CN105534724A - Resveratrol-coated nano solid lipid carrier and preparation method thereof - Google Patents
Resveratrol-coated nano solid lipid carrier and preparation method thereof Download PDFInfo
- Publication number
- CN105534724A CN105534724A CN201610034448.4A CN201610034448A CN105534724A CN 105534724 A CN105534724 A CN 105534724A CN 201610034448 A CN201610034448 A CN 201610034448A CN 105534724 A CN105534724 A CN 105534724A
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- Prior art keywords
- resveratrol
- oil
- peg
- solid
- solid lipid
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- 150000002632 lipids Chemical class 0.000 title claims abstract description 119
- 239000007787 solid Substances 0.000 title claims abstract description 117
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 title claims abstract description 96
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 title claims abstract description 96
- 235000021283 resveratrol Nutrition 0.000 title claims abstract description 96
- 229940016667 resveratrol Drugs 0.000 title claims abstract description 96
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 150000003904 phospholipids Chemical class 0.000 claims abstract description 39
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000007788 liquid Substances 0.000 claims abstract description 24
- 239000003755 preservative agent Substances 0.000 claims abstract description 22
- 230000002335 preservative effect Effects 0.000 claims abstract description 18
- 229910017053 inorganic salt Inorganic materials 0.000 claims abstract description 17
- 239000008367 deionised water Substances 0.000 claims abstract description 16
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 16
- 150000005846 sugar alcohols Polymers 0.000 claims abstract description 16
- 239000002245 particle Substances 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims abstract description 9
- 229920005862 polyol Polymers 0.000 claims abstract description 6
- 150000003077 polyols Chemical class 0.000 claims abstract description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 24
- 229930182478 glucoside Natural products 0.000 claims description 24
- 239000002994 raw material Substances 0.000 claims description 21
- -1 PEG-8 distearate Chemical compound 0.000 claims description 19
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 18
- 239000003921 oil Substances 0.000 claims description 18
- 235000019198 oils Nutrition 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 16
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 claims description 14
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 150000008131 glucosides Chemical class 0.000 claims description 14
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 14
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 12
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 12
- 229940083466 soybean lecithin Drugs 0.000 claims description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 10
- 239000004359 castor oil Substances 0.000 claims description 10
- 235000019438 castor oil Nutrition 0.000 claims description 10
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 claims description 10
- 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 10
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 claims description 10
- 229960000541 cetyl alcohol Drugs 0.000 claims description 9
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 9
- 239000011248 coating agent Substances 0.000 claims description 8
- 238000000576 coating method Methods 0.000 claims description 8
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims description 8
- 239000001103 potassium chloride Substances 0.000 claims description 8
- 235000011164 potassium chloride Nutrition 0.000 claims description 8
- SOROIESOUPGGFO-UHFFFAOYSA-N diazolidinylurea Chemical compound OCNC(=O)N(CO)C1N(CO)C(=O)N(CO)C1=O SOROIESOUPGGFO-UHFFFAOYSA-N 0.000 claims description 7
- 229960001083 diazolidinylurea Drugs 0.000 claims description 7
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 7
- GKAVWWCJCPVMNR-UHFFFAOYSA-N tridecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCC GKAVWWCJCPVMNR-UHFFFAOYSA-N 0.000 claims description 7
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 claims description 6
- 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 claims description 6
- FLPJVCMIKUWSDR-UHFFFAOYSA-N 2-(4-formylphenoxy)acetamide Chemical compound NC(=O)COC1=CC=C(C=O)C=C1 FLPJVCMIKUWSDR-UHFFFAOYSA-N 0.000 claims description 6
- WREAKAFXVZGTPL-UHFFFAOYSA-N OCC1(NC(=O)NCNC(=O)NC2(CO)NC(=O)NC2=O)NC(=O)NC1=O.OCC1(NC(=O)NCNC(=O)NC2(CO)NC(=O)NC2=O)NC(=O)NC1=O.C(C(C)O)O Chemical compound OCC1(NC(=O)NCNC(=O)NC2(CO)NC(=O)NC2=O)NC(=O)NC1=O.OCC1(NC(=O)NCNC(=O)NC2(CO)NC(=O)NC2=O)NC(=O)NC1=O.C(C(C)O)O WREAKAFXVZGTPL-UHFFFAOYSA-N 0.000 claims description 6
- 229940074979 cetyl palmitate Drugs 0.000 claims description 6
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosanyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- PXDJXZJSCPSGGI-UHFFFAOYSA-N hexadecanoic acid hexadecyl ester Natural products CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 claims description 6
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 claims description 6
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 6
- 229960002216 methylparaben Drugs 0.000 claims description 6
- 229940078812 myristyl myristate Drugs 0.000 claims description 6
- 150000004671 saturated fatty acids Chemical class 0.000 claims description 6
- 239000011780 sodium chloride Substances 0.000 claims description 6
- DZKXJUASMGQEMA-UHFFFAOYSA-N tetradecyl tetradecanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCC DZKXJUASMGQEMA-UHFFFAOYSA-N 0.000 claims description 6
- HBXWUCXDUUJDRB-UHFFFAOYSA-N 1-octadecoxyoctadecane Chemical class CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCC HBXWUCXDUUJDRB-UHFFFAOYSA-N 0.000 claims description 5
- TXBCBTDQIULDIA-UHFFFAOYSA-N 2-[[3-hydroxy-2,2-bis(hydroxymethyl)propoxy]methyl]-2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(CO)(CO)COCC(CO)(CO)CO TXBCBTDQIULDIA-UHFFFAOYSA-N 0.000 claims description 5
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims description 5
- 235000021357 Behenic acid Nutrition 0.000 claims description 5
- LVDKZNITIUWNER-UHFFFAOYSA-N Bronopol Chemical compound OCC(Br)(CO)[N+]([O-])=O LVDKZNITIUWNER-UHFFFAOYSA-N 0.000 claims description 5
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 5
- 235000018330 Macadamia integrifolia Nutrition 0.000 claims description 5
- 240000000912 Macadamia tetraphylla Species 0.000 claims description 5
- 235000003800 Macadamia tetraphylla Nutrition 0.000 claims description 5
