JP2020045338A - External composition - Google Patents
External composition Download PDFInfo
- Publication number
- JP2020045338A JP2020045338A JP2019160123A JP2019160123A JP2020045338A JP 2020045338 A JP2020045338 A JP 2020045338A JP 2019160123 A JP2019160123 A JP 2019160123A JP 2019160123 A JP2019160123 A JP 2019160123A JP 2020045338 A JP2020045338 A JP 2020045338A
- Authority
- JP
- Japan
- Prior art keywords
- berberine
- composition
- mass
- ethanol
- external composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 67
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 claims abstract description 36
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 26
- 150000003836 berberines Chemical class 0.000 claims abstract description 21
- 229940058015 1,3-butylene glycol Drugs 0.000 claims abstract description 18
- 235000019437 butane-1,3-diol Nutrition 0.000 claims abstract description 18
- 239000002537 cosmetic Substances 0.000 claims abstract description 9
- 150000005846 sugar alcohols Polymers 0.000 claims abstract description 9
- VKJGBAJNNALVAV-UHFFFAOYSA-M Berberine chloride (TN) Chemical group [Cl-].C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 VKJGBAJNNALVAV-UHFFFAOYSA-M 0.000 claims description 24
- 229940093265 berberine Drugs 0.000 claims description 11
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 claims description 11
- 235000011187 glycerol Nutrition 0.000 claims description 11
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 claims description 10
- 229920002253 Tannate Polymers 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 8
- 238000009472 formulation Methods 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000008213 purified water Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 230000000052 comparative effect Effects 0.000 description 14
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 7
- 238000001556 precipitation Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- FWKQNCXZGNBPFD-UHFFFAOYSA-N Guaiazulene Chemical compound CC(C)C1=CC=C(C)C2=CC=C(C)C2=C1 FWKQNCXZGNBPFD-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- -1 polyoxyethylene Polymers 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 2
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- OJVABJMSSDUECT-UHFFFAOYSA-L berberin sulfate Chemical compound [O-]S([O-])(=O)=O.C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2.C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 OJVABJMSSDUECT-UHFFFAOYSA-L 0.000 description 2
- FUWUEFKEXZQKKA-UHFFFAOYSA-N beta-thujaplicin Chemical compound CC(C)C=1C=CC=C(O)C(=O)C=1 FUWUEFKEXZQKKA-UHFFFAOYSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 229960002350 guaiazulen Drugs 0.000 description 2
- 239000003676 hair preparation Substances 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- IJALWSVNUBBQRA-UHFFFAOYSA-N 4-Isopropyl-3-methylphenol Chemical compound CC(C)C1=CC=C(O)C=C1C IJALWSVNUBBQRA-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 235000015701 Artemisia arbuscula Nutrition 0.000 description 1
- 235000002657 Artemisia tridentata Nutrition 0.000 description 1
- 235000003261 Artemisia vulgaris Nutrition 0.000 description 1
- 240000006891 Artemisia vulgaris Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 244000124209 Crocus sativus Species 0.000 description 1
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- 241000186427 Cutibacterium acnes Species 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 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
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 244000061508 Eriobotrya japonica Species 0.000 description 1
- 235000009008 Eriobotrya japonica Nutrition 0.000 description 1
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 1
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- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
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- 241001093501 Rutaceae Species 0.000 description 1
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- 239000004288 Sodium dehydroacetate Substances 0.000 description 1
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- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
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- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 1
- FWYFZZHHADLSHQ-UHFFFAOYSA-M sodium;azulene-1-sulfonate Chemical compound [Na+].C1=CC=CC=C2C(S(=O)(=O)[O-])=CC=C21 FWYFZZHHADLSHQ-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- UIERGBJEBXXIGO-UHFFFAOYSA-N thiamine mononitrate Chemical compound [O-][N+]([O-])=O.CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N UIERGBJEBXXIGO-UHFFFAOYSA-N 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 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
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- 229930007845 β-thujaplicin Natural products 0.000 description 1
Landscapes
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
本発明は、ベルベリン塩を含有し、製剤安定性に優れた外用組成物に関する。 The present invention relates to an external composition containing a berberine salt and having excellent formulation stability.
