CN109999201B - Taste-masking mate agent and application thereof - Google Patents
Taste-masking mate agent and application thereof Download PDFInfo
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- CN109999201B CN109999201B CN201910319283.9A CN201910319283A CN109999201B CN 109999201 B CN109999201 B CN 109999201B CN 201910319283 A CN201910319283 A CN 201910319283A CN 109999201 B CN109999201 B CN 109999201B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
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- A—HUMAN NECESSITIES
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
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Abstract
The invention provides a novel taste-masking chaperone agent, which consists of an amphiphilic block copolymer, cyclodextrin and an artificial sweetener. The novel taste-masking chaperone agent of the invention unexpectedly and greatly reduces the original bad taste of the medicine while ensuring the safety and effectiveness of the medicine, improves the medicine taking compliance of patients, avoids adding a large amount of flavoring agents, reduces the dosage of sweetening agents in the prescription and reduces the production cost; has obvious taste masking effect, does not increase the dosage of patients, and is simple, convenient and practical.
Description
Technical Field
The invention particularly relates to a novel taste-masking chaperone and application thereof.
Background
The unpleasant taste of the drug includes sour, bitter, salty, astringent, fishy, etc., with the bitter taste being the most unacceptable. For some pharmaceutical preparations or forms of preparations, such as solid preparations, chemical pharmaceutical preparations with single ingredients, etc., pharmaceutical workers can achieve the purpose of taste masking by means of pharmaceutical means, such as coating, encapsulating, inclusion, microencapsulation or by means of chemical means, such as chemical modification, etc. However, these taste masking approaches are often ineffective for other high dose, multi-component liquid or solid formulations. The traditional Chinese medicine decoction is one of the most representative bad taste medicine forms, and the bitter taste of the traditional Chinese medicine decoction is usually used for people to make people 'go away', so that the advantages of traditional Chinese medicine treatment are weakened. Therefore, the taste masking research of the oral Chinese medicine preparation, especially the Chinese medicine decoction, aiming at the bad taste of the medicine is an important subject in the front of pharmaceutical workers. The common taste-masking "tribasic yeast" is bitter-suppressing "," sweetening "and" perfuming ". The first step of bitter suppression in the three-part yeast is fundamental and critical, and the sweetening and perfuming are auxiliary and strengthening. For bitter taste, many drugs have high bitterness, and if bitter taste is not effectively inhibited by a bitter inhibitor and the like, the purpose of taste masking cannot be fundamentally achieved by adding a sweetening agent and an aromatic agent alone, but the taste of the drugs is probably more five tastes and old. Therefore, the research of safe, efficient, universal and stable taste-masking chaperones is the key of the taste-masking research of medicines.
Binding of bitter tasting substances (ligands) to receptors is the first step in bitter taste formation. Currently, as to how bitter substances activate receptors, the three-point contact theory suggests that both bitter molecules and bitter receptors should have AH (electrophilic group), B (nucleophilic group) and X (hydrophobic group), wherein bitter substance AH binds to receptor a ', X binds to receptor X ', and B ' is in the open position to form bitter taste. Because the amphiphilic block copolymer has a hydrophobic group, and a hydrophilic end can form barrier between the components and a receptor, the amphiphilic block copolymer can theoretically perform invisible modification on bitter components and can also form micelles by self-assembly in water, but whether the amphiphilic block copolymer has the function of masking the poor taste of the medicine or not is not researched and reported.
The cyclodextrin molecule has a slightly tapered hollow cylindrical three-dimensional ring structure, and in the hollow structure, the upper end (larger opening end) of the outer side is formed by C 2 And C 3 Is composed of secondary hydroxyl groups, the lower end (smaller open end) is composed of C 6 The primary hydroxyl group is hydrophilic, and a hydrophobic region is formed in the cavity due to the shielding effect of a C-H bond. Thus, it provides a hydrophobic binding site that serves as a host to encapsulate various suitable guests, entrapping the hydrophobic groups of the bitter molecule in the cavity, forming a barrier between the bitter substance and the receptor. The cyclodextrin includes alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin and modified cyclodextrin derivatives thereof.