- 235000021314 Palmitic acid Nutrition 0.000 claims description 5
- NKSOSPOXQKNIKJ-CLFAGFIQSA-N Polyoxyethylene dioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCCOC(=O)CCCCCCC\C=C/CCCCCCCC NKSOSPOXQKNIKJ-CLFAGFIQSA-N 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 229940116226 behenic acid Drugs 0.000 claims description 5
- 239000001110 calcium chloride Substances 0.000 claims description 5
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 5
- 229940073669 ceteareth 20 Drugs 0.000 claims description 5
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 claims description 5
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 5
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 5
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 claims description 5
- 239000010466 nut oil Substances 0.000 claims description 5
- 229940032052 peg-8 dioleate Drugs 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 5
- 239000008158 vegetable oil Substances 0.000 claims description 5
- 239000001993 wax Substances 0.000 claims description 5
- 239000010497 wheat germ oil Substances 0.000 claims description 5
- HOVAGTYPODGVJG-UVSYOFPXSA-N (3s,5r)-2-(hydroxymethyl)-6-methoxyoxane-3,4,5-triol Chemical compound COC1OC(CO)[C@@H](O)C(O)[C@H]1O HOVAGTYPODGVJG-UVSYOFPXSA-N 0.000 claims description 4
- BANXPJUEBPWEOT-UHFFFAOYSA-N 2-methyl-Pentadecane Chemical compound CCCCCCCCCCCCCC(C)C BANXPJUEBPWEOT-UHFFFAOYSA-N 0.000 claims description 4
- RHXUZFJBEKLEPQ-UHFFFAOYSA-N 5-bromo-5-nitro-1,3-dioxane propane-1,2-diol Chemical compound CC(O)CO.[O-][N+](=O)C1(Br)COCOC1 RHXUZFJBEKLEPQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 claims description 4
- 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 claims description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
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- 125000005456 glyceride group Chemical group 0.000 claims description 4
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- HOVAGTYPODGVJG-UHFFFAOYSA-N methyl beta-galactoside Natural products COC1OC(CO)C(O)C(O)C1O HOVAGTYPODGVJG-UHFFFAOYSA-N 0.000 claims description 4
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- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 claims description 4
- 150000003431 steroids Chemical class 0.000 claims description 4
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- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 claims description 4
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- DMBUODUULYCPAK-UHFFFAOYSA-N 1,3-bis(docosanoyloxy)propan-2-yl docosanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCCCCCC DMBUODUULYCPAK-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/14—Liposomes; Vesicles
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/55—Phosphorus compounds
- A61K8/553—Phospholipids, e.g. lecithin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
- A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
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- Birds (AREA)
- Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Emergency Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开一种包覆白藜芦醇的纳米固体脂质载体及制备方法,所述包覆白藜芦醇的纳米固体脂质载体按重量百分比计算由0.1~15%白藜芦醇、0.5~5%磷脂、3~30%固态乳化剂、2~15%固体脂质、3~18%液体脂质、5~20%多元醇、0.02~1%无机盐、0.01~0.8%防腐剂和余量去离子水组成。其制备方法,将白藜芦醇、磷脂、固态乳化剂、固体脂质及液态脂质组成的油相熔融并分散均匀,同时将由多元醇、无机盐和去离子水组成的水相加热,搅拌水相,加入油相,混合后超声,再搅拌冷却加入防腐剂,形成包覆白藜芦醇的纳米固体脂质载体。其粒径在50~200nm,可有效的渗透进入角质层。
The invention discloses a nanometer solid lipid carrier coated with resveratrol and a preparation method thereof. The nanometer solid lipid carrier coated with resveratrol consists of 0.1 to 15% resveratrol, 0.5% ~5% phospholipid, 3~30% solid emulsifier, 2~15% solid lipid, 3~18% liquid lipid, 5~20% polyol, 0.02~1% inorganic salt, 0.01~0.8% preservative and The remainder consisted of deionized water. Its preparation method is to melt and disperse the oil phase composed of resveratrol, phospholipid, solid emulsifier, solid lipid and liquid lipid evenly, and simultaneously heat the water phase composed of polyhydric alcohol, inorganic salt and deionized water, and stir The water phase is added to the oil phase, mixed, ultrasonicated, then stirred and cooled, and preservatives are added to form a nano-solid lipid carrier coated with resveratrol. Its particle size is 50-200nm, which can effectively penetrate into the stratum corneum.
Description
技术领域technical field
本发明涉及一种包覆白藜芦醇的纳米固体脂质载体及其制备方法,属于化工领域。The invention relates to a nanometer solid lipid carrier coated with resveratrol and a preparation method thereof, belonging to the field of chemical industry.
背景技术Background technique
天然功效成分白藜芦醇又称芪三酚,为无色针状结晶,难溶于水,易溶于乙醇、丙酮等有机溶剂。其熔点在253~255℃,261℃即升华,其结构式为作为一种非黄酮类多酚化合物,既有植物多酚的一些共性,又具其独特的生物活性,研究发现多酚物质大多具有显著的抗氧化、抗自由基的作用。The natural functional ingredient resveratrol, also known as stilbene triphenol, is a colorless needle-like crystal, insoluble in water, but easily soluble in organic solvents such as ethanol and acetone. Its melting point is 253-255°C, and it sublimates at 261°C. Its structural formula is As a non-flavonoid polyphenol compound, it not only has some common characteristics of plant polyphenols, but also has its unique biological activity. Studies have found that most polyphenols have significant antioxidant and anti-free radical effects.
研究表明,白藜芦醇被应用于化妆品中具有很好的美白祛斑功效。但是白藜芦醇难溶于水,仅易溶于乙醇、丙酮等有机溶剂,丙酮不能直接用于化妆品中,乙醇容易引起皮肤过敏。同时生物相容性差,不易透过皮肤;另一方面,白藜芦醇对光和热不稳定,在避光条件下仅在中性pH环境下稳定。这些因素都限制了白藜芦醇在化妆品中的应用。Studies have shown that resveratrol has good whitening and anti-freckle effects when used in cosmetics. But resveratrol is insoluble in water, only easily soluble in organic solvents such as ethanol, acetone, acetone can not be directly used in cosmetics, ethanol can easily cause skin allergies. At the same time, it has poor biocompatibility and is not easy to penetrate through the skin; on the other hand, resveratrol is unstable to light and heat, and is only stable in a neutral pH environment under dark conditions. These factors limit the application of resveratrol in cosmetics.
纳米固体脂质载体(NLC),是固体油脂在冷却或相分离过程中固化和结晶形成的固体微粒。作为一种新型的载体,纳米固体脂质载体具备生理相容性好、可生物降解、载药能力强、物理化学存储稳定、成本低、利于大规模生产等优点。作用于化妆品中,可以增强活性成分的渗透性、提高闭合作用和水合作用,同时作为包覆载体可以提高活性成分的稳定性。Nano solid lipid carrier (NLC) is a solid particle formed by solidification and crystallization of solid oil during cooling or phase separation. As a new type of carrier, nano-solid lipid carrier has the advantages of good physiological compatibility, biodegradability, strong drug-loading capacity, stable physical and chemical storage, low cost, and large-scale production. Acting in cosmetics, it can enhance the permeability of active ingredients, improve the closure effect and hydration, and at the same time, as a coating carrier, it can improve the stability of active ingredients.
