WO2006090557A1 - Agent de prevention ou therapeutique pour l’accident vasculaire cerebral ou les sequelles de l'accident vasculaire cerebral comprenant, en tant que principal composant, l’ acide salvianolique b ou analogue - Google Patents

Agent de prevention ou therapeutique pour l’accident vasculaire cerebral ou les sequelles de l'accident vasculaire cerebral comprenant, en tant que principal composant, l’ acide salvianolique b ou analogue Download PDF

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WO2006090557A1
WO2006090557A1 PCT/JP2006/301417 JP2006301417W WO2006090557A1 WO 2006090557 A1 WO2006090557 A1 WO 2006090557A1 JP 2006301417 W JP2006301417 W JP 2006301417W WO 2006090557 A1 WO2006090557 A1 WO 2006090557A1
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stroke
sal
sequelae
group
control group
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PCT/JP2006/301417
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Japanese (ja)
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Torao Ishida
Ming Gao
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Juridical Person, Suzuka University Of Medical Science
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives

Definitions

  • the present invention relates to a novel agent for preventing or treating stroke or stroke sequelae.
  • Patent Document 1 treatment of thrombotic symptoms in atherosclerotic stroke with thromboxane A2 synthesis inhibitor (Patent Document 1), prevention of recurrence of stroke at a dose that does not lower blood pressure (Patent Document 2), NR2B subtype selective NMDA reception Stroke treatment combining somatic antagonists with various drugs (Patent Document 3), Stroke preventive agent containing phosphatidylcholine as an active ingredient (Patent Document 4), Peroxidation containing phofen as an active ingredient is reduced Preventive stroke (patent document 5), stroke preventive agent containing xanthine as an active ingredient (patent document 6), stroke preventive agent by improving hypertension symptoms containing dioxanecyclo [3, 3, 0] octane derivative as an active ingredient ( Patent literature 7) etc.
  • Patent Document 8 1-aminocyclopropanecarboxylic acid and its prodrugs and their pharmaceutically acceptable salts and their hydrate powers for the prevention of stroke or stroke sequelae based on selected compounds or A therapeutic drug was developed (Patent Document 8) . However, it is still desirable to develop new drugs for the prevention or treatment of stroke or stroke sequelae.
  • Tansan has long been known as a medicine for angina pectoris, myocardial infarction and stroke.
  • an acyl derivative of salvianolic acid A hereinafter abbreviated as Sal'A
  • Sal'A an acyl derivative of salvianolic acid A
  • one of the inventors of the present invention is characterized in that a neural system characterized by proliferating, Z, or differentiating neural stem cells while protecting neural stem cells or neural stem cells and their corresponding neural cells.
  • a neural system characterized by proliferating, Z, or differentiating neural stem cells while protecting neural stem cells or neural stem cells and their corresponding neural cells.
  • An object of the present invention is to provide a new agent for preventing or treating stroke or sequelae of stroke.
  • the present inventors have separated the red ginseng component, and using the separated components, the blood pressure-lowering effect, stroke incidence, severity of stroke sequelae, major organs in stroke-prone rats SHRSP In comparison with the control rats, the effect on the life span was compared with that of the control rats, and it was confirmed that Sal • B was a significant effect in the prevention or treatment of stroke or stroke sequelae in stroke-prone rats SHRSP. As a result of further research based on this, the present invention was completed.
  • Sal ⁇ ⁇ is one of the water-soluble components of Dansang
  • stroke or stroke sequelae is one of the diseases caused by the deterioration or loss of tissue or organ function due to degeneration, decrease, cell death, injury or exclusion of nerve cells.
  • the present invention is based on the preventive or therapeutic action of dansan stroke or sequelae of stroke, and neuronal degeneration, reduction, cell death, injury, exclusion, including Sal ⁇ B described in Japanese Patent Application No. 2004-341367 as an active ingredient. It falls under the selection invention of a therapeutic agent for diseases caused by functional or organ function decline or loss.
  • the present invention provides "a new drug for preventing or treating stroke or sequelae of stroke” ⁇ Sal'B and its prodrugs, and pharmaceutically acceptable salts thereof and their hydrate powers.
  • Prophylactic or therapeutic agents are provided.
