阅读说明：本技术 一种药物组合物及制备方法 (Pharmaceutical composition and preparation method thereof ) 是由 张峰 郁晨燕 李晓明 于 2019-12-17 设计创作，主要内容包括：本发明公开了一种药物组合物,其包括雷诺嗪或其可药用盐以及功能性辅料。本公开的药物组合物能够快速发挥主药的疗效,又能够减少现有制剂的起效慢的不足,具有稳定血药浓度较低副作用的优点。(The invention discloses a pharmaceutical composition, which comprises ranolazine or pharmaceutically acceptable salts thereof and functional auxiliary materials. The pharmaceutical composition disclosed by the invention can quickly exert the curative effect of the main drug, can reduce the defect of slow effect of the existing preparation, and has the advantage of low side effect of stabilizing blood concentration.)

1. A pharmaceutical composition comprising ranolazine or a pharmaceutically acceptable salt thereof and a functional excipient.

2. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable salt of ranolazine is selected from the group consisting of hydrochloride, sulfate, hydrobromide, citrate, succinate, phosphate, lactate, pyruvate, acetate, benzenesulfonate, p-benzenesulfonate, glutamate, or mixtures thereof, preferably the functional adjuvant is selected from the group consisting of hypromellose acetate succinate, hypromellose phthalate, acrylic resin, methacrylic acid copolymer, or mixtures thereof, preferably the weight ratio of ranolazine or a pharmaceutically acceptable salt thereof to the functional adjuvant is from 1:1 to 5: 1.

3. The pharmaceutical composition of claim 1 or 2, further comprising a non-functional excipient selected from microcrystalline cellulose, hydroxypropyl methylcellulose, talc, magnesium stearate, opadry or mixtures thereof.

4. The pharmaceutical composition of any one of claims 1-3, wherein the pharmaceutical composition is a tablet, capsule, or granule.

5. A method of preparing a pharmaceutical composition comprising:

dissolving ranolazine or a pharmaceutically acceptable salt thereof and a functional auxiliary material in an organic solvent, and evaporating the organic solvent;

solidifying and crushing to obtain the medicinal composition.

6. A process for the preparation of a pharmaceutical composition as claimed in claim 5, wherein the pharmaceutically acceptable salt of ranolazine is selected from hydrochloride, sulfate, hydrobromide, citrate, succinate, phosphate, lactate, pyruvate, acetate, benzenesulfonate, p-toluenesulfonate, glutamate or mixtures thereof, preferably the functional excipient is selected from hypromellose acetate succinate, propylmethylcellulose phthalate, acrylic resin, methacrylic acid copolymer or mixtures thereof, preferably the weight ratio of ranolazine or a pharmaceutically acceptable salt thereof to the functional excipient is 1:1 to 5:1, preferably the weight ratio of organic solvent to ranolazine or a pharmaceutically acceptable salt thereof is 1:6 to 1:3 in parts by weight.

7. The process for the preparation of a pharmaceutical composition according to claim 5 or 6, wherein the organic solvent is selected from ethanol, acetone, dichloromethane or mixtures thereof, preferably an ethanol-dichloromethane mixture, preferably a weight ratio of ethanol to dichloromethane in the ethanol-dichloromethane mixture is from 1:3 to 1: 5.

8. A process for the preparation of a pharmaceutical composition according to any one of claims 5 to 7, wherein the organic solvent is evaporated by constant temperature stirring, preferably at a temperature of 40 ℃ to 100 ℃, preferably 60 ℃ to 80 ℃, more preferably 70 ℃.

9. A process for the preparation of a pharmaceutical composition according to any one of claims 5 to 8, wherein the solidification is carried out by freeze-drying, preferably at a temperature of from 0 ℃ to-30 ℃, preferably from 0 ℃ to-10 ℃, more preferably-4 ℃, and the solidification time is optimized to be from 0 to 5 hours, preferably from 1 to 2 hours.

10. A process for the preparation of a pharmaceutical composition as claimed in any one of claims 5 to 9 wherein the particle size after comminution is from 20 to 100 mesh, more preferably from 50 to 70 mesh, more preferably 60 mesh.

Detailed Description

In one aspect, the disclosure relates to a pharmaceutical composition comprising ranolazine or a pharmaceutically acceptable salt thereof and a functional excipient.

In certain embodiments, illustrative examples of pharmaceutically acceptable salts of ranolazine that can be used in the present disclosure include, but are not limited to, hydrochloride, sulfate, hydrobromide, citrate, succinate, phosphate, lactate, pyruvate, acetate, benzenesulfonate, p-benzenesulfonate and glutamate salts of ranolazine.

In certain embodiments, illustrative examples of functional excipients that can be used in the present disclosure include, but are not limited to, hypromellose acetate succinate, propylmethylcellulose phthalate, acrylic resins, and methacrylic copolymers.

In certain embodiments, the weight ratio of ranolazine or a pharmaceutically acceptable salt thereof to the functional excipient is from 1:1 to 5: 1.

In some embodiments, the composition further comprises non-functional auxiliary materials,

in certain embodiments, illustrative examples of non-functional excipients that can be used in the present disclosure include, but are not limited to, microcrystalline cellulose, hydroxypropylmethylcellulose, talc, magnesium stearate, and opadry.

In certain embodiments, the pharmaceutical composition is a tablet, capsule, or granule.

In another aspect, the present disclosure relates to a method of preparing a pharmaceutical composition comprising:

dissolving ranolazine or a pharmaceutically acceptable salt thereof and a functional auxiliary material in an organic solvent, and evaporating the organic solvent;

solidifying and crushing to obtain the medicinal composition.

In certain embodiments, illustrative examples of pharmaceutically acceptable salts of ranolazine that can be used in the present disclosure include, but are not limited to, hydrochloride, sulfate, hydrobromide, citrate, succinate, phosphate, lactate, pyruvate, acetate, benzenesulfonate, p-benzenesulfonate and glutamate salts of ranolazine.

In certain embodiments, illustrative examples of functional excipients that can be used in the present disclosure include, but are not limited to, hypromellose acetate succinate, propylmethylcellulose phthalate, acrylic resins, and methacrylic copolymers.

In certain embodiments, the weight ratio of ranolazine or a pharmaceutically acceptable salt thereof to the functional excipient is from 1:1 to 5: 1.

In certain embodiments, it is preferred that the weight ratio of organic solvent to ranolazine or a pharmaceutically acceptable salt thereof be from 1:6 to 1:3, parts by weight.

In certain embodiments, illustrative examples of organic solvents that can be used in the present disclosure include, but are not limited to, ethanol, acetone, and dichloromethane.

In certain embodiments, illustrative examples of organic solvents that can be used in the present disclosure include, but are not limited to, ethanol-dichloromethane mixtures,

in certain embodiments, illustrative examples of organic solvents that can be used in the present disclosure include, but are not limited to, mixtures of ethanol-dichloromethane, wherein the weight ratio of ethanol to dichloromethane is from 1:3 to 1: 5.

In certain embodiments, the organic solvent is an organic solvent that is evaporated by constant temperature stirring.

In certain embodiments, the temperature of the constant temperature agitation is from 40 ℃ to 100 ℃.

In certain embodiments, the temperature of the constant temperature agitation is 60 ℃ to 80 ℃.

In certain embodiments, the temperature of the isothermal agitation is 70 ℃.

In certain embodiments, the solidification is performed by freeze-drying.

In certain embodiments, the curing temperature is from 0 ℃ to-30 ℃.

In certain embodiments, the curing temperature is from 0 ℃ to-10 ℃.

In certain embodiments, the curing temperature is-4 ℃.

In certain embodiments, the curing time is from 0 to 5 hours.

In certain embodiments, the curing time is 1 to 2 hours.

In certain embodiments, the particle size after pulverization is from 20 to 100 mesh.

In certain embodiments, the particle size after pulverization is from 50 to 70 mesh.

In certain embodiments, the particle size after pulverization is 60 mesh.