阅读说明：本技术 一种伊维菌素注射液及其制备方法 (Ivermectin injection and preparation method thereof ) 是由 崔赢予 井旭东 唐伟 苏景 徐丽 郝敬友 杨宁 张宇田 梁文静 张萍 于 2021-09-16 设计创作，主要内容包括：本发明公开了一种伊维菌素注射液及其制备方法,伊维菌素注射液包括伊维菌素、莫奈太尔、阿苯达唑亚砜盐酸盐、助悬剂、乳化剂、丙二醇、乙基纤维素、油酸乙酯,非离子表面活性剂。采用伊维菌素、莫奈太尔和阿苯达唑亚砜盐酸盐作为杀虫的有效成分,通过载体溶剂的优选,使用丙二醇和甘油甲缩醛作为溶剂和助溶剂,油酸乙酯作为缓释剂,能够很好地提高产品质量和生物利用度,驱虫效果显著,并且有利于维持药物活性,促进药物相互协同作用,由此扩大了杀虫谱,提高了杀虫效果,能有效减缓抗药性的产生。(The invention discloses an ivermectin injection and a preparation method thereof, and the ivermectin injection comprises ivermectin, monel, albendazole sulfoxide hydrochloride, a suspending agent, an emulsifying agent, propylene glycol, ethyl cellulose, ethyl oleate and a nonionic surfactant. The ivermectin, the monel and the albendazole sulfoxide hydrochloride are used as effective insecticidal components, the propylene glycol and the glycerol methylal are used as a solvent and a cosolvent through the optimization of a carrier solvent, the ethyl oleate is used as a slow release agent, the product quality and the bioavailability can be well improved, the insect repelling effect is obvious, the medicinal activity can be favorably maintained, the synergistic effect of medicines is promoted, the insecticidal spectrum is expanded, the insecticidal effect is improved, and the generation of drug resistance can be effectively slowed down.)

1. The ivermectin injection is characterized by comprising the following components in parts by weight: 0.2-0.6 part of ivermectin, 0.1-0.3 part of monel, 0.2-0.6 part of albendazole sulfoxide hydrochloride, 0.02-0.07 part of suspending agent, 0.08-0.1 part of emulsifying agent, 10-16 parts of propylene glycol, 2-4 parts of ethyl cellulose, 4-8 parts of ethyl oleate and 0.2-0.4 part of nonionic surfactant.

2. The ivermectin injection according to claim 1, wherein the suspending agent is one or more of methylcellulose, pluronic F-68, carboxymethylcellulose, sodium alginate, aluminum monostearate, silicone oil, polyvinylpyrrolidone, gelatin, mannitol and sorbitol.

3. The ivermectin injection according to claim 1, wherein the emulsifier is one or more selected from polysorbate-80, lecithin, soybean lecithin, polyoxyethylene castor oil and calcium dodecylbenzene sulfonate.

4. The ivermectin injection according to claim 1, wherein the non-ionic surfactant is tween-80, tween-60 or tween-40.

5. A process for the preparation of ivermectin injection according to claims 1 to 4, characterized in that it comprises the following steps:

(1) weighing the raw materials in proportion;

(2) and adding ivermectin, monel, albendazole sulfoxide hydrochloride, a suspending agent, an emulsifier, propylene glycol, ethyl cellulose, ethyl oleate and a nonionic surfactant into the liquid preparation tank, stirring to completely dissolve all the components, filtering, filling and sealing, and sterilizing to obtain the ivermectin injection.

6. The method for preparing ivermectin injection according to claim 5, wherein the stirring temperature in the step (2) is 15-25 ℃, and the stirring speed is 500-1000 r/min.

7. The method for preparing ivermectin injection according to claim 5, wherein the sterilization in the step (2) is cobalt 60 ray sterilization.

Technical Field

The invention relates to the technical field of veterinary medicines, and particularly relates to an ivermectin injection and a preparation method thereof.

Background

Ivermectin is a novel broad-spectrum, high-efficiency and low-toxicity antibiotic anti-parasitic drug, has good expelling and killing effects on parasites in vivo and in vitro, particularly on nematodes and arthropods, is effective on microfilaria of onchocerciasis, and is also effective on dung garden filaria only in intestinal tracts. The ivermectin is widely applied clinically, and the peak value of the blood reaches 2 to 4 hours after the oral administration of the ivermectin in livestock and poultry. However, the oral bioavailability is only 41% of the injection administration, which limits the wide application of the oral preparation. Although ivermectin injection is developed, different solvents are used in preparation, so that different problems exist in product quality. Recent studies have confirmed that the slow release formulation of ivermectin can slow the development of drug resistance.

However, most of the existing ivermectin sustained-release medicaments are single medicament varieties, which not only limit the application of medicaments, but also have narrow insecticidal spectrum of single medicaments, and are easy to generate drug resistance. Therefore, the problem to be solved by the technical personnel in the field is how to provide a high-efficiency ivermectin injection preparation capable of long-acting slow-release broad-spectrum sterilization and disinsection.

