CN117427110B - 一种组合物及其在制备促进毛发再生的制剂中的应用 - Google Patents
一种组合物及其在制备促进毛发再生的制剂中的应用 Download PDFInfo
- Publication number
- CN117427110B CN117427110B CN202311754879.4A CN202311754879A CN117427110B CN 117427110 B CN117427110 B CN 117427110B CN 202311754879 A CN202311754879 A CN 202311754879A CN 117427110 B CN117427110 B CN 117427110B
- Authority
- CN
- China
- Prior art keywords
- preparation
- inos
- extract
- hesperidin
- formulation
- 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.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 239000000203 mixture Substances 0.000 title claims abstract description 25
- 230000003660 hair regeneration Effects 0.000 title claims abstract description 13
- 230000001737 promoting effect Effects 0.000 title claims abstract description 12
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 claims abstract description 37
- 239000000284 extract Substances 0.000 claims abstract description 36
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 claims abstract description 32
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 claims abstract description 32
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 claims abstract description 32
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 claims abstract description 32
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229940025878 hesperidin Drugs 0.000 claims abstract description 32
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 claims abstract description 32
- 241000218202 Coptis Species 0.000 claims abstract description 8
- 235000002991 Coptis groenlandica Nutrition 0.000 claims abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
- 108090000623 proteins and genes Proteins 0.000 claims description 30
- 201000004384 Alopecia Diseases 0.000 claims description 16
- 101150109636 Inos gene Proteins 0.000 claims description 10
- 238000009472 formulation Methods 0.000 claims description 9
- 230000003659 hair regrowth Effects 0.000 claims description 8
- 230000022131 cell cycle Effects 0.000 claims description 7
- 230000007812 deficiency Effects 0.000 claims description 7
- 230000019491 signal transduction Effects 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 230000001105 regulatory effect Effects 0.000 claims description 5
- 230000011664 signaling Effects 0.000 claims description 5
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 claims description 4
- 101150037241 CTNNB1 gene Proteins 0.000 claims description 4
- 101000899390 Homo sapiens Bone morphogenetic protein 6 Proteins 0.000 claims description 4
