CN101553497A - Anti-tumor compounds for inhibiting cancer growth - Google Patents

Anti-tumor compounds for inhibiting cancer growth Download PDF

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CN101553497A
CN101553497A CNA2007800407444A CN200780040744A CN101553497A CN 101553497 A CN101553497 A CN 101553497A CN A2007800407444 A CNA2007800407444 A CN A2007800407444A CN 200780040744 A CN200780040744 A CN 200780040744A CN 101553497 A CN101553497 A CN 101553497A
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陈沛光
麦美送
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Pacific Arrow Ltd
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Abstract

This invention provides a method for treating cancer by blocking the migration, metastasis of cancer cells, growth of cancers wherein the cancers comprise breast cancer, leukocyte cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer or cervix cancer. This invention provides uses of compositions comprising a triterpenoidal saponin, triterpenoid, triterpenoidal compound or sapongenin, comprising at least two side groups selected from the group consisting of angeloyl groups, tigloyl groups and senecioyl groups, wherein the side groups are attached to carbon 21, 22 or/and 28 of triterpenoidal sapogenin, triterpenoid, triterpenoidal compound or other sapongenin backbones.

Description

The antineoplastic compound that can restrain growth of cancer cells
This patent requires to obtain U.S. Patent application book (U.S.Serial NO.60/841.727, on September 1st, 2006 submitted, U.S.Serial NO.60/890,380, on February 16th, 2007 submitted) and international patent application book (NO.PCT/US2006/016158, on April 27th, 2006 submitted) in desired right or right of priority.Above-mentioned U.S. Patent application book and international patent application book require to obtain desired right or right of priority in the following application for patent again, they are (1) U.S. Patent application book (U.S.Serial NO.11/289,142, on November 28th, 2005 submitted, U.S.SerialNO.11/267,523, on November 4th, 2005 submitted), (2) the international patent application book (NO.PCT/US2005/031900, on September 7th, 2005 submitted, this application book requires to obtain the U.S. Patent application book again, U.S.Serial NO.60/617, on October 8th, 379,2004 was submitted U.S.SerialNO.60/613,811, submitted NO.60/607 on September 27th, 2004, desired right or right of priority in submitting on September 7th, 858,2004 with U.S.Serial.), (3) U.S. Patent application book U.S.Serial NO.11/131 submitted on May 17th, 551,2005 and (4) U.S. Patent application book U.S.Serial NO.11/117, and on April 27th, 760,2005 submitted.This patent also is U.S. Patent application book U.S.Serial NO.10/906, the continuation of 303 (on February 14th, 2005 submitted), and U.S. Patent application book U.S.Serial NO.10/906,303 (on February 14th, 2005 submitted) are again and international patent application book (NO.PCT/US04/43465, on December 23rd, 2004 submitted) continuation, and international patent application book (NO.PCT/US04/43465, on December 23rd, 2004 submitted) be again international patent application book (NO.PCT/US04/33359, on October 8th, 2004 submitted) continuation, and international patent application book (NO.PCT/US04/33359, on October 8th, 2004 submitted) obtain U.S. Patent application book (U.S.Serial NO.60/532.101 again, on December 23rd, 2003 submitted, U.S.Serial NO.60/509, on October 9th, 851,2003 submitted)) in desired right of priority right.The content of the application for patent that these are being authorized thereby should include in the present patent application all sidedly.
Invention field
The present invention relates to energy is antitumor or restrain the cancer growth compound and chemical constitution thereof.
Background of invention
We have proved that the extract that extracts has the effect of restraining growth of cancer cells from this kind of plant of Wood of Shinyleaf Yellowhorn (Xanthoceras sorbifolia Bunge).This compound that can restrain growth of cancer cells is purified from extract and is accredited as new triterpenoid saponin, called after Xanifolia-Y and family thereof.
Varix is the swelling and the kink of vein, and varix can take place at any position of human body, particularly at the sura position, and the inboard of shank or anus.Escin (ascin) is used for treating varix and chronic venous insufficiency is respond well for many years.Escin is the saponin mixture that extracts from the horse-chestnut of Hippocastanaceae (Nippocastanaceae) (Aesculus nippocastanum L.) seed.Escin is a main activeconstituents wherein.Find that in a comparative experimental research escin can be used for treating chronic venous insufficiency as a kind of alternative medicine in as pressure therapy.The effect of this alternative medicine also in various animal models, be confirmed (asking for an interview the test of the department of pharmacy of Milan, ITA university, Via Balzaretti 9,20133 Milano).International patent application book (NO.PCT/US04/33359, on October 8th, 2004 submitted) and U.S. Patent application book (U.S.Serial NO.10/906,303) have disclosed the new saponin compound that has two angeloyl groups.Chen Yingjie etc. have reported the 4 kinds of saponins (Chem.Pharm.Bull.33 (1): 127-134 that separates from Wood of Shinyleaf Yellowhorn; 1985,198533 (3): 1043-1048; 1985,33 (4): 1387-1394).The research of the relevant saponin that other is relevant has: Voutquenne etc. (2002) isolate triterpenoid saponin and acyl group sapogenin from breathe out general wood (Harpolliaaustro-caledonica); Zhong (1999) etc. isolates 6 kinds of triterpenoid saponins from Root of Japanese Maesa (Maesa laxiflora); separate the triterpenoid saponin that makes new advances in the Young green colored pittosporum tobiras (Pittosporum viridiflorum) from the Madagascar rainforest such as (2002); Yang etc. (1999) isolate the triterpenoid saponin of anti-HIV-1 proteolytic enzyme from Chinese horse-chestnut (Aesculus chinensis) seed; Lu etc. (2000) isolate triterpenoid saponin from (Camellia sinensis var.assamica) root; Apers etc. (1999) separate the acyl group triterpenoid saponin that makes new advances from band leaf Root of Japanese Maesa (Maesa laxiflora); (2002) such as D ' Acquanca isolate 4 kinds of new triterpenoid saponins and esterification saponin from pittosporum tobira (Pittosporum tobira) fruit; and the research of chemical structure; (U.S.patent 6 for United States Patent (USP); 210,680) disclosed the method for preventing and treating chronic venous insufficiency.The document of present patent application has also comprised the content of above-mentioned document.
The present invention proves that the saponin of two angeloyl groups has the vigor of very strong supression growth of cancer cells, blood vessel formation against function, and the effect of hemorrhoid is dwindled in the effect of treatment chronic venous insufficiency, restrains postoperative edema and the rheumatismal effect of treatment.
The present invention discloses those special structures in the saponin has the ability of restraining growth of cancer cells and brings out cancer cell-apoptosis.
Surrounded by water around the human cell.Water outer membrane protein (aquaporin) is that the water of supermembrane transmits protein, and it is great in the effect of dredging through cell and epithelium in the moisture process.The present invention proves that the vigor that two angeloyl groups triterpenoid saponins have very strong supression growth of cancer cells reaches by the function that influences film.Two angeloyl groups triterpenoid saponins can influence the penetrativity of water outer membrane protein and cytolemma.
Summary
The brief summary of patent of the present invention, obvious for the emphasis clause radical valence that makes invention, the content of other clauses may be simplified in this summary even omit, and still, this does not show that patent of the present invention only limits to the content that these are mentioned in summary.More detailed description will be carried out by chapters and sections below.
Patent disclosure of the present invention the purposes of one class saponin; it is characterized in that described compound contains triterpene or other sapogenin; former or other saponin of this triterpenoid saponin is former to have two Radix Angelicae Sinensis acid amides or at least two side chain compounds are made up of following group: angeloyl groups; crotonyl (tigloyl) and/or squaw weed acyl group (senecioyl); and these two side chains will be bound up on the former (triperpenoidal of triterpenoid saponin; triperpenoid) and on the carbon 21 of the former female ring of other saponins and 22, or/and on 28 in the carbon.The method of purifying and measuring these compounds ask for an interview international patent application book (NO.PCT/US05/31900, on September 7th, 2005 submitted) and U.S. Patent application book (U.S.Serial NO.11/289142, September 28 in 2005 submitted; U.S.Serial NO.11/131551, May 17 in 2005 submitted).The document of present patent application has also comprised the content of above-mentioned document.
We have proved that the extract that extracts has the effect of restraining growth of cancer cells from this kind of plant of Wood of Shinyleaf Yellowhorn (Xanthoceras sorbifolia Bunge).This compound that can restrain growth of cancer cells is purified from extract, and be accredited as new triterpenoid saponin, called after Xanifolia-Y and family thereof, see U.S. Patent application book (U.S.Serial NO.10/906,303) and international patent application book (NO.PCT/US2004/033359) for details.
A lot of human body ovarian cancers are implanted in the intravital experimental result of mouse and show, Xanifolia-Y can prolong the life of the mouse of human body ovarian cancer transplanting, and this explanation Xanifolia-Y can be used for the treatment of the cancer of mammal.Here concretely, Xanifolia-Y also may be used for the treatment of people's cancer, as ovarian cancer.
Xanifolia-Y can prolong the life of the mouse of human body ovarian cancer transplanting, is because Xanifolia-Y has stoped the transfer of cancer cells.Here concretely, Xanifolia-Y can influence proteinic bonding, or the function of interfere with cancer cells or mesothelial cell's molecule.The growth of cancers that suppresses mammal.So Xanifolia-Y can be used for the treatment of cancer.See test 7,8,9 and 10 for details.
The invention discloses the ability that the saponin with special chemical structure possesses anticancer growth and angiogenesis inhibitor.
The invention provides the treatment method for cancer, it is characterized in that bringing out the described cancer of cancer cell-apoptosis and comprise mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, melanoma cancer, kidney, or cervical cancer.
The present invention relates to the mechanism of anticancer growth, it is characterized in that described mechanism is that all compounds with triterpene and two Radix Angelicae Sinensis acid amides can be by regulating and control and influence the function anticancer growth of the water outer membrane protein of cancer cells.What here refer to concretely, is exactly to have angeloyl groups, particularly two angeloyl groups saponins.
The present invention relates to the approach of water outer membrane protein, it is characterized in that the function anticancer of the water outer membrane protein that described approach is two angeloyl groups saponins by influence cancer cells is grown.
The detailed description of figure
Fig. 1. the chemical structure of two angeloyl groups saponins.
Fig. 2 A, the chemical structure of 2B. saponin.
Fig. 3. the chemical structure of saponin.
Fig. 4 A and B. compound Y (two angeloyl groups saponin) and compounds X (single Radix Angelicae Sinensis acyl saponin) suppress the comparison of ovarian cancer cell energy for growth.The IC50 of compound Y is 1.5 μ g/ml and compounds X IC50 is 30 μ g/ml.
The compound Y that Fig. 4 C. purifies suppresses the skin cancer cell growth.The IC50 of compound Y is 0.23 μ g/ml.
Fig. 4 D.Xanifolia-X, B-Escin, the hemolytic action of ACH-Y and AKOH-Y.
Fig. 5 .A. measures compound Y with mtt assay with ovarian cancer cell, Y8, the ability of the anticancer growth of Y9 and Y10.
5.B. the growth that compound Y1 that purifies and Y2 can suppress ovarian cancer cell.
5.C. can suppress the ovarian cancer cell growth, IC50 is 4 μ g/ml.Compounds X only has the ability of angeloyl groups inhibition ovarian cancer cell growth lower in 22 in carbon, and IC50 is 6 μ g/ml.The compd A CH-Y that is removed sugar chain but preserves angeloyl groups also preserves the ability of 40% inhibition ovarian cancer cell growth, and IC50 is 9.5 μ g/ml.When the compd A KOH-Y after being removed fully of acyl group that returns of compound Y has then completely lost the ability that suppresses the ovarian cancer cell growth, IC50 is 120 μ g/ml.Angeloyl groups in these test-results proofs Y series compound is most important to the ability that suppresses the ovarian cancer cell growth.
Fig. 5 .D. compounds X anifolia-Y, B-Escin, the comparison of the ability of Xanifolia-X and the growth of AKOH-Y anticancer.
Fig. 6. the ability (C and D) that the mtt assay of comparative compound Ys and saponin is grown with the mensuration anticancer, and hemolytic action (A and B).
Fig. 7. be used for the saponin Y of MTT test, X, compd B-Escin, the purification of B-Escin and AKOH-Y, the mensuration of chemical structure (with nucleus magnetic resonance and mass spectroscopy).
The nuclear-magnetism spectrum (NMR 1H) of Fig. 8 .A. compound Y0, the nuclear-magnetism spectrum (NMR 13C) of B. compound Y0.
The TOSCSY of Fig. 9 .A. compound Y0, the HMQC of B. compound Y0.
The HNBC of Figure 10 .A. compound Y0, the NOESY of B. compound Y0.
Figure 11. the structure of compound Y0.
Figure 12-16. compounds X anifolia-Y1 suppresses the ability of following growth of cancer cells: leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, melanoma cancer, ovarian cancer, kidney, prostate cancer and mammary cancer.
Figure 17-
Figure A20078004074400151
Compounds X anifolia-Y2 suppresses the ability of following growth of cancer cells: leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, melanoma cancer, ovarian cancer, kidney, prostate cancer and mammary cancer.
Figure 22. experimentation on animals is the result show, transplanted cancer and the A of medication group mouse is just not dead at 19-22 days.Transplant cancer and used the B group mouse of medicine can survive more than 50 day.Do not transplant cancer also not the C of medication group mouse also survived more than 50 day.
Figure 23. experimentation on animals is the result show, transplanted cancer and the A of medication group mouse is just not dead at the 24th day.Transplanted cancer and used the D group mouse of 9 times medicine all to survive at the 4th day.Transplant cancer and used 10 times the E group mouse of medicine only under 50% survival on the 10th day.
Figure 24. experimentation on animals is the result show, the tumour of having transplanted the mouse of cancer medication is to have transplanted cancer and 45% of the mouse of medication (in 10 days) not.
Figure 25. the cancer cell-apoptosis experimental result shows that cancer cell-apoptosis is to bring out apoptotic principal mode by compounds X anifolia-Y.
Figure 26 .EM experimental result shows, compounds X anifolia shows that to the influence of film the cell discovery cytolemma of being handled by Xanifolia-Y has spot shape den (Fig.34B), but in contrast, do not find that at the cell of being handled by DMSO (Fig.34A) or AKOH-Y (Fig.34C) cytolemma has spot shape den.The diameter of these dens is from 80A to 500A.These dens are the holes that form on cytolemma.The arrangement of den has characteristics very much, and little den (80A) is positioned at the periphery, and big den (500A) is positioned at the center.Big hole is to form (Fig.34D) by little hole is warm.The image A of cytolemma: DMSO solvent treatment 60min (X 60,000), contrast; B:Xanifolia-Y 5 μ m handle 60min (X 60,000); C:AKOH-Y 20 μ m handle 60min (X 60,000) and D:Xanifolia-Y 5 μ m handle 60min (X 20,000).
Figure 27. the comparison of the ability of compounds X anifolia and the growth of taxol anticancer.
Figure 28. the vigor of compound Ys.
Figure 29. the animals survived test.
Figure 30. the nuclear-magnetism spectrum of compound Y7, A:HNMR; B:HMBC.
Figure 31. the nuclear-magnetism spectrum of compound Y7, A:HMQC; B:NOESY.
Figure 32. the evaluation of water outer membrane protein.
Figure 33. compound triterpenoid saponin compound suppresses the comparison of the ability of ovarian cancer and cervical cancer cell growth.
Figure 34-36. compounds X anifolia Y0 suppresses the ability of following growth of cancer cells: leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, melanoma cancer, ovarian cancer, kidney, prostate cancer and mammary cancer.
Figure 37-39. compounds X anifolia-Y9 suppresses the ability of following growth of cancer cells: leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, melanoma cancer, ovarian cancer, kidney, prostate cancer and mammary cancer.
The detailed description of patent application
The invention provides us and screen the result of active compound research from the plant of self-sow, said here plant mainly is the plant of Sapindaceae (Sapidaceae), and it has 140-150 to belong to and the 1400-2000 kind of plant.In this research, the method of purification extract and the method for biological assay, the method that comprises MTT ask for an interview international patent application book (NO.PCT/US05/31900, on September 7th, 2005 submitted) and U.S. Patent application book (U.S.Serial NO.11/289142, September 28 in 2005 submitted; U.S.Serial NO.11/131551, May 17 in 2005 submitted).The document of present patent application has also comprised the content of above-mentioned document.
Patent disclosure of the present invention contain the purposes of triterpenoid saponin compound compositions; it is characterized in that described saponin contains triterpenes or other sapogenin; sugar chain; two Radix Angelicae Sinensis acid amides or at least two side chains are made up of following group: angeloyl groups; along root of Dahurian angelica acyl group (tigloyl) and/or squaw weed acyl group (senecioyl), and these two side chains will be bound up on the carbon 21 of the former female ring of saponin and 22.Here, following at least group is connected on the side chain: angeloyl groups, along root of Dahurian angelica acyl group and/or squaw weed acyl group, alkyl; benzoyl, chain is played acyl group, alkenoyl, the alkanoyl l that the phenmethyl alkyl replaces; aromatic base, acyl group, heterogeneous ring compound or heterocyclic aromatic compounds.Here the sugar chain of said saponin contains one or more following sugar and uronic acid at least: glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar ... and uronic acid, as D-glucuronic acid and D-galacturonic acid; Or their derivative, or the various combinations of above-mentioned carbohydrate.Glucuronic acid in this case, semi-lactosi and pectinose are the selections of the best in these sugar.
Patent disclosure of the present invention the composition of a composition; it is characterized in that form at least two side chains and form by following group: angeloyl groups; along root of Dahurian angelica acyl group and squaw weed acyl group; and these two side chains will be bound up on triterpenoid saponin, and former (triperpenoidal is triperpenoid) and on the former female ring of the former female ring saponin of other saponin.These compounds of forming composition extract or synthetic from above-mentioned indicated plant.
The invention discloses the processing method of the above-mentioned saponin of preparation, it is characterized in that described processing method is as follows: (1) uses the shell of the above-mentioned indicated plant of organic solvent lixiviate, branch, do leaf, kernel, root, bark, or plant shell and get the organic solvent extractive substance, it is characterized in that described organic solvent is ethanol or methyl alcohol; (2) collect the organic solvent extractive substance; (3) reflux heat is carried, and gets extract for the second time; (4) reclaim organic solvent and get fluid extract; (5) dry and sterilization fluid extract gets the powdery crude extract; (7) usable highly effective liquid chromatography (HPLC) and quick-acting liquid chromatography (FPLC) are with C18 silicagel column or other corresponding solid phase material) powdered extract is separated into one or more component; (8) if use high performance liquid chromatography (HPLC) and quick-acting liquid chromatography (FPLC), detecting absorbing wavelength is that 207nm is to 500nm; (9) bioactive component is provided in evaluation from said components; (10) separate with quick-acting liquid chromatographies (FPLC) and the composition of the above-mentioned biologically active of purifying; (11) use high performance liquid chromatography (HPLC) to isolate the compound of biologically active again.
The invention discloses the mtt assay of measuring saponin or other compound anti-cancering activity, it is characterized in that described antitumour activity draws by the mtt assay check with 11 kinds of human cancer cells.These 11 kinds of human body cells are: HTB-9 (bladder), HeLa-S3 (uterine neck), DU145 (prostate gland), H460 (lung), MCF-7 (mammary gland), k562 (white corpuscle), HCT116 (colon), HepG2 (liver), U20S (bone), T98G (brain), and OVCAR-3 (ovary).These 11 kinds of human body cells are to obtain from US mode DSMZ (American Type CultureCollection).Cultivate: HeLa-S3 (uterine neck), DU145 (prostate gland), MCF-7 (mammary gland), HepG2 (liver) and T98G (brain) cell cultures are on MEN (Earle salt) substratum.HTB-9 (bladder), H460 (lung), 562 (white corpuscles) and OVCAR-3 (ovary) cultivate on the RPMI-1640 substratum, and other cell is on the McCoy-5A substratum.These substratum all will add 10% fetal bovine serum, glutamine and antibiotic.At CO 2Concentration is 5% interior cultivation of incubator.
