JP4170061B2 - Cold application liquid - Google Patents
Cold application liquid Download PDFInfo
- Publication number
- JP4170061B2 JP4170061B2 JP2002303276A JP2002303276A JP4170061B2 JP 4170061 B2 JP4170061 B2 JP 4170061B2 JP 2002303276 A JP2002303276 A JP 2002303276A JP 2002303276 A JP2002303276 A JP 2002303276A JP 4170061 B2 JP4170061 B2 JP 4170061B2
- Authority
- JP
- Japan
- Prior art keywords
- oil
- cold
- polyoxyethylene
- coating solution
- hlb value
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000007788 liquid Substances 0.000 title claims description 12
- -1 polyoxyethylene cetyl ether Polymers 0.000 claims description 64
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 41
- 201000009240 nasopharyngitis Diseases 0.000 claims description 33
- 239000011248 coating agent Substances 0.000 claims description 32
- 238000000576 coating method Methods 0.000 claims description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 31
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 22
- 239000002736 nonionic surfactant Substances 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 16
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 claims description 14
- 239000004359 castor oil Substances 0.000 claims description 14
- 235000019438 castor oil Nutrition 0.000 claims description 13
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 13
- 239000010642 eucalyptus oil Substances 0.000 claims description 13
- 229940044949 eucalyptus oil Drugs 0.000 claims description 13
- 239000000194 fatty acid Substances 0.000 claims description 13
- 229930195729 fatty acid Natural products 0.000 claims description 13
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 13
- 229940041616 menthol Drugs 0.000 claims description 13
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 11
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 11
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 11
- 239000003921 oil Substances 0.000 claims description 10
- 235000019198 oils Nutrition 0.000 claims description 10
- 239000002562 thickening agent Substances 0.000 claims description 10
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 claims description 8
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 8
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 150000004665 fatty acids Chemical class 0.000 claims description 6
- 239000000171 lavandula angustifolia l. flower oil Substances 0.000 claims description 6
- 241000723346 Cinnamomum camphora Species 0.000 claims description 5
- 239000001293 FEMA 3089 Substances 0.000 claims description 5
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- 235000019864 coconut oil Nutrition 0.000 claims description 5
- 239000003240 coconut oil Substances 0.000 claims description 5
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
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- 229940058015 1,3-butylene glycol Drugs 0.000 claims description 4
- 235000019437 butane-1,3-diol Nutrition 0.000 claims description 4
- 235000011187 glycerol Nutrition 0.000 claims description 4
- 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 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 3
- 244000215068 Acacia senegal Species 0.000 claims description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 3
- 229920000084 Gum arabic Polymers 0.000 claims description 3
- 229920002125 Sokalan® Polymers 0.000 claims description 3
- 235000010489 acacia gum Nutrition 0.000 claims description 3
- 239000000205 acacia gum Substances 0.000 claims description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 3
- 229920000609 methyl cellulose Polymers 0.000 claims description 3
- 235000010981 methylcellulose Nutrition 0.000 claims description 3
- 239000001923 methylcellulose Substances 0.000 claims description 3
- 239000001627 myristica fragrans houtt. fruit oil Substances 0.000 claims description 3
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- 239000000661 sodium alginate Substances 0.000 claims description 3
