CN115397522A - 包含天然来源的防腐剂的组合物 - Google Patents
包含天然来源的防腐剂的组合物 Download PDFInfo
- Publication number
- CN115397522A CN115397522A CN202180023994.7A CN202180023994A CN115397522A CN 115397522 A CN115397522 A CN 115397522A CN 202180023994 A CN202180023994 A CN 202180023994A CN 115397522 A CN115397522 A CN 115397522A
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- China
- Prior art keywords
- composition
- weight
- sodium
- sulfate
- surfactant
- Prior art date
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- Granted
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- 239000000203 mixture Substances 0.000 title claims abstract description 225
- 239000003755 preservative agent Substances 0.000 title claims abstract description 65
- 230000002335 preservative effect Effects 0.000 claims abstract description 30
- -1 alkyl ether sulfates Chemical class 0.000 claims description 61
- 239000004094 surface-active agent Substances 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 21
- 239000003945 anionic surfactant Substances 0.000 claims description 21
- 239000002888 zwitterionic surfactant Substances 0.000 claims description 21
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 claims description 19
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 18
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 17
- 229920005862 polyol Polymers 0.000 claims description 15
- 150000003077 polyols Chemical class 0.000 claims description 13
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 13
- 235000010234 sodium benzoate Nutrition 0.000 claims description 13
- 239000004299 sodium benzoate Substances 0.000 claims description 13
- SMVRDGHCVNAOIN-UHFFFAOYSA-L disodium;1-dodecoxydodecane;sulfate Chemical group [Na+].[Na+].[O-]S([O-])(=O)=O.CCCCCCCCCCCCOCCCCCCCCCCCC SMVRDGHCVNAOIN-UHFFFAOYSA-L 0.000 claims description 11
- 229960003237 betaine Drugs 0.000 claims description 10
- 230000000845 anti-microbial effect Effects 0.000 claims description 9
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 8
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 7
- UXPUMTCLHVWFKC-UHFFFAOYSA-N 2-dodecanoyloxyethanesulfonic acid Chemical compound CCCCCCCCCCCC(=O)OCCS(O)(=O)=O UXPUMTCLHVWFKC-UHFFFAOYSA-N 0.000 claims description 6
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 6
- 150000008051 alkyl sulfates Chemical class 0.000 claims description 6
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 229940071096 lauroyl isethionate Drugs 0.000 claims description 6
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 6
- 235000010235 potassium benzoate Nutrition 0.000 claims description 6
- 239000004300 potassium benzoate Substances 0.000 claims description 6
- 229940103091 potassium benzoate Drugs 0.000 claims description 6
- 229940048106 sodium lauroyl isethionate Drugs 0.000 claims description 6
- BRMSVEGRHOZCAM-UHFFFAOYSA-M sodium;2-dodecanoyloxyethanesulfonate Chemical compound [Na+].CCCCCCCCCCCC(=O)OCCS([O-])(=O)=O BRMSVEGRHOZCAM-UHFFFAOYSA-M 0.000 claims description 6
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims description 6
- MRUAUOIMASANKQ-UHFFFAOYSA-N cocamidopropyl betaine Chemical compound CCCCCCCCCCCC(=O)NCCC[N+](C)(C)CC([O-])=O MRUAUOIMASANKQ-UHFFFAOYSA-N 0.000 claims description 5
- 239000004264 Petrolatum Substances 0.000 claims description 4
- 229940066842 petrolatum Drugs 0.000 claims description 4
- 235000019271 petrolatum Nutrition 0.000 claims description 4
- 229940104261 taurate Drugs 0.000 claims description 4
