CN103356486A - Preparation method of fenofibrate and pravastatin sodium compound preparation - Google Patents
Preparation method of fenofibrate and pravastatin sodium compound preparation Download PDFInfo
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- CN103356486A CN103356486A CN2012100891806A CN201210089180A CN103356486A CN 103356486 A CN103356486 A CN 103356486A CN 2012100891806 A CN2012100891806 A CN 2012100891806A CN 201210089180 A CN201210089180 A CN 201210089180A CN 103356486 A CN103356486 A CN 103356486A
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Abstract
The invention provides a preparation method of a compound composition containing active ingredients fenofibrate and pravastatin sodium. The preparation method is characterized in that the pravastatin sodium exists in the composition in the form of quick-release pellets; the fenofibrate exists in the composition in the form of solid dispersoid or semi-solid particles. The preparation method of the composition aims to solve the problem about the bioavailability of the fenofibrate and the pravastatin sodium with completely different solubility and the problem about the stability when the fenofibrate and the pravastatin exist in the same component commonly.
Description
Technical field
The invention belongs to field of pharmaceutical preparations.More particularly, the present invention relates to a kind ofly to contain simultaneously fenofibrate, pravastatin sodium is the preparation method of the pharmaceutical composition of active component.
Background technology
Fenofibrate is chlorine shellfish butanoic acid derivative class blood lipid regulation medicine, also its catabolism is increased by the generation that suppresses very low density lipoprotein (VLDL) and triglyceride, reduces blood low density lipoprotein, LDL, cholesterol and triglyceride; Apolipoprotein A1 and A11 are generated to be increased, thus high density lipoprotein increasing.This product still has the blood uric acid effect that reduces normal person and Patients with Hyperuricemia.
Pharmacokinetic is the result show, after this product was oral, gastrointestinal absorption was good, with clothes the absorption of fenofibrate increased with food.About 4～7 hours blood drug level peakings after oral.Half-life α and half-life β were respectively 4.9 hours and 26.6 hours behind the single oral dose, and apparent volume of distribution is 0.9L/kg; Half-life β is 21.7 hours behind the continued treatment.Plasma protein binding rate is approximately 99%, does not find behind the multiple dose administration to accumulate.It is many to distribute in liver, kidney, intestinal after absorbing, and is lung, the heart and adrenal gland secondly, has a small amount of in testis, spleen, skin.In liver and the nephridial tissue intracellular metabolite, through carboxyl reduction and glucuronic acid, metabolite is in the great majority with the glucuronic acid product, through the radiation labelling, about 60% metabolite is arranged through renal excretion, and 25% metabolite is through the stool discharge.The elimination half-life of this product is 20 hours, therefore once a day administration.
Pravastatin sodium is for being 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase competitive inhibitor.The HMG-CoA reductase is the rate-limiting enzyme that catalysis Biosynthesis of cholesterol initial stage HMG-CoA is converted into mevalonic acid, this product reversible inhibition HMG-CoA reductase, thereby the biosynthesis of inhibition cholesterol.This product is brought into play its effect for reducing fat by two aspects, first is the amount decrease to some degree that reversible inhibition HMG-CoA reductase activity makes the cell inner cholesterol, cause the increase of low density lipoprotein, LDL (LDL) acceptor number of cell surface, thereby strengthened the removing by LDL-C in the catabolism of receptor-mediated LDL-C and the blood.The second, the precursor-very low density lipoprotein (VLDL) (VLDL-C) by suppressing LDL-C thus the generation of the synthetic LDL-C of inhibition in liver.
Pharmacokinetic is the result show, the pravastatin oral absorption is fast, and peak time is 1-1.5 hour.Calculate according to the response rate of isotopic labeling medicine in urine, average pravastatin official ceremonial dress absorbance is 34%, and absolute bioavailability is 17%.
The compound recipe compound recipe fenofibrate Pravastatin Sodium Capsule listing of Belgian SMB tecnology s.a company, trade name: pravafenix have been ratified in Europe EMEA people's medication product meeting (CHMP) in February, 2011.Be first so far unique will definitely fenofibrate and the statins compound preparation of uniting use.By the EMEA appraisal report of this product as can be known, contain the fenofibrate of 160mg and the pravastatin sodium of 40mg (in pravastatin sodium) in this product.