MTT detects detection method substantially according to the method for Carmicheal et al.1987.These cell cultures in the vesicle of the culture dish that 96 vesicles are arranged 24 hours; Every cave 10,000 HTB-9 (bladder), HeLa-S3 (uterine neck), H460 (lung), HCT116 (colon), T98G (brain), and the cell of OVCAR-3 (ovary); Every cave 1.5 ten thousand DU145 (prostate gland), MCF-7 (mammary gland), the cell of HepG2 (liver) and U20S (bone); Every cave 40,000 k562 (white corpuscle).Then, the sample of Lignum Xanthoceratis extract is put into the cave, cultivate 48 hours (liver and osteocarcinoma cell 72 hours, breast cancer cells 96 hours again.Then, MTT (0.5mg/ml) adds in each cave, cultivates 1 hour.The formazan that produces is dissolved in DMSO, uses ELISA reader (Dynatech, Model R700) to survey its O.D. value (TD) then.Adding the preceding MTTO.D. value (TO) of sample also will measure.The percentage ratio (%G) of every kind of cell growth can be obtained by following formula
％G＝(TD-TO/TC-TO)x100(1)
(TC is the O.D. value of control cells group)
When TO＞TD, then cell-specific toxic reaction (LC) value is:
％LC＝(TD-TO/TO)x100(2)
Patent disclosure of the present invention can anticancer the composition of growth, it is characterized in that described cancer comprises but is not limited to bladder cancer, osteocarcinoma, the cancer of the brain and ovarian cancer.
Patent disclosure of the present invention can treat the composition of following disease, it is characterized in that described composition contains the triterpenoid saponin compound of some amount, Xanifolia Y, Y1, Y2, Y7, Y8, Y9, Y10 and Y0 and derivative thereof.Medicable illness comprises: chronic venous insufficiency, chronic venous disease, varix, varix symptom, venous stasis, eliminate the phlegm, the peripheral vessel disorder, cerebral tissue is fainted from fear, cerebral circulation disorder, cerebral edema, psychosis, dysmenorrhoea, hemorrhoid, episiotomy, the tip oedema forms, and postoperative edema reduces the skelagia symptom, reduces the stomachache symptom, itch, shank swelling, thrombosis, thrombophlebitis, rheumatosis, stomach ulcer, antispastic and antitumor.
The present invention discloses the mechanism of restraining growth of cancer cells, it is characterized in that described mechanism is to reach by the function that influences the water outer membrane protein.The present invention has also disclosed the method for restraining growth of cancer cells, it is characterized in that described method is to reach by the consumption of adjusting influence or acting on the compound of cancer cells surface water outer membrane protein.Here said compound is the compound that contains two angeloyl groups, and their chemical structural formula has 5 kinds: (1), and (1A); (1B), (1C) and (1D), this compound contains triterpene sapogenin; two angeloyl groups and sugar chain; it is following Xanifolia series: Y, Y1, Y2; Y7; Y8, Y9, Y10 and Y0 compound a kind of.Under a certain situation, this compound is Xanifolia (x), and Escin or Aecin's is a kind of.In another case, this compound is a kind of of compd A-X in this application for patent and A1-X1.
Patent disclosure of the present invention suppress the method for cancer cell growth, it is characterized in that described method is the static load that increases cancer cells, here be exactly to increase water in the cancer cells to flow and pass the cytolemma kill cancer cell.The compound that this patent provides can be started passage to protein, or for the ion family of opening the door, makes protein molecule or ion pass the cytolemma kill cancer cell.
Here the vocabulary of usefulness " inhibition " means the growth and the kill cancer cell of overslaugh cancer cells.
Patent disclosure of the present invention a kind of interference water outer membrane protein method, regulate the channel of water by disturbing the water outer membrane protein, adjust uropoiesis, regulate the water metabolism of the health of water, reduce urine amount and number of micturitions, treatment enuresis disease and frequent micturition.And influence or act on the water outer membrane protein on cancer cells surface by the method that adjusting is used for the dosage of cancer cells compound.Here said compound is the compound that contains two angeloyl groups, and their chemical structural formula has: (1), and (1A); (1B) and (1D); this compound contains triterpene sapogenin, two Radix Angelicae Sinensis acid amides and sugar chain, and it is following Xanifolia series: Y; Y1; Y2, Y7, Y8; Y9, Y10 and Y0 compound a kind of.Under a certain situation, this compound is Xanifolia (x), and Escin or Aecin's is a kind of.In another case, this compound is a kind of of compd A-X in this application for patent and A1-X1.
Patent disclosure of the present invention a kind of triterpene sapogenin that contains; the compound of two angeloyl groups; it is characterized in that described compound interference cell water outer membrane protein method; regulate the passage of water by disturbing the water outer membrane protein; secrete adjustment Fen; bring out cancer cell-apoptosis, suppress tumor growth and stop cancer metastasis, kill cancer cell.Patent disclosure of the present invention a kind of composition, it is characterized in that described composition regulates the passage of water by interference cell water outer membrane protein, bring out cancer cell-apoptosis, make the tumor growth that the medicine inhibitor suppresses the overexpression of cellular water outer membrane protein.Said composition contains following arbitrary compound of some amount: Y, Y1, and Y2, Y7, Y8, Y9, Y10 and Y0, or its salt, the ester meta-bolites, or derivatives thereof suppresses tumour or growth of cancer cells as a kind of medicine, the treatment cancer.Here the cancer of saying comprises mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, melanoma cancer, kidney, or cervical cancer.
The water outer membrane protein be a series of in fluid transmission the passage of many endotheliums and deckzelle homologous water.Mammals water outer membrane protein contains 11 members, and water outer membrane protein 0-10, each member have its special tissue.Their function test shows that Mammals water outer membrane protein 1,2,4,5 and 8 may be water delivery, and water outer membrane protein 3,7,9 and 10 is also carried glycerine and other little solute.The water outer membrane protein is expressed at some positions of water outer membrane protein of cytolemma.The water outer membrane protein is that cornea and lacteal vessel and other organize strong expression to come out at most of microvasculars of brain endothelium outside,
Water outer membrane protein 1 is very general on the film of the microvascular of all ovary epidermis tumours and [, but less on the tenuigenin of tumour.In addition, water outer membrane protein 1 is also found to be present on the mesenchymal cell film of ovarian tumor and was observed.Please refer to Yang, JH (2006IGCS): The influence of aquaporin-1 andmicrovessel density on ovarian carcinogenesis and ascites formation.International Journal of Gynecological Cancer 16 (suppl.1) KazuyoshiMurata et al. (2000): Structural determinats of water permeationthrough aquaporin-1.Nature, Vol.407, October 5.
The water outer membrane protein 1,2,3,4 on different cells, and 5,6,7,8, the quantity of 9,10 distribution is different.Different tumour cells all has a certain special water outer membrane protein to show strongly.The abnormal function of finding these water outer membrane proteins increases relevant with the interference number of times.The compound of Xanifolia series can disturb and suppress the function of these cancer cells water outer membrane proteins.See international patent application book (NO.PCT/US2005/31900, on September 7th, 2005 submitted) and U.S. Patent application book (U.S.Serial NO.11/131551, May 17 in 2005 submitted) for details.
Western blotting is a molecular biology, and method commonly used is used for identifying the protein in even matter or the nonuniformity tissue in biological chemistry and the immunology.It comes isolated protein with gel electrophoresis, the protein after separating is taken out from gel be placed on usefulness on the film then, uses the special antibody of this water outer membrane protein is differentiated it.Can reflect the in this way quantity of the water outer membrane protein of surveying the sample of giving and the level of more several groups of water outer membrane proteins.Other method also can be reflected and be surveyed the water outer membrane protein of (immunocytochemistry) in tissue (immunohistochemistry) and the cell in addition.Mirror survey method in addition, as the Bradford protein determination, ultraviolet spectroscopy, the Biuret protein determination, the Lowry protein determination, Bicichonic acid protein assay method also is the method for using always.
A lot of about research water outer membrane protein as the article of the binding substances () of cancer cells, not can be used as the transfer that a kind of method stops cancer cells but there is one piece of article to mention adjusting or influence the water outer membrane protein, suppress or kill cancer cell.
Patent of the present invention has been described by regulating or influencing the water outer membrane protein and has been brought out cancer cell-apoptosis, the method for anticancer breeding or kill cancer cell.The water outer membrane protein can be regulated or influence to the saponin that contains two Radix Angelicae Sinensis acid amides here, thus anticancer breeding or kill cancer cell.But this compound following compounds is a kind of: (1), (1A), (1B) and (1D), this compound contains triterpene sapogenin, two angeloyl groups and sugar chain, and it is following Xanifolia series: Y, Y1, Y2, Y7, Y8, Y9, Y10 and Y0 compound a kind of.Under a certain situation, this compound is Xanifolia (x), and Escin or Aecin's is a kind of.In another case, this compound is a kind of of compd A-X in this application for patent and A1-X1.
Under certain conditions, this method is by adjusting or influences the breeding that the water outer membrane protein comes anticancer.In another case, this method is to come kill cancer cell by the penetrating ability of regulating or influence the water outer membrane protein and increase the cell film water.In another case, this method is to make extra water enter cancer cells with the damage cancer cells by regulating or influencing the water outer membrane protein.In another case, this method is to make the solute relevant with glycerine enter cancer cells with the damage cancer cells by regulating or influencing the water outer membrane protein.In another case, this method be by regulate or influence the water outer membrane protein regulate enter cancer cells water to damage cancer cells.In a little methods, be used to regulate or the compound that influences the water outer membrane protein is following Xanifolia series: Y Y1, Y2, Y7, Y8, Y9, Y10 and Y0 compound a kind of.
Under certain conditions, this method is to flow by the fluidic in the cell of regulating water outer membrane protein surplus to adjust extracellular concentration of fluid to cause the damage of cancer cells.This patent achieves the above object with the after birth permeability that attenuates, and the penetrating variation of cytolemma is caused by some water outer membrane proteins surpluses.
The regulating power of the compound of Xanifolia series is water outer membrane protein difference (water outer membrane protein 1,2,3,4,5,6,7,8,9,10) because of the different carcinoma cytolemma and difference.
Water outer membrane protein 1,2,3,4,5,6,7,8,9,10 quantity at different type cancer cells (as OCAR3, SKOV3, TOV21G and ES2) film on be different, so when with these cancer cells of compound treatment of Xanifolia series, the ability performance of its anticancer is also different.The compound of Xanifolia series contains triterpene sapogenin, the saponin of two angeloyl groups and sugar chain, but their structure differences, and the ability performance of anticancer is also different.The IC50 of Xanifolia Y is 1.5-4.5ug/ml, and the chemical structure of Xanifolia X and Xanifolia Y are very approximate, but in 22 in carbon an angeloyl groups is only arranged, and its IC50 is 6ug/ml.Remove sugar chain from Xanifolia Y, behind the two angeloyl groups (becoming ACH-Y) of reservation, the ability of anticancer has reduced but still has kept, and IC50 is 9.5ug/ml.
But, remove two angeloyl groups (becoming AKOH-Y) from Xanifolia Y after, the ability of anticancer has also just completely lost, although consumption is up to 120ug/ml.These results of study show that the two angeloyl groups in the Xanifolia compound are most important to anticancer.Thereby it is great in the effect that influences aspect the water outer membrane protein anticancer.
We are to compounds X anifolia Y (#63Y); the hemolytic action of the saponin standard substance of Escin and SIGMA compares; Xanifolia Y contains two angeloyl groups, and Escin contains an angeloyl groups, and the saponin standard substance of SIGMA extract from the Quillaia bark.The result shows that Xanifolia Y (#63Y) hemolytic action is higher than the saponin standard substance of Escin and SIGMA, and (NO.PCT/US2006/016158, on April 27th, 2006 submitted, Dkt#804-K-PCT) legend 6A to see the international patent application book for details.
Under certain conditions, these compounds that this patent provides are to increase by the static load that increases cancer cells to enter the moisture that increases cancer cells, make the cancer cells breakage.
This patent is described a kind of method, it is characterized in that described method is by regulating or influence the albumen on cancer cells surface or change the function of the intercellular film of cancer cells, or adjusting passes the fluid of cancer cells, or softening skin, or the structure of change skin, or the consumption system of adjusting cancer cells.
This patent is described a kind of water outer membrane protein method of regulating or influence, and it is characterized in that described method is to use the constituent that contains triterpenoid saponin to reach this purpose.Here triterpenoid saponin contains triterpenes or other sapogenin; one or more sugar chain, two angeloyl groups, or at least two side chains are made up of following group: angeloyl groups; along root of Dahurian angelica acyl group and/or squaw weed acyl group, and these two side chains will be bound up on the carbon 21 of the former female ring of saponin and 22.Here the sugar chain of said saponin contains one or more following sugar and uronic acid at least: glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination.Glucuronic acid in this case, semi-lactosi and pectinose are the selections of the best in these sugar.
Here at least two side chains of chemical structure of containing of this method compositions for use are made up of following group: angeloyl groups; along root of Dahurian angelica acyl group or squaw weed acyl group; and these two side chains will be bound up on triterpenoid saponin, and former (triperpenoidal is triperpenoid) and on the former female ring of the former female ring saponin of other saponin.These compounds of forming composition extract or synthetic from above-mentioned indicated plant.
This patent discloses and has been used to form 6 kinds of new saponins (Y, Y1, Y2, Y8, Y9 and Y10) that contain two angeloyl groups of used constituent and their chemical structure (face as follows).These the 6 kinds new saponins that contain two angeloyl groups all have anticancer and hemolytic action, and these 6 kinds of new saponin compounds were determined in international patent application book (NO.PCT/US2005/31900) and U.S. Patent application book (U.S.Serial NO.10/906303 and U.S.Serial NO.11/131551) already.The document of present patent application has also comprised the content of above-mentioned document.
Figure A20078004074400201
The chemical structure of these compounds, chemical name and common name are listed in table 1.
Chemical structure, chemical name and the common name of six new compounds of table 1. (Y, Y1, Y2, Y8, Y9 and Y10)
Six kinds of new compounds of table 1 (Y, Y1, Y2, Y8, Y9, molecular formula Y10), chemical name and title
Common name Molecular formula Chemical name
Xanifolia-Y(Y3) C 57H 88O 23 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, acyl group-3 β, 15 α return in the two parties of 22-O-; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin
Xanifolia-Y1 C 65H 100O 27 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O (3; acyl group is returned by the two parties of 4-)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin
Xanifolia-Y2 C 57H 88O 24 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3) β-D-glucuronic acid pyrans acyl group-21, the two parties of 22-O-are returned
Acyl group-3 β, 15 α, 16 α, 21 β, 22 α, 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin
Xanifolia-Y8 C 57H 87O 23 3-O-[β-glucose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β, 16 α return in the two parties of 22-O-; 21 β; 22 α, 24 β, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin
Xanifolia-Y9 C 65H 100O 27 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3; acyl group is returned by the two parties of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin
Xanifolia-Y10 C 57H 88O 22 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β returns, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-
This patent has been announced a kind of compounds X anifolia X of biologically active, and the olea triterpenoid saponin is characterized in that described compound has 3 sugar chains in 3 in carbon, and X contains, and in 22 in carbon an angeloyl groups is arranged.This compound is separated from Wood of Shinyleaf Yellowhorn (Xanthoceras sorbifolia Bunge) extract.The molecular formula of Xanifolia X is C 58H 92O 22Chemical name is 3-O-{[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyranoside butyl ester }-the 21-O-ethanoyl; acyl group-3 β returns in 22-O-party; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin, its chemical structure is as follows.
Figure A20078004074400211
Title: Xanifolia X.
This patent has also been announced a kind of compounds X anifolia Y0 of biologically active; the chemical name that it is characterized in that described compound is 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group; 22-O-(2-formyl propionyl)-3 β; 15 α; 16 α, 21 β, 22 α; 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin, its chemical structure as follows.
Figure A20078004074400221
This patent has also been announced a kind of compounds X anifolia Y7 of biologically active; the chemical name that it is characterized in that described compound is 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group; 28-O-(2-methylbutyryl base)-3 β; 15 α; 16 α, 21 β, 22 α; 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin, its chemical structure as follows.
This patent has also been announced a kind of method for the treatment of mammalian cancer, it is characterized in that described method is to give Mammals a certain amount of medicine that contains the compound that this patent announces.Here the cancer of saying comprises mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, CNC cancer, melanoma cancer, kidney, or cervical cancer.Here the compound of saying is compounds X anifolia Y0, Y, Y1, Y2, Y, Y7, Y8, Y9 and Y10) and its esters, ester class or its meta-bolites, derivative.These compounds can be from natural resources or synthetic.
See also the experimental result of Fig. 1-18, with international patent application book (NO.PCT/US05/31900, on September 7th, 2006 submitted), U.S. Patent application book (U.S.Serial NO.10/906303, on February 14th, 2005 submitted, international patent application book (NO.PCT/US04/43465, on December 23rd, 2004 submitted), international patent application book (NO.PCT/US04/33359, on October 8th, 2004 submitted) and U.S. Patent application book (U.S.Serial NO.11/131551 submitted in 2,005 twenty months 7 days).The document of present patent application has also comprised the content of above-mentioned document.
This patent has also been announced the above-claimed cpd salt compounds, it is characterized in that the sylvite class that described salt is, sodium salt class or calcium salt class.These salts be following compound (a, b, c, d, e, f, g, salt h):
Figure A20078004074400231
These salts can be used for treating chronic venous insufficiency, chronic venous disease, varix, varix symptom, venous stasis, eliminate the phlegm, the peripheral vessel disorder, cerebral tissue is fainted from fear, cerebral circulation disorder, cerebral edema, psychosis, dysmenorrhoea, hemorrhoid, episiotomy, the tip oedema forms, and postoperative edema reduces the skelagia symptom, reduces the stomachache symptom, itch, shank swelling, thrombosis, thrombophlebitis, rheumatosis, stomach ulcer, antispastic and antitumor.
