CN101912612A - Dispersible tablet containing fibrate and statin drug and application thereof - Google Patents
Dispersible tablet containing fibrate and statin drug and application thereof Download PDFInfo
- Publication number
- CN101912612A CN101912612A CN2010102758364A CN201010275836A CN101912612A CN 101912612 A CN101912612 A CN 101912612A CN 2010102758364 A CN2010102758364 A CN 2010102758364A CN 201010275836 A CN201010275836 A CN 201010275836A CN 101912612 A CN101912612 A CN 101912612A
- Authority
- CN
- China
- Prior art keywords
- fenofibrate
- calcium
- acid
- rosuvastain
- atorvastatin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a novel dispersible tablet consisting of a certain amount of fibrate drug or pharmaceutically acceptable salts or esters or derivatives of the fibrate drug and a certain amount of statin drug or pharmaceutically acceptable salts or esters and pharmaceutically acceptable carriers of the statin drug for treating dyslipidemia of patients. Compared with the ordinary tablet or capsule, the dispersible tablet has the characteristics of rapid and even dispersion, short disintegration time, rapid drug digestion, high bioavailability, good stability and convenient taking.
Description
Technical field
The present invention relates to a kind of novel dispersible tablet, it is made up of a certain amount of fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof and a certain amount of statins or its pharmaceutically acceptable salt or ester and pharmaceutically acceptable carrier, be used for the treatment of patient's dyslipidemia, 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 raises based on ischemic cardiovascular (comprising coronary heart disease and the cerebral infarction) sickness rate of 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).
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, closely related with the socio-economic development level, point out challenge and the opportunity that we face in the dyslipidemia preventing and controlling of economic transition phase and deposit.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 other atherosclerosis.
Fibrate also claims fibrate drug, this type of medicine is by peroxide activator enzyme accretion prism activated receptor α (PPAR α), stimulate lipoprotein lipase (LPL), apo A I and apo AII expression of gene, and inhibition apo CIII 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.The special class indication of shellfish is a hypertriglyceridemia or based on the combined hyperlipidemia familial and the low hdl mass formed by blood stasis of 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 may delay the progress of coronary atherosclerosis, reduces main coronary artery events.
Statins (statins) also claims 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 may have effects such as antiinflammatory, protection vascular endothelial function, and these effects may reduce relevant with coronary event.It is current hypercholesterolemia and the very important medicine of atherosclerosis prevented and treated that recent two decades comes the clinical studies show Statins.
In order to improve the blood fat compliance rate, reduce incidence rate of adverse reaction simultaneously, the use in conjunction of different classes of fat regulation medicine is a rational approach.Because the statins effect is sure, untoward reaction is few, can reduce general mortality rate and the outer pleiotropic effects of effect for reducing fat is arranged, associating blood fat reducing scheme is many to be made up of statins and another kind of lipid lowerers.Statins and fibrate therapeutic alliance are applicable to the combined hyperlipidemia familial patient abroad at present, purpose is that the level of TC, LDL-C and TG is obviously reduced, and the level of HDL-C obviously raises.This kind drug combination also is applicable to the treatment of atherogenicity dyslipidemia, especially when diabetes and metabolism syndrome with dyslipidemia.Therapeutic alliance can obviously improve plasma lipid profile (non-patent literature).
The benefit of drug combination also is: the fat regulation medicine of different mechanism of action 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.Therefore the current domestic and international consistent scheme of combination drug therapy treatment dyslipidemia patient who recommends to adopt the compound preparation that comprises the dosage fixed mixing ratio reduces the untoward reaction of medicine as far as possible, increases drug safety.
Patent documentation 1 discloses the adjustment release preparation that comprises activating agent in hydrophilic polymer substrate, and wherein said activating agent is the salt of fenofibrate acid, and the rate of release of wherein said preparation in external stripping do not rely on the ionic strength of dissolution medium basically.
Patent documentation 2 discloses and has related to oral formulations; it comprises activating agent; described activating agent comprises 2-[4-(4-chlorobenzene formacyl) phenoxy group]-2-methyl-propanoic acid, 2-[4-(4-chlorobenzene formacyl) phenoxy group]-salt or buffered 2-[4-(4-chlorobenzene formacyl) phenoxy group of 2-methyl-propanoic acid]-at least a in 2-methyl-propanoic acid.
Patent documentation 3 discloses the method that is prepared fenofibrate by fenofibric acid, this method prepares the fenofibric acid chloride by act on described fenofibric acid reaction in-situ with chlorinating agent, do not separate described fenofibric acid chloride subsequently, reacting with isopropyl alcohol makes fenofibrate.
Patent documentation 4～5 discloses a kind of preparation, it comprises i) fenofibric acid, its physiologically acceptable salt or derivant and other optional active substances, the adhesive component that ii) comprises at least a enteric solubility binding agent, and the optional iii) acceptable excipient of other physiology.In these preparations, fenofibric acid, its physiologically acceptable salt or derivant are preferably the form of molecular dispersoid.The present invention has also described and a kind ofly has been used to prepare, particularly prepares the favorable method of described preparation and the purposes that said preparation is used for Orally administered fenofibric acid, its physiologically acceptable salt or derivant by melt extrusion.
Patent documentation 6 discloses the new method of the quaternary ammonium salt that relates to preparation acid, in particular to the preparation method of the quaternary ammonium salt of Carboxymethylcellulose.In particular, this method makes it possible to prepare economically highly purified fenofibrate acid choline salt, and this fenofibrate acid choline salt can directly be used as the active substance of human medicine.
Patent documentation 7 discloses the using method and the purposes of fenofibrate acid.
Dispersible tablet of the present invention, administration every day 1～2 time is preferably once a day, 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: China adult dyslipidemia guideline of prevention and treatment is worked out joint committee. China adult dyslipidemia guideline of prevention and treatment. and Chinese cardiovascular diseases's magazine, 35 (5), in May, 2007,390-419
Patent documentation 1: Chinese patent CN101677981A
Patent documentation 2: Chinese patent CN101217944A
Patent documentation 3: Chinese patent CN101730675A
Patent documentation 4: Chinese patent CN1726024A
Patent documentation 5: Chinese patent CN101480384A
Patent documentation 6: Chinese patent CN101296894A
Patent documentation 7: U.S. Pat 7741374 (B1), US7569612 (B1), US7741373 (B1)
Summary of the invention
The object of the present invention is to provide a kind of dispersible tablet of forming by a certain amount of fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof and a certain amount of statins or its pharmaceutically acceptable salt or ester and pharmaceutically acceptable carrier, wherein said fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are preferably fenofibrate or fenofibrate acid, and described statins or its pharmaceutically acceptable salt or ester are preferably atorvastatin, Rosuvastatin, simvastatin, Pitavastatin, lovastatin, or its pharmaceutically acceptable salt or ester.
Another object of the present invention also is to provide above-mentioned dispersible tablet to be used for the treatment of application in the medicine of patient's dyslipidemia in preparation.
The technical scheme that the present invention solves is as follows:
(1) a kind of dispersible tablet is characterized in that, it is made up of following several parts:
(I) a certain amount of fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof;
(II) a certain amount of statins or its pharmaceutically acceptable salt or ester; And
(III) at least a pharmaceutically acceptable carrier.
A certain amount of fibrate of the present invention or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate (Fenofibrate), fenofibrate acid (fenofibric acid), bezafibrate (Bezafibrate), clofibrate (Clofibrate), ciprofibrate (Ciprofibrate), gemfibrozil (Gemfibrozil), etofylline clofibrate (Etofylline Clofibrate), simfibrate (Simfibrate), clinofibrate (Clinofibrate), etofibrate (Etofibrate), aluminum clofibrate (AluminumClofibrate), biclofibrate (Biclofibrate), binifibrate (Binifibrate), calcium clofibrate (Calcium Clofibrate), cinnarizine clofibrate (Cinnarizine Clofibrate), 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 or derivatives thereof; Be preferably those that have gone on the market; More preferably fenofibrate, fenofibrate acid, bezafibrate, clofibrate, ciprofibrate, gemfibrozil, clinofibrate, etofibrate, simfibrate or etofylline clofibrate;
For fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof, unit dose is 17.5～1000mg, is preferably 35～500mg, more preferably 80～300mg, more preferably 80～200mg.
The acid of wherein said a certain amount of fenofibrate or its pharmaceutically acceptable salt or ester or derivatives thereof such as patent documentation CN1726024A, CN101480384A, CN100473378 (C) described those; Be preferably: fenofibrate acid, fenofibrate, fenofibrate acid choline salt, the hydrochlorate of fenofibrate acid, trifluoroacetate, hydrobromate, nitrate, ammonium sulfate, tartrate, fumarate, benzoate, mesylate, benzene sulfonate, butene dioic acid salt, tosilate, maleate, sulfate, phosphate, fumarate, succinate, acetate, malate, hemifumarate, citrate, succinate, perchlorate, hydrofluoride, hydriodate, the diisopropyl amine salt, acetate, lactate, malonate, oxalates, fluoroform sulphonate, esilate, ethanolamine salt, diethanolamine salt, hexanamine salt, ammonia fourth three esters, cyclohexylamine salt, meglumine salt, the diethyl amine salt, ethylenediamine salt, glycinate, lysinate, arginine salt, ornithine salt, glutamate, Glu or aspartate; More preferably: fenofibrate acid or fenofibrate;
For fenofibrate acid or its pharmaceutically acceptable salt or ester or derivatives thereof, unit dose is 35～300mg, be preferably 35～200mg, 80～200mg more preferably, more preferably about 80mg, about 105mg, about 110mg, about 120mg, about 130mg, about 135mg, about 145mg or about 160mg most preferably are about 80mg, about 135mg, about 145mg or about 160mg.