而对于包覆白藜芦醇的纳米固体脂质载体制备研究较多的是高压均质法和普通乳化法。高压均质法的优点是制备的纳米粒粒径小,缺点是操作复杂,容易破坏结构。而普通乳化法操作简单,但制备得到的样品会分散不均一,粒径大,不利于活性成分的渗透。However, the preparation of nano-solid lipid carriers coated with resveratrol is more researched on the high-pressure homogenization method and the common emulsification method. The advantage of the high-pressure homogenization method is that the prepared nanoparticles have a small particle size, but the disadvantage is that the operation is complicated and the structure is easily damaged. The ordinary emulsification method is simple to operate, but the prepared samples will be unevenly dispersed and have large particle sizes, which is not conducive to the penetration of active ingredients.
专利CN102614091A(公布日2012年8月01日),公开的包覆白藜芦醇的纳米结构脂质载体,由于其中的乳化剂主要为吐温、脂肪醇聚氧乙烯醚系列,属于含聚氧乙烯单元的非离子型表面活性剂,这样得到的包覆白藜芦醇的纳米结构脂质载体由于含聚氧乙烯单元的非离子型表面活性剂会将二噁烷带入到化妆品中,进而渗透皮肤而引起不安全性。Patent CN102614091A (published on August 1, 2012), discloses a nanostructured lipid carrier coated with resveratrol. Since the emulsifiers are mainly Tween and fatty alcohol polyoxyethylene ether series, it belongs to polyoxygen-containing The nonionic surfactant of ethylene unit, the nano-structure lipid carrier of coating resveratrol that obtains like this can bring dioxane into cosmetics because of the nonionic surfactant containing polyoxyethylene unit, and then Penetrates the skin and causes unsafe conditions.
进一步,专利CN103040754A(公布日2013年4月17日)公开的包覆白藜芦醇的纳米脂质体,由于制备过程中采用的溶剂为乙醇、甲醇、氯仿、乙醚、石油醚等,因此,该包覆白藜芦醇的纳米脂质体由于体系中还有溶剂,这些溶剂在化妆品中均属于禁用、限用原料,该包覆技术应用于化妆品中也会有一定的不安全性。Further, the nanoliposomes coated with resveratrol disclosed in patent CN103040754A (published on April 17, 2013), since the solvents used in the preparation process are ethanol, methanol, chloroform, ether, petroleum ether, etc., therefore, Since the resveratrol-coated nanoliposomes also contain solvents in the system, these solvents are banned and restricted raw materials in cosmetics, and the application of this coating technology in cosmetics will also be unsafe.
专利CN101874763A(公布日2011年11月03日)主要通过薄膜蒸发法并加入有机溶剂得到白藜芦醇脂质体体系,该技术同样有残留溶剂存在,不可以直接作为化妆品原料包覆载体应用于化妆品产品体系中。Patent CN101874763A (published on November 3, 2011) mainly obtains the resveratrol liposome system by thin film evaporation method and adding organic solvents. This technology also has residual solvents and cannot be directly used as a coating carrier for cosmetic raw materials. In the cosmetic product system.
综上所述,现有技术中的包覆白藜芦醇的纳米结构脂质载体均存在直接应用于化妆品中的安全性问题。而本发明正是为了解决该技术问题而提出的。In summary, the nanostructured lipid carriers coated with resveratrol in the prior art all have safety issues when directly applied to cosmetics. And the present invention just proposes in order to solve this technical problem.
发明内容Contents of the invention
本发明的目的之一是为了解决上述的白藜芦醇不稳定,渗透性差,利用率低等技术问题而提供一种以磷脂作为其中一种脂质原料的包覆白藜芦醇的纳米固体脂质载体,该包覆白藜芦醇的纳米固体脂质载体中,白藜芦醇稳定,渗透性好,同时提高了其利用率。One of the purposes of the present invention is to provide a nano-solid coated resveratrol with phospholipid as one of the lipid raw materials in order to solve the technical problems of above-mentioned resveratrol instability, poor permeability and low utilization rate Lipid carrier, in the nanometer solid lipid carrier coated with resveratrol, resveratrol is stable, has good permeability, and improves its utilization rate at the same time.
本发明的目的之二是提供上述的一种包覆白藜芦醇的纳米固体脂质载体的制备方法。The second object of the present invention is to provide a method for preparing the above-mentioned nano solid lipid carrier coated with resveratrol.
本发明的技术方案Technical scheme of the present invention
一种包覆白藜芦醇的纳米固体脂质载体,其粒径在50~200nm,按重量百分比计算,其原料组成及含量如下:A nanometer solid lipid carrier coated with resveratrol, the particle size is 50-200nm, calculated by weight percentage, its raw material composition and content are as follows:
余量为去离子水;The balance is deionized water;
其中,所述的磷脂为磷脂酰胆碱(以下简称PC)含量为50%~95%的大豆卵磷脂、蛋黄卵磷脂及氢化卵磷脂中的一种或两种以上的组合;优选为磷脂酰胆碱含量为50%-90%的大豆卵磷脂、磷脂酰胆碱含量为70%的蛋黄卵磷脂或磷脂酰胆碱含量为95%的氢化卵磷脂;Wherein, the phospholipid is one or a combination of two or more of soybean lecithin, egg yolk lecithin, and hydrogenated lecithin with a phosphatidylcholine (hereinafter referred to as PC) content of 50% to 95%; preferably phosphatidylcholine Soybean lecithin with a choline content of 50%-90%, egg yolk lecithin with a phosphatidylcholine content of 70%, or hydrogenated lecithin with a phosphatidylcholine content of 95%;
所述的固态乳化剂为鲸蜡硬脂醇聚醚类、PEG酯类、葡糖苷类、聚甘油-3甲基葡糖二硬脂酸酯、硬酯酰谷氨酸钠、双子星乳化剂或聚甘油-6双硬脂酸酯;Described solid emulsifier is cetearethers, PEG esters, glucosides, polyglycerol-3 methylglucose distearate, sodium stearyl glutamate, Gemini star emulsifier or polyglyceryl-6 distearate;
