CN111228234A - Coated lidocaine and preparation method and application thereof - Google Patents

Coated lidocaine and preparation method and application thereof Download PDF

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CN111228234A
CN111228234A CN202010049914.2A CN202010049914A CN111228234A CN 111228234 A CN111228234 A CN 111228234A CN 202010049914 A CN202010049914 A CN 202010049914A CN 111228234 A CN111228234 A CN 111228234A
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coated
sodium butyrate
weight
coating layer
acrylic resin
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宋凤香
吕延飞
阮丽青
徐洪星
王琰
张吉猛
李艳霞
陆桂英
王伟
王明月
白耀国
魏一华
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2886Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806Coating materials
    • A61K9/2833Organic macromolecular compounds
    • A61K9/284Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806Coating materials
    • A61K9/2833Organic macromolecular compounds
    • A61K9/286Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/12Antidiarrhoeals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00General protective or antinoxious agents

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Toxicology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Discloses coated thalidomide, which comprises a sodium butyrate drug-loaded pill core, an ethyl cellulose coating layer and an acrylic resin coating layer from inside to outside; the acrylic resin is selected from acid-insoluble acrylic resins. The intestinal tract can be accurately positioned, and the release of most of sodium butyrate in the caecum and colon can be ensured; in addition, the piglet feed is beneficial to improving the technical problems of slow average daily gain of piglets, high feed conversion ratio and diarrhea rate.

Description

Coated lidocaine and preparation method and application thereof
Technical Field
The invention belongs to the technical field of veterinary drug additives, relates to a mixed veterinary drug additive preparation, and particularly relates to coated thalidomide and a preparation method and application thereof.
Background
In recent years, the pig raising industry in China is facing a plurality of serious problems, including increasing feed cost, african pig suffering, stricter environmental policy, mountain-ride price fluctuation of pork, degradation of market consumption level and the like. Pig raising enterprises and feed production enterprises are facing a new round of industry shuffling. In the shuffling process, large-scale cultivation has become a trend.
Under the condition of large-scale breeding, the production rhythm of pig raising enterprises is more compact, and a full-in and full-out batch production mode is implemented. The early weaning technology of the piglets is popularized and applied in a large scale so as to improve the breeding utilization rate of the sows. When the piglets are weaned, because the development of organs of the body is immature and the functions are incomplete, no physical preparation for coping with the external environment is made, and the stress response of the piglets is caused by a plurality of factors such as environmental uncertainty, pathogenic microorganisms and the like, wherein the factors comprise poor appetite, dyspepsia, diarrhea and the like after weaning. These stress responses are collectively referred to as "early weaning stress syndrome". The disease is a common problem faced by pig raising enterprises, and the early weaning stress syndrome causes the immunity and the resistance of piglets to be in a low state, causes morbidity and mortality, and causes economic loss. Research shows that the incidence rate of early weaning stress syndrome in pig raising enterprises in China is high, and the survival rate of piglets is 8-10 percent lower than that of the piglets in developed countries.
In order to prevent early weaning stress syndrome such as piglet diarrhea, pig raising enterprises generally add antibiotics and high-content copper and zinc into feed, so that the death rate of weaned piglets can be reduced, but negative effects such as drug-resistant strains, drug residues, resource waste and environmental pollution are easily generated.
Ridomide, chemical name is sodium butyrate. After sodium butyrate is absorbed by intestinal epithelial cells, transported to the liver for further metabolism or used as energy expenditure for digestive tract epithelial cells, and butyric acid oxidation can provide 70% of energy for colon mucosal cells. As a veterinary drug and additive in pig feed, the sodium butyrate can promote the proliferation of goblet cells, improve the morphological structure of small intestine mucosa epithelial cells and promote the digestion and absorption functions of the small intestine; protects colon and caecum mucosa epithelial cells, improves the immunity level, maintains the intestinal microbial balance, and has better effects in the aspects than antibiotics.
However, sodium butyrate has special cheese sour odor, is easy to absorb moisture, deliquesce or agglomerate, and has poor storage and transportation convenience; in addition, after the sodium butyrate is imported, most of the sodium butyrate is absorbed by the stomach and the small intestine and is difficult to reach the caecum and the colon, so that the feed conversion ratio is difficult to reduce.
