WO2014142607A1 - 약제학적 복합제제 - Google Patents
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- WO2014142607A1 WO2014142607A1 PCT/KR2014/002178 KR2014002178W WO2014142607A1 WO 2014142607 A1 WO2014142607 A1 WO 2014142607A1 KR 2014002178 W KR2014002178 W KR 2014002178W WO 2014142607 A1 WO2014142607 A1 WO 2014142607A1
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- fimasartan
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/133—Amines having hydroxy groups, e.g. sphingosine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
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- A61P9/12—Antihypertensives
Definitions
- the present invention relates to a pharmaceutical co-formulation with improved dissolution including fimasartan and rosuvastatin.
- Hypertension is not a treatment for blood pressure itself, but it is important to keep blood pressure in a normal range to prevent cardiovascular complications such as coronary artery disease such as life-threatening stroke, heart failure, myocardial infarction, and kidney failure. It is important to control your blood pressure. Blood pressure medications are required to be taken for a long time, so care must be taken in the selection of therapeutic drugs. Therefore, rather than selecting one drug to maintain a constant blood pressure over a long period of time, it is necessary to reduce the side effects that can be caused by long-term drug use by using a combination of drugs with different mechanisms and reducing the use of a single drug by co-administration. have.
- drugs differ in their action characteristics such as transporters, metabolic enzymes, and genes that are involved in the absorption, metabolism, distribution, drug expression and excretion of individual drugs when two or more components are taken. Because of this, there is a problem such as the drug efficacy and side effects occur due to the drug combination. For example, when the drug crosses the barrier in the first stage, enters the liver in the secondary stage, metabolizes and activates in the hepatocytes in the tertiary stage, and hepatic cells through the biliary tract in the fourth stage. Drugs can cause problems with absorption, metabolism, and excretion at various stages, such as when exiting. In particular, the disintegration and dissolution pattern of the active ingredient according to pH causes a lot of problems in the efficacy of the drug in the combination treatment.
- Angiotensin-2-receptor blocker is an agent that blocks the binding of the angiotensin-2, one of the sources of vasoconstriction, to the AT1 receptor in the angiotensin receptor, and thus lowers the blood pressure in both myocardial systolic and diastolic.
- the group of compounds has over 10 species, including pharmaceutically available salts.
- they are used alone or in combination with angiotensin converting enzyme inhibitors that have anti-hypertensive effects in patients with mild to moderate symptoms associated with hypertension [Angiotension II Receptor Antagonist: An Overview, Am. J. Health-Syst. Pharm. 57 (13): 1231-1238, 2000].
- Fimasaltan one of the Angiotensin II Receptor Blockers (ARBs), is 2-n-butyl-5-dimethylaminothiocarbonylmethyl-6-methyl-3-[[2- (1H-tetrazol -5-yl) biphenyl-4-yl] methyl] pyrimidin-4 (3H) -one ⁇ 2-n-butyl-5-dimethylamino thiocarbonyl methyl-6-methyl-3-[[2- (1H-tetrazol -5-yl) biphenyl-4-yl] methyl] pyrimidin-4 (3H) -one ⁇ , having the structure of Formula 1 below, and is currently marketed under the KANARB ® license. 10-1058284).
- HMG-CoA reductase inhibitors are used in hyperlipidemia, hypercholesterolemia and atherosclerosis because they prevent HMG-CoA from reducing to mevalonate and lower blood lipid concentrations and cholesterol.
- HMG-CoA 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, HMG-CoA) reductase inhibitors, rosuvastatin
- HMG-CoA HMG-CoA reductase inhibitors
- rosuvastatin is (E) -7- [4- (4-fluorophenyl) -6-iso Propyl-2- [methyl (methylsulfonyl) amino] pyrimidin-5-yl]-(3R, 5S) -3,5-dihydroxyhept-6-enoic acid, having the structure of Formula 2 It regulates the cholesterol synthesis pathway, and is currently marketed under the CRESTOR ® name (Registration No. 10-0105432).
- Fimasartan and rosuvastatin combinations having different mechanisms of action may be usefully used in the treatment of hypertension, but these combinations have a problem of affecting the disintegration and dissolution of each active ingredient due to mutual interference effects on each. That is, fimasartan shows a very good dissolution pattern at relatively high pH such as purified water and pH 6.8, but has low solubility at low pH (for example, pH 1.0 to pH 4.0), and is currently available KANARB ® also exhibits the same dissolution pattern.
