CN101194920A - Lithospermum and application of its active ingredient in preparing medicament for treating tumour stem cell - Google Patents
Lithospermum and application of its active ingredient in preparing medicament for treating tumour stem cell Download PDFInfo
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- CN101194920A CN101194920A CNA2007101810311A CN200710181031A CN101194920A CN 101194920 A CN101194920 A CN 101194920A CN A2007101810311 A CNA2007101810311 A CN A2007101810311A CN 200710181031 A CN200710181031 A CN 200710181031A CN 101194920 A CN101194920 A CN 101194920A
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- stem cell
- shikonin
- radix
- alkannin
- tumor stem
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Abstract
The invention provides a lithospermum and the application of active ingredients of the lithospermum in the process of preparing a medicament for curing tumour stem cell. The active ingredients of the lithospermum comprise alkannin, an iso- antimer which is an antimer of the alkannin, and derivations of the alkannin and the iso-antimer, which comprises alkannin derivatives, iso-antimer derivatives, alkannin and lithospermum furans and the like. The lithospermum and the application of active ingredients of the lithospermum in the preparing of medicament for curing tumour stem cell has the advantages that the invention discloses new uses of lithospermum and the active ingredients, such as alkannin can effectively remove tumour stem cell, the efficiency of removing tumour stem cell of an extract of lithospermum is obviously better than alexan, which provides a basis for the screening of new drugs, and the invention has excellent curative effect, which has a great development prospect.
Description
(1) technical field
The present invention relates to Radix Arnebiae (Radix Lithospermi) and the effectively application of pharmaceutical component in the medicine of preparation treatment tumor stem cell thereof.
(2) background technology
Tumor cell in the tumor can be divided into two classes.One class is common tumor cell, and a class is a tumor stem cell.Common tumor cell has quick division, to anticancer susceptibility sense, does not have characteristics such as self updating ability.Therefore, common tumor cell can be dead behind the certain algebraically of division.Tumor stem cell then has following characteristics: generally remain static, promptly splitting status not is insensitive to anticarcinogen, has self updating ability, promptly has the ability of unlimited breeding.In chemotherapy of tumors, a large amount of tumor cells is killed (because to chemotherapeutic sensitivity), yet tumor stem cell can survive (because insensitive to chemotherapeutic).The recurrence of tumor is because the chemotherapy of tumors medicine is invalid to tumor stem cell.In other words, present chemotherapy of tumors medicine mainly is at tumor cell, rather than tumor stem cell (Wicha WS, Liu S, Dontu G.Cancer Stem Cells:An Old Idea-A Paradigm Shift.Cancer Res66:1883-1890,2005.Donnenberg VS﹠amp; Donnerberg AD.Multidrug Resistance In CancerRevisited:The Cancer Stem Cell Hypothesis.J Clin Parmacol 45:872-877,2005.Ravandi F﹠amp; Estrov Z. Eradication of Leukemia Stem Cells As a New Goal of Therapy inLeukemia.Clin Cancer Res 12:340-344,2006.Dick JE﹠amp; Lapidot T.Biology ofNormal and Acute Myeloid Leukemia Stem Cells.Int J Hematol 82:1-8,2005).In fact, most of chemotherapy of tumors medicines are only effective to tumor cell, and invalid to tumor stem cell.The medicine that tumor stem cell can be effectively treated in searching is a current direction.The key that whether can eradicate tumor does not lie in can kill common tumor cell, and is to eradicate tumor stem cell.
Have antineoplastic action though Radix Arnebiae (Radix Lithospermi) is in the news, yet report explanation Radix Arnebiae (Radix Lithospermi) and effective ingredient thereof do not have the effect of resisting tumour stem cells.The present invention illustrates that Radix Arnebiae (Radix Lithospermi) and effective ingredient thereof have the function of resisting tumour stem cells efficiently.Existing document illustrates, medicine great majority with antitumor action are invalid to tumor stem cell, therefore, though being in the news, Radix Arnebiae (Radix Lithospermi) has the function of killing tumor cell, but those skilled in the art can not be easy to expect that Radix Arnebiae (Radix Lithospermi) and effective ingredient thereof have the function of killing tumor cells stem cell according to this point, on the contrary, those skilled in the art can think that Radix Arnebiae (Radix Lithospermi) and effective ingredient thereof are invalid to tumor stem cell probably, because most of known antitumor drug is to tumor stem cell therapeutic effect very little (seeing above list of references and wherein applied document).Therefore, preparing the medicine for the treatment of tumor stem cell with Radix Arnebiae (Radix Lithospermi) and effective ingredient thereof is that those skilled in the art are unknown.
