WO2012003802A1 - 5α-雄甾(烷)-3β,5,6β-三醇在制备神经元保护药物中的应用 - Google Patents
5α-雄甾(烷)-3β,5,6β-三醇在制备神经元保护药物中的应用 Download PDFInfo
- Publication number
- WO2012003802A1 WO2012003802A1 PCT/CN2011/076967 CN2011076967W WO2012003802A1 WO 2012003802 A1 WO2012003802 A1 WO 2012003802A1 CN 2011076967 W CN2011076967 W CN 2011076967W WO 2012003802 A1 WO2012003802 A1 WO 2012003802A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- group
- neurons
- spinal cord
- ischemia
- glutamic acid
- Prior art date
Links
Classifications
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- 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
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0007—Androstane derivatives not substituted in position 17
Definitions
- the present invention relates to a novel pharmaceutical use of the compound 5 ⁇ -androst( ⁇ :)-3 ⁇ ,5,6 ⁇ -triol (abbreviated as YC-6). Background technique
- the treatment of acute ischemic stroke mainly through two ways: one is to dissolve thrombus, and the other is neuroprotection.
- the latter refers to the prevention of a series of pathological changes in brain tissue caused by ischemia in the treatment of acute ischemic stroke. Biochemical reactions, interfere with all aspects of the ischemic waterfall response, and prolong the survival of drugs or measures of neurons.
- neuroprotective therapy for acute ischemic stroke has become a research hotspot in the treatment of stroke.
- Many neuroprotective agents are currently undergoing clinical development experiments, and their mechanism of action is to block various harmful pathological processes caused by ischemia. Occurs, thereby preventing or limiting brain damage caused by ischemia, reducing brain tissue death and promoting functional recovery.
- neuroprotective agents can reduce the area of cerebral infarction, do not cause bleeding, no bleeding complications during thrombolysis and anticoagulant therapy, no detailed diagnosis of the cause is required before use, making early treatment possible, thus neuroprotective agents The treatment effect and prospects are encouraging.
- CBs calcium channel blockers
- GABA gamma-aminobutyric acid
- neuroactive bodies have a widespread effect on neuroprotection and are receiving increasing attention. These levels of neuroactive steroids are associated with the development of central nervous system (CNS) diseases, and have significant regulatory effects on neuronal damage, death, and various central nervous system diseases.
- CNS central nervous system
- NAS neuroactive steroids
- Estrogen is one of the most known neuroprotective NASs. In menopausal women, ovaries stop producing estrogen, which can cause beta-amyloid protein ( ⁇ ) deposition, leading to Alzheimer's disease (Alzheimer s disease).
- estrogen to AD can significantly reduce the level of ⁇ in the brain.
- Clinical use of estrogen for the treatment of AD has received good results.
- 5 ⁇ - ⁇ :) -3 ⁇ ,5,6 ⁇ -triol (YC-6) is a neuroprotective compound we found during neurosteroid studies. Its chemical structure is shown in the figure. According to our literature search, to date, no reports of pharmacological effects of YC-6 have been reported, and no studies have reported that YC-6 has active or neuroprotective effects on nervous tissues.
- An object of the present invention is to provide a use of 5 ⁇ -androstidine-3 ⁇ ,5,6 ⁇ -triol for the preparation of a neuroprotective drug, thereby providing a novel drug for the treatment of neuronal diseases.
- YC-6 has neuroprotective effects in vivo
- focal cerebral ischemia model and 2) blocked spinal aorta-induced spinal cord injury model, and studied YC-6 on rat cerebral ischemia.
- YC-6 has obvious protective effect on brain neuron injury.
