CN108619097A - 一种高效抗癌抗氧化复合脂质体 - Google Patents
一种高效抗癌抗氧化复合脂质体 Download PDFInfo
- Publication number
- CN108619097A CN108619097A CN201810575687.XA CN201810575687A CN108619097A CN 108619097 A CN108619097 A CN 108619097A CN 201810575687 A CN201810575687 A CN 201810575687A CN 108619097 A CN108619097 A CN 108619097A
- Authority
- CN
- China
- Prior art keywords
- liposome
- complex
- seed oil
- coix seed
- beta carotene
- 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.)
- Granted
Links
- 239000002502 liposome Substances 0.000 title claims abstract description 51
- 230000001093 anti-cancer Effects 0.000 title claims abstract description 16
- 230000003078 antioxidant effect Effects 0.000 title claims abstract description 13
- 239000003963 antioxidant agent Substances 0.000 title claims abstract description 9
- 235000006708 antioxidants Nutrition 0.000 title claims abstract description 9
- 244000077995 Coix lacryma jobi Species 0.000 claims abstract description 36
- 235000015112 vegetable and seed oil Nutrition 0.000 claims abstract description 36
- 238000002360 preparation method Methods 0.000 claims abstract description 17
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 15
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 8
- 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 abstract description 6
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 claims description 19
- 239000011648 beta-carotene Substances 0.000 claims description 19
- 235000013734 beta-carotene Nutrition 0.000 claims description 19
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 claims description 19
- 229960002747 betacarotene Drugs 0.000 claims description 19
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 16
- 235000019441 ethanol Nutrition 0.000 claims description 10
- 235000019198 oils Nutrition 0.000 claims description 8
- 239000008363 phosphate buffer Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 6
- 238000013019 agitation Methods 0.000 claims description 5
- 239000006210 lotion Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 230000010355 oscillation Effects 0.000 claims description 3
- 125000005909 ethyl alcohol group Chemical group 0.000 claims description 2
- 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 2
- 150000002632 lipids Chemical class 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 230000003647 oxidation Effects 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 2