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.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), W02009024685 (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), JP Kokai 7340777, those that JP Kokai 7430377 is announced are incorporated herein by reference this in full at this.
A certain amount of statins of the present invention or its pharmaceutically acceptable salt or ester are atorvastatin (Atorvastatin), Rosuvastatin (Rosuvastatin), simvastatin (Simvastatin), 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 those that have gone on the market; More preferably Atorvastatin calcium, rosuvastain calcium, simvastatin, lovastatin, Pitavastatin Calcium, pravastatin sodium, fluvastatin sodium, atorvastatin magnesium or Pitavastatin sodium;
For statins or its pharmaceutically acceptable salt or ester, unit dose is 0.25～160mg, is preferably 0.25～80mg;
For atorvastatin, simvastatin, lovastatin, pravastatin or fluvastatin, unit dose is 5～160mg, is preferably 5～40mg; More preferably be approximately 5mg, 10mg, 20mg, 40mg or 80mg; For Rosuvastatin, unit dose is 2.5～80mg, is preferably 5～40mg; More preferably be approximately 2.5mg, 5mg, 10mg, 20mg or 40mg; For Pitavastatin, unit dose is 0.25～8mg, is preferably 0.5～4mg; 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.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), W08402131 (A1), US4739073 (A), DE19475017 (12), EP0114027 (A1), DE2524355 (A1), those that US3983140 (A) is announced are incorporated herein by reference this in full at this.
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 an organ or health to the part of another organ or health, as 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 examples that can be used as the material of pharmaceutically acceptable excipient comprise: (a) saccharide, as lactose, dextrose plus saccharose; (b) starch based is as corn starch and potato starch; (c) cellulose and derivant thereof are as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (d) pulverous Tragacanth; (e) Fructus Hordei Germinatus; (f) gelatin; (g) Talcum; (h) excipient is as cupu oil and suppository wax; (i) oils is as Oleum Arachidis hypogaeae semen, Oleum Gossypii semen, safflower oil, Oleum sesami, olive oil, Semen Maydis oil and soybean oil; (j) glycols is as propylene glycol; (k) polyalcohols is as glycerol, Sorbitol, mannitol and Polyethylene Glycol; (1) esters is as ethyl oleate and ethyl laurate; (m) agar; (n) buffer agent class is as 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 Autoadhesive, filler, disintegrating agent, lubricant, fluidizer, wetting agent, correctives, aromatic, coloring agent, dissolubility promoter, surfactant or their combination preferably.The amount of pharmaceutically acceptable every kind of carrier 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;
Described enteric solubility binding agent be patent documentation CN1726024A, CN100473378C, CN101480384A described those; Be preferably enteric polymer, as suitable cellulose derivative, for example cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate trimellitate, carboxyalkyl (alkyl) cellulose and hydroxyalkyl (alkyl) cellulose phthalate; Suitable polyvinyl polymer and copolymer, for example adjacent benzene first of polyvinyl acetate two acid esters, polyethylene butanoic acid acetate, vinylacetate one copolymer-maleic anhydride, styrene one maleic acid monoester copolymer; With suitable acrylic acid/methacrylate polymer and copolymer, for example alkyl acrylate-methacrylic acid copolymer such as acrylic acid methyl ester .-methacrylic acid copolymer, and alkyl methacrylate-methacrylic acid one alkyl acrylate copolymer such as methacrylate-methacrylic acid one 1-Octyl acrylate copolymer;
Preferred enteric solubility binding agent is acceptable acrylic acid/methacrylate polymer of pharmacy and copolymer; Comprising the copolymer with anion feature, for example (methyl) acrylic acid methyl ester. based on (methyl) acrylic acid and (methyl) alkyl acrylate; These copolymers preferably have the weight average molecular weight of about 50000-300000, particularly 100000-150000, and according to appointment 135000.The free carboxy of described copolymer and the ratio of esterifying carboxyl group are preferably about 2: 1-1: in 3 the scope, particularly 1: 1-1: 2; The instantiation of described copolymer comprises acrylic resin, and it is respectively the methacrylic acid and the methyl methacrylate of about 1: 1 and 1: 2 based on the ratio of free carboxy and esterifying carboxyl group;
Other preferred enteric solubility binding agents are acceptable cellulose derivative of pharmacy or casein; Described cellulose derivative comprises carboxymethylethylcellulose (CMEC) and sodium carboxymethyl cellulose (hydroxy acid cellulose sodium), and more preferably hydroxypropylmethyl cellulose phthalate, especially hydroxypropylmethyl cellulose phthalate (hypromellose phthalate), hydroxypropyl methylcellulose acetate succinate (AQOAT), cellulose acetate phthalate (CAP) and cellulose acetate trimellitate (CAT).Be preferably cellulose acetate O-phthalic vinegar, cellulose acetate phthalate aqueous dispersion, hydroxypropylmethyl cellulose phthalate or hydroxypropyl methylcellulose acetate succinate aqueous dispersion especially;
Described non-enteric solubility binding agent preferably from:
(A) synthetic polymer such as polyvinyl lactam class, particularly polyvinyl adjoin pyrrolidone (PVP); Vinyl lactam such as N-vinyl pyrrolidone, N-vinyl piperidones and N-vinyl-epsilon-caprolactams, particularly N-vinyl pyrrolidone and (methyl) acrylic acid and/or (methyl) acrylate such as long-chain (methyl) acrylate, (methyl) stearyl acrylate ester for example, can quaternised (methyl) propenoic acid dialkyl aminoalkyl ester and maleic anhydride, vinyl esters, vinylacetate particularly, vinyl formamide, the copolymer of vinyl sulfonic acid or quaternised vinyl imidazole; The copolymer of vinylacetate and .beta.-methylacrylic acid; The polyvinyl acetate of partial hydrolysis; Polyvinyl alcohol; (methyl) acrylic resin is as poly-((methyl) acrylic acid hydroxy alkyl ester), poly-(methyl) acrylate, acrylate copolymer; Poly alkylene glycol such as polypropylene glycol and Polyethylene Glycol, preferred molecular weight be higher than 1000, especially preferably be higher than 2000 and very particularly preferably be higher than 4000 (for example polyethylene glycol 6000s); Polyalkylene oxide is as poly(propylene oxide) and particularly poly(ethylene oxide), preferred high-molecular weight polyalkylene oxide, especially weight average molecular weight is higher than 100000; Polyacrylamide; Polyvinyl formamide (if suitable, partly or entirely hydrolysis);
Modified natural polymers, for example modified starch and modified cellulose, as cellulose esters and preferred cellulose ether, methylcellulose and ethyl cellulose, hydroxy alkyl cellulose particularly hydroxypropyl emthylcellulose or Cellulose ethyl hydroxypropyl ether of hydroxypropyl cellulose, hydroxyalkyl alkylcellulose particularly for example; Starch decomposition products, particularly diastasic action product such as maltodextrin, Icing Sugar, syrup, rubber cement or starch slurry;
(B) natural or mainly be natural polymer, as gelatin, polyhydroxy-alkanoates, for example poly butyric and polylactic acid, polyamino acid, for example polylysine, poly-asparagine, poly-two uh alkane (polydioxane) and polypeptide and mannan, particularly galactomannan; With
(C) non-polymeric binding agent such as polyhydric alcohol, those that describe at WO98/22094 and EP0435450 for example, particularly sugar alcohol such as maltose alcohol, mannitol, Sorbitol, cellubitol (cellobiitol), lactose, xylitol and red aquatic foods are pure, and hydroxyl isomaltulose (isomalt, Palatinit);
Above-mentioned in those, preferred polymeric binding agent, particularly modified natural polymers, especially modified starch and cellulose ether, and the copolymer of synthetic polymer, especially polyvinyl pyrrolidone and vinyl lactam particularly;
Especially preferably from polyvinyl pyrrolidone, N-vinyl pyrrolidone/vinyl acetate co-polymer especially copolyvidone (copovidone) and cellulose derivative such as hydroxypropyl cellulose and hydroxypropyl emthylcellulose.
Suitable filler can be selected from microcrystalline Cellulose, optimize microcrystalline Cellulose, Powderd cellulose, pre-paying starch, lactose, mannitol, sorbitol, dextrin, Icing Sugar, starch, saccharide, sugar derivatives, Polyethylene Glycol, sodium bicarbonate, calcium carbonate, calcium sulfate, calcium hydrogen phosphate, Citric acid 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, 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, stearic acid, calcium silicates, Pulvis Talci 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 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-methylglucosamine 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 derivant, 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 salt or ester, 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; Can randomly carry out film coating or sweet tablet; Can be the gastric solubleness coating, also can be enteric coating.
For fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof, can adopt micronization processes, also can adopt nanorize 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 dispersible tablet can be contained in to suck clothes in the mouth or swallow.
