CN101816632A - Composite functional liposome and preparation method and application thereof - Google Patents
Composite functional liposome and preparation method and application thereof Download PDFInfo
- Publication number
- CN101816632A CN101816632A CN 201010160533 CN201010160533A CN101816632A CN 101816632 A CN101816632 A CN 101816632A CN 201010160533 CN201010160533 CN 201010160533 CN 201010160533 A CN201010160533 A CN 201010160533A CN 101816632 A CN101816632 A CN 101816632A
- Authority
- CN
- China
- Prior art keywords
- liposome
- composite functional
- water
- preparation
- cholesterol
- 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 69
- 239000002131 composite material Substances 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 42
- 239000003814 drug Substances 0.000 claims abstract description 40
- 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 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 31
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims abstract description 30
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229930003268 Vitamin C Natural products 0.000 claims abstract description 20
- 239000000839 emulsion Substances 0.000 claims abstract description 20
- 235000019154 vitamin C Nutrition 0.000 claims abstract description 20
- 239000011718 vitamin C Substances 0.000 claims abstract description 20
- 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 abstract description 19
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 18
- 239000008347 soybean phospholipid Substances 0.000 claims abstract description 18
- 239000007853 buffer solution Substances 0.000 claims abstract description 15
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229960004889 salicylic acid Drugs 0.000 claims abstract description 15
- 229940079593 drug Drugs 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 239000000243 solution Substances 0.000 claims abstract description 9
- 239000000872 buffer Substances 0.000 claims abstract description 5
- 238000004945 emulsification Methods 0.000 claims abstract description 5
- 239000004530 micro-emulsion Substances 0.000 claims abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 32
- 210000003022 colostrum Anatomy 0.000 claims description 17
- 235000021277 colostrum Nutrition 0.000 claims description 17
- 230000001804 emulsifying effect Effects 0.000 claims description 10
- 238000002525 ultrasonication Methods 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000005345 coagulation Methods 0.000 claims description 2
- 230000015271 coagulation Effects 0.000 claims description 2
- 238000004821 distillation Methods 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 125000001033 ether group Chemical group 0.000 claims 1
- 230000007794 irritation Effects 0.000 claims 1
- 239000004531 microgranule Substances 0.000 claims 1
- 239000002537 cosmetic Substances 0.000 abstract description 15
- 239000012071 phase Substances 0.000 abstract description 12
- 239000008346 aqueous phase Substances 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 229940107161 cholesterol Drugs 0.000 abstract 1
- 230000000857 drug effect Effects 0.000 abstract 1
- 229940083466 soybean lecithin Drugs 0.000 abstract 1
- 238000005292 vacuum distillation Methods 0.000 abstract 1
- 239000007864 aqueous solution Substances 0.000 description 11
- 150000003904 phospholipids Chemical class 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000012856 packing Methods 0.000 description 5
- 230000035943 smell Effects 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 230000003064 anti-oxidating effect Effects 0.000 description 3
- 230000006866 deterioration Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000001165 hydrophobic group Chemical group 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000008307 w/o/w-emulsion Substances 0.000 description 3
- 229920000832 Cutin Polymers 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 235000013402 health food Nutrition 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000006981 Skin Abnormalities Diseases 0.000 description 1
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000010612 desalination reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000011229 interlayer Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 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 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 231100000245 skin permeability Toxicity 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000001550 time effect Effects 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
Abstract
