KR101588841B1 - Composition for Preventing or Treating Hair Loss or Stimulating Hair Sprouting or Hair Growth Comprising Ocimene as Active Ingredients - Google Patents
Composition for Preventing or Treating Hair Loss or Stimulating Hair Sprouting or Hair Growth Comprising Ocimene as Active Ingredients Download PDFInfo
- Publication number
- KR101588841B1 KR101588841B1 KR1020150164918A KR20150164918A KR101588841B1 KR 101588841 B1 KR101588841 B1 KR 101588841B1 KR 1020150164918 A KR1020150164918 A KR 1020150164918A KR 20150164918 A KR20150164918 A KR 20150164918A KR 101588841 B1 KR101588841 B1 KR 101588841B1
- Authority
- KR
- South Korea
- Prior art keywords
- hair
- hair growth
- composition
- growth
- present
- Prior art date
Links
- 230000003779 hair growth Effects 0.000 title claims abstract description 84
- 239000000203 mixture Substances 0.000 title claims abstract description 60
- 201000004384 Alopecia Diseases 0.000 title claims abstract description 51
- 208000024963 hair loss Diseases 0.000 title claims abstract description 48
- 230000003676 hair loss Effects 0.000 title claims abstract description 39
- 150000007823 ocimene derivatives Chemical class 0.000 title claims description 40
- XJPBRODHZKDRCB-UHFFFAOYSA-N trans-alpha-ocimene Natural products CC(=C)CCC=C(C)C=C XJPBRODHZKDRCB-UHFFFAOYSA-N 0.000 title claims description 29
- 239000004480 active ingredient Substances 0.000 title claims description 18
- 210000004209 hair Anatomy 0.000 title description 44
- 230000004936 stimulating effect Effects 0.000 title description 2
- 230000001737 promoting effect Effects 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 239000002537 cosmetic Substances 0.000 claims abstract description 15
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 235000013376 functional food Nutrition 0.000 claims abstract description 11
- 230000003752 improving hair Effects 0.000 claims abstract description 9
- 230000002265 prevention Effects 0.000 claims abstract description 9
- 230000014509 gene expression Effects 0.000 claims description 23
- 108090000623 proteins and genes Proteins 0.000 claims description 11
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 claims description 8
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 claims description 8
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 claims description 8
- 102100037852 Insulin-like growth factor I Human genes 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 7
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 7
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 7
- 230000012010 growth Effects 0.000 claims description 7
- 102100021259 Frizzled-1 Human genes 0.000 claims description 4
- 102000001267 GSK3 Human genes 0.000 claims description 4
- 101000819438 Homo sapiens Frizzled-1 Proteins 0.000 claims description 4
- 108060006662 GSK3 Proteins 0.000 claims description 2
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 claims description 2
- 230000002708 enhancing effect Effects 0.000 claims description 2
- NFVJNJQRWPQVOA-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-2-[3-(4-ethyl-5-ethylsulfanyl-1,2,4-triazol-3-yl)piperidin-1-yl]acetamide Chemical compound CCN1C(SCC)=NN=C1C1CN(CC(=O)NC=2C(=CC=C(C=2)C(F)(F)F)Cl)CCC1 NFVJNJQRWPQVOA-UHFFFAOYSA-N 0.000 claims description 2
- 102000016362 Catenins Human genes 0.000 claims 1
- 108010067316 Catenins Proteins 0.000 claims 1
- 101001043594 Homo sapiens Low-density lipoprotein receptor-related protein 5 Proteins 0.000 claims 1
- 102100021926 Low-density lipoprotein receptor-related protein 5 Human genes 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 16
- 229940079593 drug Drugs 0.000 abstract description 14
- 235000013305 food Nutrition 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 11
- 230000001684 chronic effect Effects 0.000 abstract description 2
- 229930014626 natural product Natural products 0.000 abstract description 2
- 231100000957 no side effect Toxicity 0.000 abstract description 2
- 208000017667 Chronic Disease Diseases 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 210000003491 skin Anatomy 0.000 description 22
- 210000001519 tissue Anatomy 0.000 description 20
- 108060000903 Beta-catenin Proteins 0.000 description 14
- 102000015735 Beta-catenin Human genes 0.000 description 14
- 210000003780 hair follicle Anatomy 0.000 description 14
- 230000001965 increasing effect Effects 0.000 description 14
- 239000013642 negative control Substances 0.000 description 14
- 239000000523 sample Substances 0.000 description 13
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 description 11
- -1 tracant Substances 0.000 description 11
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 229960003632 minoxidil Drugs 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 239000008363 phosphate buffer Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 239000000843 powder Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 210000002268 wool Anatomy 0.000 description 6
- IHPKGUQCSIINRJ-CSKARUKUSA-N (E)-beta-ocimene Chemical compound CC(C)=CC\C=C(/C)C=C IHPKGUQCSIINRJ-CSKARUKUSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 241000196324 Embryophyta Species 0.000 description 5
- 102000001770 Low Density Lipoprotein Receptor-Related Protein-5 Human genes 0.000 description 5
- 108010015167 Low Density Lipoprotein Receptor-Related Protein-5 Proteins 0.000 description 5
- 102000013814 Wnt Human genes 0.000 description 5
- 108050003627 Wnt Proteins 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 238000010162 Tukey test Methods 0.000 description 4
- 230000003698 anagen phase Effects 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 230000031774 hair cycle Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 238000001543 one-way ANOVA Methods 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 230000003658 preventing hair loss Effects 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000000284 resting effect Effects 0.000 description 4
- 210000004761 scalp Anatomy 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 101150030271 AXIN1 gene Proteins 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000256844 Apis mellifera Species 0.000 description 3
- 102000051172 Axin Human genes 0.000 description 3
- 108700012045 Axin Proteins 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 description 3
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 3