- 101100232272 Mus musculus Hoxc13 gene Proteins 0.000 claims description 4
- 101150025022 WNT11 gene Proteins 0.000 claims description 4
- 102000043366 Wnt-5a Human genes 0.000 claims description 4
- 108700020483 Wnt-5a Proteins 0.000 claims description 4
- 101100485097 Xenopus laevis wnt11b gene Proteins 0.000 claims description 4
- 101100540688 Xenopus tropicalis wnt11b-1 gene Proteins 0.000 claims description 4
- 101100540689 Xenopus tropicalis wnt11b-2 gene Proteins 0.000 claims description 4
- 108020004999 messenger RNA Proteins 0.000 claims description 4
- -1 padi3 Proteins 0.000 claims description 4
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 claims description 3
- 101150025841 CCND1 gene Proteins 0.000 claims description 3
- 102000002664 Core Binding Factor Alpha 2 Subunit Human genes 0.000 claims description 3
- 108010043471 Core Binding Factor Alpha 2 Subunit Proteins 0.000 claims description 3
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 claims description 3
- 101150109862 WNT-5A gene Proteins 0.000 claims description 3
- 102000013814 Wnt Human genes 0.000 claims description 3
- 108050003627 Wnt Proteins 0.000 claims description 3
- 241000037740 Coptis chinensis Species 0.000 claims description 2
- 239000000865 liniment Substances 0.000 claims description 2
- 229940040145 liniment Drugs 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 241000207929 Scutellaria Species 0.000 claims 1
- 239000010404 Scutellaria baicalensis extract Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 9
- 239000000463 material Substances 0.000 abstract description 4
- 239000004615 ingredient Substances 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 241000050051 Chelone glabra Species 0.000 abstract 1
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 49
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 49
- 241000699670 Mus sp. Species 0.000 description 30
- 239000003153 chemical reaction reagent Substances 0.000 description 28
- 210000003491 skin Anatomy 0.000 description 13
- 210000004209 hair Anatomy 0.000 description 12
- 229940052810 complex b Drugs 0.000 description 11
- 231100000360 alopecia Toxicity 0.000 description 10
- 210000003780 hair follicle Anatomy 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 238000011813 knockout mouse model Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 210000002615 epidermis Anatomy 0.000 description 5
- 230000003779 hair growth Effects 0.000 description 5
