TW200400828A - A composition for cancer therapy - Google Patents

Abstract

Compositions for cancer therapy comprising two or more saponins and/or sapogenins as provided. The compositions have enhanced anti-cancer activity when compared to each individual component alone. Also provided are pharmaceutical and non-pharmaceutical formulations comprising the compositions for use in the treatment of mammalian subjects having cancer, and pharmaceutical kits comprising such compositions or formulations.

Description

200400828 (Description of invention should be stated ... The technical field to which the invention belongs, prior art, content, embodiments, and drawings are briefly explained.) [Technical field to which the invention belongs] The present invention relates to a combination for the treatment of cancer More specifically, the present invention relates to the use of saponin S and / or saponin amidin in the treatment of cancer. [Previous Technology] Due to the continued demand for new anticancer drugs and drug combinations, anticancer research has increasingly turned to discovering new anticancer drugs from natural resources, and discovering and formulating synthetic compounds from natural resources. . Ginseng has long been recognized as a tonic and is a benign and safe herbal medicine. Many ingredients in ginseng have been identified and classified as: ginsenoside, carbohydrate 'nitrogenous compound ) 'Fat-soluble compound ^^ (fat-soluble compound), vitamins and minerals, extracted from ginseng (s ^) 〇nin), also known as ginseng officer lt (ginsen〇 side), is the main active ingredient of ginseng φ. Generally speaking, saponins are composed of glycosyl and aglycon, and the sapogenin of glycosides in ginseng is further divided into three Major categories: dammarane, tetracyclic terpenoids, protopanaxadiol and protopanaxatriol, and qi; oleanoic acid 〇 original ginsenotriol The saponin aglycon protopanaxatriol (aPPT) has the following continuation pages. (When the description page of the invention is insufficient, please note and use the continuation page.) 200400828 Description of the invention continued page

^ llMA # ^ S? ^^ ®BS (aglyconprotopanaxadiol, aPPD)

More than 25 types of Damain-type saponins have been isolated from Korean ginseng, but the amount and type of monosaccharides left by various saponins in the sugar side chain are different. The single ginseng lane It is named Rx based on its activity in thin-layer chromatography plates. For example, known ginseng glycosides include those derived from

Sa to saponins from Ra to Rh, and recently a novel Damain type alloside (Rkl, Rk2, Rk3) obtained from three® heat-treated ginseng (see see Park, IH (2002) Arch Pharm Res. 25: 428- 32) . In recent years, the effectiveness of ginsenosides in the treatment of cancer has been reported frequently. For example, US Patent Application No. 09 / 910,887 (Bulletin No .: 20030087835) and the US DPRK petition] d] Continued page (Explanation of the invention When the page is inadequate, please note and use the continuation page) 200400828 Invention description: The new ginsenoside compound with anticancer activity disclosed in No. 09 / 982,018 (Announcement No. 20030087836), similarly, US Patent No. 5,776,460 The number also discloses that coffee ginseng stomach [3-OpD-glucopyranosyl-20 (s) _protopanaxadiol]) has anticancer activity, and coffee has the following chemical structure, where "Glc" stands for glycan or glucose:

It has been reported in the literature that Rh2 can induce differentiation and apoptosis of cancer cells (KikucW Y. et al. (1991) Anti-cancer Drugs. 2: 63-7; Lee KY et al. (1996) Cancer Lett. 110: 193-200; Oh M et al. (1999) Int J Oncol. 18: 869-75; Ota T et al. (1997) Life Sci. 60: PL39-88; Nakata H et al. (1998 ) Jpn J Cancer Res. 89: 733-80; Kim HE et al. (1999) Life Sci. 65: PL33-80; Park JA et al. (1997) Cancer Lett. 121: 73 · 81); by oral feeding Rh2 silencing inhibits the growth of human ovarian cancer in nude mice (Nakata H et al. (1998) Jpn J Cancer Res. 89: 733-80); Rh2 and other chemical compounds are added in stealing. When used in combination, it can kill multi-drug resistant cancer cells (ti_drug resistant, MDR) (refer to US Patent Application No. 60 / 204,785). Ginsenoside Rg3 [3-0- [β-ϋ-glucopyranosyl (1-2) -β ~ 0-glucopyranosy 1]]-20 (S) Ginsengdiol (protopanaxadiol)] has the ability to inhibit the metastasis of different cancer cells (Shinkai K et al (1996) Jpn J Cancer

Res. 87: 357-62), including v // w for AM prostate cancer cells (prostate cancer cells) τι Continued pages (when the invention description page is insufficient, please note and use the continued page) 200400828 Invention description continued page (Liu WK et al. (2000) Life Sci. 07 (11): 1297-306), cancer cell MΦΙΙ # (Iishi H et al. (1997) on mice, and cancer cell peritoneal metastasis on rats (Mochizuki M et al. (1995) Biol Pharm Bull. 18: 1197-202), in addition, U.S. Patent Application No. 09 / 957,082 (Bulletin No. 20030092638) discloses two saponin protopanaxadiols and protopanaxa When used in combination with other chemotherapeutics, mvi, for example, can increase the sensitivity of multidrug-resistant cancer cells to chemotherapy. In addition to the isolated ginseng 1C with anti-cancer activity, in the vfvo test, some The isolated oleanane-type pentacyclic compound (pentacyclic terpenoid compounck) also has anticancer activity (Shibata ^ S. (2001) J. Korean Med. Sci., 16 Suppl .: S28-37). The above background information is provided based on the applicant's opinion that it may be related to the present invention. , Any of the foregoing information is not intended to constitute a prior art counter to the present invention, and the publications of all the technical descriptions herein are placed in the table of contents. [Content] An object of the present invention is to provide a combination for cancer treatment And the application of the composition in the treatment of cancer, corresponding to one aspect of the present invention, here is provided a group with enhanced anti-cancer live injection > the group contains two kinds of alloside and / Corresponding to another aspect of the present invention, there is provided a pharmaceutical formulation for cancer treatment, which comprises a pharmaceutically effective dose of a carrier for the aforementioned composition. Correspondingly in another aspect, a non-pharmaceutical continuation page for cancer treatment is provided here (when the description sheet is insufficient, please note and use the continuation sheet) 200400828 Invention Description Continuation Sheet Formula (non-pharmaceutical formulation), the The formulation contains a pharmaceutically effective carrier suitable for the aforementioned composition. Corresponding to yet another aspect of the present invention, provided herein An application of the composition is provided for the treatment of cancer in cancer patients. Brief Description of the Drawings Figure 1 provides treatment of human neurotumor cancer cells with different saponins and saponin ligands and a composition of the present invention ( human glioma tumor cells) After U87, the cell survival rate is ΙμΙτγ. Figure 2 provides cells treated with different saponins and saponin ligands and a composition of the present invention after treating mouse melanoma cells SB16 B16. Graphical representation of survival rates; Figure 3 provides a graphical representation of cell survival rates after treating human breast cancer cells MCF7 with different saponins and saponin ligands and a composition of the present invention; Figure 4a provides Graphical illustration of cell survival rate of pancreatic cancer cells (BXCP-3) after treatment of pancreatic cancer cells (BXCP-3) at different doses of the composition of the present invention; Figure 4b provides treatment of pancreatic cancer cells (pancreatic cancer cells) at different doses of the composition of the present invention ) Graphical representation of cell viability after CAPAN-1; Figure 5 shows the treatment of cancer cells with v / w at different doses of the composition of the invention Inhibitory effect. Invention_Detailed Description The present invention was based on the discovery that the use of a composition containing ginseng alloside and saponin aglycone has stronger fineness than using those known saponin or alloside aglycone having anticancer activity alone. " T "! Continued page (When the description page of the invention is not enough, please note and use the continuation page) 200400828 Invention description Continued page: ..... · The cell killing effect, that is, the composition used to treat cancer cells, has Unexpected enhancement of cell killing. Therefore, the composition of the present invention has stronger anti-cancer effect and efficacy than using any one of the ingredients in the composition alone. The single-use composition in the composition can be used as a component, and if this level of anti-cancer efficacy and efficacy is to be achieved Very high doses must be used. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the prior art to which this invention relates. "Extract" means a composition that is physically or chemically extracted from plant materials and contains one or more saponins and / or saponin ligands. Persons who have common knowledge of prior art will be based on the information provided here. Known methods can produce extracts, for example, a solvent is used on plant raw materials. The extract can be a crude extract or a partially purified extract. 