WO2004009106A1

WO2004009106A1 - Preparation extracted from stephania tetrandra s. moor and the use thereof

Info

Publication number: WO2004009106A1
Application number: PCT/CN2002/000505
Authority: WO
Inventors: Zhimin Wang; Zuguang Ye; Aihua Liang
Original assignee: Institute Of Chinese Materia Medica, China Academy Of Traditional Chinese Medicine
Priority date: 2002-07-18
Filing date: 2002-07-18
Publication date: 2004-01-29
Also published as: AU2002318715A1; CN1658890A; CN1282466C

Abstract

The present invention relates to a preparation extracted from Stephania tetrandra S. Moor and its use for manufacture of medecine for enhancing the sensitivity or effect of chemotherapy, enhancing the sensitivity of radiotherapy, improving the level of leukocytes in body, and having antineoplastic and antianaphylaxis effects. Said preparation is mainly composed of tetrandrine and fangchinoline with the ratio of 9:1 to 8:2 (moles), which is obtained by the following process: (1) the powder or piece of Stephania tetrandra S. Moor is extracted with dilute acid with the cool acid extract being collected; and washed with water with the aqueous extract being collected; then the cool acid extract and aqueous extract are combined, adjusted with base pH 10 to 12, kept overnight; (2) the fluid of Step (1) is filtered, the solid dried, pulverized to give Powder 1; (3) Powder 1 is heated under reflux in alcohol for 30 min.; (4) the alcohol extract from Step (3) is concentrated, kept, filtered to give Solid 2; (5) Solid 2 is dissolved in warm ammoniac ethanol, kept for crystallization. The present invention also relates to the use of tetrandrine and the pharmaceutically acceptable salt thereof for manufacture of medecine for improving the level of leukocytes in body.

Description

Preparation from self-protecting powder and anti-self extraction and use thereof

Technical field

The invention relates to a preparation prepared from powder and self-protection and its use. In addition, the present invention also relates to one of the main ingredients of the preparation, the use of tetrandrine in the preparation of a medicament for increasing the level of white blood cells. Background technique

Tumors are one of the diseases with a high mortality rate in humans, and their incidence is increasing year by year. Chemotherapy and radiation therapy are currently the main methods for clinical treatment of tumors. Current anti-tumor drugs, especially cytotoxic drugs, are mostly immunosuppressants. Patients are prone to multi-drug resistance after prolonged application, which leads to treatment failure. Therefore, it is necessary to find chemotherapy-sensitizing drugs that can eliminate the body The resistance to chemotherapeutic drugs can make tumor tissues regain their sensitivity to chemotherapeutic drugs, or can make chemotherapeutic drugs easily enter cells and increase the cumulative concentration of chemotherapeutic drugs in cells, or they have antitumor effects, and Chemotherapy drugs work synergistically to enhance sensitization chemotherapy. In radiation therapy, large doses of radiation are usually required to achieve therapeutic purposes, which makes patients unbearable due to the suppression of the immune system. Therefore, it is necessary to develop a method that can increase the sensitivity of tumor tissues to radiation. Sexual drugs enable low-dose radiation therapy to achieve therapeutic goals. In addition, chemotherapy and radiation therapy usually cause severe toxic side effects, mainly manifested in reduced white blood cell levels and nausea, vomiting, hair loss, etc., lower white blood cell levels increase the probability of various infections in patients, so it is necessary to find ways to reduce chemotherapy and Toxic effects of radiotherapy, especially drugs that increase white blood cell levels.

Fangfangji is the dried root of Fangfangchi (Stephenia tetrandra S. Moor), which is also known as Fangfang and downed arch. Beginning in "Shen Nong's Materia Medica". The taste is bitter and cold. Go to the bladder and lung meridians. It has the effects of diuresis and swelling, expelling wind and relieving pain. For water Swelling athlete's foot, unfavorable urination, eczema, sore, rheumatic pain, hypertension. The total alkaloids in tetrandrine account for about 0.5-5% of the root, mainly including tetrandrine (also known as tetrandrine, tetrandrine), tetrandrine (fangchinoline, also known as tetrandrine), Normantine, hanfangchin C, menisine, menisidine, cyclanoline, berbamine, oxidized tetrandrine Oxofangchirine, stephanthrine, fenfangjine A, B, C, D, (+) — 2—N—methyl tetrandrine, (+) — 2—N—methyl tetrandrine ( (+) -N-methyltetrandrine), 2,2'- Ν, Ν-dimethylchlorotrandrine and the like. Among the above-mentioned alkaloids, tetrandrine and tetrandrine are predominant in the roots, accounting for 50-80% of the total alkaloids.

