CN101810576B - Puerarin self-microemulsion composition based on mixed oil and preparation method thereof - Google Patents
Puerarin self-microemulsion composition based on mixed oil and preparation method thereof Download PDFInfo
- Publication number
- CN101810576B CN101810576B CN2010101578699A CN201010157869A CN101810576B CN 101810576 B CN101810576 B CN 101810576B CN 2010101578699 A CN2010101578699 A CN 2010101578699A CN 201010157869 A CN201010157869 A CN 201010157869A CN 101810576 B CN101810576 B CN 101810576B
- Authority
- CN
- China
- Prior art keywords
- puerarin
- self
- microemulsion
- emulsifier
- microemulsion composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 title claims abstract description 105
- 239000004530 micro-emulsion Substances 0.000 title claims abstract description 104
- RXUWDKBZZLIASQ-UHFFFAOYSA-N Puerarin Natural products OCC1OC(Oc2c(O)cc(O)c3C(=O)C(=COc23)c4ccc(O)cc4)C(O)C(O)C1O RXUWDKBZZLIASQ-UHFFFAOYSA-N 0.000 title claims abstract description 102
- 239000000203 mixture Substances 0.000 title claims abstract description 63
- 238000002360 preparation method Methods 0.000 title description 20
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 78
- 239000002245 particle Substances 0.000 claims abstract description 27
- 239000003921 oil Substances 0.000 claims description 74
- 239000007957 coemulsifier Substances 0.000 claims description 39
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 23
- 239000012895 dilution Substances 0.000 claims description 21
- 238000010790 dilution Methods 0.000 claims description 21
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 20
- -1 polyoxyethylene Polymers 0.000 claims description 20
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 17
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 17
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 17
- 239000005642 Oleic acid Substances 0.000 claims description 17
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 17
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 17
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 17
- WECGLUPZRHILCT-GSNKCQISSA-N 1-linoleoyl-sn-glycerol Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@@H](O)CO WECGLUPZRHILCT-GSNKCQISSA-N 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- 239000004359 castor oil Substances 0.000 claims description 12
- 235000019438 castor oil Nutrition 0.000 claims description 12
- 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 12
- STORWMDPIHOSMF-UHFFFAOYSA-N decanoic acid;octanoic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCC(O)=O.CCCCCCCCCC(O)=O STORWMDPIHOSMF-UHFFFAOYSA-N 0.000 claims description 11
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical class CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 4
- 229960003511 macrogol Drugs 0.000 claims description 4
- 239000007901 soft capsule Substances 0.000 claims description 4
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 3
- FMMOOAYVCKXGMF-MURFETPASA-N ethyl linoleate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC FMMOOAYVCKXGMF-MURFETPASA-N 0.000 claims description 3
- 229940031016 ethyl linoleate Drugs 0.000 claims description 3
- FMMOOAYVCKXGMF-UHFFFAOYSA-N linoleic acid ethyl ester Natural products CCCCCC=CCC=CCCCCCCCC(=O)OCC FMMOOAYVCKXGMF-UHFFFAOYSA-N 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 claims description 3
- 229920002651 Polysorbate 85 Polymers 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 229940041672 oral gel Drugs 0.000 claims description 2
- 229940113171 polysorbate 85 Drugs 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 25
- 239000000839 emulsion Substances 0.000 abstract description 13
- 238000010521 absorption reaction Methods 0.000 abstract description 12
- 229940079593 drug Drugs 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 4
- 239000006185 dispersion Substances 0.000 abstract description 2
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 239000008346 aqueous phase Substances 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 238000009472 formulation Methods 0.000 description 14
- 230000009286 beneficial effect Effects 0.000 description 9
- 238000005259 measurement Methods 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 241000700159 Rattus Species 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229920001213 Polysorbate 20 Polymers 0.000 description 4
- 230000003203 everyday effect Effects 0.000 description 4
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
- 229940068977 polysorbate 20 Drugs 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 235000010575 Pueraria lobata Nutrition 0.000 description 2
- 241000219781 Pueraria montana var. lobata Species 0.000 description 2
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- ZQSIJRDFPHDXIC-UHFFFAOYSA-N daidzein Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(O)=CC=C2C1=O ZQSIJRDFPHDXIC-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 229930003944 flavone Natural products 0.000 description 2
- 150000002212 flavone derivatives Chemical class 0.000 description 2
- 235000011949 flavones Nutrition 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- GOMNOOKGLZYEJT-UHFFFAOYSA-N isoflavone Chemical compound C=1OC2=CC=CC=C2C(=O)C=1C1=CC=CC=C1 GOMNOOKGLZYEJT-UHFFFAOYSA-N 0.000 description 2
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 description 2
- 235000008696 isoflavones Nutrition 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000012875 nonionic emulsifier Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 206010061373 Sudden Hearing Loss Diseases 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 238000003916 acid precipitation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000004064 cosurfactant Substances 0.000 description 1
- 235000007240 daidzein Nutrition 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 238000000703 high-speed centrifugation Methods 0.000 description 1
- 230000036732 histological change Effects 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000001865 kupffer cell Anatomy 0.000 description 1
- 235000021374 legumes Nutrition 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000000593 microemulsion method Methods 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 210000004279 orbit Anatomy 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000013595 supernatant sample Substances 0.000 description 1
- 239000010729 system oil Substances 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a puerarin self-microemulsion composition, which consists of puerarin, mixed oil, an emulsifier and an auxiliary emulsifier by weight percent, wherein the puerarin accounts for 0.5-5 percent; the mixed oil accounts for 36-61 percent; the emulsifier accounts for 10-50 percent; and the auxiliary emulsifier accounts for 5-30 percent. The puerarin self-microemulsion composition prepared in the invention not only solves the problems of the traditional emulsion such as large particle size, and poor stability, large storage volume and the like due to existence of the aqueous phase, but also improves the solubility and dispersion of puerarin, increases the in vivo absorption of drugs, and enhances the bioavailability. The invention has the advantages of low viscosity, stable quality and the like, and can improve the drug absorption, enhance the bioavailability and reduce the toxic and side effects.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of puerarin self-microemulsion composition and preparation method thereof, particularly a kind of self-microemulsion method for preparing that can reduce emulsifying agent use amount in the self-microemulsion system.
