KR20170047812A - A anticancer pharmaceutical composition comprising herbal mixture extract of akebia quinata seed extract and panax ginseng, and lipopolysacharide - Google Patents

Abstract

The present invention relates to an anticancer pharmaceutical composition comprising a herbal mixture extract of Akebia quinata seed extracts and Panax ginseng, and lipopolysacharide. The herbal mixture extract has no toxicity to human bodies but shows strong cytotoxicity to cancer cells, and increases anticancer abilities of other anticancer components, thereby being used as an anticancer pharmaceutical composition.

Description

[0001] The present invention relates to an anticancer pharmaceutical composition containing an extract of Panax ginseng, a panax ginseng, and a lipopolysaccharide,

The present invention relates to a herbal mixed extract obtained by mixing ginseng seed extract and ginseng, and an anticancer pharmaceutical composition containing endotoxin.

Cells, the smallest unit of the body, divide and grow by the regulatory function of the cell itself under normal conditions, and self-destruct when their lifespan is damaged or damaged, thereby maintaining an overall balance of numbers. However, if there is a problem with the regulation function of the cell itself due to various reasons, abnormal cells that normally should die are over-proliferated. In some cases, they penetrate into surrounding tissues and organs to form a mass, This condition can be defined as cancer. Cancer is one of the intractable diseases that humanity needs to solve. There is enormous capital invested in development to heal it globally, and medical technology is also developing progressively, nevertheless cancer deaths are steadily increasing . In Korea, about 100,000 cases are diagnosed annually, and about 60,000 or more are dead.

In addition, when the cancer progresses and progress is continued, treatment with chemotherapy or radiotherapy is intensively performed in combination with surgical treatment such as surgery, but side effects such as hematopoiesis and immunosuppression are emerging as a serious problem .

As a new approach to cancer therapy, research is underway to develop anticancer drugs with low side effects and high efficacy from natural substances with relatively low toxicity. Taxol, which is derived from natural wood, is one of the typical anticancer drugs derived from natural products. However, it has been reported that taxol acts not only on the death of cancer cells but also on other normal cells in the body, and has low toxicity and side effects due to low solubility in water. In addition, there are many plants that have been studied to date for cytotoxicity or anticancer activity, but only the substances isolated from some plants, such as the spotlight and Changchunhwa, are practically used. Cytotoxic or anticancer substances studied in numerous laboratories are only in the academic literature due to their lack of toxicity, side effects or effects on the human body. In order to ensure both stability and therapeutic effects, it is necessary to develop cancer drugs based on various approaches. .

Endotoxin is one of a group of substances forming the outer surface of cells of Gram-negative bacteria (Escherichia coli, Salmonella, Red bacteria, Brucellosis, etc.). When it enters the blood of an animal, it participates in the immune system and causes fever, hypotension, inflammation reaction, And in severe cases, septic shock is caused to lead to death. Chemically, it belongs to lipopolysaccharides (LPS). When it is present in blood, it activates macrophages, monocytes, natural killer-cells (NK-cells) Especially, when macrophages are activated, tumor necrosis factor-alpha (TNF-α) is secreted and cytotoxicity against cancer cells is shown. Previous studies [Goto, S. et al., 1996] have shown that cancerous patients exhibit a certain anticancer effect when intravenously injected with cyclophosphamide while subcutaneously injecting lipopolysaccharide into the cancer patient.

Saponin among plant components plays a role in formulation as well as pharmacological effects that soften joints or regenerate hepatocytes or have anticancer effects, because it exhibits soap effect and increases the water solubility or suspension of the extract. Therefore, it is possible to easily make the saponin-containing extract as a main agent.

Panax ginseng is a perennial plant that has been used traditionally for the prevention and treatment of various diseases in Korea and China. It has been known to have excellent effects and no side effects even when used for a long time. It is also known as a representative saponin herbal medicine containing 27 saponins of ginsenoside, which is good for cancer, diabetes, hypertension, arteriosclerosis, dementia, prevention of osteoporosis, prevention of aging, promotion of brain activity, menopausal disorder, .

In particular, hexane extract or ethyl acetate extract containing fat-soluble components of ginseng exhibits strong cytotoxicity against cancer cells, which is a polyacetylene consisting of nine such as panaxydol and panaxyriol In particular, it is known that pancytopenia is a potent cytotoxic agent against cancer cells (Ahn, BZ et al., 1985).