This patent has also been announced a kind of purposes of constituent, it is characterized in that described constituent contains a certain amount of following compound, or its salt, acids, and meta-bolites or derivative, the chemical structural formula of this compound (1) is as follows
Figure A20078004074400241
Wherein R1 and R2=angeloyl groups, R3=H or OH, R4=CH 2OR 6, R6=H wherein, R5=has a sugar chain at least, and this sugar chain is made up of sugared or derivatives thereof, and R8 may be OH.In one case, R1 and R2 are angeloyl groups, R3=H or OH, R4=COOR6, wherein R6=H.In another case, R1=H; The R2=angeloyl groups, R3=H or OH, R4=CH 2OR 6Or COOR6, wherein R6=angeloyl groups.Under another situation, R4=CH 2OR 6Or COOR6, R1, at least two is angeloyl groups or pentasaccharides acid among R2 and the R6, R3=H or OH, R6 are angeloyl groups, H, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group or contain the acid of 2-5 carbon atom; Form by one or more sugared or derivatives thereofs.Under another situation, in the angeloyl groups of R1 or R2 is by ethanoyl at least, and along root of Dahurian angelica acyl group, squaw weed acyl group or the acid that contains 2-5 carbon atom replace, and R3=contains H or OH, and R4 contains CH 2OR 6Or COOR6, wherein R6=angeloyl groups.Under another situation, R4 contains CH 2OR 6Or COOR6, wherein R6=H or ethanoyl.Under another situation, R1 at least, R2 and R4 contain sugar chain or side chain contains sugar or his derivative, and here sugar chain contains two angeloyl groups at least, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group or contain the acid of 2-5 carbon atom, or their derivative.Under another situation, R5 contains sugar chain, and this sugar chain contains one or more following carbohydrate: glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination.Under another situation, R5 contains sugar chain, and this sugar chain contains two following carbohydrates: D-glucose, and the D-semi-lactosi, or derivatives thereof, or their combination, but be not again above-mentioned carbohydrate.Under another situation, R5 contains sugar chain, and this sugar chain contains three following carbohydrates: D-glucose, and the D-semi-lactosi, the L-rhamnosyl, L-arabinose, D-wood sugar, or uronic acid, as the D-glucuronic acid, D-galacturonic acid, or derivatives thereof, or their combination.Under another situation, R5 contains sugar chain, and this sugar chain contains three following carbohydrates: D-glucose, D-semi-lactosi, L-rhamnosyl, L-arabinose, D-wood sugar, or derivatives thereof, or their combination.Under another situation, R5 contains sugar chain, and this sugar chain contains a following carbohydrate at least: D-glucose, the D-semi-lactosi, the L-rhamnosyl, L-arabinose, D-wood sugar, or uronic acid, as the D-glucuronic acid, D-galacturonic acid, or derivatives thereof, or their combination, but be not again above-mentioned carbohydrate.Under another situation, R5 contains sugar chain, and this sugar chain contains following carbohydrate: glucose, semi-lactosi, pectinose, or uronic acid, or derivatives thereof, or their combination.In another case, R5 contains a side chain, and the effect of this side chain is equivalent to a sugar chain.Under another situation, R5=H.Under another situation, R4=H, OH or CH 3Under another situation, R1 is or/and R2 is the active group that an effect is equivalent to angeloyl groups, and R5 contains R5 and contains a side chain, and the effect of this side chain is equivalent to a sugar chain.
Sugar chain is a side chain in the compound, it is characterized in that described side chain contains one or more sugar, or itself or uronic acid, or derivatives thereof.The chemical group of in the above-claimed cpd one or several is replaced by other several chemical groups, remove, or to have increased one or several chemical group again is a technology contents of present patent application.And the chemical group of one or several in the above-claimed cpd is replaced by other several chemical groups, removes, or has increased one or several chemical group again and can fundamentally not influence the bioactive of them.
This patent has also been announced a kind of purposes of constituent, it is characterized in that described constituent contains a certain amount of following compound, or its salt, acids, and meta-bolites or derivative, the chemical structural formula of this compound (1A) is as follows
Wherein R1 and R2 respectively contain an angeloyl groups, R3=H or OH, R4=CH 2OR 6(wherein R6=H), R8 may be OH, and R5=has a sugar chain at least, and this sugar chain is made up of sugared or derivatives thereof.In one case, R1 and R2 respectively contain an angeloyl groups, R3=H or OH, and R4=COOR6 (wherein R6=H), R5 has a sugar chain or derivatives thereof at least.In one case, R1=H, R2 contains angeloyl groups, and R3 contains H or OH, and R4 contains CH 2OR 6Or COOR6 (wherein R6 is an angeloyl groups), R5=has a sugar chain or derivatives thereof at least.Under another situation, R3 contains H or OH, and R4 contains CH 2OR 6Or COOR6, here R6 is an angeloyl groups, H, and ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group or contain the acid of 2-5 carbon atom; By one or more sugar, or derivatives thereof is formed, R1, and at least two contain angeloyl groups or pentasaccharides acid among R2 and the R6, and R5 has a sugar chain or derivatives thereof at least.
In another case, a quilt in the angeloyl groups of R1 and R2 is by ethanoyl at least, and along root of Dahurian angelica acyl group, squaw weed acyl group or the acid that contains 2-5 carbon atom replace, and R3=contains H or OH, and R4 contains CH 2OR 6Or COOR6 (wherein R6=angeloyl groups), R5=has a sugar chain or derivatives thereof at least.Under another situation, R4 contains CH 2OR 6Or COOR6, R1 here, at least two contain two angeloyl groups among R2 and the R6, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group or pentasaccharides acid, or their combination.Under another situation, 24 in compound carbon contains CH 3Or CH 2OH.Under another situation, 23 in compound carbon, 24,25,26,29 and 30 respectively contain CH 3Or CH 2OH.Under another situation, 23 in compound carbon, 24,25,26,29 and 30 respectively contain CH 3, CH 2OH, CHO, COOH, COO alkyl, COO-aromatic base, COO-heterogeneous ring compound, COO-heterocyclic aromatic compounds, CH 2The O-aromatic base, CH 2The O-heterocyclic aromatic compounds, alkyl compound, acetyl compounds, or derivatives thereof.Under another situation, R5 contains sugar chain, and this sugar chain contains following carbohydrate: glucose, semi-lactosi, pectinose, or uronic acid, or derivatives thereof, or their combination.Under another situation, R5 contains sugar chain, and this sugar chain contains a following carbohydrate at least: D-glucose, the D-semi-lactosi, the L-rhamnosyl, L-arabinose, D-wood sugar, or uronic acid, as the D-glucuronic acid, D-galacturonic acid, or derivatives thereof, or their combination, but be not again above-mentioned carbohydrate.Under another situation, R5 contains sugar chain, and this sugar chain contains two following carbohydrates: D-glucose, D-semi-lactosi, L-rhamnosyl, L-arabinose, D-wood sugar, or uronic acid are as the D-glucuronic acid, the D-galacturonic acid, or derivatives thereof, or their combination, but be not again above-mentioned carbohydrate.Under another situation, R5 contains sugar chain, and this sugar chain is to three following carbohydrates are arranged: D-glucose, D-semi-lactosi, L-rhamnosyl, L-arabinose, D-wood sugar, or uronic acid are as the D-glucuronic acid, the D-galacturonic acid, or derivatives thereof, or their combination, but be not again above-mentioned carbohydrate.Under another situation, R5 contains sugar chain, and this sugar chain contains one or more following carbohydrate: glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination, but be not again above-mentioned carbohydrate.Under another situation, R5 contains sugar chain, and this sugar chain contains three following carbohydrates: glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination, but be not again above-mentioned carbohydrate.Under another situation, R5 contains sugar chain, and this sugar chain contains three following carbohydrates: glucose, and semi-lactosi, rhamnosyl, pectinose, wood sugar or fructose, or/and its derivative, or/and their combination, but be not again above-mentioned carbohydrate.Under another situation, R5 contains a compound, and the effect of this compound is equivalent to a sugar chain.Under another situation, R5=H.Under another situation, R4=H, OH or CH 3Under another situation, R1 is or/and R2 is the active group that an effect is equivalent to angeloyl groups, and R5 contains R5 and contains a side chain, and the effect of this side chain is equivalent to a sugar chain.Under another situation, R1 or/and R2 form by following compound: angeloyl groups, ethanoyl; along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl; dibenzoyl; alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds.Under another situation, R1 and R2 contain following compound: angeloyl groups, and ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, benzoyl, or alkenoyl.Under another situation, R4=CH 2OR 6, R1 has at least two to be made up of following compound: angeloyl groups among R2 and the R6; ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl; benzoyl, dibenzoyl, alkanoyl; alkenoyl; alkanoyl, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds that the phenmethyl alkyl replaces.Under another situation, R4=CH 2OR 6, R1 has at least two to be made up of following compound among R2 and the R6: angeloyl groups, and ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group or alkenoyl.Under another situation, R4=CH 2OR 6, R1 has at least two to be made up of following compound: angeloyl groups, benzoyl, or alkenoyl among R2 and the R6.Under another situation, R1 and R2 are made up of following compound: H, ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; acyl group, benzoyl, dibenzoyl; alkanoyl; alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base; heterogeneous ring compound or heterocyclic aromatic compounds, R4=CH 2OR 6, or COOR6 (wherein R6 is made up of following compound: H, COCH 3, angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof).Under another situation, R4=CH 2OR 6, COOR6 or CH 2OOOR6, R1 has at least two to be made up of following compound: angeloyl groups among R2 and the R6; ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl; benzoyl, dibenzoyl, alkanoyl; alkenoyl; alkanoyl, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds that the phenmethyl alkyl replaces.Under another situation, R1 has at least two to be made up of following compound: angeloyl groups among R2 and the R6; ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, dibenzoyl; alkanoyl; alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base; heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R1 has at least two to be made up of following compound among R2 and the R6: angeloyl groups, and ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, benzoyl, alkanoyl, alkenoyl, or derivatives thereof.Under another situation, R1 has at least two to contain a side chain among R2 and the R6, it is characterized in that the effect of described side chain is equivalent to angeloyl groups.Under another situation, R1 has at least two to contain a side chain among R2 and the R6, it is characterized in that the effect of described side chain is equivalent to benzoyl.Under another situation, R4=CH 2OR 6, COOR6 or CH 2OOOR6, R1 has at least two to be made up of following compound among R2 and the R6: angeloyl groups, along root of Dahurian angelica acyl group, squaw weed acyl group, benzoyl, alkanoyl, alkenoyl, or derivatives thereof.Under another situation, R4=CH 2OR 6, COOR6 or CH 2OOOR6, R1, R2 and/or R6 one of them or be sugar chain entirely; it is characterized in that described sugar chain contains H, angeloyl groups, ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; benzoyl, dibenzoyl, alkanoyl; alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base; acyl group, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R4=CH 2OR 6, COOR6 or CH 2OOOR6, R1, R2 and/or R6 one of them or be sugar chain entirely; it is characterized in that described sugar chain contains two kinds of compounds in the following compound at least: angeloyl groups, ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl; dibenzoyl, alkanoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group; heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R4=CH 2OR 6, COOR6 or CH 2OOOR6, R1, R2 and/or R6 one of them or be sugar chain entirely, it is characterized in that described sugar chain contains two kinds of compounds in the following compound at least: angeloyl groups, along root of Dahurian angelica acyl group, squaw weed acyl group, benzoyl, alkanoyl, alkenoyl, or derivatives thereof.Under another situation, R4=CH 2OR 6, COOR6 or CH 2OOOR6, R1, R2 and/or R6 one of them or be sugar chain entirely, it is characterized in that described sugar chain contains two kinds of compounds in the following compound at least: angeloyl groups, benzoyl, alkenoyl, or derivatives thereof.Under another situation, the compound with chemical structure 1A contains two kinds of compounds in the following compound at least: acyl group, and angeloyl groups, along root of Dahurian angelica acyl group, squaw weed acyl group, or effect is equivalent to the chemical group of angeloyl groups.Under another situation, the compound with chemical structure 1A contains two kinds of compounds in the following compound at least: angeloyl groups, acyl group; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; benzoyl, dibenzoyl, alkanoyl; alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group; heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation; compound with chemical structure 1A contains the side chain that a sugar chain or function are equivalent to sugar chain; it is characterized in that described sugar chain or side chain contain two kinds of compounds in the following compound at least: acyl group; angeloyl groups; along root of Dahurian angelica acyl group; the squaw weed acyl group, or effect is equivalent to the chemical group of angeloyl groups, or derivatives thereof.Under another situation, the compound with chemical structure 1A contains the side chain that a sugar chain or effect are equivalent to sugar chain, it is characterized in that described sugar chain or side chain contain two kinds of compounds in the following compound at least: acyl group; angeloyl groups, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, dibenzoyl; alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base; acyl group, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R1 and R2 with compound of chemical structure 1A contain following compound: H, angeloyl groups; ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, dibenzoyl; alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base, acyl group, heterogeneous ring compound or heterocyclic aromatic compounds; or derivatives thereof, R4 contains CH 2OCOCH 3, CH 2The COO-alkyl, CH 2OH, COOH, angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Sugar chain is that or derivatives thereof is formed by one or more sugar or its uronic acid.The compound of present patent application can extract from natural resources or synthetic.
Above-mentioned chemical group is replaced by other chemical group, remove, or to have increased one or several chemical group again is a technology contents of present patent application.And the chemical group of one or several in the compound in present patent application is replaced by other several chemical groups, removes, or has increased one or several chemical group again and can fundamentally not influence the bioactive of them.
This patent has also been announced a kind of composition, it is characterized in that described composition contains a certain amount of compound with above-mentioned chemical structure, or its esters, lipid, meta-bolites, or derivative, said composition can be used for making medicine and suppresses tumour or growth of cancer cells and the following cancer of pharmacological agent of bringing out cancer cell-apoptosis: mammary cancer, the white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the CNC cancer, the melanoma cancer, kidney, or cervical cancer.
This patent has also been announced a kind of compound, its salt, and acids, the purposes of meta-bolites or derivative is characterized in that the chemical structural formula of described compound (1B) is as follows:
Figure A20078004074400281
The R1 of this compound contains in subordinate's chemistry group: H, angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group, the squaw weed acyl group, alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl, the loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group, the heterocyclic aromatic base acyl group contains the acid of 2-6 carbon atom, or derivatives thereof; The R2 of this compound contains in subordinate's chemistry group: H, angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group, the squaw weed acyl group, alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl, the loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group, the heterocyclic aromatic base acyl group contains the acid of 2-6 carbon atom, or derivatives thereof; The R4 of this compound is CH 2O R6 or COOR6, here R6 contains in the following chemical group one: H, angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl, the loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group, the heterocyclic aromatic base acyl group contains the acid of 2-6 carbon atom, or derivatives thereof; The R3 of this compound is H or OH, and in one case, R3 contains following compound: alkyl, cycloalkyl, aromatic base, heterocyclic aromatic compounds, acyl group, alkanoyl, alkenoyl, loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group, heterocyclic aromatic base acyl group.In one case, R5 contains in the subordinate chemistry group one: H, alkyl, cycloalkyl, aromatic base, heterocyclic aromatic compounds, acyl group, alkanoyl, alkenoyl, loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group.In one case, R1 contains sugar chain, it is characterized in that described sugar chain contains two kinds of compounds in the following compound at least: angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl, the loop chain alkyloyl, the loop chain enoyl-, aromatic base acyl group, heterocyclic aromatic base acyl group, contain the acid of 2-6 carbon atom, or derivatives thereof; Under another situation, R1 contains sugar chain, it is characterized in that described sugar chain contains a kind of compound in the following compound at least: angeloyl groups; ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; benzoyl; dibenzoyl, alkanoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces; aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl; the loop chain enoyl-, aromatic base acyl group, heterocyclic aromatic base acyl group; contain the acid of 2-6 carbon atom, or derivatives thereof.In one case, R2 contains sugar chain, it is characterized in that described sugar chain contains a kind of compound in the following compound at least: angeloyl groups; ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; benzoyl; dibenzoyl, alkanoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces; aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl; the loop chain enoyl-, aromatic base acyl group, heterocyclic aromatic base acyl group; contain the acid of 2-6 carbon atom, or derivatives thereof.Under another situation, R2 contains sugar chain or side chain, it is characterized in that described sugar chain or side chain contain two kinds of compounds in the following compound at least: angeloyl groups; ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; benzoyl; dibenzoyl, alkanoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces; aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl; the loop chain enoyl-, aromatic base acyl group, heterocyclic aromatic base acyl group; contain the acid of 2-6 carbon atom, or derivatives thereof.Under another situation, R4 contains COOR6, CH 2OR6, wherein R6 is a sugar chain, it is characterized in that described sugar chain contains a kind of compound in the following compound at least: angeloyl groups, ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl; dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group; the heterocyclic aromatic base acyl group contains the acid of 2-6 carbon atom, or derivatives thereof.Under another situation, R4 contains COOR6, CH 2OR6, wherein R6 is a sugar chain, it is characterized in that described sugar chain contains two kinds of compounds in the following compound at least: angeloyl groups; ethanoyl; along root of Dahurian angelica acyl group (tigloyl), squaw weed acyl group (senecioyl), alkyl; benzoyl; dibenzoyl, alkanoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces; aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl; the loop chain enoyl-, aromatic base acyl group, heterocyclic aromatic base acyl group; contain the acid of 2-6 carbon atom, or derivatives thereof.Under another situation, R4 contains COOR6, CH 2OR6, wherein R6 is a sugar chain, it is characterized in that described sugar chain contains two kinds of compounds in the following compound at least: angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group (tigloyl), squaw weed acyl group (senecioyl), or alkyl.Under another situation, R4 contains COOR6, CH 2OR6, wherein R6 is a sugar chain, it is characterized in that described sugar chain contains two kinds of compounds in the following compound at least: angeloyl groups, ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl; dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group; the heterocyclic aromatic base acyl group contains the acid of 2-6 carbon atom, or derivatives thereof.Under another situation, R4 contains the COOR6 in the chemical structural formula (1B), CH 2OR6, R1 at least wherein, following compound is contained in two chemical groups among R2 and the R6: angeloyl groups, ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl; dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group; the heterocyclic aromatic base acyl group contains the acid of 2-6 carbon atom, or derivatives thereof.Under another situation, R4 contains the COOR6 in the chemical structural formula (1B), CH 2OR6, R1 at least wherein, following compound is contained in two chemical groups among R2 and the R6: angeloyl groups, benzoyl, alkenoyl, or derivatives thereof.Under another situation, R4 is the side chain that contains following compound a: CH 2OCOCH 3, CH 2The OO-alkyl, CH 2OH, COOH, angeloyl groups, ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl; dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group; the heterocyclic aromatic base acyl group contains the acid of 2-6 carbon atom, or derivatives thereof.In one case, R5 contains the group that a sugar chain or function are equivalent to sugar chain.Under another situation, R5 is H.In one case, R4 is H, OH or CH 3In one case, 23 in the carbon of compound (1B), 24,25,26 in carbon, 29 and 30 respectively contain CH 3, CH 2OH, CHO, COOH, COO-alkyl, COO-aromatic base, COO-heterogeneous ring compound, COO-heterocyclic aromatic compounds, CH 2The O-aromatic base, CH 2The O-heterocyclic aromatic compounds, alkyl compound, acetyl compounds, or derivatives thereof.Under another situation, 23 in the carbon of compound (1B), 24,25,26 in carbon, 29 and 30 respectively contain alkyl; cycloalkyl, alkenoyl, aromatic base, assorted aromatic base, ethanoyl; alkanoyl, loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group, or assorted aromatic base acyl group.In one case, R1 contains a sugar chain or side chain, it is characterized in that described sugar chain or side chain contain two angeloyl groups.R1 and R2 respectively contain benzoyl in one case.R1 is a sugar chain under another situation, it is characterized in that described sugar chain contains two benzoyls.R3 is H in one case, or OH.R8 may be OH in one case.Under another situation, R8 contains alkyl, cycloalkyl, alkenoyl, aromatic base, assorted aromatic base, ethanoyl, alkanoyl, alkenoyl, loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group, or assorted aromatic base acyl group.In one case, R3, R4, R8 or R5 contain N.In one case, spatially adjacent OH derives and forms five rings or a hexacyclic compound or a cyclic carbonate salt that contains dioxole.Any chemical group in the above-claimed cpd is replaced by other chemical group, remove, or to have increased one or several chemical group again is a technology contents of present patent application.And the chemical group of one or several in the compound in present patent application is replaced by other several chemical groups, removes, or has increased one or several chemical group again and can fundamentally not influence the bioactive of them.This patent has also been announced a kind of composition, it is characterized in that described composition contains a certain amount of compound with above-mentioned chemical structure, or its esters, lipid, meta-bolites, or derivative, said composition can be used for making the tumor growth of medicine inhibitor water outer membrane protein capable of inhibiting cell overexpression, and said composition can be used for making medicine and suppresses tumour or growth of cancer cells and the following cancer of pharmacological agent of bringing out cancer cell-apoptosis: mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, melanoma cancer, kidney, or cervical cancer.