其中硬脂醇聚醚类为鲸蜡硬脂醇聚醚-25、鲸蜡硬脂醇聚醚-6、鲸蜡硬脂醇聚醚-12、鲸蜡硬脂醇聚醚-20、鲸蜡硬脂醇聚醚-30、硬脂醇聚醚-2、硬脂醇聚醚-21或三鲸蜡硬酯醇醚-4磷酸;Wherein the stearyl ethers are ceteareth-25, ceteareth-6, ceteareth-12, ceteareth-20, ceteareth Steareth-30, Steareth-2, Steareth-21, or Ciceteareth-4 phosphoric acid;
PEG酯类为PEG-20三山嵛酸甘油酯、PEG-8双油酸酯、PEG-8双硬脂酸酯、PEG-4月桂酸酯、PEG-8油酸酯、PEG-8硬脂酸酯、PEG-8蜂蜡、PEG-20硬脂酸酯、PEG-32硬脂酸酯、PEG-40氢化蓖麻油、PEG-20十八醇醚、PEG-15十六十八醇醚、PEG-2十六醇醚、PEG-10十六醇醚或PEG-4月桂酸酯;PEG esters are PEG-20 glyceryl tribehenate, PEG-8 dioleate, PEG-8 distearate, PEG-4 laurate, PEG-8 oleate, PEG-8 stearate Esters, PEG-8 beeswax, PEG-20 stearate, PEG-32 stearate, PEG-40 hydrogenated castor oil, PEG-20 stearyl ether, PEG-15 cetostearyl ether, PEG- 2 cetyl alcohol ether, PEG-10 cetyl alcohol ether or PEG-4 laurate;
葡糖苷类为鲸蜡硬脂基葡糖苷、羟基硬脂醇与羟基硬脂糖苷、蔗糖酯、花生醇葡糖苷、山嵛醇葡糖苷、鲸蜡硬脂基葡糖苷、鲸蜡硬脂醇葡糖苷、椰油基葡糖苷、PEG-20甲基葡萄糖苷倍半硬脂酸酯或甲基葡萄糖苷倍半硬脂酸酯;Glucosides are Cetearyl Glucoside, Hydroxystearyl Alcohol and Hydroxystearyl Glucoside, Sucrose Esters, Arachidyl Alcohol Glucoside, Behenyl Alcohol Glucoside, Cetearyl Glucoside, Cetearyl Alcohol Glucoside Glucoside, coco glucoside, PEG-20 methyl glucoside sesquistearate or methyl glucoside sesquistearate;
所述的固体脂质为饱和脂肪酸类、类固醇类、甘油酯类、蜡质类、醇类、氢化蓖麻油、鲸蜡硬酯醇、硬酯醇或季戊四醇二硬脂酸酯;The solid lipids are saturated fatty acids, steroids, glycerides, waxes, alcohols, hydrogenated castor oil, cetearyl alcohol, stearyl alcohol or pentaerythritol distearate;
其中饱和脂肪酸类为硬脂酸、棕榈酸、癸酸或二十二酸;Wherein the saturated fatty acid is stearic acid, palmitic acid, capric acid or behenic acid;
类固醇类为胆固醇;Steroids are cholesterol;
甘油酯类为硬脂酸甘油酯、鲸蜡硬酯醇辛酸酯、单硬脂酸甘油酯、棕榈酸鲸蜡酯、三硬脂酸甘油酯或三月桂酸甘油酯;The glyceryl esters are glyceryl stearate, cetearyl caprylate, glyceryl monostearate, cetyl palmitate, glyceryl tristearate or glyceryl trilaurate;
蜡质类为季戊四醇四山俞酸酯、季戊四醇四辛酸/癸酸酯、季戊四醇四油酸酯、季戊四醇四硬脂酸酯、肉豆蔻酸十四烷酯、乳酸鲸蜡酯、蓖麻油酸鲸蜡酯、肉豆蔻酸肉豆蔻酯、棕榈酸十六酯、十八酸十八酯、鲸蜡醇棕榈酸酯或二季戊四醇六辛酸/癸酸酯;Waxes are pentaerythritol tetrabehenate, pentaerythritol tetracaprylate/caprate, pentaerythritol tetraoleate, pentaerythritol tetrastearate, myristyl myristate, cetyl lactate, cetyl ricinoleate esters, myristyl myristate, cetyl palmitate, stearyl stearyl, cetyl palmitate or dipentaerythritol hexacaprylic/capric acid;
醇类为十六醇、十八醇、二十二碳醇或十六十八醇;The alcohols are cetyl alcohol, stearyl alcohol, behenyl alcohol or cetostearyl alcohol;
所述的液体脂质为植物油脂、矿物油脂及合成油脂的一种或两种以上的组合;The liquid lipid is one or a combination of two or more of vegetable oil, mineral oil and synthetic oil;
其中植物油脂为霍霍巴油、澳洲坚果油、橄榄油、甜杏仁油、葡萄籽油、鳄梨油、米糠油、红花油、椰子油、蓖麻油、向日葵仔油、小麦胚芽油或薰衣草油等;The vegetable oil is jojoba oil, macadamia nut oil, olive oil, sweet almond oil, grapeseed oil, avocado oil, rice bran oil, safflower oil, coconut oil, castor oil, sunflower seed oil, wheat germ oil or lavender oil Wait;
矿物油脂为白油;Mineral grease is white oil;
合成油脂为肉豆蔻酸异丙酯、异硬脂酸异丙酯、硬酯酸十三酯、硬脂酸甘油酯、异壬酸异壬酯、异构十六烷烃、棕榈酸异辛酯、棕榈酸异丙酯、辛酸/癸酸三甘油酯、肉豆蔻酸肉豆蔻酯、角鲨烷、油酸乙酯、硬脂酸十三酯或异硬脂酸异辛酯;Synthetic oils are isopropyl myristate, isopropyl isostearate, tridecyl stearate, glyceryl stearate, isononyl isononanoate, iso-hexadecane, isooctyl palmitate, Isopropyl palmitate, caprylic/capric triglycerides, myristyl myristate, squalane, ethyl oleate, tridecyl stearate or isooctyl isostearate;
所述的多元醇为甘油、山梨醇、丙二醇及1,3丁二醇中的一种或两种以上的组合;The polyhydric alcohol is one or a combination of two or more of glycerin, sorbitol, propylene glycol and 1,3-butanediol;
所述的无机盐为氯化钠、氯化钾或氯化钙中的一种或两种以上组成的混合物;The inorganic salt is one or a mixture of two or more of sodium chloride, potassium chloride or calcium chloride;
所述的防腐剂为苯甲酸类、山梨酸类、尼泊金酯类、杰马类、卡松类、二羟甲基海因、1,2-苯并异噻唑啉-3-酮、苯甲酸甲酯、甲基异噻唑啉酮、三氯对称二苯脲、2-溴-2-硝基-1.3-丙二醇(布罗波尔)、甘油单月桂酸酯、重氮烷基脲、丙二醇-5-溴-5硝基-1,3-二惡烷、脱氢醋酸、丙二醇-5-溴-5硝基-1,3-二惡烷、丙二醇-双咪唑烷基脲、双咪唑烷基脲/羟苯甲酯/丙二醇、碘代丙炔基丁基甲氨酸酯中的一种或两种以上的组合;The preservatives are benzoic acids, sorbic acids, paraben esters, genmas, carsons, dimethylol hydantoin, 1,2-benzisothiazolin-3-one, benzoic acid Methyl formate, methylisothiazolinone, trichlorodiphenyl urea, 2-bromo-2-nitro-1.3-propanediol (Bropol), glyceryl monolaurate, diazolidinyl urea, propylene glycol -5-Bromo-5-nitro-1,3-dioxane, dehydroacetic acid, propylene glycol-5-bromo-5-nitro-1,3-dioxane, propylene glycol-bis-imidazolidinyl urea, bis-imidazolidine One or a combination of two or more of urea/methylparaben/propylene glycol, iodopropynyl butyl carbamate;
所述的尼泊金酯类优选为尼泊金甲酯;Described parabens are preferably methyl parabens;
杰马类为咪唑烷基脲、双咪唑烷基脲。Gemmas are imidazolidinyl urea and bis-imidazolidinyl urea.