- 229940005550 sodium alginate Drugs 0.000 claims description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
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- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims 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 claims 2
- 239000000243 solution Substances 0.000 description 30
- 238000002360 preparation method Methods 0.000 description 24
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 20
- 230000000052 comparative effect Effects 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 10
- 238000009472 formulation Methods 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 8
- 235000007866 Chamaemelum nobile Nutrition 0.000 description 7
- 244000042664 Matricaria chamomilla Species 0.000 description 7
- 235000007232 Matricaria chamomilla Nutrition 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000008213 purified water Substances 0.000 description 7
- 229940098465 tincture Drugs 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000002470 solid-phase micro-extraction Methods 0.000 description 6
- 239000004094 surface-active agent Substances 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
- 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 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 229940113120 dipropylene glycol Drugs 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 229920001451 polypropylene glycol Polymers 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003125 aqueous solvent Substances 0.000 description 3
- 230000036760 body temperature Effects 0.000 description 3
- 239000003205 fragrance Substances 0.000 description 3
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 3
- 150000002334 glycols Chemical class 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 150000005215 alkyl ethers Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 229940124579 cold medicine Drugs 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 229960003720 enoxolone Drugs 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000004668 long chain fatty acids Chemical class 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 229960004063 propylene glycol Drugs 0.000 description 2
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
- 230000002040 relaxant effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000003009 skin protective agent Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- 238000009834 vaporization Methods 0.000 description 2
- 230000008016 vaporization Effects 0.000 description 2
- 229940112065 vicks vaporub Drugs 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical class CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
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- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- 240000002657 Thymus vulgaris Species 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
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- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
【０００１】
【発明の属する技術分野】
本発明は感冒用塗布液剤に関する。より詳細には、本発明は（ａ）感冒用揮発性成分および（ｂ）７〜２０のＨＬＢ値を有する非イオン性界面活性剤を含有することを特徴とする感冒用塗布液剤に関する。
【０００２】
【従来の技術】
感冒は、「かぜ」、「かぜ症候群」、「感冒症候群」ともいわれ、日常、最も多く見られる疾患である。感冒は、息苦しさ、鼻づまり、鼻汁、くしゃみ、咳、痰、喉の傷み等の症状を伴うことが多く、これらの症状を緩和させるため、主として経口投与用製剤が用いられている。
【０００３】
感冒を予防・治療するためには、上記の経口投与製剤以外にも、軟膏剤やハップ剤のような外用剤および吸入型製剤等が知られている。
【０００４】
軟膏剤としては、例えば「 ＶＩＣＫＳ ＶａｐｏＲｕｂ」なる商品名の軟膏剤が市販されている。
【０００５】
しかし、軟膏剤は流動性が低いため塗布面に局在させることは容易である反面、塗布部がべたべたして衣類に付着したりするとともに、指で塗布するために衛生的でない欠点がある。
【０００６】
パップ剤としては、例えば、特開平１−８３０２４号公報に、ポリアクリル酸ナトリウムおよび／またはポリアクリル酸並びにアルミニウム化合物を含有する膏体に、感冒用揮発性生薬成分および感冒用不揮発性生薬成分を配合してなるかぜ用パップ剤が開示されている。
【０００７】
しかし、パップ剤は使用中に剥がれ落ちて薬効が得られなかったり、粘着剤などによって、皮膚がかぶれたりする等の欠点がある。
【０００８】
一方、上記問題を解決するために、例えば、特開平５−９７６６３号公報には、気化性薬物を多孔質繊維よりなる片状支持体に含有させた感冒用吸入型製剤が開示されている。
【０００９】
上記吸入型製剤は、気化性薬物が多孔性繊維から揮発し、その揮発成分を吸入することによって感冒の予防や治療に用いられるという点では適しているものの、上記繊維と吸入口である鼻腔などとの距離が一定に保ちにくいために効果にばらつきが出やすいことや持続性が乏しいなどの問題点があった。
【００１０】
上記の課題を解決するために、感冒用の液剤についても提案されている。
【００１１】
例えば、特開昭６２−５９２１９号公報には、有効成分と基剤成分である低級アルコール及びグリコールに水を加えた液剤が記載されている。
【００１２】
しかしながら、上記液剤には界面活性剤の記載がなく、界面活性剤が配合されていない場合には、当該液剤中の有効成分を均一に混合または分散しづらいことが判明した。
【００１３】
