CN110585055B - AcSDKP在增加成纤维细胞分泌Ⅲ型胶原蛋白含量的应用 - Google Patents
AcSDKP在增加成纤维细胞分泌Ⅲ型胶原蛋白含量的应用 Download PDFInfo
- Publication number
- CN110585055B CN110585055B CN201910791188.9A CN201910791188A CN110585055B CN 110585055 B CN110585055 B CN 110585055B CN 201910791188 A CN201910791188 A CN 201910791188A CN 110585055 B CN110585055 B CN 110585055B
- Authority
- CN
- China
- Prior art keywords
- type iii
- acskp
- collagen
- fibroblasts
- increasing
- 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.)
- Expired - Fee Related
Links
- 102000001187 Collagen Type III Human genes 0.000 title claims abstract description 31
- 108010069502 Collagen Type III Proteins 0.000 title claims abstract description 31
- 210000002950 fibroblast Anatomy 0.000 title claims abstract description 26
- HJDRXEQUFWLOGJ-AJNGGQMLSA-N Ac-Ser-Asp-Lys-Pro-OH Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(O)=O HJDRXEQUFWLOGJ-AJNGGQMLSA-N 0.000 title abstract description 17
- 108010031357 goralatide Proteins 0.000 title abstract description 16
- 230000028327 secretion Effects 0.000 title description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 20
- 229920001184 polypeptide Polymers 0.000 claims description 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 15
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 15
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical group NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 12
- 229940015975 1,2-hexanediol Drugs 0.000 claims description 8
- MVORZMQFXBLMHM-QWRGUYRKSA-N Gly-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CN=CN1 MVORZMQFXBLMHM-QWRGUYRKSA-N 0.000 claims description 8
- FHKSXSQHXQEMOK-UHFFFAOYSA-N hexane-1,2-diol Chemical compound CCCCC(O)CO FHKSXSQHXQEMOK-UHFFFAOYSA-N 0.000 claims description 8
- 229940093441 palmitoyl oligopeptide Drugs 0.000 claims description 7
- IHRKJQSLKLYWBQ-QKDODKLFSA-N (2s)-2-[[(2s)-1-[(2s)-5-amino-2-[[2-(hexadecanoylamino)acetyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O IHRKJQSLKLYWBQ-QKDODKLFSA-N 0.000 claims description 6
- 235000002961 Aloe barbadensis Nutrition 0.000 claims description 6
- 244000186892 Aloe vera Species 0.000 claims description 6
- 235000011399 aloe vera Nutrition 0.000 claims description 6
- 150000002632 lipids Chemical class 0.000 claims description 6
- 229960003966 nicotinamide Drugs 0.000 claims description 6
- 235000005152 nicotinamide Nutrition 0.000 claims description 6
- 239000011570 nicotinamide Substances 0.000 claims description 6
- 229940094946 palmitoyl tetrapeptide-7 Drugs 0.000 claims description 6
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 5
- 229910052802 copper Inorganic materials 0.000 claims description 5
- 239000010949 copper Substances 0.000 claims description 5
