A diltiazem hydrochloride and pregabalin composition and a preparation method thereof and its application. The composition of the invention is a lyophilizing agent prepared by adding an adequate amount of pregabalin hydrochloride solution, adding excipient and stirring until transparent. The lyophilizing agent will not produce crystallization after dissolution. In addition, by combining proper amount of pregabalin with sufficient amount of diltiazem hydrochloride into an injection, the efficacy of the original diltiazem hydrochloride can be guaranteed, and the adverse reactions such as dyspnea, spasm, skin itching and urticaria can be prevented or reduced.
A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 31/554 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
2.
SYNTHESIS AND APPLICATION OF DILTIAZEM HYDROCHLORIDE
The invention belongs to the field of drug synthesis, the invention discloses a synthetic method and application of diltiazem hydrochloride. The synthesis method is through the condensation ring closing and esterification of cis-(2S,3S) compound 1 and compound 2, then add hydrochloric acid to form salt, get the diltiazem hydrochloride. The invention has the following advantages, shortens the synthesis steps, improves the reaction yield, reduces the industrial production cost, and saves the time cost of the synthesis. The method is used for the synthesis of diltiazem hydrochloride, and the synthesized diltiazem hydrochloride is used to prepare diltiazem hydrochloride for injection.
C07D 281/10 - Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
3.
FREEZE-DRIED DILTIAZEM HYDROCHLORIDE POWDER INJECTION FOR INJECTION AND PREPARATION METHOD THEREFOR
The present invention relates to the technical field of drug preparation, and provides a freeze-dried diltiazem hydrochloride powder injection for injection and a preparation method therefor. The preparation method comprises: taking water for injection, and adding 1.15 to 1.73 parts by weight citric acid and 3.47 to 4.27 parts by weight sodium citrate and dissolving same; next, adding 6 to 8 parts by weight mannitol and 1 to 2 parts by weight diltiazem hydrochloride and dissolving same; and then adjusting the pH value, decolorizing, sterilizing, filtering and freeze-drying to obtain the freeze-dried diltiazem hydrochloride powder injection for injection. In the present invention, by means of adding citric acid and sodium citrate, the hydrolysis of diltiazem hydrochloride during the preparation of a powder injection may be effectively inhibited, the stability of diltiazem hydrochloride is maintained, and the quality of the prepared freeze-dried diltiazem hydrochloride powder injection for injection is improved.
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 31/554 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
4.
METHOD FOR SYNTHESIZING DILTIAZEM HYDROCHLORIDE AND USE THEREOF
The present invention belongs to the field of drug synthesis, and discloses a method for synthesizing diltiazem hydrochloride and the use thereof. The method for synthesizing diltiazem hydrochloride provided by the present invention comprises: carrying out a ring-closing condensation reaction and an esterification reaction on cis-(2S,3S) compound 1 and compound 2, and then adding hydrochloric acid to form a salt, namely diltiazem hydrochloride. The method for synthesizing diltiazem hydrochloride provided by the present invention reduces the synthetic steps, improves the reaction yield, reduces the industrial production cost, and reduces the time cost of synthesis. The present invention is applicable to the synthesis of diltiazem hydrochloride, and the synthesized diltiazem hydrochloride is used for preparing diltiazem hydrochloride for injection.
C07D 281/10 - Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
A61K 31/554 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
A61K 9/00 - Medicinal preparations characterised by special physical form
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
5.
LEVAMLODIPINE BESYLATE TABLET AND PREPARATION METHOD THEREFOR
The present invention provides a levamlodipine besylate tablet and a preparation method therefor, and belongs to the technical field of drug preparation. The preparation method comprises: taking 3.47-7 parts by weight of levamlodipine besylate, 40-120 parts by weight of microcrystalline cellulose, 30-90 parts by weight of sodium starch glycolate, 0.5-1 part by weight of calcium phosphate, and 5-10 parts by weight of xylitol, thoroughly mixing, and tableting same to obtain a levamlodipine besylate tablet. In the present invention, calcium phosphate and xylitol are used in appropriate proportions as glidants. The prepared levamlodipine besylate tablet is complete, has good gloss and a stable tablet weight; in addition, the angle of repose is less than 39°, and the hardness is greater than 55 N.
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Disclosed are a method for synthesizing vidarabine monophosphate and the use thereof, which belong to the field of drug synthesis. The synthesis method comprises subjecting 5-iodo-2-((phosphonooxy)methyl)-4-(tosyloxy)tetrahydrofuran-3-yl acetate and tert-butyl(8-hydroxy-9H-purin-6-yl)carbamate to condensation, epoxidation, ring opening and desulfurization reactions in order to synthesize vidarabine monophosphate. The provided method for synthesizing vidarabine monophosphate further simplifies the industrial production steps, improves the total reaction yield, and reduces the industrial production cost. The synthesis method is suitable for the synthesis of vidarabine monophosphate, and the synthesized vidarabine monophosphate is used for preparing vidarabine monophosphate for injection.
The present invention relates to the technical field of drug preparation, and provides a preparation method of a vidarabine monophosphate freeze-dried powder injection, comprising: taking water for injection, adjusting the pH value thereof to 8.0-8.5, adding vidarabine monophosphate for dissolving, then performing decolorization, sterile filtration, and subpackaging, and subjecting the obtained feed liquid to pre-freezing, to sublimation drying four times and to desorption drying three times, so as to obtain a vidarabine monophosphate freeze-dried powder injection. According the present invention, by adjusting the pH value, the hydrolysis reaction of vidarabine monophosphate is reduced, and the impurity content of the finished product is reduced; the settings of technological parameters in the sublimation drying process and the desorption drying process avoid solute migration in liquid medicine, and ensure the fullness and looseness of the finished product, so that the surface of the finished product is smoother. The preparation method provided by the present invention can effectively improve the drug stability, appearance shape and looseness of the finished product.
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
F26B 5/06 - Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum the process involving freezing
8.
DILTIAZEM HYDROCHLORIDE AND PREGABALIN COMPOSITION AND PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
The present invention relates to a diltiazem hydrochloride and pregabalin composition and a preparation method therefor and an application thereof. The composition is a lyophilized agent prepared by adding a proper amount of pregabalin into a sufficient amount of diltiazem hydrochloride solution, then adding an excipient and stirring the mixture to be transparent. The lyophilized agent can be dissolved without crystallization; moreover, after an injection is prepared by a proper amount of pregabalin and a sufficient amount of diltiazem hydrochloride, a drug effect of the original diltiazem hydrochloride can be ensured, and possible adverse reactions, which are caused thereby, of dyspnea, spasm, skin itch and urticaria can be prevented or reduced.
A61K 9/19 - Particulate form, e.g. powders lyophilised
A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
patents