ベルベリンは、キハダ（ミカン科）やオウレン（キンポウゲ科）などの植物に含まれるベンジルイソキノリンアルカロイドの１種であり、対アニオンの種類の違いにより、ベルベリン塩化物、ベルベリン硫酸塩、タンニン酸ベルベリン等が知られる。これらベルベリン塩は、アズレンスルホン酸ナトリウム、グアイアズレンスルホン酸などのアズレン類と同様に、抗炎症効果、抗菌効果等を目的として外用剤として例えば点眼剤等に広く配合されている成分である。化粧料などの皮膚外用の組成物においてベルベリンは、メラノサイトのデンドライト伸長抑制作用を有することが知られており、皮膚の美白に好適な予防或いは改善手段であることが示唆されている（特許文献１）。また、皮膚常在菌であるプロピオニバクテリウムアクネス（Propionibacterium acnes）に対して、極めて高い抗菌力を発揮するため、ニキビ肌用皮膚外用組成物としても提案されている（特許文献２）。
しかし、このベルベリンに関して、長期間に亘り保存すると、残存率が低下するという問題が生じており、これまでに香料成分の添加やポリオキシエチレン硬化ヒマシ油により改善されること等が提案されている（特許文献３〜５）。
Berberine is a type of benzylisoquinoline alkaloid contained in plants such as yellowfin (Rutaceae) and spinach (Ranunculaceae). Depending on the type of counter anion, berberine chloride, berberine sulfate, berberine tannate, and the like are different. known. These berberine salts, like azulene such as sodium azulene sulphonate and guaiazulene sulphonic acid, are components widely used as external preparations such as eye drops for the purpose of anti-inflammatory effect, antibacterial effect and the like. Berberine is known to have a melanocyte dendrite elongation inhibitory effect in compositions for external use on skin such as cosmetics, and it has been suggested that it is a suitable preventive or ameliorating means for skin whitening (Patent Document 1). ). In addition, it has been proposed as a skin external composition for acne skin because it exhibits extremely high antibacterial activity against Propionibacterium acnes, which is a resident bacterium (Patent Document 2).
However, with respect to this berberine, when it is stored for a long period of time, there is a problem that the residual ratio is reduced, and it has been proposed that the berberine is improved by addition of a fragrance component or polyoxyethylene hydrogenated castor oil. (Patent Documents 3 to 5).
本発明者らは、ベルベリン塩を含有した外用組成物を調製し、低温にて保存したところ、ベルベリン塩由来と考えられる結晶の析出が認められ、製剤安定性が劣るといった課題を見出した。したがって、本発明はベルベリン塩を含有し、製剤安定性に優れた外用組成物を提供することを課題とする。 The present inventors have prepared a topical composition containing a berberine salt and stored it at a low temperature. As a result, it has been found that crystals which are considered to be derived from the berberine salt are precipitated, and the stability of the preparation is poor. Therefore, an object of the present invention is to provide an external composition containing a berberine salt and having excellent formulation stability.
本発明者らは、上記課題を解決すべく鋭意検討を重ねた結果、ベルベリン塩と一定量以上のエタノールと特定の多価アルコールを配合し、かつ、ベルベリン塩に対して前記多価アルコールを特定の割合で配合すると上記課題を解決できることを見出し、本発明を完成するに至った。 The present inventors have conducted intensive studies to solve the above problems, and as a result, blended berberine salt, a certain amount or more of ethanol and a specific polyhydric alcohol, and specified the polyhydric alcohol with respect to the berberine salt. It has been found that the above-mentioned problems can be solved by blending at a ratio of 2. The present invention has been completed.
すなわち本発明は、
（１）（ａ）ベルベリン塩、（ｂ）４０〜９６質量％のエタノール、（ｃ）４〜３０質量％のグリセリン及び１，３−ブチレングリコールからなる群から選ばれる少なくとも１種の多価アルコール、を含有し、（ａ）１質量部に対して（ｃ）が２０質量部以上であることを特徴とする外用組成物、
（２）（ａ）ベルベリン塩が、ベルベリン塩化物またはタンニン酸ベルベリンである（１）に記載の外用組成物、
（３）化粧料、又は毛髪用剤であることを特徴とする（１）又は（２）に記載の外用組成物、
である。
That is, the present invention
(1) at least one polyhydric alcohol selected from the group consisting of (a) berberine salt, (b) 40 to 96% by mass of ethanol, (c) 4 to 30% by mass of glycerin and 1,3-butylene glycol Wherein (c) is at least 20 parts by mass per 1 part by mass of (a),
(2) The composition for external use according to (1), wherein (a) the berberine salt is berberine chloride or berberine tannate.
