RU2201759C2 - Pharmaceutical composition of antitumor activity (versions) and method for its obtaining (versions) - Google Patents

Abstract

FIELD: pharmaceutical industry. SUBSTANCE: composition includes Pulsatillae root and/or Ulmaceae bark at the quantity ranged 0-100%. The composition in question is obtained due to extracting powder-reduced Pulsatillae root and/or powder-reduced Ulmaceae bark and, not obligatory, powder-reduced ginseng and Glycyrrhizae root in solvent at below 60 C, extract's filtration and lyophilization, or due to mixing extracted solution with ordinary additional substances, filtration and lyophilization of obtained mixture, preparing pharmaceutical preparation out of lyophilized powder. The present innovation enables to increase product's stability. EFFECT: higher efficiency. 8 cl, 12 ex

Description

 The invention relates to a pharmaceutical composition having antitumor activity, which as a main ingredient contains drugs of herbal origin, and to a method for its preparation.

State of the art
The inventor invented a pharmaceutical composition of herbal medicines with antitumor activity, and a method for its preparation, and the invention is protected by Korean Patent 72982.

 This patent discloses a pharmaceutical composition containing Pulsatillae root (Pulsatilla koreana Nakai, P. cernua, P. danurica, P. ratensis, Chinese Pulsatillae, Mongolian Pulsatillae) and / or Clematis Chinensis Osbecio (so-called Chinese clematis) as main ingredients and, optionally, Ulmaceae bark, Armeniacae seed, ginseng root and Glycyrrhizae root, and a method for producing it.

 Pulsatillae species are wild-growing and are found all over the world, and Pulsatillae root has been used as an anti-inflammatory, astringent and hemostatic, and thus has been used to treat dysentery in Korea. Pulsatillae root is known to contain anemonin, protoanemonin and saponin. Protoanemonin is a precursor to anemonin, and both can dissolve in water, alcohol, chloroform, methylene chloride and the like.

 Clematis root contains anemonin, anemonol, and saponin. It has been used as a treatment for gout, a diuretic, and a treatment for side effects associated with menstruation.

 Ulmaceae bark contains mucin and tannin and has been used as a painkiller and glue.

 Ginseng root has been known since ancient times in the Far East as a miracle cure. It has been used as a tonic, as a treatment for acute gastritis, and as a treatment for various bleeding disorders. Recently, a message appeared that ginseng root has antitumor activity and contains alkaloids, saponins, essential oil, etc.

 Glycyrrhizae root contains glycyrrhizin, lycirithin, lyricoridin and lycirithoside and has been used as a cough medicine, expectorant, diaphoretic, and gastritis medication.

 The above invention relates to a pharmaceutical composition having antitumor activity and containing, as main ingredients, an extract or powder of Pulsatillae root and / or Clematis root and, optionally, an extract or powder of Ulmaceae bark, Armeniacae seed, ginseng root and Glycyrrhizae root.

Using a method known from the prior art, the composition can be obtained by drying and grinding into fine powder each of the herbal ingredients; by extracting the herbal ingredients in a solvent selected from water, lower alcohol, chloroform, methylene chloride and others that can dissolve the effective herbal ingredients at a temperature of 0 ^{° C.} — the boiling point of the solvent used — for 30 minutes to 24 hours, and then evaporating the solvent used to obtain the extract; or by dissolving said extract in water, alcohol or a mixture thereof. When extracting effective ingredients, each type of herb can be extracted independently, or two or more types of herb can be extracted together. The extract is then pulverized and a pharmaceutical composition is formulated using carriers such as lactose, various sugars, sucrose, mannitol, sorbitol and inorganic acid salts such as calcium phosphate, calcium sulfate, aluminum silicate and calcium carbonate; binders such as sucrose, glucose, starch, gelatin, carboxymethyl cellulose, methyl cellulose, gum arabic, tragacanth, ethyl cellulose, sodium alginate, hydroxypropyl methyl cellulose, polyvinylpyrrolidone and soluble cellulose; disintegrants such as starch, carboxymethyl cellulose, methyl cellulose and crystalline cellulose; lubricants such as magnesium stearate and calcium stearate; wetting agents such as glycerin, propylene glycol and sorbitol; preservatives such as sodium benzoate, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, benzalkonium chloride, chlorobutanol and sodium dehydroacetate; solvents, such as soluble alcohols and their derivatives, and various surfactants; antioxidants such as sodium sulfite, sodium polysulfate, sodium metasulfate, sodium bisulfite, rongalite and ascorbic acid; isotonic agents such as sodium chloride and dextrose; pain relievers (indolent), such as benzyl alcohol and chlorobutanol; and ointment bases such as petrolatum, liquid paraffin, various vegetable oils, waxes and lanolin; and other conventional excipients or carriers.

