Unlock instant, AI-driven research and patent intelligence for your innovation.

Preparation method for stable valnemulin hydrochloride composition

A technology of warnemulin hydrochloride and composition, which is applied in the field of warnemulin hydrochloride composition, can solve the problems of the company's production, strong moisture absorption, gastric mucosal hyperemia, etc., and achieve reduced stimulation, low preparation cost, and extended shelf life Effect

Inactive Publication Date: 2018-12-04
北京科百大科技有限责任公司
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, warnemulin hydrochloride has a strong irritant to the gastric mucosa, and long-term use can easily lead to gastric mucosal hyperemia, ulcers, bleeding and other side effects, and can easily cause vomiting, anorexia and other reactions, affecting the feed intake of livestock and poultry; in addition, Wernemulin hydrochloride has strong hygroscopicity, is unstable to light, and is easy to decompose when in contact with feed
More importantly: warnemulin hydrochloride is very unstable, and its raw material medicine degrades more than 9% after being placed at room temperature for 3 months. Most of the domestic powders have a shelf life of about 6 months, and some have a shelf life of less than 3 months. caused some companies to abandon the production of the product
The above are the main reasons why there are no more companies producing solid preparations containing warnemulin hydrochloride even though it has been on the market in China for more than 10 years.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1. the impact of the content ratio of solid dispersion medium and warnemulin hydrochloride on the stability of warnemulin hydrochloride

[0027] (1) Basic formula (weight ratio): 1,2-propanediol 0.8%, BHA0.015%, PG0.007%, monoglyceride and the content ratio of warnemulin hydrochloride are shown in Table 1, with 60-160 mesh sieve Add corncob meal between holes to 100%.

[0028] (2) Preparation method: Prepare according to the method described in paragraph [0022] to [0023].

[0029] Table 1 The effect of the content ratio of solid dispersion medium to warnemulin hydrochloride on the stability of warnemulin hydrochloride

[0030] The content ratio of monoglyceride to Warney hydrochloride

90 days accounted for % of the labeled amount

180 days accounted for % of the marked amount

5 to 1

85.2.7-87.6

83.4-84.7

10 to 1

93.9-95.6

92.06-93.8

20 to 1

95.4-97.2

94.8-96.3

30 to 1

97.7-99.6

96.5-97.4

...

Embodiment 2

[0033] Embodiment 2. The stability test and the result of the preferred warnemulin hydrochloride composition

[0034] (1) Basic formula (weight ratio): 1%, 1,2-propanediol 1.2%, BHA0.015%, PG0.007%, solid dispersion medium see table 2, with 60-160 mesh sieve hole Add corncob meal in between to 100%.

[0035] (2) Preparation method: Prepare according to the method described in paragraph [0022] to [0023].

[0036] (3) Stability test: The composition recorded in Table 2 and the control sample (spraying warnemulin hydrochloride directly on the starch) prepared by a conventional method were subjected to a stability test. The samples were packed in aluminum / plastic composite bags, sealed and stored at 38-40°C, samples were taken at 0 days, 90 days and 180 days, and the content of warnemulin was detected by HPLC. The results are shown in Table 2.

[0037] Table 2 Preferred Composition Stability Studies

[0038] solid dispersion medium

content(%)

90 days accounted ...

Embodiment 3

[0041] Embodiment 3. prepare warnemulin hydrochloride composition with enteric-coated acrylic resin II

[0042]Take 8 grams of enteric-coated acrylic resin No. II and mix with 70 ml of 95% ethanol, stir and dissolve, then add 4 grams of warnemulin hydrochloride, 0.012 grams of BHA, and 0.005 grams of PG, stir and dissolve, and prepare a solution of warnemulin hydrochloride; Mix the warnemulin hydrochloride solution with 188 grams of corncob powder passed through a 40-mesh sieve, dry at 40-60° C., and pass through a 30-mesh sieve to obtain an enteric-coated composition containing the warnemulin hydrochloride. Measured according to the method in the Pharmacopoeia, the in vitro release rate of the composition in 0.1 mol / L hydrochloric acid solution for 2 hours is less than 15%, and the in vitro release rate in phosphate buffer solution with a pH value of 6.8 is greater than 93%. Treated at 38-40°C for 90 days, the content of warnemulin hydrochloride is 92.8-93.6% of the initial a...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention takes corn cob powder as a vector and applies a solid dispersion technology to prepare a compostion containing valnemulin hydrochloride. The method can effectively embed the valnemulin hydrochloride so that the valnemulin hydrochloride can be separated from air, and therefore, the attack of oxygen in the air can be blocked; solid dispersion media protect valnemulin hydrochloride molecules, so that the amide bonds of the valnemulin hydrochloride molecules cannot be or less be damaged, and drug shelf life can be prolonged; the selected composition is in a phosphate buffer with pH 6.8, the releasing rate of the valnemulin hydrochloride is larger than 90%, and less than 9% in a hydrochloric acid solution of 0.1 mol / L for 2 hours, which means that the composition overcomes the defect of the gastric irritation by the valnemulin hydrochloride; and the corn cob powder can be taken as the vector of a solid dispersion containing the valnemulin hydrochloride. The distinctive advantages of the preparation technology are that operation is easy, and preparation costs are low. The composition contains (by weight / weight ratio) 0.5-10% of the valnemulin hydrochloride, 5-25% of the solid dispersion media, and 0.02-0.5% of an anti-oxidant, with the balance being the corn cob powder; and 0.5-2% of 1,2-propylene glycol can be also added in the composition.

Description

technical field [0001] The invention relates to the technical field of preparation of veterinary drug preparations, in particular to using corn cob powder as a carrier and applying solid dispersion technology to prepare a stable vornemulin hydrochloride composition with longer shelf life and enteric coating characteristics. Background technique [0002] Warnemulin hydrochloride is a new generation of pleuromutilin semi-synthetic antibiotics. It belongs to the same class of drugs as tiamulin fumarate. It is a special antibacterial drug for animals. It is mainly used to prevent and treat mycoplasma diseases in pigs, cattle, sheep and poultry. and Gram-positive bacterial infections. Warnemulin is mainly concentrated in the lungs and is an ideal drug for the treatment of various mycoplasma-induced lung diseases. However, warnemulin hydrochloride has a strong irritant to the gastric mucosa, and long-term use can easily lead to gastric mucosal hyperemia, ulcers, bleeding and othe...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K47/46A61K47/32A61K47/10A61K47/14A61K31/22A61P31/04
CPCA61K9/145A61K9/146A61K9/148A61K31/22
Inventor 王玉万戴晓曦沈力
Owner 北京科百大科技有限责任公司