上述的一种包覆白藜芦醇的纳米固体脂质载体的制备方法,包括如下步骤:The above-mentioned preparation method of a nano-solid lipid carrier coated with resveratrol comprises the following steps:
(1)、将磷脂、白藜芦醇、固体脂质、液体脂质、固态乳化剂加入到容器中,控制温度为85~100℃下熔融,并分散均匀,得到油相;(1) Add phospholipids, resveratrol, solid lipids, liquid lipids, and solid emulsifiers into the container, control the temperature to melt at 85-100°C, and disperse evenly to obtain an oil phase;
(2)、将多元醇、无机盐和去离子水加入到另一容器中,加热到85~100℃,以800rpm速率均质,得到水相;(2) Add polyols, inorganic salts and deionized water into another container, heat to 85-100°C, and homogenize at 800rpm to obtain a water phase;
(3)、将步骤(1)所得的油相加入到步骤(2)均质的水相中,继续以800rpm的速率均质3~6min,得到乳化体系;(3) Add the oil phase obtained in step (1) into the homogeneous water phase in step (2), and continue homogenizing at a rate of 800 rpm for 3 to 6 minutes to obtain an emulsified system;
(4)、将步骤(3)所得乳化体系以80~800W的功率超声4~20min,然后以200~800r/min的速度边搅拌边冷却,温度降至40~60℃时,加入防腐剂并搅拌均匀,随后冷却到室温,即得包覆白藜芦醇的纳米固体脂质载体。(4) Ultrasonicate the emulsified system obtained in step (3) for 4-20min with a power of 80-800W, then cool while stirring at a speed of 200-800r/min, when the temperature drops to 40-60°C, add a preservative and Stir evenly, and then cool to room temperature to obtain a nanometer solid lipid carrier coated with resveratrol.
本发明的有益效果:Beneficial effects of the present invention:
本发明的一种包覆白藜芦醇的纳米固体脂质载体,由于白藜芦醇被包覆于纳米固体脂质载体结构中,避免了光线的直接照射,因此提高了白藜芦醇的稳定性;A kind of nano-solid lipid carrier coated with resveratrol of the present invention, because resveratrol is coated in the nano-solid lipid carrier structure, has avoided the direct irradiation of light, therefore has improved the resveratrol stability;
进一步,本发明的一种包覆白藜芦醇的纳米固体脂质载体,由于在该纳米固体脂质载体结构中含有磷脂,磷脂结构与皮肤脂质结构的相似性,提高了包覆白藜芦醇纳米固体脂质载体结构在皮肤上的粘附性,因此,促进了白藜芦醇的渗透性;Further, a kind of nano-solid lipid carrier coated resveratrol of the present invention, owing to contain phospholipid in this nano-solid lipid carrier structure, the similarity of phospholipid structure and skin lipid structure has improved coating resveratrol Adhesion of the resveratrol nano-solid lipid carrier structure on the skin, thus, promoting the permeability of resveratrol;
进一步,由于白藜芦醇被包覆于纳米固体脂质载体结构中,形成水悬浮液,有利于分散在水介质中,白藜芦醇以分子结构存在于载体结构中;同时载体结构促进了活性成分的渗透,因此白藜芦醇利用率高。Further, because resveratrol is coated in the nano-solid lipid carrier structure to form an aqueous suspension, it is beneficial to disperse in the aqueous medium, and resveratrol exists in the carrier structure with molecular structure; at the same time, the carrier structure promotes Penetration of active ingredients and therefore high availability of resveratrol.
进一步,本发明的一种包覆白藜芦醇的纳米固体脂质载体,由于采用了脂质体主原料磷脂应用于固体脂质载体结构中,在固体脂质载体结构优势的基础上,增加了脂质体与皮肤良好亲和性的特点,并避免了脂质体与固体脂质载体单一结构的缺点,如脂质体结构极易受到表面活性剂的破坏,以及固体脂质微粒载体因与皮肤亲和性不够等方面的不足,结合本发明的包覆白藜芦醇的纳米固体脂质载体的制备方法,可以有效控制包覆白藜芦醇的纳米固体脂质体的粒径在50~200nm,以更有利于其粘附于角质层,促进了活性成分白藜芦醇在角质层上的渗透,从而提高了白藜芦醇的利用率。Further, a kind of nano-solid lipid carrier coated with resveratrol of the present invention, owing to adopted liposome main raw material phospholipid to be applied in solid lipid carrier structure, on the basis of solid lipid carrier structure advantage, increase It not only improves the characteristics of good affinity between liposome and skin, but also avoids the disadvantages of single structure of liposome and solid lipid carrier, such as liposome structure is easily damaged by surfactant, and solid lipid particle carrier is With the deficiencies in aspects such as insufficient skin affinity, in combination with the preparation method of the nano-solid lipid carrier coated with resveratrol of the present invention, the particle diameter of the nano-solid liposome coated with resveratrol can be effectively controlled. 50-200nm, which is more conducive to its adhesion to the stratum corneum, and promotes the penetration of the active ingredient resveratrol on the stratum corneum, thereby improving the utilization rate of resveratrol.
附图说明Description of drawings
图1、实施例6所得的包覆白藜芦醇的纳米固体脂质载体的扫描电镜图。Fig. 1, the scanning electron micrograph of the nano-solid lipid carrier coated with resveratrol obtained in Example 6.
具体实施方式detailed description
下面结合具体实例对本发明做进一步描述,但本发明的保护范围并不仅限于此。The present invention will be further described below in conjunction with specific examples, but the protection scope of the present invention is not limited thereto.
本发明的各实施例中所用的原料,如固体脂质、液体脂质、白藜芦醇、磷脂、固态乳化剂及多元醇、无机盐等,除特殊说明的外,均为化妆品中常用原料,为市售。The raw materials used in each embodiment of the present invention, such as solid lipids, liquid lipids, resveratrol, phospholipids, solid emulsifiers, polyols, inorganic salts, etc., are common raw materials in cosmetics unless otherwise specified. , is commercially available.