- 239000003906 humectant Substances 0.000 claims description 5
- OGNHOGPWQTWKGQ-VGWMRTNUSA-N (2S)-5-amino-2-[[(2S)-1-[2-[[(2S)-5-amino-2-[[(2S)-1-(2-aminoacetyl)pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoic acid Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N1[C@H](C(=O)N[C@@H](CCC(N)=O)C(O)=O)CCC1 OGNHOGPWQTWKGQ-VGWMRTNUSA-N 0.000 claims description 4
- 210000004207 dermis Anatomy 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- WSGCRSMLXFHGRM-DEVHWETNSA-N (2s)-2-[[(2s)-6-amino-2-[[(2s,3r)-2-[[(2s,3r)-2-[[(2s)-6-amino-2-(hexadecanoylamino)hexanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]hexanoyl]amino]-3-hydroxypropanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O WSGCRSMLXFHGRM-DEVHWETNSA-N 0.000 claims description 3
- LODWEXDBRZBADB-XEVVZDEMSA-N (2s)-6-amino-2-[[(2s)-2-[[(2s)-6-amino-2-(hexadecanoylamino)hexanoyl]amino]-3-methylbutanoyl]amino]hexanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(O)=O LODWEXDBRZBADB-XEVVZDEMSA-N 0.000 claims description 3
- BYUQATUKPXLFLZ-UIOOFZCWSA-N CCCCCCCCCCCCCCCC(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(O)=O)CC1=CN=CN1 Chemical compound CCCCCCCCCCCCCCCC(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(O)=O)CC1=CN=CN1 BYUQATUKPXLFLZ-UIOOFZCWSA-N 0.000 claims description 3
- 239000006071 cream Substances 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 239000000499 gel Substances 0.000 claims description 3
- 229940094912 palmitoyl tripeptide-5 Drugs 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 239000003002 pH adjusting agent Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 6
- 238000004519 manufacturing process Methods 0.000 claims 6
- 239000012141 concentrate Substances 0.000 claims 1
- 102000008186 Collagen Human genes 0.000 abstract description 11
- 108010035532 Collagen Proteins 0.000 abstract description 11
- 229920001436 collagen Polymers 0.000 abstract description 11
- 230000035755 proliferation Effects 0.000 abstract description 7
- 239000004480 active ingredient Substances 0.000 abstract description 6
- 102000000503 Collagen Type II Human genes 0.000 abstract description 5
- 108010041390 Collagen Type II Proteins 0.000 abstract description 5
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 abstract description 4
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 abstract description 4
- 210000002744 extracellular matrix Anatomy 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 230000003712 anti-aging effect Effects 0.000 abstract description 2
- 230000008021 deposition Effects 0.000 abstract description 2
- 210000003491 skin Anatomy 0.000 description 14
- 102000012422 Collagen Type I Human genes 0.000 description 10
