WO2010117170A2 - 화상 손상의 치료 또는 예방용 약학 조성물 - Google Patents
화상 손상의 치료 또는 예방용 약학 조성물 Download PDFInfo
- Publication number
- WO2010117170A2 WO2010117170A2 PCT/KR2010/002070 KR2010002070W WO2010117170A2 WO 2010117170 A2 WO2010117170 A2 WO 2010117170A2 KR 2010002070 W KR2010002070 W KR 2010002070W WO 2010117170 A2 WO2010117170 A2 WO 2010117170A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tetrafluoro
- benzylamino
- benzoic acid
- trifluoromethyl
- hydroxy
- Prior art date
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Images
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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
Definitions
- the present invention relates to pharmaceutical compositions useful for the treatment or prevention of burn injury and methods of treating or preventing burn damage.
- Burns are mainly caused by accidents, and may be classified into burns by heat, burns by electric current, burns by chemical substances, burns by radiation, and the like, depending on the cause.
- the severity of the burn is divided into 1st, 2nd, 3rd, and 4th degree burns, depending on the width, depth of the burn, the temperature and contact time of the object that caused the burn, and the condition of the skin. And require hospital treatment.
- First-degree burns are accompanied by pain such as reddening of the skin and tingling. It causes damage to the epidermis, the outermost layer of the skin, and swells with pain and erythema. The symptoms disappear in a few days, but there may be a slight fallout and pigmentation in place. No scars remain after recovery. Sun burn is an example of the most common first degree burns.
- Second-degree burns affect both the epidermis and the dermis, causing erythema, pain, edema, and blistering within 24 hours of the accident. This burn also affects the gland and pores. Awakening is burning and painful. When the blisters burst, they show erosions and a large amount of secretion. Special care should be taken when the burned area reaches more than about 15% of the body surface area. Heals within a few weeks, but pigmentation and discoloration often remain in place. The secondary infection causes more local symptoms and lasts longer.
- Third-degree burns affect the epidermis, dermis, and hypodermis, resulting in darkening or translucent whitening of the skin and clotting of blood vessels just below the surface of the skin.
- the burn may become numb, but the patient feels extreme pain, necrosis of the skin tissue and structure, which takes a lot of time to heal and scars. Two weeks after the accident, the scab peels off and the ulcer surface appears.
- There is a lot of secretion and easy to bleed but gradually new tissue develops, the epidermis regenerates, leaving scars and healing.
- healing may be delayed and the surface of the scar may become irregular, resulting in keloids or deformations or movement disorders.
- Special care should be taken when the burned area covers more than 10% of the body surface area.
- a fourth degree burn is a case where the burned area tissue is carbonized and turned black, and a fat burn, ligament, fascia, muscle, and bone tissue located under the skin layer is burned. It occurs mainly in high-voltage electrical burns, and can sometimes occur when fungal infections occur in deep 2-3 degree burns. If the burn range is more than 20%, a systemic physical reaction may occur, such as hypotension, shock, acute renal failure due to excessive fluid loss, and later wound infection, pneumonia, sepsis, multiple organ failure syndrome, etc. This happens too.
- the present invention is to provide a pharmaceutical composition useful for the treatment or prevention of burn injury, and the medical use of such a pharmaceutical composition.
- the present invention comprises a tetrafluorobenzyl derivative represented by the following formula (1) or a pharmaceutically acceptable salt or solvate thereof as an active ingredient treatment of burn injury Or it provides a preventive pharmaceutical composition.
- R 1 , R 2 and R 3 are independently of each other hydrogen or halogen
- R 4 is hydroxy, alkyl, alkoxy, halogen, alkoxy substituted by halogen, alkanoyloxy or nitro;
- R 5 is carboxylic acid, carboxylic acid substituted by alkyl group, carboxyamide, sulfonic acid, halogen or nitro.
- the present invention provides a pharmaceutical composition and a pharmaceutical use of the above tetrafluorobenzyl derivatives and pharmaceutically acceptable salts or solvates thereof for the treatment or prevention of burn injury.
- alkyl is preferably alkyl having 1 to 5 carbon atoms, and more preferably alkyl having 1 or 3 carbon atoms.
- the alkyl is preferably methyl, ethyl, propyl, isopropyl, butyl, secondary-butyl and tert-butyl, but is not limited thereto.
- alkoxy is C1-C5 alkoxy, and it is more preferable that it is C1-C3 alkoxy.
- Halogen is preferably, but not limited to, fluorine, chlorine, bromine and iodine.
