Taste-masking enteric-coated traditional Chinese medicine extract particles and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine extract preparation, and discloses taste-masking enteric-coated traditional Chinese medicine extract particles which comprise drug-loaded pellets and enteric-coated coatings coating the drug-loaded pellets. The invention relates to a drug-loaded pellet. The coating comprises 20-45 parts of pure powder of the traditional Chinese medicine extract and 5-10 parts of dextrin; according to the taste-masking enteric-coated traditional Chinese medicine extract particle and the preparation method thereof, a stable barrier is formed in gastric juice through a carboxymethyl chitosan-lipidosome copolymer coating, and the degradation rate of effective components is reduced to 1t from 40-60% of a traditional preparation; the pH-responsive coating ensures that the rapid release rate of the intestinal tract is as high as 90%, the bioavailability is improved by 2-3 times, the bitter taste is completely covered by the coating layer, and the coating layer can be mixed with food to feed pets; the prepared sustained-release dosage form prolongs the action time of the medicine, reduces the medication frequency, reduces the medication cost of pet owners, and improves pet welfare.

Description

Technical Field

[0001] The invention relates to the technical field of preparation of traditional Chinese medicine extracts, in particular to taste-masked enteric-coated traditional Chinese medicine extract granules and a preparation method thereof. Background Art

[0002] With the continuous deepening of traditional Chinese medicine research, Chinese herbal extracts have been widely used in the fields of medicine, health products and food. Chinese herbal extracts have rich bioactive ingredients and significant therapeutic effects, but traditional Chinese medicine preparations have certain limitations;

[0003] When traditional Chinese medicine extract granules are taken orally, the active ingredients are easily degraded by gastric acid. This phenomenon seriously affects the efficacy of the drug, making it difficult to improve the utilization rate of Chinese medicine extracts and achieve better therapeutic and health care functions. In addition, Chinese medicine extracts usually have a bitter taste, and directly mixing them into pet feed can easily cause pets to refuse to eat. These problems lead to low bioavailability, poor palatability and insufficient release control of Chinese medicine extract granules during application. Therefore, we proposed a taste-masked enteric-coated Chinese medicine extract granule and its preparation method to solve the above-mentioned problems. Summary of the Invention

[0004] In view of the shortcomings of the existing technology, the present invention provides a taste-masked enteric-coated Chinese medicine extract granule and a preparation method thereof, which solves the problems of low bioavailability, poor palatability and insufficient release control of traditional Chinese medicine extract granules.

[0005] To achieve the above objectives, the present invention is implemented through the following technical solutions: a taste-masked enteric-coated Chinese medicine extract granule, comprising a drug-loaded pellet and an enteric coating covering the drug-loaded pellet;

[0006] Drug-loaded micropellets, including 20-45 parts of pure Chinese herbal medicine extract powder and 5-10 parts of dextrin

[0007] The coating comprises 60-80 parts of carboxymethyl chitosan, 20-30 parts of mono- and distearic glycerides, 0.5-5 parts of plasticizer and 0.01-0.03 parts of nano silicon dioxide.

[0008] Preferably, the Chinese herbal medicine extract may be a plant-derived or animal-derived extract.

[0009] Preferably, the plasticizer is one or more combinations of polyethylene glycol 400, triethyl citrate or glycerol.

[0010] Preferably, the drug-loaded micropellets are 0.5-1.5 mm in size, and after coating, the dissolution rate of the drug-loaded micropellets in gastric juice with a pH < 5 is < 8% within 2 hours, and the disintegration and release rate in intestinal juice with a pH ≥ 6.8 is ≥ 90% within 30 minutes, wherein the coating thickness is 30-80 μm.

[0011] Preferably, the carboxymethyl chitosan and mono- and distearic glyceryl together constitute a carboxymethyl chitosan-liposome copolymer carrier, wherein the weight ratio of carboxymethyl chitosan to mono- and distearic glyceryl is 3:1.

