CN102335125A - Adrenaline hydrochloride injection and preparation process thereof - Google Patents

Abstract

The invention discloses an adrenaline hydrochloride injection and a preparation process thereof. The preparation process comprises the following steps: (1) adding water for injection in a container and inserting CO2 for 15 min, wherein, the volume of the water is 90% of the total volume, and the temperature of the water is less than 30 DEG C; (2) dissolving sodium chloride in proper amount of water for injection having a temperature of below 30 DEG C; (3) dissolving disodium edetate with boiled water for injection; (4) dissolving sodium chloride solution, disodium edetate solution, sodium pyrosulfite and epinephrine respectively in water for injection; (5) measuring the pH value of the solution, regulating the pH value to 3.6-4.0 with 1 mol/L hydrochloric acid, adding water for injection to reach the total amount, and uniformly stirring; (6) filtering; and (7) carrying out aseptic filling and sealing, and inserting N2 in ampoules when filling and sealing; or carrying out filling and sealing according to operating procedures of filling and sealing, inserting N2 in the ampoules when filling and sealing , and carrying out disinfection for 30 min at the temperature of 100 DEG C. The process realizes aseptic production, and products produced by the preparation process satisfy the national medicine quality standards.

Description

Adrenalin hydrochloride injection and preparation process thereof

[technical field]

The present invention relates to pharmaceutical field, especially relate to the chemical drugs injection.

[background technology]

State Food and Drug Administration evaluates the center and has issued [2008] No. 7 literary compositions of state's food medicine prison notes in 2008---and " about issuing the notice that the biochemical medicine injection basic fundamental of chemical drugs injection and multicomponent requires "; Its literary composition regulation: small-volume injection should be taked terminal sterilization technology, and the suggestion first-selection is excessively killed method (F ₀>=12), the condition of excessively killing can not be tolerated, remaining probabilistic method (8≤F can be considered to adopt like product ₀＜12), but all should guarantee that the SAL (sterilization guarantees horizontal sterility assurance level) after the product sterilization is not more than 10 ^-6Adopt other F ₀Value will not be approved less than the technology of 8 terminal sterilization condition in principle.Can not adopt terminal sterilization technology if any sufficient according to proof, and be the kind of clinical necessary drug administration by injection, can consider to adopt sterile production technology, but should guarantee that SAL is not more than 10 ^-3Adopted the auxiliary kind of sterilizing of flowing steam simultaneously for filtration sterilization technology, proposed amendments is a terminal sterilization technology, to adopting the kind of terminal sterilization technology really, should be revised as sterile production technology.

And the adrenalin hydrochloride injection adopts in the prior art is 100 ℃ of sterilizations 30 minutes, can not guarantee that the SAL after the product sterilization is not more than 10 ^-6, so be necessary to seek more advanced preparation technology, in view of these article after 121 ℃ of sterilizations in 12 minutes, each item index is difficult to reach the quality standard of two adrenalin hydrochloride injection of Chinese Pharmacopoeia version in 2010, so show it is adopted sterile production.

The adrenalin hydrochloride injection mainly is applicable to because of severe dyspnea due to the bronchospasm, and the anaphylactic shock that causes such as cushion also can be used for prolonging the action time of infiltration anesthesia medication rapidly.The sudden cardiac arrest that causes for a variety of causes is carried out the main rescue medication of cardio-pulmonary resuscitation.

Adrenalin hydrochloride, chemical name are (R)-4 [2-(methylamino)-1-hydroxyethyl]-1,2-Benzodiazepines hydrochlorate, and structural formula is following:

Molecular formula: C ₉H ₁₃NO ₃HCl, molecular weight: 219.67.

[summary of the invention]

First purpose of the present invention provides a kind of adrenalin hydrochloride injection.

Second purpose of the present invention provides a kind of preparation process of adrenalin hydrochloride injection.

For realizing above-mentioned purpose, the present invention discloses following technical scheme: a kind of adrenalin hydrochloride injection comprises following composition:

Every 100kg includes,

Epinephrine 99.3g

Sodium pyrosulfite 99.3g

Sodium chloride 794.4g

Disodium edetate 29.8g

1mol/L hydrochloric acid is an amount of

Water for injection adds to 100kg

Said being meant in right amount uses an amount of 1mol/L hydrochloric acid to transfer pH to 3.6～4.0.

The preparation process of described adrenalin hydrochloride injection comprises following steps:

(1) in the preparation container, adds the water for injection below 30 ℃ of preparing cumulative volume amount 90%, logical CO ₂15 minutes, make it saturated;

(2) sodium chloride is dissolved in an amount of water for injection below 30 ℃, saidly accounts for total amount of preparation 5% in right amount;

(3) with disodium edetate, with the water for injection dissolving of boiling;

(4) disodium edetate solution that the sodium chloride solution that step (2) is obtained, step (3) obtain and sodium pyrosulfite and epinephrine are dissolved in respectively in the water for injection of above-mentioned steps (1) acquisition, stir and make dissolving;

(5) survey the pH that step (4) obtains solution, transfer pH to 3.6～4.0, add water for injection to total amount and stir with 1mol/L hydrochloric acid;

(6) solution that obtains with the filter membrane filtration step (5) of 0.45um, 0.22 μ m;

(7) solution that step (6) is obtained carries out aseptic embedding by the embedding operation sequence, logical N in ampoule during embedding ₂Or carry out embedding by the embedding operation sequence, logical N in ampoule during embedding ₂, 100 ℃ of sterilizations in 30 minutes.

Good effect of the present invention:, obtain to satisfy the product of Chinese Pharmacopoeia adrenalin hydrochloride injection quality standard through sterile production technology.

[specific embodiment]

Below in conjunction with embodiment the present invention is done detailed explanation, embodiment is intended to explain and non-limiting technical scheme of the present invention.

Preparation embodiment 1

(1) in the preparation container, adds the water for injection below 30 ℃ of preparing total amount 90%, logical CO ₂15 minutes, make it saturated;

(2) sodium chloride is dissolved in an amount of water for injection below 30 ℃, saidly accounts for total amount of preparation 5% in right amount;

(3) with disodium edetate, with the water for injection dissolving of boiling;

(4) disodium edetate solution that the sodium chloride solution that step (2) is obtained, step (3) obtain and sodium pyrosulfite and epinephrine are dissolved in respectively in the water for injection of above-mentioned steps (1) acquisition, stir and make dissolving;

(5) survey the middle pH that step (4) obtains solution, transfer pH to 3.6～4.0, add water for injection to total amount and stir with 1mol/L hydrochloric acid;

(6) solution that obtains with the filter membrane filtration step (5) of 0.45um, 0.22 μ m;

(7) solution that step (6) is obtained carries out aseptic embedding by the embedding operation sequence, logical N in ampoule during embedding ₂Or carry out embedding by the embedding operation sequence, logical N in ampoule during embedding ₂, 100 ℃ of sterilizations in 30 minutes.

Preparation embodiment 2

(1) adds the water for injection below 30 ℃ of 900g in the container in preparation, logical CO ₂15 minutes, make it saturated;

(2) sodium chloride 7.944g is dissolved in the water for injection of 50g below 30 ℃;

(3) with disodium edetate 0.298g, with the water for injection 10g dissolving of boiling;

(4) disodium edetate solution that the sodium chloride solution that step (2) is obtained, step (3) obtain and sodium pyrosulfite 0.993g and epinephrine 0.993g are dissolved in respectively in the water for injection of above-mentioned steps (1) acquisition, stir and make dissolving;

(5) survey the pH that step (4) obtains solution, transfer pH to 3.6～4.0, add water for injection and stir to 1000g with 1mol/L hydrochloric acid;

(6) solution that obtains with the filter membrane filtration step (5) of 0.45um, 0.22 μ m;

(7) solution that step (6) is obtained carries out aseptic embedding by the embedding operation sequence, logical N in ampoule during embedding ₂Or carry out embedding by the embedding operation sequence, logical N in ampoule during embedding ₂, 100 ℃ of sterilizations in 30 minutes.

Preparation embodiment 3

(1) adds the water for injection below 30 ℃ of 1800g in the container in preparation, logical CO ₂15 minutes, make it saturated;

(2) sodium chloride 15.888g is dissolved in the water for injection of 100g below 30 ℃;

(3) with disodium edetate 0.596g, with the water for injection 20g dissolving of boiling;

(4) disodium edetate solution that the sodium chloride solution that step (2) is obtained, step (3) obtain and sodium pyrosulfite 1.986g and epinephrine 1.986g are dissolved in respectively in the water for injection of above-mentioned steps (1) acquisition, stir and make dissolving;

(5) survey the pH that step (4) obtains solution, transfer pH to 3.6～4.0, add water for injection and stir to 2000g with 1mol/L hydrochloric acid;

(6) solution that obtains with the filter membrane filtration step (5) of 0.45um, 0.22 μ m;

(7) solution that step (6) is obtained carries out aseptic embedding by the embedding operation sequence, logical N in ampoule during embedding ₂Or carry out embedding by the embedding operation sequence, logical N in ampoule during embedding ₂, 100 ℃ of sterilizations in 30 minutes.

The above only is a preferred implementation of the present invention; Should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention; Can also make some improvement and retouching, these improvement and retouching also should be regarded as protection scope of the present invention.

Claims (2)

1. an adrenalin hydrochloride injection is characterized in that, comprises following composition:

Every 100kg includes,

Epinephrine 99.3g

Sodium pyrosulfite 99.3g

Sodium chloride 794.4g

Disodium edetate 29.8g

1mol/L hydrochloric acid is an amount of

Water for injection adds to 100kg

Said being meant in right amount uses an amount of 1mol/L hydrochloric acid to transfer pH to 3.6～4.0.

2. the preparation process of the described adrenalin hydrochloride injection of claim 1 is characterized in that, comprises following steps:

(1) in the preparation container, adds the water for injection below 30 ℃ of preparing cumulative volume amount 90%, logical CO ₂15 minutes, make it saturated;

(2) sodium chloride is dissolved in an amount of water for injection below 30 ℃, saidly accounts for total amount of preparation 5% in right amount;

(3) with disodium edetate, with the water for injection dissolving of boiling;

(4) disodium edetate solution that the sodium chloride solution that step (2) is obtained, step (3) obtain and sodium pyrosulfite and epinephrine are dissolved in respectively in the water for injection of above-mentioned steps (1) acquisition, stir and make dissolving;

(5) survey the pH that step (4) obtains solution, transfer pH to 3.6～4.0, add water for injection to total amount and stir with 1mol/L hydrochloric acid;

(6) solution that obtains with the filter membrane filtration step (5) of 0.45um, 0.22 μ m;

(7) solution that step (6) is obtained carries out aseptic embedding by the embedding operation sequence, logical N in ampoule during embedding ₂Or carry out embedding by the embedding operation sequence, logical N in ampoule during embedding ₂, 100 ℃ of sterilizations in 30 minutes.