- YC-6 has protective effects on neuronal damage caused by cerebral ischemia, spinal cord ischemia and hypoxia. To date, there have been no reports of YC-6 activity or neuroprotective effects on neural tissue. DRAWINGS
- Figure 1 is a protective effect of YC-6 on glutamate-induced cerebellar granule neurons, spinal motor neurons, and cerebral cortical neurons excitatory damage, in which A is cerebellar granule neurons and B is spinal motor neurons, C For cerebral cortical neurons, D is the release rate of LDH, E is the survival rate of neurons; * and ** indicate that there is a significant difference between the YC-6 group and the glutamate (Glu) group of cerebellar granule neurons, *P ⁇ 0.05 , ** ⁇ 0.01; # ⁇ ## respectively indicate that there is a significant difference between the YC-6 group and the glutamate (Glu) group in spinal motor neurons, #P ⁇ 0.05, ## ⁇ 0.01; $ and $ $ indicates that there is a significant difference between the cerebral cortical neurons YC-6 group and the glutamic acid (Glu) group, ⁇ O.OS , ⁇ P O.OL Figure 2 is a protective effect of YC-6 on hypoxia-induced cortical
- Figure 3 is a neuroprotective effect of YC-6 on rabbit spinal cord ischemia induced by abdominal aortic clipping, in which A is a neurological function score, B is a histopathological section, and C is a normal spinal motor neuron count.
- Figure 4 shows the neuroprotective effect of YC-6 on focal cerebral ischemia model, in which A is the neurological function score, B is the cerebral infarction slice, and C is the cerebral infarct volume comparison.
- SD rats were isolated from the spinal cord for 15 days of pregnancy to remove the meninges and blood membranes.
- the fetal rat spinal cord tissue was digested with 0.125% trypsin, centrifuged, and the middle layer containing abundant motor neurons was removed. After centrifugation to remove the cell debris, the differential wall was attached. 1 h, select suspended spinal motor neurons with slow adherence. After 24 h of inoculation, cytarabine was added, and the whole amount was changed on the third day, and the culture was continued with L-15 serum-free medium, and the medium was changed every half 2-3 days. Experiments were performed on days 3-5.
- the cortex of the meninges and blood vessels of the rats in which the Id was taken out was removed, and after digesting with 0.25 g/L trypsin, the cells were blown into a single cell suspension by a 0.05 g/L DNase I blowing solution, centrifuged, and a precipitate was taken. Diluted with DMEM-F12 medium containing 5% (v/v) FBS and 2% B27 and seeded in polylysine pre-coated petri dishes. After 24 hours of inoculation, lO M Ara-C was added to inhibit the growth and proliferation of non-neuronal cells, and then changed 2-3 times a week. Experiment on the 10th day.
- the cerebellar granule neurons were cultured for 8 days, and the normal control group, the glutamic acid group, the MK801+ glutamic acid, and the YC-6+ glutamic acid group were respectively set.
- the normal control group did not do any treatment.
- the glutamic acid group was added with 200 ⁇ glutamic acid.
- the other groups were pre-added with MK801 ( ⁇ ) and different concentrations of YC-6. After incubation at 37 ° C for 30 minutes, glutamic acid was added and used for 24 h.
- the morphology of the nerve cells was observed by phase contrast microscopy; the cells were counted by FDA staining, inverted fluorescence microscopy, and the survival rate of neurons was calculated. The activity of each group of lactate dehydrogenase was measured.
- YC-6 has a concentration dependence, see Figure 1-A, D, E. In the above dose range, YC-6 had no effect on the survival rate of normal nerve cells.
- the cortical neurons were cultured for 10 days, and the normal control group, the glutamic acid group, the MK801+ glutamic acid, and the YC-6+ glutamic acid group were respectively set.
- the normal control group did not do any treatment.
- the glutamic acid group was added with 200 ⁇ M glutamic acid.
- the other groups were pre-charged with solvent, MK801 ( ⁇ ) and different concentrations of YC-6. After incubation at 37 ° C for 30 minutes, glutamic acid was added. After h, the morphology of the nerve cells was observed by phase contrast microscope, stained with FDA, inverted fluorescence microscope, cell count, and the survival rate of neurons was calculated. The activity of each group of lactate dehydrogenase was measured.
- MTT assay showed that hypoxia treatment significantly reduced neuronal survival (P ⁇ 0.05), while YC-6 showed a high concentration-dependent increase in neuron survival due to hypoxia damage (Fig. 2B).
- the LDH release results were consistent with the MTT method, and the YC-6 pretreatment group reduced the neuronal damage caused by hypoxia in a concentration-dependent manner (Fig. 2-C, ⁇ 0.05).