This patent has also been announced a kind of compound, its salt, and acids, the purposes of meta-bolites or derivative is characterized in that the chemical structural formula of described compound (1C) is as follows:
The R1 of this compound and R2 respectively contain an angeloyl groups, and R3 is H, or OH, and R4 contains CH 2OR6, here R6 is H, and R5 contains sugar chain, and this sugar chain contains one or more following carbohydrates at least: D-glucose, D-semi-lactosi, R7 are COOH.Under another situation, the R1 of this compound and R2 respectively contain an angeloyl groups, and R3 is H, or OH, and R4 contains COOR6, and here R6 is H, and R5 contains sugar chain, and this sugar chain contains one or more following carbohydrates at least: D-glucose, D-semi-lactosi, R7 are COOH.Under another situation, the R1 of this compound is H, and R2 respectively contains an angeloyl groups, and R3 is H, or OH, and R4 contains CH 2OR6 or COOR6, here R6 contains an angeloyl groups or ethanoyl.Under another situation, the R1 of this compound, R2 and R6 contain an angeloyl groups or five carbonic acid, and R3 is H, or OH, and R4 contains CH 2OR6 or COOR6, here R6 is an angeloyl groups, H, ethanoyl is along root of Dahurian angelica acyl group, squaw weed acyl group, two carbonic acid or five carbonic acid.Under another situation, have an angeloyl groups among the R1 of this compound or the R2 at least by ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, two carbonic acid or five carbonic acid substitute, and R3 is H, or OH, and R4 contains CH 2OR6 or COOR6, here R6 is an angeloyl groups.Under another situation, R4 contains CH 2OR6 or COOR6, R1 has one to be the sugar chain that contains following compound: two angeloyl groups, ethanoyl, suitable root of Dahurian angelica acyl group, squaw weed acyl group, two carbonic acid or five carbonic acid, or their combination among R2 or the R6 at least.Under another situation, 24 in the carbon of this compound contains CH 3Or CH 2OH.In one case, R7 is CH 3, CH 2OH, CHO, COOH, COO-alkyl, COO-aromatic base, COO-aromatic base, COO-heterogeneous ring compound, COO-heterocyclic aromatic compounds, CH 2The O-aromatic base, CH 2The O-heterocyclic aromatic compounds, alkyl compound, acetyl compounds, or derivatives thereof.Under another situation, 24 in the carbon of this compound, 24 in carbon, 25 in carbon, 26 in carbon, 29 in carbon and 30 in carbon respectively contain CH 3Or CH 2OH.Under another situation, 24 in the carbon of this compound, 24 in carbon, 25 in carbon, 26 in carbon, 29 in carbon and 30 in carbon contain CH respectively 3, CH 2OH, CHO, COOH, COO-alkyl, COO-aromatic base, COO-aromatic base, COO-heterogeneous ring compound, COO-heterocyclic aromatic compounds, CH 2The O-aromatic base, CH 2The O-heterocyclic aromatic compounds, alkyl compound, acetyl compounds, or derivatives thereof.Under another situation, R5 contains sugar chain, and this sugar chain contains one or more following carbohydrate: glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination.Under another situation, R5 is H.In one case, R4 contains H, OH or CH 3CH 2OR6, here R6 contains H or an angeloyl groups.In one case, R1 and/or R2 are the groups that a function is equivalent to angeloyl groups.Under another situation, R5 is the side chain that a function is equivalent to sugar chain.In one case, R1 and R2 contain following compound: angeloyl groups, and ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base, acyl group, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R1 and/or R2 are sugar chains, and this sugar chain contains two groups in the following chemical group: angeloyl groups; ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, alkanoyl; alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group; heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.In one case, R1 and R2 contain following chemical group: H, angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group, the squaw weed acyl group, alkyl, benzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound or heterocyclic aromatic compounds; R4 contains CH 2OR6 or COOR6, here R6 contains following chemical group: H, COCH 3, angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R4 contains CH 2OR6, COOR6 or CH 2COOR6, R1, R2 and/or R6 are sugar chains; this sugar chain contains two group: H in the following chemical group, angeloyl groups, ethanoyl at least; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; benzoyl, alkanoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group; heterogeneous ring compound, heterocyclic aromatic compounds, or derivatives thereof.In one case, the compound with chemical structural formula (C1) contains two groups in the following chemical group at least: angeloyl groups, and ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, and derivative, or function is equivalent to the group of angeloyl groups.Under another situation, the compound with chemical structural formula (C1) contains two groups in the following chemical group at least: angeloyl groups, ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; benzoyl, alkanoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces; aromatic base, acyl group, heterogeneous ring compound; heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R and R2 with compound of chemical structural formula (C1) contain following chemical group: H, angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group, alkyl, benzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, or derivatives thereof; R4 contains CH 2OCOCH 3, CH 2The COO-alkyl, CH 2OH, COOH, angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, or derivatives thereof.
Any chemical group in the above-claimed cpd is replaced by other chemical group, remove, or to have increased one or several chemical group again is a technology contents of present patent application.And the chemical group of one or several in the compound in present patent application is replaced by other several chemical groups, removes, or has increased one or several chemical group again and can fundamentally not influence the bioactive of them.
This patent has also been announced a kind of compound, its salt, and acids, the purposes of meta-bolites or derivative is characterized in that the chemical structural formula of described compound is shown in (1D):
Figure A20078004074400311
The R1 of this compound contains following chemical group: H, angeloyl groups, and ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group, alkyl, benzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, or derivatives thereof; R2 contains following chemical group: H, angeloyl groups, and ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl, alkanoyl, alkenoyl, the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, or derivatives thereof; R4 contains CH 2OR6 and COOR6, here R6 contains following chemical group: H, angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group, alkyl, benzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, or derivatives thereof; R3 is H, or OH; R5 contains sugar chain, D-glucose or D-semi-lactosi; R7 is CH 3, CH 2OH, CHO, COOH, COO-alkyl, COO-aromatic base, COO-aromatic base, COO-heterogeneous ring compound, COO-heterocyclic aromatic compounds, CH 2The O-aromatic base, CH 2The O-heterocyclic aromatic compounds, alkyl compound, acetyl compounds, or derivatives thereof.Under another situation, R1 is a compound, and this compound contains a sugar chain; this sugar chain contains two groups in the following chemical group at least: angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl; alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base; acyl group, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R1 is a compound, and this compound contains a sugar chain; this sugar chain contains a group in the following chemical group at least: angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl; alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base; acyl group, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R2 is a compound, and this compound contains a sugar chain; this sugar chain contains a group in the following chemical group at least: angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl; alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base; acyl group, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R2 is a compound, and this compound contains a sugar chain or compound; this sugar chain or compound contain two groups in the following chemical group at least: angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl; alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base; acyl group, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.In one case, R4 contains CH 2OR6 and COOR6, here R6 is a sugar chain chain, this sugar chain contains a group in the following chemical group at least: angeloyl groups; ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, alkanoyl; alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group; heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R4 contains CH 2OR6 and COOR6, here R6 is a sugar chain chain, this sugar chain contains two groups in the following chemical group at least: angeloyl groups; ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, alkanoyl; alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group; heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R4 contains CH 2OR6 and COOR6, here R6 is a sugar chain chain, this sugar chain contains two groups in the following chemical group at least: angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group or alkyl.Under another situation, R4 contains CH 2OR6 and COOR6, here R6 is a sugar chain chain, this sugar chain contains two groups in the following chemical group at least: angeloyl groups; ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, alkanoyl; alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group; heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R4 contains CH 2OR6 and COOR6 here at R1, have two at least and contain following compound: angeloyl groups among R2 and the R6; ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, alkanoyl; alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group; heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof.Under another situation, R4 is a compound, and this compound contains CH 2OCOCH 3, CH 2The COO-alkyl, CH 2OH, COOH, angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group alkyl, benzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, or derivatives thereof.In one case, R5 contains sugar chain, and this sugar chain contains one or more following carbohydrate: glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or alduronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination.Under another situation, R5 contains the compound that function is equivalent to sugar chain.And R5 contains a hydrogen.Under another situation, R4 is H, OH or CH 3
In one case, 24 in the carbon of this compound contains CH 3, or CH 2OH.Under another situation, 24 in the carbon of this compound, 24 in carbon, 25 in carbon, 26 in carbon, 29 in carbon and 30 in carbon respectively contain CH 3, CH 2OH, CHO, COOH, COO-alkyl, COO-aromatic base, COO-aromatic base, COO-heterogeneous ring compound, COO-heterocyclic aromatic compounds, CH 2The O-aromatic base, CH 2The O-heterocyclic aromatic compounds, alkyl compound, acetyl compounds, or derivatives thereof.Under another situation, R5 contains a sugar chain, and this sugar chain contains D-glucose, the D-semi-lactosi, and the L-rhamnosyl is or/and L-arabinose.Under another situation, R1 and R2 contains an angeloyl groups.Under another situation, R1 is a sugar chain or the sugar chain that contains rhamnosyl, and this sugar chain contains two angeloyl groups.
In one case, R3 is H, or OH.Above-claimed cpd can propose or synthetic from natural resources.
Sugar chain is an integral part of compound, and it contains the component of one or more sugar.Any chemical group in the above-claimed cpd is replaced by other chemical group, remove, or to have increased one or several chemical group again is a technology contents of present patent application.And the chemical group of one or several in the compound in present patent application is replaced by other several chemical groups, removes, or has increased one or several chemical group again and can fundamentally not influence the bioactive of them.
This patent has been announced a kind of method for the treatment of and preventing following various diseases: venous insufficiency, particularly hemorrhoid prevent that leg is swollen, the tip oedema, anti-lipid, chronic venous disease, varix, venous stasis eliminates the phlegm, the peripheral vessel obstacle, the brain organ is fainted from fear, disturbance of cerebral circulation, cerebral edema, psychosis, dysmenorrhoea, episiodemies, postoperative edema; Ease the pain, alleviate the symptom of stomach pain, alleviate the symptom of shank pain, the treatment itch, edeam of legs is fat, thrombosis, thrombophlebitis, stomach ulcer.This method comprises adjusts to optimal dosage to dosage (if desired), and said this medicine is the arbitrary compound compositions that contains among above-mentioned arbitrary compound or Fig. 1-3, or contains a compound of triterpene; this compound contains two angeloyl groups (or two along root of Dahurian angelica acyl groups, or two squaw weed acyl groups, are good with angeloyl groups); with the sugar chain that contains following carbohydrate: glucose, semi-lactosi, rhamnosyl; pectinose, wood sugar, Fucose; Ah coughing up's sugar, altrose, gulose; idose, lyxose, seminose; ribose, sorbose, tagatose; talose, fructose, or uronic acid; glucuronic acid; galacturonic acid, or derivatives thereof, or their combination is (with glucose; semi-lactosi; pectinose, glucuronic acid, galacturonic acid are good.
This patent has been announced a kind of method of anticancer growth, and this method comprises adjusts to optimal dosage to dosage (if desired), and said this medicine contains triterpenoid saponin; this triterpenoid saponin contains two or more angeloyl groups, or contains the compound of the chemical structural formula among Fig. 1-3, or contains a compound of triterpene; this compound contains two angeloyl groups (or two along root of Dahurian angelica acyl groups, or two squaw weed acyl groups, are good with angeloyl groups); with the sugar chain that contains following carbohydrate: glucose, semi-lactosi, rhamnosyl; pectinose, wood sugar, Fucose; Ah coughing up's sugar, altrose, gulose; idose, lyxose, seminose; ribose; sorbose, tagatose, talose; fructose; or uronic acid, glucuronic acid, galacturonic acid; or derivatives thereof; or their combination (with glucose, semi-lactosi, pectinose; glucuronic acid, galacturonic acid are good.
This patent has also been announced a kind of composition, it is characterized in that described composition contains a certain amount of arbitrary compound with above-mentioned chemical structure, or its esters, lipid, meta-bolites, or derivative, said composition can be used for making the tumor growth of medicine inhibitor water outer membrane protein capable of inhibiting cell overexpression, and said composition can be used for making medicine and suppresses tumour or growth of cancer cells and the following cancer of pharmacological agent of bringing out cancer cell-apoptosis: mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, CNC cancer, melanoma cancer, kidney, or cervical cancer.
Specifically, the above-mentioned composition that is used for medicine contains the arbitrary triterpenoid saponin compound with following chemical structure:
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyranoside butyl ester }-21-O-ethanoyl-22-O-party returns acyl group-3 β; 16 α; 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, acyl group-3 β, 15 α return in the two parties of 22-O-; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(3; acyl group is returned by the two parties of 4-)-α-L-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, acyl group-3 β, 15 α return in the two parties of 22-O-; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
3-O-[β-glucose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, acyl group-3 β, 16 α return in the two parties of 22-O-; 21 β; 22 α, 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O (3; acyl group is returned by the two parties of 4-)-α-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β returns, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-party returns acyl group, 22-O-(methyl pyrans acyl group)-3 β, 15 α; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group-28-O-2-methylbutyryl base-3 β; 15 α, 16 α, 21 β; 22 α, 28 hexahydroxy-s olea-12-alkene pentacyclic triterpenoid saponin.
This patent provides a kind of composition that contains above-claimed cpd, it is characterized in that described composition can be used to make the tumor growth of medicine inhibitor water outer membrane protein capable of inhibiting cell overexpression, making medicine suppresses the growth of following cancer and brings out cancer cell-apoptosis: bladder cancer, osteocarcinoma, skin carcinoma, and ovarian cancer, but do not terminate in above-mentioned cancer.
This patent also provides a kind of can cure venous insufficiency, particularly hemorrhoid, prevents that leg is swollen, or suppresses the growth composition of cancer, it is characterized in that described composition contains any compound in the following compound:
A) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L pectinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, acyl group-3 β, 15 α return in the two parties of 22-O-; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
B) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O (3; acyl group is returned by the two parties of 4-)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
C) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3) β-D-glucuronic acid pyrans acyl group-21, acyl group-3 β, 15 α return in the two parties of 22-O-; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin
D) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21; acyl group-3 β, 16 α, 21 β return in the two parties of 22-O-; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
E) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O (3; acyl group is returned by the two parties of 4-)-α-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
F) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β returns, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
G) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
H) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O (3; the two benzoyls of 4-)-α-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
I) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3) β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
J) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α; 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
K) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O (3; the two benzoyls of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
L) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12 alkene pentacyclic triterpenoid saponin.
M) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
N) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(3; the two benzoyls of 4-)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
O) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-β-D wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
P) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-β-D wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
Q) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3; the two benzoyls of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
R) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two angeloyl groups-3 β of 22-O-, 15 α; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
S) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(3; the two angeloyl groups of 4-)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
T) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two angeloyl groups-3 β of 22-O-, 15 α; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
U) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, two angeloyl groups-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
V) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3; the two angeloyl groups of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
W) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, the two angeloyl groups of 22-O-)-3 β, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
This patent also provides a kind of tumor growth that can be used to make the overexpression of medicine inhibitor water outer membrane protein capable of inhibiting cell, make medicine and suppress the growth of cancer and bring out the cancer cell-apoptosis composition, it is characterized in that described composition contains any compound in the following compound:
A1) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D glucuronic acid pyrans acyl group-21-O-party returns acyl group, 22-O-benzoyl-3 β, 15 α; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
B1) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-(acyl group is returned to D-glucuronic acid pyrans acyl group-21-O-by 3-party; the 4-phenmethyl)-α-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
C1) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group; 22-O-benzoyl-3 β; 15 α; 16 α; 21 β; 22 α, 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
D1) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-party returns acyl group, 22-O-benzoyl-3 β, 15 α; 16 α; 21 β, 22 α, 28 penta hydroxy groups olea-12-alkene pentacyclic triterpenoid saponin.
E1) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-(acyl group is returned to beta-glucuronic acid pyrans acyl group-21-O-by 3-party; the 4-benzoyl)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
F1) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-party returns acyl group; 22-O-benzoyl-3 β, 16 α, 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
G1) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-benzoyl, acyl group-3 β, 15 α return in 22-O-party; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
H1) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D glucuronic acid pyrans acyl group-21-O-(3-benzoyl; acyl group is returned by 4-party)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
I1) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-benzoyl, acyl group-3 β, 15 α return in 22-O-party; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
J1) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-β D-glucuronic acid pyrans acyl group-21-O-benzoyl; acyl group-3 β, 16 α, 21 β return in 22-O-party; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
K1) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3-benzoyl; acyl group is returned by 4-party)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
L1) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-benzoyl; acyl group-3 β, 16 α, 21 β return in 22-O-party; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
M1) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-angeloyl groups, 22-O-benzoyl-3 β, 15 α; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
N1) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(3-angeloyl groups; the 4-benzoyl)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 15 α; 16 α; 21 β; 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
O1) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group, 22-O-benzoyl-3 β, 15 α; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyl oleas 12 alkene pentacyclic triterpenoid saponins.
P1) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group; 22-O-benzoyl-3 β, 16 α, 21 β; 22 α, 28 penta hydroxy groups olea-12-alkene pentacyclic triterpenoid saponin.
Q1) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3-benzoyl; acyl group is returned by 4-party)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
R1) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-angeloyl groups; 22-O-benzoyl-3 β, 16 α, 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
S1) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-benzoyl, 22-O-angeloyl groups-3 β, 15 α; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
T1) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(3-benzoyl; acyl group is returned by 4-party)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
U1) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-benzoyl, 22-O-angeloyl groups-3 β, 15 α; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
V1) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-benzoyl; 22-O-angeloyl groups-3 β, 16 α, 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
W1) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3-benzoyl; acyl group is returned by 4-party)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
X1) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-benzoyl; acyl group is returned by 22-O-party)-3 β, 16 α, 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
This patent also provides a kind of tumor growth that can be used to make the overexpression of medicine inhibitor water outer membrane protein capable of inhibiting cell, suppress to make the growth of medicine cancer and bring out the cancer cell-apoptosis composition, it is characterized in that described composition contains any compound in the following compound:
1) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group; 22-O-(acyl group-2-methylbutyryl base is returned by party)-3 β; 15 α; 16 α; 21 β; 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
2) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(2-methylpropionyl); 22-O-(2-methylpropionyl)-3 β; 15 α; 16 α; 21 β; 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
3) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group, 22-O-benzoyl-3 β, 15 α; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
4) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(2-methylpropionyl)-O-angeloyl groups; 22-O-(2-methylpropionyl)-3 β; 15 α; 16 α; 21 β; 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
5) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(2-methylpropionyl)-O-angeloyl groups; 22-O-(2-methylbutyryl base)-3 β; 15 α; 16 α; 21 β; 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
The triterpenoid saponin compound of announcing at this patent with said structure characteristics can be used to cure venous insufficiency, particularly hemorrhoid, prevents that leg is swollen.Simultaneously can also be used to make the tumor growth of medicine inhibitor water outer membrane protein capable of inhibiting cell overexpression, be used to suppress or slow down the growth of cancer or bring out cancer cell-apoptosis, these cancers comprise mammary cancer, the white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, melanoma cancer, kidney, or cervical cancer, but be unlikely to these cancers.Can influence the structure and the adhesion process of cytolemma at the triterpenoid saponin with said structure characteristics of this patent announcement.In one case, these triterpenoid saponins can binding proteins matter stop the transfer and the growth of cancer cells.