By the EMEA appraisal report also as can be known, taked special preparation technology for the bioavailability that guarantees fenofibrate and this product of stability of pravastatin sodium.Be about to pravastatin sodium and be prepared into tablet, because pravastatin sodium is easily oxidized and unstable under acidic condition, so in tablet formulation, added the alkaline environment that sodium bicarbonate is kept prescription, added simultaneously vitamin C as antioxidant.Also by tablet being carried out coating pravastatin sodium tablet and the semi-solid part that contains fenofibric acid are isolated to prevent that two principal agent compositions from interacting.Because fenofibrate belongs to classII (low dissolving high infiltration) class medicine, institute thinks and guarantees its bioavailability, itself and glycerol acetate, lauric acid polyethylene glycol 1500 and Polyethylene Glycol has been prepared into the semi-solid granule of solid dispersion form.Then tablet is namely obtained this product with the semi-solid granule of the solid dispersion hard capsule of packing into.This explanation whole Formulation of pravafenix and preparation method are more loaded down with trivial details, and the at present domestic capsule production line that does not also have while fill capsule and tablet is so this technique is difficult to realize suitability for industrialized production at home.
The compound preparation of the present invention's preparation is to improve on pravafenix formulation and technology basis, wherein tablet is improved to micropill, both compare, and have the following advantages: 1. compare with tablet, piller belongs to multiple-unit release dosage form, each capsule or tablet can comprise ten even hundreds of micropills, so micropill is compared with small pieces, the release site is more, and is less to GI irritation, larger at the gastrointestinal tract distribution area, bioavailability is higher.2. the release unit is less, is subjected to the impact of gastric emptying less, so micropill is not subjected to the impact of gastric emptying substantially, the interior infiltration rate of the body of medicine is more even and bioavailability among individuals difference is less.3. the flowability of micropill is good than tablet, and size is more even, easier coating and divided dose.4. micropill not only can incapsulate, and also can be pressed into tablet.5. from preparation technology, the preparation of micropill is especially extruded spheronization and is prepared the wet-granulation process that micropill only is equivalent to tablet, and then convection drying is just passable, has saved sheeting process, and preparation efficiency is higher, more is conducive to the stability of medicine.6. on the slave unit, the present domestic capsule production line that does not also have to fill simultaneously tablet and granule, and micropill and granule can be produced with common capsule production line simultaneously, more are conducive to carry out extensive Industry Promotion.And along with domestic understanding to this good dosage form of micropill is goed deep into gradually, the micropill production line of oneself has been set up in increasing domestic pharmaceutical factory, and the commercial processes of micropill is very ripe.
Summary of the invention
An object of the present invention is to overcome the shortcoming and defect of above-mentioned prior art, provide a kind of prescription and preparation technology more reasonable easier, be more suitable for industrialization, clinically safely and effectively fenofibrate, pravastatin sodium compound preparation.
Another object of the present invention provides the preparation method of a kind of fenofibrate, pravastatin sodium compound preparation.Because dissolubility, the permeability difference of fenofibrate and pravastatin sodium are very large, if with both as in the same component, cause easily difference and the stability decreases problem of both bioavailability.Separately each can guarantee both bioavailability like this as in a kind of independent component so we are with both, can guarantee again both stability.Then two kinds of components are mixed rear filled capsules or be pressed into tablet.
The component that contains pravastatin sodium is a kind of release pills, the mode that round as a ball or centrifugal granulating were added medicine to, extruded to soon pravastatin sodium employing fluid bed prepares micropill, and then will contain pill core and carry out coating with the gastric solubility film coating pre-mix dose, can guarantee that like this pravastatin sodium discharges in vivo fast, can effectively with pravastatin sodium and fenofibrate effective separation, guarantee stability again.
The component that contains fenofibrate is a kind of solid or semi-solid granule of solid dispersion form, namely fenofibrate is dissolved in the solvent that contains in right amount cosolvent first, and then add in the semi-solid solid dispersion of solid excipient or melting, be prepared into granule by mode dry or cooling.By the preparation solid dispersion fenofibrate is existed with a kind of unbodied micromolecule or particulate forms, can greatly improve its bioavailability.