0 "Plant raw materials" One or more parts obtained from a group of plants, including but not limited to leaves, flowers, rhizomes, seeds, stems, berries and the like. "Natural extract" means an extract obtained from a plant in its natural unprocessed state. "Partially purified" means that the extract is in a state that contains less protein, nucleotides, lipids, carbohydrates, or other similar raw materials that naturally occur in plants than natural extracts. It is a partially purified jujube. "Live thief" refers to those ingredients with anticancer activity in the composition. The live thief of the composition of the present invention includes saponin and / or saponin. "Saponin" refers to a plant glycoside that can pass through Digestion releases one sugar and one saponin with the continuation page (When the description page of the invention is insufficient, please note and use the continuation page) 200400828 __ Description of the invention ®;!; Saponin is also called 4 'ginsenoside. "" Saponin "Ligand" refers to the sugar-free portion of saponin, which is usually obtained by hydrolysis. It does not have a complex terpene structure (αοΜρΙεχίεφεηοίά). "Enhancing effect", in terms of the combined use of two or more active ingredients , Refers to the combined activity of two or more ingredients over the activity of each ingredient when used alone. "Enhancing activity Qi II / enhancing activity ratio" refers to a dose of one ingredient in the present invention sufficient to produce an enhancing effect, such as The other components of the composition of the invention enhance the cell killing ability when used in combination. "Efficacy" refers to the effect of combining honest ingredients to kill cancer cells. "Potency" refers to the efficacy of a composition or an ingredient in relation to the dose used. "Multi-drug resistant cancer (MDR), which refers to the primary or acquired resistance of a cancer or tumor cell to a treatment. Generally, primary multidrug resistant cancer (Prime MDR) is considered to be a cancer that does not respond to chemotherapy without treatment, and Secondary MDR cancer develops resistance during the course of treatment, as understood by those skilled in the art " "Multi-dmg resistant cancer" refers to resistance caused by several mechanisms: Decreased drug accumulation (for example, a chemotherapeutic drug is automatically driven by a protein pump (P-glycoprotein) Excretion (eg, active excretion of the chemotherapeutic by a protein pump (P-glycoprotein)), acceleration of drug metabolism and other changes in drug metabolism, and enhancement of the ability of cells to repair drug damage. In the present invention, "resistance to drugs" "Drug resistant cancer" includes cancers that are resistant to one or more chemotherapeutics, regardless of the mechanism of resistance. "Day-exempt cancer (A "dvanced Cancer" refers to an open cancer (overt cancer ΓΤ1 continuation page on the patient (when the invention description page is insufficient, please note and use the continuation page) 200400828 invention description _ page), this open cancer is often not limited to local And has no face for local treatments such as surgery or radiation therapy. "Primary cancer," refers to the original tumor or primary tumor, and is usually named after the part of the body it is suffering from "Metastatic cancer" refers to the type of cancer that has spread from an original site (primary cancer chain 0 to other sites (secondary cancer 'disease). In fact, all cancers can develop into metastatic cancer. Therefore, the term is not limited to any particular type of cancer. Metastatic cancer is usually resistant. "Recurrent cancer" refers to the recurrence of a cancer that is considered to have cured or the condition has resolved, Cancer recurrence can occur after several weeks, months, years, or years. The recurrence of cancer as understood by those skilled in the art refers to the original Initiate treatments such as chemotherapy, radiotherapy, heterotherapy, and other cancers that have not been removed or eliminated by cancer. The soap test and the saponin base are provided. The present invention provides two or more saponins and / or saponin compounds. The composition of the present invention is used for the treatment of cancer. The composition of the present invention may include, for example, two or more saponins, two or more aglycones, one or more allosides and one or more saponins, Corresponding to one aspect of the present invention, the composition has an enhanced effect of inhibiting the growth of cancer cells when compared with the use of each component alone, and this enhanced effect of the composition may or may not be synergistic. The use effect of the composition of the present invention is increased by at least about 5% compared with the effect when each equivalent amount of the ingredient is used alone. In one aspect of the present invention, the use effect of the composition is separate from each equal amount of the ingredient. Compared with the effect when used, it is increased by at least about 5%. Another aspect of the present invention is that the use effect of the composition is increased by at least about 15¾. In another aspect of the present invention, the group [T] continuation page (Please note and use the continuation sheet when applying.) 200400828 Description of the invention The use effect of the continuation composition is at least about 20%. In other aspects of the present invention, the use effect of the composition is increased by at least about 23% and about 25%. , About 27%, and about 30%. The alloside and alloside used in the group are extracted from ginseng plants (plants 0f gemjs). Suitable saponins include protopanaxadiol and protopanaxatriol and oleanolic acid. The present invention In one aspect, the composition comprises one or more of aglyconprotopanaxadiol (aPPD) and aglyconprotopanaxatriol (aPPT)) ° from ginseng Many saponins extracted from it have been widely known and are suitable for use in the composition of the present invention. The saponins can be protopanaxadiol saponins, protopanaxatriol-type glucosides, or homogenous acid saponins. Examples of suitable saponins Including but not limited to: Rai, Ra2, Rbl, Rb2, Rb3, Rc, gluco-Rc, Rd, Re, Rf, 20-gluco-Rf, Rg1? Rg2, Rg3, Rhl5

Rh2, Rh4, notoginsenoside Rl5 koryoginsenoside R2, RSl, Rs2, Ql, and chikusetsusaponinV. Those skilled in the art will understand that the natural form of most ginseng island tests is 20S. 20R can be obtained when extracting and processing from plant raw materials. Type compounds, saponins used in the present invention include 20S and 20R structure saponins. In one aspect of the invention, the group contains a variety of protopanaxadiol saponins and / or mono-faceted ginsenotriol saponins, and in another aspect of the present invention, the group contains Rh2 saponin. In another aspect of the present invention, In one aspect, the complex contains Rg3 saponin. In the invention, in one aspect, the composition comprises a composition of saponin and / or aglycone selected from the group of Rh2, aPPT and aPPD. In another specific aspect of the present invention, the complex contains Composition containing saponin and / or saponin selected from Rh2 'Rg3' aPPT and aPPD _, the composition may also contain a small amount of one or more ~ 9] Continued page (Please note when the invention description page is insufficient And use continuation) 200400828 Description of the invention The content of each ingredient contained in the composition is different, approximately between 1% and 鄕, the test content is approximately between 1% and 50%, and the content of each saponin is approximately between 5% and 75%. In another aspect of the present invention, the content of the alloside in the parent species is approximately 5% to 40%, and the content of each alloside is approximately 10% to 70%. A typical composition of the present invention contains 1 to 90% R112, 1 to 90% aPPT, and 1 to 90% aPPD. In one aspect of the present invention, the composition contains 1 to 50%, 5 to 40%, and 5 to 75% aPPD, in another aspect of the present invention, the composition contains 5 ~ village, 10 ~ 35% aPPT and 10 ~ 70% aPPD, and in another aspect of the present invention, the composition contains 742% sen 2, 15 ~ 30% aPPT and 40 ~ 700 / 〇aPPD 〇 The saponin and saponin used in the composition of the present invention are produced separately or in mixture from the treated ginseng extract. Many saponins and / or saponins are also commercially available (ie, from Pe8asus Pharmaceuticals, Inc ”purchased from Richmond, British Columbia, Canada) or can be obtained by chemical or biosynthetic methods using techniques widely known to those skilled in the art (see, for example, Shibata ^ S. (2001) J. Korean Med. Sci ·, 16 Siq) pl ·: S28-37, and others). The composition of the present invention can be prepared directly from a partially purified plant extract, that is, by simply diluting it to an appropriate concentration, or Adjust the active ingredient ratio to the required content , You can add one or more island test and / or aglycone to the plant extract, or the composition can also be ~ 101 continuation page (if the invention description page is not enough, please note and use the continuation page) 200400828 _ Description of the invention The continuation sheet is prepared by mixing two or more separate saponins and / or saponin ligands according to the ratio of enhanced activity. The separate saponin and saponin ligands can be completely purified or partially purified. Raw materials In one aspect of the present invention, saponin and / or saponin are all extracted from plant raw materials, and in another aspect of the present invention, a portion of the saponin and / or alloside containing an enhanced active fraction is purified Plant extracts can be used to prepare compositions. Corresponding to the present invention, the plant raw materials suitable for extracting extracts are derived from ginseng plants, including but not limited to Panax aureus, Panax bipinnatifidus (also Called Panax major and Panax pseudoginseng var bipinnatifidus), Panax ginseng CA Meyer (also known as Panax schinseng), Panax japonicus (also known as Panax ps eudoginseng subsp. Japonicus' Panax pseudoginseng var. japonicus Panax repens), Panax notoginseng (also known as Aralia quinquefolia var. notoginseng and Panax pseudoginseng var. notoginseng), Panax