CN100339067C - Nanometer emulsion and preparation method thereof - Google Patents
Nanometer emulsion and preparation method thereof Download PDFInfo
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- CN100339067C CN100339067C CNB031417388A CN03141738A CN100339067C CN 100339067 C CN100339067 C CN 100339067C CN B031417388 A CNB031417388 A CN B031417388A CN 03141738 A CN03141738 A CN 03141738A CN 100339067 C CN100339067 C CN 100339067C
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- 239000000839 emulsion Substances 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims description 20
- 238000004945 emulsification Methods 0.000 title claims description 7
- 239000003814 drug Substances 0.000 claims abstract description 23
- 239000012071 phase Substances 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000002552 dosage form Substances 0.000 claims abstract description 13
- 238000003756 stirring Methods 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 239000006184 cosolvent Substances 0.000 claims abstract description 6
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 6
- 230000001954 sterilising effect Effects 0.000 claims abstract description 6
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 5
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 5
- 239000008346 aqueous phase Substances 0.000 claims abstract description 4
- 238000001914 filtration Methods 0.000 claims abstract description 4
- 238000012856 packing Methods 0.000 claims abstract description 4
- 238000004659 sterilization and disinfection Methods 0.000 claims abstract description 4
- 239000007908 nanoemulsion Substances 0.000 claims description 30
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 18
- 239000003921 oil Substances 0.000 claims description 18
- 235000019198 oils Nutrition 0.000 claims description 16
- -1 fatty acid ester Chemical class 0.000 claims description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 229920002545 silicone oil Polymers 0.000 claims description 6
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 4
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 4
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 4
- 230000002421 anti-septic effect Effects 0.000 claims description 4
- 235000006708 antioxidants Nutrition 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 229960001631 carbomer Drugs 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
- 239000003925 fat Substances 0.000 claims description 4
- 235000019197 fats Nutrition 0.000 claims description 4
- 229930195729 fatty acid Natural products 0.000 claims description 4
- 239000000194 fatty acid Substances 0.000 claims description 4
- 239000000787 lecithin Substances 0.000 claims description 4
- 235000010445 lecithin Nutrition 0.000 claims description 4
- 229940067606 lecithin Drugs 0.000 claims description 4
- 229920001983 poloxamer Polymers 0.000 claims description 4
- 229920000136 polysorbate Polymers 0.000 claims description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 4
- 238000004137 mechanical activation Methods 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- 235000019737 Animal fat Nutrition 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- ZJJGPUQRMUBVBE-UHFFFAOYSA-N C(CCC)OC(=O)C1=CC=C(O)C=C1.[Ca] Chemical compound C(CCC)OC(=O)C1=CC=C(O)C=C1.[Ca] ZJJGPUQRMUBVBE-UHFFFAOYSA-N 0.000 claims description 2
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 claims description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 claims description 2
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims description 2
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 claims description 2
- KWKVAGQCDSHWFK-VNKDHWASSA-N Methyl sorbate Chemical compound COC(=O)\C=C\C=C\C KWKVAGQCDSHWFK-VNKDHWASSA-N 0.000 claims description 2
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 229940087168 alpha tocopherol Drugs 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
- 235000015165 citric acid Nutrition 0.000 claims description 2
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 claims description 2
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
- 238000011049 filling Methods 0.000 claims description 2
- 229960002449 glycine Drugs 0.000 claims description 2
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims description 2
- 229960000367 inositol Drugs 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 239000002480 mineral oil Substances 0.000 claims description 2
- 235000010446 mineral oil Nutrition 0.000 claims description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
- 235000002949 phytic acid Nutrition 0.000 claims description 2
- 239000000467 phytic acid Substances 0.000 claims description 2
- 229940068041 phytic acid Drugs 0.000 claims description 2
- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical compound [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 claims description 2
- 229940043349 potassium metabisulfite Drugs 0.000 claims description 2
- 235000010263 potassium metabisulphite Nutrition 0.000 claims description 2
- 229960004063 propylene glycol Drugs 0.000 claims description 2
- 235000013772 propylene glycol Nutrition 0.000 claims description 2
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims description 2
- 238000007789 sealing Methods 0.000 claims description 2
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 2
- 235000010378 sodium ascorbate Nutrition 0.000 claims description 2