(3) The composition for external use according to (1) or (2), which is a cosmetic or a hair agent,
It is.
本発明により、ベルベリン塩を含有し、経時的な低温での結晶の析出が抑制された外用組成物を提供することが可能になった。 ADVANTAGE OF THE INVENTION By this invention, it became possible to provide the external composition which contains a berberine salt and which suppressed precipitation of the crystal | crystallization at a low temperature with time.
本発明の外用組成物において用いる各成分は、通常医薬品、医薬部外品及び／又は化粧品に用いられる品質のものを適宜使用することができる。
本発明のベルベリン塩としては、例えばベルベリン塩化物、タンニン酸ベルベリン、ベルベリン硫酸塩、ベルベリン塩酸塩などが挙げられる。
As each component used in the composition for external use of the present invention, those having the quality usually used for pharmaceuticals, quasi-drugs, and / or cosmetics can be appropriately used.
Examples of the berberine salt of the present invention include berberine chloride, berberine tannate, berberine sulfate, and berberine hydrochloride.
本発明の外用組成物中におけるベルベリン塩の含有量は、０．００１〜５ｗ／ｗ％が好ましく、０．０１〜１ｗ／ｗ％がより好ましい。 The content of the berberine salt in the composition for external use of the present invention is preferably 0.001 to 5 w / w%, more preferably 0.01 to 1 w / w%.
本発明の外用組成物中におけるエタノール含有量は、本発明の効果の点から４０〜９６ｗ／ｗ％が好ましく、４０〜７０ｗ／ｗ％が好ましい。 The ethanol content in the external composition of the present invention is preferably from 40 to 96 w / w%, more preferably from 40 to 70 w / w%, from the viewpoint of the effects of the present invention.
本発明の外用組成物中におけるグリセリン及び／又は１，３−ブチレングリコールの含有量（２種配合の場合は合計量）は、使用感の点から４〜３０ｗ／ｗ％が好ましく、４〜２０ｗ／ｗ％がより好ましい。 The content of glycerin and / or 1,3-butylene glycol in the composition for external use of the present invention (the total amount in the case of two kinds) is preferably 4 to 30 w / w% from the viewpoint of feeling of use, and 4 to 20 w. / W% is more preferred.
また、本発明のベルベリン塩及びグリセリン及び／又は１，３−ブチレングリコールの含有比率は、本発明の効果の点からベルベリン塩１質量部に対して、グリセリン及び／又は１，３−ブチレングリコールを２０質量部以上（２種配合の場合は合計量）とする必要がある。更に必要により、本発明の効果を損なわない範囲でグリセリンと１，３−ブチレングリコール以外の各種多価アルコールを配合することができる。 In addition, the content ratio of the berberine salt and glycerin and / or 1,3-butylene glycol of the present invention is such that glycerin and / or 1,3-butylene glycol is added to 1 part by mass of the berberine salt from the viewpoint of the effect of the present invention. It is necessary to be 20 parts by mass or more (total amount in the case of mixing two kinds). Further, if necessary, various polyhydric alcohols other than glycerin and 1,3-butylene glycol can be blended as long as the effects of the present invention are not impaired.