pseudoginseng (also known as Aralia pseudoginseng Panusanax pseudoginseng) (Also known as Panax pseudoginseng var. Wangianus), Panax quinquefolius' Panax stipuleanatus' Panax trifolius' Panax vietnamensis Panax zingiberensis ° Plant materials that can be used in the present invention, including those taken from a single or group of plants § 5 or Many parts, including but not limited to leaves, roots, seeds, berries, stems and other parts. As known to those skilled in the art, the chemical composition and effects of plant extracts are due to the life of plants. The invention description page is not enough, please note and use the continuation page) 200400828 Invention description The continuation page phenological age, the humidity ratio of the viewing material, the part of the plant selected for extraction, and the method of extraction. Open technology Method may be applied to this surface by those of ordinary skill in the art controls extract and extract of mass. In one aspect of the present invention, the plant material extracted from ginseng is used to extract an extract containing saponin and / or saponin, and in another aspect of the present invention, the 'plant material is from North America # (iWc 分 L. ), In another aspect of the present invention, the plant raw material is extracted from Panax notoginseng. In addition to the biological climate of plants, the areas and areas where plants are harvested, the humidity ratio of harvested plants, the parts of the plants selected for extraction, and the method of extraction, the chemical composition of the extracts, etc. Pretreatment of plant materials is affected, for example, when plants are stressed, some biochemical processes are activated, in addition to the basic products already described, many new compounds are synthesized, in addition to harmful substances, mold, and other Pathogenic attack, stressors also include dryness, heat, 7Jc soaking and mechanical damage. Therefore, disturbing plants can be used as a tool to increase the content of one or more desired compounds. Those skilled in the art know how to apply The above-mentioned one kind of disturbance source or a plurality of different kinds of disturbance sources are used for this purpose. For example, the effects of mechanical damage can be increased by adding compounds that are naturally synthesized by plants when they are received, including jasmonic acid (JA). Analogs of oral secretions can also be used in this way to enhance plants Disturbance source (reaction). In one aspect of the present invention, the composition of the present invention is prepared from plant raw material extracts. □ I] Continued pages (when the description page of the invention is insufficient, please note and use the continuation page) 200400828 __ Invention description continued page into The aforementioned plant raw materials are pretreated, for example, chemical or mechanical damage, drying, heating, or cooling methods, or a combination of the above methods is used to disturb the plants before the plant raw materials are collected and extracted. Identification of plants and live thieves. Extracts can be obtained by processing plant raw materials through standard methods of known techniques. There are different ways to obtain extracts from plant raw materials. Which method is selected is based on the combination that can extract the invention. The work fg of the method of the required ingredients of the material, and examples of suitable methods for obtaining extracts include, but are not limited to: hydro-distillation, direct steam distillation, and solvent extraction ), And Microwave Assisted Process (MAP ™) ° Therefore, for example, boiled water can be used to process plant raw materials, the ingredients are released into the water, and these ingredients are obtained by distillation and cooling, as an alternative Plant raw materials can also be treated with steam, so that the components in the molecular film slowly disperse and are mixed with water vapor. The ingredients can be concentrated to obtain extracts, and organic solvents can also be used. Non-limiting examples of organic solvents used to extract live thieves, including methanol, ethanol ( etjjanoi), hexane, and methylene chloride. As an alternative to water or organic solvents, microwaves can be used to activate water and liver in plant palpation, causing cell rupture and release. Produces compounds that are present outside the plant's raw materials. The essential ingredients (ie, honesty and / or saponin) in the flour extracts can be continued on the next page (when the description page of the invention is not enough, please note and use the continued page) 200400828 For continued description of the invention Different analytical techniques in known technologies, for example, these include chromatographic separation of organic molecules, or the use of spectroscopic techniques (such as infra-red, ultraviolet) (ultra-violet) nuclear magnetic resonance spectroscopy). Determination of group cancer activity According to the preparation of candidate compositions, the anticancer activity of the composition can be compared and measured with the anticancer activity of a single ingredient. 'Many test methods well known to those skilled in the art can be used to test the miscellaneous components of the present invention. Anti-cancer activity of bio-groups and formula [sheng. 1) In vitro In order to determine the effect of the composition of the present invention initially, a test technique can be applied. For example, you can use ^ 111 'experiment (〇883 丫 £ 〇1 * 3- (4,5- (1111 ^ 11 丫 11: 111 commits 1-2- > 1) -2,5-diphenyltetrazolium bromide (MTT )) »Or aglycone, for cytotoxic activities of different cancer cell lines (ceU lines), the technology is mainly to seed cancer cells on a 96-well flat-bottom precision test plate (96-well plate) Incubate 24 / J in candidate composition, remove the intermediates from the test plate, and replace with MTT solvent. After analyzing the test plate, calculate the pass from each absorbance of the 5701 dish in each test plate containing cancer cells. The number of surviving cells of the composition after treatment is compared with the untreated control group or the control group treated with one component of the composition alone. The method and standard deviation of each component at various concentrations (standard deviation), you can use standard statistical methods for miscellaneous calculations. 14 | Continued (When the description page of the invention is not enough, please note and use the continued page) 200400828 _ Invention description_ page Another method is to use tumor Cancer cells grow independently ge-independent growth) to determine the inhibitory ability of the composition. Cell independent growth (anchorage-independent growth) is a well-known tumor genetic indicator (tumorigenicity) in this field-generally, by A suitable cancer cell line is colonized in soft agar, and after an appropriate incubation period, the number of cloned cells is determined to evaluate the independent growth of the cells. The growth rate of the cells treated with the candidate composition can be used with appropriate control Compare the growth rate of treated cells (that is, cells treated with saponin and / or saponin aglycone component alone) > and compare with the growth rate of non-faced cells ° Cytotoxicity of the composition The v / experiment can be measured using standard techniques, such as treating the main human fibroblasts with the composition in the W / ro experiment, and then using the standard survival test method to test the survival test, and then Test at different time points, the aforementioned standard survival test methods such as trypan-blue exclusion assay can also be tested by test Test the cell's ability to synthesize its DNA. For example, use thymidine incorporation assay to use standard cell sorting assay in combination with fluorocytometer cell sorter (FACS). 2) In vivo at Jn Vivo In experiments, the ability of the composition to inhibit the growth and reproduction of pupillary tumors can be determined through appropriate animal models using standard techniques known in the art (see, for example, Enna ^ i al, Current Protocols in Pharmacology, J. Wiley & Sons, Inc., New York, NY). I 15 I Continued page (Please note and use the continuation page when the invention description page is inadequate.) 200400828 _ Invention description _ In general, the animal model for screening antitumor compounds is now xenograft models. Through this type of model, a human tumor is transplanted on a tender, and examples of xenograft surfaces of human cancer include, but are not limited to: in a tumor growth test, human solid tumors are transplanted into mice by subcutaneous injection. In the tumor growth test, human solid tumors were transplanted into mice in the same line by fat injection. In the survival test, mice were tested for lymphoma and leukemia, and the test surface of mouse Wf # was tested. For example, the composition can be tested with mice in a solid tumor plus v / w test. At the beginning of the test, the mice were transplanted with two to sixty milligrams of swollen swollen fragments. The tumor-bearing animals were treated differently and Before the control, the mixture was mixed. In the test for the treatment of advanced tumors, after the tumors developed to the expected size, the mice whose tumors did not reach sufficient development were removed. The selected animals were then randomly allocated into treatment groups and control groups. The cytotoxic effect of tumor-specific effects, mice without tumors can also be treated the same as mice with tumors. Depending on the tumor », chemotherapy is started 3 to 22 days after tumor implantation. And observe it daily. The composition of the present invention can be administered to animals by, for example, gavage of nine medicines. Different animals' viscera are weighed 3 to 4 times a week until or the maximum amount of