Akebia quinata is a saponin-containing herbal medicine containing a large amount of 7 kinds of akebia saponins (A to G), and is known as a medicinal substance for the inflammation, diuretic, I write. Korean Patent Registration No. 10-0573375 discloses an anticancer effect of saponin-containing extracts by aging seeds of Crane seeds in water.

The roots of anthriscus sylvestris are known as Toejang or Assam and have traditionally been used for coughing, asthma, and headache due to colds (Chang-bok, 2006; The major components are deoxypodophyllotoxin, anthricin, isoanthricin, and α-pinene. Pharmacological actions include stimulation of bronchial mucus secretion, Arterial blood flow, anti-influenza virus, anti-ulcer, anti-convulsive, anti-allergic, anti-cancer and anti-bacterial effects. In particular, it has been disclosed that deoxypodophyllotoxin has the effect of inhibiting cancer cells as an anticancer agent in Korean Patent Laid-Open No. 2009-0119123 and the prior art [Kim, Y. et al., 2002].

The roots of lithospermum erythrorhizon are used in herbal medicine as herbal medicine called 草 草. It is effective for bleeding, nosebleeds, urine bleeding and measles. It is used as a disinfectant for burns, bronchitis, eczema, rash, skin ulcers and the like. In addition, it contains a 1,4-naphthoquinone-based substance and has strong cytotoxicity against cancer cells by inhibiting DNA topoisomerase-I. et al., 1995).

As described above, various pharmacological effects and anticancer effects on ginseng, Rhododendron sp., Chunho and Dill are known from the prior literature. However, the anticancer pharmaceutical composition containing the mixed extract and the endotoxin .

Korean Unexamined Patent Publication No. 1999-0013196, New anticancer composition, published on February 25, 1999. Korean Patent Laid-Open No. 2009-0119123, Use of deoxyplastin toxin as an anticancer agent, published Nov. 19, 2009. Korean Patent No. 10-0573375, an anticancer composition comprising a crude Aspergillus oryzae extract and a method for preparing the same, Registered on Apr. 17, 2006.

Jang Chang-soo, herbal medicine book, book publication Kyungwon, 386, 1997. Lee Chang - bok, Elementary Colored Plants Book, Fukmunsa, 818, 2006. Ahn, B. Z. et al., Antineoplastic Natural Products and the Analogues VI-Panaxydol, the Cytotoxic Principle of the Panax Ginseng Root Against L1210 Cell, Archives of Pharmacal Research, 8 (4), 283-284, 1985. Ahn, B. Z. et al., Acylshikonin analogues: synthesis and inhibition of DNA topoisomerase-I, J Med Chem., 38 (6), 1044-1047, Goto, S. et al., Intradermal administration of lipopolysaccharide in tratment of human cancer, Cancer Immunol Immunother., 42 (4), 255-261, 1996. Kim, Y. et al., Deoxypodophyllotoxin; the cytotoxic and antiangiogenic component from Pulsatilla koreana, Planta Medica, 68 (3), 271-274, 2002. Utsugi, T. et al., Antitumor activity of a novel podophyllotoxin derivative (TOP-53) against lung cancer and lung metastatic cancer, Cancer Res., 56 (12), 2809-2814, 1996.

It is an object of the present invention to provide a medicinal herbal composition extract containing ginseng seed extract and ginseng, and an anticancer pharmaceutical composition containing endotoxin.

The present invention relates to an anticancer pharmaceutical composition comprising an extract of a herbal medicine mixed with an extract of akebia quinata seed and panax ginseng, and a lipopolysaccharide.

The vine seed extract is prepared by mixing the crude vine seed powder and water at a weight ratio of 1: 1 to 3 and aging at 35 to 40 ° C for 1 to 4 hours (step 1); Heating the aged material in one step at a temperature of 70 to 90 DEG C for 15 to 60 minutes (step 2); And hexane is added to the product of step 2, the hexane layer is removed, and the aqueous layer is concentrated under reduced pressure (step 3); . ≪ / RTI >

In addition, the herbal medicine mixed extract is obtained by extracting and concentrating the crude vine seed extract extracted from 100 parts by weight of the crude vine seed with 40 to 60 parts by weight of ginseng with the lower alcohol of C1 to C4.