- 241000257303 Hymenoptera Species 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 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 description 3
- 238000009395 breeding Methods 0.000 description 3
- 230000001488 breeding effect Effects 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000002500 effect on skin Effects 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 239000000344 soap Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 229960002920 sorbitol Drugs 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108010045438 Frizzled receptors Proteins 0.000 description 2
- 102000005698 Frizzled receptors Human genes 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000013614 RNA sample Substances 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 231100000360 alopecia Toxicity 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000378 calcium silicate Substances 0.000 description 2
- 229910052918 calcium silicate Inorganic materials 0.000 description 2
- 235000012241 calcium silicate Nutrition 0.000 description 2
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000003016 pheromone Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000001294 propane Substances 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 230000037390 scarring Effects 0.000 description 2
- 239000002453 shampoo Substances 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000003797 telogen phase Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- OSUJYLRDFDGEHZ-NYVDXTBYSA-N (3E)-3,7-dimethylocta-1,3,6-triene Chemical group CC(C)=CC\C=C(/C)C=C.CC(C)=CC\C=C(/C)C=C OSUJYLRDFDGEHZ-NYVDXTBYSA-N 0.000 description 1
- 108030004091 (E)-beta-ocimene synthases Proteins 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 108020005065 3' Flanking Region Proteins 0.000 description 1
- 108020005029 5' Flanking Region Proteins 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 238000011814 C57BL/6N mouse Methods 0.000 description 1
- 208000019300 CLIPPERS Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 208000005156 Dehydration Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 101000993347 Gallus gallus Ciliary neurotrophic factor Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- GVVPGTZRZFNKDS-YFHOEESVSA-N Geranyl diphosphate Natural products CC(C)=CCC\C(C)=C/COP(O)(=O)OP(O)(O)=O GVVPGTZRZFNKDS-YFHOEESVSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 206010024769 Local reaction Diseases 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 240000000249 Morus alba Species 0.000 description 1
- 235000008708 Morus alba Nutrition 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 206010058667 Oral toxicity Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 238000010240 RT-PCR analysis Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- ULUAUXLGCMPNKK-UHFFFAOYSA-N Sulfobutanedioic acid Chemical compound OC(=O)CC(C(O)=O)S(O)(=O)=O ULUAUXLGCMPNKK-UHFFFAOYSA-N 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 244000126002 Ziziphus vulgaris Species 0.000 description 1
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 201000002996 androgenic alopecia Diseases 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000001166 anti-perspirative effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003213 antiperspirant Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-M bromate Inorganic materials [O-]Br(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-M 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003778 catagen phase Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
- 208000021930 chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Diseases 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 239000005712 elicitor Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000002979 fabric softener Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 230000006408 female gonad development Effects 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000021582 food-grade substance Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- GVVPGTZRZFNKDS-JXMROGBWSA-N geranyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CO[P@](O)(=O)OP(O)(O)=O GVVPGTZRZFNKDS-JXMROGBWSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 201000000079 gynecomastia Diseases 0.000 description 1
- 230000034756 hair follicle development Effects 0.000 description 1
- 230000003646 hair health Effects 0.000 description 1
- 230000003659 hair regrowth Effects 0.000 description 1
- 230000036732 histological change Effects 0.000 description 1
- 235000020256 human milk Nutrition 0.000 description 1
- 210000004251 human milk Anatomy 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical class C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 238000012151 immunohistochemical method Methods 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 231100000016 inhalation toxicity Toxicity 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 231100000418 oral toxicity Toxicity 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000037039 plant physiology Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940117382 propecia Drugs 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000001373 regressive effect Effects 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940071089 sarcosinate Drugs 0.000 description 1
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- IHPKGUQCSIINRJ-UHFFFAOYSA-N β-ocimene Natural products CC(C)=CCC=C(C)C=C IHPKGUQCSIINRJ-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
- A61K31/01—Hydrocarbons
-
- A23L1/30—
-
- 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
- A61K8/31—Hydrocarbons
-
- 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
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
Abstract
The present invention relates to a pharmaceutical composition for prevention or treatment of hair loss or for promoting hair growth or hair growth comprising ocimen or a pharmaceutically acceptable salt thereof; And a quasi-drug, a cosmetic composition, a functional food composition or a food composition for improving hair loss or promoting hair growth or hair growth. According to the present invention, the composition of the present invention not only contains a natural compound having no side effects even in chronic treatment for hair loss, which is a chronic disease, but also has an excellent and stable effect on hair growth and hair growth, Cosmetics for the promotion of hair growth or hair growth / cosmetics / functional food / food composition.