- 229960005055 sodium ascorbate Drugs 0.000 claims description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 2
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims description 2
- PESXGULMKCKJCC-UHFFFAOYSA-M sodium;4-methoxycarbonylphenolate Chemical compound [Na+].COC(=O)C1=CC=C([O-])C=C1 PESXGULMKCKJCC-UHFFFAOYSA-M 0.000 claims description 2
- IXMINYBUNCWGER-UHFFFAOYSA-M sodium;4-propoxycarbonylphenolate Chemical compound [Na+].CCCOC(=O)C1=CC=C([O-])C=C1 IXMINYBUNCWGER-UHFFFAOYSA-M 0.000 claims description 2
- 235000010199 sorbic acid Nutrition 0.000 claims description 2
- 239000004334 sorbic acid Substances 0.000 claims description 2
- 229940075582 sorbic acid Drugs 0.000 claims description 2
- 229960000984 tocofersolan Drugs 0.000 claims description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 2
- 239000008158 vegetable oil Substances 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- 239000002076 α-tocopherol Substances 0.000 claims description 2
- 235000004835 α-tocopherol Nutrition 0.000 claims description 2
- 239000006185 dispersion Substances 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract description 2
- 238000010438 heat treatment Methods 0.000 abstract 2
- 238000004090 dissolution Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 2
- 239000009969 fructus bruceae Substances 0.000 description 2
- 229920001993 poloxamer 188 Polymers 0.000 description 2
- 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 description 1
- 241000158621 Brucea Species 0.000 description 1
- 206010022086 Injection site pain Diseases 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000004064 cosurfactant Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000001297 phlebitis Diseases 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Abstract
The present invention relates to a new medicine dosage form, namely a nanometer emulsion which is in an oil-in-water structure. The average grain size of an oil phase is smaller than 100 nanometers, and the oil phase comprises a medicine and one or a plurality of auxiliary materials, such as solvent oil, an emulsifying agent, a cosolvent, an antioxidant and an anticorrosion agent. A preparing method comprises the following steps: firstly, heating the medicine, the solvent oil and the emulsifying agent to 60 DEG C; fully stirring the mixture for uniform dispersion; heating the cosolvent and a proper amount of water to 80 DEG C for dissolution; dripping an aqueous phase into the oil phase at a temperature of 60 DEG C while stirring; dispersing the mixture by using a high-pressure emulsion-homogenizing machine; finally, carrying out filtration, packing and sterilization to obtain the nanometer emulsion. The nanometer emulsion can be used as a medicinal carrier with large application potential.
Description
Technical field
The present invention relates to a kind of novel form of medicine, relate in particular to the preparation method of nano-emulsion dosage form.
Background technology
Some insoluble drugs, fat-soluble medicine and some Chinese medicine extract, relatively poor in the intravital absorption of people, bioavailability is low.Generally traditionally they are made emulsion, with emulsion as pharmaceutical carrier, but the particle diameter of this traditional emulsion oil phase is bigger, generally greater than 100nm, common emulsion is thermodynamic unstable system, needs energy during preparation, centrifugal back layering, and this emulsion easily produces precipitation in storage process, influences the curative effect of medicine.
Nano-emulsion is the oil-in-water type emulsion body, oil phase is prepared emulsion through a sub-high pressure dispersing emulsification machine mechanical activation comminution in aqueous phase at least, the granularity of oil droplet is minimum, nano-emulsion and traditional emulsion have many similarities, as including water in the component, oil phase and surfactant also can be divided into O/W type and w/o type etc. on the structure.But they are diverse two states, exist difference in essence.At first in appearance, nano-emulsion is different from general emulsion, is transparent or slightly opalescent translucent, and viscosity generally approaches water and is far smaller than the emulsion of corresponding water-oil factor example; Secondly on structure is formed, the required surface-active contents of nano-emulsion is apparently higher than common emulsion. and about about 5%-30%, the existence that more needs cosurfactant sometimes could form nano-emulsion; The 3rd, nano-emulsion not as emulsion like that with the difference of type can only with oil phase or water mixing, nano-emulsion within the specific limits can with the oil phase mixing again can with the water mixing, nano-emulsion can be co-continuous phase form and exists in the definite composition scope; The 4th, the of paramount importance structural difference of nano-emulsion and emulsion is the size of particle diameter, and the particle diameter of nano-emulsion is even, and generally between 10-100nm, and particle diameter one Yin Dynasty of common emulsion is greater than 100nm, and skewness; The 5th, common emulsion is thermodynamic unstable system, needs energy during preparation, and centrifugal back layering, and nano-emulsion is a thermodynamic stable system can be placed and centrifugal not stratified for a long time.
Summary of the invention
The object of the present invention is to provide a kind of novel form of medicine---the preparation method of nano-emulsion.
