CN-116327697-B - Noradrenal bitartrate injection and its preparation process

Abstract

The invention aims to provide a bitartrate norepinephrine injection capable of effectively controlling the colors of norepinephrine sulfonate and products and a preparation method thereof, the bitartrate norepinephrine injection comprises active ingredients of norepinephrine, edetate disodium, L-cysteine, sodium chloride, hydrochloric acid and water, wherein the auxiliary ingredients comprise 20g of bitartrate norepinephrine, 80g of sodium chloride, 2.5-3.0g of edetate disodium, 4.0-5.0g of L-cysteine, and the scheme of the invention can effectively control the impurities of the norepinephrine sulfonate, other oxidized impurities and the colors of the products.

Inventors

• TANG PAN
• ZHOU XUDONG
• CHEN ZHILI
• ZHOU JIAN
• RAN XIUQIONG
• QIU JUNYAN
• ZHANG LIANLI
• XU FEI
• LAN CHANGYUN

Assignees

• 福安药业集团庆余堂制药有限公司

Dates

Publication Date

20260508

Application Date

20230417

Claims (1)

1. 1. The norepinephrine bitartrate injection is characterized by comprising the following components of 20g of norepinephrine bitartrate, 80g of sodium chloride, 2.5-3.0g of disodium edentate, 4.0-5.0g of L-cysteine, wherein the pH value of the injection is regulated to 2-4 by hydrochloric acid; the preparation process of the norepinephrine bitartrate injection comprises the following steps of: (1) Adding injection water accounting for 90% of the total preparation amount into a preparation container, wherein the temperature of the injection water is 30-50 ℃; (2) Adding edetate disodium, sodium chloride, L-cysteine and norepinephrine bitartrate into the water for injection obtained in the step (1), stirring to dissolve completely, stirring at 150-160rpm for 10-20 min, adjusting pH value to 2-4 with hydrochloric acid, and adding water for injection to constant volume total amount to obtain norepinephrine bitartrate liquid medicine; (3) Filtering the liquid medicine obtained in the step (2) through a filter element, wherein the filtering filter element is a filter element with the thickness of 0.45 mu m and 0.22 mu m; (4) And (3) filling and sealing the liquid medicine obtained in the step (3) according to a filling and sealing program, and sterilizing at 121 ℃ for 15 minutes.

Description

Noradrenal bitartrate injection and its preparation process Technical Field The invention relates to the technical field of pharmacy, in particular to norepinephrine bitartrate injection and a preparation process thereof. Background Norepinephrine bitartrate, which is chemically named as (R) -4- (2-amino-1-hydroxyethyl) -1, 2-benzenediol bitartrate monohydrate, is known as 'norepinephrine', and is mainly used for controlling blood pressure in certain acute hypotensive states (such as pheochromocytotomy, sympatholytic atherectomy, poliomyelitis, myocardial infarction, septicemia, blood transfusion and drug reaction), and the research on the preparation process of the norepinephrine bitartrate injection has great economic value and social significance. Many reports about the synthesis route of norepinephrine bitartrate in the prior art are mostly obtained by using catechol as a raw material and performing chloracetyl, ammoniation, palladium-carbon catalytic hydrogenation and splitting of L-tartaric acid into salts (see, for example, non-patent document 1 ((-) -norepinephrine synthesis research, liang Dawei, wang Yueqiu, chemical technology and development, 2014, stage 8). The adopted production process is an excessive killing method of a terminal sterilization process, the Chinese pharmacopoeia confirms that the product is easy to deteriorate when meeting air and is oxidized into impurities such as norepinephrine, quinone and the like, currently, the marketed products and reference preparations are both prepared by adding antioxidant sodium metabisulfite or adopting nitrogen protection in production to prevent oxidation, but the prescription and the process can produce norepinephrine sulfonate impurities and other impurities. Disclosure of Invention The invention aims to provide a norepinephrine bitartrate injection and a preparation process thereof, which are used for realizing the technical effect of reducing sulfonate impurities and other impurities in the norepinephrine bitartrate injection. The invention is realized by the following technical scheme: A norepinephrine bitartrate injection comprises 20g of norepinephrine bitartrate, 80g of sodium chloride, 2.5-3.0g of disodium edentate and 4.0-5.0g of L-cysteine in per 10000 ml. According to the scheme, 20g of norepinephrine bitartrate, 80g of sodium chloride, 2.5-3.0g of edetate disodium and 4.0-5.0g of L-cysteine are added into every 10000ml of the pharmaceutical composition, and the pharmaceutical composition is composed of the norepinephrine bitartrate serving as an active ingredient, disodium edetate serving as an auxiliary material, L-cysteine, sodium chloride, hydrochloric acid and water, so that the impurities of norepinephrine sulfonate, other oxidized impurities and the color of products can be effectively controlled. In order to better realize the invention, hydrochloric acid is further used for adjusting the pH value of the injection to 2-4. A preparation process of norepinephrine bitartrate injection, which comprises the following steps: (1) Adding 90% of injection water in the total amount into a preparation container; (2) Adding edetate disodium, sodium chloride, L-cysteine and norepinephrine bitartrate into the water for injection obtained in the step (1), rotating and stirring to completely dissolve, adjusting the pH value to 2-4 by hydrochloric acid, and adding the water for injection to the total volume to obtain the norepinephrine bitartrate liquid medicine; (3) Filtering the liquid medicine obtained in the step (2) through a filter element; (4) And (3) filling and sealing the liquid medicine obtained in the step (3) according to a filling and sealing program, and sterilizing at 121 ℃ for 15 minutes. In order to better realize the invention, the temperature of the water for injection in the preparation container in the step (1) is 30-50 ℃. In order to better realize the invention, the stirring speed of the step (2) is 150-160rpm, and the stirring time is 10-20 minutes. In order to better realize the invention, the filter element in the step (3) is a 0.45 μm and 0.22 μm filter element. The invention has the beneficial effects that the growth of the norepinephrine sulfonate impurity and other impurities of the product can be stably controlled by controlling the selection of auxiliary materials and the control of the process, the problem of color change of the product is solved, the prescription can still effectively control the impurity of the norepinephrine sulfonate, other oxidized impurities and the color of the product under the sterilization condition of 15 minutes at 121 ℃, the stability period is accelerated for 6 months, the impurity of the norepinephrine sulfonate is not detected, and the color of the product is colorless. Detailed Description The present invention is described in detail below with reference to examples, which are intended to illustrate but not to limit the technical solution of the present invention. A norepinep