- IPQKDIRUZHOIOM-UHFFFAOYSA-N Oroxin A Natural products OC1C(O)C(O)C(CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IPQKDIRUZHOIOM-UHFFFAOYSA-N 0.000 description 4
- 230000004156 Wnt signaling pathway Effects 0.000 description 4
- IKIIZLYTISPENI-ZFORQUDYSA-N baicalin Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 IKIIZLYTISPENI-ZFORQUDYSA-N 0.000 description 4
- 229960003321 baicalin Drugs 0.000 description 4
- AQHDANHUMGXSJZ-UHFFFAOYSA-N baicalin Natural products OC1C(O)C(C(O)CO)OC1OC(C(=C1O)O)=CC2=C1C(=O)C=C(C=1C=CC=CC=1)O2 AQHDANHUMGXSJZ-UHFFFAOYSA-N 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 208000024963 hair loss Diseases 0.000 description 4
- 230000003676 hair loss Effects 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000036566 epidermal hyperplasia Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000016507 interphase Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- 239000009513 Coptidis rhizoma extract Substances 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000003698 anagen phase Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 210000004207 dermis Anatomy 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 210000001208 inner root sheath cell Anatomy 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000022983 regulation of cell cycle Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 235000003276 Apios tuberosa Nutrition 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 101150061927 BMP2 gene Proteins 0.000 description 1
- 101100273639 Carassius auratus ccna1 gene Proteins 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 240000000950 Hippophae rhamnoides Species 0.000 description 1
- 235000003145 Hippophae rhamnoides Nutrition 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010027940 Mood altered Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 238000003559 RNA-seq method Methods 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 240000004534 Scutellaria baicalensis Species 0.000 description 1
- 235000017089 Scutellaria baicalensis Nutrition 0.000 description 1
- 241001300423 Strophostyles Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000003778 catagen phase Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 210000002768 hair cell Anatomy 0.000 description 1
- 230000034756 hair follicle development Effects 0.000 description 1
- 230000009583 hair follicle growth Effects 0.000 description 1