- Control group made rabbit spinal cord ischemia model
- YC-6 group received 2 mg.Kg_EH YC-6 via ear vein 30 minutes before spinal cord ischemia
- Vehicle group the same volume of hydroxypropyl cyclodextrin (lml.Kg- 1 ) was injected in the same manner 30 min before spinal cord ischemia; the Sham group only exposed the abdominal aorta without blocking.
- the physiological parameters between the groups were measured immediately before ischemia, 10 min after ischemia and 20 min after reperfusion.
- the functional scores of rabbits in each group were scored by Talov score [5]: 0 points, complete paralysis of hind limbs; 1 point, joint movement of hind limbs can be detected; 2 points, hind limbs can move freely but can not stand; 3 points, can stand but can not Walking; 4 points, the hindlimb motor function is fully restored and can walk normally.
- the lumbar spinal cord tissue (L 5 -L 7 ) was taken under anesthesia, and the paraffin was embedded and sectioned, HE staining, and the pathology of the spinal cord was observed under light microscope by an observer who did not understand the grouping. Change and count normal motor neurons in the anterior horn of the spinal cord. The normal neurons in the anterior horn of the spinal cord of each animal were counted as the mean of 3 slice counts.
- YC-6 has a significant protective effect on spinal cord ischemia.
- MCAO middle cerebral artery occlusion
- the rats were sacrificed by decapitation, and the brains of the rats were quickly taken out, sliced, and quickly stained with TTC solution for 30 min, and then fixed with paraformaldehyde buffer. After 24 hours, take a photo with a digital camera, input the computer, and calculate the infarct area with image processing software (ADOBE, PHOTOSHOP 8. 0) (the pink area is normal brain tissue, and the white area is infarct area:). In order to correct the deviation of the infarct volume caused by cerebral edema, the infarct volume is expressed as a percentage of the normal volume of the contralateral side.
- image processing software ADOBE, PHOTOSHOP 8. 0
- Infarct volume percentage (contralateral normal tissue volume - volume of ipsilateral normal tissue:) I contralateral normal tissue volume x l 00%.
- NNS neurobehavioral score
- YC-6 ie, male ⁇ ( ⁇ ) -3 ⁇ , 5 ⁇ , 6 ⁇ -triol has protective effects on neuronal damage caused by hypoxia, cerebral ischemia and spinal cord ischemia.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Claims
Priority Applications (17)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SG2012088688A SG186135A1 (en) | 2010-07-09 | 2011-07-08 | Use of 5a-androstane (alkyl)-3b,5,6b-triol in preparing neuroprotective drugs |
CA2802133A CA2802133C (en) | 2010-07-09 | 2011-07-08 | Use of 5.alpha.-androstane(alkyl)-3.beta.,5,6.beta.-triol in preparation of neuroprotective drugs |
LTEP11803155.8T LT2591785T (lt) | 2010-07-09 | 2011-07-08 | 5-androstan(alkil)-3,5,6-triolio panaudojimas neuroprotekcinių vaistų gamybai |
EP11803155.8A EP2591785B1 (en) | 2010-07-09 | 2011-07-08 | Use of 5-androstane (alkyl)-3,5,6 -triol in preparing neuroprotective drugs |