In order to solve the technical problems, the chinese patent application CN101301030A discloses a formula of a feed butyric acid derivative coated particle, which comprises a wall material and a core material, wherein the core material is 15-50% by weight of feed butyric acid derivative powder, and the wall material is 50-85% by weight of feed solid ester or solid fatty acid. The formula can reduce the hygroscopicity of the butyric acid derivative, is beneficial to product storage, greatly reduces the generated peculiar smell, and does not generate chemical change. However, the product has a fast release speed, most of the product is released in gastric juice, and accurate intestinal release cannot be realized.
Chinese patent CN103238730A discloses an animal feed additive microencapsulated coated sodium butyrate. Mixing hydroxypropyl methyl cellulose, chitosan and silicon dioxide, boiling and expanding at 230 ℃ in a fluidized bed, spraying a sodium butyrate aqueous solution on the mixture of the three substances, drying at high temperature, solidifying at low temperature to solidify and form sodium butyrate particles, dissolving coating materials including carnauba wax, palm oil and polyethylene glycol in an organic solvent, and performing bottom spraying coating in the fluidized bed to obtain sodium butyrate particles with uniform coating, wherein the mass percentage of the sodium butyrate is 30-70%. The feed-grade sodium butyrate powder is subjected to microencapsulation coating treatment, so that the loss of sodium butyrate in pig stomach is avoided, the rear section of small intestine is reached, the whole intestinal tract is covered, meanwhile, the odor is overcome, the deliquescence is prevented, and the sodium butyrate is protected from loss in the feed processing process. However, the retention time of the feed in the colon of the pig is only about 10 hours, so that the feed is released slowly in the colon segment, and most of the feed cannot be fully utilized.
Summarizing, the prior art has major disadvantages: the vast majority of sodium butyrate is absorbed by the stomach and small intestine and is difficult to reach the caecum and colon; even if the accurate positioning of the intestinal tract can be realized, the release of most of the sodium butyrate in the caecum and the colon is difficult to ensure, so that the average daily gain of piglets is slow, the feed conversion rate is high, and the diarrhea rate is difficult to ensure.
In view of the technical defects, a coated thalidomide (sodium butyrate preparation) which can realize accurate positioning of intestinal tracts and ensure that most of sodium butyrate is released in caecum and colon, and a preparation method and application thereof still need to be found.
Disclosure of Invention
One of the purposes of the invention is to provide coated thalidomide (sodium butyrate preparation) which can realize accurate positioning of intestinal tracts and ensure that most of sodium butyrate is released in caecum and colon, and a preparation method and application thereof.
In order to achieve the above object, in one aspect, the technical solution adopted by the present invention is as follows:
a coated Ridomino comprises a sodium butyrate drug-loaded pill core, an ethyl cellulose coating layer and an acrylic resin coating layer from inside to outside; characterized in that the acrylic resin is selected from acid-insoluble acrylic resins.
According to the coated Ridomino, the sodium butyrate medicine-carrying pill core is obtained from sodium butyrate and a microcrystalline cellulose blank pill core, and the weight ratio of the sodium butyrate medicine-carrying pill core to the microcrystalline cellulose blank pill core is 0.5-2: 1.
Preferably, the weight ratio of the sodium butyrate to the microcrystalline cellulose blank pellet core is 0.6-1.8: 1; more preferably, the weight ratio of the sodium butyrate to the microcrystalline cellulose blank pellet core is 0.8-1.5: 1; and, most preferably, the weight ratio of sodium butyrate to microcrystalline cellulose blank pellet core is 0.9-1.2: 1.
In a specific embodiment, the weight ratio of sodium butyrate to microcrystalline cellulose blank pellet core is 1: 1.
The coated thalidomide of the present invention, wherein the weight of the ethylcellulose coating layer is 3.0-7.0 wt%, based on the weight of the sodium butyrate medicated pellet core.