本发明公开了一种复合功能脂质体及其制备方法和应用。本发明复合功能脂质体包括如下组分：大豆磷脂、胆固醇、维生素C和水杨酸，四者的质量比为5～7∶1.3～1.5∶0.8～1.5∶1。本发明复合功能脂质体的制备方法是将大豆磷脂、胆固醇和水杨酸用有机溶剂溶解作为油相，含维生素C的缓冲液作为水相，经乳化形成油包水微乳液，再与缓冲溶液乳化，最终形成水/油/水的复乳，乳化过程由超声破碎完成，再通过减压蒸馏除去有机溶剂，得到复合功能脂质体。本发明复合功能脂质体的性质稳定，同时包含脂溶性药物和水溶性药物，发挥多种药物的药效，使脂质体的功能复合化，应用于化妆品中，提高了药物的稳定性，降低了生产成本。The invention discloses a composite functional liposome, its preparation method and application. The composite functional liposome of the present invention comprises the following components: soybean lecithin, cholesterol, vitamin C and salicylic acid, and the mass ratio of the four is 5-7:1.3-1.5:0.8-1.5:1. The preparation method of the composite functional liposome of the present invention is that soybean phospholipid, cholesterol and salicylic acid are dissolved with an organic solvent as an oil phase, and a buffer solution containing vitamin C is used as an aqueous phase, which is emulsified to form a water-in-oil microemulsion, and then mixed with a buffer The solution is emulsified to finally form a water/oil/water double emulsion. The emulsification process is completed by ultrasonic crushing, and then the organic solvent is removed by vacuum distillation to obtain a composite functional liposome. The compound functional liposome of the present invention has stable properties, contains fat-soluble drugs and water-soluble drugs at the same time, exerts the drug effects of various drugs, makes the functions of the liposome compound, and is applied in cosmetics to improve the stability of the drug. Reduced production costs.
Description
Technical field
The present invention relates to the preparation method of liposome, be specifically related to a kind of composite functional liposome and its production and application.
Background technology
Liposome (Liposome) is found by doctor Bangham and names that its structure dimension is the closed vesicle of interlayer cyst wall with the bimolecular film in nineteen sixty-five.Various lipids and lipid mixture all can be used for preparing liposome, and phospholipid is the most frequently used.The main component of phospholipid is phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, Phosphatidylserine, phosphatidyl glycerol, phosphatidic acid etc.Phospholipid is the main component of cell membrane, thus liposome in similar in human body cell, to human body cell have the height affinity.Phospholipid is amphipathic molecule, contains hydrophilic group (phosphate group and nitrogenous base) in its structure, and hydrophobic group (two long hydrocarbon chains).Under a certain specific concentrations condition, polar group is towards the both sides water, and the hydrocarbon chain of non-polar group faces each other and associates into a stable bilayer structure.Utilize the construction features of liposome can in the middle of double-deck molecule, load the lipophile composition, and at centre of sphere place sealing embedding hydrophilic composition.The another kind of material that constitutes lipid is a cholesterol, and its hydrophobicity is strong than hydrophilic, is embedded in the middle of the bilayer of phospholipid formation, mainly plays a part to change pure phospholipid layer character, and it plays a part to regulate membrane structure " flowability " as " buffer agent ".
Liposome is widely used in medicine, health food, cosmetics and genetic engineering field.One of them important use is as pharmaceutical carrier.The water that pharmaceutical pack is rolled in liposome and film mutually in, the targeting of control liposome makes it be enriched in diseased region with drug release, thereby can reduce the dosage of required medicine, has also avoided the infringement of medicine to the normal position of human body greatly.The development of sterically stabilized liposome has in recent years improved liposome stability in vivo greatly, makes liposome move towards the practical stage as pharmaceutical carrier aspect the diseases such as treatment cancer.Along with cosmetics develop to functionalization, specialization and seriation, biological engineering preparations such as hyaluronic acid, liposome, ceramide and epidermal growth factor are applied in the skin care item morely, and French Lancome companies in 1986 release the liposome cosmetics of " Capture " by name first.After the stability of liposome improves, be used as the transmission system of cosmetic active component, increase effect, storage and the protection component of cosmetics; May command discharges the effect of (slow release) lipid composition during use.
Vitamin C also is ascorbic acid, it is a kind of water miscible vitamin, has good anti-oxidation function, can be used for promoting that ossein and mucopolysaccharide synthesize, reduce infringement, the slow down aging of radical pair skin, simultaneously can suppress the deposition of skin abnormality pigment and the activity of tryrosinase, reduce melanic formation, thus be widely used in whiten and antioxidation beauty and skin care cosmetics in.But vitamin C is easy to oxidation deterioration, if with commonsense method it is directly added the white substrate of cream, three months will be all ineffective, and vitamin C is water miscible, is difficult for the horny layer that penetrates to the skin, so be difficult to give full play to effectiveness.If after liposomal encapsulated, can increase ascorbic stability, and make it have long effect.