- Alkanoyl is preferably an alkanoyl having 2 to 10 carbon atoms, and more preferably an alkanoyl having 2 or 5 carbon atoms. Specifically, the alkanoyl is preferably ethanoyl, propanoyl, and cyclohexancarbonyl, but is not limited thereto.
- Alkanoyloxy is preferably an alkanoyloxy having 1 to 4 carbon atoms.
- Preferred examples of the tetrafluorobenzyl derivative represented by Formula 1 include 2-hydroxy-5- (2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino) benzoic acid (2-Hydroxy -5- (2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino) -benzoic acid) (hereinafter referred to as '2-hydroxy-TTBA'), 2-nitro-5- (2,3,5 , 6-tetrafluoro-4-trifluoromethyl-benzylamino) -benzoic acid (2-Nitro-5- (2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino) -benzoic acid), 2- Chloro-5- (2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino) -benzoic acid (2-Chloro-5- (2,3,5,6-tetrafluoro-4-triflu
- a burn generally refers to a phenomenon in which skin cells are destroyed or necrosed by heat, for example, a fire burn by fire, a hot bath burn by hot liquid (water, oil, etc.), a hot object (electric Iron, rice cooker, etc.), such as contact images, strong acids, chemical images of strong alkalis, and other sun-rays of intense ultraviolet rays in the summer or radiation and X-rays of radiation images, but is not limited thereto.
- the image of the present invention may also be an image of 1 degree, 2 degrees, 3 degrees or 4 degrees.
- Tetrafluorobenzyl derivatives of the formula (1) and their pharmaceutically acceptable salts or solvates according to the invention may be used for the treatment or prevention of these burn injuries, but the specific type of burn and the degree of burn (severity) It is not limited.
- Tetrafluorobenzyl derivatives or pharmaceutically acceptable salts thereof of the present invention may be prepared according to the preparation methods disclosed in US Pat. No. 6,927,303, but the present invention is not limited to these preparation methods.
- some compounds may be administered in the form of pharmaceutically acceptable salts.
- “Pharmaceutically acceptable salts” refer to salts that are made from non-toxic or less acid or base. If the compounds of the present invention are relatively acidic, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base and a suitable inert solvent. Pharmaceutically acceptable base addition salts include, but are not limited to, salts consisting of lithium, sodium, potassium, calcium, ammonium, magnesium or organic amino. When the compounds of the present invention are relatively basic, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid and a suitable inert solvent.
- Pharmaceutically acceptable acid addition salts include propionic acid, isobutyl acid, oxalic acid, malic acid, malonic acid, benzoic acid, succinic acid, suberic, fumaric acid, manderic acid, phthalic acid, benzenesulfonic acid, p-torylsul Phonic acid, citric acid, tartaric acid, methanesulfonic acid, hydrochloric acid, bromic acid, nitric acid, carbonic acid, monohydrogencarbonic acid, phosphoric acid, monohydrogenphosphate, dihydrogen phosphate, sulfuric acid, monohydrosulfuric acid, hydrogen iodide, phosphorous acid Salts formed of, and the like, but are not limited thereto. It also includes, but is not limited to, salts of amino acids such as arginate and analogs of organic acids such as glucuronic or galactunoric acids.
- the present invention also includes solvates, in particular hydrate forms, of the compounds, as well as solvated forms (eg hydrates) as well as unsolvated forms.
- the compounds of the present invention may exist in crystalline or amorphous form, and all such physical forms are included in the scope of the present invention.
- the compounds of the present invention may have asymmetric carbon atoms or double bonds, which are optical centers, depending on the compound, so there may be racemates, enantiomers, diastereomers, geometric isomers, etc., and these are also included in the scope of the present invention. do.
- the present invention also provides a pharmaceutical composition
- a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable excipient or additive.
- the compounds of the present invention or pharmaceutically acceptable salts / solvates thereof may be administered alone or in admixture with any convenient carrier, excipient, etc., and such dosage forms may be single or repeated dose formulations.
- the pharmaceutical composition of the present invention may be a solid preparation or a liquid preparation.
- Solid preparations include, but are not limited to, powders, granules, tablets, capsules, suppositories, and the like.
- Solid form preparations may include, but are not limited to, excipients, flavors, binders, preservatives, disintegrants, lubricants, fillers and the like.
- Liquid formulations include, but are not limited to, solutions such as water, propylene glycol solutions, suspensions, emulsions, and the like, and may be prepared by adding suitable colorants, flavors, stabilizers, viscosity agents, and the like.
- powders may be prepared by simply mixing the tetrafluoro benzyl derivative compounds of the present invention with suitable pharmaceutically acceptable excipients such as lactose, starch, microcrystalline cellulose.