本发明的实施例3所得的含磷脂的包覆白藜芦醇的纳米固体脂质载体与实施例3的对照实施例所得的不含磷脂的包覆白藜芦醇的纳米固体脂质载体进行白藜芦醇渗透性数据。The nano-solid lipid carrier coated with resveratrol containing phospholipid obtained in Example 3 of the present invention is carried out with the obtained nano-solid lipid carrier coated resveratrol without phospholipid obtained in the comparative example of embodiment 3 Resveratrol permeability data.
测定方法如下:The determination method is as follows:
1、所用仪器:Agilent1260高效液相色谱仪,HS-02水平透皮扩散渗透仪。1. Instruments used: Agilent1260 high performance liquid chromatography, HS-02 horizontal transdermal diffusion and penetration instrument.
2、操作步骤:2. Operation steps:
(1)配置接收液:40%的PBS缓冲溶液+60%的无水乙醇。(1) Prepare receiving solution: 40% PBS buffer solution + 60% absolute ethanol.
(2)体外透皮扩散实验(2) In vitro transdermal diffusion test
①用2mL的移液管移取2mL待测实施例3所得的含磷脂的包覆白藜芦醇的纳米固体脂质载体于10mL容量瓶中,用去离子水定容至10mL,摇晃均匀,即将原样品稀释为0.8%白藜芦醇的纳米脂质载体,备用液1;同时移取2mL实施例 3的对照实施例所得的不含磷脂的包覆白藜芦醇的纳米固体脂质载体,做同样处理,用去离子水定容至10mL,摇匀,备用液2;①Use a 2mL pipette to pipette 2mL of the phospholipid-containing resveratrol-coated nano-solid lipid carrier obtained in Example 3 to be tested into a 10mL volumetric flask, dilute to 10mL with deionized water, shake evenly, Dilute the original sample to 0.8% resveratrol nano-lipid carrier, stock solution 1; simultaneously pipette 2mL of the obtained phospholipid-free nano-solid lipid carrier coated with resveratrol in the comparative example of Example 3 , do the same treatment, dilute to 10mL with deionized water, shake well, spare solution 2;
②在接收池内装入搅拌子,并装满接收液,将人造皮肤固定在扩散池的供给池和接收池之间(亮面朝供给池,暗面朝接收池),使皮肤浸入到溶液中;②Put a stirrer in the receiving tank and fill it with receiving solution, fix the artificial skin between the supply tank and the receiving tank of the diffusion tank (the bright side faces the supply tank, and the dark side faces the receiving tank), so that the skin is immersed in the solution;
③在供给池中装满(1)中的备用液1作为供给液,同时在另一个供给池中装满备用液2,作为供给液,同时对比两个样品的渗透性;③ Fill the supply tank with the reserve solution 1 in (1) as the supply solution, and fill the other supply tank with the reserve solution 2 as the supply solution, and compare the permeability of the two samples at the same time;
④保持循环水的温度为37℃,在一定的转速下,分别在1h、2h、4h、6h、8h、10h、12h、24h、36h时用1mL医用无菌注射器抽取1mL接收液,同时补充同体积新鲜接收液。样品经过0.22μm过滤膜过滤后,用高效液相测滤液中白藜芦醇的浓度。④Keep the temperature of the circulating water at 37°C, draw 1mL of the receiving solution with a 1mL medical sterile syringe at a certain speed at 1h, 2h, 4h, 6h, 8h, 10h, 12h, 24h, and 36h, and replenish the same volume of fresh receiver solution. After the sample was filtered through a 0.22 μm filter membrane, the concentration of resveratrol in the filtrate was measured by high performance liquid chromatography.
实验结果:Experimental results:
其中Cn:第n次取样时接收液中药物浓度,μg/mL;Where C n : drug concentration in the receiving solution at the nth sampling, μg/mL;
V:接收室中接收液体积,7mL;V: the volume of receiving liquid in the receiving chamber, 7mL;
Ci:第i次取样时接收液中药物浓度,μg/mL;C i : drug concentration in the receiving solution at the i-th sampling, μg/mL;
1.0:每次取样体积,mL;1.0: Each sampling volume, mL;
S:有效渗透面积,1cm2;S: effective permeable area, 1cm 2 ;
Q:渗透率,μg/cm2。Q: Permeability, μg/cm 2 .
实施例1Example 1
一种包覆白藜芦醇的纳米固体脂质载体,按100g的总量计算,其原料组成及含量如下:A nano-solid lipid carrier coated with resveratrol, calculated according to the total amount of 100g, its raw material composition and content are as follows:
余量为去离子水;The balance is deionized water;
所述的磷脂为PC含量为50%的大豆卵磷脂,北京美亚斯磷脂技术有限公司生产的食品级产品;The phospholipid is soybean lecithin with a PC content of 50%, a food-grade product produced by Beijing Meas Phospholipid Technology Co., Ltd.;
所述的固态乳化剂为鲸蜡硬脂醇聚醚-20;Described solid emulsifier is ceteareth-20;
所述的固体脂质为单硬脂酸甘油酯;Described solid lipid is glyceryl monostearate;
所述的液体脂质为澳洲坚果油;The liquid lipid is macadamia nut oil;
所述的多元醇为丙二醇;Described polyhydric alcohol is propylene glycol;
所述的无机盐为氯化钾;Described inorganic salt is potassium chloride;
所述的防腐剂为重氮烷基脲。The preservative is diazolidinyl urea.
上述包覆白藜芦醇的纳米固体脂质载体,其特征在于具体包括如下步骤:The nano-solid lipid carrier coated with resveratrol is characterized in that it specifically includes the following steps:
(1)、将磷脂、白藜芦醇、固体脂质、液体脂质、固态乳化剂加入到容器中,控制温度为85~100℃下熔融,并分散均匀,得到油相;(1) Add phospholipids, resveratrol, solid lipids, liquid lipids, and solid emulsifiers into the container, control the temperature to melt at 85-100°C, and disperse evenly to obtain an oil phase;
(2)、将多元醇、无机盐和去离子水加入到另一容器中,加热到85~100℃,以800rpm速率均质,得到水相;(2) Add polyols, inorganic salts and deionized water into another container, heat to 85-100°C, and homogenize at 800rpm to obtain a water phase;
(3)、将步骤(1)所得的油相加入到步骤(2)均质的水相中,继续以800rpm的速率均质3~6min,得到乳化体系;(3) Add the oil phase obtained in step (1) into the homogeneous water phase in step (2), and continue homogenizing at a rate of 800 rpm for 3 to 6 minutes to obtain an emulsified system;
(4)、将步骤(3)所得乳化体系以80~800W的功率超声4~20min,然后以200~800r/min的速度边搅拌边冷却,温度降至40~60℃时,加入防腐剂并搅拌均匀,随后冷却到室温,即得包覆白藜芦醇的纳米固体脂质载体。(4) Ultrasonicate the emulsified system obtained in step (3) for 4-20min with a power of 80-800W, then cool while stirring at a speed of 200-800r/min, when the temperature drops to 40-60°C, add a preservative and Stir evenly, and then cool to room temperature to obtain a nanometer solid lipid carrier coated with resveratrol.