The present invention forms with the prescription of the standby pravastatin sodium micropill of fluid bed medicine-feeding legal system:
(1) ball core prescription:
(2) coating prescription:
Gastric solubility film coating pre-mix dose 2～5%
The preparation method of pravastatin sodium micropill of the present invention and step:
Contain the pill core preparation method: pravastatin sodium is dissolved in an amount of solvent that contains binding agent, celphere is added in the fluidising chamber, regulate air quantity, most of micropill is blown afloat in fluidising chamber, regulate materialization pressure and constant flow pump flow velocity, make medical liquid atomizing respond well, the medicine-feeding of then spraying, it is complete to add medicine to, and logical hot blast carried out drying in 5 minutes.
Coating method is selected fluidized bed coating, and concrete steps are with ball core medicine-feeding step.
The present invention is as follows with the adjuvant of the standby pravastatin sodium micropill of fluid bed medicine-feeding legal system:
(1) celphere be selected from one or more components wherein such as microcrystalline Cellulose, sucrose, starch, silicon dioxide can direct applied celphere such as the Shanghai card " Su Lixin " of health.
(2) alkaline, inorganic salts is selected from sodium carbonate, sodium bicarbonate, calcium carbonate, calcium hydrogen phosphate, calcium phosphate, wherein one or more of magnesium carbonate.
(3) antioxidant is selected from one or more in sodium sulfite, sodium thiosulfate, vitamin C, BHT, BHA, the propyl gallate.
(4) binding agent is selected from wherein one or more such as hypromellose, polyvidone, carboxymethyl cellulose, is made into aqueous solution or ethanol-water solution during use.
The present invention forms with the pravastatin sodium prescription of extruding round as a ball or centrifugal granulation preparation:
(1) ball core prescription:
(2) coating prescription:
Gastric solubility film coating pre-mix dose 2～5%
The preparation method of pravastatin sodium micropill of the present invention and step:
(1) contain the pill core preparation method: microsphere and its preparation is selected and is extruded spheronization or centrifugal granulation, form preparation according to above-mentioned ball core prescription, wherein extruding spheronization prepares pravastatin sodium to contain the pill core concrete steps as follows: 1. get the raw materials ready and batch mixing: raw material is crossed 100 mesh sieves, with diluent, alkaline, inorganic salts, the abundant mixing of antioxidant is soft material processed 2.: add binding agent and make soft material, 3. soft material is extruded: soft material is extruded into bar through extruder, become smooth brachyplast shape, 4. round as a ball: as the rapid gradation of extrudate to be added in the spheronizator round as a ball, to take out behind the certain hour and make micropill; 5. oven dry: with the micropill that makes in 50 ℃ of oven dry pastille micropill that gets product.
(2) coating method is selected fluidized bed coating, and concrete steps are with ball core medicine-feeding step.
The present invention is as follows with the adjuvant of the standby pravastatin sodium micropill of fluid bed medicine-feeding legal system:
(1) diluent be selected from one or more components wherein such as microcrystalline Cellulose, lactose, sucrose, starch, Pulvis Talci can direct applied celphere such as the Shanghai card " Su Lixin " of health.
(2) alkaline, inorganic salts is selected from sodium carbonate, sodium bicarbonate, calcium carbonate, calcium hydrogen phosphate, calcium phosphate, wherein one or more of magnesium carbonate.
(3) antioxidant is selected from one or more in sodium sulfite, sodium thiosulfate, vitamin C, BHT, BHA, the propyl gallate.
(4) binding agent is selected from wherein one or more such as hypromellose, polyvidone, carboxymethyl cellulose, is made into aqueous solution or ethanol-water solution during use.
Fenofibrate solid particle prescription of the present invention forms:
The preparation method of fenofibrate solid particle of the present invention and step:
Common granulation: 1. medicinal liquid preparation: fenofibrate is dissolved in contains in cosolvent and the bonding an amount of solvent; 2. soft material processed: medicinal liquid is added soft material processed in the diluent again; 3. granulate: soft material is granulated through facility for granulating; 4. dry: that wet granular is drying to obtain in 50～60 ℃.
Fluidized bed granulation: 1. medicinal liquid preparation: fenofibrate is dissolved in an amount of solvent that contains cosolvent; 2. granulate: diluent is added in the fluidising chamber, regulate air quantity, make diluent be the boiling shape, regulate materialization pressure and constant flow pump flow velocity, make medical liquid atomizing respond well, then adopt the top spray mode to spray, it is complete to spray, and logical hot blast carried out drying in 5 minutes, namely got granule.
The adjuvant of fenofibrate solid particle of the present invention is as follows:
(1) diluent is selected one or more in the pharmaceutically acceptable excipient such as lactose, each kind of starch, mannitol, microcrystalline Cellulose, dextrin.