A kind of preparation method of nano-emulsion dosage form is come the very little emulsion of prepared sizes through a sub-high pressure dispersing emulsification machine mechanical activation comminution in aqueous phase at least with oil phase, and the mean diameter of oil phase is less than 100 nanometers; Be filled in certain container by filling machine, make through sealing, sterilizing then, concrete steps are as follows:
(1), it is even medicine, solvent naphtha, emulsifying agent to be heated to 60 ℃ of abundant dispersed with stirring;
(2), cosolvent and suitable quantity of water are heated to 80 ℃ of dissolvings;
(3), under the condition that keeps 60 ℃ of temperature, while stirring water is dripped to oil phase;
(4), disperse, filtration, packing, sterilization are promptly through the high pressure dispersing emulsification machine.
Above-mentioned solvent naphtha is one or more in vegetable oil, animal fat, mineral oil, artificial oil, the silicone oil.
Above-mentioned emulsifying agent is one or more in polyglyceryl fatty acid ester, sucrose, fat, lecithin, tween, span, pluronic, silicone oil, carbomer, glycerol, the sodium lauryl sulphate.
Above-mentioned cosolvent is one or more in polyglyceryl fatty acid ester, sucrose, fat, lecithin, tween, span, pluronic, silicone oil, carbomer, glycerol, the sodium lauryl sulphate.
The preparation method of above-mentioned nano-emulsion dosage form also comprises adding antioxidant and antiseptic.
Above-mentioned antioxidant is one or more in ethylenediaminetetraacetic acid, disodium EDTA, dibenzylatiooluene, D-xylose, xylitol, glycine, alpha-tocopherol, α-tocopheryl acetate, inositol, ascorbic acid, sodium ascorbate, malic acid, hydroquinone, citric acid, succinic acid, phytic acid, sodium pyrosulfite, the potassium metabisulfite.
Above-mentioned antiseptic is one or more in Oleum Caryophylli, propylene glycol, sorbic acid, sorbic acid methyl ester, parabens, butyl p-hydroxybenzoate calcium, Sodium Methyl Hydroxybenzoate, Sodium Propyl Hydroxybenzoate, benzyl alcohol, the benzoic acid.
The nano-emulsion preparation that the present invention makes can improve the dissolubility of insoluble drug, promotes the macromole water soluble drug in the intravital absorption of people, improves these medicines bioavailability in vivo.Nano-emulsion can contain different fat-soluble medicines simultaneously, improves the stability of some labile drugs; Because the particle diameter of nano-emulsion is little and even, can improve the dispersion that is encapsulated in medicine wherein, also can promote the Transdermal absorption of medicine.Nano-emulsion has great application potential as pharmaceutical carrier.Mainly have following advantage: (1) is the isotropic transparent or semitransparent liquid of tool, Thermodynamically stable, and can filter.Be easy to preparation and preservation; (2) different fat-soluble medicines of solubilising simultaneously; (3) viscosity is low, reduces the phlebitis in the clinical practice, can not cause pain during injection; (4) medicine good dispersion is beneficial to absorption, can improves bioavailability of medicament; (5) medicine that is easy to hydrolysis being made water-in-oil type nanoemulsion can play a protective role; (6) can prolong the drug release time of water soluble drug; (7) can increase transdermal absorption factor.
The specific embodiment
Embodiment 1: the agent of preparation brucea fruit oil nanometer emulsion
Prescription: Oleum Fructus Bruceae 100 grams
Glycerol 25 grams
Soybean lecithin 20 grams
Pluronic F68 5 grams
Water for injection adds to 1000ml
Full dose 1000ml
Preparation technology:
1., phospholipid, glycerol, Oleum Fructus Bruceae are heated to 60 the degree abundant dispersed with stirring even;
2., pluronic F68 and suitable quantity of water are heated to 80 degree dissolvings;
3., under constant temperature 60 degree conditions, while stirring water is dripped to oil phase;
4., disperse, filtration, packing, sterilization are promptly through high pressure dispersing emulsification machine repeatedly.
Gained nano-emulsion mean diameter is 65 nanometers, steady quality, and bioavailability improves, and side effect reduces.
Claims (8)
1. the preparation method of a nano-emulsion dosage form is characterized in that oil phase is come the very little emulsion of prepared sizes through a sub-high pressure dispersing emulsification machine mechanical activation comminution in aqueous phase at least, and the mean diameter of oil phase is less than 100 nanometers; Be filled in certain container by filling machine, make through sealing, sterilizing then, concrete steps are as follows:
(1), it is even medicine, solvent naphtha, emulsifying agent to be heated to 60 ℃ of abundant dispersed with stirring;
(2), cosolvent and suitable quantity of water are heated to 80 ℃ of dissolvings;
(3), under the condition that keeps 60 ℃ of temperature, while stirring water is dripped to oil phase;
(4), disperse, filtration, packing, sterilization are promptly through the high pressure dispersing emulsification machine.