- 235000013402 health food Nutrition 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 abstract 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 abstract 1
- 235000019799 monosodium phosphate Nutrition 0.000 abstract 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound 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 3
- 230000003064 anti-oxidating effect Effects 0.000 description 3
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 3
- 230000007760 free radical scavenging Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 239000000787 lecithin Substances 0.000 description 3
- 229940067606 lecithin Drugs 0.000 description 3
- 235000010445 lecithin Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 230000005907 cancer growth Effects 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 1
- HVYWMOMLDIMFJA-UHFFFAOYSA-N 3-cholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 HVYWMOMLDIMFJA-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000006701 autoxidation reaction Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 201000008006 pharynx cancer Diseases 0.000 description 1
- 238000007539 photo-oxidation reaction Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 230000036299 sexual function Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1277—Processes for preparing; Proliposomes
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
- A61K36/8994—Coix (Job's tears)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Mycology (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Botany (AREA)
- Dispersion Chemistry (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明属于保健食品及药品的技术领域，提供了一种高效抗癌抗氧化的复合脂质体及其制备方法。所述的复合脂质体主要由蛋黄卵磷脂、薏苡仁油、β‑胡萝卜素、胆固醇、磷酸氢二钠、磷酸二氢钠为原料组成。本发明所制备的复合脂质体具有较强的抗氧化活性及抗癌效果。相对于常规薏苡仁油脂质体、β‑胡萝卜素脂质体而言其抗氧化和抗癌活性显著提高。且该复合脂质体制备工艺简单，成本低廉，具有良好的应用前景。
Description
技术领域
本发明涉及保健食品和药品领域，具体涉及一种同时包含薏苡仁油和β-胡萝卜素两种活性成分的复合脂质体，且该复合脂质体制备工艺简单，具有较好的抗癌抗氧化活性。
背景技术
薏苡仁油作为一种药食同源性功能性油脂，具有广谱的抗癌活性，尤其对肝癌、鼻咽癌、乳腺癌、食道癌等具有较好的疗效。但薏苡仁油水溶性差，生物利用率低；组分中不饱和脂肪酸含量超过70％，易氧化分解产生有害物质，不但影响其功效发挥，且有害健康，其临床应用受到一定的限制。因此，添加一定量的脂溶性抗氧化保护剂的同时，通过载体包埋保护形式转变薏苡仁油物态，是改善薏苡仁油水溶性，提高其生物利用率，保证薏苡仁油安全应用的技术前提。
脂质体技术是一种新型的活性物质包埋技术，制备过程中利用磷脂分子的自组装行为在形成磷脂双分子层的同时，将脂溶性物质包埋于磷脂双分子层中，可提高其稳定性，降低光、氧等对活性成分的破坏，同时，脂质体还具有较好的缓释作用、靶向性、细胞亲和性、无毒性与组织相容性。但脂质体的主要膜材成分-磷脂含有一定量的不饱和脂肪酸成分，易氧化分解产生溶血磷脂等有害成分，降低体系pH的同时易引起包埋物的渗漏，产生聚集、分层现象。因此，现存脂质体制剂为延缓体系氧化，提高稳定性，多采用冷藏方式进行保存，而已有的薏苡仁油脂质体制剂的氧化稳定性也有待提高。另一方面，为了降低脂质体的粒径，提高均一性，在脂质体制备过程中多采用造价较高的高压均质、微射流乳化或超声处理等外力输入方式，工艺复杂，不仅造成生产成本提高，且工业化程度较低。