一方、界面活性剤を配合した外用感冒薬としては、例えば、特開平９−３２３９３８号公報には、気化性感冒薬剤成分を含有する油性剤と、水およびグリコール類と、該油性成分を水およびグリコール類に分散させる界面活性剤とを含有する外用感冒薬であって、該感冒薬全量中における水とグリコール類との合計の配合量が５４〜７５重量％の範囲内にあり、かつ該油性剤中に炭素数８〜２２の直鎖状長鎖アルコールおよび／または炭素数８〜２２の直鎖状長鎖脂肪酸を１〜１５重量％、そして高分子増粘剤を０．０５〜５重量％の量で含有していることを特徴とする外用感冒薬が開示されている。
【００１４】
しかし、当該油性基剤中に炭素数８〜２２の直鎖状長鎖アルコールおよび／または炭素数８〜２２の直鎖状長鎖脂肪酸が入っているため上記と同様に当該液剤中の有効成分を均一に混合または分散しづらいという問題点があった。
【００１５】
【発明が解決しようとする課題】
本発明者等は、かかる欠点を有さず、有効成分である揮発性成分を持続的に揮発させ得る新しいタイプの感冒用塗布液剤の開発を目的として種々検討した。
【００１６】
【課題を解決するための手段】
種々検討を行った結果、感冒用揮発性成分を配合してなる感冒用塗布液剤が本発明の目的に適うことを見出し、本発明を完成させた。
【００１７】
【発明の実施の形態】
以下、本発明を詳細に説明する。
【００１８】
本発明に用いる感冒用揮発性成分としては、感冒の前記症状に有効で、かつ、常温または室温で固体状態で昇華する特性を持つもの、あるいは液体状態で体温付近の温度で揮発する特性を持つものであれば特に限定されるものではない。例えば、これらの薬物としては、カンフル、メントール、ユーカリ油、ニクズク油、チミアン油、テレビン油、ラベンダー油、チモール、ハッカ油、チョウジ油、トウヒ油、チンピ油等が挙げられる。また、これらの中でカンフル、メントールのように天然型もしくは非天然型の存在するものは、そのいずれであっても良い。
【００１９】
本発明に用いられる、非イオン性界面活性剤としては、７〜２０のＨＬＢ値を有する非イオン性界面活性剤である。
【００２０】
これは、ＨＬＢ値が７未満あるいは２０を越える界面活性剤を用いた場合、本発明の液剤中の感冒用揮発性成分と水あるいは水性溶媒が均一に混合または分散しないという問題点があることに起因する。
【００２１】
７〜２０のＨＬＢ値を有する非イオン性界面活性剤の具体例としては、ポリオキシエチレンセチルエーテル、ポリオキシエチレンラウリルエーテル、ポリオキシステアリルエーテル等のポリオキシエチレンアルキルエーテル、モノヤシ油脂肪酸ポリオキシエチレンソルビタン、モノパルミチン酸ポリオキシエチレンソルビタン、モノオレイン酸ポリオキシエチレンソルビタン等のポリオキシエチレンソルビタン脂肪酸エステル、モノステアリン酸ポリエチレングリコール、モノラウリン酸ポリエチレングリコール等のポリエチレングリコール脂肪酸エステル、モノステアリン酸ポリオキシエチレングリセリル、モノオレイン酸ポリオキシエチレングリセリル等のポリオキシエチレングリセリル脂肪酸エステル、ポリオキシエチレンポリオキシプロピレンセチルエーテル、テトラオレイン酸ポリオキシエチレンソルビット、ポリオキシエチレン硬化ヒマシ油等のＨＬＢ値が７〜２０のものが挙げられる。この中でも、ポリオキシエチレンセチルエーテル、ポリオキシエチレン硬化ヒマシ油およびポリオキシエチレンヤシ油脂肪酸ソルビタンが好ましく、より好ましくは、１０〜１７のＨＬＢ値を有する、上記の非イオン性界面活性剤である。
【００２２】
７〜２０のＨＬＢ値を有する非イオン性界面活性剤の配合比率は用いる種類によっても異なるが、通常感冒用塗布液剤の総重量に対して１〜１０重量％、好ましくは３．５〜１０重量％である。
【００２３】
本発明に用いられる増粘剤としては、特に限定されるものではないが、例えば、グリセリン、ヒドロキシプロピルセルロース、ポリオキシエチレンポリオキシプロピレングリコール、カルボキシビニルポリマー、アラビアゴム、キサンタンガム、アルギン酸ナトリウム、カルメロースナトリウム、メチルセルロース、カルボキシメチルセルロース、ポリビニルピロリドン、ポリビニルアルコール等が挙げられる。この中でも、特にヒドロキシプロピルセルロースまたはポリオキシエチレンポリオキシプロピレングリコールがより好ましい。増粘剤の配合比率は、用いる種類によっても異なるが、通常感冒用塗布液剤の総重量に対して０．１〜５重量％、好ましくは０．２〜２重量％である。
【００２４】
本発明の感冒用塗布液剤（以下、本発明製剤という）は、感冒用揮発性成分がメントールのような固体の場合には下記溶媒に溶解するか、ユーカリ油のような液状の場合にはそれらに溶解するか、あるいは、非イオン性界面活性剤によって溶解もしくは懸濁して調製した製剤であって、所望により、これに医薬品あるいは医薬部外品の製造に通常用いられる増粘剤、乳化剤、懸濁化剤、保存剤、抗酸化剤、ｐH調整剤、皮膚保護剤等を適宜添加することができる。
【００２５】
溶媒としては水の他に、水性溶媒としてエタノール、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、ヘキシレングリコール、アセトンが挙げられ、これらの２種以上の混合溶媒を用いることができる。
【００２６】
その中でも水、エタノールあるいは水、エタノール、１，３−ブチレングリコールおよびジプロピレングリコールの混合溶媒が好ましい。
【００２７】
溶媒の配合比率は用いる種類によっても異なるが、エタノールの場合、感冒用塗布液剤の全重量に対して、５〜５０重量％、好ましくは１５〜３０重量％である。
【００２８】
乳化剤としては、前述の７〜２０のＨＬＢ値を有する非イオン性界面活性剤の他、プロピレングリコール脂肪酸エステル、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、ソルビタン脂肪酸エステル、ポリオキシエチレンラウリル硫酸ナトリウム、ポリオキシエチレンアルキルエーテル硫酸塩、ポリオキシエチレンラウリルエーテルリン酸塩、レシチン誘導体等が挙げられる。
【００２９】
懸濁化剤としては、アラビアゴム、アルギン酸ナトリウム、カルメロースナトリウム、メチルセルロース、ベントナイト等が挙げられる。
【００３０】
保存剤としては、パラオキシ安息香酸メチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル、パラオキシ安息香酸ブチル等が挙げられる。
【００３１】
抗酸化剤としては、亜硫酸水素ナトリウム、アスコルビン酸等が挙げられる。
【００３２】
ｐH調整剤としては、水酸化ナトリウム、水酸化カリウム、ジイソプロパノールアミン、塩酸等が挙げられる。
【００３３】
皮膚保護剤としては、グリチルリチン酸等が挙げられる。
【００３４】
なお、本発明製剤においては、上記感冒用揮発性成分以外に感冒用不揮発性成分、芳香性香気成分等を添加することもできる。
【００３５】
感冒用不揮発性成分としては、例えば、カミツレエキスが挙げられる。
【００３６】
芳香性香気成分としては、精神的ストレスを和らげ、リラックスさせるための香気療法、いわゆるアロマテラピーに有用な成分であれば、特に限定されないが、ラベンダー油、ペパーミント油、スペアミント油等が挙げられる。
【００３７】
本発明製剤は、胸や喉等、揮発性成分が鼻腔から吸入しやすい箇所に適量を１日１〜数回塗布して用いられる。特に、就寝時に、感冒の前記症状を緩和させる目的で好適に使用される。
【００３８】
【発明の効果】
本発明製剤は、皮膚から吸収され、炎症を抑えると共に、これらの成分が体温によって気化し、呼吸器から直接扁桃腺や気管支に供給されて炎症を抑えるなど速やかに効果を発揮する。しかも、本発明製剤中に配合されている７〜２０のＨＬＢ値を有する非イオン性界面活性剤によって感冒用揮発性成分を持続的に揮発させ得るので、効果が長時間持続する。
【００３９】
また、カンフルおよびメントールなどの感冒用揮発性成分は気化する際に気化熱を奪うので、発熱している場合には体温の低下を図るといった効果もある。
従って、本発明製剤は、感冒に対して即効性があり、かつ持続性も有する感冒用塗布液剤として有用である。
【００４０】
以下に、試験例を挙げて本発明を詳細に説明する。なお、揮発性成分の揮発持続時間は、メントールを指標成分として行った。
【００４１】
試験例１（溶解性試験）
（１）試験方法
表１に示す処方１〜８の溶解性について検討した。ユーカリ油以下テレビン油までの各成分を混合し、異なるＨＬＢ値を有する非イオン性界面活性剤、グリチルレチン酸、ジプロピレングリコールを加え、７０〜８０℃に加温しながら溶解した。当該溶解液にヒドロキシプロピルセルロース水溶液を徐々に加え可溶化した後、４０℃以下に冷却し、さらに別に調製したｄｌ−カンフルおよびｌ−メントールのエタノール溶液を加え、処方１〜８の感冒用塗布液剤を得た。
（２）結果
表１に結果を示す。
表１から明らかなように、ＨＬＢ値が７〜２０を有する非イオン性界面活性剤を添加した処方（処方１〜６）は溶解した。しかし、ＨＬＢ値が７未満（処方７および処方８）の界面活性剤を添加した処方は感冒用揮発性成分と水あるいは水性溶媒が分離した。
【００４２】
【表１】
試験例２（感冒用揮発性成分の揮発性試験）
（１） 試料
（ａ）参考例３〜５、実施例４〜７で得られた本発明製剤
（ｂ）比較例１および比較例２で得られた製剤
（２）試験方法