The dispersible tablet listing is abroad promptly arranged in the eighties in last century.British Pharmacopoeia version in 1980 has promptly been recorded dispersible tablet, and European Pharmacopoeia version in 2003 is also recorded.At present, the dispersible tablet of a plurality of kinds of China national Drug Administration approved enters clinical research and listing, for example fenofibrate dispersible tablet, simvastatin dispersible tablet, Lovastatin dispersible tablet, bezafibrate dispersible tablet, Azithromycin dispersible tablet, roxithromycin dispersing tablet, Nateglinide dispersible tablet and cefixime dispersible tablet.
Because fibrate (for example fenofibrate or fenofibrate acid) and statins (for example Atorvastatin calcium, rosuvastain calcium, simvastatin, Pitavastatin Calcium or lovastatin) all are insoluble in water, therefore the present invention makes dispersible tablet with fibrate and statins, not only meet the Chinese Pharmacopoeia requirement, and has an advantage that, drug effect faster than conventional tablet and capsule disintegrate performance is faster, dissolution is high, the bioavailability significance improves, bring convenience to clinical application, obtained beyond thought therapeutic effect.
(2) as the described dispersible tablet of claim (1), it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, fenofibrate acid or its pharmaceutically acceptable salt or the ester or derivatives thereof of 35～300mg, and described statins or its pharmaceutically acceptable salt or ester are atorvastatin, Rosuvastatin, simvastatin, Pitavastatin, lovastatin or its pharmaceutically acceptable salt or the ester of 0.25～160mg.
More preferably, the percentage by weight of wherein said fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof and statins or its pharmaceutically acceptable salt or ester is 1.25-680: 1; 1.25-160 more preferably: 1.
For fenofibrate acid or its pharmaceutically acceptable salt or ester or derivatives thereof, unit dose is 35～300mg, be preferably 35～200mg, 80～200mg more preferably, more preferably about 80mg, about 105mg, about 110mg, about 120mg, about 130mg, about 135mg, about 145mg or about 160mg most preferably are about 80mg, about 135mg, about 145mg or about 160mg.
For atorvastatin, simvastatin, lovastatin, pravastatin or fluvastatin, unit dose is 5～160mg, is preferably 5～40mg; More preferably be approximately 5mg, 10mg, 20mg, 40mg or 80mg; For Rosuvastatin, unit dose is 2.5～80mg, is preferably 5～40mg; More preferably be approximately 2.5mg, 5mg, 10mg, 20mg or 40mg; For Pitavastatin, unit dose is 0.25～8mg, is preferably 0.5～4mg; More preferably be approximately 0.5mg, 1mg, 2mg or 4mg.
A preferred version is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are the fenofibrate of 35～300mg, are preferably 80～200mg; Described statins or its pharmaceutically acceptable salt or ester are atorvastatin, Rosuvastatin, simvastatin, Pitavastatin, lovastatin or its pharmaceutically acceptable salt or the ester of 0.25～160mg, are preferably 0.25～80mg; The percentage by weight of wherein said fenofibrate and statins or its pharmaceutically acceptable salt or ester is 1.25-680: 1; 1.25-160 more preferably: 1.
A preferred version is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are the fenofibrate acid of 35～300mg, are preferably 80～200mg; Described statins or its pharmaceutically acceptable salt or ester are atorvastatin, Rosuvastatin, simvastatin, Pitavastatin, lovastatin or its pharmaceutically acceptable salt or the ester of 0.25～160mg, are preferably 0.25～80mg; The percentage by weight of wherein said fenofibrate and statins or its pharmaceutically acceptable salt or ester is 1.25-680: 1; 1.25-160 more preferably: 1.
Patent documentation CN1423634A, CN1373753A, CN1379760A, CN101215253A, CN1561341A, CN1489463A, CN1487921A, CN1543468A, CN101048141A, CN101263114A, CN101268047A, CN101370774A, CN101395132A, CN101437791A, CN101492406A, CN101516842A, CN101538238A, CN101560176A, CN101560177A, CN101600688A, CN101643443A, CN101668740A, CN101684090A, CN101805279A, CN101613312A, CN101203496A, CN1807418A, CN1733737A, CN1872841A, CN101376647A, CN101490015A, CN1451000A, CN1290261A, CN1318046A, CN1318063A, CN1368948A, CN101190907A, CN1583737A, CN1612872A, CN1493570A, CN1543468A, CN1754870A, CN1951901A, CN1795165A, CN101381356A, CN101473040A, CN101575286A, CN101575287A, CN101195603A, CN101219991A, CN101219992A, CN1543468A, CN1747934A, CN1790012A, CN1876633A, CN101766618A, CN1318046A, CN1318063A, CN1373208A, CN1640880A, CN101659923A, CN101691590A, CN1505502A, CN101823956A, those that CN101594850A announced are incorporated herein by reference this in full at this.
(3) as claim (1), (2) each described dispersible tablet, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, described statins or its pharmaceutically acceptable salt or ester are Atorvastatin calcium, and described fenofibrate and Atorvastatin calcium are selected from the combination of following fixed dosage:
About 5mg Atorvastatin calcium and about 80mg fenofibrate; About 10mg Atorvastatin calcium and about 80mg fenofibrate; About 20mg Atorvastatin calcium and about 80mg fenofibrate; About 40mg Atorvastatin calcium and about 80mg fenofibrate; About 80mg Atorvastatin calcium and about 80mg fenofibrate; About 5mg Atorvastatin calcium and about 100mg fenofibrate; About 10mg Atorvastatin calcium and about 100mg fenofibrate; About 20mg Atorvastatin calcium and about 100mg fenofibrate; About 40mg Atorvastatin calcium and about 100mg fenofibrate; About 80mg Atorvastatin calcium and about 100mg fenofibrate; About 5mg Atorvastatin calcium and about 110mg fenofibrate; About 10mg Atorvastatin calcium and about 110mg fenofibrate; About 20mg Atorvastatin calcium and about 110mg fenofibrate; About 40mg Atorvastatin calcium and about 110mg fenofibrate; About 80mg Atorvastatin calcium and about 110mg fenofibrate; About 5mg Atorvastatin calcium and about 120mg fenofibrate; About 10mg Atorvastatin calcium and about 120mg fenofibrate; About 20mg Atorvastatin calcium and about 120mg fenofibrate; About 40mg Atorvastatin calcium and about 120mg fenofibrate; About 80mg Atorvastatin calcium and about 120mg fenofibrate; About 5mg Atorvastatin calcium and about 130mg fenofibrate; About 10mg Atorvastatin calcium and about 130mg fenofibrate; About 20mg Atorvastatin calcium and about 130mg fenofibrate; About 40mg Atorvastatin calcium and about 130mg fenofibrate; About 80mg Atorvastatin calcium and about 130mg fenofibrate; About 5mg Atorvastatin calcium and about 145mg fenofibrate; About 10mg Atorvastatin calcium and about 145mg fenofibrate; About 20mg Atorvastatin calcium and about 145mg fenofibrate; About 40mg Atorvastatin calcium and about 145mg fenofibrate; About 80mg Atorvastatin calcium and about 145mg fenofibrate; About 5mg Atorvastatin calcium and about 160mg fenofibrate; About 10mg Atorvastatin calcium and about 160mg fenofibrate; About 20mg Atorvastatin calcium and about 160mg fenofibrate; About 40mg Atorvastatin calcium and about 160mg fenofibrate; And about 80mg Atorvastatin calcium and about 160mg fenofibrate;
Be preferably: about 10mg Atorvastatin calcium and about 80mg fenofibrate; About 20mg Atorvastatin calcium and about 80mg fenofibrate; About 10mg Atorvastatin calcium and about 145mg fenofibrate; About 20mg Atorvastatin calcium and about 145mg fenofibrate; About 40mg Atorvastatin calcium and about 145mg fenofibrate; About 5mg Atorvastatin calcium and about 160mg fenofibrate; About 10mg Atorvastatin calcium and about 160mg fenofibrate; The weight of wherein said Atorvastatin calcium is pressed atorvastatin and is calculated.