Endotoxin is mixed at 1.0 × 10 ^-8 to 1.0 × 10 ^-7 parts by weight based on 100 parts by weight of the herbal medicine mixed extract, and the pharmaceutical formulation of the anticancer pharmaceutical composition is an injectable composition.

In addition, the herbal medicine mixed extract of the present invention may be prepared by mixing 0.5 to 3 parts by weight of anthriscus sylvestris or 0.5 to 3 parts by weight of an extract of Angelica keiskei koidz. lithospermum erythrorhizon), and extracting and concentrating the same with C1 to C4 lower alcohols, wherein the endotoxin is contained in an amount of 1.0 × 10 ^-8 to 1.0 × 10 ^-7 parts by weight.

Hereinafter, the present invention will be described in detail.

The present invention relates to an anticancer pharmaceutical composition comprising an extract of a herbal medicine mixed with an extract of akebia quinata seed and panax ginseng, and a lipopolysaccharide.

The vine seed extract is prepared by mixing seeds of Crassulaceae seeds and water in a weight ratio of 1: 1 to 3, aging at 35 to 40 ° C for 1 to 4 hours, heating at 70 to 90 ° C for 15 to 60 minutes After adding hexane and shaking, the hexane layer was removed and the aqueous layer was concentrated under reduced pressure. Preferably, the crude seeds are mixed with water at a weight ratio of 1: 1.5 to 2, aged at 38 to 39 ° C for 2 to 3 hours, heated at 75 to 85 ° C for 25 to 45 minutes, After removing the hexane layer, the water layer is concentrated under reduced pressure to obtain a crude vine seed extract.

In addition, the herbal medicine mixed extract may be prepared by extracting the crude vine seed extract extracted from 100 parts by weight of the crude vine seed with 40 to 60 parts by weight of ginseng with C1 to C4 lower alcohols, and the C1 to C4 lower alcohols Ethanol (or an aqueous methanol solution or an aqueous ethanol solution of 98% [v / v] or more) of methanol, ethanol, propanol, isopropanol, butanol or the like can be used. Can be prevented.

The present invention also relates to a pharmaceutical composition comprising the herbal composition, wherein the endotoxin is mixed at 1.0 × 10 ^-8 to 1.0 × 10 ^-7 parts by weight, preferably 5.0 × 10 ^-8 to 1.0 × 10 ^-7 parts by weight, Can be mixed. If the amount of the endotoxin is more than the above range, toxicity may appear, which is undesirable. If the endotoxin is contained in the above range, the anticancer effect is not good.

The pharmacological formulation of the anticancer pharmaceutical composition of the present invention is an injectable composition. The pharmacologically mixed extract of the present invention can be obtained by extraction with an organic solvent (alcohol, ether, acetone, etc.), separation and extraction of plant components May be used alone or in a suitable combination thereof. Preferably, the herbal medicine mixed extract may be dissolved in a solvent, and then filtered with a microflora to be used as an injection.

In addition, the herbal medicine mixed extract may be prepared by adding 0.5 to 3 parts by weight of anthriscus sylvestris or a lithospermum erythrorhizon to an admixture of 40 to 60 parts by weight of ginseng extract, 1 to 5 parts by weight of at least one herbal medicine is further mixed and extracted with C1 to C4 lower alcohols and concentrated.

The present invention also relates to a pharmaceutical composition for anti-cancer. The cancer is also referred to as malignant tumor. The tumor is abnormally grown as a result of autonomous overgrowth of body tissue. As a result, It refers to diseases that spread or metastasize to parts of the body and are life-threatening, including carcinoma and sarcoma. Cancer, cancer of the endometrium, cancer of the uterine cervix, cancer of the uterine cervix, cancer of the uterine cervix, cancer of the cervix, cancer of the cervix, cancer of the cervix, cancer of the cervix, Cancer of the prostate, cancer of the prostate, cancer of the prostate, cancer of the prostate, chronic or acute leukemia, lymphoma, multiple myeloma, thymoma, mesothelioma, renal cancer, blood cancer, brain cancer, central nervous system Tumor, brainstem glioma, and pituitary adenoma.