Disclosure of Invention

In view of the above, the invention provides an ivermectin injection and a preparation method thereof, and other medicines with synergistic effect are jointly used for preparing a sustained-release medicament, so that the ivermectin injection has longer-acting performance and avoids drug resistance.

In order to achieve the purpose, the invention adopts the following technical scheme:

the ivermectin injection comprises the following components in parts by weight: 0.2-0.6 part of ivermectin, 0.1-0.3 part of monel, 0.2-0.6 part of albendazole sulfoxide hydrochloride, 0.02-0.07 part of suspending agent, 0.08-0.1 part of emulsifying agent, 10-16 parts of propylene glycol, 2-4 parts of ethyl cellulose, 4-8 parts of ethyl oleate and 0.2-0.4 part of nonionic surfactant.

Preferably, the suspending agent is one or more of methylcellulose, pluronic F-68, carboxymethylcellulose, sodium alginate, aluminum monostearate, silicone oil, polyvinylpyrrolidone, gelatin, mannitol and sorbitol.

Preferably, the emulsifier is one or more of polysorbate-80, lecithin, soybean lecithin, polyoxyethylene castor oil and calcium dodecylbenzene sulfonate.

Preferably, the non-ionic surfactant is tween-80, tween-60 or tween-40.

The invention also provides a preparation method of the ivermectin injection in the technical scheme, which comprises the following steps:

(1) weighing the raw materials in proportion;

(2) and adding ivermectin, monel, albendazole sulfoxide hydrochloride, a suspending agent, an emulsifier, propylene glycol, ethyl cellulose, ethyl oleate and a nonionic surfactant into the liquid preparation tank, stirring to completely dissolve all the components, filtering, filling and sealing, and sterilizing to obtain the ivermectin injection.

Preferably, the stirring temperature in the step (2) is 15-25 ℃, and the stirring speed is 500-1000 r/min.

Preferably, the sterilization in step (2) is cobalt 60 radiation sterilization.

Through the technical scheme, compared with the prior art, the invention provides the ivermectin injection and the preparation method thereof, the ivermectin, the monel and the albendazole sulfoxide hydrochloride are used as effective insecticidal components, the propylene glycol and the glycerol formal are used as a solvent and a cosolvent through the optimization of a carrier solvent, the ethyl oleate is used as a slow release agent, the product quality and the bioavailability can be well improved, the insect expelling effect is remarkable, the medicinal activity can be favorably maintained, the synergistic effect of medicaments is promoted, the insecticidal spectrum is expanded, the insecticidal effect is improved, and the generation of drug resistance can be effectively slowed down; in addition, the suspending agent and the emulsifying agent are added into the injection, so that the injection forms a stable system and is not easy to be oxidized. The invention has simple production process, stable product quality, long standing time without deterioration, no need of existing preparation, large-scale production, safety, no toxicity, obvious curative effect, small side effect, longer administration interval time, simple administration operation and small irritation, is particularly suitable for large-area prevention and treatment of livestock parasitic diseases, has low cost and obvious insect expelling effect, can fully exert the pharmacological activity of ivermectin, thereby improving the synergistic effect of the drug effect and other insecticidal drugs and providing a better solution for clinical treatment and prevention of the livestock parasitic diseases.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

The ivermectin injection comprises the following components in parts by weight: 0.2-0.6 part of ivermectin, 0.1-0.3 part of monel, 0.2-0.6 part of albendazole sulfoxide hydrochloride, 0.02-0.07 part of suspending agent, 0.08-0.1 part of emulsifying agent, 10-16 parts of propylene glycol, 2-4 parts of ethyl cellulose, 4-8 parts of ethyl oleate and 0.2-0.4 part of nonionic surfactant.

Wherein the suspending agent is selected from one or more of methylcellulose, pluronic F-68, carboxymethylcellulose, sodium alginate, aluminum monostearate, silicone oil, polyvinylpyrrolidone, gelatin, mannitol, and sorbitol; the emulsifier is one or more of polysorbate-80, lecithin, soybean lecithin, polyoxyethylene castor oil and calcium dodecyl benzene sulfonate; the non-ionic surfactant is tween-80, tween-60 or tween-40.

Example 1

The ivermectin injection comprises the following components in parts by weight: 0.2-0.6 part of ivermectin, 0.1-0.3 part of monel, 0.2-0.6 part of albendazole sulfoxide hydrochloride, 0.02-0.07 part of suspending agent, 0.08-0.1 part of emulsifying agent, 10-16 parts of propylene glycol, 2-4 parts of ethyl cellulose, 4-8 parts of ethyl oleate and 0.2-0.4 part of nonionic surfactant.

Wherein the suspending agent is selected from one or more of methylcellulose, pluronic F-68, carboxymethylcellulose, sodium alginate, aluminum monostearate, silicone oil, polyvinylpyrrolidone, gelatin, mannitol, and sorbitol; the emulsifier is one or more of polysorbate-80, lecithin, soybean lecithin, polyoxyethylene castor oil and calcium dodecyl benzene sulfonate; the non-ionic surfactant is tween-80, tween-60 or tween-40.

