CN103599081A - Novel niacin compound slow-release preparation for treating hyperlipoidemia - Google Patents
Novel niacin compound slow-release preparation for treating hyperlipoidemia Download PDFInfo
- Publication number
- CN103599081A CN103599081A CN201310606072.6A CN201310606072A CN103599081A CN 103599081 A CN103599081 A CN 103599081A CN 201310606072 A CN201310606072 A CN 201310606072A CN 103599081 A CN103599081 A CN 103599081A
- Authority
- CN
- China
- Prior art keywords
- nicotinic acid
- slow
- release
- preparation
- niacin
- 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
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a novel niacin compound slow-release preparation for treating hyperlipoidemia. The novel niacin compound slow-release preparation comprises a quick-release part and a slow-release part, wherein the quick-release part comprises statins and pharmaceutical excipients; the slow-release part comprises niacin, polyvinylpyrrolidone k90 and pharmaceutical excipients; the weight ratio of the statins to niacin in the preparation is 1:(10-100), the weight ratio of polyvinylpyrrolidone k90 to niacin in the slow-release part is 1:(20-80), and the dosage form of the compound preparation is slow-release coating tablets. The compound preparation provided by the invention is suitable for treating hyperlipoidemia of Asian people. Compared with the existing niacin statin slow-release preparation, the compound preparation provided by the invention is less in the content of statins and can achieve a very good treatment effect at the same time, so that the toxic and side effects of medicaments are greatly reduced.
Description
The application is that patent of invention, the number of patent application of 2012-11-23 application is " 201210480605.6 ", and denomination of invention is divided an application for " a kind of new nicotinic acid compound slow release preparation that is used for the treatment of hyperlipidemia ".
Technical field
The present invention relates to a kind of new nicotinic acid compound slow release preparation for the treatment of hyperlipidemia, belong to chemicals medicine field.
Background technology
Hyperlipidemia is " origin of hundreds of diseases ", and the death toll finally causing reaches 51% of the total death toll in the whole world.Meanwhile, dyslipidemia becomes younger also more and more obvious.Hyperlipidemia is a kind of systemic disease, refers to that T-CHOL in blood (TC) and/or triglyceride (TG) are too high or HDL-C (HDL-C) is too low, and modern medicine is referred to as dyslipidemia.It is too high or be a kind of common clinical with the too low hyperlipidemia as feature of serum High Density Lipoprotein Cholesterol level wherein to take cholesterol and triglyceride levels, is the main cause that causes atherosclerosis and then cause coronary heart disease, hypertension and cerebrovascular disease.According to the degree of the level of aggregation of the T-CHOL in hyperlipidemia, LDL-C, HDL-C, TG, can be divided into slight hyperlipidemia, medium and high blood fat, severe hyperlipidemia.The open effective blood lipid-lowering medicine of research has become the problem of global concern.
The medicine that can effectively treat at present hyperlipidemia has 1, fibrate 2, trihydroxy methyl glutaryl-CoA-reductase inhibitors 3, nicotinic acid class 4, polyunsaturated fatty acid class 5, pantethine 6, Sargassum diesteras 7, Semen Ginkgo class.
Nicotinic acid is one of vitamin B complex, is the classical medicine of nicotinic acid class lipid lowerers, as anti-(leprosy) pellagra factor, works.Nicotinic acid chemically just known since 1867, but as vitamin by C.A.Elvehjem(1937) illustrate.Yeast, liver, beast bird meat, all contain a large amount of nicotinic acid in leaf vegetables.In human body, also comprise its derivant nicotiamide or niacin amide.Nicotinic acid is converted into nicotiamide in human body, and nicotiamide is nadide and coenzyme II ingredient, participates in HypercholesterolemicRats, the process that the oxidizing process of Tissue respiration and saccharide anaerobic are decomposed.Nicotinic acid has stronger expansion peripheral vessels and effect for reducing blood fat, clinical headache, migraine, tinnitus, the auditory vertigo etc. of being used for the treatment of.
When nicotinic acid consumption surpasses the metering as vitamin effect, can there is the effect of obvious adjusting blood fat.Nicotinic acid can be distributed widely in body tissue from gastrointestinal absorption, and the half-life is about 45 minutes.At intrahepatic metabolism, heavy dose of when oral, main metabolites is nitocinoylglycine, N-methylnicotinamide and 2-Pyridione derivatives.
It is the formation that suppresses cAMP that nicotinic acid regulates the main mechanism of blood fat, cause triglyceride enzymatic activity to reduce, lipolysis in fatty tissue slows down, and the concentration of non-esterified fatty acid in blood (NEFA) reduces the synthetic VLDL of liver and reduces, and further makes IDL and LDL also reduce.In addition, nicotinic acid can synthesize nitocinoylglycine with glycine under the effect of coenzyme A (COA), thereby hinder hepatocyte, utilizes COA synthetic cholesterol.Blood lipid level before nicotinic acid regulates the curative effect of blood fat and dosage and takes medicine is relevant, and blood lipid level is extremely more obvious, and medication dose should be greatly, and curative effect is also more obvious.Nicotinic acid can be used for the hyperlipidemia of any type except homozygote familial hypercholesterolemia and I type hyperlipoproteinemia.