Radix Arnebiae (Radix Lithospermi) and effective ingredient thereof the application report in preparation tumor stem cell medicine is not arranged so far.
(3) summary of the invention
The invention provides the application in the medicine of preparation treatment tumor stem cell of Radix Arnebiae (Radix Lithospermi) and effective ingredient thereof.
Described Radix Arnebiae (Radix Lithospermi) is extract of organic solvent of Radix Arnebiae (Radix Lithospermi) or the extract that obtains with supercritical process.Described organic solvent is the alcoholic solution that contains 1~6 carbon atom, preferred alcohol.
Described treatment tumor stem cell medicine also contains drug excipient or carrier, can be made into one of following dosage form: 1. injection; 2. tablet; 3. capsule; 4. granule; 5. decoction.The anticarcinogen that also can also contain other in the medicine of described treatment tumor stem cell.
Radix Arnebiae (Radix Lithospermi) effective ingredient of the present invention includes the enantiomer iso-alkannin of shikonin, shikonin and their derivant, as materials such as Gronwell naphthaquinone chemical compound, different Gronwell naphthaquinone chemical compound, Lithospermum element, shikinofurans.
Part shikonin naphthoquinone compound structural formula is as follows:
Shikonin (Shikonin) R=-OH
Deoxyshikonin (Deoxyshikonin) R=-H
Acetylshikonin (Acetylshikonin) R=-OCOCH
3
Isobutyryl shikonin (Isobutyrylshikonin) R=-OCOCH (CH3)
2
Beta-hydroxyisovalerylshiderivative (the R=-OCOCH of β-hydroxyisovalerylshikonin)
2C (CH3)
2OH
Isovaleryl shikonin (Isovalerylshikonin) R=-OCOCH
2CH (CH3)
2
Alpha-Methyl-positive butyryl shikonin (R=-OCOCH (the CH of α-methyl-n-butyrilshikonin)
3) CH
2CH
3
β, beta-dimethyl-third rare acyl shikonin (β, the R=-OCOCH=C (CH of β-dimethylacrylshikonin)
3)
2
2,3-dimethyl pentene acyl shikonin (Teracrylshikonin) R=-OCOCH
2C (CH
3)=C (CH3)
2
4-hydroxyl-2,5-dimethyl pentene acyl shikonin R=-OCOC (CH
3)=CHC (CH
3)
2OH
Propionyl shikonin (Propionylshikonin) R=-OCOCH
2CH
3
1-methoxyl group-shikonin 1-methoxy-shikonin R=-OH
1-methoxyl group-β, beta-dimethyl-third rare acyl shikonin
(1-methoxy-β,β-dimethylacrylshikonin) R=-OCOCH=C(CH
3)
2
1-methoxyl group-acetylshikonin (1-methoxy-acetylshikonin) R=-OCOCH
3
Shikonine
The different Gronwell naphthaquinone structural formula of compound of part is as follows:
Deoxidation iso-alkannin (Deoxyalkannin) R=-H
Iso-alkannin (Alkannin) R=-OH
Anhydroalkannin (anhydroakanin) R=-CH=CHCH=C (CH
3)
2
β, beta-dimethyl-third rare acyl iso-alkannin (β, the R=-OCOCH=C (CH of β-dimethylacrylalkannin)
3)
2
Acetyl iso-alkannin (Acetylalkannin) R=-OCOCH
3
The beta-hydroxy isovaleryl iso-alkannin (R=-OCOCH of β-hydroxyisovalerylalkannin)
2C (CH3)
2OH
α-acetoxyl group isovaleryl iso-alkannin (α-acetoxyisovalerylalkannin)
R=-OCOCH
2CCH
3OCOCH
3
Alpha-Methyl-positive butyryl iso-alkannin (R=-OCOCH (the CH of α-methyl-n-butyrilalkannin)
3) CH
2CH
3
