
1.一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法，尤其是细胞生长因子和/或蛋白质，如表皮生长因子与成纤维生长因子，其特征在于，包括以下步骤：提供分散相，在常温常压下，蛋白质在所述分散相中并入无水介质中，所述无水介质由油性成分形成，所述油性成分具有亲水性残基，可确保与蛋白质的相互作用，同时保持蛋白质的天然构象。
2.如权利要求1所述的用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法，其特征在于，所述油性成分包括葡萄籽油。
3.如权利要求1或2所述的用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法，其特征在于，所述油性成分包括基底，所述基底由以下物质组成：辛酸/癸酸甘油三酯、PEG－18蓖麻油二油酸酯、丙二醇、季戊四醇四(双-t-苄基羟基氢化肉桂酸)酯、生育酚和三异丙醇胺。
4.如权利要求1-3任一项所述的用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法，其特征在于，所述油性成分包括丁基羟基甲苯。
5.如权利要求1所述的用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法，其特征在于，所述油性成分为葡萄籽油、丁基羟基甲苯和基底，所述基底由以下物质组成：辛酸/癸酸甘油三酯、PEG－18蓖麻油二油酸酯、丙二醇、季戊四醇四(双-t-苄基羟基氢化肉桂酸)酯、生育酚和三异丙醇胺。
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES201331394A ES2502691B1 (es) | 2013-09-25 | 2013-09-25 | Método de conservación y estabilización de proteínas, aplicable para desarrollos industriales de formulaciones de productos sanitarios, farmacéuticos y cosméticos |
| ESP201331394 | 2013-09-25 | ||
| PCT/ES2014/000151 WO2015011308A1 (es) | 2013-09-25 | 2014-09-23 | Método de conservación y estabilización de proteínas, aplicable para desarrollos industriales de formulaciones de productos sanitarios, farmacéuticos y cosméticos |
| CN201480028046.2A CN105209476A (zh) | 2013-09-25 | 2014-09-23 | 一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480028046.2A Division CN105209476A (zh) | 2013-09-25 | 2014-09-23 | 一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117402206A true CN117402206A (zh) | 2024-01-16 |
Family
ID=51626311
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311351237.XA Pending CN117402206A (zh) | 2013-09-25 | 2014-09-23 | 一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法 |
| CN201480028046.2A Pending CN105209476A (zh) | 2013-09-25 | 2014-09-23 | 一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480028046.2A Pending CN105209476A (zh) | 2013-09-25 | 2014-09-23 | 一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法 |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US20160030584A1 (zh) |
| EP (2) | EP3050894A4 (zh) |
| JP (1) | JP6959002B2 (zh) |
| KR (1) | KR20160055720A (zh) |
| CN (2) | CN117402206A (zh) |
| BR (1) | BR112015020658B1 (zh) |
| CA (1) | CA2913394A1 (zh) |
| ES (1) | ES2502691B1 (zh) |
| MX (1) | MX2016001476A (zh) |
| RU (1) | RU2642277C2 (zh) |
| WO (1) | WO2015011308A1 (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105055265A (zh) * | 2015-07-21 | 2015-11-18 | 北京博士园科技发展有限公司 | 一种美容养颜产品及其制备方法 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3998753A (en) * | 1974-08-13 | 1976-12-21 | Hoffmann-La Roche Inc. | Water dispersible carotenoid preparations and processes thereof |
| GB8604983D0 (en) * | 1986-02-28 | 1986-04-09 | Biocompatibles Ltd | Protein preservation |
| US4806343A (en) * | 1986-03-13 | 1989-02-21 | University Of Southwestern Louisiana | Cryogenic protectant for proteins |