weight loss. Weigh at least once a week until the end of the test. The size of the swelling is measured 2 to 3 times a week until the swelling reaches the predetermined size and / or the predetermined weight, or until the animal dies, if this occurs before the swelling reaches the predetermined size and / or the predetermined weight. Dissection was performed for fibrous analysis to measure tumor size and / or growth. In order to investigate the effect of the composition on leukemia, animals were transplanted with a certain number of cancer cells. The 1 16 I continuation page (when the description page of the invention is insufficient, please note and use the continuation page) 200400828 The control group compared treated mice with increased survival time to determine their antitumor activity. In order to investigate the effect of the composition of the present invention on tumor metastasis, tumor cells were first treated with the composition, and then injected into appropriate experimental animals, and the tumor cells were observed from the injection site for an appropriate period of time. diffusion. Such as νζ · ν〇, the cytotoxic effect of the composition can be measured by measuring the effect of the composition on the animal's body weight during processing, by performing a hematological analysis, and performing liver enzyme enrichment in dissected animals > Heterocytotoxic effects ° Figure 1: Examples of regulatory cancers Tumor Growth Assay Human solid tumor xenografts in mice (sub-cutaneous injection) Prostate ( PC-3, DUl45) Breast cancer (MDA-MB-231, MVB-9) Colorectal cancer Colon (HT-29) Lung cancer Lung (NCI-H460, NCI-H209) Pancreatic cancer Pancreatic (ASPC-1, SU86.86 ) Pancreatic: drug resistant (BxPC-3) Skin Cancer (A2058, C8161) Cervical (SIHA, HeLa-S3) Cervical: drug resistant (HeLa S3-HU-resistance) Liver cancer (HepG2) Brain cancer Brain (U87-MG) Renal cancer Renal (Caki-1, A498) Ovarian cancer Ovary (SK-OV-3) Tumor Growth Assay Human solid tumor transplanted in mouse Human solid tumor isografts in mice (fat pad in jection) Breast: drug resistant (MDA-CDDP-S4, MDA-MB435-T0.1) Survival Assay Experimental model of lymphoma and leukaemia in mice Human: Burkitts lymphoma (Non -Hodgkin ^) (raji) Murine: erythroleukemia (CB7 Friend retro virus-induced) Experimental model of lung metastasis in mice Human: melanoma (C8161) Murine: fibrosarcoma (R3) 17 Continued page (when the invention description page is insufficient, Please note and use the continuation page) 200400828 _ Description of the Invention Continuing Group Therapeutic Application The composition of the present invention is suitable for treating patients with cancer. Cancer species that can be treated and stabilized with the set of the present invention include, but are not limited to, leukaemia, carcinomas, adenocarcinomas, melanoma and sarcomas, cancer Gland cancers, melanomas, and malignant sarcomas are also commonly referred to as "solid tumors." Cancers that frequently erupt with solid tumors include, but are not limited to, the following cancers: chest, miscellaneous, cervical, large intestine, head and neck, kidney, lung, Cancer of the ovary, face, prostate, stomach and uterus, non-small cell lung cancer, and colorectal cancer. "Leukemia" here refers generally to malignant diseases that make up the blood organs. The characteristics of leukemia are manifested in the abnormal reproduction and growth of white blood cells and their precursors in the blood and bone marrow, as well as other affecting red blood cells such as erythroleukaemia. Growth malignant blood cell disease, leukemia is usually classified clinically according to the following basics: ⑴ duration and characteristics of the disease --- ^ Note or proliferative; involved ^ / greasy species-cell myeloid (myelogenous), Lymphoid (lymphogenous) or monocytic cells; and (3) the growth or non-growth of the number of abnormal cells in the blood, such as leukemia including the following types: acute nonlymphocytic leukaemia, chronic lymphocytic leukaemia, acute granulocytic leukaemia, chronic granulocytic leukaemia, acute promyelocytic leukaemia, adult T-cell leukaemia, aleukaemic leukaemia, aleukocythemic leukaemia, basophylic leukaemia, blast cell leukaemia, bovine leukaemia, chronic myelocytic leukaemia, leukaemia cutis, embryonal leukaemia, eosinophilic leukaemia, Gross' le ukaemia, hairy-cell leukaemia, hemoblastic leukaemia, 1 18 I continuation page (if the invention description page is insufficient, please note and use the continuation page) 200400828-invention description continuation page hemocytoblastic leukaemia, histiocytic leukaemia, stem cell leukaemia, acute monocytic leukaemia, leukopenic leukaemia, lymphatic leukaemia, lymphoblastic leukaemia, lymphocytic leukaemia, lymphogenous leukaemia, lymphoid leukaemia, lymphosarcoma cell leukaemia, mast cell leukaemia, megakaryocytic leukaemia, micromyeloblastic leukaemia, monocytic leukaemia, myeloeloicic leukauka, leukaemia, Naegeli leukaemia, plasma cell leukaemia, plasmacytic leukaemia, promyelocytic leukaemia, Rieder cell leukaemia, Schilling's leukaemia, stem cell leukaemia, subleukaemic leukaemia, and undifferentiated cell leukaemia. "sarcoma, usually refers to origins such as muscle, bone, cartilage or fat A tumor that is a con-nective tissue and is connected by a tissue similar to an embryo Composed of, often consisting of tightly implanted fibrid or homogenous somatic cells) Or, sarcomas include the following fl types: Sarcomas include soft tissue sarcomas, chondrosarcoma, fibrosarcoma, lymphosarcoma, melanosarcoma, myxosarcoma, osteosarcoma, Abemethy ^ sarcoma, adipose sarcoma , liposarcoma, alveolar soft part sarcoma, ameloblastic sarcoma, botryoid sarcoma, chloroma sarcoma, chorio carcinoma, embryonal sarcoma, Wilms5 tumor sarcoma, endometrial sarcoma, stromal sarcoma, Ewing5s sarcoma, fascial sarcoma, comcommica, comic, sarcoma ^ sarcoma, idiopathic multiple pigmented haemorrhagic sarcoma, immunoblastic sarcoma of B cells, lymphoma, immunoblastic sarcoma of T-cells, Jensen's sarcoma, Kaposi's sarcoma, Kupffer cell sarcoma, angiosarcoma, leukosarcoma, comatic, align align me , serocystic sarcoma, synovial sarcoma, and telangiectaltic sarcoma. "Melanoma " refers to skin and Tumors of the melanin system of other organs, melanoma package I 19 | Continued page (When the description page of the invention is insufficient, please note and use the continuation page) 200400828 The description page of the invention description includes the following buildings: melanoma, benign juvenile melanoma, Cloudman's melanoma, S91 melanoma, Harding-Passey melanoma, juvenile melanoma, lentigo maligna melanoma, malignant melanoma, nodular melanoma, subungal melanoma, and superficial spreading melanoma. "Carcinoma" refers to the malignant growth of the skin, making the upper skin Cells attack tissue surfaces and cause metastases. Examples of cancers include the following cancer types: acinar carcinoma, acinous carcinoma, adenocystic carcinoma, adenoid cystic carcinoma, carcinoma adenomatosum, carcinoma of adrenal cortex, alveolar carcinoma, alveolar cell carcinoma, basal cell carcinoma, carcinoma basocellulare, basaloid carcinoma, basosquamous cell carcinoma, bronchioalveolar carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, cerebriform carcinoma, cholangiocellula r carcinoma, chorionic carcinoma, colorectal carcinoma, colloid carcinoma, comedo carcinoma, corpus carcinoma, cribriform carcinoma, carcinoma en cuirasse, carcinoma cutaneum, cylindrical carcinoma, cylindrical cell carcinoma, duct carcinoma, carcinoma durum, embryonal carcinoma, encephaloid carcinoma, epiermoid carcinoma, carcinoma epitheliale adenoides, exophytic carcinoma, carcinoma ex ulcere, carcinoma flbrosum, gelatiniform carcinoma, gelatinous carcinoma, giant cell carcinoma, carcinoma gigantocellulare, glandular carcinoma, granulosa cell carcinoma, hair-matrix carcinoma, haematoid carcinoma, hepato cellular carcinoma, Hurthle cell carcinoma, hyaline carcinoma, hypemephroid carcinoma, infantile embryonal carcinoma, carcinoma in situ, intraepidermal carcinoma, intraepithelial carcinoma, Krompecher's carcinoma, Kulchitzky-cell carcinoma, large-cell carcinoma, lenticular carcinoma, carcinoma lenticulare, lipomatous carcinoma, lymphoepithelial carcinoma, carcinoma medullare, medullar y carcinoma, melanotic carcinoma, carcinoma molle, mucinous carcinoma, carcinoma muciparum, carcinoma 1 20 1 Continued on the page (If the description page of the invention is not enough, please note and use the continuation page) 200400828 Continuation page on mucocellulare, mucoepidermoid carcinoma, carcinoma mucosum , mucous carcinoma, carcinoma myxomatodes, naspharyngeal carcinoma, oat cell carcinoma, non-small cell carcinoma, carcinoma ossificans, osteoid carcinoma, papillary carcinoma, periportal carcinoma, preinvasive carcinoma, prickle cell carcinoma, pultaceous carcinoma, renal cell carcinoma of kidney, reserve cell carcinoma, carcinoma sarcomatodes, Schneiderian carcinoma, scirrhous carcinoma, carcinoma scroti, signet-ring cell carcinoma, carcinoma simplex, small-cell carcinoma, solanoid carcinoma, spheroidal cell carcinoma, spindle cell carcinoma, carcinoma spongiosum, squamous carcinoma, squamous cell carcinoma, string carcinoma, carcinoma telangiectaticum, carcinoma telangiectodes, transitional cell carcinoma, carcinoma tuberos um, tuberous carcinoma, verrucous carcinoma, and carcinoma villosum. "Cancer" also includes adenocarcinomas. Adenocarcinomas originate from the production of cells with glandular (secretory) organs, or Cells originating from the hollow viscera of the line, such as the gastrointestinal tract or bronchial epithelia. Examples of cancer include, but are not limited to, breast cancer, lung cancer, and cancerous adenocarcinoma. The cancers used in the present invention also include: Hodgkin's disease, Non-Hodgkins lymphoma, multiple myeloma, and neuroblastoma ), Rhabdomyosarcoma, primary thrombocytosis, primary