CN102920704A - Pharmaceutic preparation containing biguanide and thiazolidinedione derivatives - Google Patents

Abstract

The invention discloses pharmaceutic preparation containing biguanide and thiazolidinedione derivatives. The preparation comprises a core, a semi-permeable membrane which is coated outside the core, a quick release layer coating which is coated outside the semi-permeable membrane and a shading sealing coating which is coated outside the quick release layer coating. Compared with the prior art, two layers of sealing secondary coatings are reduced, and a toxic and side effect is avoided. Acceleration tests prove that, the ability of the thiazolidinedione derivatives can be improved, after the feeding of the preparation for 8-12 hours, the peak plasma concentration (Tmax) of anti-hyperglycemia medicines is reached, and the drug treatment level in the whole day is maintained. The peak plasma concentration of metformin hydrochloride for 8-12 hours and the peak plasma concentration of pioglitazone hydrochloride for 1-4 hours can be provided.

Description

Contain the pharmaceutical preparation of biguanide and thiazolidine diketone derivative

Technical field

The present invention relates to contain the preparation of biguanide and thiazolidine diketone derivative.

Background technology

Biguanide, for example metformin or butyl biguanide or its pharmaceutically acceptable salt are a kind of antidiabetic medicines, with itself and the second active medicine, such as the pioglitazone coupling, can effectively be used for the treatment of diabetes.

At present, used many technology, disclose to provide control to discharge and the preparation of slow releasing pharmaceutical, to keep the Drug therapy serum-concentration and to reduce the impact that the patient lacks the caused drug dose deficiency of compliance.

For example, slow releasing tablet is described to have the drug core of the osmotically active that is wrapped up by semipermeable membrane.The function of these tablets be make the water sample liquid component for example gastro-intestinal Fluid infilter coating membrane and lytic activity composition, the drug solution that therefore produces can be released by the passage on the coating membrane.Perhaps, if active component does not dissolve in penetrating fluid, it can by extender for example hydrogel make by passing hole channel.In United States Patent(USP) Nos. 3,845,770; 3,916,899; 4,034,758; Can find some representative instances of these permeability tablet systems in 4,077,407 and 4,783,337.U.S. Patent No. 3,952,741 have instructed a kind of permeability device, wherein only have shown enough pressure in the film and on the thin part of film so that the film cracking or break after, active substance just discharges from the core of being wrapped up by semipermeable membrane.

The patent No. is that the Chinese patent of ZL 03822362.7 discloses a kind of medicine that contains biguanide and thiazolidine diketone derivative, and this pharmaceutical preparation comprises:

(A) control discharges osmotic tablet, and this tablet comprises:

(i) core, this core comprises:

(a) account for biguanide or its pharmaceutically acceptable salt of core 50-98wt%;

(b) account for the binding agent of core 0.1-40wt%;

(c) account for the absorption enhancer of core 0-20wt%; With

(d) account for the lubricant of core 0-5wt%;

(ii) the optional primary seal coating that surrounds described core; With

(iii) semipermeable membrane, this film contains:

(a) account for the polymer of semipermeable membrane 50-99wt%;

(b) account for the fluidizer of semipermeable membrane 0-40wt%;

(c) account for the plasticizer of semipermeable membrane 0-25wt%, described film has at least one passage that forms therein and is used for discharging metformin or its pharmaceutically acceptable salt;

(B) randomly for the secondary seal coating on the described control release tablet; With

(C) coating that contains pioglitazone or its pharmaceutically acceptable salt of rapid release, wherein said rapid release pioglitazone or its pharmaceutically acceptable salt coating contain

(i) pioglitazone or its pharmaceutically acceptable salt;

(ii) binding agent; With

(iii) be selected from following excipient: absorption enhancer or surfactant.

The open defect that the technology that this patent discloses exists is: the dosage form structure is too complicated, technological process is too much, cause preparation cost higher, differences between batches are difficult to control, introduced simultaneously too much adjuvant, such as absorption enhancers such as sodium lauryl sulphates, when using with the other medicines compatibility, may cause compatibility reaction.

Summary of the invention

The purpose of this invention is to provide a kind of pharmaceutical preparation that contains biguanide and thiazolidine diketone derivative, the defective that exists to overcome prior art satisfies the needs of clinical practice.