Description
The present invention relates to a composition for preventing or treating hair loss, or for promoting hair growth or hair growth, comprising ocimene or a pharmaceutically acceptable salt thereof as an active ingredient.
According to the National Health Insurance Corporation 's Health Insurance Policy Institute' s analysis of health insurance payment data from 2001 to 2008, the number of patients treated with 'hair loss disease' increased from 103,000 in 2001 to 142,000 in 2005, In 2008, it reached 165,000, which has increased by 60% over the past seven years. By age, the number of patients in their 20s and 40s was 114,000, accounting for 69.5% of the patients, and the number of patients under 10 was more than 22,000. As of 2008, the number of patients treated by gender was 84,000 men and 80,000 women, with males slightly more than females. The number of patients treated with 'hair loss' (13,000), scarring alopecia (20,000), androgenic alopecia (9,000), and other non-scarring hair loss (8,000).
The prevalence rate of hair loss in overseas countries is estimated to be 250 million people in the world and 30-65% in the age group of 24-50 years, according to the International Hair and Cosmetic Research Debate on June, 2003. As of 2008, China's hair loss population is about 300 million, 30% of the male population in their 30s, and 50% of the male population in their 50s have hair loss symptoms, and the number of hair loss patients increases by 10-15% . In Japan, the rate of hair loss was 26.5%, and the estimated number of patients with hair loss was estimated at 12.93 million.
Currently, treatments for hair loss treatments are classified into pharmaceuticals, quasi-drugs, and cosmetics. The specialty medicine that can be purchased with a doctor's prescription is "Propecia", which is developed and sold by Merck, USA. Its main ingredient, Finasteride, was approved by the US FDA for hair loss treatment in December 1997. Pinasteride is an inhibitor of 5-α-reductase enzymes that convert testosterone to dihydrotestosterone (DHT), which is responsible for the growth of hair into thick, long hair. This is effective in improving hair loss in the short term, but side effects such as erectile dysfunction, sexual dysfunction and male breast enlargement are reported. Minoxidil has been approved as safe and effective and can be purchased without doctor's prescription. In December 1997, it was approved as FDA's first hair loss treatment. This drug has the effect of promoting hair growth by improving blood circulation and opening the potassium channel, but local reactions such as itching, rash, and tachycardia may occur.
Among the quasi-drug products approved by the KFDA for the prevention of hair loss and hair growth, there are CJ Lion's 'Hair Force Competent', Morlacle's 'Hair Tonic' and LG Household & Health Care's 'Mo.Moa'. Cosmetics include shampoo or skin , Products used for scalp or hair to maintain or promote hair health are being sold.
Human hair loss cycle is largely divided into anagen, catagen, and telogen. The growing period is the time when the activity of the breast milk is active and the cell division is vigorous and the hair grows at a high speed. The lifespan of the growing period varies depending on the type of hair, but in the case of hair, it is about 3-6 years. Growing hair accounts for 80-90% of total hair, and the person with hair loss progresses to shortening of growing period and having a long hair cycle, so that the specific gravity of growing hair in total hair is decreased. The regressive period is the period when the growth of the hair ends and the production of the hair is slowed down. As a result, cell division and growth are stopped. The life of the retrograde period is about 1-1.5 months, and about 1% of the total hair belongs to this stage. The resting stage is the final stage of growth, in which the hair follicles and hair follicles are completely separated and the hair follicles are contracted, and the hair follicles are further raised upward and hair is removed. The rest period lasts 3-4 months and 4-14% of total hairs are in this stage. When the dormant period is over and the activity of the dermal papilla becomes active again, the new dermal papilla is made, and the hair at the dormant pillar is pushed out completely out of the scalp.
Ocimene is a monoterpin compound and its IUPAC name is (3E) -3,7-dimethylocta-1,3,6-triene [(3E) -3,7-dimethylocta-1,3,6-triene] . The formula is C 10 H 16 and the molecular weight is 136.2 g / mol. Ocimene is a colorless or pale yellow transparent liquid that does not dissolve in water but dissolves in oil and ethanol. Ocimene is known to be a constituent of flower fragrance of various plants. Ocimene, a volatile substance released from plants, plays a role in defending plants from predatory insects. In other words, ocimene is biosynthesized from geranyl diphosphate by the catalytic action of an enzyme called 'beta-ocimene synthase' present in plants, And the plant defense elicitor [http://en.wikipedia.org/wiki/Pasquale Cascone et al.]. (E) -beta-ocimene_synthase; Journal of Plant Physiology 173: 2832, 2015]. In addition, E-β-ocimene is a major component of the volatile pheromone secreted by bees (Apis mellifera; western bees), and it focuses primarily on suppressing the ovarian development of worker bees and increasing food storage for racial maintenance. (E) -β-Ocimene, a volatile blood pheromone involved in social regulation in the honey bee colony (Apis mellifera). PLoS ONE 5 (10): e13531, 2010]. On the other hand, little research has been reported on the physiological activity of the osmium component in the animal body. Ocimene has been used commercially for lotions, antiperspirants, fabric softeners, glass cleaners, shampoos and soaps. Ocimene is also known as a safe and safe food grade substance. It is also known as Flavor and Extract Manufacturers Association (FEMA), Food and Drug Administration (FDA), Korea Food and Drug Administration (KFDA), European Community, ) And JECFA (Joint FAO / WHO Expert Committee on Food Additives) have been approved as flavor and frag- ment agents, and have been used for industrial taste and flavor. An oral toxicity study in rats reported an LD 50 value of 5,000 mg / kg and reported no transdermal and inhalation toxicity. However, there is no report on oshimene hair loss prevention or hair growth promoting activity.
Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.
The present inventors have made intensive researches in order to discover natural-derived compounds that can prevent hair loss or promote hair growth or hair growth without side effects. As a result, the present invention was completed by confirming that ocimer effectively promotes hair growth and hair growth and prevents hair loss.
Accordingly, an object of the present invention is to provide a pharmaceutical composition for prevention or treatment of hair loss or promoting hair growth or hair growth comprising ocimen or a pharmaceutically acceptable salt thereof as an active ingredient; And a quasi-drug, a cosmetic composition, a functional food composition or a food composition for improving hair loss or promoting hair growth or hair growth.
Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.
According to one aspect of the present invention, there is provided a pharmaceutical composition for prevention or treatment of hair loss, or hair growth promoting hair growth, comprising ocimen or a pharmaceutically acceptable salt thereof as an active ingredient.
The present inventors have made intensive researches in order to discover natural-derived compounds that can prevent hair loss or promote hair growth or hair growth without side effects. As a result, it was confirmed that ocimer effectively promotes hair growth and hair growth and prevents hair loss.
As used herein, the term " hair loss " refers to a phenomenon in which the hair completely comes out of the scalp. People who are undergoing hair loss have a shorter growth period and a longer hair cycle. As demonstrated in the following examples, ocimene converts hair from a resting state to a growth phase (Fig. 1) (Figs. 4A, 4B and 5A to 5C), it was confirmed that hair loss was prevented, improved or treated.
The term " hair growth " as used herein means that the hair grows in the scalp, and the term " hair growth " as used herein means that the length of hair becomes longer (i.e., hair growth) Wool "is used in the same sense. As demonstrated in the following example, ocimene promotes hair growth (Fig. 1), increases hair length by 188% (Fig. 2), increases the number and diameter of hair follicles 3c), and the expression of hair growth and wool-related growth factors in skin tissue was increased (Figs. 4a, 4b and 5a to 5c).
The ocimene of the present invention can be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. As the free acid, inorganic acid and organic acid can be used.
Specifically, the pharmaceutically acceptable salts of ocimene of the present invention include the hydrochloride, bromate, sulfate, phosphate, citrate, acetate, trifluoroacetate, lactate, tartrate, maleate, fumarate, , Methanesulfonate, glycolate, succinate, 4-toluenesulfonate, gluturonate, ebonate, glutamate, or aspartate, but is not limited to, And salts formed using various inorganic acids and organic acids used. The ocimene of the present invention may also exist in the form of a solvate (for example, a hydrate).
According to one embodiment of the present invention, the composition of the present invention comprises Wnt10b, FZD1 (Frizzled receptor 1), LRP5 (Low-density lipoprotein receptor-related protein 5), Insulin- factor 1), beta -catenin, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and keratocyte growth facor (KGF). According to one embodiment of the present invention, the composition of the present invention reduces the expression of GSK3? (
According to the present invention, the composition of the present invention can be manufactured from a pharmaceutical composition for prevention or treatment of hair loss, or for promoting hair growth or hair growth. When the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the present invention and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).
The pharmaceutical composition of the present invention may be administered orally or parenterally, and may be administered parenterally according to one embodiment of the present invention, and transdermally administered according to another embodiment of the present invention.
The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . A preferred dosage of the pharmaceutical composition of the present invention is within the range of 0.0001-100 mg / kg on an adult basis.
The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of excipients, powders, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
According to another aspect of the present invention, there is provided a quasi-drug composition for improving hair loss or promoting hair growth or hair growth comprising ocimen or a pharmaceutically acceptable salt thereof as an active ingredient.
When the composition of the present invention is used as a quasi-drug composition, the above oscimene or a pharmaceutically acceptable salt thereof may be directly added or used together with other quasi-drugs, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). According to one embodiment of the present invention, the quasi-drug composition of the present invention may be a disinfectant cleaner, a shower foam, a gagrin, a wet tissue, a detergent soap, a hand wash, a humidifier filler, a mask, an ointment agent or a filter filler.
According to another aspect of the present invention, there is provided a cosmetic composition for improving hair loss or for promoting hair growth or hair growth comprising ocimen or a pharmaceutically acceptable salt thereof as an active ingredient.