- the granulating agent is a tetrafluoro benzyl derivative of the present invention; Pharmaceutically acceptable excipients; And a suitable pharmaceutically acceptable binder such as polyvinylpyrrolidone and hydroxypropyl cellulose, and then prepared by using a wet granulation method using a solvent such as water, ethanol, isopropanol, or a dry granulation method using a compressive force.
- Tablets may also be prepared by mixing the granules with a suitable pharmaceutically acceptable glidant such as magnesium stearate and then tableting using a tableting machine.
- compositions of the present invention may be administered orally, by injection (eg, intramuscular injection, intraperitoneal injection, intravenous injection, infusion, subcutaneous injection, implant), inhalants, nasal injections, depending on the condition and condition of the individual to be treated. It may be administered as a vaginal agent, rectal agent, sublingual agent, transdermal agent, topical agent, and the like, but is not limited thereto. It may be formulated into a suitable dosage unit dosage form comprising a pharmaceutically acceptable carrier, excipient, vehicle, conventionally used and nontoxic, depending on the route of administration. Depot formulations capable of continually releasing the drug for a period of time are also within the scope of the present invention.
- the present invention also provides a method of treating or preventing burn injury comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula 1, a pharmaceutically acceptable salt or solvate thereof. to provide.
- a compound of the present invention or a pharmaceutically acceptable salt or solvate thereof may be administered from about 0.1 mg / kg to about 1000 mg / kg daily, from about 2.5 mg / kg to about A daily dose of 500 mg / kg is preferred.
- the dosage may vary depending on the condition of the patient (age, sex, weight, etc.), the severity of the condition being treated, the compound used and the like. If desired, the total daily dose may be divided for convenience and divided several times throughout the day.
- the present invention provides a pharmaceutical composition useful for the treatment or prevention of burn injury, comprising the compound of Formula 1, a pharmaceutically acceptable salt or solvate thereof as an active ingredient.
- the present invention also provides the use of the compound of formula 1, a pharmaceutically acceptable salt or solvate thereof for the treatment or prevention of burn injury.
- the invention also provides a method of treating or preventing burn injury comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula 1, a pharmaceutically acceptable salt or solvate thereof. to provide.
- Figure 2 is a photograph of the back skin observed on day 7 after the burn injury. When 2-hydroxy-TTBA is administered, burn damage can be recovered relatively quickly.
- Figure 3 is a photograph of the epithelial state of the analysis tissue site observed through hematoxylin eosin staining.
- FIG. 4 is a microscopic photograph of the whole skin tissue state of a zone of stasis or zone of tissue injury through hematoxylin eosin staining at 10-fold magnification.
- FIG. 5 shows microscopic images of living cells of zoned tissue (zone of stasis or zone of tissue injury) skin tissue at 10-fold magnification through Cresyl violet staining.
- FIG. 6 shows the results of microscopic observation of collagen and muscle fibers of stagnation skin tissue through Masson's trichrom staining.
- Table 1 Groups Normal control Burn control Vehicle administration group 2-hydroxy-TTBA Administration group Total experimental animals 6 9 8 7 Number of animals killed N / A 2 0 0
- Lactate dehydrogenase is an enzyme distributed in almost all tissues that catalyzes the reversible conversion between pyruvic acid and lactic acid. When tissues and cells are destroyed, it is said to flow into the blood and raise the LDH in the blood. Therefore, the amount of LDH in each group was examined from serum except for hemolytic specimens that might interfere with the test. The results are shown in FIG.
- the LDH of the burn control group was increased by about twice as compared to the normal control group, and LDH was significantly decreased in the 2-hydroxy-TTBA-administered group compared to the burn control group.
- FIG. 2 is a photograph of the back skin observed on day 7 after the burn injury.
- Whole skin burns were induced into four 10 ⁇ 20 mm rectangular shapes using a brass comb preheated on both sides of the rats.
- Two hours after induction four coagulation zones (zone of coagulation or zone of tissue necrosis) and three zones of tissue (zone of stasis or zone of tissue injury) were developed.
- Coagulation zones are irreversible cell damage areas that cannot be recovered over time, and stagnation zones are areas where cell necrosis occurs without special treatment within 24-48 hours, causing ischemia due to continuous fibrin deposition, vasoconstriction, and blood clots. It is a part to do.
- Figure 3 is a result of comparing the state of the epithelial layer by staining hematoxylin eosin for each tissue analysis group.
- normal epithelial layers parts indicated by arrows
- normal epithelial cells were not observed except for inflammatory cells by forming a crust in the burn control group.
- the regeneration of the epithelial layer was progressing. Hyperplasia of epidermis was observed even above the normal epithelial thickness.
