KR20090130538A - Pharmaceutical compositions for prevention and treatment of cancer containing astilbe chinensis extracts, fractions, the isolated triterpene compound therefrom or the pharmaceutically acceptable salts as an active ingredient - Google Patents

Abstract

PURPOSE: A pharmaceutical composition containing triterpene compound isolated from Astilbe chinensis for preventing and treating cancer is provided to reduce adhesion ability of cancer cells and proliferation of the cancer cells. CONSTITUTION: A pharmaceutical composition for preventing and treating cancer contains Astilbe chinensis extract as an active ingredient. The Astilbe chinensis extract is obtained using water, alcohol of C1-C4 or their mixture solution. The pharmaceutical composition for preventing and treating cancer contains Astilbe chinensis fraction as an active ingredient. The Astilbe chinensis fraction is obtained by suspensing the Astilbe chinensis extract in the water, fractioning with hexane or through column chromatography using mixture solvent of hexane, chloroform, and methanol as elution solution. The pharmaceutical composition for preventing and treating cancer contains triterpene compound and its pharmaceutically acceptable salt.

Description

Pharmaceutical compositions for prevention and treatment of cancer containing Astilbe chinensis extracts, fractions from roe deer urine extracts, fractions, triterpene compounds isolated therefrom or pharmaceutically acceptable salts thereof as active ingredients , the isolated Triterpene compound therefrom or the 黄 acceptable salts as an active ingredient}

The present invention relates to a pharmaceutical composition for preventing and treating cancer containing roe deer urinary extract, fraction, triterpene compound isolated therefrom or a pharmaceutically acceptable salt thereof as an active ingredient.

The interaction of Integrin with the extracellular matrix (ECM) allows the cell to attach to the right place and the binding between the two eventually regulates the activity and localization of various signaling molecules in the cell. It can be controlled even function or behavior of the cell (Thiery, JP Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer , 2 , pp. 442-54, 2002; Brakebusch, C. and Fassler, R., The integrin-actin connection, an eternal love affair., EMBO J , 22 , pp.2324-33, 2003). When the extracellular site of Integrin interacts with the ECM in focal adhesion, various cell adsorption molecules are collected at the intracellular tail of the integrin, including the intermediate. Paxillin and p130Cas, which act as proteins, are local signaling kinase (FAK), c-Src, etc. (DeMali, KA et al., K. Integrin signaling to the actin cytoskeleton, Curr). Opin Cell Biol . , 15 , pp. 572-82, 2003; Carragher, NO and Frame, MC, Focal adhesion and actin dynamics: a place where kinases and proteases meet to promote invasion, Trends Cell Biol , 14 , pp. 241-9, 2004). The gathering of various intracellular signal transduction molecules in Integrin eventually leads to their activation, resulting in rearrangement of the actin cytoskeleton, leading to morphological changes required by the cells (Juliano, RL et al., Integrin regulation). of cell signaling and motility, Biochem Soc Trans , 32 , pp. 443-6, 2004). Because integrins of focal adhesion are linked to the actin cytoskeleton through binding to protein complexes (especially through the tail of the cytoplasm), the molecules that make up these complexes do not bind effectively. Failure to do so or abnormal reconstitution of the actin filament results in the breakdown of focal adhesions resulting in rounded cells, which eventually lead to the release of epithelial cells from the basement membrane (Hirohashi, S and Kanai, Y., Cell adhesion system and human cancer morphogenesis, Cancer Sci , 94 , pp. 575-81, 2003). In other words, normal epithelial cells can survive in a single layer on the ECM-rich basement membrane to effectively transmit extracellular signals from the ECM, but when the cell adsorption is disrupted, anikis are induced and released from the basement membrane.

Cancer cells can metastasize from the site of origin to the second site through abnormal cell- extracellular matrix (ECM) and cell-cell intersorption due to various mutations and instability of the genome. In the microenvironment around cancer cells in the metastatic state, growth factors and cytokines secreted by the cancer cells themselves or by surrounding fibroblasts, leukocytes, and endothelial cells Plays an important role in cell contact, adsorption, migration and infiltration (Stamenkovic, I. Extracellular matrix remodelling: the role of matrix metalloproteinases, J Pathol , 200 , pp. 448-64, 2003). The metastasizing cancer cells undergo intravasation through the basement membrane and stromal region to the bloodstream, and then travel through the bloodstream to undergo extravasation to settle in the second place. Integrin and ECM interactions are important factors in determining metastatic potential of cancer cells (Liotta, LA, et al., Biochemical interactions of tumor cells with the basement membrane, Annu) Rev Biochem , 55 , pp. 1037-57, 1986). Only cancer cells that have defeated anikis in the circulation of blood cells or lymph flow out of the place originally originated for metastasis can settle and proliferate in the second place, causing new cancers (Thiery , JP, Epithelial-mesenchymal transitions in tumour progression, Nat Rev Cancer , 2 , pp. 442-54, 2002).

Therefore, if you can find a substance that induces anikis (cancer) only on cancer cells without affecting normal cells, it would be an ideal anticancer agent with anticancer effect and anti-metastatic effect.

TM4SF5 (or L6H), known as an analog of the tumor antigen L6, is a L6 family of membrane proteins that, along with L6, IL-TMP, L6D, have four properties that cross the cell membrane (Wright, MD et al., The L6 membrane proteins-a). new fourtransmembrane superfamily, Protein Sci , 9 , pp. 1594-600, 2000). TM4SF5 can be used for pancreatic adenocarcinoma, gastric cancer, colon cancer, papilla vateri carcinoma, soft-tissue sarcoma, nonendocrine lung tumor and corticotrophin-bronchial carcinoid. tumors) (Pascual-Le Tallec, L. et al., Identification of genes associated with the corticotroph phenotype in bronchial carcinoid tumors, J Clin Endocrinol Metab , 87 , pp. 5015-22, 2002). Recently, we have overexpressed TM4SF5 in liver cancer, eventually leading to oncogenic proliferation through the rearrangement of actin, epithelial-mesenchymal transition (ETM), and the inhibition of cell proliferation by cell contact. announced that he (Lee SA et al., Tetraspanin TM4SF5 dediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma, J. Clin. Invest, 118, pp.1354-1366, 2008) it brings. Overexpression of TM4SF5 in fibroblasts has resulted in rearrangement of actin cytoskeleton and generation and disruption of focal adhesion (Lee, SY et al., Focal adhesion and actin organization by a cross). -talk of TM4SF5 with integrin α2 are regulated by serum treatment, Exp Cell Res , 312 , pp.2983-99, 2006). TM4SF (or known as tetraspanin or tetraspan) is a 25-50 kDa hydrophobic membrane protein with four transmembrane domains, two extracellular loops and two short cytoplasmic tails. (Stipp, CS et al., Functional domains in tetraspanin proteins, Trends Biochem Sci , 28 , pp. 106-12, 2003). TM4SF forms a structure known as tetraspanin-web and forms various bonds with molecules involved in cell adsorption such as integrin, which plays an important role in cell adsorption and migration (Berditchevski, F, Complexes). of tetraspanins with integrins: more than meets the eye, J Cell Sci , 114 , pp.4143-51, 2001). Therefore, searching for a compound that inhibits the proliferation of cells expressing TM4SF5 will find an ideal anticancer agent that does not affect normal cells.

On the other hand, Astilbe Chinensis var. davidii) It is a perennial herb distributed in Japan, Manchuria, China, Amur, and Usulli, 30 ~ 70 cm high, with long brown hairs, and the rhizome is thick and stretches laterally. Flowers blossom in July and August, reddish purple, and cone flowers hang at the end of main stem, about 30 cm long, with many flowers, with short hairs. The rhizome of this is thick and red, and is called a red riding horse. Plants belonging to this genus include A. dicaricata , A. Koreana , and A. simplicifolia .

The outpost on the ground contains cyanide and the flowers contain quercetin. In general, it is known that the plant of the genus of roe deer contains 2-hydroxyphenylacetic acid, astilbic acid as a triterpenic acid, and astilbin as a flavonoid.

Roe deer urine improves blood circulation, releases blood, lowers fever, releases poison, stops cramps, and suppresses pain. It is used to cure bruises, joint pain, post-operative pain, and snake bites (Korean medicinal plants, Kyohaksa, 2000, p.204, Bae Hwan-hwan).

Looking at the prior art using a roe deer urine, Korean Patent Registration No. 10-0112187 discloses an analgesic composition containing 3 beta-hydroxy oleane-12-ene-27 phosphoic acid and its salt as a main component isolated from the roe deer urine Also, Korean Patent Registration No. 10-0523463 discloses an anti-inflammatory or anti-allergic composition containing a roe deer urine extract or an astilbic acid and feltokininolic acid derivative isolated therefrom. On the other hand, Japanese Patent Publication No. 2000-128730 discloses Astilbe A cosmetic composition containing a thunbergii extract is disclosed, and 2002-255839 discloses a composition for inhibiting obesity containing the extract, and other uses for inhibiting hyperlipidemia and lipase activity. However, the use of the conventional roe deer urine extract and compounds isolated therefrom for cancer prevention and treatment have not been disclosed at all.

Accordingly, the present inventors found that the roe deer urine extract, fraction or triterpene compound isolated therefrom induces anikis only in cells expressing TM4SF5, and has an effect of inducing cell death by reducing proliferation of cancer cell lines. By confirming that the present invention was completed, the present invention was completed.

An object of the present invention is to provide a pharmaceutical composition for cancer prevention and treatment containing roe deer urine extract, roe deer urine fraction, triterpene compound isolated therefrom or a pharmaceutically acceptable salt thereof as an active ingredient.