| US5416242A (en) * | 1992-09-25 | 1995-05-16 | Nippon Hypox Laboratories Incorporated | Hydroquinone derivative |
| US6267985B1 (en) * | 1999-06-30 | 2001-07-31 | Lipocine Inc. | Clear oil-containing pharmaceutical compositions |
| KR100366439B1 (ko) * | 2000-02-21 | 2003-01-09 | 주식회사 대웅 | 상피세포 성장인자를 유효성분으로 하는 안정한 약제학적조성물 |
| FR2814672B1 (fr) * | 2000-10-03 | 2003-03-21 | Oreal | Composition cosmetique a phase continue lipophile comprenant un pigment goniochromatique multicouche et son utilisation en maquillage |
| EP1343521A2 (en) * | 2000-12-01 | 2003-09-17 | Battelle Memorial Institute | Method for the stabilizing biomolecules (e.g. insulin) in liquid formulations |
| ES2232305B1 (es) * | 2003-11-07 | 2006-07-16 | Miguel Angel Palomo S.A. | Procedimiento de obtencion de alimentos texturizados y termoestables a partir de materias primas naturales y productos obtenidos a partir del mismo. |
| WO2006000226A1 (en) * | 2004-06-25 | 2006-01-05 | Ferrosan A/S | Compositions suitable for treating cutaneous signs of aging |
| US20080102128A1 (en) * | 2006-07-28 | 2008-05-01 | Flamel Technologies, Inc. | Modified-release microparticles based on amphiphilic copolymer and on active principles(s) and pharmaceutical formulations comprising them |
| FR2910318B1 (fr) * | 2006-12-20 | 2009-07-03 | Flamel Technologies Sa | Dispersion de polyaminoacides dans une phase lipidique continue. |
| ES2319061B1 (es) * | 2007-09-11 | 2010-02-10 | Biomedal, S.L. | Metodo de conservacion de peptidos o proteinas. |
| US20110020519A1 (en) * | 2008-01-04 | 2011-01-27 | Aveka, Inc. | Encapsulation of oxidatively unstable compounds |
| IL188647A0 (en) * | 2008-01-08 | 2008-11-03 | Orina Gribova | Adaptable structured drug and supplements administration system (for oral and/or transdermal applications) |
| RU2552324C2 (ru) * | 2008-09-17 | 2015-06-10 | Киазма Инк. | Фармацевтические композиции и соответствующие способы доставки |
-
2013
- 2013-09-25 ES ES201331394A patent/ES2502691B1/es active Active
-
2014
- 2014-09-23 JP JP2016544774A patent/JP6959002B2/ja active Active
- 2014-09-23 MX MX2016001476A patent/MX2016001476A/es unknown
- 2014-09-23 WO PCT/ES2014/000151 patent/WO2015011308A1/es active Application Filing
- 2014-09-23 EP EP14830029.6A patent/EP3050894A4/en not_active Ceased
- 2014-09-23 BR BR112015020658-1A patent/BR112015020658B1/pt active IP Right Grant
- 2014-09-23 KR KR1020157018008A patent/KR20160055720A/ko not_active IP Right Cessation
- 2014-09-23 US US14/759,320 patent/US20160030584A1/en not_active Abandoned
- 2014-09-23 CN CN202311351237.XA patent/CN117402206A/zh active Pending
- 2014-09-23 CA CA2913394A patent/CA2913394A1/en active Pending
- 2014-09-23 EP EP23175038.1A patent/EP4241783A1/en active Pending
- 2014-09-23 CN CN201480028046.2A patent/CN105209476A/zh active Pending
- 2014-09-23 RU RU2016107313A patent/RU2642277C2/ru active
-
2017
- 2017-12-27 US US15/855,338 patent/US20180193467A1/en not_active Abandoned
-
2019