Tetrandrine is used clinically to treat silicosis, hypertension, and coronary heart disease. The body alkaloids of Fangfang total alkaloids have been shown to have analgesic effects (Zhao Yi, Fangyanhusuo, scopolamine components, analgesic effect, Chinese Medical Journal, 1955, 41 (10), 931-935). We have published that tetrandrine can reverse the resistance of chemotherapy-resistant drugs such as vincristine, doxorubicin and other tumor cells (KB cells, etc.) in vitro (Ye Zuguang et al. Reversal of drug resistance of human cancer cells by voxel or vincristine-resistant strains, Chinese Journal of Chinese Materia Medica, 1996; 21 (6): 369-371), reverse the body's resistance to malaria drugs, such as chloroquine (Ye Zu-guang et al The potentiating action of tetrandrine in combinaton with c loroquine against chloroquine- sensitive and resistant falciparum malaria Biochem. Biophys. Res.

Commim. 1989; 165: 758-65), combined with vincristine and doxorubicin, have antitumor effects (Sun Ai-Xu, Ye Zu-Guang et al Synergistic anticancer effects of tetrandrine conbined with doxorubicin or vincristine in vitro Chinese Journal of Pharmacology, 1999; 20 (1): 69-73). Summary of the Invention

The present inventors devoted themselves to the development of new pharmacological uses of alkaloids. As a result, it was found that from the powder of Fangfang and its genus or Batumi iMenispermum dauricum DC.) Or hair Extracts from plants such as Cydea barbata (Wall.) Miers), which mainly contain tetrandrine and tetrandrine have chemosensitization, radiosensitization, and increase leukocyte levels and antiallergic effects. In addition, the inventors of the present invention also found that tetrandrine has an effect of increasing leukocyte levels.

It is an object of the present invention to provide a preparation extracted from the powder of Fangshen and its genus, or plants such as Batata or Hairy Leaf Ring Vine, which is obtained by the following method:

(1) Extract the powder of tangle powder or decoction with dilute acid, and collect the acid cold infusion; then rinse with water to collect the water; combine the acid and water, add alkali to adjust the pH to 10-12, and leave it overnight;

(2) filtering the liquid in step (1), drying and pulverizing the solid to obtain powder 1;

(3) extract powder 1 by heating under reflux with alcohol for 30 minutes;

(4) the alcohol solution in step (3) is concentrated, left, and filtered to obtain solid 2;

(5) The solid 2 is dissolved in hot ammoniated ethanol, and the precipitate is left to stand.

The preparation mainly contains tetrandrine of molecular formula (I) and tetrandrine of molecular formula (II). The molar ratio of the two is 9: 1 to 6: 4, and the total content of the two is greater than 50%.

The preparation of the present invention can be used for the preparation of a chemotherapeutic sensitization, a radiotherapy sensitization, an increase in the level of white blood cells, or an antiallergic drug.

In addition, tetrandrine has the effect of increasing the level of white blood cells in the body, so it can be used to prepare drugs that increase the level of white blood cells. The experimental research of the present inventors has shown that the preparation of the present invention has a more effective effect of reversing the multidrug resistance of tumor tissues to chemotherapeutic drugs than the application of tetrandrin alone, and the effect of increasing the concentration of chemotherapeutic drugs in tumor cells Combined with chemotherapeutic drugs, it has a sensitizing or synergistic effect on chemotherapeutic drugs; the preparation of the present invention is used in advance, and then radiation treatment is performed on tumor patients, showing that the preparation has the effect of improving the comprehensive curative effect of radiation therapy without any occurrence The toxic and side effects of which are better for squamous cell carcinoma; the preparation of the present invention, tetrandrine and its salt have a strong effect on increasing the level of leukocytes in low levels of leukocytes of immunosuppressed animals, and the increase range is 100 The preparation of the present invention also has a certain anti-tumor effect, and the inhibition rate on various tumors is in the range of 30-80%. detailed description.

The preparation of the present invention is obtained by the following method:

(1) Extract the powder of tetrum powder or decoction pieces with dilute acid for at least 24 hours, and collect the acid extract; then dip it in water to collect the water solution; combine the acid solution and the water solution, add alkali to adjust the pH to 10-12, and leave it overnight;

(2) filtering the liquid of step (1), drying and pulverizing the solid to obtain powder 1;

(3) extract powder 1 by heating under reflux with alcohol for 30 minutes;

(5) The solid 2 is dissolved in hot ammoniated ethanol and left to obtain a precipitate.