- PSBDWGZCVUAZQS-UHFFFAOYSA-N (dimethylsulfonio)acetate Chemical compound C[S+](C)CC([O-])=O PSBDWGZCVUAZQS-UHFFFAOYSA-N 0.000 claims description 3
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 claims description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- MZKKJVZIFIQOPP-UHFFFAOYSA-M potassium;4-aminobenzoate Chemical compound [K+].NC1=CC=C(C([O-])=O)C=C1 MZKKJVZIFIQOPP-UHFFFAOYSA-M 0.000 claims description 3
- IKGKWKGYFJBGQJ-UHFFFAOYSA-M sodium;2-(dodecanoylamino)acetate Chemical compound [Na+].CCCCCCCCCCCC(=O)NCC([O-])=O IKGKWKGYFJBGQJ-UHFFFAOYSA-M 0.000 claims description 3
- 229940117986 sulfobetaine Drugs 0.000 claims description 3
- 241000589513 Burkholderia cepacia Species 0.000 claims description 2
- 241000222122 Candida albicans Species 0.000 claims description 2
- 241000588914 Enterobacter Species 0.000 claims description 2
- 241000588747 Klebsiella pneumoniae Species 0.000 claims description 2
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims description 2
- 241000191967 Staphylococcus aureus Species 0.000 claims description 2
- 229940095731 candida albicans Drugs 0.000 claims description 2
- 229940073507 cocamidopropyl betaine Drugs 0.000 claims description 2
- 238000011081 inoculation Methods 0.000 claims description 2
- 229940064734 aminobenzoate Drugs 0.000 claims 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims 2
- 241001331781 Aspergillus brasiliensis Species 0.000 claims 1
- XETSAYZRDCRPJY-UHFFFAOYSA-M sodium;4-aminobenzoate Chemical group [Na+].NC1=CC=C(C([O-])=O)C=C1 XETSAYZRDCRPJY-UHFFFAOYSA-M 0.000 claims 1
- HSFQBFMEWSTNOW-UHFFFAOYSA-N sodium;carbanide Chemical group [CH3-].[Na+] HSFQBFMEWSTNOW-UHFFFAOYSA-N 0.000 claims 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 abstract description 30
- 239000005711 Benzoic acid Substances 0.000 abstract description 15
- 235000010233 benzoic acid Nutrition 0.000 abstract description 15
- 230000000699 topical effect Effects 0.000 abstract description 5
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 19
- 239000000194 fatty acid Substances 0.000 description 17
- 238000009472 formulation Methods 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 13
- 235000014113 dietary fatty acids Nutrition 0.000 description 12
- 229930195729 fatty acid Natural products 0.000 description 12
- 125000000217 alkyl group Chemical class 0.000 description 10
- 239000000463 material Substances 0.000 description 9
- 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 8
- 244000005700 microbiome Species 0.000 description 8
- 239000002736 nonionic surfactant Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 239000003093 cationic surfactant Substances 0.000 description 7
- 235000010980 cellulose Nutrition 0.000 description 7
- 229920002678 cellulose Polymers 0.000 description 7
- 235000013399 edible fruits Nutrition 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 125000002252 acyl group Chemical group 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 235000011187 glycerol Nutrition 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229940048053 acrylate Drugs 0.000 description 5
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 5
- 150000002191 fatty alcohols Chemical class 0.000 description 5
- 229930002330 retinoic acid Natural products 0.000 description 5
- 239000002562 thickening agent Substances 0.000 description 5
- 229960001727 tretinoin Drugs 0.000 description 5
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 210000002421 cell wall Anatomy 0.000 description 4