In one case, this compound is that a triterpenoid saponin or saponin are former, it is characterized in that described compound contains angeloyl groups at least, along one or two group in root of Dahurian angelica acyl group and the squaw weed acyl group, or their combination.And these groups directly can be connected on 21 in the former carbon of saponin and/or 22 in succession, or on 28, or be connected on the sugar chain.Compound with these constructional features can be used for the treatment of venous insufficiency, particularly hemorrhoid, prevents that leg is swollen, or suppresses the growth of cancer.Under another situation, this compound is a pentacyclic triterpenoid saponin compound, it is characterized in that described compound contains angeloyl groups at least, along two groups (or their composition) and the sugar chain in root of Dahurian angelica acyl group and the squaw weed acyl group.Angeloyl groups is connected on the side chain of the former end of five rings saponin, and sugar chain is connected on the side chain of the other end.Under another situation, this compound contains two angeloyl groups at least, and one along root of Dahurian angelica acyl group or a squaw weed acyl group (or their combination) and a sugar chain.Angeloyl groups and sugar chain are connected on the former side chain of saponin.Under another situation, angeloyl groups can be replaced by the group that function is equivalent to angeloyl groups.Under another situation, sugar chain or side chain are connected on 3 in carbon or other position, it is characterized in that described sugar chain or side chain contain following carbohydrate (but not terminating in these carbohydrates): glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination is (with D-glucose, the D-semi-lactosi, pectinose, D-glucuronic acid, the D-galacturonic acid, or their derivative is good).And CH3, CH2OH, COOH or ethanoyl may be connected to carbon 23-30 position.Its structure is depended in the influence of a saponin or the effect that suppresses growth of tumour cell, that is to say to have the picture angeloyl groups, and along root of Dahurian angelica acyl group, squaw weed acyl group or ethanoyl (or or their combination) be the function group structure like this.
Compound Y1 and Y2 contain two angeloyl groups, so all have the ability (see figure 4) of very strong anticancer growth.
Compound Y, Y1, Y2, Y8, Y9 and Y10 contain two angeloyl groups, so can suppress ovarian cancer cell growth (see figure 5).
Compound (X) and Escin contain an angeloyl groups, so anticancer growth and hemolytic ability just are weaker than the compound (seeing Fig. 5,6 and 7) that contains two angeloyl groups.
Compound does not have angeloyl groups just not have anticancer growth and hemolytic ability (seeing Fig. 5,6 and 7).
Compound contains two angeloyl groups is making the growth of medicine anticancer; reduce the leg edema; alleviate chronic venous dysfunction; lower the tip oedema, anti-lipid, prevent and treat chronic venous disease and varix; alleviate cirsoid symptom; venous stasis is cured the ability aspect of peripheral circulation disorders, is better than the compound that only contains an angeloyl groups.
This patent also provides a kind of composition, it is characterized in that described composition contains the compound with following chemical structure:
Figure A20078004074400391
Compound (a) or R1 (b) and R2 contain angeloyl groups, and along root of Dahurian angelica acyl group, squaw weed acyl group, ethanoyl or their combination are good to contain angeloyl groups.Under another situation, R1 and R2 contain following group: angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl, two benzoyls; alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base; acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl, loop chain enoyl-, aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.
Figure A20078004074400392
The R1 and the R2 of compound (c) contain angeloyl groups, and along root of Dahurian angelica acyl group, squaw weed acyl group, ethanoyl or their combination are good to contain angeloyl groups.
Under another situation, R1 and R2 contain following group: angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl, two benzoyls; alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base; acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl, loop chain enoyl-, aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.
Under another situation, compound (c) contains sugar chain.This sugar chain contains glucose, semi-lactosi, pectinose, or their combination.
Under another situation, this sugar chain contains a sugar at least, glucose, semi-lactosi, pectinose, rhamnosyl, wood sugar, alduronic acid, glucuronic acid, galacturonic acid, and derivative, or their combination.
Under another situation, R1 and R2 may be connected on other position of compound.
Figure A20078004074400401
The R1 of this compound (d), R2 or R3 contain angeloyl groups, along root of Dahurian angelica acyl group, squaw weed acyl group, ethanoyl or their combination, preferably R1 has two at least and contains angeloyl groups among R2 or the R3.Under another situation, R1 has two at least and contains following group: angeloyl groups, ethanoyl among R2 or the R3; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl; two benzoyls, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base, acyl group, heterogeneous ring compound, heterocyclic aromatic compounds; cycloalkyl, loop chain alkyloyl, loop chain enoyl-, aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.
Under another situation, R1 has one at least and contains sugar chain among R2 or the R3, and this sugar chain contains two groups in the following chemical group: angeloyl groups; ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; benzoyl, two benzoyls, alkanoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound; heterocyclic aromatic compounds, cycloalkyl, loop chain alkyloyl, loop chain enoyl-; aromatic alkyl, heteroaromatic alkyl, two carbon, six carbonic acid, or derivatives thereof.
In one case, compound (d) contains a sugar chain, and this sugar chain is connected the R1 of compound (d), the relative end of R2 and R3, and it contains glucose, semi-lactosi, pectinose, or their combination.
Under another situation, this sugar chain contains a sugar at least, glucose, semi-lactosi, pectinose, rhamnosyl, wood sugar, alduronic acid, glucuronic acid, galacturonic acid, and derivative, or their combination.Under another situation, this sugar chain contains one or more sugar at least, and these sugar are glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination, but terminate in these sugar.Under another situation, R1, R2 and R3 may be connected on other position of compound.
Under another situation; this compound is a triterpenoid saponin compound, it is characterized in that described compound contains angeloyl groups at least, along root of Dahurian angelica acyl group; two angeloyl groups are preferably contained at least in two groups (or their composition) in squaw weed acyl group or the ethanoyl.
Under another situation, this compound contains two groups in the following chemical group at least: angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl, two benzoyls; alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base; acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl, loop chain enoyl-, aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.
Under another situation, this compound has at least a side chain to contain sugar chain, and this sugar chain contains two groups in the following chemical group: angeloyl groups, ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl; two benzoyls, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base, acyl group, heterogeneous ring compound, heterocyclic aromatic compounds; cycloalkyl, loop chain alkyloyl, loop chain enoyl-, aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.
Under another situation, this compound contains a sugar chain, and this sugar chain contains glucose, semi-lactosi, pectinose, or their combination.
Under another situation, this sugar chain contains a sugar at least, glucose, semi-lactosi, pectinose, rhamnosyl, wood sugar, uronic acid, glucuronic acid, galacturonic acid, and derivative, or their combination.
Under another situation, this sugar chain contains one or more sugar at least, and these sugar are glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or alduronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination, but terminate in these sugar.Under another situation, R1, R2 and R3 may be connected on other position of compound.
This patent also provides a kind of have antitumour activity or antiviral triterpenoid, it is characterized in that described composition contains the compound with following chemical structure:
Figure A20078004074400411
The R1 of this compound, R2 or R3 contain angeloyl groups, along root of Dahurian angelica acyl group, squaw weed acyl group, ethanoyl or their combination, preferably R1 has two at least and contains angeloyl groups among R2 or the R3.Under another situation, R1 has two at least and contains following group: angeloyl groups, ethanoyl among R2 or the R3; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl; two benzoyls, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base, acyl group, heterogeneous ring compound, heterocyclic aromatic compounds; cycloalkyl, loop chain alkyloyl, loop chain enoyl-, aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.
Under another situation, R1 has one at least and contains sugar chain among R2 or the R3, and this sugar chain contains two groups in the following chemical group: angeloyl groups; ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; benzoyl, two benzoyls, alkanoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound; heterocyclic aromatic compounds, cycloalkyl, loop chain alkyloyl, loop chain enoyl-; aromatic alkyl, heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.
Under another situation, the R5 of this compound contains a sugar chain, and this sugar chain contains glucose, semi-lactosi, pectinose, or their combination.
Under another situation, this sugar chain contains a sugar at least, glucose, semi-lactosi, pectinose, rhamnosyl, wood sugar, uronic acid, glucuronic acid, galacturonic acid, and derivative, or their combination.
Under another situation, this sugar chain contains one or more sugar at least, and these sugar are glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination, but terminate in these sugar.Under another situation, R1, R2 and R3 may be connected on other position of compound.
Under another situation; this compound is a triterpenoid saponin compound, it is characterized in that described compound contains angeloyl groups at least, along root of Dahurian angelica acyl group; two angeloyl groups are preferably contained at least in two groups (or their composition) in squaw weed acyl group or the ethanoyl.
Under another situation, this compound contains two groups in the following chemical group at least: angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl, two benzoyls; alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base; acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl, loop chain enoyl-, aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.
Under another situation, this compound has at least a side chain to contain sugar chain, and this sugar chain contains two groups in the following chemical group: angeloyl groups, ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, benzoyl; two benzoyls, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces; aromatic base, acyl group, heterogeneous ring compound, heterocyclic aromatic compounds; cycloalkyl, loop chain alkyloyl, loop chain enoyl-, aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.
This patent has also been announced a kind of composition, it is characterized in that described composition contains a certain amount of arbitrary compound with above-mentioned chemical structure, or its esters, lipid, meta-bolites, or derivative, said composition can be used for suppressing the following cancer of pharmacological agent of tumour or growth of cancer cells: mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, the melanoma cancer, kidney, or cervical cancer.
Under another situation, have above-mentioned chemical structure (d) or compound (e) anticancer or antiviral activity is arranged.
This patent has also been announced a kind of anticancer or antiviral composition that contains triterpenoid, it is characterized in that described at least two side chains of compound that contain triterpene contain angeloyl groups, and these two side chains trans (trans) are connected on the adjacent carbon potential.Be connected on the carbon potential of being separated by in these two side chain cis (cis) under another situation.Be connected on the carbon potential of being separated by at these two side chains trans (trans) under another situation.
Under another situation, these two side chain cis (cis) are connected on the non-conterminous carbon potential.Under another situation, these two side chains contain the chemical group that function is equivalent to angeloyl groups.
This patent has also been announced a kind of composition, it is characterized in that described composition can adjust the proteinic function of cell surface, or changes the function of the functional protein of intracellular membrane.Composition that this patent is announced and compound can be adjusted moisture and pass the structure that cell walls removes softening skin or improves skin.
This patent has also been announced a kind of composition, it is characterized in that described composition contains the compound for the treatment of and prevent following disease that this patent provides: cancer, suppress virus, brain aging improves memory and brain function, the enuresis, the urgent urination frequent micturition, dementia, presenile dementia, autism, brain injury, Parkinson's disease, or other disease that causes by brain insufficiency, sacroiliitis, rheumatism, it is bad to circulate, arteriosclerosis, Reynolds illness, stenocardia, the heart function disorder, coronary heart disease, headache, dizzy and renal function disorder, cardiovascular disorder, suppress NF-Kappa B activation, cerebral edema is breathed urgent symptom grouping, respiratory virus disease (respiratory viraldiseases); Chronic venous insufficiency; Ypotension; Chronic venous disease; Ivy extract; Anti-inflammatory; Haemonhoids, the tip oedema; Varix; Influenza; Oedema after the wound; Postoperative swelling; Suppress thrombosis, suppress ethanol and absorb; Hypoglycemic; Adjust the level of thyroliberin and Kendall compound, premature ejaculation, impotence and treatment diabetes.See also U.S. Patent application book (U.S.Serial No.10/906,303, on February 14th, 2005 submitted, U.S.Serial No.11/131551, on May 17th, 2005 submitted) and the international patent application book (No.PCT/US05/31900, on September 7th, 2006 submitted, No.PCT/US04/43465, on December 23rd, 2004 passed and No.PCT/US04/33359, and filed October submitted on October 8th, 8,2004).The document of present patent application has also comprised the content of above-mentioned document.
Patent has also been announced a kind of composition, it is characterized in that described composition can treat and prevent following disease: antiMS, aneurysma, asthma, anibradykinic; capillary hemorrhage, headache, cervicobrachialgia, eclampsia, oedema; encephalitis, epiglottitis is oozed out, influenza, fracture; oulitis, hemotoncus, bleb, histamine shock; hydrarthrosis, meningitis, antioxygenation, periodontitis; phlebitis, pleuritis, trachyphonia, rhinitis; tonsillitis, ulcer, varix, dizzy; cancer metastasis causes Kendall compound and takes place, and diuresis is antimycotic; hemolytic action, hyaluronidase inhibitor, sharp lymph agent, natriuresis; sterilant, sharp mucus agent, thymolytic, the effect of protection blood vessel and vein.
This patent has also been announced a kind of composition of useful as drug, it is characterized in that described composition contains a certain amount of compound Y0, Y1, Y2, Y (Y3), Y7, Y8, the arbitrary compound among Y9 and the Y10, or its esters, lipid, meta-bolites, or derivative, said composition can be used for bringing out cancer cell-apoptosis, suppresses the following cancer of pharmacological agent of tumour or growth of cancer cells: mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, melanoma cancer, kidney, or cervical cancer.
This kind be as the composition palatable of medicine clothes, but or under special situation peritoneal injection, intravenous injection or vein drip.
Xanifolia Y0, Y1, Y2, Y, Y7, Y8, Y9, Y10 medicinal soluble be in Glucose Liquid or sodium-chlor liquid, intravenous injection or vein drip.
Example 1: vein drip: per kilogram consumption 0.05-0.2mg is dissolved in 10% the glucose solution of 250ml or 0.9% sodium chloride solution of 250ml.
Example 2: intravenous injection: every day per kilogram consumption 0.05-0.2mg, be dissolved in 10% glucose solution or 0.9% sodium chloride solution of 10-20ml.Medication process 7-10 days.
Example 3: vein drip: every day per kilogram consumption 0.1-0.2mg, be dissolved in 10% the glucose solution of 250ml or 0.9% sodium chloride solution of 250ml.Medication process 7-10 days.
Example 4: intravenous injection: every day per kilogram consumption 0.1-0.2mg, be dissolved in 10% glucose solution or 0.9% sodium chloride solution of 10-20ml.Medication process 7-10 days.
Example 5: peritoneal injection: every day per kilogram consumption 2.5-0.2mg, be dissolved in 10% glucose solution or 0.9% sodium chloride solution.Medication process 7-10 days.
This kind is as the composition palatable clothes of medicine, Mammals dosage per kilogram 1-10mg.This kind is as the composition palatable clothes of medicine, dosage per kilogram 10-30mg, 30-60mg and 60-90mg.。
But this kind is used as the composition intravenous injection or the vein drip of medicine, dosage per kilogram 0.01-0.1mg, and 0.1-0.2mg, 0.2-0.4mg and 0.4-0.6mg.
But this kind is as the composition peritoneal injection of medicine, dosage per kilogram 1-3mg, 3-5mg, 4-6mg and 6-10mg.
This patent has also been announced a kind of method of making the pharmacological agent mammalian cancer, it is characterized in that described method is to give this Mammals a certain amount of medicine, this medicine is a composition, and said composition has the above-mentioned chemical structure that this patent provides or contains the compound with above-mentioned chemical structure.Said composition can be used for treating mammiferous following cancer: mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, the melanoma cancer, kidney, or cervical cancer, but be unlikely to above-mentioned cancer.Said compound comprises Xanifolia Y0, Y1, Y2, Y, Y7, Y8, Y9, Y10, or its esters, ester class, meta-bolites, derivative.See also Fig. 4-6, the experimental result among 11-23 and the 37-38.
This patent has also proposed a kind of method, it is characterized in that described method can influence and adjust the proteinic function of cell surface, or changes the function of the functional protein of intracellular membrane, or adjusts the process that fluid passes cell walls and remove kill cancer cell.This method is to give the compound that a certain amount of this patent provides, and this compound has above-mentioned chemical structure (1), (1A), and (1B), (1C), (1D), compounds X anifoliaY0 preferably, Y1, Y2, Y, Y7, Y8, Y9, Y10.In one case, compounds X anifoliaY0, Y1, Y2, Y, Y7, Y8, Y9, Y10 act on the protein of cytolemma, open the passage of water or other solute, and the cancer cells that has absorbed water or other solute can rise brokenly dead.
Under another situation, compounds X anifolia Y0, Y1, Y2, Y, Y7, Y8, Y9, the protein bound of Y10 and cytolemma is opened the passage of water or other solute, and the cancer cells that has absorbed water or other solute can rise brokenly dead.
Compounds X anifolia Y0, Y1, Y2, Y, Y7, Y8, Y9, Y10 can dilute the outer solution of cancer cells, be that more moisture enters cancer cells, and the one or more water outer membrane protein in the cancer cell membrane ( AQPs 1,2, and 3,4,5,6,7,8,9, with 10) can be too express, thereby can be for Whom or ion provide more passage to enter cancer cells, a cancer cell death.
The method that this patent has also proposed a kind of anticancer growth and brought out cancer cell-apoptosis is characterized in that described method is to make the overexpression of water outer membrane protein and destruction of cancer cells, and said here cancer cells is following cancer cells: mammary cancer, the white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, the melanoma cancer, kidney, or cervical cancer.Under another situation, said cancer cells is an ovarian cancer.
This patent has also been announced a kind of method for the treatment of mammalian cancer, it is characterized in that described method is to give this Mammals a certain amount of medicine, this medicine is a composition, and said composition has the above-mentioned chemical structure that this patent provides or contains the compound with above-mentioned chemical structure.Said composition can be used for treating mammiferous following cancer: mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, the melanoma cancer, kidney, or cervical cancer, but do not terminate in above-mentioned cancer.Said compound comprises Xanifolia Y0, Y1, Y2, Y, Y7, Y8, Y9, Y10, or its esters, ester class, meta-bolites, derivative.
Alkenyl (Alkenyl) is the chemical structure wire that one or more pairs of keys are arranged or branch-like that contains 17 carbon, as vinyl, and propenyl, pseudoallyl, butenyl, s-butenyl, t-butenyl, pentenyl, hexenyl, butadienyl, pentadienyl, hexadienyl.
Aromatic base is the organic molecule function group of deriving and from carbocyclic ring shape aromatic compound (as benzene), contains the carbocyclic ring shape aromatic compound of 6-14 carbon of 1-3 phenyl ring.If plural aromatic nucleus links together, adjacent ring has common key, as phenyl and naphthyl.Aromatic base can be by one or more alkyl, halogen, and alkoxy substitutes.
Organic acid removes carboxyl can obtain acyl group.The molecular formula of acyl group is-COR a pair of key to be arranged between carbon and Sauerstoffatom.The chemical name of aromatic base is all with-yl ending, as formyl radical, and ethanoyl, propionyl, butyryl radicals and phenmethyl.
Phenmethyl is a kind of of aromatic base, writing C 6H 5CO-R, phenylformic acid remove carboxyl can obtain phenmethyl.
Heterogeneous ring compound is the compound that contains the heteroatomic nonaromatic heterocycles of 1-4, can be that a monocycle or a heterocycle and other 3-7 alicyclic ring connect together, this alicyclic ring contains 0-4 heteroatoms, aromatic base and assorted aromatic base, said here heterogeneous ring compound comprises pyrrolidyl, pipyrazinyl, morpholinyl, trahydrofuranyl, imidazolinyl, thiomorpholinyl etc.Remove a hydrogen atom and will derive heterogeneous ring compound from any ring of Heteroarene.
Alkyloyl (Alkanoyl) is an organic functions group, writing RCO-, and wherein R is a hydrogen, or alkyl, preferably ethanoyl, propionyl, butyryl radicals, pentanoyl and caproyl.
