Pharmaceutical composition containing silybin and ve

Abstract

A pharmaceutical composition is prepared from the following raw materials (in parts by weight): silybin (8.75-60), phospholipid (15-65), a Pu'er tea extract (25-200), and vitamin E (6.25-40). The composition has the effect of treating non-alcoholic fatty liver diseases.

Claims

1. A pharmaceutical granule consisting essentially of bulk drugs, wherein the bulk drugs consist of 8.75-60 parts by weight of silybin; 15-65 parts by weight of phospholipid; 25-200 parts by weight of Pu'er tea extract; and 6.25-40 parts by weight of vitamin E; and, wherein the pharmaceutical granule consists of a first particle consisting of the Pu'er tea extract coated with a mixture of the phospholipid and the silybin, and additional particles consisting of the vitamin E, and, optionally, pharmaceutically acceptable carriers.

2. The pharmaceutical granule of claim 1, wherein the bulk drugs consist of 25-40 by weight parts of silybin; 30-50 parts by weight of phospholipid; 80-120 parts by weight of Pu'er tea extract; and 20-30 parts by weight of vitamin E.

3. The pharmaceutical granule of claim 1 wherein the vitamin E is vitamin E acetate.

4. The pharmaceutical granule of claim 1, wherein the pharmaceutically acceptable carriers are 0.1-99.9% of the total weight of the pharmaceutical granule.

5. The pharmaceutical granule of 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 D, 1-dodecylazacycloheptan-2-one, 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 derivatives 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, kaolin, talc, calcium stearate, magnesium stearate, microcrystalline cellulose, and a carbonate, acetate, or phosphate salt of a monovalent alkali metal or aqueous solution thereof.

6. A dosage form comprising the pharmaceutical granule of claim 4, wherein the dosage form 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 agent, solution, injection, suppository, ointment, emplastrum, creme, spray, and patch.

7. The pharmaceutical granule of claim 2 wherein the vitamin E is vitamin E acetate or vitamin E succinate.

8. The pharmaceutical granule of claim 1 wherein the vitamin E is vitamin E succinate.

9. The pharmaceutical granule of claim 2, wherein the pharmaceutically acceptable carriers are 0.1-99.9% of the total weight of the pharmaceutical composition.

10. The pharmaceutical granule of claim 9, 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 D, 1-dodecylazacycloheptan-2-one, 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 derivatives 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, kaolin, talc, calcium stearate, magnesium stearate, microcrystalline cellulose, and a carbonate, acetate, or phosphate salt of a monovalent alkali metal or aqueous solution thereof.

11. A dosage form comprising the pharmaceutical granule of claim 9, wherein the dosage form 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 agent, solution, injection, suppository, ointment, emplastrum, creme, spray, and patch.

12. A pharmaceutical granule consisting essentially of bulk drugs, wherein the bulk drugs consist of 6.3-17.3 parts by weight of silybin; 11-29 parts by weight of phospholipid; 40-73 parts by weight of Pu'er tea extract; and 7.7-20 parts by weight of vitamin E; and, wherein the pharmaceutical granule consists of a first particle consisting of the Pu'er tea extract coated with a mixture of the phospholipid and the silybin, and additional particles consisting of the vitamin E, and, optionally, pharmaceutically acceptable carriers.

13. The pharmaceutical granule of claim 12, wherein the vitamin E is vitamin E acetate or vitamin E succinate.

14. The pharmaceutical granule of claim 12, wherein the pharmaceutically acceptable carriers are 0.1-99.9% of the total weight of the pharmaceutical composition.

15. The pharmaceutical granule of 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 D, 1-dodecylazacycloheptan-2-one, 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 derivatives 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, kaolin, talc, calcium stearate, magnesium stearate, microcrystalline cellulose, and a carbonate, acetate, or phosphate salt of a monovalent alkali metal or aqueous solution thereof.

16. A dosage form comprising the pharmaceutical granule of claim 14, wherein the dosage form 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 agent, solution, injection, suppository, ointment, emplastrum, creme, spray, and patch.

17. The pharmaceutical granule of claim 12, wherein the bulk drugs consist of 14 parts by weight of silybin; 26 parts by weight of phospholipid; 40 parts by weight of Pu'er tea extract; and 20 parts by weight of vitamin E.

18. The pharmaceutical granule of claim 17, wherein the bulk drugs consist of 105 mg of silybin; 195 mg of phospholipid; 300 mg of Pu'er tea extract; and 150 mg of vitamin E.

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 silybin-phospholipid-Pu'er tea compositions prepared in embodiments 16-20.

DETAILED DESCRIPTION OF THE INVENTION

(2) The present invention is further illustrated by the following specific examples, but not intended to limit the present invention.