- 235000020971 citrus fruits Nutrition 0.000 description 4
- 229920001577 copolymer Polymers 0.000 description 4
- 239000002537 cosmetic Substances 0.000 description 4
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 235000021317 phosphate Nutrition 0.000 description 4
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 4
- 229920002545 silicone oil Polymers 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 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
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 239000004721 Polyphenylene oxide Substances 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 235000021355 Stearic acid Nutrition 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 125000000129 anionic group Chemical group 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 239000003906 humectant Substances 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 210000001724 microfibril Anatomy 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
- 229920000570 polyether Polymers 0.000 description 3
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- 229910052700 potassium Inorganic materials 0.000 description 3
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- 150000005207 1,3-dihydroxybenzenes Chemical class 0.000 description 2
- ULQISTXYYBZJSJ-UHFFFAOYSA-N 12-hydroxyoctadecanoic acid Chemical compound CCCCCCC(O)CCCCCCCCCCC(O)=O ULQISTXYYBZJSJ-UHFFFAOYSA-N 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- IOHPVZBSOKLVMN-UHFFFAOYSA-N 2-(2-phenylethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CCC1=CC=CC=C1 IOHPVZBSOKLVMN-UHFFFAOYSA-N 0.000 description 2
- BANXPJUEBPWEOT-UHFFFAOYSA-N 2-methyl-Pentadecane Chemical compound CCCCCCCCCCCCCC(C)C BANXPJUEBPWEOT-UHFFFAOYSA-N 0.000 description 2
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-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
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- CBKLICUQYUTWQL-XWGBWKJCSA-N methyl (3s,4r)-3-methyl-1-(2-phenylethyl)-4-(n-propanoylanilino)piperidine-4-carboxylate;oxalic acid Chemical compound OC(=O)C(O)=O.CCC(=O)N([C@]1([C@H](CN(CCC=2C=CC=CC=2)CC1)C)C(=O)OC)C1=CC=CC=C1 CBKLICUQYUTWQL-XWGBWKJCSA-N 0.000 description 2
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- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
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- CAVXVRQDZKMZDB-UHFFFAOYSA-M sodium;2-[dodecanoyl(methyl)amino]ethanesulfonate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CCS([O-])(=O)=O CAVXVRQDZKMZDB-UHFFFAOYSA-M 0.000 description 2
- FWFUWXVFYKCSQA-UHFFFAOYSA-M sodium;2-methyl-2-(prop-2-enoylamino)propane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CC(C)(C)NC(=O)C=C FWFUWXVFYKCSQA-UHFFFAOYSA-M 0.000 description 2
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Abstract
本发明涉及适用于局部应用的组合物,其包含具有苯甲酸或其衍生物的天然来源的防腐剂。该组合物在用天然来源的防腐剂防腐时和在高于皮肤的天然pH至高达7.25的pH下是稳定的。
Description
技术领域
本发明涉及包含天然来源的防腐剂的组合物。更具体地,本发明涉及一种pH超过皮肤的天然pH,并且包含特定的两性离子与阴离子表面活性剂体系的组合物。出乎意料地,该组合物用包含苯甲酸和/或其衍生物的天然来源的防腐剂防腐。令人惊奇地,该防腐剂为具有两性离子表面活性剂与阴离子表面活性剂重量比为1:8至1:2的表面活性剂体系的组合物提供了优异的抗微生物益处,即使当这样的组合物被配制成具有超过皮肤的天然pH至高达7.25的pH和小于8.0重量%的总硫酸盐基表面活性剂时。除了具有抗菌稳定性之外,本发明的组合物是温和的,在45℃下储存3个月之后保持无变色、脱水收缩和异味。
背景技术
DMDM乙内酰脲、对羟基苯甲酸酯、甲基异噻唑啉酮以及甲基氯异噻唑啉酮是消费品中常用的防腐剂。这些防腐剂已经安全地使用多年,并且已知在保持某些最终用途组合物的完整性和稳定性方面效果良好。适用于消费品的另一种防腐剂是苯甲酸钠。然而,苯甲酸钠虽然通常被认为是安全的,但其众所周知用于完全在酸性pH范围内和在皮肤的天然pH下的组合物中。尽管如此,仍希望使用天然来源的防腐剂,特别是包含适用于在超过皮肤天然pH的pH下配制的全系列消费品中良好发挥作用的组分的防腐剂。此外,这样的天然来源的防腐剂应该有效地对产品防腐,不使皮肤敏感,并且不会对其所配制的消费品(特别是局部施用的那些)的感官特性产生不利地影响。它们也不应对其所添加的产品引起任何负面的组成特征,如颜色变化、异味或脱水收缩。