Technical background
Puerarin (puerarin) is from legume pueraria lobata (puerarialobata), to extract, separate the effective ingredient isoflavone aglycone that obtains, and chemistry is called 4,7-dihydroxy-8-β-D-glucone isoflavone.Clinical research shows that puerarin can coronary artery dilator, and protection global ischemia cardiac muscle and myocardial ischemia reperfusion injury reduce the acute myocardial infarction area, reduce myocardial oxygen consumption, prevent platelet adhesion, gathering and formation.As vasodilator, puerarin can be used for treating coronary heart disease, angina pectoris and heart and brain circulatory disturbance diseases associated and arteria retina and diseases such as vein obstruction, sudden deafness.Because puerarin water solublity extreme difference, oral administration biaavailability is extremely low, is restricted so puerarin oral preparation is used.Existing market puerarin common formulations is an injection; Commercially available said puerarin oral dosage form " puerarin sheet " and " puerarin soft capsule " effective ingredient are " daidzein "; And drug administration by injection uses inconvenience, independently administration of patient, poor compliance and costing an arm and a leg.Therefore, solve puerarin oral and absorb the key that problem just becomes the clinical practice of expansion puerarin.
Microemulsion is by oil phase, water and emulsifying agent and the spontaneous by a certain percentage a kind of outward appearance clear that forms of co-emulsifier, Thermodynamically stable, optical isotropy, low viscosity, the size droplet diameter mixed system at 10-100nm; As the oral drugs carrier; Microemulsion can increase dissolubility, the raising bioavailability of insoluble drug; Preparation is simple, does not need the external force effect, and prescription rationally can spontaneously form.Self-microemulsion is homogeneous, the clear solution that is formed by oil, emulsifying agent and co-emulsifier, oral back meet body fluid can spontaneous formation size droplet diameter under gastrointestinal is wriggled the microemulsion that is 10-100nm.Patent application: 200310113509.9 have reported a kind of puerarin oral preparation; Its composition also comprises oil, surfactant, cosurfactant; We carry out granularmetric analysis to the listed prescription of this patent working example; The result shows that the prescription particle diameter in the 100-1000nm scope, should not belong to self-microemulsion and microemulsion category.Chinese patent 02135329.8 has been reported a kind of puerarin oral preparation and preparation method thereof; Though its prescription also has phospholipid, polyoxyethylene sorbitan monoleate in forming, this oral formulations is a solid puerarin-phosphatide disperse object of utilizing electric charge migration, hydrogen bond action and Van der Waals force between phospholipid and the puerarin to form, and polyoxyethylene sorbitan monoleate is solubilizing agent; And phospholipid, polyoxyethylene sorbitan monoleate are to use as emulsifying agent in the microemulsion self-microemulsion; Therefore this oral formulations does not belong to microemulsion and self-microemulsion category, patent application: 200510025418.9 have reported a kind of self-microemulsion puerarin oral preparation, and this patent gives an actual example 2; The oil phase mass percent is 55%; The prescription particle diameter is 341.2nm, does not belong to the microemulsion category equally, and this patent right qualification oil phase mass percent is 5-35%.Patent application: 200510038570.0 have reported puerarin self-emulsifying microemulsified composition and preparation method thereof; This patent report be a kind of microemulsion concentrated solution, its prescription medium oil, emulsifying agent and co-emulsifier can not dissolve each other, and must add could form the homogeneous system after entry forms microemulsion (microemulsion concentrated solution); The product stability deleterious impact is given in the adding of water simultaneously; According to the definition of self-microemulsion in the pharmaceutics, the adding of water is arranged in this microemulsion concentrated solution, do not belong to the self-microemulsion system.Chinese patent 03133574.8 has been reported a kind of Radix Puerariae flavone self-emulsification soft capsules and preparation method thereof, and the Radix Puerariae flavone self-microemulsion of its preparation does not belong to the category of microemulsion equally at the Emulsion that can form under ambient temperature and the gentle agitation about 5 μ m.
