CN1686115A - Indole-3-methanol and its dimer application in preparation of medicnie for preventing and treating bred blood vessel disease - Google Patents
Indole-3-methanol and its dimer application in preparation of medicnie for preventing and treating bred blood vessel disease Download PDFInfo
- Publication number
- CN1686115A CN1686115A CN 200510057006 CN200510057006A CN1686115A CN 1686115 A CN1686115 A CN 1686115A CN 200510057006 CN200510057006 CN 200510057006 CN 200510057006 A CN200510057006 A CN 200510057006A CN 1686115 A CN1686115 A CN 1686115A
- Authority
- CN
- China
- Prior art keywords
- dimer
- indole
- cell
- treatment
- dim
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An application of indole-3-methanol and/or its dipolymer 3,3'-diindolemethane in preparing the medicines for preventing and treating hyperplastic vascular diseases, such as atherosclerosis and vascular renerrow, is disclosed.
Description
Technical field
The present invention relates to chemical substance Indole-3-carbinol (indole-3-carbinol contained in a kind of known food, I3C) and in the main metabolites 3 of gastric, 3 '-di-indole methyl hydride (3,3 '-Diindolylmethane, the DIM) application in the medicine of restenosis behind conduct preparation control proliferative angiopathy such as atherosclerosis, the vascular interventional treatment.
Background technology
A. Indole-3-carbinol (I3C) is to be present in Cruciferae (as Brassica oleracea L. var. botrytis L., Brassica oleracea L.var.capitata L., Radix Raphani etc.) and other brassicaceae and a kind of active skull cap components in the brassica vegetable, produce by the hydrolysis of glucose brassin, be isothiocyanate metabolite (Food Chem Toxicol, 1984,22 (12): 977～982), be easy to chemosynthesis, molecular weight 147, molecular formula is as follows:
A series of condensation reactions take place in Indole-3-carbinol (I3C) in gastric acid environment, produce dimer 3, oligomer such as 3 '-di-indole methyl hydride (DIM), trimer, the tetramer, and wherein DIM is a main metabolites.After pharmacokinetic was found oral I3C, I3C mainly was present in the liver, and I3C clearance rate in blood plasma and tissue is very fast; And its dimer (DIM) still can detect in liver after 24 hours taking I3C, and the detected DIM of different time is similar to plasma concentration in the concentration of tissue.Known I3C and main acid condensation substance DIM thereof all have biologic activity such as antitumorgienesis.Its dimer (DIM) molecular weight 246, molecular formula is as follows:
B. through a large amount of molecular levels, cellular level, living animal experiment, its dimer of I3C (DIM) has entered clinical trial, is mainly used in the prevention and the treatment of some tumors, existing at present commercially available I3C product.
It is as follows that the life extension company description of product is pressed in the part pharmacological action of I3C:
■ helps the regulation and control estrogen metabolism
■ suppresses cellular abnormality propagation to a certain extent and promotes apoptosis
■ promote first mutually with second mutually the Detoxication
■ protection body is resisted some common carcinogenic toxins and is damaged as two oxa-glutinous rehmannias (dioxin)
■ repairs the p21 suppressor gene
■ provides anti-oxidation protection
Some clinical research results that deliver recently show that I3C can obviously alleviate, control, even the developing of reversing tumor.In patient CIN that biopsy confirms, use the sick inspection of oral about 50% the patient of I3C 200-400mg result to alleviate, (GynecologicOncology 2000,78 (2): 123-129) and none example of use placebo person alleviates.Utilize I3C to handle recurrent respiratory tract papilloma, 39 routine recurrent respiratory papillomatosis people surgical excision postoperatives give I3C and handle, twice of dosage 200mg every day is oral, and patient's tumor of 2/3rds is controlled or alleviate (J Voice2004,18 (2): 248-253).Give DIM 108mg/d postclimacteric early-stage breast cancer patient, can make 2-hydroxyestrone increase (Nutr Cancer.2004 in the urine; 50 (2): 161-167).