 The inventor continued intensive research to improve the antitumor composition and found that the composition known from the prior art is very unstable during storage, as a result of which it can easily lose its pharmaceutical activity after 3-6 months.

SUMMARY OF THE INVENTION
It is an object of the present invention to provide an improved pharmaceutical composition that is stable and retains its pharmaceutical efficacy even after storage for several years and includes, as main herbal ingredients, lyophilized powder of Pulsatillae root, Ulmaceae bark or a mixture thereof and, optionally, one or more additional herbal ingredients selected from ginseng root and Glycyrrhizae root, and common excipients, such as the ingredients used in previous invention (Korean Patent 72982).

In particular, the author completed the present invention with the discovery that, in order to maintain the effectiveness of the composition and store it for a long time, the herbal ingredients should be extracted in a solvent at a temperature below 60 ^o C and immediately lyophilized.

DETAILED DESCRIPTION OF THE INVENTION
The pharmaceutical composition of the present invention as the main active herbal ingredients includes from 0 to 100 wt.% Pulsatillae root and from 0 to 100 wt.% Ulmaceae bark and, optionally, from 0 to 70 wt.% Ginseng root and from 0 to 70 wt.% The root of Glycyrrhizae, and the content of the components is presented as the amount of dried herbal ingredients. Preferably, the content of Pulsatillae root and / or Ulmaceae bark is more than 30% by weight.

A pharmaceutical composition having antitumor activity in accordance with the present invention can be obtained using:
extracting powdered Pulsatillae root and / or powdered Ulmaceae bark and optionally one or more herbal ingredients selected from powdered ginseng root and powdered Glycyrrhizae root in a solvent at a temperature below 60 ^{° C.} , filtering and lyophilizing the extract and mixing the lyophilized powder with conventional excipients, alternatively, by mixing the above extracted solution with excipients, followed by filtration and lyophilization of the mixture, and then preparation of the pharmaceutical preparation from the lyophilized powder using the usual method used in pharmacy.

 When the composition is to be used as an injection, it is recommended to add excipients to the extracted solution before lyophilization, including a preservative, such as methylparaben, ethylparaben and propylparaben, an isotonic agent, such as sodium chloride, and a pain reliever, such as benzyl alcohol.

 When the composition is to be used in the form of a capsule, tablet, ointment or the like, except for the injection form, the extracted solution of the herbal ingredients is lyophilized, and then the lyophilized powder is mixed with conventional excipients, such as the ingredients used in the invention of Korea patent 72982, for obtaining a pharmaceutical preparation using a conventional method used in pharmacy.

 The solvent for extracting the herbal ingredients may include water, lower alcohol, acetone, ethyl acetate, hexane, and mixtures thereof.

The herbal ingredients are extracted in a solvent at a temperature below 60 ^{° C.} and immediately lyophilized. The lyophilized powder of herbal ingredients, as described above, can be poured into a vial and can be used by adding distilled water for injection, or the lyophilized powder can be prepared in the form of a capsule, tablet or ointment using the usual method used in pharmacy.

 Approximately 100 mg to 5 g of a composition based on lyophilized powder can be administered in a single day from once every 1 week to 1-3 times once a day. The dose of the composition may vary taking into account gender, age, severity of the disease of patients, etc.

 The present invention will be explained in more detail by the following examples and experiments.

Comparative Example 1
6.26 g of powdered Pulsatillae root is added to 90 ml of purified water and the mixture is heated to 60 ^° C and stirred for 60 minutes, and then centrifuged at 3500 rpm for 30 minutes. 50 ml of a centrifuged solution is filtered in a sterile room at a temperature below 60 ^o C. The resulting solution is converted into an isotonic solution by adding NaCl under aseptic conditions, then filtered again under sterile conditions and under aseptic conditions, 2.5 ml of the solution is poured into ampoules with a capacity 3 ml and sealed them to obtain ampoules with a solution for injection.