除了提供优良的抗微生物有益效果之外,天然来源的防腐剂不应对环境有害,并且对于最脆弱的消费者婴儿来说足够温和。
因此,本发明涉及具有特定表面活性剂比率和天然来源的防腐剂的组合物。防腐剂包含苯甲酸和/或其衍生物,其令人惊讶地为具有1:8至1:2的两性离子表面活性剂与阴离子表面活性剂重量比的组合物提供优异的抗微生物益处,即使当这样的组合物被配制成具有超过皮肤的天然pH至高达7.25的pH和小于8.0重量%的总硫酸盐基表面活性剂时。此外,这种防腐剂体系出乎意料地不会不利地影响组合物的稳定性、颜色和气味,并且当在其中配制时提供优异的抗微生物益处
附加信息
已经公开了制备防腐剂体系的尝试。在美国公开的专利申请2012/0190744A1中,公开了用于化妆品制剂的防腐剂体系。
还公开了制备防腐剂体系的一些其他尝试。在美国专利申请US2018/0193243A1中,公开了无毒的防腐剂组合物。
甚至已经公开了制备协同混合物的其他尝试。在美国专利号7,582,681B2中,公开了具有1,2-烷二醇的抗微生物活性化合物。
然而,还描述了制备个人洗涤组合物的其他尝试。在美国专利号5,872,111中,描述了包含糖基酰胺(glycosylamide)表面活性剂的组合物。
以上附加信息都没有描述如本发明所述和要求保护的具有天然来源的防腐剂体系及重量比为1:8-1:2的两性离子和阴离子表面活性剂的组合物。
发明内容
在第一方面,本发明涉及一种组合物,包含:
(a)包含苯甲酸和/或其衍生物的防腐剂;
(b)阴离子表面活性剂,其包含烷基硫酸盐、烷基醚硫酸盐或其混合物以及羟乙基磺酸盐、牛磺酸盐、甘氨酸盐或其混合物;
(c)两性离子表面活性剂,其包含甜菜碱、磺基甜菜碱或其混合物;
(d)1至9重量%的多元醇;以及
(e)水,
所述组合物具有5.75至7.25的pH,超过5.0重量%的总表面活性剂,和1:8至1:2的两性离子表面活性剂与阴离子表面活性剂的重量比,其中羟乙基磺酸盐为至少50重量%的月桂酰羟乙基磺酸盐,并且所述组合物包含小于8.0重量%的硫酸盐基表面活性剂。
在第二方面,本发明涉及通过使皮肤与本发明第一方面的组合物接触而美容性处理皮肤的方法。
通过接下来的说明和实施例,本发明的所有其他方面将更容易变得清楚。
如本文所用,皮肤意指包括手臂(包括腋下)、面部、足部、颈部、胸部、手部、腿部、臀部和头皮(包括头发)上的皮肤。如本文所用,天然来源的防腐剂是指可以是天然衍生的并且包含苯甲酸和/或其衍生物的防腐剂。为了避免疑义,可以合成制备包含苯甲酸和/或其衍生物的防腐剂,并且它们在确定的pH值下也适用于本发明的组合物。如本文所用,组合物意指最终用途组合物,包括准备用于局部施用的组合物,诸如乳膏、洗剂、香膏、精华素、凝胶、摩丝、气雾剂、除臭剂、止汗剂、洗发剂、护发素、化妆品或个人洗剂,包括条状物和液体。这样的组合物也可以是家庭护理组合物如硬表面清洁剂或洗衣洗涤剂组合物。在一个实施方案中,组合物是液体个人洗涤组合物,最优选液体沐浴露。在另一个实施方案中,组合物是洗发剂组合物。如下文所述,本发明的组合物可任选地包含加入其中的皮肤有益成分,例如润肤剂、维生素和/或其衍生物、间苯二酚类、视黄酸前体、着色剂、保湿剂、防晒剂、其混合物等。皮肤有益成分可以是水溶性或油溶性的。因此,该组合物是pH为5.75-7.25的水基组合物,且该组合物可以是水或油连续的,但优选是水连续的。硫酸盐基意指具有SO4基团,如月桂基硫酸钠中的SO4基团,由此温和表面活性剂体系意指小于8.0重量%的硫酸盐基表面活性剂。如本文所用,粘度是用适合于各向同性组合物的Brookfield RV5在20rpm下30秒和在25℃下测得的。在另一个实施方案中,本发明的组合物为非治疗的和美容的组合物,其为液体个人洗剂、免洗型皮肤洗剂或乳膏。在没有另外明确说明的情况下,本文所述的所有范围意在包括涵盖其中的所有范围。颜色稳定性是指没有负面的和可辨别的颜色变化,如由受过训练的专门小组成员观察到的白色至棕色的颜色变化。优异的抗微生物益处是指在7天时至少有3log的细菌杀灭,以及在7天时至少有2log的酵母和霉菌杀灭,所有这些都在美国药典(USP)的通则51章中描述。术语"包含"是指包括“基本上由…组成”和“由…组成”的术语。为了避免疑义,并且为了说明,包含阴离子和两性离子表面活性剂、水、苯甲酸钠和多元醇的本发明的组合物意指包括基本由其组成的组合物和由其组成的组合物。除了在操作对比例中,或另外明确指出的情况中,本说明书中表示材料或条件的量或比率和/或材料的物理性质和/或用途的所有数字应理解为由词语“约”修饰。在本发明最优选的实施方案中,本发明的组合物是粘度为750-22000mPa.s(cps)的沐浴露组合物,包括涵盖其中的所有范围。
具体实施方案
关于适用于本发明的天然来源的防腐剂,其包括苯甲酸和/或其衍生物。在本发明的实施方案中,天然来源的防腐剂是基于准备供消费者使用的组合物中所用防腐剂的总重量的80-100重量%的苯甲酸、苯甲酸衍生物或其混合物。在本发明的任选实施方案中,额外的天然来源的防腐剂可以与苯甲酸和/或其衍生物一起使用。关于可以使用的额外的天然来源的防腐剂的唯一限制是其适用于由消费者使用的组合物中,特别是用于局部应用。可用于本发明的额外的还任选的天然来源的防腐剂的说明性示例包括葡糖酸内酯、葡糖酸钙、葡糖醛酸内酯、百里酚、厚朴酚提取物、biopein、suprapein、neopein、山梨酸、柠檬酸、迷迭香提取物、山梨酸钾、其混合物或类似物。在优选的实施方案中,用于本发明的天然来源的防腐剂是基于所用防腐剂的总重量的90-100wt%的苯甲酸、苯甲酸衍生物或其混合物。在最优选的实施方案中,用于本发明的天然来源的防腐剂是基于所用防腐剂的总重量的95-100wt%的苯甲酸、苯甲酸衍生物或其混合物。在本发明的另一个实施方案中,基于所用防腐剂的总重量,用于本发明的天然来源的防腐剂全部(100%重量)是苯甲酸、苯甲酸衍生物或其混合物。在再另一个优选的实施方案中,用于本发明的天然来源的防腐剂(即,苯甲酸衍生物)是苯甲酸钠、苯甲酸钾、氨基苯甲酸盐或其混合物。当使用时,用于本发明组合物的优选的氨基苯甲酸盐是对氨基苯甲酸钠或对氨基苯甲酸钾或其混合物。在再另一个优选的实施方案中,用于本发明的天然来源的防腐剂是苯甲酸钠。因此,可能优选的是,基于组合物中存在的防腐剂的总重量,本发明组合物中存在的所有(100重量%)防腐剂优选为苯甲酸、苯甲酸衍生物或其混合物。更优选地,用于本发明的防腐剂是苯甲酸钠、苯甲酸钾、氨基苯甲酸盐或其混合物。当使用时,用于本发明组合物的优选的氨基苯甲酸盐是对氨基苯甲酸钠或对氨基苯甲酸钾或其混合物。最优选地,用于本发明的防腐剂是苯甲酸钠。苯甲酸钠、苯甲酸钾、氨基苯甲酸盐或其混合物优选是天然来源的。
关于本发明中使用的天然来源的防腐剂的量,其通常占组合物重量的0.20-2.0%,优选0.3-1.5%,最优选0.35-1.5%,包括其中包含的所有范围。在另一个实施方案中,天然来源的防腐剂占组合物重量的0.4-0.65%,包括其中包含的所有范围。
适用于本发明的阴离子表面活性剂包括烷基硫酸盐、烷基醚硫酸盐或其混合物。适合使用的烷基硫酸盐(例如,C12-C18烷基硫酸盐)包括月桂基硫酸盐、烷醇聚醚硫酸盐(pareth sulfate)、肉豆蔻醇聚醚硫酸盐、硬脂基硫酸盐、癸基硫酸盐或其混合物的钠盐、钾盐、铵盐或取代铵盐。关于适用于本发明的烷基醚硫酸盐(包括烷基甘油醚硫酸盐),这些包括具有下式的表面活性剂:
RO(CH2CH2O)nSO3M
其中R是具有8至18个碳,优选12至18个碳的烷基或烯基,n具有至少1,优选小于5,并且最优选1至4的平均值,并且M是增溶阳离子,如钠、钾、铵或取代的铵。关于本发明中使用的阴离子硫酸盐基表面活性剂(即,不是羟乙基磺酸盐、牛磺酸盐和/或甘氨酸盐),适合使用的优选的烷基醚硫酸盐是月桂基醚硫酸钠,并且优选的烷基硫酸盐是月桂基硫酸钠。也可以使用月桂基醚硫酸钠和月桂基硫酸钠的混合物。在本发明的实施方案中,基于组成组合物中所使用的构成硫酸盐基表面活性剂的月桂基醚硫酸钠和月桂基硫酸钠的总重量,所使用的硫酸盐基表面活性剂为至少35重量%,优选至少40重量%,最优选45-95重量%的月桂基醚硫酸钠。用于本发明的月桂基醚硫酸钠可具有1、2、2.5、3、4、5或6个聚(环氧乙烷)单元(例如EO单元)或其混合物。在通常优选的实施方案中,所使用的月桂基醚硫酸钠是具有1、2和3个EO单元的表面活性剂的混合物。基于混合物的总重量,这种混合物通常具有10-90重量%的月桂基醚硫酸钠。在另一个优选的实施方案中,基于组合物中硫酸盐基表面活性剂的总量,混合物具有45至65重量%的月桂基醚硫酸钠和35至55重量%的月桂基硫酸钠,包括其中包含的所有范围。