The preparation mainly contains tetrandrine of molecular formula (I) and tetrandrine of molecular formula (II), and the molar ratio of the two is 9.8: 0.2-6: 4, and the total content of the two is more than 50%, preferably The ratio is 9.5: 0.5 to 8: 2, more preferably 9: 1 to 8: 2, and most preferably 8.5: 1.5 to 6.5: 3.5.

Preferably, the method further comprises the following steps:

(6) The precipitate obtained in step (5) is dissolved in alcohol, and an equivalent amount of a pharmaceutically acceptable acid is added to form a salt, and the mixture is allowed to stand and filtered. The pKa of the pharmaceutically acceptable acid is preferably 0.1 to 4.5, more preferably From 1.75 to 2.5, preferred inorganic acids include, for example, hydrobromic acid, hydrochloric acid, and sulfuric acid; preferred organic acids include, for example, methanesulfonic acid, tartaric acid, maleic acid, and citric acid. The most preferred acid is hydrochloric acid.

The dilute acid used in step (1) of the method is preferably dilute sulfuric acid; the base used is preferably calcium oxide and calcium hydroxide.

In addition to tetrandrine and tetrandrine, the preparation of the present invention may also contain berbamine, oxotetrandrine, oxofangchinoline, and the like.

The quantitative analysis of each component in the preparation of the present invention can be performed by a method known to those skilled in the art, and usually chromatography is used, such as high performance liquid chromatography.

As mentioned above, the preparations of the present invention have various pharmacological activities, and tetrandrine has the effect of increasing the body's white blood cell level, so they can be used to prepare drugs with corresponding pharmacological activities, which are used for chemosensitization , Radiation sensitization, elevated white blood cell levels, or anti-allergy.

The pharmaceutical preparation can be prepared according to methods known to those skilled in the art, and can be For tablets, pills, powders, suspensions, emulsions, syrups, capsules, sterile injection solutions and other common dosage forms.

The pharmaceutical preparation of the present invention can be administered by various routes including oral, transdermal, subcutaneous, intravenous and intramuscular administration, and the dosage is usually in the range of 0.02-1.5 g / day depending on the weight and symptoms of the subject to be administered.

The following examples serve to further illustrate the invention, but they are not intended to limit the scope of the invention in any way. Example 1

Preparation, preparation of tetrandrine and tetrandrine

A. Preparation

Add 20 liters of powder of tangleproof powder or approximately 1.2 mm thick piece of decoction to add 20 liters of 1% dilute sulfuric acid for extraction for 24 hours, collect the acid cold soaking solution, and soak the remaining 10 liters of water for 30 minutes to collect the water liquid; The acid cold soaking-washing treatment cycle is performed 3 times, and the acid cold soaking solution and the water solution are combined each time, and calcium oxide or calcium hydroxide is added thereto to adjust the pH to 10-12, and the mixture is left overnight. The supernatant is decanted and discarded The lower turbid liquid was filtered with a filter cloth to obtain about 2 kg of precipitate, dried, crushed (10-40 mesh sieve), heated under reflux with 95% ethanol, poured out of the alcohol solution, concentrated, left, filtered, and the obtained solid was dissolved in In ammonia-based ethanol, it is left to precipitate, and the obtained crystals are dissolved in ethanol, a predetermined amount of acid is added, and the solution is allowed to stand and filtered to obtain the desired preparation.

B. tetrandrine

Ten grams of the solid obtained from ammoniacal ethanol was taken and recrystallized from acetone to obtain 5 grams of white needle-like crystals of tetrandrine with a purity of more than 98%. Example 2

Preparation and Tetrandrine's whitening effect on cyclophosphamide-induced low leukocytes in mice. The mice were injected intraperitoneally with an antitumor drug cyclophosphamide 75mg / kg. The number of white blood cells in peripheral blood decreased significantly. On the same day that cyclophosphamide was injected into mice, the preparation obtained in Example A was orally or intramuscularly injected once a day for 3 consecutive days. The results are shown in Table 1, Table 2 and Table. 3. It can be seen that the tetrandrin and the preparation can obviously inhibit the leukocyte decrease caused by cyclophosphamide, which shows that it has a certain attenuating effect on the toxic and side effects of the low leukocyte caused by cyclophosphamide.