- 210000004919 hair shaft Anatomy 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 101150044508 key gene Proteins 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000007510 mood change Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000003068 pathway analysis Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- NNNVXFKZMRGJPM-KHPPLWFESA-N sapienic acid Chemical compound CCCCCCCCC\C=C/CCCCC(O)=O NNNVXFKZMRGJPM-KHPPLWFESA-N 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 230000008410 smoothened signaling pathway Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000003797 telogen phase Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
- A61K36/718—Coptis (goldthread)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/539—Scutellaria (skullcap)
-
- 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
- A61K8/60—Sugars; Derivatives thereof
- A61K8/602—Glycosides, e.g. rutin
-
- 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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/59—Mixtures
- A61K2800/592—Mixtures of compounds complementing their respective functions
- A61K2800/5922—At least two compounds being classified in the same subclass of A61K8/18
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Dermatology (AREA)
- Alternative & Traditional Medicine (AREA)
- Medical Informatics (AREA)
- Birds (AREA)
- Molecular Biology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Abstract
本发明涉及一种组合物及其在制备促进毛发再生的制剂中的应用,属于生物医药及化工技术领域,包括橙皮苷、黄芩提取物和黄连提取物,该组合物中将橙皮苷与多种提取物进行复配,可有效抑制皮肤炎症,明显增强其促进毛发再生的功效,针对于因iNOS基因缺陷导致的脱发后的再生障碍疗效显著。另外,本发明成分明确、疗效确切、安全可靠、稳定性好,可选择性地加入其他常用辅料进行制剂,具有广阔的应用前景。
Description
技术领域
本发明属于生物医药及化工技术领域,尤其涉及一种组合物及其在制备促进毛发再生的制剂中的应用。
背景技术
毛发生长是由毛囊驱动的循环再生过程,毛囊是皮肤附属器官,它横穿皮肤的真皮层和表皮层,包括毛干、毛球、真皮乳头、毛基质、内根鞘(IRS)、外根鞘(ORS)及皮脂腺等附属结构,其中ORS直接连接表皮基底层。毛囊干细胞(hair follicle stem cells,HFSCs),主要存在于ORS的隆突部位。毛囊在生长期、退行期和休止期不断循环再生,在这个过程中HFSCs可以动员再生新的毛囊。HFSCs可从毛囊中分离并根据其特异性细胞表面标记物体外扩增。到目前为止,已经分离鉴定出了大量的HFSCs干细胞亚群,如CD34阳性细胞等。
脱发是毛发分化过程异常的表现,最直接的表现是毛囊萎缩,头发脱落。随着社会压力的不断增大,全世界脱发人口也在增加,并且趋于年轻化。脱发最直接的原因是毛囊微环境的恶化,饮食不健康,作息不规律,情绪变化,内分泌失调,吸烟饮酒等种种原因都会导致脱发。另外,也有一些遗传因素会导致脱发症状。虽然轻微脱发对身体健康影响不大,但是严重脱发可使人失去信心,焦虑不安,甚至导致抑郁等心理疾病,严重影响患者的生活质量。
CN101172103A公开一种治疗妇女更年期综合征和骨质疏松症等多种疾病的药物,通过沙棘果油脂肪酸的信号转导作用,激活人体的内分泌系统,激活环核苷酸和特异蛋白等受体功能,十六烷酸和十六碳烯酸等脂肪酸能显著性提高机体毛发组织CAMP水平,使透明质酸酶灭活,阻断毛发细胞过快增生。CN104547449A通过引入补肝肾药物隔山撬、野料豆,补气活血药物雪灵芝、牛尾菜等来治疗因肝肾两虚、气血不足造成的脱发。CN101862374A还公开一种利用莲子心治疗脂溢性脱发的方案。但由于造成脱发的原因很多,只有对症治疗才是有效的。
因此,急需开发出更多可以治疗不同脱发原因的药物,以满足现阶段的需求。
发明内容
本发明所要解决的技术问题是提供一种组合物及其在制备促进毛发再生的制剂中的应用。
为解决上述技术问题,本发明采用的技术方案是:一种组合物,包括橙皮苷、黄芩提取物和黄连提取物。
进一步地,按重量份数计,橙皮苷0.05-1份、黄芩提取物0.05-0.8份、黄连提取物0.5-10份。
进一步地,按重量份数计,所述橙皮苷0.1-0.5份、黄芩提取物0.2-0.5份、黄连提取物1-5份。