Artificial sweeteners are a class of synthetic or semi-synthetic sucrose-replacing organic compounds that are widely used in foods, beverages, pharmaceuticals and personal care products and are known as non-caloric sugars since most artificial sweeteners are hardly converted by the human body. In addition, artificial sweeteners can interfere with central transmission of bitter signals, and bitter suppression can be achieved by competing for signal pathway transmission. Bitter taste perception occurs mainly by binding of bitter substances to T2Rs on taste buds, activating the alpha-gustducin-PDE (effector enzyme) -cNMP pathway or activating the beta, gamma-gustducin-PLC-IP 3/DAG pathwayRemoval of Ca 2+ Released, leading to membrane depolarization and neurotransmitter release. Although the sweet taste receptor is T1R2+ T1R3, the perception pathway in taste perception cells and bitter taste are partially overlapped, and the sweet taste reaction pathway stimulated by the artificial sweetener is consistent with the bitter taste beta, gamma-gustducin-PLC-IP 3/DAG pathway, so that the integration of neural central taste signals is interfered to achieve the purpose of taste masking.
At present, no amphiphilic block copolymer is reported to be used for masking the bad taste of the medicine, and no research on the combination of the amphiphilic block copolymer, cyclodextrin and artificial sweetener to prepare a novel taste masking chaperone agent is provided.
Disclosure of Invention
The invention aims to provide a novel taste-masking mate and application thereof. The invention also aims to provide the application of the amphiphilic block copolymer alone and the application of the amphiphilic block copolymer in masking the bad taste of the medicine after two of the amphiphilic block copolymer and the novel taste masking chaperone are combined.
The invention provides a novel taste-masking chaperone agent, which consists of an amphiphilic block copolymer, cyclodextrin and an artificial sweetener.
Furthermore, the weight ratio of the amphiphilic block copolymer is 0.01-20 parts, the weight ratio of the cyclodextrin is 0-20 parts, and the weight ratio of the artificial sweetener is 0-15 parts.
Furthermore, the weight ratio of the amphiphilic block copolymer is 0.01-1 part, the weight ratio of cyclodextrin is 0.5-5 parts, and the weight ratio of artificial sweetener is 0.01-1 part.
Furthermore, the weight ratio of the amphiphilic block copolymer is 0.16 part, the weight ratio of the cyclodextrin is 2 parts, and the weight ratio of the artificial sweetener is 0.125 part.
Furthermore, the amphiphilic block copolymer is any one or more of amphiphilic diblock copolymers or copolymers with more than two diblock copolymers, preferably amphiphilic diblock copolymers, and more preferably mPEG-PLA.
Further, the cyclodextrin is any one or more of alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin or cyclodextrin derivatives, preferably gamma-cyclodextrin.
Further, the artificial sweetener is one or more of saccharin, sodium cyclamate, aspartame, neotame, acesulfame potassium, NHDC and sucralose, and preferably aspartame.
The invention also provides application of the novel taste-masking chaperone agent in preparing a medicament with good mouthfeel.
Further, the good mouthfeel is a bitter, astringent, fishy, salty and/or sour taste of the masking drug.
Furthermore, the dosage form of the medicine is granule, tablet, decoction of traditional Chinese medicine, mixture or aromatic water.
The novel taste-masking chaperone agent of the invention unexpectedly and greatly reduces the original bad taste of the medicament while ensuring the safety and effectiveness of the medicament, improves the medicament compliance of patients, avoids adding a large amount of flavoring agents, reduces the dosage of sweetening agents in the prescription and reduces the production cost; has obvious taste masking effect, does not increase the dosage of patients, and is simple, convenient and practical.
The test proves that: the amphiphilic block copolymer has a good taste masking effect, can better mask the bad taste of the medicine when being mixed with any one of cyclodextrin and artificial sweetener, has the best effect of masking the bad taste of the medicine when being combined together, can be used for preparing various oral preparations (solving the taste problem) which cannot be realized by the traditional process, particularly special preparations (such as granules, dispersible tablets and the like) for certain specific groups (such as children and old people with difficulty in swallowing), has the advantages of simple and convenient operation, low cost, contribution to large-scale production and good application prospect.
