CN110251478B - High-temperature-resistant enteric coating process for micro-dropping pills - Google Patents
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5015—Organic compounds, e.g. fats, sugars
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
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Abstract
The invention relates to the technical field of biomedicine, and discloses a high-temperature-resistant enteric coating process for micro-dropping pills, which comprises the following components in parts by weight: 50-55 parts of methacrylic acid copolymer, 10-15 parts of succinic acetic acid hydroxypropyl methyl cellulose, 3-7 parts of silicone elastomer, 1-5 parts of triethyl citrate and 3-5 parts of nano silicon dioxide. The high-temperature resistant enteric coating has good stability and heat resistance in a gastric acid environment and high drug release efficiency in an intestinal juice environment. The high-temperature resistant enteric coating process for the micro-dropping pills is convenient to operate, and the prepared dropping pill preparation has a smooth surface, is antibacterial, has no adhesion and is convenient to store and transport.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to a high-temperature-resistant enteric coating process for micro-dropping pills.
Background
The enteric coating can prevent the drug from disintegrating or dissolving within 2h in the artificial gastric juice at 37 ℃, and disintegrating or dissolving within 1h in the artificial intestinal juice, and releasing the drug coating, and can prevent the drug from destroying in the stomach and the irritation of the drug to the stomach. At present, when the enteric coating is applied to the critical part, the problems of pill sticking on the inner wall of the guide barrel, long coating period, poor disintegration and the like are easy to occur.
The Chinese patent with the application number of CN201510231542.4 discloses an enteric-coated venenum bufonis pellet premix and a preparation method thereof. The venenum bufonis pellet premix consists of a drug-loaded pellet core containing venenum bufonis, a diluent, a binder and a disintegrating agent and an enteric coating containing acrylic resin and ethanol; preparing acrylic resin and ethanol into coating solution, and spraying the medicine into the coating solution for coating. The enteric coated venenum Bufonis pellet premix can reduce irritation of venenum Bufonis to oral cavity and esophagus, so that it is not dissolved and absorbed in stomach, and can reduce gastrointestinal discomfort. However, the enteric coated venenum bufonis pellet premix has poor heat resistance and is easy to cause adhesion at higher temperature.
Disclosure of Invention
In order to solve the technical problems, the invention provides a high-temperature resistant enteric coating process for micro-dripping pills. According to the invention, the methacrylic acid is modified by luteolin, and the methacrylic acid copolymer prepared from the modified methacrylic acid has high heat resistance when being used as an enteric coating material. The high-temperature resistant enteric coating has good stability in a gastric acid environment, good heat resistance and high drug release efficiency in an intestinal juice environment. The high-temperature resistant enteric coating process for the micro-dropping pills is convenient to operate, and the prepared dropping pill preparation has a smooth surface, is antibacterial, has no adhesion and is convenient to store and transport.
The specific technical scheme of the invention is as follows: a high-temperature resistant enteric coating process for micro-dropping pills comprises the following components in parts by weight: 50-55 parts of methacrylic acid copolymer, 10-15 parts of succinic acetic acid hydroxypropyl methyl cellulose, 3-7 parts of silicone elastomer, 1-5 parts of triethyl citrate and 3-5 parts of nano silicon dioxide.
Enteric coatings prepared in the prior art are easy to adhere at a higher temperature, have poor heat resistance, and enteric coating materials which are quickly dissolved in intestinal juice have poor stability in gastric acid, so that more medicaments are often dissolved out. The high-temperature resistant enteric coating used in the high-temperature resistant enteric coating process of the micro-dropping pill has good stability and heat resistance in a gastric acid environment and high drug release efficiency in an intestinal juice environment. The high-temperature resistant enteric coating process for the micro-dropping pills is convenient to operate, and the prepared dropping pill preparation has a smooth surface, is antibacterial, has no adhesion and is convenient to store and transport. The hydroxypropyl methyl cellulose acetate succinate can be quickly dissolved in intestinal tracts; the silicone elastomer can increase the elasticity of the enteric coating, so that the coating surface is smooth and has no cracks; the triethyl citrate has the antibacterial effect while enhancing the elasticity of the enteric coating, and is beneficial to the storage of the dripping pill preparation; the existence of the nano silicon dioxide can prevent the adhesion of the methacrylic acid copolymer, and meanwhile, the nano silicon dioxide can be uniformly distributed among the components and filled in the gaps of the material.
Preferably, the content of the modified methacrylic acid in the methacrylic acid copolymer is 35-40%. According to the invention, methacrylic acid contained in the methacrylic acid copolymer is modified, so that the thermal stability of the methacrylic acid copolymer is improved, and the prepared enteric coating stably exists at a higher temperature and does not adhere.