[0012] The present invention provides a method for preparing taste-masked enteric-coated Chinese medicine extract granules;

[0013] S1. Mix the pure powder of Chinese herbal extract and dextrin in proportion, and pass through an 80-100 mesh sieve to ensure uniform dispersion;

[0014] S2, using an extruder to extrude the mixed material into strips to form a continuous extrudate, and then using a spheronizer to cut the extrudate into small segments, and rolling them on a high-speed rotating spherical disc to form dense spherical pellets;

[0015] S3, dissolving carboxymethyl chitosan and mono / distearic glycerol in an organic solvent, adding a plasticizer and nano-silicon dioxide, and homogenizing to form a copolymer coating solution;

[0016] S4. Use fluidized bed bottom spray coating technology to evenly spray the coating liquid on the surface of the drug-loaded micropellets. Control the inlet air temperature at 40-60°C and the material temperature at 35-45°C. Coating is carried out until the target weight gain is achieved.

[0017] S5. After coating, the drug-loaded micropellets were dried at 40°C for 2 hours and sieved to obtain enteric-coated granules with uniform particle size.

[0018] Preferably, in S2, the organic solvent is an ethanol-water mixed solvent, and the volume concentration of ethanol is 70%-90%.

[0019] Preferably, in said S3, the homogenization treatment conditions are:

[0020] The shear rate is 8000-12000 rpm, the temperature is controlled at 55-65° C., the homogenization time is 15-30 minutes, and the dynamic viscosity of the obtained coating solution is in the range of 200-500 mPa·s.

[0021] Preferably, in S4, the coating liquid spraying rate is 2-5 mL / min, and the atomization pressure is 0.2-0.4 MPa.

[0022] Preferably, in S5, the coated drug-loaded micropellets of 0.6-1.8 mm are sieved and collected.

[0023] Beneficial effects

[0024] The present invention provides a taste-masked enteric-coated Chinese herbal extract granule and a preparation method thereof. Compared with the prior art, it has the following advantages:

[0025] The taste-masked enteric-coated Chinese herbal extract granules and their preparation method form a stable barrier in gastric juice through carboxymethyl chitosan-liposome copolymer coating, reducing the degradation rate of active ingredients from 40-60% of traditional preparations to less than 10%. The pH-responsive coating ensures rapid intestinal release of up to 90%, increasing bioavailability by 2-3 times, and completely masking the bitter taste. The pet feeding rate is increased from 60% to over 95%. The addition of nano-SiO2 increases the mechanical strength of the coating by 50%, extending the storage period to 24 months. The dosage form can mask the bitter taste of the Chinese herbal extract and can be mixed with food to feed pets. The formulation of the sustained-release dosage form prolongs the drug's action time, reduces the frequency of medication, reduces medication costs for pet owners, and improves pet welfare. Therefore, the present invention has significant advantages in protecting active ingredients, controlling release, improving palatability, etc., and is particularly suitable for the development of Chinese herbal preparations for pets. DETAILED DESCRIPTION

[0026] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0027] A taste-masked enteric-coated Chinese medicine extract granule, comprising a drug-loaded pellet and an enteric coating covering the drug-loaded pellet;

[0028] Drug-loaded micropellets, comprising: 20-45 parts of pure powder of Chinese herbal medicine extract and 5-10 parts of dextrin, wherein the Chinese herbal medicine extract can be of plant or animal origin;

[0029] The coating comprises: 60-80 parts of carboxymethyl chitosan, 20-30 parts of mono- and distearic glycerol, 0.5-5 parts of a plasticizer, and 0.01-0.03 parts of nano-silicon dioxide, wherein the plasticizer is one or more of polyethylene glycol 400, triethyl citrate, or glycerol; the carboxymethyl chitosan and the mono- and distearic glycerol together constitute a carboxymethyl chitosan-liposome copolymer carrier, wherein the weight ratio of the carboxymethyl chitosan to the mono- and distearic glycerol is 3:1;

[0030] The drug-loaded micropellets are 0.5-1.5 mm in diameter. After coating, the dissolution rate of the drug-loaded micropellets in gastric juice with a pH value less than 5 is less than 8% within 2 hours, and the disintegration and release rate in intestinal juice with a pH value greater than or equal to 6.8 is greater than or equal to 90% within 30 minutes. The coating thickness is 30-80 μm.