RU2012151400/15A RU2541093C2 (ru) | 2010-07-09 | 2011-07-08 | Применение 5а-андростан-3в,5,6в-триола для изготовления нейропротекторных лекарственных средств |
SI201131126A SI2591785T1 (sl) | 2010-07-09 | 2011-07-08 | Uporaba 5-androstan(alkil)-3,5,6-triola pri pripravi nevroprotektivnega zdravila |
RS20170319A RS55845B1 (sr) | 2010-07-09 | 2011-07-08 | Upotreba 5-androstan (alkil)-3,5,6 -triola u pripremanju neuroprotektivnih lekova |
DK11803155.8T DK2591785T3 (en) | 2010-07-09 | 2011-07-08 | USE OF 5-ANDROSTANE (ALKYL) -3,5,6-TRIOL FOR THE PREPARATION OF NEURO PROTECTIVE MEDICINE |
ES11803155.8T ES2620754T3 (es) | 2010-07-09 | 2011-07-08 | Uso de 5-androstano (alquil)-3,5,6-triol en la preparación de fármacos neuroprotectores |
KR1020127032524A KR101463477B1 (ko) | 2010-07-09 | 2011-07-08 | 5a-안드로스탄(알킬)-3β,5,6β-트리올의 신경보호 약물 제조에서의 용도 |
AU2011276800A AU2011276800B2 (en) | 2010-07-09 | 2011-07-08 | Use of 5a-androstane (alkyl)-3B,5,6B-triol in preparing neuroprotective drugs |
JP2013516989A JP5681931B2 (ja) | 2010-07-09 | 2011-07-08 | ニューロン保護薬の製造のための5α−アンドロスタン−3β,5,6β−トリオールの使用 |
BR112012031861A BR112012031861B1 (pt) | 2010-07-09 | 2011-07-08 | uso de 5a-androstano-3ß,5,6ß-triol |
US13/805,436 US8809309B2 (en) | 2010-07-09 | 2011-07-08 | Use of 5α-androstane (alkyl)-3β,5,6β-triol in preparation of neuroprotective drugs |
US14/332,338 US9320743B2 (en) | 2010-07-09 | 2014-07-15 | Use of 5α-androstane-3β,5,6β-triol in preparation of neuroprotective drugs |
HRP20170418TT HRP20170418T1 (hr) | 2010-07-09 | 2017-03-14 | Uporaba 5-androstan (alkil)-3,5,6-triola u pripravi neuroprotektivnih lijekova |
CY20171100375T CY1118789T1 (el) | 2010-07-09 | 2017-03-27 | Χρηση 5α-ανδροστανο(αλκυλο)-3β,5-6β-τριολης σε παρασκευη νευροπροστατευτικων φαρμακων |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2010102241733A CN101884638B (zh) | 2010-07-09 | 2010-07-09 | 5α-雄甾(烷)-3β,5,6β-三醇在制备神经元保护药物中的应用 |
CN201010224173.3 | 2010-07-09 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/805,436 A-371-Of-International US8809309B2 (en) | 2010-07-09 | 2011-07-08 | Use of 5α-androstane (alkyl)-3β,5,6β-triol in preparation of neuroprotective drugs |
US14/332,338 Continuation US9320743B2 (en) | 2010-07-09 | 2014-07-15 | Use of 5α-androstane-3β,5,6β-triol in preparation of neuroprotective drugs |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2012003802A1 true WO2012003802A1 (zh) | 2012-01-12 |
Family
ID=43070839
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2011/076967 WO2012003802A1 (zh) | 2010-07-09 | 2011-07-08 | 5α-雄甾(烷)-3β,5,6β-三醇在制备神经元保护药物中的应用 |
Country Status (21)
Country | Link |
---|---|
US (2) | US8809309B2 (zh) |
EP (1) | EP2591785B1 (zh) |
JP (1) | JP5681931B2 (zh) |
KR (1) | KR101463477B1 (zh) |
CN (1) | CN101884638B (zh) |
AU (1) | AU2011276800B2 (zh) |
BR (1) | BR112012031861B1 (zh) |
CA (1) | CA2802133C (zh) |
CY (1) | CY1118789T1 (zh) |
DK (1) | DK2591785T3 (zh) |
ES (1) | ES2620754T3 (zh) |
HR (1) | HRP20170418T1 (zh) |
HU (1) | HUE032159T2 (zh) |
LT (1) | LT2591785T (zh) |
PL (1) | PL2591785T3 (zh) |
PT (1) | PT2591785T (zh) |
RS (1) | RS55845B1 (zh) |