- the present invention relates to a pharmaceutical co-formulation of pimasartan and rosuvastatin containing meglumine, which provides an excellent co-formulation that improves disintegration and dissolution rate, prevents drug interaction, and facilitates administration in a single dose. It is for that purpose.
- the invention provides fimasartan, a pharmaceutically acceptable salt thereof, an isomer thereof, or a hydrate or solvate thereof; Rosuvastatin, pharmaceutically acceptable salts thereof, isomers thereof, or hydrates or solvates thereof; And meglumine.
- the pharmaceutical combination preparations of the present invention are greatly improved disintegration and dissolution rate and prevent drug interactions and facilitate the administration in a single dose, and have very good bioavailability.
- the pharmaceutical co-formulations of the present invention may be used as pharmacologically active ingredients such as fimasartan, a pharmaceutically acceptable salt thereof, an isomer thereof, or a hydrate or solvate thereof; Rosuvastatin, pharmaceutically acceptable salts thereof, isomers thereof, or hydrates or solvates thereof.
- isomers include optical isomers, diastereomers and mixtures thereof.
- Fimasaltan a pharmaceutically acceptable salt thereof, an isomer thereof, or a hydrate or solvate thereof is from 5.0 mg to 240.0 mg, preferably from 5.0 mg to 120.0 mg, more preferably from 30.0 mg to 120.0 mg in unit dosage form. Rosuvastatin, pharmaceutically acceptable salts thereof, isomers thereof, or hydrates or solvates thereof may be included from 5.0 mg to 20.0 mg in unit dosage form.
- fimasartan potassium a pharmaceutically acceptable salt of fimasartan, more preferably fimasartan potassium trihydrate, and rosuvastatin calcium, a pharmaceutically acceptable salt of rosuvastatin.
- Meglumine of the present invention is an amino sugar derived from sorbitol has a structure of formula (3).
- Meglumine is an excipient of the present invention for suppressing the disintegration and reduction of dissolution rate due to the interference of pimasartan and rosuvastatin, and has the effect of suppressing interference of the active ingredient, and disintegration and dissolution rate increase.
- Such meglumine may be included in an amount of 1.0 to 30.0% by weight based on the total weight of the co-formulation, preferably 2.0 to 15.0% by weight, more preferably 2.0 to 10.0% by weight.
- the pharmaceutical preparation of the present invention is for the prevention or treatment of cardiovascular diseases, cardiovascular diseases are hypertension or complications of those with metabolic syndrome, such as diabetes, obesity, hyperlipidemia, coronary artery disease, etc.
- the co-formulation of the present invention may further include a pharmaceutically acceptable additive, if necessary, for example, pharmaceutically acceptable stabilizers, binders, disintegrants, glidants within the scope of not impairing the effects of the present invention. It may be formulated to include additives such as diluents, coatings, pH adjusting agents, dissolution aids, surfactants.
- the stabilizer may be dibasic or tribasic calcium phosphate, tribasic magnesium phosphate, tribasic aluminum phosphate and the like.
- the stabilizer may be included in an amount of 1.0 to 50.0% by weight, preferably 2.0 to 30.0% by weight, and more preferably 2.0 to 10.0% by weight, based on the total weight of the co-formulation.
- the binder may be hydroxypropyl cellulose, hydroxypropyl methyl cellulose, starch, gelatin, glucose syrup, polyvinylpyrrolidone, polyethylene glycol 6000, methyl cellulose, ethyl cellulose, carboxymethyl cellulose or a mixture thereof. Preferably it may include at least one material selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methyl cellulose and polyvinylpyrrolidone. In addition, the binder is preferably included in an amount of 0.2 to 5.0% by weight, preferably 0.5 to 4.0% by weight relative to the total weight of the co-formulation.
- the disintegrant may be a starch or modified starch such as sodium starch glycolate, corn starch, potato starch or starch gelatinized starch; Clay such as bentonite, montmorillonite, or veegum; Celluloses such as microcrystalline cellulose, hydroxypropyl cellulose or carboxymethyl cellulose; Algins such as sodium alginate or alginic acid; Cross-linked celluloses such as croscarmellose sodium; Gums such as guar gum and xanthan gum; Crosslinked polymers such as crospovidone; Effervescent agents such as sodium bicarbonate, citric acid, or mixtures thereof can be used. Preferably a mixture of croscarmellose sodium and crospovidone can be used.
- the disintegrant is preferably included in an amount of 2.0 to 30.0% by weight, preferably 5.0 to 20.0% by weight, based on the total weight of the co-formulation.
- the lubricant may be magnesium stearate, calcium stearate, stearic acid, sodium fumarate, polyethylene glycol or silicon dioxide.
- the lubricant is preferably included in an amount of 0.2 to 5.0% by weight, preferably 0.5 to 3.0% by weight relative to the total weight of the co-formulation.
- the diluent may be cellulose, lactose, starch, microcrystalline cellulose, lactose monohydrate, glucose, mannitol, alginate, alkaline earth metal salts, clay, polyethylene glycol, dicalcium phosphate, or a mixture thereof.
- the diluent may be used in an amount of about 15.0 to about 90.0 wt%, preferably about 30.0 to about 70.0 wt%, more preferably 35.0 to 65.0 wt%, based on the total weight of the co-formulation.
- the coating agent may contain hydroxypropyl methyl cellulose, ethyl cellulose, polyvinyl acetate, polyethylene glycol, titanium dioxide, iron oxide, etc., or trade name of opadry ® (Opadry ®).
- the coating agent can be included, for example, from 0.5 to 10.0 weight percent, preferably from 1.0 to 6.0 weight percent, more preferably from 2.0 to 5.0 weight percent of the tablet composition. Coating of tablets is particularly desirable because it reduces the rate of formation of the photolysis product of the formulation and improves the storage stability of the product by moisture and heat.
- the pH adjusting agent may be used a basic agent such as precipitated calcium carbonate, ammonia water and the like.
- the dissolution aid can be used polyoxyethylene sorbitan fatty acid esters such as sodium lauryl sulfate, polysorbate, docusate sodium and the like.
- sodium lauryl sulfate, cremophore, poloxamer, docusate, pharmaceutically acceptable docusate salt, and the like can be used.
- the formulation of the present invention may be formulated using various pharmaceutically acceptable additives selected from colorants and fragrances, and the additives usable in the present invention are not limited to the above additives.
- the additives may be formulated to contain a range of usual doses by selection.
- the pharmaceutical combination preparation of the present invention may be formulated as an oral preparation such as tablets, powders, granules, or capsules such as uncoated tablets, coated tablets, multilayer tablets, or nucleated tablets.
- the pharmaceutical formulation of the present invention may be in an uncoated tablet prepared by mixing the fimasartan granules and the rosuvastatin mixed portion followed by tableting.
- Fimasartan granules may be prepared by dry granulation or wet granulation, preferably by wet granulation.
- the pharmaceutical formulation of the present invention may be in the form of a coated tablet including a coating layer additionally outside the granules of fimasartan and rosuvastatin.
- the method of forming the coating layer can be appropriately selected by the choice of those skilled in the art from the method of forming a film-like coating layer on the surface of the tablet layer, it is possible to apply a method such as fluidized bed coating method, fan coating method, dry coating method. .
- the pharmaceutical formulation of the present invention may be in the form of a nucleated tablet consisting of an inner layer consisting of Fimasartan granules and an outer layer consisting of a rosuvastatin mixing unit surrounding the outer surface of the inner core.
- the human dosage of the formulation of the present invention is appropriately selected depending on the absorption rate, inactivation rate and excretion rate of the active ingredient in the body, the age, sex and condition of the patient, but in general, the adult is 30.0-120.0 mg per day, Rosuvastatin can be administered 5.0 to 20.0 mg daily to prevent and treat cardiovascular diseases.
- the present invention also provides a pharmaceutical composition comprising the co-formulation.
- the pharmaceutical composition of the present invention has a remarkable effect on the prevention and treatment of cardiovascular diseases.
- the present invention also relates to fimasartan, pharmaceutically acceptable salts thereof, isomers thereof, or hydrates or solvates thereof; Rosuvastatin, pharmaceutically acceptable salts thereof, isomers thereof, or hydrates or solvates thereof; And it provides a method of treating cardiovascular diseases comprising the administration of a therapeutically effective amount of a combination formulation comprising meglumine.
- the method of treating cardiovascular disease using the co-formulation of the present invention includes administration of a therapeutically effective amount of the co-formulation of the present invention.
- therapeutically effective amount refers to the amount of the combination formulation of the invention effective for the prevention or treatment of cardiovascular diseases.
- Cardiovascular diseases include both hypertension and complications of those with metabolic syndrome, including hypertension or diabetes mellitus, obesity, hyperlipidemia, and coronary artery disease, including chronic stable angina pectoris, vascular spasms, stroke, myocardial infarction, Transient ischemic attacks, congestive heart failure, insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, diabetic nephropathy, dyslipidemia, cognitive decline and dementia.
- the co-formulation of the present invention may additionally be used in a treatment method in combination with one or more therapeutic agents.
- the invention also provides fimasartan, a pharmaceutically acceptable salt thereof, an isomer thereof, or a hydrate or solvate thereof for the manufacture of a medicament for the treatment of cardiovascular diseases; Rosuvastatin, pharmaceutically acceptable salts thereof, isomers thereof, or hydrates or solvates thereof; And the use of a co-formulation comprising meglumine.
- the co-formulation of the present invention for the preparation of a medicament may be mixed with the above-mentioned acceptable additives and the like, for example, pharmaceutically acceptable stabilizers, binders, disintegrants, within the scope that does not impair the effects of the present invention, It may be prepared by including additives such as lubricants, diluents, coating agents, pH adjusting agents, dissolution aids, surfactants.
- the present invention also relates to fimasartan, pharmaceutically acceptable salts thereof, isomers thereof, or hydrates or solvates thereof; Rosuvastatin, pharmaceutically acceptable salts thereof, isomers thereof, or hydrates or solvates thereof; And it provides a use for the treatment of cardiovascular diseases using a combination formulation comprising meglumine.
- the pharmaceutical combination preparation of the present invention solves the problem of delayed disintegration and dissolution due to the interference effect of pimasartan and rosuvastatin at low pH using meglumine, thereby preventing or treating cardiovascular diseases. Zero shows excellent effect.
- 1 is a diagram showing the results of analyzing the dissolution pattern of a pharmaceutical combination formulation containing meglumine and fimasartan and rosuvastatin as active ingredients.
- the permasartan granules of Example 1 were prepared so as to have the weight as shown in Table 1 per unit formulation.
- fimasartan potassium trihydrate was added to some microcrystalline cellulose and mixed for about 2 minutes.
- the apples were sieved twice in a 30 mesh sieve.
- the apple mixture, the remaining microcrystalline cellulose, and some croscarmellose sodium were placed in a high speed mixer and mixed for about 3 minutes.
- hydroxypropyl cellulose was dissolved in 65 ml of purified water to prepare a binding solution.
- the prepared binder solution was put into a high speed stirrer, wet granulated with the mixed solution, and then sieved to a 20 mesh sieve and dried.
- the remaining croscarmellose sodium was added to the dried fimasartan granules and mixed in a double cone mixer for about 5 minutes, and then magnesium stearate was added thereto and further mixed for about 5 minutes to prepare fimasartan granules.
- the rosuvastatin mixing part of Example 1 was prepared to have a weight as shown in Table 1 per unit formulation.
- rosuvastatin calcium was mixed with meglumine and some lactose for about 2 minutes.
- the apples were sieved twice in a 30 mesh sieve.
- the apple mixture and the remaining lactose, microcrystalline cellulose and crospovidone were placed in a double cone mixer and mixed for about 3 minutes.
- Magnesium stearate was added as a lubricant and mixed for about 5 minutes.
- the weight of one tablet of the Pimasaltan granules and the rosuvastatin mixed portion may be 249 to 251 mg (theoretical weight 250.0 mg) and the hardness is 9 to 10 kp.
- the tablets were compressed by compression to prepare a composite tablet.
- the degree of wear was measured using a wear rate measuring system (25 rpm, 100 free falls). The degree of wear was 0.1% or less, and the strength of the tablet was good.
- Tablets were prepared according to the contents of Table 1 in the same manner as in Example 1 and changing the content of meglumine to 5.0 mg.
- Tablets were prepared according to the contents of Table 1 in the same manner as in Example 1 and changing the content of meglumine to 20.0 mg.
- Fimasartan granules of Comparative Example 1 were prepared so as to have the weight as shown in Table 2 per unit formulation.
- fimasartan potassium trihydrate was added to some microcrystalline cellulose and mixed for about 2 minutes.
- the apples were sieved twice in a 30 mesh sieve.
- the apple mixture, the remaining microcrystalline cellulose, and some croscarmellose sodium were placed in a high speed mixer and mixed for about 3 minutes.
- hydroxypropyl cellulose was dissolved in purified water to prepare a binding solution.
- the prepared binder solution was put into a high speed stirrer, wet granulated with the mixed solution, and then sieved to 20 mesh, and dried.
- the remaining croscarmellose sodium was added to the dried fimasartan granules and mixed in a double cone mixer for about 5 minutes, and then magnesium stearate was added thereto and further mixed for about 5 minutes to prepare fimasartan granules.
- Tablets of the Comparative Example were prepared so as to have the weight as shown in Table 2 per unit formulation.
- the apples were sieved twice in a 30 mesh sieve.
- the apple mixture and the remaining lactose, microcrystalline cellulose and crospovidone (Comparative Example 1) were placed in a double cone mixer and mixed for about 3 minutes.
- Magnesium stearate was added as a lubricant and mixed for about 5 minutes.
- a tablet of about 20 kN was used so that one tablet of Pimasaltan granules and a rosuvastatin mixed tablet weighed 249-251 mg (theoretical weight 250.0 mg) and hardness was 9-10 kp.
- the tablets were compressed by positive pressure to prepare a composite tablet.
- the degree of wear was measured using a wear rate measuring system (25 rpm, 100 free falls). The wear degree was 0.1% or less, and the tablet had a good strength.
- Comparative Example 2 was prepared in the same manner as in Preparation Example 1, except that crospovidone was changed to croscarmellose sodium as a disintegrant.
- Example 1 was found to significantly improve the disintegration and dissolution due to the interference effect of fimasartan and rosuvastatin significantly less than the other formulations, the effect is the Crestor (CRESTOR ® sold as a single agent It was confirmed that the result is almost the same level as). On the other hand, the comparative example does not contain meglumine was confirmed that the disintegration and dissolution rate is very low by the interference phenomenon.
- the co-formulations according to the invention can be used to safely or effectively prevent or treat cardiovascular diseases.
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Abstract
Description
Claims (22)
- 피마살탄, 이의 약제학적으로 허용가능한 염, 이의 이성질체, 또는 이들의 수화물 또는 용매화물; 로수바스타틴, 이의 약제학적으로 허용가능한 염, 이의 이성질체, 또는 이들의 수화물 또는 용매화물; 및 메글루민을 포함하는 약제학적 복합제제.
- 제1항에 있어서, 피마살탄의 약제학적 허용 가능한 염은 피마살탄 칼륨인 약제학적 복합제제.
- 제1항에 있어서, 상기 수화물은 피마살탄 칼륨삼수화물인 약제학적 복합제제.
- 제1항에 있어서, 상기 피마살탄, 이의 약제학적으로 허용가능한 염, 이의 이성질체, 또는 이들의 수화물 또는 용매화물은 단위 제형 중 5.0 mg 내지 240.0 mg으로 포함되는 약제학적 복합제제.
- 제1항에 있어서, 로수바스타틴, 이의 약제학적으로 허용가능한 염, 이의 이성질체, 또는 이들의 수화물 또는 용매화물의 약제학적 허용 가능한 염은 로수바스타틴 칼슘인 약제학적 복합제제.
- 제1항에 있어서, 로수바스타틴 성분은 단위 제형 중 5.0 mg 내지 20.0 mg으로 포함되는 약제학적 복합제제.
- 제1항에 있어서, 상기 메글루민은 복합제제 총 중량에 대하여 1.0 내지 30 중량%의 양으로 포함되는 약제학적 복합제제.
- 제1항에 있어서, 상기 약제학적 복합제제는 심혈관계 질환 치료용인 약제학적 복합제제.
- 제8항에 있어서, 상기 심혈관계 질환은 고혈압, 당뇨병, 비만증, 고지혈증, 관상 동맥 질환, 만성 안정성 협심증, 혈관경련성 협심증, 뇌졸중, 심근경색증, 일시적 허혈발작, 울혈성 심부전증, 인슐린 내성, 손상된 글루코스 내성, 예비당뇨병, 2형 진성 당뇨병, 당뇨성 신증, 이상지질혈증, 인지기능저하, 치매, 및 이들의 조합으로부터 선택되는 질환인 약제학적 복합제제.
- 제1항 내지 제9항 중 어느 한 항에 있어서, 안정화제, 결합제, 붕해제 또는 활택제 중 선택되는 어느 하나 이상을 더 포함하는 약제학적 복합제제.
- 제10항에 있어서, 상기 안정화제는 복합제제 총 중량에 대하여 1.0 내지 50.0 중량%의 양으로 포함되는 약제학적 복합제제.
- 제10항에 있어서, 상기 결합제는 복합제제 총 중량에 대하여 0.2 내지 5.0 중량%의 양으로 포함되는 약제학적 복합제제.
- 제10항에 있어서, 상기 붕해제는 복합제제 총 중량에 대하여 2.0 내지 30.0 중량%의 양으로 포함되는 약제학적 복합제제.
- 제10항에 있어서, 상기 활택제는 복합제제 총 중량에 대하여 0.2 내지 5.0 중량%의 양으로 포함되는 약제학적 복합제제.
- 제10항에 있어서, 상기 희석제는 복합제제 총 중량에 대하여 15.0 내지 90.0 중량%의 양으로 포함되는 약제학적 복합제제.
- 제1항 내지 제9항 중 어느 한 항에 있어서, 복합제제는 정제 형태인 약제학적 복합제제.
- 제16항에 있어서, 복합제제는 외부에 코팅층을 추가로 포함하는 코팅정 형태인 약제학적 복합제제.
- 제1항 내지 제17항 중 어느 한 항에 따른 복합제제를 포함하는 약제학적 조성물.
- 제1항 내지 제17항 중 어느 한 항에 따른 복합제제의 치료학적으로 유효한 양의 투여를 포함하는 심혈관계 질환의 치료 방법
- 제19항에 있어서, 상기 심혈관계 질환은 고혈압, 당뇨병, 비만증, 고지혈증, 관상 동맥 질환, 만성 안정성 협심증, 혈관경련성 협심증, 뇌졸중, 심근경색증, 일시적 허혈발작, 울혈성 심부전증, 인슐린 내성, 손상된 글루코스 내성, 예비당뇨병, 2형 진성 당뇨병, 당뇨성 신증, 이상지질혈증, 인지기능저하, 치매, 및 이들의 조합으로부터 선택되는 질환인 심혈관계 질환의 치료 방법.
- 심혈관계 질환 치료용 약제의 제조를 위한 제1항 내지 제17 항 중 어느 한 항에 따른 복합제제의 용도.
- 심혈관계 질환의 치료를 위한 제1항 내지 제17 항 중 어느 한 항에 따른 복합제제의 용도.
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BR112015022000-2A BR112015022000B1 (pt) | 2013-03-14 | 2014-03-14 | Preparação de combinação farmacêutica, composição farmacêutica e uso da preparação de combinação |
CA2905686A CA2905686C (en) | 2013-03-14 | 2014-03-14 | Pharmaceutical combination drug |
CN201480015539.2A CN105120845A (zh) | 2013-03-14 | 2014-03-14 | 药物组合药物 |
AU2014230182A AU2014230182B2 (en) | 2013-03-14 | 2014-03-14 | Pharmaceutical combination drug |
ES14762250T ES2747098T3 (es) | 2013-03-14 | 2014-03-14 | Fármaco de combinación farmacéutica |
EP14762250.0A EP2974719B1 (en) | 2013-03-14 | 2014-03-14 | Pharmaceutical combination drug |
RU2015142255A RU2639818C2 (ru) | 2013-03-14 | 2014-03-14 | Фармацевтическое комбинированное лекарственное средство |
US14/774,927 US9592233B2 (en) | 2013-03-14 | 2014-03-14 | Pharmaceutical combination drug |
JP2015562935A JP6068765B2 (ja) | 2013-03-14 | 2014-03-14 | 薬学的複合製剤 |
SG11201507305SA SG11201507305SA (en) | 2013-03-14 | 2014-03-14 | Pharmaceutical combination drug |
MX2015011988A MX368148B (es) | 2013-03-14 | 2014-03-14 | Farmaco de combinacion farmaceutica. |
SA515361123A SA515361123B1 (ar) | 2013-03-14 | 2015-09-14 | مستحضر توليفة صيدلانية تشتمل على فيماستاران ورسيوفاستاتين لعلاج مرض القلب الوعائي |
PH12015502108A PH12015502108B1 (en) | 2013-03-14 | 2015-09-14 | Pharmaceutical combination drug |
ZA2015/07576A ZA201507576B (en) | 2013-03-14 | 2015-10-12 | Pharmaceutical combination drug |
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US (1) | US9592233B2 (ko) |
EP (1) | EP2974719B1 (ko) |
JP (1) | JP6068765B2 (ko) |
KR (1) | KR101502031B1 (ko) |
CN (2) | CN110123771A (ko) |
AU (1) | AU2014230182B2 (ko) |
CA (1) | CA2905686C (ko) |
ES (1) | ES2747098T3 (ko) |
MX (1) | MX368148B (ko) |
MY (1) | MY174729A (ko) |
PH (1) | PH12015502108B1 (ko) |
RU (1) | RU2639818C2 (ko) |
SA (1) | SA515361123B1 (ko) |
SG (1) | SG11201507305SA (ko) |
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WO2017091041A1 (ko) * | 2015-11-26 | 2017-06-01 | 보령제약 주식회사 | 피마살탄의 신규 염 |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
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KR101545268B1 (ko) | 2015-02-05 | 2015-08-20 | 보령제약 주식회사 | 정제 및 이의 제조방법 |
CN105784867B (zh) * | 2016-03-28 | 2019-01-01 | 北京睿创康泰医药研究院有限公司 | 用于分析非马沙坦有关物质的hplc方法及这些杂质作参比标准的用途 |
KR102078691B1 (ko) * | 2017-11-30 | 2020-02-19 | 보령제약 주식회사 | 피마살탄을 포함하는 고체 분산체 |
KR102201396B1 (ko) * | 2017-11-30 | 2021-01-11 | 보령제약 주식회사 | 피마살탄을 포함하는 약학적 조성물 |
KR101997652B1 (ko) * | 2018-01-22 | 2019-07-08 | 보령제약 주식회사 | 약학적 제제 |
KR101992400B1 (ko) * | 2018-04-30 | 2019-06-24 | 보령제약 주식회사 | 약학적 제제 |
KR102022694B1 (ko) * | 2019-02-20 | 2019-09-18 | 주식회사 네비팜 | 약학 조성물 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101058284B1 (ko) | 2010-01-22 | 2011-08-22 | 보령제약 주식회사 | 2-(2-n-부틸-4-히드록시-6-메틸-피리미딘-5-일)-N,N-디메틸아세트아미드의 신규한 제조방법 |
KR20110097168A (ko) * | 2010-02-24 | 2011-08-31 | 근화제약주식회사 | 고지혈증 치료용 약제학적 복합제제 |
KR20110126020A (ko) * | 2010-05-14 | 2011-11-22 | 한미홀딩스 주식회사 | HMG-CoA 환원효소 억제제 및 이베살탄을 포함하는 이층정 약제학적 복합제제 |
CN102485228A (zh) * | 2010-12-02 | 2012-06-06 | 鲁南制药集团股份有限公司 | 一种药物组合物及其用途 |
KR101168136B1 (ko) * | 2011-08-08 | 2012-07-24 | 보령제약 주식회사 | 혈압 강하용 약제학적 조성물 |
KR20120117986A (ko) * | 2009-11-20 | 2012-10-25 | 지피 팜, 에스. 에이. | 활성 약학적 성분 및 고도불포화지방산 에스테르로 이루어진 심혈관 질환 치료용 캡슐 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2648897B2 (ja) | 1991-07-01 | 1997-09-03 | 塩野義製薬株式会社 | ピリミジン誘導体 |
CA2657076A1 (en) * | 2003-08-28 | 2005-03-17 | Teva Pharmaceutical Industries Ltd. | Process for the preparation of rosuvastatin calcium |
CN101461799B (zh) * | 2008-12-31 | 2011-06-29 | 苏州中化药品工业有限公司 | 一种稳定的普伐他汀药物组合物及其制备方法 |
WO2011090323A2 (en) | 2010-01-21 | 2011-07-28 | Boryung Pharmaceutical Co., Ltd | Novel preparation method of 2-(2-n-butyl-4-hydroxy-6-methyl-pyrimidin-5-yl)-n,n-dimethylacetamide |
CN101972260B (zh) * | 2010-11-24 | 2012-05-02 | 天津市汉康医药生物技术有限公司 | 一种瑞舒伐他汀钙口服药物组合物 |
MY160432A (en) * | 2011-04-12 | 2017-03-15 | Boryung Pharm | Antihypertensive pharmaceutical composition |
-
2014
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- 2014-03-14 RU RU2015142255A patent/RU2639818C2/ru active
- 2014-03-14 CN CN201910375600.9A patent/CN110123771A/zh active Pending
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- 2014-03-14 WO PCT/KR2014/002178 patent/WO2014142607A1/ko active Application Filing
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- 2014-03-14 CN CN201480015539.2A patent/CN105120845A/zh active Pending
- 2014-03-14 KR KR1020140030190A patent/KR101502031B1/ko active IP Right Grant
-
2015
- 2015-09-14 PH PH12015502108A patent/PH12015502108B1/en unknown
- 2015-09-14 SA SA515361123A patent/SA515361123B1/ar unknown
- 2015-10-12 ZA ZA2015/07576A patent/ZA201507576B/en unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20120117986A (ko) * | 2009-11-20 | 2012-10-25 | 지피 팜, 에스. 에이. | 활성 약학적 성분 및 고도불포화지방산 에스테르로 이루어진 심혈관 질환 치료용 캡슐 |
KR101058284B1 (ko) | 2010-01-22 | 2011-08-22 | 보령제약 주식회사 | 2-(2-n-부틸-4-히드록시-6-메틸-피리미딘-5-일)-N,N-디메틸아세트아미드의 신규한 제조방법 |
KR20110097168A (ko) * | 2010-02-24 | 2011-08-31 | 근화제약주식회사 | 고지혈증 치료용 약제학적 복합제제 |
KR20110126020A (ko) * | 2010-05-14 | 2011-11-22 | 한미홀딩스 주식회사 | HMG-CoA 환원효소 억제제 및 이베살탄을 포함하는 이층정 약제학적 복합제제 |
CN102485228A (zh) * | 2010-12-02 | 2012-06-06 | 鲁南制药集团股份有限公司 | 一种药物组合物及其用途 |
KR101168136B1 (ko) * | 2011-08-08 | 2012-07-24 | 보령제약 주식회사 | 혈압 강하용 약제학적 조성물 |
Non-Patent Citations (1)
Title |
---|
"Angiotensin n Receptor Antagonist: An Overview", AM. J. HEALTH-SYST. PHARM., vol. 57, no. 13, 2000, pages 1231 - 1238 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017091041A1 (ko) * | 2015-11-26 | 2017-06-01 | 보령제약 주식회사 | 피마살탄의 신규 염 |
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US20160022679A1 (en) | 2016-01-28 |
US9592233B2 (en) | 2017-03-14 |
CN105120845A (zh) | 2015-12-02 |
EP2974719A4 (en) | 2016-08-03 |
KR20140113512A (ko) | 2014-09-24 |
EP2974719B1 (en) | 2019-08-28 |
BR112015022000A2 (pt) | 2017-07-18 |
AU2014230182A1 (en) | 2015-09-24 |
JP2016512234A (ja) | 2016-04-25 |
EP2974719A1 (en) | 2016-01-20 |
MX2015011988A (es) | 2015-12-01 |
CN110123771A (zh) | 2019-08-16 |
MX368148B (es) | 2019-09-20 |
SA515361123B1 (ar) | 2018-04-29 |
MY174729A (en) | 2020-05-11 |
SG11201507305SA (en) | 2015-10-29 |
ES2747098T3 (es) | 2020-03-10 |
CA2905686A1 (en) | 2014-09-18 |
CA2905686C (en) | 2017-06-27 |
RU2015142255A (ru) | 2017-04-26 |
KR101502031B1 (ko) | 2015-03-12 |
PH12015502108A1 (en) | 2016-01-18 |
BR112015022000A8 (pt) | 2023-01-17 |
RU2639818C2 (ru) | 2017-12-22 |
JP6068765B2 (ja) | 2017-01-25 |
ZA201507576B (en) | 2017-01-25 |
AU2014230182B2 (en) | 2016-12-22 |
PH12015502108B1 (en) | 2016-01-18 |
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