本発明の外用組成物は、上記した各成分の他に、本発明の効果を損なわない範囲で、通常の化粧料、医薬部外品、医薬品などに用いられる各種成分を加えることができる。例えば、賦形剤、香料、清涼化剤（メントール、ハッカ油、カンフル等）、抗炎症剤（グアイアズレン、サリチル酸、グリチルリチン酸塩、グリチルレチン酸等）、殺菌剤（グルコン酸クロルヘキシジン、イソプロピルメチルフェノール、第４級アンモニウム塩、ピロクトンオラミン等）、防腐剤（パラベン類（メチルパラベン、ブチルパラベン、プロピルパラベン等）、安息香酸又はその塩、デヒドロ酢酸ナトリウム、ヒノキチオール等）、保湿剤（ヒアルロン酸又はその塩、コンドロイチン硫酸等）、ｐＨ調整剤（クエン酸、リン酸、乳酸、塩酸、グルコン酸、酢酸、硫酸、ホウ酸、酒石酸、硝酸、マレイン酸、又はこれらの塩等）、各種動植物（イチイ、ボタンピ、カンゾウ、オトギリソウ、附子、ビワ、カワラヨモギ、コンフリー、アシタバ、サフラン、サンシシ、ローズマリー、セージ、モッコウ、セイモッコウ、ホップ、プラセンタ、ノコギリヤシ、パンプキンシード等）の抽出物、ビタミン類（酢酸レチノール、アスコルビン酸、硝酸チアミン、シアノコバラミン、ビオチン、リボフラビン等）、抗酸化剤（ジブチルヒドロキシトルエン、ピロ亜硫酸ナトリウム、トコフェロール、エデト酸ナトリウム、アスコルビン酸、イソプロピルガレート等）、溶解補助剤（各種植物油、各種動物油、アルキルグリセリルエーテル、炭化水素類等）、代謝賦活剤、ゲル化剤（水溶性高分子等）、粘着剤、界面活性剤から成る群より選ばれた成分が挙げられる。 The external composition of the present invention may contain, in addition to the components described above, various components used in ordinary cosmetics, quasi-drugs, pharmaceuticals, and the like as long as the effects of the present invention are not impaired. For example, excipients, fragrances, fresheners (menthol, peppermint oil, camphor, etc.), anti-inflammatory agents (guaiazulene, salicylic acid, glycyrrhizinate, glycyrrhetinic acid, etc.), fungicides (chlorhexidine gluconate, isopropylmethylphenol, Quaternary ammonium salts, pyroctone olamine, etc.), preservatives (parabens (methylparaben, butylparaben, propylparaben, etc.), benzoic acid or a salt thereof, sodium dehydroacetate, hinokitiol, etc.), humectant (hyaluronic acid or a salt thereof) , Chondroitin sulfate, etc.), pH adjusters (citric acid, phosphoric acid, lactic acid, hydrochloric acid, gluconic acid, acetic acid, sulfuric acid, boric acid, tartaric acid, nitric acid, maleic acid, or salts thereof), various animals and plants (yew, buttonpicks) , Licorice, hypericum, fushi, loquat, sagebrush, comfrey, Extracts of Citava, Saffron, Sanshishi, Rosemary, Sage, Mokko, Sea Mokko, Hop, Placenta, Saw Palmetto, Pumpkin Seed, etc.), Vitamins (Retinol Acetate, Ascorbic Acid, Thiamine Nitrate, Cyanocobalamin, Biotin, Riboflavin, etc.), Anti- Oxidizing agents (dibutylhydroxytoluene, sodium pyrosulfite, tocopherol, sodium edetate, ascorbic acid, isopropyl gallate, etc.), solubilizing agents (various vegetable oils, various animal oils, alkyl glyceryl ethers, hydrocarbons, etc.), metabolic activators, gels And a component selected from the group consisting of an agent (a water-soluble polymer, etc.), a pressure-sensitive adhesive, and a surfactant.
これら選択成分の添加量は、特に制約はなく、使用感等を考慮しながら実験的に定めることができる。 The amounts of these optional components to be added are not particularly limited, and can be experimentally determined in consideration of the feeling of use and the like.
本発明の外用組成物のｐＨは、３．５〜９が好ましく、さらに好ましくは４〜８である。 The pH of the composition for external use of the present invention is preferably from 3.5 to 9, and more preferably from 4 to 8.
本発明の外用組成物は化粧料、医薬部外品、医薬品などの用途に使用できる。また、本発明の外用組成物は、粘膜適用液剤、化粧料及び／又は毛髪用剤等として使用すること好ましく、より好ましくは、化粧料及び／又は毛髪用剤である。 The composition for external use of the present invention can be used for cosmetics, quasi-drugs, pharmaceuticals and the like. In addition, the composition for external use of the present invention is preferably used as a liquid preparation for mucous membrane, a cosmetic and / or a hair preparation, and more preferably a cosmetic and / or a hair preparation.
本発明の外用組成物の調製は、常法に従い、上記各成分を含有することにより調製される。 The composition for external use of the present invention is prepared by containing the above components according to a conventional method.
以下に、実施例、比較例及び試験例を記載し、本発明をさらに具体的に説明するが、本発明はこれら実施例等により何ら制約されるものではない。 Hereinafter, the present invention will be described more specifically with reference to Examples, Comparative Examples, and Test Examples, but the present invention is not limited by these Examples and the like.