Alkenoyl is the alkene carbonyl, wherein alkenyl as mentioned above, alkene carbonyl such as amylene carbonyl (along root of Dahurian angelica acyl group), hexene carbonyl (angeloyl groups).
Alkyl is the chain of carbon containing and hydrogen atom only, branch-like, ring-type, the compound of double-ring or their combination, 1-18 carbon atom arranged, as methyl, ethyl, propyl group, sec.-propyl, butyl, s-butyl, t-butyl, amyl group, hexyl, heptyl, octyl group, nonyl, dodecyl, tridecyl, tetradecyl, pentadecyl, cyclopropane base, tetramethylene base, pentamethylene base and cyclohexyl.
Benzoyl, alkyl alternate alkyloyl are to have the alkyloyl of the straight chain of 1-6 carbon or branched chain to be replaced by at least one benzoyl and an alkyl, and benzoyl is to be connected on the alkyloyl of 1-6 carbon of straight chain or branched chain the phenacyl isobutyryl.
Sugar chain is a side chain in the compound, it is characterized in that described side chain contains one or more sugar, or itself or uronic acid, or derivatives thereof.
Isobutyryl is the different name of 2-methylpropionyl.
Y and Y3 are same compounds.
The anti-cancer ability of research compound is to use the cancer cells of human Different Organs in present patent application, and observes this compound plays growth to cancer cells influence.In these preliminary experiments, we find the influence of Wood of Shinyleaf Yellowhorn plant milk extract to this a series of growth of cancer cells.We have studied the influence of Wood of Shinyleaf Yellowhorn plant milk extract to the growth of cancer cells of the human Different Organs of 10-15 series with mtt assay, find ovarian cancer cell OVCAR3 the most responsive (IC50=14.5 μ g/ml).Referring to international patent application book (NO.PCT/US2004/33359 and U.S. Patent application book US NO.10/906,303.
Activeconstituents in the Wood of Shinyleaf Yellowhorn plant milk extract is purified through separating, called after Xanifolia-Y, and its chemical structure has been done Analysis and Identification with two dimensional NMR and mass spectrum.Xanifolia-Y is a new triterpenoid saponin compound, and this compound contains two angeloyl groups, and two angeloyl groups are connected an end of triterpene structure, and carbohydrate or sugar chain are connected the other end of triterpene structure.In one case, two angeloyl groups are connected the carbon 21 of triterpene structure and 23, and carbohydrate or sugar chain are connected 3 in the carbon of triterpene structure.Two angeloyl groups are very important for the antitumour activity of compound.Separate the antitumour activity that the compound of purifying has been used to detect 60 cancer cell series.Detected result shows that the IC50 value is between 0.1-1 μ M.
In our early stage research, ovarian cancer cell OVCAR3 is to Xanifolia-Y the most responsive (IC50=14.5 μ g/ml) in the cancer cells of all checks.We have then checked 10 kinds of other ovarian cancer cell series again, and the result shows that all inspected ovarian cancer cells are all very sensitive to Xanifolia-Y, and the IC50 value is between 2-12 μ M.Please referring to experiment 11.
In the experiment made on the living of people's ovarian cancer cell being transplanted to the white mouse of nude, people's ovarian cancer thin (ES2) is seeded in the peritoneal cavity of white mouse of nude, then to mouse with Xanifolia-Y ( experiment 7,8,9).Medication in the 1st, 4 and 10 day after ovarian cancer cell is transplanted, Xanifolia-Y ten days (i.p.).The result shows that the mouse mean survival time of not medication is about 20-24, and none death of mouse of the medication in the 1st day after ovarian cancer cell is transplanted; The mouse of the medication in the 4th day after ovarian cancer cell is transplanted, none death during to the 50th day; The mouse of the medication in the 10th day after ovarian cancer cell is transplanted, 50% mouse death during to the 50th day.The compound that this experimental result explanation this patent provides can prolong the mammiferous survival time.
The mouse of the medication in the 4th day after ovarian cancer cell is transplanted, mean survival time are about 58 (the prolongation survival time reaches 141%); The mouse of the medication in the 10th day after ovarian cancer cell is transplanted, mean survival time are about 31 (the prolongation survival time reaches 29%).The compounds X anifolia-Y that this experimental result explanation this patent provides can prolong the mammiferous survival time of cancer cell transplantation, and it can be as treatment people's ovarian cancer.
In gynecologic malignant tumor, it is the highest causing women's mortality ratio in U.S.'s ovarian cancer, finds 16,000 new dead cases (data is from the NIH net) in 2005.Ovarian cancer is causing that the high reason of women's mortality ratio is that at first, illness is not obvious, mistaken diagnosis easily.When diagnosing out, cancer cells shifts.Treatment ovarian cancer usual method is cis-platinum or similar compounds and taxol combine (McGuire etc., 1996; Ozols etc., 2003).Patient's prolonged survival period behind the intraperitoneal administration extended to 65.6 months from 49.7 months, and such result is unsafty far away (Armstrong etc., 2006).If make medication direct and cancer cells effect meeting raising result of treatment.
As above said, the living animal experimental result that we imitate the human body situation shows that compounds X anifolia-Y can prolong the mammiferous survival time of cancer cell transplantation effectively.When the examination mouse the peritonaeum intraluminal grafting behind the ovarian cancer cell (ES2), (being equivalent to the human ovarian carcinoma later stage) peritoneal cavity innerlich anwenden (Xanifolia-Y) in the process of cancer diffusion finds that Xanifolia-Y can prolong the survival time of having transplanted ovarian cancer cell examination mouse.And medication more early effect is good more.
According to our experimental result, the reason that Xanifolia-Y can prolong the survival time of having transplanted ovarian cancer cell examination mouse is to have stoped to have transplanted the transfer of ovarian cancer cell toward the mesothelium of peritoneal cavity.But the Xanifolia-Y anticancer adheres on the flask and (sees experiment 13) in external test tube experiment.Known in the process that ovarian cancer cell shifts the adhesion of molecule play an important role (Skubitz, 2002; Shaller, 1996; Zetter, 1993).The main path that ovarian cancer cell shifts is to adhere on the mesothelium of peritoneal cavity (Gardner etc., 1955) by ovarian cancer cell.Xanifolia-Y has stoped the sticking action of molecule.In one case, Xanifolia-Y has stoped the effect that molecule is adhered on the cancer cells.Under this kind situation, effect that Xanifolia-Y has stoped molecule to be adhered on the ovarian cancer cell has stoped molecule to go up adhesion toward the mesothelial cell of peritoneal cavity.Under another situation, the protein bound of adhering on Xanifolia-Y and the cytolemma (covering protein) stops the protein of adhesion and its acceptor to act on mutually.
Under another situation, Xanifolia-Y acts on the function that cytolemma influences adhesion protein matter on the cytolemma.In the direct or indirect effect of the such cell membrane adhesion protein of Xanifolia-Y matter, cancer cells has just lost the ability of adhesion.
Most of adhesion protein matter is glycoprotein.Carbohydrate on sugar chain on the adhesion protein matter and the other molecule is as saponin or Xanifolia-Y reaction.Xanifolia-Y contains a trisaccharide in 3 in carbon, and Xanifolia-Y lost carbohydrate, and its activity will reduce (Fig. 4 D and 5C).Our EM studies show that Xanifolia-Y influences the structure of cytolemma, and can form hole on film.The damage of membrane structure can change the conformation of adhesion protein matter, by with other molecule in conjunction with disturbing, even make them lose anti-base on the film.
We studies show that to Xanifolia-Y's Xanifolia-Y can be used for the treatment of cancer, particularly advanced ovarian cancer.Can suppress the result of mammiferous growth of cancer cells from Xanifolia-Y, this class saponin and have the compound of similar structures to can be used for cancer therapy.
When the influencing of research Xanifolia-Y cell membrane structure, after cytolemma is handled with Xanifolia-Y, with the morphologic variation of electron microscopic observation cytolemma.In this experiment, cancer cells K562 handled 60 minutes with the Xanifolia-Y of 5 μ M, and DMSO solvent (60 minutes) and AKOH-Y (Xanifolia-Y sloughs the derivative of angeloyl groups, does not have anticancer activity, 20 μ M, 60 minutes) handle in contrast.Cancer cells is used electron microscopic observation after with 1% USc dyeing.As can be seen from Figure 25 on the cytolemma that Xanifolia-Y handled, occur blocks of alveole (Figure 25 B, X20000), and the DMSO solvent (Figure 25 A, X60000) and AKOH-Y (Figure 25 C, X60000) cancer cells of Chu Liing does not have the alveole appearance.The diameter of these alveoles is at 80A-500A.Alveole occurs showing and has occurred hole on the cytolemma.The characteristics of the arrangement of alveole are, the 80A alveole be arranged in edge, the center that is arranged in of 500A alveole.Aperture merges and has formed macropore (Figure 25 D).Experimental result shows that Xanifolia-Y can change the cancer cell membrane structure, but i.e. Xanifolia-Y destruction of cancer cells film.
Xanifolia-Y can be used for suppressing following growth of cancer cells, or handles following cancer cells: mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, melanoma cancer, kidney, or cervical cancer, particularly ovarian cancer, but be unlikely to above-mentioned cancer.In our research, in the different cancer cells series, ovarian cancer cell is the most responsive.Human cancer cell suppresses to show to the experimental result of mouse that Xanifolia-Y can prolong the survival time of examination mouse.
In the past, in treatment for cancer, medicine also of no use used the precedent of medicine at cancer cell membrane or cancer cell membrane component.Xanifolia-Y is first at the new drug of cancer cell membrane or the medication of cancer cell membrane component treatment cancer, and it can influence cancer cell membrane or cancer cell membrane component really, and the medicine of this and any treatment cancer in the past is all different.
This patent provides a kind of treatment method for cancer, it is characterized in that described treatment method for cancer is the characteristics that change cancer cell membrane, thereby stops cancer metastasis, and the anticancer growth stops revascularization (angiogenesis).
This patent provides a kind of characteristics by the change cancer cell membrane, thereby stops cancer metastasis, and the method for anticancer growth is characterized in that the characteristics of described cytolemma comprise adhesion protein matter, described cancer is a mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, the melanoma cancer, kidney, or cervical cancer; Described method is to use Xanifolia Y0, Y1, and Y2, Y, Y7, Y8, Y9, Y10, or its esters, the ester class, meta-bolites, derivative are handled above-mentioned cancer cells.Under another situation, be to remove to handle cancer cells with the compound that this patent provides with above-mentioned chemical structure.
This patent provides a kind of characteristics by the change cancer cell membrane, thereby stops cancer metastasis, and the composition of anticancer growth is characterized in that described cancer is a mammary cancer, the white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, the melanoma cancer, kidney, or cervical cancer.
Present patent application shows that Xanifolia-Y is that the anticancer of a kind of inhibition DNA type or microtubule target type (microtubule-targeting) substitutes or complementary medicine.Single with or and other medicines (prevention M-phase process or DNA synthetic medicine) when share, all can be resultful.We test the growth that Xanifolia-Y and taxol share anticancer ES2 comprehensive effect (seeing experiment 15 for details).
Our experimentation on animals result shows that Xanifolia-Y can prolong the survival time (asking for an interview experiment 7,8,9 and 10) of the examination mouse of cancer cell transplantation.If medication (Xanifolia-Y) is postponed, the examination mouse death time is (the relatively result of medication in 1,4 and 10 day after cancer cell transplantation) just in advance.Experimental result shows that Xanifolia-Y can stop the transfer of the cancer cells of transplanting.The adhesion molecule of ovarian cancer cell is very high.Adhesion protein matter is present in cancer cells and the mesothelial cell.Because Xanifolia-Y and adhesion protein matter are in conjunction with the possibility of just having blocked protein adhesion.In this case, Xanifolia-Y acts on the bonded place that cancer cell membrane has just changed adhesion protein matter indirectly.
We have proved that Xanifolia-Y has deleterious cellular effects to cancer cells, it has killed ovarian cancer cell in this case, Xanifolia-Y has suppressed the growth of cancer cells, prolonged the survival time of the examination mouse of cancer cell transplantation, and, medication (Xanifolia-Y) more early, the survival time that prolongs the examination mouse is just long more.Xanifolia-Y can stop the transfer of the cancer cells of transplanting.Postponement medication (Xanifolia-Y) time can increase the chance of cancer metastasis to intracutaneous between peritoneal cavity, thereby cancer cells can increase, and the survival time chance of examination mouse shortens.Adhesion molecule also plays an important role in cancer metastasis.Our experimental result shows that Xanifolia-Y can stop cell adhesion cultivating on the beaker.Xanifolia-Y can disturb the function of adhesion molecule, and in this case, Xanifolia-Y covers adhesion protein matter directly in conjunction with adhesion protein matter.Under another situation, Xanifolia-Y changes the structure of cancer cell membrane, causes that proteinic conformation or position change, thereby makes it lose the ability of adhesion.
The experiment detailed results
About extracting, the separation purification (using HPLC) of extract, measure, measure the ability of Xanifolia-Y anticancer growth with mtt assay, the separation purification (using FPLC) of active substance, the purification of Y series compound (with the HPLC for preparing), the experiment detailed results of the mensuration of chemical structure is at international patent application book (NO.PCT/US05/031900), U.S. Patent application book (U.S.Serial NO.11/289,142, U.S.SerialNO.10/906,303 and U.S.Serial NO.11/131,551) announce in.The document of present patent application has also comprised the content of above-mentioned document.
Experiment 1: the mensuration of the hemolytic action of the compound Y that from Wood of Shinyleaf Yellowhorn, proposes
Method:
1. blood of human body obtains (Houston Gulf Coast Blood Center2) from gulf, Houston bank Blood Center.
2. erythrocyte proposes with following method: blood of human body (being dissolved among the EDTA) dilutes with PBS: 1: 1.Inject 4ml Histopaque-1077 (SIGMA), centrifugal 30 minutes (400g).
3. collect erythrocyte (RBC), and wash 3 times with PBS.
4. it is standby to make 10% erythrocyte (RBC) suspension with erythrocyte (RBC).50ul erythrocyte (RBC) suspension adds the suspension that the 2ml saponin is mixed with different concns.
5. suspension and vortexing mix the back room temperature placement 60 minutes.
6. centrifugal 5 minutes of suspension (3000rpm).Measure the spectral absorption of supernatant liquor at 540nm.
The result
In this experiment, compared Xanifolia-Y (#63Y), the hemolytic action of Escin and saponin (SIGMA).Saponin (SIGMA) is the thick saponin of bark of Quillaia, and Escin contains an angeloyl groups, and compound Y contains two angeloyl groups.Experimental result shows, ((IC50=1ug/ml) is than Escin and saponin (SIGMA, IC50=5ug/ml) all strong (seeing Fig. 6 A) for compound Y (#63Y) hemolytic action.
Test 2 compound Y and remove hemolytic action behind angeloyl groups or the sugar chain and the mensuration of MTT
Method:
(A) Xanifolia-Y of the basic hydrolysis of Xanifolia-Y: 20mg is dissolved in the 1M NaOH solution of 0.5ml, cultivates 4 hours in the 80C water-bath then.When the solution cool to room temperature,, use propyl carbinol 2ml lixiviate 3 times again with the 1N HCl neutralization (pH is transferred to about 3) of 0.5ml.Collect the propyl carbinol thing, and lyophilize.With HPLC (C-18 post and 25% second eyeball) wash-out purifying.
(B) Xanifolia-Y of the acid hydrolysis of Xanifolia-Y: 15mg is dissolved in the 1ml methyl alcohol, adds the 2N HCl of 1ml.In 80 ℃ of water-baths, refluxed 5 hours, with the 1N NaOH neutralization (pH arrives 3-4 at last) of 2ml.With 3ml ethyl acetate extraction hydrolyzed solution three times, collect and propose glucosides.Further separate the glucosides that proposes with HPLC (80% second eyeball constant gradient wash-out).
The result:
Hemolytic experiment is the result show, by basic hydrolysis, after the angeloyl groups of compound Y is removed, just lost hemolytic action.By acid hydrolysis, after the sugar of compound Y was removed, hemolytic action reduced.This shows that the existence of angeloyl groups is a key point to the hemolytic action of this compound, and the existence of sugar only is complementary to the hemolytic action of this compound.(seeing Fig. 4 D).The MTT assay shows, has just lost the MTT effect after the angeloyl groups of compound Y is removed.After the sugar of compound Y was removed, the MTT effect reduced (seeing Fig. 5 C and 5D).Compound Y, the hemolytic action comparing result of Escin and saponin (SIGMA) is seen Fig. 7.Compound Y, compound Y angeloyl groups is removed, and sugared removed hemolytic action comparing result is seen Fig. 6 A and 6B.Compound Y angeloyl groups is removed (AKOH-Y), and sugar is removed the chemical structure of (ACH-Y) and sees Fig. 7 respectively.
Test 3 compound Y in the effect that alleviates venous insufficiency (particularly hemorrhoid)
Ask for an interview international patent application book (NO.PCT/US2006/016158, on April 27th, 2006 submitted)
Test 4 compound Y in that to alleviate (bringing out mouse pin swollen model by carrageenin) mouse pin swollen
Effect
Ask for an interview international patent application book (NO.PCT/US2006/016158, on April 27th, 2006 submitted)
Experiment 5 separates the purification activeconstituents from extract
(A) with FPLC isolating active composition from plant milk extract
Ask for an interview international patent application book (NO.PCT/US05/31900, on September 7th, 2006 submitted), U.S. Patent application book (U.S.Serial No.10/906, on February 14th, 303,2005 was submitted U.S.SerialNo.11/131551, on May 17th, 2005 submitted) and international patent application book (No.PCT/US04/43465, on December 23rd, 2004 passed and No.PCT/US04/33359, and filedOctober submitted on October 8th, 8,2004).The document of present patent application has also comprised the content of above-mentioned document.
(B) with preparation HPLC component Ys separation is purified out
Method:
Chromatographic column: adopt preparation Waters Delta Pak C18-300A post.
Wash-out: 45% constant gradient wash-out.Flow rate: 1.0ml/ branch.
Component supervisory wavelength: 207nm, and collection and vacuum lyophilization.
The result:
The Y component comprises Y1, Y2, and Y (Y3) and Y4 are separated well, and respectively
Collected.Again isolated Y component is done stratographic analysis with the anti-phase C18 post of HPLC, only show one unimodal.Again to isolated Y8, Y9and Y10 component is done stratographic analysis with the anti-phase C18 post of HPLC, also only show respectively one unimodal.
(C) final Y1 component outward appearance of purifying is the white powder of indefinite form.Dissolve in by (methyl alcohol and ethanol) in the alcohol, in 50% second eyeball and 100% the pyridine.
(D) the MTT detected result of compound Ys
The result shows, compound Y, and growth has restraining effect (seeing Fig. 5 A) to ovarian cancer (OCAR-3) for Y8, Y9 and Y10.Figure 27 shows the restraining effect of compound Ys to ovarian cancer (OCAR-3) growth.
Test the mensuration of 6 chemical structures
Method:
Nucleus magnetic resonance (NMR) is analyzed:
Pure Lignum Xanthoceratis extract Y component sample is dissolved among the pyridine-d5 (pydine-D5) that contains 0.05%TMS, with have QXI probe ( 1H/ 13C/ 15N/ 31P) Bruker Avance 600MHz nuclear magnetic resonance analyser, the 298k nuclear magnetic resonance spectrum of acquisition all samples.One dimension 1The scanning times of the nuclear magnetic resonance spectrum of H (16-128) depends on the concentration of sample.Two dimension HMQC nuclear magnetic resonance spectrum, spectrum width 6000x24000Hz, the material point of t1 and t2 dimension is respectively 2024x256, and scanning times is 4-128.Two dimension HMBC nuclear magnetic resonance spectrum, spectrum width 6000x30000Hz, the material point of t1 and t2 dimension is respectively 2024x256, and scanning times is 64.These 2-D datas carry out the Fourier conversion by mathematics calculation and utilization XWIN-NMR software, the scale of the two-dimentional HMQC that obtains at last and the matrix of HMBC nuclear magnetic resonance spectrum be respectively 2048x256 and 2048x512 (datapoints, F2xF1).