(2) binding agent is selected from wherein one or more such as hypromellose, polyvidone, carboxymethyl cellulose.Be made into aqueous solution or ethanol-water solution during use.
(3) emulsifying agent be selected from that the smooth class of fatty acid Pyrusussuriensis, Polysorbate are poly-, oxygen ethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether class, polyoxyethylene one polyoxypropylene polymer class, polyoxyethylene hydrogenated Oleum Ricini class, Gelucire 44/14 apoplexy due to endogenous wind one or more, such as Tween 80, polyoxyethylene hydrogenated Oleum Ricini, poloxamer F188, Gelucire 44/14 etc.
(4) binding agent is selected from wherein one or more such as hypromellose, polyvidone, carboxymethyl cellulose, is made into aqueous solution or ethanol-water solution during use.
The semi-solid granule prescription of fenofibrate of the present invention forms:
The preparation method of fenofibrate solid particle of the present invention and step:
1. fenofibrate is dissolved in an amount of solvent that contains cosolvent 2. with solid dispersible carrier heating and melting; 3. drug solution is added 4. cooling in the solid dispersion of melting, pulverize, sieve, namely get granule.
The adjuvant of the semi-solid granule of fenofibrate of the present invention is as follows
(1) the solid dispersion carrier is selected from one or more of polyethylene glycols, polyethylene glycol glycerol lipid etc.
(2) emulsifying agent be selected from that the smooth class of fatty acid Pyrusussuriensis, Polysorbate are poly-, oxygen ethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether class, polyoxyethylene one polyoxypropylene polymer class, polyoxyethylene hydrogenated Oleum Ricini class, Gelucire 44/14 apoplexy due to endogenous wind one or more, such as Tween 80, polyoxyethylene hydrogenated Oleum Ricini, poloxamer F188, Gelucire 44/14 etc.
(3) solvent is selected from one or more in ethanol, propylene glycol, glycerol, the glycerol acetate.
The present invention mixes the pravastatin sodium micropill with fenofibrate solid particle or semi-solid granule, fill capsule or compacting are in flakes.
The fenofibrate, the pravastatin sodium compound preparation that adopt the present invention to make, according to dissolution method (two appendix X of Chinese Pharmacopoeia version in 2010 C the second method), take water 900ml as dissolution medium, Revolution Per Minute 50 turns, and in accordance with the law operation is in the time of 5,10,15,30,45,60 minutes, get solution 10ml (replenishing with the volume dissolution medium simultaneously), filter, shake up, as need testing solution; Other gets fenofibrate, the pravastatin sodium reference substance is an amount of, and is accurately weighed, and the solution that is mixed with respectively 178 μ g/ml, 44 μ g/ml is product solution, in contrast product solution in contrast.Get each 20 μ l of above-mentioned two kinds of solution, the injection liquid chromatography records chromatogram respectively.By the stripping quantity of external standard method with every of calculated by peak area.With the time (minute) 6 accumulation stripping quantity (%) is made curve, namely get the stripping curve of each batch sample.The results are shown in Table 1, table 2 and Fig. 1, Fig. 2.
The fenofibrate, the pravastatin sodium compound preparation that adopt the present invention to make, test with reference to Chinese Pharmacopoeia (2010 editions) stability test guideline and carry out, to make respectively sample by oneself and the listing sample is placed under 40 ℃ ± 2 ℃ of temperature, relative humidity 75% native 5% environment and carries out accelerated test, detect 0 month, January, February, March respectively, investigate its stability.The results are shown in Table 3.
Description of drawings
Fig. 1: different embodiment pravastatin sodium stripping curves relatively
Fig. 2: different embodiment fenofibrate stripping curves relatively
The specific embodiment
The below will the invention will be further described by embodiment, and these descriptions are not that content of the present invention is done further to limit.One skilled in the art will understand that to be equal to replacement to what content of the present invention was done, or corresponding the improvement, still belong within protection scope of the present invention.
Embodiment 1
Pravastatin sodium micropill prescription:
The semi-solid granule prescription of fenofibrate:
Preparation method:
Pravastatin sodium micropill preparation: pravastatin sodium, sodium bicarbonate, vitamin C, PVP K30 are dissolved in 50% alcohol solvent, celphere is added in the fluidising chamber, regulate air quantity, most of micropill is blown afloat in fluidising chamber, regulate materialization pressure and constant flow pump flow velocity, make medical liquid atomizing respond well, the medicine-feeding of then spraying, it is complete to add medicine to, and logical hot blast carried out drying in 5 minutes.Dry complete, continue to adopt the mode identical with medicine-feeding to carry out coating, and get final product.