macroglobu Unei ^ a, small-cell lung tumors, original hair type Primary brain tumors, malignant pancreatic insulanoma, malignant carcinoid, bladder cancer, premalignant skin (continued on the pages of the invention) Please note and use the continuation page) 200400828 Description of the invention Continuing Mongolian Lesions), gliomas, testis cancer, esophagus cancer, genitourinary tract cancer, malignant blood Malignant hypercalcemia, endometrial cancer, adrenal cortical cancer, mesomas thelioma and medulloblastoma ° In one aspect of the present invention, cancers using the composition of the present invention for treatment and stabilization are selected from the group consisting of pancreatic cancer, lung cancer ), Stomach cancer, esophagus cancer, colon and rectum cancer, breast cancer, ovary cancer, liver cancer, kidney cancer cancer, laryx cancer, bone cancer, multiple myeloma, mehnoma, breast cancer, prostate cancer, bladder cancer , Cancer in body of uterus, oral cavity c caer, thyroid c rib cer, cervical cancer (cervix cancer), testis cancer, non-hejie Non-Hodgkins lymphoma, leukemia, Hodgkin's disease, skin cancer, and soft tissue cancer ° The composition of the present invention may also be used Applied to treatment and Given late, and / or metastasis of the cancer, including the above-described late stage of cancer, are often surface melting cancer resistance, and a bonding composition of the present invention may also be used in the treatment of relapsed or difficult to control the types of cancer. The cancer to which the present invention is applied also includes, for example, the origin and metastasis of different tissues and / or organs 1 22 1 Continued pages (when the description page of the invention is insufficient, please note and use the continuation page) 200400828 Invention Description_ stomach 'Multidrug-resistant cancer' includes, but is not limited to, onset of muscle, bone, or connective tissue, skin, brain, lung, sex organs, lymph or kidney system, breast or blood cells, liver, digestive tract, and thyroid or adrenal ducts Cancers, including solid tumors, ovarian cancer, breast cancer, brain cancer, prostate cancer, colon cancer, gastric cancer, kidney cancer, or cancer, Kaposi's sarcoma, bile duct tumor, chorionic tumor, neuroblastoma, Wilms tumor, Ho Jenkin's disease, melanoma, multiple myeloma, lymphocytic leukemia, and acute or chronic [granulocytic lymphoma. The development of cancer resistance is a major problem in cancer treatment. One of the traditional methods surrounding the problem of drug resistance is to use different active mechanisms and cytotoxic potential of multiple drugs to perform hybridization. A drug that overcomes multidrug resistance can be used alone as a chemotherapeutic drug or in combination with other drugs. The potential benefits of mixing one drug with chemotherapy can use less toxic compounds, save costs, or enhance Effect to reduce the number of treatments. By using the composition of the present invention in conjunction with one or more chemotherapeutics, the present invention is intended to be applied to patients with multidrug resistant cancer as part of mixed chemotherapy. Therefore, in the case of cancer, the present invention The composition can be used alone or in synergy with other pharmacologically active _ chemotherapy drugs. Medicinal adjuvants The composition of the present invention can be formulated with a suitable pharmacologically and pathologically acceptable carrier, ## agent (diluent), excipient or vehicle. Combined with the composition of the pharmaceutical formula for drug use, the pharmaceutical formula can also be l ~ 23l continuation page (when the invention description page is not enough, please note and use the continuation page) 200400828 invention description continuation page is a kind of chemotherapeutic drug composition for a certain object Take simultaneous medication. The pharmaceutical formulations of the present invention can be prepared by inhalation, spray, or through dosage unit formulations such as dosage unit formulations, using traditional pharmaceutically acceptable non-toxic carriers, adjuvants Oral medication (oraUy), topical medication, parenterally, and injection with the medium, including injections under the skin (subcutaneous injections), intravenous (intravenous), intramuscular (intramuscular), peritoneal ( intrastemal injection or infusion techniques. Pharmaceutical formulations may be in a form suitable for oral use, such as in tablets, troches, lozenges, aqueous or oily suspensions ), Can be divided into female powder or granules (dispersible powders or granules), emulsions (emulsion), hard or soft capsules (hard or soft capsules), or sugar paddles (syrups) or oral liquids (elixirs), pharmaceuticals intended to be used orally The formula can be prepared according to the methods known to the pharmaceutical industry, in order to prepare pharmacologically beautiful and palatable The preparation can be prepared from sweetening agents, flavouring agents, coloring agents, and preserving agents by selecting one or more auxiliary agents, and the tablet contains a live thief Mixing with suitable pharmaceutically acceptable non-toxic acceptable excipients, including, for example, such as calcium carbonate, sodium carbonate, lactose, f§ (calcium) phosphate) or inert diluents of sodium phosphate, such as com starch, or granulating and disintegrating agents of alginic acid, such as Source powder (starch), white gelatin or arabic [24 1 Continued (When the description page of the invention is insufficient, please note and use the color) 200400828 Invention of binding agents for gelatine or acacia , And lubricating agents such as magnesium ste_, stearic add (talc), tablets can be uncoated Or coating the tablet with known techniques to delay its digestion and absorption in the gastrointestinal tract to provide sustained action over a long period of time, for example, glycerol mono Glyceryl monostearate or glyceryl distearate is used as a slow-release substance. Pharmaceutical formulations intended for oral use can also be in the form of hard white gelatin capsules in which the active ingredient is mixed with an inert solid diluent such as calcium carbonate, calcium phosphate or kaolin, and is intended for oral use. The pharmaceutical formulation of the pharmaceutical composition can also be a soft white gelatin capsule Kaido, its active ingredients and 7] < or an oil medium such as peanut oil, liquid paraffin or olive oil is mixed. Aqueous suspensions contain the active compound and are mixed with suitable excipients. Such excipients include: sodium sodium methylcellulose (80 € 1111111 (: 311 dishes 711 ^ 1 611 611 € from ), Methyl cellulose, hydropropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth, and gum arabic suspending agents such as gum acacia, dispersing or wetting agents such as naturally-occurring phosphatide, such as lecithin, or polyoxyethyene stearate ) Condensed products of alkyleneoxide and fatty acids, or ethylene oxide such as hepta-decaethyleneoxycetanol and "^ 51 Continued" Note and use continuation page) 200400828 __ Description of the invention Continuation page Concentrated products of long-chain aliphatic alcohols, or polyoxyethylene sorbitol monooleate (p olyoxyethylene sorbitol monooleate is a concentrated product of ethylene oxide and monoesters extracted from fatty acids and hexitol, or polyoxyethylene sorbitan monooleate ) Concentrated product of ethylene oxide and partial esters extracted from fatty acids and hexitol anhydrides, 7j < Aqueous suspensions may contain one or more preservatives, such as ethyl or n-propyl j > hydroxy-benzoate, a One or more coloring agents, one or more flavouring agents are one or more sweetening agents such as sucrose or saccharin. Oily suspensions may By suspending in vegetable oil such as arachis oil, olive oil, sesame oil, coconut oil or mineral oil such as liquid paraffin The active ingredient is prepared. The oily suspension may contain thickening agents such as beeswax, hard paraffin or cetyl alcohol, and the aforementioned sweetening agents. And / or 111¾ the addition of J (flavouring agents), can be mouth-to-mouth and palatable, the pharmaceutical composition can be added by anti-oxidant such as ascorbic acid (anti-oxidant) Preservative preservation. The active powders and 酔 ules are suitable for preparing aqueous suspensions, and the active compounds are added to dispersants or wetting agents (dispersing \ ~ 26) by adding water. Continued page (inventory description page is insufficient, please note and use the continuation page) 200400828 Invention description continued page or wetting agent), a suspension agent and one or more preservatives are prepared by mixing, suitable dispersant or wetting agent It refers to the examples of the additives mentioned above, and additional agents such as sweeteners, flavoring agents, and pigment doughs can also be added. The pharmaceutical formula of the present invention can also be in the form of an oil-water emulsion, and the oil part can be, for example, peanut oil (arachis oil), olive oil, vegetable oil or mineral oil such as liquid paraffin, or a mixture of some oils, suitable milk {德 物 (emuisifying agents) ) Can be natural resins (naturaUy-occmring gums) such as gum tragacanth and gum acacia, and can be naturally-occurring natural phospholipids such as soy beans and lecithin phosphatides) Esters or partial esters extracted from fatty acids and hexitol anhydrides, such as sorbitan monooleate, and the above partial partial esters esters) and ethylene oxide concentrated products such as polyoxyethylene sorbitan monooleate. Emulsions can also contain 1 »agents and flavors. 