Traditional Chinese medicine composition for treating prostate cancer, preparation method and application thereof

• US 10,639,338 B2
• Filed: 07/20/2016
• Issued: 05/05/2020
• Est. Priority Date: 08/10/2015
• Status: Active Grant

• Current Assignee: Shanghai Zhongyao Bio-Technology Co., Ltd.
• Original Assignee: Shanghai Zhongyao Bio-Technology Co., Ltd.
• Inventors: Yang, Yihong
• Primary Examiner(s): Mi, Qiuwen
• Application Number:
  US15/552,550
• Publication Number:
  US 20180050073A1
• Time in Patent Office: 1,385 Days
• Field of Search: None
• CPC Class Codes: A61K 2236/33 involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
• CPC Class Codes: A61K 2236/331 using water, e.g. cold water, infusion, tea, steam distillation, decoction subcritical water extraction A61K2236/37
• CPC Class Codes: A61K 2236/333 using mixed solvents, e.g. 70% EtOH
• CPC Class Codes: A61K 2236/51 Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
• CPC Class Codes: A61K 2236/53 Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 36/074 Ganoderma
• CPC Class Codes: A61K 36/258 Panax (ginseng)
• CPC Class Codes: A61K 36/484 Glycyrrhiza (licorice)
• CPC Class Codes: A61K 36/53 Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
• CPC Class Codes: A61K 36/539 Scutellaria (skullcap)
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention relates to a traditional Chinese medicine composition for treating prostate cancer and its preparation method and application. The composition is prepared from Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza as raw materials in a weight ratio of 2-3:1-2:1-2:0.5-1.5:0.5-1.5 and prepared by mixed extraction or object extraction. The present inventions simplifies the prescription of the composition, is conducive to quality control, and reduces production cost, while the product curative effect remains unaffected, thus has a good application prospect.

Claims

1. A traditional Chinese medicine composition for treating prostate cancer, characterized by:

the composition is prepared from raw materials consisting of Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza in a weight ratio of 2-3;

1-2;

1-2;

0.5-1.5;

0.5-1.5.

2. The traditional Chinese medicine composition for treating prostate cancer according to claim 1, characterized by:

the composition is prepared from raw materials consisting of Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza in a weight ratio of 2-3;

1.5-2;

1.5-2;

1-1.5;

1-1.5.

3. The traditional Chinese medicine composition for treating prostate cancer according to claim 2, characterized by:

the composition is prepared from raw materials consisting of Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza in a weight ratio of 3;

2;

2;

1;

1.

4. The traditional Chinese medicine composition for treating prostate cancer according to claim 2, characterized by:

the composition is prepared from raw materials consisting of Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza in a weight ratio of 2;

1.5;

2;

1.5;

1.

5. The traditional Chinese medicine composition for treating prostate cancer according to claim 1, characterized by:

the traditional Chinese medicine composition is composed of alkaloid, polysaccharide, lactone, saponin, coumarin and total flavones extracted from the mixture of Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza.

6. The traditional Chinese medicine composition for treating prostate cancer according to claim 2, characterized by:

the traditional Chinese medicine composition is composed of alkaloid, polysaccharide, lactone, saponin, coumarin and total flavones extracted from the mixture of Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza.

7. The traditional Chinese medicine composition for treating prostate cancer according to claim 3, characterized by:

the traditional Chinese medicine composition is composed of alkaloid, polysaccharide, lactone, saponin, coumarin and total flavones extracted from the mixture of Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza.

8. The traditional Chinese medicine composition for treating prostate cancer according to claim 4, characterized by:

the traditional Chinese medicine composition is composed of alkaloid, polysaccharide, lactone, saponin, coumarin and total flavones extracted from the mixture of Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza.

9. The traditional Chinese medicine composition for treating prostate cancer according to claim 1, characterized by:

the traditional Chinese medicine composition is composed of Ganoderma lucidum polysaccharide, baicalin, oridonin, notoginsenoside, liquiritigenin and isoliquiritigenin extracted from Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza respectively.