Still another object of the present invention is to provide a health food composition for cancer prevention or improvement comprising roe deer urine extract, roe deer urine fraction, triterpene compound isolated therefrom or a pharmaceutically acceptable salt thereof as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing and treating cancer containing roe deer urine extract, roe deer urine fraction, triterpene compound isolated therefrom or a pharmaceutically acceptable salt thereof as an active ingredient. do.

 In another aspect, the present invention provides a health food composition for cancer prevention or improvement containing a roe deer urine extract, a roe deer urine fraction, a triterpene compound isolated therefrom or a pharmaceutically acceptable salt thereof as an active ingredient.

The present invention relates to a pharmaceutical composition for preventing and treating cancer containing roe deer urine extract, roe deer urine fraction, triterpene compound isolated therefrom or a pharmaceutically acceptable salt thereof as an active ingredient, and extracts and fractions of the present invention. Or the compound induces anokis (aniokis) in the case of only the TMS4SF5 expression cell line, and thus inhibit the growth of the tumor, can be useful as an anticancer agent that can kill only cancer cells without affecting normal cells.

Hereinafter, the present invention will be described in detail.

The present invention provides a pharmaceutical composition for preventing and treating cancer containing roe deer urinary extract as an active ingredient.

The roe deer urine extract is preferably obtained by extracting from the roe deer urine dried, the roe deer urine can be used without limitation, such as cultivated or commercially available.

The method for preparing the roe deer urine extract is to collect the roe deer urine grass, and then pulverized and powdered, and extracted by using water, alcohol or a mixture thereof of about 2 to 20 times the weight of the roe deer urine sample weight as an extraction solvent. Can be. Extraction method may be a conventional extraction method in the art, such as hot water extraction, cold needle extraction, reflux extraction, ultrasonic extraction.

The alcohol in the extraction solvent is preferably C ₁ to C ₄ lower alcohols, such as methanol, ethanol and butanol, and methanol is more preferable. When using a mixture of water and alcohol, water and alcohol may be used in a mixing ratio of about 1: 0.1 to 1:10.

The extraction temperature is preferably 20 to 50 ℃, the extraction time is preferably 10 to 48 hours, more preferably carried out for 20 to 30 hours. In addition, the number of extraction is preferably repeated 2 to 3 times.

After the extraction, according to a conventional method, it is possible to obtain a roe deer urine extract according to the present invention by additionally performing a method such as filtration, concentration and lyophilization.

The present invention also provides a pharmaceutical composition for preventing and treating cancer containing the roe deer urine fraction as an active ingredient.

The roe deer urine fraction is suspended in roe deer urine extract, and then added to a nonpolar solvent, such as chloroform, hexane, ethyl acetate, in an amount of about 1 to 100 times, preferably about 1 to 5 times, the volume of the suspension. Once, preferably 1 to 5 times, the nonpolar solvent soluble layer may be obtained by extraction and separation, and further, a conventional fractionation process may be performed (Harborne JB, a guide to modern techniques of plant analysis. 3. pp 6-7, 1998)

For example, the roe deer urine fraction may be obtained by suspending the roe deer urine extract in water and fractionated with hexane, when using the mixed solvent of hexane and chloroform as the eluent, hexane and chloroform mixture 50: 1 to 0: Four fractions can be obtained by performing normal phase silica gel column chromatography with a concentration gradient eluent of sequentially increasing the solvent polarity of 100.

Fraction 1 was separated into six small fractions (A-F) by performing normal phase column chromatography with hexane and ethyl acetate mixed solution 8: 1 to 2: 1 eluent. The fraction of 1-A is purified by reverse phase silica gel column chromatography using acetonitrile as eluent to obtain compounds 16 and 17 purely. The 1-B fraction was purified by normal phase column chromatography using chloroform and methanol mixture 40: 1 as eluent to obtain pure compound 1. The 1-C fraction was subjected to normal phase column chromatography using hexane and ethyl acetate mixture 4: 1 as eluent to obtain compound 10. The 1-D fraction was purified by reverse phase column chromatography using acetonitrile and a mixture of water 10: 1 as the eluent to obtain pure compound 2. The 1-E fraction was subjected to reverse phase column chromatography using acetonitrile and water mixture 6: 1 as eluent to obtain compounds 9, 11 and 21. The 1-F fraction was subjected to reverse phase column chromatography using acetonitrile and water mixture 3: 1 as eluent to obtain compounds 5, 8 and 14.

Fraction 2 was subjected to reverse phase column chromatography using acetonitrile and water mixture 2: 1 to obtain four small fractions (A-D). The 2-A fraction is subjected to reverse phase column chromatography using acetonitrile as eluent to obtain compounds 18, 19 and 20. The 2-B fraction was subjected to reverse phase column chromatography using methanol and water mixture 3: 1 as eluent to obtain compound 7. The 2-C fraction is subjected to reverse phase column chromatography using acetonitrile and water mixture 2: 1 to obtain compounds 4 and 12. 2-D fractions were subjected to reverse phase column chromatography using acetonitrile and water mixture 3: 2 as eluent to afford compounds 13 and 15.

Each compound purely separated by the above procedure was purified using HPLC-MS (UPLC-QTOF premier: Hybrid Tandem Mass Spectrometer, Waters) high-speed fluid chromatography-mass spectrometer (UPLC-ESI-MS). The structure is determined using NMR (Varian Unity 400).

Furthermore, the present invention provides a pharmaceutical composition for preventing and treating cancer, which contains one or more triterpene compounds of the following Chemical Formulas 1 to 21 or their pharmaceutically acceptable salts as an active ingredient.

The triterpene compounds of Formulas 1 to 21 are as follows.

1) 3beta-hydroxyolean-12-ene-27-ioic acid;

2) 3 alpha-acetoxyoleane-12-ene-27-eoic acid;

3) 3beta, 24-dihydroxyolean-12-ene-27-oic acid;

4) astilbic acid;

5) 3beta-acetoxy-6beta-hydroxyolean-12-ene-27-oic acid;

6) 3beta, 6beta, 24-trihydroxyolean-12-ene-27-oic acid;

7) 3beta, 6beta-dihydroxy-24-norolean-12,4 (23) -diene-27-oic acid;

8) 3beta-hydroxyolean-12-ene-27-ioic acid;

9) 3beta-hydroxyolean-12-ene-27-al;

10) 3beta-hydroxyl-12-ene-27-oic acid;

11) 3beta-acetoxyurse-12-ene-27-ioic acid;

12) 3beta, 24-dihydroxyurse-12-ene-27-oic acid;

13) 3beta, 6beta-dihydroxyurse-12-ene-27-oic acid;

14) 3beta-acetoxy-6β-hydroxyurse-12-ene-27-ioic acid;

15) 3beta, 6beta, 24-trihydroxyurse-12-ene-27-oic acid;

16) 3-alpha-acetoxyurse-12-ene-27-eoic acid;

17) 18 alpha-oleanan-3 beta, 19 alpha-diol;

18) 18 alpha-uric acid-3 beta, 6 alpha, 19 beta-triol;

19) 18 alpha-uric acid-3 beta, 6 alpha, 20 beta-triol;

20) 6 alpha-acetoxy-18 alpha-uric acid-3 beta, 20 beta-diol; And

21) olean-11,13 (18) -diene-3beta, 16 alpha-diol;

Table 1 summarizes the structural formulas of the triterpene compounds represented by Chemical Formulas 1 to 21.

Structural formula of triterpene compound isolated from roe deer urine Chemical number constitutional formula One

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

The triterpene compounds of Formulas 1 to 21 may be separated from a roe deer urine extract or a roe deer urine fraction, or may be synthesized by an organic chemical synthesis method.

The triterpene compounds of Chemical Formulas 1 to 21 according to the present invention are representative active ingredients present in roe deer urine, and a method for separating the compounds may be performed as follows.

Extracting the roe deer urine with water, C ₁ ~ C ₄ alcohol or a mixed solution thereof to obtain a roe deer urine extract (step 1);

Suspending the roe deer urine extract obtained in step 1 in water and fractionating with hexane to obtain a roe deer urine fraction (step 2);

Performing column chromatography on the roe deer urine fraction obtained in step 2 to obtain a fraction containing the triterpene compound as a main component (step 3); And

The fraction obtained in step 3 provides a method for preparing a triterpene compound of Chemical Formulas 1 to 21, which comprises separating the triterpene compound (step 4) by performing a combination of a normal phase, reverse phase column chromatography or a solvent recrystallization method. .

Step 1 according to the present invention is a step of obtaining a roe deer urine extract by extracting the roe deer urine dried water, C ₁ ~ C ₄ alcohol or a mixed solvent thereof. The alcohol may be a lower alcohol such as methanol, ethanol, propanol, butanol, preferably methanol or ethanol, and most preferably methanol.

In step 1 according to the present invention, the method of obtaining the alcohol extract is pulverized dried roe urum to an appropriate size and put into an extraction container and extracted by adding an appropriate amount of alcohol at 20 to 50 ℃ to obtain an extract. The process may be repeated several times or more to increase the extraction efficiency of the roe deer urine. The extract is filtered and concentrated under reduced pressure to prepare an alcohol extract of roe deer urine.

Step 2 according to the present invention is a step of obtaining a roe deer urine fraction by suspending the roe deer urine extract obtained in step 1 in water and fractionated with hexane.

Step 3 according to the present invention is a step of obtaining a fraction containing a triterpene compound as a main component by performing column chromatography on the roe deer urine fraction obtained in step 2.

The step using a mixed solvent of hexane and chloroform as the eluent, silica gel column chromatography can be performed with a concentration gradient eluent sequentially increasing the solvent polarity of hexane and chloroform mixture 50: 1 to 0: 100.