本发明的另一目的是提供上述组合物在制备促进毛发再生的制剂中的应用。
进一步地,所述制剂为膏剂、喷剂、搽剂、贴剂中的一种(所述的制剂是采用本领域常规制备方法制备成的常用剂型)。
进一步地,所述制剂还包括药学上可接受的辅料。
进一步地,所述辅料为乙醇、丙二醇、甘油等。
进一步地,当所述辅料为乙醇时,每ml70%乙醇溶液的中,所述橙皮苷的浓度为0.001-0.005g/ml;黄芩提取物的浓度为0.001-0.003g/ml;黄连提取物的浓度为0.03-0.05g/ml。
进一步地,所述制剂可应用于药物、化妆品、保健品及医疗器械产品中。
进一步地,所述制剂促进因iNOS基因缺陷导致的脱发后再生障碍的毛发再生。
进一步地,所述制剂通过降低Wnt信号通路关键基因、BMP信号通路关键基因以及细胞周期调控关键基因的mRNA表达水平以促进毛发再生。
进一步地,所述Wnt信号通路关键基因包括Wnt5a、Wnt11、Ctnnb1、Padi3、Hoxc13和Dlx3;所述BMP信号通路关键基因包括BMP2、BMP6和Runx1;所述细胞周期调控关键基因包括Ccnd1、Ccnd2和Ccna2。
本发明的有益效果为:
本发明的组合物中将橙皮苷与多种药物提取物进行复配使用,安全可靠,并且通过小鼠实验发现,该组合物制备的制剂可有效抑制皮肤炎症,针对于因iNOS基因缺陷导致的脱发后的再生障碍疗效显著,能够有效改善iNOS基因缺陷诱导的毛囊微环境,缓解毛囊炎症,能够修复iNOS缺失导致的休止期阻滞,使其得以向生长期转化实现毛发再生,进而改善iNOS基因缺陷导致的脱发。本发明的制剂具体是通过降低Wnt5a、Wnt11、Ctnnb1、Padi3、Hoxc13和Dlx3在内的Wnt信号通路关键基因,BMP2、BMP6和Runx1在内的BMP信号通路关键基因以及Ccnd1、Ccnd2和Ccna2在内的细胞周期调控关键基因的mRNA表达水平,促进毛发再生的,疗效确切、成分明确、稳定性好,具有广阔的应用前景。
附图说明
下面通过参考附图并结合实例具体地描述本发明,本发明的优点和实现方式将会更加明显,其中附图所示内容仅用于对本发明的解释说明,而不构成对本发明的任何意义上的限制,在附图中:
图1为本发明验证iNOS基因与毛发生长关联性实验中各组小鼠的毛发照片。
图2为本发明实施例1中各种处理方法对小鼠毛发再生影响的实验照片。
图3为本发明实施例1中iNOS基因缺失小鼠差异皮肤组织的差异表达基因。
图4为本发明实施例1中各组小鼠的Wnt信号通路关键基因的数据对比。
图5为本发明实施例1中各组小鼠的BMP信号通路关键基因的数据对比。
图6为本发明实施例1中各组小鼠的细胞周期调控关键基因的数据对比。
图7为本发明实施例2中各组小鼠的实验照片和HE染色对比。
具体实施方式
为了使本技术领域的技术人员更好地理解本发明的技术方案,下面结合附图和最佳实施例对本发明作进一步的详细说明。
1、验证iNOS基因与毛发生长的关联性:
准备两组8周龄小鼠,第一组为野生型小鼠(3只),记为WT,第二组为iNOS基因敲除型小鼠(12只),记为iNOS KO,在同一生长环境下培养8周、12周、24周、48周,然后观察其毛发变化情况。
如图1所示,可以看出,iNOS基因敲除型小鼠的毛发会逐渐脱落,具体表现为iNOS基因敲除型小鼠从第8周开始在鼻子两侧出现毛发生长抑制并伴随稍许斑秃的现象,然而野生型小鼠并未出现此现象。由此可知,iNOS基因及其信号通路的缺失可能与毛发的正常发育密切相关。
2、验证制备的制剂对小鼠毛发再生的影响:
实施例1:
(1)小鼠模型准备:
准备两组8周龄小鼠,第一组为野生型小鼠(3只),第二组为iNOS基因敲除型小鼠(12只)。使用剃毛器剔除小鼠背部毛发(动作轻微,以免伤及表皮),裸露背部皮肤。其中,野生型小鼠以“WT”表示,iNOS基因敲除型小鼠以“iNOS KO”表示。
(2)各组试剂配制:
对照试剂:70%乙醇;
橙皮苷试剂:称取0.2g橙皮苷,溶解入100mL70%的乙醇溶液中;
复合物A(提取物试剂):称取黄芩提取物0.3克、黄连提取物3克,溶解入100ml70%的乙醇溶液中;
复合物B(橙皮苷+提取物的复合试剂):称取橙皮苷0.2克、黄芩提取物0.3克、黄连提取物3克,溶解入100ml 70%的乙醇溶液中。
其中,复合物B即为本发明的制剂。
橙皮苷、黄芩、黄连均购于药店。
(3)处理方法:
WT+对照试剂组:将70%乙醇均匀涂抹至WT小鼠背部皮肤裸露部位,涂抹量为200μL,每天2次,连续涂抹10天,
iNOS KO+对照试剂组:将70%乙醇均匀涂抹至iNOS KO小鼠背部皮肤裸露部位,涂抹量为200μL,每天2次,连续涂抹10天;
iNOS KO+复合物A组:将提取物试剂均匀涂抹至iNOS KO小鼠背部皮肤裸露部位,涂抹量为200μL,每天2次,连续涂抹10天;
iNOS KO+橙皮苷组:将橙皮苷试剂均匀涂抹至iNOS KO小鼠背部皮肤裸露部位,涂抹量为200μL,每天2次,连续涂抹10天;
iNOS KO+复合物B组:将橙皮苷+提取物的复合试剂均匀涂抹至iNOS KO小鼠背部皮肤裸露部位,涂抹量为200μL,每天2次,连续涂抹10天。
每组小鼠均为3只。
(4)结果分析:
如图2所示,iNOS KO+复合物A组、iNOS KO+橙皮苷组、iNOS KO+复合物B组小鼠的背部裸露区域有黑色素形成,皮肤颜色变黑,并且在皮肤表面发现有微小的毛发生成,iNOSKO+复合物B组效果最明显。而WT+对照试剂组和iNOS KO+对照试剂组小鼠的背部裸露区域均未出现上述现象。
为了确认橙皮苷+提取物复合联用可促进毛发再生的机制,首先取3只6月龄WT小鼠和3只6月龄iNOS KO小鼠皮肤组织,进行RNA-seq(转录组测序技术)。