試料０．３ｇを５．０ｃｍ×５．０ｃｍのろ紙に塗布し、当該ろ紙を中栓付きサンプル瓶（２２５ｍｌ）に垂直に立てかけて蓋をし、３７℃で３分間加温後、保温状態で固相マイクロ抽出法（ＳＰＭＥ法）で用いるＳＰＭＥ抽出器[ＳＰＭＥファイバー：１００μｍ（ポリジメチルシロキサン、メチルシリコン）、ＳＰＭＥ抽出器（ユニット）、スペルコ製]を挿入し、さらに３分間放置することによりヘッドスペースガス中のｌ−メントールを抽出した。ＳＰＭＥ抽出器はすばやくガスクロマトグラフ−質量分析装置（以下、ＧＣ−ＭＳという）（島津製作所製）に注入し、分析を開始した。引き続き、ろ紙を設置した中栓付きサンプル瓶を３７℃で保温し、ゴム栓をした中栓付きサンプル瓶に流量計で流量を１００ｍｌ／分に保ちながら窒素を流し入れ、排気口から排気することで、揮発性成分の排出を続けた。３０、６０、９０および１２０分後に同様にサンプリングを行い、ＧＣ−ＭＳ装置を用いて分析することによって経時的に揮発性成分を測定した。なお、ＧＣ−ＭＳ装置におけるＧＣおよびＭＳの条件は、以下の通りである。
【００４４】
〔ＧＣ条件〕
・分離カラム：ＤＢ−５（０．５３ｍｍφ×３０ｍ、液相：（５％−フェニル）
−メチルポリシロキサン））（ジェイ アンド ダブル サイエンティフィック製）
・気化室温度：２７０℃
・フローコントローラ：スプリット／スプリットレス（Ｃｌｏｓｅｄ １分 ）
・キャリアガス圧力：６０ｋＰａ
・全流量：１２６．２ｍｌ／分
・サンプリング時間：１分
・インターフェイス温度：２３０℃
・分離カラム温度：初期温度５０℃、３分間定温とし、その後昇温速度９℃／分で３００℃まで昇温し、最終温度３００℃、５分間定温とする。
【００４５】
〔ＭＳ条件〕
・検出器電圧：１．４１ｋＶ
・溶媒溶出時間：３分
・走査質量範囲：２１−３５０
・スキャンインターバル：０．５秒
・しきい値：１０００
（３）結果
揮発によって減少するメントール濃度の半減期を表２および表３に示す。表２から明らかなように、感冒用揮発性成分に非イオン性界面活性剤を添加した本発明の製剤（参考例３および参考例４）は増粘剤および非イオン性界面活性剤のいずれも添加しない製剤（比較例１）、または増粘剤のみを添加し、非イオン性界面活性剤を添加しない製剤（比較例２）と比べて感冒用揮発性成分であるメントールを持続的に揮発した。また、表２および表３から明らかなように、感冒用揮発性成分に非イオン性界面活性剤および増粘剤を併用して添加した本発明の製剤（参考例５、実施例４〜７）は非イオン性界面活性剤を添加しない製剤（比較例２）と比べてよりメントールをさらに持続的に揮発した。
【００４６】
【表２】
【表３】
試験例３（感冒用揮発性成分の揮発性試験）
（１） 試料
（ａ）実施例１２で得られた本発明製剤
（ｂ）比較例３および比較例４で得られた製剤
（ｃ）参考例１（マックスファクター社製「ＶＩＣＫＳ ＶａｐｏＲｕｂ」）および参考例２（山之内製薬社製「カコナールかぜパップ」）
（２）試験方法
３０分、１時間およびそれ以降は１時間毎に８時間までサンプリングを行った以外は試験例２と同様に試験を行った。
（３）結果
揮発によって減少するメントール濃度の半減期を表４に示す。
表４から明らかなように、感冒用揮発性成分に本発明の非イオン性界面活性剤を添加した製剤（実施例１２）は増粘剤および本発明の非イオン性界面活性剤のいずれも添加しない製剤（比較例４）、または増粘剤のみを添加し、本発明の非イオン性界面活性剤を添加しない製剤（比較例３）および市販製剤（参考例１および２）と比べて感冒用揮発性成分であるメントールを持続的に揮発した。
【００４９】
【表４】
【実施例】
以下に実施例および比較例を挙げて本発明を具体的に説明する。
【００５１】
参考例３
（処方）
成分 （重量％）
―――――――――――――――――――――――――――――――
１．ユーカリ油 ２．０
２．チミアン油 １．５
３．ニクズク油 ０．５
４．ラベンダー油 ０．５
５．カミツレチンキ ２．５
６．ポリオキシエチレン硬化ヒマシ油（６０）（ＨＬＢ値１４．０）
６．０
７．エタノール ５０．０
８．ｄｌ−カンフル ５．０
９．ｌ−メントール ３．０
１０．精製水 適量
―――――――――――――――――――――――――――――――
合計 １００．０
（製造方法）ユーカリ油以下カミツレチンキまでの各成分を混合し、８０℃に加温しながら、ポリオキシエチレン硬化ヒマシ油（６０）で可溶化した後、エタノールおよび精製水を加える。さらにｄｌ−カンフルおよびｌ−メントールを加え、溶解させ、参考例３の感冒用塗布液剤を得た。
【００５２】
参考例４
ポリオキシエチレン硬化ヒマシ油（６０）（ＨＬＢ値１４．０）をポリオキシエチレンヤシ油脂肪酸ソルビタン（２０）（ＨＬＢ値１６．７）に代えた以外は、参考例３と同様に調製し、参考例４の感冒用塗布液剤を得た。
【００５３】
参考例５
（処方）
成分 （重量％）
―――――――――――――――――――――――――――――――
１．ユーカリ油 ２．０
２．チミアン油 １．５
３．ニクズク油 ０．５
４．ラベンダー油 ０．５
５．カミツレチンキ ２．５
６．ポリオキシエチレン（２０）セチルエーテル（ＨＬＢ値１７．
０） ６．０
７．エタノール ５０．０
８．ｄｌ−カンフル ５．０
９．ｌ−メントール ３．０
１０．精製水 適量
１１．ヒドロキシプロピルセルロース（２％水溶液）１０．０
１２．ポリオキシエチレン（１６０）ポリオキシプロピレン（３０）
グリコール １．０
―――――――――――――――――――――――――――――――
合計 １００．０
（製造方法）ユーカリ油以下カミツレチンキまでの各成分を混合し、８０℃に加温しながら、ポリオキシエチレン（２０）セチルエーテルで可溶化した後、エタノールおよび精製水を加える。さらにｄｌ−カンフルおよびｌ−メントールを加え、溶解させた後、ヒドロキシプロピルセルロース水溶液、ポリオキシエチレン（１６０）ポリオキシプロピレン（３０）グリコールの順に加え、参考例５の感冒用塗布液剤を得た。
【００５４】
実施例４
ポリオキシエチレン（２０）セチルエーテル（ＨＬＢ値１７．０）をポリオキシエチレン硬化ヒマシ油（６０）（ＨＬＢ値１４．０）に代えた以外は、実施例３と同様に調製し、実施例４の感冒用塗布液剤を得た。
【００５５】
実施例５
ポリオキシエチレン（２０）セチルエーテル（ＨＬＢ値１７．０）をポリオキシエチレンヤシ油脂肪酸ソルビタン（２０）（ＨＬＢ値１６．７）に代えた以外は、実施例３と同様に調製し、実施例５の感冒用塗布液剤を得た。
【００５６】
実施例６
ポリオキシエチレン（２０）セチルエーテル（ＨＬＢ値１７．０）６．０重量％をポリオキシエチレン（２０）セチルエーテル（ＨＬＢ値１７．０）４．０重量％およびポリオキシエチレン硬化ヒマシ油（６０）（ＨＬＢ値１４．０）２．０重量％に代えた以外は、実施例３と同様に調製し、実施例６の感冒用塗布液剤を得た。
【００５７】
実施例７
ポリオキシエチレン（２０）セチルエーテル（ＨＬＢ値１７．０）６．０重量％をポリオキシエチレン（２０）セチルエーテル（ＨＬＢ値１７．０）４．０重量％およびポリオキシエチレン硬化ヒマシ油（６０）（ＨＬＢ値１４．０）５．０重量％に代えた以外は、実施例３と同様に調製し、実施例７の感冒用塗布液剤を得た。
【００５８】
実施例８
ポリオキシエチレン（２０）セチルエーテル（ＨＬＢ値１７．０）６．０重量％をポリオキシエチレン（２０）セチルエーテル（ＨＬＢ値１７．０）４．０重量％およびポリオキシエチレンヤシ油脂肪酸ソルビタン（２０）（ＨＬＢ値１６．７）５．０重量％に代えた以外は、実施例３と同様に調製し、実施例８の感冒用塗布液剤を得た。
【００５９】
実施例９
ポリオキシエチレン（２０）セチルエーテル（ＨＬＢ値１７．０）６．０重量％をポリオキシエチレン（２０）セチルエーテル（ＨＬＢ値１７．０）４．０重量％およびモノオレイン酸ポリオキシエチレンソルビタン（６）（ＨＬＢ値１０．０）５．０重量％に代えた以外は、実施例３と同様に調製し、実施例９の感冒用塗布液剤を得た。
【００６０】
ユーカリ油以下カミツレチンキまでの各成分を混合し、８０℃に加温しながら、ポリオキシエチレン（２０）セチルエーテルおよびポリオキシエチレン硬化ヒマシ油（６０）で可溶化した後、エタノールおよび精製水を加える。さらにｄｌ−カンフルおよびｌ−メントールを加え、溶解させた後、ヒドロキシプロピルセルロース水溶液、ポリオキシエチレン（１６０）ポリオキシプロピレン（３０）グリコールおよび濃グリセリンの順に加え、実施例１０の感冒用塗布液剤を得た。
【００６１】
ユーカリ油以下テレビン油までの各成分を混合し、ポリオキシエチレン硬化ヒマシ油（６０）、グリチルレチン酸、１，３−ブチレングリコールおよびジプロピレングリコールを加え、７０〜８０℃に加温しながら溶解する。当該溶解液にヒドロキシプロピルセルロース水溶液を徐々に加え可溶化した後、４０℃以下に冷却し、さらに別に調製したｄｌ−カンフルおよびｌ−メントールのエタノール溶液を加え、実施例１１の感冒用塗布液剤を得た。
【００６２】
実施例１１と同様に調製し、実施例１２の感冒用塗布液剤を得た。
【００６３】
実施例１１と同様に調製し、実施例１３の感冒用塗布液剤を得た。
【００６４】
実施例１１と同様に調製し、実施例１４の感冒用塗布液剤を得た。
【００６５】
実施例１１と同様に調製し、実施例１５の感冒用塗布液剤を得た。