Step 4 according to the present invention is a step of separating the triterpene compounds of Formulas 1 to 21 from the fraction containing the triterpene compound obtained in step 3 as a main component.

The step is performed by performing normal phase column chromatography using a mixed solvent of hexane and ethyl acetate as an eluent, followed by a combination of a normal phase, reverse phase or solvent recrystallization method, or performing reverse phase chromatography with a mixed solvent of acetonitrile and water as an eluent. Reverse phase column chromatography can then be re-run.

The roe deer urine extract, roe deer urine fraction, or triterpene compounds isolated therefrom exhibit tumor suppression activity, and thus can be usefully used as pharmaceutical compositions for preventing and treating cancer.

The cancer includes liver cancer, stomach cancer, colon cancer, breast cancer, lung cancer, non-small cell lung cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, skin or eye melanoma, cervical cancer, ovarian cancer, colon cancer, small intestine cancer, rectal cancer, anus Proximal cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small intestine cancer, lymph gland cancer, bladder cancer, gallbladder cancer, endocrine gland cancer, thyroid cancer, parathyroid cancer, adrenal cancer , Soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic or acute leukemia, lymphocyte lymphoma, bladder cancer, kidney or ureter cancer, renal cell carcinoma, renal pelvic carcinoma, central nervous system (CNS) tumor, primary CNS Any one selected from the group consisting of lymphoma, spinal cord tumor, brain stem glioma and pituitary adenoma is included in the subject, but is not limited thereto.

The present invention includes not only the triterpene compounds represented by Chemical Formulas 1 to 21 and pharmaceutically acceptable salts thereof, but also all possible solvates, hydrates, racemates or stereoisomers which can be prepared therefrom.

The triterpene compounds of Formulas 1 to 21 of the present invention can be used in the form of pharmaceutically acceptable salts, and acid addition salts formed by pharmaceutically acceptable free acids are useful as salts. Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid and aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes. Obtained from non-toxic organic acids such as dioates, aromatic acids, aliphatic and aromatic sulfonic acids. Such pharmaceutically nontoxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, and iodide. Id, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suverate , Sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitro benzoate, hydroxybenzoate, meth Oxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesul Nate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1- Sulfonates, naphthalene-2-sulfonates or mandelate.

The acid addition salts according to the invention are dissolved in conventional methods, for example, by dissolving the derivatives of the formulas (1-21) in an excess of aqueous acid solution, which salts are water-miscible organic solvents such as methanol, ethanol, acetone or acetonitrile. It can be prepared by precipitation using.

Equivalent amounts of the compounds of formulas 1 to 21 and acids or alcohols in water may be heated and then the mixture is evaporated to dryness or the precipitated salts may be prepared by suction filtration.

Bases can also be used to make pharmaceutically acceptable metal salts. Alkali metal or alkaline earth metal salts are obtained, for example, by dissolving a compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare sodium, potassium or calcium salt as the metal salt. Corresponding silver salts are also obtained by reacting alkali or alkaline earth metal salts with a suitable negative salt (eg, silver nitrate).

The composition may be used as a pharmaceutical composition, and may be various oral or parenteral formulations. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin. In addition to simple excipients, lubricants such as magnesium stearate, talc and the like are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The composition of the present invention may be administered parenterally or orally as desired, and may be administered in one to several times so as to be administered in an amount of 0.1 to 500 mg, preferably 1 to 100 mg per kg of body weight per day. have. The dosage for a particular patient may vary depending on the patient's weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion, severity of the disease, and the like.

In addition, the present invention provides a health food composition for cancer prevention or improvement comprising a roe deer urine extract, a roe deer urine fraction, a triterpene compound isolated therefrom or a pharmaceutically acceptable salt thereof as an active ingredient.

The composition according to the present invention can be added to the dietary supplements such as food, beverages, etc. for the prevention or amelioration of cancer, roe urum extract, roe urum fraction, triterpene compounds isolated therefrom or pharmaceutically acceptable salts thereof. have. In this case, the roe deer urine extract, the triterpene compound isolated therefrom or a pharmaceutically acceptable salt thereof may be added in an amount of 0.01 to 20% by weight, preferably 0.1 to 5% by weight, based on the raw materials when used as a food additive. Can be. The blending amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment). However, in the case of long-term intake for health and hygiene purposes or health control purposes, the amount may be below the above range, and since there is no problem in terms of stability, the active ingredient may be used in an amount above the above range. The extract or a compound separated therefrom may be used with other food or food ingredients, and may be appropriately used according to conventional methods.

There is no particular limitation on the kind of food. Examples of the food to which the extract, the triterpene compound isolated therefrom, or a pharmaceutically acceptable salt thereof may be added include meat, sausage, bread, chocolate, candy, snacks, confectionary, pizza, ramen, other noodles, gum, Dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes, etc., and includes all of the health food in the usual sense.

The food supplement additive of the present invention may use various flavors or natural carbohydrates. The natural carbohydrates are sugars such as glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, xylitol, sorbitol, and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 parts by weight, preferably 0.02 to 0.03 parts by weight, per 100 parts by weight of the composition according to the present invention.

In addition to the above, the composition according to the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, Alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the composition according to the present invention may contain a pulp for the production of natural fruit juices and vegetable drinks. These components can be used independently or in combination, and the proportion of the additive is not critical, but is usually selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition according to the present invention.

Hereinafter, the present invention will be described in detail through production examples and experimental examples. However, the following preparation examples are only illustrative of this invention, and the content of this invention is not limited by the following preparation examples.

Production Example  1: Preparation of roe deer urine extract

After grinding and pulverizing 15.3 kg of the outpost of the dried roe deer urine pool, 50 L of methanol was added and stirred at room temperature for 24 hours, and the supernatant was recovered by vacuum filtration. This process was repeated twice to collect the supernatant, and then concentrated under reduced pressure to obtain a methanol extract (2000 g).

Production Example  2: roe deer pee Fraction  Produce

The methanol extract obtained in Preparation Example 1 was suspended in water, and then the solvent was fractionated with hexane, filtered and concentrated under reduced pressure to remove the solvent to obtain 160 g of roe deer urethane hexane fraction.

Thereafter, 160 g of the hexane fraction was subjected to pure silica gel column chromatography using a mixed solvent of hexane and chloroform with a gradient gradient eluent of hexane and chloroform mixture from 50: 1 to 0: 100 while sequentially increasing the solvent polarity. Four fractions were obtained (fraction 1: 20.0 g, fraction 2: 10.0 g, fraction 3: 3.0 g, fraction 4: 120 g). At this time, the fractions 1, 2, and 3 contained triterpene compounds as main components.

Production Example  3: Triterpenes  Isolation and Structure Identification of Compounds

Triterpene compounds represented by the following Chemical Formulas 1 to 21 were obtained by performing a combination of a normal phase, reverse phase column chromatography, or a solvent recrystallization method to fractions 1, 2, and 3 containing the triterpene compound obtained in Preparation Example 2. Compounds separated from each fraction A, B and C are shown in FIG.

Specifically, fraction 1 was subjected to normal phase column chromatography with hexane and ethyl acetate mixture 8: 1 to 2: 1 eluent, and then divided into six small fractions (A-F). The fraction of 1-A was subjected to reverse phase silica gel column chromatography using acetonitrile as the eluent, and then purified 16 times (10 mg) and 17 times (9 mg) were purified by solvent recrystallization. The 1-B fraction was purified by column chromatography using a mixture of chloroform and methanol 40: 1 as eluent and subjected to normal phase chromatography to obtain Compound 1 (1.24 g) purely. 1-C fractions were purified by column chromatography using hexane and ethyl acetate mixture 4: 1 as eluent to obtain compound No. 10 (1.30 g) purely. The 1-D fraction was subjected to reverse phase column chromatography using acetonitrile and a water mixture of 10: 1 as eluent to obtain Compound 2 (77 mg) purely. 1-E fractions were subjected to reverse phase column chromatography using acetonitrile and water mixture 6: 1 as eluents, and 9 (4 mg), 11 (12 mg) and 21 (2 mg) were separated, respectively. Obtained purely. The 1-F fraction was subjected to reverse phase column chromatography using acetonitrile and water mixture 3: 1 as eluent to separate compounds 5 (43 mg), 8 (10 mg) and 14 (17 mg), respectively. Obtained purely.

Fraction 2 was subjected to reverse phase column chromatography using acetonitrile and water mixture 2: 1 to obtain four small fractions (A-D). The 2-A fraction was purified by reverse phase column chromatography using acetonitrile as eluent to separate compounds 18 (15 mg), 19 (15 mg) and 20 (6 mg), respectively. The 2-B fraction was subjected to reverse phase column chromatography using methanol and water mixture 3: 1 as an eluent to obtain compound 7 (12 mg). 2-C fractions were purified by reverse phase column chromatography using acetonitrile and water mixture 2: 1 to separate compounds 4 (2.1 g) and 12 (600 mg). 2-D fractions were purified by reverse phase column chromatography using acetonitrile and a mixture of water 3: 2 as eluent to isolate compounds No. 13 (566 mg) and No. 15 (700 mg), respectively.

For structural analysis of the triterpene compound, NMR analysis and mass analysis were performed as described below. Molecular weight and molecular formula Waters UPLC-QTOF premier (Hybrid Tandem Mass Spectrometer) high-speed liquid chromatography-mass spectrometry (UPLC-ESI-MS) a was determined by the molecular weight measurement using nuclear magnetic resonance (Varian 400 ㎒ NMR) for using ¹ H, ¹³ C-NMR spectrum (spectrum) analysis (spectrum) to the structure was identified as in the formula 1 to 21 (M. Iinuma et al. Phytochemistry 33: 1241, 1993). The analysis results are as follows.