(2) the semi-solid granule of fenofibrate prepares: fenofibrate is dissolved in contains in the glycerol acetate; With Gelucire 44/14, Gelucire 44/14 heating and melting; Drug solution is added in the solid dispersion of melting, cooling is pulverized, is sieved, and namely gets granule.
(3) with pravastatin sodium micropill, the semi-solid granule mix homogeneously of fenofibrate, fill is in hard capsule.
Embodiment 2
Pravastatin sodium micropill prescription:
Fenofibrate solid particle prescription:
Preparation method:
Pravastatin sodium micropill preparation: pravastatin sodium, sodium bicarbonate, BHT, PVP K30 are dissolved in 50% alcohol solvent, celphere is added in the fluidising chamber, regulate air quantity, most of micropill is blown afloat in fluidising chamber, regulate materialization pressure and constant flow pump flow velocity, make medical liquid atomizing respond well, the medicine-feeding of then spraying, it is complete to add medicine to, and logical hot blast carried out drying in 5 minutes.Dry complete, continue to adopt the mode identical with medicine-feeding to carry out coating, and get final product.
(2) fenofibrate solid particle preparation: fenofibrate, polyoxyethylene hydrogenated Oleum Ricini, PVP K30 are dissolved in 50% ethanol; With lactose, pregelatinized Starch mix homogeneously, add medicinal liquid soft material processed; 20 mesh sieves are granulated, 50～60 ℃ of dryings, 20 mesh sieve granulate.
(3) with pravastatin sodium micropill, fenofibrate solid particle mix homogeneously, fill capsule.
Embodiment 3
Pravastatin sodium micropill prescription:
Fenofibrate solid particle prescription:
Preparation method:
(1) pravastatin sodium micropill preparation: raw material is crossed 100 mesh sieves, with microcrystalline Cellulose, calcium hydrogen phosphate, the abundant mixing of sodium sulfite; Add hypromellose 50% alcoholic solution and make soft material; Soft material is extruded into bar through extruder, becomes smooth brachyplast shape; The rapid gradation of extrudate is added in the spheronizator round as a ball, takes out behind the certain hour and make micropill; : with the micropill that makes in 50 ℃ of oven dry pastille micropill that gets product.At last the pastille micropill is put and carried out coating in the fluid bed.
(2) fenofibrate solid particle preparation: fenofibrate, poloxamer F188, PVP K30 are dissolved in 50% ethanol; With lactose, microcrystalline Cellulose mix homogeneously, add medicinal liquid soft material processed; 20 mesh sieves are granulated, 50～60 ℃ of dryings, 20 mesh sieve granulate.
(3) with pravastatin sodium micropill, fenofibrate solid particle mix homogeneously, fill capsule.
Each embodiment pravastatin sodium stripping curve of table 1 is measured
Each embodiment fenofibrate stripping curve of table 2 is measured
Each embodiment study on the stability of table 3
Claims (7)
1. one kind comprises fenofibrate and pravastatin sodium is the preparation method of the pharmaceutical composition of active component.It is characterized in that: pravastatin sodium is present in the compositions with the form of micropill, and fenofibrate is present in the compositions with the form of solid, semi-solid granule.
2. compositions as claimed in claim 1 is characterized in that the fenofibrate single dose is 160mg, and the pravastatin sodium single dose is 40mg, and take once every day.
3. one kind comprises fenofibrate and pravastatin sodium is the pharmaceutical composition preparation method of active component, it is characterized in that this preparation method comprises following prescription and step:
(1) pravastatin sodium micropill preparation: the ball core method of directly adding medicine to
Ball core prescription:
The coating prescription:
Gastric solubility film coating pre-mix dose 2～5%
Preparation method: pravastatin sodium is dissolved in an amount of solvent that contains binding agent, sprays the medicine method at the bottom of then adopting fluid bed, it is sprayed on the celphere, select again at last fluidized bed coating to carry out coating to containing pill core, and get final product.