β-胡萝卜素是胡萝卜素家族中的主要成员，其特殊的富电子共轭体系，可通过猝灭单线态氧和清除自由基发挥较好的抗氧化活性，在抵抗由自由基氧化引起的各种病变：癌症、心脑血管疾病、白内障、衰老等方面有显著的功能，同时也是维护人体健康不可缺少的营养素。另研究表明：自由基是诱发心脑血管疾病，衰老、癌症的重要因素。因此，摄食有效清除自由基的功能性成分是防癌、保健、健康长寿的重要出路。
发明内容
本发明旨在针对现有配方产品的功能及技术缺陷，制备一种同时包埋薏苡仁油和β-胡萝卜素的复合脂质体制剂，该制剂一方面能够给薏苡仁油提供保护屏障，有效减缓其降解速度；另一方面能综合利用β-胡萝卜素的抗氧化作用及薏苡仁油的抗癌作用，提供一种高效抗癌抗氧化复合脂质体制剂。
本发明要解决的另一技术问题是现有薏苡仁油脂质体稳定性差、易氧化，稳定性有待提高。
本发明要解决的再一技术问题是现有β-胡萝卜素脂质体功能单一，抗癌效果不理想。
本发明要解决的又一技术问题是现有技术中以薏苡仁油为有效成分的癌症治疗药物，其抗癌效果有待提升。
本发明要解决的又一技术问题是现有技术中脂质体生产工艺复杂，生产成本较高。
为实现以上技术目的，本发明采用以下技术方案：
一种高效抗癌抗氧化复合脂质体，其特征在于：每25mL复合脂质体中含蛋黄卵磷脂140mg，胆固醇20mg，薏苡仁油6mg，β-胡萝卜素0.6mg，余量是浓度为20mM/L的磷酸缓冲液；
所述制备方法包括以下步骤：
1)取配方量的薏苡仁油、蛋黄卵磷脂和胆固醇，溶解于10mL无水乙醇中；
2)取β-胡萝卜素，制备成浓度为1mg/mL的β-胡萝卜素-二氯甲烷储备液溶液，4℃闭光保存；
3)取步骤2)所得β-胡萝卜素-二氯甲烷储备液溶液0.6mL加入步骤1)所得混合物中，摇匀，得油相；
4)取步骤3)所得油相缓慢注入到恒温43℃且处于磁力搅拌状态下的磷酸缓冲液中，加入完毕后，控制温度和转速不变，继续搅拌20min，随后将样品转移至水浴摇床中，45℃100r/min振荡20min，得脂质体粗乳液；
5)振荡完成后，将样品转移至旋转蒸发仪，于43℃真空条件下整除乙醇及二氯甲烷，得复合脂质体。
作为优选，步骤2)中在所述磷酸缓冲液浓度为20mM/L，pH为6.8。
在以上技术方案中，所述复合脂质体，是指利用脂质体同时包埋薏苡仁油和β-胡萝卜素所得产物。所述蛋黄卵磷脂其磷脂酰胆碱含量≥98％。
本发明提供了一种高效抗癌抗氧化复合脂质体。该技术方案首先对包埋物成分进行了创新性设计，针对薏苡仁油易氧化失活的问题引入了β-胡萝卜素成分，β-胡萝卜素自身的抗氧化作用有助于提升薏苡仁油的化学稳定性，同时对脂质体原料磷脂的自氧化、光氧化现象也具有缓解效果。更为重要的是，β-胡萝卜素本身对人体具有确切的抗衰老、提升免疫力、抗癌等功效，将其与薏苡仁油联用有助于提升抗癌效果，并具有抗氧化功能。
此外，本发明改进了脂质体的制备工艺，通过二次水化的方式：磁力搅拌水化+振荡水化使获得的脂质体分散液更为均匀，后续无需超声或均质处理处理就可获得粒度分布均匀的稳定产品。β-胡萝卜素包封率高达84.46％，平均粒径为186nm，多分散系数为0.104，平均Zeta电位为-30.33。
在以上技术思路的指引下，本发明对薏苡仁油、磷脂、β-胡萝卜素、胆固醇以及所用溶剂的具体用量进行了优化设计，在保证包埋效果的基础上提升了贮藏稳定性和治疗效果，大大改变了常规脂质体制剂只可冷藏的劣势，所制备的复合脂质体室温放置6个月、冷藏放置19个月仍未见分层聚集现象。除此之外，本发明方法所制备的复合脂质体经MTT实验及系列抗氧化实验证实其抗氧化活性及对癌细胞的抑制率均显著高于薏苡仁油脂质体及β-胡萝卜素脂质体。具有较好的应用前景。
附图说明
图1是本发明实施例1所制备的复合脂质体DPPH自由基清除率图：L-CSO：薏苡仁油脂质体；L-βC：β胡萝卜素脂质体；L-βC-CSO:复合脂质体，其中1：1，1：5，1：10，1：15表示β胡萝卜素与薏苡仁油的质量比。
图2是本发明实施例1所制备的复合脂质体对Caco-2癌细胞生长抑制情况：L-CSO：薏苡仁油脂质体；L-βC：β胡萝卜素脂质体；L-βC-CSO:复合脂质体，其中1：1，1：5，1：10，1：15表示β胡萝卜素与薏苡仁油的质量比。
具体实施方式
实施例1
称取卵磷脂140mg、胆固醇20mg、薏苡仁油6mg溶于10mL乙醇，取β-胡萝卜素-二氯甲烷溶液(1mg/mL)0.6mL加入以上乙醇溶液中混匀得油相，将所得油相缓慢注入到25mL20mM/L，pH为6.8的磷酸缓冲液中(恒温43℃且处于磁力搅拌状态)，加入完毕后，控制温度和转速不变，继续搅拌20min，随后将样品转移至水浴摇床中，45℃100r/min振荡20min，得脂质体粗乳液；振荡完成后，将样品转移至旋转蒸发仪，于45℃真空条件下整除乙醇及二氯甲烷，得复合脂质体。
实施例2
称取卵磷脂560mg、胆固醇80mg、薏苡仁油24mg溶于40mL乙醇，取β-胡萝卜素-二氯甲烷溶液(1mg/mL)2.4mL加入以上乙醇溶液中混匀得油相，将所得油相缓慢注入到100mL20mM/L，pH为6.8的磷酸缓冲液中(恒温43℃且处于磁力搅拌状态)，加入完毕后，控制温度和转速不变，继续搅拌20min，随后将样品转移至水浴摇床中，45℃100r/min振荡20min得脂质体粗乳液；振荡完成后，将样品转移至旋转蒸发仪，于45℃真空条件下整除乙醇及二氯甲烷，得复合脂质体。
对比例1
制备方法同实施例1，未添加薏苡仁油。