Microemulsion and self-microemulsion are very huge as its development of pharmaceutical carrier and application potential, but still have many problems.Though emulsifying agent is generally all selected the nonionic emulsifier of low toxicity, good biocompatibility for use in microemulsion and the self-microemulsion, because the emulsifying agent of microemulsion and self-microemulsion middle and high concentration and co-emulsifier use, it still has certain zest to gastrointestinal mucosa; Whole body there is chronic toxic and side effects [Liu star; Wang Yiming, Luo Guoan. the progress of self-microemulsion drug delivery system, pharmacy progress; 2006,30 (9): 397-400].In addition; If the absorbed words of surfactant may be destroyed storehouse Schwann Cells (kupffer cells) [Nadai T., kondo R.; TatematusAand Sezaki H.Drug-induced histological changes and its consequences on thepermeability of the small intestinal mucosa.I.EDTA; Tetracycline, and sodiumlaurylsulfate.Chem Pharm Bull, 1139-1144 (1972)].At present both at home and abroad; Relevant microemulsion and self-microemulsion patent and document are more; But abroad except that minority self-micro emulsion formulations such as early stage sandimmun neoral successfully go on the market; Rarely have the successful listing of microemulsion and self-micro emulsion formulation in recent years, the domestic market is blank especially, and one of its most important reason brings the risk of untoward reaction bigger just because of a large amount of uses of emulsifying agent and co-emulsifier in microemulsion and the self-micro emulsion formulation.The inventor finds in research process, with single oil during as the oil phase of self-microemulsion system, if when obtaining the self-microemulsion system of ability dilution; Oil: blended emulsifier (emulsifying agent and co-emulsifier) generally all was less than or equal to 1: 9, and pertinent literature also shows that most of self-microemulsion emulsifying agents of bibliographical information, co-emulsifier consumption all are 90%; Oil phase only accounts for about 10% [Li Zhaoming; Chen Zhi, Yu Feng etc. the progress of self-micro emulsion formulation, Shandong medicine thing Qinlu Pharmaceutical Affairs; 2009 vol.28, No.2:98-100].As previously mentioned; Though the toxicity of nonionic emulsifier is low than anion emulsifier in microemulsion and the self-micro emulsion formulation, a large amount of use still has certain potential toxicity; So the microemulsion and the self-micro emulsion formulation of a success, the use amount of its emulsifying agent must be in the safety scope.Like polyoxyethylene sorbitan monoleate, polysorbate 20; People's every day oral safe dose limit be 25mg/kg [Luo Mingsheng, Gao Tianhui. pharmaceutic adjuvant is complete works of, Sichuan science and technology publishing house; 1993.]; Body weight is by 60kg for each person, takes polyoxyethylene sorbitan monoleate, the polysorbate 20 of 1.5 grams so for each person every day at most, and microemulsion and the contained polyoxyethylene sorbitan monoleate of being processed by polyoxyethylene sorbitan monoleate, polysorbate 20 so of self-micro emulsion formulation dosage every day, polysorbate 20 must be in 1.5 grams; Patent application: 200510025418.9 embodiment, 4 puerarin 0.5g, polyoxyethylene sorbitan monoleate 4g, ethanol 4g; Isopropyl myristate 1.5g; Oil phase: blended emulsifier (polyoxyethylene sorbitan monoleate+ethanol) is 1.5: 8, because of the oral formulations of puerarin does not have successfully listing, if to contain the yufeng ningxin tablets, yufeng ningxin pian of puerarin; Puerarin per day for adults dose is 190mg; If with these patent working example 4 listed prescription administrations, obeying polyoxyethylene sorbitan monoleate for each person every day is 1.52g, has exceeded the limit 1.5g of the oral safe dose of polyoxyethylene sorbitan monoleate.So microemulsion and self-micro emulsion formulation must reduce the consumption of emulsifying agent as far as possible under certain drug loading; The consumption that how to reduce emulsifying agent, co-emulsifier in microemulsion and the self-micro emulsion formulation has become the emphasis of pharmaceutics research, and relating to puerarin self-microemulsion related patent U.S. Patent No. and document does not have with the report of miscella as self-microemulsion system oil phase.Therefore, how to select suitable prescription, seek the emulsifying agent and the co-emulsifier of high-efficiency low-toxicity, try to explore to optimize the technology of preparation microemulsion and self-microemulsion, the consumption that reduces surfactant emulsion agent and co-emulsifier just becomes microemulsion and self-microemulsion drug-delivery preparation development key.
Summary of the invention
One of the object of the invention significantly improves puerarin self-microemulsion system fuel load in order to provide a kind of exactly, thereby reduces the method for emulsifying agent and co-emulsifier use amount in the puerarin self-microemulsion system.
Another object of the present invention is exactly for the method for preparing of the puerarin self-microemulsion composition that a kind of steady quality, bioavailability are high, toxicity is little is provided.