如图3所示,图3的左侧热图显示差异基因的变化,图中“WT1、WT2、WT3”为三只WT小鼠,“KO1、KO2、KO3”为三只iNOS KO小鼠。图3的右侧火山图显示差异基因的变化,按照变化倍数(Fold Change,FC)>1.5和p-value<0.05的标准,与WT小鼠相比,iNOS KO小鼠皮肤组织中上调基因1107个,下调基因769个。
接下来,将差异基因进行IPA(Ingenuity Pathway Analysis)分析,发现iNOS基因缺陷导致毛囊发育相关通路均表达上调,Shh信号通路、Wnt信号通路、BMP信号通路以及细胞增殖过程关键基因均表达上调。
通过qRT-PCR(实时荧光定量PCR)检测了毛囊生长发育相关通路关键基因的表达变化,如图4至图6所示,较WT+对照试剂组,iNOS KO+对照试剂组的Wnt信号通路关键基因(Wnt5a、Wnt11、Ctnnb1、Padi3、Hoxc13、Dlx3)、BMP信号通路关键基因(BMP2、BMP6、Runx1)及细胞周期调控关键基因(Ccnd1、Ccnd2、Ccna2)表皮mRNA水平均明显升高。而iNOS KO+橙皮苷组、iNOS KO+复合物A组和iNOS KO+复合物B组的上述指标均有所下降,且复合物B组效果最佳。可以确定iNOS缺失可导致毛发调控关键通路Wnt、BMP以及细胞周期调控关键基因表达升高,而橙皮苷+提取物的联合作用及橙皮苷和提取物试剂单独作用后均可逆转iNOS缺失导致的上述关键通路基因的升高,橙皮苷+提取物联合应用效果最佳。
图4至图6中,**表示KO+复合物B与KO+对照试剂相比,以及与KO+橙皮苷和KO+复合物A相比,差异均具有统计学意义,p<0.01。
实施例2:
(1)小鼠模型准备:
准备四组6周龄iNOS基因敲除型小鼠,每组三只,iNOS基因敲除型小鼠以“iNOSKO”表示。
(2)各组试剂配制:
对照试剂:70%乙醇;
橙皮苷试剂:称取0.2g橙皮苷,溶解入100mL70%的乙醇溶液中;
复合物A(提取物试剂):称取黄芩提取物0.3克、黄连提取物3克,溶解入100ml70%的乙醇溶液中;
复合物B(橙皮苷+提取物的复合试剂):称取0.2g橙皮苷、黄芩提取物0.3克、黄连提取物3克,溶解入100ml70%的乙醇溶液中。
(3)处理方法:
iNOS KO+对照试剂组:将70%乙醇均匀涂抹至iNOS KO小鼠背部无毛区域,涂抹量为200μL,每天2次;
iNOS KO+橙皮苷组:将橙皮苷试剂均匀涂抹至iNOS KO小鼠背部无毛区域,涂抹量为200μL,每天2次;
iNOS KO+复合物A组:将提取物试剂均匀涂抹至iNOS KO小鼠背部无毛区域,涂抹量为200μL,每天2次;
iNOS KO+复合物B组:将橙皮苷+提取物的复合试剂均匀涂抹至iNOS KO小鼠背部无毛区域,涂抹量为200μL,每天2次。
(4)结果分析:
如图7所示,iNOS KO+橙皮苷组、iNOS KO+复合物A组和iNOS KO+复合物B组小鼠的头背部无毛区域在涂抹药物第32天时有毛发形成,而iNOS KO+对照试剂组的背部裸露区域均未出现毛发生长现象,说明橙皮苷和提取物复合试剂可促进iNOS缺陷小鼠脱发部位的毛发再生,并且橙皮苷和提取物复合试剂联合使用效果明显优于橙皮苷和提取物单独使用。
通过苏木素-伊红(HE)染色发现,iNOS KO+橙皮苷组、iNOS KO+复合物A组呈现休止期向生长期的转化,iNOS KO+复合物B组也呈现出异常休止期向正常休止期的转化,而iNOS KO+对照试剂组无此现象。此外,HE染色结果显示:iNOS KO+对照试剂组,表皮增生明显,表皮及真皮层均存在明显炎细胞浸润、大量炎性介质以及组织水肿,iNOS KO+橙皮苷以及iNOS KO+复合物A组上述情况有所缓解,iNOS KO+复合物B组表皮增生以及炎细胞浸润和组织水肿现象明显改善(如图7箭头所示)。
可见,橙皮苷联合提取物能够明显抑制炎性介质的释放、缓解皮肤炎症,抑制表皮增生。
以上对本发明的实施例进行了详细说明,但所述内容仅为本发明的较佳实施例,不能被认为用于限定本发明的实施范围。凡依本发明范围所作的均等变化与改进等,均应仍归属于本专利涵盖范围之内。
Claims (5)
1.一种组合物在制备促进毛发再生的制剂中的应用,其特征在于:组合物由0.2g橙皮苷、0.3g黄芩提取物和3g黄连提取物组成。
2.根据权利要求1所述的组合物在制备促进毛发再生的制剂中的应用,其特征在于:所述制剂为喷剂、搽剂、贴剂中的一种。
3. 根据权利要求1所述的组合物在制备促进毛发再生的制剂中的应用,其特征在于:所述制剂还包括乙醇,每ml 70%乙醇溶液中,所述橙皮苷的浓度为0.002g/ml;黄芩提取物的浓度为0.003g/ml;黄连提取物的浓度为0.03g/ml。
4.根据权利要求1所述的组合物在制备促进毛发再生的制剂中的应用,其特征在于:所述制剂促进因iNOS基因缺陷导致的脱发后再生障碍的毛发再生。
5.根据权利要求1所述的组合物在制备促进毛发再生的制剂中的应用,其特征在于:所述制剂通过降低Wnt信号通路关键基因、BMP信号通路关键基因以及细胞周期调控关键基因的mRNA表达水平以促进毛发再生,所述Wnt信号通路关键基因包括Wnt5a、Wnt11、Ctnnb1、Padi3、Hoxc13和Dlx3;所述BMP信号通路关键基因包括BMP2、BMP6和Runx1;所述细胞周期调控关键基因包括Ccnd1、Ccnd2和Ccna2。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202311754879.4A CN117427110B (zh) | 2023-12-20 | 2023-12-20 | 一种组合物及其在制备促进毛发再生的制剂中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202311754879.4A CN117427110B (zh) | 2023-12-20 | 2023-12-20 | 一种组合物及其在制备促进毛发再生的制剂中的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN117427110A CN117427110A (zh) | 2024-01-23 |