Salicylic acid is a kind of cosmetics additive commonly used, and the cutin of removal, pore refining, removing blackhead are arranged, the effect of desalination microgroove and wrinkle.Its action principle is that salicylic acid can dissolve the formation shape material between cutin, horny layer is produced come off, and gathers blocked up horny layer so can remove, and enhances metabolism.But it is acid that salicylic aqueous solution is, and certain zest is arranged, and be generally and be dissolved in ethanol earlier and add in the cosmetics again, will add certain ethanol, so can cause discomfort even allergy to the skin of sensitivity.
Summary of the invention
The objective of the invention is to apt to deteriorate or problem such as zest arranged according to existing cosmetics additive, a kind of composite functional liposome is provided, can be with multiple cosmetics additive embedding, delayed the oxidation deterioration of medicine, utilize the cellular affinity of liposome and effective trap that short skin permeability increases medicine, reduce the zest of medicine.
Another purpose of the present invention is to provide the preparation method of above-mentioned composite functional liposome.
A further object of the invention is to provide the application of above-mentioned composite functional liposome.
Above-mentioned purpose of the present invention is achieved by the following technical programs:
A kind of composite functional liposome comprises following component: soybean phospholipid, cholesterol, vitamin C and salicylic acid, four mass ratio are 5 ~ 7: 1.3 ~ 1.5: 0.8 ~ 1.5: 1, be preferably 9: 2: 1.8: 1.6.
The preparation method of composite functional liposome of the present invention comprises the steps: with soybean phospholipid, cholesterol, salicylic acid and organic solvent as oil phase, contain ascorbic buffer as water, form water-in-oil microemulsion through the emulsifying first time, carry out the emulsifying second time with buffer solution again, the final emulsion that forms water/oil/water, emulsion process is finished by ultrasonication, removes organic solvent by distilling under reduced pressure again, obtains composite functional liposome.
The present invention is primarily aimed at the application in cosmetics, in the therefore liposome embedded medicine, has selected for use salicylic acid as fat-soluble medicine, and vitamin C is as water soluble drug.But when fat-soluble medicine and water soluble drug are other medicines, still can use preparation method of the present invention.
In the above-mentioned preparation method, described soybean phospholipid, cholesterol and salicylic mass ratio are preferably 4.6 ~ 8: 1 ~ 1.7: 1, most preferably be 5: 1.3: 1.The concentration of soybean phospholipid is one of significant effects factor in the preparation, to emulsive time effects is bigger for the second time.Experiment showed, that soybean phospholipid has wider amount ranges when keeping other condition constant, and the concentration of phospholipid is high more is difficult to form stabilized liposomes more, the emulsive time is long more for the second time; And the too little embedding rate that reaches higher of being difficult to of concentration because the fat-soluble medicine composition is the centre that loads on double-deck molecule, has certain limitation to phospholipid concentration.It is that medicine is separated out at aqueous phase that the fat-soluble medicine envelop rate is crossed the consequence that can cause when hanging down, and layering occurs with the liposome gathering.Experimental data shows that the mass ratio of soybean phospholipid and fat-soluble medicine can not be less than 4.6: 1 when being fat-soluble medicine with the salicylic acid.
As a kind of preferred version, the described organic solvent of preparation method of the present invention is an ether, and the amount of adding is as the criterion to dissolve raw material fully.