The components contained in the cosmetic composition of the present invention include components commonly used in cosmetic compositions in addition to ocimene or its pharmaceutically acceptable salts as an active ingredient and include, for example, antioxidants, stabilizers, solubilizers, vitamins, Customary adjuvants such as perfumes, and carriers.
The cosmetic composition of the present invention can be prepared into any of the formulations conventionally produced in the art and can be used as a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, , Oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto.
When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .
In the case where the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. Especially, in the case of a spray, a mixture of chlorofluorohydrocarbons, propane / Propane or dimethyl ether.
When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.
In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.
When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters.
According to still another aspect of the present invention, there is provided a functional food composition or food composition for enhancing hair loss or promoting hair growth or hair growth comprising ocimene or a pharmaceutically acceptable salt thereof as an active ingredient.
When the composition of the present invention is prepared with a functional food composition or a food composition, it includes not only ocimene or its pharmaceutically acceptable salt as an active ingredient, but also components which are conventionally added in the production of a functional food or a food, For example, it includes proteins, carbohydrates, fats, nutrients, seasoning and flavoring agents. Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavorings such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavorings (saccharine, aspartame, etc.) can be used as flavorings.
When the functional food or the food composition of the present invention is prepared with a drink, it may contain citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, mulberry extract, Jujube extract or licorice extract may be further included.
Since the quasi-drugs, cosmetics, functional foods and food compositions of the present invention share the above-mentioned pharmaceutical composition with the active ingredients and uses thereof, the common content in relation to the pharmaceutical composition is not limited to the above- The description is omitted.
The features and advantages of the present invention are summarized as follows:
(a) a pharmaceutical composition for preventing or treating hair loss, or for promoting hair growth or hair growth; And a quasi-drug, a cosmetic composition, a functional food composition or a food composition for improving hair loss, or for promoting hair growth or hair growth.
(b) The composition of the present invention not only contains a natural compound having no side effects even in chronic treatment for alopecia, but also exhibits an excellent and stable effect on hair growth and hair growth, thus showing an effective hair loss preventing or treating agent, Cosmetics / functional foods / food compositions for accelerating hair growth.
FIG. 1 is a diagram showing a result of observing regrowth of hair with the elapsed days of administration of each sample in a hair model mouse model. FIG.
FIG. 2 is a graph showing hair lengths grown during the experimental period in a mouse to which each sample is applied. Each value is the mean ± SE of 8 mice. ns = p > 0.05, ** = p <0.01 [one-way ANOVA, Tukey's test].
Fig. 3 shows the result of histological observation of skin such as a mouse to which each sample was applied for 4 weeks. FIG. 3 (a) is a result of confirming the increase in the number of hair follicles, FIG. 3 (b) is a result of evaluating the hair follicle diameter, and FIG. Each value is the mean ± SE of 8 mice. ns = p > 0.05, ** = p <0.01, *** = p <0.001 [one-way ANOVA, Tukey's test].
Fig. 4 shows protein expression changes in skin tissues such as mice coated with each sample. 4A is an immunohistological result, and FIG. 4B is a Western blot result. Western blot results are the mean ± SE of three independent experiments in each group (n = 2 or 3 for each experiment). ns = p > 0.05, ** = p <0.01 [one-way ANOVA, Tukey's test].
FIG. 5 is a graph showing changes in gene expression of skin tissues such as mice to which each sample is applied. Western blot results are the mean ± SE of three independent experiments in each group (n = 2 or 3 for each experiment). ns = p > 0.05, * = p <0.05, ** = p <0.01, *** = p <0.001 [one-way ANOVA, Tukey's test].
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .
Example
Example 1: Efficacy of Ocimene to promote hair growth
1-1. Breeding of experimental animals and application of samples
Preparation of sample
Vehichle (ethanol: water: propylene glycol = 5: 3: 2), the reference drug minoxidil (MXD) and the test substance ocimene (OCM) were purchased from Sigma Aldrich.
Breeding of experimental animals
Twenty-four male C57BL / 6N mice were purchased from Orient Biotech Co., Ltd., and were adapted to the breeding environment for 2 weeks. Negative control (Con group), positive control group (MXD group) and oocimen group (OCM group) The results are summarized as follows. The animals were kept at a temperature of 21 ± 2.0 ° C and a relative humidity of 50 ± 5% for 12 hours. During the experimental period, the mice were fed free of general solid feed (chow) and water.
Skin application and gross observation method of sample
In order to investigate hair loss prevention, hair growth or wool effect, 8-week-old mice with resting hairs whose pink color was seen on the dorsal skin were used. After removing the hairs of the mouse back plate using a clipper for a mouse, each sample was applied once a day at 4:00 PM for 4 weeks. Minoxidil (3 mg / mouse / day) used as a test substance and ocimen (3 mg / mouse / day) as an experimental substance were dissolved and applied in a vehicle (ethanol: water: propylene glycol = 5: 3: 2) Only the vehicle was applied to the negative control group.
At the end of 1, 2, 3, and 4 weeks of application, the animals were lightly anesthetized with ether and photographed. Hair length was measured using a ruler to evaluate the extent of hair growth.