Compound name: 3beta-hydroxyolean-12-en-27-oic acid

Molecular Formula: C ₃₀ H ₄₈ O ₃

Molecular Weight: 456.7

¹ H NMR (400 MHz, Pyridine) δ 0.75 (3H, s, H-24), 0.90 (3H, s, H-29), 1.04 (3H, s, H-30), 1.05 (3H, s, H -28), 1.06 (3H, s, H-25), 1.11 (3H, s, H-23), 1.16 (3H, s, H-26), 3.31 (1H, dd, J = 4.6, 11.4 Hz, H-3), 5.80 (1H, s, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 17.1 (C-24), 17.2 (C-25), 19.0 (C-26), 19.4 (C-6), 23.5 (C-15), 23.9 (C-11 ), 24.3 (C-30), 28.7 (C-16), 28.9 (C-2), 29.1 (C-23), 29.1 (C-28), 31.7 (C-20), 33.9 (C-29) , 33.9 (C-17), 35.2 (C-22), 37.5 (C-7), 37.8 (C-10), 37.9 (C-21), 39.7 (C-1), 39.8 (C-4), 40.4 (C-8), 44.9 (C-19), 48.0 (C-9), 50.4 (C-18), 56.3 (C-5), 57.0 (C-14), 78.4 (C-3), 126.0 (C-12), 139.1 (C-13), 178.9 (C-27).

Helvetica chimica acta-vol. 86 (2003).

Name of the compound: 3 alpha-acetoxyolean-12-ene-27-oic acid (3α-acetoxyolean-12-en-27-oic acid)

Molecular Formula: C ₃₂ H ₅₀ O ₄

Molecular Weight: 498.7

¹ H NMR (400 MHz, Pyridine) δ 4.79 (1 H, s, H-3), 5.81 (1 H, d, J = 2.2 Hz, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 16.7 (C-25), 18.9 (C-6), 19.0 (C-26), 21.3 (C-32), 23.4 (C-15), 22.4 (C-24 ), 23.5 (C-11), 23.7 (C-16), 24.3 (C-30), 28.8 (C-2), 28.4 (C-23), 29.1 (C-28), 31.7 (C-20) , 33.9 (C-17), 34.7 (C-7), 33.9 (C-29), 35.2 (C-21), 37.1 (C-10), 37.7 (C-8), 37.5 (C-22), 37.5 (C-1), 40.4 (C-4), 44.9 (C-19), 47.8 (C-18), 50.4 (C-9), 50.9 (C-5), 57.0 (C-14), 78.4 (C-3), 125.8 (C-12), 139.1 (C-13), 170.6 (C-31), 178.7 (C-27).

J. Org . Chem . 1983, 48, 3525-3531

Compound name: 3beta, 24-dihydroxyolean-12-ene-27-oic acid (3β, 24-dihydroxyolean-12-en-27-oic acid)

Molecular Formula: C ₃₀ H ₄₈ O ₄

Molecular Weight: 472.7

¹ H NMR (400 MHz, Pyridine) δ 0.74 (3H, s, H-29), 0.90 (3H, s, H-30), 0.95, 2.07 (2H, m, H-2), 1.02 (6H, s , H-25,28), 1.06, 1.37 (2H, m, H-21), 1.10 (3H, s, H-26), 1.16, 1.68 (2H, m, H-1), 1.25, 1.49 (2H , m, H-22), 1.35, 1.80 (2H, m, H-19), 1.40 (3H, s, H-23), 1.44, 1.72 (2H, m, H-6), 1.73, 1.90 (2H , m, H-7), 1.85, 2.48 (2H, m, H-16), 1.88, 2.43 (2H, m, H-15), 1.96, 2.15 (2H, m, H-11), 2.18 (1H , dd, J = 3.6, 13.6 Hz, H-18), 2.75 (1H, J = 5.2, 11.4 Hz, H-9), 3.48 (1H, dd, J = 4.4, 11.6 Hz, H-3), 3.71 (1H, d, J = 10.9 Hz, H-24b), 4.51 (1h, d, J = 10.9 Hz, H-24a), 5.78 (1H, t, J = 2.5 Hz, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 17.5 (C-25), 18.9 (C-26), 19.7 (C-6), 23.5 (C-15), 23.9 (C-23), 24.1 (C-11 ), 24.3 (C-30), 28.9 (C-16), 29.0 (C-2), 29.1 (C-28), 31.7 (C-20), 33.8 (C-17), 33.9 (C-29) , 35.2 (C-21), 37.5 (C-22), 37.7 (C-10), 38.2 (C-7), 39.5 (C-1), 40.4 (C-8), 43.6 (C-4), 44.9 (C-19), 48.0 (C-9), 50.3 (C-18), 56.8 (C-5), 56.9 (C-14), 65.1 (C-24), 80.4 (C-3), 125.8 (C-12), 139.1 (C-13), 178.9 (C-27).

Name of compound: Astilbic Acid

Molecular Formula: C ₃₀ H ₄₈ O ₄

Molecular Weight: 472.7

¹ H NMR (400 MHz, Pyridine) δ 0.76 (3H, s, H-29), 0.91 (3H, s, H-30), 1.05 (3H, s, H-28), 1.29 (3H, s, H-23), 1.71 (3H, s, H-26), 1.74 (3H, s, H-25), 1.75 (3H, s, H-24), 3.34 (1H, dd, J = 4.1, 11.5 Hz , H-3), 4.87 (1H, s, H-6), 5.89 (1H, t, J = 3.1 Hz, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 18 (C-25), 18.1 (C-24), 20.4 (C-26), 23.1 (C-15), 23.6 (C-11), 23.8 (C-30 ), 28.5 (C-2), 28.5 (C-16), 28.5 (C-28), 28.7 (C-23), 31.2 (C-20), 33.5 (C-17), 33.5 (C-29) , 34.8 (C-21), 37.1 (C-22), 37.3 (C-10), 39.6 (C-8), 40.4 (C-4), 41.5 (C-1), 44.5 (C-19), 45.1 (C-7), 48.1 (C-9), 49.9 (C-18), 56.1 (C-5), 56.9 (C-14), 67.5 (C-6), 78.4 (C-3), 125.9 (C-12), 138.1 (C-13), 178.8 (C-27).

Helvetica chimica acta-vol. 86 (2003).

Compound name: 3beta-acetoxy-6beta-hydroxyolean-12-ene-27-oic acid (3β-acetoxy-6β-hydroxyolean-12-en-27-oic acid)

Molecular Formula: C ₃₂ H ₅₀ O ₅

Molecular Weight: 514.7

¹ H NMR (400 MHz, Pyridine) δ 0.83, 2.12 (2H, m, H-2), 0.84 (3H, s, H-29), 0.86 (3H, s, H-30), 0.88 (3H, s , H-28), 0.90 (3H, s, H-23), 1.03, 1.43 (2H, m, H-19), 1.07, 1.38 (2H, m, H-21), 1.22, 1.41 (2H, m , H-22), 1.28 (6H, s, H-24, 26), 1.29, 1.42 (2H, m, H-1), 1.30 (1H, m, H-5), 1.38 (3H, s, H -25), 1.44, 1.84 (2H, m, H-7), 1.55, 2.07 (2H, m, H-11), 1.79, 2.02 (2H, m, H-15), 2.00 (3H, s, H -32), 2.01 (2H, m, H-16), 2.02 (1H, m, H-18), 2.38 (1H, dd, J = 6.2, 10.5 Hz, H-9), 4.32 (1H, br s , H-6), 4.53 (1H, t, J = 3.0 Hz, H-3), 5.61 (1H, dd, J = 2.9, 4.1 Hz, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 17.8 (C-25), 20.4 (C-26), 21.3 (C-32), 23.5 (C-15), 23.9 (C-11), 24.0 (C-16 ), 24.3 (C-30), 28.6 (C-23), 29.1 (C-28), 29.2 (C-2), 32.1 (C-20), 34.0 (C-29), 34.2 (C-17) , 35.8 (C-21), 37.5 (C-1), 37.9 (C-4), 38.0 (C-22), 38.5 (C-10), 40.4 (C-8), 45.0 (C-7), 45.5 (C-19), 48.6 (C-9), 50.9 (C-18), 51.4 (C-5), 57.9 (C-14), 68.5 (C-6), 81.4 (C-3), 127.0 (C-12), 138.7 (C-13), 172.7 (C-31), 180.5 (C-27).

Compound name: 3beta, 6beta, 24-trihydroxyolean-12-ene-27-oic acid (3β, 6β, 24-trihydroxyolean-12-en-27-oic acid)

Molecular Formula: C ₃₀ H ₄₈ O ₅

Molecular Weight: 488.7

¹ H NMR (400 MHz, Pyridine) δ 3.47 (1 H, dd, J = 4.2, 11.9 Hz, H-3), 4.47 (1 H, d, J = 11.3 Hz, Hb-24), 4.69 (1 H , d, J = 11.3 Hz, Ha-24), 4.83 (1 H, s, H-6), 5.88 (1 H, t, J = 3.3 Hz, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 18.5 (C-25), 20.9 (C-26), 23.5 (C-23), 23.6 (C-15), 24.2 (C-11), 24.4 (C-30) , 28.9 (C-2), 29.2 (C-28), 29.0 (C-16), 31.7 (C-20), 33.9 (C-29), 33.9 (C-17), 35.3 (C-21), 37.8 (C-10), 37.6 (C-22), 40.0 (C-8), 42.2 (C-1), 43.6 (C-7), 45.0 (C-19), 45.8 (C-4), 48.8 (C-9), 50.4 (C-18), 57.6 (C-14), 57.9 (C-5), 64.1 (C-24), 66.9 (C-6), 79.5 (C-3), 126.1 ( C-12), 138.9 (C-13), 179.4 (C-27).