2,3-dimethyl pentene acyl iso-alkannin (Teracrylalkannin) R=-OCOCH
2C (CH
3)=C (CH3)
2
The plain structural formula of Lithospermum is as follows:
Plain A (Lithospermidin A) R=-COCH (CH of Lithospermum
3) CH
2CH
3
Plain B (Lithospermidin B) R=-COCH (CH of Lithospermum
3) CH
3
The shikinofuran structural formula is as follows:
Shikinofuran A (Shikonofuran A) R=-CH
3
Shikinofuran B (Shikonofuran B) R=-CH (CH
3) CH
2CH
3
Shikinofuran C (Shikonofuran C) R=-CH2CH (CH
3)
2
Shikinofuran D (Shikonofuran D) R=-CH (CH
3)
2
Shikinofuran E (Shikonofuran E) R=-CH=C (CH
3)
2
The effective ingredient of described Radix Arnebiae (Radix Lithospermi) is one of following:
(1) shikonin; (2) deoxyshikonin; (3) acetylshikonin; (4) isobutyryl shikonin;
(5) beta-hydroxyisovalerylshiderivative; (6) isovaleryl shikonin; (7) Alpha-Methyl-positive butyryl shikonin;
(8) β, beta-dimethyl-third rare acyl shikonin; (9) 2,3-dimethyl pentene acyl shikonin;
(10) 4-hydroxyl-2,5-dimethyl pentene acyl shikonin; (11) propionyl shikonin (Propionylshikonin); (12) iso-alkannin;
(13) deoxidation iso-alkannin; (14) acetyl iso-alkannin; (15) anhydroalkannin (Anhydroalkannin);
(16) β, beta-dimethyl-third rare acyl iso-alkannin; (17) beta-hydroxy isovaleryl iso-alkannin;
(18) α-acetoxyl group isovaleryl iso-alkannin; (19) Alpha-Methyl-positive butyryl iso-alkannin;
(20) Alpha-Methyl-positive butyryl iso-alkannin; (21) 2,3-dimethyl pentene acyl iso-alkannins;
(22) 1-methoxyl group-shikonin; (23) 1-methoxyl group-β, beta-dimethyl-third rare acyl shikonin;
(24) 1-methoxyl group-acetylshikonin; (25) the plain A of Lithospermum; (26) the plain B of Lithospermum;
(27) shikinofuran A; (28) shikinofuran B; (29) shikinofuran C; (30) shikinofuran D; (31) shikinofuran E; (32) Shikonine.
Especially, the effective ingredient of described Radix Arnebiae (Radix Lithospermi) is one of following:
(1) shikonin; (2) acetylshikonin; (3) isobutyryl shikonin; (4) beta-hydroxyisovalerylshiderivative; (5) isovaleryl shikonin; (6) Alpha-Methyl-positive butyryl shikonin; (7) β, beta-dimethyl-third rare acyl shikonin.
Described treatment tumor stem cell medicine also contains drug excipient or carrier, can be made into one of following dosage form:
1. injection; 2. tablet; 3. capsule; 4. granule; 5. slow releasing agent.The anticarcinogen that also can also contain other in the medicine of described treatment tumor stem cell.
The application in preparation treatment tumor stem cell medicine of Radix Arnebiae (Radix Lithospermi) of the present invention and effective ingredient thereof, beneficial effect is mainly reflected in: the new purposes of having pointed out Radix Arnebiae (Radix Lithospermi) and effective ingredient thereof, can remove tumor stem cell effectively as shikonin, the drug effect that Radix Arnebiae extract is removed tumor stem cell is significantly strong than cytosine arabinoside, this provides the foundation for new medicament screen, good effect has great DEVELOPMENT PROSPECT.
