CN-122005447-A - Penehyclidine hydrochloride injection and preparation method thereof

Abstract

The invention provides a penehyclidine hydrochloride injection and a preparation method thereof, which comprises the step of filling penehyclidine hydrochloride intermediate liquid medicine into a polypropylene medicinal plastic ampoule bottle. The invention does not need to pre-acidify the inner wrapping material and control the intermediate liquid medicine in a narrower pH range. By adopting the technical scheme of the invention, the problems of rising of the pH and lowering of the content of the liquid medicine in the high-temperature sterilization process and the stability placing process can be solved, and meanwhile, the wider intermediate pH range (pH 4.5-6.0) is controlled in the production, so that the operability of the production is facilitated, the wrapping material is easy to obtain, the production process is simple and convenient, and the production effect is improved.

Inventors

• DENG QIUYING
• HU TING
• SHI XIANGJIE
• SHAN JIAMING
• WANG LEI
• ZHAO ZHOUMING

Assignees

• 浙江华海药业股份有限公司

Dates

Publication Date

20260512

Application Date

20251111

Priority Date

20241111

Claims (10)

1. 1. A preparation method of penehyclidine hydrochloride injection is characterized by comprising the step of filling penehyclidine hydrochloride intermediate liquid medicine into a medicinal plastic ampoule bottle.
2. 2. The method of claim 1, wherein the pharmaceutical plastic ampoule is a polypropylene plastic ampoule.
3. 3. The preparation method of claim 1, wherein the penehyclidine hydrochloride intermediate liquid has a pH of 4.5-6.0.
4. 4. The preparation method of the penehyclidine hydrochloride intermediate liquid medicine is characterized by comprising the steps of adding a prescribed amount of penehyclidine hydrochloride raw material medicine into 80% of prescribed amount of injection water, stirring for dissolution, adjusting the pH of the liquid medicine to 4.5-6.0 by using a pH regulator, adding the injection water to the prescribed amount, and stirring and uniformly mixing to obtain the penehyclidine hydrochloride intermediate liquid medicine.
5. 5. The preparation method according to claim 4, wherein the prescription is penehyclidine hydrochloride 0.5mg or 1mg, and water for injection is added to 1.0ml.
6. 6. The method according to claim 4, wherein the pH adjuster is an aqueous hydrochloric acid solution or an aqueous sodium hydroxide solution, and the concentration of the aqueous hydrochloric acid solution is preferably 0.1 to 0.5mol/L, and the concentration of the aqueous sodium hydroxide solution is preferably 0.1 to 0.5mol/L.
7. 7. The preparation method of the penehyclidine hydrochloride injection according to claim 4, further comprising the step of filtering the penehyclidine hydrochloride intermediate liquid medicine through a filter membrane, preferably having a membrane pore size of 0.22 μm, before filling.
8. 8. The preparation method of the penehyclidine hydrochloride injection according to claim 4, further comprising the steps of sealing after filling and sterilizing, wherein the sterilization is preferably carried out at a high temperature of 121-124 ℃ for 12-15min.
9. 9. The penehyclidine hydrochloride injection is characterized by comprising a penehyclidine hydrochloride bulk drug, a pH regulator and water for injection, wherein the pH value of the injection is 4.5-6.5, and an inner package material of the injection is a polypropylene medicinal plastic ampoule bottle.
10. 10. The injection according to claim 9, wherein the pH adjuster is aqueous hydrochloric acid or aqueous sodium hydroxide.

Description

Penehyclidine hydrochloride injection and preparation method thereof Technical Field The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to penehyclidine hydrochloride injection and a preparation method thereof. Background Penehyclidine hydrochloride is a novel selective anticholinergic agent, can be combined with M, N choline receptor, can inhibit smooth muscle and gland physiological functions of postganglionic cholinergic innervation, can resist muscarinic and nicotinic actions of acetylcholine and other cholinergic medicaments, can permeate blood brain barrier, and has stronger and comprehensive central and peripheral anticholinergic actions, and has the structural formula: The common preparation form of the penehyclidine hydrochloride is injection, is used for administration before anesthesia to inhibit salivary gland and airway gland secretion, and is used for first aid treatment of organophosphorus poison (pesticide) poisoning and maintenance of atropine after late poisoning or cholinesterase (ChE) aging. In the national drug standard, the pH value of the penehyclidine hydrochloride injection needs to be controlled at 4.5-6.5. The inventor's experimental study in Chinese patent CN102525909B shows that the penehyclidine hydrochloride compound is dissolved in water and then directly filled in any existing commercial ampoule bottle and penicillin bottle which are not pretreated, the stability is poor, obvious changes of pH value rise and content decline occur after long-term storage for 8 months, the quality and curative effect of the medicine are unstable due to the pH value and content change, and even the medicine exceeds the qualified limit, so that the medicine becomes a disqualified medicine. In order to solve the problem, the application discloses that the pH value of penehyclidine hydrochloride intermediate liquid is adjusted to 4.6-4.8, and then the solution is filled into a medicinal glass ampoule bottle or a penicillin bottle. Chinese patent CN102525910B is used for solving the problems of pH rise and content drop of the penehyclidine hydrochloride injection in the process of stability placement, preventing unqualified products, and carrying out acidification heat treatment on an inner packing material (ampoule or penicillin bottle) by using acid liquor with different concentrations in advance before filling. Chinese patent CN103271872B discloses a preparation method of penehyclidine hydrochloride injection, dissolving penehyclidine hydrochloride with water for injection, adding 0.01% active carbon, stirring, decarbonizing for 15 min by titanium rod circulation, adjusting pH to 4.30 by hydrochloric acid solution, fine filtering by filter membrane, and filling in low-boron silicon or medium-boron silicon ampoule bottle. Chinese patent CN103284943B discloses a preparation process of penehyclidine hydrochloride injection, which comprises heat treating inner package material (ampoule bottle or penicillin bottle) with hydrochloric acid, sulfuric acid, acetic acid, phosphoric acid, nitric acid or oxalic acid solution, and controlling intermediate liquid pH to be 4.6-4.8, so as to solve the problems of rise in pH and fall in content of penehyclidine hydrochloride injection during stable placement, and prevent unqualified products. Chinese patent CN112716889B discloses a preparation method of penehyclidine hydrochloride injection, which comprises the steps of adjusting pH value of penehyclidine hydrochloride liquid, circulating and once filtering through a large-aperture filter element and a small-aperture filter element in series until the pH value is stable, and then sterilizing through secondary filtration until the filling and sealing. In view of the prior art, a new solution is still necessary to provide, so that the penehyclidine hydrochloride injection prescription process is simple, and the product quality is qualified within the shelf life. Disclosure of Invention The invention provides a preparation method of penehyclidine hydrochloride injection, which comprises the step of filling penehyclidine hydrochloride intermediate liquid medicine into a medicinal plastic ampoule bottle. In some embodiments, the pharmaceutical plastic ampoule is a polypropylene pharmaceutical plastic ampoule. In some embodiments, the pH of the penehyclidine hydrochloride intermediate solution is 4.5-6.0. In some specific embodiments, the penehyclidine hydrochloride intermediate liquid medicine is prepared by adding a prescription amount of penehyclidine hydrochloride raw material medicine into 80% of injection water, stirring and dissolving, adjusting the pH of the liquid medicine to 4.5-6.0 by using a pH regulator, adding the injection water to the prescription amount, and stirring and mixing uniformly to obtain the penehyclidine hydrochloride intermediate liquid medicine. In some embodiments, the formulation is penehyclidine hydrochloride 0.5mg or 1mg, and water fo