〇 〇 syrups and oral liquid (syrups and elixirs) can be prepared from sweeteners such as glycerol, propylene glycol, sorbitol or sucrose, and the composition can contain demulcent, preservatives Preservatives and / or flavoring agents and pigments 0 Pharmaceutical formulations can be prepared in the form of sterile injectable aqueous or oily suspensions, which can be prepared according to known techniques by using the appropriate dispersants or Wetting agents and suspensions are prepared. Sterile injectable preparations can be sterile injectable solutions or diluted in injectable without ~ 27 ~ 1 Continued pages (if the invention description page is insufficient, please note and make (Continued) 200400828 Description of the invention Continuation page Toxic dilutions or suspensions in solvents, such as 1,3-butanediol solution, acceptable media and solvents that can be used, including but not limited to column F: water, Compound sodium chloride injection (Ringer's solution), lactated Ringer's solution and isotonic sodium chloride solution (isotonic sodium chloride solution) Other examples are traditional-ί two used as dissolution suspension Sterile, non-volatile oils in liquid media, and various irritating, non-volatile oils such as synthetic mono-glycerides or diglycerides, and fatty acids such as oleic acid The fatty acids pool can be used in the preparation of injectable groups. Other methods of preparing pharmaceutical formulations and compositions are known and described in the prior art in this field, for example, published by Williams & Wilkins, Philidelphia, PA (2000), by Gennaro, A " Lippincott's "Remi Post on: The Science and Practice of Pharmacy" source is called post oiKPiiannaceuifcaiSdeiK ^ s ") described ^ Non-pharmaceutical formula Non-pharmaceutical formula refers to government agencies that do not need to go through the management of drugs and biological products, Formulas that can enter the market are pre-approved by the U.S. Food and Drug Administration (FDA). Those skilled in the art will know that a formula can exist as either a pharmaceutical or non-pharmaceutical formula, such as a plant formula It can be regarded as both a pharmaceutical formula and a non-pharmaceutical formula, and a non-medicinal βϋ prescription, which can be formulated according to the same method and form of the aforementioned pharmaceutical formula and a pharmaceutically acceptable medium or carrier. Non-pharmaceutical formulas can be in the following forms, such as natural pharmaceutical composition (nutraceutical QCI continuation page (when the invention description page is insufficient, please note and use the continuation page) 200400828 invention description continuation composition, food, food ( health food), natural health product (MMS), functional food, nutritional supplement, food supplement [J (diet 町 supplement), herbal supplement flow [Kherbal s chatlement ), Herbs, alternative medidne, and naturopathic products. The non-pharmaceutical formula disclosed herein may be a tablet, a capsule, or an ointment. Mode of administration and dosage regimen According to the present invention, a therapeutically effective dose containing the composition or formulation of the present invention is administered to a subject to treat cancer, and the composition or formulation can be administered according to a conventional chemical treatment. The dosage of the composition of the present invention is based on the type of cancer being treated, the condition of the cancer patient, and the size of the subject to be treated. Those skilled in the art can easily make decisions on this. However, when treating different types of cancer, it can be done in accordance with this field. Known technology determines the dosage of medication and the frequency of medication according to the actual situation. For example, the therapeutically effective dose of each ingredient in the composition may be between 0.01 mg and 1000 mg per kilogram of body weight per day. In one aspect of the present invention, the composition contains a therapeutically effective dose of Rh2 per kilogram. Body weight is between 0.01 mg and 1000 mg per day. In another aspect of the present invention, the composition contains a therapeutically effective dose of desugared ginsengtriol, between 0.01 mg and 1000 mg per kg of body weight per day. In one aspect, the composition contains a therapeutically effective dose of desugared ginsengdiol, between 0.01 mg and 1000 mg per day of body weight. Γ29] Continued pages (Notes and use of continuation pages when the invention description page is insufficient) 200400828-Description of the continuation page Pharmaceutical components The present invention can also provide therapeutic components containing the composition of the present invention in the form of pharmaceutical formulations (therapeutic kite), used for cancer treatment, individual components of the package will be packaged in separate containers, along with these containers, there are instructions in a format prescribed by government agencies that regulate the production, use or sale of drugs and biological products, which reflects the government Agency approval for the production, use, or sale of human drugs. When the component of the drug assembly is one or more liquid solutions, the liquid solution may be aqueous mm5 $ DiE®7jci # ^ (sterile aqueous solution)-«Mf MT ^» ^ (container means), and may be an inhalant , Syringe (syringe), pipette, eye dropper (apparatus), or other similar devices (apparatus), the composition can be administered to the subject via these devices Or lyophilized form, and the medicinal component may additionally contain a suitable solvent to reduce the lyophilized part, the medicinal component of the present invention may also include a device for assisting medication to the subject of the medication, regardless of the type and quantity of the container, The device can be an inhalant, a syringe, a pipette, forceps, a measured spoon, an eye dropper, or any other approved medication ( delivery vehicle) ° Further, when the drug component administers the drug to the subject, it may further include one or more other chemotherapeutic drugs for use in combination with the composition of the present inventionIn order to facilitate a better understanding of this invention, the following examples are listed, these listed examples should be understood for the purpose of explanation only, so these examples should not limit this Pages (Notes on Insufficient Use of Inventive Pages, please note and use continuation pages) 200400828 ___ Description of Inventive Continued Items The scope of the invention. L ~ —- [Embodiment] The embodiment contains Rh2 'deglycogenated ginseng third instar (PPT) and deglycogenated ginseng glycol (aPPD), and compared with the anti-cancer effect of each JP component, The composition is prepared according to the ratio of various ingredients of the following agents: Group Miscellaneous Composition Composition Nao (3) Rh2 7.3% 14.3% 41.2% aPPT 26.3% 16.5% 17.6% aPPD 66.4% 69.2% 41.2% Total 100% 100% 100 % Cytotoxicity measurement using standard microculture tetrazolium assay (MTT) (Alley, MC et al, Cancer Research 48: 589-601, 1988), exponentially growing tumor cells (including multiple Culture of drug-resistant cell lines) for microtiter plate cultures. Cells were cultured in 96-well plates at 1.2x103 cells per well and cultured overnight at 37 ° C iSS. Then, the test compound is added, and the cells are treated for 24 hours, and the MTT test MTT dye (3- (4,5-dimethylthiazol-2-yl) -2,5-Diphenyltetrabromide diphenyltetra zolium bromide in saline), to determine the number of cell survival per well. Example 1: Contains Rh2, deglycogenated ginsenotriol (aPPT) and deglycogenated ginseng triol (aPPD) Zhao Zao Chuan Noodles U87 Zengqiang County I 31 | Continued page (Insufficient invention pages, please use Note and use continuation page) 200400828 Invention_i_Stomach-Exclusive use of different doses of Rh2, deglycogenated ginstriol (aPPT) and deglycogenated ginseng glycol (aPPD) to treat human glioma cells (U87) 'Similarly, human glioma cells (U87) were treated with different doses of a composition containing Rh2, deglycogenated ginsenotriol (aPPT), and deglycogenated ginsengdiol (aPPD) saponin and saponin, in The composition used in this example} has the following chemical components: 7,3% Rh2, 26.3% aPPT, and 66.4% aPPD. After 24 hours of treatment according to the MTT standard method, the cell survival number is determined. Figure 1 shows the enhanced effect of Composition 1 on the treatment of human glioma (U87). As shown in the legend, Composition 1 at 15 pg / mL kills nearly 100% (99%) of cancer cells, while similar doses The single component Rh2, deglycogenated ginsenotriol (aPPT), and deglycogenated ginseng triol (aPPD) can only kill 64%, 29%, and 52% of cancer cells, respectively. The results of this example show that: The composition is more effective and effective compared to the same dosage of each individual ingredient used alone. Example 2: Enhancement of aura melanoma B16 cells containing Rh2, deglycogenated ginsenotriol (aPPT) and deglycogenated ginseng diol (aPPD), using different doses of Rh2, deglycogenated ginseng III alone (APPT) and deglycogenated ginseng diol (aPPD) murine melanoma B16 cells, the same, using different doses containing Rh2, deprotonated ginseng triol (aPPT) and deglycogenated ginseng diol (aPPD) A combination of saponin and saponin glycosyl to treat murine melanoma B16 cells. Composition 2 used in this example has the following chemical components: 14.3% Rh2, 16.5% aPPT, and 69.2% aPPD, according to MTT Cell viability was determined after 24 hours of standard practice. Figure 2 shows the potentiating effect of Composition 2 on the treatment of murine melanoma B16 cells. As shown in the example, Composition 2 at 10 pg / mL killed nearly 81% of cancer cells, and at the same time a similar dose