The safety issue that C.I3C uses: as coming from natural food supplement, the overwhelming majority studies show that using is safe (Altern Med Rev 2003,8 (2): 156-170; CancerEpidemiolBiomarkers Prev 1994,3 (7): 591-595).Though some Research of Animal Model for Study in one's early years show, in using the inductive animal tumor model of carcinogen, I3C can promote colon, and (Cancer Lett 1987,35 (1): 71-77), (Cancer Lett 1997,118 (1): 87-94 for liver; Carcinogenesis 1999,20 (3): 453-458) etc. tumor takes place or increases; Use aspergillus flavus toxin B
1After use I3C again and can promote hepatocarcinoma that (J Natl Cancer Inst1987,78 (5): 931-934.), then obviously suppress aspergillus flavus toxin B but use the I3C pretreatment take place
1Inductive hepatocarcinoma.Use I3C and carry out the animal toxicity experiment, feed 3 ~ December, the weight of animals as a result, liver function (ALT with 50mg/kg/day (10 times to human taking dose), AST, totalprotein, albumin, caicium, glucose, BUN, globulins, GGT, cholesterol, amylase amylase, bilirubin bilirubin, creatinine inosine), hepatic tissue pathology checks that all (Toxicological Sciences 2003,74 (1): 10-21) less than changing for bone density.Several the clinical researches of delivering recently then show, use every day 300-400mg I3C can obtain good biological effect, be used for the prevention and the treatment of tumor than short-term (4 week) and long-term (average 4.8 years), do not find the acute and prolonged application side effect relevant with I3C, confirm the safety of I3C, and can prolonged application.U.S. FDA as natural supplement, has the capsule of market sale by I3C.
D. the active component 3-indole methyl glucobrassicin in the brassicaceous vegetable (as Brassica oleracea L. var. botrytis L., Brassica oleracea L.var.capitata L.) can be hydrolyzed to indole derivatives under some endogenic enzyme effects, and wherein most important chemical compound is an Indole-3-carbinol.Have at molecule, cell and living animal a large amount of experimental results show that I3C and dimer (DIM) thereof and have cell proliferation, suppress the activity of some enzyme, show active anticancer thereby the protection body avoids damaging propagation; Existing a lot of experiment and clinical research show that AKt and NF-kB are active to be suppressed cell proliferation and promote its apoptosis (NutrCancer.2004,48 (1): 84-94 by suppressing for I3C and dimer thereof (DIM); Cancer Res.2005 Jan 1; 65 (1): 364-71); Suppress rectum cancer cell strain propagation, and (corectal Disease 2002,4 (3): 205-207) to be dose-dependence; Induce G
1The phase cell is stagnated, downward modulation CDK6 gene expression, and stimulate interferon gamma receptor 1 gene expression, stimulate p21
Waf1/Cip1Express, (Carcinogenesis 2004,25 (7): 1119-1128 for interferon activity in the enhancing breast cancer cell; Carcinogenesis.2002Aug; 23 (8): 1297-305); Suppress prostate LNCaP tumor cell proliferation, cell cycle regulation makes G
1The phase cell is static, and (Cancer 2003,98 (11): 2511-2520).Therefore, existing clinical trial certificate can prevent the generation of malignant tumor safely and effectively as the I3C of composition of food.
E. vascular restenosis etc. is the common disease that the world today threatens human health behind proliferative angiopathy such as atherosclerosis, the interventional therapy, and for causing human mortality's one of the main reasons, therefore, control proliferative angiopathy becomes the focus of research in recent years.People use oral drugs such as angiotensin converting enzyme inhibitor, 17-hydroxy-11-dehydrocorticosterone on probation to fail to obtain satisfactory effect, at present, still do not have the oral drugs that any Clinical Practice confirms effectively to prevent the proliferative angiopathy; The methods such as heparin, 17-hydroxy-11-dehydrocorticosterone, carborundum that are coated with on support do not obtain promising result yet; The in recent years clinical coating stent of medicine that begins to use, mainly form through laser engraving by medical 316L rustless steel, medicine (thunderous handkerchief mycin, taxol etc.) infiltrates in the not aggressive polymer, the drug-polymer substrate repaste that 5um is thick is distributed in rack surface, be quick-release support (FR), its eluting almost completely in back 15 days of implantation, as at polymeric matrix surface repaste one deck drug release polymer, as the disperse barrier, promptly become slow release type support (SR), it can make pharmaceutical release time extend to more than 28 days.Suitable coating material is very important to the application of drug stent, require it nontoxic as the rack surface coating material, with human body the good compatibility and certain mechanicalness are arranged, degradation cycle is that 60d is between the 90d, as the PLA of present employing, poly hydroxyacetic acid, polybutyl methacrylate etc.; Though coating stent of medicine has been obtained effect preferably clinically, but still exist that thrombosis in the support, nagiopasthyrosis, hemangioma form, long-term effect is uncertain, to carrying out problems such as position treatment difficulty, drug stent that support implants cost an arm and a leg.
Have not yet to see experiment and the clinical research report that I3C and dimer (DIM) thereof is used for resisting vascular smooth muscle cell proliferation and prevents and treats restenosis behind proliferative angiopathy such as atherosclerosis, the vascular interventional treatment arranged both at home and abroad.
Goal of the invention
The objective of the invention is to provide Indole-3-carbinol and dimer thereof in pharmaceutically new purposes, be about to Indole-3-carbinol or/and its dimer passes through the mode of oral administration (or topical), be used to prevent and treat the proliferative angiopathy, as be used for to carry out the atherosclerotic's of intervene operation treatment; Or after being used for percutaneous aortic sac plasty and Stent, reducing new intima and medial thickness behind the vascular interventional treatment, pre-preventing restenosis of blood vessel further improves the clinical effectiveness of interventional therapy, reduces the expense of vascular interventional treatment etc.
Discover, the abnormality proliferation of vascular smooth muscle cell is the major reason of proliferative angiopathy such as atherosclerosis, blood vessel (as coronary artery, cerebral arteries, renal artery etc.) restenosis after interventional therapy, therefore, suppress the main target spot that the vascular smooth muscle cell hyper-proliferative is a control proliferative angiopathy.I3C and dimer thereof (DIM) can be by influencing the cell signal transmission, regulating cell cycle, cell death inducing, the modes such as activity that influence enzyme suppress the abnormality proliferation cell, non-tumor cells such as pancreas, mammary gland then there is not the obvious suppression effect, showing its effect has the specificity of tumor cell (Nutr Cancer 2003,45 (1): 101-112).The proliferative angiopathy has a large amount of proto-oncogenes to activate (J Virol 1999,73 (9): 7745-7751), to a certain degree, certain phase is similar to growth of tumour cell, produces to a certain degree inhibition so use I3C and dimer (DIM) thereof to be expected vascular smooth muscle cell to hyper-proliferative.
The present invention introduces I3C and dimer (DIM) thereof in the medicine of preparation treatment proliferative angiopathy first, and the method by systemic administration can make injured blood vessel avoid hyperplasia, makes the treatment of some proliferative angiopathy can not need intervene operation; And may only need the row balloon dilatation to the pathological changes of former placing rack; The described medicine that the present invention relates in addition very easy to use has lower treatment price, may produce material impact to the treatment general layout of vascular restenosis behind present proliferative angiopathy such as atherosclerosis, the interventional therapy.
Described I3C and dimer thereof (DIM) be natural food additive still, and by the FDA authentication, dosage is identical with usage and prophylaxis of tumours, so safety is its considerable advantage.
Concrete technical approach
A. implement experiment 1: cell experiment
Purpose: the Indole-3-carbinol (Indole-3-caibinol I3C) of observing variable concentrations is to vascular smooth muscle cell (VSMCs) propagation of cultivation and the influence of apoptosis, for restenosis (restenosis RS) after utilizing I3C control proliferative angiopathy such as atherosclerosis, vascular interventional treatment provides the infrastest foundation.
Method: experiment is divided into 8 groups, matched group (no medicine group): the conventional cultivation; DMSO group: add and the isopyknic DMSO of medicine group in the culture medium; Experimental group: add I3C in each group and make that final concentration is respectively 25,50,100,200,400,800 μ M (the cell clone test increases by 10 μ M group) in the culture fluid.With the MTT colorimetry 120 hours growing state of variable concentrations I3C effect VSMCs is described; Influence by plate clone laboratory observation I3C effect 3 all on cell proliferation; PCNA cellular immunization chemical method and TUNEL method (under 400 times of light microscopics) are respectively applied for and detect I3C effect influence to VSMCs propagation and apoptosis after 72 hours.Relatively with Dunnett t check (q ' check), p＜0.05 is for there being significant difference for experimental group and matched group.
The result:
1.MTT method is measured the growth curve of VSMCs: the growth of the I3C pair cell of each concentration has all produced depression effect in various degree.After the dosing 120 hours, 50 μ M group O.D value obviously reduces (0.733 ± 0.029vs, 0.821 ± 0.014 p＜0.05) than matched group, and I3C concentration is high more, and corresponding O.D value reduces remarkable more (p＜0.01).I3C makes the growth curve of VSMCs smooth in 120 hours simultaneously, and is wherein the most obvious with 400 μ M group.
2. plate clone experiment: I3C acts on the formation that can obviously suppress cell clone in 3 weeks of VSMCs.25 μ M group forms the clone and lacks (25 ± 2,69 ± 1,143 ± 4vs 35 ± 1,81 ± 1,173 ± 2 p＜0.05) than matched group; I3C concentration is high more, and clone's number of formation is just few more;
3.PCNA the mensuration of positive rate: the I3C effect is after 72 hours, obvious reduction relatively appears in PCNA positive rate and the matched group of VSCMs in the 50-400 μ M group: 75.3 ± 2.5%, 46.5 ± 3.3%, 37.6 ± 1.8%, 25.2 ± 2.3%vs 96.8 ± 1.7%, (p＜0.05 or 0.01).
4.TUNEL method was found the I3C effect after 72 hours, 50-400 μ M group VSMCs apoptosis rate significantly increases (24.7 ± 3.3%, 40.5 ± 1.5%, 61.6 ± 2.1%, 80.5 ± 2.3%vs6.5 ± 0.9%, p＜0.05 or 0.01) than matched group.
5.DMSO the growth kinetics to VSMCs does not have obvious influence, and is all dead in the cell 36h in each test during 800 μ M.
Conclusion:
In 72 hours observation period, the I3C of 50-400 μ M can significantly suppress the propagation of VSMCs and induce it obvious apoptosis to occur; And the I3C of lower concentration (25 μ M) grew in the observation period in (3 week), can obviously reduce the formation of cell clone.When concentration reached 800 μ M, the I3C pair cell had tangible toxic action.Growth has remarkable inhibition and is the concentration dependence I3C that this experiment shows range of doses to VSMCs, and prompting I3C is the medicine of restenosis behind a kind of potential control proliferative angiopathy such as atherosclerosis, the vascular interventional treatment.
B. implement experiment 2: zoopery
Purpose: observe of the influence of the Indole-3-carbinol (Indole-3-carbinol) of various dose, inquire into the probability that I3C is used for restenosis (restenosis RS) behind control control proliferative angiopathy such as atherosclerosis, the vascular interventional treatment to rat carotid artery balloon expandable intimal proliferation later and smooth muscle cell apoptosis.
Method: 35 male SD rats, body weight 300 ± 50g is divided into 2 groups at random, simple balloon injured group (matched group, n=5), balloon injured+I3C treatment group (the treatment group, n=30).Wherein, the treatment group is divided into 6 subgroups (n=5) again, irritates stomach and give I3C after balloon injured, and dosage is respectively 12.5mg/d, 25mg/d, 50mg/d; Administration time was respectively 4 days, 7 days.Draw materials after feeding for 2 weeks, carry out the dyeing of HE dyeing and elastic fibers then respectively, adopt the computer image analysis system detect respectively new intima thickness (H), new intima area (NIA), media area (MA), interior elastic plate around area (IEM), outer elastic plate is around area (EEM) and calculate new intima area/media area (NIA/MA), luminal stenosis index (NIA/IEM).PCNA and TUNEL labelling method (under 400 times of light microscopics) detect propagation and the percentile change of apoptotic cell respectively, to observe the influence of I3C to vascular smooth muscle cell proliferation and apoptosis.
The result:
1. pathomorphology detects: in 2 weeks of balloon expandable postoperative, each is organized specimen and sees that all smooth muscle cell proliferation in various degree moves.Treatment group and matched group are relatively, the ratio of new intima thickness, new intima area, NIA/MA all has minimizing in various degree, the luminal stenosis degree alleviates to some extent, with 50mg/d, the 7d group is (73.628 ± 21.689vs92.455 ± 39.092 the most obviously, 0.086 ± 0.018vs0.102 ± 0.033,0.539 ± 0.132vs0.605 ± 0.192, P＞0.05); Relatively give low dose of I3C (12.5mg/d with matched group, 4d) treatment back new intima thickness, new intima area, inner membrance/media area are than (NIA/MA), no significant difference (P＞0.05) is analysed in credit by statistics, and other five groups all have obvious reduction trend, with matched group comparing difference significantly (P＜0.05 or P＜0.01).
2.PCNA the mensuration of positive rate: the PCNA positive cell rate is higher than the treatment group at matched group, remove 12.5mg/d, 4d group outer (P＞0.05), obvious reduction (37.9 ± 3.9) % relatively appears in all the other five groups PCNA positive rates and matched group, (35.9 ± 1.4) %, (34.0 ± 1.9) %, (27.6 ± 1.7) %, (21.5 ± 1.8) %vs (55.6 ± 1.9) %, P＜0.01.
3.TUNEL%:I3C induces VSMCs apoptosis and drug dose and action time to be dependency.12.5mg/d 4d organizes apoptosis rate (24.6 ± 1.9) % than matched group height (23.4 ± 1.6) %, but does not have significant difference (p＞0.05), all the other each groups significant difference (P＜0.01) more all occurs with matched group.Conclusion:
I3C can significantly suppress vascellum endometrial hyperplasia and be tangible dose-dependence, may and induce its apoptosis relevant with its inhibition smooth muscle cell proliferation.This research PRELIMINARY RESULTS shows, the I3C of oral optimal dose can prevention of restenosis in zoopery, points out oral I3C may become restenosis means behind a kind of potential control control proliferative angiopathy such as atherosclerosis, the vascular interventional treatment.
C. implement experiment 3: human experimentation
The indication of this programme: because higher restenosis rate and I3C side effect seldom behind proliferative angiopathy such as atherosclerotic high incidence, the vascular interventional treatment, this programme is applicable to restenosis case behind the general proliferative angiopathy of no contraindication such as atherosclerosis, the vascular interventional treatment, and the contraindication of this programme has:
All kinds of tumor patients
The hepatic and renal function injure person
Disease in the blood system patient
Gestation and nursing women
Contact strong carcinogen crowd
The Designed Nutritional Products.Inc oral capsule product of therapeutic scheme by U.S. FDA authentication, from implementing the interventional therapy operation a few days ago, finishes to postoperative 200mg every day twice.
Topical therapeutic is for use carrying the two coating brackets of I3C polymer: the rack surface bag that is formed through laser engraving by medical 316L rustless steel is by I3C-PLA substrate, at polymeric matrix surface repaste one deck drug release polymer poly hydroxyacetic acid, as the disperse barrier, promptly become slow release type support (SR).It is 1mg (low dose) or 3mg (heavy dose) that support adopts PLA/poly hydroxyacetic acid (PLGA) coating embedding I3C drug dose, and medicine complete release time is 60-90 days.
Advantage of the present invention
A. as a kind of food active component, I3C and dimer thereof (DIM) show many useful Biological effect the time, the security of its general therapeutic dose obtains zoopery and clinical testing Extensive approval, be mainly used in tumor prevention, regulate hormonal balance, promote the aspect such as body detoxifcation. Authenticate by U.S. FDA as food additives I3C. The main metabolites of I3C in stomach is DIM, thus use this medicine and dimer (DIM) thereof that the patient is almost had no side effect, safe.
B. the research of applicant's serial experiment shows first, is in the VSMC of vegetative state To the I3C sensitivity, can significantly suppress vascular smooth muscle cell proliferation, promote simultaneously its apoptosis; Very low dense Degree (50uM) can work, and pharmaceutical efficacy is obvious dose-dependence, inhibitory action with Dosage increases and the time prolongs and increases gradually. The rat carotid artery damage model is used I3C's The short-term experiment made on the living shows, uses every day 12.5mg I3C gavage can very effectively reduce damage in 7 days The thickness of blood trouble pipe new intima reduces endangium/middle level ratio, alleviates the stenosis of tube chamber, More all there were significant differences with control group, and more remarkable with the increase difference of dosage. The applicant's is preliminary Animal experiment study shows that intimal proliferation after I3C is to injury of blood vessel has obvious inhibition and unique excellent Gesture. Because the main metabolites of I3C in stomach is DIM, the plasma half-life of DIM is bright than I3C The aobvious prolongation, and lot of experiments finds that I3C and dimer (DIM) thereof can pass through many common ways The footpath affects cell signal transmission, adjusting cell cycle, cell death inducing, affects the activity of enzyme, from And the abnormality proliferation cell is suppressed, so we are from cell and zooperal results presumption DIM Inhibition to a certain degree be can produce the VSMC of hyper-proliferative, and its apoptosis, two promoted The person share also can produce identical pharmacological action undoubtedly. So the I3C among the present invention and dimer thereof (DIM) Be expected to control such as atherosclerotic treatment or in the blood vessel intervention for the treatment of human pcna vascular diseases After the treatment, reduce new intima and medial hyperplasia, reduce balloon angioplasty art and support and implant Losing of the effective lumen of vessels of postoperative footpath finally reduced the restenosis rate of vascular interventional treatment, improves it and faces The bed prognosis greatly reduces the case that needs the revascularization procedure treatment.
C. the beneficial effect of in this programme injured blood vessel being repaired may be got involved vascular treatment with improving Mode. Because the minimizing of ISR for some simple pathologies, is used I3C and dimer (DIM) thereof After, can only carry out simple balloon angioplasty, and need not placing rack; For some littler blood vessels Proliferative lesion both had been unsuitable for simple balloon expandable originally, also was unsuitable for the pathology that support is implanted, can Consider to use I3C and dimer (DIM) treatment thereof.
D. it is very convenient that scheme is used enforcement. Only need to use that capsule is oral get final product, even picture uses and ties up It is equally convenient to give birth to plain ball, and drug treatment is short, only needs get final product in one month.
E. use this programme very economical, only need tens of dollars the whole course of treatment, than Therapeutic Method such as ordinary stent and drug stent implantation extremely strong price advantage arranged.
Claims (1)
1. Indole-3-carbinol is or/and its dimer 3, the application of 3`-di-indole methyl hydride medicine of restenosis after preparation is used for preventing and treating proliferative angiopathy such as atherosclerosis, vascular interventional treatment.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100570063A CN1332659C (en) | 2005-04-06 | 2005-04-06 | Indole-3-methanol and its dimer application in preparation of medicnie for preventing and treating bred blood vessel disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100570063A CN1332659C (en) | 2005-04-06 | 2005-04-06 | Indole-3-methanol and its dimer application in preparation of medicnie for preventing and treating bred blood vessel disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1686115A true CN1686115A (en) | 2005-10-26 |
| CN1332659C CN1332659C (en) | 2007-08-22 |
Family
ID=35304156
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100570063A Expired - Fee Related CN1332659C (en) | 2005-04-06 | 2005-04-06 | Indole-3-methanol and its dimer application in preparation of medicnie for preventing and treating bred blood vessel disease |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1332659C (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101428016B (en) * | 2008-12-23 | 2011-06-15 | 南京大学 | Uses of di-indole methyl hydride and its derivant in treating rheumatoid arthritis |
| CN102327262A (en) * | 2011-10-08 | 2012-01-25 | 合肥博太医药生物技术发展有限公司 | Indole-3-methanol, diindolylmethane and application of derivative thereof in preparation of drug for treating diabetes |
| CN102335168A (en) * | 2011-10-25 | 2012-02-01 | 合肥博太医药生物技术发展有限公司 | Application of indole-3-carbinol, diindolyl methane and derivatives thereof in preparation of medicaments for treating osteoporosis |
| CN102335169A (en) * | 2011-10-25 | 2012-02-01 | 合肥博太医药生物技术发展有限公司 | Application of indole-3-carbinol, diindolyl methane and derivatives thereof in preparation of medicaments for treating senile dementia |
| CN102389419A (en) * | 2011-10-08 | 2012-03-28 | 合肥博太医药生物技术发展有限公司 | Application of indole-3-carbinol, diindolylmethane and derivatives thereof to preparation of medicine for preventing and controlling atherosclerosis |
| CN102526030A (en) * | 2010-12-07 | 2012-07-04 | 南京大学 | Application of 3,3'-diindolylmethane in treating inflammatory bowel disease |
| CN106377524A (en) * | 2016-08-16 | 2017-02-08 | 黄晶 | Application of indole-3-carbinol or dimer thereof |
-
2005
- 2005-04-06 CN CNB2005100570063A patent/CN1332659C/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101428016B (en) * | 2008-12-23 | 2011-06-15 | 南京大学 | Uses of di-indole methyl hydride and its derivant in treating rheumatoid arthritis |
| CN102526030A (en) * | 2010-12-07 | 2012-07-04 | 南京大学 | Application of 3,3'-diindolylmethane in treating inflammatory bowel disease |
| CN102327262A (en) * | 2011-10-08 | 2012-01-25 | 合肥博太医药生物技术发展有限公司 | Indole-3-methanol, diindolylmethane and application of derivative thereof in preparation of drug for treating diabetes |
| CN102389419A (en) * | 2011-10-08 | 2012-03-28 | 合肥博太医药生物技术发展有限公司 | Application of indole-3-carbinol, diindolylmethane and derivatives thereof to preparation of medicine for preventing and controlling atherosclerosis |
| CN102335168A (en) * | 2011-10-25 | 2012-02-01 | 合肥博太医药生物技术发展有限公司 | Application of indole-3-carbinol, diindolyl methane and derivatives thereof in preparation of medicaments for treating osteoporosis |
| CN102335169A (en) * | 2011-10-25 | 2012-02-01 | 合肥博太医药生物技术发展有限公司 | Application of indole-3-carbinol, diindolyl methane and derivatives thereof in preparation of medicaments for treating senile dementia |
| CN102335169B (en) * | 2011-10-25 | 2014-03-19 | 合肥博太医药生物技术发展有限公司 | Application of indole-3-carbinol, diindolyl methane and derivatives thereof in preparation of medicaments for treating senile dementia |
| CN102335168B (en) * | 2011-10-25 | 2014-04-02 | 合肥博太医药生物技术发展有限公司 | Application of indole-3-carbinol, diindolyl methane and derivatives thereof in preparation of medicaments for treating osteoporosis |
| CN106377524A (en) * | 2016-08-16 | 2017-02-08 | 黄晶 | Application of indole-3-carbinol or dimer thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1332659C (en) | 2007-08-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Edwards et al. | Phosphatidylinositol 3-kinase/Akt signaling in the response of vascular endothelium to ionizing radiation | |
| Greish | Enhanced permeability and retention effect for selective targeting of anticancer nanomedicine: are we there yet? | |
| Singh et al. | Case report of a pituitary macroadenoma treated with artemether | |
| CN104114168A (en) | Combination therapy (vemrufenib and a MDM2 inhibitor) for the treatment proliferative disorders | |
| EP2343051B1 (en) | Anti-cancer formulation | |
| CN105267205B (en) | Pharmaceutical formulation for treating pancreatic cancer and application thereof | |
| KR100861428B1 (en) | Fatty acid analogues for the treatment of cancer | |
| CN107714684A (en) | Pharmaceutical composition and its application comprising α methyl DL tyrosine | |
| CN112807434B (en) | Application of PERK inhibitor in preparation of synergist of liver cancer drug | |
| JP5580409B2 (en) | Composition for injection for topical administration for anti-cancer treatment containing hydroxychloroquine | |
| Wada et al. | Efficacy of an MPC-BMA co-polymer as a nanotransporter for paclitaxel | |
| Bazeed et al. | Pancreatic cancer: challenges and opportunities in locoregional therapies | |
| CN111343984A (en) | Pharmaceutical composition for preventing or treating cancer comprising streptonigrin and rapamycin as active ingredients | |
| CN1332659C (en) | Indole-3-methanol and its dimer application in preparation of medicnie for preventing and treating bred blood vessel disease | |
| Yi et al. | Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel | |
| TW201106947A (en) | Anticancer formulation | |
| CN118059108B (en) | Pharmaceutical composition and application thereof in preparation of antitumor drugs | |
| CN107865967A (en) | Pharmaceutical composition and its application containing Amlexanox and mTOR inhibitor | |
| CN102170881B (en) | 3, 3', 4, 4' -tetrahydroxy-2, 2' -bipyridine-n, n' -dioxides for the treatment of renal cell carcinoma | |
| CN110022882A (en) | Promote the compound vitamin composition of gastronintestinal system power | |
| CN1057908C (en) | Use of hyaluronic acid and forms to prevent arterial restenosis | |
| CN101965191A (en) | Improved anticancer treatments | |
| CN101732345A (en) | Cisplatin spinal tumor slow-release implant and preparation method thereof | |
| CN1872049A (en) | Combination of erigeron breviscapus and medication of chemotherapy in platinum class | |
| CN113893256A (en) | Application of compound or pharmaceutically acceptable salt, dimer or trimer thereof in preparation of medicine for treating cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070822 Termination date: 20140406 |