Chinese Chemical Letters 17 (5) 628-630, 2006.

Compound name: 3beta, 6beta-dihydroxy-24-norolean-12,4 (23) -diene-27-oic acid (3β, 6β-dihydroxy-24-norolean-12, 4 (23)- dien-27-oic acid)

Molecular Formula: C ₂₉ H ₄₄ O ₄

Molecular Weight: 456.7

¹ H NMR (400 MHz, Pyridine) δ 0.75 (3H, s, H-29), 0.88 (3H, s, H-30), 0.94, 2.50 (2H, m, H-16), 1.01 (3H, s , H-28), 1.04, 1.37 (2H, m, H-21), 1.22, 1.47 (2H, m, H-22), 1.38, 1.81 (2H, m, H-19), 1.40, 1.86 (2H , m, H-1), 1.52 (3H, s, H-25), 1.74 (3H, s, H-26), 1.93, 2.16 (2H, m, H-2), 1.97 (1H, m, H -5), 2.02, 2.49 (2H, m, H-15), 2.04, 2.35 (2H, m, H-7), 2.22 (1H, m, H-18), 2.29 (2H, m, H-11 ), 3.09 (1H, dd, J = 5.3, 11.2 Hz, H-9), 4.20 (1H, dd, J = 5.5, 11.2 Hz, H-3), 4.72 (1H, br s, H-6), 5.87 (1H, broad doublet, J = 2.1 Hz, H-12), 5.96, 6.06 (2H broad br, H-23).

¹³ C NMR (100 MHz, Pyridine) δ 17.6 (C-25), 21.6 (C-26), 23.5 (C-15), 24.3 (C-30), 24.9 (C-11), 28.9 (C-16 ), 29.2 (C-28), 31.7 (C-20), 34.0 (C-2), 34.0 (C-17), 34.0 (C-29), 35.3 (C-21), 37.6 (C-22) , 39.4 (C-10), 40.5 (C-8), 41.8 (C-1), 44.1 (C-7), 45.0 (C-19), 46.0 (C-9), 50.6 (C-18), 53.1 (C-5), 57.7 (C-14), 69.7 (C-6), 73.4 (C-3), 105.8 (C-23), 126.5 (C-12), 139.1 (C-13), 153.7 (C-4), 179.2 (C-27).

Compound name: 3beta-hydroxyolean-12-en-27-oic acid

Molecular Formula: C ₃₀ H ₄₆ O ₃

Molecular Weight: 454.7

¹ H NMR (400 MHz, Pyridine) δ 0.95 (3H, s, H-25), 0.97, 1.66 (2H, m, H-22), 1.03 (3H, s, H-23), 1.03 (3H, s , H-26), 1.13 (3H, m, H-29), 1.14 (3H, m, H-28), 1.32, 1.92 (2H, m, H-21), 1.35 (2H, m, H-16 ), 1.43 (2H, m, H-2), 1.46 (1H, m, H-9), 1.54 (2H, m, H-1), 1.54, 1.91 (2H, m, H-15), 1.59 ( 3H, s, H-30), 1.67 (3H, s, H-24), 1.77 (2H, m, H-19), 1.83, 1.95 (2H, m, H-11), 1.95 (2H, H- 7), 2.12 (1H, m, H-18), 3.45 (1H, br s, H-3), 5.09 (1H, t, J = 5.6 Hz, H-6), 5.58 (2H, br t, H -12).

¹³ C NMR (100 MHz, Pyridine) δ 16.1 (C-265), 17.9 (C-30), 18.1 (C-25), 19.6 (C-2), 21.8 (C-28), 24.7 (C-11 ), 25.4 (C-7), 26.0 (C-29), 26.2 (C-24), 29.4 (C-15), 30.2 (C-23), 30.4 (C-16), 30.9 (C-14) , 33.2 (C-20), 34.1 (C-22), 35.6 (C-1), 36.8 (C-10), 37.4 (C-17), 38.7 (C-8), 41.6 (C-49), 42.0 (C-19), 46.3 (C-9), 52.0 (C-18), 77.1 (C-3), 121.3 (C-12), 125.6 (C-6), 132.4 (C-13), 144.4 (C-5), 172.9 (C-27).

Compound name: 3beta-hydroxyolean-12-ene-27-al

Molecular Formula: C ₃₀ H ₄₈ O ₂

Molecular Weight: 440.7

¹ H NMR (400 MHz, Pyridine) δ 0.74 (1H, m, H-5), 0.79 (3H, s, H-30), 1.83, 1.95 (2H, m, H-16), 0.88 (3H, s , H-29), 0.93 (3H, s, H-28), 0.95 (3H, s, H-25), 0.95, 1.21 (2H, m, H-19), 0.99, 1.63 (2H, m, H -1), 1.02 (3H, s, H-26), 1.02, 1.28 (2H, m, H-21), 1.03 (3H, s, H-24), 1.14 (3H, s, H-23), 1.17, 1.44 (2H, m, H-22), 1.32, 1.65 (2H, m, H-7), 1.33, 1.54 (2H, m, H-6), 1.65, 2.17 (2H, m, H-15 ), 1.81 (1H, m, H-9), 1.85 (2H, m, H-2), 2.05, 2.16 (2H, m, H-11), 2.12 (1H, m, H-18), 3.38 ( 1 H, dd, J = 5.9, 10.2 Hz, H-3), 5.78 (1H, br t, J = 3.2, H-12). 10.07 (1H, broad singlet, H-27).

¹³ C NMR (100 MHz, Pyridine) δ 16.8 (C-25), 17.0 (C-24), 18.3 (C-26), 19.1 (C-6), 19.7 (C-15), 24.4 (C-11 ), 24.5 (C-29), 27.2 (C-16), 28.5 (C-2), 28.8 (C-28), 29.0 (C-23), 31.5 (C-20), 33.0 (C-17) , 33.6 (C-30), 34.9 (C-21), 36.1 (C-7), 37.2 (C-22), 39.8 (C-4), 42.1 (C-8), 44.8 (C-19), 48.4 (C-18), 50.2 (C-9), 56.2 (C-5), 59.2 (C-14), 78.1 (C-3), 128.2 (C-12), 138.5 (C-13), 207.8 (C-27).

Compound name: 3beta-hydroxyurs-12-en-27-oic acid

Molecular Formula: C ₃₀ H ₄₈ O ₃

Molecular Weight: 456.7

¹ H NMR (400 MHz, Pyridine) δ 2.78 (1 H, dd, J = 5.0, 11.5 Hz, H-9), 3.34 (1 H, dd, J = 4.5, 11.3 Hz, H-3), 5.73 ( 1 H, d, J = 3.1 Hz, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 17.1 (C-24), 17.3 (C-25), 19.1 (C-29), 19.4 (C-6), 19.1 (C-26), 22.0 (C-30 ), 23.7 (C-15), 23.8 (C-11), 28.7 (C-2), 29.1 (C-23), 30.3 (C-16), 30.0 (C-28), 31.3 (C-21) , 34.6 (C-17), 38.0 (C-7), 37.9 (C-10), 38.5 (C-20), 39.8 (C-1), 39.8 (C-4), 40.6 (C-8), 40.3 (C-19), 41.9 (C-22), 47.8 (C-9), 56.2 (C-5), 57.2 (C-14), 61.3 (C-18), 78.5 (C-3), 128.7 (C-12), 135.2 (C-13), 178.3 (C-27).

Helvetica chimica acta-vol. 86 (2003).

Compound name: 3beta-acetoxyurs-12-en-27-oic acid

Molecular Formula: C ₃₂ H ₅₀ O ₄

Molecular Weight: 498.7

¹ H NMR (400 MHz, Pyridine) δ 0.75 (3H, s, H-23), 1.81 (3H, d, J = 6.3 Hz, H-30), 0.90 (3H, s, H-24), 0.91 ( 1H, m, H-19), 0.96 (3H, s, H-25), 0.99 (3H, s, H-28), 1.04, 2.47 (2H, m, H-16), 1.06, 1.58 (2H, m, H-1), 1.11 (3H, s, H-26), 1.13 (3H, d, J = 6.1 Hz, H-29), 1.31 (2H, m, H-21), 1.31, 1.49 (2H , m, H-22), 1.34 (1H, m, H-20), 1.34, 1.47 (2H, m, H-6), 1.48 (1H, d, J = 10.6, H-18), 1.67 (2H , m, H-2), 1.68, 1.88 (2H, m, H-7), 1.93, 2.07 (2H, m, H-11), 1.95, 2.40 (2H, m, H-15) 2.04 (3H, s, H-32), 2.75 (1H, dd, J = 5.2, 11.4 Hz, H-9), 4.61 (1H, dd, J = 6.4, 9.9 Hz, H-3), 5.69 (1H, d , J = 2.8 Hz, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 17.1 (C-25), 17.5 (C-24), 19.0 (C-29), 19.0 (C-26), 19.0 (C-6), 21.5 (C-32 ), 23.7 (C-15), 23.7 (C-11), 24.4 (C-2), 28.5 (C-23), 29.9 (C-28), 30.2 (C-16), 31.3 (C-21) , 34.6 (C-17), 37.6 (C-10), 37.7 (C-7), 38.3 (C-4), 38.5 (C-20), 39.0 (C-1), 40.3 (C-19), 40.4 (C-8), 41.8 (C-22), 47.6 (C-9), 56.0 (C-5), 57.1 (C-14), 61.2 (C-18), 81.1 (C-3), 128.4 (C-12), 135.2 (C-13), 170.9 (C-31), 178.3 (C-27).