Table 1. Intramuscular injection of tetrandrine and preparations against leukopenia induced by cyclophosphamide (n = 10)

Table 3. Effect of preparations on the proportion of nucleated cells in bone marrow after cyclophosphamide chemotherapy (n = 10)

Note: Compared with model group * P <0.05, ** P <0.01 Example 3

^Whitening effect of the preparation on ^6Q Co radiotherapy mice

Mice were inoculated with S ₁₈ . After the sarcoma, the preparation obtained in Example A was orally or intramuscularly injected, and the animals received ^6Q Co irradiation (500 rad, 1 minute 56 seconds) on the second day after the administration, and then continued the administration. The non-administration group was the model group, and the non-irradiated normal control group was set up. The results showed that the peripheral blood leukocytes of the model group were significantly lower than normal after irradiation, and the preparation obtained in Example 1 A 25 mg kg and 100 mg / kg was orally administered to the peripheral blood on the 3rd and 7th day after radiotherapy, respectively. Has a significant leukocyte effect. When administered by injection, it also has a certain degree of promotion effect on peripheral blood leukocytes, and the promotion rate is as high as 59%. The results are shown in Table 4.

Table 4. ^Whitening effect of the preparation on ^0Q Co radiotherapy mice

Note: * P <0.05, ** P <0.01 (compared with model group) Example 4

Preparation of adriamycin treatment resistant S _18. Tumor sensitization

Doxorubicin-resistant S _18Q ascites tumor cells induced in vivo were cultured in vitro, and then doxorubicin was added; the results showed that this tumor cell was significantly resistant to doxorubicin and was sensitive to 3 ₁₈ . Compared with ascites tumor cells, the resistance multiple of drug-resistant tumor cells is 62 times. However, when doxorubicin is added at the same time as the preparation obtained in Example A, the resistance multiple is significantly reduced, and even the resistance is almost Completely reversed (when the concentration of the preparation was 1.0 ^. 0 μιηοΙ ¹ ), the results are shown in Table 5. Table 5. Sensitization of preparations to doxorubicin-resistant S _18Q tumors

Note: Preparation of IC ₅ for S _18Q / S. It is 5.64 ± 0.94μπιο1 丄^-1 , for 8 ₁₈₀ / in (11 "of 1 ( _5. Is 2.14 ± 0.74μπιο1 丄^-1) Example 5

Reversal activity of preparation against S _lso / Adr

When S _{1SQ doxorubicin} resistant doxorubicin was administered intramuscularly, doxorubicin did not significantly inhibit tumors. The survival time of mice in the doxorubicin treatment group was similar to that of mice in the untreated group. Oral or intramuscular injection of doxorubicin given the preparation obtained in Example 1 can significantly prolong the survival time of tumor-bearing mice, indicating that the preparation can reverse the drug resistance of S _18Q / Adr. The results are listed in Table 6 and Table 7. Table 6. Preparations for reversing S _18Q / Adr drug resistance (oral preparations)

Note: * P <0.05, ** P <0.01, compared with doxorubicin alone group in the same dose group. Table 7. Reversal activity of preparations against S ₁₈₀ / Adr resistance (preparation by intraperitoneal injection)

** P <0.01, compared with doxorubicin alone group. Example 6

Determination of accumulated concentration of daunorubicin in cells

One of the main reasons why tumor cells are resistant to anti-tumor drugs is due to the overexpression of a P glycoprotein on tumor cells. When treated with anti-tumor drugs, the drug concentration in tumor cells is reduced, so that the tumor cells cannot be inhibited. Grow. We use the sensitive strain S ₁₈ . Test with drug-resistant strain S _18Q tumor cells. After adding daunorubicin, the fluorescence intensity of the daunorubicin drug concentration in the cell was measured by flow cytometry. It was found that the fluorescence intensity in the drug-resistant tumor cells was higher than that of the sensitive strain cells. It is about 1 times lower. When the preparation obtained in Example A and daunorubicin are administered in combination, the daunorubicin concentration in drug-resistant cells can be significantly increased, which is close to the drug concentration level in sensitive cells. The results are shown in the table. 8. It can be seen that the preparation can increase the concentration of anticancer drugs in tumor cells, so that it can reach the level of inhibiting the growth of tumor cells.