Jl] Continued pages (If the description page of the invention is insufficient, please note and use the continuation page.) Individual components of the continued page Rh2, faceless ginseng triol (Er), and deglycogenated ginseng glycol (& ρρ 聊It can only kill 56% '47% and 44% of germ cells'. The results show that the same amount of nut tender as the single chick with each single ingredient, the decoration is more effective and potent. 3 · Contains coffee 2. Decogen ginsenotriol (31 >? talk about deglycogen ginseng diol (a ™) group * treatment of cancer cell MCF7 to enhance the use alone can not be used 丨 I star of Rh2, deglycogen ginsenotriol ⑽ 叩 and Deglycogenated ginseng glycol (aPPD) human breast cancer cell MCF7 'Similarly, different doses of glycosides, deglycogenated ginsenotriol (aPPT), and deglycogenated ginseng glycol (aPPD) saponin and saponin were used. Composition to treat human breast cancer cell MCF7. Composition 3 used in this example has the following chemical components: 41.2% Rh2, 17.6% aPPT, and 41.2% aPPD, determined after 24 hours of treatment in accordance with the MTT standard method Cell survival number. Figure 3 shows the effect of Composition 3 on the treatment of shoulder lion cancer cell MCF7, such as For example, the combination of 15 'pg / mL ^ 3 tested about 92% of cancerous lions, and at the same time, a single dose of Rh2, a deglycogenated ginseng triol (aPPT and deglycogenated ginseng diol (Qingdao) It can only kill 68%, 68%, and 69% of cancer cells separately. The results of this example show that the composition is more effective than using the same dose of each individual component individually. Example 4: Contains Rh2, glycogen ginsenotriol (aPPT), glycogen ginseng diol (apPD), Zhao Heti treatment of multi-faceted drugs / cancer cells ^ with Rh2, glycogen-free ginseng triol (_ and glycogen) A combination of panaxadiol (aPPD) alloside and saponin to treat resistant pancreatic cancer cells (BXCP-3) and (CAPAN-1). The group 1 used in this example has the following chemistry Ingredients: 7.3% Rh2, 26.3% Γ ~ 33 ~ | continuation page (when the description page of the invention is insufficient, please note and use the continuation page) 200400828 invention description aPPT and 66.4% aPPD, according to the MTT standard Cell viability was determined after 24 hours of treatment. Figure 4a shows different doses of composition 1 resistant to treatment of pancreatic cancer (BXCP-3), Figure 4b shows the effect of different doses of Composition 1 on the treatment of resistant pancreatic cancer face cells (CAPAN-1). The noodle cells have a killing effect. Example 5: Inhibition of anti-cancer county composition 4 of different cancer cells by a composition containing Rh2, deglycogenated ginstriol (aPPT) and deglycogenated ginseng diol (aPPD) The effect of cancer cells in different aspects is shown in the following chart: The minimum dose of MCF7 / adr for breast cancer cell line is 100% to kill the cancer cell line. MCF7 / adr breast cancer 40ug / ml resistant MDA435LCC6M cancer 40 ug / ml resistant MCF-7 / c3 cancer 40ug / ml Caspase-3 1¾¾ 9L breast tumor 25 ug / ml SF188 breast tumor 20ug / ml LNCaP prostate cancer 25 ug / ml PC3 prostate cancer 40 ug / ml HCT15 gastrointestinal system tumor 40 ug / ml Keto gastrointestinal system may 35 ug / ml H460 Lung cancer 40 ug / ml Example 6: Inhibition effect of composition 4 on different cancer cells in In Vivo Content of various ingredients of composition 4: RJulZ 8% Rg3 2% saponin 70% unknown ginseng 20% I 34 I Continued pages (Please note and use continuation pages when the invention description page is insufficient) 200400 828 __ Description of the invention The anticancer activity of the continuation group 4 was also confirmed in the Vivo test. Brain tumor cells were seeded in the rat brain. Oral feeding was performed when the tumor had formed on the 10th day after seeding. Three doses of Composition 4, as shown in Figure 5, after two 5-day treatments of Composition 4, there was a significant difference in survival between the treatment group and the control PBS (biological water) animals, especially the 25 mg Of the animals treated with / kg and 50 mg / kg, 40% of the rats survived more than 42 days, compared with an average of 18 days for the animals in the control group. Autopsy showed that tumors in more than 50% of the surviving animals completely resolved. . Example 7: Facials of group 4_ Standard 4 acute and chronic toxicity experiments were performed on composition 4. In the acute toxicity test, rats were orally administered with composition 4 at a dose of 4,000 mg / kg at one time, and the animals were administered within 30 minutes after taking the drug. Eyes closed, quiet, decreased activity, and lethargy. These symptoms disappeared within four hours, and the animals' activities, eating, and water intake also returned to normal. No animal died within seven days after administration. The autopsy results showed heart , Liver, spleen, lung, kidney, stomach, and intestine were normal. In the chronic toxicity experiment, the animals were divided into three groups of high, medium, and low doses, which were orally administered with 333.3 mg / kg, 131.0 mg / kg, and 51.5 mg / kg combination. Drug 4, which was administered for eight weeks, was observed for two weeks after the end of the administration, and the results were as follows: in the high-dose group, there was a transient prostatic enlargement within 24 / J. (The degree of silence was 187%). Ovarian swelling (124% swelling degree), also in the Zhongqizhuang group, a transient anterior swelling swelling (156% swelling) was observed, but after two weeks of continuous administration, the swelling disappeared. In addition, Some mild toxic reactions were also observed only in the high-dose group, including the third to third doses. Weekly drowsiness and slight weight loss at the end of administration (4-9 weeks) (no statistical significance, P > 0.05), blood routine and organ histological examinations were not issued in the high, medium and low groups abnormal. I 35 | Continued pages (Notes and use of continuation pages when the Instruction Sheet is not enough) 200400828 Inventory The results of the acute toxicological test of Composition 4 on Continuation Sheet are as follows: l. Big ear rabbits) injected composition 4 through the ear vein once a day for 7 consecutive days, each injection amount was 5 ralTkg (Img / mi), there was no visible change at the injection site, and microscopic examination of the sacral section did not reveal that the injection site was quiet Infiltration of blood, water pirate inflammation, and other phenomena. Conclusion: Composition 4 does not cause irritation to blood vessels. II. Endotoxin test The Limulus Amebocyte (LAL) interference test method is used to determine the endotoxin level of composition 4. The minimum endotoxin level that can be measured by the LAL test is 0.125 EU / ml-0.25 EU / ml in the composition. In the case of 4 gadolinium numbers of 1 mg / ml, 0.5 mg / ml, 0.25 mg / ml and 0.125 mg / ml, no endotoxin interference was observed. Conclusion: The endotoxin level of 1 mg of composition 4 is less than 1 EU. m. Hemolysis experiment: The whole blood of rabbits was mixed with the composition 4 of different dilutions, and the absorbance of the upper mash was measured at a wavelength of 545 nM with a spectrophotometer to determine the hemolysis. Miscellaneous 4 (group Miscellaneous 4: raw water = 1: 3), less than 1% (normal 値 < 5%) of hemolytic response caused by winter concentration (lmg / ml), undiluted composition 4 (4mg / ml) had mild hemolysis (51%). CONCLUSION: In the case of using the normal saline 1: 3 for composition 4, there is no hemolytic reaction. Πόΐcontinuation page (if the description page of the invention is insufficient, please note and use the continuation page) 200400828 _ description of the page continued IV. The allergy test is performed by a knee mouse, 0.5 ml of the composition 4 is injected intraperitoneally, once every other day, A total of (3 injections) 'In addition, the same knee rat was injected intravenously with 1 ml of composition 4 on the 14th and 21st days, and the typical allergies were observed within 15 minutes after each injection, including: cough, skin Response, respiratory response, and more. Conclusion: Composition 4 does not cause allergic reactions. V. Half of group 4 (LD50) Five groups of mice were intravenously injected with 5 different doses of composition 4 (concentrations from 85.5mg / kg to 160.0mg / kg). Animals were observed for 7 days after injection, and the half was tested by the Bliss method The lethal dose (LD50), at the concentrations of 136 mg / kg and 160 mg / kg, animals have severe toxic reactions and death. Decreasing the concentration significantly reduced the toxic reactions. The blank solvent experiment found that the solvent itself had the same lethal concentration. It was proved that the group 4 toxicity was completely caused by the solvent injection. Conclusion: The JLD50 of Composition 4 is 121.9 mg / kg, with a 95% confidence level between 105.0 and 141.6 mg / kg. Example 8: Informal Linlaicha A non-IE phase I clinical trial was completed at the Liaoning Provincial Institute of Traditional Chinese Medicine. Forty patients with different types of malignant parenchymal tumors were treated with the informal composition 4 In the first phase of clinical observation, all patients either failed first-line antitumor treatment or refused conventional treatment. The cancer patients who participated in clinical observation had the following cancer views: lung cancer (10 cases), liver cancer (6 cases), _ cancer ( 5 cases), 1 37 I Continued pages (When the description page of the invention is insufficient, please note and use the display) 200400828 __ Description of the invention continued page intestinal cancer (4 cases), uterine cancer (3 働, _ cancer (2 働) , Nasopharyngeal cancer (1 case), esophageal cancer (1 case), bile duct cancer (α case), gastric cancer (1 case), testicular cancer (1%, kidney cancer (1%), bladder cancer (1%, urethral cancer (1%) 1. Oral cancer (1 case), and cirrhosis (1 case, the average age of 40 patients was 56.1 to 11.5 years old, treated with a composition of 200 mg / day 4 oral dosage form, the average course of treatment was 53.7 to 25.4 days. Group_ 4 The main observation indicators of toxicity are nausea, vomiting, gastritis, hair loss, neurological symptoms, and skin abnormalities. Patients issued more than 0 dogs, so their clinical toxicity was grade zero. Although the purpose of this clinical trial was mainly to observe toxicity rather than efficacy, the initial observations on fiber were encouraging. According to reports, 75% of patients After treatment with Chelate 4, the clinical symptoms showed improvement to varying degrees, and some patients had significantly reduced tumors. Case Case 1: Female, 58 years old, lower bile duct cancer (3.0 X 2.6 cm) Symptoms: Sharp weight Reduction, nausea, occupation, fatigue, upper abdominal pain, jaundice, etc. Treatment: 114 days, 200 mg per day improvement: tumor size reduced to 1.8 X 1.4 cm, all the above symptoms disappeared, and I felt good. Case 2: Female, 74 years old , Esophageal cancer (umbrella), 6.0cm long (X-ray image) Symptoms: difficulty swallowing, pain, diarrhea, frequent snoring Treatment: 110 days, 200 mg per day Improvement: tumor size shrinks to 1.5 cm, no difficulty swallowing, The number of snorings has been greatly reduced, no more pain, and I feel good about myself. [~ 38l continuation page (when the invention description page is insufficient, please note and use the continuation page) 200400828 Case 3: Male, 66 years old, pancreatic cancer 45x4.5x3. 