[0031] The present invention provides a method for preparing taste-masked enteric-coated Chinese medicine extract granules;

[0032] S1. Mix the pure powder of Chinese herbal extract and dextrin in proportion, and pass through an 80-100 mesh sieve to ensure uniform dispersion;

[0033] S2, using an extruder to extrude the mixed material into strips to form a continuous extrudate, and then using a spheronizer to cut the extrudate into small segments, and rolling them on a high-speed rotating spherical disc to form dense spherical pellets;

[0034] S3. Dissolving carboxymethyl chitosan and mono / distearic glycerol in an organic solvent, adding a plasticizer and nano-silica, and homogenizing to form a copolymer coating solution. The organic solvent is an ethanol-water mixed solvent, the ethanol volume concentration is 70%-90%, and the homogenization conditions are: a shear rate of 8000-12000 rpm, a temperature controlled at 55-65° C., and a homogenization time of 15-30 minutes. The resulting coating solution has a dynamic viscosity in the range of 200-500 mPa·s.

[0035] S4. Use fluidized bed bottom spray coating technology to evenly spray the coating liquid on the surface of the drug-loaded micropellets. Control the inlet air temperature at 40-60°C and the material temperature at 35-45°C. Coating is carried out until the target weight gain is achieved. The coating liquid spray rate is 2-5 mL / min and the atomization pressure is 0.2-0.4 MPa.

[0036] S5. After coating, the drug-loaded micropellets were dried at 40° C. for 2 hours and sieved to obtain enteric-coated granules with uniform particle size. The coated drug-loaded micropellets with a particle size of 0.6-1.8 mm were sieved and collected.

[0037] It should be noted that Chinese herbal medicine extracts can be of plant or animal origin. For plant-derived Chinese herbal medicine extracts, such as Coptis chinensis extract, the core ingredients are berberine (≥85%) and palmatine, which inhibit bacterial diarrhea secondary to canine parvovirus (CPV). For Astragalus membranaceus extract, the core ingredients are astragaloside (≥0.5%) and polysaccharides, which are used to increase white blood cell counts (adjuvant treatment for chemotherapy dogs).

[0038] For animal-derived extracts, earthworm (earthworm) extract, the core ingredient is lumbrokinase (≥2000IU / g), which can reduce the incidence of DVT in bedridden dogs after surgery by 60%. Specific needs can be flexibly used according to actual needs.

[0039] Example 1;

[0040] Raw material formula: drug-loaded micropellets: including 35 parts of pure powder of Chinese herbal medicine extract (Coptis rhizome) and 8 parts of dextrin, coating materials: 75 parts of carboxymethyl chitosan, 25 parts of mono / distearic glycerol, 3 parts of triethyl citrate, and 0.02 parts of nano-SiO2;

[0041] Preparation process;

[0042] The Coptidis rhizome extract and dextrin were mixed and passed through a 100-mesh sieve, and drug-loaded micropellets with a size of 1.0 ± 0.2 mm were prepared by the extrusion-spheronization method;

[0043] Dissolve carboxymethyl chitosan in 85% ethanol aqueous solution, add melted mono / distearic glycerol, homogenize at 60°C and 10,000 rpm for 20 minutes, add plasticizer and nano-SiO2;

[0044] Fluidized bed bottom spray coating was used with an inlet air temperature of 45°C, a material temperature of 38°C, a spray rate of 3 mL / min, and a coating weight gain of 20%.

[0045] After coating, the pellets were dried at 40°C for 2 hours and passed through a 20-mesh sieve to collect particles of 0.8-1.5 mm.

[0046] Specific performance: coating thickness: 55±5μm, gastric juice protection: 2-hour dissolution rate of 6.3% in artificial gastric juice at pH 1.2, enteric release: 25-minute release rate of 95% in artificial intestinal juice at pH 6.8, and feeding rate of 98% after mixing into dog food, compared with only 62% of the uncoated group, thereby improving feeding effect;

[0047] In this solution, the carboxymethyl chitosan-liposome copolymer coating forms a stable barrier in gastric juice, and the degradation rate of the active ingredient is reduced from 40-60% of traditional preparations to <10%. The pH-responsive coating ensures rapid intestinal release (≥90%), and the bioavailability is increased by 2-3 times. The coating layer completely masks the bitter taste, and the pet feeding rate is increased from 60% to more than 95%. The addition of nano-SiO2 increases the mechanical strength of the coating by 50%, and the storage period is extended to 24 months. This dosage form can mask the bitter taste of the traditional Chinese medicine extract and can be mixed with food to feed pets; the preparation of a sustained-release dosage form prolongs the drug's action time, reduces the number of medication times, reduces the cost of medication for pet owners, and improves pet welfare. It can be seen that the present invention has significant advantages in protecting active ingredients, controlling release, and improving palatability, and is particularly suitable for the development of traditional Chinese medicine preparations for pets.

[0048] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art will be able to modify the technical solutions described in the aforementioned embodiments or substitute equivalents for some of the technical features. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A taste-masked enteric-coated Chinese medicine extract granule, characterized in that: It includes drug-loaded pellets and an enteric coating covering the drug-loaded pellets; Drug-loaded micropellets, including 20-45 parts of pure Chinese herbal medicine extract powder and 5-10 parts of dextrin The coating comprises 60-80 parts of carboxymethyl chitosan, 20-30 parts of mono- and distearic glycerides, 0.5-5 parts of plasticizer and 0.01-0.03 parts of nano silicon dioxide.

2. The taste-masked enteric-coated Chinese medicine extract granules according to claim 1, characterized in that: The Chinese medicine extract can be a plant-derived or animal-derived extract.

3. The taste-masked enteric-coated Chinese medicine extract granules according to claim 1, characterized in that: The plasticizer is one or more combinations of polyethylene glycol 400, triethyl citrate or glycerol.

4. The taste-masked enteric-coated Chinese medicine extract granules according to claim 1, characterized in that: The drug-loaded micro-pellets are 0.5-1.5 mm in size. After coating, the drug-loaded micro-pellets dissolve less than 8% in gastric juice with a pH less than 5 within 2 hours, and disintegrate and release ≥90% in intestinal juice with a pH greater than or equal to 6.8 within 30 minutes. The coating thickness is 30-80 μm.

5. The taste-masked enteric-coated Chinese medicine extract granules according to claim 1, characterized in that: The carboxymethyl chitosan and mono- and distearic glyceryl together constitute a carboxymethyl chitosan-liposome copolymer carrier, wherein the weight ratio of the carboxymethyl chitosan to the mono- and distearic glyceryl is 3:

1.

6. The method for preparing the taste-masked enteric-coated Chinese medicine extract granules according to any one of claims 1 to 5, characterized in that ； S1. Mix the pure powder of Chinese herbal extract and dextrin in proportion, and pass through an 80-100 mesh sieve to ensure uniform dispersion; S2, using an extruder to extrude the mixed material into strips to form a continuous extrudate, and then using a spheronizer to cut the extrudate into small segments, and rolling them on a high-speed rotating spherical disc to form dense spherical pellets; S3, dissolving carboxymethyl chitosan and mono / distearic glycerol in an organic solvent, adding a plasticizer and nano-silicon dioxide, and homogenizing to form a copolymer coating solution; S4. Use fluidized bed bottom spray coating technology to evenly spray the coating liquid on the surface of the drug-loaded micropellets. Control the inlet air temperature at 40-60°C and the material temperature at 35-45°C. Coating is carried out until the target weight gain is achieved. S5. After coating, the drug-loaded micropellets were dried at 40°C for 2 hours and sieved to obtain enteric-coated granules with uniform particle size.

7. The method for preparing the taste-masked enteric-coated Chinese medicine extract granules according to claim 6, characterized in that: In the above-mentioned S2, the organic solvent is an ethanol-water mixed solvent, and the volume concentration of ethanol is 70%-90%.

8. The method for preparing the taste-masked enteric-coated Chinese medicine extract granules according to claim 6, wherein: In said S3, the homogenization treatment conditions are: The shear rate is 8000-12000 rpm, the temperature is controlled at 55-65° C., the homogenization time is 15-30 minutes, and the dynamic viscosity of the obtained coating solution is in the range of 200-500 mPa·s.

9. The method for preparing the taste-masked enteric-coated Chinese medicine extract granules according to claim 6, characterized in that: In the above-mentioned S4, the coating liquid spraying rate is 2-5 mL / min, and the atomization pressure is 0.2-0.4 MPa.

10. The method for preparing taste-masked enteric-coated Chinese medicine extract granules according to claim 6, characterized in that: In S5, the coated drug-loaded micropellets with a size of 0.6-1.8 mm are collected by sieving.