Table 8. Cumulative intracellular daunorubicin concentration of preparations

Group Average Fluorescence Average Twice Average Light Intensity Light Intensity

Sensitive strain Control 4.13 5.41 4.77

Daunorubicin (20 μM) 162.18 174.81 168.5 ± 8.93 * resistant strain control 10.12 8.08 9.1

Daunorubicin (20 μM) 94.89 97.24 96.07 ± 1.66 Daunorubicin (20 μM) + Preparation (10 μM) 187.99 170.83 179.41 ± 12.13 Daunorubicin (20 μM) + Preparation (5 μM) 146.08 164.80 155.44 + 13.24 Note: * P <0.05 (compared to the control of sensitive plants), #P <0.05 (compared to the control of resistant ξ) Example 7

Analgesic effect of the preparation

The analgesic effect of the preparation obtained in A of Example 1 was observed using a warm-induced pain model and a chemical peritonitis model. The results showed that: in the mouse tail-flick test, the preparation was given once by intramuscular injection at doses of 5 mg / kg and 10 mg / kg, both of which could prolong the warm-induced tail tail latency of mice, indicating that the preparation caused pain by warming Has a certain analgesic effect. The inhibitory effect of the preparation on chemical peritonitis pain was observed using a model of writhing response caused by acetic acid. The results showed that intramuscular injection of the preparation 12.5-50 mg kg significantly prolonged the incubation period of writhing and reduced the number of writhing, indicating that the preparation The compounds have obvious analgesic effects on pain caused by chemical stimulation. The results are shown in Tables 9 and 10.

Table 9. Effects of preparations on thermal tail flick in mice (n = 10)

Note: * P <0.05, ** P <0.01 (compared with control group) Table 10. Effect of preparations on mouse acetate torsion (n = 10)

Note: * P <0 · 05, ** P <0 · 01 (compared with control group) Example 8

Preparation of in vivo and in vitro antitumor effects

50 mg / kg (intramuscular) preparation compared with the survival time of Ehrlich ascites cancer mice The model group was significantly prolonged, with an elongation rate of 161.0%.

The MTT method was used to determine the in vitro half inhibitory concentration of the preparation on various tumor cells. The results are shown in Table 11.

Table 11. Preparations with inhibitory concentrations IC _5Q (μM. Ι ¹ ) for different tumor strains

Example 9

Radiotherapy synergism of preparation

Give the lung cancer patient the preparation obtained in Example A in Example 1 100-300 mg / times intravenously or intravenously 2 hours before radiotherapy, or take a small dose of radiation treatment 2 days after taking the preparation tablet in advance, each time the tumor volume is radiated 150-160 rads, 5 times a week, with a total radiation of 1500-3000 rads; 5 days of medication, 5 days of discontinuation, tablets of its preparation taken orally during the discontinuation period, 300 mg / time, 300- 600 mg / day. The total effective rate for the treatment of advanced lung cancer is more than 60%, and all patients have no obvious side effects of radiotherapy. Example 10

Anti-inflammatory effect of the preparation

Air was injected subcutaneously into the back of the rat to form a balloon, and carrageenan 25 mg / kg was injected into the balloon 6 days later to induce inflammation. The administration group was injected with the preparation obtained in Example 1 A intraperitoneally 30 minutes before inflammation. Evans blue was injected intravenously. After 6 hours, the balloon was washed with Hank's solution, the cell fluid was collected, the number of cells was counted, and the OD of the cystic fluid was measured with a spectrophotometer. The results showed that after administration of the preparation, the exudation of Evans blue in the capsule was significantly reduced, and the number of white blood cells was significantly reduced, indicating that the preparation has a significant inhibitory effect on the increase in capillary permeability caused by carrageenan-induced inflammation. . White fines in exudate after administration of preparation The number of cells was significantly reduced, indicating that the preparation had an inhibitory effect on the inflammatory response. The results are shown in Table 12.

Table 12. Anti-inflammatory effects of the preparations

* P <0.05, ** P <0.01 (compared with control group) Example 10

Antiallergic effect of the preparation

Four weeks after sensitization with trichosanthin injection in the toes of rats, the lung resistance of the rats increased sharply with 95% increase in lung resistance and 93% reduction in lung compliance when the trichosantamine solution was injected again. After 15 minutes, when injected with trichosanthin, the lung resistance increased by only 4%, and the lung compliance decreased by 3%, indicating that the preparation can inhibit allergic asthma in rats. Example 11

Preparation of preparations for injection

Dissolve 50 g of the preparation obtained in Example 1 with water for injection, add 2 g of sodium sulfite and water for injection to 1000 ml, and filter with No. 3 vertical melting glass funnel or other filter media (such as ultra-microfiltration membranes) To clear, potting, sterilization, you can. Each pack contains 50 nig of preparation. Example 12

Preparation of preparation tablets

To 300 g of the preparation obtained in Example A was added an appropriate amount of lactose and microcrystalline fiber. Vitamine, polyethylene glycol 3000, sodium carboxymethyl starch, dry compressed granules, add an appropriate amount of magnesium stearate, press into 1000 tablets, sterilize, and coat with film. Each tablet contains 300 mg of preparation. Example 13

Preparation of preparation capsules

300 g of the S IJ preparation obtained in Example 1 was added with an appropriate amount of auxiliary materials such as lactose, microcrystalline cellulose and the like, and then pressed and granulated, and then sterilized and gelatinized to make 1000 granules. Each capsule contains 300 mg of preparation. Example 14

Preparation and compound medicine preparation process

1. Mix 100 g of Astragalus membranaceus extract (containing flavonoids and saponins) and 200 g of the preparation obtained in Example 1 A, add lactose, microcrystalline cellulose, magnesium stearate in an appropriate amount, granulate, capsule, and / or Press into tablets to make 1000 tablets or 1000 tablets.

2. Mix 20 g of ginseng extract (containing polysaccharides and saponins), 20 g of cold-soaked extract of salvia miltiorrhiza, 200 g of the preparation obtained in Example 1 A, and add lactose, microcrystalline cellulose, and magnesium stearate. Appropriate amount, granulated, filled with capsules and / or compressed into 1000 or 1000 tablets.

Claims

Rights request

What is claimed is: 1. A preparation prepared from powdered tetrandrine, which mainly contains tetrandrine and tetrandrine, wherein the ratio of tetrandrine and tetrandrine is 9.8: 0.2 to 8: 2 (mole), preferably It is 9: 1 to 8: 2, and the total content of the two is greater than 50%. The preparation is obtained by the following method:

(1) Extract the powder of tetrum powder or decoction with dilute acid, preferably dilute sulfuric acid, and collect the acid cold soaking solution; then dip it in water to collect the water solution; combine with the acid cold soaking solution, add alkali, preferably calcium oxide or hydrogen Calcium oxide, adjust the pH to 10-12, and leave it overnight;

(3) extract powder 1 by heating under reflux with alcohol for 30 minutes;

(4) the alcohol solution of step (3) is concentrated, left, and filtered to obtain 'solid 2;

(5) dissolve the solid 2 in an alkaline ethanol solution, dissolve it by heating, place it, and collect the precipitate;

(6) The precipitate obtained in step (5) is dissolved in an alcohol, an equivalent amount of a pharmaceutically acceptable acid is added to make a salt, and it is left to stand and filtered.

2. The preparation according to claim 1, wherein the pKa of the pharmaceutically acceptable acid used in step (6) of the method is in the range of 0.1-4.5, preferably the pKa is in the range of 1.75-2.5.

3. The preparation of claim 2, wherein the pharmaceutically acceptable acid is selected from the group consisting of hydrochloric acid, phosphoric acid, maleic acid, tartaric acid, citric acid, fumaric acid, taurine and malic acid.

4. Use of the preparation according to any one of claims 1 to 3 in the preparation of a chemosensitization or synergistic drug.

5. The use of claim 4, wherein the drug achieves chemotherapy sensitization or enhancement by reversing the multidrug resistance of tumor tissue antitumor drugs, wherein the multidrug resistance is selected from the following antitumor drugs Induction: doxorubicin, vincristine, paclitaxel, cisplatin, cisplatin, daunorubicin, harringtonine, hydroxycamptothecin. Wherein, the drug realizes the sensitization or enhancement of chemotherapy through the synergistic effect of antitumor drugs.

6. The use according to claim 5, wherein the antineoplastic agent is selected from the group consisting of doxorubicin, changchun Nerine, vinblastine, paclitaxel, cisplatin, cisplatin, daunorubicin, harringtonine, bleomycin, and cytarabine.

7. Use of a preparation according to any one of claims 1 to 3 in the manufacture of a medicament for enhancing the sensitivity of radiotherapy.

8. Use of the preparation of any one of claims 1 to 3 in the manufacture of a medicament for increasing the level of white blood cells in the body.

9. Use of a preparation according to any one of claims 1 to 3 for the preparation of an antitumor drug.

10. Use of tetrandrine or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for increasing the level of white blood cells in the body.