Pharmaceutical composition containing silibinin

Abstract

Disclosed is a pharmaceutical composition containing silibinin, which is prepared from the following bulk drugs by weight ratio: 8.75-60 parts of silibinin, 15-65 parts of phospholipid, and 25-200 parts of Pu'er tea extract. The drug has the function of treating non-alcoholic fatty liver.

Claims

1. A pharmaceutical composition comprising a mixture of three bulk drugs, wherein the mixture consists of 8.75-60 parts by weight of silibinin; 15-65 parts by weight of phospholipid; and 25-200 parts by weight of Pu'er tea extract, wherein parts by weight is the weight ratio of each bulk drug in the mixture.

2. A pharmaceutical composition according to claim 1 comprising 25-40 parts by weight of silibinin; 30-50 parts by weight of phospholipid; and 80-120 parts by weight of Pu'er tea extract.

3. A pharmaceutical composition according to claim 1 comprising 35 parts by weight of silibinin; 42 parts by weight of phospholipid; and 100 parts by weight of Pu'er tea extract.

4. A pharmaceutical preparation comprising the pharmaceutical composition according to claim 1, further comprising pharmaceutically acceptable carriers; wherein the pharmaceutical preparation consists of the mixture of the three bulk drugs and the pharmaceutically acceptable carriers, and wherein the pharmaceutically acceptable carriers are 0.1-99.9% by weight of the pharmaceutical preparation.

5. The pharmaceutical preparation according to claim 4, wherein the pharmaceutically acceptable carriers are selected from the group consisting of mannitol, sorbitol, sorbic acid or sylvite, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, cysteine hydrochloride, mercaptoacetic acid, methionine, vitamin A, vitamin C, vitamin E, vitamin D, azone, disodium EDTA, calcium disodium EDTA, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose or a derivate thereof, alginate, gelatin, polyvinyl pyrrolidone, glycerine, propylene glycol, ethanol, polysorbate 60-80, sorbitan monooleate, beeswax, lanolin, liquid paraffin, cetyl alcohol, gallic acid esters, agar, triethanolamine, basic amino acid, urea, allantoin, calcium carbonate, calcium bicarbonate, surfactant, polyethylene glycol, cyclodextrin, beta-cyclodextrin, phospholipid, kaolin, talc, calcium stearate, magnesium stearate, microcrystalline cellulose, and a carbonate, acetate, or phosphate salt of a monovalent alkali metal.

6. The pharmaceutical preparation according to claim 4, wherein the pharmaceutical preparation is selected from the group consisting of a tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, oral agent, granule, pill, powder, paste, sublimed preparation, suspensoid, solution, injection, suppository, ointment, emplastrum, creme, spray, and patch.

7. A method of preparing the pharmaceutical preparation according to claim 4, comprising: (1) taking a prescription amount of raw materials for later use; (2) preparing a silybin complex liquid by weighing a prescription amount of silybin and a phospholipid, and dissolving them in anhydrous ethanol, heating and refluxing to clarify the solution and continuing to heat for a time, then concentrating the clear solution under reduced pressure to a concentrated volume, to obtain the silybin complex liquid; (3) granulating by weighing a prescription amount of Pu'er tea extract as a base material, taking the silibinin complex liquid prepared in step (2) as a feed liquid, preparing granules by a fluidization spray method with a fluidized bed, and then drying to obtain the granules; (4) combining the granules of step (3) and the pharmaceutically acceptable carriers to obtain the pharmaceutical preparation.

8. The method according to claim 7, wherein step (2), the heating time is 0.5-1.5 hours; and concentrating at 60-80 C. to the concentrated volume that is 5%-20% of the original volume.

9. The method according to claim 7, wherein step (3), during the granulation process the temperature of the fluidized bed is 40-65 C., and adjusting fan frequency, inlet air temperature and infusion frequency to keep the granules fluidized; and wherein the granules are dried for 10-60 minutes at 55-65 C.

10. A method of using the pharmaceutical composition of claim 1 for treating non-alcoholic fatty liver, comprising administering a therapeutically effective amount of the pharmaceutical preparation to a subject in need thereof.

11. A pharmaceutical preparation comprising the pharmaceutical composition according to claim 2, further comprising pharmaceutically acceptable carriers; wherein the pharmaceutical preparation consists of the mixture of three bulk drugs and the pharmaceutically acceptable carriers, and wherein the pharmaceutically acceptable carriers are 0.1-99.9% by weight of the pharmaceutical preparation.

12. The pharmaceutical preparation according to claim 11, wherein the pharmaceutically acceptable carriers are selected from the group consisting of mannitol, sorbitol, sorbic acid or sylvite, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, cysteine hydrochloride, mercaptoacetic acid, methionine, vitamin A, vitamin C, vitamin E, vitamin D, azone, disodium EDTA, calcium disodium EDTA, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose or a derivate thereof, alginate, gelatin, polyvinyl pyrrolidone, glycerine, propylene glycol, ethanol, polysorbate 60-80, sorbitan monooleate, beeswax, lanolin, liquid paraffin, cetyl alcohol, gallic acid esters, agar, triethanolamine, basic amino acid, urea, allantoin, calcium carbonate, calcium bicarbonate, surfactant, polyethylene glycol, cyclodextrin, beta-cyclodextrin, phospholipid, kaolin, talc, calcium stearate, magnesium stearate, microcrystalline cellulose, and a carbonate, acetate, or phosphate salt of a monovalent alkali metal.

13. The pharmaceutical preparation according to claim 11, wherein the pharmaceutical preparation is of a tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, oral agent, granule, pill, powder, paste, sublimed preparation, suspensoid, solution, injection, suppository, ointment, emplastrum, creme, spray, and patch.

14. A pharmaceutical preparation comprising the pharmaceutical composition according to claim 3, further comprising pharmaceutically acceptable carriers; wherein the pharmaceutical preparation consists of the mixture of three bulk drugs and the pharmaceutically acceptable carriers, and wherein the pharmaceutically acceptable carriers are 0.1-99.9% by weight of the pharmaceutical preparation.

15. The pharmaceutical preparation according to claim 14, wherein the pharmaceutically acceptable carriers are selected from the group consisting of mannitol, sorbitol, sorbic acid or sylvite, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, cysteine hydrochloride, mercaptoacetic acid, methionine, vitamin A, vitamin C, vitamin E, vitamin D, azone, disodium EDTA, calcium disodium EDTA, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acid, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivative, cellulose and derivate thereof, alginate, gelatin, polyvinyl pyrrolidone, glycerine, propylene glycol, ethanol, polysorbate 60-80, sorbitan monooleate, beeswax, lanolin, liquid paraffin, cetyl alcohol, gallic acid esters, agar, triethanolamine, basic amino acid, urea, allantoin, calcium carbonate, calcium bicarbonate, surfactant, polyethylene glycol, cyclodextrin, beta-cyclodextrin, phospholipid material, kaolin, talc, calcium stearate, magnesium stearate, microcrystalline cellulose, and a carbonate, acetate, or phosphate salt of a monovalent alkali metal.

16. The pharmaceutical preparation according to claim 14, wherein the pharmaceutical preparation is selected from the group consisting of a tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, oral agent, granule, pill, powder, paste, sublimed preparation, suspensoid, solution, injection, suppository, ointment, emplastrum, creme, spray, or patch.

17. A method of preparing the pharmaceutical preparation according to claim 14, comprising: (1) taking a prescription amount of raw materials for later use; (2) preparing a silybin complex liquid by weighing a prescription amount of silybin and a phospholipid, and dissolving them in anhydrous ethanol, heating and refluxing to clarify the solution and continuing to heat for a time, then concentrating the clear solution under reduced pressure to a concentrated volume, to obtain the silybin complex liquid; (3) granulating by weighing a prescription amount of Pu'er tea extract as a base material, taking the silibinin complex liquid prepared in step (2) as a feed liquid, preparing granules by a fluidization spray method with a fluidized bed, and then drying to obtain the granules; (4) combining the granules of step (3) and the pharmaceutically acceptable carriers to obtain the pharmaceutical preparation.

18. The method according to claim 17, wherein step (2), the heating time is 0.5-1.5 hours; and concentrating at 60-80 C. to the concentrated volume that is 5%-20% of the original.

19. The method according to claim 17, wherein step (3), during the granulation process the temperature of the fluidized bed is 40-65 C., and adjusting fan frequency, inlet air temperature and infusion frequency to keep the granules fluidized; and wherein the granules are dried for 10-60 minutes at 55-65 C.

20. A method of using the pharmaceutical preparation of claim 4 for treating non-alcoholic fatty liver, comprising administering a therapeutically effective amount of the pharmaceutical preparation to a subject in need thereof.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is an in vitro release curve, wherein, each sample is: reference preparation of Shui Lin Jia, Shui Lin Jia without Pu'er tea, and silibinin-phospholipid-Pu'er tea compositions prepared in embodiments 16-20.

DETAILED DESCRIPTION OF THE INVENTION

(2) Hereinafter, detailed description of the present invention will be described in further detail with reference to embodiments and experimental examples so as to more clearly describe the advantages and features of the present invention. But these embodiments are only exemplary and are not intended to limit the scope of the present invention. It will be understood by those skilled in the art that various modifications and substitutions may be made to the details and forms of the present invention without departing from the spirit and scope of the present invention, but that such modifications and substitutions fall within the scope of the present invention. The present invention is further illustrated by the following specific embodiments, but is not intended to be limiting of the present invention.

Embodiment 1

(3) Taking 26.25 g of silibinin, 45 g of soybean phospholipid, 75 g of Pu'er tea extract.

(4) {circle around (1)} Preparation of silibinin complex liquid: weighing a prescription amount of silibinin, soybean phospholipid, and dissolving them in the anhydrous ethanol, heating and refluxing to clarify the solution and continuing to heat for 1 h, then concentrated under reduced pressure and recycling the ethanol to 15% of the original volume for later use;
{circle around (2)} Granulation: weighing a prescription amount of Pu'er tea extract as a base material, taking the silibinin complex liquid prepared in step {circle around (1)} as a feed liquid, preparing granules by a fluidization spray method with a fluidized bed, controlling the temperature of materials at 40 C., drying at 60 C. for 20 min after the liquid complexes are all sprayed in, bagging, made into 1,000 bags of granules.

Embodiment 2

(5) Taking 180 g of silibinin, 195 g of soybean phospholipid, 450 g of Pu'er tea extract.

(6) {circle around (1)} Preparation of silibinin complex liquid: weighing a prescription amount of silibinin, soybean phospholipid, and dissolving them in the anhydrous ethanol, heating and refluxing to clarify the solution and continuing to heat for 1.5 h, then concentrated under reduced pressure and recycling the ethanol to 20% of the original volume for later use;
{circle around (2)} Granulation: weighing a prescription amount of Pu'er tea extract as a base material, taking the silibinin complex liquid prepared in step {circle around (1)} as a feed liquid, preparing the granules by a fluidization spray method with a fluidized bed, controlling the temperature of materials at 65 C., drying at 65 C. for 60 min after the liquid complexes are all sprayed in, bagging, made into 1,000 bags of granules.

Embodiment 3

(7) Taking 26.25 g of silibinin, 195 g of soybean phospholipid, 450 g of Pu'er tea extract.

(8) {circle around (1)} Preparation of silibinin complex liquid: weighing a prescription amount of silibinin, soybean phospholipid, and dissolving them in the anhydrous ethanol, heating and refluxing to clarify the solution and continuing to heat for 0.5 hours, then concentrated under reduced pressure and recycling the ethanol to 5% of the original volume for later use;
{circle around (2)} Granulation: weighing a prescription amount of Pu'er tea extract as a base material, taking the silibinin complex liquid prepared in step {circle around (1)} as a feed liquid, preparing the granules by a fluidization spray method with a fluidized bed, controlling the temperature of materials at 50 C., drying at 55 C. for 10 min after the liquid complexes are all sprayed in, bagging, made into 1,000 bags of granules.

Embodiment 4

(9) Taking 26.25 g of silibinin, 195 g of soybean phospholipid, 75 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 5

(10) Taking 180 g of silibinin, 45 g of soybean phospholipid, 75 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 6

(11) Taking 180 g of silibinin, 45 g of soybean phospholipid, 450 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 7

(12) Taking 180 g of silibinin, 195 g of soybean phospholipid, 75 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 8

(13) Taking 26.25 g of silibinin, 48.75 g of soybean phospholipid, 75 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 9

(14) Taking 26.25 g of silibinin, 48.75 g of soybean phospholipid, 300 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 10

(15) Taking 52.5 g of silibinin, 97.5 g of soybean phospholipid, 300 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 11

(16) Taking 75 g of silibinin, 90 g of soybean phospholipid, 240 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 12

(17) Taking 90 g of silibinin, 108 g of soybean phospholipid, 270 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 13

(18) Taking 105 g of silibinin, 126 g of soybean phospholipid, 300 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 14

(19) Taking 105 g of silibinin, 195 g of soybean phospholipid, 300 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 15

(20) Taking 120 g of silibinin, 150 g of soybean phospholipid, 360 g of Pu'er tea extract, and preparing 1,000 bags of granules according to the method of embodiment 1.

Embodiment 16

(21) Taking the granules of embodiment 8, adding 494 g of microcrystalline cellulose and 56 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 capsules.

Embodiment 17

(22) Taking the granules of embodiment 9, adding 269 g of microcrystalline cellulose and 56 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 capsules.

Embodiment 18

(23) Taking the granules of embodiment 10, adding 194 g of microcrystalline cellulose and 56 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 capsules.

Embodiment 19

(24) Taking the granules of embodiment 13, adding 169 g of microcrystalline cellulose, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 capsules.

Embodiment 20

(25) Taking the granules of embodiment 14, adding 44 g of microcrystalline cellulose and 56 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 capsules.

Embodiment 21

(26) Taking the granules of embodiment 8, adding 400 g of lactase, 94 g of starch and 56 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 capsules.

Embodiment 22

(27) Taking the granules of embodiment 13, adding 80 g of lactase, 10 g of talc and 79 g of low-substituted hydroxypropyl cellulose, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 capsules.

Embodiment 23

(28) Taking the granules of embodiment 13, adding into 169 g of microcrystalline cellulose, mixing uniformly, tablet pressing to obtain 1,000 tablets.