The chemical name of fenofibrate of the present invention is 2-methyl-2-[4-(4-chlorobenzene formacyl) phenoxy group] isopropyl propionate, English name is Fenofibrate, molecular formula is C
20H
21ClO
4, molecular weight is 360.84, its chemical structural formula is suc as formula shown in (I):
The chemical name of Atorvastatin calcium of the present invention is (R-(R
x, R
x))-2-(4-fluorophenyl)-β, δ-dihydroxy-5-(1-methyl-ethyl)-3-phenyl-4-((phenyl amino)-carbonyl)-1H-pyrroles-1-enanthic acid calcium (2: 1) trihydrate, English name is atorvastatin Ca1cium, molecular formula is (C
33H
34FN
2O
5)
2Ca3H
2O, molecular weight are 1209.42, and its chemical structural formula is suc as formula shown in (II):
(4) as claim (1), (2) each described dispersible tablet, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, described statins or its pharmaceutically acceptable salt or ester are rosuvastain calcium, and described fenofibrate and rosuvastain calcium are selected from the combination of following fixed dosage:
About 2.5mg rosuvastain calcium and about 80mg fenofibrate; About 5mg rosuvastain calcium and about 80mg fenofibrate; About 10mg rosuvastain calcium and about 80mg fenofibrate; About 20mg rosuvastain calcium and about 80mg fenofibrate; About 40mg rosuvastain calcium and about 80mg fenofibrate; About 2.5mg rosuvastain calcium and about 100mg fenofibrate; About 5mg rosuvastain calcium and about 100mg fenofibrate; About 10mg rosuvastain calcium and about 100mg fenofibrate; About 20mg rosuvastain calcium and about 100mg fenofibrate; About 40mg rosuvastain calcium and about 100mg fenofibrate; About 2.5mg rosuvastain calcium and about 110mg fenofibrate; About 5mg rosuvastain calcium and about 110mg fenofibrate; About 10mg rosuvastain calcium and about 110mg fenofibrate; About 20mg rosuvastain calcium and about 110mg fenofibrate; About 40mg rosuvastain calcium and about 110mg fenofibrate; About 2.5mg rosuvastain calcium and about 120mg fenofibrate; About 5mg rosuvastain calcium and about 120mg fenofibrate; About 10mg rosuvastain calcium and about 120mg fenofibrate; About 20mg rosuvastain calcium and about 120mg fenofibrate; About 40mg rosuvastain calcium and about 120mg fenofibrate; About 2.5mg rosuvastain calcium and about 130mg fenofibrate; About 5mg rosuvastain calcium and about 130mg fenofibrate; About 10mg rosuvastain calcium and about 130mg fenofibrate; About 20mg rosuvastain calcium and about 130mg fenofibrate; About 40mg rosuvastain calcium and about 130mg fenofibrate; About 2.5mg rosuvastain calcium and about 145mg fenofibrate; About 5mg rosuvastain calcium and about 145mg fenofibrate; About 10mg rosuvastain calcium and about 145mg fenofibrate; About 20mg rosuvastain calcium and about 145mg fenofibrate; About 40mg rosuvastain calcium and about 145mg fenofibrate; About 2.5mg rosuvastain calcium and about 160mg fenofibrate; About 5mg rosuvastain calcium and about 160mg fenofibrate; About 10mg rosuvastain calcium and about 160mg fenofibrate; About 20mg rosuvastain calcium and about 160mg fenofibrate; And about 40mg rosuvastain calcium and about 160mg fenofibrate;
Be preferably: about 5mg rosuvastain calcium and about 80mg fenofibrate; About 10mg rosuvastain calcium and about 80mg fenofibrate; About 5mg rosuvastain calcium and about 145mg fenofibrate; About 10mg rosuvastain calcium and about 145mg fenofibrate; About 20mg rosuvastain calcium and about 145mg fenofibrate; About 5mg rosuvastain calcium and about 160mg fenofibrate; About 10mg rosuvastain calcium and about 160mg fenofibrate;
The weight of wherein said rosuvastain calcium is pressed Rosuvastatin and is calculated.
The chemical name of rosuvastain calcium of the present invention is two-{ (E-7-(4-(the fluorine-based phenyl of 4-)-6-isopropyl-2-(methyl (mesyl) amino)-pyrimidine-5-yl) (3R; 5S)-3; 5-hydroxyl heptan-6-olefin(e) acid } calcium salt (2: 1); English name is rosuvastatin Calcium, and molecular formula is (C
22H
27FN
3O
6S)
2Ca, molecular weight are 1001.14, and its chemical structural formula is suc as formula shown in (III):
(5) as claim 1,2 each described dispersible tablets, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, described statins or its pharmaceutically acceptable salt or ester are simvastatin, and described fenofibrate and simvastatin are selected from the combination of following fixed dosage:
About 5mg simvastatin and about 80mg fenofibrate; About 10mg simvastatin and about 80mg fenofibrate; About 20mg simvastatin and about 80mg fenofibrate; About 40mg simvastatin and about 80mg fenofibrate; About 80mg simvastatin and about 80mg fenofibrate; About 5mg simvastatin and about 100mg fenofibrate; About 10mg simvastatin and about 100mg fenofibrate; About 20mg simvastatin and about 100mg fenofibrate; About 40mg simvastatin and about 100mg fenofibrate; About 80mg simvastatin and about 100mg fenofibrate; About 5mg simvastatin and about 110mg fenofibrate; About 10mg simvastatin and about 110mg fenofibrate; About 20mg simvastatin and about 110mg fenofibrate; About 40mg simvastatin and about 110mg fenofibrate; About 80mg simvastatin and about 110mg fenofibrate; About 5mg simvastatin and about 120mg fenofibrate; About 10mg simvastatin and about 120mg fenofibrate; About 20mg simvastatin and about 120mg fenofibrate; About 40mg simvastatin and about 120mg fenofibrate; About 80mg simvastatin and about 120mg fenofibrate; About 5mg simvastatin and about 130mg fenofibrate; About 10mg simvastatin and about 130mg fenofibrate; About 20mg simvastatin and about 130mg fenofibrate; About 40mg simvastatin and about 130mg fenofibrate; About 80mg simvastatin and about 130mg fenofibrate; About 5mg simvastatin and about 145mg fenofibrate; About 10mg simvastatin and about 145mg fenofibrate; About 20mg simvastatin and about 145mg fenofibrate; About 40mg simvastatin and about 145mg fenofibrate; About 80mg simvastatin and about 145mg fenofibrate; About 5mg simvastatin and about 160mg fenofibrate; About 10mg simvastatin and about 160mg fenofibrate; About 20mg simvastatin and about 160mg fenofibrate; About 40mg simvastatin and about 160mg fenofibrate; And about 80mg simvastatin and about 160mg fenofibrate;
Be preferably: about 10mg simvastatin and about 80mg fenofibrate; About 20mg simvastatin and about 80mg fenofibrate; About 10mg simvastatin and about 145mg fenofibrate; About 20mg simvastatin and about 145mg fenofibrate; About 40mg simvastatin and about 145mg fenofibrate; About 5mg simvastatin and about 160mg fenofibrate; About 10mg simvastatin and about 160mg fenofibrate.
The chemical name of simvastatin of the present invention is 2, and 2-acid dimethyl-8-{ (4R, 6R)-6-{2-[(1S, 2S, 6R, 8S, 8aR)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl] ethyl } tetrahydrochysene-4-hydroxyl-2H-pyran-2-one } ester, English name is simvastatin, and molecular formula is C
25H
380
5, molecular weight is 418.57, its chemical structural formula is suc as formula shown in (IV):
(6) as claim (1), (2) each described dispersible tablet, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, described statins or its pharmaceutically acceptable salt or ester are Pitavastatin Calcium, and described fenofibrate and Pitavastatin Calcium are selected from the combination of following fixed dosage:
About 0.25mg Pitavastatin Calcium and about 80mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 80mg fenofibrate; About 1mg Pitavastatin Calcium and about 80mg fenofibrate; About 2mg Pitavastatin Calcium and about 80mg fenofibrate; About 4mg Pitavastatin Calcium and about 80mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 100mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 100mg fenofibrate; About 1mg Pitavastatin Calcium and about 100mg fenofibrate; About 2mg Pitavastatin Calcium and about 100mg fenofibrate; About 4mg Pitavastatin Calcium and about 100mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 110mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 110mg fenofibrate; About 1mg Pitavastatin Calcium and about 110mg fenofibrate; About 2mg Pitavastatin Calcium and about 110mg fenofibrate; About 4mg Pitavastatin Calcium and about 110mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 120mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 120mg fenofibrate; About 1mg Pitavastatin Calcium and about 120mg fenofibrate; About 2mg Pitavastatin Calcium and about 120mg fenofibrate; About 4mg Pitavastatin Calcium and about 120mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 130mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 130mg fenofibrate; About 1mg Pitavastatin Calcium and about 130mg fenofibrate; About 2mg Pitavastatin Calcium and about 130mg fenofibrate; About 4mg Pitavastatin Calcium and about 130mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 145mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 145mg fenofibrate; About 1mg Pitavastatin Calcium and about 145mg fenofibrate; About 2mg Pitavastatin Calcium and about 145mg fenofibrate; About 4mg Pitavastatin Calcium and about 145mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 160mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 160mg fenofibrate; About 1mg Pitavastatin Calcium and about 160mg fenofibrate; About 2mg Pitavastatin Calcium and about 160mg fenofibrate; And about 4mg Pitavastatin Calcium and about 160mg fenofibrate;
Be preferably: about 0.5mg Pitavastatin Calcium and about 80mg fenofibrate; About 1mg Pitavastatin Calcium and about 80mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 145mg fenofibrate; About 1mg Pitavastatin Calcium and about 145mg fenofibrate; About 2mg Pitavastatin Calcium and about 145mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 160mg fenofibrate; About 1mg Pitavastatin Calcium and about 160mg fenofibrate.