7 cm Symptoms: Fatigue, dizziness, pain in the upper abdomen and liver, GPT, GOT, and hyperglycemia. Treatment: 200 mg per day for 90 days. Improvement: Very little pain. GPT, GOT, and glycemic index are normal. Although disclosed here. Various aspects of the present invention can be changed and modified within the scope of the present invention based on the common knowledge of those skilled in the art. Such modifications should not be regarded as beyond the scope of the present invention, and The obvious modifications are included in the scope of the following patent applications. I 39 I Continued pages (Note when the invention description page is inadequate, please note and use the continuation page) 200400828 _ Invention description ^ page [Simplified illustration of the figure] Figure 1 provides the use of different saponins and saponin ligands and one of the invention Graphical representation of cell survival rate after treatment of human glioma tumor cells U87 by the composition; Figure 2 provides treatment of murine melanoma cancer cells with different saponins and saponin ligands and a composition of the present invention (Mouse melanoma cells) A graphical representation of cell survival rates after B16; Figure 3 provides cell survival rates after treating human breast cancer cells MCF7 with different saponins and saponin ligands and a composition of the present invention Figure 4a provides a graphical representation of the cell survival rate of pancreatic cancer cells BXCP-3 treated with different doses of the composition of the present invention; Figure 4b provides the difference of using the composition of the present invention Graphical representation of cell survival after pancreatic cancer cells CAPAN-1 was dosed; Figure 5 shows Inhibition of cancer treatment doses. 40

Claims (1)

200400828 Scope of patent application 1. A composition comprising two or more allosides, two or more saponin ligands, or one or more saponin and one or more active ingredients in combination to enhance the active dose, the composition has Anticancer live injection. 2. As described in item 1 of the scope of the patent application, the alloside and saponin ligands in the composition are selected from the group consisting of: 2, aglycon Protopanaxatriol, and aglycon ginsenodiol (agiyCon Protopanaxadiol's group. 〇3. According to the scope of patent application No. 2, the composition contains Rh2, deglycogen ginsenotriol (agiycon Protopanaxatriol), and deglycogen ginseng glycol (aglycon protopanaxadiol) between 1 ~ 90% between. 4. As described in item 3 of the scope of patent application, the composition contains 1 to 50% Rh2, 5 to 40% aglycon protopanaxatriol, and 5 to 75% aglycon protopanaxatriol. protopanaxadiol) ° 5. According to item 4 of the scope of patent application, the composition contains 5 to 40% Rh2, 10 to 35% aglycon protopanaxatriol, and 10 to 70% deglycon ginseng II Aglycon protopanaxadiol. 6. As described in item 3 of the scope of patent application, the composition contains 7 to 42% Rh2, 15 to 30% aglycon protopanaxatriol, and 40 to 70% aglycon protopanaxadiol ) ° 7. As described in item 1 of the scope of patent application, which refers to one or more island glycosides and saponin aglycones are continued from the plant to π (When the scope of the patent application page is insufficient, please note and use the continuation page) 200400828 Patent applications are continually extracted from raw materials. 8 According to item 7 of the scope of patent application, the plant raw material referred to by 舯 is derived from one or more species. 9. As in the scope of patent application No. 8, the plant referred to is Asian ginseng (pa service hall ^). 10. If the scope of the patent application is No. 8, the plant referred to is North American ginseng (pa 駆 11 · If the application is _8, the plant is Sanqi. 12. If the application is __ 1, the towel Job—The thief face is gambling. It is synthetic. 13.—A pharmaceutical formula for treating cancer, which includes a therapeutic dose of the composition in the scope of application for patent application and a pharmaceutically acceptable carrier. K. A non-pharmaceutical for treating cancer The formula includes the group of _ therapeutically effective doses and pharmaceutically acceptable carriers as described in item i of the scope of patent application. 15. If the scope of patent applications is 13 and 14, the formula is orally prescribed. 16. If applied Items 13 and 14 of the scope of patents, the formula of which is injectable form. 17. If the scope of applications for the patents 13, 14 of which the formula is a form for external use (_ 物 form) ° 18. If the scope of patent applications 13, 14 items, of which the therapeutically effective dose of the leg is between 0.01 mg and 1000 mg per kilogram of body weight per day. _! _] Continued pages (please note and use the continuation pages when the patent application page is not enough, please use the continuation page) 200400828 Patent application range Continued 19 For example, the scope of application for patents Nos. 13 and 14, in which the therapeutically effective dose of aglycon protopanaxatriol is between 0.01 mg and 1000 mg per day. 20. If applied The scope of the patent is No. 13, 14 in which the therapeutically effective dose of aglycon protopanaxadiol is between 0.01 mg and 1,000 mg per day for the body weight of the sensitive cat. 21. If applying for a patent The composition referred to in scope item 1 is used to treat cancer patients. 22. According to the scope of application for patent scope item 21, the cancer referred to is selected from the group consisting of the following cancers: glioma tumor, melanin Melanoma, breast cancer, pancreatic cancer, brain tumor, gastrointestinal system cancer (intestinal and gastric cancers), prostate cancer (prostate cancer), and lung cancer ° 23. According to the scope of patent application No. 21, the cancer referred to is selected from the group consisting of stomach cancer, esophagus cancer, colon and rectal cancer tum cancer, ovary cancer, liver cancer, kidney cancer, laryx cancer, bone cancer, multiple myeloma, and wrist cancer ( bladder cancer, cancer in body of uterus, oral cavity cancer, thyroid cancer, cervix cancer, testis cancer, non-Hodgkin Non-Hodgkins lymphoma, leukemia, Hodgkin (s disease), skin H (skin H) continuation pages (if the patent application page is insufficient, please note and use (Continued) 200400828 patent) and soft tissue cancer. 24. As claimed in item 21 of the aR patent scope, the cancer referred to therein is a multi-drug resistant cancer. 25. According to item 24 of the scope of patent application, the multi-drug resistant cancer referred to is selected from the group of primary cancers containing the following cancers: onset of muscle, bone pathways or connected tissues, skin, brain, lungs, sex organs, Cancer of the lymphatic or renal system, breast or blood cells, liver, digestive tract, pancreas and thyroid or adrenal ducts, including solid tumors, ovarian cancer, breast cancer, brain cancer, anterior cancer, colon cancer, stomach cancer, kidney cancer Or K9 cancer 'Kap〇S1 sarcoma, cholangiomas, chorionic tumor, neuroblastoma, Wilms tumor, Hodgkin's disease, melanoma, multiple myeloma, lymphocytic leukemia, and acute or slow granulation Lymphoma. 26. According to item 24 of the scope of patent application, the multi-drug resistant cancer referred to is selected from the group of recurrent cancers containing the following cancers: pancreatic cancer, lung cancer, stomach cancer , Esophagus cancer, colon and rectum cancer, brain cancer, ovary cancer, liver cancer, kidney cancer, larynx cancer, bone cancer, multiple myeloma, melanoma, breast cancer, prostate cancer, bladder cancer, cancer in uterus body of uterus, oral cavity cancer, thyroid cancer, cervix cancer, testis cancer, Non-Hodgkins lymphoma, Leukemia, Hodgkin's disease, skin cancer (skin R1 continuation page (if the patent application page is insufficient, please note and use the continuation page) 200400828 patent application continuation cancer), and soft Woven cancer (soft tissue cancer). 27. The application according to any one of claims 21 to 26, wherein the composition referred to is used in combination with one or more chemotherapeutic drugs. 28. The application of the first composition in the scope of patent application for the manufacture of cancer treatment drugs. 29. A pharmaceutical component for treating cancer, the component comprising a composition as defined in item 1 of the scope of patent application and one or more containers. 5