  • the drug of the present invention is useful as a drug for preventing or treating stroke or stroke sequelae.
  • the present invention is a novel drug for preventing or treating stroke or sequelae of stroke.
  • the main components of the drug of the present invention are SA and B and prodrugs thereof, and pharmaceutically acceptable salts and hydrate powers thereof.
  • SAL'B may be a natural substance or a synthetic product.
  • Sal'B is one of the plants of the family Lamiaceae (scientific name: Salvia ⁇ miltiorrhiza ⁇ Bunge ;, Antan ('child name: Salvia ⁇ yunnanens IS' CH Wright), blood bonsai (scientific name: Salvia 'cavaleriei' Levl. var. simplicif elia ⁇ Peter-Stibal), Akinotamurasou (scientific name: Salvia 'chinensis' Benth), Salvia' Kava Reliei.
  • Lamiaceae scientific name: Salvia ⁇ miltiorrhiza ⁇ Bunge ;, Antan ('child name: Salvia ⁇ yunnanens IS' CH Wright), blood bonsai (scientific name: Salvia 'cavaleriei' Levl. var. simplicif elia ⁇ Peter-Stibal), Akinotamurasou (scientific
  • TAS ⁇ Dinores (scientific name: Salvia ⁇ flava ⁇ Forrest ⁇ ex ⁇ Diels), Sanorevia ⁇ Bowleyana ⁇ Dunn (scientific name: Salvia ⁇ bowleyana ⁇ Dunn), Sanorevia ⁇ Priotis ⁇ Hanse (scientific name: Salvia-prionitis -Hance) (Non-Patent Document 2), etc., extracted with water, hot water, methanol-water solution, etc., and then purified by column chromatography or counter 'current' chromatography.
  • Ral chromatograph is used to adsorb Sal 'B, and after flowing an aqueous acetate solution such as magnesium acetate or calcium acetate, the fraction eluted with methanol solution is collected and further purified.
  • aqueous acetate solution such as magnesium acetate or calcium acetate
  • the fraction eluted with methanol solution is collected and further purified.
  • Patent Document 10 hot water extract of Tansan is adsorbed on a rosin column and eluted with 50% -95% ethanol
  • Patent Document 11 the ethanol / aqueous solution extract of Dansan is extracted with normal-hexane.
  • Non-patent Document 3 It is obtained by purifying with a high-speed counter 'current' chromatography of a two-layer solvent system consisting of 'ethyl acetate' ethanol 'water (3: 7: 1: 9 volume Z volume) (Non-patent Document 3).
  • the quality control of Sal'B can be carried out by adsorbing the Sal'B sample to an analytical DS column (ODS ⁇ column) and methanol ⁇ 5% acetic acid solution (35: 65 volumes).
  • Non-patent document 4 High-pressure liquid chromatography (HPLC) eluting at 281 nanometer wavelength is detected (Non-patent document 4), and 20 microliters of Sal'B sample is analyzed using C18 (Discovery'C18, 4.6 (Millimeter x 25cm) adsorbed on a column and detected in methanol-water-glacial acetic acid (40: 60: 2, volume Z volume) at a flow rate of 0.5 ml Z min. Non-patent document 5). However, if there are Sal'B-containing plants other than these plants, they can be synthesized if they can be separated from the plants and synthesized.
  • Sal ⁇ B is currently marketed in China (Jingtian Biological Process Co., Ltd.) and the United States (Ivy ⁇ Fine ⁇ Chemicals' Corporation). Sal'B is the main component of this product, even if other compounds such as isolated but not sufficiently purified, unpurified and unisolated compounds coexist in addition to the isolated and purified product.
  • the mixed compound can be used as long as the object of the present invention is not impaired.
  • the prodrug of SAL'B may be any prodrug as long as it is pharmaceutically acceptable as long as it undergoes hydrolysis or the like and becomes SAB.
  • examples of such prodrugs include, but are not limited to, methyl ester derivatives or ethyl ester derivatives at the carboxyl group in the SAL • B molecule and acetyl derivatives at the amino group in the SAL • B molecule. It may be synthesized in the future.
  • the salts of SAL'B and the prodrugs of SA and B are limited to pharmaceutically acceptable salts.