1-2. Measurement of weight change
The weight of the experimental animals was measured weekly from immediately before application of the sample to the end of application. There was no significant difference in the initial body weights of the negative control group (Con), test group (OCM group), and positive control group (MXD group).
1-3. Measurement of changes in hair growth and hair length
Gross features of hair growth
The sample was applied to the back part of the mouse for 4 weeks, and the appearance of the hair growing each week was photographed and confirmed. The mice that entered the telogen were pink when the hair was removed. In the control group (Con group), the hair did not grow even after 3 weeks. In the OCM group, the hair began to grow from the 3rd week after application, and the body surface color changed to black. The hair cycle entered the anagen from the resting period. Thereafter, it was observed that the hair grows evenly and vigorously in a larger number of individuals than in the negative control group (Fig. 1).
Change in hair length
The length of the hair was measured every week for the duration of the experiment (4 weeks). The hair length of the OCM group was significantly increased from the 3rd week to the negative control group, and increased by 188% after 4 weeks compared to the negative control group (FIG. 2). Therefore, it can be seen that ocimene has an excellent effect of promoting hair growth.
1-4. Histological analysis of skin
Four weeks after the application of each sample, the test animal was sacrificed and the dermal tissue sample was extracted with scissors and forceps around the area to which the test substance was applied, and fixed with formalin. Stepwise dehydration treatment with alcohol and xylene, embedding with paraffin, and 5 μm slice using a microtome were repeated to remove paraffin with alcohol and xylene. Hematoxylin-eosin (H & E) staining was performed and histological changes of the hair follicles were observed under an optical microscope. Histopathologists were examined to evaluate the hair growth cycle, and hair follicle volume and diameter were measured on an optical microscope.
The results of measurement of the number of hair follicles in each test group under an optical microscope of 40 magnification are shown in FIG. The number of hair follicles was significantly increased in the OCM group and the MXD group as compared to the negative control group (Fig. 3a). Image analysis was performed to evaluate the follicle diameter of each test group, which was significantly increased in the OCM group and the MXD group as compared to the negative control group (FIG. 3B). In addition, in the OCM group and the MXD group, the hair follicle was prolonged and the skin was expressed, thereby confirming the effect of accelerating the hair growth of ocimene and minoxidil (FIG. 3C).
Example 2: Regulation of protein and gene expression in mouse skin tissue by ocimene
2-1. Changes in hair-related protein expression in skin tissue
Immunohistochemical analysis
Recently, it has been shown that the intracellular signal transduction activating factors such as Wnt /? -Catenin plays a role in hair growth and elimination, and the factor is attracting attention as a new target of drugs for suppressing hair loss and promoting hair growth. Therefore, we investigated the activation of Wnt / β-catenin signal transduction system, which is involved in the prevention of hair loss and promotion of hair growth (or hair growth), in the dorsal skin tissue by 4 weeks of application of the sample by immunohistochemical method.
To observe the expression of IGF1 and β-catenin associated with hair growth in skin tissue, the primary antibody against IGF1 and β-catenin was diluted 1:50, respectively, and then added to tissue sections and allowed to react at room temperature for 12 hours . Dilution of the primary antibody was performed by mixing 1% normal goat serum (Vector Laboratories Inc.) and 0.3% Triton X-100 (Sigma) in 0.1 M phosphate buffer (PB) The tissue sections were washed with 0.1 M PB twice for 15 min at room temperature and then reacted with secondary antibody (biotinylated anti-rabbit IgG (Vector Laboratories Inc.)) diluted 1: 200 for 1 h at room temperature. After washing twice with 0.1 M PB for 15 minutes, the cells were immersed in peroxidase-labeled ABC (avidin-biotin complexex) solution and reacted at room temperature for 1 hour. After washing with 0.1 M PB for 15 minutes twice, 30 mg of 3-3 'diaminobenzidine was dissolved in 150 ml of 0.1 M PB for 5 minutes. Then, hydrogen peroxide was added at a concentration of 0.005% Brown color reaction was performed for about 5 minutes. After completion of the reaction, tissues were washed again with 0.1 M PB several times, counterstained with hematoxylin for 20 seconds, dehydrated and clarified according to a conventional method, sealed, and observed with an optical microscope.
As a result, β-catenin and IGF1 were detected more in the OCM group than in the negative control group. It was observed that the ocimene-induced increase in the expression of β-catenin and IGF1 in dorsal skin tissue was more excellent than that of minoxidil (FIG. 4A).
Western blot analysis
A certain amount of skin tissue was homogenized with a liquid nitrogen and a lysis buffer in a mortar and then centrifuged at 13,000 × g at 4 ° C. for 20 minutes. Then, the middle layer was taken and the protein was quantified by the Bradford method. 50 μg of the protein was electrophoresed on SDS polyacrylamide gel, electroblotted onto PVDF hyperfilm, and the antibody, β-catenin, β-actin (all from Cell-signaling Technology Inc., USA) Respectively. The signal of each protein was visualized with a chemiluminescent detection system (Amersham) and the band thickness was quantified using Quantity One Analysis Software (Bo-Rad Laboratories).