The object of the invention is realized through following technical scheme:
Puerarin self-microemulsion composition involved in the present invention comprises puerarin, miscella, emulsifying agent, co-emulsifier, and its mass percent is:
Puerarin 0.5-5%
Miscella 36-61%
Emulsifying agent 10-50%
Co-emulsifier 5-30%
Compared with prior art, oil phase is brought up to 36-61% by 5%-35% among the present invention, because of self-microemulsion is made up of oil phase, emulsifying agent, co-emulsifier; Oil phase biggest quality percentage ratio is 35% in the prior art; Mean that the total amount minimum of emulsifying agent and co-emulsifier is 65% in this invention, the oil phase largest percentage is 61% among the present invention, and just the total amount of emulsifying agent and co-emulsifier is reduced to 39%; The two is compared, and has significantly reduced the consumption of emulsifying agent and co-emulsifier.
The miscella of the present invention mixture that to be the oil phase that dissolves each other 1 form with oil phase 2.Oil phase 1 is a MCT Oil, comprises Capterx300; Captex355 (U.S. Abitec Company products); GTCC (Lanxi, Zhejiang thing beautifies worker's company limited product); Labrafac CC (French Jia Fasai (Gattefoss é) Company products); MCT oil (Chinese Tieling Beiya Medical Oil Co., Ltd. product); Miglyol 812N (German husky rope (Sasol) Company products); NeobeeM5 (U.S. Si Taipan (Stepan) Company products), the present invention is preferably Miglyol 812N.Oil phase 2 is selected from a kind of or its mixture in glyceryl linoleate (Masine 35-1), oleic acid, the Ethyl linoleate.
Emulsifying agent of the present invention is selected from polyoxyethylene castor oil, a kind of or its mixture in polyoxyethylene hydrogenated Oleum Ricini, polyoxyethylene sorbitan monoleate, the polysorbate 85.
Co-emulsifier of the present invention is selected from a kind of or its mixture in TC, PEG400 (PEG400), Macrogol 200 (PEG200), Macrogol 600 (PEG600), isopropyl alcohol and the propylene glycol.
The method for preparing of puerarin self-microemulsion composition involved in the present invention is specially: the oil phase 1 and the oil phase 2 of recipe quantity mixed, stirs, and subsequent use; In proportion, emulsifying agent and co-emulsifier are mixed, stir; With the puerarin of recipe quantity at 40 ℃ of-50 ℃ of following ultrasonic dissolutions in the mixed liquor of emulsifying agent and co-emulsifier, after the cooling, add subsequent use mixing oil phase, magnetic agitation is even, promptly gets puerarin self-microemulsion composition.
Take for the ease of the patient, can give medically acceptable carrier, adopt method well known in the art to be prepared as tablet, capsule, soft capsule, oral liquid, oral gel or granule etc. puerarin self-microemulsion composition of the present invention.
Described medical science carrier is meant in the pharmaceutical field conventional pharmaceutical carrier, like diluent, excipient such as water etc., and adsorbent such as mannitol, citric acid, microcrystalline Cellulose etc., binding agent, like polyvinylpyrrolidone etc., lubricant is like Pulvis Talci, magnesium stearate etc.
The present invention has following beneficial effect:
The puerarin self-microemulsion composition of the present invention preparation can solve on the one hand traditional Emulsion particle diameter big, since water exist the emulsion stability that causes poor, store problems such as volume is big; The dissolubility and the dispersion of puerarin have been improved on the other hand; Increase interior absorption of body of medicine, improve bioavailability.What is more important; Research process of the present invention is found; When adopting single oil phase to prepare self-microemulsion; Oil phase and blended emulsifier (emulsifying agent+co-emulsifier) ratio is generally less than or equals 1: 9 in the self-microemulsion system, and the present invention adopts and mixes oil phase as self-microemulsion system medium oil phase time, and the ratio of oil phase and blended emulsifier can be brought up to 4-6: 6-4; Significantly reduced the ratio of emulsifying agent in the self-microemulsion system, thereby reduced self-micro emulsion formulation because a large amount of uses of emulsifying agent bring the risk of untoward reaction.Compared with prior art, oil phase is brought up to 36-61% by 5%-35% among the present invention, because of self-microemulsion is made up of oil phase, emulsifying agent, co-emulsifier; Oil phase biggest quality percentage ratio is 35% in the prior art; Mean that the total amount minimum of emulsifying agent and co-emulsifier is 65% in this invention, the oil phase largest percentage is 61% among the present invention, and just the total amount of emulsifying agent and co-emulsifier is reduced to 39%; The two is compared, and has significantly reduced the consumption of emulsifying agent and co-emulsifier.Simultaneously; As a kind of new pharmaceutical carrier; The present invention is the appearance transparent formed of oil, emulsifying agent, co-emulsifier, the mixture of good fluidity, and water dilutes in back 8 hours particle diameter, puerarin content not to be had significance and change, so the present invention possesses characteristics such as low viscosity, steady quality; And improve drug absorption, improve bioavailability, reduce toxicity.
Description of drawings
Fig. 1 is the particle size distribution figure of puerarin self-microemulsion composition after the water dilution of the embodiment of the invention 5 preparations.
Fig. 2 is that puerarin self-microemulsion composition and the puerarin suspension of the embodiment of the invention 8 preparation is at rat vivo medicine concentration-time plot.
The specific embodiment
Below in conjunction with accompanying drawing embodiments of the invention are elaborated: present embodiment provided detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment being to implement under the prerequisite with technical scheme of the present invention.