Reference Example 2
4 g of powdered Pulsatillae root, 2 g of powdered Ulmaceae bark, 2 g of powdered ginseng root and 1 g of powdered Glycyrrhizae root are added to 90 ml of purified water and the mixture is stirred for 60 minutes at approximately 80 ^{° C.} by adding the amount of purified water corresponding to the amount of distilled water. The resulting solution was cooled to room temperature, centrifuged at 3500 rpm for 30 minutes to obtain 46 ml of the extracted solution. NaCl is added to the extract to produce an isotonic solution. The isotonic solution is filtered using the usual method in a sterile room, filtered under sterile conditions and 2 ml of the solution are poured into 3 ml ampoules, sealed and stored in the refrigerator.

Reference Example 3
62.6 g of powdered Pulsatillae root, 31.3 g of powdered ginseng root and 10 g of powdered Glycyrrhizae root are added to 900 ml of purified water and extracted for 60 minutes at approximately 60 ^{° C.} with the addition of purified water, corresponding to the amount of distilled water. 40 ml of the resulting solution was filtered and concentrated to obtain 26.4 g of a concentrated extract.

Example 1
6 g of pulverized Pulsatillae root is added to 100 ml of distilled water and extracted for 60 minutes at a temperature below 60 ^° C with stirring. After centrifuging the extract at 5000 rpm, 900 ml of NaCl as an isotonic agent and 160 mg of methyl paraoxybenzoate are added to it, filtered under sterile conditions in a sterile room and poured into 5 ml of solution in 20 bottles, immediately lyophilized at a temperature below -40 ^o С and hermetically close them to obtain powder for injection.

Example 2
6 g of powdered Pulsatillae root, 4 g of powdered Ulmaceae bark and 0.9 g of powdered root Glycyrrhizae are added to 100 ml of distilled water and extracted for 60 minutes at a temperature below 60 ^{° C.} with stirring. After centrifuging the extracted solution at 5000 rpm, 900 ml of NaCI as an isotonic agent and 160 mg of methyl paraoxybenzoate as a preservative are added. The resulting mixture was filtered under sterile conditions in a sterile room, poured into 5 ml of solution in 20 vials, immediately lyophilized at a temperature below -40 ^o C and hermetically closed to obtain powder for injection.

Example 3
6 g of powdered Pulsatillae root, 3 g of powdered ginseng root and 0.9 g of powdered Glycyrrhizae root are added to 100 ml of distilled water and extracted for 60 minutes at a temperature below 60 ^° C with stirring and the amount of distilled water is added. corresponding to its consumption during distillation. After centrifuging the extracted solution at 5000 rpm, 900 ml of NaCl as an isotonic agent and 160 mg of propyl paraoxybenzoate as a preservative are added. The resulting mixture was filtered under sterile conditions in a sterile room and poured into 20 bottles with a capacity of 5 ml, immediately lyophilized at a temperature below -40 ^o C and hermetically closed to obtain powder for injection.

Example 4
60 g of powdered Pulsatillae root, 40 g of powdered Ulmaceae bark and 9 g of powdered Glycyrrhizae root are added to 1000 ml of distilled water and extracted for 60 minutes at a temperature below 60 ^° C with stirring with the addition of distilled water corresponding to the amount of distilled water. The extracted solution is centrifuged at 5000 rpm and immediately lyophilized at a temperature below -40 ^o To obtain 38.150 mg of lyophilized powder.

Example 5
60 g of powdered Pulsatillae root, 60 g of powdered Ulmaceae bark and 9 g of powdered Glycyrrhizae root are added to 1000 ml of 50% (v / v) ethanol and extracted for 60 min at a temperature of 50-60 ^o С with the addition of an amount of alcohol corresponding to the amount of distilled alcohol. The extracted solution is centrifuged at 5000 rpm and immediately lyophilized at a temperature below -40 ^o To obtain 45.150 mg of lyophilized powder.

Example 6
60 g of powdered Pulsatillae root, 30 g of powdered ginseng root and 9 g of powdered Glycyrrhizae root are added to 1000 ml of a 50% (vol./about.) Aqueous solution of acetone and extracted for 60 minutes at a temperature of 50-60 ^o With the addition of an amount of solvent corresponding to the amount of distilled solvent. The extracted solution is centrifuged at 5000 rpm and immediately lyophilized at a temperature below -40 ^o With to obtain 34.650 mg of lyophilized powder.