As a result, beta -catenin protein expression was significantly increased in the OCM group as compared with the negative control group (Fig. 4B).
2-2. Analysis of hair-related gene expression in skin tissue
RNA isolation using the Trizol method
To quantify the total RNA in skin tissue of experimental animals, 1 mL of the trizol solution was added to 50-100 mg of skin tissue, homogenized, and centrifuged at 12,000 × g for 10 minutes at 4 ° C. The supernatant was transferred to a new tube, and then 200 μL of chloroform was added and vortexed. This process was repeated twice, then the supernatant was transferred to a new tube and isopropanol and supernatant were added at a ratio of 1: 1. After 10 minutes of shaking, the mixture was allowed to stand at room temperature for 10 minutes, and centrifuged at 12,000 × g for 10 minutes at 4 ° C. After removing the supernatant, 1 ml of 70% ethanol was added to the remaining precipitate to obtain 7,500 × g, Lt; / RTI > for 5 minutes. After removing the ethanol, the tube containing the RNA precipitate was dried at room temperature for 5 minutes, and the RNA precipitate was dissolved using nuclease free water. The concentration of RNA samples extracted at 260 nm and 280 nm wavelengths was measured using a UV / VIS spectrophotometer (Beckman coulter, DU730) and agarose gel electrophoresis was performed to confirm the integrity of the RNA samples.
Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method
RNA was isolated and reverse transcribed using oligo dT primer and Superscript reverse transcriptase (GIBCOBRL, Gaithersburg, USA) to synthesize cDNA. PCR was carried out using the cDNA obtained through reverse transcription as a template and the 5 'and 3' flanking sequences of the cDNA of the gene to be amplified as primers. The necessary primers were used for the synthesis of biona Co., Ltd. These primer sequences are shown in Table 1 below. Add 1 μL each of the 10X reaction buffer [100 mM KCL, 20 mM Tris-HCl (pH 8.0), 2.5 mM MgCl 2 ], 4 μL of 10 mM dNTP, 0.2 μM sense and antisense primer, And 2.5 units of Taq polymerase (Takara, Japan) were added to each well, and the volume was adjusted to 50 μL with distilled water. PCR was performed using PCR instrument. PCR conditions were 94 ° C (4 min), 94 ° C (30 sec), 30 cycles [52 ° C (30 sec), 72 ° C (45 sec)] and 72 ° C (10 min). 1 μL of the amplified product was electrophoresed on 1% agarose gel to confirm the DNA band to evaluate gene expression amount.
Regulation of Expression of Hairy Related Gene
The expression of Wnt / β-catenin signaling agent, which is known as a mechanism of hair loss prevention, hair growth (or hair growth), in the dorsal skin of mice that had been applied for 4 weeks was analyzed by RT-PCR analysis. As a result, Wnt10b And Wnt10b receptors, FZD1 (frizzled receptor 1) and LRP5 (low-density lipoprotein receptor-related protein 5), were significantly increased in the OCM group compared to the negative control group. Thus, GSK3β (glycogen synthase kinase 3β) and Axin, which were inhibited by Wnt10b, were significantly decreased in the OCM group compared to the negative control group. The expression of beta -catenin was significantly increased in the OCM group as compared to the negative control according to the activation of the Wnt / beta -catenin signal transduction system (FIGS. 5A and 5C).
In addition, the expression of endocrine factors affecting hair growth was evaluated in order to investigate the mechanism of hair loss prevention, hair growth or hair growth promoting action of ocimer. (VEGF), HGF (hepatocyte growth factor), and KGF (keratocyte growth fac- tor), which are growth factors affecting hair growth and wool in skin tissue , The expression of the four genes was significantly increased in the OCM group as compared with the negative control group (Figs. 5B and 5C).
Therefore, ocimer accelerates the growth of the hair follicle, thereby activating the hair follicle to return to the growth phase. In addition, by increasing the expression of IGF1, HGF, VEGF and KGF in the skin tissue, hair regrowth is promoted to prevent hair loss, .
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.