适用于本发明的羟乙基磺酸盐(即额外的阴离子表面活性剂)与含硫酸盐的表面活性剂一起将包含至少50重量%的月桂酰羟乙基磺酸盐。可与月桂酰羟乙基磺酸盐一起使用的另外的酰基羟乙基磺酸盐包括通常分类为C8-C18酰基羟乙基磺酸盐的那些(如月桂酰羟乙基磺酸盐)。适用于本发明的羟乙基磺酸盐表面活性剂通过碱金属羟乙基磺酸盐与具有6-18个碳原子且碘值小于20的混合脂族脂肪酸之间的反应来制备。至少75%的混合脂肪酸具有12-18个碳原子,和至多25%的混合脂肪酸具有6-10个碳原子。
适合使用的酰基羟乙基磺酸盐还可以包括烷氧基化的羟乙基磺酸盐,如描述于Ilardi等人,美国专利号5,393,466,标题“Fatty Acid Esters of Polyalkoxylatedisethonic acid”;Feb.28,1995授权中的那些,其通过引用并入本文。此类表面活性剂具有以下通式:
R1C--O(O)--C(X)H--C(Y)H--(OCH2—CH2)m----SO3M
其中R1为具有8至18个碳的烷基基团,m为1至4的整数,X和Y各自独立地为氢或具有1至4个碳的烷基基团,并且M为如前所述的增溶阳离子。在本发明的优选实施方案中,除了月桂酰羟乙基磺酸盐之外使用的羟乙基磺酸盐是椰油酰羟乙基磺酸盐、月桂酰基甲基羟乙基磺酸盐或其混合物,其中这些羟乙基磺酸盐用阳离子溶解,所述阳离子通常是钠、钾、铵或取代的铵。在本发明的实施方案中,用于本发明的羟乙基磺酸盐的总重量的至少75重量%是月桂酰羟乙基磺酸钠。在另一个实施方案中,用于本发明组合物的羟乙基磺酸盐总重量的至少85重量%,优选至少95重量%是月桂酰羟乙基磺酸钠。在本发明的再另一个实施方案中,用于本发明的所有(100%)羟乙基磺酸盐是月桂酰羟乙基磺酸钠。
至于可以使用的牛磺酸盐,这些包括酰基牛磺酸盐,包括甲基酰基牛磺酸盐。通常,可用于本发明的牛磺酸盐包括通常由下式表示的那些:
R5CONR6CH2CH2SO3M
其中R5是C8-C20烷基,R6是C1-C4烷基。
M是如前所述的增溶阳离子。
在本发明的实施方案中,当使用牛磺酸盐时,甲基月桂酰基牛磺酸钠、甲基椰油酰基牛磺酸钠或其混合物通常是优选的。
关于适合使用的甘氨酸盐,这些包括酰基甘氨酸盐,如月桂酰基甘氨酸钠、椰油酰甘氨酸钠或其混合物。
通常,阴离子表面活性剂占组合物(例如最终使用的液体个人洗涤组合物)的4重量%至15重量%,并且优选5重量%至12重量%,并且最优选6重量%至10重量%,包括其中包含的所有范围,条件是基于组合物的总重量,硫酸盐基的阴离子表面活性剂的总重量小于8.0重量%,优选小于7.5重量%,最优选小于7.2重量%。在通常期望的实施方案中,硫酸盐基表面活性剂占组合物总重量的至少4.0重量%。基于组合物中所用羟乙基磺酸盐的总量,作为至少50重量%的月桂酰羟乙基磺酸钠的羟乙基磺酸盐通常占组合物的0.4-4重量%,优选0.5-2重量%,最优选0.75-1.5重量%。
至于用于本发明并且包含甜菜碱、磺基甜菜碱(sultaine)或其混合物的两性离子表面活性剂,其包括下式的简单甜菜碱:
R2--N+--(R3)(R4)CH2CO2 -
和下式的酰氨基甜菜碱:
R2--CONH(CH2)t--N+--(R3)(R4)CH2CO2 -,其中t是2或3。
在两个式中,R2独立地为具有7至18个碳原子的烷基或烯基;R3和R4各自独立地为1至3个碳原子的烷基、羟烷基或羧烷基;特别地,R2可以是衍生自椰子油的C12和C14烷基的混合物,使得基团R2的至少一半,优选至少四分之三具有10-14个碳原子。R3和R4优选为甲基。
另一种可能性是两性离子表面活性剂是下式的磺基甜菜碱:
R2--N+--(R3)(R4)(CH2)3SO3 -
或
R2--CONH(CH2)u--N+--(R3)(R4)(CH2)3SO3 -
其中u是2或3,或其中--(CH2)3SO3 -被--CH2C(OH)(H)CH2SO3 -替代的变体。
在这些式中,R2,R3和R4如前面所定义。
适用的两性离子表面活性剂的说明示例包括甜菜碱,如椰油二甲基羧甲基甜菜碱、椰油酰胺丙基甜菜碱、月桂酰胺丙基甜菜碱或其混合物。适用的另外的两性离子表面活性剂包括椰油酰胺丙基磺基甜菜碱。在本发明的实施方案中,所使用的两性离子表面活性剂为甜菜碱,并且基于所使用的两性离子表面活性剂的总重量,为至少65重量%,优选至少80重量%,最优选至少95重量%的椰油酰胺丙基甜菜碱。在本发明的特别优选的实施方案中,所使用的两性离子表面活性剂全部是椰油酰胺丙基甜菜碱。这类两性离子表面活性剂可从供应商如Stepan公司商购获得。
所用甜菜碱通常占组合物重量的0.8-7%,优选1.0-5%,最优选1.5-3.5%。在另一个优选的实施方案中,甜菜碱占组合物重量的2-3%,包括其中包含的所有范围。
本发明中两性离子表面活性剂与阴离子表面活性剂的重量比为1:8-1:2,优选1:6-1:2,最优选1:5-1:3,包括其中包含的所有重量比。在本发明的实施方案中,两性离子表面活性剂与阴离子表面活性剂的重量比为1:4至1:3,包括其中包含的所有范围。
适用于本发明的多元醇仅限于适用于局部组合物且是水溶性的程度。可用于本发明的多元醇的说明性和非限制性示例包括山梨醇、甘油、甘露醇、木糖醇、麦芽糖醇或其混合物。在本发明的实施方案中,基于组合物中使用的多元醇的总重量,使用的多元醇为至少50重量%的甘油。在本发明的另一个实施方案中,所使用的多元醇全部是甘油(100重量%)。多元醇通常占组合物的1.5-9重量%,优选占洗涤组合物的2-8重量%,最优选占组合物的2-7重量%,包括其中包含的所有范围。多元醇,优选甘油,可以基于组合物的重量,优选以4-9重量%,更优选3-8重量%,甚至更优选4-8重量%,甚至更优选4-7重量%,最优选5-8重量%的量存在,包括其中包含的所有范围。
本发明的组合物将包含40-90重量%的水,更优选45-85重量%的水,最优选50-80重量%的水。这种组合物的pH为5.75-7.25,优选6-7,最优选6.2-6.8。在本发明的另一个实施方案中,组合物的pH为6.25-6.75。
本发明组合物的粘度通常为750-22000mPa.s(cps),优选2000-18000mPa.s(cps),最优选5000-16000mPa.s(cps)。这样的组合物是各向同性的,并且通常是半透明或透明的。如用Aqualab Activity Meter测量的,本发明组合物的水分活度通常低于1,优选0.94-0.99,最优选0.95-0.98。水分活度(Aw)在25℃下测量,优选使用露点湿度计,例如Aqualab Activity Meter。Aw是溶液中水的分蒸气压除以水的标准状态分蒸气压。影响Aw的成分是例如多元醇的含量。
油可任选地用于本发明的组合物中。适用的油包括硅油。硅油可分为挥发性和非挥发性种类。如本文所用,术语“挥发性”是指在环境温度下具有可测量的蒸气压的那些材料。挥发性硅油优选选自含有3-9个,优选4-5个硅原子的环状或直链聚二甲基硅氧烷。可用于本发明的非挥发性硅油包括聚烷基硅氧烷、聚烷基芳基硅氧烷和聚醚硅氧烷共聚物。可用于本文的此类基本上非挥发性的聚烷基硅氧烷包括例如在25℃下粘度为5至100000厘沲的聚二甲基硅氧烷(如二甲硅油)。通常优选的硅酮源是环五硅氧烷和二甲硅油溶液。