Example 7
6 g of powdered Pulsatillae root, 4 g of powdered Ulmaceae bark and 0.9 g of powdered root Glycyrrhizae are added to 100 ml of 70% (v / v) ethanol and extracted for 60 minutes at a temperature below 60 ^o C with stirring and adding an amount of solvent corresponding to the amount of distilled solvent. After centrifuging the extracted solution at 5000 rpm, 900 ml of NaCl as an isotonic agent and 160 mg of methyl paraoxybenzoate as a preservative are added. The resulting mixture was filtered under sterile conditions in a sterile room, poured into 5 ml of solution into 20 vials, immediately lyophilized at a temperature below -40 ^o C and sealed to obtain powder for injection.

Example 8
10 g of powdered Ulmaceae bark is added to 100 ml of 50% (v / v) ethanol and extracted for 60 minutes at a temperature below 60 ^{° C.} with stirring. The extracted solution was centrifuged at 5000 rpm and 900 ml of NaCl as an isotonic agent and 160 mg of methyl paraoxybenzoate as a preservative were added to it. The resulting mixture was filtered under sterile conditions in a sterile room, poured into 5 ml of solution into 20 vials with a capacity of 20 ml, immediately lyophilized at a temperature below -40 ^o C and sealed them to obtain powder for injection.

Example 9
60 g of powdered Pulsatillae root, 60 g of powdered Ulmaceae bark and 9 g of powdered Glycyrrhizae root are added to 1000 ml of hexane and extracted for 90 minutes at a temperature below 60 ^° C with stirring and adding an amount of hexane corresponding to the amount of distilled hexane. The extracted solution is centrifuged at 5000 rpm and the resulting solution is immediately lyophilized at a temperature below -40 ^{° C.} to obtain a lyophilized powder.

Example 10
Lyophilized extract obtained in example 4, mg - 150
Crystalline cellulose, mg - 50
Lactose, mg - 50
Magnesium stearate, mg - 3
The above ingredients are compressed into tablets using a conventional method and sealed in aluminum foil.

Example 11
Lyophilized extract obtained in example 6, mg - 150
Lactose, mg - 30
Corn starch, mg - 30
Talc, mg - 5
Magnesium stearate, mg - 3
The above ingredients are poured into hard gelatin capsules using a conventional method and sealed in aluminum foil.

Example 12
Lyophilized extract obtained in example 5, mg - 1000
Normal ointment base - How much is needed
The above ingredients are mixed in 10 g ointments, placed in an aluminum tube and sealed.

Experiment 1
Acute toxicity
The lyophilized powder obtained in Example 1 was administered to 8 rats weighing 234-276 g, resulting in an established LD _{50 of} 800 mg / kg.

Experiment 2
Antitumor effect
To develop tumors, 30 mice weighing about 25 g are injected subcutaneously with 0.1 ml of a suspension of sarcoma 160 cells (1 x 10 ⁶ cells). After 6 days, 10 mice 1 time / day are injected subcutaneously with 0.15 ml of an injection solution prepared by dissolving the powder for injection obtained in example 1 in 5 ml of distilled water, and another 10 mice are injected subcutaneously once a day with 0.15 ml of solution for injection, obtained in comparative example 1. At the same time, 10 other mice (control group) were injected with 0.15 ml of physiological saline for 10 days.

 9 mice from each group treated with injections of the solution of Example 1 and Comparative Example 1 were cured by injection for 15 days. In each of these groups, one mouse died on the 16th day, while in the control group, starting from the 10th to the 15th day, all 10 mice died.

Experiment 3
Antitumor effect
To develop tumors, 30 mice weighing about 25 g are injected subcutaneously with 0.1 ml of a suspension of 180 sarcoma cells (1 x 10 ⁶ cells). After 6 days, 10 mice 1 time / day are injected subcutaneously with 0.15 ml of the injection solution prepared by dissolving the powder for injection obtained in example 1 in 5 ml of distilled water (group 1), and the other 10 mice are injected subcutaneously once / day with 0 , 15 ml of the injection solution obtained in comparative example 1, stored for 6 months in a refrigerator (group 2), and 10 other mice were injected with 0.15 ml of physiological saline for 10 days (group 3).