- 108010022452 Collagen Type I Proteins 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 238000012258 culturing Methods 0.000 description 6
- 231100000241 scar Toxicity 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 239000000835 fiber Substances 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 210000001626 skin fibroblast Anatomy 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 244000309466 calf Species 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000003754 fetus Anatomy 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000037311 normal skin Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- 239000000686 essence Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 229960002385 streptomycin sulfate Drugs 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 108010081750 Reticulin Proteins 0.000 description 1
- 108010087230 Sincalide Proteins 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- VSIVTUIKYVGDCX-UHFFFAOYSA-M sodium;4-[2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].COC1=CC([N+]([O-])=O)=CC=C1[N+]1=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=NN1C1=CC=C([N+]([O-])=O)C=C1 VSIVTUIKYVGDCX-UHFFFAOYSA-M 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- 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
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
-
- 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
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Cosmetics (AREA)
- Peptides Or Proteins (AREA)
Abstract
本发明公开了AcSDKP在增加成纤维细胞分泌Ⅲ型胶原蛋白含量的应用，所述AcSDKP作为抑制成纤维细胞繁殖的活性成分、抑制细胞外基质中胶原蛋白沉积的活性成分、维持皮肤中Ⅰ、Ⅲ型胶原蛋白比例的活性成分或者抗衰老活性成分。
Description
技术领域
本发明属于组织修复技术领域，具体来说，涉及一种AcSDKP在增加成纤维细胞分泌Ⅲ型胶原蛋白含量的应用。
背景技术
胶原是细胞外基质中的主要成分，在人体皮肤组织中Ⅰ、Ⅲ型胶原纤维是最主要的构成部分。Ⅰ型胶原粗大，是构成皮肤的主体，Ⅲ型胶原细小、是皮肤中网状纤维的主要部分，其含量越高纤维束越细，从形态学上可见胶原纤维直径与Ⅲ型胶原的比例呈负相关，正常皮肤的Ⅰ、Ⅲ型胶原比例在发育过程中呈协调表达，Ⅰ、Ⅲ型胶原的正常比例维持着皮肤的正常组织结构。在对胎儿的无瘢痕愈合研究中证实，胎儿真皮层以Ⅲ型胶原为主，其相对含量明显高于成年皮肤，随着孕龄增大，皮肤外伤后，出现由无瘢痕——过度期瘢痕——瘢痕的过程。病理性瘢痕的形成过程中，Ⅰ型胶原纤维的增加和Ⅲ型胶原的减少都起着至关重要的作用，粗大的Ⅰ型胶原是瘢痕组织的病理基础。在病理性瘢痕的细胞外基质中，Ⅰ型胶原纤维占主要成份，瘢痕疙瘩组织中Ⅰ型胶原的合成比正常皮肤明显增加，Ⅰ：Ⅲ型胶原的比值明显增大。因此，一方面抑制Ⅰ型胶原过度表达，另一方面抑制成纤维细胞过度增殖，已经成为病理性瘢痕防治的两个关键。
1977 年首次从胎牛骨髓中提取的一种四肽 N-乙酰基-丝氨酰-天冬氨酰-赖氨酰-脯氨酸（AcSDKP），最初发现其对造血功能具有调节作用，进一步的研究发现，AcSDK 在调节胶原的合成与代谢方面也发挥着重要作用，也被认为是一种多功能生理调节因子，对抗器官纤维化有着潜在的临床应用价值。
发明内容
针对瘢痕防治的技术问题，本发明公开了一种AcSDKP在增加成纤维细胞分泌Ⅲ型胶原蛋白含量的应用。
为实现上述目的，本发明采用的技术发方案是：
AcSDKP在增加成纤维细胞分泌Ⅲ型胶原蛋白含量的应用，所述AcSDKP作为抑制成纤维细胞繁殖的活性成分、抑制细胞外基质中胶原蛋白沉积的活性成分、维持皮肤中Ⅰ、Ⅲ型胶原蛋白比例的活性成分或者抗衰老活性成分。
优选地，所述 AcSDKP作为维持Ⅰ型和Ⅲ型胶原蛋白比例的活性成分，促进损伤性皮肤修护。
本发明还提供了增加真皮中Ⅲ型胶原蛋白含量的AcSDKP组合物，AcSDKP在组合物中的质量浓度为0.1-5％，还包括：0.1-5％的其它多肽、0.1-1％的pH调节剂、2-5％的保湿剂、2-5％的脂类物质和0.1-2％的1,2-己二醇。
优选地，所述的其它多肽选自六肽-9、三肽-1、棕榈酰四肽-7、棕榈酰五肽-4、棕榈酰三肽-1、棕榈酰三肽-5和三肽-1铜中的至少一种。
优选地，所述的pH调节剂选自三乙胺。
优选地，所述的保湿剂选自芦荟胶。
优选地，所述的脂类物质选自烟酰胺。
本发明所述组合物剂型为精华液、粉剂、乳剂、霜剂、凝胶、面膜或者敷料。