Mass spectroscopy:
The quality of Lignum Xanthoceratis extract sample is measured by MALDI-TOF mass spectrum and ESI-MS mass spectrometry.(A) MALDI-TOF mass spectrum: at first sample is dissolved in the second eyeball right and CHCA mother liquor mixing (α-cyanogen-4-hydroxyl meat silicic acid 10mg/ml is dissolved among 50: 50 water/second eyeballs and the 0.1%TFA).Sample is dissolved in the second eyeball fully and mother liquor still keeps dissolved state after mixing.Molecular weight is measured by high-resolution mass spectrograph.(B) ESI-MS mass spectrum: with sample ionsization and be dissolved in the second eyeball, sample is analyzed with LCQ DECA XP Plus (Thermo Finnigan) then.
The result
Proton NMR spectrum figure sees Fig. 8 A, 8B, 9A, 9B, 10A and 10B.1H, 13C, TOCSY, HMQC, HMBC and NOESY nmr spectrum illustrate respectively in the drawings.
According to these data and analysis, the chemical structure of compound Y0 is as shown below:
Figure A20078004074400501
This patent provides an active compound Y0.Its chemical name is:
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group; 22-O-(dimethyl propylene acyl group)-3 β; 15 α; 16 α; 21 β; 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
Test 7 experimentation on animalies
Method:
● athymic Nu/Nu mouse is divided into 3 groups (A, B and C), every group of 4 mouse.
● from the 0th day, transplant human ovarian cancer (ES2) cell at the intraperitoneal of A group and B group mouse.
● B and C group mouse were accepted medicine (Xanifolia-Y) in first day and handle (i.p.), 5mg/kg.
● the 2nd to 4 day, played B and C group on the the 7th to 11 day and accept medicine (Xanifolia-Y) every day and handle (i.p.), 2.5mg/kg.
● A group mouse is not accepted medicine (Xanifolia-Y) and handles.
The death in 19-22 days of result: A group mouse.B group mouse survived more than 50 days.C group mouse survived more than 50 days.See also Figure 21.
Test 8 experimentation on animalies
Method:
● athymic Nu/Nu mouse is divided into 3 groups (A, D and E), every group of 4 mouse.
● from the 0th day, transplant human ovarian cancer (ES2) cell at the intraperitoneal of A group and B group mouse.
● D group mouse rose on the 4th day accepts medicine (Xanifolia-Y) processing (i.p.), 2.5mg/kg, totally 9 days every day.
● E group mouse rose on the 10th day accepts medicine (Xanifolia-Y) processing (i.p.), 2.5mg/kg, totally 10 days every day.
● A group mouse is not accepted medicine (Xanifolia-Y) and handles.
Result: A group mouse is all dead in 24 days.D group mouse all survives.Only half survival of E group mouse.
See also Figure 22.
Test 9 experimentation on animalies
Method:
● athymic Nu/Nu mouse, 2-3 month, transplant human ovarian cancer (ES2) cell.
● transplanted behind human ovarian cancer (ES2) cell the 5th day, and be divided into 2 groups (H and J), every group of 2 mouse.
● H group mouse was transplanted behind human ovarian cancer (ES2) cell 1-5 days and accepted medicine (Xanifolia-Y) 8-10 days every days and handle (i.p.), 2.5mg/kg.
● J group mouse is not accepted medicine (Xanifolia-Y) and handles.
18 millimeters big of result: J group mouse tumors.H group mouse is in 10 days, and 10 millimeters in tumour is big, is 45% of J group mouse tumor.See also Figure 23.
Test 10 experimentation on animalies
Method:
● athymic Nu/Nu mouse 5-6 month, is divided into 3 groups (O, P and Q), every group of 5-6 mouse.
● from the 0th day, the intraperitoneal of all mouse was transplanted human ovarian cancer (ES2) cell.
● P group mouse 4-8 days, 11-15 days, 18-22 days, 25-29 days, 32-36 days, accept medicine (Xanifolia-Y) 39-43 days every days and handle (i.p.), 2.5mg/kg.
● P group mouse 10-15 days, 18-22 days, 25-29 days, 32-36 days, accept medicine (Xanifolia-Y) 39-43 days every days and handle (i.p.), 2.5mg/kg.
● O group mouse is not accepted medicine (Xanifolia-Y) and handles.
Result: O group mouse is not accepted medicine (Xanifolia-Y) and handles, and mean survival time is 24 days.The mouse mean survival time of accepting medicine (Xanifolia-Y) processing on the 4th day is 58 days, has prolonged 141%.
The mouse mean survival time of accepting medicine (Xanifolia-Y) processing on the 10th day is 31 days, has prolonged 29%.See also Figure 28.
Experiment 11Xanifolia-Y is to the MTT detected result of Proliferation of Human Ovarian Cell series
Very responsive to compounds X anifolia-Y since our finder's ovarian cancer cell, we have just done further check to other Proliferation of Human Ovarian Cell series.Most of ovarian cancer takes place from the epidermal surface of ovary, belongs to the histology hypotype of clear-cells serum cancer.Experiment is done by the Proliferation of Human Ovarian Cell system that we have obtained the histology hypotype of 10 swollen this clear-cells serum cancers, suppresses the ability of ovarian cancer cell with mtt assay detection compound Xanifolia-Y.Following table is that fruit was tied in experiment.
The result:
The MTT value of table 2.10 kind of Proliferation of Human Ovarian Cell (IC50 μ M)
Ovarian cancer cell line Type IC50μM
OVCAR3 Serum 2.2
TOV-21G Clear-cells 2.2
ES2 Clear-cells 4.4
RMG2 Clear-cells 8.8
OVCA 429 Serum 7
OVCA 432 Serum 4.4
OVCA 433 Serum 8.8
Caov 3 Serum 7
SKOV 3 Serum 10.5
Hey 8A Serum 10.5
Xanifolia-Y to the MTT value of this 10 kinds of Proliferation of Human Ovarian Cell system between 2-10 μ M.This result shows that Xanifolia-Y is very low to the effective concentration of Proliferation of Human Ovarian Cell system, in the scope of μ M, and can be beautiful with other cancer therapy drug ratio.
Experiment 12Xanifolia-Y brings out the research of cancer cell-apoptosis
The apoptosis of the OVCAR3 ovarian cancer cell that process Xanifolia-Y handles detects with wandering cells counter and propidium iodide.The result show (seeing Figure 25) early apoptosis (right upper quadrant) and late period apoptosis or necrosis (right lower quadrant) appear at ovarian cancer cell 24 hours after Xanifolia-Y handles, and the cancer cells quantity of early apoptosis wants high.The result shows that Xanifolia-Y causes that the apoptosis of ovarian cancer cell is the principal mode (Figure 24) of cancer cell death.
Experiment 13Xanifolia-Y influences the research of membrane structure
Xanifolia-Y has the potential hemolytic action to red blood corpuscle.With the influence of the structure of electron microscopic observation Xanifolia-Y cell membrane, morphologic variation.In this experiment, the K562 cell was handled 60 minutes with the Xanifolia-Y of 5 μ M.DMSO solvent and AKOH-Y (Xanifolia-Y sloughs the derivative of angeloyl groups, does not have anticancer activity) are in contrast.Cancer cells dyes with 1% UAc, uses electron microscopic observation.
As can be seen from Figure 25 on the cytolemma that Xanifolia-Y handled, occur blocks of alveole (Figure 25 B, X20000), and the DMSO solvent (Figure 25 A, X60000) and AKOH-Y (Figure 25 C, X60000) cancer cells of Chu Liing does not have the alveole appearance.The diameter of these alveoles is at 80A-500A.Alveole occurs showing and has occurred hole on the cytolemma.The characteristics of the arrangement of alveole are, the 80A alveole be arranged in edge, the center that is arranged in of 500A alveole.Aperture merges and has formed macropore (Figure 25 D).
Experimental result shows that Xanifolia-Y can change the cancer cell membrane structure, but i.e. Xanifolia-Y destruction of cancer cells film.
Experiment 14Xanifolia-Y influences the research of cell adhesion
Method:
Ovarian cancer cancer cells ES2 or Hey 8A are placed in the flask, and the T25 flask has the Xanifolia-Y substratum that contains 5 μ g/ml, cultivate 5 hours.From flask, propose the cell paid by tryptic effect, and measure its quantity.
The result:
With do not have comparing of Xanifolia-Y, the ES2 cell of 86+4% and the cell of Hey 8A67+8% are being paid on flask.Under the Xanifolia-Y of 5 μ g/ml handled, the cell above 90% was not pay, and cultivated in the cultivation of no Xanifolia-Y by cotton blue detection with them again, proved that they live.But, under the Xanifolia-Y of 10 μ g/ml handles, only have to be less than 40% cell and to pay on flask.And much be dead cell.The process of paying of experimental result explanation Xanifolia-Y anticancer.
The research of the combined effect of experiment 15Xanifolia-Y and taxol
Method:
(i) ovarian cancer cancer cells ES2 handles with the Xanifolia-Y of following concentration: 40,20,10,5,2.5 and 1.25 μ g/ml;
(ii) ovarian cancer cancer cells ES2 is with the taxol treatment of following concentration: 10,5,2.5,0.62 and 0.031ng/ml;
The (iii) taxol that adds 10ng/ml with the Xanifolia-Y and the taxol comprehensive treating process cancer cells ES2:40 μ g/mlXanifolia-Y of following concentration, 20 μ g/ml Xanifolia-Y add the taxol of 5ng/ml etc.Detect the IC50 value of cancer cells with MTT.
The result:
Single IC50 value of handling with Xanifolia-Y is 5 μ g/ml, and the IC50 value of taxol is 1.25ng/ml.When Xanifolia-Y and taxol comprehensive treating process cancer cells, extra effect shows, and the IC50 value of Xanifolia-Y is that the IC50 value of 2.5 μ g/ml and taxol is 0.625ng/ml, has all reduced with comparing the IC50 value with single.
Experiment 16 detects the water outer membrane protein of ovarian cancer cancer cells HeLa and OVCAR3
Method:
1.HeLa and the cell cultures of OVCAR3 is in the ROMI1640 substratum, 37 ℃, and 5% CO 2Concentration.
2. collecting cell and wash with PBS.
3. the protein of cell is dissolved in the SDS damping fluid that contains proteinase inhibitor (PMSF and Leupentin), cultivates 20 minutes at 70 ℃.
4. on 12% sds gel, the protein of equivalent is separated from HeLa and OVCAR3 cell, then on the digestion fibrous paper, made Western blot.
5. Western blot is with antibody anti-AQ1 (Chemicon/SIGMA)) and second antibody treatment, second antibody and alkaline phosphatase coupling.
The result:
The result of Western blot shows at Figure 31.
1) on the cell of OVCAR3, observed water outer membrane protein-1 (arrow indication), but few on the cell of HeLa.
2) protein of HeLa and OVCAR3 equivalent is infused on 12% the sds gel, and still, water outer membrane protein 1 concentration that the OVCAR3 cell contains is higher than HeLa.
Because than HeLa cell sensitivity, water outer membrane protein-1 concentration that the OVCAR3 cell contains is higher than HeLa to the OVCAR3 cell to Xanifolia-Y, show that Xanifolia-Y has the potential ability of the growth of cancer cells that suppresses the overexpression of water outer membrane protein.
Reference
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2.Zhong Jaing，Jean-francois Gallard，Marie-Therese Adeline，Vincent Dumontet，Mai VanTri，Thierry Sevenet，and Mary Pais″Six Triterpennoid Saponins from Maesa laxiflora.″.J.Nat.Prod.(1999)，62，873-876.
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4.Xiu-Wei Yang，Jing Zhao，Xue-Hui Lui，Chao-Mei Ma，Masao Hattori，and Li He Zhang″Anti-HIV-1 Protease Triterpenoid Saponins from the Seeds of Aesculus chinensis.″J.Nat.Prod.(1999)，62，1510-1513.
5.Yi Lu，Tatsuya Umeda，Akihito Yagi，Kanzo Sakata，Tirthankar Chaudhuri，D.K.Ganguly，Secion Sarma.″Triterpenoid Saponins from the roots of the tea plant (Camelliasinensis var.Assamica).″Phytochchemistry 53(2000)941-946.
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8.Method for prevention and treatment of chronic venous insufficiency，Jia et al.，U.S.Patent No.6210680
9.Novel analgestic compounds，extracts containing same and methods of preparation.Quinn Ronald，WO 2005/051969
Claims (according to the modification of the 19th of treaty)
1, a kind of purposes that is used to make the composition of medicine, it is characterized in that described medicine can suppress the growth of the cancer cells of water outer membrane protein overexpression (overexpressing) as inhibitor, can prolong the cancered mammiferous survival time and increase survival rate, reduce the size of tumour, melt cancer cell membrane, be used to bring out cancer cell-apoptosis, compatibility can strengthen the anticancer effect of taxol.Described here cancer is a mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, the refreshing The cancer of CNC, melanoma cancer, kidney, or cervical cancer.Described composition (reaching its esters, ester class, meta-bolites and derivative) contains a compound and contains following structural formula (1B):
Figure A20078004074400931
Wherein the R1 of this compound contains in the subordinate chemistry group one: H, angeloyl groups (angeloyl), ethanoyl, along root of Dahurian angelica acyl group (tigloyl), squaw weed acyl group (senecioyl), alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl, loop chain alkyloyl (cycloalkanoyl), loop chain enoyl-(cycloalkenoyl), aromatic base acyl group, heterocyclic aromatic base acyl group, contain the acid of 2-6 carbon atom, or derivatives thereof; The R2 of this compound contains in subordinate's chemistry group: H, angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group, the squaw weed acyl group, alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl, the loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group, the heterocyclic aromatic base acyl group contains the acid of 2-6 carbon atom, or derivatives thereof; The R4 of this compound is CH 2O R6 or COOR6, here R6 contains in the following chemical group one: H, angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl, the loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group, the heterocyclic aromatic base acyl group contains the acid of 2-6 carbon atom, or derivatives thereof; The R3 of this compound is H or OH, and R8 is H; R5 contains H or sugar chain, and this sugar chain contains one or more following carbohydrate: glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination; 23 in the carbon of compound (1B), 24,25,26 in carbon, 29 and 30 respectively contain CH 3, CH 2OH, CHO, COOH, COO-alkyl, COO-aromatic base, COO-heterogeneous ring compound, COO-heterocyclic aromatic compounds, CH 2The O-aromatic base, CH 2The O-heterocyclic aromatic compounds, alkyl compound, cycloalkyl, loop chain alkyloyl, loop chain enoyl-, aromaticacyl radical, assorted aromaticacyl radical, particularly CH 3, CH 2OH.
2, the purposes as the composition of medicine as described in 1 of the claim the is characterized in that described composition contains a compound, and this compound is R1 at least, following chemical group is contained in two groups among R2 and the R4: angeloyl groups, and ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group, alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof; Or R1 at least, sugar chain is contained in a group among R2 and the R4, and this sugar chain contains two in the following at least chemical group: angeloyl groups, ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; acyl group, benzoyl, dibenzoyl; alkanoyl, alkenoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group; heterogeneous ring compound or heterocyclic aromatic compounds contain the acid of 2-6 carbon atom, or derivatives thereof.
3, the purposes as the composition of medicine as described in 1 of the claim the is characterized in that described composition contains a compound, and the R4 of this compound contains CH 2OR6, R6 is H here.The R1 of this compound and R2 respectively contain an angeloyl groups, or R1 at least, and two among R2 and the R6 contain angeloyl groups, or R1 at least, and one among R2 and the R6 contains sugar chain, and this sugar chain contains two angeloyl groups.The R5 of this compound contains sugar chain, and this sugar chain contains glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination.
4, the purposes as the composition of medicine as described in 1 of the claim the is characterized in that described composition contains a compound, and this compound contains following chemical structure:
A) this compound contains chemical structure Xanifolia (Y),
Figure A20078004074400951
Chemical name:
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group
-21, acyl group-3 β returns, 15 α, 16 α, 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
B) this compound contains chemical structure Xanifolia (Y1),
Figure A20078004074400952
Chemical name:
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O (3; acyl group is returned by the two parties of 4-)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
C) this compound contains chemical structure Xanifolia (Y2),
Figure A20078004074400961
Chemical name:
3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3) β-D-glucuronic acid pyrans acyl group
-21, acyl group-3 β returns, 15 α, 16 α, 21 β, 22 α, 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
D) this compound contains chemical structure Xanifolia (Y8),
Figure A20078004074400962
Chemical name:
3-O-[β-glucose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β returns, 16 α, 21 β, 22 α, 24 β, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
E) this compound contains chemical structure Xanifolia (Y9),
Figure A20078004074400963
Chemical name:
3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3; acyl group is returned by the two parties of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
F) this compound contains chemical structure Xanifolia (Y10),
Figure A20078004074400971
Chemical name:
3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β returns, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
G) this compound contains chemical structure Xanifolia (Y0),
Figure A20078004074400972
Chemical name:
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group; 22-O-(2-methylpropionyl)-3 β; 15 α; 16 α; 21 β; 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
H) this compound contains chemical structure Xanifolia (X),
Chemical name: 3-O-{[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyranoside butyl ester }-the 21-O-ethanoyl; acyl group-3 β returns in 22-O-party; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
I) this compound contains chemical structure Xanifolia (Y7),
Figure A20078004074400981
Chemical name:
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group; 28-O-(2-methylbutyryl base)-3 β; 15 α; 16 α; 21 β; 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
5, the purposes as the composition of medicine as described in 1 of the claim the is characterized in that described composition contains following compound:
A) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D glucuronic acid pyrans acyl group-21, acyl group-3 β, 15 α return in the two parties of 22-O-; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
B) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D glucuronic acid pyrans acyl group-21-O (3; acyl group is returned by the two parties of 4-)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
C) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3) β-D-glucuronic acid pyrans acyl group-21, acyl group-3 β, 15 α return in the two parties of 22-O-; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin
D) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β returns, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12 alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
E) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O (3; acyl group is returned by the two parties of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
F) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β returns, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12 alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
G) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
H) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O (3; the two benzoyls of 4-)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
I) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3) β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
J) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
K) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O (3; the two benzoyls of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
L) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
M) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
N) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(3; the two benzoyls of 4-)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
O) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-β-D wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
P) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
Q) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3; the two benzoyls of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
R) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
S) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two angeloyl groups-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
T) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(3; the two angeloyl groups of 4-)-L-α-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
U) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two angeloyl groups-3 β of 22O-, 15 α; 16 α, 21 β, 22 α; 24 β, 28 7 hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
V) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, two angeloyl groups-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
W) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3; the two angeloyl groups of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
X) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two angeloyl groups-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
Y) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-pectinose pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3; the two angeloyl groups of 4-)-α-Fucose pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
6, the purposes as the arbitrary composition in the composition of medicine as described in the claim the 1-5 item is characterized in that described purposes is to do medicine with this compound can prolong cancered mammiferous life, or dwindle its tumour size.
