AU2021248301B2 - Pharmaceutical composition containing ginsenosides Rh3, PPD, and Rh2 - Google Patents

Abstract

A pharmaceutical composition containing rare tumor-fighting ginsenosides, containing a therapeutically effective dose of ginsenoside Rh3, ginsenoside PPD, and ginsenoside Rh2, serving as active ingredients, and a pharmaceutically acceptable carrier, the mass ratio between the ginsenoside Rh3, the ginsenoside PPD, and the ginsenoside Rh2 being 1:(1-2):(1-2). Experimental results indicate: the inhibition of tumor cells by the present pharmaceutical composition is markedly increased over individual ginsenosides, and joint use of the three ginsenosides has a stronger synergistic effect.

Description

PHARMACEUTICAL COMPOSITION CONTAINING

GINSENOSIDES RH3, PPD, AND RH2

TECHNICAL FIELD

The application relates to the field of biomedicine, in particular to a rare ginsenoside

Rh3/PPD/Rh2 composition with anti-tumor activity.

BACKGROUND ART

Tumor is one of the malignant diseases with the highest fatality rate in the world,

seriously endangering human life and health. The number of cancer cases in China exceeds 3

million every year, and the incidence of lung cancer, breast cancer and gastric cancer is

increasing year by year. Over the past 30 years, the mortality rate of breast cancer has

increased by 96%, and the mortality rate of lung cancer has soared by 465%. Therefore, the

cancer prevention and treatment work in China is urgent and the situation is grim.

At present, the most common methods of cancer treatment include surgical therapy,

radiotherapy, chemotherapy and biotherapy, etc. These methods have obvious limitations and

certain side effects on the patient's body. Surgical therapy should take into account the

patient's physical capacity, resection effect and other factors, and the postoperative recovery

effect is not ideal. Radiotherapy uses the radiation effect of some rays to achieve the effect of

killing tumor cells, but it generally produces local myelosuppression, resulting in a significant

increase in the occurrence of radiation pericarditis. The body of a patient who has experienced

radiation exposure is likely to suffer irreversible damage. Chemotherapy is a commonly used

cancer treatment means at present, and is generally an adjuvant treatment means for cancer

patients by using some specific chemicals such as gefitinib, cyclophosphamide, methotrexate,

cisplatin, etc. However, chemotherapy can only temporarily inhibit tumors and cannot cure

solid tumors at all, at the same time the side effects are very large. When acting on target cells

a drug often hurt the normal cells, producing side effects such as low immune function, organ

damage, etc. The most common adverse drug reactions include diarrhea, rash, vomiting, hair

loss, etc. Therefore, oral or injectable drugs with exact anti-tumor effect and small side effects

are urgently needed clinically.

Ginsenosides may be obtained by extracting from Araliaceae plants including ginseng,

Panax notoginseng and American ginseng. Ginsenosides may be divided into panaxadiol

saponins and panaxatriol saponins, wherein the panaxadiol saponins include Rbl, Rb2, Rb3,

Rc, etc. Panaxadiol saponins may be hydrolyzed to obtain rare ginsenosides Rg3, Rkl, Rg5,

Rh2, Rk2, Rh3, PPD, etc. Studies have found that ginsenosides Rg3, Rkl, Rg5 and

ginsenoside Rh2 have obvious therapeutic effects in promoting tumor cell apoptosis,

inhibiting tumor cell proliferation and invasion and metastasis. Compared with ginsenosides

Rg3, Rkl and Rg5, ginsenosides Rh2, Rk2, Rh3 and PPD have less glycosyl groups and lower

molecular polarity. Chinese Patent application CN106109483A discloses a rare ginsenoside

composition of panaxadiol /panaxatriol saponins with anti-tumor activity, which is a

combination of ginsenosides Rkl, Rg5, Rk3, and Rh4 in a specific ratio, and the anti-tumor

effect is superior to that of each ginsenoside alone. Chinese Patent application

CN106109482A discloses a rare ginsenoside composition of panaxadiol saponins with

anti-tumor activity, which is a combination of ginsenosides Rkl, Rg5 and Rg3 together, the

anti-tumor effect is also superior to that of each ginsenoside alone. However, the anti-tumor

effect of rare ginsenoside compositions with less glycosyl groups and less polarity has not

been reported.

The discussion of documents, acts, materials, devices, articles and the like is included in this

specification solely for the purpose of providing a context for the present invention. It is not

suggested or represented that any or all of these matters formed part of the prior art base or were

common general knowledge in the field relevant to the present invention as it existed before the

priority date of each claim of this application.

CONTENTS OF THE INVENTION

The present application describes a rare ginsenoside composition based on rare

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2, which is synergistic and has

anti-tumor effect. In addition, present application also describes use of the above-mentioned

rare ginsenoside composition in the preparation of an anti-tumor medicament.

After extensive experimental studies, the inventors verified the anti-tumor effect of

multiple rare ginsenosides in vitro by combining two saponins or three saponins. Particularly, the MTT colorimetry was used to detect the inhibition rate of tumor cells and calculate the combination index; AV/PI staining was used to detect tumor cell apoptosis; flow cytometry was used to detect tumor cell cycle distribution; Western blotting was used to detect protein expression related to tumor cell apoptosis. The experimental results showed that: the

2a inhibition rate of the rare ginsenoside Rh3/Rh2/PPD composition on tumor cells is significantly increased as compared with the single ginsenoside group, and the combination index (CI) values are all less than 0.7, indicating that the combination of the three ginsenosides has a strong synergistic effect; the apoptosis rate of the rare ginsenoside

Rh3/Rh2/PPD composition group is significantly higher than that of single ginsenoside group;

the S phase cells of the rare ginsenoside Rh3/Rh2/PPD composition group are significantly

more than those of the single ginsenoside group; the rare ginsenoside Rh3/Rh2/PPD

composition group can significantly down-regulate the expression of Caspase-3, PARP, and

Bcl-2 proteins as compared with the single ginsenoside group, thereby inducing cancer cell

apoptosis. Therefore, the composition Rh3/PPD/Rh2 has a superior anti-tumor effect on

gastric cancer, liver cancer, and colon cancer than other compositions. Then, the inventors

further conducted a comparative study on the anti-tumor effects of Rh3/PPD/Rh2

compositions in different ratios of various monomer saponins, and finally selected the

composition with synergistic effect and the best anti-tumor effect, and then completed the

present application.

That is, the present application comprises:

1. A rare ginsenoside pharmaceutical composition (rare ginsenoside pharmaceutical

composition A of the present application) with anti-tumor effect, comprising therapeutically

effective amount of ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2, and a

pharmaceutically acceptable carrier,

wherein in the rare ginsenoside pharmaceutical composition, the weight ratio of the

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:(1-2): (1-2).

2. The aforementioned rare ginsenoside pharmaceutical composition, wherein in the rare

ginsenoside pharmaceutical composition, the weight ratio of ginsenoside Rh3, ginsenoside

PPD and ginsenoside Rh2 is 1:(1-1.1): (1.9-2).

3. The aforementioned rare ginsenoside pharmaceutical composition, wherein in the rare

ginsenoside pharmaceutical composition, the weight ratio of the ginsenoside Rh3, ginsenoside

PPD and ginsenoside Rh2 is 1:1:2.

4. The aforementioned rare ginsenoside pharmaceutical composition, wherein the rare

ginsenoside pharmaceutical composition does not comprise other ginsenosides.

5. The aforementioned rare ginsenoside pharmaceutical composition, wherein the rare

ginsenoside pharmaceutical composition comprises ginsenoside Rh3, ginsenoside PPD and

ginsenoside Rh2 as the only anti-tumor active ingredients.

6. Use of a composition comprising ginsenoside Rh3, ginsenoside PPD and ginsenoside

Rh2 in the preparation of an anti-tumor medicament, wherein

in the composition, the weight ratio of ginsenoside Rh3, ginsenoside PPD and

ginsenoside Rh2 is 1:(1-2): (1-2); and

the anti-tumor medicament comprises ginsenoside Rh3, ginsenoside PPD and ginsenoside

Rh2 as active ingredients.

7. The aforementioned use, wherein in the composition, the weight ratio of the

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is: 1:(1-1.1): (1.9-2).

8. The aforementioned use, wherein in the composition, the weight ratio of the

ginsenoside Rh3, the ginsenoside PPD and the ginsenoside Rh2 is 1:1:2.

9. The aforementioned use, wherein the composition does not comprise other

ginsenosides.

10. The aforementioned use, wherein the composition comprises ginsenoside Rh3,

ginsenoside PPD and ginsenoside Rh2 as the only anti-tumor active ingredients.

The inventors also found that, at a specific ratio (for example, the weight ratio of

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:(1-2): (1-2), preferably 1:(1-1.1):

(1.9-2), more preferably 1:1:2), in the rare ginsenoside pharmaceutical composition A of the

present application, not only a combination of ginsenoside Rh3, ginsenoside PPD and

ginsenoside Rh2 are synergistic, but also a combination of any two of the above three are

synergistic.

Therefore, the present application also comprises:

11. A rare ginsenoside pharmaceutical composition (rare ginsenoside pharmaceutical

composition B, C, or D of the present application) with anti-tumor effect, comprising

therapeutically effective amount of ginsenoside Rh3 and ginsenoside PPD (or ginsenoside Rh3

and ginsenoside Rh2, or ginsenoside PPD and ginsenoside Rh2), and a pharmaceutically

acceptable carrier,

wherein in the rare ginsenoside pharmaceutical composition, the weight ratio of ginsenoside Rh3 and ginsenoside PPD is 1:(1-2) (or the weight ratio of ginsenoside Rh3 and ginsenoside Rh2 is 1:(1-2), or the weight ratio of ginsenoside PPD and ginsenoside Rh2 is

(1-2): (1-2)).

12. The rare ginsenoside pharmaceutical composition according to item 11, wherein in

the rare ginsenoside pharmaceutical composition, the weight ratio of ginsenoside Rh3 and

ginsenoside PPD is 1:(1-1.1) (or the weight ratio of ginsenoside Rh3 and ginsenoside Rh2 is

1:(1.9-2), or the weight ratio of ginsenoside PPD and ginsenoside Rh2 is (1-1.1): (1.9-2)).

13. The rare ginsenoside pharmaceutical composition according to item 11 or 12, wherein

in the rare ginsenoside pharmaceutical composition, the weight ratio of the ginsenoside Rh3

and ginsenoside PPD is 1:1 (or the weight ratio of ginsenoside Rh3 and ginsenoside Rh2 is 1:2,

or the weight ratio of ginsenoside PPD and ginsenoside Rh2 is 1:2.

14. The rare ginsenoside pharmaceutical composition according to any one of items 11 to

13, wherein the rare ginsenoside pharmaceutical composition does not comprise other

ginsenosides.

15. The rare ginsenoside pharmaceutical composition according to any one of items 11 to

14, wherein the rare ginsenoside pharmaceutical composition comprises ginsenoside Rh3 and

ginsenoside PPD (or ginsenoside Rh3 and ginsenoside Rh2, or ginsenoside PPD and

ginsenoside Rh2) as the only anti-tumor active ingredients.

16. Use of a composition comprising ginsenoside Rh3 and ginsenoside PPD (or

ginsenoside Rh3 and ginsenoside Rh2, or ginsenoside PPD and ginsenoside Rh2) in the

preparation of an anti-tumor medicament, wherein

in the composition, the weight ratio of ginsenoside Rh3 and ginsenoside PPD is 1:(1-2)

(or the weight ratio of ginsenoside Rh3 and ginsenoside Rh2 is 1:(1-2), or the weight ratio of

ginsenoside PPD and ginsenoside Rh2 is (1-2): (1-2)); and

the anti-tumor medicament comprises ginsenoside Rh3 and ginsenoside PPD (or

ginsenoside Rh3 and ginsenoside Rh2, or ginsenoside PPD and ginsenoside Rh2) as active

ingredients.

17. The use according to item 16, wherein in the composition, the weight ratio of

ginsenoside Rh3 and ginsenoside PPD is 1:(1-1.1) (or the weight ratio of ginsenoside Rh3 and

ginsenoside Rh2 is 1:(1.9-2), or the weight ratio of ginsenoside PPD and ginsenoside Rh2 is

(1-1.1): (1.9-2)).

18. The use according to item 16 or 17, wherein in the composition, the weight ratio of

the ginsenoside Rh3 and ginsenoside PPD is 1:1 (or the weight ratio of ginsenoside Rh3 and

ginsenoside Rh2 is 1: 2, or the weight ratio of ginsenoside PPD and ginsenoside Rh2 is 1:2.

19. The use according to any one of items 16 to 18, wherein the composition does not

comprise other ginsenosides.

20. The use according to any one of items 16 to 19, wherein the composition comprises

ginsenoside Rh3 and ginsenoside PPD (or ginsenoside Rh3 and ginsenoside Rh2, or

ginsenoside PPD and ginsenoside Rh2) as the only anti-tumor active ingredients.

21 A method of treating tumors comprising administering to a patient in need a

composition comprising ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2, wherein in

the composition, the weight ratio of ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is

1:(1-2): (1-2); and the composition comprises ginsenoside Rh3, ginsenoside PPD and

ginsenoside Rh2 as active ingredients.

22. The method according to item 21, wherein in the composition, the weight ratio of

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:(1-1.1): (1.9-2).

23. The method according to item 21, wherein in the composition, the weight ratio of

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:1:2.

24. The method according to any one of items 21 to 23, wherein the composition does not

comprise other ginsenosides.

25. The method according to any one of items 21 to 24, wherein the composition

comprises ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 as the only anti-tumor

active ingredients.

In the present specification, in some cases the rare ginsenoside pharmaceutical

composition A of the present application and the rare ginsenoside pharmaceutical

compositions B, C, and D of the present application are collectively referred to as the rare

ginsenoside pharmaceutical composition of the present application.

The present application also relates to use of the rare ginsenoside pharmaceutical

composition of the present application in the preparation of an anti-tumor medicament. The

tumor may be, for example, gastric cancer, liver cancer, or pancreatic cancer.

The rare ginsenoside pharmaceutical composition of the present application may be, for

example, oral preparation or injection preparation. The oral preparation may be, for example,

hard capsules, soft capsules, slow-release capsules, sugar-coated tablets, powders, granules,

dropping pills, water-honeyed pills, syrups or oral liquids; the injection preparation is solution

type, suspension type, emulsion type or lyophilized powder. The rare ginsenoside

pharmaceutical composition of the present application may comprise an adjuvant or other

pharmaceutically acceptable carrier. The adjuvant may be, for example, one or more of sodium

hyaluronate, sodium alginate, chitosan and collagen.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a diagram showing the induction of apoptosis in gastric cancer cells by

ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2, and ginsenoside Rh3/PPD/Rh2

composition.

Fig. 2 is a diagram showing the effects of ginsenoside Rh3, ginsenoside PPD, ginsenoside

6a

Rh2, and ginsenoside Rh3/PPD/Rh2 composition on the cell cycle distribution of gastric

cancer.

Fig. 3 is a diagram showing the effects of ginsenoside Rh3, ginsenoside PPD, ginsenoside

Rh2, and ginsenoside Rh3/PPD/Rh2 composition on the expression of proteins related to

apoptosis in gastric cancer cells as detected by Western blotting.

Fig. 4 is a diagram showing changes in body weight and tumor volume of nude mice 30

days after administration in ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2, and

ginsenoside Rh3/PPD/Rh2 combination groups.

Fig. 5 is a diagram showing the effects on water intake, food intake and body weight of

mice after treatment of ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2, and ginsenoside

Rh3/PPD/Rh2 composition.

Fig. 6 is a diagram showing the effects on the liver and kidney functions of mice after

treatment of ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2, and ginsenoside

Rh3/PPD/Rh2 composition.

SPECIFIC EMBODIMENTS

The present application will be described in detail below with reference to specific

embodiments. In the absence of conflict, scientific terms in the present specification have the

meanings commonly understood by those skilled in the art, and in case of conflict, the definitions in

the present specification shall prevail.

Firstly, in one aspect, the present application provides a rare ginsenoside pharmaceutical

composition with anti-tumor effect (rare ginsenoside pharmaceutical composition of the present

application, hereinafter also referred to as a pharmaceutical composition of the present application

or a pharmaceutical composition), it comprises therapeutically effective amount of ginsenoside Rh3,

ginsenoside PPD and ginsenoside Rh2 as active ingredients, and a pharmaceutically acceptable

carrier,

wherein in the rare ginsenoside pharmaceutical composition, the weight ratio of ginsenoside

Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:(1-2): (1-2).

In the present specification, ginsenoside Rh3 refers to a compound represented by the

following chemical formula 1.

[Chemical formula 1]

OH___ H OH OH HO OH

The above-mentioned ginsenoside Rh3 is a known compound, and may be prepared by a

method known in the art, for example, ginsenoside Rh3 may be prepared by enzymolysis of

ginsenoside Rb1.

In the present specification, ginsenoside PPD (protopanaxadiol) refers to a compound

represented by the following chemical formula 2.

[Chemical formula 2]

o OH OH

H HOH

The above-mentioned ginsenoside PPD (protopanaxadiol) is a known compound, and may be

prepared by a method known in the art, for example, ginsenoside PPD (protopanaxadiol) may be

prepared by enzymolysis of ginsenoside Rb.

In the present specification, ginsenoside Rh2 refers to a compound represented by the

following chemical formula 3.

[Chemical formula 3]

OH OH HO HOH H OH

The above-mentioned ginsenoside Rh2 is a known compound, and may be prepared by a

method known in the art, for example, ginsenoside Rh2 may be prepared by enzymolysis of

ginsenoside Rb1.

The inventors found that a combination of ginsenoside Rh3, ginsenoside PPD and ginsenoside

Rh2 in the ratio range defined in the present application not only shows significant synergy in

anti-tumor effect (CI value is less than 1, preferably CI value is less than 0.7), but also shows low

toxicity characteristics. The inventors also found that within the above ratio range, a combination of

ginsenoside Rh3 and ginsenoside PPD (or ginsenoside Rh3 and ginsenoside Rh2, or ginsenoside

PPD and ginsenoside Rh2) is also synergistic and low in toxicity. Moreover, the inventors found

that if the content ratio of ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 in the

pharmaceutical composition is not within the ratio range defined in the present application, there is

no synergistic effect. Considering the significant synergistic effect (CI value is less than 0.7), in the

composition the weight ratio of the ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is

preferably 1: (1-1.1): (1.9-2), more preferably 1:1:2.

The pharmaceutical composition of the present application may comprise other ginsenosides,

or may not comprise other ginsenosides. In the case that the pharmaceutical composition of the

present application comprises other ginsenosides, considering from the viewpoint of obtaining

better synergistic effect, the content of ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 (or

ginsenoside Rh3 and ginsenoside PPD, or ginsenoside Rh3 and ginsenoside Rh2, or ginsenoside

PPD and ginsenoside Rh2) is preferably 50 parts or more by weight, more preferably 60 parts or

more by weight, more preferably 70 parts or more by weight, more preferably 80 parts or more by

weight, more preferably 90 parts or more by weight, more preferably 95 parts or more by weight, more preferably 99 parts or more by weight, more preferably 100 parts by weight (that is, the pharmaceutical composition only comprises the above three ginsenosides, or only comprising two of the above three ginsenosides), based on 100 parts by weight of the total ginsenosides comprised in the pharmaceutical composition. The purity of ginsenoside Rh3 used in the pharmaceutical composition of the present application may be 99% or more, the purity of ginsenoside PPD may be

% or more, and the purity of ginsenoside Rh2 may be 98% or more.

The content of the total ginsenosides may be determined by the vanillin method, and the

contents of the ginsenosides Rh3, PPD and Rh2 may be determined by the HPLC method.

The pharmaceutical composition of the present application may comprise other anti-tumor

active ingredients, or may not comprise other anti-tumor active ingredients (that is, ginsenoside Rh3,

ginsenoside PPD and ginsenoside Rh2 (or ginsenoside Rh3 and ginsenoside Rh2, or ginsenoside

PPD and ginsenoside Rh2) as the only anti-tumor active ingredients).

On the other hand, the inventors found that the pharmaceutical composition of the present

application has a significant anti-tumor effect. Therefore, the present application also provides use

of the pharmaceutical composition of the present application in the preparation of an anti-tumor

medicament.

The pharmaceutical composition of the present application may comprise a pharmaceutically

acceptable carrier, such as an adjuvant. There are no special restrictions on the adjuvant in the

pharmaceutical composition of the present application, for example, the adjuvant commonly used in

pharmaceuticals or health products in the art may be used. Particularly, the adjuvant is starch,

dextrin, lactose, mannitol, sodium hypromellose, xanthan gum, or proteoglycan, etc.

There are no special restrictions on the dosage form of the pharmaceutical composition of the

present application, for example, it may be an oral dosage form or an injection dosage form. The

oral dosage form may be a liquid dosage form or a solid dosage form. The oral dosage form may be,

for example, hard capsules, soft capsules, slow-release capsules, compressed tablets, sugar-coated

tablets, powders, granules, dropping pills, water-honeyed pills, syrups or oral liquids; the injection

dosage form may be, for example, solution form, suspension type, emulsion type or lyophilized

powder. The mode of administration of the pharmaceutical composition for improving sleep may be,

for example, oral, dripping or injection administration.

When preparing a solid preparation for oral use, tablets, coated tablets, granules, fine granules, pulvis, capsules, etc. may be prepared according to a conventional method after adding an excipient and optionally a binder, a disintegrating agent, a lubricant, a coloring agent, a flavoring agent, etc.

to the basic remedy.

As an excipient, for example, lactose, corn starch, white sugar, glucose, sorbitol, crystalline

cellulose, silicon dioxide, etc. may be used; as a binder, for example, polyvinyl alcohol, ethyl

cellulose, methyl cellulose, Arabic gum, hydroxypropyl cellulose, hydroxypropyl methylcellulose,

etc. may be used; as a lubricant, for example, magnesium stearate, talc, silicon dioxide, etc. may be

used; as a coloring agent, coloring agents allowed to be added to pharmaceuticals may be used; as a

flavoring agent, cocoa powder, menthol, aromatic acid, peppermint oil, borneol, and cinnamon

powder may be used. Of course, the above-mentioned tablets and granules may also be coated with

sugar coating, gelatin coating, and other necessary outer coatings.

When preparing an injection preparation, a pH-adjusting agent, a buffering agent, a suspending

agent, a solubilizing agent, a stabilizing agent, an isotonic agent, a preservative, etc. may be added

to the basic remedy as required, and then an intravenous, subcutaneous, or intramuscular injection

preparation may be prepared according to a conventional method. At this time, a freeze-dried

product may be prepared by a conventional method as required.

As a suspending agent, examples may be listed, such as methyl cellulose, Tween 80,

hydroxyethyl cellulose, Arabic gum, gum tragacanth powder, sodium carboxymethyl cellulose,

polyoxyethylene sorbitan monolaurate, etc.

As a solubilizing agent, examples may be listed, such as polyoxyethylene hydrogenated castor

oil, Tween 80, niacinamide, polyoxyethylene sorbitan monolaurate, polyethylene glycol, castor oil

fatty acid ethyl ester, etc.

Moreover, as a stabilizing agent, examples may be listed, such as sodium sulfite, sodium

metasulfite, etc.; as a preservative, examples may be listed, such as methylparaben, ethylparaben,

sorbic acid, phenol, cresol, chlorocresol, etc.

Administration of the pharmaceutical composition of the present application to a subject in

need thereof may treat tumors. The subject may be a mammal, such as a human, a rat, a rabbit, a

sheep, a pig, a cow, a cat, a dog, a monkey, etc., preferably a human.

The pharmaceutical composition of the present application may be administered orally or

non-orally. The administration amount varies depending on the degree of symptoms, patient age, sex, body weight, difference in sensitivity, administration method, administration period, administration interval, the nature of the pharmaceutical preparation, the type of active ingredient, etc. There are no special restrictions on the administration amount, but it is generally 1pg-30000mg per day for an adult (with a body weight of 60Kg), preferably 10pg-3000mg, more preferably 100pg-2000mg, more preferably 1mg-1000mg, more preferably 10mg-500mg, more preferably 100mg-300mg (in terms of the total amount of ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 (or ginsenoside Rh3 and ginsenoside Rh2, or ginsenoside PPD and ginsenoside Rh2)), the above administration amount may generally be administered 1 to 3 times per day.

EXAMPLES The examples given below are for the convenience of understanding the present application, and do not limit the scope of the claims of the present application in any way.

Example 1: Inhibitory effects of ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2, and ginsenoside Rh3/PPD/Rh2 composition, Rh3/PPD composition, PPD/Rh2 composition, Rh3/Rh2 composition on gastric cancer cells, liver cancer cells, or pancreatic cancer cells The aqueous solutions of Rh3, PPD and Rh2 with a concentration of 150 g/mL were prepared respectively. Aqueous solutions comprising Rh3, PPD, and Rh2 with a total concentration of 150pg/mL were prepared according to the weight ratios of ginsenoside Rh3: PPD: Rh2 of 1:1:1, 1:1:2, 1:2:1, 1:0.5:0.5, and 1:3:3, respectively, which were referred to as composition 1, composition 2, composition 3, composition 4 and composition 5. Aqueous solutions comprising Rh3 and PPD, PPD and Rh2, Rh3 and Rh2 with a total concentration of 150pg/mL were prepared according to the weight ratios of ginsenoside Rh3: PPD, PPD: Rh2, and Rh3:Rh2 of 1:1, 1:2, and 1:2 respectively, which were referred to as composition 6, composition 7 and composition 8. Aqueous solutions comprising Rh3 and PPD, PPD and Rh2, Rh3 and Rh2 with a total concentration of 150pg/mL were prepared according to the weight ratios of ginsenoside Rh3: PPD, PPD: Rh2, and Rh3: Rh2 of 1:0.5, 0.5:0.5, and 1:0.5 respectively, which were referred to as composition 9, composition 10 and composition 11. Aqueous solutions comprising Rh3 and PPD, PPD and Rh2, Rh3 and Rh2 with a total concentration of 150pg/mL were prepared according to the weight ratios of ginsenoside Rh3: PPD, PPD: Rh2, and Rh3:Rh2 of 1:3, 3:3, and 1:3 respectively, which were referred to as composition 12, composition 13, and composition 14.

The above-mentioned ginsenosides Rh3, PPD, Rh2 and compositions 1-14 were respectively

used for inhibition experiments on cancer cells of gastric cancer, liver cancer, and pancreatic cancer.

The specific steps were as follows: human gastric cancer cells, gastric cancer cells, liver cancer

cells and pancreatic cancer cells were respectively inoculated into sterile 96-well plate, then

150pg/mL ginsenoside Rh3, 150pg/mL ginsenoside PPD, 150pg/mL ginsenoside Rh2, and

150pg/mL ginsenoside compositions 1-14 were added respectively (100pL per well, RPMI 1640

culture medium for cell culture). Three replicate wells were set for each concentration of

administration group, and an equal volume of culture medium was added to the blank control group,

placing in a 37°C incubator for 48 h. Then the supernatant was discarded, 100L of culture medium

and 50tL of MTT solution were added to each well, shaking well, and placing into the incubator for

4h. After 4h the mixture was sucked out, and 150tL of DMSO was added to dissolve the purple

crystal formazan, shaking for 10min, and placing into the microplate reader to measure the

absorbance value of each well at the detection wavelength of 570nm.

Inhibition rate = (OD of blank group - OD of experimental group) x 100%/ OD of blank group

At the same time, the interaction index CI = ABC/(AxBxC) was calculated, wherein T is the

OD value of cells in the experimental group, C is the OD value of cells in the control group, ABC is

the T/C value of the combination group, A, B, and C are the T/C values of groups in which each

ginsenoside acts individually (if two ginsenosides are used in combination, the formula is

CI=AB/(AxB)). When CI < 1, it indicates that the combinations have a synergistic effect; and when

CI < 0.7, the synergistic effect is very significant. (referring to David H. Kern, Carol R. Morgan,

and Susanne U. Hildebrand-Zanki. In vitro and in vivo interaction between cisplatin and topotecan

in ovarian carcinoma systems [J]. Cancer Research, 1988, 48., and LI Xingqi. Study on the

inhibitory effect of lidamycin on neuroglioma and the synergistic effect of combining with

temozolomide [D]. Peking Union Medical College, 2009)

The inhibition rates of the above-mentioned ginsenosides Rh3, PPD, Rh2 and compositions

1-14 on various cancer cells are shown in Table 2. Table 4 shows the combination index results of

compositions 1-14 on various tumor cells.

Table 1: OD values of ginsenosides Rh3, PPD, Rh2 and compositions 1-14 on various tumor cells

Gastric cancer Liver cancer Pancreatic cancer

Control 1.012 0.912 0.824

Rh3 0.353 0.409 0.415 PPD 0.382 0.461 0.335 Rh2 0.453 0.451 0.358

Composition 1 0.047 0.083 0.059

Composition 2 0.036 0.070 0.049 Composition 3 0.046 0.076 0.062 Composition 4 0.168 0.174 0.197

Composition 5 0.323 0.285 0.320

Composition 6 0.085 0.094 0.104 Composition 7 0.108 0.122 0.118

Composition 8 0.112 0.110 0.112 Composition 9 0.177 0.155 0.189

Composition 10 0.415 0.400 0.315

Composition 11 0.268 0.259 0.209

Composition 12 0.332 0.362 0.310

Composition 13 0.193 0.207 0.269

Composition 14 0.301 0.268 0.308

Table 2: Inhibitory rates of ginsenosides Rh3, PPD, Rh2 and compositions 1-14 on various tumor

cells Gastric cancer Liver cancer Pancreatic cancer

Rh3 65.10% 55.20% 49.60% PPD 62.30% 49.50% 59.30%

Rh2 55.20% 50.50% 56.60%

Composition 1 95.40% 90.90% 92.90% Composition 2 96.40% 92.30% 94.10% Composition 3 95.50% 91.70% 92.50%

Composition 4 83.41% 82.76% 80.56% Composition 5 68.08% 71.87% 68.34% Composition 6 91.60% 90.70% 89.70% Composition 7 89.34% 87.95% 88.30% Composition 8 88.90% 89.10% 88.90% Composition 9 82.51% 84.73% 81.36% Composition 10 58.98% 60.45% 68.87% Composition 11 73.51% 74.45% 79.35% Composition 12 67.18% 64.25% 69.32%

Composition 13 80.97% 79.53% 73.43% Composition 14 70.21% 73.53% 69.57%

Table 3: T/C values of compositions 1-14 on various tumor cells Gastric cancer Liver cancer Pancreatic cancer

Rh3 0.349 0.448 0.504 PPD 0.377 0.505 0.407 Rh2 0.448 0.495 0.434

Composition 1 0.046 0.091 0.071 Composition 2 0.036 0.077 0.059 Composition 3 0.045 0.083 0.075 Composition 4 0.166 0.172 0.194 Composition 5 0.319 0.281 0.317 Composition 6 0.084 0.093 0.103 Composition 7 0.107 0.121 0.117 Composition 8 0.111 0.109 0.111 Composition 9 0.175 0.153 0.186

Composition 10 0.410 0.396 0.311

Composition 11 0.265 0.256 0.207

Composition 12 0.328 0.358 0.307 Composition 13 0.190 0.205 0.266 Composition 14 0.298 0.265 0.304

Table 4: Combination index (CI) results of compositions 1-14 on various tumor cells

Gastric cancer Liver cancer Pancreatic cancer

Composition 1 0.78 0.81 0.80 Composition 2 0.61 0.69 0.66 Composition 3 0.76 0.74 0.84 Composition 4 2.81 2.92 3.30 Composition 5 5.42 4.77 5.37 Composition 6 0.64 0.71 0.78 Composition 7 0.63 0.71 0.69 Composition 8 0.71 0.70 0.71 Composition 9 1.33 1.16 1.42 Composition 10 2.43 2.34 1.84 Composition 11 1.69 1.63 1.32 Composition 12 2.49 2.72 2.33 Composition 13 1.13 1.21 1.57 Composition 14 1.91 1.69 1.95

It can be seen from the results of the above Example 1 that, compared with Rh3, PPD, and Rh2

monomers, the composition 1, composition 2, composition 3, composition 6, composition 7, and

composition 8 of the present application significantly improve the inhibition rates of cancer cells of

gastric cancer, liver cancer and pancreatic cancer. All the combination indexes of the six

compositions against gastric cancer, liver cancer and pancreatic cancer are less than 1. Moreover, by

adjusting the weight ratio of Rh3, PPD and Rh2 monomers in the composition, a better cancer cell

inhibitory effect may be obtained. Particularly, all the combination indexes of composition 2 on

cancer cells of gastric cancer, liver cancer, and pancreatic cancer are less than 0.7, indicating that the synergistic effects of the combination of the three monomeric saponins at this weight ratio of

1:1:2 on the inhibitions of cancer cells of gastric cancer, liver cancer, and pancreatic cancer are

extremely significant. All the combination indexes of composition 6, composition 7, and

composition 8 on cancer cells of gastric cancer, liver cancer, and pancreatic cancer are less than 1,

indicating that inhibitions of cancer cells of gastric cancer, liver cancer and pancreatic cancer are

synergistic at Rh3: PPD=1:1, PPD: Rh2=1:2, and Rh3: Rh2=1: 2. All the combination indexes of

composition 4, composition 5, composition 9, composition 10, composition 11, composition 12,

composition 13, and composition 14 on cancer cells of gastric cancer, liver cancer and pancreatic

cancer are greater than 1, indicating that none of these 8 compositions play a synergistic effect.

Example 2: Effects of ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2, and

ginsenoside Rh3/PPD/Rh2 composition 2, composition 6, composition 7, and composition 8 in

inducing apoptosis of gastric cancer cells

Taking gastric cancer cells as an example, the cells were inoculated into sterile 6-well plates,

after culturing for 24 hours, ginsenoside Rh3 with a concentration of 150tg/mL, 150 g/mL

ginsenoside PPD, 150 g/mL ginsenoside Rh2, and 150 g/mL ginsenoside compositions were added.

The ginsenoside compositions were ginsenoside composition 2, composition 6, composition 7, and

composition 8 in Example 1. In the control group, an equal volume of 1640 culture medium was

added, and 5 replicate wells were set for each concentration. After culturing for 24 hours, ice-cold

PBS was added to wash 2-3 times, and 1 x Binding Buffer was added, pipetting evenly, then an

appropriate amount of AV/PI mixed dye solution was added dropwise, incubating for 15min in the

dark, and apoptosis was detected by a flow cytometer.

Fig. 1 is a diagram of the experimental results for the detection of induction of apoptosis in

gastric cancer cells by ginsenoside Rh3 group, ginsenoside PPD group, ginsenoside Rh2 group, and

composition 2, composition 6, composition 7 and composition 8 by flow cytometry, a cell

histogram composed of our quadrants is obtained. Area QI represents cells with mechanical

damage during the experimental operation, area Q2 represents cells undergoing late apoptosis, area

Q3 represents cells with normal function and morphology, and area Q4 represents cells undergoing early apoptosis. It can be seen from this figure that, with the increase of the concentration of

ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2 and ginsenoside Rh3/PPD/Rh2 composition group, the percentage of cells undergoing apoptosis represented by area Q4 shows a gradually increasing trend. When the concentration of ginsenoside Rh3 is 150[tg/mL, the early apoptosis rate of gastric cancer cells is 10.25% (the early apoptosis rate of the control group is 3.21%); when the concentration of ginsenoside PPD is 150g/mL, the early apoptosis rate of gastric cancer cells is

12.76% (the early apoptosis rate of the control group is 3.21%); and when the concentration of

ginsenoside Rh2 is 150tg/mL, the early apoptosis rate of gastric cancer cells is 13.30% (the early

apoptosis rate of the control group is 3.21%); while the early apoptosis rate of gastric cancer cells

corresponding to the composition 2 group is 55.28%. It can be seen from the data in Table 8 that,

the ginsenoside Rh3/PPD/Rh2 composition group 2 has a synergistic effect on the apoptosis of

gastric cancer cells with CI<0.7, the synergistic effect is significant; the apoptosis synergy index CI

of composition 6, composition 7, or composition 8 on gastric cancer cells is less than 1; indicating

that the combinations of two of the three saponins also have synergistic effects on the apoptosis of

gastric cancer cells.

At the same time, the interaction index CI=ABC/AxBxC was calculated, T is the survival

fraction of cells in the experimental group after apoptosis, C is the survival fraction of cells in the

control group after apoptosis; ABC is the T/C value of the combination group, A, B and C are the

T/C values of groups in which each ginsenoside acts individually (if two ginsenosides are used in

combination, the formula is CI=AB/(AxB)). When CI < 1, it indicates that the combinations have a

synergistic effect; and when CI < 0.7, the synergistic effect is very significant. The calculation

shows that the combination index CI value of composition 2 is 0.62, CI<0.7, indicating that the

synergistic effect is very significant; the combinations of the two saponins in combination 6,

composition 7, and composition 8 also have synergistic effects on the apoptosis of gastric cancer

cells.

Table 5: Combination index (CI) results of ginsenosides Rh3, PPD, Rh2 and composition 2,

composition 6, composition 7 and composition 8 on the apoptosis rate of gastric cancer cells Apoptosis T/C CI value of compositions rate

Control group 3.21% -- -

Rh3 10.25% 0.927 -

PPD 12.76% 0.901 -

Rh2 13.30% 0.896 -

Composition 2 55.28% 0.462 0.62

Composition 6 41.74% 0.602 0.72

Composition 7 39.63% 0.624 0.77 Composition 8 39.89% 0.621 0.75

Example 3: Effects of ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2, and

ginsenoside Rh3/PPD/Rh2 composition 2, composition 6, composition 7, and composition 8 on

the distribution of gastric cancer cell cycle

Taking gastric cancer cells as an example, cells in the logarithmic growth phase were

inoculated into 6-well plates at 1x105 cells/well, then the final concentration of 150g/mL

ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2 and composition 2, composition 6,

composition 7, and composition 8 were added. The control group was added with the same volume

of RPMI-1640 culture medium as the ginsenoside-added groups, and 5 replicate wells were set for

each concentration. After culturing for 48h, the cells were digested and centrifuged, the supernatant

was removed, and PBS pre-cooled at 4°C was added to wash for 2-3 times, then 75% ethanol

pre-cooled at 4°C was added, finally the cells were fixed overnight at 4°C. The next day, the cells

were centrifuged to discard the supernatant, then PBS pre-cooled at 4°C was added to wash for 2-3

times, and an appropriate amount of PI solution was added dropwise, incubating in the dark at room

temperature for 30min, and the cell cycle distribution was analyzed by flow cytometry detection.

Fig. 2 shows the effects of ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2, and

ginsenoside Rh3/PPD/Rh2 composition 2, composition 6, composition 7, and composition 8 on the

distribution of gastric cancer cell cycle. Compared with the control group, in composition 2,

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 groups the proportion of cells in GI phase

is significantly decreased, the proportion of cells in S phase is significantly increased, and the

proportion of cells in G2 phase does not significantly change. The proportion of cells in S phase is

increased by Ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2 and composition 2, composition

6, composition 7, and composition 8 respectively to 33.9%, 36.49%, 33.49%, 46.49%, 45.02%,

44.80%, 42.85%. The results indicate that all the gastric cancer cells treated with composition 2,

composition 6, composition 7, composition 8, ginsenoside Rh3, ginsenoside PPD, and ginsenoside

Rh2 are blocked in S phase.

Table 6: Effects of ginsenosides Rh3, PPD, Rh2 and composition 2, composition 6, composition 7,

and composition 8 on gastric cancer cells in S phase Growth rate of cells in S phase

Control group 25.97%

Rh3 33.90%

PPD 36.49%

Rh2 33.49%

Composition 2 46.49%

Composition 6 45.02%

Composition 7 44.80%

Composition 8 42.85%

Example 4: Western blotting detection of ginsenoside Rh3, ginsenoside PPD, ginsenoside

Rh2, and ginsenoside Rh3/PPD/Rh2 composition 2 on expression of proteins related to

apoptosis of gastric cancer cells

Taking gastric cancer cells as an example, the cells were treated with 150g/mL ginsenoside

Rh3, ginsenoside PPD, ginsenoside Rh2 and the composition respectively for 48 hours, then the

cells were collected to add lysate for extracting total protein; and the protein concentration was

detected by BCA Protein Assay kit. The protein was separated by 10% SDS-PAGE and transferred

to PVDF membrane; after blocking with 2% nonfat milk powder on a shaker at room temperature

for 2h, GAPDH, Caspase-3, PARP, and Bcl-2 primary antibody (1:1000) were added, then

incubating overnight at 4°C. The next day, the membrane was washed three times with TBST, and

the secondary antibody rabbit anti-IgG (1:10000) was added to incubate for 2h at room temperature,

and then the membrane was washed three times. After addition of the on-site prepared ECL

luminescent solution to infiltrate the PVDF membrane, the membrane was scanned with a

chemiluminescence gel imager, and the protein bands were analyzed by densitometric analysis

through Image J software.

Fig. 3 is a diagram showing the experimental results of Western blotting detection of

ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2, and ginsenoside Rh3/PPD/Rh2 composition 2 on expression of proteins related to apoptosis of gastric cancer cells. Compared with ginsenoside

Rh3, ginsenoside PPD and ginsenoside Rh2 groups, in the composition 2 group the expression of

apoptosis-related proteins such as Caspase-3, Bcl-2, and PARP is significantly decreased, indicating

that composition 2 and ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2 may induce apoptosis

of gastric cancer cells by regulating the down-regulation of these proteins.

Example 5: Inhibitory effects of ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2, and

ginsenoside composition 2, composition 6, composition 7, and composition 8 on gastric cancer

tumors

Referring to the Example 6 of Chinese patent application CN109045052A, a slight

modification was conducted. Human gastric cancer cells were xeno-inoculated into female BALB/c

nude mice, and each nude mouse was injected with 3-4x106 cells. 20 days after the inoculation, it

was observed that there were tumor masses growing subcutaneously in the left armpit of nude mice,

only the size of a rice grain. After continuing to feed nude mice for 4 days, when the tumor size

exceeded 100mm 3, the nude mice were randomly divided into blank control group, ginsenoside Rh3

treatment group, ginsenoside PPD treatment group, ginsenoside Rh2 treatment group, and

ginsenoside Rh3/PPD/Rh2 composition treatment groups which were the ginsenoside composition

2, composition 6, composition 7, and composition 8 in Example 1. The blank group was

intraperitoneally injected with physiological saline solution according to body weight, while the

ginsenoside Rh3 treatment group, the ginsenoside PPD treatment group, the ginsenoside Rh2

treatment group, and the ginsenoside Rh3/PPD/Rh2 composition groups were intraperitoneally

injected with physiological saline solution comprising Rh3, PPD, Rh2, and the compositions in

respective at a concentration of 30mg/kg/d once a day for 30 consecutive days.

The results of this example are shown in Fig. 4. Compared with the control group, the body

weight of mice in the ginsenoside Rh3, PPD, Rh2 treatment groups, and the composition treatment

groups shows a slow increase trend. The volumes of the xenograft tumors of mice in the

ginsenoside Rh3, PPD, Rh2 treatment groups, and the ginsenoside composition treatment groups

were lower than those of mice in the control group, and the volumes of the xenograft tumors of

mice in the ginsenoside composition 2, composition 6, composition 7, composition 8 treatment

groups were lower than those of mice in the single ginsenoside Rh3, PPD, Rh2 treatment groups.

At the same time, the interaction index CI=ABC/(AxBxC) was calculated, T is the tumor

inhibition rate of the experimental group, C is the tumor inhibition rate of the control group, ABC is

the T/C value of the combination group, A, B, and C are the T/C values of groups in which each of

the three ginsenosides acts individually (if the two ginsenosides are used in combination, the

formula is CI=AB/(AxB)). When CI<1, it indicates that the compositions have a synergistic effect;

and when CI<0.7, the synergistic effect is very significant. The calculation shows that the

combination index CI values of composition group 2, composition 6, composition group 7, and

composition 8 are 0.72, 0.75, 0.78, and 0.74 respectively, indicating that all the combinations of the

three saponins as well as any two of the three saponins in these compositions have synergistic

effects.

Table 7: Combination index (CI) results of tumor inhibition rate of ginsenosides Rh3, PPD,

Rh2 and composition 2, composition 6, composition 7, and composition 8 in gastric cancer (taking

the tumor volume data on day 35 as an example) Tumor volume T/C CI value of composition

Control group 1607 -- -

Rh3 1228 0.764 -

PPD 1123 0.699 -

Rh2 924 0.575 -

Composition 2 355 0.221 0.72

Composition 6 640 0.398 0.75 Composition 7 502 0.312 0.78 Composition 8 521 0.324 0.74

Example 6: In vivo safety evaluation of ginsenoside Rh3, ginsenoside PPD, ginsenoside

Rh2, and ginsenoside Rh3/PPD/Rh2 composition

Male healthy ICR mice were fed in a room temperature environment with free diet, a relative

humidity of 50-60%, 12h day/12h night. They were fed for 1 week to adapt to the environment, and

then fasted for 12h. After 12 h, the mice were randomly divided into 5 groups: (1) control group; (2)

mg/kg ginsenoside Rh3 group; (3) 30mg/kg ginsenoside PPD group; (4) 30mg/kg ginsenoside

Rh2; (5) 30mg/kg ginsenoside Rh3/PPD/Rh2 group. The above 5 groups were all treated by gavage.

After 6h of administration, the fasting was canceled, and the mice were fed normally for 15 days.

Changes in water intake, food intake, body weight, and liver and kidney function of mice were

observed.

Changes in body weight, food intake and water intake of mice within 15 days after

administration are shown in Figure 5. It can be seen from this figure that, the body weight, food

intake and water intake of the mice in the ginsenoside Rh3 group, the ginsenoside PPD group, the

ginsenoside Rh2 group, and the ginsenoside Rh3/PPD/Rh2 groupe are not significantly different

from the control. As shown in Fig. 6, after 15 days of administration of ginsenoside to mice, in the

ginsenoside Rh3 group, the ginsenoside PPD group, the ginsenoside Rh2 group and the ginsenoside

Rh3/PPD/Rh2 group, the liver and kidney weights, the contents of alanine aminotransferase and

creatinine in serum were not significantly different from the blank group, indicating that

ginsenoside Rh3, ginsenoside PPD, ginsenoside Rh2, and the ginsenoside Rh3/PPD/Rh2

composition is safe for in vivo treatment of mice.

It should be noted that, on the premise that it can be implemented without obviously violating

the spirit of the application, any technical feature or a combination of technical features described in

the present specification as a constituent part of a technical solution can also be applied to other

technical solutions; and on the premise that it can be implemented without obviously violating the

spirit of the application, among the technical features described as constituent parts of different

technical solutions, they can also be combined in any way to form other technical solutions. The

present application also encompasses technical solutions obtained by a combination in the

above-mentioned situations, and these technical solutions are equivalent to being described in the

present specification.

The present application has been described above through specific embodiments and examples,

but those skilled in the art should understand that these are not intended to limit the scope of the

present application, which should be determined by the claims.

Industrial Applicability

The present application provides a rare ginsenoside pharmaceutical composition comprising

rare ginsenosides Rh3, PPD and Rh2, and the composition has a synergistic and anti-tumor effect.

Throughout the description and claims of this specification, the word "comprise" and variations

of the word, such as "comprising" and "comprises", is not intended to exclude other additives,

components, integers or steps.

23a

Claims (15)

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

1. A rare ginsenoside pharmaceutical composition with anti-tumor effect, comprising

therapeutically effective amount of ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 as

active ingredients, and a pharmaceutically acceptable carrier,

wherein in the rare ginsenoside pharmaceutical composition, the weight ratio of

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:(1-2): (1-2).

2. The rare ginsenoside pharmaceutical composition according to claim 1, wherein in the

rare ginsenoside pharmaceutical composition, the weight ratio of ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:(1-1.1): (1.9-2).

3. The rare ginsenoside pharmaceutical composition according to claim 1, wherein in the

rare ginsenoside pharmaceutical composition, the weight ratio of ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:1:2.

4. The rare ginsenoside pharmaceutical composition according to any one of claims 1 to 3,

wherein the rare ginsenoside pharmaceutical composition does not comprise other

ginsenosides.

5. The rare ginsenoside pharmaceutical composition according to any one of claims 1 to 4,

wherein the rare ginsenoside pharmaceutical composition comprises ginsenoside Rh3,

ginsenoside PPD and ginsenoside Rh2 as the only anti-tumor active ingredients.

6. Use of a composition comprising ginsenoside Rh3, ginsenoside PPD and ginsenoside

Rh2 in the preparation of an anti-tumor medicament, wherein

in the composition, the weight ratio of ginsenoside Rh3, ginsenoside PPD and

ginsenoside Rh2 is 1:(1-2): (1-2);

and the anti-tumor medicament comprises ginsenoside Rh3, ginsenoside PPD and

ginsenoside Rh2 as active ingredients.

7. The use according to claim 6, wherein in the composition, the weight ratio of

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:(1-1.1): (1.9-2).

8. The use according to claim 6, wherein in the composition, the weight ratio of

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:1:2.

9. The use according to any one of claims 6 to 8, wherein the composition does not comprise other ginsenosides.

10. The use according to any one of claims 6 to 9, wherein the composition comprises

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 as the only anti-tumor active

ingredients.

11. A method of treating tumors comprising administering to a patient in need a

composition comprising ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2, wherein

in the composition, the weight ratio of ginsenoside Rh3, ginsenoside PPD and

ginsenoside Rh2 is 1:(1-2): (1-2);

and the composition comprises ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2

as active ingredients.

12. The method according to claim 11, wherein in the composition, the weight ratio of

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:(1-1.1): (1.9-2).

13. The method according to claim 11, wherein in the composition, the weight ratio of

ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 is 1:1:2.

14. The method according to any one of claims 11 to 13, wherein the composition does

not comprise other ginsenosides.

15. The method according to any one of claims 11 to 14, wherein the composition

comprises ginsenoside Rh3, ginsenoside PPD and ginsenoside Rh2 as the only anti-tumor

active ingredients.