Prescription component and percentage by weight thereof:
Puerarin 3.5%, polyoxyethylene sorbitan monoleate 29.0%, polyoxyethylene castor oil 14.5%, propylene glycol 14.5%, MCT oil 28.9%, oleic acid 9.6%
Puerarin self-microemulsion composition preparation technology in the present embodiment is: the MCT oil and the oleic acid of recipe quantity mixed, stirs, and subsequent use; In proportion, with polyoxyethylene sorbitan monoleate, polyoxyethylene castor oil and mixed with propylene glycol, stir; With the puerarin of recipe quantity at 40 ℃ of-50 ℃ of following ultrasonic dissolutions in the mixed liquor of polyoxyethylene sorbitan monoleate, polyoxyethylene castor oil and propylene glycol, after the cooling, add subsequent use MCT oil and oleic acid miscella, stir, promptly get.
After 100 times of the water dilutions, adopting Ma Erwen granularity potential measurement appearance (Nano-ZS90) to measure particle size distribution is 18.99nm.
The beneficial effect of present embodiment is: (1) is oil phase when adopting MCT oil or oleic acid respectively; Polyoxyethylene castor oil or polyoxyethylene sorbitan monoleate are emulsifying agent, when propylene glycol is co-emulsifier, if when obtaining the self-microemulsion of ability dilution; Oil: the ratio of blended emulsifier is less than or equals 1: 9; Present embodiment adopts MCToil: the miscella of oleic acid=3: 1 is done oil phase, oil phase: the ratio of blended emulsifier is 4: 6, has obviously reduced the quality of blended emulsifier.(2) puerarin dissolves compound for shipwreck property, and [king becomes document, Liu Yuling, the dissolubility of the outstanding puerarin of paddy generation and the research of complexation hydrotropy thereof; Chinese Pharmaceutical Journal, 1993,28 (5): 294] report that puerarin dissolubility in water is about 4.62mg/mL, the content of puerarin in self-emulsion composition is 35mg/g in the present embodiment, has significantly improved the dissolubility of puerarin; (3) because particle diameter is little, the medicine degree of scatter is high, thereby has increased the degree of absorption of medicine, improves its bioavailability.
Embodiment 2
Prescription component and percentage by weight thereof:
Puerarin 1.5%, polyoxyethylene castor oil 32.8%, isopropyl alcohol 16.5%, GTCC 24.6%, glyceryl linoleate 24.6%.
Method for preparing is with embodiment 1.After 100 times of the water dilutions, adopting Ma Erwen granularity potential measurement appearance to measure particle size distribution is 34.07nm.
The beneficial effect of present embodiment is: (1) is oil phase when adopting GTCC or glyceryl linoleate respectively; Polyoxyethylene castor oil is an emulsifying agent, when isopropyl alcohol is co-emulsifier, if when obtaining the self-microemulsion of ability dilution; Oil: the ratio of blended emulsifier is less than or equals 1: 9; Present embodiment adopts GTCC: the miscella of glyceryl linoleate=1: 1 is done oil phase, oil phase: the ratio of blended emulsifier is 5: 5, has significantly reduced the quality of blended emulsifier.(2) content of puerarin in self-emulsion composition is 15mg/g in the present embodiment, has significantly improved the dissolubility of puerarin.(3) because particle diameter is little, the medicine degree of scatter is high, thereby has increased the degree of absorption of medicine, improves its bioavailability.
Embodiment 3
Prescription is formed and percentage by weight:
Puerarin 2.0%, polyoxyethylene hydrogenated Oleum Ricini 26.1%, TC 13.1%, glyceryl linoleate 29.4%, Miglyol 812N29.4%.
Method for preparing is with embodiment 1.After 100 times of the water dilutions, adopting Ma Erwen granularity potential measurement appearance to measure particle size distribution is 46.98nm.
The beneficial effect of present embodiment is: (1) is oil phase when adopting Miglyol 812N or glyceryl linoleate respectively; Polyoxyethylene hydrogenated Oleum Ricini is an emulsifying agent; When TC is co-emulsifier; If when obtaining the self-microemulsion of ability dilution, oil: the ratio of blended emulsifier is less than or equals 1: 9, present embodiment adopts Miglyol 812N: the miscella of glyceryl linoleate=1: 1 is done oil phase; Oil phase: the ratio of blended emulsifier is 6: 4, has significantly reduced the quality of blended emulsifier.(2) puerarin is that shipwreck is dissolved compound, and dissolubility is about 4.62mg/mL in water, and the content of puerarin in self-emulsion composition is 20mg/g in the present embodiment, has significantly improved the dissolubility of puerarin.(3) because particle diameter is little, the medicine degree of scatter is high, thereby has increased the degree of absorption of medicine, improves its bioavailability.
Embodiment 4
Prescription component and percentage by weight thereof:
Puerarin 3.0%, polyoxyethylene hydrogenated Oleum Ricini 32.3%, TC 16.1%, glyceryl linoleate 24.3%, Labrafac cc 24.3%.
Method for preparing is with embodiment 1.After 100 times of the water dilutions, adopting Ma Erwen granularity potential measurement appearance to measure particle size distribution is 44.72nm.