Statins is hydroxy-methyl-glutaryl coenzyme A (HMG-COA) reductase inhibitor, wherein represents that medicine has lovastatin, simvastatin, pravastatin, mevastatin, fluvastatin, atorvastatin, cerivastatin, rosuvastatin.This type of medicine is by synthetic rate-limiting enzyme (HMG-COA) reductase of competitive inhibition endogenous cholesterol, hydroxyl first valeric acid metabolic pathway in blocking-up cell, make the synthetic minimizing of cell inner cholesterol, thereby feedback irritation cell film surface (being mainly hepatocyte) low density lipoprotein, LDL (LDL) acceptor quantity and activity increase, make, serum cholesterol removing increases, level reduces.Statins also can suppress liver synthetic fat protein B-100, thereby reduces the synthetic and secretion of being rich in triglyceride AV, lipoprotein.In most of the cases, lipid therapy be take to statins as first-selected, but concerning quite a few hyperlipemic patients, the independent treatment of statins is inadequate, the main untoward reaction of statins is the impact on liver, kidney and musculature, and drug combination is a kind of good selection that alleviates or avoid side effect.
Polyvinylpyrrolidone k90 is as a kind of synthesizing water-solubility macromolecular compound; the general aspects with water-soluble high-molecular compound; colloid protective effect, film property, caking property, hygroscopicity, solubilising or cohesion; but it is most characteristic, thereby what be subject to that people pay attention to is its excellent solubility property and physiological compatibility.Both water-soluble as PVP in synthetic macromolecule, be dissolved in again actually rare that majority of organic solvent, toxicity are very low, physiology intermiscibility is good, particularly in medicine, food, cosmetics these and the closely-related field of health of people, along with the reduction of its raw material butyrolactone price, will show the good prospect of its development.
In the nicotinic acid Statins slow releasing preparation of prior art, statins content is higher, toxic and side effects for asian population is also very large, take niacin simvastatin sustained-release coated tablet as example: in its sustained release coating sheet, during the percentage composition 0.5%～1% of simvastatin, be mainly used in treating slight hyperlipidemia; When the percentage composition of simvastatin is 1%～2%, be mainly used in treating the hyperlipidemia of moderate; When the percentage composition of simvastatin is 2%～3.2%, be mainly used in treating the hyperlipidemia of severe.Although these preparations can effectively be treated corresponding hyperlipemic patients, corresponding toxic and side effects is also very large.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art part, a kind of new nicotinic acid compound slow release preparation that is used for the treatment of hyperlipidemia is provided.
The new nicotinic acid compound slow release preparation that is used for the treatment of hyperlipidemia of the present invention, comprises immediate release section and slow-released part, and said immediate release section comprises statins and pharmaceutic adjuvant; Said slow-released part comprises nicotinic acid, polyvinylpyrrolidone k90 and pharmaceutic adjuvant, it is characterized in that, in said preparation, the weight ratio of statins and nicotinic acid is 1:(10～100), in said slow-released part, the weight ratio of polyvinylpyrrolidone k90 and nicotinic acid is 1:(20～80).
Further in preferred said preparation, the weight ratio of statins and nicotinic acid is 1:(12.5～50), in said slow-released part, the weight ratio of polyvinylpyrrolidone k90 and nicotinic acid is 1:(30～40).。
Said statins is selected from lovastatin, simvastatin, pravastatin, mevastatin, fluvastatin, atorvastatin, cerivastatin or rosuvastatin;
The pharmaceutic adjuvant of said immediate release section is solvent, antioxidant, plasticizer and excipient, said cosolvent is ethanol, one or several in propylene glycol, said antioxidant is vitamin E, butylhydroxy anisole, vitamin C, dibenzylatiooluene, propyl gallate, one or several in tert-butyl hydroquinone, said plasticizer is Polyethylene Glycol, glycerol, diethyl phthalate, one or several of dimethyl phthalate and dibutyl phthalate, said excipient is hypromellose, sucrose, mannitol, sorbitol, alginate, sodium carboxymethyl cellulose, carbomer, ethyl cellulose, polyoxyethylene, acrylic resin, polyethylene, Glyceryl Behenate, stearic acid, hard alcohol, babassu ester, one or several in starch,
The pharmaceutic adjuvant of said slow-released part is slow-release material and lubricant, said slow-release material is one or several in hydroxypropyl methylcellulose, alginate, sodium carboxymethyl cellulose, carbomer, ethyl cellulose, polyoxyethylene, acrylic resin, polyethylene, Glyceryl Behenate, stearic acid, hard alcohol, babassu ester, starch, and said lubricant is one or several in stearic acid, stearate, differential silica gel, Pulvis Talci, calcium phosphate;
The dosage form of said compound preparation is sustained release coating sheet, sustained-release double-layer tablet and slow releasing capsule;
Composition and the content of said sustained release coating sheet are as follows:
The preparation method of said sustained release coating sheet, comprises the steps:
1) prepare slow-released part: in prescription ratio by principal agent nicotinic acid, polyvinylpyrrolidone k90 and part slow-release material, mix lubricant, then carry out wet granulation, wet granulate, dry, dry granulate, then add additional residue slow-release material to mix, finally according to target patch, heavily carry out tabletting.
2) prepare immediate release section: first use purified water swelling dispersant, then according to formulation and technology, add successively principal agent and pharmaceutic adjuvant, make suspension, with this suspension, above-mentioned niacin sustained release is partly carried out to coating, at slow release label, form one deck release layer outward and form the sustained release coating sheet that contains nicotinic acid and two kinds of principal agents of Statins.
Composition and the content of said sustained-release double-layer tablet are as follows:
The preparation method of said sustained-release double-layer tablet, comprises the steps:
1) prepare slow-released part: in prescription ratio by principal agent nicotinic acid, polyvinylpyrrolidone k90 and part slow release
Material, mix lubricant, then carry out wet granulation, wet granulate, dry, dry granulate, then adds additional residue slow-release material mix homogeneously standby;
2) prepare immediate release section: in prescription ratio, principal agent statins and antioxidant, plasticizer, part mixed with excipients is even, carry out wet granulation, wet granulate, dry, dry granulate, then add additional residue mixed with excipients evenly standby;
3) tabletting: slow-released part and immediate release section are added in bi-layer tablet press and are prepared respectively, form the sustained-release double-layer tablet that contains nicotinic acid and two kinds of principal agents of Statins.
Composition and the content of said slow releasing capsule are as follows:
The preparation method of said slow releasing capsule, comprises the steps:
1) prepare slow-released part: in prescription ratio, by principal agent nicotinic acid, polyvinylpyrrolidone k90 and slow-release material, mix lubricant, add suitable quantity of water, put into and extrude spheronizator, prepare slow-releasing granules, both dried and obtain, standby;
2) prepare immediate release section: in prescription ratio, principal agent statins and antioxidant, plasticizer, mixed with excipients is even, put into and extrude spheronizator, prepare immediate-release granules, both dry, standby.
3) tabletting: slow-releasing granules and immediate-release granules are added in capsule filling machine and prepared respectively, be just prepared into the slow releasing capsule that contains nicotinic acid and two kinds of principal agents of Statins.
Compound preparation of the present invention is applicable to Asian hyperlipidemia treatment, compound preparation of the present invention is compared with existing nicotinic acid Statins slow releasing preparation, the content of statins reduces, and also can reach good therapeutic effect simultaneously, and the toxic and side effects of medicine is all reduced greatly.
The specific embodiment
Embodiment 1: the preparation of nicotinic acid (300mg) lovastatin (6mg) slow releasing capsule
Niacin sustained release part A:
Lovastatin immediate release section B:
The preparation A of niacin sustained release micropill: the nicotinic acid, polyvinylpyrrolidone k90, microcrystalline Cellulose, ethyl cellulose, the stearic acid that weigh recipe quantity; first nicotinic acid is crossed to 60 mesh sieves; then nicotinic acid is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain niacin sustained release micropill.
The preparation B of lovastatin fast release micropill: the lovastatin, starch, microcrystalline Cellulose, dextrin, the lactose that weigh recipe quantity; lovastatin is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain simvastatin fast release micropill.
Use double threaded screw filling machine by the above-mentioned A preparing, the filling of B material, obtain.
Capsule prepared by said method is nicotinic acid (300mg) lovastatin (6mg) slow releasing capsule, is used for the treatment of slight hyperlipidemia.
Embodiment 2: the preparation of nicotinic acid (1200mg) lovastatin (14mg) double-layer tablet
Niacin sustained release part A:
Simvastatin part B:
Niacin slow-release tablet part A: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (K15M), stearic acid, mix, standby.
Simvastatin immediate release section B: the simvastatin, microcrystalline Cellulose, pregelatinized Starch, lactose, the stearic acid that take recipe quantity.Using purified water as wetting agent, manual granulation, the wet granulate of 16 orders for soft material, baking oven 50～55 is dried 2～5 hours, with the dry granulate of 14 mesh sieve, adds stearic acid to mix, standby.
By bi-layer tablet press, by material A and B tabletting, obtain.
Slice, thin piece prepared by said method is nicotinic acid (1200mg) lovastatin (14mg) double-layer sustained release tablets, is used for the treatment of medium and high blood fat.
Embodiment 3: the preparation of nicotinic acid (800mg) lovastatin (16mg) double-layer tablet
Niacin sustained release part A:
Simvastatin part B:
Niacin slow-release tablet part A: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (K15M), stearic acid, mix, standby.
Simvastatin immediate release section B: the simvastatin, microcrystalline Cellulose, pregelatinized Starch, lactose, the stearic acid that take recipe quantity.Using purified water as wetting agent, manual granulation, the wet granulate of 16 orders for soft material, baking oven 50～55 is dried 2～5 hours, with the dry granulate of 14 mesh sieve, adds stearic acid to mix, standby.
By bi-layer tablet press, by material A and B tabletting, obtain.
Slice, thin piece prepared by said method is nicotinic acid (800mg) lovastatin (16mg) double-layer sustained release tablets, is used for the treatment of medium and high blood fat.
Embodiment 4: the preparation of nicotinic acid (1000mg) lovastatin (24mg) slow releasing tablet
Niacin sustained release label:
Simvastatin release layer:
Film-coat layer:
Niacin slow-release tablet core segment: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (K15M), stearic acid, mix.Tabletting obtains niacin sustained release part label.
Simvastatin immediate release section: the simvastatin, hypromellose (E5), Polyethylene Glycol (1450), butylhydroxy anisole, ethanol (95%), the purified water that take recipe quantity.Preparation coating solution, obtains finely dispersed suspension.Plain sheet is placed in high-efficiency coating machine, plain sheet is carried out to coating, target weightening finish 119.3mg, after reaching target weightening finish and get final product.
Color film-coat part: the film-coat material, the purified water that take recipe quantity.Preparation film-coat material coating solution.The tablet that has wrapped simvastatin layer is placed in to coating in high-efficiency coating machine, and target weightening finish 23mg, reaches the rear cooling slice of target weightening finish, obtains.