本发明的有益效果在于：AcSDKP能抑制成纤维细胞的过度增殖，同时还能促进皮肤中Ⅲ型胶原蛋白含量的增加，维持皮肤中Ⅰ、Ⅲ型胶原蛋白比例正常，对促进损伤性皮肤修护效果显著。
附图说明
图1为AcSDKP 对成纤维细胞的增殖影响随浓度变化图。
图2为成纤维细胞Ⅰ型和Ⅲ型胶原蛋白表达的灰度扫描图。
具体实施方式
下面结合附图对本发明的实施例进行详细说明。
实施例1
增加成纤维细胞分泌Ⅲ型胶原蛋白含量的AcSDKP组合物，AcSDKP在组合物中的质量浓度为0.1％，还包括：0.1％的其它多肽、0.1％的pH调节剂、2％的保湿剂、2％的脂类物质和0.1％的1,2-己二醇。
所述的其它多肽选自棕榈酰四肽-7。
实施例2
增加成纤维细胞分泌Ⅲ型胶原蛋白含量的AcSDKP组合物，AcSDKP在组合物中的质量浓度为5％，还包括： 5％的其它多肽、1％的三乙胺、5％的保湿剂、5％的脂类物质和2％的1,2-己二醇。
所述的其它多肽选自六肽-9、棕榈酰四肽-7、棕榈酰三肽-1、棕榈酰三肽-5和三肽-1铜。
实施例3
增加成纤维细胞分泌Ⅲ型胶原蛋白含量的AcSDKP组合物，AcSDKP在组合物中的质量浓度为1％，还包括：0.6％的其它多肽、0.2％的三乙胺、3％的芦荟胶、3％的烟酰胺和0.2％的1,2-己二醇。
所述的其它多肽选自三肽-1、棕榈酰四肽-7和三肽-1铜。
实施例4
增加成纤维细胞分泌Ⅲ型胶原蛋白含量的AcSDKP组合物，AcSDKP在组合物中的质量浓度为2％，还包括：1％的其它多肽、0.6％的三乙胺、2.5％的芦荟胶。2.5％的烟酰胺和1％的1,2-己二醇。
所述的其它多肽选自棕榈酰五肽-4和三肽-1铜。
实施例5
增加成纤维细胞分泌Ⅲ型胶原蛋白含量的AcSDKP组合物，AcSDKP在组合物中的质量浓度为4％，还包括：2％的其它多肽、0.3％的三乙胺、3％的芦荟胶、3％的烟酰胺和0.5％的1,2-己二醇。
所述的其它多肽选自六肽-9和棕榈酰四肽-7。
实施例6
增加成纤维细胞分泌Ⅲ型胶原蛋白含量的AcSDKP组合物，AcSDKP在组合物中的质量浓度为2％，还包括：1％的其它多肽、0.2％的三乙胺、2％的芦荟胶、2％的烟酰胺和1％的1,2-己二醇。
本发明所述组合物剂型为精华液、粉剂、乳剂、霜剂、凝胶、面膜或者敷料。
细胞实验
标本：正常皮肤组织
培养基的配制：将－20℃贮存胎牛血清放在 4℃冰箱过夜，完全溶解后，取 DMEM无血清高糖培养基，加入胎牛血清使终浓度达到 10%，4℃保存备用。
原代细胞培养：
(1) 手术切取皮肤组织,立即放入4℃有DMEM培养液的离心试管中，密封后即带入超净台内操作。
(2) 将标本置于含有100 U·ml－1氨苄青霉素和100 u·ml- 1硫酸链霉素的灭菌溶液中,反复漂洗30min。
(3) 用眼科剪或手术刀仔细刮除表皮，剪弃脂肪和结缔组织。
(4) 把处理好的皮肤组织切成 0.5mm3左右大小的组织块，用含有 100 U·ml－1氨苄青霉素和 100 u·ml - 1硫酸链霉素的 PBS 再漂洗一次。
(5) 将皮肤小块浸入少量含 10%胎牛血清的 DMEM 培养液中，，置于 37℃，5%CO2培养箱中，每隔 48h 更换一次培养基，待细胞长满则用 0.25%的胰蛋白酶-EDTA 消化细胞，传代。实验选用第 2-3 代对数生长期的细胞。
检测 AcSDKP 对皮肤成纤维细胞增殖影响
选取第 2 代皮肤成纤维细胞，胰酶消化后行活细胞计数调整细胞浓度为1.5X104/m L，接种于 96 孔板，每孔 100u L。用含 10%小牛血清的 DMEM 预培养一天，改用无血清培养基培养 24h 后，换用含 AcSDKP 浓度分别为 10-7，10-8，10-9，10-10，10-11mol/l的培养基，另设空白对照，每组 6 复孔，作用 48h。用 CCK-8 试剂盒检测 AcSDKP 对细胞增殖影响。检测方法如下：
（1）吸去培养基。
（2）每孔加入 200ul 新鲜培养基及 10ul WST-8 试剂，混匀，置入培养箱内继续培养。
（3）30min 后，吸上清，450nm 处测吸光值。
结果测得不同浓度的 AcSDKP 作用 48h 后，各浓度组 D 值与对照组相比差异有统计学意义（P﹤0.05），AcSDKP 对成纤维细胞的增殖抑制作用呈剂量依赖性，从 10-7mol/l至 10-10mol/l 其抑制作用逐渐增强，其中以 10-10mol/l 浓度组抑制作用最强（见图 1）。
Ⅰ型和Ⅲ型胶原蛋白的表达
Western blot法检测, 选取第 2 代皮肤成纤维细胞，接种于 96 孔板，每孔100u L。用含 10%小牛血清的 DMEM 预培养一天，改用无血清培养基培养 24h 后，换用含AcSDKP 浓度分别为 10-7(A)，10-8(B)，10-9(C)，10-10(D)，10-11(E)mol/l的培养基，另设空白对照，每组 6 复孔，于37℃、5％CO2培养箱内孵育培养48ｈ，弃培养液，预冷 PBS 洗后每组加入250μl新鲜配制的细胞裂解液，冰上震荡裂解30min，收集裂解细胞，4℃ 12000r／min离心15min，收集上清液，-70℃保存备用。以考马斯亮蓝R-250染色测定蛋白浓度后，以15μg／孔上样，电泳并转膜。5％牛血清白蛋白37℃封闭１ｈ，Ⅰ型、Ⅲ型胶原单克隆抗体（1:1000 稀释）4℃孵育过夜，二抗（1:3000稀释）37℃孵育１ｈ，BCIP／NBT（1:50稀释）显色3min。以ImageJ软件对蛋白表达条带进行灰度扫描。
以上所述实施例仅表达了本发明的具体实结果可见，与空白组相比，各浓度组成纤维细胞Ⅰ型胶原表达均明显下降（P＜0.05），而Ⅲ型胶原表达均明显增强（P﹤0.05），见图2。
以上所述实施例仅表达了本发明的实施方式，其描述较为具体和详细，但并不能因此而理解为对本发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。
Claims (6)
1.AcSDKP在制备增加成纤维细胞分泌Ⅲ型胶原蛋白含量的药物中的应用，其特征在于， AcSDKP以组合物形式应用于增加真皮分泌Ⅲ型胶原蛋白含量，AcSDKP在组合物中的质量浓度为0.1-5％，还包括：0.1-5％的其它多肽、0.1-1％的pH调节剂、2-5％的保湿剂、2-5％的脂类物质和0.1-2％的1,2-己二醇。
