Potassium dehydroandrographolide succinate injection and preparation method

A technology for Chuanhuning and water for injection, which is applied in the field of medicine, can solve the problems of easy hydrolysis of aqueous solutions, decreased content, and deepening of product color and luster.

Active Publication Date: 2013-10-02

CHENGDU TIANTAISHAN PHARMA

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AI-Extracted Technical Summary

Problems solved by technology

It is believed that there are bridge-shaped conjugated structures, α and β-unsaturated lactone bonds in the molecular structure of Chuanhuning drug, and its aqueous solution is prone to hydrolysis, resulting in darker color and lower content of the product

Common chemical stability is manifested by the increase of impurities and/or the decrease of content, such as Fu Chunmei et al. Research, Journal of Pharmaceutical Analysis, 2005, 25(2): 157) reported: "Injection stability investigation found that the peak area of...

Abstract

The invention relates to potassium dehydroandrographolide succinate injection and a preparation method, in particular to a pharmaceutical composition which comprises potassium dehydroandrographolide succinate, alkali metal salt and water for injection. The preparation method of the pharmaceutical composition comprises steps as follows: auxiliary materials such as the alkali metal salt and the like are dissolved in an appropriate amount of the water for injection, the potassium dehydroandrographolide succinate is added to the solution and stirred to be dissolved, about 0.1%-0.5% of activated carbon is added to the solution and stirred for absorption for 30 minutes, and filtration is performed to remove carbon; the water for injection is refilled to a full dose, a pH value of the solution is checked, and if necessary, an acidifying or alkalizing agent is used for adjusting the pH value of the solution to be in the range from 6.5 to 8.0; 0.4 mu m and 0.22 mu m millipore filtering films are used for filtering a liquid medicine, the liquid medicine is split and filled in glass bottles, then sealed and autoclaved at the temperature of 115 DEG C for 30 minutes, and the potassium dehydroandrographolide succinate injection is obtained. The prepared potassium dehydroandrographolide succinate injection has a good pharmaceutical property.

Application Domain

Organic active ingredientsPharmaceutical delivery mechanism +3

Technology Topic

Activated carbonChemistry +7

Image

Examples

Experimental program(7)
Effect test(3)

Example Embodiment

[0086] Preparation Example 1. Preparation of Injection Containing Chuanhuning

[0087] formula:

[0088] Compounds of formula I

[0089] Preparation:

[0090] (a) dissolve alkali metal salt, cysteine or its pharmaceutically acceptable salt, cyclodextrin in about 85% water for injection of recipe quantity;

[0091] (b) adding trishuning to the above-mentioned solution, stirring to dissolve;

[0092](c) adding about 0.3% activated carbon to the solution, stirring and adsorbing for 30 minutes, filtering and decarbonizing;

[0093] (d) Add water for injection to the full amount, check the pH value of the solution, and adjust the pH value of the solution to 7.3 with an acid-base regulator if necessary; filter the medicinal liquid with 0.4 μm and 0.22 μm microporous membranes, and divide the medicinal liquid into Packed into glass bottles, sealed, sterilized by autoclaving at 115°C for 30min, and obtained.

[0094] In the present invention, the sample of this preparation example 1 may be abbreviated as Ex1-01.

Example Embodiment

[0095] In this preparation example, the following preparation process is supplemented as a supplementary preparation example:

[0096] Supplementary Preparation Example 1: In different formulas, except that the amount of sodium bicarbonate is changed to the amount listed in the second row (mg row) of the following table, other elements in the formula and the preparation process are the same as the above-mentioned preparation example 1. The first row (No. row) in the table is the serial number of the obtained injection sample, the complete serial number of No. 01 is Eb1-01, which means to supplement the No. 01 injection obtained in Preparation Example 1, the complete serial number of No. 02 is Eb1-02, and there are also Similar meaning.

[0097] No.

[0098] Investigate the above samples of Ex1-01 and Eb1-01 to Eb1-06:

[0099] Appearance: Colorless clear liquid.

[0100] The stability test of high temperature treatment was carried out and tested according to the method of "A, Test Method Example" above, and the results were as follows:

[0101] Content residual percentage (%): The residual percentage (%) of each sample of Ex1-01, Eb1-03 and Eb1-04 is between 95% and 99%, for example, the residual percentage of Ex1-01 is 98.8%; The residual percentage (%) of each sample of -01, Eb1-02, Eb1-05 and Eb1-06 is between 75% and 88%, for example, the residual percentage of Eb1-01 and Eb1-02 is 77.5% respectively , 86.4%;

[0102] Total related substance change value (%): The total related substance change value (%) of each sample of Ex1-01, Eb1-03 and Eb1-04 is between 0.07% and 0.21%, for example, the total related substance of Ex1-01 The change value (%) is 0.18%; while the total related substance change value (%) of each sample of Eb1-01, Eb1-02, Eb1-05, and Eb1-06 is between 0.86% and 1.74%, for example, Eb1- The change value (%) of the total related substances of 01 and Eb1-02 were 1.13% and 0.96%, respectively.

[0103] In addition, it was determined that the pH values of each sample Ex1-01 and Eb1-01 to Eb1-06 before and after high temperature treatment were between 6.8 and 7.6, for example, Ex1-01 and Eb1-03 were both at high temperature. The pH values after treatment were 7.13 and 7.04, respectively.

[0104] The above results show that when the sodium bicarbonate consumption of the formula of the present invention is within the range of 12 to 17 parts by weight (with respect to every 100 parts by weight of trisunin), the injection of the present invention has good stability, but when the sodium bicarbonate consumption deviates from the above In the range, even if the pH value of the chemical solution was adjusted in the range of 6.5 to 8.0, unsatisfactory stability was exhibited.

Example Embodiment

[0105] Supplementary Preparation Example 2: In different formulas, except that the amount of cysteine is changed to the amount listed in the second row (mg row) of the following table, other elements in the formula and the preparation process are the same as the above preparation example 1. The first row (No. row) in the table is the serial number of the obtained injection sample, the complete serial number of No. 01 is Eb2-01, which means to supplement the No. 01 injection obtained in Preparation Example 2, the complete serial number of No. 02 is Eb2-02, and there are also Similar meaning.

[0106] No.

[0107] Investigate the above samples from Eb2-01 to Eb2-06:

[0108] Appearance: Colorless clear liquid.

[0109] The stability test of high temperature treatment was carried out and tested according to the method of "A, Test Method Example" above, and the results were as follows:

[0110] Content residual percentage (%): The residual percentage (%) of each sample of Eb2-03 and Eb2-04 is between 97% and 99%, for example, the residual percentage of Eb2-03 is 98.6%; while Eb2-01, Eb2 The residual percentages (%) of the samples of -02, Eb2-05 and Eb2-06 are all between 71% and 89%, for example, the residual percentages of Eb2-01 and Eb1-02 are 71.3% and 84.6% respectively;

[0111] Total related substance change value (%): The total related substance change value (%) of each sample of Eb2-03 and Eb2-04 is between 0.11% and 0.20%, for example, the total related substance change value of Eb2-03 (% ) was 0.17%; while the total related substances change values (%) of Eb2-01, Eb2-02, Eb2-05, and Eb2-06 samples were all between 0.7% and 2.7%, such as Eb2-01, Eb2- 02 The total related substance change value (%) of the two groups was 2.64% and 1.26%, respectively.

[0112] In addition, it was determined that the pH values of each sample from Eb2-01 to Eb2-06 before and after high temperature treatment were between 6.8 and 7.6, for example, the pH values of Eb2-01 and Eb2-02 after high temperature treatment The values are 7.06 and 6.94, respectively.

[0113] The above results show that when the L-cysteine dosage of the present invention is within the range of 3 to 7 parts by weight (with respect to per 100 parts by weight of trisunin), the injection of the present invention has good stability, but when L-cysteine is used When the amount of cystine deviates from the above range, even if the pH value of the chemical solution is adjusted within the range of 6.5 to 8.0, unsatisfactory stability is exhibited.

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