7, the purposes as the arbitrary composition in the composition of medicine as described in the claim the 1-6 item is characterized in that described composition contains a triterpene compound; this compound contains following chemical group: angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl; two benzoyls, alkanoyl, alkenoyl; the alkanoyl that the benzoyl alkyl replaces; aromatic base, acyl group, heterogeneous ring compound; heterocyclic aromatic compounds; cycloalkyl, loop chain alkyloyl, loop chain enoyl-; aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.Particularly R1 and R2 contain angeloyl groups.
8, the purposes as the arbitrary composition in the composition of medicine as described in the claim the 1-7 item is characterized in that described composition is used as medicine intravenous injection or vein drip.The vein drip: per kilogram consumption 0.05-0.2mg is dissolved in 10% the glucose solution of 250ml or 0.9% sodium chloride solution of 250ml.Intravenous injection: every day per kilogram consumption 0.05-0.2mg, be dissolved in 10% glucose solution or 0.9% sodium chloride solution of 10-20ml.The vein drip: every day per kilogram consumption 0.1-0.2mg, be dissolved in 10% the glucose solution of 250ml or 0.9% sodium chloride solution of 250ml.Intravenous injection: every day per kilogram consumption 0.1-0.2mg, be dissolved in 10% glucose solution or 0.9% sodium chloride solution of 10-20ml.Also can peritoneal injection: every day per kilogram consumption 2.5-0.2mg, be dissolved in 10% glucose solution or 0.9% sodium chloride solution.This kind also can be oral as the composition of medicine, Mammals dosage per kilogram 1-10mg.This kind is as the composition palatable clothes of medicine, dosage per kilogram 1-10mg 10-30mg, 30-60mg or 60-90mg.This described composition is used as medicine intravenous injection or vein drip, Mammals per kilogram consumption 0.01-0.10mg, 0.1-0.20mg, 0.2-0.4mg, or 0.4-0.6mg.The Mammals peritoneal injection: every day per kilogram consumption 1-3mg, 3-5mg, 4-6mg, or 6-10mg.
9, the purposes as the arbitrary composition in the composition of medicine as described in the claim the 1-8 item is characterized in that described composition is used as the pharmacological agent cancer, it is characterized in that the moisture film protein overexpression of the cancer cells of this cancer.
10, the purposes of stating the arbitrary composition in the composition as claim the 1-9 item institute medicine, it is characterized in that described composition is used as medicine by regulating or influence the albumen on cancer cells surface or change the function of the intercellular film of cancer cells, or regulate the fluid that passes cancer cells, or the destruction cytolemma.
11, the purposes as the arbitrary composition in the composition of medicine as described in the claim the 1-8 item is characterized in that described composition is used as medicine and can treats chronic venous insufficiency, the tip oedema; anti-lipid, chronic venous disease, varix, varix symptom; venous stasis eliminates the phlegm, the peripheral vessel disorder; cerebral tissue is fainted from fear, cerebral circulation disorder, cerebral edema; psychosis, dysmenorrhoea, hemorrhoid; episiodemies, haemonhoids, postoperative edema; alleviate the symptom of shank pain, the treatment itch, edeam of legs is fat; thrombosis, thrombophlebitis, stomach ulcer; preventing thrombosis forms, anti-oedema, anti-inflammatory; adjust the release of PGF2, antagonism 5-HT and histamine lower the catabolism of organizing mucopolysaccharide; anti-MS, anti-aneurysma, anti-asthma; anti-bradykinin, anti-capillary hemorrhage, anti-headache; anti-cervicobrachialgia, anti-eclampsia, Ivy extract; anti-encephalitis, epiglottitis, exudation resistance; anti influenza, anti-fracture, gingivitis; anti-hemotoncus, herpes, histamine shock; hydrarthrosis, meningitis, antioxygenation; periodontitis, phlebitis, pleuritis; trachyphonia, rhinitis, tonsillitis; ulcer, varix, dizzy; cancer metastasis causes Kendall compound diuresis takes place; antimycotic, hemolytic action, hyaluronidase inhibitor; sharp lymph agent, natriuresis, sterilant; sharp mucus agent, thymolytic, the effect of protection blood vessel and vein; the treatment enuresis, frequent micturition, urgent urination; the treatment and the hemolytic action diseases associated, or with the blood circulation diseases associated, lower thrombotic danger.

Claims (11)

1, a kind of being used to made the purposes that medicine suppresses the composition of cancer growth, it is characterized in that described cancer is: mammary cancer, white corpuscle cancer, liver cancer, ovarian cancer, bladder cancer, prostate cancer, skin carcinoma, osteocarcinoma, the cancer of the brain, leukemia, lung cancer, colorectal carcinoma, CNC cancer, melanoma cancer, kidney, or cervical cancer.Described composition (reaching its esters, ester class, meta-bolites and derivative) contains a compound and contains following structural formula (1B):
Figure A2007800407440002C1
Wherein the R1 of this compound contains in the subordinate chemistry group one: H, angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group, alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl, loop chain alkyloyl (cycloalkanoyl), loop chain enoyl-(cycloalkenoyl), aromatic base acyl group, heterocyclic aromatic base acyl group, contain the acid of 2-6 carbon atom, or derivatives thereof; The R2 of this compound contains in subordinate's chemistry group: H, angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group, the squaw weed acyl group, alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl, the loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group, the heterocyclic aromatic base acyl group contains the acid of 2-6 carbon atom, or derivatives thereof; The R4 of this compound is CH 2O R6 or COOR6, here R6 contains in the following chemical group one: H, angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, heterogeneous ring compound or heterocyclic aromatic compounds, cycloalkyl, the loop chain alkyloyl, loop chain enoyl-, aromatic base acyl group, the heterocyclic aromatic base acyl group contains the acid of 26 carbon atoms, or derivatives thereof; The R3 of this compound is H or OH, and R8 is H; R5 contains H or sugar chain, and this sugar chain contains one or more following carbohydrate: glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination; 23 in the carbon of compound (1B), 24,25,26 in carbon, 29 and 30 respectively contain CH 3, CH 2OH, CHO, COOH, COO-alkyl, COO-aromatic base, COO-heterogeneous ring compound, COO-heterocyclic aromatic compounds, CH 2The O-aromatic base, CH 2The O-heterocyclic aromatic compounds, alkyl compound, cycloalkyl, loop chain alkyloyl, loop chain enoyl-, aromaticacyl radical, assorted aromaticacyl radical, particularly CH 3, CH 2OH.
2, as described in 1 of claim the, it is characterized in that described composition contains compound R1 at least, following chemical group is contained in two groups among R2 and the R4: angeloyl groups, ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group, alkyl, acyl group, benzoyl, dibenzoyl, alkanoyl, alkenoyl, alkenoyl, the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group, heterogeneous ring compound or heterocyclic aromatic compounds, or derivatives thereof; At least R1, sugar chain is contained in a group among R2 and the R4, and this sugar chain contains two in the following at least chemical group: angeloyl groups, ethanoyl; along root of Dahurian angelica acyl group, squaw weed acyl group, alkyl; acyl group, benzoyl, dibenzoyl; alkanoyl, alkenoyl, alkenoyl; the alkanoyl that the phenmethyl alkyl replaces, aromatic base, acyl group; heterogeneous ring compound or heterocyclic aromatic compounds contain the acid of 2-6 carbon atom, or derivatives thereof.
3, as described in 1 of claim the, it is characterized in that described composition contains a compound, the R4 of this compound contains CH 2OR6, R6 is H here.The R1 of this compound and R2 respectively contain an angeloyl groups, or R1 at least, and two among R2 and the R6 contain angeloyl groups, or R1 at least, and one among R2 and the R6 contains sugar chain, and this sugar chain contains two angeloyl groups.The R5 of this compound contains sugar chain, and this sugar chain contains glucose, semi-lactosi, rhamnosyl, pectinose, wood sugar, Fucose, Ah coughing up's sugar, altrose, gulose, idose, lyxose, seminose, ribose, sorbose, tagatose, talose, fructose, or uronic acid, glucuronic acid, galacturonic acid, or derivatives thereof, or their combination.
4, as described in 1 of claim the, it is characterized in that described composition contains a compound, this compound contains following chemical structure:
A) this compound contains chemical structure Xanifolia (Y),
Chemical name:
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group
-21, acyl group-3 β returns, 15 α, 16 α, 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
B) this compound contains chemical structure Xanifolia (Y1),
Figure A2007800407440004C2
Chemical name:
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O (3, acyl group is returned by the two parties of 4-)-α-
L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
C) this compound contains chemical structure Xanifolia (Y2),
Figure A2007800407440005C1
Chemical name:
3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3) β-D-glucuronic acid pyrans acyl group
-21, acyl group-3 β returns, 15 α, 16 α, 21 β, 22 α, 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
D) this compound contains chemical structure Xanifolia (Y8),
Figure A2007800407440005C2
Chemical name:
3-O-[β-glucose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β returns, 16 α, 21 β, 22 α, 24 β, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
E) this compound contains chemical structure Xanifolia (Y9),
Figure A2007800407440005C3
Chemical name:
3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3; acyl group is returned by the two parties of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
F) this compound contains chemical structure Xanifolia (Y10),
Figure A2007800407440006C1
Chemical name:
3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β returns, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
G) this compound contains chemical structure Xanifolia (Y0),
Figure A2007800407440006C2
Chemical name:
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group; 22-O-(2-methylpropionyl)-3 β; 15 α; 16 α; 21 β; 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
H) this compound contains chemical structure Xanifolia (X),
Figure A2007800407440006C3
Chemical name: 3-O-{[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyranoside butyl ester }-the 21-O-ethanoyl; acyl group-3 β returns in 22-O-party; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
I) this compound contains chemical structure Xanifolia (Y7),
Figure A2007800407440007C1
Chemical name:
3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-party returns acyl group; 28-O-(2-methylbutyryl base)-3 β; 15 α; 16 α; 21 β; 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
5, as described in 1 of claim the, it is characterized in that described composition contains following compound:
A) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, acyl group-3 β, 15 α return in the two parties of 22-O-; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
B) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O (3; acyl group is returned by the two parties of 4-)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
C) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3) β-D-glucuronic acid pyrans acyl group-21, acyl group-3 β, 15 α return in the two parties of 22-O-; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin
D) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β returns, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
E) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O (3; acyl group is returned by the two parties of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
F) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, acyl group-3 β returns, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin in the two parties of 22-O-.
G) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α; 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
H) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O (3; the two benzoyls of 4-)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
I) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-α-L-arabinose furans acyl group (1 → 3) β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
J) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
K) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O (3; the two benzoyls of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
L) 3-O-[beta galactose pyrans acyl group (1 → 2)]-α-pectinose furans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α; 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
M) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D- Wood sugarPyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α, 16 α, 21 β, 22 α, 28-hexahydroxy-olea-12-alkene pentacyclic triterpenoid saponin.
N) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(3; the two benzoyls of 4-)-α-L-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
O) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-β-D wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 15 α; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
P) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3-β-D-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
Q) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3; the two benzoyls of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
R) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, two benzoyl-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
S) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two angeloyl groups-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
T) 3-O-[β-D-glucose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21-O-(3; the two angeloyl groups of 4-)-L-α-rhamnosyl pyrans acyl group-22-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
U) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D glucuronic acid pyrans acyl group-21, two angeloyl groups-3 β of 22-O-, 15 α; 16 α, 21 β, 22 α; 24 β, 28-seven hydroxyls olea-12-alkene pentacyclic triterpenoid saponin.
V) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21, two angeloyl groups-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
W) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-wood sugar pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group--21-O-(3; the two angeloyl groups of 4-)-α-rhamnosyl pyrans acyl group-28-O-ethanoyl-3 β; 16 α; 21 β; 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
X) 3-O-[β-D-semi-lactosi pyrans acyl group (1 → 2)]-β-D-wood sugar pyrans acyl group (1 → 3)-β-D-glucuronic acid pyrans acyl group-21, two angeloyl groups-3 β of 22-O-, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
Y) 3-O-[beta galactose pyrans acyl group (1 → 2)]-β-pectinose
Pyrans acyl group (1 → 3)-beta-glucuronic acid pyrans acyl group-21-O-(3, the two angeloyl groups of 4-)-α-Fucose pyrans acyl group-28-O-ethanoyl-3 β, 16 α, 21 β, 22 α, 28-penta hydroxy group olea-12-alkene pentacyclic triterpenoid saponin.
6, the purposes as the arbitrary composition in the composition as described in the claim the 1-5 item is characterized in that described purposes is to do medicine with this compound can prolong cancered mammiferous life, or dwindle its tumour size.
7, the purposes as the arbitrary composition in the composition as described in the claim the 1-6 item is characterized in that described composition contains a compound, and this compound contains following chemical structure:
Figure A2007800407440009C1
Wherein R1 and R2 contain angeloyl groups, ethanoyl, and along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, two benzoyls, alkanoyl; alkenoyl, the alkanoyl that the benzoyl alkyl replaces, aromatic base, acyl group; heterogeneous ring compound, heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl, loop chain enoyl-, aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.Particularly R1 and R2 contain angeloyl groups.R1 and R2 also contain sugar chain, and this sugar chain contains glucose, semi-lactosi, pectinose, rhamnosyl, wood sugar, uronic acid, glucuronic acid, galacturonic acid, and derivative, or their combination.This compound or contain following chemical structure (d)
Figure A2007800407440009C2
The R1 of (d) wherein, R2 and R3 contain angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl, two benzoyls; alkanoyl, alkenoyl, the alkanoyl that the benzoyl alkyl replaces, aromatic base; acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl, loop chain enoyl-, aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.Particularly, R1 has two at least and contains two angeloyl groups among R2 and the R3; or R1, having one among R2 and the R3 at least and contain sugar chain, this sugar chain contains two groups of following group: angeloyl groups; ethanoyl, along root of Dahurian angelica acyl group, the squaw weed acyl group; alkyl, benzoyl, two benzoyls; alkanoyl, alkenoyl, the alkanoyl that the benzoyl alkyl replaces; aromatic base, acyl group, heterogeneous ring compound; heterocyclic aromatic compounds; cycloalkyl, loop chain alkyloyl, loop chain enoyl-; aromatic alkyl; the heteroaromatic alkyl, two carbon-six carbonic acid, or derivatives thereof.Particularly contain two angeloyl groups.Compound or contain following chemical structure:
Figure A2007800407440010C1
The R1 of this compound, R2 or R3 contain following group: angeloyl groups, ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl, two benzoyls; alkanoyl, alkenoyl, the alkanoyl that the benzoyl alkyl replaces, aromatic base; acyl group, heterogeneous ring compound, heterocyclic aromatic compounds, cycloalkyl; the loop chain alkyloyl, loop chain enoyl-, aromatic alkyl; the heteroaromatic alkyl, two carbon-five carbonic acid, or its combination.R1 particularly, having two among R2 and the R3 at least, to contain angeloyl groups be good.Or R1, having two among R2 and the R3 at least and contain angeloyl groups, ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl, two benzoyls; alkanoyl, alkenoyl, the alkanoyl that the benzoyl alkyl replaces, aromatic base; acyl group, heterogeneous ring compound, heterocyclic aromatic compounds; cycloalkyl, loop chain alkyloyl, loop chain enoyl-; aromatic alkyl, heteroaromatic alkyl, two carbon, six carbonic acid.Or R1, R2 and
Have at least one to contain sugar chain among the R3, this sugar chain contains two groups in the following chemical group: angeloyl groups, and ethanoyl is along root of Dahurian angelica acyl group; the squaw weed acyl group, alkyl, benzoyl, two benzoyls; alkanoyl, alkenoyl, the alkanoyl that the benzoyl alkyl replaces, aromatic base; acyl group, heterogeneous ring compound, heterocyclic aromatic compounds; cycloalkyl, loop chain alkyloyl, loop chain enoyl-; aromatic alkyl, heteroaromatic alkyl, two carbon-six carbonic acid.The R5 of this compound contains a sugar chain, and this sugar chain contains glucose, semi-lactosi, pectinose, rhamnosyl, wood sugar, uronic acid, glucuronic acid, galacturonic acid, and derivative, or their combination.
8, the purposes as the arbitrary composition in the composition as described in the claim the 1-7 item is characterized in that described composition is used as medicine intravenous injection or vein drip.The vein drip: per kilogram consumption 0.05-0.2mg is dissolved in 10% the glucose solution of 250ml or 0.9% sodium chloride solution of 250ml.Intravenous injection: every day per kilogram consumption 0.05-0.2mg, be dissolved in 10% glucose solution or 0.9% sodium chloride solution of 10-20ml.The vein drip: every day per kilogram consumption 0.1-0.2mg, be dissolved in 10% the glucose solution of 250ml or 0.9% sodium chloride solution of 250ml.Intravenous injection: every day per kilogram consumption 0.1-0.2mg, be dissolved in 10% glucose solution or 0.9% sodium chloride solution of 10-20ml.Also can peritoneal injection: every day per kilogram consumption 2.5-0.2mg, be dissolved in 10% glucose solution or 0.9% sodium chloride solution.This kind also can be oral as the composition of medicine, Mammals dosage per kilogram 1-10mg.This kind is as the composition palatable clothes of medicine, dosage per kilogram 10-30mg, 30-60mg and 60-90mg.。
But this kind is used as the composition intravenous injection or the vein drip of medicine, dosage per kilogram 0.01-0.1mg, and 0.1-0.2mg, 0.2-0.4mg and 0.4-0.6mg.
But this kind is as the composition peritoneal injection of medicine, dosage per kilogram 1-3mg, 3-5mg, 4-6mg and 6-10mg.
9, the purposes as the arbitrary composition in the composition as described in the claim the 1-8 item is characterized in that described composition is used as the pharmacological agent cancer, the moisture film protein overexpression of the cancer cells of this cancer.
10, purposes as the arbitrary composition in the composition as described in the claim the 1-9 item, it is characterized in that described composition is used as medicine by regulating or influence the function of the intercellular film of the albumen on cancer cells surface or change cancer cells, or the fluid of cancer cells is passed in adjusting, or softening skin, or the structure of change skin.
11, the purposes as the arbitrary composition in the composition as described in the claim the 1-8 item is characterized in that described composition is used as medicine and can treats chronic venous insufficiency, the tip oedema; anti-lipid, chronic venous disease, varix, varix symptom; venous stasis eliminates the phlegm, the peripheral vessel disorder; cerebral tissue is fainted from fear, cerebral circulation disorder, cerebral edema; psychosis, dysmenorrhoea, hemorrhoid; episiodemies, haemonhoids, postoperative edema; alleviate the symptom of shank pain, the treatment itch, edeam of legs is fat; thrombosis, thrombophlebitis, stomach ulcer; preventing thrombosis forms, anti-oedema, anti-inflammatory; adjust the release of PGF2, antagonism 5-HT and histamine lower the catabolism of organizing mucopolysaccharide; anti-MS, anti-aneurysma, anti-asthma; anti-bradykinin, anti-capillary hemorrhage, anti-headache; anti-cervicobrachialgia, anti-eclampsia, Ivy extract; anti-encephalitis, epiglottitis, exudation resistance; anti influenza, anti-fracture, gingivitis; anti-hemotoncus, herpes, histamine shock; hydrarthrosis, meningitis, antioxygenation; periodontitis, phlebitis, pleuritis; trachyphonia, rhinitis, tonsillitis; ulcer, varix, dizzy; cancer metastasis causes Kendall compound diuresis takes place; antimycotic, hemolytic action, hyaluronidase inhibitor; sharp lymph agent, natriuresis, sterilant; sharp mucus agent, thymolytic, the effect of protection blood vessel and vein; the treatment enuresis, frequent micturition, urgent urination; the treatment and the hemolytic action diseases associated, or with the blood circulation diseases associated, lower thrombotic danger.
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