(4) specific embodiment
The present invention is described further below in conjunction with specific embodiment, but protection scope of the present invention is not limited in this:
Embodiment 1: the preparation of Radix Arnebiae (Radix Lithospermi) ethanol extraction
Lithospermum euchromum Royle 1000g, with 75% ethanol percolation of 6 times of quality, percolation speed 15ml/min.Reclaim the ethanol leachate, decompression recycling ethanol concentrates to such an extent that proportion is the extractum of 1.10g/ml to there not being the ethanol flavor, adds the pure water of 10 times of quality, left standstill 1 hour, centrifugal (5000G) 5 minutes gets precipitation, be the Radix Arnebiae (Radix Lithospermi) ethanol extraction, be designated as ethanol extraction I (down together), standby.Adopting arnebia guttata Bunge with above-mentioned same procedure is raw material, makes the Radix Arnebiae (Radix Lithospermi) ethanol extraction, is designated as ethanol extraction II (down together), standby.
Arbitrary value between the above concentration of alcohol optional 75~95%, various alcohol such as also available methanol, propanol replace.
Embodiment 2: the preparation of Radix Arnebiae (Radix Lithospermi) supercritical extract
Supercritical extraction: Radix Arnebiae (Radix Lithospermi) 1000g is ground into coarse powder (crossing 40 mesh sieves), puts the 1L supercritical CO
2In the extraction kettle, regulate pressure: 25MPa, temperature: 45 ℃, flow: 30kg/h, extraction time: 2h.Collection obtains the 10g extract.
Embodiment 3: Radix Arnebiae (Radix Lithospermi) is to the evaluation of pesticide effectiveness of tumor stem cell
Experimental technique: acute myeloid leukemia cell (acute myeloid leukemia) and acute transformation phase chronic myelogenous leukemia (blast criss chronic myeloid keukemia) patient's peripheral blood or medullary cell.Peripheral blood cells is removed erythrocyte, medullary cell 150mM NH with the leukocyte separating medium
4Cl and 10mM NaHCO
3Handle and removed erythrocyte in 5 minutes.Cell is given a baby a bath on the third day after its birth time with serum-free medium, adds Radix Arnebiae extract (final concentration is 0,5,10 μ g/ml) and handles 4 hours, or add cytosine arabinoside (final concentration is 0,5,10 μ g/ml).Give a baby a bath on the third day after its birth all over removing Radix Arnebiae extract with serum-free medium then, with methylcellulose IMDM culture fluid (1% methylcellulose, 30% bovine serum albumin, 0.2mM mercaptoethanol, 2mM glutamy acyl ammonia, 50ng/ml rhMGF, 10/ml Granulocyte Colony-stimulating, 10ng/ml recombination human interleukin-3,3 units/ml erythropoietin, 50ng/ml granular leukocyte colony somatomedin) be made into 50000 cells/ml, put into CO2 gas incubator, cultivated the observation of cell colony 10-14 days.
The result: above cell colony method is a kind of generally acknowledged method of observing tumor stem cell or having self updating ability tumor cell, the cell that can grow into colony is considered to tumor stem cell or precursor (Guzman ML, RossiRM, Kamischky L, et al..The sesquiterpene lactone parthenolide induces apoptosis ofhuman acute myelogenous leukemia stem and progenitor cells.Blood105:4163-4169,2005).Cytosine arabinoside be one be widely used in treatment acute myeloid leukemia, chronic myelogenous leukemia, acute pouring is leukemia and lymphadenomatous a kind of anticarcinogen.From the result, cytosine arabinoside can not effectively be removed tumor stem cell, and Radix Arnebiae extract is removed the drug effect of tumor stem cell significantly than cytosine arabinoside strong (table 1-2).
Table 1, Radix Arnebiae extract and cytosine arabinoside suppress the CFE of acute myeloid leukemia stem cell.
Patient | Contrast | Radix Arnebiae extract | Cytosine arabinoside | ||
5μg/ml | 10μg/ml | 5μg/ml | 10μg/ml | ||
1 | 100% | 35% | 26% | 65% | 39% |
2 | 100% | 32% | 19% | 72% | 36% |
3 | 100% | 37% | 28% | 63% | 43% |
4 | 100% | 42% | 25% | 59% | 43% |
5 | 100% | 46% | 28% | 61% | 42% |
Table is annotated: contrast to there not being the cell of drug treating, the data in the table are 100% for the colony number of cell of contrast, and the cell colony percentage ratio of drug treating group is=(handling groups of cells colony number/control cells group colony number) * 100%.