The chemical name of Pitavastatin Calcium of the present invention is two-(3R, 5S, 6E)-7-(2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl)-3,5-dihydroxy-6-heptenoic acid) calcium salt (2: 1), English name is Pitavastatin Calcium, and molecular formula is C
50H
46CaF
2N
2O
8, molecular weight is 880.98, chemical structural formula is shown in formula V:
(7) as claim (1), (2) each described dispersible tablet, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, described statins or its pharmaceutically acceptable salt or ester are lovastatin, and described fenofibrate and lovastatin are selected from the combination of following fixed dosage:
About 5mg lovastatin and about 80mg fenofibrate; About 10mg lovastatin and about 80mg fenofibrate; About 20mg lovastatin and about 80mg fenofibrate; About 40mg lovastatin and about 80mg fenofibrate; About 80mg lovastatin and about 80mg fenofibrate; About 5mg lovastatin and about 100mg fenofibrate; About 10mg lovastatin and about 100mg fenofibrate; About 20mg lovastatin and about 100mg fenofibrate; About 40mg lovastatin and about 100mg fenofibrate; About 80mg lovastatin and about 100mg fenofibrate; About 5mg lovastatin and about 110mg fenofibrate; About 10mg lovastatin and about 110mg fenofibrate; About 20mg lovastatin and about 110mg fenofibrate; About 40mg lovastatin and about 110mg fenofibrate; About 80mg lovastatin and about 110mg fenofibrate; About 5mg lovastatin and about 120mg fenofibrate; About 10mg lovastatin and about 120mg fenofibrate; About 20mg lovastatin and about 120mg fenofibrate; About 40mg lovastatin and about 120mg fenofibrate; About 80mg lovastatin and about 120mg fenofibrate; About 5mg lovastatin and about 130mg fenofibrate; About 10mg lovastatin and about 130mg fenofibrate; About 20mg lovastatin and about 130mg fenofibrate; About 40mg lovastatin and about 130mg fenofibrate; About 80mg lovastatin and about 130mg fenofibrate; About 5mg lovastatin and about 145mg fenofibrate; About 10mg lovastatin and about 145mg fenofibrate; About 20mg lovastatin and about 145mg fenofibrate; About 40mg lovastatin and about 145mg fenofibrate; About 80mg lovastatin and about 145mg fenofibrate; About 5mg lovastatin and about 160mg fenofibrate; About 10mg lovastatin and about 160mg fenofibrate; About 20mg lovastatin and about 160mg fenofibrate; About 40mg lovastatin and about 160mg fenofibrate; And about 80mg lovastatin and about 160mg fenofibrate;
Be preferably: about 10mg lovastatin and about 80mg fenofibrate; About 20mg lovastatin and about 80mg fenofibrate; About 10mg lovastatin and about 145mg fenofibrate; About 20mg lovastatin and about 145mg fenofibrate; About 40mg lovastatin and about 145mg fenofibrate; About 5mg lovastatin and about 160mg fenofibrate; About 10mg lovastatin and about 160mg fenofibrate.
The chemical name of lovastatin of the present invention is (S)-2-Methyl Butyric Acid (1S, 3S, 7S, 8S, 8aR)-1,2,3,7,8,8a-six hydrogen-3,7-dimethyl-8-[2-[(2R, 4R)-4-hydroxyl-6-oxo-2-THP trtrahydropyranyl]-ethyl]-1-naphthalene ester, English name is lovastatin, molecular formula is C
24H
360
5, molecular weight is 404.55, its chemical structural formula is suc as formula shown in (VI):
(8) as claim 1,2 each described dispersible tablets, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate acid, described statins or its pharmaceutically acceptable salt or ester are Atorvastatin calcium, and described fenofibrate acid and Atorvastatin calcium are selected from the combination of following fixed dosage:
About 5mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 105mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 105mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 105mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 105mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 105mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 110mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 110mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 110mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 110mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 110mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 120mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 120mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 120mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 120mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 120mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 130mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 130mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 130mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 130mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 130mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 160mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 160mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 160mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 160mg fenofibrate; And about 80mg Atorvastatin calcium and the acid of about 160mg fenofibrate;
Be preferably: about 10mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 160mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 160mg fenofibrate; The weight of wherein said Atorvastatin calcium is pressed atorvastatin and is calculated.
The chemical name of fenofibrate acid of the present invention is 2-methyl-2-[4-(4-chlorobenzene formacyl) phenoxy group] propanoic acid, English name is Fenofibric acid, molecular formula is C
17H
15ClO
4, molecular weight is 318.75, its chemical structural formula is suc as formula shown in (VII):
(9) as claim 1,2 each described dispersible tablets, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate acid, described statins or its pharmaceutically acceptable salt or ester are rosuvastain calcium, and described fenofibrate acid and rosuvastain calcium are selected from the combination of following fixed dosage:
About 2.5mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 105mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 105mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 105mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 105mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 105mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 110mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 110mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 110mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 110mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 110mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 120mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 120mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 120mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 120mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 120mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 130mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 130mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 130mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 130mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 130mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 160mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 160mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 160mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 160mg fenofibrate; And about 40mg rosuvastain calcium and the acid of about 160mg fenofibrate;
Be preferably: about 5mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 160mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 160mg fenofibrate; The weight of wherein said rosuvastain calcium is pressed Rosuvastatin and is calculated.
(10) be used for the treatment of application in the medicine of patient's dyslipidemia as each described dispersible tablet of claim (1) to (9) in preparation.
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 and (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.
The specific embodiment
Describe the present invention in detail below in conjunction with embodiment.
Embodiment 1: Atorvastatin calcium fenofibrate dispersible tablet
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) | Dosage 3 (mg) |
| Atorvastatin calcium | 10.85※ | 10.85 | 21.70 | 5.42 |
| Fenofibrate | 80.00 | 145.00 | 145.00 | 160.00 |
| Microcrystalline Cellulose | 30.00 | 30.00 | 30.00 | 30.00 |
| Mannitol | 119.65 | 54.65 | 43.80 | 45.08 |
| Sucralose | 1.50 | 1.50 | 1.50 | 1.50 |
| 30 POVIDONE K 30 BP/USP 30 | 30.00 | 30.00 | 30.00 | 30.00 |
| Sodium lauryl sulphate | 3.00 | 3.00 | 3.00 | 3.00 |
| The L-hydroxypropyl cellulose | 15.00 | 15.00 | 15.00 | 15.00 |
| Carboxymethylstach sodium | 4.00 | 4.00 | 4.00 | 4.00 |
| Magnesium stearate | 6.00 | 6.00 | 6.00 | 6.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount | In right amount |
| Sheet is heavy | 300.00 | 300.00 | 300.00 | 300.00 |
※ presses anhydride and calculates, and Atorvastatin calcium 10.85g is equivalent to atorvastatin 10.00g, down together.
Embodiment 2: rosuvastain calcium fenofibrate dispersible tablet
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) |
| Rosuvastain calcium | 5.20 | 10.40※ | 20.80 |
| Fenofibrate | 145.00 | 145.00 | 145.00 |
| Microcrystalline Cellulose | 30.00 | 30.00 | 30.00 |
| Mannitol | 60.30 | 55.10 | 44.70 |
| Sucralose | 1.50 | 1.50 | 1.50 |
| 30 POVIDONE K 30 BP/USP 30 | 30.00 | 30.00 | 30.00 |
| Sodium lauryl sulphate | 3.00 | 3.00 | 3.00 |
| The L-hydroxypropyl cellulose | 15.00 | 15.00 | 15.00 |
| Carboxymethylstach sodium | 4.00 | 4.00 | 4.00 |
| Magnesium stearate | 6.00 | 6.00 | 6.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount |
| Sheet is heavy | 300.00 | 300.00 | 300.00 |
※ presses anhydride and calculates, and rosuvastain calcium 10.40g is equivalent to Rosuvastatin 10.00g, down together.