RU (1) | RU2541093C2 (zh) |
SG (1) | SG186135A1 (zh) |
SI (1) | SI2591785T1 (zh) |
WO (1) | WO2012003802A1 (zh) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015511587A (ja) * | 2012-03-08 | 2015-04-20 | グァンチョウ セルプロテック ファーマシューティカル カンパニー リミテッド | アンドロスタン−3β,5α,6β−トリオールの結晶形化合物及びその製造方法 |
JP2015514731A (ja) * | 2012-04-19 | 2015-05-21 | ユニベルシテ・ド・リエージュUniversite De Liege | 神経障害の処置における使用のためのエストロゲン成分 |
US9320743B2 (en) | 2010-07-09 | 2016-04-26 | Guangzhou Cellprotek Pharmaceutical Ltd. | Use of 5α-androstane-3β,5,6β-triol in preparation of neuroprotective drugs |
JP2016514729A (ja) * | 2013-03-28 | 2016-05-23 | グァンチョウ セルプロテック ファーマシューティカル カンパニー リミテッド | 2β,3α,5α−トリヒドロキシ−アンドロスタ−6−オン、その製造方法及びその用途 |
RU2672264C2 (ru) * | 2014-04-25 | 2018-11-13 | Гуанчжоу Селпротек Фармасьютикал Ко., Лтд. | Нейропротективные агенты и их применение |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101961311B (zh) * | 2010-09-21 | 2012-11-21 | 中山大学 | 一种5α-雄甾(烷)-3β,5,6β-三醇注射剂及其制备方法 |
CN113350359B (zh) * | 2017-12-29 | 2022-08-16 | 广州市赛普特医药科技股份有限公司 | 5α-雄甾-3β,5,6β-三醇在制备治疗出血性脑卒中药物中的应用 |
CN109985049B (zh) * | 2017-12-29 | 2022-02-22 | 广州市赛普特医药科技股份有限公司 | 5α-雄甾-3β,5,6β-三醇在制备治疗脑小血管病的药物中的应用 |
US11516173B1 (en) * | 2018-12-26 | 2022-11-29 | Snap Inc. | Message composition interface |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008155534A2 (en) * | 2007-06-20 | 2008-12-24 | Bionature E.A. Ltd. | Neurosteroid compounds |
CN101884638A (zh) * | 2010-07-09 | 2010-11-17 | 中山大学 | 5α-雄甾(烷)-3β,5,6β-三醇在制备神经元保护药物中的应用 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2191576A (en) * | 1936-11-21 | 1940-02-27 | Soc Of Chemical Ind | 3,5,6-trihydroxy androstane and pregnane compounds |
US6046185A (en) * | 1996-07-11 | 2000-04-04 | Inflazyme Pharmaceuticals Ltd. | 6,7-oxygenated steroids and uses related thereto |
US20030060425A1 (en) * | 1998-11-24 | 2003-03-27 | Ahlem Clarence N. | Immune modulation method using steroid compounds |
JP2007512344A (ja) * | 2003-11-24 | 2007-05-17 | メルク エンド カムパニー インコーポレーテッド | エストロゲン受容体調節剤 |
CN1557829A (zh) * | 2004-01-19 | 2004-12-29 | 复旦大学 | 化合物5α-雄甾烷-1α,3β,17β-三醇17-醋酸酯和衍生物,及其制备方法 |
US8354396B2 (en) * | 2006-11-17 | 2013-01-15 | Harbor Therapeutics, Inc. | Drug identification and treatment method |
CN101683348B (zh) * | 2008-09-23 | 2012-07-04 | 中山大学 | 胆甾烷-3β,5α,6β-三醇在制备神经元保护药物中的应用 |
CN101961311B (zh) * | 2010-09-21 | 2012-11-21 | 中山大学 | 一种5α-雄甾(烷)-3β,5,6β-三醇注射剂及其制备方法 |
-
2010
- 2010-07-09 CN CN2010102241733A patent/CN101884638B/zh active Active
-
2011
- 2011-07-08 AU AU2011276800A patent/AU2011276800B2/en active Active
- 2011-07-08 RS RS20170319A patent/RS55845B1/sr unknown
- 2011-07-08 EP EP11803155.8A patent/EP2591785B1/en active Active
- 2011-07-08 LT LTEP11803155.8T patent/LT2591785T/lt unknown
- 2011-07-08 KR KR1020127032524A patent/KR101463477B1/ko active IP Right Grant
- 2011-07-08 CA CA2802133A patent/CA2802133C/en active Active
- 2011-07-08 PL PL11803155T patent/PL2591785T3/pl unknown
- 2011-07-08 HU HUE11803155A patent/HUE032159T2/en unknown
- 2011-07-08 SG SG2012088688A patent/SG186135A1/en unknown