【００６６】
ユーカリ油以下カミツレチンキまでの各成分を混合し、８０℃に加温しながら、エタノールおよび精製水を加える。さらにｄｌ−カンフルおよびｌ−メントールを加え、溶解させ、比較例１の液剤を得た。
【００６７】
ユーカリ油以下カミツレチンキまでの各成分を混合し、８０℃に加温しながら、エタノールおよび精製水を加える。さらにｄｌ−カンフルおよびｌ−メントールを加え、溶解させた後、ヒドロキシプロピルセルロース水溶液、ポリオキシエチレン（１６０）ポリオキシプロピレン（３０）グリコールの順に加え、比較例２の液剤を得た。
【００６８】
比較例３
ポリオキシエチレン硬化ヒマシ油（６０）を除く以外は実施例１２と同様に調製して、比較例３の感冒用塗布液剤を得た。
【００６９】
比較例４
ポリオキシエチレン硬化ヒマシ油（６０）およびヒドロキシプロピルセルロースを除く以外は実施例１２と同様に調製して、比較例４の感冒用塗布液剤を得た。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a cold-use coating solution. More particularly, the present invention relates to a cold-applying coating solution characterized by comprising (a) a volatile component for cold and (b) a nonionic surfactant having an HLB value of 7 to 20.
[0002]
[Prior art]
The common cold is also called “cold”, “cold syndrome”, and “cold syndrome” and is the most common disease in daily life. The common cold often accompanies symptoms such as stuffy breath, nasal congestion, nasal discharge, sneezing, coughing, sputum, and sore throat, and preparations for oral administration are mainly used to alleviate these symptoms.
[0003]
In order to prevent and treat the common cold, in addition to the above-mentioned oral preparations, external preparations such as ointments and haptics, inhalable preparations, and the like are known.
[0004]
As an ointment, for example, an ointment having a trade name of “VICKS VapoRub” is commercially available.
[0005]
However, since the ointment has low fluidity, it is easy to localize it on the application surface. However, the application part is sticky and adheres to clothing, and it is not hygienic because it is applied with fingers.
[0006]
As a poultice, for example, Japanese Patent Application Laid-Open No. 1-83024 discloses a cold volatile medicinal component and a cold medicinal component for cold in a plaster containing sodium polyacrylate and / or polyacrylic acid and an aluminum compound. A cold patch used in combination is disclosed.
[0007]
However, the poultices have drawbacks such as peeling off during use and no medicinal effects being obtained, and skin rashes due to adhesives and the like.
[0008]
On the other hand, in order to solve the above problem, for example, Japanese Patent Application Laid-Open No. 5-97663 discloses an inhalation-type preparation for the common cold in which a vaporizable drug is contained in a flaky support made of porous fibers.
[0009]
The inhalable preparation is suitable in that the vaporizable drug is volatilized from the porous fiber and used for the prevention and treatment of the common cold by inhaling the volatile component, but the fiber and the nasal cavity which is the inhalation port, etc. There is a problem that it is difficult to maintain a constant distance from and the effect is likely to vary and the sustainability is poor.
[0010]
In order to solve the above-mentioned problems, a liquid medicine for the common cold has also been proposed.
[0011]
For example, Japanese Patent Application Laid-Open No. 62-59219 describes a liquid agent in which water is added to an active ingredient and a base alcohol, which is a base ingredient, and glycol.
[0012]
However, there is no description of the surfactant in the liquid agent, and it has been found that when the surfactant is not blended, it is difficult to uniformly mix or disperse the active ingredient in the liquid agent.
[0013]
On the other hand, as an external cold medicine containing a surfactant, for example, JP-A-9-323938 discloses an oily agent containing a vaporizable cold drug component, water and glycols, and the oily component as water and An external cold remedy containing a surfactant dispersed in glycols, wherein the total amount of water and glycols in the total amount of the cold remedy is in the range of 54 to 75% by weight, and the oily property 1 to 15% by weight of linear long-chain alcohol having 8 to 22 carbon atoms and / or linear long-chain fatty acid having 8 to 22 carbon atoms and 0.05 to 5% by weight of polymer thickener An external cold medicine characterized in that it is contained in an amount of% is disclosed.
[0014]
However, since the oily base contains a linear long-chain alcohol having 8 to 22 carbon atoms and / or a linear long-chain fatty acid having 8 to 22 carbon atoms, the active ingredient in the liquid agent is the same as described above. There is a problem that it is difficult to uniformly mix or disperse.
[0015]
[Problems to be solved by the invention]
The inventors of the present invention have made various studies for the purpose of developing a new type of common cold coating solution that does not have such drawbacks and can continuously volatilize a volatile component as an active ingredient.
[0016]
[Means for Solving the Problems]
As a result of various investigations, the present inventors have found that a common cold coating solution containing a volatile component for common cold meets the purpose of the present invention, and has completed the present invention.
[0017]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, the present invention will be described in detail.
[0018]
The volatile component for cold used in the present invention is effective for the symptoms of the common cold and has a property of sublimating in a solid state at room temperature or room temperature, or has a property of volatilizing at a temperature near body temperature in a liquid state. If it is a thing, it will not specifically limit. For example, these drugs include camphor, menthol, eucalyptus oil, nutmeg oil, thymian oil, turpentine oil, lavender oil, thymol, mint oil, clove oil, spruce oil, and chimpi oil. Of these, those having a natural type or non-natural type such as camphor and menthol may be used.
[0019]
The nonionic surfactant used in the present invention is a nonionic surfactant having an HLB value of 7 to 20.
[0020]
This is because when a surfactant having an HLB value of less than 7 or more than 20 is used, there is a problem that the volatile component for cold in the liquid preparation of the present invention and water or an aqueous solvent are not uniformly mixed or dispersed. to cause.
[0021]
Specific examples of nonionic surfactants having an HLB value of 7 to 20 include polyoxyethylene alkyl ethers such as polyoxyethylene cetyl ether, polyoxyethylene lauryl ether and polyoxystearyl ether, monococonut oil fatty acid polyoxyethylene Polyoxyethylene sorbitan fatty acid esters such as sorbitan, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monooleate, polyethylene glycol fatty acid esters such as polyethylene glycol monostearate and polyethylene glycol monolaurate, polyoxyethylene glyceryl monostearate , Polyoxyethylene glyceryl fatty acid esters such as polyoxyethylene glyceryl monooleate, polyoxyethylene polyoxy B pyrene cetyl ether, polyoxyethylene sorbit tetraoleate, HLB value, such as polyoxyethylene hydrogenated castor oils are those having from 7 to 20. Among these, polyoxyethylene cetyl ether, polyoxyethylene hydrogenated castor oil, and polyoxyethylene coconut oil fatty acid sorbitan are preferable, and the nonionic surfactant having an HLB value of 10 to 17 is more preferable.
[0022]
The blending ratio of the nonionic surfactant having an HLB value of 7 to 20 varies depending on the type used, but is usually 1 to 10% by weight, preferably 3.5 to 10% by weight based on the total weight of the common cold coating solution. %.
[0023]
The thickener used in the present invention is not particularly limited. For example, glycerin, hydroxypropyl cellulose, polyoxyethylene polyoxypropylene glycol, carboxyvinyl polymer, gum arabic, xanthan gum, sodium alginate, carmellose. Sodium, methyl cellulose, carboxymethyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol and the like can be mentioned. Among these, hydroxypropyl cellulose or polyoxyethylene polyoxypropylene glycol is particularly preferable. The blending ratio of the thickener is usually 0.1 to 5% by weight, preferably 0.2 to 2% by weight, based on the total weight of the common cold coating solution, although it varies depending on the type used.
[0024]
The common cold coating solution of the present invention (hereinafter referred to as the present preparation) is dissolved in the following solvent when the cold volatile component is a solid such as menthol, or when it is a liquid such as eucalyptus oil. Or a preparation prepared by dissolving or suspending with a nonionic surfactant and, if desired, a thickener, emulsifier, suspension, etc. A turbidity agent, a preservative, an antioxidant, a pH adjusting agent, a skin protecting agent, and the like can be appropriately added.
[0025]
As the solvent, in addition to water, ethanol, 1,3-butylene glycol, dipropylene glycol, propylene glycol, hexylene glycol, and acetone can be used as the aqueous solvent, and a mixture of two or more of these can be used.
[0026]
Among these, water, ethanol or a mixed solvent of water, ethanol, 1,3-butylene glycol and dipropylene glycol is preferable.
[0027]
Although the blending ratio of the solvent varies depending on the type to be used, in the case of ethanol, it is 5 to 50% by weight, preferably 15 to 30% by weight, based on the total weight of the cold coating solution.
[0028]
As the emulsifier, in addition to the above-mentioned nonionic surfactant having an HLB value of 7 to 20, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylene lauryl sodium sulfate, polyoxy Examples thereof include ethylene alkyl ether sulfate, polyoxyethylene lauryl ether phosphate, and lecithin derivatives.
[0029]
Examples of the suspending agent include gum arabic, sodium alginate, carmellose sodium, methylcellulose, bentonite and the like.
[0030]
Examples of the preservative include methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate.
[0031]
Examples of the antioxidant include sodium bisulfite and ascorbic acid.
[0032]
Examples of the pH adjusting agent include sodium hydroxide, potassium hydroxide, diisopropanolamine, hydrochloric acid and the like.
[0033]
Examples of the skin protecting agent include glycyrrhizic acid.
[0034]
In the preparation of the present invention, a non-volatile component for cold, an aromatic fragrance component and the like can be added in addition to the volatile component for cold.
[0035]
As a non-volatile component for cold, a chamomile extract is mentioned, for example.
[0036]
The aromatic fragrance component is not particularly limited as long as it is a component useful for fragrance therapy for relaxing and relaxing mental stress and so-called aromatherapy, and examples thereof include lavender oil, peppermint oil, spearmint oil and the like.
[0037]
The preparation of the present invention is used by applying an appropriate amount once or several times a day to places where volatile components are easily inhaled from the nasal cavity such as chest and throat. In particular, it is preferably used for the purpose of alleviating the symptoms of the common cold at bedtime.