可任选用于本发明的具有天然来源的防腐剂的组合物中的合适的酯包括:(1)具有10至20个碳原子的脂肪酸的烯基或烷基酯,如棕榈酸异丙酯、异硬脂酸异丙酯、异壬酸异壬酯、肉豆蔻酸油酯、肉豆蔻酸异丙酯、硬脂酸油酯和油酸油酯;(2)醚-酯,如乙氧基化脂肪醇的脂肪酸酯;(3)多元醇酯,如乙二醇单脂肪酸和二脂肪酸酯、二乙二醇单脂肪酸和二脂肪酸酯、聚乙二醇(200-6000)单脂肪酸和双脂肪酸酯、丙二醇单脂肪酸和二脂肪酸酯、聚丙二醇2000单油酸酯、聚丙二醇2000单硬脂酸酯、乙氧基化丙二醇单硬脂酸酯、甘油单脂肪酸和二脂肪酸酯、聚甘油多脂肪酸酯、乙氧基化甘油单硬脂酸酯、1,3-丁二醇单硬脂酸酯、1,3-丁二醇二硬脂酸酯、聚氧乙烯多元醇脂肪酸酯、山梨醇酐脂肪酸酯和聚氧乙烯山梨醇酐脂肪酸酯;(4)甾醇酯,其示例为大豆甾醇和胆固醇脂肪酸酯。
还可以使用的其他油包括甘油三酯(动物和/或植物),如大豆油(包括氢化大豆油)、葵花籽油、椰子油、棕榈仁油、蓖麻油、菜籽油、棕榈油、葡萄籽油、乳木果油、辛酸/癸酸甘油三酯、红花油、鱼油或其混合物。
甚至其他适用的油包括矿物油、霍霍巴油、异链烷烃、C12-C15烷基苯甲酸酯、聚α烯烃、异十六烷、凡士林、其混合物(包括与上述那些油的混合物)等。大豆油和葵花籽油通常是优选的甘油三酯油。辛酸/癸酸甘油三酯是另一种可任选用于本发明组合物的油。
适用的这些任选的油占组合物重量的0-10%。在本发明的实施方案中,凡士林占组合物重量的0.01-6%,优选0.5-5%,最优选1.0-4.0%,包括其中包含的所有范围。
可以使用适合改变本发明组合物pH的调节剂。这样的pH调节剂包括三乙胺、NaOH、KOH、H2SO4、HCl、C6H8O7(即柠檬酸)或其混合物。pH调节剂的添加量使得组合物的最终pH如本文所定义(例如,5.75至7.25)。
在本发明的实施方案中,除了本文所述的阴离子和两性离子表面活性剂之外,本发明的组合物可包括任选的表面活性剂。当在本发明的组合物中使用此类表面活性剂时,它们通常占组合物的重量的不超过8%。在本发明的实施方案中,当使用这种附加表面活性剂时,它们通常占组合物重量的0.0001-7%,优选0.001-5%。因此,在本发明的组合物中任选地包括常规皂和/或合成洗涤剂也在本发明的范围内。
可以使用的任选的表面活性剂包括烷基磺基琥珀酸盐(包括单烷基和二烷基,例如C6-C22磺基琥珀酸盐);烷基和酰基肌氨酸盐、磺基乙酸盐、C8-C22烷基磷酸盐和膦酸盐、烷基磷酸酯和烷氧基烷基磷酸酯、酰基乳酸酯、C8-C22单烷基琥珀酸酯和马来酸酯、磺基乙酸酯、烷基葡糖苷和酰基羟乙基磺酸盐等。
在本发明的实施方案中,额外的任选的表面活性剂可以包括月桂酰基谷氨酸钠、椰油酰基谷氨酸钠或其混合物。本文所述的此类阴离子表面活性剂可从如GalaxySurfactants、Clariant、Sino Lion和Innospec的供应商处购得。
任选地可用于本发明的组合物中的两性表面活性剂(取决于pH,其可为两性离子的)包括酰基两性乙酸钠、酰基两性丙酸钠、酰基两性二乙酸二钠和酰基两性二丙酸二钠,其中酰基(即链烷酰基)可包含C7-C18烷基部分。适用于任选用途的两性表面活性剂的说明性示例包括月桂酰两性乙酸钠、椰油酰两性乙酸钠、月桂酰两性乙酸钠、椰油酰两性乙酸钠及其混合物。
非离子表面活性剂可任选地用于本发明的组合物中。当使用时,非离子表面活性剂通常以低至0.5重量%、1重量%、1.5重量%或2重量%的水平并且以高至4重量%或6重量%的水平使用。可任选使用的非离子表面活性剂特别包括具有疏水基团和反应性氢原子的化合物(例如脂肪族醇、酸、酰胺或烷基酚)与氧化烯(尤其是单独或与环氧丙烷一起的环氧乙烷)的反应产物。具体的非离子表面活性剂化合物是烷基(C6-C22)酚环氧乙烷缩合物,脂肪族(C8-C18)直链或支链伯醇或仲醇与环氧乙烷的缩合产物及通过环氧乙烷与环氧丙烷和乙二胺的反应产物缩合制备的产物。其他非离子表面活性剂包括长链叔胺氧化物、长链叔膦氧化物、二烷基亚砜等。
在本发明的实施方案中,可任选使用的非离子表面活性剂包括具有以下结构的脂肪酸/醇乙氧基化物:a)HOCH2(CH2)s(CH2CH2O)vH或b)HOOC(CH2)c(CH2CH2O)dH;其中s和v各自独立地为最大18的整数;并且c和d各自独立地为1或更大的整数。在本发明的实施方案中,s和v各自独立地为6至18;c和d各自独立地为1至30。非离子表面活性剂的其他选择包括具有式HOOC(CH2)i-CH=CH--(CH2)k(CH2CH2O)zH的那些,其中i、k各自独立地为5至15;并且z为5至50。在本发明的另一个实施方案中,i和k各自独立地为6至12;并且z为15至35。
任选的非离子表面活性剂还可以包括糖酰胺,如多糖酰胺。具体地,表面活性剂可以是1995年2月14日授予Au等人的题为“Compositions Comprising Nonionic GlycolipidSurfactants”的美国专利5,389,279中所述的乳糖酰胺之一,在此其通过引用并入本文,或者其可以是1991年4月23日授予Kelkenberg的题为“Use of N-Poly Hydroxyalkyl FattyAcid Amides as Thickening Agents for Liquid Aqueous Surfactant Systems”的美国专利5,009,814中所述的糖酰胺之一,在此通过引用并入本申请。
阳离子表面活性剂可任选地用于本发明的组合物中。
适用于任选使用的一类阳离子表面活性剂包括杂环铵盐,例如十六烷基或硬脂基氯化吡啶、烷基酰胺基乙基吡咯啉(pyrrylinodium)甲基硫酸和拉匹氯铵。
四烷基铵盐是适用的另一类有用的任选阳离子表面活性剂。实例包括十六烷基或硬脂基三甲基氯化铵或溴化铵;氢化棕榈或牛脂三甲基卤化铵;山嵛基三甲基铵卤化物或甲基硫酸盐;癸基异壬基二甲基卤化铵;二牛油基(或二硬脂基)二甲基卤化铵,和山嵛基二甲基氯化铵。
可任选使用的其他类型的阳离子表面活性剂是各种乙氧基化季胺和酯季铵盐。示例包括PEG-5硬脂基乳酸铵(例如,由Clariant制造的GenaminKSL)、PEG-2椰油氯化铵、PEG-15氢化牛脂氯化铵、PEG15硬脂基氯化铵、二棕榈酰基乙基甲基氯化铵、二棕榈酰基羟乙基甲基硫酸盐和硬脂基酰胺丙基二甲胺乳酸盐。
适用于任选用途的再其他有用的阳离子表面活性剂包括丝蛋白、小麦蛋白和角蛋白的季铵化水解产物,并且使用上述阳离子表面活性剂的混合物也在本发明的范围内。
与适合使用的其他任选表面活性剂不同,如果使用阳离子表面活性剂,它们将占组合物的重量不超过1.0%。如果存在,它们通常占组合物重量的0.001-0.7%,更通常为0.001-0.5%。
在本发明的实施方案中,仅硫酸盐基的表面活性剂;羟乙基磺酸盐、牛磺酸盐和/或甘氨酸盐;及甜菜碱和/或磺基甜菜碱用于本发明的组合物中。在又一个实施方案中,本发明的组合物中使用的表面活性剂的总量(例如,当使用任选的表面活性剂时)不应超过20重量%。
在本发明的实施方案中,本发明的组合物基本上不含(小于组合物重量的0.12%)聚合季铵化合物(包括其盐)。在另一个实施方案中,本发明的组合物包含小于0.1重量%的聚合季铵化合物。在又一个实施方案中,组合物包含小于0.01重量%的聚合季铵化合物。在甚至另一个实施方案中,组合物不含聚合季铵化合物(即0.0%)。
适用于本发明组合物的任选的皮肤有益剂仅限于它们能够局部施用并适合于在所需pH下溶解于组合物中的程度。
适用于包括在这种组合物的水部分中的有益剂的说明性示例是酸,如氨基酸,如精氨酸,缬氨酸或组氨酸。适用的其他水溶性有益剂包括维生素B2、烟酰胺(维生素B3)、维生素B6、维生素C,它们的混合物等。也可以使用这些维生素的水溶性衍生物。例如,维生素C衍生物如抗坏血酸四异棕榈酸酯、抗坏血酸磷酸镁和抗坏血酸糖苷可单独使用或彼此组合使用。适用的其他水溶性有益剂包括4-乙基间苯二酚,提取物如鼠尾草、芦荟、绿茶、葡萄籽、百里香、甘菊、蓍草、黄瓜、甘草、迷迭香提取物或其混合物。也可以使用水溶性防晒剂如恩索利唑。当存在于本发明的组合物中时,任选的水溶性有益剂(包括混合物)的总量基于组合物的总重量可在0.0重量%至10重量%,优选0.001重量%至8重量%,并且最优选0.01重量%至6重量%的范围内,并且包括其中包含的所有范围。
任选地包括油(即,非水)溶性有益剂也在本发明的范围内。对这类油溶性有益剂的唯一限制是当局部施用时,它们适用于向皮肤提供有益效果。