Obviously, many modifications, substitutions, and variations are possible in light of the above teachings of the invention, without departing from the basic technical spirit of the invention, as defined by the following claims.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Detailed description of the preferred embodiments
The raw materials and equipment used in the embodiment of the present invention are known products and commercially available products.
Example 1: improvement of bitter taste of berberine hydrochloride by amphiphilic block copolymer
1. Preparation of berberine hydrochloride copolymer micelle solution
A dissolution method is adopted: adding 4mg of berberine hydrochloride into 100mL of water, performing ultrasonic treatment until the berberine hydrochloride is completely dissolved, adding the amphiphilic block copolymer, and performing ultrasonic treatment until the copolymer is completely dissolved to obtain the berberine hydrochloride copolymer micellar solution.
2. Bitterness determination
Taste tests were performed on 10 volunteers by a single blind method, as follows: 10 mL the solution to be tasted by the volunteer was held in the mouth for 15s, and the mouth was rinsed during this time to allow the tongue to fully feel the bitter taste of the drug, and the volunteer was rated by Visual Analogue Scale (VAS) and expectorated and rinsed 5 times until no bitter taste was observed in the mouth, and another solution was evaluated after 15min (each test required tasting the stock solution).
3. Examination of the amount of mPEG2000-PLLA2000 (mPEG 2000-PLLA2000 is a block copolymer, chemical name is methoxy polyethylene glycol-poly L-lactide, where the molecular weight of methoxy polyethylene glycol is 2000 and the molecular weight of poly L-lactide is 2000)
| Dosage of | 0.12％ | 0.14％ | 0.16％ | 0.18％ | Stock solution |
| VAS score | 6 | 5 | 4 | 4.2 | 8.6 |
Test results show that different dosages of mPEG2000-PLLA2000 have the effect of masking bitter taste of berberine hydrochloride, wherein the taste masking effect is best when the dosage is 0.16%.
4. Investigation of mPEG2000-PLLA2000 (mP) and drug addition sequence
Test results show that mPEG2000-PLLA2000 with different adding sequences has the effect of masking bitter taste of berberine hydrochloride, wherein the taste masking effect is best when the berberine hydrochloride, the mPEG2000-PLLA2000 and water are added in the sequence.
5. Influence of mPEG2000-PLLA2000 and mPEG2000-PCL1140 on bitter taste of berberine hydrochloride (mPEG 2000-PCL1140 is a block copolymer with chemical name of methoxy polyethylene glycol-polycaprolactone, wherein the molecular weight of methoxy polyethylene glycol is 2000, and the molecular weight of polycaprolactone is 1140)
Test results show that mPEG2000-PLLA2000, mPEG2000-PCL1140, mPEG2000-PLLA2000 (1.5%) + mPEG2000-PCL1140 (0.5%) all have the effect of masking bitter taste of berberine hydrochloride, wherein the mPEG2000-PLLA2000 has the best effect of masking taste.
Example 2: improvement of bitterness of quinine sulfate hydrate by mPEG2000-PLLA2000
1. Preparation of quinine sulfate micellar solution
A dissolution method is adopted: adding 8mg of quinine sulfate hydrate into 100mL of water, performing ultrasonic treatment until the quinine sulfate hydrate is completely dissolved, adding mPEG2000-PLLA2000, and performing ultrasonic treatment until the amphiphilic block copolymer is completely dissolved to obtain a quinine sulfate micelle solution.
2. Bitterness determination
The bitterness of the solution was determined as in example 1.
3. Investigation of the amount of mPEG2000-PLLA2000 used
| Amount of the composition | 0.12％ | 0.14％ | 0.16％ | 0.18％ | Stock solution |
| VAS scoring | 7.3 | 6 | 5 | 5.3 | 8 |
Test results show that different dosages of mPEG2000-PLLA2000 have the effect of masking bitter taste of quinine sulfate, wherein the taste masking effect is the best when the dosage is 0.16%.
4. Inspection of mPEG2000-PLLA2000 (mP) and drug addition sequence
Test results show that mPEG2000-PLLA2000 with different adding sequences has the effect of masking bitter taste of quinine sulfate, wherein the taste masking effect is best when the quinine sulfate + mPEG2000-PLLA2000+ water is added.