- Figure 4 is a microscopic observation of the state of skin full-thickness tissue through the haematoxylin eosin staining at 10x magnification.
- the burn control group the epithelial layer, dermis layer, subcutaneous tissue and muscle layer were damaged throughout the whole layer, and the inflammatory cells were infiltrated under the epidermis, and a large number of inflammatory cells exist between the subcutaneous tissue and the muscle.
- the vehicle-administered group did not form crust-like crusts, but a significant amount of inflammatory cells were observed throughout the skin and subcutaneous tissues, with a large number of inflammatory cells still infiltrating under the regenerating epithelial layer.
- the 2-hydroxy-TTBA group the infiltration of inflammatory cells was significantly suppressed except for the muscle cells and subcutaneous tissue layer.
- the epidermal regeneration as well as the hair follicle, sebaceous gland, and muscle layer showed a protective effect.
- FIG. 5 is a photomicrograph of living cells of stagnant skin tissue through 10-fold magnification through Cresyl violet staining. Hair follicles were rarely observed in the burn-controlled and vehicle-treated groups, while large amounts of inflammatory cells were observed throughout the entire skin layer, whereas live hair follicles and epithelial layers were observed in the 2-hydroxy-TTBA-treated group and relatively few inflammatory cells were observed. .
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Abstract
Description
그룹 (Groups) | 정상대조군 | 화상대조군 | Vehicle 투여군 | 2-hydroxy-TTBA 투여군 |
총 실험 동물 수 | 6 | 9 | 8 | 7 |
사망 동물 수 | 해당 없음(N/A) | 2 | 0 | 0 |
그룹 (Groups) | 화상대조군 | 비히클 투여군 | 2-hydroxy-TTBA 투여군 |
Eschar formation (%) | 92.857 | 17.857 | 3.571 |
Wound epidermis formation (%) | 10.714 | 32.143 | 71.429 |
Claims (6)
- 제 1항에 있어서, 상기 테트라플루오로벤질 유도체는 2-하이드록시-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산, 2-니트로-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산, 2-클로로-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산, 2-브로모-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산, 2-하이드록시-5-(2,3,5,6-테트라플루오로-4-메틸벤질아미노)-벤조산, 2-메틸-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산, 2-메톡시-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산 및 5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-2-트리플루오로메톡시 벤조산으로 이루어진 군으로부터 선택된 어느 하나 이상인 것을 특징으로 하는 약학 조성물.
- 제 2항에 있어서, 상기 테트라플루오로벤질 유도체는 2-하이드록시-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노) 벤조산인 것을 특징으로 하는 약학 조성물.
- 하기 화학식 1로 표시되는 테트라플루오로벤질 유도체, 또는 이들의 약학적으로 허용 가능한 염 또는 용매화물의 치료학적으로 유효한 양을 화상 손상의 치료 또는 예방이 필요한 개체에게 투여하는 것을 특징으로 하는 화상 손상의 치료 또는 예방 방법:<화학식 1>상기 화학식 1에서, R1, R2 및 R3는 서로 독립적으로 수소 또는 할로겐이고; R4는 하이드록시, 알킬, 알콕시, 할로겐, 할로겐으로 치환된 알콕시, 알카노일옥시 또는 니트로이며; R5는 카르복시산, 탄소수 1 내지 4의 알킬기로 치환된 카르복시산, 카르복시아미드, 설폰산, 할로겐 또는 니트로임.
- 제 4항에 있어서, 상기 테트라플루오로벤질 유도체는 2-하이드록시-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산, 2-니트로-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산, 2-클로로-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산, 2-브로모-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산, 2-하이드록시-5-(2,3,5,6-테트라플루오로-4-메틸벤질아미노)-벤조산, 2-메틸-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산, 2-메톡시-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-벤조산 및 5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노)-2-트리플루오로메톡시 벤조산으로 이루어진 군으로부터 선택된 어느 하나 이상인 것을 특징으로 하는 방법.
- 제 5항에 있어서, 상기 테트라플루오로벤질 유도체는 2-하이드록시-5-(2,3,5,6-테트라플루오로-4-트리플루오로메틸-벤질아미노) 벤조산인 것을 특징으로 하는 방법.