The liposome of multi-emulsion method preparation can comprise more water soluble drug, so the concentration of water soluble drug is less to the liposome stability influence, but the vitamin C aqueous solution is unfavorable for forming liposome because of acidity is too high, so when water is the vitamin C aqueous solution in preparation, should pay attention to adjusting its pH value.In the above-mentioned preparation method, vitamin C is dissolved in Na
2HPO
4-K
2HPO
4Buffer solution is used small amount of N a
2HPO
4It is 4 ~ 5 that aqueous solution is adjusted to pH, and it is standby to be configured to concentration 0.04g/mL.Experiment showed, that working as interior water pH is easy to layering less than 4 liposomees that form.
When adopting multi-emulsion method to prepare liposome, the aqueous solution that adds oil phase is separated into little water droplet under ultrasonication.Phospholipid, cholesterol are adsorbed on water droplet surface hydrophilic group inwardly, and hydrophobic group forms one deck monomolecular film outwardly, thereby generate Water-In-Oil (W/O) colostrum.After aqueous buffer solution added emulsion, in the volatilization of ultrasonic organic solvent down, phospholipid, cholesterol unnecessary in the oil phase generate one deck monomolecular film rapidly at the oil-water interfaces with buffer, little water droplet in the oil phase passes the monomolecular film of oil-water interfaces and by its encirclement, hydrophobic group associates face-to-face, hydrophilic group forms the liposome structure of bilayer towards the both sides water at aqueous phase.
Emulsifying for the first time is easy to realize that ultrasonic time is generally 1 ~ 2min that bath temperature is 25 ~ 35 ℃.The emulsifying key is the water-oil factor example, and water can not surpass half of oil phase, is generally 1/3rd or 1/4th of oil phase.Because with the ether is organic solvent, boiling point only is 34.5 ℃, and ultrasonicly impels ether volatilization, easily reaches the phase inversion point when water is too much, phase inversion may take place when adding again when not containing the medicine water more than 2 times, promptly forms the O/W emulsion but not emulsion.Emulsive formation colostrum is even turbid solution for the first time, places not coagulation of 2min layering.
The concentration of ultrasonic power, time and soybean phospholipid is then depended in emulsifying for the second time.During emulsifying colostrum is added 2 times of waters that do not contain medicine more than the volume, adopt the Na of pH=7.4 in the experiment
2HPO
4-K
2HPO
4Buffer solution.Colostrum floats on the upper strata with oil phase, reduces by the ultrasonic agitation oil phase, occurs emulsifying in the boundary, forms emulsion and diffuses to aqueous phase, and required time is 5 ~ 10min.The ultrasonic ether that makes volatilizees rapidly, and the motion of colostrum particle is violent, can pass monomolecular film within a short period of time and form unilamelar liposome, has than small particle diameter.If ultrasonic power is too small, the time that can make the colostrum particle pass monomolecular film increases, and easily becomes uneven multilamelar liposome, and particle diameter is big and separation time is shorter, so the power of emulsifying for the second time should remain in more than the 100W.The transparency emulsion of evenly omiting the no fat piece of oil phase disappearance, formation can finish ultrasonic, avoids the long-time ultrasonic liposome that causes to break, and makes embedding rate decline.
Adopt distilling under reduced pressure to remove the residue ether in the preparation, vacuum is that 0.08 ~ 0.09Mpa distillation time is 5 ~ 15min, and bath temperature is 30 ~ 35 ℃.If transferring to higher vacuum can heat, more help protecting liposome and medicine not oxidized.
Composite functional liposome of the present invention can comprise fat-soluble medicine and water soluble drug simultaneously, during as pharmaceutical carrier, can bring into play the effectiveness of multiple medicine, and reduces the zest of medicine.
Compared with prior art, the present invention has following beneficial effect:
(1) with reference to the document record of existing liposome preparation, liposome mostly was a kind of medicine of embedding and can adds small amount of antioxidant in the past, and the function that is realized is comparatively single; Composite functional liposome of the present invention can be filled up this deficiency, can realize that the pharmaceutical pack that character differs bigger is contained in the identical liposome, on the former advantageous property that possesses of liposome, save multiple treatment step required when causing adding cosmetics, medicine again because of the pharmaceutical properties difference;
(2) composite functional liposome stable in properties of the present invention all has good envelop rate to multiple medicine of different nature, has improved stability of drug, has reduced production cost, can be widely used in medicine, health food, cosmetics and genetic engineering field;
(3) composite functional liposome of the present invention is embedded in vitamin C and salicylic acid in the liposome simultaneously, delayed the oxidation deterioration process of medicine, and utilize the cellular affinity of liposome and promote percutaneous permeability, increased effective trap of medicine, when being used to prepare cosmetics, multiple merit such as can reach antioxidation, whiten.