The beneficial effect of present embodiment is: (1) is oil phase when adopting Labrafac cc or glyceryl linoleate respectively; Polyoxyethylene hydrogenated Oleum Ricini is an emulsifying agent; When TC is co-emulsifier; If when obtaining the self-microemulsion of ability dilution, oil: the ratio of blended emulsifier is less than or equals 1: 9, present embodiment adopts Labrafac cc: the miscella of glyceryl linoleate=1: 1 is done oil phase; Oil phase: the ratio of blended emulsifier is 5: 5, has significantly reduced the quality of blended emulsifier.(2) puerarin is that shipwreck is dissolved compound, and dissolubility is about 4.62mg/mL in water, and the content of puerarin in self-emulsion composition is 32mg/g in the present embodiment, has significantly improved the dissolubility of puerarin.(3) because particle diameter is little, the medicine degree of scatter is high, thereby has increased the degree of absorption of medicine, improves its bioavailability.
Prescription component and percentage by weight thereof:
Puerarin 4.3%, polyoxyethylene hydrogenated Oleum Ricini 38.2%, TC 19.1%, glyceryl linoleate 19.2%, NeobeeM519.2%.
Method for preparing is with embodiment 1.After 100 times of the water dilutions, adopting Ma Erwen granularity potential measurement appearance to measure particle size distribution is 38.29nm.The particle diameter of dilution back microemulsion is 0,1, and particle diameter is respectively 38.29nm, 38.33nm, 38.27nm, 38.31nm, 38.35nm, no significance variation in 2,4,8 hours.
The beneficial effect of present embodiment is: (1) is oil phase when adopting NeobeeM5 or glyceryl linoleate respectively; Polyoxyethylene hydrogenated Oleum Ricini is an emulsifying agent; When TC is co-emulsifier; If when obtaining the self-microemulsion of ability dilution, oil: the ratio of blended emulsifier is less than or equals 1: 9, present embodiment adopts NeobeeM5: the miscella of glyceryl linoleate=1: 1 is done oil phase; Oil phase: the ratio of blended emulsifier is 4: 6, has significantly reduced the quality of blended emulsifier.(2) puerarin is that shipwreck is dissolved compound, and dissolubility is about 4.62mg/mL in water, and the content of puerarin in self-emulsion composition is 45mg/g in the present embodiment, has significantly improved the dissolubility of puerarin.(3) because particle diameter is little, the medicine degree of scatter is high, thereby has increased the degree of absorption of medicine, improves its bioavailability.
Embodiment 6
Prescription is formed and mass percent:
Puerarin 3.0%, polyoxyethylene sorbitan monoleate 17.8%, polyoxyethylene castor oil 17.8%, propylene glycol 17.8%, Miglyol 812N 21.8%, oleic acid 21.8%.
Method for preparing is with embodiment 1.After 100 times of the water dilutions, adopting Ma Erwen granularity potential measurement appearance to measure particle size distribution is 23.43nm.The particle diameter of dilution back microemulsion is 0,1, is respectively 24.43nm, 24.41nm, 24.44nm, 24.41nm, 24.45nm, no significance variation in 2,4,8 hours.
The beneficial effect of present embodiment is: (1) is oil phase when adopting Miglyol 812N or oleic acid respectively; Polyoxyethylene sorbitan monoleate or polyoxyethylene castor oil are emulsifying agent, when propylene glycol is co-emulsifier, if when obtaining the self-microemulsion of ability dilution; Oil: the ratio of blended emulsifier is less than or equals 1: 9; Present embodiment adopts Miglyol 812N: the miscella of oleic acid=1: 1 is done oil phase, oil phase: the ratio of blended emulsifier is 4.5: 5.5, has obviously reduced the quality of blended emulsifier.(2) puerarin is that shipwreck is dissolved compound, and dissolubility is about 4.62mg/mL in water, and the content of puerarin in self-emulsion composition is 30mg/g in the present embodiment, has significantly improved the dissolubility of puerarin.(3) because particle diameter is little, the medicine degree of scatter is high, thereby has increased the degree of absorption of medicine, improves its bioavailability.
Embodiment 7
Prescription is formed and percentage by weight:
Puerarin 2.5%, polyoxyethylene sorbitan monoleate 26.0%, polyoxyethylene castor oil 13.0%, propylene glycol 19.5%, Captex355 19.5%, oleic acid 19.5%.
Method for preparing is with embodiment 1.After 100 times of the water dilutions, adopting Ma Erwen granularity potential measurement appearance to measure particle size distribution is 23.97nm
The beneficial effect of present embodiment is: (1) is oil phase when adopting Captex355 or oleic acid respectively; Polyoxyethylene sorbitan monoleate or polyoxyethylene castor oil are emulsifying agent, when propylene glycol is co-emulsifier, if when obtaining the self-microemulsion of ability dilution; Oil: the ratio of blended emulsifier is less than or equals 1: 9; Present embodiment adopts Captex355: the miscella of oleic acid=1: 1 is done oil phase, oil phase: the ratio of blended emulsifier is 4: 6, has obviously reduced the quality of blended emulsifier.(2) puerarin is that shipwreck is dissolved compound, and bibliographical information puerarin dissolubility in water is about 4.62mg/mL, and the content of puerarin in self-emulsion composition is 25mg/g in the present embodiment, has significantly improved the dissolubility of puerarin; (3) because particle diameter is little, the medicine degree of scatter is high, thereby has increased the degree of absorption of medicine, improves its bioavailability.