The dose of the herbal medicine mixed extract and the anti-cancer pharmaceutical composition containing the endotoxin of the present invention may be appropriately determined depending on the age, sex, weight, the specific disease or pathological condition to be treated, the severity of the disease or pathological condition, . Dosage determinations based on these factors are within the level of those skilled in the art, but the endotoxin contained in the herbal medicine mixed extract of the present invention, when used in excess of 0.5 ng / kg body weight in the human body, includes fever, hypotension, Symptoms may occur and should be used below this range. Preferably, the endotoxin level is 0.005 to 0.05 ng per 1 ml of sterile injectable water, more preferably, the endotoxin level is 0.025 to 0.05 ng per 1 ml of sterile injectable water.

In addition, the pharmaceutical composition for anti-cancer including the herbal medicine mixed extract and endotoxin of the present invention can be administered to mammals such as rats, livestock, and humans in various routes. All modes of administration may be expected, for example, by rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebral injection. In addition, the anticancer effect of endotoxin disappears in the case of oral administration, and in the case of cancer such as solid cancer, it can be administered by intratumoral injection. In particular, in the case of injection into a cancerous tissue, direct injection is difficult because of the solidity of the solid cancer. Therefore, it is preferable to directly inject into the tissue after radiofrequency ablation by destroying the cancerous tissue.

The present invention relates to a herbal medicine mixed extract comprising a crude extract of ginseng seeds and ginseng, and an anticancer pharmaceutical composition containing an endotoxin. Although the herbal medicine mixed extract has little toxicity to humans, it exhibits strong cytotoxicity against cancer cells , And the anticancer properties of other anticancer components are elevated, so that they can be usefully used as anticancer pharmaceutical compositions.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graph showing average cancer growth inhibition rates (%) for anticancer pharmaceutical compositions containing herbal medicine extracts and endotoxins of Examples 1-1 to 1-13 of the present invention. FIG.

Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein but may be embodied in other forms. Rather, the intention is to provide an exhaustive, complete, and complete disclosure of the principles of the invention to those skilled in the art.

≪ Example 1: Preparation of anticancer pharmaceutical composition containing herbal medicine mixed extract and endotoxin >

In order to prepare an anticancer pharmaceutical composition containing a herbal mixture extract and a ginseng mixed extract of Angelica keiskei koidz. Seed extract of the present invention and an endotoxin, a crude kestrel seed extract was first prepared. Since the vine seed extract can produce anticancer saponins by aging in water, the vine seeds are prepared by aging in water and then used.

First, 250 g of water was added to 150 g of crumbly seeds powder, which was crushed by a crusher and then transferred to a fermenter. The plants remaining in the crusher were washed with 50 ml of water and put in a fermenter. Thereafter, the mixture was aged at 37 DEG C for 2 hours. After aging, the temperature of the fermenter was raised to 80 DEG C and heated for 30 minutes. The mixture was cooled at room temperature and then placed in a funnel. 500 mL of hexane was added thereto, The hexane layer was removed. After performing the degreasing operation once more, the remaining water layer was dried with a vacuum concentrator to obtain a crude vine seed extract, and a crude drug mixture containing endotoxin was prepared by referring to the composition of Table 1 below.

The total amount of the extract corresponding to 30 g of the crane seed powder and the dry ginseng powder, the crumb powder and the drench powder without removing the root and the root were mixed with the composition shown in Table 1, 200 ml of alcohol (methanol or ethanol) was added, Lt; / RTI > The reaction product was filtered and the filtrate was stored, and the same extraction procedure was repeated twice for the remaining plants. The obtained filtrates were combined and dried in a vacuum dryer, and 150 ml of alcohol (methanol or ethanol) was added to each dry matter, and the mixture was left to stand for 13 hours. The total amount of the herbal medicine mixed extracts was adjusted to the amount of lipopolysaccharides from Escherichia coli (Sigma-Aldrich, USA) dissolved in the following Table 1, 1000 ml of water was added and mixed. The mixture was allowed to stand for 12 hours and then filtered with a microflora to obtain Examples 1-1 to 1-13 which are anticancer pharmaceutical compositions containing the herbal medicine mixed extract and the endotoxin of the present invention. , 5 to 10 ml of the solution was placed in a vial, lyophilized and stored, and dissolved in the same amount of physiological saline at the time of use.