  • pharmaceutically acceptable salts include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as magnesium and calcium, and ammonia such as ammonium and tetramethylammonium. Salts, organic acid salts such as triethylamine, lysine and arginine, and acid addition salts with mineral acids such as hydrochloric acid, hydrobromic acid and sulfuric acid, but are not limited thereto. Any salt that can be synthesized in the future may be used as long as it is pharmaceutically acceptable as long as it is pharmaceutically acceptable. Hydrates of SAL'B and prodrugs thereof, pharmaceutically acceptable salts of SAL'B and prodrug salts thereof can also be used as the main component of the present invention.
  • the agent for preventing or treating stroke or sequelae of stroke according to the present invention is relatively stable in the absence of oxygen and moisture. However, it has an antioxidant effect and is relatively unstable in the air and in aqueous solutions. Sal'B in aqueous solution is unstable at high temperatures, 72 at 80 degrees Celsius 35% change over time, partially changed even with addition of sodium thiosulfate, sodium sulfate, sodium sulfite, sodium hydrosulfite, cystine hydrochloride, EDTA disodium salt, 80 degrees Celsius only when vitamin C is added And stable for 72 hours (Non-patent Document 6).
  • antioxidants include alpha 'carotene, beta' carotene, lycopene, rutin, flavonoids, catechins, resaveratrol, isoflavones, vitamin A, vitamin E, selenium, zinc, coenzyme Q10, Examples include dartathione and enzogenol. These antioxidants suppress Sal'B changes in hot aqueous solutions.
  • Nitrite does not completely suppress Sal'B changes. Therefore, nitrite alone is insufficient as a stabilizer. Vitamin Suppresses Sal'B changes. Therefore, vitamin C can be used as a stabilizer such as Sal'B, but vitamin C itself is relatively unstable in the air and in aqueous solution, and it can add a large amount of vitamin C to other antioxidants. Need to be used together.
  • the main component of the medicament for preventing or treating stroke or sequelae of stroke of the present invention is a non-high molecular weight molecule, it is administered orally or parenterally (suppository, intramuscular, subcutaneous, intravenous, intracerebral, etc. ) Can be administered. Even in the case of a prodrug whose main component is SAL'B, since the prodrug is activated in the body, it is not necessary to activate the prodrug in advance.
  • binder for example, polyvinylenoreconole, polyvinylinoatenole, ethinoresenorelose, methinorescenellose, arabica gum, tragacanth, gelatin, shellac, hydroxypropylcellulose, hydroxypropyl starch, polybutylpyrrolidone Etc.
  • disintegrant include starch, agar, ungelatinized, crystalline cellulose, calcium carbonate, sodium hydrogen carbonate, calcium citrate, dextran, and pectin.
  • lubricant include magnesium stearate, talc, polyethylene darcol, silica, hydrogenated vegetable oil, and the like.
  • colorant those permitted to be added to pharmaceuticals can be used.
  • a flavoring agent cocoa powder, coconut powder, coconut brain, aromatic acid, heart power oil, dragon brain, cinnamon powder and the like can be used. These tablets may be appropriately coated on the granules by sugar coating, gelatin coating, etc. if necessary.
  • an isotonic solution such as glucose or physiological saline, a pH adjuster, a buffer, the above-mentioned antioxidant and other stabilizers, a preservative, etc. are added.
  • an isotonic solution such as glucose or physiological saline, a pH adjuster, a buffer, the above-mentioned antioxidant and other stabilizers, a preservative, etc.
  • the injection may be a solid preparation or a preparation prepared for daily use by lyophilization after storing the solution in a container.
  • One dose may be stored in a container, or multiple doses may be stored in the same container.
  • a known method may be used.
  • the dose of the agent for preventing or treating stroke or sequelae of the present invention varies depending on the dosage form such as oral preparation, suppository, subcutaneous injection, intramuscular injection, intravenous injection, intracerebral injection and the like.
  • the dosage form such as oral preparation, suppository, subcutaneous injection, intramuscular injection, intravenous injection, intracerebral injection and the like.
  • adults are usually administered in daily doses of 0.01 to: LOOO milligrams, preferably 0.1 to 100 milligrams, and 1 dose is given in 1 to 1 doses or divided into 2 to 4 doses. .