Example 2

The ivermectin injection comprises the following components in parts by weight: 0.2 part of ivermectin, 0.1 part of monel, 0.6 part of albendazole sulfoxide hydrochloride, 0.02 part of a suspending agent, 0.08 part of an emulsifier, 10 parts of propylene glycol, 2 parts of ethyl cellulose, 4 parts of ethyl oleate and 0.2 part of a nonionic surfactant.

Wherein the suspending agent is selected from one or more of methylcellulose, pluronic F-68, carboxymethylcellulose, sodium alginate, aluminum monostearate, silicone oil, polyvinylpyrrolidone, gelatin, mannitol, and sorbitol; the emulsifier is one or more of polysorbate-80, lecithin, soybean lecithin, polyoxyethylene castor oil and calcium dodecyl benzene sulfonate; the non-ionic surfactant is tween-80, tween-60 or tween-40.

Example 3

The ivermectin injection comprises the following components in parts by weight: 0.4 part of ivermectin, 0.2 part of monel, 0.24 part of albendazole sulfoxide hydrochloride, 0.05 part of a suspending agent, 0.09 part of an emulsifying agent, 12 parts of propylene glycol, 23 parts of ethyl cellulose, 46 parts of ethyl oleate and 0.3 part of a nonionic surfactant.

Wherein the suspending agent is selected from one or more of methylcellulose, pluronic F-68, carboxymethylcellulose, sodium alginate, aluminum monostearate, silicone oil, polyvinylpyrrolidone, gelatin, mannitol, and sorbitol; the emulsifier is one or more of polysorbate-80, lecithin, soybean lecithin, polyoxyethylene castor oil and calcium dodecyl benzene sulfonate; the non-ionic surfactant is tween-80, tween-60 or tween-40.

Example 4

The ivermectin injection comprises the following components in parts by weight: 0.6 part of ivermectin, 0.3 part of monel, 0.2 part of albendazole sulfoxide hydrochloride, 0.07 part of a suspending agent, 0.1 part of an emulsifying agent, 16 parts of propylene glycol, 4 parts of ethyl cellulose, 8 parts of ethyl oleate and 0.4 part of a nonionic surfactant.

Wherein the suspending agent is selected from one or more of methylcellulose, pluronic F-68, carboxymethylcellulose, sodium alginate, aluminum monostearate, silicone oil, polyvinylpyrrolidone, gelatin, mannitol, and sorbitol; the emulsifier is one or more of polysorbate-80, lecithin, soybean lecithin, polyoxyethylene castor oil and calcium dodecyl benzene sulfonate; the non-ionic surfactant is tween-80, tween-60 or tween-40.

Example 5

The ivermectin injection comprises the following components in parts by weight: 0.5 part of ivermectin, 0.2 part of monel, 0.5 part of albendazole sulfoxide hydrochloride, 0.04 part of a suspending agent, 0.08 part of an emulsifying agent, 11 parts of propylene glycol, 2 parts of ethyl cellulose, 8 parts of ethyl oleate and 0.3 part of a nonionic surfactant.

Wherein the suspending agent is selected from one or more of methylcellulose, pluronic F-68, carboxymethylcellulose, sodium alginate, aluminum monostearate, silicone oil, polyvinylpyrrolidone, gelatin, mannitol, and sorbitol; the emulsifier is one or more of polysorbate-80, lecithin, soybean lecithin, polyoxyethylene castor oil and calcium dodecyl benzene sulfonate; the non-ionic surfactant is tween-80, tween-60 or tween-40.

The preparation method of the ivermectin injection in the embodiment comprises the following steps:

(1) weighing the raw materials in proportion;

(2) and adding ivermectin, monel, albendazole sulfoxide hydrochloride, a suspending agent, an emulsifier, propylene glycol, ethyl cellulose, ethyl oleate and a nonionic surfactant into the liquid preparation tank, stirring at the temperature of 15-25 ℃ for 1000r/min to completely dissolve all the components, filtering, filling and sealing the mixture, and sterilizing by cobalt 60 rays to obtain the ivermectin injection.

Comparative example

The difference from example 3 is that no monel, albendazole sulfoxide hydrochloride was added.

Examples of the experiments

The anthelmintic effect of 8 th time after 5-7 times of injection anthelmintic period is tested on livestock housed in the same environment by adopting the medicaments prepared in the examples 1-5 and the comparative example 1, and the result shows that the anthelmintic effect of the medicament prepared in the examples 1-5 is kept good and at a higher level, while the anthelmintic effect of the medicament prepared in the technical scheme of the comparative example 1 is greatly reduced, and the livestock generates drug resistance.

The embodiments in the present description are described in a progressive manner, each embodiment focuses on differences from other embodiments, and the same and similar parts among the embodiments are referred to each other.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.