Condition Composition of herbal medicine mixed extract LPS (ng) / water for injection (l) Crane seeds
(g) Ginseng
(g) No.
(g) Shag
(g) Example 1-1 30 15 - - 30 Examples 1-2 30 15 - - 5 Example 1-3 30 15 - - 50 Examples 1-4 30 15 0.3 - 30 Examples 1-5 30 15 0.5 - 30 Examples 1-6 30 15 - 0.6 30 Examples 1-7 30 15 - One 30 Examples 1-8 30 15 0.3 0.6 30 Examples 1-9 30 15 0.3 0.6 5 Example 1-10 30 15 0.3 0.6 50 Example 1-11 30 15 0.5 One 30 Examples 1-12 30 15 0.5 One 5 Examples 1-13 30 15 0.5 One 50

< Comparative Example  1. Preparation of comparative extracts - without endotoxin>

A comparative extract was prepared by reference to Korean Patent No. 573375. First, 36 g of crane seeds were added to the mortar and 40 ml of water was added and ground. The pulverized contents were put into a beaker having a size of 250 ml, and the beaker was rinsed with 14 ml of water and put into the beaker again. The surface of the beaker contents was covered with wet gauze and allowed to stand at room temperature (22 degrees) for 1 hour. After 1 hour, 80 ml of methanol (98% purity or more) was added thereto, followed by stirring for 30 minutes. The extract was filtered, and 150 ml of 80% methanol was added to the remaining plants, followed by stirring for 30 minutes. The methanol solute was obtained by filtration and combined with the first fraction. The combined methanol solubles were dried under reduced pressure, and thereto was added 30 ml of 98% methanol and stirred for 10 minutes. The methanol solution was filtered, and the insoluble matter was mixed with 10 ml of methanol and stirred for 10 minutes. After filtration, the filtrate was combined with the first fraction. The combined methanol solubles were transferred to a small separating funnel, 40 ml of hexane was added thereto, and the mixture was shaken. Then, the hexane layer was discarded and the lower layer of methanol solution was separated. Then, 40 mL of hexane was added to the lower methanol layer separated in the above process, and the mixture was allowed to stand. The methanol-dissolved portion of the lower layer was taken, completely dried, and 30 mL of 100% ethanol was added thereto. After shaking, Vine seed extract was obtained.

100 ml and 1000 ml of the water for injection were added to the mixture of the crude Aspergillus sp. Extract prepared in the above procedure, the acetone extract obtained from 5 g of ginseng and the ether extract obtained from 8 g of Aspergillus, For 2 hours, and filtered to obtain Comparative Examples 1-1 and 1-2. All liquid preparations were prepared immediately before use.

&Lt; Comparative Example 2 > Preparation of extract for comparison - including endotoxin &gt;

Each of the comparative extracts was prepared in the same manner as in Example 1 except that the conditions were as shown in Table 2 below.

Condition Composition of herbal medicine mixed extract LPS (ng) / water for injection (l) Crane seeds
(g) Ginseng
(g) No.
(g) Shag
(g) Comparative Example 2-1 30 15 - - 0.5 Comparative Example 2-2 30 15 - - 2.5 Comparative Example 2-3 30 15 - - 100 Comparative Example 2-4 30 30 - - 30 Comparative Example 2-5 30 7.5 - - 30 Comparative Example 2-6 30 15 0.5 3 30 Comparative Example 2-7 30 15 0.5 3 0.5 Comparative Example 2-8 30 15 0.5 3 100 Comparative Example 2-9 30 15 1.8 One 30 Comparative Example 2-10 30 15 1.8 One 0.5 Comparative Example 2-11 30 15 1.8 One 100 Comparative Examples 2-12 30 30 1.8 3 30 Comparative Example 2-13 30 7.5 0.3 0.15 30

< Experimental Example  One. LL / 2 &lt; / RTI &gt;

Experimental Example 1-1. LL / 2 cells (Lewis Lung Carcinoma Cell-2) and culture

The culture broth was prepared by adding 1 pack of RPMI-1640 culture medium containing L-glutamine to distilled water for sterilization, 100 ml of FBS (fetal bovine serum) inactivated by heating in a 56 ° C water bath for 30 minutes, sodium bicarbonate ), Penicillin (100,000 units) and streptomycin (100 mg) were dissolved and adjusted to pH 1 with 0.1 N HCl to give a final volume of 1 L, which was prepared by bacterial filtration. And stored. Cells were maintained for 3 days and 0.5% [w / v] trypsin and 2% [w / v] EDTA (ethylenediaminetetraacetic acid) were added to the phosphate buffered saline (PBS) acid was dissolved in the solution.