[0038]
【The invention's effect】
The preparation of the present invention is absorbed from the skin and suppresses inflammation, and these components are vaporized by body temperature, and are immediately supplied to the tonsils and bronchi directly from the respiratory tract, thereby exerting an effect quickly. And since the volatile component for common cold can be continuously volatilized by the nonionic surfactant which has the HLB value of 7-20 mix | blended in this invention formulation, an effect lasts for a long time.
[0039]
In addition, since the volatile components for the common cold such as camphor and menthol take away the heat of vaporization when vaporized, there is an effect that the body temperature is lowered when the heat is generated.
Therefore, the preparation of the present invention is useful as a coating solution for the common cold, which has an immediate effect on the common cold and also has persistence.
[0040]
Hereinafter, the present invention will be described in detail with reference to test examples. In addition, the volatilization duration of the volatile component was performed using menthol as an indicator component.
[0041]
Test Example 1 (Solubility test)
(1) Test method The solubility of formulations 1 to 8 shown in Table 1 was examined. Each component from eucalyptus oil to turpentine oil was mixed, a nonionic surfactant having a different HLB value, glycyrrhetinic acid and dipropylene glycol were added and dissolved while heating at 70 to 80 ° C. The aqueous solution of hydroxypropylcellulose is gradually added to the solution, solubilized, cooled to 40 ° C. or lower, and separately prepared ethanol solutions of dl-camphor and l-menthol are added, and the coating solution for colds of formulas 1-8 Got.
(2) Results Table 1 shows the results.
As is clear from Table 1, formulations (formulations 1 to 6) to which a nonionic surfactant having an HLB value of 7 to 20 was added were dissolved. However, in the formulation to which a surfactant having an HLB value of less than 7 (Formulation 7 and Formula 8) was added, the volatile component for cold and water or an aqueous solvent were separated.
[0042]
[Table 1]
Test Example 2 (Volatility test of volatile components for cold)
(1) Sample (a) Invention preparations obtained in Reference Examples 3 to 5 and Examples 4 to 7 (b) Preparations obtained in Comparative Examples 1 and 2 (2) Test method 0.3 g Apply to filter paper of 5.0cm x 5.0cm, cover the filter paper vertically with a stoppered sample bottle (225ml), cover it, heat at 37 ° C for 3 minutes, and keep it warm for solid-phase microextraction Insert the SPME extractor [SPME fiber: 100 μm (polydimethylsiloxane, methylsilicon), SPME extractor (unit), made by Spelco] used in (SPME method), and leave it for 3 minutes to add l in the headspace gas. -Extracted menthol. The SPME extractor was quickly injected into a gas chromatograph-mass spectrometer (hereinafter referred to as GC-MS) (manufactured by Shimadzu Corporation), and analysis was started. Next, the sample bottle with the inner stopper with the filter paper was kept at 37 ° C, and nitrogen was poured into the sample bottle with the inner stopper with a rubber stopper while keeping the flow rate at 100 ml / min. Continued emission of volatile components. Sampling was performed in the same manner after 30, 60, 90 and 120 minutes, and volatile components were measured over time by analysis using a GC-MS apparatus. In addition, the conditions of GC and MS in a GC-MS apparatus are as follows.
[0044]
[GC condition]
Separation column: DB-5 (0.53 mmφ × 30 m, liquid phase: (5% -phenyl)
-Methylpolysiloxane)) (J and Double Scientific)
・ Vaporization chamber temperature: 270 ℃
・ Flow controller: Split / Splitless (Closed 1 minute)
Carrier gas pressure: 60 kPa
・ Total flow rate: 126.2 ml / min ・ Sampling time: 1 minute ・ Interface temperature: 230 ° C.
Separation column temperature: initial temperature 50 ° C., constant temperature for 3 minutes, then heated to 300 ° C. at a heating rate of 9 ° C./minute, final temperature 300 ° C., constant temperature for 5 minutes.
[0045]
[MS conditions]
・ Detector voltage: 1.41 kV
Solvent elution time: 3 minutes Scanning mass range: 21-350
・ Scan interval: 0.5 seconds ・ Threshold: 1000
(3) Tables 2 and 3 show the half-life of the menthol concentration which decreases as a result of volatilization. As is apparent from Table 2, the preparations of the present invention in which a nonionic surfactant was added to the cold volatile component ( Reference Example 3 and Reference Example 4 ) were both thickeners and nonionic surfactants. Menthol, which is a volatile component for cold, was continuously volatilized as compared with a preparation not added (Comparative Example 1) or a thickener alone and a preparation not added a nonionic surfactant (Comparative Example 2). . Further, as is clear from Tables 2 and 3, the preparations of the present invention in which a nonionic surfactant and a thickener were used in combination with the cold volatile component ( Reference Example 5, Examples 4 to 7). Compared with the preparation (Comparative Example 2) to which no nonionic surfactant was added, menthol was volatilized more continuously.
[0046]
[Table 2]
[Table 3]
Test Example 3 (Volatility test of volatile components for cold)
(1) Sample (a) Formulation of the present invention obtained in Example 12 (b) Formulation obtained in Comparative Example 3 and Comparative Example 4 (c) Reference Example 1 ("VICKS VapoRub" manufactured by Max Factor) and Reference Example 2 (Yamanouchi Pharmaceutical Co., Ltd. “Kaconar Kaze Pup”)
(2) Test method The test was conducted in the same manner as in Test Example 2 except that sampling was performed up to 8 hours every hour for 30 minutes, 1 hour and thereafter.
(3) Table 4 shows the half-life of the menthol concentration, which decreases as a result of volatilization.
As is apparent from Table 4, the formulation (Example 12) in which the nonionic surfactant of the present invention was added to the cold volatile component was added with both the thickener and the nonionic surfactant of the present invention. Compared to the preparation (Comparative Example 4) which does not contain the nonionic surfactant of the present invention (Comparative Example 3) and the commercial preparation (Reference Examples 1 and 2). Menthol, a volatile component, was volatilized continuously.
[0049]
[Table 4]
【Example】
The present invention will be specifically described below with reference to examples and comparative examples.
[0051]
Reference example 3
(Prescription)
Ingredient (wt%)
―――――――――――――――――――――――――――――――
1. Eucalyptus oil 2.0
2. Chimian oil 1.5
3. Nutzuku oil 0.5
4). Lavender oil 0.5
5. Chamomile tincture 2.5
6). Polyoxyethylene hydrogenated castor oil (60) (HLB value 14.0)
6.0
7). Ethanol 50.0
8). dl-Camphor 5.0
9. l-Menthol 3.0
10. Appropriate amount of purified water ―――――――――――――――――――――――――――――――
Total 100.0
(Manufacturing method) Each component from eucalyptus oil to chamomile tincture is mixed and solubilized with polyoxyethylene hydrogenated castor oil (60) while heating to 80 ° C, and then ethanol and purified water are added. Furthermore, dl-camphor and l-menthol were added and dissolved to obtain the cold-use coating solution of Reference Example 3 .