Embodiment 3: simvastatin fenofibrate dispersible tablet
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) |
| Simvastatin | 10.00 | 20.00 | 40.00 |
| Fenofibrate | 145.00 | 145.00 | 145.00 |
| Microcrystalline Cellulose | 30.00 | 30.00 | 30.00 |
| Mannitol | 57.30 | 47.30 | 27.30 |
| Sucralose | 1.20 | 1.20 | 1.20 |
| 30 POVIDONE K 30 BP/USP 30 | 30.00 | 30.00 | 30.00 |
| Sodium lauryl sulphate | 1.50 | 1.50 | 1.50 |
| The L-hydroxypropyl cellulose | 15.00 | 15.00 | 15.00 |
| Carboxymethylstach sodium | 4.00 | 4.00 | 4.00 |
| Magnesium stearate | 6.00 | 6.00 | 6.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount |
| Sheet is heavy | 300.00 | 300.00 | 300.00 |
Embodiment 4: Pitavastatin Calcium fenofibrate dispersible tablet
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) |
| Pitavastatin Calcium | 1.00 | 2.00 | 4.00 |
| Fenofibrate | 145.00 | 145.00 | 145.00 |
| Optimize microcrystalline Cellulose | 15.00 | 15.00 | 15.00 |
| Mannitol | 79.50 | 78.50 | 76.50 |
| Aspartame | 3.00 | 3.00 | 3.00 |
| 30 POVIDONE K 30 BP/USP 30 | 30.00 | 30.00 | 30.00 |
| Sodium lauryl sulphate | 1.50 | 1.50 | 1.50 |
| The L-hydroxypropyl cellulose | 15.00 | 15.00 | 15.00 |
| Carboxymethylstach sodium | 4.00 | 4.00 | 4.00 |
| Magnesium stearate | 6.00 | 6.00 | 6.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount |
| Sheet is heavy | 300.00 | 300.00 | 300.00 |
Embodiment 5: lovastatin fenofibrate dispersible tablet
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) |
| Lovastatin | 10.00 | 20.00 | 40.00 |
| Fenofibrate | 145.00 | 145.00 | 145.00 |
| Powderd cellulose | 15.00 | 15.00 | 15.00 |
| Mannitol | 65.50 | 55.50 | 35.50 |
| Steviosin | 3.00 | 3.00 | 3.00 |
| 30 POVIDONE K 30 BP/USP 30 | 30.00 | 30.00 | 30.00 |
| Sodium lauryl sulphate | 1.50 | 1.50 | 1.50 |
| Cross-linking sodium carboxymethyl cellulose | 20.00 | 20.00 | 20.00 |
| Carboxymethylstach sodium | 4.00 | 4.00 | 4.00 |
| Magnesium stearate | 6.00 | 6.00 | 6.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount |
| Sheet is heavy | 300.00 | 300.00 | 300.00 |
Embodiment 6: Atorvastatin calcium fenofibrate acid dispersible tablet
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) |
| Atorvastatin calcium | 10.85 | 21.70 | 43.40 |
| Fenofibrate acid | 135.00 | 135.00 | 135.00 |
| Optimize microcrystalline Cellulose | 20.00 | 20.00 | 20.00 |
| Mannitol | 85.65 | 74.80 | 53.10 |
| Steviosin | 3.00 | 3.00 | 3.00 |
| 30 POVIDONE K 30 BP/USP 30 | 17.50 | 17.50 | 17.50 |
| Sodium lauryl sulphate | 3.00 | 3.00 | 3.00 |
| The L-hydroxypropyl cellulose | 15.00 | 15.00 | 15.00 |
| Carboxymethylstach sodium | 4.00 | 4.00 | 4.00 |
| Magnesium stearate | 6.00 | 6.00 | 6.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount |
| Sheet is heavy | 300.00 | 300.00 | 300.00 |
Embodiment 7: rosuvastain calcium fenofibrate acid dispersible tablet
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) |
| Rosuvastain calcium | 5.20 | 10.40 | 20.80 |
| Fenofibrate acid | 135.00 | 135.00 | 135.00 |
| Microcrystalline Cellulose | 15.00 | 15.00 | 15.00 |
| Mannitol | 83.80 | 78.60 | 68.20 |
| Steviosin | 3.00 | 3.00 | 3.00 |
| 30 POVIDONE K 30 BP/USP 30 | 30.00 | 30.00 | 30.00 |
| Sodium lauryl sulphate | 3.00 | 3.00 | 3.00 |
| Polyvinylpolypyrrolidone | 15.00 | 15.00 | 15.00 |
| Carboxymethylstach sodium | 4.00 | 4.00 | 4.00 |
| Magnesium stearate | 6.00 | 6.00 | 6.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount |
| Sheet is heavy | 300.00 | 300.00 | 300.00 |
Embodiment 1～7 preparation method:
(A) with two principal agents difference micronization, particle diameter is controlled between 30～150 μ m, and is standby;
(B) various pharmaceutically acceptable carriers are crossed 80 mesh sieves respectively and pulverize, then except that 30 POVIDONE K 30 BP/USP 30, carboxymethylstach sodium and magnesium stearate, other various pharmaceutically acceptable carriers mix homogeneously in trough type mixing machine;
(C) with micronized two principal agents, 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 make 5～10% 30 POVIDONE K 30 BP/USP 30 alcoholic solution in 30% 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 50 mesh sieves and granulate, 50 ℃～70 ℃ oven dry add carboxymethylstach sodium and magnesium stearate, cross 24 mesh sieve granulate, make granule, and are standby;
(F) two drug contents in the mensuration granule, it is heavy to calculate sheet;
(G) use tablet machine that granule is pressed into dispersible tablet, make 1000, promptly.
Embodiment 8: Atorvastatin calcium fenofibrate conventional tablet (contrast test)
| The supplementary material title | Dosage 1 (mg) | Dosage 2 (mg) | Dosage 3 (mg) |
| Atorvastatin calcium | 10.85 | 21.70 | 43.40 |
| Fenofibrate | 145.00 | 145.00 | 145.00 |
| Microcrystalline Cellulose | 109.15 | 98.30 | 77.60 |
| 30 POVIDONE K 30 BP/USP 30 | 15.00 | 15.00 | 15.00 |
| Sodium lauryl sulphate | 3.00 | 3.00 | 3.00 |
| Carboxymethylstach sodium | 8.00 | 8.00 | 8.00 |
| Micropowder silica gel | 3.00 | 3.00 | 3.00 |
| Magnesium stearate | 6.00 | 6.00 | 6.00 |
| 30% alcoholic solution | In right amount | In right amount | In right amount |
| Sheet is heavy | 300.00 | 300.00 | 300.00 |
Preparation method:
(A) Atorvastatin calcium and fenofibrate are crossed the pulverizing of 100 mesh sieves respectively, standby;
(B) microcrystalline Cellulose, mannitol, steviosin, L-hydroxypropyl cellulose, sodium lauryl sulphate (SDS), carboxymethylstach sodium and magnesium stearate are crossed 80 mesh sieves respectively and pulverize, then with microcrystalline Cellulose, mannitol, steviosin, L-hydroxypropyl cellulose and sodium lauryl sulphate mix homogeneously in trough type mixing machine;
(C) with micronized Atorvastatin calcium and fenofibrate, with microcrystalline Cellulose, mannitol, steviosin, L-hydroxypropyl cellulose and the SDS 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 make 5% 30 POVIDONE K 30 BP/USP 30 alcoholic solution in 30% alcoholic solution, do binding agent and use;
(E) incite somebody to action 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 30 mesh sieves and granulate, 50 ℃～70 ℃ oven dry add carboxymethylstach sodium and magnesium stearate, cross 18 mesh sieve granulate, make Atorvastatin calcium fenofibrate granule, standby;
(F) two drug contents in the mensuration Atorvastatin calcium fenofibrate granule, it is heavy to calculate sheet;
(G) use tablet machine that Atorvastatin calcium fenofibrate granule is pressed into tablet, make 1000.
Embodiment 9: study on the stability
Getting the dispersible tablet of the embodiment of the invention 1～8 preparation or conventional tablet is that 40 ± 2 ℃, relative humidity are to place 6 months under 75 ± 5% the condition in temperature, carry out accelerated test, respectively at sampling at 0,1,2,3,6 the end of month once, measure, the results are shown in Table 1 by the high spot reviews project:
Table 1 study on the stability result
Illustrate: 95.9/99.2 ※ represents fenofibrate or fenofibrate acid 95.9/ statins 99.2.Down together.
Result of the test shows, all disintegrates about 80 seconds of the sample of the embodiment of the invention 1～7 preparation, and 60 timesharing fenofibrate or fenofibrate acid dissolution are about 95%, and 30 timesharing statins dissolutions are about 98%, and related substance has no significant change; And the just all disintegrates in the time of 15 minutes of the sample (conventional tablet) of embodiment 8 preparations, 60 timesharing fenofibrate or fenofibrate acid dissolution are about 80%, 30 timesharing statins dissolutions are about 90%, be starkly lower than dispersible tablet, explanation 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, YPD-200C matrix agent hardness tester (Shanghai Huanghai Sea medicine inspection Instr Ltd.)
B, ZB-1D type intelligence disintegration tester (Tianda Tianfa Technology Co., Ltd.)
C, ZRS-8G type intelligence dissolution test instrument (Tianda Tianfa Technology Co., Ltd.)
(i), rotating speed: 75 rev/mins
(ii), dissolution medium: the phosphate buffer (pH7.0) that comprises the 0.05mol/L sodium lauryl sulphate
Embodiment 10: the dissolution rate of dispersible tablet and conventional tablet relatively
Get the dispersible tablet and the conventional tablet of the embodiment of the invention 1～5 and 8 preparations, investigate its dissolution rate and dissolution, result of the test sees Table 2:
Table 2 dissolution rate measurement result
Result of the test shows that in the time of 20 minutes, the dispersible tablet dissolution promptly reaches more than 80%, and the dissolution of conventional tablet is 50.8/78.2, the dispersible tablet disintegrate that the present invention preparation is described rapidly, be uniformly dispersed and the dissolution height, thereby raising bioavailability in significance ground has its superiority.
Obviously, the above embodiment of the present invention only is for example of the present invention clearly is described, and is not to be qualification to embodiments of the present invention.For those of ordinary skill in the field, can also make other changes in different forms on the basis of the above description.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.
Claims (10)
1. a dispersible tablet is characterized in that, it is made up of following several parts:
(I) a certain amount of fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof;
(II) a certain amount of statins or its pharmaceutically acceptable salt or ester; And
(III) pharmaceutically acceptable carrier.
2. dispersible tablet as claimed in claim 1, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, fenofibrate acid or its pharmaceutically acceptable salt or the ester or derivatives thereof of 35～300mg, and described statins or its pharmaceutically acceptable salt or ester are atorvastatin, Rosuvastatin, simvastatin, Pitavastatin, lovastatin or its pharmaceutically acceptable salt or the ester of 0.25～160mg.