Experimental Example 1-2. Animal experiments using LL / 2 cells

LL / 2 cells cultured in vitro were washed thoroughly with sterilized cold physiological saline, and the cells were counted with a haemacytometer to make a cell suspension at a concentration of 5 x 10 ⁶ cells / ml. And 0.2 ml of the solution was transplanted subcutaneously into the side of the mouse. Twenty-four hours after transplantation, each group was divided into five groups. Samples were prepared immediately before injection and injected 0.2 ml into the abdominal cavity of the experimental animals. In the control group, only physiological saline was administered at the same dose as the sample dose.

Although the injection schedule varies depending on the sample, it is generally started after 24 hours after the transplantation of cancer cells, and is administered again on days 3, 5, 7, 9, and 11, and then 16 and 17 days, respectively (Utsugi, T. et al., 1996).

In order to measure the toxicity of each sample to the mice, the body weight was measured once at intervals of 2 days. The anticancer effect was evaluated on the 11th to 19th day of the administration of the drug, , And the cancer growth inhibition rate was expressed as an average value measured three times.

[Mathematical Expression]

The volume of the arm (mm ³ ) = length (mm) x width ² (mm ² ) / 2

Cancer growth inhibition ratio (%) = (C - T) 100 / C

(C: the average arm volume of the control group (mm ³ ), and T: the average arm volume (mm ³ ) of the group treated in the example or the comparative example.

Condition Cancer growth inhibition rate%  Average % Example 1-1 75 (5), 80 (5), 81 (5) 78.7 (15) Examples 1-2 79 (5), 75 (5), 73 (5) 75.7 (15) Example 1-3 83 (5), 79 (5), 81 (5) 81.0 (15) Examples 1-4 79 (5), 82 (5), 78 (5) 79.7 (15) Examples 1-5 83 (5), 78 (5), 80 (5) 80.3 (15) Examples 1-6 75 (5), 80 (5), 78 (5) 77.7 (15) Examples 1-7 80 (5), 75 (5), 81 (5) 78.7 (15) Examples 1-8 81 (5), 85 (5), 82 (5) 82.7 (15) Examples 1-9 74 (5), 79 (5), 82 (5) 78.3 (15) Example 1-10 79 (5), 85 (5), 80 (5) 81.3 (15) Example 1-11 80 (5), 85 (5), 81 (5) 82.0 (15) Examples 1-12 83 (5), 80 (5), 79 (5) 80.7 (15) Examples 1-13 80 (5), 82 (4), 85 (5) 82.3 (14) Comparative Example 1-1 83 (5), 80 (5), 79 (5) 80.7 (15) Comparative Example 1-2 51 (5), 42 (5), 41 (5) 44.7 (15) Comparative Example 2-1 64 (5), 60 (5), 59 (5) 61.0 (15) Comparative Example 2-2 65 (5), 63 (5), 62 (5) 63.3 (15) Comparative Example 2-3 81 (4), 75 (4), 83 (4) 79.7 (12) Comparative Example 2-4 68 (5), 71 (5), 71 (5) 70.0 (15) Comparative Example 2-5 66 (5), 72 (5), 73 (5) 70.3 (15) Comparative Example 2-6 73 (4), 69 (5), 72 (5) 71.3 (14) Comparative Example 2-7 65 (5), 61 (5), 60 (5) 62.0 (15) Comparative Example 2-8 78 (3), 80 (4), 80 (4) 79.3 (11) Comparative Example 2-9 75 (4), 72 (4), 69 (5) 72.0 (13) Comparative Example 2-10 66 (5), 61 (5), 63 (5) 63.3 (15) Comparative Example 2-11 78 (4), 76 (4), 80 (3) 78.0 (11) Comparative Examples 2-12 79 (4), 73 (4), 80 (4) 77.3 (12) Comparative Example 2-13 65 (5), 63 (5), 69 (4) 65.7 (14) Cancer growth inhibition rate; Percentage of cancer size in the dosing group for the control.
* Numbers in parentheses: Number of living animals after the experiment
* Toxicity: Toxicity is toxicity when more than 5-6 dogs are killed among 15 dogs used in 3 times experiment, and toxic when 3-4 dogs are dead.