The specific embodiment
Further explain the present invention below in conjunction with embodiment, but embodiment does not do any type of qualification to the present invention.
Embodiment 1
Vitamin C is dissolved in small amount of N a
2HPO
4-K
2HPO
4Buffer solution drips Na
2HPO
4It is 5 that aqueous solution is adjusted to pH, and disposing its concentration with buffer solution is 0.04g/mL.Get the 0.15g soybean phospholipid, 0.04g cholesterol, 0.03g salicylic acid are dissolved in the 4mL ether, add 1mL said vitamin C aqueous solution, and power is 90W, and bath temperature is that ultrasonic 2min disappears to layering under 30 ℃, and the even turbid solution of formation is a colostrum.The Na that colostrum is added 10mL pH=7.4
2HPO
4-K
2HPO
4In the buffer solution, power is 100W, and bath temperature is 45 ℃ of following ultrasonication 6min, to the oil reservoir complete obiteration, forms evenly slightly transparency emulsion, is the W/O/W emulsion.Then 35 ℃ of following vacuum rotary steam 8min extremely do not have the ether abnormal smells from the patient fully.With the prepared liposome emulsion volume of packing into is the centrifuge tube of 2mL, centrifugal 1h, and rotating speed is 10000rad/min, gets supernatant and carries out uv absorption and measure, and recording ascorbic envelop rate is 45%, and salicylic envelop rate is 52%.
Embodiment 2
With the 0.15g soybean phospholipid, 0.04g cholesterol, 0.03g salicylic acid are dissolved in the 4mL ether, and adding 1mLpH is 3.8, and concentration is 0.04g/mL vitamin C aqueous solution, and power is 90W, and bath temperature is the even turbid solution that ultrasonic 2min disappears and forms to layering under 25 ℃.The Na that colostrum adds 10mL pH=7.4 will be made
2HPO
4-K
2HPO
4In the buffer solution, power is 100W, and bath temperature is 40 ℃ of following ultrasonication 7min, and disappearing to oil reservoir forms evenly slightly transparent emulsion.Then 30 ℃ of following vacuum rotary steam 10min extremely do not have the ether abnormal smells from the patient fully.With the prepared liposome emulsion volume of packing into is the centrifuge tube of 2mL, centrifugal 1h, and rotating speed is 10000rad/min, gets supernatant and carries out uv absorption and measure, and recording ascorbic envelop rate is 32%, and salicylic envelop rate is 38%.
Embodiment 3
Getting 1.5mL pH is 5, and concentration is 0.04g/mL vitamin C aqueous solution, adds 4mL and is dissolved with the 0.2g soybean phospholipid, 0.04g cholesterol is in the salicylic diethyl ether solution of 0.04g, with power 90W, bath temperature is that ultrasonic 2min disappears to layering under 30 ℃, the colostrum that formation is evenly muddy.The Na that colostrum is added 10mL pH=7.4
2HPO
4-K
2HPO
4In the buffer solution, power is 100W, and bath temperature is 45 ℃ of following ultrasonication 6min, to the oil reservoir complete obiteration, forms evenly slightly transparent emulsion.Then 35 ℃ of following vacuum rotary steam 10min extremely do not have the ether abnormal smells from the patient fully.With the prepared liposome emulsion volume of packing into is the centrifuge tube of 2mL, centrifugal 1h, and rotating speed is 10000rad/min, gets supernatant and carries out uv absorption and measure, and recording ascorbic envelop rate is 40%, and salicylic envelop rate is 39%.