3. as claim 1,2 each described dispersible tablets, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, described statins or its pharmaceutically acceptable salt or ester are Atorvastatin calcium, and described fenofibrate and Atorvastatin calcium are selected from the combination of following fixed dosage:
About 5mg Atorvastatin calcium and about 80mg fenofibrate; About 10mg Atorvastatin calcium and about 80mg fenofibrate; About 20mg Atorvastatin calcium and about 80mg fenofibrate; About 40mg Atorvastatin calcium and about 80mg fenofibrate; About 80mg Atorvastatin calcium and about 80mg fenofibrate; About 5mg Atorvastatin calcium and about 100mg fenofibrate; About 10mg Atorvastatin calcium and about 100mg fenofibrate; About 20mg Atorvastatin calcium and about 100mg fenofibrate; About 40mg Atorvastatin calcium and about 100mg fenofibrate; About 80mg Atorvastatin calcium and about 100mg fenofibrate; About 5mg Atorvastatin calcium and about 110mg fenofibrate; About 10mg Atorvastatin calcium and about 110mg fenofibrate; About 20mg Atorvastatin calcium and about 110mg fenofibrate; About 40mg Atorvastatin calcium and about 110mg fenofibrate; About 80mg Atorvastatin calcium and about 110mg fenofibrate; About 5mg Atorvastatin calcium and about 120mg fenofibrate; About 10mg Atorvastatin calcium and about 120mg fenofibrate; About 20mg Atorvastatin calcium and about 120mg fenofibrate; About 40mg Atorvastatin calcium and about 120mg fenofibrate; About 80mg Atorvastatin calcium and about 120mg fenofibrate; About 5mg Atorvastatin calcium and about 130mg fenofibrate; About 10mg Atorvastatin calcium and about 130mg fenofibrate; About 20mg Atorvastatin calcium and about 130mg fenofibrate; About 40mg Atorvastatin calcium and about 130mg fenofibrate; About 80mg Atorvastatin calcium and about 130mg fenofibrate; About 5mg Atorvastatin calcium and about 145mg fenofibrate; About 10mg Atorvastatin calcium and about 145mg fenofibrate; About 20mg Atorvastatin calcium and about 145mg fenofibrate; About 40mg Atorvastatin calcium and about 145mg fenofibrate; About 80mg Atorvastatin calcium and about 145mg fenofibrate; About 5mg Atorvastatin calcium and about 160mg fenofibrate; About 10mg Atorvastatin calcium and about 160mg fenofibrate; About 20mg Atorvastatin calcium and about 160mg fenofibrate; About 40mg Atorvastatin calcium and about 160mg fenofibrate; And about 80mg Atorvastatin calcium and about 160mg fenofibrate;
The weight of wherein said Atorvastatin calcium is pressed atorvastatin and is calculated.
4. as claim 1,2 each described dispersible tablets, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, described statins or its pharmaceutically acceptable salt or ester are rosuvastain calcium, and described fenofibrate and rosuvastain calcium are selected from the combination of following fixed dosage:
About 2.5mg rosuvastain calcium and about 80mg fenofibrate; About 5mg rosuvastain calcium and about 80mg fenofibrate; About 10mg rosuvastain calcium and about 80mg fenofibrate; About 20mg rosuvastain calcium and about 80mg fenofibrate; About 40mg rosuvastain calcium and about 80mg fenofibrate; About 2.5mg rosuvastain calcium and about 100mg fenofibrate; About 5mg rosuvastain calcium and about 100mg fenofibrate; About 10mg rosuvastain calcium and about 100mg fenofibrate; About 20mg rosuvastain calcium and about 100mg fenofibrate; About 40mg rosuvastain calcium and about 100mg fenofibrate; About 2.5mg rosuvastain calcium and about 110mg fenofibrate; About 5mg rosuvastain calcium and about 110mg fenofibrate; About 10mg rosuvastain calcium and about 110mg fenofibrate; About 20mg rosuvastain calcium and about 110mg fenofibrate; About 40mg rosuvastain calcium and about 110mg fenofibrate; About 2.5mg rosuvastain calcium and about 120mg fenofibrate; About 5mg rosuvastain calcium and about 120mg fenofibrate; About 10mg rosuvastain calcium and about 120mg fenofibrate; About 20mg rosuvastain calcium and about 120mg fenofibrate; About 40mg rosuvastain calcium and about 120mg fenofibrate; About 2.5mg rosuvastain calcium and about 130mg fenofibrate; About 5mg rosuvastain calcium and about 130mg fenofibrate; About 10mg rosuvastain calcium and about 130mg fenofibrate; About 20mg rosuvastain calcium and about 130mg fenofibrate; About 40mg rosuvastain calcium and about 130mg fenofibrate; About 2.5mg rosuvastain calcium and about 145mg fenofibrate; About 5mg rosuvastain calcium and about 145mg fenofibrate; About 10mg rosuvastain calcium and about 145mg fenofibrate; About 20mg rosuvastain calcium and about 145mg fenofibrate; About 40mg rosuvastain calcium and about 145mg fenofibrate; About 2.5mg rosuvastain calcium and about 160mg fenofibrate; About 5mg rosuvastain calcium and about 160mg fenofibrate; About 10mg rosuvastain calcium and about 160mg fenofibrate; About 20mg rosuvastain calcium and about 160mg fenofibrate; And about 40mg rosuvastain calcium and about 160mg fenofibrate;
The weight of wherein said rosuvastain calcium is pressed Rosuvastatin and is calculated.
5. as claim 1,2 each described dispersible tablets, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, described statins or its pharmaceutically acceptable salt or ester are simvastatin, and described fenofibrate and simvastatin are selected from the combination of following fixed dosage:
About 5mg simvastatin and about 80mg fenofibrate; About 10mg simvastatin and about 80mg fenofibrate; About 20mg simvastatin and about 80mg fenofibrate; About 40mg simvastatin and about 80mg fenofibrate; About 80mg simvastatin and about 80mg fenofibrate; About 5mg simvastatin and about 100mg fenofibrate; About 10mg simvastatin and about 100mg fenofibrate; About 20mg simvastatin and about 100mg fenofibrate; About 40mg simvastatin and about 100mg fenofibrate; About 80mg simvastatin and about 100mg fenofibrate; About 5mg simvastatin and about 110mg fenofibrate; About 10mg simvastatin and about 110mg fenofibrate; About 20mg simvastatin and about 110mg fenofibrate; About 40mg simvastatin and about 110mg fenofibrate; About 80mg simvastatin and about 110mg fenofibrate; About 5mg simvastatin and about 120mg fenofibrate; About 10mg simvastatin and about 120mg fenofibrate; About 20mg simvastatin and about 120mg fenofibrate; About 40mg simvastatin and about 120mg fenofibrate; About 80mg simvastatin and about 120mg fenofibrate; About 5mg simvastatin and about 130mg fenofibrate; About 10mg simvastatin and about 130mg fenofibrate; About 20mg simvastatin and about 130mg fenofibrate; About 40mg simvastatin and about 130mg fenofibrate; About 80mg simvastatin and about 130mg fenofibrate; About 5mg simvastatin and about 145mg fenofibrate; About 10mg simvastatin and about 145mg fenofibrate; About 20mg simvastatin and about 145mg fenofibrate; About 40mg simvastatin and about 145mg fenofibrate; About 80mg simvastatin and about 145mg fenofibrate; About 5mg simvastatin and about 160mg fenofibrate; About 10mg simvastatin and about 160mg fenofibrate; About 20mg simvastatin and about 160mg fenofibrate; About 40mg simvastatin and about 160mg fenofibrate; And about 80mg simvastatin and about 160mg fenofibrate.
6. as claim 1,2 each described dispersible tablets, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, described statins or its pharmaceutically acceptable salt or ester are Pitavastatin Calcium, and described fenofibrate and Pitavastatin Calcium are selected from the combination of following fixed dosage:
About 0.25mg Pitavastatin Calcium and about 80mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 80mg fenofibrate; About 1mg Pitavastatin Calcium and about 80mg fenofibrate; About 2mg Pitavastatin Calcium and about 80mg fenofibrate; About 4mg Pitavastatin Calcium and about 80mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 100mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 100mg fenofibrate; About 1mg Pitavastatin Calcium and about 100mg fenofibrate; About 2mg Pitavastatin Calcium and about 100mg fenofibrate; About 4mg Pitavastatin Calcium and about 100mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 110mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 110mg fenofibrate; About 1mg Pitavastatin Calcium and about 110mg fenofibrate; About 2mg Pitavastatin Calcium and about 110mg fenofibrate; About 4mg Pitavastatin Calcium and about 110mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 120mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 120mg fenofibrate; About 1mg Pitavastatin Calcium and about 120mg fenofibrate; About 2mg Pitavastatin Calcium and about 120mg fenofibrate; About 4mg Pitavastatin Calcium and about 120mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 130mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 130mg fenofibrate; About 1mg Pitavastatin Calcium and about 130mg fenofibrate; About 2mg Pitavastatin Calcium and about 130mg fenofibrate; About 4mg Pitavastatin Calcium and about 130mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 145mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 145mg fenofibrate; About 1mg Pitavastatin Calcium and about 145mg fenofibrate; About 2mg Pitavastatin Calcium and about 145mg fenofibrate; About 4mg Pitavastatin Calcium and about 145mg fenofibrate; About 0.25mg Pitavastatin Calcium and about 160mg fenofibrate; About 0.5mg Pitavastatin Calcium and about 160mg fenofibrate; About 1mg Pitavastatin Calcium and about 160mg fenofibrate; About 2mg Pitavastatin Calcium and about 160mg fenofibrate; And about 4mg Pitavastatin Calcium and about 160mg fenofibrate.