- 2011-07-08 WO PCT/CN2011/076967 patent/WO2012003802A1/zh active Application Filing
- 2011-07-08 ES ES11803155.8T patent/ES2620754T3/es active Active
- 2011-07-08 PT PT118031558T patent/PT2591785T/pt unknown
- 2011-07-08 JP JP2013516989A patent/JP5681931B2/ja active Active
- 2011-07-08 BR BR112012031861A patent/BR112012031861B1/pt active IP Right Grant
- 2011-07-08 RU RU2012151400/15A patent/RU2541093C2/ru active
- 2011-07-08 SI SI201131126A patent/SI2591785T1/sl unknown
- 2011-07-08 DK DK11803155.8T patent/DK2591785T3/en active
- 2011-07-08 US US13/805,436 patent/US8809309B2/en active Active
-
2014
- 2014-07-15 US US14/332,338 patent/US9320743B2/en active Active
-
2017
- 2017-03-14 HR HRP20170418TT patent/HRP20170418T1/hr unknown
- 2017-03-27 CY CY20171100375T patent/CY1118789T1/el unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008155534A2 (en) * | 2007-06-20 | 2008-12-24 | Bionature E.A. Ltd. | Neurosteroid compounds |
CN101884638A (zh) * | 2010-07-09 | 2010-11-17 | 中山大学 | 5α-雄甾(烷)-3β,5,6β-三醇在制备神经元保护药物中的应用 |
Non-Patent Citations (10)
Title |
---|
BREWER G.J.: "Isolation and culture of aldut rat hippocampal neurons", J. NEUROSCI. METH., vol. 71, 1997, pages 143 - 155 |
CELIK M. ET AL.: "Erythropoietin prevents motor neuron apopotosis and neurologic disability in experimental spinal cord ischemic injury", PROC NATL ACAD SCI USA, vol. 99, 2002, pages 2258 - 2263 |
CHEN, JINGBO ET AL.: "Studies on the Hemisuccination of Hydroxysterols", CHINESE JOURNAL OF SYNTHETIC CHEMISTRY, vol. 8, no. 5, 2000, pages 466 - 468 * |
JOHNSON SH; KRAIMER J.M.; GRAEBER G.M.: "Effects of flunarizine on neurological recovery and spinal cord blood flow in experimental spinal cord ischemia in rabbits", STROKE, vol. 24, 1993, pages 1547 - 1553 |
LEE M.M.; HSEIH M.T.: "Magnolol protects cortical neuronal cells from chemical hypoxia in rats", NEUROREPORT, vol. 9, 1998, pages 3451 - 3456 |
LI, QUN ET AL.: "Pregnane-3p,5a,6p-triol for Inhibiting Hypopotassemia Induced Apoptosis of Cerebellar Granule Neurons", CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY, vol. 15, no. 5, October 2001 (2001-10-01), pages 337 - 341 * |
LONGA E.Z.; WEINSTEIN P.R.; CARLSON S.; CUMMINS R.: "Reversible middle cerebral artery occlusion without craniectomy in rats", STROKE, vol. 20, no. 1, 1989, pages 84 - 91 |
SANG H.; CAO L.; QIU P.; XIONG L.; WANG R.; YAN G.: "Isoflurane produces delayed preconditioning against spinal cord ischemic injury via release of free radicals in rabbits", ANESTHESIOLOGY, vol. 105, 2006, pages 953 - 960 |
See also references of EP2591785A4 * |
WANG Q.; PENG Y.; CHEN S.; GOU X.; HU B.; DU J.; LU Y.; XIONG L.: "Pretreatment with electroacupuncture induces rapid tolerance to focal cerebral ischemia through regulation of endocannabinoid system", STROKE, vol. 40, no. 6, 2009, pages 2157 - 2164 |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9320743B2 (en) | 2010-07-09 | 2016-04-26 | Guangzhou Cellprotek Pharmaceutical Ltd. | Use of 5α-androstane-3β,5,6β-triol in preparation of neuroprotective drugs |
EP3112374A1 (en) * | 2012-03-08 | 2017-01-04 | Guangzhou Celprotek Pharmaceutical Co. Ltd. | Crystalline forms of 5alpha-androstane-3beta,5,6beta-triol and preparation methods therefor |