Compound name: 3-beta, 24-dihydroxyurs-12-ene-27-oic acid (3β, 24-dihydroxyurs-12-en-27-oic acid)

Molecular Formula: C ₃₀ H ₄₈ O ₄

Molecular Weight: 472.7

¹ H NMR (400 MHz, Pyridine) δ 3.52 (1 H, dd, J = 4.5, 11.6 Hz, H-3), 3.70 (1 H, d, J = 10.9 Hz, Hb-24), 4.51 (1 H , d, J = 10.9 Hz, Ha-24), 5.71 (1 H, dd, J = 2.0, 5.0 Hz, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 17.6 (C-25), 19.0 (C-29), 19.1 (C-26), 19.7 (C-6), 22.0 (C-30), 23.9 (C-23 ), 23.7 (C-15), 24.0 (C-11), 29.0 (C-2), 29.9 (C-28), 30.3 (C-16), 31.3 (C-21), 34.6 (C-17) , 37.6 (C-10), 38.3 (C-7), 38.5 (C-20), 39.6 (C-1), 40.6 (C-8), 40.3 (C-19), 41.9 (C-22), 43.6 (C-4), 47.8 (C-9), 56.8 (C-5), 57.1 (C-14), 61.3 (C-18), 65.1 (C-24), 80.5 (C-3), 128.6 (C-12), 135.2 (C-13), 178.3 (C-27).

Acta Cryst. (2007). E63, 02375-02377.

Compound name: 3beta, 6beta-dihydroxyurse-12-ene-27-oic acid (3β, 6β-dihydroxyurs-12-en-27-oic acid)

Molecular Formula: C ₃₀ H ₄₈ O ₄

Molecular Weight: 472.7

¹ H NMR (400 MHz, Pyridine) δ 3.15 (1H, brt, J = 7.2 Hz, H-9), 3.34 (1H, dd, J = 4.0, 11.4 Hz, H-3), 4.83 (1H, br s, H-6), 5.80 (1H, t, J = 3.6 Hz, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 18.5 (C-24), 18.6 (C-25), 19.4 (C-29), 21.1 (C-26), 22.0 (C-30), 24.0 (C-11 ), 24.1 (C-15), 29.0 (C-2), 29.1 (C-23), 30.1 (C-28), 30.7 (C-16), 31.5 (C-21), 34.7 (C-17) , 37.7 (C-10), 38.5 (C-20), 40.0 (C-8), 40.4 (C-19), 40.9 (C-4), 42.0 (C-1), 42.1 (C-22), 45.7 (C-7), 48.1 (C-9), 56.4 (C-5), 58.2 (C-14), 61.6 (C-18), 68.1 (C-6), 79.0 (C-3), 128.2 (C-12), 135.5 (C-13), 179.6 (C-27).

CHEMISTRY & BIODIVERSITY Vol. 5 (2008).

Compound name: 3beta-acetoxy-6β-hydroxyurse-12-ene-27-oic acid (3β-acetoxy-6β-hydroxyurs-12-en-27-oic acid)

Molecular Formula: C ₃₂ H ₅₀ O ₅

Molecular Weight: 514.7

¹ H NMR (400 MHz, CDCl ₃ ) 4.40 (1 H, dd, J = 4.5, 11.5, H-3), 4.47 (1 H, br s, H-6), 5.58 (1 H, t, J = 3.5 Hz, H-12). ¹³ C NMR (100 MHz, CDCl3) δ 17.9 (C-25), 18.1 (C-29), 18.5 (C-24), 20.2 (C-26), 21.5 (C-30), 21.6 (C-32 ), 22.9 (C-15), 24.0 (C-11), 29.1 (C-2), 28.1 (C-23), 29.9 (C-16), 29.2 (C-28), 30.6 (C-21) , 33.9 (C-17), 36.7 (C-10), 37.9 (C-20), 38.7 (C-4), 39.4 (C-8), 39.8 (C-19), 40.6 (C-1), 41.1 (C-22), 44.3 (C-7), 47.2 (C-9), 55.3 (C-5), 56.5 (C-14), 60.4 (C-18), 68.4 (C-6), 81.1 (C-3), 129.2 (C-12), 132.6 (C-13), 171.4 (C-31), 180.6 (C-27).

Chinese Chemical Letters 17 (5) 628-630, 2006.

Compound name: 3beta, 6beta, 24-trihydroxyurethane-12-ene-27-oic acid (3β, 6β, 24-trihydroxyurs-12-en-27-oic acid)

Molecular Formula: C ₃₀ H ₄₈ O ₅

Molecular Weight: 488.7

¹ H NMR (400 MHz, Pyridine) δ 0.81 (3H, d, J = 6.3 Hz, H-30), 0.92 (1H, m, H-19), 1.02 (3H, s, H-28), 1.17 ( 3H, d, J = 6.1 Hz, H-29), 1.26 (1H, m, H-5), 1.31, 1.46 (2H, m, H-22), 1.31, 1.78 (2H, m, H-1) , 1.32 (2H, m, H-21), 1.36 (1H, m, H-20), 1.48 (3H, s, H-23), 1.53 (1H, d, J = 11.2 Hz, H-18), 1.71 (3H, s, H-26), 1.77 (3H, s, H-25), 1.85, 2.10 (2H, m, H-2), 2.05, 2.51 (2H, m, H-7), 2.06, 2.51 (m, H-15), 2.29 (2H, m, H-11), 2.51 (2H, m, H-16), 3.00 (1H, br t, J = 8.3 Hz, H-9), 3.50 ( 1H, dd, J = 4.2, 11.9 Hz, H-3), 4.45 (1H, d, J = 11.3 Hz, H-24b), 4.68 (1H, d, J = 11.3 Hz, H-24a), 5.80 ( 1 H, br t, J = 3.5 Hz, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 18.6 (C-25), 19.1 (C-29), 21.0 (C-26), 22.0 (C-30), 23.5 (C-23), 23.8 (C-15 ), 24.1 (C-11), 28.9 (C-2), 30.0 (C-28), 30.3 (C-16), 31.4 (C-21), 34.6 (C-17), 37.7 (C-10) , 38.5 (C-20), 40.2 (C-8), 40.3 (C-19), 41.9 (C-22), 42.3 (C-1), 43.7 (C-7), 45.8 (C-4), 48.6 (C-9), 57.7 (C-14), 57.9 (C-5), 61.3 (C-18), 64.1 (C-24), 66.9 (C-6), 79.5 (C-3), 128.2 (C-12), 134.9 (C-13), 178.7 (C-27).

Compound name: 3 alpha-acetoxyurs-12-en-27-oic acid

Molecular Formula: C ₃₂ H ₅₀ O ₄

Molecular Weight: 498.7

¹ H NMR (400 MHz, Pyridine) δ 2.89 (1 H, dd, J 5.1, 11.6 Hz, H-9), 4.79 (1 H, t, J = 2.6 Hz, H-3), 5.73 (1 H, dd, J = 2.0, 4.9 Hz, H-12).

¹³ C NMR (100 MHz, Pyridine) δ 16.8 (C-24), 18.9 (C-6), 19.0 (C-25), 19.1 (C-29), 21.4 (C-32), 21.9 (C-26 ), 22.5 (C-30), 23.6 (C-15), 23.6 (C-11), 23.7 (C-2), 28.4 (C-23), 29.9 (C-28), 30.2 (C-16) , 31.3 (C-21), 34.6 (C-17), 34.7 (C-7), 37.1 (C-10), 37.7 (C-1), 38.4 (C-20), 40.3 (C-19), 40.6 (C-4), 41.6 (C-8), 41.8 (C-22), 47.5 (C-9), 50.8 (C-5), 57.3 (C-14), 61.3 (C-18), 78.4 (C-3), 128.5 (C-12), 135.3 (C-13), 170.7 (C-31), 178.3 (C-27).

Razdan, T. K .; Kachroo, V .; Harkar, S .; Koul, G. L. Plectranthoic acid A and B, two new triterpenoids from Plectranthus rugosus. Tetrahedron (1982), 38 (7), 991-2.

Compound name: 18 alpha-oleanan-3 beta, 19 alpha-diol (18α-oleanane-3β, 19α-diol)

Molecular Formula: C ₃₀ H ₅₂ O ₂

Molecular Weight: 444.7

¹ H NMR (400 MHz, Pyridine) δ 0.81 (1H, m, H-5), 0.85, 1.64 (2H, m, H-1), 0.90 (3H, s, H-25), 0.94 (3H, s , H-28), 1.02, 1.83 (2H, m, H-15), 1.06 (3H, s, H-24), 1.08, 1.53 (2H, m, H-16), 1.09 (3H, s, H -27), 1.11 (3H, s, H-26), 1.18 (3H, s, H-30), 1.21, 2.02 (2H, m, H-22), 1.22 (3H, s, H-29) (3H, s, H-23), 1.29, 1.69 (2H, m, H-21), 1.34, 1.57 (2H, m, H-11), 1.35 (1H, m, H-9), 1.42 (2H , m, H-7), 1.42, 1.62 (2H, m, H-6), 1.52 (1H, m, H-13), 1.56 (1H, m, H-18), 1.83 (2H, m, H -2), 1.93, 2.88 (2H, m, H-12), 3.44 (1H, dd, J = 5.3, 10.8 Hz, H-3), 3.55 (1H, d, J = 10.4 Hz, H-19) .