Preferably, the weight of the ethylcellulose coating layer is 3.5-6.5 wt% based on the weight of the sodium butyrate drug-loaded pellet core; more preferably, the ethylcellulose coating layer weight is 3.8-6.2 wt%, based on the weight of the sodium butyrate medicated pellet core; and, most preferably, the ethylcellulose coating layer weight is 4.0-6.0 wt%, based on the weight of the sodium butyrate medicated pellet core.
In a specific embodiment, the ethylcellulose coating layer weight is 5.2 wt%, based on the weight of the sodium butyrate medicated pellet core.
The coated thalidomide provided by the invention is characterized in that the average molecular weight Mn of the ethyl cellulose is 15000-24000; the ethoxy content is 47.5 to 49.5 wt.%.
Preferably, the average molecular weight Mn of the ethyl cellulose is 16000-; the ethoxy content is 47.8-49.4 wt%; more preferably, the average molecular weight Mn of the ethylcellulose is 17000-20000; the content of ethoxy is 48.0-49.2 wt%; and, most preferably, the average molecular weight Mn of the ethylcellulose is 18000-19000; the ethoxy content is 48.6-49.0 wt%.
In a specific embodiment, the ethylcellulose has an average molecular weight Mn of 18260; the ethoxy content was 48.8% by weight.
The coated briguard according to the present invention, wherein the ethylcellulose coating layer further comprises hydroxypropylmethylcellulose; the methoxyl content of the hydroxypropyl methylcellulose is 28.0-30.0 wt%; the hydroxypropoxyl content is 7.0 to 12.0 weight percent and the viscosity is 3 to 8 mPa.
In a particular embodiment, the hydroxypropylmethylcellulose is selected from HPMC E5.
According to the coated Ridomino, the weight ratio of the ethyl cellulose to the hydroxypropyl methyl cellulose is 1: 0.05-0.15.
Preferably, the weight ratio of the ethyl cellulose to the hydroxypropyl methyl cellulose is 1: 0.06-0.14; more preferably, the weight ratio of the ethyl cellulose to the hydroxypropyl methyl cellulose is 1: 0.07-0.13; and, most preferably, the weight ratio of said ethylcellulose to said hydroxypropylmethylcellulose is 1: 0.08-0.12.
In a specific embodiment, the weight ratio of the ethyl cellulose to the hydroxypropyl methylcellulose is 1: 0.10.
The coated briguard according to the present invention, wherein the acid-insoluble acrylic resin is selected from anionic polymers of methacrylic acid and methyl methacrylate, which are insoluble at pH < 7.
In a specific embodiment, the acid-insoluble acrylic resin is selected from Eudragit S100.
The coated Rifampicin provided by the invention is 45.0-70.0 wt% of the acrylic resin coating layer based on the weight of the sodium butyrate drug-loaded pellet core.
Preferably, the weight of the acrylic resin coating layer is 50.0-65.0 wt% based on the weight of the sodium butyrate drug-loaded pellet core; more preferably, the weight of the acrylic resin coating layer is 52.0-62.0 wt% based on the weight of the sodium butyrate medicated pellet core; and, most preferably, the acrylic resin coating layer weight is 55.0-60.0 wt% based on the weight of the sodium butyrate medicated pellet core.
In a specific embodiment, the acrylic resin coating layer weight is 58.6 wt% based on the weight of the sodium butyrate medicated pellet core.
Advantageously, the acrylic coating layer further comprises triethyl citrate and talc. The weight of triethyl citrate is 8-12 wt% based on the weight of the acrylic resin; the weight of the talcum powder is 15-35 wt%.
In a specific embodiment, the weight of triethyl citrate is 10.0 wt% based on the weight of the acrylic resin; the weight of the talc was 22 wt%.
In another aspect, the present invention also provides a method for preparing the coated lidocaine, comprising:
preparing sodium butyrate drug-loaded pill cores by using a rolling pill forming method;
and sequentially preparing an ethyl cellulose coating layer and an acrylic resin coating layer on the sodium butyrate drug-loaded pill core by using a fluidized bed method.
In another aspect, the invention also provides the application of the coated thalidomide in preparing a veterinary drug for treating early weaning stress syndrome. The application is beneficial to improving the technical problems of slow average daily gain of piglets, high feed conversion ratio and diarrhea rate.