Embodiment 8
Prescription component and percentage by weight thereof:
Puerarin 5.0%, polyoxyethylene sorbitan monoleate 38.0%, propylene glycol 19.0%, Miglyol 812N 19.0%, oleic acid 19.0%.
Method for preparing is with embodiment 1.After 100 times of the water dilutions, adopting Ma Erwen granularity potential measurement appearance to measure particle size distribution is 17.41nm
The beneficial effect of present embodiment is: (1) is oil phase when adopting Miglyol 812N or oleic acid respectively; Polyoxyethylene sorbitan monoleate is an emulsifying agent, when propylene glycol is co-emulsifier, if when obtaining the self-microemulsion of ability dilution; Oil: the ratio of blended emulsifier is less than or equals 1: 9; Present embodiment adopts Miglyol 812N: the miscella of oleic acid=1: 1 is done oil phase, oil phase: the ratio of blended emulsifier is 4: 6, has obviously reduced the quality of blended emulsifier.(2) puerarin is that shipwreck is dissolved compound, and dissolubility is about 4.62mg/mL in water, and the content of puerarin in self-emulsion composition is 50mg/g in the present embodiment, has significantly improved the dissolubility of puerarin.(3) because particle diameter is little, the medicine degree of scatter is high, thereby has increased the degree of absorption of medicine, improves its bioavailability.
In order to estimate assimilation effect in the puerarin self-microemulsion composition body, we have carried out with the puerarin suspension is the puerarin self-microemulsion composition rat pharmacokinetic of reference preparation.Specific embodiments is following:
Get 50 of SD rats, be divided into 10 groups at random, 5 of every groups; The corresponding time point of every group, fasting can't help water 12 hours before the experiment, and single dose 60mg/kg irritates the invention preparation that stomach gives present embodiment 8; Different time points rat eye socket is got blood 1mL and is put in the calparine pipe before administration, after the administration; The centrifugal 10min of 3500rpm/min, separated plasma is preserved for use in subzero 20 ℃ of refrigerators.Rat feeding is after two weeks, and same single dose 60mg/kg irritates stomach and gives the puerarin suspension, after the administration by different time points last time get preserve in blood, separated plasma, the subzero 20 ℃ of refrigerators for use.
Plasma sample is analyzed: precision pipettes blood plasma 0.3mL, and the accurate 6% perchloric acid precipitation's albumen that adds mixes 3min on the eddy mixer, and 10000rpm/min high speed centrifugation 10min gets supernatant sample introduction 50 μ L, with puerarin concentration in the high-performance liquid chromatogram determination blood plasma.
Calculating relative bioavailability by AUC is 276.7%, sees Fig. 2.The result shows that puerarin self-microemulsion composition has significantly improved the puerarin oral bioavailability.
Claims (9)
1. a puerarin self-microemulsion composition is made up of puerarin, miscella, emulsifying agent, co-emulsifier, and its mass percentage content is:
Wherein said miscella is one or more the mixture in the MCT Oil that dissolves each other and glyceryl linoleate, oleic acid, the Ethyl linoleate; Its mass ratio is 1-3: 1, and wherein MCT Oil is Capterx300, Captex355; GTCC; Labrafac CC, MCT oil, Miglyol812N or NeobeeM5.
2. puerarin self-microemulsion composition according to claim 1 is characterized in that emulsifying agent is a polyoxyethylene castor oil, a kind of or its mixture in polyoxyethylene hydrogenated Oleum Ricini, polyoxyethylene sorbitan monoleate, the polysorbate 85.
3. puerarin self-microemulsion composition according to claim 1 is characterized in that: co-emulsifier is a kind of or its mixture in TC, PEG400, Macrogol 200, Macrogol 600, isopropyl alcohol and the propylene glycol.
4. puerarin self-microemulsion composition according to claim 1 is characterized in that: the mass ratio of emulsifying agent and co-emulsifier is 1-3: 1.
5. according to the described puerarin self-microemulsion composition of one of claim 1-4, it is characterized in that the component of said compositions is:
6. according to the described puerarin self-microemulsion composition of one of claim 1-4, it is characterized in that the component of said compositions is:
7. according to the described puerarin self-microemulsion composition of one of claim 1-4, it is characterized in that the component of said compositions is:
8. according to the method for preparing of one of claim 1-4 described puerarin self-microemulsion composition, may further comprise the steps:
(1) in the MCT Oil of recipe quantity and glyceryl linoleate, oleic acid, the Ethyl linoleate one or more are pressed 1-3: 1 mixed stirs;
(2) in 1-3: 1 ratio is mixed emulsifying agent and co-emulsifier, stirs;
(3) with the puerarin of recipe quantity at 40 ℃ of-50 ℃ of following ultrasonic dissolutions in the mixed liquor of emulsifying agent and co-emulsifier;
(4) above-mentioned mixed liquor is added in the miscella; Stir, promptly get puerarin self-microemulsion composition, when the water with arbitrary proportion is diluted to microemulsion; Its particle size distribution is between 10-100nm, and the microemulsion that obtains after dilution particle diameter in 8 hours does not have significance to be changed.