  • the dose may be adjusted according to age and symptoms.
  • toxicity tests and medicinal effects tests acute toxicity tests, subacute toxicity tests, teratogenic toxicity tests, mutagenicity tests, leukocytes, lymphoid, neutrophils, reproductive tests, hemoglobin, GOT, serum total protein, albumin , Triglyceride, Cholesterol, Glucose, Urea, Micronucleus rate, Sperm malformation rate, Revertant bacteria, Fetal death rate, Fetal weight / Height, Tail length, Sternum deletion rate, etc.
  • the company outsources the routine analysis to routine N02ZN03, creatine, Na, K, Ca, Cl, Mg, blood albumin, globulin, GOT, GTP, gamma-daltamyl transpeptidase, urea nitrogen, Analyzes of reatune, Na, K, Ca, Cl, Mg, angiotensin 1 convertase, angiotensin 2, etc. are routinely outsourced by clinical laboratory contractors such as Shionogi 'Biomedical' Laboratories.
  • Patent Document 1 Japanese Patent Laid-Open No. 2003-26660
  • Patent Document 2 Japanese Patent Laid-Open No. 2002-370981
  • Patent Document 3 Japanese Patent Laid-Open No. 2002-332095
  • Patent Document 4 Japanese Unexamined Patent Publication No. 2000-239168
  • Patent Document 5 Japanese Patent Laid-Open No. 11-228396
  • Patent Document 6 Japanese Patent Laid-Open No. 10-182469
  • Patent Document 7 JP-A-8-268887
  • Patent Document 8 # 112005— No. 025806
  • Patent Document 9 Japanese Patent Application No. 2004-341367
  • Patent Document 10 Japanese Patent Laid-Open No. 1268682
  • Patent Document 11 US Patent 2001, 299, 910
  • Non-Patent Document 1 J. C. Dong et al., Yao'Xue'Bao, 31 ⁇ 6, p. 1996
  • Non-Patent Document 2 L. N. Li et al., J. Chinese-Pharmaceutical-Sciences, 1997 6-2, 57-64
  • Non-Patent Document 3 HB Li et al., J. Chromatogr. A. 2002 943-2 2 235-239
  • Non-Patent Document 4 QW Zhang et al., Zhongguo-Zhong-Yao-Za-Zhi, 2001 26 ⁇ 1 2 pages 848-849
  • Non-Patent Document 5 Kyokutake et al., Http: Z / www.ndc enter, com.cnZ tongxun / 2 / q uguiwul.pdf.
  • Non-patent document 6 Katsura Take et al., Http: Z / www.ndc enter, com.cnZ tongxun / 2 / q uguiwu2.pdf.
  • Toshimoto Tenkaido's 20 g of medical dandelion was filled with 150 ml of water and extracted at 30 ° C for 30 minutes while warming to 100 ° C. After filtration, add 150 ml of water again to the residue. 10 While heating at 0 ° C., extraction was further performed for 30 minutes, and then the filtrate obtained by two extractions was collected. The liquid volume decreased due to water evaporation during the extraction, and 170 ml of Tansan extract was obtained. Water was adjusted so that the amount of this solution was 222 ml. This is referred to as Tansan extract.
  • the room temperature is 22 ⁇ 1 degrees Celsius
  • the humidity is 60 ⁇ 10%
  • the lighting time is from 6 o'clock to 18 o'clock 12 hours
  • Preliminary breeding for 1 week in the breeding room set up in. Measure blood pressure and body weight of 60 rats with normal weight gain and no abnormalities in the general condition, so that 10 rats of 60 rats were divided into 6 groups so that there was no difference in blood pressure and body weight between groups. divided.
  • the B-control group was used as the group for measuring the value. During the experiment, they were fed with solid SP feed and tap water. Regarding the handling of animal experiments, we followed the “Basic Guidelines for Animal Experiments in the Physiological Field” established by the Physiological Society of Japan.