实施例2Example 2
一种包覆白藜芦醇的纳米固体脂质载体,按100g的总量计算,其原料组成及含量如下:A nano-solid lipid carrier coated with resveratrol, calculated according to the total amount of 100g, its raw material composition and content are as follows:
余量为去离子水;The balance is deionized water;
所述的磷脂为PC含量为70%的蛋黄卵磷脂,北京美亚斯磷脂技术有限公司生产的食品级产品;The phospholipid is egg yolk lecithin with a PC content of 70%, a food-grade product produced by Beijing Meas Phospholipid Technology Co., Ltd.;
所述的固态乳化剂为PEG-8双油酸酯;Described solid emulsifier is PEG-8 dioleate;
所述的固体脂质为十六醇;The solid lipid is cetyl alcohol;
所述的液体脂质为硬酯酸十三酯;Described liquid lipid is tridecyl stearate;
所述的多元醇为甘油;Described polyhydric alcohol is glycerol;
所述的无机盐为氯化钠;Described inorganic salt is sodium chloride;
所述的防腐剂为尼泊金甲酯。Described preservative is methylparaben.
上述包覆白藜芦醇的纳米固体脂质载体的制备方法,同实施例1。The preparation method of the nano-solid lipid carrier coated with resveratrol is the same as that in Example 1.
实施例3Example 3
一种包覆白藜芦醇的纳米固体脂质载体,即含磷脂的包覆白藜芦醇的纳米固体脂质载体,按100g的总量计算,其原料组成及含量如下:A nano-solid lipid carrier coated with resveratrol, that is, a nano-solid lipid carrier coated with resveratrol containing phospholipids, calculated according to the total amount of 100g, its raw material composition and content are as follows:
余量为去离子水;The balance is deionized water;
所述的磷脂为PC含量为70%的大豆卵磷脂,山西森弗天然制品有限公司生产的食品级产品;The phospholipid is soybean lecithin with a PC content of 70%, a food-grade product produced by Shanxi Senfu Natural Products Co., Ltd.;
所述的固态乳化剂为鲸蜡硬脂基葡糖苷;Described solid emulsifier is cetearyl glucoside;
所述的固体脂质为氢化蓖麻油;Described solid lipid is hydrogenated castor oil;
所述的液体脂质为棕榈酸异丙酯;Described liquid lipid is isopropyl palmitate;
所述的多元醇为1,3-丁二醇;Described polyhydric alcohol is 1,3-butanediol;
所述的无机盐为氯化钙;Described inorganic salt is calcium chloride;
所述的防腐剂为丙二醇-双咪唑烷基脲。The preservative is propylene glycol-bis-imidazolidinyl urea.
上述包覆白藜芦醇的纳米固体脂质载体,即含磷脂的包覆白藜芦醇的纳米固体脂质载体的制备方法,同实施例1。The preparation method of the resveratrol-coated nano-solid lipid carrier, that is, the phospholipid-coated resveratrol-coated nano-solid lipid carrier is the same as in Example 1.
实施例3的对照实施例Comparative example of embodiment 3
一种包覆白藜芦醇的纳米固体脂质载体,按100g的总量计算,其原料组成及含量如下:A nano-solid lipid carrier coated with resveratrol, calculated according to the total amount of 100g, its raw material composition and content are as follows:
余量为去离子水;The balance is deionized water;
所述的固态乳化剂为鲸蜡硬脂基葡糖苷;Described solid emulsifier is cetearyl glucoside;
所述的固体脂质为氢化蓖麻油;Described solid lipid is hydrogenated castor oil;
所述的液体脂质为棕榈酸异丙酯;Described liquid lipid is isopropyl palmitate;
所述的多元醇为1,3-丁二醇;Described polyhydric alcohol is 1,3-butanediol;
所述的无机盐为氯化钙;Described inorganic salt is calcium chloride;
所述的防腐剂为丙二醇-双咪唑烷基脲。The preservative is propylene glycol-bis-imidazolidinyl urea.
上述包覆白藜芦醇的纳米固体脂质载体,具体包括如下步骤:The nano-solid lipid carrier coated with resveratrol specifically includes the following steps:
(1)、将白藜芦醇、固体脂质、液体脂质、固态乳化剂加入到容器中,控制温度为85~100℃下熔融,并分散均匀,得到油相;(1) Add resveratrol, solid lipid, liquid lipid, and solid emulsifier into the container, control the temperature to melt at 85-100°C, and disperse evenly to obtain an oil phase;
(2)、将多元醇、无机盐和去离子水加入到另一容器中,加热到85~100℃,以800rpm速率均质,得到水相;(2) Add polyols, inorganic salts and deionized water into another container, heat to 85-100°C, and homogenize at 800rpm to obtain a water phase;
(3)、将步骤(1)所得的油相加入到步骤(2)均质的水相中,继续以800rpm的速率均质3~6min,得到乳化体系;(3) Add the oil phase obtained in step (1) into the homogeneous water phase in step (2), and continue homogenizing at a rate of 800 rpm for 3 to 6 minutes to obtain an emulsified system;
(4)、将步骤(3)所得乳化体系以80~800W的功率超声4~20min,然后以200~800r/min的速度边搅拌边冷却,温度降至40~60℃时,加入防腐剂并搅拌均匀,随后冷却到室温,即得不含磷脂的包覆白藜芦醇的纳米固体脂质载体。(4) Ultrasonicate the emulsified system obtained in step (3) for 4-20min with a power of 80-800W, then cool while stirring at a speed of 200-800r/min, when the temperature drops to 40-60°C, add a preservative and Stir evenly, and then cool to room temperature to obtain a resveratrol-coated nanometer solid lipid carrier without phospholipids.
对上述实施例3所得的含磷脂的包覆白藜芦醇的纳米固体脂质载体与实施例3的对照实施例所得的不含磷脂的包覆白藜芦醇的纳米固体脂质载体中进行白藜芦醇渗透性数据测定,结果见下表:In the nano-solid lipid carrier of the coated resveratrol containing phospholipid obtained in the above-mentioned embodiment 3 and the obtained nano-solid lipid carrier of the coated resveratrol not containing phospholipid obtained in the comparative example of embodiment 3 Resveratrol permeability data determination, the results are shown in the following table:
从上表中可以看出实施例3所得的含磷脂的包覆白藜芦醇的纳米固体脂质载体结构中包覆的白藜芦醇在人造皮肤上的粘附量大于实施例3的对照实施例中所得的不含磷脂的固体脂质载体结构中包覆的白藜芦醇的粘附量,高的粘附量有利于促进白藜芦醇渗透于角质层中,由此表明了含磷脂的固体脂质载体结构中包覆的白藜芦醇更有利于在皮肤上的渗透。It can be seen from the above table that the adhesion amount of the resveratrol coated in the phospholipid-containing nano-solid lipid carrier structure coated with resveratrol obtained in Example 3 on the artificial skin is greater than that of the comparison of Example 3 The adhesion amount of resveratrol coated in the solid lipid carrier structure without phospholipid obtained in the embodiment, the high adhesion amount is conducive to promoting the penetration of resveratrol in the stratum corneum, thus indicating that the content of The resveratrol encapsulated in the solid lipid carrier structure of phospholipids is more conducive to the penetration on the skin.