9. puerarin self-microemulsion composition according to claim 1 is characterized in that: said puerarin self-microemulsion composition can be made into capsule, soft capsule, tablet, oral liquid, oral gel or granule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101578699A CN101810576B (en) | 2010-04-28 | 2010-04-28 | Puerarin self-microemulsion composition based on mixed oil and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101578699A CN101810576B (en) | 2010-04-28 | 2010-04-28 | Puerarin self-microemulsion composition based on mixed oil and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101810576A CN101810576A (en) | 2010-08-25 |
| CN101810576B true CN101810576B (en) | 2012-03-21 |
Family
ID=42618040
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101578699A Expired - Fee Related CN101810576B (en) | 2010-04-28 | 2010-04-28 | Puerarin self-microemulsion composition based on mixed oil and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101810576B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101991533B (en) * | 2010-10-26 | 2012-12-19 | 西安力邦制药有限公司 | Puerarin liposome microsphere injection and preparation method thereof |
| CN102836140B (en) * | 2011-06-22 | 2015-03-18 | 鲁南制药集团股份有限公司 | Arctigenin micro-emulsion enteric soft capsule preparation |
| CN102847164B (en) * | 2012-08-15 | 2014-01-22 | 天津耀宇生物技术有限公司 | Application of chrysalis oil in improving small molecule drug bioavailability |
| CN107184587B (en) * | 2017-05-22 | 2021-05-18 | 河南科技大学 | 2-methoxyestradiol oral pharmaceutical composition, preparation method thereof and 2-methoxyestradiol soft capsule |
| CN113855631B (en) * | 2021-11-16 | 2022-12-20 | 海南大学 | Honokiol oral self-microemulsion and preparation method thereof |
| CN115737555B (en) * | 2022-05-20 | 2024-06-21 | 深圳海王医药科技研究院有限公司 | Cepharanthine self-microemulsion composition, preparation and preparation method thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1836664A (en) * | 2005-03-25 | 2006-09-27 | 江苏省中医药研究院 | Puerarin self-emulsifying microemulsified composition and its preparation method |
| CN1853643A (en) * | 2005-04-26 | 2006-11-01 | 上海医药工业研究院 | Composition of self-microemulsion puerarin oral preparation and use thereof |
| CN1907265A (en) * | 2006-08-29 | 2007-02-07 | 华东理工大学 | Self-micro-emulsifying composition comprising amphipathic polymer and process for its preparation |
-
2010
- 2010-04-28 CN CN2010101578699A patent/CN101810576B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN101810576A (en) | 2010-08-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101810576B (en) | Puerarin self-microemulsion composition based on mixed oil and preparation method thereof | |
| JP4073641B2 (en) | New cyclosporine preparation | |
| JP3391961B2 (en) | Cyclosporin-containing soft capsule composition | |
| CN101862306B (en) | New type slightly soluble oral medicine self-emulsification preparation and preparation method thereof | |
| JPH02121929A (en) | Pharmaceutical composition containing cyclosporin | |
| JP2002537317A (en) | Compositions and methods for improved delivery of hydrophobic therapeutic agents | |
| CN101596177B (en) | Coenzyme Q10 self-emulsifying composition, preparation method and application thereof | |
| JP2006519820A (en) | Impregnated powder for increasing bioavailability and / or solubility and method for producing the same | |
| JP2002505307A (en) | Pharmaceutical compositions and uses thereof | |
| JP2003500454A (en) | Substantially oil-free cyclosporin composition | |
| CN102415995B (en) | Oversaturated self-microemulsified progesterone composition and preparation method of same | |
| CN101229121B (en) | Penciclovir microemulsion gel preparation and preparation method thereof | |
| CN101390851A (en) | Double-cyclitol medicine composition containing surfactant and preparation method thereof | |
| CN101103962A (en) | Vinpocetine oral self-microemulsion drug delivery system and preparation method thereof | |
| CN101780037A (en) | Dipyridamole self-emulsifying medicament administration system and preparation method thereof | |
| CN101278912A (en) | Tetrandrine nanoemulsion injection and preparation method thereof | |
| CN105125489B (en) | Pharmaceutical composition comprising Debiopharm | |
| EP1151755B1 (en) | Pharmaceutical compositions comprising cyclosporin as active ingredient | |
| Xu et al. | Formulation and pharmacokinetic evaluation of tetracycline-loaded solid lipid nanoparticles for subcutaneous injection in mice | |
| CN103655470A (en) | Dutasteride self-microemulsion composition and preparation method thereof | |
| CN102319302B (en) | Total glucosides of paeony self-microemulsified soft capsule and preparation method thereof | |
| CN100584329C (en) | Anethol trithione soft capsule and its preparation method | |
| JP2003521495A (en) | Terbinafine-containing pharmaceutical composition | |
| Wang et al. | Preparation, in vitro and in vivo evaluation of a novel mitiglinide microemulsions | |
| CN101035511B (en) | Compositions forming non-lamellar dispersions |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120321 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |