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CN-117205163-B - Viku ammonium bromide freeze-dried agent for injection and production process thereof

CN117205163BCN 117205163 BCN117205163 BCN 117205163BCN-117205163-B

Abstract

The invention discloses a vecuronium bromide freeze-dried preparation for injection and a production process thereof, wherein the vecuronium bromide freeze-dried preparation comprises, by weight, 3-5 parts of vecuronium bromide, 0.21-1.35 parts of citric acid, 7.9-9.3 parts of disodium hydrogen phosphate, 10.5-13.2 parts of mannitol and 8.5-12.8 parts of povidone K, wherein each unit of preparation is calculated by 3-5 mg of vecuronium bromide, the preparation is prepared by adding 3-5 mg of povidone K, mannitol into water for injection to dissolve, then adding citric acid and disodium hydrogen phosphate to dissolve, then adding vecuronium bromide, supplementing water for injection, then adjusting pH to be neutral, then treating with active carbon for injection, then decarburizing and filtering, supplementing water for injection to be full, subpackaging and freeze-drying in stages. The vecuronium bromide freeze-dried solution for injection is neutral, can relieve injection pain, and has good stability.

Inventors

  • MA JING
  • DOU WENXUAN
  • PAN AIMEI
  • WANG SU
  • SHEN FEI

Assignees

  • 南京新百药业有限公司

Dates

Publication Date
20260508
Application Date
20231012

Claims (8)

  1. 1. The vecuronium bromide freeze-dried preparation for injection is characterized by comprising, by weight, 3-5 parts of vecuronium bromide, 0.21-1.35 parts of citric acid, 7.9-9.3 parts of disodium hydrogen phosphate, 10.5-13.2 parts of mannitol and 8.5-12.8 parts of povidone K, wherein the medicine of each unit preparation is calculated by 3-5 mg of vecuronium bromide; The vecuronium bromide freeze-dried agent for injection is produced by adding povidone K30 and mannitol into water for injection calculated according to the amount of 3-5 mg of vecuronium bromide corresponding to 1ml of water for injection per unit preparation to dissolve, adding citric acid and disodium hydrogen phosphate to dissolve, adding vecuronium bromide, supplementing water for injection, regulating pH to be neutral, treating with injection active carbon, decarburizing and filtering, supplementing water for injection to the whole amount, sub-packaging according to 1ml of water for injection, and then freeze-drying in stages; The staged freeze drying is carried out by rapidly cooling to 0 ℃ and then keeping for 0.5h, slowly cooling to-45 ℃ and then keeping for 2-3 h under vacuum of 5-8 Pa, gradually heating to-18 ℃ and then carrying out the first-stage freeze drying treatment, gradually heating to 0 ℃ and then carrying out the second-stage freeze drying treatment, and gradually heating to 20-25 ℃ and then carrying out the third-stage freeze drying treatment to obtain the vecuronium bromide freeze-dried powder injection for injection; the rapid cooling rate is 2-2.5 ℃ per minute, the slow cooling rate is 2-2.5 ℃ per hour, and the gradual heating rate is 0.1-0.2 ℃ per minute.
  2. 2. The vecuronium bromide freeze-dried preparation for injection according to claim 1, wherein the vecuronium bromide freeze-dried preparation for injection comprises, by weight, 4 parts of vecuronium bromide, 0.7 part of citric acid, 8.7 parts of disodium hydrogen phosphate, 12.5 parts of mannitol and 11.3 parts of povidone K, wherein the drug per unit preparation is calculated as 4mg of vecuronium bromide.
  3. 3. The vecuronium bromide freeze-dried preparation for injection according to claim 1, wherein the vecuronium bromide freeze-dried preparation for injection comprises, by weight, 5 parts of vecuronium bromide, 0.32 part of citric acid, 9.2 parts of disodium hydrogen phosphate, 11.8 parts of mannitol and 12.2 parts of povidone K, wherein the drug per unit preparation is calculated as 5mg of vecuronium bromide.
  4. 4. A process for the production of vecuronium bromide freeze-dried for injection according to any one of claims 1 to 3 characterised in that it comprises the following steps: (1) The total amount of the water for injection is calculated according to 1ml of water for injection corresponding to 3-5 mg of vecuronium bromide per unit preparation of the medicine; (2) Firstly, 80% of water for injection is taken, povidone K30 and mannitol are added and stirred until the water for injection is completely dissolved; (3) Adding citric acid and disodium hydrogen phosphate, and stirring until the solution is completely dissolved; (4) Adding vecuronium bromide, stirring until the vecuronium bromide is completely dissolved, adding water for injection to the full amount, and regulating the pH value to be neutral; (5) Adding 0.05% (w/w) of injection active carbon into water for injection, stirring for 25min, decarbonizing, filtering, collecting filtrate, adding injection water to full amount, mixing, and packaging in penicillin bottles according to 1ml injection water calculation; (6) Then freeze-drying, namely firstly rapidly cooling to 0 ℃ and then keeping for 0.5h, slowly cooling to-45 ℃ and then keeping for 2-3 h under vacuum of 5-8 Pa, gradually heating to-18 ℃ and then performing first-stage freeze-drying treatment, gradually heating to 0 ℃ and then performing second-stage freeze-drying treatment, and gradually heating to 20-25 ℃ and then performing third-stage freeze-drying treatment to obtain the vecuronium bromide freeze-dried powder injection for injection; (7) And adding an aluminum plastic cover, sterilizing, rolling the cover, and preserving at normal temperature.
  5. 5. The process for producing vecuronium bromide freeze-dried preparation for injection according to claim 4 wherein the pH value is 6.8-7.5.
  6. 6. The process for producing vecuronium bromide freeze-dried preparation for injection according to claim 4, wherein in the step (6), the first stage freeze-drying treatment condition is that the temperature is-18 ℃, the vacuum is 18-20 Pa, and the time is 3-4 hours.
  7. 7. The process for producing vecuronium bromide freeze-dried preparation for injection according to claim 4, wherein in the step (6), the second stage freeze-drying treatment condition is that the temperature is 0 ℃, the vacuum is 30-32 Pa, and the time is 2-3 h.
  8. 8. The process for producing vecuronium bromide freeze-dried preparation for injection according to claim 4, wherein in the step (6), the third stage freeze-drying treatment condition is that the temperature is 20-25 ℃, the vacuum is 40-42 Pa, and the time is 1-2 h.