2.根据权利要求1所述AcSDKP在制备增加成纤维细胞分泌Ⅲ型胶原蛋白含量的药物中的应用，其特征在于，所述的其它多肽选自六肽-9、三肽-1、棕榈酰四肽-7、棕榈酰五肽-4、棕榈酰三肽-1、棕榈酰三肽-5和三肽-1铜中的至少一种。
3.根据权利要求1所述AcSDKP在制备增加成纤维细胞分泌Ⅲ型胶原蛋白含量的药物中的应用，其特征在于，所述的pH调节剂选自三乙胺。
4.根据权利要求1所述AcSDKP在制备增加成纤维细胞分泌Ⅲ型胶原蛋白含量的药物中的应用，其特征在于，所述的保湿剂选自芦荟胶。
5.根据权利要求1所述AcSDKP在制备增加成纤维细胞分泌Ⅲ型胶原蛋白含量的药物中的应用，其特征在于，所述的脂类物质选自烟酰胺。
6.根据权利要求1所述AcSDKP在制备增加成纤维细胞分泌Ⅲ型胶原蛋白含量的药物中的应用，其特征在于，所述组合物剂型为精华液、粉剂、乳剂、霜剂、凝胶、面膜或者敷料。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910791188.9A CN110585055B (zh) | 2019-08-26 | 2019-08-26 | AcSDKP在增加成纤维细胞分泌Ⅲ型胶原蛋白含量的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910791188.9A CN110585055B (zh) | 2019-08-26 | 2019-08-26 | AcSDKP在增加成纤维细胞分泌Ⅲ型胶原蛋白含量的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110585055A CN110585055A (zh) | 2019-12-20 |
| CN110585055B true CN110585055B (zh) | 2023-06-13 |
Family
ID=68855829
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910791188.9A Expired - Fee Related CN110585055B (zh) | 2019-08-26 | 2019-08-26 | AcSDKP在增加成纤维细胞分泌Ⅲ型胶原蛋白含量的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110585055B (zh) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3112687A1 (fr) * | 2020-07-23 | 2022-01-28 | Rpm Dermatologie | Kit de soin personnalisé et personnalisable pour la peau |
| US11771637B2 (en) | 2021-01-22 | 2023-10-03 | The Procter & Gamble Company | Skin care composition and method of using the same |
| US11571378B2 (en) | 2021-01-22 | 2023-02-07 | The Procter & Gamble Company | Skin care composition and method of using the same |
| CN115154356B (zh) * | 2022-09-07 | 2022-12-06 | 广州集妍化妆品科技有限公司 | 一组胶原蛋白组合在制备抗衰老产品中的应用以及包括其的外用化妆品 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104721116A (zh) * | 2015-02-12 | 2015-06-24 | 宝健（北京）生物技术有限公司 | 一种具有抗衰老功效的组合物及其制备方法和应用 |
| CN105238743A (zh) * | 2015-11-16 | 2016-01-13 | 广州赛莱拉干细胞科技股份有限公司 | AcSDKP在角膜缘干细胞分离培养中的应用及角膜缘干细胞的培养方法 |
| CN108795844A (zh) * | 2018-06-25 | 2018-11-13 | 深圳市嘉祺生物科技有限公司 | 用于皮肤瘢痕修复的成纤维细胞的制备方法及其产品 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE292473T1 (de) * | 1998-07-30 | 2005-04-15 | Us Gov Health & Human Serv | Thymosin beta 4 stimuliert wundheilung |
| FR2809309B1 (fr) * | 2000-05-23 | 2004-06-11 | Mainelab | Microspheres a liberation prolongee pour administration injectable |
| CN101648010B (zh) * | 2008-08-13 | 2012-05-23 | 北京中科颐诺生物技术有限公司 | 促进成纤维细胞分泌细胞外基质成分的制剂及其制备方法 |
| CN105219704A (zh) * | 2015-11-16 | 2016-01-06 | 广州赛莱拉干细胞科技股份有限公司 | 角膜缘干细胞的分离方法 |
| CN107715111A (zh) * | 2017-09-18 | 2018-02-23 | 浙江大学 | 以血管紧张素转换酶类药物为有效成分的抗瘢痕外用制剂 |
-
2019
- 2019-08-26 CN CN201910791188.9A patent/CN110585055B/zh not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104721116A (zh) * | 2015-02-12 | 2015-06-24 | 宝健（北京）生物技术有限公司 | 一种具有抗衰老功效的组合物及其制备方法和应用 |
| CN105238743A (zh) * | 2015-11-16 | 2016-01-13 | 广州赛莱拉干细胞科技股份有限公司 | AcSDKP在角膜缘干细胞分离培养中的应用及角膜缘干细胞的培养方法 |