以下表１に示す処方に従い実施例１〜８及び比較例１〜８の外用組成物を常法により調製した。具体的には、常温で、ベルベリン塩及びエタノールを混合した後、多価アルコール、必要に応じてｐＨ調整剤、及び精製水を添加し混合した。 The external compositions of Examples 1 to 8 and Comparative Examples 1 to 8 were prepared by a conventional method according to the formulations shown in Table 1 below. Specifically, berberine salt and ethanol were mixed at room temperature, and then a polyhydric alcohol, a pH adjuster, and purified water were added and mixed as needed.
（実施例１）
ベルベリン塩化物０．１ｇ、エタノール５０ｇ、濃グリセリン１０ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Example 1)
An external composition was prepared using berberine chloride (0.1 g), ethanol (50 g), concentrated glycerin (10 g) and purified water to make the total amount 100 g.
（実施例２）
ベルベリン塩化物０．１ｇ、エタノール５０ｇ、１，３−ブチレングリコール１０ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Example 2)
An external composition was obtained with 0.1 g of berberine chloride, 50 g of ethanol, 10 g of 1,3-butylene glycol and 100 g of purified water.
（実施例３）
ベルベリン塩化物０．２ｇ、エタノール５０ｇ、１，３−ブチレングリコール１０ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Example 3)
An external composition having a total amount of 100 g was obtained using 0.2 g of berberine chloride, 50 g of ethanol, 10 g of 1,3-butylene glycol, and purified water.
（実施例４）
ベルベリン塩化物０．２ｇ、エタノール５０ｇ、濃グリセリン１０ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Example 4)
An external composition was obtained with 0.2 g of berberine chloride, 50 g of ethanol, 10 g of concentrated glycerin and 100 g of purified water.
（実施例５）
ベルベリン塩化物０．２ｇ、エタノール４０ｇ、１，３−ブチレングリコール１０ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Example 5)
An external composition was obtained with 0.2 g of berberine chloride, 40 g of ethanol, 10 g of 1,3-butylene glycol and 100 g of purified water.
（実施例６）
ベルベリン塩化物０．２ｇ、エタノール５０ｇ、１，３−ブチレングリコール４ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Example 6)
A composition for external use having a total amount of 100 g was obtained using 0.2 g of berberine chloride, 50 g of ethanol, 4 g of 1,3-butylene glycol, and purified water.
（実施例７）
タンニン酸ベルベリン０．２ｇ、エタノール５０ｇ、濃グリセリン１０ｇ、クエン酸適量、クエン酸ナトリウム適量、精製水で全量を１００ｇとしたｐＨが約５．０の外用組成物を得た。
(Example 7)
0.2 g of berberine tannate, 50 g of ethanol, 10 g of concentrated glycerin, an appropriate amount of citric acid, an appropriate amount of sodium citrate, and purified water were used to obtain a composition for external use having a total amount of 100 g and a pH of about 5.0.
（実施例８）
タンニン酸ベルベリン０．２ｇ、エタノール５０ｇ、１，３−ブチレングリコール１０ｇ、クエン酸適量、クエン酸ナトリウム適量、精製水で全量を１００ｇとしたｐＨが約５．０の外用組成物を得た。
(Example 8)
0.2 g of berberine tannate, 50 g of ethanol, 10 g of 1,3-butylene glycol, an appropriate amount of citric acid, an appropriate amount of sodium citrate, and an external composition having a total pH of about 5.0 with purified water and a pH of about 5.0 were obtained.
（比較例１）
ベルベリン塩化物０．１ｇ、エタノール５０ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Comparative Example 1)
An external composition was obtained in which the total amount was 100 g with berberine chloride 0.1 g, ethanol 50 g, and purified water.
（比較例２）
ベルベリン塩化物０．２ｇ、エタノール５０ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Comparative Example 2)
An external composition was prepared with 0.2 g of berberine chloride, 50 g of ethanol and purified water to make the total amount 100 g.
（比較例３）
ベルベリン塩化物０．２ｇ、エタノール５０ｇ、ジプロピレングリコール１０ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Comparative Example 3)
A composition for external use having a total amount of 100 g was obtained using 0.2 g of berberine chloride, 50 g of ethanol, 10 g of dipropylene glycol, and purified water.
（比較例４）
ベルベリン塩化物０．２ｇ、エタノール５０ｇ、プロピレングリコール１０ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Comparative Example 4)
A composition for external use having a total amount of 100 g was obtained using 0.2 g of berberine chloride, 50 g of ethanol, 10 g of propylene glycol, and purified water.