实施例4Example 4
一种包覆白藜芦醇的纳米固体脂质载体,按100g的总量计算,其原料组成及含量如下:A nano-solid lipid carrier coated with resveratrol, calculated according to the total amount of 100g, its raw material composition and content are as follows:
余量为去离子水;The balance is deionized water;
所述的磷脂为PC含量为80%的大豆卵磷脂,山西森弗天然制品有限公司生产的食品级产品;The phospholipid is soybean lecithin with a PC content of 80%, a food-grade product produced by Shanxi Senfu Natural Products Co., Ltd.;
所述的固态乳化剂为聚甘油-6双硬脂酸酯;Described solid emulsifier is polyglyceryl-6 distearate;
所述的固体脂质为二十二酸;The solid lipid is behenic acid;
所述的液体脂质为小麦胚芽油;Described liquid lipid is wheat germ oil;
所述的多元醇为丙二醇;Described polyhydric alcohol is propylene glycol;
所述的无机盐为氯化钾;Described inorganic salt is potassium chloride;
所述的防腐剂为2-溴-2-硝基-1.3-丙二醇。The preservative is 2-bromo-2-nitro-1.3-propanediol.
上述的包覆白藜芦醇的纳米固体脂质载体的制备方法,同实施例1。The preparation method of the above-mentioned nano-solid lipid carrier coated with resveratrol is the same as that in Example 1.
实施例5Example 5
一种包覆白藜芦醇的纳米固体脂质载体,按100g的总量计算,其原料组成及含量如下:A nano-solid lipid carrier coated with resveratrol, calculated according to the total amount of 100g, its raw material composition and content are as follows:
余量为去离子水The balance is deionized water
所述的磷脂为PC含量为90%的大豆卵磷脂,山西森弗天然制品有限公司生产的医药级产品;The phospholipid is soybean lecithin with a PC content of 90%, a pharmaceutical grade product produced by Shanxi Senfu Natural Products Co., Ltd.;
所述的固态乳化剂为蔗糖酯;Described solid emulsifier is sucrose ester;
所述的固体脂质为棕榈酸;The solid lipid is palmitic acid;
所述的液体脂质为肉豆蔻酸异丙酯;Described liquid lipid is isopropyl myristate;
所述的多元醇为山梨醇;Described polyhydric alcohol is sorbitol;
所述的无机盐为氯化钾;Described inorganic salt is potassium chloride;
所述的防腐剂为尼泊金甲酯。Described preservative is methylparaben.
上述的包覆白藜芦醇的纳米固体脂质载体的制备方法,同实施例1。The preparation method of the above-mentioned nano-solid lipid carrier coated with resveratrol is the same as that in Example 1.
实施例6Example 6
一种包覆白藜芦醇的纳米固体脂质载体,按100g的总量计算,其原料组成及含量如下:A nano-solid lipid carrier coated with resveratrol, calculated according to the total amount of 100g, its raw material composition and content are as follows:
余量为去离子水;The balance is deionized water;
所述的磷脂为PC含量为95%的氢化卵磷脂,上海一基生物科技有限公司提供的医药级产品;The phospholipid is a hydrogenated lecithin with a PC content of 95%, a pharmaceutical-grade product provided by Shanghai Yiji Biotechnology Co., Ltd.;
所述的固态乳化剂为双子星乳化剂;Described solid emulsifier is Gemini emulsifier;
所述的固体脂质为二季戊四醇六辛酸/癸酸酯;The solid lipid is dipentaerythritol hexacaprylic acid/caprate;
所述的液体脂质为辛酸/癸酸三甘油酯;The liquid lipid is caprylic acid/capric triglyceride;
所述的多元醇为1,3-丁二醇;Described polyhydric alcohol is 1,3-butanediol;
所述的无机盐为氯化钠;Described inorganic salt is sodium chloride;
所述的防腐剂为双咪唑烷基脲。The preservative is diazolidinyl urea.
上述的包覆白藜芦醇的纳米固体脂质载体的制备方法,同实施例1。The preparation method of the above-mentioned nano-solid lipid carrier coated with resveratrol is the same as that in Example 1.
运用Quanta200F型扫描电镜(FEIcompany,Quanta200FEG,Holland,加速电压5~30kv)对上述所得的包覆白藜芦醇的纳米固体脂质载体的外貌形态进行扫描,所得的微观形貌图如图1所示。从图1中可以看出纳米固体脂质微粒排列紧密,颗粒均匀,对白藜芦醇具有很好的包覆作用。Using a Quanta200F scanning electron microscope (FEIcompany, Quanta200FEG, Holland, accelerating voltage 5 ~ 30kv) to scan the appearance of the nano-solid lipid carrier coated with resveratrol obtained above, the resulting microscopic appearance is shown in Figure 1 Show. It can be seen from Figure 1 that the nano-solid lipid particles are closely arranged and uniform, and have a good coating effect on resveratrol.
综上所述,本发明的一种包覆白藜芦醇的纳米固体脂质载体,因在载体结构中引入磷脂,提高了载体结构在皮肤上的粘附性,进而有利于白藜芦醇在皮肤上的渗透。In summary, a nano-solid lipid carrier coated with resveratrol of the present invention improves the adhesion of the carrier structure on the skin due to the introduction of phospholipids into the carrier structure, thereby benefiting the resveratrol Penetration on the skin.
以上所述仅是本发明的实施方式的举例,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明技术原理的前提下,还可以做出若干改进和变型,这些改进和变型也应视为本发明的保护范围。The foregoing is only an example of the embodiment of the present invention. It should be pointed out that for those of ordinary skill in the art, some improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and Modifications should also be regarded as the scope of protection of the present invention.
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| CN114028272A (en) * | 2021-11-30 | 2022-02-11 | 江苏瑞霆生物科技有限公司 | Liquid crystal nano emulsion of high-permeability vegetable oil and preparation method and application thereof |
| WO2023154479A1 (en) * | 2022-02-10 | 2023-08-17 | Dyve Biosciences, Inc. | Formulations for transdermal administration of active agents |
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