10. The traditional Chinese medicine composition for treating prostate cancer according to claim 2, characterized by:

the traditional Chinese medicine composition is composed of Ganoderma lucidum polysaccharide, baicalin, oridonin, notoginsenoside, liquiritigenin and isoliquiritigenin extracted from Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza respectively.

11. The traditional Chinese medicine composition for treating prostate cancer according to claim 3, characterized by:

the traditional Chinese medicine composition is composed of Ganoderma lucidum polysaccharide, baicalin, oridonin, notoginsenoside, liquiritigenin and isoliquiritigenin extracted from Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza respectively.

12. The traditional Chinese medicine composition for treating prostate cancer according to claim 4, characterized by:

the traditional Chinese medicine composition is composed of Ganoderma lucidum polysaccharide, baicalin, oridonin, notoginsenoside, liquiritigenin and isoliquiritigenin extracted from Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza respectively.

13. A method for preparing the traditional Chinese medicine composition for treating prostate cancer according to claim 1 comprises:

the composition is prepared by mixing extraction method or object extraction method.

14. The method for preparing the traditional Chinese medicine composition for treating prostate cancer according to claim 13, characterized by:

the mixing extraction method comprises the following steps;

(1) preparing raw materials;

Ganoderma lucidum, Scutellaria baicalensis, Rabdosia rubescens, Panax notoginseng and Glycyrrhiza are crushed and mixed in a weight ratio of 2-3;

1-2;

1-2;

0.5-1.5;

0.5-1.5, and then the obtained traditional Chinese medicine mixture is divided into six equal parts;

(2) extraction of alkaloid;

i) one part of the traditional Chinese medicine mixture obtained in step (1) is lixiviated in several times or percolated with a 0.1% hydrochloric acid ethanol solution to obtain an acidic ethanol extract;

ii) the extract is concentrated under reduced pressure to give a concentrate;

iii) the concentrate is washed with acidic water, and then filtrated to obtain a residue, and the residue is washed with acidic water to obtain an acidic aqueous solution;

iv) ammonia water is added to the acidic aqueous solution obtained in step iii) to form precipitate, which is filtered to obtain the total alkaloid precipitate;

or

a) adding dilute acid to the acid aqueous solution obtained in step iii) until pH=2 and extracting it with chloroform to obtain a chloroform layer and an aqueous layer;

evaporating chloroform in the chloroform layer to obtain weak alkaloid;

b) adding base to the aqueous layer until pH=6-7, extracting it with chloroform to obtain an aqueous layer and a chloroform layer, evaporating chloroform in the chloroform layer to obtain strong alkaloid;

c) the aqueous layer obtained in the above b) is adjusted to pH 10 with a base and then extracted with butanol, and then butanol in the butanol layer is evaporated to give a water-soluble alkaloid;

d) combining the alkaloids obtained in the above a), b) and c) to obtain total alkaloids;

(3) extraction of polysaccharide;

one part of the traditional Chinese medicine mixture obtained in step (1) is extracted with hot water at 95-100°

C., and the residue is discarded, after the filtrate is left for 12 hours to obtain a supernatant, 50% or more of ethanol is added to the supernatant, and a polysaccharide precipitate is obtained by centrifugation;

(4) extraction of lactone;

one part of the traditional Chinese medicine mixture obtained in step (1) is refluxed with diethyl ether to remove pigment, and then recovering diethyl ether to obtain total lactone;

(5) extraction of saponin;

one part of the traditional Chinese medicine mixture obtained in step (1) is refluxed with petroleum ether, followed by evaporating petroleum ether to obtain a degreased crude powder, which is extracted with 90-95% ethanol, the extract is then concentrated under reduced pressure to obtain a concentrated liquid;

a) the concentrated liquid is extracted with chloroform and ethanol in turn, and then chloroform and ethanol are recovered under reduced pressure to obtain crude total glycoside which includes saponin glycoside;

or

b) the concentrated liquid is extracted with butanol, and then butanol is recovered under reduced pressure to obtain crude saponin;

(6) extraction of coumarin;

one part of the traditional Chinese medicine mixture obtained in step (1) is decocted by water for 1-2 hours, and then concentrating the decoction and adding concentrated hydrochloric acid to remove impurity of insoluble matter, the obtained clear liquor is then placed to obtain crude crystals of coumarin;

(7) extraction of flavonoids;

one part of the traditional Chinese medicine mixture obtained in step (1) is impregnated by 70-80% ethanol, and then ethanol in the ethanol solution is recovered under reduced pressure and the residue is dissolved in water and filtered to obtain an aqueous solution;

the aqueous solution is extracted with ethyl acetate and the ethyl acetate solution is concentrated under reduced pressure to obtain total flavonoids;

alkaloid, polysaccharide, lactone, saponin, coumarin and total flavonoids extracted in steps (2) to (7) are mixed to obtain the traditional Chinese medicine composition.

15. The method for preparing the traditional Chinese medicine composition for treating prostate cancer according to claim 13, characterized by:

the object extraction method comprises the following steps;

(1) extraction of baicalin;

i) adding 10-15 times volume of water to the Scutellaria baicalensis component for boiling for 1-2 hours, and then filtering;

ii) the filtrate is adjusted to pH 1-2 with acid, kept at 80-90°

C. for 30-40 minutes, and centrifuged to precipitate;

the precipitate is stirred evenly with water, and the pH is adjusted to neutral by an addition of base, followed by an additional of 3-5 times volume of ethanol, and then filtering;

iii) adding acid to the filtrate to adjust pH to 1-2, stirring, followed by maintaining at 80-90°

C. for 30-40 minutes, and then filtering;

iv) washing the resulting precipitate with water, 50% ethanol and then washing or recrystallizing with 95% ethanol to obtain baicalin;

(2) extraction of notoginsenoside;

i) extracting crude powder of the root of Panax notoginseng with methanol at a concentration below 50%, concentrating the methanol extract under reduced pressure, and then adding 3-5 times volume of water to the residue;

ii) the aqueous solution is extracted with diethyl ether, and then the aqueous layer is extracted with n-butanol, followed by evaporating to dryness under reduced pressure, and then subjected to silica gel column chromatography by eluting with CHCl₃, MeOH and H₂O in 65;

35;

10 to obtain notoginsenoside;

(3) extraction of oridonin;

extracting the dry powder of the leaf of Rabdosia rubescens with diethyl ether, discarding the residue, and then recovering diethyl ether in diethyl ether solution to obtain green-brown residue;

dissolving the residue in methanol, followed by decolorization to obtain clear methanol solution, which is concentrated under reduced pressure and then placed at room temperature overnight, and then subjected to filtration, evaporation of the methanol mother liquor, and grinding;

eluting with diethyl ether, followed by crystallization;

(4) extraction of liquiritigenin and isoliquiritigenin;

extracting Glycyrrhiza with 3-4 times volume of 90-95% ethanol, and then extracting the obtained ethanol solution by petroleum ether, followed by stirring and mixing the water layer into silica gel, then eluting with MeOH and H₂O in 7;

3, the eluate is concentrated to give a residue;

water is added to the residue to completely dissolve it, and the solution is extracted with ethyl acetate, the ethyl acetate layer is extracted with 5% Na₂CO₃ aqueous solution, and the aqueous sodium carbonate solution is adjusted with dilute acid to pH 5-6, and then extracted with ethyl acetate, the ethyl acetate solution is dried, followed by being separated by a polyamide column and eluted with a gradient of 10-90% ethanol in water to give liquiritigenin and isoliquiritigenin;

(5) Ganoderma lucidum polysaccharide containing Ganoderma lucidum glycopeptide and Ganoderma lucidum-β

-D dextran is mixed with the active components extracted in the above steps (1) to (4) to obtain the traditional Chinese medicine composition.

16. A method for treating prostate cancer by using the traditional Chinese medicine composition for treating prostate cancer according to claim 1.