Embodiment 1

(3) Taking 26.25 g of silybin, 45 g of soybean phospholipid, 75 g of Pu'er tea extract, and 18.75 g of vitamin E. {circle around (1)} Preparation of silybin complex liquid; weighing a prescription amount of silybin, 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;

(4) {circle around (2)} Granulation: weighing a prescription amount of Pu'er tea extract as a base material, taking the silybin complex liquid prepared in step CD as a feed liquid, preparing the 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 for later use; {circle around (3)} Mixing vitamin E and the granules prepared in step {circle around (2)} uniformly in an equal incremental manner , bagging, made into 1,000 bags of granules.

Embodiment 2

(5) Taking 180 g of silybin, 195 g of soybean phospholipid, 600 g of Pu'er tea extract, and 120 g of vitamin E.

(6) {circle around (1)} Preparation of silybin complex liquid: weighing a prescription amount of silybin, 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;

(7) {circle around (2)} Granulation: weighing a prescription amount of Pu'er tea extract as a base material, taking the silybin composite 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 for later use; {circle around (3)} Mixing vitamin E and the granules prepared in step {circle around (2)} uniformly in an equal incremental manner, bagging, made into 1,000 bags of granules.

Embodiment 3

(8) Taking 26.25 g of silybin, 195 g of phospholipid, 600 g of Pu'er tea extract, and 18.75 g of vitamin E, {circle around (1)} CD Preparation of silybin complex liquid: weighing a prescription amount of silybin, soybean phospholipid, and dissolving them in the anhydrous ethanol, heating and refluxing to clarify the solution and continuing to heat for 0.5 h, then concentrated under reduced pressure and recycling the ethanol to 5% of the original volume for later use;

(9) {circle around (2)} Granulation: weighing a prescription amount of Pu'er tea extract as a base material, taking the silybin composite 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 material temperature at 50° C., drying at 55° C. for 10 min after the liquid complexes are ail sprayed in for later use; {circle around (3)} Mixing vitamin E and the granules prepared in step {circle around (2)} uniformly in an equal incremental manner, bagging, made into 1,000 bags of granules.

Embodiment 4

(10) Taking 26.25 g of silybin, 195 g of phospholipid, 75 g of Pu'er tea extract and 120 g of vitamin E, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 5

(11) Taking 180 g of silybin, 45 g of phospholipid, 75 g of Pu'er tea extract and 18.75 g of vitamin E, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 6

(12) Taking 180 g of silybin, 45 g of phospholipid, 600 g of Pu'er tea extract and 12.0 g of vitamin E, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 7

(13) Taking 180 g of silybin, 195 g of phospholipid, 75 g of Pu'er tea extract and 120 g of vitamin E, and preparing, 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 8

(14) Taking 26.25 g of silybin, 48.75 g of phospholipid, 75 g of Pu'er tea extract and 37.5 g of vitamin E, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 9

(15) Taking 26.25 g of silybin, 48.75 g of phospholipid, 300 g of Pu'er tea extract and 37.5 g of vitamin E, and preparing 1,000 bags of granules according to tire method of Embodiment 1.

Embodiment 10

(16) Taking 52.5 g of silybin, 97.5 g of phospholipid, 300 g of Pu'er tea extract and 9,375 g of vitamin E, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 11

(17) Taking 75 g of silybin, 90 g of phospholipid, 240 g of Pu'er tea extract and 90 g of vitamin E, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 12

(18) Taking 90 g of silybin, 108 g of phospholipid, 270 g of Pu'er tea extract and 75 g of vitamin E, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 13

(19) Taking 105 g of silybin, 126 g of phospholipid, 300 g of Pu'er tea extract and 75 g of vitamin E, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 14

(20) Taking 105 g of silybin, 195 g of phospholipid, 300 g of Pu'er tea extract and 75 g of vitamin E, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 15

(21) Taking 120 g of silybin, 150 g of phospholipid, 360 g of Pu'er tea extract and 90 g of vitamin E, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 16

(22) Taking 105 g of silybin, 126 g of phospholipid, 300 g of Pu'er tea extract and 82.3 g of vitamin E acetate, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 17

(23) Taking 105 g of silybin, 126 g of phospholipid, 300 g of Pu'er tea extract and 92.4 g of vitamin E succinate, and preparing 1,000 bags of granules according to the method of Embodiment 1.

Embodiment 18

(24) Taking the granules of Embodiment 8, adding 549 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 granules.

Embodiment 19

(25) Taking the granules of Embodiment 9, adding 324 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 granules.

Embodiment 20

(26) Taking the granules of Embodiment 10, adding 308 g of microcrystalline cellulose and 32 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

Embodiment 21

(27) Taking the granules of Embodiment 13, adding 194 g of microcrystalline cellulose, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

Embodiment 22

(28) Taking the granules of Embodiment 14, adding 61 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

Embodiment 23

(29) Taking the composition of Embodiment 8, adding 400 g of lactose, 149 g of starch and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 granules.

Embodiment 24

(30) Taking the composition of Embodiment 13, adding 90 g of lactose, 10 g of talc and 94 g of low-substituted hydroxypropyl cellulose, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 granules.

Embodiment 25

(31) Taking the granules of Embodiment 13, adding 194 g of microcrystalline cellulose, mixing uniformly, tablet pressing to obtain 1,000 tablets.