可任选地用于本发明的最终用途组合物中的油溶性有益剂的类型的说明性示例包括例如硬脂酸、维生素如维生素A、D、E和K(及其油溶性衍生物)、防晒剂如乙基己基甲氧基肉桂酸酯、双-乙基己氧基苯酚甲氧基苯酚三嗪、2-乙基己基-2-氰基-3,3-二苯基-2-丙酸、甲酚曲唑三硅氧烷、3,3,5-三甲基环己基2-羟基苯甲酸酯、2-乙基己基-2-羟基苯甲酸酯或其混合物的组分。
适用的其他任选的油溶性有益剂包括间苯二酚类,如4-己基间苯二酚、4-苯基乙基间苯二酚、4-环戊基间苯二酚、4-环己基间苯二酚、4-异丙基间苯二酚或其混合物。此外,可以使用5-取代的间苯二酚类,如4-环己基-5-甲基苯-1,3-二醇、4-异丙基-5-甲基苯-1,3-二醇、其混合物等。5-取代的间苯二酚及其合成描述于共同转让的美国公开专利申请号2016/0000669A1中。
甚至其他适用的油溶性活性物质包括ω-3脂肪酸、ω-6脂肪酸、氯咪巴唑、法尼醇、乌索酸、肉豆蔻酸、香叶基香叶醇、油烯基甜菜碱、椰油酰基羟乙基咪唑啉、己酰基鞘氨醇、12-羟基硬脂酸、岩芹酸、共轭亚油酸、硬脂酸、棕榈酸、月桂酸、萜品醇、百里酚、其混合物等。
在本发明的实施方案中,使用的任选油溶性有益剂是视黄酸前体。在本发明的一个实施方案中,视黄酸前体是视黄醇、视黄醛、丙酸视黄酯、棕榈酸视黄酯、乙酸视黄酯或其混合物。通常优选丙酸视黄酯、棕榈酸视黄酯及其混合物。另一种适用的视黄酸前体是Molecular design international提供的名称为的市售的对甲氧基苯基氧代乙醇视黄酸酯(hydroxyanasatil retinoate)。其可与本文所述的油溶性活性物质混合使用。
当在本发明组合物的油(包括表面活性剂)相中使用任选的(即,0.0至1.5重量%)油溶性活性物质时,其通常占组合物总重量的0.001至1.3重量%,在另一个实施方案中为0.05至1.0重量%,在又一个实施方案中为0.1至0.5重量%,包括其中包含的所有范围。
虽然不是必需的,但在本发明的组合物中任选地包括传统的防腐剂(除了用于本发明的天然来源的防腐剂之外)以防止潜在有害微生物的生长也在本发明的范围内。化妆品化学家熟悉适当的防腐剂并常规地选择它们以满足防腐剂挑战测试并提供产品稳定性。适用的传统但任选的防腐剂包括乙内酰脲衍生物和丙酸盐。特别优选的防腐剂是碘代丙炔基丁基氨基甲酸酯、苯氧乙醇、1,2-辛二醇、羟基苯乙酮、乙基己基甘油、己二醇、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、咪唑烷基脲、二甲基-二甲基(DMDM)乙内酰脲和苯甲醇及其混合物。其他适用的防腐剂包括氯苯甘醚和癸二醇。防腐剂的选择应考虑组合物的用途和防腐剂与组合物中其他成分之间可能的不相容性。当使用时,这些任选的防腐剂的使用量可以是组合物总重量的0.001%至2%,包括其中包含的所有范围。在本发明的优选实施方案中,仅使用包含苯甲酸和/或其衍生物的天然来源的防腐剂,而没有任何额外的和任选的防腐剂。还应当理解,合成制备的苯甲酸和/或其衍生物适用于本发明,并且在所需的pH值下,含有或不含天然来源的防腐剂。
增稠剂任选地适用于本发明的组合物。特别有用的是多糖。示例包括纤维、淀粉、天然/合成树胶和纤维素类。淀粉的代表是化学改性淀粉,如羟丙基淀粉磷酸钠和辛烯基琥珀酸淀粉铝。木薯淀粉通常是优选的,麦芽糊精也是如此。合适的树胶包括黄原胶、菌核、果胶、刺梧桐树胶、阿拉伯树胶、琼脂、瓜尔胶(包括金合欢(Acacia senegal)胶)、角叉菜胶、藻酸盐及其组合。合适的纤维素类包括羟丙基纤维素、羟丙基甲基纤维素、乙基纤维素、羧甲基纤维素钠(纤维素胶/羧甲基纤维素)和纤维素(例如纤维素微纤丝、纤维素纳米晶体或微晶纤维素)。纤维素微纤丝的来源包括次生细胞壁材料(例如木浆、棉花)、细菌纤维素和初生细胞壁材料。优选地,初生细胞壁材料的来源选自果实、根、球茎、块茎、种子、叶及其组合的薄壁组织;更优选选自柑橘果实、番茄果实、桃果实、南瓜果实、猕猴桃果实、苹果果实、芒果果实、甜菜、甜菜根、芜菁、欧洲防风草、玉蜀黍、燕麦、小麦、豌豆及其组合;甚至更优选选自柑橘水果、番茄水果及其组合。初生细胞壁材料的最优选来源是来自柑橘类水果的薄壁组织。柑桔纤维,如由以AQPlus提供的那些也可用作纤维素微纤丝的来源。纤维素源可以通过任何已知的方法进行表面改性,包括在Colloidal Polymer Science,Kalia等人,“Nanofibrillated cellulose:surface modification and potentialapplications”(2014),Vol 292,5-31页中描述的那些。
合成聚合物是另一类有效的增稠剂。这一类别包括交联聚丙烯酸酯,如卡波姆、丙烯酸酯共聚物、丙烯酸酯/丙烯酸酯(C10-C30)烷醇丙烯酸酯交联聚合物、聚丙烯酰胺如305和牛磺酸共聚物如EG和AVC、按照相应的INCI命名法确定为丙烯酸钠/丙烯酰二甲基牛磺酸钠和丙烯酰二甲基牛磺酸/乙烯基吡咯烷酮共聚物的共聚物。另一种优选的适合于增稠的合成聚合物是由Seppic市售并以名称Simulgel INS100销售的基于丙烯酸酯的聚合物。也可以使用碳酸钙、盐如氯化钠、气相二氧化硅和硅酸镁铝。
当使用时,增稠剂的量可以为组合物重量的0.001-5%。通常,当包括凡士林时,增稠剂为组合物重量的0.8-3.5%,优选1.0-3.0%。
芳香剂、固定剂、螯合剂(如EDTA)、盐(如NaCl)和去角质剂可任选地包括在本发明的组合物中。这些物质中的每一种可以占组合物总重量的约0.03-约5重量%,优选0.1-3重量%,包括其中包含的所有范围。在使用去角质剂的情况下,所选择的那些去角质剂的颗粒大小应足够小,使得它们不妨碍用于分配本发明组合物的任何泵和致动器的性能。
除了前述的多元醇之外,常规的保湿剂可任选地用作本发明中的添加剂,以在局部施用组合物时协助皮肤保湿。这些通常是多羟基醇型物质。典型的多羟基醇包括丙二醇、二丙二醇、聚丙二醇(例如PPG-9)、聚乙二醇、山梨醇、羟丙基山梨醇、己二醇、1,3-丁二醇、异戊二醇、1,2,6-己三醇、乙氧基化甘油、丙氧基化甘油及其混合物。当使用时,保湿剂的用量可以为组合物总重量的0.0-35重量%。通常,保湿剂占组合物总重量的0.0-20重量%,优选0.001-15重量%(最优选2-12重量%)。
另一种适用的任选添加剂包括含有2.5-25重量%大麻萜酚和/或0.5-10重量%大麻二酚的大麻油。当使用时,这样的油占组合物重量的0.0001-12%,优选占组合物重量的0.01-5%,包括其中包含的所有范围。
当制备本发明的组合物时,可以使用常规设备在中等剪切和大气条件下混合期望的成分,其中温度为25至90℃。
本发明组合物的包装仅限于消费者所希望使用的程度,并且适用于承载本发明的最终用途组合物。通常,包装可以是瓶、罐、管或桶。优选地,包装是耐用但轻质的,并且包含至少10重量%或更多的消费后树脂(PCR)以确保其对环境的影响是有限的。在优选的实施方案中,本发明的防腐剂体系是天然的,且包装全部是PCR或可生物降解的。
微生物杀灭方案
用已知浓度的微生物接种组合物样品,使用1重量%的微生物接种。将样品在25℃温育28天,并在7、14和天取样。温育时间过后,将样品置于培养皿中,并在适合测试有机体的和如American Type Culture Collection(ATCC)中确定的常规条件下进一步温育,当标准由范围定义时,选择范围的中点。然后计数微生物菌落数,并将所得数字乘以适当的稀释系数以获得每个样品单位的微生物数,以便评估根除情况。
所提供的实施例是为了便于理解本发明。它们并不旨在限制权利要求的范围。
实施例
这些实施例中的制剂通过在中等剪切下、在大气条件下和在约50℃至75℃的温度下混合成分来制备,除了当添加芳香剂时温度降低至约45℃。所得制剂的pH为6.5,水分活度为约0.96。将制成的各制剂分成5个不同的等分试样并称重。然后将这5个不同的等分试样用如下确定的相应生物体或生物体混合物接种,得到挑战制剂。接种物等于制剂重量的1%,并且在开始时不改变所挑战的制剂的特征。接种后手动彻底混合所有制剂,以使相应的微生物均匀分布。然后将挑战制剂在试验的期间在约25℃下储存。将表面活性剂以所示的量加入到基质碱中。
抗微生物关键词说明
池1:铜绿假单胞菌+洋葱伯克霍尔德菌(革兰氏阴性)
池2:肺炎克雷伯氏菌+日沟维肠杆菌(革兰氏阴性)
3:金黄色葡萄球菌(Staph.aur.)