Embodiment 4
Get the 0.18g soybean phospholipid, 0.05g cholesterol, 0.03g salicylic acid are dissolved in the 5mL ether, adding 1mLpH is 5, and concentration is 0.04g/mL vitamin C aqueous solution, and power is 100W, bath temperature is that ultrasonic 1.5min disappears to layering under 25 ℃, and the even turbid solution of formation is a colostrum.The Na that colostrum is added 15mL pH=7.4
2HPO
4-K
2HPO
4In the buffer solution, power is 100W, and bath temperature is 40 ℃ of following ultrasonication 8min, to the oil reservoir complete obiteration, forms evenly slightly transparency emulsion, is the W/O/W emulsion.Then 30 ℃ of following vacuum rotary steam 12min extremely do not have the ether abnormal smells from the patient fully.With the prepared liposome emulsion volume of packing into is the centrifuge tube of 2mL, centrifugal 1h, and rotating speed is 10000rad/min, gets supernatant and carries out uv absorption and measure, and recording ascorbic envelop rate is 42%, and salicylic envelop rate is 45%.
Embodiment 5
Take by weighing the 0.16g soybean phospholipid, 0.03g cholesterol, 0.03g salicylic acid are dissolved in the 4mL ether, adding 1mL pH is 5, and concentration is the vitamin C aqueous solution of 0.04g/mL, and power is 100W, bath temperature is that ultrasonic 1min disappears to layering under 25 ℃, and the even turbid solution of formation is a colostrum.The Na that colostrum is added 12mLpH=7.4
2HPO
4-K
2HPO
4In the buffer solution, power is 100WA, and bath temperature is 50 ℃ of following ultrasonication 5min, to the oil reservoir complete obiteration, forms evenly slightly transparency emulsion, is the W/O/W emulsion.Then 35 ℃ of following vacuum rotary steam 12min extremely do not have the ether abnormal smells from the patient fully.With the prepared liposome emulsion volume of packing into is the centrifuge tube of 2mL, centrifugal 1.2h, and rotating speed is 8000rad/min, gets supernatant and carries out uv absorption and measure, and recording ascorbic envelop rate is 40%, and salicylic envelop rate is 43%.
Claims (10)
1. composite functional liposome, comprise following component: soybean phospholipid, cholesterol, vitamin C and salicylic acid, four mass ratio are 5 ~ 7: 1.3 ~ 1.5: 0.8 ~ 1.5: 1.
2. composite functional liposome according to claim 1 is characterized in that described soybean phospholipid, cholesterol, vitamin C and salicylic mass ratio are 9: 2: 1.8: 1.6.
3. the preparation method of claim 1 or 2 described composite functional liposomes, it is characterized in that comprising the steps: with soybean phospholipid, cholesterol, salicylic acid and organic solvent as oil phase, contain ascorbic buffer as water, form water-in-oil microemulsion through the emulsifying first time, carry out the emulsifying second time with buffer solution again, finally form the emulsion of water/oil/water, emulsion process is finished by ultrasonication, remove organic solvent by distilling under reduced pressure again, obtain composite functional liposome.
4. according to the preparation method of the described composite functional liposome of claim 3, it is characterized in that described soybean phospholipid, cholesterol and salicylic mass ratio are 4.6 ~ 8: 1 ~ 1.7: 1.
5. according to the preparation method of the described composite functional liposome of claim 4, it is characterized in that described soybean phospholipid, cholesterol and salicylic mass ratio are 5: 1.3: 1.
6. according to the preparation method of the described composite functional liposome of claim 3, it is characterized in that described organic solvent is an ether, the amount of adding is as the criterion to dissolve raw material fully; It is described that to contain ascorbic water be that vitamin C is dissolved in Na
2HPO
4-K
2HPO
4Buffer solution, concentration are 0.04g/ml, and pH is 4 ~ 5; Described buffer solution is the Na of pH=7.4
2HPO
4-K
2HPO
4Buffer solution.