The invention has the beneficial technical effects that the coated thalidomide can realize accurate positioning of intestinal tracts and ensure that most of sodium butyrate is released in cecum and colon; on the other hand, the piglet feed is beneficial to improving the technical problems of slow average daily gain, high feed conversion ratio and diarrhea rate of piglets.
Without wishing to be bound by any theory, a specific kind and weight of acrylic resin coating layer enables a precise positioning of the intestine; a particular type and weight of ethylcellulose coating layer in combination with a particular proportion of hydroxypropylmethylcellulose produces a synergistic effect such that the coating safety ensures that a large portion (over 85%) of the sodium butyrate is released in the caecum and colon.
Detailed Description
It must be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include both one and more than one (i.e., two, including two) unless the context clearly dictates otherwise.
Unless otherwise indicated, the numerical ranges in this disclosure are approximate and thus may include values outside of the stated ranges. The numerical ranges may be stated herein as from "about" one particular value, and/or to "about" another particular value. When such a range is expressed, another aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the numerical ranges are significant both in relation to the other endpoint, and independently of the other endpoint.
Reference in the specification and concluding claims to parts by weight of a particular element or component in a composition or article refers to the weight relationship between that element or component and any other elements or components in the composition or article, expressed as parts by weight.
Unless specifically indicated to the contrary, or implied by the context or customary practice in the art, all parts and percentages referred to herein are by weight and the weight percentages of a component are based on the total weight of the composition or product in which it is included.
References to "comprising," "including," "having," and similar terms in this specification are not intended to exclude the presence of any optional components, steps or procedures, whether or not any optional components, steps or procedures are specifically disclosed. In order to avoid any doubt, all methods claimed through use of the term "comprising" may include one or more additional steps, apparatus parts or components and/or materials unless stated to the contrary. In contrast, the term "consisting of … …" excludes any component, step, or procedure not specifically recited or recited. Unless otherwise specified, the term "or" refers to the listed members individually as well as in any combination.
Furthermore, the contents of any referenced patent or non-patent document in this application are incorporated by reference in their entirety, especially with respect to definitions disclosed in the art (where not inconsistent with any definitions specifically provided herein) and general knowledge.
In the present invention, parts are parts by weight unless otherwise indicated, temperatures are indicated in ° c or at ambient temperature, and pressures are at or near atmospheric. There are many variations and combinations of reaction conditions (e.g., component concentrations, desired solvents, solvent mixtures, temperatures, pressures, and other reaction ranges) and conditions that can be used to optimize the purity and yield of the product obtained by the process. Only reasonable routine experimentation will be required to optimize such process conditions.
Example 1
Firstly, sieving 30 parts by weight of sodium butyrate and 30 parts by weight of microcrystalline cellulose blank pellet core by a 100-mesh sieve, uniformly mixing, adding 1 part by weight of HPMC K15M soft water solution as an adhesive, and extruding into strips by using a sieve plate with the aperture of 0.6mm, wherein the extrusion rotating speed is 30 rpm; then placing the mixture in a rounding machine, and setting the rounding rotating speed to be 60 rpm; rounding for 3min to obtain spherical sodium butyrate drug-loaded pill core. The latter is dried at 50 deg.C, sieved and coated with sodium butyrate drug-loaded pellet core of 20-30 meshes. Ethyl cellulose (average molecular weight Mn of 18260; ethoxy content of 48.8 wt%) and HPMC E5 were made into an aqueous dispersion at a weight ratio of 1: 0.10, and the ethyl cellulose content was adjusted to 10 wt% to obtain an ethyl cellulose coating solution. And (3) placing the sodium butyrate drug-loaded pellet core into fluidized bed coating equipment for bottom spraying coating, wherein the air inlet temperature is 45 ℃, the working frequency is 30Hz, the spraying pressure is 0.2MPa, and the liquid spraying speed is 1 mL/min. And continuously stirring the coating solution in the coating process, and performing fluidized drying for 30min after coating to obtain the sodium butyrate drug-loaded pill core with the ethyl cellulose coating layer. By controlling the process parameters, the weight of the ethylcellulose coating layer is 5.2 wt% based on the weight of the sodium butyrate drug-loaded pellet core. Adding Eudragit S100 into absolute ethyl alcohol to fully dissolve the Eudragit S100, and then adding 10.0 wt% of triethyl citrate and 22 wt% of talcum powder into the absolute ethyl alcohol to be uniformly mixed to obtain a suspension. Subsequently, the suspension was added to an ethanol solution of Eudragit S100, and the content of Eudragit S100 was adjusted to 6% by weight to obtain an acrylic resin coating solution. And (3) placing the sodium butyrate drug-loaded pellet core with the ethyl cellulose coating layer in fluidized bed coating equipment for bottom spraying coating, wherein the air inlet temperature is 50 ℃, the working frequency is 40Hz, the spraying pressure is 0.2MPa, and the liquid spraying speed is 1 mL/min. The coating solution is continuously stirred in the coating process, and fluidized and dried for 30min after coating. The acrylic resin coating layer weight was 58.6 wt% based on the weight of the sodium butyrate pellet core. The resulting coated lidocaine product of example 1 was obtained.
Example 2
The other conditions were the same as in example 1, except that the weight of the ethylcellulose coating layer was adjusted to 3.9 wt%; the weight of the acrylic resin coating layer is 60.1 wt%; and the weight ratio of ethyl cellulose to HPMC E5 was 1: 0.081.
Example 3
The other conditions were the same as in example 1, except that the weight of the ethylcellulose coating layer was adjusted to 6.1 wt%; the weight of the acrylic resin coating layer is 55.2 wt%; and the weight ratio of ethyl cellulose to HPMC E5 was 1: 0.124.
Comparative example 1
The other conditions were the same as in example 1, except that HPMC E5 was not added.
Comparative example 2
The other conditions were the same as in example 1, but the weight ratio of ethylcellulose to HPMC E5 was adjusted to 1: 0.20.
Comparative example 3
The other conditions were the same as in example 2, except that the weight of the ethylcellulose coating layer was adjusted to 1.2 wt%.
Comparative example 4
The other conditions were the same as in example 3, except that the weight of the ethylcellulose coating layer was adjusted to 12 wt%.
Evaluation of biomimetic digestion
The influence factors of the digestibility of the dry matter of the feed are evaluated by a bionic method of Chengliang et al (Chinese agricultural science, 2013, 46(15), 3199-page 3205), namely simulated pig gastric juice, pig small intestinal juice and pig large intestinal juice are prepared, gastric buffer, small intestinal buffer and large intestinal buffer are prepared at the same time, and the digestibility of the sodium butyrate of the examples 1 to 3 and the comparative examples 1 to 4 of the invention is evaluated on a single-stomach animal bionic digestion system SDS-2 according to the evaluation method of the article. After the digestion period of each stage is finished, accurately sucking 1mL of buffer solution, and putting the buffer solution into a 10mL volumetric flask to be constant volume to a scale by using a phosphoric acid solution. 20 μ L of the extract was measured using a pipette and injected into a liquid chromatograph. The chromatographic conditions are as follows: c18 silica gel, 0.1 wt% phosphoric acid solution-acetonitrile (85: 15), detection wavelength 208 nm; the flow rate is 1 mL/min; column temperature: at 25 ℃. The absorption rate of sodium butyrate in the pig stomach, small intestine and large intestine (% based on total amount of sodium butyrate) was calculated according to the external standard method.
The results are shown in Table 1.
TABLE 1
Figure BSA0000200622330000071
Figure BSA0000200622330000081
The results show that a specific kind and weight of acrylic resin coating layer can realize accurate positioning of intestinal tract; a particular type and weight of ethylcellulose coating layer in combination with a particular proportion of hydroxypropylmethylcellulose produces a synergistic effect such that the coating safety ensures that a large portion (over 85%) of the sodium butyrate is released in the caecum and colon.
Early weaning stress syndrome
Selecting newborn piglets with the same period of delivery (requiring the same breed, the birth weight and body condition of piglets are similar, and the delivery time is similar). The test pigs are randomly selected and divided into 1 test group (sample in example 1) and 1 control group (30% of effective components of Hangzhou Zhejiang Congdright science and technology Co., Ltd.), the test groups and the control groups start to be tested 3 days before the piglets are weaned, and the test groups and the control groups are added into the basic feed according to the dosage of 1.5g/kg until the nursing after the piglets are weaned is finished. Average daily gain, feed-meat ratio and diarrhea rate were calculated from weaning (28 days) to development (68 days). See table 2 for results.
TABLE 2
Group of Average daily gain/g Meat ratio of materials Rate of diarrhea/%)
Test group 447.39±23.15 1.72 7.4±0.8
Control group 409.56±29.20 1.83 19.2±1.7
Without wishing to be bound by any theory, since the coated brix of the present invention can not only achieve accurate positioning of the intestinal tract but also ensure that most of the sodium butyrate is released in the cecum and colon; thereby improving the technical problems of slow average daily gain of piglets, high feed conversion ratio and diarrhea rate.
It should be understood that the detailed description of the invention is merely illustrative of the spirit and principles of the invention and is not intended to limit the scope of the invention. Furthermore, it should be understood that various changes, substitutions, deletions, modifications or adjustments may be made by those skilled in the art after reading the disclosure of the present invention, and such equivalents are also within the scope of the invention as defined in the appended claims.

Claims (10)

1. A coated Ridomino comprises a sodium butyrate drug-loaded pill core, an ethyl cellulose coating layer and an acrylic resin coating layer from inside to outside; characterized in that the acrylic resin is selected from acid-insoluble acrylic resins.
2. The coated rivastigmine according to claim 1, wherein the sodium butyrate drug-loaded pellet core is obtained from sodium butyrate and a microcrystalline cellulose blank pellet core in a weight ratio of 0.5-2: 1.
3. A coated thalidomide according to claim 1 or claim 2, wherein the ethylcellulose coating layer weight is from 3.0 to 7.0 wt%, based on the weight of the sodium butyrate medicated pellet core.
4. The coated thalidomide of claim 1 or 2, wherein the ethyl cellulose has an average molecular weight Mn of 15000-24000; the ethoxy content is 47.5 to 49.5 wt.%.
5. The coated thalidomide of claim 1 or 2, wherein the ethylcellulose coating layer further comprises hydroxypropylmethylcellulose; the methoxyl content of the hydroxypropyl methylcellulose is 28.0-30.0 wt%; the hydroxypropoxyl content is 7.0 to 12.0 weight percent and the viscosity is 3 to 8 mPa.
6. A coated thalidomide according to claim 1 or 2, wherein the weight ratio of ethylcellulose to hydroxypropylmethylcellulose is 1: 0.05-0.15.
7. Coated thalidomide according to claim 1 or 2, wherein the acid-insoluble acrylic resin is selected from anionic polymers of methacrylic acid and methyl methacrylate, which are insoluble at pH < 7.
8. A coated thalidomide according to claim 1 or claim 2, wherein the acrylic resin coating layer is present in an amount of from 45.0 to 70.0 wt% based on the weight of the sodium butyrate medicated pellet core.
9. A method of making the coated lidocaine of any of claims 1-8, the method comprising:
preparing sodium butyrate drug-loaded pill cores by using a rolling pill forming method;
and sequentially preparing an ethyl cellulose coating layer and an acrylic resin coating layer on the sodium butyrate drug-loaded pill core by using a fluidized bed method.
10. Use of the coated thalidomide of any one of claims 1-8 in the preparation of a veterinary drug for early weaning stress syndrome.
CN202010049914.2A 2020-01-07 2020-01-07 Coated lidocaine and preparation method and application thereof Pending CN111228234A (en)

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CN112515047A (en) * 2020-12-14 2021-03-19 重庆市六九畜牧科技股份有限公司 Tentian coating acidifier and preparation method thereof
CN112641002A (en) * 2020-12-14 2021-04-13 重庆市六九畜牧科技股份有限公司 Feed composition added with anti-coating compound acidifier
CN112641001A (en) * 2020-12-14 2021-04-13 重庆市六九畜牧科技股份有限公司 Anti-coating compound acidifier

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