Slice, thin piece prepared by said method is nicotinic acid (100mg) lovastatin (24mg) slow releasing tablet, is used for the treatment of severe hyperlipidemia.
Embodiment 5: the preparation of nicotinic acid (600mg) simvastatin (8mg) slow releasing capsule
Niacin sustained release part A:
Simvastatin immediate release section B:
The preparation of niacin sustained release micropill A: the nicotinic acid, polyvinylpyrrolidone k90, microcrystalline Cellulose, ethyl cellulose, the stearic acid that weigh recipe quantity; first nicotinic acid is crossed to 60 mesh sieves; then nicotinic acid is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain niacin sustained release micropill.
The preparation of simvastatin fast release micropill B: the simvastatin, starch, microcrystalline Cellulose, dextrin, the lactose that weigh recipe quantity; simvastatin is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain simvastatin fast release micropill.
Use double threaded screw filling machine by the above-mentioned A preparing, the filling of B material, obtain.
Capsule prepared by said method is nicotinic acid (600mg) simvastatin (8mg) slow releasing capsule, is used for the treatment of slight hyperlipidemia.
Embodiment 6: the preparation of nicotinic acid (800mg) mevastatin (10mg) double-layer tablet
Niacin sustained release part A:
Simvastatin part B:
Niacin slow-release tablet part A: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (K15M), stearic acid, mix, standby.
Simvastatin immediate release section B: the mevastatin, microcrystalline Cellulose, pregelatinized Starch, lactose, the stearic acid that take recipe quantity.Using purified water as wetting agent, manual granulation, the wet granulate of 16 orders for soft material, baking oven 50～55 is dried 2～5 hours, with the dry granulate of 14 mesh sieve, adds stearic acid to mix, standby.
By bi-layer tablet press, by material A and B tabletting, obtain.
Slice, thin piece prepared by said method is nicotinic acid (800mg) mevastatin (10mg) double-layer sustained release tablets, is used for the treatment of slight hyperlipidemia.
Embodiment 7: the preparation of nicotinic acid (1200mg) simvastatin (16mg) double-layer tablet
Niacin sustained release part A:
Simvastatin part B:
Niacin slow-release tablet part A: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (K15M), stearic acid, mix, standby.
Simvastatin immediate release section B: the simvastatin, microcrystalline Cellulose, pregelatinized Starch, lactose, the stearic acid that take recipe quantity.Using purified water as wetting agent, manual granulation, the wet granulate of 16 orders for soft material, baking oven 50～55 is dried 2～5 hours, with the dry granulate of 14 mesh sieve, adds stearic acid to mix, standby.
By bi-layer tablet press, by material A and B tabletting, obtain.
Slice, thin piece prepared by said method is nicotinic acid (1200mg) simvastatin (16mg) double-layer sustained release tablets, is used for the treatment of medium and high blood fat.
Embodiment 8: the preparation of nicotinic acid (500mg) simvastatin (20mg) slow releasing tablet
Niacin sustained release label:
Simvastatin release layer:
Film-coat layer:
Niacin slow-release tablet core segment: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in add hypromellose (E4M), in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (E4M), hypromellose (K15M), stearic acid, mix.Tabletting obtains niacin sustained release part label.
Simvastatin immediate release section: the simvastatin, hypromellose (E5), Polyethylene Glycol (1450), butylhydroxy anisole, ethanol (95%), the purified water that take recipe quantity.Preparation coating solution, obtains finely dispersed suspension.Plain sheet is placed in high-efficiency coating machine, plain sheet is carried out to coating, target weightening finish 70.5mg, after reaching target weightening finish and get final product.
Color film-coat part: the film-coat material, the purified water that take recipe quantity.Preparation film-coat material coating solution.The tablet that has wrapped simvastatin layer is placed in to coating in high-efficiency coating machine, and target weightening finish 23mg, reaches the rear cooling slice of target weightening finish, obtains.
Slice, thin piece prepared by said method is nicotinic acid (500mg) simvastatin (20mg) slow releasing tablet, is used for the treatment of severe hyperlipidemia.
Embodiment 9: the preparation of nicotinic acid (300mg) pravastatin (6mg) slow releasing capsule
Niacin sustained release part A:
Pravastatin immediate release section B:
The preparation of niacin sustained release micropill A: the nicotinic acid, polyvinylpyrrolidone k90, microcrystalline Cellulose, ethyl cellulose, the stearic acid that weigh recipe quantity; first nicotinic acid is crossed to 60 mesh sieves; then nicotinic acid is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain niacin sustained release micropill.
The preparation of pravastatin fast release micropill B: the pravastatin, starch, microcrystalline Cellulose, dextrin, the lactose that weigh recipe quantity; pravastatin is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain pravastatin fast release micropill.
Use double threaded screw filling machine by the above-mentioned A preparing, the filling of B material, obtain.
Capsule prepared by said method is nicotinic acid (300mg) pravastatin (6mg) slow releasing capsule, is used for the treatment of slight hyperlipidemia.
Embodiment 10: the preparation of nicotinic acid (800mg) mevastatin (8mg) double-layer tablet
Niacin sustained release part A:
Pravastatin part B:
Niacin slow-release tablet part A: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (K15M), stearic acid, mix, standby.
Pravastatin immediate release section B: the mevastatin, microcrystalline Cellulose, pregelatinized Starch, lactose, the stearic acid that take recipe quantity.Using purified water as wetting agent, manual granulation, the wet granulate of 16 orders for soft material, baking oven 50～55 is dried 2～5 hours, with the dry granulate of 14 mesh sieve, adds stearic acid to mix, standby.
By bi-layer tablet press, by material A and B tabletting, obtain.
Slice, thin piece prepared by said method is nicotinic acid (800mg) mevastatin (8mg) double-layer sustained release tablets, is used for the treatment of slight hyperlipidemia.
Embodiment 11: the preparation of nicotinic acid (600mg) pravastatin (10mg) slow releasing capsule
Niacin sustained release part A:
Pravastatin immediate release section B:
The preparation of niacin sustained release micropill A: the nicotinic acid, polyvinylpyrrolidone k90, microcrystalline Cellulose, ethyl cellulose, the stearic acid that weigh recipe quantity; first nicotinic acid is crossed to 60 mesh sieves; then nicotinic acid is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain niacin sustained release micropill.
The preparation of pravastatin fast release micropill B: the pravastatin, starch, microcrystalline Cellulose, dextrin, the lactose that weigh recipe quantity; pravastatin is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain pravastatin fast release micropill.
Use double threaded screw filling machine by the above-mentioned A preparing, the filling of B material, obtain.
Capsule prepared by said method is nicotinic acid (600mg) pravastatin (10mg) slow releasing capsule, is used for the treatment of slight hyperlipidemia.
Embodiment 12: the preparation of nicotinic acid (1200mg) pravastatin (14mg) double-layer tablet
Niacin sustained release part A:
Pravastatin part B:
Niacin slow-release tablet part A: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (K15M), stearic acid, mix, standby.
Pravastatin immediate release section B: the pravastatin, microcrystalline Cellulose, pregelatinized Starch, lactose, the stearic acid that take recipe quantity.Using purified water as wetting agent, manual granulation, the wet granulate of 16 orders for soft material, baking oven 50～55 is dried 2～5 hours, with the dry granulate of 14 mesh sieve, adds stearic acid to mix, standby.
By bi-layer tablet press, by material A and B tabletting, obtain.
Slice, thin piece prepared by said method is nicotinic acid (1200mg) pravastatin (14mg) double-layer sustained release tablets, is used for the treatment of medium and high blood fat.
Embodiment 13: the preparation of nicotinic acid (500mg) pravastatin (24mg) slow releasing tablet
Niacin sustained release label:
Pravastatin release layer:
Film-coat layer:
Niacin slow-release tablet core segment: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (E4M), the hypromellose (K15M) that add.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (E4M), hypromellose (K15M), stearic acid, mix.Tabletting obtains niacin sustained release part label.
Pravastatin immediate release section: the pravastatin, hypromellose (E5), Polyethylene Glycol (1450), butylhydroxy anisole, ethanol (95%), the purified water that take recipe quantity.Preparation coating solution, obtains finely dispersed suspension.Plain sheet is placed in high-efficiency coating machine, plain sheet is carried out to coating, target weightening finish 119.3mg, after reaching target weightening finish and get final product.
Color film-coat part: the film-coat material, the purified water that take recipe quantity.Preparation film-coat material coating solution.The tablet that has wrapped pravastatin layer is placed in to coating in high-efficiency coating machine, and target weightening finish 23mg, reaches the rear cooling slice of target weightening finish, obtains.
Slice, thin piece prepared by said method is nicotinic acid (500mg) pravastatin (24mg) slow releasing tablet, is used for the treatment of severe hyperlipidemia.
Embodiment 14: the preparation of nicotinic acid (600mg) fluvastatin (8mg) slow releasing capsule
Niacin sustained release part A:
Fluvastatin immediate release section B:
The preparation of niacin sustained release micropill A: the nicotinic acid, polyvinylpyrrolidone k90, microcrystalline Cellulose, ethyl cellulose, the stearic acid that weigh recipe quantity; first nicotinic acid is crossed to 60 mesh sieves; then nicotinic acid is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain niacin sustained release micropill.
The preparation of fluvastatin fast release micropill B: the fluvastatin, starch, microcrystalline Cellulose, dextrin, the lactose that weigh recipe quantity; fluvastatin is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain fluvastatin fast release micropill.
Use double threaded screw filling machine by the above-mentioned A preparing, the filling of B material, obtain.
Capsule prepared by said method is nicotinic acid (600mg) fluvastatin (8mg) slow releasing capsule, is used for the treatment of slight hyperlipidemia.
Embodiment 15: the preparation of nicotinic acid (1000mg) fluvastatin (14mg) double-layer tablet
Niacin sustained release part A:
Fluvastatin part B:
Niacin slow-release tablet part A: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (K15M), stearic acid, mix, standby.
Fluvastatin immediate release section B: the fluvastatin, microcrystalline Cellulose, pregelatinized Starch, lactose, the stearic acid that take recipe quantity.Using purified water as wetting agent, manual granulation, the wet granulate of 16 orders for soft material, baking oven 50～55 is dried 2～5 hours, with the dry granulate of 14 mesh sieve, adds stearic acid to mix, standby.
By bi-layer tablet press, by material A and B tabletting, obtain.
Slice, thin piece prepared by said method is nicotinic acid (1000mg) fluvastatin (14mg) double-layer sustained release tablets, is used for the treatment of medium and high blood fat.
Embodiment 16: the preparation of nicotinic acid (500mg) fluvastatin (16mg) slow releasing tablet
Niacin sustained release label:
Fluvastatin release layer:
Film-coat layer:
Niacin slow-release tablet core segment: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (E4M), the hypromellose (K15M) that add.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (E4M), hypromellose (K15M), stearic acid, mix.Tabletting obtains niacin sustained release part label.
Fluvastatin immediate release section: the fluvastatin, hypromellose (E5), Polyethylene Glycol (1450), butylhydroxy anisole, ethanol (95%), the purified water that take recipe quantity.Preparation coating solution, obtains finely dispersed suspension.Plain sheet is placed in high-efficiency coating machine, plain sheet is carried out to coating, target weightening finish 56.2mg, after reaching target weightening finish and get final product.
Color film-coat part: the film-coat material, the purified water that take recipe quantity.Preparation film-coat material coating solution.The tablet that has wrapped fluvastatin layer is placed in to coating in high-efficiency coating machine, and target weightening finish 23mg, reaches the rear cooling slice of target weightening finish, obtains.
Slice, thin piece prepared by said method is nicotinic acid (500mg) fluvastatin (16mg) slow releasing tablet, is used for the treatment of medium and high blood fat
Embodiment 17: the preparation of nicotinic acid (750mg) fluvastatin (20mg) slow releasing tablet
Niacin sustained release label:
Fluvastatin release layer:
Film-coat layer:
Niacin slow-release tablet core segment: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (K15M), stearic acid, mix.Tabletting obtains niacin sustained release part label.
Fluvastatin immediate release section: the fluvastatin, hypromellose (E5), Polyethylene Glycol (1450), butylhydroxy anisole, ethanol (95%), the purified water that take recipe quantity.Preparation coating solution, obtains finely dispersed suspension.Plain sheet is placed in high-efficiency coating machine, plain sheet is carried out to coating, target weightening finish 70.5mg, after reaching target weightening finish and get final product.
Color film-coat part: the film-coat material, the purified water that take recipe quantity.Preparation film-coat material coating solution.The tablet that has wrapped fluvastatin layer is placed in to coating in high-efficiency coating machine, and target weightening finish 23mg, reaches the rear cooling slice of target weightening finish, obtains.
Slice, thin piece prepared by said method is nicotinic acid (750mg) fluvastatin (20mg) slow releasing tablet, is used for the treatment of severe hyperlipidemia.
Embodiment 18: the preparation of nicotinic acid (600mg) atorvastatin (8mg) slow releasing capsule
Niacin sustained release part A:
Atorvastatin immediate release section B:
The preparation of niacin sustained release micropill A: the nicotinic acid, polyvinylpyrrolidone k90, microcrystalline Cellulose, ethyl cellulose, the stearic acid that weigh recipe quantity; first nicotinic acid is crossed to 60 mesh sieves; then nicotinic acid is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain niacin sustained release micropill.
The preparation of atorvastatin fast release micropill B: the atorvastatin, starch, microcrystalline Cellulose, dextrin, the lactose that weigh recipe quantity; atorvastatin is joined together with adjuvant and in wet granulator, add appropriate purified water soft material processed; with extruding spheronizator, make micropill; dry; screening 18～30 micropills, obtain atorvastatin fast release micropill.
Use double threaded screw filling machine by the above-mentioned A preparing, the filling of B material, obtain.
Capsule prepared by said method is nicotinic acid (600mg) atorvastatin (8mg) slow releasing capsule, is used for the treatment of slight hyperlipidemia.
Embodiment 19: the preparation of nicotinic acid (1200mg) atorvastatin (14mg) double-layer tablet
Niacin sustained release part A:
Atorvastatin part B:
Niacin slow-release tablet part A: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (K15M), stearic acid, mix, standby.
Atorvastatin immediate release section B: the atorvastatin, microcrystalline Cellulose, pregelatinized Starch, lactose, the stearic acid that take recipe quantity.Using purified water as wetting agent, manual granulation, the wet granulate of 16 orders for soft material, baking oven 50～55 is dried 2～5 hours, with the dry granulate of 14 mesh sieve, adds stearic acid to mix, standby.
By bi-layer tablet press, by material A and B tabletting, obtain.
Slice, thin piece prepared by said method is nicotinic acid (1200mg) atorvastatin (14mg) double-layer sustained release tablets, is used for the treatment of medium and high blood fat.
Embodiment 20: the preparation of nicotinic acid (750mg) atorvastatin (24mg) slow releasing tablet
Niacin sustained release label:
Atorvastatin release layer:
Film-coat layer:
Niacin slow-release tablet core segment: take recipe quantity nicotinic acid, polyvinylpyrrolidone k90, in the hypromellose (K15M) that adds.First nicotinic acid is crossed to 60 mesh sieves, then nicotinic acid is joined in wet granulator and granulated together with Nei Jia adjuvant.To the soft material the making granulate that wets, with fluid bed drying, then carry out granulate, the calculated yield of weighing.Weigh additional hypromellose (K15M), stearic acid, mix.Tabletting obtains niacin sustained release part label.
Atorvastatin immediate release section: the atorvastatin, hypromellose (E5), Polyethylene Glycol (1450), butylhydroxy anisole, ethanol (95%), the purified water that take recipe quantity.Preparation coating solution, obtains finely dispersed suspension.Plain sheet is placed in high-efficiency coating machine, plain sheet is carried out to coating, target weightening finish 119.3mg, after reaching target weightening finish and get final product.
Color film-coat part: the film-coat material, the purified water that take recipe quantity.Preparation film-coat material coating solution.The tablet that has wrapped atorvastatin layer is placed in to coating in high-efficiency coating machine, and target weightening finish 23mg, reaches the rear cooling slice of target weightening finish, obtains.
Slice, thin piece prepared by said method is nicotinic acid (750mg) atorvastatin (24mg) slow releasing tablet, is used for the treatment of severe hyperlipidemia.
Clinical trial and the result of embodiment 21 compound preparations
Tested crowd: Asia normal adults.
Test recipe, in Table 1:
The raw material components of table 1 nicotinic acid Statins slow releasing preparation, take lovastatin, simvastatin, atorvastatin is example
| Test recipe number | Nicotinic acid consumption | Statins title | Statins consumption |
| 1-1 | 300mg | Lovastatin | 40mg |
| 1-2 | 300mg | Lovastatin | 20mg |
| 1-3 | 300mg | Lovastatin | 10mg |
| 1-4 | 300mg | Lovastatin | 25mg |
| 1-5 | 300mg | Lovastatin | 15mg |
| 1-6 | 300mg | Lovastatin | 8mg |
| 2-1 | 500mg | Simvastatin | 40mg |
| 2-2 | 500mg | Simvastatin | 20mg |
| 2-3 | 500mg | Simvastatin | 10mg |
| 2-4 | 500mg | Simvastatin | 24mg |
| 2-5 | 500mg | Simvastatin | 13mg |
| 2-6 | 500mg | Simvastatin | 7mg |
| 3-1 | 750mg | Atorvastatin | 40mg |
| 3-2 | 750mg | Atorvastatin | 20mg |
| 3-3 | 750mg | Atorvastatin | 10mg |
| 3-4 | 750mg | Atorvastatin | 16mg |
| 3-5 | 750mg | Atorvastatin | 10mg |
| 3-6 | 750mg | Atorvastatin | 6mg |
Detect it and adjust fat curative effect, test method list of references: 1, Yan Zongyi, Wei Maoyuan, in astronomy. hemorheology. application [M] is detected on basis. Heilungkiang: science tech publishing house, 1993:233.2, Pan Ling, Luo Shuiguang. coronary heart disease hemorheology and lipids detection interpretation of result [J]. Chinese Clinical Medical Journals, 2005,6 (3): 5-6.Adjust fat efficacy result in Table 2:
The curative effect comparison of each compound preparation of table 2
By the compound preparation that contains high concentration statins and the compound preparation of the statins medicine that contains low concentration being adjusted in table 1 and table 2 the comparative study result of fat curative effect aspect, can find out: for asian population, the compound preparation of the statins medicine that contains low concentration has same effect with the compound preparation that contains high concentration statins, therefore under same curative effect, can reduce the consumption of statins in compound preparation, thereby reduce the generation of toxic and side effects.
Claims (7)
1. a new nicotinic acid compound slow release preparation that is used for the treatment of hyperlipidemia, comprises immediate release section and slow-released part, and said immediate release section comprises statins and pharmaceutic adjuvant; Said slow-released part comprises nicotinic acid, polyvinylpyrrolidone k90 and pharmaceutic adjuvant, it is characterized in that, in said preparation, the weight ratio of statins and nicotinic acid is 1:(10～100), in said slow-released part, the weight ratio of polyvinylpyrrolidone k90 and nicotinic acid is 1:(20～80), the dosage form of said compound preparation is sustained release coating sheet.
2. the new nicotinic acid compound slow release preparation that is used for the treatment of hyperlipidemia according to claim 1, it is characterized in that, in said preparation, the weight ratio of statins and nicotinic acid is 1:(12.5～50), in said slow-released part, the weight ratio of polyvinylpyrrolidone k90 and nicotinic acid is 1:(30～40).
3. the new nicotinic acid compound slow release preparation that is used for the treatment of hyperlipidemia according to claim 1, it is characterized in that, said statins is selected from lovastatin, simvastatin, pravastatin, mevastatin, fluvastatin, atorvastatin, cerivastatin or rosuvastatin.
4. the new nicotinic acid compound slow release preparation that is used for the treatment of hyperlipidemia according to claim 1, it is characterized in that, the pharmaceutic adjuvant of said immediate release section is solvent, antioxidant, plasticizer and excipient, said cosolvent is ethanol, one or several in propylene glycol, said antioxidant is vitamin E, butylhydroxy anisole, vitamin C, dibenzylatiooluene, propyl gallate, one or several in tert-butyl hydroquinone, said plasticizer is Polyethylene Glycol, glycerol, diethyl phthalate, one or several of dimethyl phthalate and dibutyl phthalate, said excipient is hypromellose, sucrose, mannitol, sorbitol, alginate, sodium carboxymethyl cellulose, carbomer, ethyl cellulose, polyoxyethylene, acrylic resin, polyethylene, Glyceryl Behenate, stearic acid, hard alcohol, babassu ester, one or several in starch.
5. the new nicotinic acid compound slow release preparation that is used for the treatment of hyperlipidemia according to claim 1, it is characterized in that, the pharmaceutic adjuvant of said slow-released part is slow-release material and lubricant, said slow-release material is hydroxypropyl methylcellulose, alginate, sodium carboxymethyl cellulose, carbomer, ethyl cellulose, polyoxyethylene, acrylic resin, polyethylene, Glyceryl Behenate, stearic acid, hard alcohol, babassu ester, one or several in starch, said lubricant is stearic acid, stearate, differential silica gel, Pulvis Talci, one or several in calcium phosphate.