Description

Viku ammonium bromide freeze-dried agent for injection and production process thereof Technical Field The invention relates to a vecuronium bromide freeze-dried agent for injection and a production process thereof, belonging to the technical field of medicines. Background Viku ammonium bromide, the chemical name of which is brominated 1- [3 alpha, 17 beta-diacetoxy-2-beta (1-piperidyl) -5 alpha-androstane-16 beta-yl ] -1-methylpiperidine, is a general anesthesia auxiliary drug, and can promote skeletal muscle and meat floss. The existing vecuronium bromide preparation mainly comprises injection and freeze-dried powder injection, wherein the vecuronium bromide injection can lead to the reduction of medicine quality and the poor product stability due to the poor physical and chemical stability of vecuronium bromide, and the existing vecuronium bromide freeze-dried powder injection can improve the stability of the vecuronium bromide preparation, but needs to add strong acid to increase the solubility of the vecuronium bromide, the dissolved preparation is acidic, and causes serious irritation to blood vessels to cause injection pain, and researches show that intravenous injection pain is related to the pH of the injection, and the proper improvement of the pH of the injection is favorable for alleviating the injection pain. Chinese patent CN201310489082.6 discloses a vecuronium bromide freeze-dried powder injection for injection and a preparation method thereof, wherein the freeze-dried powder injection is prepared from vecuronium bromide, mannitol, lactose, trehalose, citric acid and disodium hydrogen phosphate, but the raw materials are more in variety and higher in production cost, in addition, the lactose is used for causing serious lactose intolerance due to different physique of people, the pH value of the dissolved freeze-dried powder injection is 3.8-4.2, the injection pain is easy to be caused, and CN201410102893.0 discloses a vecuronium bromide pharmaceutical composition for injection and a preparation method thereof, and the pharmaceutical composition consists of vecuronium bromide, citric acid and disodium hydrogen phosphate, and amino acid, lactose and the like are not used, but the pH value of the dissolved pharmaceutical composition is 3.8-4.2, and the injection pain is easy to be caused. Disclosure of Invention At least aiming at one problem existing in the prior art, the invention provides a vecuronium bromide freeze-dried preparation for injection and a production process thereof, wherein the vecuronium bromide freeze-dried preparation for injection takes vecuronium bromide, citric acid, disodium hydrogen phosphate, mannitol and povidone as raw materials, so that the types and cost of the raw materials are reduced, the phenomenon of lactose intolerance is avoided, and meanwhile, the solution of the freeze-dried preparation is neutral, and the injection pain can be relieved; the production process ensures that the freeze-dried preparation has full appearance, loose and porous texture, quick redissolution and clarification, and improves the stability of the freeze-dried preparation. The vecuronium bromide freeze-dried preparation for injection comprises, by weight, 3-5 parts of vecuronium bromide, 0.21-1.35 parts of citric acid, 7.9-9.3 parts of disodium hydrogen phosphate, 10.5-13.2 parts of mannitol and 8.5-12.8 parts of povidone K, wherein the medicine of each unit preparation is calculated by 3-5 mg of vecuronium bromide. Preferably, the vecuronium bromide freeze-dried preparation for injection comprises the following raw materials, by weight, 4 parts of vecuronium bromide, 0.7 part of citric acid, 8.7 parts of disodium hydrogen phosphate, 12.5 parts of mannitol and 11.3 parts of povidone K, wherein the medicine per unit preparation is calculated by 4mg of vecuronium bromide. Preferably, the vecuronium bromide freeze-dried preparation for injection comprises the following raw materials, by weight, 5 parts of vecuronium bromide, 0.32 part of citric acid, 9.2 parts of disodium hydrogen phosphate, 11.8 parts of mannitol and 12.2 parts of povidone K, wherein the medicine per unit preparation is calculated by 5mg of vecuronium bromide. The preparation method comprises the steps of adding povidone K30 and mannitol into water for injection calculated according to 3-5 mg of the vecuronium bromide corresponding to 1ml of water for injection per unit preparation to dissolve, adding citric acid and disodium hydrogen phosphate to dissolve, adding vecuronium bromide, supplementing water for injection, adjusting pH to be neutral, treating with active carbon for injection, decarburizing and filtering, supplementing water for injection to the whole volume, sub-packaging according to 1ml of water for injection, and freeze-drying in stages, and packaging. Preferably, the production process of the vecuronium bromide freeze-dried agent for injection comprises the following steps: (1) The total amount of the wa