54 results about "MITIGLINIDE CALCIUM" patented technology

The present invention provides pharmaceutical compositions which can achieve good state of glycemic control and correct postprandial hyperglycemia and early morning fasting hyperglycemia. The present pharmaceutical composition is for administration before meal to control blood glucose, which comprises 5 to 45 mg, as a single dose, of mitiglinide or a pharmaceutically acceptable salt thereof, or a hydrate thereof (for example, mitiglinide calcium salt hydrate). And said compositions are extremely useful for prevention or treatment of, for example, type II diabetes, because the frequency of adverse drug reactions such as hypoglycemic symptoms and gastrointestinal disorders is low.

The invention discloses a preparation method of mitiglinide calcium, and the preparation method adopts (D)-phenylalanine as a raw material, and prepares mitiglinide calcium with a high yield through reactions of diazotization, hydroxy and carboxyl protection, nucleophilic substitution, hydrolysis, etc. The raw material used in the process provided by the invention has a wide source and a low price; the total yield is up to 47%; the optical purity is more than 99%; the reaction condition is mild; the reaction process is simple; disadvantages of low yield and long reaction steps of methods such as resolution, high pressure hydrogenation and the like reported in literature are avoided; and the invention provides a new selection for the preparation and production of mitiglinide calcium.

The invention relates to a preparation method for a bulk drug, i.e., Mitiglinide calcium, used for treating type II diabetes mellitus. According to the invention, improvement of the prior art is carried out: sodium methoxide is used to replace metallic sodium in the prior art, so reaction conditions are friendlier, and industrial production is easier to operate; the usage amount of benzaldehyde is reduced and argon protection is avoided, so environmental protection is benefited, and reaction yield is increased; and the usage amount of a palladium carbon (Pd/C) catalyst is reduced, which enables environmental pollution caused by excess usage of the heavy metal palladium to be reduced and cost to be lowered down.

The invention relates to a mitiglinide calcium dispersible tablet which is characterized by comprising the following materials parting parts by weight: 4-6 parts of mitiglinide calcium, 60-90 parts of starch, 12-18 parts of microcrystalline cellulose, 12.8-19.2 parts of dextrin, 0.8-1.2 parts of magnesium stearate and the balance of pure water. The invention has the advantages of rapid effect of blood sugar, short duration, capability of tabletting, good hardness and better disintegration.

The invention provides a preparation method of (S)-2-benzylsuccinic acid, and relates to a method for preparing (S)-2-benzylsuccinic acid from (R)-2-benzylsuccinic acid. After EDTA is added in an alkaline aqueous solution containing the (R)-2-benzylsuccinic acid, racemization can be implemented effectively. By the method provided by the invention, the (S)-2-benzylsuccinic acid can be prepared from a solution of 2-benzylsuccinic acid (R)-alpha-phenylethanammonium generated in a production process of mitiglinide calcium, and economic benefit is improved further.

The invention relates to the field of medicinal preparations, and relates to a rapid-dissolution mitiglinide preparation, and a preparation method and a detection method thereof. The prescription of the preparation comprises 4-6 parts of a mitiglinide raw medicine, 25-45 parts of lactose, 15-35 parts of microcrystalline cellulose, 15-35 parts of starch, 1.5-5.5 parts of hydroxypropyl methylcellulose E3 or hydroxypropyl methylcellulose E5, 3-10 parts of sodium carboxymethyl starch and 0.05-0.3 parts of magnesium stearate. The rapid-dissolution mitiglinide preparation has the advantages of easy obtaining of auxiliary materials, low cost, simple preparation method, fast in vitro digestion, realization of the 10min dissolution rate of various dissolution media reaching 90% or above, and stable quality.

The invention discloses a preparation method of mitiglinide calcium. The preparation method comprises the following steps: (I) by taking diethyl succinate and benzaldehyde as raw materials, carrying out a reaction in a sodium ethoxide solution, and then, under the action of a multiphase asymmetric catalyst Ru-SBA-16, carrying out asymmetric hydrogenation to obtain a (S)-2-benzylsuccinic acid; (II) reacting the (S)-2-benzylsuccinic acid with perhydro-isoindole so as to generate mitiglinide; and (III) complexing the mitiglinide and calcium chloride so as to obtain a target compound mitiglinide calcium. According to the method, the reaction steps can be reduced, the reaction time can be shortened, and the chiral purity of mitiglinide calcium can be improved.

The invention provides an improved mitiglinide calcium (I) preparation method, and is characterized in that the preparation method successively comprises the steps: step 1, preparation of 2-benzyl succinic acid; step 2, preparation of (S)-2-benzyl succinic acid; step 3, preparation of 2-(S)-benzyl-4-oxo-(cis-perhydroisoindole-2-yl)butyric acid; and step 4, preparation of mitiglinide calcium. The invention provides the mitiglinide calcium industrialized preparation method having the advantages of being economical and practical, simple to operate, short in reaction period and high in yield.

The invention relates to a detection method for mitiglinide calcium R-isomer. According to the method, high performance liquid chromatography is adopted. The method comprises the following steps of: 1) the preparation of a test sample solution: a proper amount of a mitiglinide calcium bulk pharmaceutical chemical test sample is taken, and is precisely weighed, a mobile phase is added to the mitiglinide calcium bulk pharmaceutical chemical test sample, so that a solution containing 0.2 mg of the mitiglinide calcium bulk pharmaceutical chemical test sample per 1ml can be prepared, and the solution is uniformly shaken, so that the test sample solution can be obtained; 2) the preparation of a mitiglinide calcium reference substance solution: a proper amount of mitiglinide calcium reference substance is taken, is precisely weighed, a mobile phase is added to the mitiglinide calcium reference substance, so that a solution containing 0.2 mg of the mitiglinide calcium reference substance per 1ml can be prepared, and the solution is uniformly shaken, so that the mitiglinide calcium reference substance solution is obtained; and (3) the preparation of a mitiglinide calcium R-isomer referencesubstance solution: a proper amount of mitiglinide calcium R-isomer reference substance is taken, and is precisely weighed, a mobile phase is added, so that a solution containing 0.2 mg of mitiglinidecalcium R-isomer reference substance per 1ml can be prepared, and the solution is uniformly shaken, so that the mitiglinide calcium R-isomer reference substance solution can be obtained; and 4) determination: 20 microliters of the solutions in the step 1), the step 2) and the step 3) are separately injected into a high performance liquid chromatograph, so that chromatograms can be obtained, and the content of the mitiglinide calcium R-isomer in the mitiglinide calcium bulk pharmaceutical chemical is calculated according to peak areas in the chromatograms and through a normalization method.

The present invention provides pharmaceutical compositions which can achieve good state of glycemic control and correct postprandial hyperglycemia and early morning fasting hyperglycemia. The present pharmaceutical composition is for administration before meal to prevent or inhibit the progression of diabetic complication, which comprises 5 to 45 mg, as a single dose, of mitiglinide or a pharmaceutically acceptable salt thereof, or a hydrate thereof (for example, mitiglinide calcium salt hydrate). And said compositions are extremely useful for prevention or inhibition of progression of, for example, diabetic microvascular complications and arteriosclerotic diseases, because the frequency of adverse drug reactions such as hypoglycemic symptoms and gastrointestinal disorders is low.

The invention relates to a preparation method of mitiglinide calcium, which includes steps of step 1, synthesis of benzal butanedioic acid; step 2, synthesis of benzylsuccinic acid; step 3, synthesisof (S)-benzylsuccinic acid (R)-alpha- phenylethylamine; step 4, synthesis of (S)-benzylsuccinic acid; step 5, synthesis of 2S-dihydro-isoindole indolebutyric acid; step 6, synthesis of crude product of mitiglinide calcium; step 7, refining of mitiglinide calcium.

The invention relates to a method for preparing improved mitiglinide calcium. The method sequentially includes the steps of 1), preparation of acyl chloride; 2), preparation of active amide; 3), preparation of 2-(S)-benzyl-4-oxo-(cis-perhydroisindole-2-base) butyric acid; 4), preparation of the mitiglinide calcium. The method is concise in process, high in yield and low in production cost; compared with an existing acid anhydride process, the process applying the method has the advantages that product purity is remarkably improved, and easiness in industrialized production is achieved.

The invention relates to a method for preparing a hypoglycemic drug mitiglinide calcium. According to the method, under the temperature of -5 DEG C-10 DEG C, 30-60g of 2-benzylidene-3-(cis-perhydro-isoindolyl-2-carbonyl)propionic acid is dissolved in 200-500 milliliters of a reaction solvent, 2-5 g of a S-configuration aminoalcohol catalyst, 8-15 g of a borohydride and 15-25 g of trimethylchlorosilane are added, the materials are stirred for a reaction for 4-8 hours, pressure reduction is carried out for steaming the solvent, 400-600 milliliters of water and 4-6 milliliters of hydrochloric acid are added, ethyl acetate is used for extraction, an extract is merged, the extract is dried and concentrated to obtain a concentrate, the concentrate is dissolved in 400-600 mL of ethanol with mass concentration of 75-95%, 3-5 g of sodium hydroxide is added, after stirring and dissolving the materials, 8-12 g of calcium chloride is added, precipitate is obtained, and then the precipitate is subjected to pumping filtration to obtain mitiglinide calcium. The preparing method has the advantages of simple process, energy saving and environmental protection, can greatly increase the overall yield and obviously reduce the production cost, is easy to industrial production, is an innovation of a medicine for treating diabetes, and has large economic and social benefits.