¹³ C NMR (100 MHz, Pyridine) δ 15.5 (C-27), 16.7 (C-26), 16.8 (C-24), 17.0 (C-25), 18.9 (C-28), 19.3 (C-6 ), 21.1 (C-30), 22.3 (C-11), 27.5 (C-15), 28.8 (C-2), 29.0 (C-12), 29.2 (C-23), 31.3 (C-29) , 35.2 (C-7), 35.7 (C-21), 37.3 (C-17), 37.7 (C-10), 38.6 (C-20), 38.9 (C-16), 39.1 (C-13), 39.2 (C-22), 39.6 (C-1), 39.9 (C-4), 42.0 (C-8), 43.6 (C-14), 46.3 (C-18), 50.8 (C-9), 56.2 (C-5), 77.5 (C-19), 78.5 (C-3).

Compound name: 18 alpha-uric acid-3 beta, 6 alpha, 19 beta-triol (18α-ursane-3β, 6α, 19β-triol)

Molecular Formula: C ₃₀ H ₅₂ O ₃

Molecular Weight: 460.7

¹ H NMR (400 MHz, Pyridine) δ 0.91 (3H, s, H-28), 0.96 (3H, s, H-27), 1.00, 1.84 (2H, m, H-15), 1.06 (3H, s , H-25), 1.12 (2H, m, H-16), 1.14, 2.04 (2H, m, H-22), 1.22 (1H, d, J = 9.4 Hz, H-5), 1.23 (3H, s, H-26), 1.27, 1.57 (2H, m, H-11), 1.32, 1.86 (2H, m, H-12), 1.34 (3H, d, J = 5.6 Hz, H-30), 1.35 (1H, m, H-20), 1.37 (1H, m, H-9), 1.40 (3H, s, H-29), 1.42 (1H, m, H-13), 1.50 (3H, s, H -24), 1.55 (1H, d, J = 9.8 Hz, H-18), 1.74, 1.84 (2H, m, H-21), 1.77 (2H, m, H-1), 1.81, 2.00 (2H, m, H-7), 1.96 (2H, m, H-2), 2.01 (3H, s, H-23), 3.59 (1H, dd, J = 5.2, 11.2 Hz, H-3), 4.38 (1H , td, J = 3.6, 10.4 Hz, H-6).

¹³ C NMR (100 MHz, Pyridine) δ 15.4 (C-27), 17.1 (C-24), 18.1 (C-25), 18.5 (C-26), 18.6 (C-28), 19.2 (C-30 ), 22.3 (C-11), 27.6 (C-15), 28.6 (C-2), 30.3 (C-12), 31.3 (C-29), 32.5 (C-23), 36.0 (C-17) , 37.0 (C-21), 38.8 (C-22), 39.1 (C-16), 39.4 (C-13), 39.1 (C-1), 39.8 (C-10), 40.1 (C-20), 40.7 (C-4), 43.3 (C-8), 43.9 (C-14), 47.9 (C-7), 48.0 (C-18), 50.2 (C-9), 61.5 (C-5), 68.3 (C-6), 72.9 (C-19), 79.0 (C-3).

Compound name: 18 alpha-uric acid-3 beta, 6 alpha, 20 beta-triol (18α-ursane-3β, 6α, 20β-triol)

Molecular Formula: C ₃₀ H ₅₂ O ₃

Molecular Weight: 460.7

¹ H NMR (400 MHz, Pyridine) δ 0.98 (3H, s, H-28), 1.02 (3H, s, H-25), 1.04, 1.80 (2H, m, H-15), 1.07 (3H, s , H-27), 1.09, 1.70 (2H, m, H-1), 1.14 (3H, d, J = 6.4 Hz, H-29), 1.15 (3H, s, H-26), 1.17, 1.41 ( 2H, m, H-16), 1.21 (1H, d, J = 10.8 Hz, H-18), 1.22, 1.54 (2H, m, H-11), 1.24 (1H, d, J = 10.4 Hz, H -5), 1.26, 1.40 (2H, m, H-22), 1.28, 2.11 (2H, m, H-12), 1.32 (3H, s, H-30), 1.44 (3H, m, H-9 ), 1.49 (3H, s, H-24), 1.75 (1H, m, H-13), 1.81, 2.13 (2H, m, H-21), 1.84, 2.01 (2H, m, H-7), 1.91 (1H, m, H-19), 1.96 (2H, m, H-2), 2.02 (3H, s, H-23), 3.58 (1H, dd, J = 5.2, 11.2 Hz, H-3) , 4.38 (1H, broad doublet, J = 9.4 Hz, H-6).

¹³ C NMR (100 MHz, Pyridine) δ 15.4 (C-27), 17.1 (C-24), 18.0 (C-25), 18.2 (C-26), 18.5 (C-29), 19.2 (C-28 ), 22.0 (C-11), 22.3 (C-30), 27.5 (C-15), 28.7 (C-2), 29.3 (C-12), 32.5 (C-23), 36.4 (C-17) , 39.0 (C-21), 39.2 (C-16), 39.3 (C-13), 39.6 (C-1), 39.8 (C-10), 40.7 (C-4), 41.2 (C-22), 42.9 (C-19), 43.1 (C-8), 43.8 (C-14), 47.8 (C-7), 48.6 (C-18), 50.0 (C-9), 61.5 (C-5), 68.4 (C-6), 74.5 (C-20), 79.0 (C-3).

Compound name: 6alpha-acetoxy-18alpha-uric acid-3beta, 20beta-diol (6α-acetoxy-18α-ursane-3β, 20β-diol)

Molecular Formula: C ₃₂ H ₅₄ O ₄

Molecular Weight: 502.8

¹ H NMR (400 MHz, Pyridine) δ 0.83, 1.65 (2H, m, H-15), 0.97 (3H, s, H-28), 0.98 (3H, s, H-25), 1.02 (3H, s , H-27), 1.03, 1.68 (2H, m, H-1), 1.14, 1.48 (2H, m, H-11), 1.15 (3H, s, H-26), 1.18 (1H, m, H -18), 1.21 (3H, s, H-24), 1.23, 2.09 (2H, m, H-12), 1.28, 1.40 (2H, m, H-22), 1.33 (3H, s, H-30 ), 1.38 (1H, m, H-5), 1.40 (1H, m, H-9), 1.41 (3H, d, J = 6.2 Hz, H-29), 1.62 (3H, s, H-23) , 1.62, 1.80 (2H, m, H-7), 1.78 (1H, m, H-13), 1.80, 2.13 (2H, m, H-21), 1.84, 1.39 (2H, m, H-16) , 1.90 (2H, m, H-2), 1.90 (2H, m, H-19), 2.17 (3H, s, H-32), 3.50 (1H, t, J = 8.8 Hz, H-3), 5.62 (1H, t d, J = 3.6, 10.8 Hz, H-6).

¹³ C NMR (100 MHz, Pyridine) δ 15.3 (C-27), 17.1 (C-24), 17.7 (C-25), 17.9 (C-26), 18.4 (C-29), 19.0 (C-28 ), 21.7 (C-11), 22.3 (C-30), 22.5 (C-32), 27.3 (C-15), 28.4 (C-2), 29.0 (C-12), 31.8 (C-23) , 36.4 (C-17), 39.0 (C-21), 39.0 (C-16), 39.1 (C-13), 39.2 (C-1), 39.9 (C-4), 40.1 (C-10), 41.2 (C-22), 42.9 (C-19), 43.1 (C-8), 43.2 (C-7), 43.8 (C-14), 48.5 (C-18), 49.7 (C-9), 59.0 (C-5), 71.9 (C-6), 74.4 (C-20), 78.0 (C-3), 170.7 (C-31).

Compound Name: Olean-11,13 (18) -diene-3beta, 16alpha-diol (Olean-11,13 (18) -diene-3β, 16α-diol)

Molecular Formula: C ₃₀ H ₄₈ O ₂

Molecular Weight: 440.7

¹ H NMR (400 MHz, Pyridine) δ 0.95 (1H, m, H-5), 0.95 (3H, s, H-26), 0.98, 1.44 (3H, s, H-7), 0.99 (3H, s , H-29), 1.02 (3H, x, H-25), 1.03 (3H, s, H-30), 1.08, 1.91 (2H, m, H-1), 1.09 (3H, s, H-24 ), 1.19 (3H, s, H-28), 1.27 (3H, s, H-23), 1.32, 2.82 (2H, m, H-22), 1.41, 1.68 (2H, m, H-21), 1.51, 1.69 (2H, m, H-6), 1.71 (3H, s, H-27), 1.73, 2.07 (2H, m, H-15), 1.92, 2.65 (2H, m, H-19), 1.96, (2H, m, H-2), 2.16 (1H, br s, H-9), 3.52 (1H, dd, J = 5.2, 10.5 Hz, H-3), 3.98 (1H, t, J = 3.0 Hz, H-16), 5.74 (1H, d, J = 10.8 Hz, H-12) 6.71 (1H, d, J = 10.8 Hz, H-11).

¹³ C NMR (100 MHz, Pyridine) δ 16.5 (C-24), 17.6 (C-26), 18.9 (C-25), 19.4 (C-6), 22.3 (C-27), 25.2 (C-29 ), 27.4 (C-28), 28.6 (C-2), 29.0 (C-23), 31.7 (C-22), 32.3 (C-15), 33.0 (C-30), 33.1 (C-7) , 33.2 (C-20), 35.9 (C-21), 37.4 (C-10), 39.0 (C-1), 39.2 (C-19), 39.8 (C-17), 40.0 (C-4), 41.7 (C-8), 42.5 (C-14), 54.4 (C-9), 55.8 (C-5), 74.4 (C-16), 78.5 (C-3), 126.2 (C-12), 126.9 (C-11), 134.0 (C-13), 135.4 (C-18).