 In group 1, 9 mice were cured by injection during 15 days and 1 mouse died on day 17. In group 2, 3 mice were cured by injection during 15 days, 1 mouse died on the 12th day, 3 mice died on the 15th day and 3 mice died on the 17th day. All 10 mice from group 3 died from day 10 to day 15.

Experiment 4
Antitumor effect
To develop tumors, 48 mice weighing about 25 g are injected subcutaneously with 0.1 ml of a suspension of sarcoma 180 cells (1 x 10 ⁶ cells). Starting from the 9th day (terminal stage of cancer), 0.15 ml of a sample of the injection solution prepared by dissolving the powder for injection obtained in Example 3 in 5 ml of distilled water (group 1) is injected subcutaneously to 7 mice 1 time per day, another 7 0.15 ml of the injection solution sample obtained in Example 3 (group 2) is subcutaneously injected into mice 2 times / day; 0.15 ml of the injection solution sample obtained in comparative example 1 (group 3) is administered 7 times 1 day / day to other mice , another 7 mice 2 times / day are injected subcutaneously with 0.15 ml of a sample of solution for injection, receive in comparative example 1 (group 4), 7 other mice 1 time / day are injected subcutaneously with 0.15 ml of a sample of the solution for injection obtained in comparative example 1, which was stored for 3 months in a refrigerator (group 5), 7 other mice 2 times / day, 0.15 ml of a sample of the injection solution obtained in comparative example 1, which was stored for 6 months in a refrigerator (group 6), was subcutaneously administered, and 6 other mice were used as a control group.

 In group 1 and group 3, due to the development of a malignant tumor, one mouse died on the 15th day, one mouse died on the 17th day, one mouse died on the 18th day and one mouse died on the 20th day , while 3 mice were cured in each group by injection for 20 days (on the 29th day of the development of the malignant tumor).

 In group 2 and group 4, due to the development of a malignant tumor, one mouse died on the 16th day, one mouse died on the 18th day, one mouse died on the 19th day and one mouse died on the 21st day, while by injection for 3 days in each group 3 mice were cured (on the 28th day of the development of a malignant tumor).

 In group 5, one mouse died on the 15th day due to the development of a malignant tumor, one mouse died on the 17th day, one mouse died on the 18th day, one mouse died on the 19th day and one mouse died on the 21st day, while 2 mice were cured by injection for 21 days.

 In group 6, one mouse died on the 15th day due to the development of a malignant tumor, one mouse died on the 16th day, one mouse died on the 18th day, one mouse died on the 19th day and two mice died on the 20th day, while one mouse was cured by injection for 20 days.

 In group 7, all mice died on day 15 due to the development of a malignant tumor.

Experiment 5
Clinical trial on a volunteer by the administration of an injection prepared by dissolving the powder for injection from Example 1 in distilled water for injection
A patient:
Name: Kim Myung-Won (age 36 years old, male)
Address: # 6-501, Moran 2cha Apt., Shingi-dong, Dong-gu, Taegu, Korea
Type of disease: Thyroid cancer
Diagnosis: delivered on May 7, 1992 at the main hospital, a branch of Yongnam University.

 Duration of drug administration: from May 16, 1992 to October 20, 1992.

 Treatment with the drug: for 4 days, intravenous injections of 12 ml were performed 1 time / day, while 2 times / day for 8 days (only 15 times), 10 ml of the injection drug was injected into the protruding tumor, and then no injection treatment was performed for 25 days. After that, the injection treatment was repeated by intravenous injection and direct injection into the protruding tumor, as described above, as a result of which the tumor completely disappeared. After 5 years, in the main hospital, a branch of Yongnam University and in the main hospital, a branch of Changnam University, it was concluded that the patient was completely cured.

Experiment 6
Clinical trial on a volunteer by injection, prepared by dissolving the powder for injection from example 2, in distilled water for injection
A patient:
Name: Kim Chul-Ki (age 50 years old, male)
Address: # 1223-404, Mokdong Apt., Shinjung-dong, Yangchon-gu, Seoul, Korea
Type of disease: Advanced lung cancer. Weight loss, cough, sputum with blood, shortness of breath due to residual cancer after surgery.