| CN108795844A (zh) * | 2018-06-25 | 2018-11-13 | 深圳市嘉祺生物科技有限公司 | 用于皮肤瘢痕修复的成纤维细胞的制备方法及其产品 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110585055A (zh) | 2019-12-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110585055B (zh) | AcSDKP在增加成纤维细胞分泌Ⅲ型胶原蛋白含量的应用 | |
| Raghu et al. | Growth factor-J31-3 | |
| EP3121196B1 (en) | Wnt family-derived peptides and use thereof | |
| Flynn et al. | Adipose tissue engineering in vivo with adipose‐derived stem cells on naturally derived scaffolds | |
| JP2001506634A (ja) | 粘膜下組織抽出物 | |
| EP2127674A1 (en) | Hair regrowth promoter | |
| Liu et al. | Hair follicle stem cells combined with human allogeneic acellular amniotic membrane for repair of full thickness skin defects in nude mice | |
| US20200121828A1 (en) | Bioactive scaffold for inducting tendon regeneration, preparation method therefor and use thereof | |
| Kurita et al. | Immunohistochemical localization of basic fibroblast growth factor in wound healing sites of mouse skin | |
| Kovacs et al. | Bovine colostrum induces the differentiation of human primary keratinocytes | |
| Li et al. | Xenogeneic dentin matrix as a scaffold for biomineralization and induced odontogenesis | |
| Levenson et al. | Some studies of wound healing: experimental methods, effect of ascorbic acid and effect of deuterium oxide | |
| Amiri et al. | The effects of insulin-like growth factor-1 gene therapy and cell transplantation on rat acute wound model | |
| Marinkovic et al. | Matrix-bound Cyr61/CCN1 is required to retain the properties of the bone marrow mesenchymal stem cell niche but is depleted with aging | |
| Sun et al. | Metformin promotes the hair-inductive activity of three-dimensional aggregates of epidermal and dermal cells self-assembled in vitro | |
| CN113846064A (zh) | 一种fgf18基因修饰的间充质干细胞及其制备方法和应用 | |
| WO2023221853A1 (zh) | 一种衰老细胞的构建方法及评价抗衰老功效的方法 | |
| CN112190531B (zh) | 抗细胞衰老制剂及其制备方法和应用、细胞及其构建方法 | |
| Hajem et al. | The regulatory role of the tetrapeptide A c SDKP in skin and hair physiology and the prevention of ageing effects in these tissues–a potential cosmetic role | |
| Zhou et al. | Angiogenin is expressed in human dermal papilla cells and stimulates hair growth | |
| CN114836377B (zh) | 一种干细胞体外成骨诱导分化方法 | |
| CN113940912B (zh) | 抗衰老的组合物及其应用 | |
| Hansson et al. | Somatomedin C as tentative pathogenic factor in neurofibromatosis | |
| Fant et al. | Human placental endothelin: expression of endothelin-1 mRNA by human placental fibroblasts in culture | |
| Yoon et al. | Rapid preparation of a noncultured skin cell suspension that promotes wound healing |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20230613 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |