CN1548036A - Medicine containing acarnine compound as active component - Google Patents

Medicine containing acarnine compound as active component Download PDF

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CN1548036A
CN1548036A CNA031287425A CN03128742A CN1548036A CN 1548036 A CN1548036 A CN 1548036A CN A031287425 A CNA031287425 A CN A031287425A CN 03128742 A CN03128742 A CN 03128742A CN 1548036 A CN1548036 A CN 1548036A
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medicine
compound
human body
alkannin
kaning
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CN100455283C (en
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王飞欣
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BEIJING JINBENCAO CHINESE HERBAL MEDICINE TECHNOLOGY DEVELOPMENT Co Ltd
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BEIJING JINBENCAO CHINESE HERBAL MEDICINE TECHNOLOGY DEVELOPMENT Co Ltd
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Abstract

The present invention is medicine containing acarnine compound or its salt, and the medicine is used in preventing and treating human microbial infectious diseases, inflammatory diseases, malignant tumor, hemorrhagic disease, hematopathy and immunological diseases.

Description

Contain the medicine of alkannin compound as active component
Technical field the present invention relates to contain the medicine of A Kaning (Alkannin) compounds or its salt, relates in particular to contain alkannin compound or its salt are used to prevent and treat the infected by microbes (containing SARA), inflammation, tumor of human body, hemorrhage, hematopathy or immune regulative disease as active component medicine.
The background technology alkannin compound is disclosed chemical compound in the bibliographical information (Xiao Peigen, Jia Xiaoguang etc. edit " Radix Arnebiae (Radix Lithospermi) ", the calendar year 2001 version P24-25 of China Traditional Chinese Medicine Publishing House), and wherein alkannin compound has following formula:
Alkannin compound is all water insoluble, and being soluble in oil, alcohol or ethers, it can obtain by extracting in comfrey such as Radix Arnebiae (Radix Lithospermi) (Lithospermun erythrorhizon Sieb.et Zucc.), lithospermum euchromum Royle (Arnebia euchroma (Royle) Johnst.), the arnebia guttata Bunge (Arnebiaguttata Bunge.) etc.The mixed extract of known Radix Arnebiae (Radix Lithospermi) has the effect of anti-inflammatory etc., but, when medication, all be to use with the form of mixed extract, about will be from the mixed extract of plant Radix Arnebiae (Radix Lithospermi) isolating alkannin compound and artificial and biosynthesis alkannin compound be used for pharmacy with independent a kind of chemical compound or a few combination of compounds, yet there are no report in the preparation especially for medicines such as the infected by microbes of prevention and treatment human body, inflammation, tumor, hemorrhage, hematopathy or immune regulative diseases.
Therefore summary of the invention the object of the present invention is to provide the medicine of a kind of infected by microbes that is used to prevent and treat human body by isolated independent a kind of chemical compound or a few compound from Radix Arnebiae extract, inflammation, tumor, hemorrhage, hematopathy or immune regulative disease.
The invention provides the medicine of the infected by microbes that is used to prevent and treat human body, inflammation, tumor, hemorrhage, hematopathy or immune regulative disease, this medicine contains alkannin compound or its esters as shown in the formula (I) expression,
When R is for OH in the formula be:
A Kaning (Alkannin);
R is (CH 3) 2C=CHC (O) during O-is:
β, and beta-dimethyl-acry-lalkannin (β, β-dimethylacrylalkannin);
R is CH 3C (O) during O-is:
Acetyl A Kaning (acetylalkannin);
R is (CH 3) 2C=C (CH 3) CH 2C (O) during O-is:
2,3-dimethyl pentene acyl A Kaning (teracrylalkannin);
R is (CH 3) 2COHCH 2C (O) during O-is:
Beta-hydroxy isovaleryl A Kaning (β-hydroxyisovalerylalkannin):
R is (CH 3) 2C[OC (O) CH 3] CH 2C (O) during O-is:
β-acetoxyl group isovaleryl A Kaning (β-acetoxyisovalerylalkannin):
Any 1-5 kind combination in the above-claimed cpd; Wherein: preferably contain A Kaning, β, the 1-3 kind among beta-dimethyl-acry-lalkannin and the acetyl A Kaning; More preferably contain β, beta-dimethyl-acry-lalkannin and/or acetyl A Kaning; Most preferably contain acetyl A Kaning.The salt of alkannin compound of the present invention comprises alkali metal, alkaline-earth metal and ammonium salt etc.
Medicine of the present invention can contain any independent a kind of chemical compound in the alkannin compound as crude drug, also can contain its a few combination of compounds, wherein the purity of each independent chemical compound is more than 80% or 80%, and preferred purity is more than 90% or 90%.When containing its a few combination of compounds, the content of effective in this a few compound compositions is more than 70% or 70%.
As required, medicine of the present invention can also contain other medicines as active component.There is no particular limitation for described other medicines, and those skilled in the art can suitably select according to the knowledge of prior art.
The content range of the alkannin compound that contains in the medicine of the present invention can suitably be selected according to different preparations and disease at 0.0001%-75% (percentage by weight).When being used for human body, the day use amount of described alkannin compound can be controlled between the 10 μ g-20g, preferred 100 μ g-10g, more preferably 1mg-8 gram, most preferably 5 grams.Can suitably select according to patient's different situations such as age, body weight, the state of an illness etc.Can single or use several times.Medicine of the present invention can be with the mode administration of for oral administration, external, injection, suction or transdermal.
The medicine that contains alkannin compound of the present invention can be used for preventing and treating the infected by microbes of human body, and this microorganism comprises, pathogenic gram-positive cocci such as staphylococcus aureus, streptococcus pneumoniae, staphylococcus epidermidis, enterococcus faecalis etc.; Pathogenic Gram-negative coccus such as Klebsiella Pneumoniae, serratia marcescens, have a liking for Fructus Hordei Germinatus bacillus etc.; Anaerobism or little aerobic pathogenic bacterium are as helicobacter pylori etc.; Deep and superficial mycosis class such as candidiasis, Aspergillus fumigatus, cryptococcus, dermatophytosis, Candida krusei, most advanced and sophisticated many spores of match mycete etc.; Various mycoplasma infections such as Ureaplasma urealyticum, mycoplasma pneumoniae etc.; Viral and the pathogenic microorganism that causes the SARS disease of virus as hepatitis B virus, influenza virus, herpesvirus, HIV, as: coronavirus and variant viral thereof etc.
The medicine that contains alkannin compound of the present invention is to the pathogenic microorganism sensitivity, but insensitive to human body beneficial's microorganism such as lactobacillus, bacillus bifidus etc.
The medicine that contains alkannin compound of the present invention can be used for preventing and treating the inflammation of human body.This inflammation comprises, for example, and phlebitis, vascular purpura, vaginitis, edema etc.
The medicine that contains alkannin compound of the present invention also can be used for preventing and treating the hemorrhage and hematopathy of human body, for example empyrosis, various dermatitis, septicemia, hemophilia, primary thrombocytosis, leukemia etc.
The medicine that contains alkannin compound of the present invention also can be used for preventing and treating the tumor, particularly malignant tumor of human body, for example ascites tumor: hepatocarcinoma, L1210; Solid tumor: W256, S180, gastric cancer 823, scale cancer 109, Lewis lung cancer etc.
The medicine that contains alkannin compound of the present invention can be used for preventing and treating the immune regulative disease of human body, can promote body nonspecific immunity and specific immunization of cell by effects such as the lymphocytic immunne response of promotion T.
Therefore, medicine of the present invention can be used for respiratory system, digestive system, urinary system, reproductive system, blood system, blood circulation and skin and the mucosal sites of human body.
Below the specific embodiment preparation and the pharmacodynamics test that contains the pharmaceutical preparation of alkannin compound of the present invention is described in detail, but content of the present invention also not exclusively is confined to this.
Preparation example 1
After 2 kilograms of pulverizing of lithospermum euchromum Royle, colourless with Petroleum ether extraction to the Radix Arnebiae (Radix Lithospermi) residue, reclaim solvent and obtain 80 gram kermesinus slurries.The slurry of gained is separated preparation through the silica gel H column liquid chromatographic, that is:, obtain the monomer of 6 kinds of alkannin compounds noted earlier respectively with 1%-20% ethyl acetate-petroleum ether gradient elution.That is: 0.712 Ke Akaning (yield 0.89%), 29.024 restrains β, beta-dimethyl-acry-lalkannin (yield 36.28%), 13.27 gram acetyl A Kaning (yield 16.59%), 6.032 grams 2,3-dimethyl pentene acyl A Kaning (yield 7.54%), 0.776 gram beta-hydroxy isovaleryl A Kaning (yield 0.97%), 0.792 gram β-acetoxyl group isovaleryl A Kaning (yield 0.99%).Through high pressure liquid chromatographic analysis, purity is all more than 90%.
Preparation example 2.
After 2 kilograms of pulverizing of lithospermum euchromum Royle, cross the 20-40 mesh sieve, use CO 2-supercritical extraction obtains red paste 70 grams, separates preparation, preparative column: silica gel H 10 μ m 50 * 300mm by high-pressure liquid phase preparative hplc (German Knauer K1001 type); That is: with 1%-20% ethyl acetate-petroleum ether gradient elution, obtain the red monomer of foregoing 6 kinds of alkannin compounds respectively.That is: 0.707 Ke Akaning (yield 1.01%), 30.877 restrains β, beta-dimethyl-acry-lalkannin (yield 44.11%), 15.869 gram acetyl A Kaning (yield 22.67%), 6.034 grams 2,3-dimethyl pentene acyl A Kaning (yield 8.62%), 0.91 gram beta-hydroxy isovaleryl A Kaning (yield 1.30%) and 0.77 gram β-acetoxyl group isovaleryl A Kaning (yield 1.10%), through high pressure liquid chromatographic analysis, purity is all more than 90%.
Embodiment 1
Prepare the tablet of independent a kind of in described 6 kinds of chemical compounds or a few combination according to the method for well known to a person skilled in the art, wherein can be made into according to actual needs in the tablet and contain the 10%-70% alkannin compound.
Under aseptic operating condition, get acetyl A Kaning (acetylalkannin), 100 gram microcrystalline celluloses, 30 gram magnesium stearate, 4 gram hydroxypropyl methylcellulose that 100 grams obtain by above-mentioned preparation example 1 or preparation example 2.Make the tablet of 0.5 gram according to known tabletting technology and equipment.
Embodiment 2
Get the compositions (A Kaning, β, the mixing ratio of beta-dimethyl-acry-lalkannin and acetyl A Kaning be 1: 1: 2) of 100 grams by the alkannin compound of above-mentioned preparation example 1 or preparation example 2 acquisitions, other is identical with embodiment 1, the tablet of preparation 0.5 gram.
Embodiment 3
The unguentum for preparing described 6 kinds of alkannin compounds according to the method for well known to a person skilled in the art.Wherein can be made into according to actual needs in the unguentum and contain the 0.0001%-10% alkannin compound.Under aseptic technique, get alkannin compound (A Kaning, β that 0.5 above-mentioned preparation example 1 of gram or preparation example 2 obtain, the mixing ratio of beta-dimethyl-acry-lalkannin, acetyl Ah card peace beta-hydroxy isovaleryl A Kaning is 0.7: 1: 1: 2: 0.5), 80 the gram vaseline, 10 the gram liquid paraffin and 10 the gram anhydrous lanolins, in mortar, grind well, product is made in packing, is used for external.Also can use this unguentum, make paster according to the method for well known to a person skilled in the art and be used for Transdermal absorption.
Embodiment 4
The injection for preparing described 6 kinds of alkannin compounds according to the method for well known to a person skilled in the art.Under aseptic technique, get the β that 0.5 above-mentioned preparation example 1 of gram or preparation example 2 obtain, 15 milliliters of beta-dimethyl-acry-lalkannin, 400 milliliters of propylene glycol, 100 milliliters of ethanol, 20 milliliters of tween 80s, benzyl alcohol, mixture is fully dissolved, add water to 1000 milliliters, behind the mix homogeneously, injection products is made in bottling.
The test of pesticide effectiveness result of the medicine that contains alkannin compound is described below.
(1) preparation of medicine
Take by weighing the A Kaning, the β that obtain in 5.0 milligrams preparation example 1 or the preparation example 2 respectively, beta-dimethyl-acry-lalkannin and acetyl A Kaning.Medicine is dissolved among 1 milliliter of DMSO.With the RPMI-1640 culture medium with 50 times of its dilutions after, packing, and further be diluted to concentration and be respectively 100,50,25,12.5,6.25,3.125,1.5625,0.78125,0.390625 (μ g/ml).
(2) sensitivity tests of medicine
The medicine branch of above-mentioned each concentration is installed in the orifice plate, and be about 10 with the bacteria concentration for preparing 3-10 6Each inoculation.
Result of the test shows: A Kaning, β, and beta-dimethyl-acry-lalkannin and acetyl A Kaning have suitable sensitivity to gram-positive golden yellow coccus, and its sensitivity range (MIC) is 0.391-12.5 μ g/ml; To common gram negative pathogenic bacteria, its sensitivity of Klebsiella pneumonia MIC scope is 0.391-6.25 μ g/ml, and the minority bacterial strain is 12.5-50 μ g/ml; Serratia marcescens (most of clinical separation strain) and have a liking for its most bacterial strain sensitivity ranges of Fructus Hordei Germinatus bacillus at 0.391-3.125 μ g/ml.Wherein especially effective to having a liking for the Fructus Hordei Germinatus bacillus, its sensitivity range is 0.391-0.781 μ g/ml, and berberine is 8-32 μ g/ml,, obviously is better than berberine that is; MIC to bacteroid especially bacteroides fragilis is 0.391-6.25 μ g/ml; Quite responsive to helicobacter pylori, its MIC is 0.391-0.781 μ g/ml.
In addition, β, the result of the external antifungal test of beta-dimethyl-acry-lalkannin shows: to candidiasis and cryptococcal MIC scope between 2.08-33.3 μ g/ml, MIC 90Be 33.3 μ g/ml, and the MIC scope of fluconazol is between 0.125-64 μ g/ml, MIC 90Be 69 μ g/ml; To the MIC scope of dermatophytosis between 4.16-8.32 μ g/ml, MIC 90Be 4.16 μ g/ml, and fluconazol to the MIC scope of most of bacterial strains of dermatophytosis between 32-64 μ g/ml, MIC 90Be 64 μ g/ml, both obvious differences.In addition, amazingly be, β, beta-dimethyl-acry-lalkannin has for the drug-fast Candida krusei of fluconazol and suppresses effect preferably, MIC is 8.32-16.6 μ g/ml, and matches the mould MIC of many spores between 4.16-8.32 μ g/ml for all insensitive tip of most antifungal drugs such as fluconazol.Acetyl A Kaning is 3.90625 μ g/ml to the MIC of Cryptococcus histolyticus in addition, is 0.90625-62.5 μ g/ml to the MIC of hungmao mentagrophyte; β, beta-dimethyl-acry-lalkannin is 3.0625-250 μ g/ml to the MIC of Aspergillus fumigatus, cryptococcus and hungmao mentagrophyte.Therefore, alkannin compound is the potent antifungal agent of a kind of wide spectrum.
In addition, alkannin compound of the present invention to the MIC of human body beneficial's microorganism such as lactobacillus and bacillus bifidus all more than 200 μ g/ml, therefore,, but insensitive by the above-mentioned data medicine that contains alkannin compound of the present invention as can be seen to human body beneficial's microorganism to the pathogenic microorganism sensitivity.
From the contrast test of the mixed extract of Radix Arnebiae (Radix Lithospermi) and the described alkannin compound of 1-3 kind as can be seen, it is as shown in table 1 that the medicine of the described alkannin compound of the 1-3 of containing kind of the present invention obviously is better than the result of its MIC of mixed extract (μ g/ml) of Radix Arnebiae (Radix Lithospermi).
Table 1
Strain name ????A ????B ????C
Staphylococcus epidermidis ????12.5 ????0.391 ????0.7812
Serratia marcescens ????25 ????0.781 ????3.125
Bacteroid ????>200 ????0.391 ????0.391
Candida albicans ????500 ????3.9062 ????250
Annotate: A is the mixed extract of Radix Arnebiae (Radix Lithospermi);
B is β, beta-dimethyl-acry-lalkannin;
C is the mixture (A Kaning, β, the mixing ratio of beta-dimethyl-acry-lalkannin and acetyl A Kaning is 1: 1: 2) of alkannin compound
A Kaning, β, beta-dimethyl-acry-lalkannin and acetyl A Kaning show the result of the fungistatic effect test of mycoplasma pneumoniae, its minimum concentration MIC that suppresses mycoplasma pneumoniae is respectively, 3.751 μ g/ml, 2 μ g/ml and 7.819 μ g/ml are equivalent to the inhibition effect of pure injection erythromycin 0.1925 μ g/ml.
Unguentum with the alkannin compound of the foregoing description 3 preparation carries out the external preparation for skin medicine to shown in the following tabulation 2 of result of the test of part disease.
Table 2
Disease Experimenter's number Effective percentage Cure rate The treatment natural law Route of administration Remarks
Empyrosis ??300 ??100% ??100% ??6-20 Affected part is directly given Scald shallow 2 degree 186 people of 92 people, dark 2 and 3 degree 114 people
Hemorrhoid ??117 ??100% ??97.4% ??15 Affected part is directly given Three examples recurred after half a year
Herpes zoster ??98 ??100% ??100% ??3-7 Affected part is directly given Wherein 12 examples add and use polyinosini
Cervical erosion ??80 ??100% ??100% ??10-20 Vagina administration
Children's's nose bleeding ??257 ??99.6% ??72.8% ??15 Nasal-cavity administration
Verruca plana ??100 ??96% ??81% ??10-30 Affected part is directly given
Chronic prostatitis ??40 ??82.5% ??57.5% ??10-20 Anum administration
Acne ??50 ??92% ??60% ??15 Affected part is directly given
Decubital ulcer ??30 ??100% ??100% ??7-21 Affected part is directly given
Eczema rhagadiforme ??98 ??94.9% ??66.3% ??10-30 Affected part is directly given
Condyloma acuminatum ??55 ??100% ??100% ??5-35 Affected part is directly given
Baby napkin dermatitis ??208 ??100% ??100% ??2-6 Affected part is directly given
As can be seen from the above table, the external preparation for skin medicine of alkannin compound is suitable for treating most abscess skin ulcer scabies, herpes, and is especially remarkable to burn and scald effect, do not stay cicatrix after healing.
A Kaning, β, beta-dimethyl-acry-lalkannin and acetyl A Kaning are to shown in the following tabulation 3 of animal test results of transplantation tumor.
Table 3
Tumor type β, beta-dimethyl-acry-lalkannin Acetyl A Kaning A Kaning
Tumour inhibiting rate Increase in life span Tumour inhibiting rate Increase in life span Tumour inhibiting rate Increase in life span
Ascitic type liver cancer ??113.4% ??112.6% ??130.8%
??S180 ??9.63% ??35.7%
Lewis lung cancer ??42.8% ??52.6%
??L1210 ??128%
??W256 ??77%
As can be seen from the above table, β, beta-dimethyl-acry-lalkannin has in various degree curative effect to hepatocarcinoma, S180, Lewis lung cancer; Acetyl A Kaning has in various degree curative effect to hepatocarcinoma, S180, L1210, Lewis lung cancer, W256; A Kaning is only effective to hepatocarcinoma.
Alkannin compound shows the result of the test of virus: the 7th day oral β behind the dhbv dna infected duck, beta-dimethyl-acry-lalkannin, 100mg/kg one day 2 times, 10 days to the inhibition effect of infected duck serum DHBV-DNA level significantly (P<0.05-0.01), non-toxic reaction; The 50mg/kg group has significant inhibitory effect (P<0.05).
β, beta-dimethyl-acry-lalkannin show that to the in vitro tests of hepatitis B virus concentration is 30 μ g/ml, are 96.2601% to the average suppression ratio of HBsAg, are 91.6056% to the average suppression ratio of HBeAg.
Ah card's peace β, the result of the test of external anti-HIV-1 reverse transcriptase of beta-dimethyl-acry-lalkannin and intergrase is as shown in table 4 below.
Table 4
????IC 50(μg/ml)
Anti-hiv reverse transcriptase Positive control PFA ????0.097
Alkannin compound ????>20
Anti-hiv integrase Positive control ABPS-Y ????0.922
Alkannin compound ????12.467
With ametycin induced mice immunologic hypofunction model, the effect of research alkannin compound.The result shows the β of lumbar injection 6mg/kg every day, beta-dimethyl-acry-lalkannin, continuous 5 days, mouse boosting cell NK cell poison improves about 20% (P<0.001), shown to make macrophage injury recovery to some extent in the mouse peritoneal, can increase intraperitoneal macrophage migration ability, increased the lymphocytic activity of T, and can promote the lymphocytic immunne response effect of T, have the body nonspecific immunity of promotion and specific immunization of cell.

Claims (13)

1. medicine that is used to prevent and treat human microorganism's infection, inflammation, tumor, hemorrhage, hematopathy or immune regulative disease, this medicine contains the alkannin compound or its esters of formula (I) expression,
Figure A031287420002C1
R is for being selected from by OH, (CH in the formula 3) 2C=CHC (O) O-, CH 3C (O) O-, (CH 3) 2C=C (CH 3) CH 2C (O) O-, (CH 3) 2COHCH 2C (O) O-, (CH 3) 2C[OC (O) CH 3] CH 2Any 1-5 kind in C (O) group that O-formed.
2. medicine as claimed in claim 1, wherein R is for being selected from OH, (CH 3) 2C=CHC (O) O-and CH 3The 1-3 kind of C (O) O-.
3. medicine as claimed in claim 2, wherein R is (CH 3) 2C=CHC (O) O-and/or CH 3C (O) O-.
4. medicine as claimed in claim 3, wherein R is (CH 3) 2C=CHC (O) O-.
5. medicine as claimed in claim 1, the purity of each chemical compound that wherein said medicine contains are more than 80% or 80%.
6. medicine as claimed in claim 1, the purity of each chemical compound that wherein said medicine contains are more than 90% or 90%.
7. medicine as claimed in claim 1, wherein when described medicine contained several combination of compounds, the content of effective in the said composition was more than 70% or 70%
8. medicine as claimed in claim 1, this medicine also can contain the other medicines active component.
9. medicine as claimed in claim 1, when being used for human body, the day use amount of described alkannin compound can be controlled between the 10 μ g-10g.
10. medicine as claimed in claim 1 can be with the mode administration of for oral administration, external, injection, suction or transdermal.
11. medicine as claimed in claim 1, this medicine is used for the treatment of or prevents the infected by microbes of each system of human body, comprises streptococcus pneumoniae, Klebsiella Pneumoniae, helicobacter pylori, candidiasis, cryptococcus, dermatophytosis, most advanced and sophisticated many spores of match mycete; Various mycoplasma infections comprise Ureaplasma urealyticum, mycoplasma pneumoniae; Or viral infection comprises hepatitis B virus, influenza virus, herpesvirus, HIV virus.
12. medicine as claimed in claim 1, this medicine are used for the treatment of or prevent the pathogenic microorganism that may cause the SARS disease of human body, as: coronavirus and variant viral thereof, negative myxovirus, chlamydia etc.
13. medicine as claimed in claim 1, this medicine are used for the treatment of or prevent ascites tumor, hepatocarcinoma, L1210, solid tumor, W256, sarcoma 180, gastric cancer 823, scale cancer 109 or the Lewis lung cancer of human body.
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CN1307987C (en) * 2005-07-25 2007-04-04 北京羚锐伟业科技有限公司 New usage of alkannin
US7622506B2 (en) 2006-04-07 2009-11-24 Sunten Phytotech Co., Ltd. Naphthalenedione compounds for treating inflammation related disorders and microbial infection
CN102198130A (en) * 2011-03-30 2011-09-28 中国人民解放军第二军医大学 Use of shikonin as antifungal medicine synergist
CN102198124A (en) * 2010-03-26 2011-09-28 山东靶点药物研究有限公司 Gromwell extract for treating rheumatoid arthritis, and soft capsules thereof
CN103919758A (en) * 2010-03-26 2014-07-16 苏州雷纳药物研发有限公司 Medical application of gromwell naphthaquinone compounds
CN105622374A (en) * 2016-03-02 2016-06-01 山东省分析测试中心 Method for separating and preparing compound with neuraminidase inhibitory activity from radix lithospermi
CN106924323A (en) * 2015-12-30 2017-07-07 姚萍 Application of the radix macrotomiae in the medicine for preparing treatment virus B hepatitis
CN110269852A (en) * 2019-08-07 2019-09-24 中美(河南)荷美尔肿瘤研究院 β, beta-dimethyl-acry-lalkannin application in preparation of anti-tumor drugs
CN115381778A (en) * 2022-08-29 2022-11-25 成都紫旺药业有限责任公司 Lithospermum naphthoquinone water-soluble solid dispersion, water-soluble preparation and preparation method

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Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1307987C (en) * 2005-07-25 2007-04-04 北京羚锐伟业科技有限公司 New usage of alkannin
US7622506B2 (en) 2006-04-07 2009-11-24 Sunten Phytotech Co., Ltd. Naphthalenedione compounds for treating inflammation related disorders and microbial infection
CN102198124B (en) * 2010-03-26 2014-10-29 山东靶点药物研究有限公司 Gromwell extract for treating rheumatoid arthritis, and soft capsules thereof
CN102198124A (en) * 2010-03-26 2011-09-28 山东靶点药物研究有限公司 Gromwell extract for treating rheumatoid arthritis, and soft capsules thereof
CN103919758A (en) * 2010-03-26 2014-07-16 苏州雷纳药物研发有限公司 Medical application of gromwell naphthaquinone compounds
CN103919758B (en) * 2010-03-26 2015-11-25 苏州雷纳药物研发有限公司 The medical usage of alkannin derivatives
CN102198130B (en) * 2011-03-30 2012-08-29 中国人民解放军第二军医大学 Use of shikonin as antifungal medicine synergist
CN102198130A (en) * 2011-03-30 2011-09-28 中国人民解放军第二军医大学 Use of shikonin as antifungal medicine synergist
CN106924323A (en) * 2015-12-30 2017-07-07 姚萍 Application of the radix macrotomiae in the medicine for preparing treatment virus B hepatitis
CN105622374A (en) * 2016-03-02 2016-06-01 山东省分析测试中心 Method for separating and preparing compound with neuraminidase inhibitory activity from radix lithospermi
CN105622374B (en) * 2016-03-02 2018-04-17 山东省分析测试中心 A kind of method that separation prepares the compound with neuraminic acid enzyme inhibition activity from Asian puccoon
CN110269852A (en) * 2019-08-07 2019-09-24 中美(河南)荷美尔肿瘤研究院 β, beta-dimethyl-acry-lalkannin application in preparation of anti-tumor drugs
CN115381778A (en) * 2022-08-29 2022-11-25 成都紫旺药业有限责任公司 Lithospermum naphthoquinone water-soluble solid dispersion, water-soluble preparation and preparation method

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