Pharmaceutical composition containing silibinin and pueraria root extract

Abstract

Disclosed are a pharmaceutical composition for treating non-alcoholic fatty liver and a method for preparing same. The composition is prepared from the following hulk drugs by weight ratio: 8.75-60 parts of silibinin, 15-65 parts of phospholipid, 25-200 parts of Pu'er tea extract, and 5-50 parts of radix puerariae extract.

Claims

1. A pharmaceutical composition comprising 8.75-60 parts by weight of silibinin; 15-65 parts by weight of phospholipid; 25-200 parts by weight of Pu'er tea extract; and 5-50 parts by weight of radix puerariae extract.

2. The pharmaceutical composition of claim 1 comprising 25-40 parts by weight of silibinin; 30-50 parts by weight of phospholipid; 80-120 parts by weight of Pu'er tea extract; and 10-35 parts by weight of radix puerariae extract.

3. The pharmaceutical composition of claim 1 comprising 35 parts by weight of silibinin; 42 parts by weight of phospholipid; 100 parts by weight of Pu'er tea extract; and 20 parts by weight of radix puerariae extract.

4. The pharmaceutical composition of claim 1, wherein puerarin in the radix puerariae extract is not less than 80%.

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

6. The pharmaceutical preparation according to claim 5, wherein the pharmaceutically acceptable carriers are selected from the group consisting of 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, kaolin, talc, calcium stearate, magnesium stearate, microcrystalline cellulose, and a carbonate, acetate, or phosphate salt of a monovalent alkali metal or aqueous solution thereof.

7. The pharmaceutical preparation according to claim 5, wherein the pharmaceutical preparation is selected from the group consisting of 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.

8. The pharmaceutical composition of claim 2, wherein puerarin in the radix puerariae extract is not less than 80%.

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

10. The pharmaceutical preparation according to claim 9, wherein the pharmaceutically acceptable carriers are selected from the group consisting of 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, 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. The pharmaceutical preparation according to claim 9, wherein the pharmaceutical preparation is selected from the group consisting of 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.

12. The pharmaceutical composition of claim 3, wherein puerarin in the radix puerariae extract is not less than 80%.

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

14. The pharmaceutical preparation according to claim 13, wherein the pharmaceutically acceptable carriers are selected from the group consisting of 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, kaolin, talc, calcium stearate, magnesium stearate, microcrystalline cellulose, and a carbonate, acetate, or phosphate salt of a monovalent alkali metal or aqueous solution thereof.

15. The pharmaceutical preparation according to claim 13, wherein the pharmaceutical preparation is selected from the group consisting of 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.

16. A method of preparing the pharmaceutical preparation according to claim 5, comprising: (1) taking a prescription amount of raw materials; (2) preparing a silybin complex liquid by weighing a prescription amount of silybin and phospholipid, and dissolving them in the anhydrous ethanol, heating and refluxing to clarify the solution, then concentrating the clear solution under reduced pressure to a concentrated volume, to obtain the silybin complex liquid; (3) granulating by spraying a prescription amount of Pu'er tea extract with the silybin complex liquid by a fluidization spray method with a fluidized bed, and drying; (4) blending by mixing radix puerariae extract and the granules of step (3) uniformly to obtain the pharmaceutical composition; and (5) combining the pharmaceutical composition with pharmaceutically acceptable carriers.

17. The method according to claim 16, 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 the 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 adjusting fan frequency, inlet air temperature and infusion frequency to keep the materials in a good fluidization state during the granulation process; and wherein after the granulation is completed, the granules are dried for 10-60 minutes at 55-65 C.

18. A method of treatment, comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 1 to a subject in need thereof, wherein the treatment is for non-alcoholic fatty liver disease, reducing fat, losing weight, or beautifying skin.

19. A method of treatment, comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 5 to a subject in need thereof, wherein the treatment is for non-alcoholic fatty liver disease, reducing fat, losing weight, or beautifying skin.

20. A method of preparing the pharmaceutical preparation according to claim 9, comprising: (1) taking a prescription amount of raw materials; (2) preparing a silybin complex liquid by weighing a prescription amount of silybin and phospholipid, and dissolving them in the anhydrous ethanol, heating and refluxing to clarify the solution, then concentrating the clear solution under reduced pressure to a concentrated volume, to obtain the silybin complex liquid; (3) granulating by spraying a prescription amount of Pu'er tea extract with the silybin complex liquid by a fluidization spray method with a fluidized bed, and drying; (4) blending by mixing radix puerariae extract and the granules of step (3) uniformly to obtain the pharmaceutical composition; and (5) combining the pharmaceutical composition with pharmaceutically acceptable carriers; 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 the 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 adjusting fan frequency, inlet air temperature and infusion frequency to keep the materials in a good fluidization state during the granulation process; and wherein after the granulation is completed, the granules are dried for 10-60 minutes at 55-65 C.

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

(3) Embodiment 1

(4) Taking 26.25 g of silibinin, 45 g of soybean phospholipid, 75 g of Pu'er tea extract, and 15 g of radix puerariae extract.

(5) {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;

(6) {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 40 C., drying at 60 C. for 20 min after the liquid complexes are all sprayed in for later use;

(7) {circle around (3)} Mixing a prescription amount of radix puerariae extract and the granules prepared in step {circle around (2)} uniformly in an equal incremental manner, bagging, made into 1,000 bags of granules.

(8) Embodiment 2

(9) Taking 180 g of silibinin, 195 g of soybean phospholipid, 600 g of Pu'er tea extract, and 150 g of radix puerariac extract.

(10) {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;

(11) {circle around (2)} Granulation: weighing a prescription amount of Pu'er tea extract as a base material, taking the silibinin 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;

(12) {circle around (3)} Mixing a prescription amount of radix puerariac extract and the granules prepared in step {circle around (2)} uniformly in an equal incremental manner, bagging, made into 1,000 bags of granules.

(13) Embodiment 3

(14) Taking 26.25 g of silibinin, 195 g of phospholipid, 600 g of Pu'er tea extract, and 15 g of radix puerariae extract.

(15) {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 h, then concentrated under reduced pressure and recycling the ethanol to 5% of the original volume for later use;

(16) {circle around (2)} Granulation: weighing a prescription amount of Pu'er tea extract as a base material, taking the silibinin 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 all sprayed in for later use;

(17) {circle around (3)} Mixing a prescription amount of radix puerariae extract and the granules prepared in step {circle around (2)} uniformly in an equal incremental manner, bagging, made into 1,000 bags of granules.

(18) Embodiment 4

(19) Taking 26.25 g of silibinin, 195 g of phospholipid, 75 g of Pu'er tea extract and 150 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(20) Embodiment 5

(21) Taking 180 g of silibinin, 45 g of phospholipid, 75 g of Pu'er tea extract and 15 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(22) Embodiment 6

(23) Taking 180 g of silibinin, 45 g of phospholipid, 600 g of Pu'er tea extract and 150 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(24) Embodiment 7

(25) Taking 180 g of silibinin, 195 g of phospholipid, 75 g of Pu'er tea extract and 150 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(26) Embodiment 8

(27) Taking 26.25 g of silibinin, 48.75 g of phospholipid, 75 g of Pu'er tea extract and 30 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(28) Embodiment 9

(29) Taking 26.25 g of silibinin, 48.75 g of phospholipid, 300 g of Pu'er tea extract and 30 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(30) Embodiment 10

(31) Taking 52.5 g of silibinin, 97.5 g of phospholipid, 300 g of Pu'er tea extract and 7.5 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(32) Embodiment 11

(33) Taking 75 g of silibinin, 90 g of phospholipid, 240 g of Pu'er tea extract and 36 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(34) Embodiment 12 Preparation of the Composition

(35) Taking 90 g of silibinin, 108 g of phospholipid, 270 g of Pu'er tea extract and 90 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(36) Embodiment 13 Preparation of the Composition

(37) Taking 105 g of silibinin, 126 g of phospholipid, 300 g of Pu'er tea extract and 60 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(38) Embodiment 14 Preparation of the Composition

(39) Taking 105 g of silibinin, 126 g of phospholipid, 300 g of Pu'er tea extract and 60 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(40) Embodiment 15 Preparation of the Composition

(41) Taking 120 g of silibinin, 150 g of phospholipid, 360 g of Pu'er tea extract and 105 g of radix puerariae extract, and preparing 1,000 bags of granules according to the method of Embodiment 1.

(42) Embodiment 16

(43) Taking the granules of Embodiment 8, adding 556 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

(44) Embodiment 17

(45) Taking the granules of Embodiment 9, adding 331 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

(46) Embodiment 18

(47) Taking the granules of Embodiment 10, adding 311 g of microcrystalline cellulose and 32 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

(48) Embodiment 19

(49) Taking the granules of Embodiment 13, adding 145 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

(50) Embodiment 20

(51) Taking the granules of Embodiment 14, adding 76 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

(52) Embodiment 21

(53) Taking the composition of Embodiment 8, adding 400 g of lactose, 156 g of starch, and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

(54) Embodiment 22

(55) Taking the composition of Embodiment 13, adding 115 g of lactose, 10 g of tale powder, and 84 g of low-substituted hydroxypropyl cellulose, mixing uniformly, encapsulated into capsules to obtain 1,000 capsules.

(56) Embodiment 23

(57) Taking the composition of Embodiment 13, adding 145 g of microcrystalline cellulose and 64 g of sodium carboxymethyl starch, mixing uniformly, encapsulated into No. 0 capsules to obtain 1,000 capsules.