  • Example 1 rats were warmed for 10 minutes in a 38 degrees Celsius warmer before and after drug administration from 11:00 am to 5:00 pm in the above-mentioned temperature and humidity room once a week. After that, the systolic blood pressure was measured using the Softron non-invasive automatic blood pressure measurement device (BP-98A) (manufactured by Softron Co., Ltd.) by the tail-cuff method without anesthesia. The diastolic blood pressure and heart rate were measured three times, and the average and standard deviation were calculated and expressed as mean standard error. The presence or absence of significant difference was examined by t-test.
  • BP-98A Softron non-invasive automatic blood pressure measurement device
  • the systolic blood pressure immediately before the start of administration of Dansang or SAl ⁇ B, 1 week, 2 weeks, 3 weeks, and 4 weeks after the start of administration was 164. 76 ⁇ 12. 98, 186. 74 ⁇ 10 respectively. 3, 206.29 ⁇ 15.36, 212.87 ⁇ 13.17, 228.54 ⁇ 10.46 (mm Hg), Dansang group force S 165.75 ⁇ 6.87, 187.37 respectively ⁇ 10. 2 203. 28 ⁇ 13. 35, 210. 6 4 ⁇ 10. 23, 218.
  • Example 2 after measuring blood pressure and heart rate 4 weeks after starting Dansang or SAL'B administration, the rats were placed in a metabolic cage, and urine was collected for 24 hours.
  • N02ZN03 in the control group, Dansang group, and SAL'B group are 8.68 ⁇ 3.26 and 8.02 ⁇ 1.58 and 6.96 ⁇ 1.32 (*) (micromonore), creatinine 38. 75 people 7. 92 and 36.
  • ACC 1-aminocyclopropanecarboxylic acid
  • ACC 1-aminocyclopropanecarboxylic acid
  • the mechanism of action of SA and B seems to be due to the difference in the mechanism of action of preventive or therapeutic agents for stroke or sequelae of stroke mainly composed of ACC.
  • Tansan also has a low force effect that shows the same tendency as Sal 'B.
  • Example 3 urine was collected for 24 hours, then fasted for 24 hours, ether anesthetized, and blood was collected from the abdominal artery.
  • Blood albumin by BCG method, albumin / globin ratio by calculation, GOT and GPT by UV method, gamma-daltamyl transpeptidase by colorimetric method, urea nitrogen by UV method, and Creathun by alkaline picrin method Na and K by ion electrode method, Ca by OCPC method, C1 by ion electrode method, Mg by xylidyl-blue method, angiotensin 1 transferase by Kasahara method, and angiotensin 2 by RIA 'Measured by DCC method.
  • the blood albumins in order were 2. 31 ⁇ 0.18 and 2.30 ⁇ 0.17 and 2.23 ⁇ 0.10 (grams / decirit nore), and anolebumin / globin it was In the river page 0. 61 ⁇ 0. 02 and 0. 61 ⁇ 0. 08 and 0.64 ⁇ 0.03 (* 2) (calculated value), GOT is in the j jet 476. 9 ⁇ 178.1 and 472. 6 ⁇ 186.2 and 455.3 3 ⁇ 139.0 (units / liter), GPT is Kawasaki 115.
  • Example 2 the incidence of stroke on the 100th day after administration of Dansang or SAL'B, the severity of the sequelae of stroke, and the survival status were observed and analyzed. Rats that died were dissected on the day and examined for the presence of stroke lesions. The experimental data were expressed as mean value standard error. The presence or absence of significant difference was examined by t-test.
  • Example 5 the severity was determined based on the behavioral neurological symptoms of the rat, and the score was evaluated. The following evaluation criteria were used. Sensation (painfulness, etc.) 1 point of hypersensitivity, one-limbed paralysis 1S Voluntary walking, 2 points to be able to eat food on the cage lid, one-limbed paralysis is present, and voluntary walking is difficult, Three points were given to eat only the food in the cage, and four points were given to death. Compared to the control group, the Dansang group scored 36 points and the SAL'B group scored 4 points, and the SA or B group significantly reduced the sequelae of stroke compared to the control group. The Tansan group also showed a tendency to reduce the sequelae of stroke, but the difference was not significant compared to the control group.
