Pharmaceutical composition containing silybin, VE and L-carnitine

Abstract

A pharmaceutical composition. The pharmaceutical composition is prepared from the following raw materials in parts by weight: 8.75-60 parts of silybin, 15-65 parts of phospholipid, 25-200 parts of a Pu'er tea extract, 6.25-40 parts of vitamin E, and 8.3-60 parts of L-carnitine. The composition can be used for treating non-alcoholic fatty liver diseases.

Claims

1. A pharmaceutical composition comprising 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; 6.25-40 parts by weight of vitamin E; and 8.3-60 parts by weight of L-carnitine.

2. The pharmaceutical composition of claim 1 comprising 25-40 parts by weight of silybin; 30-50 parts by weight of phospholipid; 80-120 parts by weight of Pu'er tea extract; 10-30 parts by weight of vitamin E; and 25-40 parts by weight of L-carnitine.

3. The pharmaceutical composition of claim 2 comprising 35 parts by weight of silybin; 42 parts by weight of phospholipid; 100 parts by weight of Pu'er tea extract; 16.7 parts by weight of vitamin E; and 33.3 parts by weight of L-carnitine.

4. The pharmaceutical composition according to claim 1, wherein the vitamin E is vitamin E acetate or vitamin E succinate.

5. The pharmaceutical composition according to claim 1, wherein the L-carnitine is L-carnitine tartrate.

6. A pharmaceutical preparation comprising the pharmaceutical composition of claim 1, further comprising pharmaceutically acceptable carriers; wherein the pharmaceutically acceptable carriers are 0.1-99.9% of the total preparation by weight.

7. The pharmaceutical preparation of claim 6, 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, and microcrystalline cellulose, and a carbonate, acetate, or phosphate salt of a monovalent alkali metal or aqueous solution thereof.

8. The pharmaceutical preparation of claim 7, wherein the pharmaceutical preparation is are 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, supensoid agent, solution, injection, suppository, ointment, emplastrum, creme, spray, and patch.

9. A method of preparing the pharmaceutical preparation according to claim 6, 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 phospholipin, 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 for later use; (3) granulating by weighing a prescription amount of Pu'er tea extract as a base material, taking the silybin complex liquid prepared in step (2) as a feed liquid, and preparing granules by a fluidization spray method with a fluidized bed, and drying after the liquid complex is all sprayed in for later use; (4) achieving total blending by mixing the vitamin E, the L-carnitine and the granules prepared in step (3) uniformly to get the pharmaceutical composition; and (5) combining the pharmaceutical composition and the pharmaceutically acceptable carriers to make a conventional preparation.

10. The method according to claim 9, wherein the heating time in step (2) is 0.5-1.5 hours; the concentrated volume is 5%-20% of the original volume and the temperature of concentration under reduced pressure is 60-80 C.; the parameters of the fluidized bed in step (3) are that the temperature of the materials is 40-65 C., and parameters such as fan frequency, the inlet air temperature and the infusion frequency are adjusted to keep the materials in a good fluidizing state during the granulation process; and wherein after granulation is completed, the granules are dried for 10-60 minutes and the drying temperature is 55-65 C.

11. A method of using the pharmaceutical composition of claim 1 for treating non-alcoholic fatty liver diseases and/or reducing fat, losing weight, and beautifying skin, comprising administering a therapeutically effective amount to a human in need thereof.

12. A pharmaceutical preparation comprising the pharmaceutical composition of claim 2, further comprising pharmaceutically acceptable carriers; wherein the pharmaceutically acceptable carriers are 0.1-99.9% of the total preparation by weight.

13. The pharmaceutical preparation of claim 12, 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, and microcrystalline cellulose, and a carbonate, acetate, or phosphate salt of a monovalent alkali metal or aqueous solution thereof.

14. The pharmaceutical preparation of claim 12, 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, supensoid agent, solution, injection, suppository, ointment, emplastrum, creme, spray, and patch.

15. A pharmaceutical preparation comprising the pharmaceutical composition of claim 3, further comprising pharmaceutically acceptable carriers; wherein the pharmaceutically acceptable carriers are 0.1-99.9% of the total preparation by weight.

16. The pharmaceutical preparation of claim 15, 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, and microcrystalline cellulose, and a carbonate, acetate, or phosphate salt of a monovalent alkali metal or aqueous solution thereof.

17. The pharmaceutical preparation of claim 15, 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, supensoid agent, solution, injection, suppository, ointment, emplastrum, creme, spray, or patch; preferably, wherein the pharmaceutical preparation is a capsule, granule, and tablet.

18. A method of preparing the pharmaceutical preparation according to claim 12, 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 phospholipin, 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 for later use; (3) granulating by weighing a prescription amount of Pu'er tea extract as a base material, taking the silybin complex liquid prepared in step (2) as a feed liquid, and preparing granules by a fluidization spray method with a fluidized bed, and drying after the liquid complex is all sprayed in for later use; (4) achieving total blending by mixing the vitamin E, the L-carnitine and the granules prepared in step (3) uniformly to get the pharmaceutical composition; and (5) combining the pharmaceutical composition and the pharmaceutically acceptable carriers to make a conventional preparation.

19. The method according to claim 18, wherein the heating time in step (2) is 0.5-1.5 hours; the concentrated volume is 5%-20% of the original volume and the temperature of concentration under reduced pressure is 60-80 C.; the parameters of the fluidized bed in step (3) are that the temperature of the materials is 40-65 C., and parameters such as fan frequency, the inlet air temperature and the infusion frequency are adjusted to keep the materials in a good fluidizing state during the granulation process; and wherein after granulation is completed, the granules are dried for 10-60 minutes and the drying temperature is 55-65 C.

20. A method of using the pharmaceutical preparation of claim 6 for treating non-alcoholic fatty liver diseases and/or reducing fat, losing weight, and beautifying skin, comprising administering a therapeutically effective amount to a human 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 silybin-phospholipin-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 is not intended to be limiting of the present invention.

Embodiment 1

(3) Taking 26.25 g of silybin, 45 g of soybean phospholipid, 75 g of Pu'er tea extract, 18.75 g of vitamin E and 25 g of L-carnitine.

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

(5) {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 {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 40 C., drying at 60 C. for 20 min after the liquid complexes are all sprayed in for later use;

(6) {circle around (3)} mixing a prescription amount of vitamin E with the L-carnitine uniformly, then mixing the mixture of the two with the granules prepared in step {circle around (2)} uniformly in an equal incremental manner, bagging, made into 1,000 bags of granules.

Embodiment 2

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

(8) {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;

(9) {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 {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;

(10) {circle around (3)} mixing a prescription amount of vitamin E with the L-carnitine uniformly, and mixing the mixture of the two with the granules prepared in step {circle around (2)} uniformly in an equal incremental manner, bagging, made into 1,000 bags of granules.

Embodiment 3

(11) Taking 26.25 g of silybin, 195 g of phospholipid, 600 g of Pu'er tea extract, 18.75 g of vitamin E and 25 g of L-carnitine.

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

(13) {circle around (2)} granulation: weighing a prescription amount of Pu'er tea extract as a base material, taking a silybin 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 material temperature at 50 C., drying at 55 C. for 10 min after the liquid complexes are all sprayed in for later use;

(14) {circle around (3)} mixing a prescription amount of vitamin E with the L-carnitine uniformly, and mixing the mixture of the two with the granules prepared in step {circle around (2)} uniformly in an equal incremental manner, bagging, made into 1,000 bags of granules.

Embodiment 4

(15) Taking 26.25 g of silybin, 195 g of phospholipid, 75 g of Pu'er tea extract, 12.0 g of vitamin E and 180 g of L-carnitine, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 5

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

Embodiment 6

(17) Taking 180 g of silybin, 45 g of phospholipid, 600 g of Pu'er tea extract, 120 g of vitamin E and 100 g of L-carnitine, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 7

(18) Taking 180 g of silybin, 195 g of phospholipid, 75 g of Pu'er tea extract, 18.75 g of vitamin E and 180 g of L-carnitine, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 8

(19) Taking 26.25 g of silybin, 48.75 g of phospholipid, 75 g of Pu'er tea extract, 37.5 g of vitamin E and 50 g of L-carnitine, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 9

(20) Taking 26.25 g of silybin, 48.75 g of phospholipid, 300 g of Pu'er tea extract, 37.5 g of vitamin E and 50 g of L-carnitine, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 10

(21) Taking 52.5 g of silybin, 97.5 g of phospholipid, 300 g of Pu'er tea extract, 9.375 g of vitamin E and 12.5 g of L-carnitine, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 11

(22) Taking 75 g of silybin, 90 g of phospholipid, 240 g of Pu'er tea extract, 30 g of vitamin E and 75 g of L-carnitine, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 12

(23) Taking 90 g of silybin, 108 g of phospholipid, 270 g of Pu'er tea extract, 60 g of vitamin E and 90 g of L-carnitine, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 13

(24) Taking 105 g of silybin, 126 g of phospholipid, 300 g of Pu'er tea extract, 75 g of vitamin E and 100 g of L-carnitine, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 14

(25) Taking 105 g of silybin, 195 g of phospholipid, 300 g of Pu'er tea extract, 75 g of vitamin E and 100 g of L-carnitine, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 15

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

Embodiment 16

(27) Taking 105 g of silybin, 126 g of phospholipid, 300 g of Pu'er tea extract, 75 g of vitamin E and 226.6 g of L-carnitine tartrate, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 17

(28) Taking 105 g of silybin, 126 g of phospholipid, 300 g of Pu'er tea extract, 82.3 g of vitamin E and 100 g of L-carnitine, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 18

(29) Taking 105 g of silybin, 126 g of phospholipid, 300 g of Pu'er tea extract, 92.4 g of vitamin E and 226.6 g of L-carnitine tartrate, and preparing 1,000 packages of granules according to the method of Embodiment 1.

Embodiment 19

(30) Taking the granules of Embodiment 8, adding 500 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

Embodiment 20

(31) Taking the granules of Embodiment 9, adding 274 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

Embodiment 21

(32) Taking the granules of Embodiment 10, adding 297 g of microcrystalline cellulose and 32 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

Embodiment 22

(33) Taking the granules of Embodiment 13, adding 30 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

Embodiment 23

(34) Taking the granules of Embodiment 14, adding 25 g of microcrystalline cellulose, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

Embodiment 24

(35) Taking the composition of Embodiment 8, adding 400 g of lactose, 100 g of starch and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

Embodiment 25

(36) Taking the composition of Embodiment 13, adding 20 g of lactose, 10 g of saponite and 64 g of low-substituted hydroxypropyl cellulose, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

Embodiment 26

(37) Taking the composition of Embodiment 13, adding 30 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, tablet pressing to obtain 1,000 tablets.