 Diagnosis: delivered on May 18, 1989 at the Wonju Christian Hospital, a branch of Yonsei University.

 Duration of drug administration: from September 3, 1989 to March 5, 1990

 Treatment using a drug: intravenous injections of 10 ml were administered 1 time / day for 4 days, and then no treatment was performed for 3 weeks. The same treatment was repeated for 7 months, as a result of which the tumor and its associated symptoms completely disappeared. After 6 years, in the main hospital, a branch of Yonsei University and in the main hospital, a branch of Chungnam University, it was concluded that the patient was completely cured.

Experiment 7
Clinical trial on a volunteer by injection, prepared by dissolving the powder for injection from example 2, in distilled water for injection
A patient:
Name: Su Sang-Bong (age 35 years old, male)
Address: 756, Shibang-ri, Jangmok-myeon, Geohje-gun, Kyungsangnam-do, Korea
Type of disease: Advanced rectal cancer. Weight loss and severe pain due to residual cancer after partial surgical removal of the tumor.

 Diagnosis: delivered on July 19, 1991 at the Goshinsky Medical Center in Busan.

 Duration of drug administration: from November 19, 1991 to May 12, 1992.

 Treatment using a drug: intravenous injections of 12 ml were administered 1 time / day for 4 days, and then no treatment was performed for 3 weeks. The same treatment was repeated for 7 months, as a result of which the residual tumor completely disappeared. 6 years after the drug was administered at the Goshinsky Medical Center and at the main hospital, a branch of Chungnam University, it was concluded that the patient was completely cured.

Experiment 8
Clinical trial on a volunteer by injection, prepared by dissolving the powder for injection from example 3 in distilled water for injection
A patient:
Name: Joo Sang Park (age 45 years old, male)
Address: 15/2, 387-3, Bugok 1-dong, Kumjeong-gu, Pusan, Korea
Type of disease: Advanced cancer of the stomach. Feeling of heaviness in the stomach, dyspepsia and weight loss.

 Diagnosis: delivered on December 29, 1989 at the Goshinsky Medical Center in Busan.

 Duration of drug administration: from March 1, 1990 to September 29, 1990

 Treatment with the drug: for 4 days, intravenous injections of 12 ml were performed 1 time / day and at the same time 4 times / day the patient took 173 mg of the drug sample inside. Intravenous injection was carried out in such a way that it was carried out for 4 days, and then for 4 weeks treatment was not carried out, while the administration of the drug continued. As a result, the symptoms completely disappeared, and a biopsy confirmed that the patient did not have a tumor. After 6 years, the conclusion was made at the Goshinsky Medical Center that the patient was completely cured.

Experiment 9
Clinical trial on a volunteer by injection, prepared by dissolving the powder for injection from example 5 in distilled water for injection
A patient:
Name: Lee Bok-Do (age 65, male)
Address: 322-81, Chosan-ri, Hwagok-myeon, Yangsan-gun, Kyungsangbuk-do, Korea
Type of disease: Advanced liver cancer. Ascites, dyspepsia, and weight loss due to residual cancer after partial surgical removal of the tumor.

 Diagnosis: delivered on April 8, 1994 at the Goshinsky Medical Center in Busan.

 Duration of drug administration: from May 31, 1994 to December 30, 1994

 Treatment using a drug: intravenous injections of 9 ml were performed for 4 days and at the same time 4 ml of the sample was injected 1 time / day directly into the residual tumor in the liver for 3 days, and then no treatment was performed for 3 weeks. The same treatment was repeated 3 times, and then from the fourth cycle of treatment only intravenous injections were carried out, as a result of which the residual tumor completely disappeared. After 3 years in the Goshin Medical Center and in the main hospital, a branch of Chungnam University, it was concluded that the patient was completely cured.

Test 1 (stability study)
Samples of the lyophilized powder for injection obtained in the examples in accordance with the present invention, were stored for 2 years, and then dissolved in distilled water for injection. The resulting light brown solution was clear and there was no precipitate.

Test 2 (stability study)
Samples of the injection solution obtained in comparative example 2 were stored for 1 month, 2 months and 3 months, respectively. In the obtained solutions, a precipitate precipitated after 1 month, and after 3 months the solutions were cloudy and could not be used for injection.