（比較例５）
ベルベリン塩化物０．２ｇ、エタノール３０ｇ、１，３−ブチレングリコール１０ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Comparative Example 5)
An external composition was obtained with 0.2 g of berberine chloride, 30 g of ethanol, 10 g of 1,3-butylene glycol and 100 g of purified water.
（比較例６）
ベルベリン塩化物０．２ｇ、エタノール５０ｇ、１，３−ブチレングリコール０．６ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Comparative Example 6)
An external composition was obtained with 0.2 g of berberine chloride, 50 g of ethanol, 0.6 g of 1,3-butylene glycol, and 100 g of purified water.
（比較例７）
ベルベリン塩化物０．２ｇ、エタノール５０ｇ、１，３−ブチレングリコール２ｇ、精製水で全量を１００ｇとした外用組成物を得た。
(Comparative Example 7)
An external composition having a total amount of 100 g was obtained using 0.2 g of berberine chloride, 50 g of ethanol, 2 g of 1,3-butylene glycol, and purified water.
（比較例８）
タンニン酸ベルベリン０．２ｇ、エタノール５０ｇ、クエン酸適量、クエン酸ナトリウム適量、精製水で全量を１００ｇとしたｐＨが約５．０の外用組成物を得た。
(Comparative Example 8)
0.2 g of berberine tannate, 50 g of ethanol, an appropriate amount of citric acid, an appropriate amount of sodium citrate, and an external composition having a total pH of about 5.0 were obtained with purified water to make the total amount 100 g.
＜試験例１：低温安定性試験＞
実施例１〜実施例８、及び比較例１〜比較例８に関し、−５℃条件下７日保存した後の製剤の状況を目視で観察し、結晶の析出が認められないものを○、結晶の析出が認められたものを×とした。結果を表２に示す。
<Test Example 1: Low-temperature stability test>
Regarding Examples 1 to 8 and Comparative Examples 1 to 8, the condition of the preparation after storage for 7 days at −5 ° C. was visually observed. The one where precipitation of was observed was evaluated as x. Table 2 shows the results.
＜試験例２：ベルベリン塩化物の溶解性確認＞
１，３−ブチレングリコール、ジプロピレングリコール、プロピレングリコール又は濃グリセリン１０ｇにベルベリン塩化物０．２ｇを添加し、１時間混合後のベルベリン塩化物の溶解性を確認した。この結果、１，３−ブチレングリコール及びプロピレングリコール群においてベルベリン塩化物の溶解が認められ、ジプロピレングリコール及び濃グリセリン群ではベルベリン塩化物が溶解されなかったことを認めた。
<Test Example 2: Confirmation of solubility of berberine chloride>
0.2 g of berberine chloride was added to 10 g of 1,3-butylene glycol, dipropylene glycol, propylene glycol or concentrated glycerin, and the solubility of berberine chloride after mixing for 1 hour was confirmed. As a result, dissolution of berberine chloride was recognized in the 1,3-butylene glycol and propylene glycol groups, and it was recognized that berberine chloride was not dissolved in the dipropylene glycol and concentrated glycerin groups.
表２から明らかなように、１，３−ブチレングリコール又はグリセリンの代わりに他の多価アルコールを使用すると、結晶の析出が認められたが（比較例３〜４）、本発明の実施例１〜８の製剤は結晶の析出が認められなかった。
また、エタノール含有量を４０重量％以下（比較例５）又は、ｃ／ａの質量比を２０未満（比較例６、７）にすると結晶の析出が認められた。なお、この析出は、試験例２の結果より、ベルベリン塩化物の各種多価アルコールへの溶解性に依存しないこともわかった。
As is clear from Table 2, when another polyhydric alcohol was used instead of 1,3-butylene glycol or glycerin, precipitation of crystals was observed (Comparative Examples 3 and 4), but Example 1 of the present invention was used. In the preparations of Nos. To 8, no precipitation of crystals was observed.
When the ethanol content was 40% by weight or less (Comparative Example 5) or the mass ratio of c / a was less than 20 (Comparative Examples 6 and 7), precipitation of crystals was observed. In addition, from the results of Test Example 2, it was found that this precipitation did not depend on the solubility of berberine chloride in various polyhydric alcohols.
本発明により、ベルベリン塩を含有していても、製剤安定性に優れた外用組成物を提供することが可能になった。 ADVANTAGE OF THE INVENTION According to this invention, even if it contained a berberine salt, it became possible to provide the topical composition excellent in formulation stability.
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