- 2019-05-14 US US16/411,782 patent/US11147882B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| MX2016001476A (es) | 2016-07-12 |
| US20160030584A1 (en) | 2016-02-04 |
| JP2017501206A (ja) | 2017-01-12 |
| RU2016107313A (ru) | 2017-09-04 |
| US11147882B2 (en) | 2021-10-19 |
| WO2015011308A1 (es) | 2015-01-29 |
| US20190290770A1 (en) | 2019-09-26 |
| US20180193467A1 (en) | 2018-07-12 |
| JP6959002B2 (ja) | 2021-11-02 |
| ES2502691A1 (es) | 2014-10-03 |
| BR112015020658A2 (pt) | 2017-07-18 |
| CA2913394A1 (en) | 2015-01-29 |
| BR112015020658B1 (pt) | 2023-12-05 |
| EP3050894A1 (en) | 2016-08-03 |
| EP3050894A4 (en) | 2017-04-19 |
| KR20160055720A (ko) | 2016-05-18 |
| EP4241783A1 (en) | 2023-09-13 |
| RU2642277C2 (ru) | 2018-01-24 |
| CN105209476A (zh) | 2015-12-30 |
| ES2502691B1 (es) | 2015-07-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Jones et al. | Collagen stimulating effect of peptide amphiphile C16–KTTKS on human fibroblasts | |
| CA2579888C (en) | Fetal skin cell protein compositions for the treatment of skin conditions, disorders or diseases and methods of making and using the same | |
| CN106265120A (zh) | 一种九寡肽组合物的细胞因子样功效与美容应用 | |
| CN107661240B (zh) | 一种亚微乳修复原液组合物、其制备方法及包含其的化妆品组合物 | |
| US20160000858A1 (en) | Compositions and methods for mitigating skin irritation and enhancing skin barrier function | |
| CN111278326A (zh) | 改善皮肤、头发和头皮健康的基于酵母的面膜 | |
| JP6846422B2 (ja) | Ｐａｌｍａｒｉａ ｐａｌｍａｔａとジャスミンとの相乗作用的抽出物、それを含む組成物およびそれらの使用 | |
| EP2745849A1 (en) | Polydeoxyribonucleotides composition and uses thereof | |
| JP2001261570A (ja) | 皮膚外用剤 | |
| MXPA01010566A (es) | Una composicion estable que comprende factor de crecimiento epidermico como un ingrediente activo. | |
| CN115698264A (zh) | 制备含有由脐带血干细胞分泌的高水平高效外来体的培养基的方法及其用途 | |
| KR20230121973A (ko) | 식물유래 유전자 절편 혼합물 제조 방법 및 이를 함유하는비수계 조성물 | |
| KR20160050173A (ko) | 신규 펩타이드 및 성장인자 콤플렉스를 함유한 상처 재생 및 피부 진정용 화장료 조성물 | |
| US11759407B2 (en) | Composition for skin whitening or wound treatment, containing liquid plasma | |
| US20170035687A1 (en) | Skin treatment formulations | |
| CN117402206A (zh) | 一种用于卫生制剂、医药及化妆品工业发展的保存和稳定蛋白质的方法 | |
| JP2014224078A (ja) | オリゴペプチドを含む皮膚外用剤及びバイオ製品 | |
| KR102053707B1 (ko) | 섬유아세포의 조건배지와 기능성 펩타이드를 포함하는 주름 개선용 화장료 조성물 | |
| Zasada et al. | The influence of retinol concentration in liquid crystal formula on epidermal growth factor, interleukin-6 and transglutaminase-1 mRNA expression in the epidermis | |
| KR20010010473A (ko) | 파이토스핑고신의 수용액의 제조 방법 | |
| KR102600182B1 (ko) | 인체제대혈 세포배양액 엑소좀, 글루타치온, pdrn 및 소듐하이알루로네이트를 포함하는 화장료 조성물 및 이의 제조방법 | |
| EP4419211A1 (en) | Production method of mammalian macrophage cell derived biotechnological product | |
| WO2024144493A1 (en) | Production method of mammalian macrophage cell derived biotechnological product | |
| TR2022022038A1 (tr) | Memeli̇ makrofaj hücresi̇ türevli̇ bi̇yoteknoloji̇k ürün üreti̇m yöntemi̇ | |
| CN113069408A (zh) | 一种调理素配方以及制备方法 |
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 |