7. as claim 1,2 each described dispersible tablets, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate, described statins or its pharmaceutically acceptable salt or ester are lovastatin, and described fenofibrate and lovastatin are selected from the combination of following fixed dosage:
About 5mg lovastatin and about 80mg fenofibrate; About 10mg lovastatin and about 80mg fenofibrate; About 20mg lovastatin and about 80mg fenofibrate; About 40mg lovastatin and about 80mg fenofibrate; About 80mg lovastatin and about 80mg fenofibrate; About 5mg lovastatin and about 100mg fenofibrate; About 10mg lovastatin and about 100mg fenofibrate; About 20mg lovastatin and about 100mg fenofibrate; About 40mg lovastatin and about 100mg fenofibrate; About 80mg lovastatin and about 100mg fenofibrate; About 5mg lovastatin and about 110mg fenofibrate; About 10mg lovastatin and about 110mg fenofibrate; About 20mg lovastatin and about 110mg fenofibrate; About 40mg lovastatin and about 110mg fenofibrate; About 80mg lovastatin and about 110mg fenofibrate; About 5mg lovastatin and about 120mg fenofibrate; About 10mg lovastatin and about 120mg fenofibrate; About 20mg lovastatin and about 120mg fenofibrate; About 40mg lovastatin and about 120mg fenofibrate; About 80mg lovastatin and about 120mg fenofibrate; About 5mg lovastatin and about 130mg fenofibrate; About 10mg lovastatin and about 130mg fenofibrate; About 20mg lovastatin and about 130mg fenofibrate; About 40mg lovastatin and about 130mg fenofibrate; About 80mg lovastatin and about 130mg fenofibrate; About 5mg lovastatin and about 145mg fenofibrate; About 10mg lovastatin and about 145mg fenofibrate; About 20mg lovastatin and about 145mg fenofibrate; About 40mg lovastatin and about 145mg fenofibrate; About 80mg lovastatin and about 145mg fenofibrate; About 5mg lovastatin and about 160mg fenofibrate; About 10mg lovastatin and about 160mg fenofibrate; About 20mg lovastatin and about 160mg fenofibrate; About 40mg lovastatin and about 160mg fenofibrate; And about 80mg lovastatin and about 160mg fenofibrate.
8. as claim 1,2 each described dispersible tablets, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate acid, described statins or its pharmaceutically acceptable salt or ester are Atorvastatin calcium, and described fenofibrate acid and Atorvastatin calcium are selected from the combination of following fixed dosage:
About 5mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 80mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 105mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 105mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 105mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 105mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 105mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 110mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 110mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 110mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 110mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 110mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 120mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 120mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 120mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 120mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 120mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 130mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 130mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 130mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 130mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 130mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 80mg Atorvastatin calcium and the acid of about 135mg fenofibrate; About 5mg Atorvastatin calcium and the acid of about 160mg fenofibrate; About 10mg Atorvastatin calcium and the acid of about 160mg fenofibrate; About 20mg Atorvastatin calcium and the acid of about 160mg fenofibrate; About 40mg Atorvastatin calcium and the acid of about 160mg fenofibrate; And about 80mg Atorvastatin calcium and the acid of about 160mg fenofibrate;
The weight of wherein said Atorvastatin calcium is pressed atorvastatin and is calculated.
9. as claim 1,2 each described dispersible tablets, it is characterized in that, described fibrate or its pharmaceutically acceptable salt or ester or derivatives thereof are fenofibrate acid, described statins or its pharmaceutically acceptable salt or ester are rosuvastain calcium, and described fenofibrate acid and rosuvastain calcium are selected from the combination of following fixed dosage:
About 2.5mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 80mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 105mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 105mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 105mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 105mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 105mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 110mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 110mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 110mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 110mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 110mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 120mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 120mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 120mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 120mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 120mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 130mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 130mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 130mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 130mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 130mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 40mg rosuvastain calcium and the acid of about 135mg fenofibrate; About 2.5mg rosuvastain calcium and the acid of about 160mg fenofibrate; About 5mg rosuvastain calcium and the acid of about 160mg fenofibrate; About 10mg rosuvastain calcium and the acid of about 160mg fenofibrate; About 20mg rosuvastain calcium and the acid of about 160mg fenofibrate; And about 40mg rosuvastain calcium and the acid of about 160mg fenofibrate;
The weight of wherein said rosuvastain calcium is pressed Rosuvastatin and is calculated.
10. be used for the treatment of application in the medicine of dyslipidemia as each described dispersible tablet of claim 1 to 9 in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102758364A CN101912612A (en) | 2010-09-08 | 2010-09-08 | Dispersible tablet containing fibrate and statin drug and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102758364A CN101912612A (en) | 2010-09-08 | 2010-09-08 | Dispersible tablet containing fibrate and statin drug and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101912612A true CN101912612A (en) | 2010-12-15 |
Family
ID=43320357
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102758364A Pending CN101912612A (en) | 2010-09-08 | 2010-09-08 | Dispersible tablet containing fibrate and statin drug and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101912612A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013035798A (en) * | 2011-08-10 | 2013-02-21 | Kyowa Yakuhin Kogyo Kk | Stabilized pharmaceutical composition containing pitavastatin |
| CN104546854A (en) * | 2014-12-20 | 2015-04-29 | 长沙佰顺生物科技有限公司 | Rosuvastatin calcium choline fenofibrate sustained-release tablets and preparation method thereof |
| CN104628564A (en) * | 2015-02-11 | 2015-05-20 | 河南中帅医药科技股份有限公司 | Fenofibric acid choline salt crystal form and preparation method thereof |
| CN104860882A (en) * | 2015-05-15 | 2015-08-26 | 苗怡文 | Drug pitavastatin calcium composition for treating hyperlipidemia |
| CN113143882A (en) * | 2021-04-30 | 2021-07-23 | 海南通用三洋药业有限公司 | Preparation method of rosuvastatin calcium capsule and rosuvastatin calcium capsule |
-
2010
- 2010-09-08 CN CN2010102758364A patent/CN101912612A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013035798A (en) * | 2011-08-10 | 2013-02-21 | Kyowa Yakuhin Kogyo Kk | Stabilized pharmaceutical composition containing pitavastatin |
| CN104546854A (en) * | 2014-12-20 | 2015-04-29 | 长沙佰顺生物科技有限公司 | Rosuvastatin calcium choline fenofibrate sustained-release tablets and preparation method thereof |
| CN104546854B (en) * | 2014-12-20 | 2018-05-18 | 长沙佰顺生物科技有限公司 | A kind of rosuvastain calcium fenofibrate choline salt sustained release tablets |
| CN104628564A (en) * | 2015-02-11 | 2015-05-20 | 河南中帅医药科技股份有限公司 | Fenofibric acid choline salt crystal form and preparation method thereof |
| CN104860882A (en) * | 2015-05-15 | 2015-08-26 | 苗怡文 | Drug pitavastatin calcium composition for treating hyperlipidemia |
| CN113143882A (en) * | 2021-04-30 | 2021-07-23 | 海南通用三洋药业有限公司 | Preparation method of rosuvastatin calcium capsule and rosuvastatin calcium capsule |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1519715B1 (en) | Nanoparticulate fibrate formulations | |
| CN102451161A (en) | Dispersible tablets containing cholesterol absorption inhibitor and lipid regulating drug, and application thereof | |
| CN100475208C (en) | Hyperlipemia therapeutic agent | |
| US20080020046A1 (en) | Pharmaceutical Formulations Comprising Metformin And A Fibrate, And Processes For Obtaining Them | |
| US20050287210A1 (en) | Sustained release L-arginine formulations and methods of manufacture and use | |
| US20060251720A1 (en) | Localized controlled absorption of statins in the gastrointestinal tract for achieving high blood levels of statins | |
| KR20070085754A (en) | Stabilized ramipril compositions and methods of making | |
| US20060029668A1 (en) | Sustained release L-arginine formulations and methods of manufacture and use | |
| KR20070104447A (en) | A stable pharmaceutical composition comprising a fixed dose combination of fenofibrate and an hmg-coa reductase inhibitor | |
| WO2015139513A1 (en) | Pharmaceutical composition of atorvastatin calcium | |
| US20120045505A1 (en) | Fixed dose drug combination formulations | |
| US20110123609A1 (en) | Multiple unit dosage form of niacin | |
| WO2008068217A2 (en) | Pharmaceutical composition comprising a coated hmg-coa reductase inhibitor and an inhibitor of the renin-angiotensin system | |
| CN101912612A (en) | Dispersible tablet containing fibrate and statin drug and application thereof | |
| US20030147957A1 (en) | Dual release formulation comprising levodopa ethyl ester and a decarboxylase inhibitor in immediate release layer with levodopa ethyl ester and a decarboxylase inhibitor in a controlled release core | |
| WO2005035001A1 (en) | Sustained release l-arginine formulations and methods of manufacture and use | |
| CN101115478A (en) | A stable pharmaceutical composition comprising a fixed dose combination of fenofibrate and an HMG-CoA reductase inhibitor | |
| US20150037414A1 (en) | Stable controlled release pharmaceutical compositions containing fenofibrate and pravastatin | |
| ES2342885T3 (en) | STABLE CONTROLLED RELEASE PHARMACEUTICAL COMPOSITIONS CONTAINING PHENOFIBRATE AND PRAVASTATIN. | |
| CN102049049A (en) | Medical composition containing aspirin salt and stanin medicaments | |
| ES2387913T3 (en) | Combination preparations of salts of O-acetylsalicylic acid | |
| CN102188419A (en) | Single preparations containing fenofibrate and atorvastatin | |
| CN106310273A (en) | Quadruple antihypertensive drug composition | |
| WO2012002921A1 (en) | Multiple dosage forms comprising fenofibrate or fenofibric acid in combination with hmg co a reductase inhibitors such as statins | |
| CN101534825A (en) | Drug formulation containing fibrate medicament and process for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20101215 |