Preferably, the modified methacrylic acid is luteolin-modified methacrylic acid, and the preparation method comprises the following steps: adding methacrylic acid into toluene, adding triethylamine, dripping thionyl chloride, and performing reflux reaction to obtain methacryloyl chloride; adding luteolin into DMF, adding sodium hydroxide, stirring for 0.5-1 h, dripping a DMF solution of methacryloyl chloride into an ice water bath, and stirring for reaction to obtain the modified methacrylic acid.
According to the invention, the methyl acrylic acid is modified by luteolin, a rigid ring in the luteolin can enhance the thermal stability of the methyl acrylic acid copolymer, and meanwhile, the luteolin can also enhance the antibacterial property of the enteric coating.
Preferably, the molar ratio of the triethylamine, the methacrylic acid and the thionyl chloride is 0.1-0.3: 1: 1-1.5. When the molar ratio of triethylamine, methacrylic acid and thionyl chloride is 0.1-0.3: 1: 1-1.5, the yield of methacryloyl chloride is highest.
Preferably, the volume ratio of the methacrylic acid to the toluene is 1: 4-7; the reflux reaction temperature is 50-60 ℃, and the reaction time is 3-5 h. The modification method is simple, mild in condition and suitable for large-scale production.
Preferably, the molar ratio of the luteolin to the sodium hydroxide to the methacryloyl chloride is 1:1: 1.1-1.5; the mass-volume ratio of luteolin to DMF is 1g: 5-10 mL; the yield of the modified methacrylic acid is highest when the molar ratio of the luteolin to the sodium hydroxide to the methacryloyl chloride is 1:1: 1.1-1.5.
Preferably, the dropping speed of the DMF solution of the methacrylic chloride is 1-2 mL/min, and the concentration of the DMF solution of the methacrylic chloride is 0.3-0.5M. The DMF solution of the methacryloyl chloride contains a polymerization inhibitor. Since methacryloyl chloride is easily self-polymerized, the concentration and dropping speed of the DMF solution of methacryloyl chloride need to be strictly controlled, and when the dropping speed is too high, the methacryloyl chloride is difficult to fully react with luteolin.
Preferably, the high-temperature resistant enteric coating process for the micro-dropping pills comprises the following steps:
(1) adding the silicone elastomer and triethyl citrate according to the formula amount into water while stirring, sequentially adding the nano silicon dioxide, the hydroxypropyl methylcellulose succinate acetate and the methacrylic acid copolymer according to the formula amount, and stirring for 3-5 hours to obtain a coating suspension;
(2) and (3) coating the dripping pill preparation by a coating machine while stirring the coating suspension.
The coating method of the high-temperature resistant enteric coating process for the micro-dropping pills is simple, easy to operate and suitable for large-scale production.
Preferably, in the step (2), the air inlet temperature of the coating treatment is 60-65 ℃, and the exhaust temperature is 30-35 ℃; the dripping pill preparation comprises herba Pileae Scriptae dripping pill, YUPINGFENG dripping pill, and YINHUANG dripping pill. The air inlet temperature of the coating treatment is 60-65 ℃, and the exhaust temperature is 30-35 ℃, so that the coating film is smooth and flat and has no cracks.
Preferably, in the step (1), the methacrylic acid copolymer is added in 3 to 4 times. The methacrylic acid copolymer is added for 3-4 times, so that the uniform dispersion is facilitated.
Compared with the prior art, the invention has the beneficial effects that: the high-temperature resistant enteric coating has good stability and heat resistance in a gastric acid environment and high drug release efficiency in an intestinal juice environment. The high-temperature resistant enteric coating process for the micro-dropping pills is convenient to operate, and the prepared dropping pill preparation has a smooth surface, is antibacterial, has no adhesion and is convenient to store and transport.
Detailed Description
The present invention will be further described with reference to the following examples. The devices, connections, and methods referred to in this disclosure are those known in the art, unless otherwise indicated.
Example 1
A high-temperature resistant enteric coating process for micro-dropping pills comprises the following components in parts by weight: 52 parts of methacrylic acid copolymer, 13 parts of succinic acetic acid hydroxypropyl methyl cellulose, 5 parts of silicone elastomer, 3 parts of triethyl citrate and 4 parts of nano silicon dioxide.
The content of the modified methacrylic acid in the methacrylic acid copolymer is 37%.
The modified methacrylic acid is luteolin modified methacrylic acid, and the preparation method comprises the following steps: adding methacrylic acid into toluene, wherein the volume ratio of the methacrylic acid to the toluene is 1:5, adding triethylamine, dripping thionyl chloride, and carrying out reflux reaction at 55 ℃ for 4 hours to obtain methacryloyl chloride, wherein the molar ratio of the triethylamine to the methacrylic acid to the thionyl chloride is 0.2:1: 1.2; adding luteolin into DMF (1 g:8 mL), adding sodium hydroxide, stirring for 0.8h, dropwise adding a methacryloyl chloride DMF solution into an ice water bath, wherein the molar ratio of luteolin to sodium hydroxide to methacryloyl chloride is 1:1:1.3, and stirring for reacting for 20min to obtain modified methacrylic acid; the dropping speed of the DMF solution of the methacrylic chloride is 1.5mL/min, and the concentration of the DMF solution of the methacrylic chloride is 0.4M. The methacryloyl chloride solution in DMF contained sodium carbonate.
A high temperature resistant enteric coating process for micro-dripping pills comprises the following steps:
(1) adding the silicone elastomer and triethyl citrate according to the formula amount into 170 parts of water while stirring, sequentially adding the nano silicon dioxide, the hydroxypropyl methyl cellulose acetate succinate and the methacrylic acid copolymer according to the formula amount, adding the methacrylic acid copolymer for 3 times, and stirring for 4 hours to obtain a coating suspension;
(2) and (3) coating the Yinhuang dropping pill by a coating machine while stirring the coating suspension, wherein the air inlet temperature of the coating treatment is 62 ℃, the exhaust temperature is 32 ℃, the spraying speed is 27g/min, the diameter of a spray gun is 1mm, and the spraying pressure is 0.9 bar.
Example 2
A high-temperature resistant enteric coating process for micro-dropping pills comprises the following components in parts by weight: 50 parts of methacrylic acid copolymer, 15 parts of succinic acetic acid hydroxypropyl methyl cellulose, 7 parts of silicone elastomer, 1 part of triethyl citrate and 4 parts of nano silicon dioxide.
The content of the modified methacrylic acid in the methacrylic acid copolymer was 35%.
The modified methacrylic acid is luteolin modified methacrylic acid, and the preparation method comprises the following steps: adding methacrylic acid into toluene, wherein the volume ratio of the methacrylic acid to the toluene is 1:4, adding triethylamine, dripping thionyl chloride, and carrying out reflux reaction at 60 ℃ for 3 hours to obtain methacryloyl chloride, wherein the molar ratio of the triethylamine to the methacrylic acid to the thionyl chloride is 0.3:1: 1.5; adding luteolin into DMF (dimethyl formamide), wherein the mass volume ratio of luteolin to DMF is 1g:10mL, adding sodium hydroxide, stirring for 1h, dropwise adding a DMF (dimethyl formamide) solution of methacryloyl chloride in an ice water bath, wherein the molar ratio of luteolin to sodium hydroxide to methacryloyl chloride is 1:1:1.1, and stirring for reacting for 30min to obtain modified methacrylic acid; the dropping speed of the DMF solution of the methacrylic chloride is 1mL/min, and the concentration of the DMF solution of the methacrylic chloride is 0.3M. The methacryloyl chloride solution in DMF contained sodium carbonate.
A high temperature resistant enteric coating process for micro-dripping pills comprises the following steps:
(1) adding the silicone elastomer and triethyl citrate according to the formula amount into 150 parts of water while stirring, sequentially adding the nano silicon dioxide, the hydroxypropyl methyl cellulose acetate succinate and the methacrylic acid copolymer according to the formula amount, adding the methacrylic acid copolymer for 4 times, and stirring for 3 hours to obtain a coating suspension;
(2) and (3) coating the glabrous sarcandra herb dripping pills by using a coating machine while stirring the coating suspension, wherein the air inlet temperature of the coating treatment is 65 ℃, the exhaust temperature is 35 ℃, the spraying speed is 25g/min, the diameter of a spray gun is 0.5mm, and the spraying pressure is 0.8 bar.
Example 3
A high-temperature resistant enteric coating process for micro-dropping pills comprises the following components in parts by weight: 55 parts of methacrylic acid copolymer, 10 parts of succinic acetic acid hydroxypropyl methyl cellulose, 5 parts of silicone elastomer, 2 parts of triethyl citrate and 5 parts of nano silicon dioxide.
The content of the modified methacrylic acid in the methacrylic acid copolymer is 40%.
The modified methacrylic acid is luteolin modified methacrylic acid, and the preparation method comprises the following steps: adding methacrylic acid into toluene, wherein the volume ratio of the methacrylic acid to the toluene is 1:7, adding triethylamine, dripping thionyl chloride, and carrying out reflux reaction at 55 ℃ for 4 hours to obtain methacryloyl chloride, wherein the molar ratio of the triethylamine to the methacrylic acid to the thionyl chloride is 0.3:1: 1.2; adding luteolin into DMF (1 g:8 mL), adding sodium hydroxide, stirring for 0.5h, dropwise adding a methacryloyl chloride DMF solution into an ice water bath, wherein the molar ratio of luteolin to sodium hydroxide to methacryloyl chloride is 1:1:1.5, and stirring for reacting for 20min to obtain modified methacrylic acid; the dropping speed of the DMF solution of the methacrylic chloride is 1mL/min, and the concentration of the DMF solution of the methacrylic chloride is 0.5M. The methacryloyl chloride solution in DMF contained sodium carbonate.
A high temperature resistant enteric coating process for micro-dripping pills comprises the following steps:
(1) adding the silicone elastomer and triethyl citrate according to the formula amount into 180 parts of water while stirring, sequentially adding the nano silicon dioxide, the hydroxypropyl methyl cellulose acetate succinate and the methacrylic acid copolymer according to the formula amount, adding the methacrylic acid copolymer for 3 times, and stirring for 5 hours to obtain a coating suspension;
(2) and (3) coating the Jade screen dropping pill by using a coating machine while stirring the coating suspension, wherein the air inlet temperature of the coating treatment is 63 ℃, the exhaust temperature is 30 ℃, the spraying speed is 26g/min, the diameter of a spray gun is 1mm, and the spraying pressure is 1 bar.
Comparative example 1
Comparative example 1 differs from example 1 in that: the hydroxypropyl methylcellulose acetate succinate was replaced by an equivalent amount of methacrylic acid copolymer. The rest of the procedure was the same as in example 1.
Comparative example 2
Comparative example 2 differs from example 1 in that: the silicone elastomer was replaced with an equal amount of triethyl citrate. The rest of the procedure was the same as in example 1.
Comparative example 3
Comparative example 3 differs from example 1 in that: the nano silicon dioxide is replaced by the same amount of triethyl citrate. The rest of the procedure was the same as in example 1.
Comparative example 4
Comparative example 4 differs from example 1 in that: the modified methacrylic acid was replaced with an equivalent amount of methacrylic acid. The rest of the procedure was the same as in example 1.
Comparative example 5
Comparative example 5 differs from example 1 in that: the dropping speed of the DMF solution of the methacrylic chloride is 2.2mL/min, and the concentration of the DMF solution of the methacrylic chloride is 0.52M. The rest of the procedure was the same as in example 1.
The appearance, heat resistance at 65 ℃, stability in simulated gastric acid environment and drug release efficiency within 10min in simulated intestinal fluid environment of the dropping pill preparations prepared by the high-temperature resistant enteric coating process of the micro dropping pills of the present invention in examples 1 to 3 and comparative examples 1 to 5 were tested, and the test results are shown in table 1.
TABLE 1
| Number of groups | Appearance of the product | Heat resistance | Stability of | Efficiency of drug release/%) |
| Example 1 | Smooth and flat | No deformation and adhesion | No dissolution and smooth surface | 81.3 |
| Example 2 | Smooth and flat | No deformation and adhesion | No dissolution and smooth surface | 80.5 |
| Example 3 | Smooth and flat | No deformation and adhesion | No dissolution and smooth surface | 80.7 |
| Comparative example 1 | Smooth and flat | No deformation and adhesion | Surface smoothing | 42.3 |
| Comparative example 2 | With micro cracks | No deformation and adhesion | Having cracks on the surface | 83.3 |
| Comparative example 3 | Micro-adhesion | No deformation and adhesion | A small amount of medicine is dissolved out | 51.3 |
| Comparative example 4 | Adhesion of the components | Deformation and adhesion | Having bubbles on the surface | 52.5 |
| Comparative example 5 | Smooth and flat | No deformation and adhesion | Having bubbles on the surface | 53.8 |
As can be seen from Table 1, the dripping pill preparation prepared by the high temperature resistant enteric coating process of the micro-dripping pill has smooth and flat appearance, good heat resistance, no adhesion on the surface of the dripping pill preparation, stable existence in simulated gastric acid environment, convenient storage and transportation, and fast drug release rate in simulated intestinal fluid environment. Comparative examples 1-3 the formulation of the high temperature resistant enteric coating of the present invention was changed, and the prepared dropping pill preparation had good appearance, good heat resistance, stability in simulated gastric acid environment and poor drug release rate in simulated intestinal fluid environment. Comparative example 4 the drop pill preparation prepared by replacing modified methacrylic acid with equivalent methacrylic acid is easy to adhere and poor in heat resistance, and bubbles are easy to generate on the surface in a simulated gastric acid environment, so that the quality requirement of enteric coating medicines cannot be met. In the comparative example 5, the dropping speed and the concentration of the DMF solution of the methacryloyl chloride exceed the range limited by the invention, and the prepared dripping pill preparation has poor heat resistance, easily generates bubbles on the surface in a simulated gastric acid environment and cannot meet the quality requirement of enteric-coated medicines. Therefore, a dripping pill preparation with excellent heat resistance, stability and drug release efficiency can be obtained only within the range defined by the high-temperature resistant enteric coating process of the microdroplet pill.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and all simple modifications, changes and equivalent structural changes made to the above embodiment according to the technical spirit of the present invention still belong to the protection scope of the technical solution of the present invention.
Claims (7)
1. A high temperature resistant enteric coating for micro-dripping pills is characterized in that: the high-temperature resistant enteric coating comprises the following components in parts by weight: 50-55 parts of methacrylic acid copolymer, 10-15 parts of succinic acetic acid hydroxypropyl methyl cellulose, 3-7 parts of silicone elastomer, 1-5 parts of triethyl citrate and 3-5 parts of nano silicon dioxide;
the content of modified methacrylic acid in the methacrylic acid copolymer is 35-40%; the modified methacrylic acid is luteolin modified methacrylic acid, and the preparation method comprises the following steps: adding methacrylic acid into toluene, adding triethylamine, dripping thionyl chloride, and performing reflux reaction to obtain methacryloyl chloride; adding luteolin into DMF, adding sodium hydroxide, stirring for 0.5-1 h, dripping 0.3-0.5M of a DMF solution of methacryloyl chloride at a speed of 1-2 mL/min in an ice water bath, and stirring for reaction to obtain the modified methacrylic acid.
2. The high temperature resistant enteric coating for microdroplets of claim 1, wherein: the molar ratio of the triethylamine to the methacrylic acid to the thionyl chloride is 0.1-0.3: 1: 1-1.5.
3. The high temperature resistant enteric coating for microdroplets of claim 1, wherein: the volume ratio of the methacrylic acid to the toluene is 1: 4-7; the reflux reaction temperature is 50-60 ℃, and the reaction time is 3-5 h.
4. The high temperature resistant enteric coating for microdroplets of claim 1, wherein: the molar ratio of the luteolin to the sodium hydroxide to the methacryloyl chloride is 1:1: 1.1-1.5; the mass-volume ratio of luteolin to DMF is 1g: 5-10 mL.
5. A method for preparing a high temperature resistant enteric coating according to any of claims 1 to 4, comprising the steps of:
(1) adding the silicone elastomer and triethyl citrate according to the formula amount into water while stirring, sequentially adding the nano silicon dioxide, the hydroxypropyl methylcellulose succinate acetate and the methacrylic acid copolymer according to the formula amount, and stirring for 3-5 hours to obtain a coating suspension;
(2) and (3) coating the dripping pill preparation by a coating machine while stirring the coating suspension.
6. The method of claim 5, wherein: in the step (2), the air inlet temperature of the coating treatment is 60-65 ℃, and the exhaust temperature is 30-35 ℃; the dripping pill preparation comprises herba Pileae Scriptae dripping pill, YUPINGFENG dripping pill, and YINHUANG dripping pill.
7. The method of claim 5, wherein: in the step (1), the methacrylic acid copolymer is added for 3-4 times.
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| CN113940395B (en) * | 2021-11-17 | 2023-05-23 | 西南科技大学 | Preparation method of probiotic preparation for piglets |
| CN115192547B (en) * | 2022-07-20 | 2023-06-27 | 浙江维康药业股份有限公司 | High-temperature-resistant enteric slow-release coating for dropping pills and honeysuckle flower and radix scutellariae dropping pills |
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| CN110251478A (en) | 2019-09-20 |
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Denomination of invention: A kind of high temperature resistant enteric coating technology for microdrop pills Effective date of registration: 20220916 Granted publication date: 20210618 Pledgee: Industrial and Commercial Bank of China Limited Lishui Economic Development Zone sub branch Pledgor: ZHEJIANG WECOME PHARMACEUTICAL CO.,LTD. Registration number: Y2022330002257 |