  • Example 1 on the 30th day after drug administration, continuous measurement of cerebral blood flow was performed using the laser-Doppler method on the rats in the B-SAL'B group and the B-control group. Two-dimensional measurement was performed. As the measurement method, the rat scalp was incised under anesthesia, the skull was exposed, and the cerebral blood flow of the rat was measured using the laser power imaging device PiM2 (Risu Power Company, Sweden) manufactured by Rishiki. . The presence or absence of significant difference was examined by t-test. Using laser Doppler method, continuous measurement and two-dimensional measurement were performed to obtain values of SAL 'B group 1.414 ⁇ 0.24 and control group 1.144 ⁇ 0.31 (P ⁇ 0.05). It was. This result shows that cerebral blood flow in SAL'B group rats This is an improvement over the rats. The cerebral blood flow of the Dansang group is 1.199 ⁇ 0.43, which is not as good as that of the SAL'B group, but improved cerebral blood flow was observed.
  • High risk factors for stroke such as hypertension, diabetes, hyperlipidemia, heart disease, transient ischemic attack, effects that may be obtained by this trial for patients who want to participate in the trial Give a written statement that you can withdraw your trial participation at any time and that you can withdraw from the trial at any time.
  • SAL'B group which receives SAL'B on top of the basic treatment
  • control group which performs only basic treatment.
  • the patient's symptoms are scored according to the Japan 'Stroke' scale questionnaire every day, the score is calculated, and the onset of the stroke is diagnosed with the calculated value according to the rules written in the questionnaire. Strokes in the control group and SAL • B group
  • the stroke prevention effect of SAL'B can be measured from the difference in incidence.
  • the contents of the Japan 'Stroke' scale questionnaire are as follows.
  • Japan ' Koma' scale [Awakened without stimulating] 9 points for normality, clearness for general consciousness, 8 points for unclearness, 7 6 points for a person's name, their name and date of birth, 5 points for easy eye-opening with a normal call, 5 points for opening with a loud voice or body shake 4 points, pain ⁇ Repeating the call while applying stimuli, barely 3 points to open eyes, [not awakening even if stimulated, state] 2 points to move away from pain stimuli, pain Stimulate the limbs or grimacing a little with a stimulus, 1 point, 0 points not responding to painful stimulation, 9 points as A, 8-3 points as B, 2-points as C.
  • 10-2.Arm Normal A, arm can be raised with elbows extended, or arm can be raised by bending elbows B, arms move to some extent but cannot be lifted or do not move at all
  • the stroke prevention or treatment effect of SAL'B can be measured from the difference in the frequency of stroke onset between the control group and SAL'B group.
  • the contents of the Stroke Motor Dysfunction Severity Scale are as follows.
  • a constant of 14.60 is added to the cumulative value of each category above, and if the value is positive, it is determined that there is sequelae of stroke. From the difference in the severity of stroke motor dysfunction between the control group and SAL'B group, it is possible to measure the effect of SA or B in preventing or treating stroke sequelae.
  • the drug of the present invention can be used as a preventive or therapeutic agent for stroke or stroke sequelae.

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Abstract

Le problème à résoudre dans le cadre de cette invention consiste à procurer un nouvel agent de prévention ou thérapeutique pour l’accident vasculaire cérébral ou les séquelles de l’accident vasculaire cérébral. La solution proposée consiste dans le développement d’un agent de prévention ou thérapeutique pour l’accident vasculaire cérébral ou les séquelles de l’accident vasculaire cérébral comprenant, en tant que principal composant, un composé sélectionné parmi l’acide salvianolique B, ses promédicaments, et leurs sels et hydrates pharmaceutiquement acceptables. Par exemple, lorsqu’il est administré à une dose de 22,5 mg/kg une fois par jour cinq fois par semaine, l’acide salvianolique B réduit la survenue d’accidents vasculaires cérébraux de 30% et même lorsqu’un accident vasculaire cérébral survient, les séquelles sont légères.
PCT/JP2006/301417 2005-02-23 2006-01-30 Agent de prevention ou therapeutique pour l’accident vasculaire cerebral ou les sequelles de l'accident vasculaire cerebral comprenant, en tant que principal composant, l’ acide salvianolique b ou analogue WO2006090557A1 (fr)

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WO2003099759A1 (fr) * 2002-05-23 2003-12-04 Tianjin Tasly Pharmaceutical Co., Ltd. Preparation et application d'acide transhintotalphenolique
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