The pharmaceutical preparation that contains biguanide and thiazolidine diketone derivative of the present invention comprises:

Core, be wrapped in the outer semipermeable membrane of described core, be wrapped in the outer release layer coating of described semipermeable membrane and be wrapped in the outer light shield layer sealing coating of described coating;

Described core contains:

Account for biguanide or its pharmaceutically acceptable salt of core 50-98wt%;

Account for the binder polymer of core 0.1-40wt%;

Account for the blocker of core 0-20wt%;

Account for the lubricant of core 0-5wt%;

Described semipermeable membrane contains:

Account for gelling or the swollen polymer of semipermeable membrane 50-99wt%;

Account for the fluidizer of semipermeable membrane 0-40wt%;

Account for the plasticizer of semipermeable membrane 0-25wt%, described semipermeable membrane has at least one and is used for discharging The passage of biguanide or its pharmaceutically acceptable salt;

Described release layer coating contains:

Account for rapid release coatings 0.1-99% thiazolidine diketone derivative;

Account for rapid release coatings 0.1-99% rapid release coatings polymer;

Described light shield layer sealing coating contains:

Account for the light shield layer polymer of light shield layer sealing coating C gross weight 0.1-80%;

Account for the opacifier of light shield layer sealing coating C gross weight 0.1-80%;

Account for light shield layer sealing coating C gross weight 0-40% surfactant.

In addition, the various diluent that disclose in Remington's Pharmaceutical Sciences (1995) Shen, excipient, lubricant, coloring agent, pigment, dispersants etc. can be used for improving the above-described form of the present invention.

In the described core, described biguanide comprises metformin, phenformin or butyl biguanide or its analog and pharmaceutically acceptable salt, example hydrochloric acid salt, isomer or derivatives thereof;

Described binder polymer refers to the pharmaceutically acceptable binding agent of any known conventional, for example polyethylene adjoins pyrrolidone, Polyethylene Glycol, hyprolose, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, ethyl cellulose, polymethacrylates etc. also can adopt the mixture of above-mentioned binding agent.Preferred binder polymer is for example polyvinylpyrrolidone of mean molecule quantity 25,000 to 30,000 of water-soluble substance, and mean molecule quantity is 1,500～6,000 Polyethylene Glycol etc.;

Described blocker is the blocker of any type well known in the art, for example oils, fatty acid, lipid, aliphatic alcohol, waxiness, polymethacrylates, carbomer or its mixture.The example of some preferred blocker is wax class such as Cera Flava, glyceryl stearate, stearic acid, octadecanol etc.;

Described lubricant is selected from magnesium stearate, silicon dioxide, Polyethylene Glycol monoesters or single monoglyceride etc.;

In the described semipermeable membrane:

Described gelling or swollen polymer refer to gelling in water or biofluid, the polymer of swelling or expansion.The exemplary of gelling or swollen polymer is hydroxypropyl emthylcellulose (for example Dow Chemical commercial use METHOCEL K100M) and the High molecular weight polyethylene oxide (for example POIYOX WSR 301, WSR 303 or WSR COAGULANT) of high molecular.Other gelling or swollen polymer are by United States Patent (USP) NO.4, and 522,625 descriptions are incorporated herein by reference.

Preferably, described gelling or swollen polymer are ethyl cellulose, cellulose esters, cellulose diester, cellulose triester, cellulose ether, cellulosic ether fat, acylated cellulose, two acylated celluloses, three acylated celluloses, cellulose acetate, diacetic acid cellulose, Triafol T, cellulose acetate propionate or cellaburate.At United States Patent (USP) N0s.3,845,770:3,916,899:4,008,719:4 in 036,228 and 4,612,008, has described other suitable polymer (being incorporated herein by reference).Most preferred semipermeable membrane material is to contain 39.3 to 40.3%(weight) cellulose acetate of acetyl content and the commodity of EaStman Fine Chemicals; Described semipermeable membrane can adopt medical industry method preparation commonly used, and the present invention repeats no more;

Described fluidizer is a kind of water-soluble substance or a kind of enteric material, preferred sodium chloride, potassium chloride, sucrose, Sorbitol, D one mannitol, Polyethylene Glycol (PEG), propylene glycol, hyprolose, hydroxypropyl emthylcellulose, hydroxypropyl methylcellulose phthalate, CAP, polyvinyl alcohol, 2-methacrylic acid, poloxamer (the LUTROI F68 of BASF commercial use for example, lUTROIF127, IUTROI F108), in the Polysorbate more than one, preferred fluidizer is PEG 400;

Fluidizer also can be for example metformin or its pharmaceutically acceptable salt of a kind of water-soluble medicine, or fluidizer can be a kind of medicine of enteric.If fluidizer is a kind of medicine, this dosage form has the attendant advantages that the medicine rapid release is provided, and therefore has been selected as fluidizer;

Described plasticizer is selected from adipate ester, azelate, citrate, stearate, isoebucate, SA ester, triethyl citrate, tributyl citrate, acetyl tributyl citrate ester, citrate and those are at JohnWiley﹠amp; The Encyclopedia of Polymer Science and Technology that Sons publishes, the plasticizer described in the Vol.10 (1969); Preferred plasticizer is triacetin, acetylated monoglycerides, Oleum Vitis viniferae, olive oil, Oleum sesami, acetyl tributyl citrate ester, acetyl triethyl citrate, glycerol Sorbitol, diethyl oxalate salt, ethyl maleate., diethyl fumarate, di-n-butyl succinate, diethylmalonate, dioctyl phthalate, dibutyl azelate, triethyl citrate, tributyl citrate or glycerin tributyrate and similar;

In the described release layer coating:

Described thiazolidine diketone derivative refers to the medicine for control or slow release NDDM, include but are not limited to troglitazone, rosiglitazone, pioglitazone, ciglitazone or its analog, and pharmaceutically acceptable salt, isomer or derivatives thereof, preferred pioglitazone or its pharmaceutically acceptable salt;

Described coating polymer adopts one or more in the binder polymer in the described core;

In the described light shield layer sealing coating:

Described light shield layer polymer is selected from hypromellose, ethyl cellulose, polyvidone, hyprolose or hydroxyethyl-cellulose;

Described opacifier is selected from one or more in magnesium stearate, Pulvis Talci, titanium dioxide, ferrum oxide, white carbon black or the pharmaceutically acceptable pigment;

Described surfactant is selected from Tween-80, sodium lauryl sulphate or glyceryl monostearate;

The preparation method that contains the pharmaceutical preparation of biguanide and pioglitazone of the present invention is conventional, is summarized as follows:

This tablet is by core, the semipermeable membrane coatings, and rapid release coatings and light shield layer form.The core that wherein contains the first medicine can adopt pharmaceutically commonly used the granulation and the pressed-disc technique preparation, with the semipermeable membrane material coating, then method well known in the art is adopted in punching again, outside semipermeable membrane, parcel contains described release layer coating and the light shield layer sealing coating of the second medicine successively;

In the described gross weight that contains the pharmaceutical preparation of biguanide and thiazolidine diketone derivative, the percentage by weight of various piece is:

Preferably, the percentage by weight of various piece is:

Preferably: described core contains:

Account for biguanide or its pharmaceutically acceptable salt of core 75-95wt%;

Account for the binder polymer of core 3-15wt%;

Account for the blocker of core 0.1-10wt%;

Account for the lubricant of core 0.1-2wt%;

Described semipermeable membrane contains:

Account for gelling or the swollen polymer of semipermeable membrane 60-95wt%;

Account for the fluidizer of semipermeable membrane 2-20wt%;

Account for the plasticizer of semipermeable membrane 2-25wt%,

Described release layer coating contains:

Account for rapid release coatings 30-80wt% thiazolidine diketone derivative;

Account for rapid release coatings 20-70wt% rapid release coatings polymer;

Described light shield layer sealing coating contains:

Account for the light shield layer polymer of light shield layer sealing coating C gross weight 30-80%;

Account for the opacifier of light shield layer sealing coating C gross weight 10-60%;

Account for light shield layer sealing coating C gross weight 1-10% surfactant.

With the patent No. be ZL 03822362,7 Chinese patent is compared, the present invention is mainly by core, the semipermeable membrane coatings, rapid release coatings and shading spacer form, and reduce the secondary coating of two-layer sealing, simplify production technology, reduce production costs and productive labor intensity, reduced simultaneously adding kind and the addition of adjuvant, avoided toxic and side effects.

The present invention confirms by 6 months accelerated tests, but the stability of Effective Raise thiazolidine diketone derivative.Do not wrap 60 ℃ of placements of controlled release tablet of light shield layer after 10 days, its colour changed into yellow, thiazolidinedione content.6 months accelerated stability tests of controlled release tablet of bag light shield layer are qualified.

Preparation of the present invention can be administered once every day, and each taking dose is equivalent to pioglitazone 15mg or 30mg for being equivalent to metformin hydrochloride 850mg or 1000mg.

During preferred meal or after meal, more preferably during supper or after the supper;

Preparation of the present invention can be provided at the Drug therapy level that the peak serum concentration (Tmax) that reaches between 8-12 hour after the administration with antidiabetic medicine continues whole day.Metformin hydrochloride 8-12 hour peak serum concentration and 1-4 hour peak serum concentration of hydrochloric acid pioglitazone wherein, can be provided.

Biguanide, for example the conventional administration of metformin comprises 500mg, 750mg, the dosage form of 850mg and l000mg.Thiazolidine diketone derivative is pioglitazone for example, and conventional administration comprises 15mg, the dosage form of 30mg and 45mg.

When adopting American Pharmacopeia the 2nd subtraction unit when 900ml simulated intestinal fluid (pH 7.5 phosphoric acid buffer agents) and 37 ℃ detect with 75rpm, dosage form prepared in accordance with the present invention shows following dissolution characteristics:

The release of the first active medicine

NLT-is no less than the release of the second active medicine

The specific embodiment

Embodiment 1

Be prepared as follows the control release tablet that contains metformin hydrochloride 850mg and pioglitazone 15mg:

The PVP K-30 molecular weight is approximately=50,000: viscosity (at 20 ℃ of 10%w/v solution)=5.5-8.5mPaS.

(a) granulate

Metformin hydrochloride is crossed 40 mesh sieves, and collects mixing with the polyethylene kind container of cleaning; With Cera Flava and PVP K-30 mixed dissolution in pure water.Then the metformin hydrochloride with mixing joins fluidised bed granulator and sprays under the following conditions polyvinylpyrrolidone binder solution: inlet temperature 50-70 ℃; Atomization air pressure 10pa, spray rate 10-100ml/min.

In case binder solution exhausts, at granulator inner drying granule until loss on drying less than 2%.Dried granule is crossed the pelletizing machine that is equivalent to 18 mesh sieves is housed.

(b) tabletting

Magnesium stearate is crossed 40 order stainless steel sifts, and and (a) granule that obtains of step mixed 5 minutes.After the mixing, with being furnished with 15/32 " the rotary tablet machine compressed granulate (undershoot of flat pattern is with the upper punch of about Imm matrix drift) of circular shrinkage hole, obtain tablet;

In the cellulose acetate (398-10), acetyl content 39.3-40.3%(weight);

(a) semipermeable membrane art for coating

The dissolving cellulose acetate also stirs with homogenizer simultaneously in acetone.PEG400 and triacetin join cellulose acetate and stir until obtain settled solution.Then adopt the coating spray solution of following condition handle clarification in the fluidized coating bed on described core sheet;

16-22 ℃ of production temperature; Atomisation pressure is 14psi and spray rate 120-150ml/min approximately.Coating sealing core is until reach approximately 5% theoretical coating concentration;

Then can adopt any common method punching of medical industry.

III. the second active medicine layer (release layer) (being equivalent to every inventory)

Hydrochloric acid pioglitazone 16.5mg(the second active medicine)

Hydroxypropyl emthylcellulose 30.4mg(rapid release coating polymer)

In purified water, dissolve hydroxypropyl emthylcellulose.Dissolving hydrochloric acid pioglitazone in this solution.Then the suspension that obtains is sprayed onto on the product of II step;

Dissolving Tween 80 and hydroxypropyl emthylcellulose in purified water.In this solution, add Pulvis Talci and titanium dioxide.Then the suspension that obtains is sprayed onto on the tablet of III step, obtains product;

In the described gross weight that contains the pharmaceutical preparation of biguanide and thiazolidine diketone derivative:

Controlling described core weight is 1049mg, and the weight of described semipermeable membrane is 44mg, and the weight of described coating B is 46.9mg, and the weight of described light shield layer sealing coating C is 44mg.

Embodiment 2

Be prepared as follows the control releasing piece that contains metformin hydrochloride 850mg and pioglitazone 15mg

PVP K-90 ³Molecular weight approximately=1,000,000, dynamic viscosity is (at 20 ℃ solution 10%w/v=300-700mPas.

(a) granulate, with embodiment 1;

(b) tabletting is with embodiment 1;

Cellulose acetate (398-10) acetyl content 39.3-40.3%.

(a) semipermeable membrane art for coating

The dissolving cellulose acetate also stirs with homogenizer simultaneously in acetone.PEG400 and triacetin join cellulose acetate and stir.Then adopt the coating spray solution of following condition handle clarification in the fluidized coating bed to the sealing coated tablet: 16-22 ℃ of production temperature; Atomisation pressure is 14psi and spray rate 20-150ml/min approximately.The package clothing closed kernel heart is until reach approximately 5% theoretical coating concentration.

Adopt any common method punching of medical industry.

III. the second active medicine layer (being equivalent to every inventory)

Hydrochloric acid pioglitazone 16.5mg(the second active medicine)

Polyvinylpyrrolidone k30 12.5mg(polymer)

Dissolving Tween 80 and polyvinylpyrrolidone k30 in purified water.Dissolving hydrochloric acid pioglitazone in this solution.Then the suspension that obtains is sprayed onto on the above-mentioned tablet.

Dissolving Tween 80 and hydroxypropyl emthylcellulose in purified water.In this solution, add Pulvis Talci, then the suspension that obtains is sprayed onto on the above-mentioned tablet.Obtain product;

In the described gross weight that contains the pharmaceutical preparation of biguanide and thiazolidine diketone derivative:

Controlling described core weight is 990mg, and the weight of described semipermeable membrane is 30.4mg, and the weight of described coating B is 16.5mg, and the weight of described light shield layer sealing coating C is 31mg.

Embodiment 3

Be prepared as follows the control release tablet that contains metformin hydrochloride 500mg and pioglitazone 15mg:

I. the first active medicine

Prepare as described in Example 2 the 500mg osmotic tablet.The agent of 500mg penetrating agent has following composition:

II. the second active medicine layer

Rapid release amount hydrochloric acid pioglitazone is used for the 500mg metformin hydrochloride that step I prepares.Final tablet has following composition:

The pioglitazone coating is directly used in 500mg metformin hydrochloride osmotic tablet.Prepare the pioglitazone coating with water dissolution PVP K30.In case these compositions are dissolved, just be distributed in the solution hydrochloric acid pioglitazone and homogenize.Then use 24 with following condition " 0'Hara Labcoat III coating pan, the homogenize peptizaiton is directly used in the agent of 500mg metformin hydrochloride osmotic tablet:

In case the pioglitazone coating is directly used in 500mg metformin hydrochloride osmotic tablet core, adopt 24 " the 0'HaraLabcoatIII coating pan, the light shield layer coating solution under with following condition, is sprayed on pioglitazone coated tablet surface.

In the described gross weight that contains the pharmaceutical preparation of biguanide and thiazolidine diketone derivative:

Controlling described core weight is 564.6mg, and the weight of described semipermeable membrane is 27.72mg, and the weight of described coating B is 31.53mg, and the weight of described light shield layer sealing coating C is 22.6mg.

Embodiment 4

Be prepared as follows the control release tablet that contains metformin hydrochloride 500mg and pioglitazone 15mg:

I. the first active medicine

Prepare as described in Example 2 the agent of 500mg osmotic tablet.The agent of 500mg osmotic tablet has following composition:

II. the second active medicine layer

Rapid release amount hydrochloric acid pioglitazone is used for the 500mg metformin hydrochloride that step I prepares.Final tablet has following composition:

The coating parameter:

Release layer is used for the 500mg metformin hydrochloride osmotic tablet of sealing coating.With after the PVP K30 dissolving, add hydrochloric acid pioglitazone and the preparation release layer that is uniformly dispersed with purified water.Then use Hara LabcoatIII coating pan with following condition, the homogenize peptizaiton is directly used in 500mg metformin hydrochloride osmotic tablet:

In the described gross weight that contains the pharmaceutical preparation of biguanide and thiazolidine diketone derivative:

Controlling described core weight is 564.62mg, and the weight of described semipermeable membrane is 27.55mg, and the weight of described coating B is 30.73mg, and the weight of described light shield layer sealing coating C is 46.5mg.

When adopt American Pharmacopeia the 2nd subtraction unit 900ml simulated intestinal fluid (pH 7.5 phosphoric acid buffer agents) and 37 ℃ with 75rpm

Embodiment 5

Be prepared as follows the control release tablet that contains metformin hydrochloride l000mg and pioglitazone 30mg:

I. the first active medicine

Prepare as described in Example 2 the l000mg osmotic tablet, the l000mg osmotic tablet has following composition:

II. the second active layer

Rapid release amount hydrochloric acid pioglitazone is used for the l000mg metformin hydrochloride that step I prepares.Bright whole tablet has following composition:

The pioglitazone release layer is used for the 1000mg metformin hydrochloride osmotic tablet of sealing coating.In 80% ethanol, prepare the pioglitazone release layer with agitator dissolving hypromellose.In case these composition dissolvings, the hydrochloric acid pioglitazone is dispersed in the solution and homogenize.Then use 24 with following condition " 0'Hara LabcoatIII color clothing pot, the homogenize peptizaiton is directly used in l000mg metformin hydrochloride osmotic tablet:

Behind above-mentioned osmotic tablet employing pioglitazone release layer coating, wrap subsequently light shield layer, the application of the similar above-mentioned sealing coating of the condition that adopts.

In the described gross weight that contains the pharmaceutical preparation of biguanide and thiazolidine diketone derivative:

Controlling described core weight is 1135.35mg, and the weight of described semipermeable membrane is 20.02mg, and the weight of described coating B is 43.06mg, and the weight of described light shield layer sealing coating C is 43.1mg.

Embodiment 6

Be prepared as follows the control release tablet that contains metformin hydrochloride l000mg and pioglitazone 30mg:

I. the first active medicine

Prepare as described in Example 2 the l000mg osmotic tablet, the l000mg osmotic tablet has following composition:

II. the second active medicine layer

Rapid release amount hydrochloric acid pioglitazone is for the l000mg metformin hydrochloride for preparing at step I.Final tablet has following composition:

The metformin hydrochloride osmotic tablet

The pioglitazone release layer is used to seal the l000mg metformin hydrochloride osmotic tablet of coating.Prepare the pioglitazone release layer by 80% dissolve with ethanol hypromellose.The hydrochloric acid pioglitazone slowly is distributed in the solvent mixture and was stirred subsequently 10 minutes.Stir the pioglitazone suspension until in the coating process suspension depleted.Under the following condition, using 24 " 0'Hara Labcoat III coating pan is sprayed onto dispersion on the metformin hydrochloride osmotic tablet core of l000mg sealing coating.

In case the pioglitazone release layer is used to seal the l000mg metformin hydrochloride osmotic tablet of coating, light shield layer also is used to the pioglitazone coated tablet.Under the following condition, use O'Hara Labcoat'III coating pan that the light shield layer suspension is sprayed onto on the hydrochloric acid pioglitazone coated tablet.Obtain product;

In the described gross weight that contains the pharmaceutical preparation of biguanide and thiazolidine diketone derivative:

Controlling described core weight is 1135.35mg, and the weight of described semipermeable membrane is 18.54mg, and the weight of described coating B is 43.06mg, and the weight of described light shield layer sealing coating C is 27.4mg.

When adopting when rotating with l00rpm in the buffer solution of pH 2.0HCl-0.3M KC1 with reference to USP1 type device, the final finished tablet shows following hydrochloric acid pioglitazone dissolution characteristics:

When certain invention embodiment that preferably reaches selection had reached disclosed purpose, those skilled in the art can improve the embodiment that discloses.Therefore, additional claim will cover all embodiments of the present invention and without prejudice to the improvement of the spirit and scope of the invention.

Claims (7)

1. contain the pharmaceutical preparation of biguanide and thiazolidine diketone derivative, it is characterized in that, comprising: core, be wrapped in the outer semipermeable membrane of described core, be wrapped in the outer release layer coating of described semipermeable membrane and be wrapped in the outer light shield layer sealing coating of described coating.

2. the pharmaceutical preparation that contains biguanide and thiazolidine diketone derivative according to claim 1 is characterized in that, described core contains:

Account for biguanide or its pharmaceutically acceptable salt of core 50-98wt%;

Account for the binder polymer of core 0.1-40wt%;

Account for the blocker of core 0-20wt%;

Account for the lubricant of core 0-5wt%;

Described semipermeable membrane contains:

Account for gelling or the swollen polymer of semipermeable membrane 50-99wt%;

Account for the fluidizer of semipermeable membrane 0-40wt%;

Account for the plasticizer of semipermeable membrane 0-25wt%, described semipermeable membrane has a passage that is used for discharging biguanide or its pharmaceutically acceptable salt at least;

Described release layer coating contains:

Account for rapid release coatings 0.1-99% thiazolidine diketone derivative;

Account for rapid release coatings 0.1-99% rapid release coatings polymer;

Described light shield layer sealing coating 4 contains:

Account for the light shield layer polymer of light shield layer sealing coating C gross weight 0.1-80%;

Account for the opacifier of light shield layer sealing coating C gross weight 0.1-80%;

Account for light shield layer sealing coating C gross weight 0-40% surfactant.

3. the pharmaceutical preparation that contains biguanide and thiazolidine diketone derivative according to claim 2 is characterized in that, in the described core, described biguanide comprises metformin, phenformin or butyl biguanide or its analog and pharmaceutically acceptable salt.

4. the pharmaceutical preparation that contains biguanide and thiazolidine diketone derivative according to claim 3 is characterized in that, in the described light shield layer sealing coating:

Described light shield layer polymer is selected from hypromellose, ethyl cellulose, polyvidone, hyprolose or hydroxyethyl-cellulose;

Described opacifier is selected from one or more in magnesium stearate, Pulvis Talci, titanium dioxide, ferrum oxide, white carbon black or the pharmaceutically acceptable pigment;

Described surfactant is selected from Tween-80, sodium lauryl sulphate or glyceryl monostearate.

5. each described pharmaceutical preparation that contains biguanide and thiazolidine diketone derivative is characterized in that according to claim 1～4, and in the described gross weight that contains the pharmaceutical preparation of biguanide and thiazolidine diketone derivative, the percentage by weight of various piece is:

6. the pharmaceutical preparation that contains biguanide and thiazolidine diketone derivative according to claim 5, it is characterized in that, in the described gross weight that contains the pharmaceutical preparation of biguanide and thiazolidine diketone derivative, the percentage by weight of various piece is: the percentage by weight of various piece is:

7. the pharmaceutical preparation that contains biguanide and thiazolidine diketone derivative according to claim 6 is characterized in that, described core contains:

Account for biguanide or its pharmaceutically acceptable salt of core 75-95wt%;

Account for the binder polymer of core 3-15wt%;

Account for the blocker of core 0.1-10wt%;

Account for the lubricant of core 0.1-2wt%;

Described semipermeable membrane contains:

Account for gelling or the swollen polymer of semipermeable membrane 60-95wt%;

Account for the fluidizer of semipermeable membrane 2-20wt%;

Account for the plasticizer of semipermeable membrane 2-25wt%,

Described release layer coating contains:

Account for rapid release coatings 30-80wt% thiazolidine diketone derivative;

Account for rapid release coatings 20-70wt% rapid release coatings polymer;

Described light shield layer sealing coating contains:

Account for the light shield layer polymer of light shield layer sealing coating C gross weight 30-80%;

Account for the opacifier of light shield layer sealing coating C gross weight 10-60%;

Account for light shield layer sealing coating C gross weight 1-10% surfactant.