Effects of the invention
As can be seen from the above experiments, the antitumor compositions known from the previous level are sensitive to moisture and even when stored in the refrigerator they easily deteriorate and their effectiveness decreases sharply, as a result of which they cannot be stored for a long time, and therefore they cannot be used as a medicine.

However, the compositions of the present invention, which are obtained by extracting the herbal ingredients at a temperature below 60 ^° C and after extraction are immediately lyophilized, the quality and effectiveness of the extracts do not change after prolonged storage, as a result of which they can be used safely.

Claims (8)

1. A pharmaceutical composition having antitumor activity obtained by extracting from 0 to 100 wt.% Powdered Pulsatillae root and from 0 to 100 wt.% Powdered Ulmaceae bark, provided that the content of both components is not zero at the same time, in solvent at a temperature below 60 ^o C, filtration and lyophilization of the extract, and then admixing the lyophilized powder with conventional auxiliaries, or admixing the above extracted solution with auxiliaries Then filtering and lyophilizing the mixture, and then give lyophilized powder of the pharmaceutical preparation by a conventional method used in pharmacy. 2. A pharmaceutical composition having antitumor activity obtained by extracting from 0 to 100 wt.% Powdered Pulsatillae root and from 0 to 100 wt.% Powdered Ulmaceae bark, provided that the content of Pulsatillae root and Ulmaceae bark is more than 30 wt.%, and one or more ingredients selected from 0-70 wt.% powdered ginseng root and 0-70 wt.% Glycyrrhizae root in a solvent at a temperature below 60 ^{° C.} , filtering and lyophilizing the extract, and mixing the lyophilized powder with auxiliary substances by mixing or mixing the extracted solution with excipients, filtering and lyophilizing the mixture, and then obtaining the pharmaceutical preparation from the lyophilized powder using the usual method used in pharmacy.  3. The pharmaceutical composition according to claim 1 or 2, in which the solvent is selected from water, alcohol, acetone, ethyl acetate and mixtures thereof, and the composition is prepared in a form selected from a powder, granule, tablet, capsule, powder for injection and ointment.  4. The pharmaceutical composition according to claim 1 or 2, in which the auxiliary substances are one or more compounds selected from a diluent, a binding agent, a disintegrating agent, a preservative, an agent that reduces pain sensitivity, an isotonic agent, and a lubricant. 5. A method of obtaining a pharmaceutical composition having antitumor activity, comprising extracting from 0 to 100 wt.% Powdered Pulsatillae root and from 0 to 100 wt.% Powdered Ulmaceae bark, provided that the content of both components is not zero at the same time in a solvent at a temperature below 60 ^o C, filtering and lyophilizing the extract, and mixing the lyophilized powder with excipients or mixing the above extracted solution with conventional auxiliaries vesch stvami, then filtering and lyophilizing the mixture, and then obtaining powder of the lyophilized pharmaceutical preparation by a conventional method used in pharmacy. 6. A method of obtaining a pharmaceutical composition having antitumor activity, comprising extracting from 0 to 100 wt.% Powdered Pulsatillae root and from 0 to 100 wt.% Powdered Ulmaceae bark, provided that the content of Pulsatillae root and Ulmaceae bark more than 30 wt. %, and one or more ingredients selected from 0-70 wt. % powdered ginseng root and 0-70 wt.% Glycyrrhizae root in a solvent at a temperature below 60 ^o C, filtering and lyophilization of the extract, and mixing the lyophilized powder with excipients or mixing the extracted solution with excipients, filtering and lyophilizing the mixture, and then obtaining from a lyophilized powder a pharmaceutical preparation using the conventional method used in pharmacy.  7. The method according to claim 5 or 6, in which the solvent is selected from water, alcohol, acetone, ethyl acetate and mixtures thereof, and the composition is prepared in a form selected from a powder, granule, tablet, capsule, powder for injection and ointment.  8. The method according to claim 5 or 6, in which the auxiliary substances are one or more compounds selected from a diluent, a binding agent, a disintegrating agent, a preservative, an agent that reduces pain sensitivity, an isotonic agent, and a lubricant. Priority on points:
11/03/1998 and 11/11/1998 according to claims 1, 3-5, 7, 8;
11.11.1998 according to claims 2 and 6.