Claims (7)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020150164918A KR101588841B1 (en) | 2015-11-24 | 2015-11-24 | Composition for Preventing or Treating Hair Loss or Stimulating Hair Sprouting or Hair Growth Comprising Ocimene as Active Ingredients |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020150164918A KR101588841B1 (en) | 2015-11-24 | 2015-11-24 | Composition for Preventing or Treating Hair Loss or Stimulating Hair Sprouting or Hair Growth Comprising Ocimene as Active Ingredients |
Publications (1)
Publication Number | Publication Date |
---|---|
KR101588841B1 true KR101588841B1 (en) | 2016-01-26 |
Family
ID=55307565
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020150164918A KR101588841B1 (en) | 2015-11-24 | 2015-11-24 | Composition for Preventing or Treating Hair Loss or Stimulating Hair Sprouting or Hair Growth Comprising Ocimene as Active Ingredients |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR101588841B1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101733065B1 (en) | 2016-10-13 | 2017-05-08 | 연세대학교 산학협력단 | Composition comprising Decanal or as active ingredients for preventing hair loss or stimulating hair growth |
KR20220070611A (en) * | 2020-11-23 | 2022-05-31 | 국립낙동강생물자원관 | Composition for Hair Growth Stimulation or Hair Loss Prevention Using an Extract of Carex dispalata |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20150074537A (en) * | 2013-12-24 | 2015-07-02 | 주식회사 코씨드바이오팜 | Cosmetic composition containing Ocimum basilicum seed extract |
-
2015
- 2015-11-24 KR KR1020150164918A patent/KR101588841B1/en active IP Right Grant
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20150074537A (en) * | 2013-12-24 | 2015-07-02 | 주식회사 코씨드바이오팜 | Cosmetic composition containing Ocimum basilicum seed extract |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101733065B1 (en) | 2016-10-13 | 2017-05-08 | 연세대학교 산학협력단 | Composition comprising Decanal or as active ingredients for preventing hair loss or stimulating hair growth |
WO2018070706A1 (en) * | 2016-10-13 | 2018-04-19 | 연세대학교 산학협력단 | Composition for preventing hair loss or promoting hair growth comprising decanal or pharmaceutically acceptable salt thereof as active ingredient |
KR20220070611A (en) * | 2020-11-23 | 2022-05-31 | 국립낙동강생물자원관 | Composition for Hair Growth Stimulation or Hair Loss Prevention Using an Extract of Carex dispalata |
KR102516857B1 (en) | 2020-11-23 | 2023-03-31 | 국립낙동강생물자원관 | Composition for Hair Growth Stimulation or Hair Loss Prevention Using an Extract of Carex dispalata |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6196275B2 (en) | Isocrisis extract | |
JP6145106B2 (en) | Hair growth promoting agent, IGF-1 expression increasing agent, VEGF expression increasing agent, HGF expression increasing agent, KGF expression increasing agent, and β-catenin expression increasing agent comprising a purified secoiridoid glucoside derivative | |
US10617612B2 (en) | Composition comprising decanal or as active ingredients for preventing hair loss or stimulating hair growth | |
KR101588841B1 (en) | Composition for Preventing or Treating Hair Loss or Stimulating Hair Sprouting or Hair Growth Comprising Ocimene as Active Ingredients | |
JP6339189B2 (en) | Composition for promoting hair growth and hair growth | |
CA2948937A1 (en) | Association of a tetrapeptide and a glyceryl ester for treating androgenic alopecia | |
KR101620088B1 (en) | Composition for Preventing or Treating Hair Loss or Stimulating Hair Sprouting or Hair Growth Comprising Geranic Acid as Active Ingredients | |
KR101725461B1 (en) | Composition for Preventing or Treating Hair Loss or Stimulating Hair Sprouting or Hair Growth Comprising Diosmin as Active Ingredients | |
KR101587612B1 (en) | Composition for Preventing or Treating Hair Loss or Stimulating Hair Sprouting or Hair Growth Comprising Pinocarveol as Active Ingredients | |
US20190151256A1 (en) | Composition Including Nonanal As Active Ingredient For Preventing Hair Loss Or Stimulating Hair Development | |
KR102115667B1 (en) | Composition comprising irone for preventing hair loss or stimulating hair growth | |
KR102149957B1 (en) | Composition for preventing hair loss or promoting hair growth containing gintonin | |
EP3595627B1 (en) | Association of aqueous extracts of cress and nasturtium and atp in the treatment of alopecia | |
KR102013803B1 (en) | A composition for improving alopecia containing novel compounds isolated from chestnut bur | |
KR101741808B1 (en) | Composition for Preventing Hair Loss or Stimulating Hair Growth Comprising Sphinganine and Pterostilbene as Active Ingredients | |
KR101868208B1 (en) | Compositions for preventing, improving or treating hair loss comprising deoxycholic acid as an active component | |
US20190125648A1 (en) | Composition for preventing, improving or treating hair loss comprising deoxycholic acid as active ingredient | |
KR20180041046A (en) | Composition comprising Linallol or as active ingredients for preventing hair loss or stimulating hair growth | |
KR101177500B1 (en) | Hair growth stimulating composition | |
KR101467731B1 (en) | Composition for preventing hair loss or promoting hair growth comprising extract of Miscanthus sinensis var. purpurascens | |
TW201636013A (en) | Composition for promoting hair growth and/or restoration containing psoralidin and application thereof | |
KR101594116B1 (en) | Composition for inhibiting growth of body hair comprising 5-HTP as an effective ingredient | |
KR20190075193A (en) | Compositions for preventing or treating Psoriasis comprising extract of Rumex acetosella | |
EP2821052A1 (en) | Combination of miliacin and polar lipids, in particular of sphingolipids and/or phospholipids, for care of the hair and scalp | |
FR2996127A1 (en) | Use of (2S)-2-aminopentanoic acid in a composition e.g. hair care composition, preferably shampoo, hair setting lotion and styling cream or gel for treating seborrhea of skin and scalp and for slowing down hair loss |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A302 | Request for accelerated examination | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant |