CN102451161A

CN102451161A - Dispersible tablets containing cholesterol absorption inhibitor and lipid regulating drug, and application thereof

Info

Publication number: CN102451161A
Application number: CN2010105098953A
Authority: CN
Inventors: 王丽燕
Original assignee: Individual
Current assignee: Individual
Priority date: 2010-10-18
Filing date: 2010-10-18
Publication date: 2012-05-16

Abstract

The present invention provides dispersible tablets containing a cholesterol absorption inhibitor and a lipid regulating drug, and an application thereof. The present invention relates to novel dispersible tablets, which comprise: a certain amount of a cholesterol absorption inhibitor or a pharmaceutically-acceptable salt of the cholesterol absorption inhibitor or a pharmaceutically-acceptable ester of the cholesterol absorption inhibitor or a mixture thereof, optionally a certain amount of a lipid regulating drug or a pharmaceutically-acceptable salt of the lipid regulating drug or a pharmaceutically-acceptable ester of the lipid regulating drug or a mixture thereof, and at least a pharmaceutically-acceptable carrier, wherein the cholesterol absorption inhibitor is ezetimibe, avasimibe or pactimibe, the lipid regulating drug is simvastatin, atorvastatin calcium, rosuvastatin calcium, lovastatin, pitavastatin calcium, fenofibrate, fenofibric acid, nicotinic acid or lomitapide. The dispersible tablets of the present invention are adopted for treatment or prevention of dyslipidemia or vascular diseases. Compared to the ordinary tablets or the ordinary capsules, the dispersible tablets of the present invention have characteristics of rapid and uniform dispersion, short disintegration time, rapid drug absorption, high bioavailability, good stability and easy taking.

Description

Comprise the dispersible tablet and the application thereof of cholesterol absorption inhibitor and lipid-regulation medicine

Technical field

The present invention relates to a kind of novel dispersible tablet; It is made up of a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester or its mixture and optional a certain amount of lipid-regulation medicine or its pharmaceutically acceptable salt or ester or its mixture and pharmaceutically acceptable carrier; Be used for treatment or prevention patient's dyslipidemia or angiopathy, belong to medical technical field.

Background technology

The cardiovascular diseases has become first cause of death of China city and rural crowd, and China cardiovascular diseases's characteristics are that apoplexy is occurred frequently and Incidence of CHD is lower, but year Incidence of CHD and mortality rate progressively rise surplus in the of nearly 20; In economic development big city such as Beijing faster; Monitoring result shows; The hemorrhagic apoplexy sickness rate was obvious downward trend from 1984 to 1999; And the cerebral infarction sickness rate obviously rises, and indication is that ischemic cardiovascular (comprising coronary heart disease and the cerebral infarction) sickness rate on basis raises with the atherosclerosis.The cohort study of China shows that it is one of independent hazard factor of coronary heart disease and cerebral infarction that serum total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) raise.For this reason, to the control of dyslipidemia must attach the importance early (non-patent literature 1).

Though Chinese population blood lipid level and dyslipidemia prevalence still are lower than most western countries, along with The development in society and economy, the raising of living standards of the people and the variation of life style, the serum TC level of people's group mean just progressively raises.Meanwhile, also very common with closely-related diabetes of dyslipidemia and metabolism syndrome in China.Investigation finds that there are tangible regional difference in Chinese population serum lipids level and unusual rate; The characteristic distributions of serum TC and LDL-C rate of rise is that the city is significantly higher than the rural area; The big city is higher than small and medium-sized cities; Rich rural area is higher than poor rural area, and is closely related with the socio-economic development level, points out challenge and the opportunity that we face in the dyslipidemia preventing and controlling of economic transition phase and deposits.The control of dyslipidemia should with city and rich rural area, middle-aged male and after climacteric the women attach most importance to.

Dyslipidemia also belongs to metabolic disease as the performance of lipidosis, but its to the infringement of health then mainly at cardiovascular system, cause coronary heart disease and angiopathy.Its medicine is mainly cholesterol absorption inhibitor, statins, fibrate, Squalene synthetic inhibitor, nicotinic acid class medicine or cholic acid chelating agent.

Statins (statins) is also claimed 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor; Activity with rate-limiting enzyme in the synthetic early process of competitive inhibition cell inner cholesterol; Then raise the cell surface ldl receptor; Quicken the catabolism of blood plasma LDL, can suppress the synthetic of VLDL in addition.Therefore statins can significantly reduce TC, LDL-C and apo B, also reduces TG level and slight rising HDL-C.In addition, Statins also possibly have effects such as antiinflammatory, protection vascular endothelial function, and these effects possibly reduce relevant with coronary event.

Fibrate is also claimed fibrate drug, and this type of medicine stimulates lipoprotein lipase (LPL), apo A I and apo A II expression of gene through peroxide activator enzyme accretion prism activated receptor α (PPAR α); And inhibition apo C III expression of gene; Strengthen the lipolytic activity of LPL, help removing the lipoprotein that is rich in TG in the blood circulation, reduce plasma TG and improve the HDL-C level; Promote the antiport of cholesterol, and make the LDL hypotype by small and dense granule to big and loose particles changes.Special type of indication of shellfish is hypertriglyceridemia or is master's combined hyperlipidemia familial and low hdl mass formed by blood stasis with the TG rising.Clinical trial comprises that Helsinki cardiac studies (HHS), the HDL-C of US veteran population management board intervene test (VA-HIT), bezafibrate myocardial infarction Prevention Research (BIP), DAIS and fenofibrate in diabetics intervention prevention incident test ((FIELD) confirmation; Fibrate possibly delay the progress of coronary atherosclerosis, reduces main coronary artery events.

In order to improve the blood fat compliance rate, reduce incidence rate of adverse reaction simultaneously, the Combined application of different classes of fat regulation medicine is a rational approach.The drug combination purpose is that the level of TC, LDL-C and TG is obviously reduced, and the level of HDL-C obviously raises; Also be applicable to the treatment of atherogenicity dyslipidemia, especially when diabetes and metabolism syndrome with dyslipidemia; Can obviously improve plasma lipid profile (non-patent literature 1,2,3,4).

The benefit of drug combination also is: the fat regulation medicine of different effects mechanism is transferred the fat effect can add up, work in coordination with or is complementary, and the reverse adjusting of passivation is compensatory, improves and transfers the fat curative effect; It is excessive and the adverse effect that causes increases drug safety to reduce single survival dose; Take into account multiple risk factor and relevant disease that the patient exists, help individualized treatment; Improve patient's quality of life, improve patient's compliance; Can work in coordination with the protection of reinforcement to organ.According to Ezetimibe+statins, according to the special type medicine of Ezetimibe+shellfish, according to Ezetimibe+MTP (MTP) inhibitor, finished II or III clinical trial phase according to the special type medicine of Ezetimibe+statins+shellfish or according to Ezetimibe+slow release nicotinic acid; Go on the market according to Ezetimibe simvastatin sheet.

Patent documentation discloses according to Ezetimibe or its salt, and through taking the method for The compounds of this invention reduction serum cholesterol; The compounds of this invention can be taken separately, perhaps merges with cholesteral biosynthesis inhibitor and takes.The invention also discloses the Pharmaceutical composition that contains said chemical compound, and the method for preparing them.

Dispersible tablet of the present invention, administration every day 1～3 time is preferably every day 1 time, and the patient is very easy to use like this, has improved the compliance that the patient takes medicine simultaneously, improves patient's quality of life.

Non-patent literature 1: adult Chinese dyslipidemia guideline of prevention and treatment is worked out joint committee. adult Chinese dyslipidemia guideline of prevention and treatment. and Chinese cardiovascular diseases's magazine, 35 (5), in May, 2007,390-419

Non-patent literature 2: Vasculocardiology Deparment doctor branch of Chinese doctors'associations. cholesterol absorption inhibitor clinical practice China expert common recognition. cardiovascular and cerebrovascular disease control, 2010 06 month, 10 (3), 169-170

Non-patent literature 3: Lu Guoping opens quick. and accent fat is treated the present situation of drug combination and is looked forward. the old many organ diseases magazine of China, 2005 06 month, 4 (2), 93-95

Non-patent literature 4: Liu Jieying, Yan Xiaowei. strengthen the developing direction of his spit of fland blood fat reducing treatment. clinical drug therapy magazine,, 6 (2), 43-46 in 2008

Patent documentation: Chinese patent CN1131416 (A), European patent EP 0720599 (A1)

Summary of the invention

The object of the present invention is to provide a kind of novel dispersible tablet, it is made up of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester or its mixture and optional lipid-regulation medicine or its pharmaceutically acceptable salt or ester or its mixture and pharmaceutically acceptable carrier.Wherein said cholesterol absorption inhibitor is preferably according to Ezetimibe, avasimibe or handkerchief for wheat cloth; Described lipid-regulation medicine is preferably statins, fibrate, MTP inhibitor, nicotinic acid class, cholic acid chelating agent, Squalene synthetic inhibitor or its pharmaceutically acceptable salt or ester or its mixture.Compare with conventional tablet or capsule, dispersible tablet have disperse rapidly evenly, disintegration time is short, drug absorption is fast, bioavailability is high, the characteristics of good stability and taking convenience.

Another object of the present invention also is to provide above-mentioned dispersible tablet to be used for treating or preventing the application of the medicine of patient's dyslipidemia or angiopathy in preparation.

The technical scheme that the present invention solves is following:

(1) a kind of dispersible tablet is characterized in that, it is made up of following several parts:

(I) a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester or its mixture and optional a certain amount of lipid-regulation medicine or its pharmaceutically acceptable salt or ester or its mixture; And

(II) at least a pharmaceutically acceptable carrier.

A certain amount of cholesterol absorption inhibitor of the present invention or its pharmaceutically acceptable salt or ester or its mixture are preferably according to Ezetimibe (Ezetimibe), avasimibe (Avasimibe), handkerchief for wheat cloth (Pactimibe), eldacimibe (Eldacimibe), Yi Lumaibu (Eflucimibe) or its pharmaceutically acceptable salt or ester or its mixture; More preferably replace wheat cloth or its pharmaceutically acceptable salt or ester or its mixture according to Ezetimibe, avasimibe, handkerchief; More preferably according to Ezetimibe.

Chemical name according to Ezetimibe is 1-(4-fluorophenyl)-3 (R)-[3-(4-fluorophenyl)-3 (S)-hydroxypropyls]-4 (S)-(4-hydroxyphenyl)-2-azetidine (azetidine) ketone, and molecular formula is C ₂₄H ₂₁F ₂NO ₃, molecular weight is 409.43, structural formula is shown below:

For cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester, UD is preferably 0.1～1000mg, more preferably 0.5～1000mg; 1～500mg more preferably; More preferably 2.5～500mg, more preferably 10～500mg, more preferably 25～500mg;

For according to Ezetimibe or its pharmaceutically acceptable salt or ester, UD is preferably 2.5～80mg, 2.5～40mg more preferably, and more preferably 5～20mg further is preferably about 2.5mg, about 5mg, about 10mg, about 20mg, about 40mg or about 80mg; Further be preferably 5mg or 10mg;

For avasimibe or its pharmaceutically acceptable salt or ester; UD is preferably 25～1000mg; 25～500mg more preferably; 50～500mg more preferably, more preferably 50～250mg further is preferably about 25mg, about 50mg, about 100mg, about 200mg, about 250mg or about 500mg.

Cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester can crystallizations, partially crystallizable or amorphous forms, solvate especially hydrate or polycrystalline form exist, also can laevoisomer, dextroisomer, raceme or optical isomer exist.Patent documentation WO9508532, US5767115, CN1131416 (A), WO9426702, US5491172 announced those, at this this is incorporated herein by reference in full.

A certain amount of lipid-regulation medicine of the present invention or its pharmaceutically acceptable salt or ester or its mixture are selected from: statins; Fibrate; The MTP inhibitor; Nicotinic acid class medicine; Cholic acid chelating agent; Omega-fatty acid; Acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitor; The Squalene synthetic inhibitor; Cyclooxygenase inhibitors of squalene; Intramolecularly has the beta-lactam cholesterol absorption inhibitor of C-glucosides; The low density lipoprotein receptor activator; Water-soluble fiber; The ileal bile acid transfer inhibitor; Cholesterol alienation excretion promoter; Bile acids medicine; The bile acid cell reabsorption inhibitor; Probucol; Or its pharmaceutically acceptable salt or ester or its mixture.Those that patent documentation CN101822836A, CN101822667A, CN101732718A, CN101822837A, CN101291662A are announced are incorporated herein by reference this at this in full.

Wherein said statins or its pharmaceutically acceptable salt or ester or its mixture are simvastatin (Simvastatin); Atorvastatin (Atorvastatin); Rosuvastatin (Rosuvastatin); Lovastatin (Lovastatin); Pitavastatin (Pitavastatin); Pravastatin (Pravastatin); Fluvastatin (Fluvastatin); Mevastatin (Mevastatin); Bervastatin (Bervastatin); Crilvastatin (Crilvastatin); Dalvastatin (Dalvastatin); The lattice logical sequence is cut down his spit of fland (Glenvastatin); For cutting down his spit of fland (Tenivastatin); Cerivastatin (Cerivastatin); Or its pharmaceutically acceptable salt or ester; Be preferably simvastatin, Atorvastatin calcium, rosuvastain calcium, lovastatin or Pitavastatin Calcium;

For statins or its pharmaceutically acceptable salt or ester, each UD is 0.25～160mg, is preferably 0.25～80mg; 0.5～80mg more preferably;

For atorvastatin, simvastatin, lovastatin, pravastatin, fluvastatin or its pharmaceutically acceptable salt or ester, UD is 5～160mg, is preferably 5～80mg, more preferably is approximately 5mg, 10mg, 20mg, 40mg or 80mg;

For Rosuvastatin or its pharmaceutically acceptable salt or ester, UD is 2.5～80mg, is preferably 5～40mg, more preferably is approximately 2.5mg, 5mg, 10mg, 20mg or 40mg;

For Pitavastatin or its pharmaceutically acceptable salt or ester, UD is 0.25～16mg, is preferably 0.25～8mg; 0.25～4mg more preferably; More preferably be approximately 0.5mg, 1mg, 2mg or 4mg;

Statins or its pharmaceutically acceptable salt or ester can crystallizations, partially crystallizable or amorphous forms, solvate especially hydrate or polycrystalline form exist, also can laevoisomer, dextroisomer, raceme or optical isomer exist.Those that patent documentation EP409281 (A1), US5273995 (A), EP1061073 (A1), EP521471 (A1), US5260440 (A), JP5178841 (A), EP33538 (A2), US4444784 (A), JP56122375 (A), US4293496 (A), EP304063 (A2), US5011930 (A), JP1279866 (A), US5856336 (A), US4231938 (A), EP0022478 (A1), JP56008689 (A), JP57163374 (A), DE3122499 (A1), US4346227 (A), FR2483912 (A1), JP57002240 (A), US4410629 (A), WO8402131 (A1), US4739073 (A), DE19475017 (I2), EP0114027 (A1), DE2524355 (A1), US3983140 (A) are announced are incorporated herein by reference this at this in full.

Wherein said fibrate or its pharmaceutically acceptable salt or ester or its mixture are fenofibrate (Fenofibrate); Fenofibrate acid (fenofibric acid); Fenofibrate choline (CholineFenofibrate); Bezafibrate (Bezafibrate); Clofibrate (Clofibrate); Ciprofibrate (Ciprofibrate); Gemfibrozil (Gemfibrozil); Etofylline clofibrate (Etofylline Clofibrate); Simfibrate (Simfibrate); Clinofibrate (Clinofibrate); Etofibrate (Etofibrate); Aluminum clofibrate (Aluminum Clofibrate); Biclofibrate (Biclofibrate); Binifibrate (Binifibrate); Calcium clofibrate (Calcium Clofibrate); Cinnarizine clofibrate (CinnarizineClofibrate); Dulofibrate (Dulofibrate); Fenirofibrate (Fenirofibrate); Lifibrate (Lifibrate); Magnesium clofibrate (Magnesium Clofibrate); Nicofibrate (Nicofibrate); Picafibrate (Picafibrate); Pirifibrate (Pirifibrate); Ponfibrate (Ponfibrate); Ronifibrate (Ronifibrate); Salafibrate (Salafibrate); Serfibrate (Serfibrate); Sitofibrate (Sitofibrate); Tiafibrate (Tiafibrate); Timofibrate (Timofibrate); Tocofibrate (Tocofibrate); Urefibrate (Urefibrate); Xantifibrate (Xantifibrate); Or its pharmaceutically acceptable salt or ester; Be preferably fenofibrate, fenofibrate acid, bezafibrate, clofibrate, ciprofibrate, gemfibrozil, clinofibrate, etofibrate, simfibrate or etofylline clofibrate;

For fibrate or its pharmaceutically acceptable salt or ester, UD is 1～1000mg, is preferably 17.5～1000mg, is preferably 35～1000mg, is preferably 35～500mg, more preferably 100～300mg;

For fenofibrate, fenofibrate acid or its pharmaceutically acceptable salt or ester; UD is 1～500mg; Be preferably 35～300mg; More preferably 100～300mg further is preferably about 80mg, about 105mg, about 110mg, about 120mg, about 130mg, about 135mg, about 145mg, about 160mg, about 200mg or about 267mg, most preferably is about 120mg, about 130mg, about 145mg, about 160mg or about 200mg;

Fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof can crystallizations, partially crystallizable or amorphous forms, solvate especially hydrate or polycrystalline form exist, also can laevoisomer, dextroisomer, raceme or optical isomer exist.Those that patent documentation DE2250327 (A1), DE2003430 (A1), DE2065956 (A1), US4058552 (A), US3907792 (A), US3914286 (A), US4233298 (A), US7741374 (B1), US7569612 (B1), US7741373 (B1), CN101677981A, CN101296894A, EP1651194 (B1), WO2005013940 (A1), US2007092567 (A1), CA2534910 (A1), CN1726024A, CN101480384A, CN100473378 (C), EP1572190 (B1), US7259186 (B2), US2004248861 (A1), WO2004054568 (A1), US2009263477 (A1), US2010081715 (A1), US2005148594 (A1), US7259186 (B2), FR2918662 (A1), FR2918662 (B1), FR2918367 (A1), CN101730675 (A), FR2918662 (B1), WO2009024685 (A1), CN101217944 (A), EP2074992 (A1), EP2081563 (A1), WO2006135480 (A2), WO2008046052 (A1), US2008152714 (A1), ZA200709485 (A), US2008275270 (A1), US7714163 (B2), WO2009004029 (A1), WO2009085766 (A2), WO2009091967 (A2), US7741374 (B1), US2010185008 (A1), WO2010086700 (A2), SG161256 (A1), DE2230383 (A1), DE2149070 (A1), US3781328 (A), US3262850 (A), GB860303 (A), DE1915497 (A1), DE2343606 (A1), JP49056958 (A), JP58083649 (A), GB1225575 (A), US3674836 (A), DE2308826 (A1), US3984413 (A), DE1518241 (B1), GB1087694 (A), US3494957 (A), DE2017331 (A1), JP50010298 (B), JP49039995 (B), DE1941217 (A1), US3723446 (A), FR2476095 (A1), BE884722 (A1), DE1620024 (A1), US3369025 (A), DE2432322 (A1), US3971798 (A) are announced are incorporated herein by reference this at this in full.

Wherein said MTP inhibitor or its pharmaceutically acceptable salt or ester or its mixture are preferably Lomitapide (AEGR-733), LAB687, CP346086 or its pharmaceutically acceptable salt or ester or its mixture; Be preferably Lomitapide or its pharmaceutically acceptable salt or ester.For Lomitapide or its pharmaceutically acceptable salt or ester, UD is 1～240mg, is preferably 2.5～120mg, and more preferably 5～120mg is more preferably 5mg, 10mg, 20mg, 40mg, 60mg, 80mg or 120mg.

Wherein said nicotinic acid class medicine is preferably nicotinic acid, acipimox or Buddhist nun and restrains More or its pharmaceutically acceptable salt or ester or its mixture; Nicotinic acid has rapid release agent and two kinds of dosage forms of slow releasing agent; Rapid release agent untoward reaction is obvious, generally is difficult to tolerance; The untoward reaction of spacetabs type nicotinic acid obviously alleviates, and is prone to tolerance; Preferred spacetabs type nicotinic acid.For nicotinic acid, UD is 0.25～2g, is preferably 0.5～2g, is preferably 0.5g, 1g or 2g.

Wherein said cholic acid chelating agent or its pharmaceutically acceptable salt or ester or its mixture are preferably colestyramine (Colestyramin), colestipol (Colestipol), colesevelam (Colesevelam), Colestilan (Colestilan), colestolone (colestolone) or its pharmaceutically acceptable salt or ester or its mixture; More preferably colestyramine, colestipol hydrochloride, hydrochloric acid colesevelam or Colestilan.For cholic acid chelating agent or its pharmaceutically acceptable salt or ester, UD is preferably 0.1～30g, is preferably 0.25～30g, is preferably 0.25～10g, is preferably 0.25～5g.

Wherein said omega-fatty acid or its pharmaceutically acceptable salt or ester or its mixture are preferably 20 carbon penetenoic acid (EPA; C20:5n-3), 22 carbon olefin(e) acid (DHA, C22:6n-3), Folium Perillae polyenoic fatty acid, Adeps Phocae vitulinae omega-3 polyunsaturated fatty acids, fatty acid mixed or its pharmaceutically acceptable salt or ester or its mixture; 20 carbon penetenoic acid ethyl esters, 22 carbon olefin(e) acid ethyl ester, Folium Perillae polyene fatty acid ethylester, Adeps Phocae vitulinae omega-3 polyunsaturated fatty acids or mixed fatty glycerides more preferably.

A preferred version of the present invention; It is characterized in that the percentage by weight of wherein said principal agent and pharmaceutically acceptable carrier total amount is 0.01～99.9%, is preferably 0.05～90%; More preferably 0.1～70%; More preferably 0.2～50%, more preferably 0.5～50%, more preferably 1～50%.

Pharmaceutically acceptable carrier of the present invention is art-recognized; And refer to participate in to deliver or transport any theme composition or its component pharmaceutically acceptable material, component or carrier from the part of part to another organ or the health of an organ or health, like liquid or solid filler, diluent, excipient, solvent or encapsulating material.With theme composition and the compatible meaning of component thereof on, every kind of carrier must be acceptable and be harmless to the patient.Some instances that can be used as the material of pharmaceutically acceptable excipient comprise: (a) saccharide, like lactose, dextrose plus saccharose; (b) starch based is like corn starch and potato starch; (c) cellulose and composition thereof is like sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (d) pulverous Tragacanth; (e) Fructus Hordei Germinatus; (f) gelatin; (g) Talcum; (h) excipient is like cupu oil and suppository wax; (i) oils is like Oleum Arachidis hypogaeae semen, Oleum Gossypii semen, safflower oil, Oleum sesami, olive oil, Semen Maydis oil and soybean oil; (j) glycols is like propylene glycol; (k) polyalcohols is like glycerol, Sorbitol, mannitol and Polyethylene Glycol; (l) esters is like ethyl oleate and ethyl laurate; (m) agar; (n) buffer agent class is like magnesium hydroxide and aluminium hydroxide; (o) alginic acid; (p) pyrogen-free water; (q) isotonic saline solution; (r) fluid used of intravenous includes but not limited to Ringer's mixture, contains the water of 5% glucose and manages saline half a lifetime; (s) ethanol; (t) phosphate buffer; (v) used nontoxic compatible material in the other drug preparation.

Wherein said pharmaceutically acceptable carrier is selected from binding agent, filler, disintegrating agent, lubricant, fluidizer, wetting agent, correctives, aromatic, coloring agent, dissolubility promoter, surfactant or their combination.The amount of the acceptable every kind of carrier of pharmacy in pharmaceutical composition can change in the normal ranges of this area.

Suitable bonding is preferably enteric solubility binding agent or non-enteric solubility binding agent;

Wherein said enteric solubility binding agent be patent documentation CN1726024A, CN100473378C, CN101480384A described those; Be preferably enteric polymer, more preferably carboxymethylethylcellulose, sodium carboxymethyl cellulose or HPMCP;

Wherein said non-enteric solubility binding agent is selected from: synthetic polymer such as polyvinyl lactam class, modified natural polymers, natural or mainly be natural polymer or non-polymeric binder such as polyhydric alcohol; More preferably polyvinylpyrrolidone (PVP), 30 POVIDONE K 30 BP/USP 30, N-vinyl pyrrolidone, methylcellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, Cellulose ethyl hydroxypropyl ether, maltodextrin, Icing Sugar, syrup, starch slurry, gelatin, mannan, maltose alcohol, mannitol, sorbitol, lactose or xylitol.

Suitable filler can be selected from microcrystalline Cellulose, optimize microcrystalline Cellulose, Powderd cellulose, pre-paying starch, lactose, mannitol, sorbitol, xylitol, red algae alcohol, dextrin, Icing Sugar, starch, saccharide, sugar mixture, Polyethylene Glycol, sodium bicarbonate, calcium carbonate, calcium sulfate, calcium hydrogen phosphate calcium or their combination.

Suitable disintegrants can be selected from carboxymethylstach sodium, crosslinked carboxymethylstach sodium, polyvinylpolypyrrolidone, primojel, L-hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, sodium carboxymethyl cellulose, dried starch, hydroxypropyl starch, sodium lauryl sulphate, polyoxyethylene sorbitan monoleate or their combination.

Examples of suitable lubricants can be selected from magnesium stearate, calcium stearate, calcium silicates, Talcum or their combination.

Suitable fluidizer can be selected from micropowder silica gel, Pulvis Talci, magnesium trisilicate, cellulose powder, starch or their combination.

Suitable wetting agent or solvent can be selected from water, ethanol, Polyethylene Glycol or ethanol water; Be preferably water or ethanol water; Ethanol water is preferably 30%～90% ethanol water.

Suitable correctives is selected from sucrose, Icing Sugar, sucralose, steviosin, saccharin sodium, aspartame, lactose or their combination.

Suitable aromatic is selected from water quality essence, emulsifying essence, Water/oil dual-purpose essence, panchromatic essence or their combination, and wherein water quality essence is selected from strawberry essence, apple essence, flavoring banana essence, flavoring pineapple essence, flavoring orange essence, honey peach essence, Fructus Citri Limoniae essence, fragrant citrus essence, hami melon essence, Fructus Fragariae Ananssae powdered flavor, Fructus Ananadis comosi powdered flavor or their combination.

Suitable coloring agent be selected from carmine, lemon yellow, sunset yellow, amaranth, erythrosine, newly red, red pigment of cowberry, capsanthin of red, indigo, light blue, beet red, lac, red rice is red or their combination.

Suitable dissolubility promoter or dissolution promoter can be selected from polyvinylpolypyrrolidone, polyvidone, sodium lauryl sulphate, polyoxyethylene sorbitan monoleate or their combination.

Suitable surfactant can be selected from sodium lauryl sulphate, Polysorbate, poloxamer, span (Span), lecithin, dodecyl sodium sulfate or their combination.

Pharmaceutically acceptable salt of the present invention or ester refer to can be according to normally used nontoxic salt or ester or derivant in the pharmaceutical industries of method preparation well known in the art.On the one hand, based on inorganic acid salts such as the halogen acid salt of the preferred hydrofluoride of the salt of basic group, hydrochlorate, hydrobromate, hydriodate and so on, nitrate, perchlorate, sulfate, phosphate; Acylates such as the aromatic sulfonic acid salt of the lower alkane sulfonate of mesylate, fluoroform sulphonate, esilate and so on, benzene sulfonate, tosilate and so on, maleate, acetate, malate, fumarate, hemifumarate, succinate, citrate, succinate, Ascorbate, tartrate, acetate, trifluoroacetate, lactate, malonate, tosilate, oxalates; And the amino acid salts of glycinate, lysinate, arginine salt, ornithine salt, glutamate, Glu, aspartate and so on; On the other hand, based on alkali salt, the aluminum salt of the alkali metal salt of the salt particular certain cancers of acidic-group, potassium salt, lithium salts and so on, calcium salt, magnesium salt and so on, slaines such as iron salt; The inorganic salt of ammonium salt and so on, t-octanylamine salt, dibenzyl amine salt, alkylbenzyldimethylasaltsum saltsum, glucosamine salt, phenylglycine alkyl ester salt, ethylenediamine salt, N-NMG salt, guanidinesalt, diethyl amine salt, triethylamine salt, hexanamine salt, N, the amine salt such as organic salt of N '-dibenzyl ethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzyl-1-phenylethylamine salt, piperazine salt, tetramethyl ammonium, three (methylol) aminomethane salt and so on; And the amino acid salts of glycinate, lysinate, arginine salt, ornithine salt, glutamate, Glu, aspartate and so on.Should be understood that described nontoxic salt comprises pharmaceutically acceptable pharmacological activity mixture; Or with the chemical compound of its significant correlation, include but not limited to mixture, crystallization, partially crystallizable, amorphous forms or polycrystalline form, solvate, hydrate, oxide, fragment or the radiosiotope of any ratio of pharmaceutically acceptable salt or ester, prodrug, active metabolite, various isomer or these isomers.

Dispersible tablet of the present invention can prepare with the conventional method in the pharmaceuticals industry; Can adopt wet granulation, dry granulation, fluidized bed granulation, spray-drying process, wet-mixed granulation, spherocrystal pelletize or solid dispersion to granulate; Can adopt the direct powder compression tabletting; Also can adopt double-deck tabletting, three laminate or multilamellar tabletting.Wherein said dispersible tablet can randomly carry out film coating or sweet tablet; Can be the gastric solubleness coating, also can be enteric coating.

For cholesterol absorption inhibitor or lipid-regulation medicine or its pharmaceutically acceptable salt or ester or its mixture, can adopt micronization or nanorize to handle, also can adopt solid dispersion to handle, can also adopt melt state or fritting body state processing.

Often because of disintegrate and the slow abundant absorption that influences medicine of medicine stripping, the patient of old man, child and dysphagia often takes and has any problem conventional tablet; Big or need once take the sheet number more for a long time when drug dose, specification, problem is particularly outstanding.Though the liquid preparation taking convenience, less stable, all inconvenience of packing, transportation, storage, and be difficult for accurately grasp taking dose.Dispersible tablet has the advantage of tablet and liquid preparation concurrently, has overcome both deficiencies; Compare with conventional tablet, dispersible tablet have disperse rapidly evenly, disintegration time is short, the medicine stripping is rapid, drug absorption is fast, bioavailability is high, untoward reaction is few and take characteristics easily.Dispersible tablet can add after the aqueous dispersion oral, also can dispersible tablet be contained in and suck clothes in the mouth or swallow.

The dispersible tablet listing is abroad promptly arranged in the eighties in 20th century.British Pharmacopoeia version in 1980 has promptly been recorded dispersible tablet, and European Pharmacopoeia 2003 editions also records.At present; The dispersible tablet of a plurality of kinds of China national Drug Administration approved gets into clinical research or listing, for example simvastatin dispersible tablet, Lovastatin dispersible tablet, atorvastatin calcium dispersible tablet, Rosuvastatin calcium dispersible tablet, Pitavastatin calcium dispersible tablet and Amlodipine Besylate Tablet atorvastatin calcium dispersible tablet.

Because cholesterol absorption inhibitor for example replaces wheat cloth according to Ezetimibe, avasimibe or handkerchief; Statins is simvastatin, Atorvastatin calcium, rosuvastain calcium, lovastatin or Pitavastatin Calcium for example; Fibrate is fenofibrate, fenofibrate acid, bezafibrate, clofibrate, ciprofibrate, gemfibrozil, clinofibrate, etofibrate, simfibrate or etofylline clofibrate for example; All be insoluble in water; Therefore the present invention processes dispersible tablet with itself or its compositions; Not only meet the Chinese Pharmacopoeia requirement; And have the advantage faster than conventional tablet and capsule disintegrate, that the drug effect performance is faster, dissolution is high, the bioavailability significance improves, and brought convenience to clinical application, obtained beyond thought therapeutic effect.

The purposes of dispersible tablet of the present invention is preferred for treatment or prevention patient's dyslipidemia or angiopathy.

Like the described dispersible tablet of claim (1), it is characterized in that (2) it is made up of a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester and at least a pharmaceutically acceptable carrier.More preferably; The percentage by weight of the total amount of wherein said a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester and pharmaceutically acceptable carrier is 0.01～99.9%; Be preferably 0.1～90%; More preferably 0.2～70%, more preferably 0.2～50%, more preferably 0.5～30%.

A certain amount of cholesterol absorption inhibitor of the present invention or its pharmaceutically acceptable salt or ester are preferably according to Ezetimibe, avasimibe, handkerchief for wheat cloth, eldacimibe, Yi Lumaibu or its pharmaceutically acceptable salt or ester; More preferably replace wheat cloth according to Ezetimibe, avasimibe, handkerchief; More preferably according to Ezetimibe.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of according to Ezetimibe or its pharmaceutically acceptable salt or ester and pharmaceutically acceptable carrier 2.5～80mg's.Be preferably according to Ezetimibe according to Ezetimibe or its pharmaceutically acceptable salt or ester; Each UD according to Ezetimibe is 2.5～80mg; Be preferably 2.5～40mg; 2.5～20mg more preferably; More preferably 2.5mg, 5mg, 10mg, 20mg, 40mg or 80mg; More preferably 5mg or 10mg.More preferably; The percentage by weight of wherein said total amount according to Ezetimibe or its pharmaceutically acceptable salt or ester and pharmaceutically acceptable carrier is 0.01～99.9%, is preferably 0.1～90%, more preferably 0.2～70%; More preferably 0.5～50%, more preferably 0.5～30%.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of the avasimibe of 25～1000mg or its pharmaceutically acceptable salt or ester and at least a pharmaceutically acceptable carrier.Avasimibe or its pharmaceutically acceptable salt or ester are preferably avasimibe; Each UD of avasimibe is 25～1000mg; Be preferably 25～500mg; 50～250mg more preferably; Be more preferably 25mg, 50mg, 100mg, 200mg, 250mg or 500mg; Be more preferably 100mg, 200mg or 250mg.More preferably, the percentage by weight of the total amount of wherein said avasimibe or its pharmaceutically acceptable salt or ester and pharmaceutically acceptable carrier is 0.1～99.9%, is preferably 0.5～90%, more preferably 1～70%, more preferably 2.5～50%.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of for Mai Bu or its pharmaceutically acceptable salt or ester and at least a pharmaceutically acceptable carrier a certain amount of handkerchief.

(3) like the described dispersible tablet of claim (1); It is characterized in that it is made up of a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester and a certain amount of lipid-regulation medicine or its pharmaceutically acceptable salt or ester or its mixture and pharmaceutically acceptable carrier.More preferably; The percentage by weight of wherein said cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester and lipid-regulation medicine or its pharmaceutically acceptable salt or ester or its mixture is 0.0001: 1～1000: 1; Be preferably 0.001: 1～500: 1; More preferably 0.01: 1～100: 1, more preferably 0.05: 1～50: 1, more preferably 0.1: 1～20: 1.

Cholesterol absorption inhibitor of the present invention or its pharmaceutically acceptable salt or ester preferred above-mentioned described those; More preferably according to Ezetimibe.Each UD preferred respectively above-mentioned described those.

Lipid-regulation medicine of the present invention or its pharmaceutically acceptable salt or ester preferred above-mentioned described those; More preferably simvastatin, Atorvastatin calcium, rosuvastain calcium, lovastatin, Pitavastatin Calcium, fenofibrate, fenofibrate acid, nicotinic acid or Lomitapide.Each UD preferred respectively above-mentioned described those.

For Pitavastatin or its pharmaceutically acceptable salt or ester, UD is 0.25～16mg, is preferably 0.25～8mg; 0.25～4mg more preferably; More preferably be approximately 0.5mg, 1mg, 2mg or 4mg.

For fenofibrate, fenofibrate acid or its pharmaceutically acceptable salt or ester; UD is 1～500mg; Be preferably 35～300mg; More preferably 100～300mg further is preferably about 80mg, about 105mg, about 110mg, about 120mg, about 130mg, about 135mg, about 145mg, about 160mg, about 200mg or about 267mg, most preferably is about 120mg, about 130mg, about 145mg, about 160mg or about 200mg.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of according to the slow release nicotinic acid of Ezetimibe and 0.25～2g or its pharmaceutically acceptable salt or ester and pharmaceutically acceptable at least carrier 2.5～80mg's.More preferably; Wherein said percentage by weight according to Ezetimibe and slow release nicotinic acid or its pharmaceutically acceptable salt or ester is 0.001: 1～100: 1; Be preferably 0.001: 1～50: 1; More preferably 0.002: 1～25: 1, more preferably 0.05: 1～10: 1, more preferably 0.01: 1～1: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of slow release nicotinic acid and the pharmaceutically acceptable at least carrier according to Ezetimibe, statins or its pharmaceutically acceptable salt or ester and 0.25～2g of 2.5～80mg.More preferably; Wherein said percentage by weight according to Ezetimibe, statins or its pharmaceutically acceptable salt or ester and slow release nicotinic acid is 0.001～0.32: 0.0001～0.64: 1; Be preferably 0.002～0.16: 0.002～0.32: 1, be preferably 0.01～0.16: 0.001～0.32: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of according to the Lomitapide of Ezetimibe and 2.5～120mg or its pharmaceutically acceptable salt or ester and at least a pharmaceutically acceptable carrier 2.5～80mg's.More preferably; Wherein said percentage by weight according to Ezetimibe and Lomitapide or its pharmaceutically acceptable salt or ester is 0.001: 1～1000: 1; Be preferably 0.01: 1～100: 1; Be preferably 0.05: 1～50: 1, be preferably 0.05: 1～20: 1, more preferably 0.1: 1～10: 1.

(4) like the described dispersible tablet of claim (3); It is characterized in that it is made up of a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester and a certain amount of statins or its pharmaceutically acceptable salt or ester and at least a pharmaceutically acceptable carrier.More preferably; The percentage by weight of wherein said cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester and statins or its pharmaceutically acceptable salt or ester is 0.01: 1～1000: 1; More preferably 0.01: 1～320: 1; More preferably 0.03: 1～80: 1, more preferably 0.06: 1～40: 1, more preferably 0.1: 1～20: 1.

Cholesterol absorption inhibitor of the present invention or its pharmaceutically acceptable salt or ester preferred above-mentioned described those; More preferably according to Ezetimibe; Each UD preferred respectively above-mentioned described those.

Statins of the present invention or its pharmaceutically acceptable salt or ester are preferably simvastatin, Atorvastatin calcium, rosuvastain calcium, lovastatin or Pitavastatin Calcium; Each UD preferred respectively above-mentioned described those.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of according to the statins of Ezetimibe and 0.25～160mg or its pharmaceutically acceptable salt or ester and at least a pharmaceutically acceptable carrier 2.5-80mg's.More preferably; Wherein said percentage by weight according to Ezetimibe and statins or its pharmaceutically acceptable salt or ester is 0.01: 1～320: 1; Be preferably 0.01: 1～160: 1; More preferably 0.03: 1～80: 1, more preferably 0.06: 1～40: 1, more preferably 0.1: 1～20: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of simvastatin and the pharmaceutically acceptable carrier according to Ezetimibe and 5～160mg of 2.5-80mg.More preferably, wherein said percentage by weight according to Ezetimibe and simvastatin is 0.01: 1～16: 1, more preferably 0.03: 1～8: 1, and more preferably 0.06: 1～4: 1, more preferably 0.06: 1～1: 1, more preferably 0.1: 1～1: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of Atorvastatin calcium and at least a pharmaceutically acceptable carrier according to Ezetimibe and 5～160mg of 2.5-80mg.More preferably, wherein said percentage by weight according to Ezetimibe and Atorvastatin calcium is 0.01: 1～16: 1, more preferably 0.06: 1～4: 1, and more preferably 0.06: 1～1: 1, more preferably 0.1: 1～1: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of rosuvastain calcium and at least a pharmaceutically acceptable carrier according to Ezetimibe and 2.5～80mg of 2.5-80mg.More preferably, wherein said percentage by weight according to Ezetimibe and rosuvastain calcium is 0.03: 1～32: 1, more preferably 0.03: 1～16: 1, and more preferably 0.06: 1～4: 1, more preferably 0.1: 1～2: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of lovastatin and the pharmaceutically acceptable carrier according to Ezetimibe and 5～160mg of 2.5-80mg.More preferably, wherein said percentage by weight according to Ezetimibe and lovastatin is 0.01: 1～16: 1, more preferably 0.03: 1～8: 1, and more preferably 0.06: 1～4: 1, more preferably 0.06: 1～1: 1, more preferably 0.1: 1～1: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of Pitavastatin Calcium and at least a pharmaceutically acceptable carrier according to Ezetimibe and 0.25～8mg of 2.5-80mg.More preferably, wherein said percentage by weight according to Ezetimibe and Pitavastatin Calcium is 0.3: 1～320: 1, more preferably 0.3: 1～160: 1, and more preferably 0.5: 1～40: 1, more preferably 1: 1～20: 1.

(5) like the described dispersible tablet of claim (3); It is characterized in that it is made up of a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester and a certain amount of fibrate or its pharmaceutically acceptable salt or ester and at least a pharmaceutically acceptable carrier.

Fibrate of the present invention or its pharmaceutically acceptable salt or ester are selected from fenofibrate, fenofibrate acid, bezafibrate, clofibrate, ciprofibrate, gemfibrozil, clinofibrate, etofibrate, simfibrate, etofylline clofibrate or its pharmaceutically acceptable salt or ester; Be preferably fenofibrate, fenofibrate acid, bezafibrate, clofibrate, ciprofibrate, gemfibrozil, clinofibrate, etofibrate, simfibrate or etofylline clofibrate; Fenofibrate or fenofibrate acid more preferably; Each UD preferred respectively above-mentioned described those.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of according to the fibrate of Ezetimibe and 1～1000mg or its pharmaceutically acceptable salt or ester and at least a pharmaceutically acceptable carrier 2.5-80mg's.More preferably; Wherein said percentage by weight according to Ezetimibe and fibrate or its pharmaceutically acceptable salt or ester is 0.002: 1～320: 1; Be preferably 0.002: 1～160: 1; More preferably 0.01: 1～80: 1, more preferably 0.01: 1～40: 1, more preferably 0.01: 1～20: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of fenofibrate and at least a pharmaceutically acceptable carrier according to Ezetimibe and 35～300mg of 2.5-80mg.More preferably, wherein said percentage by weight according to Ezetimibe and fenofibrate is 0.008～2.29: 1, is preferably 0.016～1.15: 1, be preferably 0.015～0.1: and 1, be preferably 0.025～0.084: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of fenofibrate acid and the pharmaceutically acceptable at least carrier according to Ezetimibe and 35～300mg of 2.5-80mg.More preferably, wherein said percentage by weight according to Ezetimibe and fenofibrate acid is 0.008～2.29: 1, is preferably 0.016～1.15: 1, be preferably 0.015～0.1: and 1, be preferably 0.025～0.084: 1.

(6) like the described dispersible tablet of claim (3); It is characterized in that it is made up of a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester, a certain amount of statins or its pharmaceutically acceptable salt or ester and a certain amount of fibrate or its pharmaceutically acceptable salt or ester and at least a pharmaceutically acceptable carrier.

Statins of the present invention or its pharmaceutically acceptable salt or ester preferred above-mentioned described those; More preferably simvastatin, Atorvastatin calcium, rosuvastain calcium, lovastatin or Pitavastatin Calcium; Each UD preferred respectively above-mentioned described those.

Fibrate of the present invention or its pharmaceutically acceptable salt or ester preferred above-mentioned described those; More preferably fenofibrate, fenofibrate acid, bezafibrate, clofibrate, ciprofibrate, gemfibrozil, clinofibrate, etofibrate, simfibrate or etofylline clofibrate; Fenofibrate or fenofibrate acid more preferably; Each UD preferred respectively above-mentioned described those.

A preferred version of the present invention; It is characterized in that described dispersible tablet is made up of according to the fibrate of the statins of Ezetimibe or its pharmaceutically acceptable salt or ester, 0.25～160mg or its pharmaceutically acceptable salt or ester, 35～1000mg or its pharmaceutically acceptable salt or ester and at least a pharmaceutically acceptable carrier 2.5～80mg's.More preferably; Wherein said percentage by weight according to Ezetimibe or its pharmaceutically acceptable salt or ester, statins or its pharmaceutically acceptable salt or ester and fibrate or its pharmaceutically acceptable salt or ester is 0.0025～2.29: 0.00025～4.58: 1; Be preferably 0.005～2.29: 0.0005～4.58: 1; Be preferably 0.005～1.15: 0.001～2.29: 1; More preferably 0.025～0.08: 0.0025～0.67: 1, more preferably 0.025～0.08: 0.0025～0.34: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of according to the simvastatin of Ezetimibe, 5～160mg and fenofibrate and at least a pharmaceutically acceptable carrier of 100～300mg 2.5～80mg's.More preferably; Wherein said percentage by weight according to Ezetimibe, simvastatin and fenofibrate is 0.008～0.8: 0.016～1.6: 1; Be preferably 0.016～0.8: 0.032～1.6: 1; More preferably 0.016～0.4: 0.032～0.8: 1, more preferably 0.025～0.08: 0.05～0.67: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of according to the Atorvastatin calcium of Ezetimibe, 5～160mg and fenofibrate and the pharmaceutically acceptable carrier of 100～300mg 2.5～80mg's.More preferably; Wherein said percentage by weight according to Ezetimibe, Atorvastatin calcium and fenofibrate is 0.008～0.8: 0.016～1.6: 1; Be preferably 0.016～0.8: 0.032～1.6: 1; More preferably 0.016～0.4: 0.032～0.8: 1, more preferably 0.025～0.08: 0.05～0.67: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of according to the rosuvastain calcium of Ezetimibe, 2.5～80mg and fenofibrate and the pharmaceutically acceptable carrier of 100～300mg 2.5～80mg's.More preferably; Wherein said percentage by weight according to Ezetimibe, rosuvastain calcium and fenofibrate is 0.008～0.8: 0.008～0.8: 1; Be preferably 0.016～0.8: 0.016～0.8: 1; More preferably 0.016～0.4: 0.016～0.4: 1, more preferably 0.025～0.08: 0.025～0.34: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of according to the lovastatin of Ezetimibe, 5～160mg and fenofibrate and at least a pharmaceutically acceptable carrier of 100～300mg 2.5～80mg's.More preferably; Wherein said percentage by weight according to Ezetimibe, lovastatin and fenofibrate is 0.008～0.8: 0.016～1.6: 1; Be preferably 0.016～0.8: 0.032～1.6: 1; More preferably 0.016～0.4: 0.032～0.8: 1, more preferably 0.025～0.08: 0.05～0.67: 1.

A preferred version of the present invention is characterized in that, described dispersible tablet is made up of according to the Pitavastatin Calcium of Ezetimibe, 0.25～16mg and fenofibrate and the pharmaceutically acceptable carrier of 100～300mg 2.5～80mg's.More preferably; Wherein said percentage by weight according to Ezetimibe, Pitavastatin Calcium and fenofibrate is 0.008～0.8: 0.0008～0.16: 1; Be preferably 0.016～0.8: 0.0016～0.16: 1; Be preferably 0.016～0.4: 0.0025～0.08: 1, more preferably 0.025～0.08: 0.0025～0.04: 1.

(7) like the described dispersible tablet of claim (4); It is characterized in that; Described cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester are according to Ezetimibe; Described statins or its pharmaceutically acceptable salt or ester are simvastatin, and the described combination that is selected from following fixed dosage according to Ezetimibe and simvastatin:

About 2.5mg is according to Ezetimibe and about 5mg simvastatin; About 2.5mg is according to Ezetimibe and about 10mg simvastatin; About 2.5mg is according to Ezetimibe and about 20mg simvastatin; About 2.5mg is according to Ezetimibe and about 40mg simvastatin; About 2.5mg is according to Ezetimibe and about 80mg simvastatin;

About 5mg is according to Ezetimibe and about 5mg simvastatin; About 5mg is according to Ezetimibe and about 10mg simvastatin; About 5mg is according to Ezetimibe and about 20mg simvastatin; About 5mg is according to Ezetimibe and about 40mg simvastatin; About 5mg is according to Ezetimibe and about 80mg simvastatin;

About 10mg is according to Ezetimibe and about 5mg simvastatin; About 10mg is according to Ezetimibe and about 10mg simvastatin; About 10mg is according to Ezetimibe and about 20mg simvastatin; About 10mg is according to Ezetimibe and about 40mg simvastatin; About 10mg is according to Ezetimibe and about 80mg simvastatin;

About 20mg is according to Ezetimibe and about 5mg simvastatin; About 20mg is according to Ezetimibe and about 10mg simvastatin; About 20mg is according to Ezetimibe and about 20mg simvastatin; About 20mg is according to Ezetimibe and about 40mg simvastatin; About 20mg is according to Ezetimibe and about 80mg simvastatin;

About 40mg is according to Ezetimibe and about 5mg simvastatin; About 40mg is according to Ezetimibe and about 10mg simvastatin; About 40mg is according to Ezetimibe and about 20mg simvastatin; About 40mg is according to Ezetimibe and about 40mg simvastatin; About 40mg is according to Ezetimibe and about 80mg simvastatin;

About 80mg is according to Ezetimibe and about 5mg simvastatin; About 80mg is according to Ezetimibe and about 10mg simvastatin; About 80mg is according to Ezetimibe and about 20mg simvastatin; About 80mg is according to Ezetimibe and about 40mg simvastatin; About 80mg is according to Ezetimibe and about 80mg simvastatin.

(8) like the described dispersible tablet of claim (5); It is characterized in that; Described cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester are according to Ezetimibe; Described fibrate or its pharmaceutically acceptable salt or ester are fenofibrate, and the described combination that is selected from following fixed dosage according to Ezetimibe and fenofibrate:

About 2.5mg is according to Ezetimibe and about 120mg fenofibrate; About 2.5mg is according to Ezetimibe and about 130mg fenofibrate; About 2.5mg is according to Ezetimibe and about 145mg fenofibrate; About 2.5mg is according to Ezetimibe and about 160mg fenofibrate; About 2.5mg is according to Ezetimibe and about 200mg fenofibrate;

About 5mg is according to Ezetimibe and about 120mg fenofibrate; About 5mg is according to Ezetimibe and about 130mg fenofibrate; About 5mg is according to Ezetimibe and about 145mg fenofibrate; About 5mg is according to Ezetimibe and about 160mg fenofibrate; About 5mg is according to Ezetimibe and about 200mg fenofibrate;

About 10mg is according to Ezetimibe and about 120mg fenofibrate; About 10mg is according to Ezetimibe and about 130mg fenofibrate; About 10mg is according to Ezetimibe and about 145mg fenofibrate; About 10mg is according to Ezetimibe and about 160mg fenofibrate; About 10mg is according to Ezetimibe and about 200mg fenofibrate;

About 20mg is according to Ezetimibe and about 120mg fenofibrate; About 20mg is according to Ezetimibe and about 130mg fenofibrate; About 20mg is according to Ezetimibe and about 145mg fenofibrate; About 20mg is according to Ezetimibe and about 160mg fenofibrate; About 20mg is according to Ezetimibe and about 200mg fenofibrate;

About 40mg is according to Ezetimibe and about 120mg fenofibrate; About 40mg is according to Ezetimibe and about 130mg fenofibrate; About 40mg is according to Ezetimibe and about 145mg fenofibrate; About 40mg is according to Ezetimibe and about 160mg fenofibrate; About 40mg is according to Ezetimibe and about 200mg fenofibrate;

About 80mg is according to Ezetimibe and about 120mg fenofibrate; About 80mg is according to Ezetimibe and about 130mg fenofibrate; About 80mg is according to Ezetimibe and about 145mg fenofibrate; About 80mg is according to Ezetimibe and about 160mg fenofibrate; About 80mg is according to Ezetimibe and about 200mg fenofibrate.

(9) like the described dispersible tablet of claim (6); It is characterized in that; Described cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester are according to Ezetimibe; Described statins or its pharmaceutically acceptable salt or ester are simvastatin, and described fibrate or its pharmaceutically acceptable salt or ester are fenofibrate, and the described combination that is selected from following fixed dosage according to Ezetimibe, simvastatin and fenofibrate:

About 5mg is according to Ezetimibe, about 5mg simvastatin and about 145mg fenofibrate; About 5mg is according to Ezetimibe, about 10mg simvastatin and about 145mg fenofibrate; About 5mg is according to Ezetimibe, about 20mg simvastatin and about 145mg fenofibrate; About 5mg is according to Ezetimibe, about 40mg simvastatin and about 145mg fenofibrate; About 5mg is according to Ezetimibe, about 80mg simvastatin and about 145mg fenofibrate;

About 10mg is according to Ezetimibe, about 5mg simvastatin and about 145mg fenofibrate; About 10mg is according to Ezetimibe, about 10mg simvastatin and about 145mg fenofibrate; About 10mg is according to Ezetimibe, about 20mg simvastatin and about 145mg fenofibrate; About 10mg is according to Ezetimibe, about 40mg simvastatin and about 145mg fenofibrate; About 10mg is according to Ezetimibe, about 80mg simvastatin and about 145mg fenofibrate;

About 20mg is according to Ezetimibe, about 5mg simvastatin and about 145mg fenofibrate; About 20mg is according to Ezetimibe, about 10mg simvastatin and about 145mg fenofibrate; About 20mg is according to Ezetimibe, about 20mg simvastatin and about 145mg fenofibrate; About 20mg is according to Ezetimibe, about 40mg simvastatin and about 145mg fenofibrate; About 20mg is according to Ezetimibe, about 80mg simvastatin and about 145mg fenofibrate;

About 5mg is according to Ezetimibe, about 5mg simvastatin and about 160mg fenofibrate; About 5mg is according to Ezetimibe, about 10mg simvastatin and about 160mg fenofibrate; About 5mg is according to Ezetimibe, about 20mg simvastatin and about 160mg fenofibrate; About 5mg is according to Ezetimibe, about 40mg simvastatin and about 160mg fenofibrate; About 5mg is according to Ezetimibe, about 80mg simvastatin and about 160mg fenofibrate;

About 10mg is according to Ezetimibe, about 5mg simvastatin and about 160mg fenofibrate; About 10mg is according to Ezetimibe, about 10mg simvastatin and about 160mg fenofibrate; About 10mg is according to Ezetimibe, about 20mg simvastatin and about 160mg fenofibrate; About 10mg is according to Ezetimibe, about 40mg simvastatin and about 160mg fenofibrate; About 10mg is according to Ezetimibe, about 80mg simvastatin and about 160mg fenofibrate;

About 20mg is according to Ezetimibe, about 5mg simvastatin and about 160mg fenofibrate; About 20mg is according to Ezetimibe, about 10mg simvastatin and about 160mg fenofibrate; About 20mg is according to Ezetimibe, about 20mg simvastatin and about 160mg fenofibrate; About 20mg is according to Ezetimibe, about 40mg simvastatin and about 160mg fenofibrate; About 20mg is according to Ezetimibe, about 80mg simvastatin and about 160mg fenofibrate;

About 5mg is according to Ezetimibe, about 5mg simvastatin and about 200mg fenofibrate; About 5mg is according to Ezetimibe, about 10mg simvastatin and about 200mg fenofibrate; About 5mg is according to Ezetimibe, about 20mg simvastatin and about 200mg fenofibrate; About 5mg is according to Ezetimibe, about 40mg simvastatin and about 200mg fenofibrate; About 5mg is according to Ezetimibe, about 80mg simvastatin and about 200mg fenofibrate;

About 10mg is according to Ezetimibe, about 5mg simvastatin and about 200mg fenofibrate; About 10mg is according to Ezetimibe, about 10mg simvastatin and about 200mg fenofibrate; About 10mg is according to Ezetimibe, about 20mg simvastatin and about 200mg fenofibrate; About 10mg is according to Ezetimibe, about 40mg simvastatin and about 200mg fenofibrate; About 10mg is according to Ezetimibe, about 80mg simvastatin and about 200mg fenofibrate;

About 20mg is according to Ezetimibe, about 5mg simvastatin and about 200mg fenofibrate; About 20mg is according to Ezetimibe, about 10mg simvastatin and about 200mg fenofibrate; About 20mg is according to Ezetimibe, about 20mg simvastatin and about 200mg fenofibrate; About 20mg is according to Ezetimibe, about 40mg simvastatin and about 200mg fenofibrate; About 20mg is according to Ezetimibe, about 80mg simvastatin and about 200mg fenofibrate.

(10) be used for treating or preventing the application of the medicine of patient's dyslipidemia or angiopathy in preparation like each described dispersible tablet of claim (1) to (9).

Term " patient " refers to animal, preferred mammal, and optimum is chosen, and comprises masculinity and femininity.

Term " dyslipidemia " be often referred in the blood plasma cholesterol with (or) the sweet ester of glycerol (TG) raises, and is commonly called as hyperlipemia.In fact hyperlipemia is also made a general reference the various dyslipidemia that comprise the low hdl mass formed by blood stasis.

Term " angiopathy " is often referred to cardiovascular disease, cerebrovascular disease or peripheral vascular disease.

Term " medicine ", " chemical compound ", " active matter ", " active substance " and " activating agent " can use with exchanging; And refer to a kind of material such as chemical compound or complex; Said material is when using with effective dose; Health had measurable useful physiological effect, like the treatment effect in the treatment of disease or obstacle; Further; When using these terms; Or when specific active matter passes through title or kind specific recognition; Should be understood that and saidly enumerate expection and comprise active matter itself; With and pharmaceutically acceptable pharmacological activity derivant, or with the chemical compound of its significant correlation, include but not limited to mixture, different crystal forms or armorphous, solvate, hydrate, oxide, fragment and the radiosiotope of any ratio of salt or ester, pharmaceutically acceptable salt or ester, prodrug, active metabolite, various isomer or these isomers.

The specific embodiment

Specify the present invention below in conjunction with embodiment.

Embodiment 1: according to the Ezetimibe dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	2.50	5.00	10.00	20.00
Microcrystalline Cellulose	15.00	30.00	60.00	120.00
					Mannitol	20.75	41.50	83.00	166.00
Sucralose	0.25	0.50	1.00	2.00
					30 POVIDONE K 30 BP/USP 30	5.00	10.00	20.00	40.00
Sodium lauryl sulphate	0.50	1.00	2.00	4.00
					The L-hydroxypropyl cellulose	2.50	5.00	10.00	20.00
Carboxymethylstach sodium	1.00	2.00	4.00	8.00
					Magnesium stearate	1.50	3.00	6.00	12.00
The Fructus Fragariae Ananssae powdered flavor	1.00	2.00	4.00	8.00
					30% alcoholic solution	In right amount	In right amount	In right amount	In right amount
Sheet is heavy	50.00	100.00	200.00	400.00

Embodiment 2: according to Ezetimibe simvastatin dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	10.00	10.00	10.00	10.00
Simvastatin	10.00	20.00	40.00	80.00
					Optimize microcrystalline Cellulose	29.00	58.00	116.00	116.00
Mannitol	17.50	45.00	120.00	80.00
					Sodium hydrogen phosphate	11.00	22.00	44.00	44.00
Sucralose	1.50	3.00	6.00	6.00
					30 POVIDONE K 30 BP/USP 30	8.00	16.00	32.00	32.00
The Fructus Fragariae Ananssae powdered flavor	1.00	2.00	4.00	4.00
					Sodium lauryl sulphate	2.00	4.00	8.00	8.00
The L-hydroxypropyl cellulose	5.00	10.00	20.00	20.00
					Carboxymethylstach sodium	3.00	6.00	12.00	12.00
Magnesium stearate	2.00	4.00	8.00	8.00

30% alcoholic solution	In right amount	In right amount	In right amount	In right amount
					Sheet is heavy	100.00	200.00	400.00	400.00

Embodiment 3: according to Ezetimibe atorvastatin calcium dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	10.00	10.00	10.00	10.00
Atorvastatin calcium	10.85	21.70	43.40	86.80
					Microcrystalline Cellulose	30.00	60.00	40.00	60.00
Mannitol	19.65	49.30	27.60	65.20
					Sodium citrate	10.00	20.00	40.00	80.00
Sucralose	1.50	3.00	3.00	6.00
					30 POVIDONE K 30 BP/USP 30	5.00	10.00	10.00	40.00
The Fructus Fragariae Ananssae powdered flavor	1.00	2.00	2.00	4.00
					Polyoxyethylene sorbitan monoleate	2.00	4.00	4.00	8.00
Cross-linking sodium carboxymethyl cellulose	5.00	10.00	10.00	20.00
					Carboxymethylstach sodium	3.00	6.00	6.00	12.00
Magnesium stearate	2.00	4.00	4.00	8.00
					30% alcoholic solution	In right amount	In right amount	In right amount	In right amount
Sheet is heavy	100.00	200.00	200.00	400.00

Embodiment 4: according to Ezetimibe Rosuvastatin calcium dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	10.00	10.00	10.00	10.00
Rosuvastain calcium	5.20	10.40	20.80	41.60
					Microcrystalline Cellulose	35.00	70.00	140.00	120.00
Xylitol	20.30	50.60	111.20	90.40
					Sodium hydrogen phosphate	5.00	10.00	20.00	40.00
Sucralose	1.50	3.00	6.00	6.00
					30 POVIDONE K 30 BP/USP 30	10.00	20.00	40.00	40.00

The Fructus Ananadis comosi powdered flavor	1.00	2.00	4.00	4.00
					Sodium lauryl sulphate	2.00	4.00	8.00	8.00
Sodium carboxymethyl cellulose	5.00	10.00	20.00	20.00
					Carboxymethylstach sodium	3.00	6.00	12.00	12.00
Magnesium stearate	2.00	4.00	8.00	8.00
					30% alcoholic solution	In right amount	In right amount	In right amount	In right amount
Sheet is heavy	100.00	200.00	400.00	400.00

Embodiment 5: according to the Ezetimibe Lovastatin dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	10.00	10.00	10.00	10.00
Lovastatin	10.00	20.00	40.00	80.00
					Powderd cellulose	30.00	60.00	120.00	120.00
Xylitol	16.00	42.00	94.00	14.00
					Sodium hydrogen phosphate	10.00	20.00	40.00	80.00
Aspartame	3.00	6.00	12.00	12.00
					30 POVIDONE K 30 BP/USP 30	8.00	16.00	32.00	32.00
The Fructus Ananadis comosi powdered flavor	1.00	2.00	4.00	4.00
					Polyoxyethylene sorbitan monoleate	2.00	4.00	8.00	8.00
The L-hydroxypropyl cellulose	5.00	10.00	20.00	20.00
					Carboxymethylstach sodium	3.00	6.00	12.00	12.00
Magnesium stearate	2.00	4.00	8.00	8.00
					30% alcoholic solution	In right amount	In right amount	In right amount	In right amount
Sheet is heavy	100.00	200.00	400.00	400.00

Embodiment 6: according to Ezetimibe Pitavastatin calcium dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	10.00	10.00	10.00	10.00
Pitavastatin Calcium	0.50	1.00	2.00	4.00

Microcrystalline Cellulose	30.00	30.00	30.00	30.00
					Mannitol	35.00	34.00	32.00	28.00
Sodium hydrogen phosphate	0.50	1.00	2.00	4.00
					Steviosin	3.00	3.00	3.00	3.00
30 POVIDONE K 30 BP/USP 30	8.00	8.00	8.00	8.00
					The Fructus Fragariae Ananssae powdered flavor	1.00	1.00	1.00	1.00
Polyoxyethylene sorbitan monoleate	2.00	2.00	2.00	2.00
					Polyvinylpolypyrrolidone	5.00	5.00	5.00	5.00
Carboxymethylstach sodium	3.00	3.00	3.00	3.00
					Magnesium stearate	2.00	2.00	2.00	2.00
50% alcoholic solution	In right amount	In right amount	In right amount	In right amount
					Sheet is heavy	100.00	100.00	100.00	100.00

Embodiment 7: according to Ezetimibe fenofibrate dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	10.00	10.00	10.00	10.00
Fenofibrate	130.00	145.00	160.00	200.00
					Microcrystalline Cellulose	80.00	80.00	80.00	50.00
Mannitol	82.00	67.00	52.00	42.00
					Sucralose	6.00	6.00	6.00	6.00
30 POVIDONE K 30 BP/USP 30	40.00	40.00	40.00	40.00
					The Fructus Fragariae Ananssae powdered flavor	4.00	4.00	4.00	4.00
Sodium lauryl sulphate	8.00	8.00	8.00	8.00
					The L-hydroxypropyl cellulose	20.00	20.00	20.00	20.00
Carboxymethylstach sodium	12.00	12.00	12.00	12.00
					Magnesium stearate	8.00	8.00	8.00	8.00
30% alcoholic solution	In right amount	In right amount	In right amount	In right amount
					Sheet is heavy	400.00	400.00	400.00	400.00

Embodiment 8: according to Ezetimibe fenofibrate acid dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	2.50	5.00	10.00	20.00
Fenofibrate acid	135.00	135.00	135.00	135.00
					Microcrystalline Cellulose	80.00	80.00	80.00	80.00
Mannitol	88.50	86.00	81.00	71.00
					Steviosin	5.00	5.00	5.00	5.00
30 POVIDONE K 30 BP/USP 30	40.00	40.00	40.00	40.00
					The Fructus Ananadis comosi powdered flavor	4.00	4.00	4.00	4.00
Polyoxyethylene sorbitan monoleate	5.00	5.00	5.00	5.00
					The L-hydroxypropyl cellulose	20.00	20.00	20.00	20.00
Carboxymethylstach sodium	12.00	12.00	12.00	12.00
					Magnesium stearate	8.00	8.00	8.00	8.00
50% alcoholic solution	In right amount	In right amount	In right amount	In right amount
					Sheet is heavy	400.00	400.00	400.00	400.00

Embodiment 9: according to Ezetimibe simvastatin fenofibrate dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	10.00	10.00	10.00	10.00
Simvastatin	10.00	20.00	20.00	20.00
					Fenofibrate	145.00	145.00	160.00	200.00
Microcrystalline Cellulose	80.00	80.00	80.00	80.00
					Mannitol	147.00	127.00	112.00	72.00
Sodium citrate	10.00	20.00	20.00	20.00
					Sucralose	6.00	6.00	6.00	6.00
30 POVIDONE K 30 BP/USP 30	40.00	40.00	40.00	40.00
					Strawberry essence	4.00	4.00	4.00	4.00
Sodium lauryl sulphate	8.00	8.00	8.00	8.00
					The L-hydroxypropyl cellulose	20.00	20.00	20.00	20.00

Carboxymethylstach sodium	12.00	12.00	12.00	12.00
					Magnesium stearate	8.00	8.00	8.00	8.00
30% alcoholic solution	In right amount	In right amount	In right amount	In right amount
					Sheet is heavy	500.00	500.00	500.00	500.00

Embodiment 10: according to Ezetimibe Atorvastatin calcium fenofibrate dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	10.00	10.00	10.00	10.00
Atorvastatin calcium	21.70	21.70	21.70	21.70
					Fenofibrate	130.00	145.00	160.00	200.00
Optimize microcrystalline Cellulose	80.00	80.00	80.00	80.00
					Mannitol	128.30	113.30	98.30	58.30
Sodium hydrogen phosphate	20.00	20.00	20.00	20.00
					Steviosin	5.00	5.00	5.00	5.00
30 POVIDONE K 30 BP/USP 30	40.00	40.00	40.00	40.00
					The Fructus Fragariae Ananssae powdered flavor	5.00	5.00	5.00	5.00
Polyoxyethylene sorbitan monoleate	10.00	10.00	10.00	10.00
					Sodium carboxymethyl cellulose	25.00	25.00	25.00	25.00
Carboxymethylstach sodium	15.00	15.00	15.00	15.00
					Magnesium stearate	10.00	10.00	10.00	10.00
50% alcoholic solution	In right amount	In right amount	In right amount	In right amount
					Sheet is heavy	500.00	500.00	500.00	500.00

Embodiment 11: according to Ezetimibe rosuvastain calcium fenofibrate dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	10.00	10.00	10.00	10.00
Rosuvastain calcium	10.40	20.80	10.40	10.40
					Fenofibrate	145.00	145.00	160.00	200.00
Powderd cellulose	80.00	80.00	80.00	80.00

Xylitol	146.60	126.20	131.60	91.60
					Sodium citrate	10.00	20.00	10.00	10.00
Sucralose	6.00	6.00	6.00	6.00
					30 POVIDONE K 30 BP/USP 30	40.00	40.00	40.00	40.00
The Fructus Ananadis comosi powdered flavor	4.00	4.00	4.00	4.00
					Sodium lauryl sulphate	8.00	8.00	8.00	8.00
Primojel	20.00	20.00	20.00	20.00
					Carboxymethylstach sodium	12.00	12.00	12.00	12.00
Magnesium stearate	8.00	8.00	8.00	8.00
					30% alcoholic solution	In right amount	In right amount	In right amount	In right amount
Sheet is heavy	500.00	500.00	500.00	500.00

Embodiment 12: according to Ezetimibe lovastatin fenofibrate dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	10.00	10.00	10.00	10.00
Lovastatin	10.00	20.00	20.00	20.00
					Fenofibrate	145.00	145.00	160.00	200.00
Powderd cellulose	80.00	80.00	80.00	80.00
					Mannitol	157.00	147.00	132.00	92.00
Aspartame	6.00	6.00	6.00	6.00
					30 POVIDONE K 30 BP/USP 30	40.00	40.00	40.00	40.00
Flavoring orange essence	4.00	4.00	4.00	4.00
					Sodium lauryl sulphate	8.00	8.00	8.00	8.00
The L-hydroxypropyl cellulose	20.00	20.00	20.00	20.00
					Carboxymethylstach sodium	12.00	12.00	12.00	12.00
Magnesium stearate	8.00	8.00	8.00	8.00
					50% alcoholic solution	In right amount	In right amount	In right amount	In right amount
Sheet is heavy	500.00	500.00	500.00	500.00

Embodiment 13: according to Ezetimibe Pitavastatin Calcium fenofibrate dispersible tablet

The supplementary material title	Dosage 1 (mg)	Dosage 2 (mg)	Dosage 3 (mg)	Dosage 4 (mg)
					According to Ezetimibe	10.00	10.00	10.00	10.00
Pitavastatin Calcium	1.00	2.00	1.00	1.00
					Fenofibrate	145.00	145.00	160.00	200.00
Microcrystalline Cellulose	80.00	80.00	80.00	80.00
					Xylitol	164.00	161.00	149.00	109.00
Sodium citrate	2.00	4.00	2.00	2.00
					Sucralose	6.00	6.00	6.00	6.00
30 POVIDONE K 30 BP/USP 30	40.00	40.00	40.00	40.00
					The Fructus Fragariae Ananssae powdered flavor	4.00	4.00	4.00	4.00
Sodium lauryl sulphate	8.00	8.00	8.00	8.00
					Sodium carboxymethyl cellulose	20.00	20.00	20.00	20.00
Carboxymethylstach sodium	12.00	12.00	12.00	12.00
					Magnesium stearate	8.00	8.00	8.00	8.00
30% alcoholic solution	In right amount	In right amount	In right amount	In right amount
					Sheet is heavy	500.00	500.00	500.00	500.00

Embodiment 1～13 method for preparing:

(A) with the principal agent micronization, particle diameter is controlled between 5～120 μ m, and is subsequent use;

(B) various pharmaceutically acceptable carriers being crossed 100 mesh sieves respectively pulverizes; Except that 30 POVIDONE K 30 BP/USP 30, carboxymethylstach sodium and magnesium stearate, with other various pharmaceutically acceptable carriers mix homogeneously in mixer;

(C) with micronized principal agent, with other various pharmaceutically acceptable carriers of mix homogeneously in V-Mixer by the equivalent method mix homogeneously that progressively increases;

(D) take by weighing 30 POVIDONE K 30 BP/USP 30, be dissolved in and process 5～15% 30 POVIDONE K 30 BP/USP 30 alcoholic solution in 30% or 50% alcoholic solution, do binding agent and use;

(E) will be the various supplementary materials of mix homogeneously, add and make soft material in above-mentioned 30 POVIDONE K 30 BP/USP 30 alcoholic solution, cross 40 orders or 50 mesh sieves and granulate, 60 ℃～80 ℃ oven dry add carboxymethylstach sodium and magnesium stearate, cross 24 orders or 18 mesh sieve granulate, make granule, and are subsequent use;

(F) drug content in the mensuration granule, it is heavy to calculate sheet;

(G) use tablet machine that granule is pressed into dispersible tablet, process 1000, promptly get.

Embodiment 14: dispersible tablet and conventional tablet mainly detect the index comparative result

Get the dispersible tablet and the commercially available conventional tablet of the embodiment of the invention 1～13 preparation: according to Ezetimibe sheet (benefit is fitted pure), according to Ezetimibe simvastatin sheet (extremely can preserve); To main detection index: disintegration, dissolution, dispersing uniformity and hardness detect, and the result sees table 1:

The main index comparative result that detects of table 1

Result of the test shows; The all disintegrates about 60～90 seconds of the sample of the embodiment of the invention 1～13 preparation; Dissolution is about 95～100%; Hardness is about 35～60 newton, explain by the dispersible tablet of the present invention preparation improve drug bioavailability and stable aspect its superiority is arranged, obtained beyond thought effect.

Testing instruments model and producer:

(A), ZRS-8G type intelligence dissolution test appearance (Tianda Tianfa Technology Co., Ltd.)

(B), YPD-200C matrix agent hardness tester (Shanghai Huanghai Sea medicine inspection Instr Ltd.)

(C), ZB-1D type intelligence disintegration tester (Tianda Tianfa Technology Co., Ltd.)

Embodiment 15: the dissolution rate of dispersible tablet and conventional tablet relatively

Get dispersible tablet and the commercially available conventional tablet (that benefit is fitted is pure, preserve to can) of the embodiment of the invention 1～2, investigate its dissolution rate, result of the test is seen table 2:

Table 2 dissolution rate is measured result (%)

Result of the test shows that the dispersible tablet dissolution reaches more than 90% in the time of 20 minutes, and the dissolution of the right pure and mild luxuriant growth of conventional tablet benefit to ability has only about 79%; The dispersible tablet dissolution reaches more than 98% in the time of 30 minutes, and the dissolution of the right pure and mild luxuriant growth of conventional tablet benefit to ability only is about 93%.The dispersible tablet disintegrate that the present invention preparation is described rapidly, be uniformly dispersed and dissolution high, thereby raising bioavailability in significance ground has its superiority.

Obviously, the above embodiment of the present invention only be for clearly the present invention is described and is done for example, and be not to be qualification to embodiment of the present invention.For the those of ordinary skill in affiliated field, on the basis of above-mentioned explanation, can also make other multi-form variation or change.Here need not also can't give exhaustive to all embodiments.And these belong to conspicuous variation or the change that spirit of the present invention extended out and still are among protection scope of the present invention.In addition, patent documentation that the present invention quoted and non-patent literature are incorporated herein by reference this at this in full.

Claims

1. a dispersible tablet is characterized in that, it is made up of following several parts:

(II) pharmaceutically acceptable carrier.

2. dispersible tablet as claimed in claim 1 is characterized in that, it is made up of a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester and pharmaceutically acceptable carrier.

3. dispersible tablet as claimed in claim 1; It is characterized in that it is made up of a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester and a certain amount of lipid-regulation medicine or its pharmaceutically acceptable salt or ester or its mixture and pharmaceutically acceptable carrier.

4. dispersible tablet as claimed in claim 3; It is characterized in that it is made up of a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester and a certain amount of statins or its pharmaceutically acceptable salt or ester and pharmaceutically acceptable carrier.

5. dispersible tablet as claimed in claim 3; It is characterized in that it is made up of a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester and a certain amount of fibrate or its pharmaceutically acceptable salt or ester and pharmaceutically acceptable carrier.

6. dispersible tablet as claimed in claim 3; It is characterized in that it is made up of a certain amount of cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester, a certain amount of statins or its pharmaceutically acceptable salt or ester and a certain amount of fibrate or its pharmaceutically acceptable salt or ester and pharmaceutically acceptable carrier.

7. dispersible tablet as claimed in claim 4; It is characterized in that; Described cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester are according to Ezetimibe; Described statins or its pharmaceutically acceptable salt or ester are simvastatin, and the described combination that is selected from following fixed dosage according to Ezetimibe and simvastatin:

8. dispersible tablet as claimed in claim 5; It is characterized in that; Described cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester are according to Ezetimibe; Described fibrate or its pharmaceutically acceptable salt or ester are fenofibrate, and the described combination that is selected from following fixed dosage according to Ezetimibe and fenofibrate:

9. dispersible tablet as claimed in claim 6; It is characterized in that; Described cholesterol absorption inhibitor or its pharmaceutically acceptable salt or ester are according to Ezetimibe; Described statins or its pharmaceutically acceptable salt or ester are simvastatin, and described fibrate or its pharmaceutically acceptable salt or ester are fenofibrate, and the described combination that is selected from following fixed dosage according to Ezetimibe, simvastatin and fenofibrate:

10. be used for treating or prevent the application of the medicine of dyslipidemia or angiopathy in preparation like each described dispersible tablet of claim 1 to 9.