Table 2, Radix Arnebiae extract and cytosine arabinoside suppress the CFE of acute transformation phase chronic myelogenous leukemia stem cell.
Patient | Contrast | Radix Arnebiae extract | Cytosine arabinoside | ||
5μg/ml | 10μg/ml | 5μg/ml | 10μg/ml | ||
1 | 100% | 41% | 23% | 59% | 38% |
2 | 100% | 38% | 25% | 61% | 39% |
3 | 100% | 31% | 17% | 63% | 41% |
4 | 100% | 35% | 19% | 65% | 36% |
Table is annotated: contrast to there not being the cell of drug treating, the data in the table are 100% for the colony number of cell of contrast, and the cell colony percentage ratio of drug treating group is=(handling groups of cells colony number/control cells group colony number) * 100%.
Embodiment 4: the Radix Arnebiae (Radix Lithospermi) effective ingredient is to the evaluation of pesticide effectiveness of tumor stem cell
Experimental technique: acute myeloid leukemia cell (acute myeloid leukemia) and acute transformation phase chronic myelogenous leukemia (blast criss chronic myeloid keukemia) patient's peripheral blood or medullary cell.Peripheral blood cells is removed erythrocyte, medullary cell 150mM NH with the leukocyte separating medium
4Cl and 10mM NaHCO
3Handle and removed erythrocyte in 5 minutes.Cell is given a baby a bath on the third day after its birth time with serum-free medium, adds shikonin (final concentration is 0,5,10 μ M) and handles 4 hours, or add arabinose born of the same parents former times (final concentration is 0,5,10 μ M).Give a baby a bath on the third day after its birth all over removing Radix Arnebiae extract with serum-free medium then, with methylcellulose IMDM culture fluid (1% methylcellulose, 30% bovine serum albumin, 0.2mM mercaptoethanol, 2mM glutamy acyl ammonia, 50ng/ml rhMGF, 10/ml Granulocyte Colony-stimulating, 10ng/ml recombination human interleukin-3,3 units/ml erythropoietin, 50ng/ml granular leukocyte colony somatomedin) be made into 50000 cells/ml, put into CO2 gas incubator, cultivated the observation of cell colony 10-14 days.
Table 3, shikonin and cytosine arabinoside suppress the CFE of acute myeloid leukemia stem cell.
Patient | Contrast | Shikonin | Cytosine arabinoside | ||
5μM | 10μM | 5μM | 10μM | ||
1 | 100% | 9% | 0% | 92% | 52% |
2 | 100% | 5% | 1% | 88% | 67% |
3 | 100% | 6% | 0% | 79% | 59% |
4 | 100% | 3% | 0% | 81% | 51% |
5 | 100% | 8% | 0% | 85% | 52% |
Table is annotated: contrast to there not being the cell of drug treating, the data in the table are 100% for the colony number of cell of contrast, and the cell colony percentage ratio of drug treating group is=(handling groups of cells colony number/control cells group colony number) * 100%.
Table 4, shikonin and cytosine arabinoside suppress the CFE of acute transformation phase chronic myelogenous leukemia stem cell.
Patient | Contrast | Shikonin | Cytosine arabinoside | ||
5μg/ml | 10μg/ml | 5μg/ml | 10μg/ml | ||
1 | 100% | 6% | 0% | 89% | 46% |
2 | 100% | 12% | 0% | 91% | 51% |
3 | 100% | 8% | 0% | 83% | 47% |
4 | 100% | 15% | 0% | 85% | 43% |
Table is annotated: contrast to there not being the cell of drug treating, the data in the table are 100% for the colony number of cell of contrast, and the cell colony percentage ratio of drug treating group is=(handling groups of cells colony number/control cells group colony number) * 100%.
Table 5, other effective ingredient of Radix Arnebiae (Radix Lithospermi) (10 μ M) suppress the CFE of acute myeloid leukemia stem cell.
Patient | Contrast | Acetylshikonin | Isobutyryl shikonin | Beta-hydroxyisovalerylshiderivative | The isovaleryl shikonin | β, beta-dimethyl-third rare acyl shikonin |
1 | 100% | 5% | 8% | 10% | 9% | 6% |
2 | 100% | 7% | 6% | 5% | 3% | 1% |
3 | 100% | 3% | 3% | 6% | 1% | 7% |
4 | 100% | 6% | 9% | 7% | 6% | 3% |
Table is annotated: contrast to there not being the cell of drug treating, the data in the table are 100% for the colony number of cell of contrast, and the cell colony percentage ratio of drug treating group is=(handling groups of cells colony number/control cells group colony number) * 100%.
Table 6, other effective ingredient of Radix Arnebiae (Radix Lithospermi) (10 μ M) suppress the CFE of acute transformation phase chronic myelogenous leukemia stem cell.
Patient | Contrast | Acetylshikonin | Isobutyryl shikonin | Beta-hydroxyisovalerylshiderivative | The isovaleryl shikonin | β, beta-dimethyl-third rare acyl shikonin |
1 | 100% | 15% | 12% | 26% | 11% | 15% |
2 | 100% | 11% | 16% | 21% | 16% | 22% |
3 | 100% | 9% | 24% | 16% | 32% | 27% |
4 | 100% | 13% | 20% | 17% | 19% | 33% |
Table is annotated: contrast to there not being the cell of drug treating, the data in the table are 100% for the colony number of cell of contrast, and the cell colony percentage ratio of drug treating group is=(handling groups of cells colony number/control cells group colony number) * 100%.
Embodiment 5, shikonin are to the evaluation of pesticide effectiveness of tumor stem cell
Experimental technique: acute myeloid leukemia cell (acute myeloid leukemia) and acute transformation phase chronic myelogenous leukemia (blast criss chronic myeloid keukemia) patient's peripheral blood or medullary cell.Peripheral blood cells is removed erythrocyte, medullary cell 150mM NH with the leukocyte separating medium
4Cl and 10mM NaHCO
3Handle and removed erythrocyte in 5 minutes.Cell is given a baby a bath on the third day after its birth time with serum-free medium, adds shikonin (final concentration is 0,5,10 μ M) and handles 18 hours, or add cytosine arabinoside (final concentration is 0,5,10 μ M) and handled 18 hours.Use then propidium iodide (propidium iodide, PI), the anti-CD34 antibody of fluorescein FITC labelling, fluorescein PE-Cy
TMThe anti-CD38 antibody pair cell of 5 labellings is done dyeing, dyes back stream type cell analyzer analysis of cells.
The painted cell of result: PI is a dead cell, and the cell of PI non-staining is a living cells.The CD34 positive/CD38 feminine gender is tumor stem cell (Guzman ML, Rossi RM, Kamischky L, et al..The sesquiterpene lactoneparthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitorcells.Blood 105:4163-4169,2005).The presentation of results of table 3 and table 4, shikonin can be removed tumor stem cell effectively.
Table 7, shikonin and cytosine arabinoside are to the survival rate influence of acute myeloid leukemia stem cell.
Table is annotated: contrast to there not being the cell of drug treating.Percentage ratio in the table is the percentage ratio of the CD34 positive/CD38 negative cells alive, and the CD34 positive/CD38 negative cells that equals among the PI negative cells group multiply by 100% again divided by the CD34 positive/CD38 negative cells in the PI positive and the negative cells.
Table 8, shikonin and cytosine arabinoside are to the survival rate influence of acute myeloid leukemia stem cell.
Patient | Contrast | Shikonin | Cytosine arabinoside | ||
5μg/ml | 10μg/ml | 5μg/ml | 10μg/ml | ||
1 | 96% | 21% | 6% | 92% | 64% |
2 | 97% | 26% | 9% | 86% | 69% |
3 | 95% | 25% | 11% | 89% | 67% |
4 | 96% | 23% | 9% | 88% | 65% |
Table is annotated: contrast to there not being the cell of drug treating.Percentage ratio in the table is the percentage ratio of the CD34 positive/CD38 negative cells alive, and the CD34 positive/CD38 negative cells that equals among the PI negative cells group multiply by 100% again divided by the CD34 positive/CD38 negative cells in the PI positive and the negative cells.
Above embodiment illustrates that Radix Arnebiae (Radix Lithospermi) and effective ingredient thereof have the application prospect in the good treatment tumor stem cell medicine.
Claims (10)
1. the application of Radix Arnebiae (Radix Lithospermi) in preparation treatment tumor stem cell medicine.
2. the application of Radix Arnebiae (Radix Lithospermi) as claimed in claim 1 in preparation treatment tumor stem cell medicine is characterized in that:
Described Radix Arnebiae (Radix Lithospermi) is extract of organic solvent of Radix Arnebiae (Radix Lithospermi) or the extract that obtains with supercritical process.
3. the application of Radix Arnebiae (Radix Lithospermi) as claimed in claim 2 in preparation treatment tumor stem cell medicine is characterized in that:
Described organic solvent is the alcoholic solution that contains 1~6 carbon atom.
4. the application of Radix Arnebiae (Radix Lithospermi) as claimed in claim 3 in preparation treatment tumor stem cell medicine is characterized in that:
Described organic solvent is an ethanol.
5. Radix Arnebiae (Radix Lithospermi) as claimed in claim 1 is preparing the application for the treatment of in the tumor stem cell medicine, it is characterized in that can also containing in the described medicine other anticarcinogen.
6. the application of the effective ingredient of Radix Arnebiae (Radix Lithospermi) in preparation treatment tumor stem cell medicine is characterized in that described effective ingredient is one of following:
(1) shikonin; (2) deoxyshikonin; (3) acetylshikonin; (4) isobutyryl shikonin;
(5) beta-hydroxyisovalerylshiderivative; (6) isovaleryl shikonin; (7) Alpha-Methyl-positive butyryl shikonin;
(8) β, beta-dimethyl-third rare acyl shikonin; (9) 2,3-dimethyl pentene acyl shikonin;
(10) 4-hydroxyl-2,5-dimethyl pentene acyl shikonin; (11) propionyl shikonin;
(12) iso-alkannin; (13) deoxidation iso-alkannin; (14) acetyl iso-alkannin;
(15) anhydroalkannin; (16) β, beta-dimethyl-third rare acyl iso-alkannin;
(17) beta-hydroxy isovaleryl iso-alkannin; (18) α-acetoxyl group isovaleryl iso-alkannin;
(19) Alpha-Methyl-positive butyryl iso-alkannin; (20) Alpha-Methyl-positive butyryl iso-alkannin;
(21) 2,3-dimethyl pentene acyl iso-alkannins; (22) 1-methoxyl group-shikonin;
(23) 1-methoxyl group-β, beta-dimethyl-third rare acyl shikonin; (24) 1-methoxyl group-acetylshikonin;
(25) the plain A of Lithospermum; (26) the plain B of Lithospermum; (27) shikinofuran A; (28) shikinofuran B;
(29) shikinofuran C; (30) shikinofuran D; (31) shikinofuran E; (32) Shikonine.
7. the application of the effective ingredient of Radix Arnebiae (Radix Lithospermi) as claimed in claim 6 in preparation treatment tumor stem cell medicine is characterized in that described Radix Arnebiae (Radix Lithospermi) effective ingredient is one of following:
(1) shikonin; (2) acetylshikonin; (3) isobutyryl shikonin; (4) beta-hydroxyisovalerylshiderivative;
(5) isovaleryl shikonin; (6) Alpha-Methyl-positive butyryl shikonin; (7) β, beta-dimethyl-third rare acyl shikonin.
8. the application of the effective ingredient of Radix Arnebiae (Radix Lithospermi) as claimed in claim 6 in preparation treatment tumor stem cell medicine, it is characterized in that: described treatment tumor stem cell medicine also contains drug excipient or carrier.
9. the application of the effective ingredient of Radix Arnebiae (Radix Lithospermi) as claimed in claim 6 in preparation treatment tumor stem cell medicine, it is characterized in that: described treatment tumor stem cell medicine also contains other anticarcinogen.
10. the application of the effective ingredient of Radix Arnebiae (Radix Lithospermi) as claimed in claim 6 in preparation treatment tumor stem cell medicine is characterized in that described treatment tumor stem cell medicine makes one of following dosage form: 1. injection; 2. tablet;
3. capsule; 4. granule; 5. slow releasing agent.
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