Of the compounds represented by Chemical Formulas 1 to 21, the compounds represented by Chemical Formulas 3, 5, 7, 8, 9, 11, 15, 17, 18, 19, 20, and 21 were found to be novel compounds.

Hereinafter, an example of a pharmaceutical preparation or health food containing a roe deer urine extract, a roe deer urine fraction, a triterpene compound or a pharmaceutically acceptable salt thereof will be described.

Formulation example  1: Preparation of Pharmaceutical Formulations

1-1. Powder  Produce

Roe deer urine extract, fraction, triterpene compound or salt 2 g

1 g lactose

After mixing the above components, the airtight cloth was filled to prepare a powder.

1-2. Manufacture of tablets

Roe deer urine extract, fraction, triterpene compound or salt 100 mg

100 mg corn starch

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

1-3. Preparation of Capsules

Roe deer urine extract, fraction, triterpene compound or salt 100 mg

100 mg corn starch

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.

1-4. Preparation of Injection

10 µg / ml roe deer urine extract, fraction, triterpene compound or salt

Dilute hydrochloric acid BP until pH 3.5

Injectable sodium chloride BP up to 1 ml

Dissolve the roe deer urine extract or triterpene compound isolated therein in an appropriate volume of sodium chloride BP for injection, adjust the pH of the resulting solution to pH 3.5 with dilute hydrochloric acid BP, and adjust the volume with sodium chloride BP for injection. Adjusted and mixed well. The solution was filled into a 5 ml Type I ampoule made of clear glass, encapsulated under an upper grid of air by dissolving the glass, and sterilized by autoclaving at 120 ° C. for at least 15 minutes to prepare an injection solution.

Production Example  2: manufacture of health food

2-1. Manufacture of beverages

522 mg of honey

Chioctosanamide 5 mg

Nicotinamide 10 mg

Riboflavin Sodium Hydrochloride 3 mg

Pyridoxine hydrochloride 2 mg

Inositol 30 mg

Orthoic acid 50 mg

Roe deer urine extract, fraction, triterpene compound or salt 0.48-1.28 mg

200 ml of water

With the above composition and content, drinks were prepared using conventional methods.

2-2. Chewing gum  Produce

Gum base 20%

Sugar 76.36-76.76%

Roe deer urine extract, fraction, triterpene compound or salt 0.24-0.64%

1% fruit flavor

Water 2%

Chewing gum was prepared using conventional methods using the above composition and content.

2-3. Candy

50-60% sugar

Starch syrup 39.26 ~ 49.66%

Roe deer urine extract, fraction, triterpene compound or salt 0.24-0.64%

Orange flavor 0.1%

Candy was prepared using conventional methods with the above composition and content.

2-4. Manufacture of Flour Food

0.5 to 5 parts by weight of a roe deer urine extract, fraction, triterpene compound or salt according to the present invention is added to 100 parts by weight of flour, and the bread, cake, cookies, crackers and noodles are prepared using the mixture to prepare foods for health promotion. Prepared.

2-5. dairy product( dairy products Manufacturing

5-10 parts by weight of a roe deer urine extract, fraction, triterpene compound or salt according to the present invention was added to 100 parts by weight of milk, and various dairy products such as butter and ice cream were prepared using the milk.

2-6. Linear  Produce

Brown rice, barley, glutinous rice, and yulmu were alphad by a known method, and then dried and roasted.

Black beans, black sesame seeds, and perilla were also steamed and dried by a known method, and then powdered into powder having a particle size of 60 mesh.

The grains and seeds prepared above and the roe deer urine extract, fraction, triterpene compound or salt according to the present invention were formulated in the following ratio.

Brown Rice 30%

15% rate

Barley 20%

Perilla 7%

Black Bean 7%

7% black sesame seeds,

Roe deer urine extract, fraction, triterpene compound or salt 3%

Ganoderma 0.5%

Foxglove 0.5%

Figure 1 is a simplified schematic of the preparation of extracts, fractions and compounds isolated from the present invention.

Claims (14)

A pharmaceutical composition for preventing and treating cancer containing roe deer urine extract as an active ingredient. The pharmaceutical composition for preventing and treating cancer according to claim 1, wherein the roe deer urine extract is an extract extracted from water, C ₁ to C ₄ alcohol or a mixture thereof. The pharmaceutical composition for preventing and treating cancer of claim 2, wherein the roe deer urine extract is an extract extracted with C ₁ ~ C ₄ alcohol. According to claim 2, wherein the alcohol is a pharmaceutical composition for preventing and treating cancer, characterized in that methanol or ethanol. A pharmaceutical composition for preventing and treating cancer, containing roe deer urine fraction as an active ingredient. According to claim 5, The roe urum fraction is obtained by suspending the roe urum extract of claim 1 in water and fractionated with hexane or by performing column chromatography using a mixed solvent of hexane, chloroform and methanol as an eluent A pharmaceutical composition for preventing and treating cancer, characterized in that obtained. A pharmaceutical composition for preventing and treating cancer, containing any one or more selected from the group consisting of the triterpene compounds of 1) to 21) and pharmaceutically acceptable salts thereof as an active ingredient. 1) 3beta-hydroxyolean-12-ene-27-ioic acid; 2) 3 alpha-acetoxyoleane-12-ene-27-eoic acid; 3) 3beta, 24-dihydroxyolean-12-ene-27-oic acid; 4) astilbic acid; 5) 3beta-acetoxy-6beta-hydroxyolean-12-ene-27-oic acid; 6) 3beta, 6beta, 24-trihydroxyolean-12-ene-27-oic acid; 7) 3beta, 6beta-dihydroxy-24-norolean-12,4 (23) -diene-27-oic acid; 8) 3beta-hydroxyolean-12-ene-27-ioic acid; 9) 3beta-hydroxyolean-12-ene-27-al; 10) 3beta-hydroxyl-12-ene-27-oic acid; 11) 3beta-acetoxyurse-12-ene-27-ioic acid; 12) 3beta, 24-dihydroxyurse-12-ene-27-oic acid; 13) 3beta, 6beta-dihydroxyurse-12-ene-27-oic acid; 14) 3beta-acetoxy-6β-hydroxyurse-12-ene-27-ioic acid; 15) 3beta, 6beta, 24-trihydroxyurse-12-ene-27-oic acid; 16) 3-alpha-acetoxyurse-12-ene-27-eoic acid; 17) 18 alpha-oleanan-3 beta, 19 alpha-diol; 18) 18 alpha-uric acid-3 beta, 6 alpha, 19 beta-triol; 19) 18 alpha-uric acid-3 beta, 6 alpha, 20 beta-triol; 20) 6 alpha-acetoxy-18 alpha-uric acid-3 beta, 20 beta-diol; And 21) olean-11,13 (18) -diene-3beta, 16 alpha-diol; The pharmaceutical composition for preventing and treating cancer according to claim 7, wherein the triterpene compounds of 1) to 21) are separated from the roe deer urine extract of claim 1 or the roe deer urine fraction of claim 5. The method according to claim 7, wherein the triterpene compounds of 1) to 21) are Extracting the roe deer urine with water, C ₁ ~ C ₄ alcohol or a mixed solvent thereof to obtain a roe deer urine extract (step 1); Fractionating the roe deer urine extract obtained in step 1 with hexane to obtain a roe deer urine fraction (step 2); Performing a silica gel column chromatography on the roe deer urine fraction obtained in step 2 to obtain a fraction containing the triterpene compound as a main component (step 3); And A pharmaceutical composition for preventing and treating cancer, characterized in that the fraction obtained in step 3 is separated by performing a combination of normal phase, reverse phase column chromatography or solvent recrystallization to separate the triterpene compound (step 4). . The pharmaceutical composition of claim 9, wherein the alcohol of step 1 is methanol or ethanol. 10. The method of claim 9, wherein the step 3 is to prevent the cancer, characterized in that to perform the normal silica gel column chromatography while increasing the solvent polarity of the hexane and chloroform mixed solvent in a concentration gradient eluent of 50: 1 to 0: 100 sequentially And therapeutic compositions. 10. The method of claim 9, wherein Step 4 is performed by performing a normal phase column chromatography using a mixed solvent of hexane and ethyl acetate as an eluent and then combining a normal phase, reverse phase or solvent recrystallization method, or a mixed solvent of acetonitrile and water as an eluent. After performing reverse phase chromatography as a reverse phase column chromatography, characterized in that the pharmaceutical composition for preventing and treating cancer. The cancer according to any one of claims 1 to 12, wherein the cancer is liver cancer, stomach cancer, colon cancer, breast cancer, lung cancer, non-small cell lung cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, skin or ocular melanoma, uterus Cervical cancer, ovarian cancer, colon cancer, small intestine cancer, rectal cancer, anal muscle cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small intestine cancer, lymph node cancer, Bladder cancer, gallbladder cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate cancer, chronic or acute leukemia, lymphocyte lymphoma, bladder cancer, kidney or ureter cancer, kidney cell carcinoma, renal pelvic carcinoma, Pharmaceutical nervous system for preventing and treating cancer, characterized in that it is one selected from the group consisting of central nervous system (CNS) tumor, primary CNS lymphoma, spinal cord tumor, brain stem glioma and pituitary adenoma. Water. A health food composition for cancer prevention or improvement comprising the roe deer urine extract, roe deer urine fraction, triterpene compound or pharmaceutically acceptable salt thereof as an active ingredient of any one of claims 1 to 12.

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