CN117427110B true CN117427110B (zh) | 2024-03-12 |
Family
ID=89552003
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202311754879.4A Active CN117427110B (zh) | 2023-12-20 | 2023-12-20 | 一种组合物及其在制备促进毛发再生的制剂中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN117427110B (zh) |
-
2023
- 2023-12-20 CN CN202311754879.4A patent/CN117427110B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN117427110A (zh) | 2024-01-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6215364B2 (ja) | MC−1R、MC−2R、およびμオピオイド受容体調節 | |
CN110540958B (zh) | 脐带间充质干细胞分泌因子的制备及其在生发中的应用 | |
WO2011065719A2 (ko) | 홍삼 다당체 추출물을 함유하는 피부 외용제 조성물 | |
Li et al. | Cardiac progenitor cell‑derived exosomes promote H9C2 cell growth via Akt/mTOR activation | |
CN114699446A (zh) | 一种用于治疗脱发的外泌体复合液及其制备方法 | |
TW201323005A (zh) | 皮膚之胸腺素β-4之調節 | |
KR20170093283A (ko) | Gdf11을 포함하는 조성물 및 그의 용도 | |
TWI784229B (zh) | 金銀花發酵物的製備方法及其改善皮膚外觀與抗老化的用途 | |
CN117427110B (zh) | 一种组合物及其在制备促进毛发再生的制剂中的应用 | |
Li et al. | Paeonol suppresses lipid formation and promotes lipid degradation in adipocytes | |
JP5905258B2 (ja) | 血小板由来成長因子−bb産生亢進剤、並びにそれを含む間葉系幹細胞産生促進剤、幹細胞安定化剤、及び真皮再生化剤 | |
Lee et al. | Effects of Pueraria lobata root ethanol extract on adipogenesis and lipogenesis during 3T3-L1 differentiation into adipocytes | |
AU2024203693A1 (en) | Use of flibanserin in preparation of drug for treating androgenic alopecia | |
Pekmezci et al. | Proprietary herbal extract downregulates the gene expression of IL-1α in HaCaT Cells: Possible implications against nonscarring alopecia | |
WO2012093804A2 (ko) | 사포닌 Rd와 Re를 유효성분으로 포함하는 발모용 조성물 | |
JP5496951B2 (ja) | 血小板由来成長因子(pdgf)−bb産生亢進剤、及びそれを含む幹細胞安定化剤 | |
WO2015141926A1 (ko) | 능실 추출물을 유효성분으로 함유하는 스트레스 자극에 의한 피부노화 억제 또는 개선용 조성물 | |
KR20180013422A (ko) | 암라 추출물을 함유하는 탈모방지 또는 발모촉진용 조성물 | |
KR101313724B1 (ko) | 감태 추출물을 주성분으로 하는 발모제 및 이를 함유하는 화장료 조성물 | |
Bottini et al. | Identification of an AP-1-like sequence in the promoter region of calcyclin, a S-100-like gene. Enhancement of binding during retinoic acid-induced neuroblastoma cell differentiation | |
CN105168065A (zh) | 一种多效美白祛斑精华霜及其制备方法 | |
CN110354154A (zh) | 一种可缓解干燥性皮肤炎症的沙枣多糖提取物及制备方法 | |
KR20070067364A (ko) | 히알루론산의 생성촉진을 위한 조성물 | |
Augustyniak et al. | Dietary marine-derived ingredients for stimulating hair cell cycle | |
Bojanowski et al. | Transbuccal platform for delivery of lipogenic actives to facial skin: Because fat matters |
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 |