7. according to the preparation method of the described composite functional liposome of claim 3, it is characterized in that the described first time, emulsive bath temperature was 25 ~ 35 ℃, ultrasonic time is 1 ~ 2min, and power is 90 ~ 100W; The described second time, emulsive bath temperature was 40 ~ 50 ℃, and ultrasonic time is 5 ~ 8min, and power is 100W.
8. according to the preparation method of the described composite functional liposome of claim 3, it is characterized in that described colostrum is even turbid solution, place not coagulation of 2min layering; Described emulsion is evenly to omit transparency emulsion, and decentralized photo is the microgranule of colostrum, and continuous phase is not for containing the water of water soluble drug.
9. according to the preparation method of the described composite functional liposome of claim 3, the vacuum that it is characterized in that described distilling under reduced pressure is 0.08 ~ 0.09Mpa, and bath temperature is 30 ~ 35 ℃, and distillation time is 5 ~ 15min.
10. claim 1 or 2 described composite functional liposomes are as pharmaceutical carrier, the application in reducing medicine irritation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101605338A CN101816632B (en) | 2010-04-23 | 2010-04-23 | Composite functional liposome and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101605338A CN101816632B (en) | 2010-04-23 | 2010-04-23 | Composite functional liposome and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101816632A true CN101816632A (en) | 2010-09-01 |
| CN101816632B CN101816632B (en) | 2012-08-22 |
Family
ID=42652013
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101605338A Expired - Fee Related CN101816632B (en) | 2010-04-23 | 2010-04-23 | Composite functional liposome and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101816632B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108576779A (en) * | 2018-02-11 | 2018-09-28 | 湖北工业大学 | Konjaku glucomannan-liposome composite Nano food delivering system and its preparation method and application |
| CN108969751A (en) * | 2017-06-02 | 2018-12-11 | 中国科学院过程工程研究所 | A kind of medicament slow-release microsphere and its preparation method and application |
| CN111035579A (en) * | 2019-12-20 | 2020-04-21 | 四川大学 | A kind of composite liposome/chitosan antioxidant preparation and preparation method thereof |
| CN112823666A (en) * | 2019-11-21 | 2021-05-21 | 江苏省农业科学院 | Nano-liposome simultaneously containing xanthophyll and cordyceps militaris alcohol extract and preparation method thereof |
| CN114425038A (en) * | 2022-01-27 | 2022-05-03 | 沈阳信康药物研究有限公司 | 20(S) -PPD liposome emulsion complex oral administration preparation and preparation method and application thereof |
| CN118948662A (en) * | 2024-07-26 | 2024-11-15 | 王叔和生物医药(武汉)有限公司 | A transdermal VC ethyl ether liposome emulsion and its preparation method and application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1660059A (en) * | 2004-02-25 | 2005-08-31 | 重庆华邦制药股份有限公司 | Composite liposome of vitaminaacid as well as preparation method and application |
| CN101491499A (en) * | 2009-02-19 | 2009-07-29 | 陶灵刚 | Composite liposome for injection containing 12 vitamins and preparation method thereof |
-
2010
- 2010-04-23 CN CN2010101605338A patent/CN101816632B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1660059A (en) * | 2004-02-25 | 2005-08-31 | 重庆华邦制药股份有限公司 | Composite liposome of vitaminaacid as well as preparation method and application |
| CN101491499A (en) * | 2009-02-19 | 2009-07-29 | 陶灵刚 | Composite liposome for injection containing 12 vitamins and preparation method thereof |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108969751A (en) * | 2017-06-02 | 2018-12-11 | 中国科学院过程工程研究所 | A kind of medicament slow-release microsphere and its preparation method and application |
| CN108576779A (en) * | 2018-02-11 | 2018-09-28 | 湖北工业大学 | Konjaku glucomannan-liposome composite Nano food delivering system and its preparation method and application |
| CN108576779B (en) * | 2018-02-11 | 2021-11-12 | 湖北工业大学 | Konjac glucomannan-liposome composite nano food delivery system and preparation method and application thereof |
| CN112823666A (en) * | 2019-11-21 | 2021-05-21 | 江苏省农业科学院 | Nano-liposome simultaneously containing xanthophyll and cordyceps militaris alcohol extract and preparation method thereof |
| CN111035579A (en) * | 2019-12-20 | 2020-04-21 | 四川大学 | A kind of composite liposome/chitosan antioxidant preparation and preparation method thereof |
| CN111035579B (en) * | 2019-12-20 | 2022-04-19 | 四川大学 | Composite liposome/chitosan antioxidant preparation and preparation method thereof |
| CN114425038A (en) * | 2022-01-27 | 2022-05-03 | 沈阳信康药物研究有限公司 | 20(S) -PPD liposome emulsion complex oral administration preparation and preparation method and application thereof |
| CN114425038B (en) * | 2022-01-27 | 2023-03-10 | 沈阳信康药物研究有限公司 | 20 (S) -PPD liposome emulsion complex oral administration preparation and preparation method and application thereof |
| CN118948662A (en) * | 2024-07-26 | 2024-11-15 | 王叔和生物医药(武汉)有限公司 | A transdermal VC ethyl ether liposome emulsion and its preparation method and application |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101816632B (en) | 2012-08-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20210251948A1 (en) | Nanoemulsion hydrophobic substances | |
| van Hoogevest et al. | Phospholipids in cosmetic carriers | |
| Lin et al. | Combination of calcipotriol and methotrexate in nanostructured lipid carriers for topical delivery | |
| Fang et al. | Enhancement of the transdermal delivery of catechins by liposomes incorporating anionic surfactants and ethanol | |
| RU2462236C2 (en) | Liposomal nanocapsule | |
| WO2020028694A1 (en) | Liposomal compositions and methods of use | |
| CN101816632A (en) | Composite functional liposome and preparation method and application thereof | |
| Wang et al. | Oil-in-oil-in-water pre-double emulsions stabilized by nonionic surfactants and silica particles: A new approach for topical application of rutin | |
| JP6580018B2 (en) | Transparent lotion | |
| KR102177196B1 (en) | Nanoparticle multi-layered lamellar niosomes which is formed by nanoparticlation after being formed large niosomes in a supercritical state and cosmetic composition thereof | |
| Manosroi et al. | Transdermal absorption enhancement of rice bran bioactive compounds entrapped in niosomes | |
| Behtash et al. | New generation of fluconazole: a review on existing researches and technologies | |
| KR20070074223A (en) | Base composition which nanoencapsulates high concentration of idebenone, preparation method thereof, and cosmetics containing same | |
| Tarnowska et al. | The effect of vehicle on skin absorption of Mg2+ and Ca2+ from thermal spring water | |
| Abdelalim et al. | Oleosomes encapsulating sildenafil citrate as potential topical nanotherapy for palmar plantar erythrodysesthesia with high ex vivo permeation and deposition | |
| KR102044908B1 (en) | High natural oil content nano emulsion composition improved clarity, and cosmetic composition comprising the same, and method for preparing same | |
| Setapar et al. | Nanotechnology for the preparation of cosmetics using plant-based extracts | |
| DE4021083A1 (en) | Phospholipid formulations for medicinal and cosmetic baths - contg. phosphatidyl choline, oil component e.g. wax ester, alcohol, stabiliser, active ingredient and opt. auxiliaries | |
| KR20190102753A (en) | elastic liposome composition for accelerating skin absorption, elastic liposome containing thereof and manufacturing method thereof | |
| US20240226060A1 (en) | Topical liposome polyphenol compositions for treating and preventing various skin disorders and methods of preparation thereof | |
| JP6959596B2 (en) | Topical skin agents and skin barrier function improvers | |
| IT202000004450A1 (en) | Topical composition including cannabidiol | |
| CN106821789A (en) | A kind of preparation method of B B-complex nourishing cream and its liposomal thing | |
| JP2016056198A (en) | Cosmetic | |
| Jindal et al. | Lipid nanocarriers for dermal delivery of lutein |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120822 Termination date: 20130423 |