EP2889303A4 (en) * | 2012-03-08 | 2016-02-17 | Guangzhou Celprotek Pharmaceutical Co Ltd | CONNECTION OF A CRYSTAL FORM OF ANDROSTA-3B, 5A, 6B-TRIOL AND METHOD FOR THE PRODUCTION THEREOF |
JP2015511587A (ja) * | 2012-03-08 | 2015-04-20 | グァンチョウ セルプロテック ファーマシューティカル カンパニー リミテッド | アンドロスタン−3β,5α,6β−トリオールの結晶形化合物及びその製造方法 |
RU2608894C2 (ru) * | 2012-03-08 | 2017-01-26 | Гуанчжоу Селлпротек Фармасьютикал Ко., Лтд. | КРИСТАЛЛИЧЕСКИЕ ФОРМЫ 5α-АНДРОСТАН-3β,5,6β-ТРИОЛА И СПОСОБЫ ИХ ПОЛУЧЕНИЯ |
US9688716B2 (en) | 2012-03-08 | 2017-06-27 | Guangzhou Cellprotek Pharmaceutical Co., Ltd. | Crystalline forms of 5α-androstane-3β,5,6β-triol and preparation methods therefor |
US9944673B2 (en) | 2012-03-08 | 2018-04-17 | Guangzhou Cellprotek Pharmaceutical Co., Ltd. | Crystalline forms of 5α-androstane-3β,5,6β-triol and preparation methods therefor |
US9944672B2 (en) | 2012-03-08 | 2018-04-17 | Guangzhou Cellprotek Pharmaceutical Co., Ltd. | Crystalline forms of 5α-androstane-3β,5,6β-triol and preparation methods therefor |
JP2015514731A (ja) * | 2012-04-19 | 2015-05-21 | ユニベルシテ・ド・リエージュUniversite De Liege | 神経障害の処置における使用のためのエストロゲン成分 |
JP2016514729A (ja) * | 2013-03-28 | 2016-05-23 | グァンチョウ セルプロテック ファーマシューティカル カンパニー リミテッド | 2β,3α,5α−トリヒドロキシ−アンドロスタ−6−オン、その製造方法及びその用途 |
EP2980096A4 (en) * | 2013-03-28 | 2016-11-16 | Guangzhou Cellprotek Pharm Co Ltd | 2,3,5-trihydroxy-androst-6-one, as well as method of preparation and use thereof |
KR101771192B1 (ko) | 2013-03-28 | 2017-08-24 | 광저우 셀프로텍 파마슈티컬 컴퍼니 리미티드 | 2β,3α,5α-트리하이드록시-안드로스트-6-원 및 이의 제조 방법 및 이의 용도 |
RU2672264C2 (ru) * | 2014-04-25 | 2018-11-13 | Гуанчжоу Селпротек Фармасьютикал Ко., Лтд. | Нейропротективные агенты и их применение |
US10357500B2 (en) | 2014-04-25 | 2019-07-23 | Guangzhou Cellprotek Pharmaceutical Co., Ltd. | Neuro-protective agents and uses thereof |
Also Published As
Publication number | Publication date |
---|---|
US9320743B2 (en) | 2016-04-26 |
CN101884638B (zh) | 2011-11-09 |
SG186135A1 (en) | 2013-01-30 |
EP2591785A1 (en) | 2013-05-15 |
EP2591785B1 (en) | 2017-01-04 |
KR20130038286A (ko) | 2013-04-17 |
SI2591785T1 (sl) | 2017-07-31 |
ES2620754T3 (es) | 2017-06-29 |
AU2011276800B2 (en) | 2013-11-21 |
RU2012151400A (ru) | 2014-08-20 |
AU2011276800A9 (en) | 2013-11-21 |
HUE032159T2 (en) | 2017-09-28 |
PL2591785T3 (pl) | 2017-08-31 |
US20140329790A1 (en) | 2014-11-06 |
AU2011276800A1 (en) | 2013-01-10 |
US8809309B2 (en) | 2014-08-19 |
JP5681931B2 (ja) | 2015-03-11 |
CA2802133A1 (en) | 2012-01-12 |
HRP20170418T1 (hr) | 2017-06-16 |
US20130157993A1 (en) | 2013-06-20 |
EP2591785A4 (en) | 2013-12-11 |
LT2591785T (lt) | 2017-06-26 |
BR112012031861B1 (pt) | 2020-02-04 |
RS55845B1 (sr) | 2017-08-31 |
PT2591785T (pt) | 2017-04-04 |
JP2013529657A (ja) | 2013-07-22 |
BR112012031861A2 (pt) | 2016-11-08 |
CA2802133C (en) | 2014-01-14 |
DK2591785T3 (en) | 2017-03-27 |
KR101463477B1 (ko) | 2014-11-19 |
CN101884638A (zh) | 2010-11-17 |
RU2541093C2 (ru) | 2015-02-10 |
CY1118789T1 (el) | 2018-03-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2012003802A1 (zh) | 5α-雄甾(烷)-3β,5,6β-三醇在制备神经元保护药物中的应用 | |
Wang et al. | Autophagy in ischemic stroke | |
CN104382848B (zh) | 一种他克莫司混悬型滴眼液及其制备方法 | |
JPH08505602A (ja) | Δ5−アンドロステンでのアルツハイマー病の治療および免疫系の調節 | |
Meyer et al. | The progesterone receptor agonist Nestorone holds back proinflammatory mediators and neuropathology in the wobbler mouse model of motoneuron degeneration | |
CN101134042A (zh) | 七叶皂苷的药物组合物及其制备方法和其用途 | |
US11065263B2 (en) | Sterol composition in pumpkin seed oil and application thereof, and drug for treating benign prostatic hyperplasia | |
WO2024007684A1 (zh) | 一种新型Nrf2激活剂及用途 | |
EP1307205B1 (en) | Use of 7alpha-hydroxy-estradiol, 7alpha-hydroxy-dehydroepiandrosterone and 7alpha-hydroxy-pregnenolone derivatives for treating acute cellular degeneration | |
WO2005079792A1 (ja) | 重症糖尿病網膜症の予防又は治療剤 | |
ULRICHSEN | Alterations in serotonin receptor subtypes in ethanol-dependent rats | |
AU2001233856A1 (en) | Use of 7Alpha-hydroxy-estradiol, 7Alpha-hydroxy-dehydroepiandrosterone and 7alpha-hydroxy-pregnenolone derivatives for treating acute cellular degeneration | |
AU2001267709A1 (en) | 7-hydroxyepiandrosterone having neuroprotective activity | |
WO2002000225A1 (en) | 7-hydroxyepiandrosterone having neuroprotective activity | |
US20140378426A1 (en) | Methods and compositions for enhancing visual function | |
WO2020262497A1 (ja) | ニコチンアミドモノヌクレオチド(nmn)およびニコチンアミドリボシド(nr)の新規用途 | |
EP4289426A1 (en) | Application of riluzole- and borneol-containing composition in preparation of medication for treating cerebrovascular diseases | |
JP2003514858A (ja) | リルゾールおよびギャバペンチンの組み合わせ剤ならびに医薬としてのその使用 | |
JP4848117B2 (ja) | 副腎脳白質ジストロフィーを予防および治療するためのリルゾールもしくはその塩の使用 | |
CN115068466A (zh) | 7,4′二羟基-8-甲氧基高异黄烷防治帕金森病的应用 | |
KR20010040671A (ko) | 소뇌 기능장애 예방 또는 치료를 위한2-아미노-6-트리플루오로메톡시-벤조티아졸의 용도 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 11803155 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10696/DELNP/2012 Country of ref document: IN |
|
ENP | Entry into the national phase |
Ref document number: 2802133 Country of ref document: CA |
|
ENP | Entry into the national phase |
Ref document number: 20127032524 Country of ref document: KR Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2013516989 Country of ref document: JP Kind code of ref document: A |
|
REEP | Request for entry into the european phase |
Ref document number: 2011803155 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2011803155 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 13805436 Country of ref document: US |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2011276800 Country of ref document: AU Date of ref document: 20110708 Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2012151400 Country of ref document: RU Kind code of ref document: A |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112012031861 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 112012031861 Country of ref document: BR Kind code of ref document: A2 Effective date: 20121213 |
|
WWE | Wipo information: entry into national phase |
Ref document number: P-2017/0319 Country of ref document: RS |