(2) pravastatin sodium micropill preparation: extrude round as a ball or centrifugal granulation
Ball core prescription:
The coating prescription:
Gastric solubility film coating pre-mix dose 2～5%
Preparation method: adopt by above prescription and to extrude spheronization or centrifugal granulation, can make and contain pill core.Select again fluidized bed coating to carry out coating to containing pill core, and get final product.
(3) fenofibrate solid particle preparation
Preparation method: fenofibrate is dissolved in an amount of solvent that contains cosolvent, and then granulates, be drying to obtain in the adding diluent.
(4) the semi-solid granule preparation of fenofibrate
Preparation method: fenofibrate is dissolved in an amount of solvent that contains cosolvent, and then adds in the solid dispersible carrier of melting, cool off, sieve and get final product.
(5) the pravastatin sodium micropill is mixed with fenofibrate solid particle or semi-solid granule after fill capsule or be pressed into tablet.
4. the usefulness as claimed in claim 3 standby pravastatin sodium micropill of legal system of directly adding medicine to is characterized in that:
(1) celphere be selected from one or more components wherein such as microcrystalline Cellulose, sucrose, starch, silicon dioxide can direct applied celphere such as the Shanghai card " Su Lixin " of health.
(2) alkaline, inorganic salts is selected from sodium carbonate, sodium bicarbonate, calcium carbonate, calcium hydrogen phosphate, calcium phosphate, wherein one or more of magnesium carbonate.
(3) antioxidant is selected from one or more in sodium sulfite, sodium thiosulfate, vitamin C, BHT, BHA, the propyl gallate.
(4) binding agent is selected from wherein one or more such as hypromellose, polyvidone, carboxymethyl cellulose, is made into aqueous solution or ethanol-water solution during use.
5. usefulness as claimed in claim 3 is extruded round as a ball or centrifugal granulation prepares the pravastatin sodium micropill and it is characterized in that:
(1) diluent be selected from one or more components wherein such as microcrystalline Cellulose, lactose, sucrose, starch, Pulvis Talci can direct applied celphere such as the Shanghai card " Su Lixin " of health.
(2) alkaline, inorganic salts is selected from sodium carbonate, sodium bicarbonate, calcium carbonate, calcium hydrogen phosphate, calcium phosphate, wherein one or more of magnesium carbonate.
(3) antioxidant is selected from one or more in sodium sulfite, sodium thiosulfate, vitamin C, BHT, BHA, the propyl gallate.
(4) binding agent is selected from wherein one or more such as hypromellose, polyvidone, carboxymethyl cellulose, is made into aqueous solution or ethanol-water solution during use.
6. fenofibrate solid particle preparation method as claimed in claim 3 is characterized in that:
(1) diluent is selected one or more in the pharmaceutically acceptable excipient such as lactose, each kind of starch, mannitol, microcrystalline Cellulose, dextrin.
(2) binding agent is selected from wherein one or more such as hypromellose, polyvidone, carboxymethyl cellulose.Be made into aqueous solution or ethanol-water solution during use.
(3) emulsifying agent be selected from that the smooth class of fatty acid Pyrusussuriensis, Polysorbate are poly-, oxygen ethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether class, polyoxyethylene one polyoxypropylene polymer class, polyoxyethylene hydrogenated Oleum Ricini class, Gelucire 44/14 apoplexy due to endogenous wind one or more, such as Tween 80, polyoxyethylene hydrogenated Oleum Ricini, poloxamer F188, Gelucire 44/14 etc.
(4) binding agent is selected from wherein one or more such as hypromellose, polyvidone, carboxymethyl cellulose, is made into aqueous solution or ethanol-water solution during use.
7. the semi-solid preparation method of granules of fenofibrate as claimed in claim 3 is characterized in that:
(1) the solid dispersion carrier is selected from one or more of polyethylene glycols, polyethylene glycol glycerol lipid etc.
(2) emulsifying agent be selected from that the smooth class of fatty acid Pyrusussuriensis, Polysorbate are poly-, oxygen ethylene fatty acid ester, polyoxyethylene aliphatic alcohol ether class, polyoxyethylene one polyoxypropylene polymer class, polyoxyethylene hydrogenated Oleum Ricini class, Gelucire 44/14 apoplexy due to endogenous wind one or more, such as Tween 80, polyoxyethylene hydrogenated Oleum Ricini, poloxamer F188, Gelucire 44/14 etc.
(3) solvent is selected from one or more in ethanol, propylene glycol, glycerol, the glycerol acetate.
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