CN111249231A

CN111249231A - Oxytocin injection taking ethanol as chlorobutanol solvent and preparation method thereof

Info

Publication number: CN111249231A
Application number: CN202010193344.4A
Authority: CN
Inventors: 史凌洋; 宋永红; 杨芳
Original assignee: Chengdu Haitong Pharmaceutical Co ltd
Current assignee: Chengdu Haitong Pharmaceutical Co ltd
Priority date: 2020-03-18
Filing date: 2020-03-18
Publication date: 2020-06-09

Abstract

The invention provides an oxytocin injection taking ethanol as a chlorobutanol solvent, which consists of the following raw and auxiliary materials in parts by weight: 5000-10000 parts of oxytocin, 2-9 parts of chlorobutanol, 2-6 parts of ethanol, 0.6-1.2 parts of sodium acetate and 1000 parts of water. The oxytocin injection has the advantages of uniform titer distribution and high stability in the period of validity. The invention also provides a preparation method of oxytocin injection by taking ethanol as a chlorobutanol solvent, which is characterized in that the chlorobutanol is dissolved in the ethanol and then is mixed with oxytocin and water, so that the chlorobutanol in the injection is more stable, the oxytocin is more uniformly distributed, and the preparation method has practical application and popularization values.

Description

Oxytocin injection taking ethanol as chlorobutanol solvent and preparation method thereof

Technical Field

The invention relates to oxytocin injection taking ethanol as a chlorobutanol solvent and a preparation method thereof.

Background

The oxytocin injection is colorless clear or almost clear liquid, is a medicine for induced labor, uterine bleeding caused by uterine atony or poor contraction after delivery and abortion and for understanding placenta reserve function (oxytocin irritation test), and mainly comprises oxytocin, chlorobutanol, glacial acetic acid and water for injection.

Clinical application finds that oxytocin injections often have adverse reactions, so that the quality control of the injections has very important clinical significance, and most of the oxytocin injections sold in the market at present contain chlorobutanol and are used as a stabilizer and used for relieving pain during injection. However, chlorobutanol has very low solubility in cold water and is very volatile in hot water, so that the distribution of chlorobutanol in the injection is influenced by the traditional preparation process, and the stability of the preparation in the period of validity is influenced.

Disclosure of Invention

In order to solve the technical problems, the invention provides an oxytocin injection taking ethanol as a chlorobutanol solvent, which is composed of the following raw and auxiliary materials in parts by weight:

5000-10000 parts of oxytocin, 2-9 parts of chlorobutanol, 2-6 parts of ethanol, 0.6-1.2 parts of sodium acetate and 1000 parts of water by volume.

Further, the feed additive consists of the following raw materials in parts by weight:

5000 parts of oxytocin, 3-8 parts of chlorobutanol, 3-5 parts of ethanol, 0.8-1 part of sodium acetate and 1000 parts of water by volume;

or:

10000 parts of oxytocin, 3-8 parts of chlorobutanol, 3-5 parts of ethanol, 0.8-1 part of sodium acetate and 1000 parts of water by volume.

Further, the water is water for injection, and the ethanol is 70% ethanol.

The invention also provides a method for preparing the oxytocin injection, which comprises the following steps:

(1) weighing the raw and auxiliary materials according to the proportion

(2) Adding ethanol into the chlorobutanol for dissolving to obtain a solution A; adding oxytocin into water below 40 ℃ for dissolving to obtain solution B;

(3) mixing solution A and solution B, adjusting pH to 3.4-4.5 with sodium acetate solution, mixing, and filtering.

Further, the dissolving in the step 2) is stirring dissolving, and the ethanol is 70% (ml/ml) ethanol; the water is water for injection.

Further, in the step 3), the solution A and the solution B are uniformly mixed, namely, the solution A is transferred into the solution B and uniformly mixed.

Further, the sodium acetate solution in the step 3) is prepared by dissolving sodium acetate in water for injection to prepare a solution with the concentration of 2 mol/L.

Further, the filtration in the step 3) is twice filtration by using a 0.22 μm hydrophilic sterilization filter element.

The oxytocin injection taking ethanol as the chlorobutanol solvent has uniform titer distribution and high stability in the period of validity. The invention firstly dissolves the chlorobutanol in the ethanol, and then mixes the chlorobutanol with the oxytocin and the water, so that the chlorobutanol in the injection is more stable, the oxytocin is more uniformly distributed, and the invention has practical application and popularization values.

Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.

The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.

Detailed Description

Example 1 preparation of oxytocin injection according to the invention

The formula is as follows: 5000IU of oxytocin, 3-8 g of chlorobutanol, 3-5 g of 70% (ml/ml) ethanol, 0.8-1 g of sodium acetate and 1000ml of water for injection.

The preparation method comprises the following steps:

(1) adding 70% ethanol into the container 1, adding chlorobutanol, and stirring to dissolve completely;

(2) adding water for injection into the container 2, cooling to below 40 ℃, adding oxytocin raw material, stirring and dissolving completely;

(3) transferring the solution in the container 1 into a container 2, stirring uniformly, adjusting the pH value of the liquid medicine to 3.4-4.5 by using 2mol/L sodium acetate solution (the sodium acetate solution is prepared by using injection water), adding the injection water to a constant volume, and stirring and mixing uniformly;

(4) filtering with 0.22 μm hydrophilic sterilizing filter core for twice sterilizing, and bottling.

Example 2 preparation of oxytocin injection according to the invention

The formula is as follows: 10000IU of oxytocin, 3-8 g of chlorobutanol, 3-5 g of 70% (ml/ml) ethanol, 0.8-1 g of sodium acetate and 1000ml of injection water.

The preparation method comprises the following steps:

(2) adding hot water for injection into the container 2, cooling to below 40 ℃, adding oxytocin raw material, stirring and dissolving completely;

The advantageous effects of the present invention are further described below by way of test examples.

Test example 1 comparison of the present invention with oxytocin injection

1. Preparation of oxytocin injection

1.1 preparation method of oxytocin injection of the invention is the same as example 1

1.2 preparation method of the oxytocin injection:

the formula is as follows: 5000IU of oxytocin, 1-3 g of chlorobutanol and 1000ml of water for injection

The process comprises the following steps:

(1) adding 25% of water for injection into the container 1, controlling the water temperature at 70 +/-5 ℃, adding chlorobutanol, stirring to dissolve completely, and cooling to 30 +/-5 ℃.

(2) Adding 50% of water for injection into the container 2, controlling the water temperature at 30 +/-5 ℃, transferring the solution into the container 2, adding the formula amount of oxytocin, and stirring until the oxytocin is completely dissolved.

(3) The solution in vessel 1 was transferred to vessel 2 and mixed well with stirring. Adjusting pH of the medicinal liquid to 3.4-4.5 with 1mol/L sodium acetate solution (prepared from sodium acetate solution with water for injection), adding water for injection to constant volume, stirring, and mixing.

2 results of detection

The injection and the oxytocin injection are respectively taken and respectively detected in three batches, and the specific detection method comprises the steps of taking the injection as a test solution, respectively and precisely weighing trichloro-tert-butyl alcohol and an oxytocin reference substance, and adding methanol to prepare solutions containing 5mg of trichloro-tert-butyl alcohol and 8.3 mu g of oxytocin in each 1ml of solution as a reference substance solution. A proper amount of the test solution and the reference solution are precisely taken and injected into a chromatograph for measurement, and the results are shown in table 1.

TABLE 1 comparison of oxytocin injection detection data

Note: the calculation mode of the chlorobutanol content result is that 5mg of chlorobutanol is used for calculating, and the detected numerical value is compared with 5mg (namely, the content is the percentage of the marked amount); the calculation mode of the oxytocin content result is that 8.3 mug oxytocin is counted, and the detected value is compared with 8.3 mug (namely, the content is the percentage of the marked amount).

As can be seen from table 1: the oxytocin injection prepared by the preparation method effectively avoids the volatilization of the chlorobutanol without obvious reduction. Meanwhile, the degradation of oxytocin is effectively protected due to the stability of the chlorobutanol, so that the obtained product has good correspondence with the formula marked amount, the instability of the quality of the injection caused by the instability of the chlorobutanol is avoided, and the medication safety of patients is ensured.

In conclusion, the oxytocin injection containing ethanol has the advantages of uniform titer distribution and high stability in the period of validity. The invention firstly dissolves the chlorobutanol in the ethanol, and then mixes the chlorobutanol with the oxytocin and the water, so that the chlorobutanol in the injection is more stable, the oxytocin is more uniformly distributed, and the invention has practical application and popularization values.

Claims

1. An oxytocin injection taking ethanol as a chlorobutanol solvent is characterized in that: the composite material consists of the following raw and auxiliary materials in parts by weight:

2. The injection according to claim 1, which is prepared from the following raw materials in parts by volume:

or:

3. The injection according to claim 1, wherein the water is water for injection and the ethanol is 70% (ml/ml) ethanol.

4. A method for preparing an oxytocin injection as claimed in any one of claims 1 to 3, characterized in that: it comprises the following steps:

(1) weighing the raw and auxiliary materials according to the proportion;

(2) adding ethanol into the chlorobutanol for dissolving to obtain a solution A; dissolving oxytocin in water below 40 deg.c to obtain solution B;

5. The method according to claim 4, wherein the dissolving in the step (2) is stirring dissolving; the ethanol is 70% (ml/ml) ethanol; the water is water for injection.

6. The method according to claim 4, wherein the step (3) of mixing solution A and solution B is carried out by transferring solution A into solution B and mixing.

7. The method of claim 4, wherein: and 3) the sodium acetate solution is prepared by dissolving sodium acetate in water for injection to prepare a solution with the concentration of 2 mol/L.

8. The method according to claim 4, wherein the filtration in step (3) is performed twice by using a 0.22 μm hydrophilic sterilizing filter.