对比例2
制备方法同实施例1，未添加β-胡萝卜素。
对比例3
制备方法同实施例1，薏苡仁油为0.6mg。
对比例4
制备方法同实施例1，薏苡仁油为3mg。
对比例5
制备方法同实施例1，薏苡仁油为9mg。
将本发明实施例1制得的复合脂质体，对比例1制得的β胡萝卜素脂质体、对比例2制得的薏苡仁油脂质体，对比3、4、5制得的复合脂质体进行DPPH自由基清除率、Caco-2癌细胞生长抑制情况测试，其结果见说明书附图1、2，从图中可以看出本发明制备的复合脂质体，在β-胡萝卜素与薏苡仁油质量比为1：10时，产生的最佳协同作用，可以使DPPH自由基清除率和Caco-2癌细胞生长抑制率显著提高。
Claims (3)
1.一种高效抗癌抗氧化复合脂质体，其特征在于：每25mL复合脂质体中含蛋黄卵磷脂140mg，胆固醇20mg，薏苡仁油6mg，β-胡萝卜素0.6mg，余量为浓度为20mM/L的磷酸缓冲液；
制备方法包括以下步骤：
1)取配方量的薏苡仁油、蛋黄卵磷脂和胆固醇，溶解于10mL无水乙醇中；
2)取β-胡萝卜素，制备成浓度为1mg/mL的β-胡萝卜素-二氯甲烷储备液溶液，4℃闭光保存；
3)取步骤2)所得β-胡萝卜素-二氯甲烷储备液溶液0.6mL加入步骤1)所得混合物中，摇匀，得油相；
4)取步骤3)所得油相缓慢注入到恒温43℃且处于磁力搅拌状态下的磷酸缓冲液中，加入完毕后，控制温度和转速不变，继续搅拌20min，随后将样品转移至水浴摇床中，45℃100r/min振荡20min得脂质体粗乳液；
5)振荡完成后，将样品转移至旋转蒸发仪，于43℃真空条件下蒸除乙醇及二氯甲烷，得复合脂质体。
2.根据权利要求1所述的复合脂质体，其特征在于：所述蛋黄卵磷脂中磷脂酰胆碱的含量≥98％。
3.根据权利要求1所述的制备方法，其特征在于：步骤2)中在所述磷酸缓冲液浓度为20mM/L，pH为6.8。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810575687.XA CN108619097B (zh) | 2018-06-06 | 2018-06-06 | 一种高效抗癌抗氧化复合脂质体 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810575687.XA CN108619097B (zh) | 2018-06-06 | 2018-06-06 | 一种高效抗癌抗氧化复合脂质体 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108619097A true CN108619097A (zh) | 2018-10-09 |
| CN108619097B CN108619097B (zh) | 2020-11-17 |
Family
ID=63691089
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810575687.XA Active CN108619097B (zh) | 2018-06-06 | 2018-06-06 | 一种高效抗癌抗氧化复合脂质体 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108619097B (zh) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114224837A (zh) * | 2021-11-09 | 2022-03-25 | 成都科建生物医药有限公司 | 一种抗氧化脂质体的制备方法 |
| CN115299581A (zh) * | 2022-08-12 | 2022-11-08 | 安徽省凤阳县御膳油脂有限公司 | 一种富含β-胡萝卜素的芝麻酱生产方法 |
| CN116602959A (zh) * | 2023-05-24 | 2023-08-18 | 广州中妆美业化妆品有限公司 | 一种具有抗炎镇痛功效的含茶活性成分的组合物脂质体及其应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101780232A (zh) * | 2010-03-23 | 2010-07-21 | 南昌大学 | 一种薏苡仁油前体脂质体及其制备方法 |
| CN105796497A (zh) * | 2016-04-29 | 2016-07-27 | 江西科技师范大学 | 一种高贮藏稳定性薏苡仁油温敏脂质体的制备方法 |
-
2018
- 2018-06-06 CN CN201810575687.XA patent/CN108619097B/zh active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101780232A (zh) * | 2010-03-23 | 2010-07-21 | 南昌大学 | 一种薏苡仁油前体脂质体及其制备方法 |
| CN105796497A (zh) * | 2016-04-29 | 2016-07-27 | 江西科技师范大学 | 一种高贮藏稳定性薏苡仁油温敏脂质体的制备方法 |
Non-Patent Citations (4)
| Title |
|---|
| BAI,ET AL: "A Comparison Investigation of Coix Seed Oil Liposomes Prepared by Five Different Methods", 《JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY》 * |
| 刘玉珍等: "薏苡仁油脂质体的制备及质量评价", 《食品科学》 * |
| 李亮等: "薏苡仁油脂质体制备工艺研究", 《食品科技》 * |
| 许海燕等: "《纳米生物医学技术》", 28 February 2009, 中国协和医科大学出版社 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114224837A (zh) * | 2021-11-09 | 2022-03-25 | 成都科建生物医药有限公司 | 一种抗氧化脂质体的制备方法 |
| CN115299581A (zh) * | 2022-08-12 | 2022-11-08 | 安徽省凤阳县御膳油脂有限公司 | 一种富含β-胡萝卜素的芝麻酱生产方法 |
| CN116602959A (zh) * | 2023-05-24 | 2023-08-18 | 广州中妆美业化妆品有限公司 | 一种具有抗炎镇痛功效的含茶活性成分的组合物脂质体及其应用 |
| CN116602959B (zh) * | 2023-05-24 | 2024-05-17 | 广州中妆美业化妆品有限公司 | 一种具有抗炎镇痛功效的含茶活性成分的组合物脂质体及其应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108619097B (zh) | 2020-11-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101022786B (zh) | 用自乳化制剂释放亲脂性辅酶Q10（CoQ10）及其他膳食组分 | |
| US9775910B2 (en) | Stable aqueous suspension | |
| CN108619097A (zh) | 一种高效抗癌抗氧化复合脂质体 | |
| CN101474156B (zh) | 一种维生素c前体脂质体及其应用 | |
| EP3666265A1 (en) | Improved complexes and compositions containing curcumin | |
| DE60219174T2 (de) | Mikronährstoff-phosphate als nahrungsergänzungsmittel und mittel zur förderung der gesundheit | |
| CN101396346B (zh) | 紫杉醇脂质复合物 | |
| CN104306333B (zh) | 一种卡巴他赛脂质微球注射液及其制备方法 | |
| CN105777770B (zh) | 一种饱和长链脂肪酸修饰的7-乙基-10-羟基喜树碱化合物及其长循环脂质体 | |
| CN102614127A (zh) | 一种白藜芦醇纳米分散体及其制备方法 | |
| CN101584663A (zh) | 新型的注射用多西他赛脂质体给药系统及其制备方法 | |
| CN106727324B (zh) | 纳米银脂质体及其制备方法和应用 | |
| Zhai et al. | Synthesis and characterization of polyoxometalates loaded starch nanocomplex and its antitumoral activity | |
| Zabodalova et al. | Liposomal beta-carotene as a functional additive in dairy products. | |
| CN101869302B (zh) | 微乳钙制剂及其制备方法和应用 | |
| CN105125592A (zh) | 一种含蟾酥脂溶物的药物及其制备方法 | |
| CN104288100A (zh) | 一种替尼泊苷纳米混悬剂及其制备方法 | |
| CN104274826B (zh) | 一种水包油型复方粘菌素纳米乳 | |
| US20150110866A1 (en) | Complexes and compositions containing curcumin | |
| CN108434101A (zh) | 一种新型的用于抗癌的Tivozanib脂质体、制剂及其制备方法和应用 | |
| CZ2005796A3 (cs) | Farmaceutická kompozice obsahující derivát taxanuse zlepsenou terapeutickou úcinností | |
| EP2452577B1 (fr) | Solution aqueuse de phytine et utilisation de ladite solution pour la préparation d'un complément alimentaire liquide ou d'une composition cosmétique | |
| CN105232465A (zh) | 一种芬苯达唑脂质体制剂及其制备方法 | |
| Mangrulkar et al. | A comprehensive review on pleiotropic effects and therapeutic potential of soy lecithin | |
| CN105853361B (zh) | 一种四嗪二甲酰胺脂质体制剂及其制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |