CN1513448A - Pharmaceutical composition preparation of gambogic acid and gambogic acid compound - Google Patents

Abstract

The present invention is a pharmaceutical composition prepared by mixing gambogic acid with general formula (I) and gambogic acid with different bases or ions to form pharmaceutical complexes and pharmaceutically acceptable drug carriers, B represents metal ions Or _C1 - _C8 nitrogen-containing organic base or amino acid, its dosage form is any dosage form mentioned in pharmacy, and the invention also discloses the application of this kind of pharmaceutical composition preparation in the treatment of liver cancer, lung cancer and other tumors .

Description

Pharmaceutical composition preparation of gambogic acid and gambogic acid compound

Technical field

The present invention relates to a novel pharmaceutical composition preparation which forms pharmaceutical complexes with gambogic acid compounds and different bases or ions, and the application of the pharmaceutical composition preparation in treating liver cancer, lung cancer and other tumors.

Background technique

In the prior art, Chinese Patent Publication No. 1309125 and Application No. 01108049.3 disclose a patent application titled "Compound of Gambogic Acid Compounds with Anticancer Activity and Preparation Method thereof", which involves novel Forming complexes (general formula I) with gambogic acid compounds and different bases or ions, and a preparation method thereof, wherein B is a nitrogen-containing organic base of C#-[1]-C#-[8], preferably alkaline Compared with gambogic acid compounds, the compound has higher efficacy in treating liver cancer, lung cancer and other tumors, and has lower irritation and toxicity. However, this application has not yet shown various preferred pharmaceutical composition preparations of gambogic acid and its complexes and the preparation methods of the preparations.

Contents of the invention

The technical problem to be solved by this invention is to propose a novel pharmaceutical composition preparation that forms a pharmaceutical complex with gambogic acid compounds and different bases or ions for the deficiencies of the prior art. This pharmaceutical preparation can be used for liver cancer, Treatment of lung cancer and other tumors.

The technical problem to be solved by the present invention is achieved through the following technical solutions. The present invention is a pharmaceutical composition prepared by mixing gambogic acid with the following general formula (I) and gambogic acid with different bases or ions to form pharmaceutical complexes and pharmaceutically acceptable drug carriers,

B represents a metal ion or a C ₁ -C ₈ nitrogen-containing organic base or amino acid. Described pharmaceutically acceptable carrier refers to the drug carrier of pharmaceutical field, for example: diluent, excipient and water etc., filler such as starch, sucrose, lactose, microcrystalline cellulose etc.; Binding agent such as cellulose Derivatives, alginate, gelatin and polyvinylpyrrolidone; wetting agents such as Tween, glycerin; disintegrants such as sodium carboxymethyl starch, hydroxypropyl cellulose, croscarmellose, agar, calcium carbonate and Sodium bicarbonate; absorption enhancers such as quaternary ammonium compounds; surfactants such as cetyl alcohol, sodium lauryl sulfate; adsorption carriers such as kaolin and bentonite; lubricants such as talc, calcium and magnesium stearate, micronized powder Silica gel and polyethylene glycol, etc. In addition, other adjuvants such as flavoring agents and sweetening agents can also be added to the composition.

The technical problem to be solved by the present invention can be further realized through the following technical solutions. The above-mentioned pharmaceutical composition preparation is characterized in that its dosage form is any dosage form mentioned in pharmacy, including tablet, capsule, soft capsule, spray, gel, gel inhalation, oral formulations, suspensions, granules, patches, ointments, pills, powders, injections, infusions, freeze-dried injections, liposome injections, targeted drug injections, suppositories, sustained-release preparations or controlled-release preparations.

The technical problem to be solved by the present invention can be further realized through the following technical solutions. The above-mentioned pharmaceutical composition preparation is characterized in that it is a tablet or capsule composed of gambogic acid and gambogic acid and a pharmaceutical compound formed with different bases or ions, fillers, and disintegrants; Or it is a slow-release tablet or capsule composed of gambogic acid and gambogic acid and a pharmaceutical compound formed by different bases or ions, fillers, hypromellose K4M; or gambogic acid dispersed in oil Gambogic acid soft capsules were obtained in the phase.

The technical problem to be solved by the present invention can be further realized through the following technical solutions. The above-mentioned pharmaceutical composition preparation is characterized in that, the described filler is sucrose, lactose, microcrystalline cellulose, dextrin, starch or calcium phosphate; the described disintegrant is hydroxypropyl cellulose sodium starch glycolate, crospovidone or croscarmellose sodium;

The technical problem to be solved by the present invention can be further realized through the following technical solutions. The above-mentioned pharmaceutical composition preparation is characterized in that it is an injection formed by gambogic acid and a solubilizer or a cosolvent; or a lyophilized injection powder formed by gambogic acid; or a gambogic An emulsion for injection obtained by dispersing the acid in the oil phase, or a suspension injection. The suspension injection is obtained by mixing gambogic acid micropowder and polysorbate 80, and then dissolving it in a mixture containing potassium dihydrogen phosphate , Dipotassium hydrogen phosphate, paraben and sodium carboxymethyl cellulose aqueous solution, prepared by grinding.

The technical problem to be solved by the present invention can be further realized through the following technical solutions. The above-mentioned pharmaceutical composition preparation is characterized in that a binder, a wetting agent or a lubricant is also provided in the preparation.

The technical problem to be solved by the present invention can be further realized through the following technical solutions. The above-mentioned pharmaceutical composition preparation is characterized in that the oil phase is soybean oil, polyethylene glycol 400, cottonseed oil, peanut oil, sesame oil, corn oil or olive oil; Add solubilizer or cosolvent or antioxidant.

The technical problem to be solved by the present invention can be further realized through the following technical solutions. Above-mentioned pharmaceutical composition preparation, it is characterized in that, described solubilizing agent is polyoxyethylene ether castor oil, Tween, Pluronic F-68; Described solubilizing agent is arginine, meglumine , diethylamine, ethylenediamine, urea, nicotinamide, proline, glucose, citric acid and its sodium salt.

The technical problem to be solved by the present invention can be further realized through the following technical solutions. The above-mentioned pharmaceutical composition preparation is characterized in that the pharmaceutical composition preparation can be used to treat liver cancer, lung cancer and other tumors.

The formulations of the pharmaceutical compositions of the present invention may be administered orally or parenterally to patients in need of such treatment. When used for oral administration, it can be made into conventional solid preparations such as tablets, capsules, powders, granules, etc., into liquid preparations such as water or oil suspensions or other liquid preparations such as syrup, oral liquid, elixirs, etc.; For parenteral administration, it can be made into injection solutions, powder injections, water or oily suspensions, etc. Preferred forms are tablets, coated tablets, capsules, granules, oral solutions and injections.

Gambogic acid among the present invention forms the preparation method of pharmaceutical complex with different bases or ions and comprises the following steps:

a. the dried resin secreted by Garcinia hanburyi is extracted with an organic solvent, and chromatographic separation is obtained to obtain Gambogic acid;

b. Dissolving gambogic acid in a suitable solvent, reacting with hydroxides of alkali metals or alkaline earth metals or other metals, or organic acid salts of these metals, or nitrogen-containing organic bases, or amino acids.

c. The prepared complex can be isolated, and can also be directly used to prepare preparations.

The preparation method of various dosage forms of the pharmaceutical composition preparation of the present invention is, compound with gambogic acid or gambogic acid as active component and mix with one or more carriers described above, then make it into required dosage form.

The pharmaceutical composition of the present invention preferably contains 0.1%-99.5% by weight of gambogic acid or gambogic acid complex active ingredients, most preferably contains 0.5%-95% by weight of gambogic acid or gambogic acid complex active ingredients.

The administration amount of the pharmaceutical composition of the present invention can be changed according to the route of administration, patient age, body weight, body surface area, type and severity of the disease to be treated, and its daily dose can be 0.01-100 mg/ ^m Body surface area, preferably 10-100mg/m ² body surface area. Administration can be one or more times.

Detailed ways

The following examples can enable those skilled in the art to understand the present invention more comprehensively, but do not limit the present invention in any way.

Embodiment 1 The preparation of gambogic acid capsules

Gambogic acid 10g

Microcrystalline Cellulose 30g

Lactose 50g

Sodium carboxymethyl starch 7g

2% HPMCE5 solution (containing 5% Tween 80) Appropriate amount

Magnesium stearate 1g

Gambogic acid, microcrystalline cellulose, lactose, and sodium carboxymethyl starch were passed through a 100-mesh sieve and mixed evenly, and the HPMC solution containing Tween 80 was used as a binder to make a soft material, which was passed through a 20-mesh sieve to make granules, and the wet granules were placed in Dry in an oven at 50--60°C with air blast; pass the dry granules through a 20-mesh sieve, mix them with magnesium stearate, and fill them into capsules.

The preparation of embodiment 2 gambogic acid capsules

Gambogic acid complex 20g

Microcrystalline Cellulose 30g

Lactose 30g

Sodium carboxymethyl starch 5g

2% HPMCE5 solution (containing 5% Tween 80) Appropriate amount

Magnesium stearate 1g

Gambogic acid compound, microcrystalline cellulose, lactose, and sodium carboxymethyl starch were passed through a 100-mesh sieve and mixed evenly, and the HPMC solution containing Tween 80 was used as a binder to make a soft material, passed through a 20-mesh sieve to make granules, wet The granules are air-dried in an oven at 50-60°C; the dried granules are sieved through a 20-mesh sieve, mixed with magnesium stearate, and filled into capsules.

Embodiment 3 The preparation of gambogic acid tablet

Gambogic acid 30g

Microcrystalline Cellulose 30g

Lactose 50g

Sodium carboxymethyl starch 7g

2% HPMCE5 solution (containing 5% Tween 80) Appropriate amount

Magnesium stearate 1g

Gambogic acid, microcrystalline cellulose, lactose, and sodium carboxymethyl starch were passed through a 100-mesh sieve and mixed evenly, and the HPMC solution containing Tween 80 was used as a binder to make a soft material, which was passed through a 20-mesh sieve to make granules, and the wet granules were placed in Dry in an oven at 50--60°C with air blast; pass the dry granules through a 20-mesh sieve for granulation, mix with magnesium stearate, and press into tablets.

The preparation of embodiment 4 gambogic acid tablet

Gambogic acid complex 20g

Microcrystalline Cellulose 30g

Lactose 30g

Sodium carboxymethyl starch 5g

2% HPMCE5 solution (containing 5% Tween 80) Appropriate amount

Magnesium stearate 1g

Gambogic acid compound, microcrystalline cellulose, lactose, and sodium carboxymethyl starch were passed through a 100-mesh sieve and mixed evenly, and the HPMC solution containing Tween 80 was used as a binder to make a soft material, passed through a 20-mesh sieve to make granules, wet The granules are air-dried in an oven at 50-60°C; the dried granules are sieved through a 20-mesh sieve, mixed with magnesium stearate, and pressed into tablets.

Embodiment 5 Preparation of Gambogic Acid Sustained Release Capsules

Gambogic acid 100g

Povidone 100g

Microcrystalline Cellulose 30g

Hypromellose K4M 100g

3% hydroxypropylmethylcellulose (E5) aqueous solution Appropriate amount

Talc powder 4g

Dissolve gambogic acid and povidone in a small amount of ethanol, evaporate the ethanol under reduced pressure, and pass the obtained solid through a 100-mesh sieve; mix the above-mentioned solid with microcrystalline cellulose and hypromellose K4M through a 60-mesh sieve , adding 3% hydroxypropylmethylcellulose (E5) aqueous solution to prepare soft material in an appropriate amount, passing through a 20-mesh sieve to granulate. 40-50 ℃ oven blast drying. The dry granules are passed through a 20-mesh sieve for granulation, and the prescribed amount of talcum powder is added and mixed evenly. Fill in capsules according to the prescription amount.

Embodiment 6 Preparation of Gambogic Acid Sustained Release Capsules

Gambogic Acid Complex 160g

Microcrystalline Cellulose 30g

Hypromellose K4M 200g

3% hydroxypropylmethylcellulose (E5) aqueous solution Appropriate amount

Talc powder 2g-5g

Mix the gambogic acid compound, microcrystalline cellulose, and hypromellose K4M through a 60-mesh sieve, add 3% hydroxypropyl methylcellulose (E5) aqueous solution to make a soft material, and pass through a 20-mesh sieve to granulate. 40-50 ℃ oven blast drying. The dry granules are passed through a 20-mesh sieve for granulation, and the prescribed amount of talcum powder is added and mixed evenly. Fill in capsules according to the prescription amount.

Example 7 Preparation of Gambogic Acid Sustained Release Tablets

Gambogic acid 100g

Povidone 100g

Lactose 30g

Hypromellose K4M 200g

3% hydroxypropylmethylcellulose (E5) aqueous solution Appropriate amount

Talc powder 2g

Dissolve gambogic acid and povidone in a small amount of ethanol, reduce pressure to remove ethanol, and pass the solid through a 100-mesh sieve; mix the above-mentioned solid with lactose and hypromellose K4M through a 60-mesh sieve, add 3 Appropriate amount of aqueous solution of % hydroxypropylmethylcellulose (E5) is used to make soft materials, and granulated through a 20-mesh sieve. 40-50 ℃ oven blast drying. The dry granules are passed through a 20-mesh sieve for granulation, and the prescribed amount of talcum powder is added, mixed evenly, and compressed into tablets.

Example 8 Preparation of Gambogic Acid Sustained Release Tablets

Gambogic Acid Complex 160g

Lactose 30g

Hypromellose K4M 200g

3% hydroxypropylmethylcellulose (E5) aqueous solution Appropriate amount

Talc powder 2g

Mix the gambogic acid compound, lactose, and hypromellose K4M through a 60-mesh sieve, add 3% hydroxypropyl methylcellulose (E5) aqueous solution to make a soft material, and pass through a 20-mesh sieve to granulate. 40-50 ℃ oven blast drying. The dry granules are passed through a 20-mesh sieve for granulation, and the prescribed amount of talcum powder is added, mixed evenly, and compressed into tablets.

The above examples can also choose other auxiliary materials, disintegrants such as: hydroxypropyl starch, hydroxypropyl cellulose, sodium carboxymethyl starch, calcium carboxymethyl cellulose, crospovidone, croscarmellose sodium etc.; fillers such as: lactose, sucrose, mannitol, microcrystalline cellulose, dextrin, starch, calcium phosphate, calcium hydrogen phosphate, calcium sulfate, calcium carbonate, cyclodextrin, micronized cellulose, etc.; wetting agents and viscose Mixtures such as: pregelatinized starch, povidone, sodium carboxymethylcellulose, hypromellose; lubricants such as: talcum powder, stearic acid, magnesium stearate, calcium stearate, micronized silica gel, Hydrogenated vegetable oil, polyethylene glycol 4000 and 6000; wetting agents such as: sodium lauryl sulfate, Tween 80; skeleton materials such as: hypromellose, ethyl cellulose, etc.

Example 9 Gambogic acid soft capsules

Contents Each capsule contains plastic shell

Gambogic Acid 50mg Gelatin 46.00%

Soybean Oil 0.5ml Glycerin 17.82%

Water 36.18%

Dissolve gambogic acid in soybean oil, and make the solution into soft capsules. Each capsule contains 50mg of gambogic acid.

The soft capsule of the present embodiment can also select the following auxiliary materials: solvent such as: polyethylene glycol 400, cottonseed oil, peanut oil, sesame oil, corn oil, olive oil, etc.; solubilizer or latent solvent such as: Tween 80, polyoxyethylene ether Castor oil, benzyl benzoate, ethyl lactate, ethyl oleate, phospholipids, etc.; antioxidants such as: propyl gallate, tert-butylphenol (BHT), vitamin E, etc. The ratio of gelatin, glycerin and water in the plastic shell can be adjusted appropriately. For example, the ratio of gelatin/glycerin/water is 1:0.3～0.4:0.7～1.4. Other ingredients can also be added to the plastic shell, such as preservatives: A, B, C, butyl p-hydroxybenzoate, etc.; plasticizers such as sorbitol, etc.; stabilizers such as gum arabic, etc.; opacifiers such as: titanium dioxide, barium sulfate, precipitated calcium carbonate, etc.

Example 10 Preparation of Gambogic Acid Injectable Emulsion

Gambogic acid 20g

soybean oil 50g

Soy Lecithin 12g

Glycerin 25g

Add water for injection to 1000ml

Under nitrogen flow, add soy lecithin into soybean oil and stir to dissolve, add glycerin and gambogic acid and stir to dissolve, slowly add water for injection under stirring conditions, emulsify through two-step high-pressure homogenizer; still under nitrogen flow, use No. 4 Filter under reduced pressure on a vertically fused glass funnel, bottle and cap under nitrogen flow, preheat and then sterilize at 121°C for 15 minutes. After sterilization, pour hot water and gradually cool down.

In this example, the following auxiliary materials can also be selected: oil for injection such as: ethyl oleate, polyethylene glycol 400, cottonseed oil, peanut oil, sesame oil, corn oil, olive oil, isopropyl myristate, etc.; antioxidants such as : Propyl gallate, tert-butylphenol (BHT), vitamin E, etc.; surfactants such as: Tween, polyoxyethylene ether castor oil, phospholipids, Pluronic, etc.

Example 11 Gambogic acid injection

Gambogic acid 20g

Polyoxyethylene ether castor oil 1.0g

Absolute ethanol 0.5L

Add water for injection to 5.0L

Dissolve gambogic acid in absolute ethanol, add 20% polyoxyethylene ether castor oil (CremophorELP), mix well, evaporate under reduced pressure to remove ethanol, add appropriate amount of water for injection and mix well to form a clear and transparent solution, pass through a 0.22 μm microporous membrane Filter, pack and seal, and sterilize at 100°C for 30 minutes to obtain the product. Each tube contains 20 mg of gambogic acid.

Example 12 Gambogic acid injection

Gambogic acid 20.0g

Arginine 22.2g

Sodium Chloride Appropriate amount

Add water for injection to 2000mL

Take gambogic acid and arginine, put them in a suitable container, add 1800ml of water for injection, stir evenly, sonicate until dissolved, add sodium chloride and stir to dissolve, add water for injection to 2000ml, filter through a 0.22μm microporous membrane, and divide Seal it, and sterilize it by circulating steam at 100°C for 30 minutes. Each tube contains 20mg of gambogic acid.

Example 13 Preparation of Gambogic Acid Powder Injection for Injection

Gambogic acid 20.0g

Arginine 22.2g

Mannitol 32.0g

Water for injection up to 2000ml

Take gambogic acid and arginine in a suitable container, add 1800ml of water for injection, stir evenly, sonicate until dissolved, add mannitol and stir to dissolve; add 0.1% activated carbon for needles, stir for 30 minutes, and decarbonize through titanium sand core Suction filter into a clean container, add water for injection to 2000ml, stir the solution for 5 minutes to make it uniform, then filter through a 0.22μm microporous membrane, fill the filtrate in 7ml vials, 2ml per bottle, and then partially stopper Put on the butyl rubber stopper, send it to the plate layer in the freeze-drying box, insert the temperature probe, and close the box door. Freeze-dry according to the freeze-drying curve, and the final drying temperature is above 35°C and kept for 2 hours. Sealing, deflation, out of the box, capping. Each bottle contains 20mg of gambogic acid.

Example 14 Gambogic acid suspension injection

Gambogic acid 20g

Sodium Carboxymethyl Cellulose 10g

Polysorbate 80 0.1g

Ethylparaben 0.5g

Propylparaben 0.5g

Potassium dihydrogen phosphate 16.7g

Dipotassium hydrogen phosphate 1.7g

Add water for injection to 2.0L

The gambogic acid is subjected to jet crushing to obtain a fine powder with a particle size of less than 10 μm. Dissolve potassium dihydrogen phosphate and dipotassium hydrogen phosphate in water for injection, add ethyl paraben and propyl paraben, then add carboxymethylcellulose sodium, dissolve all at 60°C, and filter. Put the micronized gambogic acid in a container, add polysorbate 80 to grind it into a fine paste, add the above solution gradually, stir evenly, and grind 5 to 10 times in a colloid mill. After the content is qualified according to the routine determination method, it is divided into ampoules and sterilized at 100°C for 30 minutes to obtain the product. Each tube contains 20 mg of gambogic acid.

The injection of the present embodiment can also select the following auxiliary materials: solubilizers such as: Tween, Pluronic F-68, polyoxyethylene ether castor oil, etc.; cosolvents such as: amino acid compounds such as histidine, lysine , ornithine amide compounds such as urea, acetamide, thiourea, benzamide, etc., compounds containing hydroxyl or carboxyl groups such as sucrose, citric acid and its sodium salt, lactic acid, sodium salicylate, etc.; suspending agents such as : sodium carboxymethylcellulose, povidone, hydroxypropylmethylcellulose, etc.; preservatives such as: paraben A, B, C and butyl ester; pH regulators such as: citric acid and citrate, Phosphate, etc.; solvents such as: water for injection, ethanol for injection, propylene glycol, etc.

Example 15 Inhibitory Effects of THS iV on S ₁₈₀ , EC and Heps Transplanted Tumors in Mice

Experimental method: Kunming mice with a body weight of 18-22 g were used in the experiment, and S ₁₈₀ , EC, and Heps solid tumors were inoculated according to the transplanted tumor research method. 50 mice were inoculated for each tumor type, and the mice were weighed 24 hours after inoculation. They were randomly divided into 5 groups, the blank control group and the hydroxycamptothecin group were negative and positive control groups respectively, and the THS group was set up in three dose groups of high, medium and low (8, 4, 2 mg/kg). The tumor-bearing mice were sacrificed on the second day after drug withdrawal and weighed, and the tumor mass was separated and weighed, and the obtained data were subjected to statistical processing (t test). The results are shown in Tables 1, 2, and 3.

Table 1 The inhibitory effect of THS iv on mouse xenograft tumor Heps ( X±SD) (n=10)

Dose Weight (g) Tumor Weight Tumor Inhibition Rate

Number of Experiments Group

           (mg/kg) (mg/kg) Before Administration After Administration (g) (%)

The first batch of control group 19.9±0.99 26.2±2.30 2.00±0.56

THS group 8 19.9±1.20 25.7±2.21 0.76±0.30 ^** 62.00

4 20.2±1.48 25.8±1.99 1.19±0.33 ^** 40.50

2 20.0±1.33 26.0±2.45 1.43±0.39 ^* 28.50

Hydroxycamptothecin 3 19.8±1.14 25.7±2.21 0.98±0.26 ^** 51.00

The second batch of control group 19.5±1.51 26.5±2.37 2.11±0.57

THS 8 19.8±1.03 26.0±1.83 0.85±0.29 ^** 60.00

4 19.7±1.16 27.1±2.51 1.28±0.28 ^** 39.30

2 19.6±1.26 26.6±2.46 1.57±0.38 ^* 25.60

Hydroxycamptothecin 3 19.5±1.27 26.3±2.67 1.04±0.24 ^** 50.72

The third batch of control group 19.90±1.20 27.2±1.93 2.06±0.37

THS group 8 19.70±1.42 26.6±2.22 0.86±0.37 ^** 58.25

4 19.70±1.34 27.0±1.94 1.28±0.29 ^** 37.86

2 19.6±0.84 26.9±2.51 1.54±0.52 ^* 25.24

Hydroxycamptothecin 3 19.8±1.32 26.6±2.32 1.04±0.28 ^** 49.51

^* P＜0.05 ^** P＜0.01 compared with normal saline control group

Table 2 The inhibitory effect of THS iv on transplanted tumor EC in mice ( X±SD) (n=10)

^* P＜0.05 ^** P＜0.01 compared with normal saline control group

Dose Weight (g) Tumor Weight Tumor Inhibition Rate

Number of Experiments Group

(mg/kg) Before administration After administration (g) (%)

The first batch of control group 20.2±1.40 27.2±1.23 2.21±0.53

THS group 8 19.8±1.32 27.1±1.52 0.91±0.32 ^** 58.80

4 19.9±1.20 27.3±1.57 1.35±0.38 ^** 39.00

2 20.1±1.37 27.3±1.49 1.66±0.30 ^* 24.90

Hydroxycamptothecin 3 20.0±1.15 27.0±1.15 1.05±0.35 ^** 52.49

The second batch of control group 19.9±1.20 27.2±1.75 2.165±0.48

THS group 8 19.7±1.16 27.0±2.71 0.918±0.33 ^** 57.60

4 19.9±1.45 27.2±0.92 1.351±0.36 ^** 37.80

2 19.9±1.45 27.0±1.76 1.596±0.39 ^** 26.30

Hydroxycamptothecin 3 19.8±1.14 27.1±1.79 1.006±0.30 ^** 53.46

The third batch of control group 20.10±1.37 27.40±0.84 2.19±0.50

THS group 8 20.00±1.49 26.40±1.71 0.97±0.18 ^** 55.91

4 19.80±1.48 26.80±0.79 1.30±0.38 ^** 40.95

2 19.90±1.37 27.2±1.03 1.69±0.32 ^* 22.94

Hydroxycamptothecin 3 20.10±1.20 27.0±1.41 1.09±0.23 ^** 50.16

Dose Weight (g) Tumor Weight Tumor Inhibition Rate

Number of Experiments Group

(mg/kg) Before administration After administration (g) (%)

The first batch of control group 20.2±1.40 27.2±1.23 2.21±0.53

THS group 8 19.8±1.32 27.1±1.52 0.91±0.32 ^** 58.80

4 19.9±1.20 27.3±1.57 1.35±0.38 ^** 39.00

2 20.1±1.37 27.3±1.49 1.66±0.30 ^* 24.90

Hydroxycamptothecin 3 20.0±1.15 27.0±1.15 1.05±0.35 ^** 52.49

The second batch of control group 19.9±1.20 27.2±1.75 2.165±0.48

THS group 8 19.7±1.16 27.0±2.71 0.918±0.33 ^** 57.60

4 19.9±1.45 27.2±0.92 1.351±0.36 ^** 37.80

2 19.9±1.45 27.0±1.76 1.596±0.39 ^** 26.30

Hydroxycamptothecin 3 19.8±1.14 27.1±1.79 1.006±0.30 ^** 53.46

The third batch of control group 20.10±1.37 27.40±0.84 2.19±0.50

THS group 8 20.00±1.49 26.40±1.71 0.97±0.18 ^** 55.91

4 19.80±1.48 26.80±0.79 1.30±0.38 ^** 40.95

2 19.90±1.37 27.2±1.03 1.69±0.32 ^* 22.94

Hydroxycamptothecin 3 20.10±1.20 27.0±1.41 1.09±0.23 ^** 50.16

Table 3 The inhibitory effect of THS iv on transplanted tumor S ₁₈₀ in mice (X±SD) (n=10)

Dose Weight (g) Tumor Weight Tumor Inhibition Rate

Number of Experiments Group

(mg/kg) Before administration After administration (g) (%)

The first batch of control group 19.7±1.57 27.5±1.08 1.97±0.40

THS group 8 19.8±1.40 26.7±2.00 0.88±0.31 ^** 55.30

4 20.1±1.20 27.3±1.95 1.21±0.44 ^** 38.60

2 19.9±1.20 27.3±1.34 1.43±0.38 ^** 27.40

Hydroxycamptothecin 3 19.9±1.52 27.2±1.14 1.02±0.21 ^** 48.22

The second batch of control group 19.8±1.32 27.4±0.97 2.045±0.41

THS group 8 19.8±1.32 26.8±1.81 0.898±0.34 ^** 56.00

4 19.8±1.23 27.1±2.77 1.292±0.34 ^** 37.00

2 19.6±1.26 27.6±2.50 1.583±0.31 ^* 23.00

Hydroxycamptothecin 3 19.6±1.07 27.3±1.70 1.038±0.25 ^** 49.27

The third batch of control group 19.9±0.74 27.5±2.12 2.01±0.34

THS group 8 19.8±1.32 26.6±1.35 0.84±0.41 ^** 58.21

4 19.7±0.95 27.3±1.83 1.25±0.38 ^** 37.81

2 19.8±1.14 27.4±2.55 1.60±0.34 ^* 21.40

Hydroxycamptothecin 3 19.8±1.14 27.3±2.06 1.05±0.36 ^** 47.76

^* P＜0.05 ^** P＜0.01 compared with normal saline control group

The results showed that compared with normal saline control group, THS (8, 4mg/kg) group and hydroxycamptothecin group all had significant inhibitory effects on the tumor growth of S ₁₈₀ , EC, and Heps (P<0.01). There was no significant effect on the weight gain of mice. The experiment was repeated 3 times with similar results.

Example 16 The life-prolonging effect of THS ip on transplanted S ₁₈₀ , EAC, Heps ascites tumors in mice

Experimental method: Inoculate S ₁₈₀ , EAC, Heps ascites mice according to the transplanted tumor research method, inoculate 50 mice for each tumor type, weigh them on the first day after inoculation, and divide them into 5 groups randomly, 10 mice in each group. Rats, half male and half female, THS (1.5, 0.75, 0.375 mg/kg) three dosage groups, hydroxycamptothecin group (2 mg/kg) and blank control group. Intraperitoneal injection, once every 2 days, totally administered 4 times, during the period of administration and after drug withdrawal, the number of dead mice was recorded every day and the number of survival days was calculated (the mice that survived more than 60 days were counted as 60 days) and the survival rate ( Survival more than 60 days, and asymptomatic mice). The obtained data were processed statistically. The experimental results are shown in Tables 4, 5, and 6.

Table 4 THSip prolongs the life of Heps ascites mice (X ± SD) (n = 10)

                                                                                                                                                                       

Number of Experiments Group

(mg/kg) (g) (day) (%) (%)

The first batch of control group 19.9±1.52 11.4±2.32 0

THS group 1.5 20.0±1.33 43.5±14.07 ^** 281.6 10

0.75 20.1±0.99 25.4±7.92 ^** 122.8 0

0.375 19.8±1.23 19.9±6.17 ^** 74.6 0

Hydroxycamptothecin 2 19.7±1.34 35.5±12.32 ^** 211.4 0

The second batch of control group 19.9±1.20 11.1±1.73 0

THS group 1.5 19.8±1.62 42.1±12.35 ^** 272.8 10

0.75 19.9±1.37 25.6±7.18 ^** 130.6 0

0.375 19.8±1.32 18.5±6.24 ^** 66.7 0

Hydroxycamptothecin 2 19.8±1.23 34.2±9.81 ^** 208.1 0

The third batch of control group 19.8±0.92 10.9±2.02 0

THS group 1.5 19.8±0.92 41.7±15.30 ^** 282.57 30

0.75 19.9±1.10 24.7±7.96 ^** 130.84 0

0.375 20.1±1.20 16.7±3.23 ^** 56.07 0

Hydroxycamptothecin 2 19.8±1.48 31.9±9.67 ^** 198.13 0

^** P＜0.01 compared with normal saline control group

Table 5 THSip prolongs the life of EAC ascites mice (X ± SD) (n = 10)

                                                                                                                                                         

Number of Experiments Group

(mg/kg) (g) (day) (%) (%)

The first batch of control group 19.9±1.20 10.7±2.63 0

THS group 1.5 19.8±1.55 34.3±10.34 ^** 203.5 0

0.75 19.9±0.88 24.8±7.22 ^** 119.5 0

0.375 19.8±1.32 18.5±3.98 ^** 63.7 0

Hydroxycamptothecin 2 19.9±1.60 33.2±12.03 ^** 193.8 0

The second batch of control group 19.8±1.32 10.3±2.31 0

THS group 1.5 19.9±1.20 34.3±10.25 ^** 233.01 0

0.75 20.1±1.20 22.9±8.72 ^** 122.33 0

0.375 19.9±1.20 16.7±5.17 ^** 62.13 0

Hydroxycamptothecin 2 19.8±1.32 31.1±10.33 ^** 201.94 0

The third batch of control group 19.7±1.34 11.1±2.13 0

THS group 1.5 19.8±1.23 35.9±11.84 ^** 223.42 0

0.75 19.8±0.79 23.9±8.39 ^** 115.31 0

0.375 19.7±1.34 16.3±4.83 ^** 46.84 0

Hydroxycamptothecin 2 20.1±1.20 32.8±8.92 ^** 195.49 0

^** P＜0.01 compared with normal saline control group

Table 6 THSip prolongs the life of S ₁₈₀ ascites mice (X±SD) (n=10)

                                                                    

Number of Experiments Group

(mg/kg) (g) (day) (%) (%)

The first batch of control group 19.8±1.32 8.8±0.79 0

THS group 1.5 19.7±1.25 24.7±11.76 ^** 180.7 0

0.75 19.7±1.16 18.4±5.82 ^** 109.1 0

0.375 19.7±1.16 13.7±4.42 ^** 55.7 0

Hydroxycamptothecin 2 19.9±1.37 25.6±11.29 ^** 190.9 0

The second batch of control group 19.7±1.34 10.4±1.17 0

THS group 1.5 20.0±1.15 29.7±11.70 ^** 185.6 0

0.75 19.8±0.92 21.5±7.09 ^** 106.7 0

0.375 20.0±1.49 15.8±4.02 ^** 51.9 0

Hydroxycamptothecin 2 19.7±1.42 28.9±11.44 ^** 177.9 0

The third batch of control group 19.7±1.34 10.3±1.64 0

THS group 1.5 19.8±1.14 29.5±12.70 ^** 186.41 0

0.75 19.7±1.34 21.9±7.40 ^** 112.62 0

0.375 19.9±1.37 14.9±4.01 ^** 44.66 0

Hydroxycamptothecin 2 19.8±1.32 28.9±11.44 ^** 177.9 0

^** P＜0.01 compared with normal saline control group

The experimental results showed that compared with the blank control group, the THS (1.5, 0.75mg/kg) dose group and the hydroxycamptothecin group all had a very significant prolongation of the survival days of S ₁₈₀ , EAC, and Heps ascites mice (P< 0.01). The experiment was repeated 3 times with similar results.

Example 17 Experimental therapeutic effect of THS on human hepatocellular carcinoma SMMC-7721 and human lung cancer A-549 transplanted tumors in nude mice

Experimental method: The tumor tissue in the vigorous growth stage was cut into about 1.5 mm ³ , and inoculated subcutaneously in the right armpit of nude mice under sterile conditions. The diameter of the transplanted tumor in nude mice was measured with a vernier caliper, and the animals were randomly divided into groups after the tumor grew to 100-300 mm ³ . Use the method of measuring tumor diameter to dynamically observe the anti-tumor effect of the test substance. Tumor diameters were measured twice a week, and mice were weighed at the same time as each measurement. The experimental group was intravenously administered 3 times a week, the positive control group was administered intravenously 3 times a week, and the negative control group was given the same amount of normal saline at the same time. The formula for calculating tumor volume (TV) is:

TV=1/2×a×b ²

Where a and b represent the length and width, respectively. The relative tumor volume (RTV) was calculated according to the measurement results, and the calculation formula was: RTV=V _t /V ₀ . Wherein, V ₀ is the tumor volume measured during administration in separate cages (ie, d ₀ ), and V _t is the tumor volume at each measurement. The evaluation index of anti-tumor activity is the relative tumor proliferation rate T/C (%), and the calculation formula is as follows:

$\mathrm{<span\; class="notranslate">\; T</span>}<span\; class="notranslate">\; /</span>\mathrm{<span\; class="notranslate">\; C</span>}<span\; class="notranslate">\; (</span><span\; class="notranslate">\; \%</span><span\; class="notranslate">\; )</span><span\; class="notranslate">\; =</span>\frac{{\mathrm{<span\; class="notranslate">\; T</span>}}_{\mathrm{<span\; class="notranslate">\; RTV</span>}}}{{\mathrm{<span\; class="notranslate">\; C</span>}}_{\mathrm{<span\; class="notranslate">\; RTV</span>}}}<span\; class="notranslate">\; \&times;</span>\mathrm{<span\; class="notranslate">\; 100</span>}$

T _RTV : RTV of the treatment group; C _RTV : RTV of the negative control group.

See Table 7 and Table 8 for the experimental treatment results of THS on SMMC-7721 transplanted tumor in nude mice with human liver cancer. See Table 9 and Table 10 for the experimental treatment results of THS on human lung cancer transplanted tumor A-549 in nude mice.

Table 7. Experimental therapeutic effect of THS on human liver cancer xenograft SMMC-7721 in nude mice (1)

Group Dose Number of animals administered Body weight (g) TV(x±SD) RTV T/C P value

mg/kg mode start last start last d ₀ d ₁₄ (x±SD) (%)

NS 0.20ml/piece iv 12 12 19.5 23.3 150±54 949±384 6.5±1.9

OPT 3 iv 6 6 18.7 22.8 172±69 891±420 5.7±3.4 86.9＞0.05

THS 2 iv 6 6 19.7 23.5 152±62 472±127 3.7±1.9 56.8＜0.05

THS 4 iv 6 5 19.2 23.5 150±45 485±225 3.2±1.7 48.8＜0.05

THS 8 iv 6 4 19.2 21.8 129±20 430±106 3.4±0.4 52.7＜0.05

d ₀ : The time of drug administration in separate cages

Table 8. Experimental therapeutic effect of THS on human liver cancer xenograft tumor SMMC-7721 in nude mice (2)

Group Dose Number of animals administered Body weight (g) TV(x±SD) RTV T/C P value

mg/kg method start last start last d ₀ d ₇ (x±SD) (%)

NS 0.20ml/piece iv 12 12 19.2 21.3 240±119 687±347 2.9±0.7

OPT 3 iv 6 6 6 19.7 20.7 257±99 508±227 1.9±0.3 66.6＞0.05

THS 2 iv 6 6 19.3 20.7 232±115 395±224 1.8±0.6 62.0＞0.05

THS 4 iv 6 6 19.7 21.2 245±109 398±269 1.5±0.4 51.7＜0.05

THS 8 iv 6 6 6 19.7 21.3 216±59 343±110 1.6±0.2 55.0＜0.05

The results of two batches of experiments showed that when THS was administered intravenously at a dose of 2 mg/kg on the 7th to 14th day of the test, the lowest T/C (%) for human hepatocellular carcinoma SMMC-7721 was 56.8-62.0; , the lowest T/C (%) is 48.8-51.7; 8mg/kg dose, the lowest T/C (%) is 52.7-55.0.

Table 9. Experimental therapeutic effect of THS on human lung cancer xenograft tumor A-549 in nude mice (1)

Group Dose Number of animals administered Body weight (g) TV(x±SD) RTV T/C P value

mg/kg mode start last start last d ₀ d ₁₀ (x±SD) (%)

NS 0.20ml/piece iv 12 12 18.2 22.3 117±49 517±295 4.5±1.2

OPT 3 iv 6 6 19.2 21.8 122±37 423±125 3.5±0.5 81.4＞0.05

THS 2 iv 6 6 18.5 22.5 104±36 270±104 2.9±0.6 64.5＞0.05

THS 4 iv 6 6 18.8 22.4 110±38 297±197 2.5±1.0 55.7＜0.05

THS 8 iv 6 5 18.8 21.8 104±55 211±78 2.3±0.4 52.3＜0.05

Table 10. Experimental therapeutic effect of THS on human lung cancer xenograft tumor A-549 in nude mice (2)

Group Dose Number of animals administered Body weight (g) TV(x±SD) RTV T/C P value

mg/kg mode start last start last d ₀ d ₁₄ (x±SD) (%)

NS 0.20ml/piece iv 12 12 21.1 22.5 267±128 5326±1655 21.5±5.6

OPT 3 iv 6 5 20.8 20.4 265±101 4880±886 20.8±7.7 96.6＞0.05

THS 2 iv 6 6 20.2 21.2 280±85 4354±1045 17.4±6.9 81.1＞0.05

THS 4 iv 6 5 20.7 20.8 277±81 3537±853 13.4±4.0 62.5＞0.05

THS 8 iv 6 5 20.2 21.2 245±125 2286±1342 12.1±5.5 56.2＜0.05

The results of two batches of experiments showed that when THS was administered intravenously at a dose of 2 mg/kg on the 10th to 14th day of the test, the lowest T/C (%) for human lung cancer A-549 was 64.5-81.1; when the dose was 4 mg/kg, the lowest T/C (%) The /C (%) is 55.6-62.5; when the dose is 8 mg/kg, the lowest T/C (%) is 52.3-56.2, and there is a good dose-effect relationship.

Intravenous administration of THS has a certain growth inhibitory effect on human hepatocellular carcinoma SMMC-7721 and human lung cancer A-549 transplanted tumors in nude mice, and the effect on liver cancer is slightly stronger than that on lung cancer.

Example 18 Effect of THS iv on the number of white blood cells in the peripheral blood of tumor-bearing mice

Experimental method: Take 50 mice of the above-mentioned specifications, inoculate Heps solid tumor according to the transplanted tumor research method, weigh the mice 24 hours after inoculation, and divide them into 5 groups randomly, with 10 mice in each group, half male and half female, normal saline group and The 5-Fu group (30mg/kg) was respectively the negative control group and the positive control group, and THS was set up as high, middle and low dose groups. 24 h iv administration after inoculation, once every 2 days, a total of 4 administrations, sacrificed and dissected on the 2nd day after drug withdrawal, weighed before execution and collected blood from the orbital vein, examined the total number of white blood cells under the microscope, and dissected and separated the tumor mass at the same time , Weighing tumor weight and performing statistical analysis (t test). The results are shown in Table 11.

Table 11 The effect of THS iv on the number of leukocytes in the peripheral blood of tumor-bearing mice ( X±SD) (n=10)

Mice body weight (g)

Dose Wbc Inhibition rate

(109/L) (%)

Tumor weight (g)

Experimental group

    (mg/kg)   Before administration   After administration

Blank control 19.6±1.51 26.4±1.25 2.13±0.39 9.52±1.66

8 19.6±1.29 25.4±1.12 0.96±0.21 ^** 9.26±1.37 54.93

THS 4 19.5±0.93 26.0±1.25 1.23±0.34 ^** 9.63±1.54 42.3

2 19.5±1.08 26.1±1.34 1.63±0.29 ^** 9.46±1.60 23.5

5-Fu 30 19.8±1.47 21.8±1.62 ^** 0.64±0.18 ^* 4.04±1.08 ^**## 70.0

^** P＜0.01 compared with blank group, ^** P＜0.01 compared with THS group

The results showed that, compared with the normal saline control group, the THS (8, 4, 2mg/kg) three dose groups and the 5-Fu group all had a very significant effect on inhibiting the growth of the mouse Heps tumor (P<0.01), 5- Fu can significantly inhibit the weight gain of mice and significantly reduce the leukocytes in peripheral blood of mice (P<0.01), but THS has no significant effect on the weight gain of mice and the number of leukocytes in peripheral blood of mice within the effective dose range.

Example 19 THS iv Toxicity Study on Normal Rats

Experimental method: Take 50 rats of the above-mentioned specifications, half male and half male, and randomly divide them into 5 groups, 10 rats in each group. The normal saline group and the cyclophosphamide group (30mg/kg) were respectively negative and positive control groups, and the THS group was set up with high, medium and low dose groups (6, 3, 1.5mg/kg), administered once every other day, A total of 4 doses were administered, and blood was collected from the orbital vein on the second day after the last dose, and the total number of white blood cells was examined under a microscope. According to references, take a femur after being anesthetized with 20% urethane (0.6ml/100g), wash out all the bone marrow cells with 10ml of 3% acetic acid solution and count the number of nucleated cells in the bone marrow; and weigh the thymus and spleen for statistics Scientific treatment (t test). The experimental results are shown in Table 12 and Table 13.

Table 12 Effect of THS iv on the number of white blood cells in peripheral blood and bone marrow nucleated cells in normal rats

( X±SD) (n=10)

The number of bone marrow nucleated cells (×

Dose Mouse body weight (g) Wbc 10 ⁴ )

Experimental group

(mg/kg) Before administration After administration (10 ⁹ /L)

Blank control 125.4±5.38 149.6±10.13 8.52±1.58 8528±2540.17

6 121.3±12.66 145.3±11.96 6.84±1.51 7390±1830.08

THS 3 121.0±9.67 145.0±12.31 7.28±1.43 7906±2129.04

                                                                       

Cy 30 123.0±9.78 131.0±8.75 ^** 1.62±0.42 ^**## 3314±839.31 ^**##

^** P＜0.01 compared with blank group, ^** P＜0.01 compared with THS group

The results show that, compared with the normal saline control group, cyclophosphamide group (Cy) can significantly inhibit the growth of rat body weight and significantly reduce the effect of white blood cells in rat peripheral blood (P < 0.01), THS (6, 3, 1.5 mg/kg) three dose groups had no significant effect on the weight gain of rats and the number of leukocytes in peripheral blood of rats.

Table 13 The influence of THS iv on the thymus and spleen organ coefficients of normal rats ( X±SD) (n=10)

Dose Thymus Spleen

Experimental group

  (mg/kg)   Weight (g)   Factor     Weight (g)     Factor

Blank control 0.26±0.05 0.17±0.03 0.33±0.07 0.22±0.04

6 0.23±0.07 0.16±0.04 0.34±0.05 0.24±0.04

THS 3 0.22±0.06 0.15±0.03 0.31±0.04 0.22±0.03

                                                                 

Cy 30 0.19±0.05 ^** 0.14±0.03 ^** 0.24±0.03 ^**## 0.19±0.03 ^**##

^** P＜0.01 compared with blank group, ^## P＜0.01 compared with THS group

The results showed that, compared with the normal saline control group, the cyclophosphamide group (Cy) had the effect of significantly inhibiting the growth of rat thymus and spleen (P<0.01), three doses of THS (6, 3, 1.5mg/kg) group had no significant effect on the growth of rat thymus and spleen.

Embodiment 20 The impact of THS on the immune function of animals--THS is on the impact of serum hemolysin in mice

Experimental method: Take mice weighing 18-22 grams, half male and half male, and randomly divide them into 5 groups, 10 mice in each group. Physiological saline and cyclophosphamide group (30mg/kg) were negative and positive control groups respectively, THS set up three administration groups of high, middle and low, the doses were 8, 4, 2mg/kg respectively, all were administered through tail vein. According to the experimental method, the mice were injected with 0.5ml sheep red blood cells (2.5%) into the abdominal cavity for initial immunization, and at the same time, iv administration was given once every other day, for a total of 4 administrations, and the half hemolysis value HC50 was measured and calculated 1 hour after the last administration, A t test was performed between groups to compare the significance of the differences. The experimental results are shown in Table 14.

The influence of table 14 THS on serum hemolysin ( X±SD, n=10)

Dosage Weight (g)

Experimental group

(mg/kg) Before administration After administration HC ₅₀

Blank control 19±1.57 25±4.10 259.31±59.67

THS 8 20±1.60 26±1.90 212.35±47.00

4 20±1.27 25±2.07 231.78±43.98

2 19±1.02 25±0.90 229.35±47.78

Cy 30 19±1.28 25±2.00 173.28±101.82 ^*

^* P＜0.05 compared with normal saline control group

The results showed that THS had no significant effect on the serum half hemolysis value of normal mice, and there was no significant difference compared with the normal saline group, indicating that THS had no significant effect on the serum hemolysis value of normal mice.

Example 21 The Effect of THS on Animal Immune Function--The Effect of THS on Mouse Macrophage Phagocytosis

Experimental method: get mice with a body weight of 18-22 grams, male and female, and divide them into negative control group, cyclophosphamide group (30mg/kg) and THS high, middle and low three administration groups at random, the doses are 8, 4. 2mg/kg, the drug and normal saline were given through the tail vein respectively. During the experiment, 0.05ml/10g of Indian ink was injected into the tail vein of each mouse, and after 1 (t1) and 5 (t2) minutes, 20ul of blood was taken from the orbital vein respectively, added to 2ml, 0.1% NaCO The spectrophotometer is colorimetric at 680nm, and the optical density is measured (OD1 and OD5 are used to represent the optical density of blood samples taken at 1 minute and 5 minutes respectively), and the clearance index k value is calculated according to the following formula. After conversion by body weight and liver and spleen weight, the phagocytosis index α value was obtained, and the K value and α value of the treatment group and the control group were expressed by X±SD, and the t test between groups was performed to compare the significance of the difference. The results are shown in Table 15.

The influence of table 15 THS on the phagocytic function of normal mouse macrophages ( X±SD, n=10)

Dosage

Group K value α value

(mg/kg)

Normal saline group 0.03391±0.01674 5.1147±0.9577

THS group 8 0.03124±0.02211 5.2602±1.4642

                                  4.                              

                                                                          

Cy group 30 0.008052±0.005354** 3.9055±1.4400 ^*

The experimental results showed that THS had no significant effect on the phagocytic index α value of the mouse serum, and there was no significant difference compared with the normal saline group, indicating that THS had no significant effect on the phagocytic function of mouse macrophages.

Claims (9)

1. The following general formula is that gambogic acid of (I) and gambogic acid form pharmaceutical complexes with different bases or ions and are mixed with pharmaceutically acceptable drug carriers to form a pharmaceutical composition preparation, B represents a metal ion or a C ₁ -C ₈ nitrogen-containing organic base or amino acid. 2. The pharmaceutical composition preparation according to claim 1, characterized in that its dosage form is any dosage form mentioned in pharmacy, including tablets, capsules, soft capsules, sprays, gels, gels, etc. Gel inhalation, oral preparation, suspension, granule, patch, ointment, pill, powder, injection, infusion, lyophilized injection, liposome injection, targeted drug injection, suppository, sustained release preparation or controlled release preparation. 3. The pharmaceutical composition preparation according to claim 2, characterized in that it is a tablet composed of gambogic acid and a pharmaceutical compound formed by gambogic acid and different bases or ions, fillers and disintegrants or capsules; or slow-release tablets or capsules composed of gambogic acid and gambogic acid with different bases or ions; fillers, hypromellose K4M; or gambogic Gambogic acid soft capsules are obtained by dispersing gambogic acid in the oil phase. 4. The pharmaceutical composition preparation according to claim 3, wherein the filler is sucrose, lactose, microcrystalline cellulose, dextrin, starch or calcium phosphate; the disintegrant is hydroxypropyl Cellulose, sodium starch glycolate, crospovidone, or croscarmellose sodium. 5. The pharmaceutical composition preparation according to claim 2, characterized in that it is an injection formed of gambogic acid and a solubilizer or a cosolvent; or a lyophilized injection powder formed of gambogic acid; or a gambogic acid An emulsion for injection obtained by dispersing gambogic acid in the oil phase, or a suspension injection. The suspension injection is obtained by mixing gambogic acid micropowder and polysorbate 80, and then dissolving it in the dihydrogen phosphate-containing Potassium, dipotassium hydrogen phosphate, paraben and sodium carboxymethylcellulose in water, prepared by grinding. 6. The pharmaceutical composition preparation according to claim 3, wherein a binder, a wetting agent or a lubricant is also provided in the preparation. 7. The pharmaceutical composition preparation according to claim 3 or 5, wherein the oil phase is soybean oil, polyethylene glycol 400, cottonseed oil, peanut oil, sesame oil, corn oil or olive oil; Also can add solubilizing agent or latent solvent or antioxidant in the above oil phase. 8. The pharmaceutical composition preparation according to claim 5, characterized in that, the solubilizer is polyoxyethylene ether castor oil, Tween, Pluronic F-68; the solubilizer is arginine acid, meglumine, diethylamine, ethylenediamine, urea, niacinamide, proline, glucose, citric acid and its sodium salt. 9. The application of the pharmaceutical composition preparation described in any one of claims 1-8 in the treatment of liver cancer, lung cancer and other tumors.