As shown in Table 3, Comparative Example 1-1 was prepared in a similar manner to the herbal medicine mixed extract disclosed in Korean Patent No. 573375, and the inhibition rate of cancer growth was measured. The endotoxin was not included, &Lt; / RTI &gt; and endotoxin, respectively. However, in Comparative Example 1-1, unlike Examples 1-1 to 1-13 of the present invention, 100 ml of the water for injection containing the herbal medicine mixed extract was 10 times More herbal mixed extracts are included in the water for injection. Thus, in the case of Comparative Example 1-2 in which crude drug mixture extract was added to 1000 ml of water for injection under the same conditions as in Examples 1-1 to 1-13 of the present invention, unlike the result of Comparative Example 1-1, Is reduced by a factor of two. On the other hand, the cancer growth inhibition rates of Examples 1-1 to 1-13 of the present invention are equivalent to those of Comparative Example 1-1, even though the herbal medicine mixed extract contained in the injection water is 10 times smaller than that of Comparative Example 1-1, It is confirmed that the anticancer pharmaceutical composition containing the mixed extract and the endotoxin synergistically acts on the anticancer effect and shows an excellent cancer growth inhibition rate.

Further, in the case of Comparative Examples 2-1 to 2-13 in which the compositional contents of the anticancer pharmaceutical composition of the present invention were deviated from those of Comparative Examples 1-1 and 1-2, The rate of blockage is low or toxic. Therefore, it can be confirmed that the herbal mixed extract containing the endotoxin prepared according to the present invention has the best effect of inhibiting cancer growth, and thus can be used as a pharmaceutical composition for anti-cancer therapy.

Claims (8)

An extract of a herbal medicine mixed with an extract of akebia quinata seed and ginseng (panax ginseng), and lipopolysacharide. The method according to claim 1,
The above-mentioned vine seed extract,
(1 step) of aging for 1 to 4 hours at 35 to 40 ° C by mixing the seeds of Crassulaceae seed powder and water in a weight ratio of 1: 1 to 3;
Heating the aged material in one step at a temperature of 70 to 90 DEG C for 15 to 60 minutes (step 2); And
Adding hexane to the product of Step 2, removing the hexane layer, and concentrating the water layer under reduced pressure (Step 3);
Wherein the extract is an extract prepared by the method according to claim 1. The method according to claim 1,
Wherein the herbal medicine mixed extract is obtained by extracting and concentrating the crude vine seed extract extracted from 100 parts by weight of the crude vine seed with 40 to 60 parts by weight of ginseng mixed with the lower alcohol of C1 to C4. 4. The method according to any one of claims 1 to 3,
Wherein the endotoxin is mixed at 1.0 × 10 ^-8 to 1.0 × 10 ^-7 parts by weight based on 100 parts by weight of the herbal medicine mixed extract. 5. The method of claim 4,
Wherein the pharmaceutical formulation of the anticancer pharmaceutical composition is an injectable composition. 4. The method according to any one of claims 1 to 3,
The herbal medicine mixed extract may be prepared by mixing 0.5 to 3 parts by weight of anthriscus sylvestris or 1 to 3 parts by weight of ginseng to a mixture obtained by mixing vinegar seed extract extracted from 100 parts by weight of ginseng seeds with 40 to 60 parts by weight of ginseng, 5 parts by weight of at least one herbal medicine is further mixed and extracted with C1 to C4 lower alcohols and concentrated. The method according to claim 6,
Wherein the endotoxin is mixed at 1.0 × 10 ^-8 to 1.0 × 10 ^-7 parts by weight based on 100 parts by weight of the herbal medicine mixed extract. 8. The method of claim 7,
Wherein the pharmaceutical formulation of the anticancer pharmaceutical composition is an injectable composition.

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