5. Effect of mPEG2000-PLLA2000 and mPEG2000-PCL1140 on the bitterness of quinine sulfate
Test results show that mPEG2000-PLLA2000, mPEG2000-PCL1140, mPEG2000-PLLA2000+ mPEG2000-PCL1140 have the effect of masking bitter taste of quinine sulfate, wherein the mPEG2000-PLLA2000 has the best taste masking effect.
Example 3: improvement of bitterness of mPEG2000-PLLA2000 decoction of Coptidis rhizoma
1. Preparation of coptis water decoction
Taking 2g of coptis medicinal material, adding 100mL of water, extracting under reflux for 2 times, each time for 30min, and combining filtrates to obtain coptis water decoction.
2. Preparation of micellar solutions
Adding mPEG2000-PLLA2000 into the rhizoma Coptidis decoction, and performing ultrasonic treatment until completely dissolved to obtain micelle solution.
3. Bitterness determination
The bitterness of the solution was determined as in example 1.
4. Investigation of the amount of mPEG2000-PLLA2000 used
| Dosage of | 0.12％ | 0.14％ | 0.16％ | 0.18％ | Stock solution |
| VAS score | 8 | 7 | 6 | 7 | 10 |
Test results show that different dosages of mPEG2000-PLLA2000 have the effect of masking bitter taste of the coptis water decoction, wherein the taste masking effect is the best when the dosage is 0.16%.
5. Influence of mPEG2000-PLLA2000 and mPEG2000-PCL1140 on bitterness of Coptidis rhizoma decoction
Test results show that mPEG2000-PLLA2000, mPEG2000-PCL1140 and mPEG2000-PLLA2000+ mPEG2000-PCL1140 have the effect of masking bitter taste of coptis water decoction, wherein the mPEG2000-PLLA2000 has the best taste masking effect.
Example 4: improvement of bitterness of coptis chinensis water decoction by mPEG2000-PLLA2000 and gamma-cyclodextrin
1. Preparation of coptis water decoction
Samples were prepared according to the assay of example 3.
2. Method for correcting taste
Respectively adding 0.16 percent of mPEG2000-PLLA2000, 2 percent of gamma-cyclodextrin and the mixture of the mPEG2000-PLLA2000 and the gamma-cyclodextrin into the water decoction, and carrying out ultrasonic treatment until the mixture is completely dissolved to obtain the flavoring solution.
3. Bitterness determination
The bitterness of the solution was determined as in example 1.
4. Trial and error in volunteer mouth
Test results show that the mPEG2000-PLLA2000 and the gamma-cyclodextrin have taste masking effects when being added independently, but the taste masking effect of the mPEG2000-PLLA2000 and the gamma-cyclodextrin after being mixed is superior to the taste masking effect when being used independently.
Example 5: bitter taste improvement of rhizoma coptidis water decoction by mPEG2000-PLLA2000 and aspartame
1. Preparation of coptis water decoction
Samples were prepared according to the assay of example 3.
2. Method for correcting taste
Adding 0.16% mPEG2000-PLLA2000, 0.125% aspartame and their mixture into water decoction, and ultrasonic treating to dissolve completely to obtain flavoring solution.
3. Bitterness determination
The bitterness of the solution was determined as in example 1.
4. The volunteer tried and tested orally
Test results show that the taste masking effect is achieved when mPEG2000-PLLA2000 and aspartame are added separately, but the taste masking effect after the two are mixed is better than the taste masking effect when the two are used separately.
Example 6: improvement of bitterness of rhizoma coptidis water decoction by gamma-cyclodextrin and aspartame
1. Preparation of coptis water decoction
Samples were prepared according to the assay of example 3.
2. Method for correcting taste
Adding 2% of gamma-cyclodextrin, 0.125% of aspartame and the mixture of the two into the water decoction respectively, and performing ultrasonic treatment until the mixture is completely dissolved to obtain the flavoring solution.
3. Bitterness determination
The bitterness of the solution was determined as in example 1.
4. Trial and error in volunteer mouth
Test results show that the single addition of the gamma-cyclodextrin and the aspartame has the taste masking effect, but the taste masking effect of the mixture of the gamma-cyclodextrin and the aspartame is better than the taste masking effect of the mixture when the gamma-cyclodextrin and the aspartame are used separately.
Example 7: improvement of bitterness of coptis chinensis water decoction by mPEG2000-PLLA2000, gamma-cyclodextrin and aspartame
1. Preparation of coptis water decoction
Samples were prepared according to the assay of example 3.
2. Method for correcting taste
Adding 0.16% mPEG2000-PLLA2000, 2% gamma-cyclodextrin, 0.125% aspartame and the mixture thereof into the decoction, and performing ultrasonic treatment until the mixture is completely dissolved to obtain the flavoring solution.
3. Bitterness determination
The bitterness of the solution was determined as in example 1.
4. Trial and error in volunteer mouth
Test results show that the single addition of mPEG2000-PLLA2000, gamma-cyclodextrin and aspartame has the taste masking effect, but the taste masking effect of the mixture of the mPEG2000-PLLA2000, the gamma-cyclodextrin and the aspartame is superior to the taste masking effect of the mixture when the mixture is singly used.
Example 8: improvement of bitter taste of glabrous sarcandra herb extract by mPEG2000-PLLA2000, gamma-cyclodextrin and aspartame
1. Herba Pileae Scriptae extract
Herba Pileae Scriptae extract is provided by pharmaceutical group of Jiangzhong, inc., and diluted by 3 times to obtain model drug.
2. Method for correcting taste
Respectively adding 0.16 percent of mPEG2000-PLLA2000, 2 percent of gamma-cyclodextrin, 0.125 percent of aspartame and the mixture of the three into the water decoction, and carrying out ultrasonic treatment until the mixture is completely dissolved to obtain the flavoring solution.
3. Bitterness determination
The bitterness of the solution was determined as in example 1.
4. The volunteer tried and tested orally
Test results show that the single addition of mPEG2000-PLLA2000, gamma-cyclodextrin and aspartame has the taste masking effect, but the taste masking effect of the mixture of the mPEG2000-PLLA2000, the gamma-cyclodextrin and the aspartame is superior to the taste masking effect of the mixture when the mixture is singly used.
Example 9: improvement of astringent taste of three-fruit soup by mPEG2000-PLLA2000, gamma-cyclodextrin and aspartame
1. Preparation of decoction of three fruit decoction
Weighing 2 parts of myrobalan, 1 part of terminalia bellerica and 1 part of emblic leafflower fruit, adding 10 times of water, and extracting twice at 100 ℃ for 1 hour each time. Mixing the extractive solutions to obtain three-fruit soup Shui Jianye.
2. Method for correcting taste
Respectively adding 0.16 percent of mPEG2000-PLLA2000, 2 percent of gamma-cyclodextrin, 0.125 percent of aspartame and the mixture of the three into the water decoction, and carrying out ultrasonic treatment until the mixture is completely dissolved to obtain the flavoring solution.
3. Measurement of astringency
Taste tests were performed on 10 volunteers by a single blind method, as follows: 10 mL a solution to be tasted by the volunteer was held in the mouth, and a time was measured for 15s, and the mouth was rinsed during this time to allow the tongue to fully feel the astringent taste of the drug, so that the volunteer was scored by Visual Analogue Scale (VAS), expectorated, rinsed 5 times until the mouth was not bitter, and another solution was evaluated after 15min (each test required tasting the stock solution).
4. The volunteer tried and tested orally
Test results show that the single addition of mPEG2000-PLLA2000, gamma-cyclodextrin and aspartame has the taste masking effect, but the taste masking effect of the mixture of the mPEG2000-PLLA2000, the gamma-cyclodextrin and the aspartame is obviously superior to the taste masking effect of the mixture when the mixture is singly used.
In conclusion, the amphiphilic block copolymer can be used for masking the bad taste of the medicine, has good taste masking effect, has better taste masking effect when being mixed with any one of cyclodextrin and artificial sweetener, has the best taste masking effect when the dosage and the proportion of the amphiphilic block copolymer, the cyclodextrin and the artificial sweetener in the medicine are respectively 0.16 percent, 2 percent and 0.125 percent, and improves the medicine taking compliance of patients. The taste-masking chaperone agent formed by combining the amphiphilic block copolymer, the cyclodextrin and the artificial sweetener avoids using a large amount of flavoring agents, reduces the dosage of the sweetener in a prescription, reduces the production cost, is simple, convenient and practical, and has practical popularization and application values.
Claims (6)
1. A taste-masking chaperone agent characterized by: it consists of amphiphilic block copolymer, cyclodextrin and artificial sweetener,
the weight ratio of the amphiphilic block copolymer is 0.01 to 1 part, the weight ratio of cyclodextrin is 0.5 to 5 parts, and the weight ratio of artificial sweetener is 0.01 to 1 part;
wherein the amphiphilic block copolymer is amphiphilic diblock copolymer mPEG-PLA;
the cyclodextrin is gamma-cyclodextrin;
the artificial sweetener is one or more of saccharin, sodium cyclamate, aspartame, neotame, acesulfame potassium, NHDC and sucralose.
2. The taste masking partner of claim 1, wherein: the amphiphilic block copolymer is 0.16 part by weight, the cyclodextrin is 2 parts by weight, and the artificial sweetener is 0.125 part by weight.
3. The taste masking partner of claim 1 or 2, characterized in that: the artificial sweetener is aspartame.
4. Use of the taste-masking chaperone agent according to claim 1 in the manufacture of a good mouthfeel medicament.
5. Use according to claim 4, characterized in that: the good mouthfeel is a bitter, astringent, fishy and/or sour taste of the masked medicament.
6. Use according to claim 5, characterized in that: the dosage form of the medicine is granules, tablets, traditional Chinese medicine decoction, mixture, oral liquid or aromatic water.
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| CN1947797A (en) * | 2005-10-14 | 2007-04-18 | 杭州市中医院 | Traditional Chinese medicine mate |
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| CN103585641A (en) * | 2013-10-21 | 2014-02-19 | 海南卫康制药(潜山)有限公司 | Lipid coating and cyclodextrin inclusion synergic flavoring method and related preparation thereof |
| CN106729739A (en) * | 2016-11-30 | 2017-05-31 | 河南牧翔动物药业有限公司 | One kind is without palatability high content berberine sulphate oral liquid and preparation method thereof |
| CN108113962A (en) * | 2018-02-23 | 2018-06-05 | 成都中医药大学 | A kind of method for reducing the oral preparation of Chinese traditional medicinal astringent taste containing polyphenol |
| CN108553449A (en) * | 2018-02-14 | 2018-09-21 | 浙江万方生物科技有限公司 | A kind of taste masking sustained release Tilmicosin pre-mixing agent and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN2013MU03373A (en) * | 2013-10-25 | 2015-07-17 | Cadila Healthcare Ltd |
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- 2019-04-19 CN CN201910319283.9A patent/CN109999201B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1947797A (en) * | 2005-10-14 | 2007-04-18 | 杭州市中医院 | Traditional Chinese medicine mate |
| CN101502656A (en) * | 2008-12-24 | 2009-08-12 | 天津瑞普生物技术股份有限公司 | Composition for eliminating bitter taste of soluble and stable macrolides medicament |
| CN103585641A (en) * | 2013-10-21 | 2014-02-19 | 海南卫康制药(潜山)有限公司 | Lipid coating and cyclodextrin inclusion synergic flavoring method and related preparation thereof |
| CN106729739A (en) * | 2016-11-30 | 2017-05-31 | 河南牧翔动物药业有限公司 | One kind is without palatability high content berberine sulphate oral liquid and preparation method thereof |
| CN108553449A (en) * | 2018-02-14 | 2018-09-21 | 浙江万方生物科技有限公司 | A kind of taste masking sustained release Tilmicosin pre-mixing agent and preparation method thereof |
| CN108113962A (en) * | 2018-02-23 | 2018-06-05 | 成都中医药大学 | A kind of method for reducing the oral preparation of Chinese traditional medicinal astringent taste containing polyphenol |
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