6. the new nicotinic acid compound slow release preparation that is used for the treatment of hyperlipidemia according to claim 1, is characterized in that, composition and the content of said sustained release coating sheet are as follows:
7. the preparation method of sustained release coating sheet as claimed in claim 6, is characterized in that, comprises the steps:
1) prepare slow-released part: in prescription ratio by principal agent nicotinic acid, polyvinylpyrrolidone k90 and part slow-release material, mix lubricant, then carry out wet granulation, wet granulate, dry, dry granulate, then add additional residue slow-release material to mix, finally according to target patch, heavily carry out tabletting.
2) prepare immediate release section: first use purified water swelling dispersant, then according to formulation and technology, add successively principal agent and pharmaceutic adjuvant, make suspension, with this suspension, above-mentioned niacin sustained release is partly carried out to coating, at slow release label, form one deck release layer outward and form the sustained release coating sheet that contains nicotinic acid and two kinds of principal agents of Statins.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310606072.6A CN103599081A (en) | 2012-11-23 | 2012-11-23 | Novel niacin compound slow-release preparation for treating hyperlipoidemia |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310606072.6A CN103599081A (en) | 2012-11-23 | 2012-11-23 | Novel niacin compound slow-release preparation for treating hyperlipoidemia |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012104806056A Division CN102921009A (en) | 2012-11-23 | 2012-11-23 | Novel niacin compound sustained release preparation for treating hyperlipidemia |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103599081A true CN103599081A (en) | 2014-02-26 |
Family
ID=50117390
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310606072.6A Pending CN103599081A (en) | 2012-11-23 | 2012-11-23 | Novel niacin compound slow-release preparation for treating hyperlipoidemia |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103599081A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107854448A (en) * | 2017-11-06 | 2018-03-30 | 广州市桐晖药业有限公司 | A kind of nicotinic acid tablet and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101390843A (en) * | 2008-11-06 | 2009-03-25 | 咸阳步长医药科技发展有限公司 | Lovastatin and niacin slow-release tablet and preparation method thereof |
| CN101785774A (en) * | 2009-10-20 | 2010-07-28 | 中国药科大学 | Compound niacin simvastatin bilayer sustained-release tablet |
-
2012
- 2012-11-23 CN CN201310606072.6A patent/CN103599081A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101390843A (en) * | 2008-11-06 | 2009-03-25 | 咸阳步长医药科技发展有限公司 | Lovastatin and niacin slow-release tablet and preparation method thereof |
| CN101785774A (en) * | 2009-10-20 | 2010-07-28 | 中国药科大学 | Compound niacin simvastatin bilayer sustained-release tablet |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107854448A (en) * | 2017-11-06 | 2018-03-30 | 广州市桐晖药业有限公司 | A kind of nicotinic acid tablet and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103800279B (en) | atorvastatin calcium composition | |
| JP4740945B2 (en) | Sustained release preparation for oral administration of HMG-CoA reductase inhibitor and method for producing the same | |
| CN103585157B (en) | A kind of double-layer tablet containing Ezetimibe and Rosuvastatin and preparation method thereof | |
| MX2007009281A (en) | A stable pharmaceutical composition comprising a fixed dose combination of fenofibrate and an hmg-coa reductase inhibitor. | |
| CN101972260B (en) | Rosuvastatin calcium oral drug composition | |
| CN103585146B (en) | Medicine composition of simvastatin | |
| CN103705484B (en) | Stable atorvastatin calcium tablet and preparation methods thereof | |
| CN102921009A (en) | Novel niacin compound sustained release preparation for treating hyperlipidemia | |
| CN107126423A (en) | Pitavastatin Calcium tablet pharmaceutical composition and its dry type or wet type preparation method | |
| CN101518518A (en) | Niacin simvastatin sustained-release preparation and preparation method thereof | |
| CN110063944B (en) | Levamlodipine besylate atorvastatin calcium tablet and preparation method thereof | |
| CN103239725A (en) | Compound preparation for treating cardiovascular and cerebrovascular diseases | |
| CN103599081A (en) | Novel niacin compound slow-release preparation for treating hyperlipoidemia | |
| CN101766594A (en) | Officinal composition for lowering blood fat | |
| CN103239449A (en) | Ezetimibe, simvastatin and nicotinic acid compound preparation and preparation method of ezetimibe, simvastatin and nicotinic acid compound preparation | |
| CN107811989B (en) | Rosuvastatin calcium pharmaceutical composition and preparation method thereof | |
| AU2005205165B2 (en) | Pharmaceutical compositions comprising higher primary aliphatic alcohols and HMG CoA reductase inhibitor and process of preparation thereof | |
| CN102600131A (en) | Medicine composition containing ezetimibe and simvastatin and preparation method of medicine composition | |
| CN101732273A (en) | Slow-release tablet of simvastatin and nicotinic acid and preparation method thereof | |
| CN103230368A (en) | Statin medicine preparation method | |
| CN103356500A (en) | Calcium rosuvastatin and fenofibric acid choline salt time-selecting osmotic pump controlled release tablet and preparation method thereof | |
| CN104644600A (en) | Coating tablet of statin medicines and preparation method | |
| KR101302306B1 (en) | complex for improving, alleviating, treating or preventing of hyperlipidemia | |
| CN111836620B (en) | Pharmaceutical composition of ezetimibe and HMG-CoA reductase inhibitor | |
| CN101961322A (en) | Medicinal composition for treating hyperlipidaemia |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20140226 |