[0052]
Reference example 4
Was used in place of polyoxyethylene hardened castor oil (60) (HLB value 14.0) polyoxyethylene coconut oil fatty acid sorbitan (20) (HLB value 16.7), are similarly prepared as in Reference Example 3, Reference The common cold coating solution of Example 4 was obtained.
[0053]
Reference Example 5
(Prescription)
Ingredient (wt%)
―――――――――――――――――――――――――――――――
1. Eucalyptus oil 2.0
2. Chimian oil 1.5
3. Nutzuku oil 0.5
4). Lavender oil 0.5
5. Chamomile tincture 2.5
6). Polyoxyethylene (20) cetyl ether (HLB value 17.
0) 6.0
7). Ethanol 50.0
8). dl-Camphor 5.0
9. l-Menthol 3.0
10. Purified water appropriate amount11. Hydroxypropylcellulose (2% aqueous solution) 10.0
12 Polyoxyethylene (160) Polyoxypropylene (30)
Glycol 1.0
―――――――――――――――――――――――――――――――
Total 100.0
(Manufacturing method) Each component from eucalyptus oil to chamomile tincture is mixed, solubilized with polyoxyethylene (20) cetyl ether while heating at 80 ° C, and then ethanol and purified water are added. Further, dl-camphor and l-menthol were added and dissolved, and then an aqueous solution of hydroxypropyl cellulose and polyoxyethylene (160) polyoxypropylene (30) glycol were added in this order to obtain a cold-use coating solution of Reference Example 5 .
[0054]
Example 4
Example 4 was prepared in the same manner as in Example 3 except that polyoxyethylene (20) cetyl ether (HLB value 17.0) was replaced with polyoxyethylene hydrogenated castor oil (60) (HLB value 14.0). A coating solution for cold was obtained.
[0055]
Example 5
Prepared in the same manner as in Example 3, except that polyoxyethylene (20) cetyl ether (HLB value 17.0) was replaced with polyoxyethylene coconut oil fatty acid sorbitan (20) (HLB value 16.7). A common cold coating solution was obtained.
[0056]
Example 6
6.0% by weight of polyoxyethylene (20) cetyl ether (HLB value 17.0) is 4.0% by weight of polyoxyethylene (20) cetyl ether (HLB value 17.0) and polyoxyethylene hydrogenated castor oil (60 ) (HLB value 14.0) The same procedure as in Example 3 was carried out except that the content was changed to 2.0% by weight, and the common cold coating solution of Example 6 was obtained.
[0057]
Example 7
6.0% by weight of polyoxyethylene (20) cetyl ether (HLB value 17.0) is 4.0% by weight of polyoxyethylene (20) cetyl ether (HLB value 17.0) and polyoxyethylene hydrogenated castor oil (60 ) (HLB value 14.0) Preparation in the same manner as in Example 3 except that 5.0% by weight was used, and the common cold coating solution of Example 7 was obtained.
[0058]
Example 8
Polyoxyethylene (20) cetyl ether (HLB value 17.0) 6.0% by weight, polyoxyethylene (20) cetyl ether (HLB value 17.0) 4.0% by weight and polyoxyethylene coconut oil fatty acid sorbitan ( 20) (HLB value 16.7) Except having replaced with 5.0 weight%, it prepared similarly to Example 3 and obtained the coating solution for the common cold of Example 8.
[0059]
Example 9
6.0% by weight of polyoxyethylene (20) cetyl ether (HLB value 17.0) is 4.0% by weight of polyoxyethylene (20) cetyl ether (HLB value 17.0) and polyoxyethylene sorbitan monooleate ( 6) (HLB value 10.0) Prepared in the same manner as in Example 3 except that 5.0% by weight was used, to obtain the common cold coating solution of Example 9.
[0060]
After mixing each component from Eucalyptus oil to chamomile tincture and heating to 80 ° C., solubilized with polyoxyethylene (20) cetyl ether and polyoxyethylene hydrogenated castor oil (60), ethanol and purified water were added. Add. Further, dl-camphor and l-menthol were added and dissolved, and then an aqueous solution of hydroxypropyl cellulose, polyoxyethylene (160) polyoxypropylene (30) glycol and concentrated glycerin were added in this order, and the common cold coating solution of Example 10 was added. Obtained.
[0061]
Each component from eucalyptus oil to turpentine oil is mixed, polyoxyethylene hydrogenated castor oil (60), glycyrrhetinic acid, 1,3-butylene glycol and dipropylene glycol are added and dissolved while heating at 70 to 80 ° C. The aqueous solution of hydroxypropylcellulose was gradually added to the solution, solubilized, cooled to 40 ° C. or lower, and separately prepared dl-camphor and l-menthol ethanol solutions were added. Obtained.
[0062]
It was prepared in the same manner as in Example 11, and the common cold coating solution of Example 12 was obtained.
[0063]
It was prepared in the same manner as in Example 11, and the common cold coating solution of Example 13 was obtained.
[0064]
It was prepared in the same manner as in Example 11 to obtain the common cold coating solution of Example 14.
[0065]
It was prepared in the same manner as in Example 11 to obtain the common cold coating solution of Example 15.
[0066]
Mix each component from Eucalyptus oil to chamomile tincture and add ethanol and purified water while heating to 80 ° C. Furthermore, dl-camphor and l-menthol were added and dissolved to obtain a liquid preparation of Comparative Example 1.
[0067]
Mix each component from Eucalyptus oil to chamomile tincture and add ethanol and purified water while heating to 80 ° C. Furthermore, after adding and dissolving dl-camphor and l-menthol, it added in order of hydroxypropyl cellulose aqueous solution and polyoxyethylene (160) polyoxypropylene (30) glycol, and the liquid agent of the comparative example 2 was obtained.
[0068]
Comparative Example 3
A common cold coating solution of Comparative Example 3 was obtained in the same manner as in Example 12 except that the polyoxyethylene hydrogenated castor oil (60) was removed.
[0069]
Comparative Example 4
It was prepared in the same manner as in Example 12 except that the polyoxyethylene hydrogenated castor oil (60) and hydroxypropylcellulose were removed, and the common cold coating solution of Comparative Example 4 was obtained.
Claims (5)
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