2. according to the preparation method of the described nano-emulsion dosage form of claim 1, it is characterized in that described solvent naphtha is one or more in vegetable oil, animal fat, mineral oil, the artificial oil.
3. according to the preparation method of the described nano-emulsion dosage form of claim 2, it is characterized in that described solvent naphtha is a silicone oil.
4. according to the preparation method of the described nano-emulsion dosage form of claim 1, it is characterized in that described emulsifying agent is one or more in polyglyceryl fatty acid ester, sucrose, fat, lecithin, tween, span, pluronic, silicone oil, carbomer, glycerol, the sodium lauryl sulphate.
5. according to the preparation method of the described nano-emulsion dosage form of claim 1, it is characterized in that described cosolvent is one or more in polyglyceryl fatty acid ester, sucrose, fat, lecithin, tween, span, pluronic, silicone oil, carbomer, glycerol, the sodium lauryl sulphate.
6. according to the preparation method of the described nano-emulsion dosage form of claim 1, it is characterized in that also comprising adding antioxidant and antiseptic.
7. according to the preparation method of the described nano-emulsion dosage form of claim 6, it is characterized in that antioxidant is one or more in ethylenediaminetetraacetic acid, disodium EDTA, dibenzylatiooluene, D-xylose, xylitol, glycine, alpha-tocopherol, α-tocopheryl acetate, inositol, ascorbic acid, sodium ascorbate, malic acid, hydroquinone, citric acid, succinic acid, phytic acid, sodium pyrosulfite, the potassium metabisulfite.
8. according to the preparation method of the described nano-emulsion dosage form of claim 6, it is characterized in that antiseptic is one or more in Oleum Caryophylli, propylene glycol, sorbic acid, sorbic acid methyl ester, parabens, butyl p-hydroxybenzoate calcium, Sodium Methyl Hydroxybenzoate, Sodium Propyl Hydroxybenzoate, benzyl alcohol, the benzoic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031417388A CN100339067C (en) | 2003-07-22 | 2003-07-22 | Nanometer emulsion and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031417388A CN100339067C (en) | 2003-07-22 | 2003-07-22 | Nanometer emulsion and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1568938A CN1568938A (en) | 2005-01-26 |
| CN100339067C true CN100339067C (en) | 2007-09-26 |
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| CNB031417388A Expired - Lifetime CN100339067C (en) | 2003-07-22 | 2003-07-22 | Nanometer emulsion and preparation method thereof |
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Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| ES2375115T3 (en) | 2005-03-31 | 2012-02-24 | Suntory Holdings Limited | EMULSION OF WATER OIL CONTAINING A LIGNANE COMPOSITE AND COMPOSITION THAT INCLUDE THE SAME. |
| CN1771911B (en) * | 2005-11-10 | 2010-05-12 | 浙江大学 | Re-dispersible nanometer particle of insoluble medicine and its preparation |
| CN101879138A (en) * | 2009-05-06 | 2010-11-10 | 上海恒瑞医药有限公司 | Vinca alkaloid nano emulsion injection and preparation method thereof |
| CN101797259B (en) * | 2010-03-15 | 2013-05-01 | 陈鹏举 | Compound vitamin nanoemulsion |
| CN102166270A (en) * | 2011-04-06 | 2011-08-31 | 西北农林科技大学 | Oil-in-water type dried orange peel oil nano-emulsion and preparation method thereof |
| CN102415996B (en) * | 2011-12-13 | 2013-06-05 | 齐鲁动物保健品有限公司 | Valnemulin hydrochloride self-emulsified oral nano emulsion for veterinary use and preparation method thereof |
| CN104856951A (en) * | 2015-05-06 | 2015-08-26 | 华侨大学 | Follicle stimulating hormone transdermal nanometer emulsion and preparation method thereof |
| CN106361758B (en) * | 2016-08-31 | 2019-02-12 | 甘肃新天马制药股份有限公司 | A kind of compound ivermectin praziquantel two-arch tunnel emulsion and preparation method thereof |
| CN108013029A (en) * | 2017-12-29 | 2018-05-11 | 咸阳职业技术学院 | A kind of compound phenol nanoemulsion and its preparation method and application |
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| US6537561B1 (en) * | 1997-02-27 | 2003-03-25 | Nippon Shinyaku Co., Ltd. | Fat emulsion for oral administration |
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