4:白色念珠菌(酵母)
5:巴西曲霉(霉菌)
完全根除(“CE”)-破坏/杀死所有存在的微生物。
表面活性剂关键词说明
SLES:月桂基醚硫酸钠,1EO
SLS:月桂基硫酸钠
SLI:月桂酰羟乙基磺酸钠
SLMI:月桂酰甲基羟乙基磺酸钠
CAPB:椰油酰胺丙基甜菜碱
牛磺酸盐:甲基月桂酰基牛磺酸钠
然后在7天和14天对挑战制剂针对活微生物进行取样。将这些样品置于培养皿中,并在适合于这些测试生物体的常规条件下温育,如American Type Culture Collection(ATCC)中确定的,当标准由范围定义时,选择范围的中点。孵育后,计数微生物菌落数,所得数字乘以适当的稀释系数以获得每个样品单位的微生物数。
配方基质
成分 | 重量%活性物质 |
水 | 余量 |
增稠剂 | 1.5 |
表面活性剂 | 如所示 |
螯合剂 | 0.1 |
苯甲酸钠 | 0.5 |
芳香剂 | 0.9 |
凡士林 | 2.0 |
硬脂酸 | 0.2 |
甘油 | 7.0 |
氯化钠 | 0.5 |
NaOH | 0.1 |
将根据本发明制备的制剂在45℃下储存3个月。令人惊讶地,在由受过训练的专门小组成员进行视觉评估后,没有制剂显示出任何负面颜色变化(褐变)或相分离,即脱水收缩。
另外,根据本发明制备的制剂出乎意料地显示出抗微生物稳定性,即使当它们在超过皮肤的天然pH的pH下用苯甲酸钠,并用小于8.0重量%的硫酸盐基表面活性剂配制时。因此,本发明产生稳定的制剂,其可以用温和的表面活性剂体系和用可以是天然来源的防腐剂制备。
Claims (15)
1.一种组合物,包含:
(a)防腐剂;
(b)阴离子表面活性剂,其包含:
·烷基硫酸盐、烷基醚硫酸盐或其混合物,以及
·羟乙基磺酸盐、甘氨酸盐、牛磺酸盐或其混合物;
(c)两性离子表面活性剂,其包含甜菜碱、磺基甜菜碱或其混合物;
(d)3至9重量%的多元醇;和
(e)水,
所述组合物具有6至7.25的pH,并且
其中两性离子表面活性剂与阴离子表面活性剂的重量比为1:8至1:2,以及
其中当存在羟乙基磺酸盐时,所述羟乙基磺酸盐为至少50重量%的月桂酰羟乙基磺酸盐,以及
其中所述组合物包含小于8.0重量%的硫酸盐基表面活性剂,
其中所述组合物中的所有防腐剂为苯甲酸钠、苯甲酸钾、氨基苯甲酸盐或其混合物,其中所述氨基苯甲酸盐为对氨基苯甲酸钠或对氨基苯甲酸钾,或其混合物。
2.根据权利要求1所述的组合物,其在25℃下使用露点湿度计测量的水分活度为0.94至0.99,最优选为0.95至0.98。
3.根据权利要求1所述的组合物,其中所述烷基硫酸盐包含月桂基硫酸钠,且所述烷基醚硫酸盐是月桂基醚硫酸钠。
4.根据权利要求1或2所述的组合物,其中所述烷基醚硫酸盐包含具有1、2和3个聚(环氧乙烷)单元的表面活性剂的混合物。
5.根据前述权利要求中任一项所述的组合物,其中所述羟乙基磺酸盐包含月桂酰羟乙基磺酸钠,所述甘氨酸盐包含月桂酰甘氨酸钠,并且所述牛磺酸盐包含甲基月桂基牛磺酸钠。
6.根据前述权利要求中任一项所述的组合物,其中所述两性离子表面活性剂包含甜菜碱,并且所述甜菜碱包含椰油酰胺丙基甜菜碱。
7.根据前述权利要求中任一项所述的组合物,其中作为硫酸盐的所述阴离子表面活性剂占所述组合物重量的4%至7.5%,和作为羟乙基磺酸盐的所述阴离子表面活性剂占所述组合物重量的0.4%至4%,并且进一步地其中作为硫酸盐的所述阴离子表面活性剂为至少35重量%的月桂基醚硫酸钠。
8.根据前述权利要求中任一项所述的组合物,其中两性离子表面活性剂与阴离子表面活性剂的重量比为1:6至1:2,并且所述组合物具有6至7的pH和在25℃下用Brookfield RV5在20rpm下30秒测量的750至22000mPa.s(cps)的粘度。
9.根据前述权利要求中任一项所述的组合物,其中两性离子表面活性剂与阴离子表面活性剂的重量比为1:4至1:3,所述组合物具有6.25至6.75的pH和在25℃下用BrookfieldRV5在20rpm下30秒测量的5000至16000mPa.s(cps)的粘度。
10.根据前述权利要求中任一项所述的组合物,其中所述防腐剂包含合成制备的苯甲酸钠、苯甲酸钾或氨基苯甲酸盐。
11.根据前述权利要求中任一项所述的组合物,其中所述防腐剂包含天然来源的苯甲酸钠、苯甲酸钾或氨基苯甲酸盐。
12.根据前述权利要求中任一项所述的组合物,其中所述多元醇包含甘油。
13.根据前述权利要求中任一项所述的组合物,其中如美国药典通则第51章中所定义,以所述组合物的1重量%接种铜绿假单胞菌+洋葱伯克霍尔德菌或肺炎克雷伯氏菌+日沟维肠杆菌或金黄色葡萄球菌或白色念珠菌或巴西曲霉在25℃下14天后,所述组合物表现出至少2log的抗微生物杀灭。
14.根据前述权利要求中任一项所述的组合物,其中所述组合物还包含0.01至6重量%的凡士林。
15.一种用于美容性处理皮肤的方法,包括以下步骤:
a)用权利要求1所述的组合物接触需要清洗的皮肤;以及
b)用水冲洗掉所述组合物。
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