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2010235334A AU2010235334A1 (en) | 2009-04-06 | 2010-04-05 | Pharmaceutical composition for treating or preventing burn injuries |
EP10761831.6A EP2417972B1 (en) | 2009-04-06 | 2010-04-05 | Pharmaceutical composition for treating or preventing burn injuries |
ES10761831.6T ES2633691T3 (es) | 2009-04-06 | 2010-04-05 | Composición farmacéutica para tratar o prevenir lesiones por quemaduras |
CN201080021109.3A CN102421430B (zh) | 2009-04-06 | 2010-04-05 | 用于预防或治疗烧伤的药物组合物 |
DK10761831.6T DK2417972T3 (en) | 2009-04-06 | 2010-04-05 | PHARMACEUTICAL COMPOSITION FOR TREATMENT OR PREVENTION OF COMBUSTION DAMAGE |
CA2757466A CA2757466C (en) | 2009-04-06 | 2010-04-05 | Pharmaceutical composition comprising tetrafluorobenzyl derivatives for treating skin burn injuries |
JP2012504572A JP5734953B2 (ja) | 2009-04-06 | 2010-04-05 | やけどによる損傷の治療または予防用薬学的組成物 |
US13/263,017 US20120289602A1 (en) | 2009-04-06 | 2010-04-05 | Pharmaceutical composition for treating or preventing burn injuries |
AU2016219606A AU2016219606B2 (en) | 2009-04-06 | 2016-08-24 | Pharmaceutical composition for treating or preventing burn injuries |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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KR20090029233 | 2009-04-06 | ||
KR10-2009-0029233 | 2009-04-06 |
Publications (2)
Publication Number | Publication Date |
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WO2010117170A2 true WO2010117170A2 (ko) | 2010-10-14 |
WO2010117170A3 WO2010117170A3 (ko) | 2011-03-10 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/KR2010/002070 WO2010117170A2 (ko) | 2009-04-06 | 2010-04-05 | 화상 손상의 치료 또는 예방용 약학 조성물 |
Country Status (10)
Country | Link |
---|---|
US (1) | US20120289602A1 (ko) |
EP (1) | EP2417972B1 (ko) |
JP (1) | JP5734953B2 (ko) |
KR (1) | KR101136513B1 (ko) |
CN (1) | CN102421430B (ko) |
AU (2) | AU2010235334A1 (ko) |
CA (1) | CA2757466C (ko) |
DK (1) | DK2417972T3 (ko) |
ES (1) | ES2633691T3 (ko) |
WO (1) | WO2010117170A2 (ko) |
Families Citing this family (2)
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CN104042598B (zh) * | 2013-03-15 | 2018-01-16 | 江苏先声药业有限公司 | 一种药物组合物及其在制备治疗烫伤药物中的应用 |
CN104055758B (zh) * | 2013-03-18 | 2018-05-08 | 江苏先声药业有限公司 | 一种药物组合物及其在制备治疗烫伤药物中的用途 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US6927303B2 (en) | 2002-06-19 | 2005-08-09 | Neurotech Co., Ltd. | Tetrafluorobenzyl derivatives and pharmaceutical composition for preventing and treating acute and chronic neurodegenerative diseases in central nervous system containing the same |
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US5013540A (en) * | 1989-11-30 | 1991-05-07 | Board Of Regents, The University Of Texas System | Using NMDA receptor antagonists to reduce damage due to laser treatment |
ZA200108038B (en) * | 2000-10-02 | 2003-04-01 | Pfizer Prod Inc | Prophylactic use of n-methyl-d-asparrate (NMDA) antagonists. |
EP1674087A1 (en) * | 2000-10-02 | 2006-06-28 | Pfizer Products Inc. | Prophylactic use of n-methyl-d-aspartate (NMDA) antagonists |
GB0108606D0 (en) * | 2001-04-05 | 2001-05-23 | Novartis Ag | Organic compounds |
CN100491374C (zh) * | 2002-08-02 | 2009-05-27 | Ab科学公司 | 2-(3-氨基芳基)氨基-4-芳基-噻唑及其作为c-kit抑制剂的应用 |
EP1402888A1 (en) * | 2002-09-18 | 2004-03-31 | Jerini AG | The use of substituted carbocyclic compounds as rotamases inhibitors |
KR100522188B1 (ko) * | 2003-01-20 | 2005-10-18 | 주식회사 뉴로테크 | 뉴로트로핀에 의해 유도되는 세포괴사 억제 방법 |
WO2005013885A2 (en) * | 2003-08-07 | 2005-02-17 | Healor Ltd. | Pharmaceutical compositions and methods for accelerating wound healing |
WO2005115385A1 (en) * | 2004-05-24 | 2005-12-08 | Ab Science | Use of c-kit inhibitors for treating acne |
WO2006126825A1 (en) * | 2005-05-23 | 2006-11-30 | Choongwae Pharma Corporation | Composition comprising tetrafluorobenzyl derivatives or salts of thereof for injection |
-
2010
- 2010-04-05 AU AU2010235334A patent/AU2010235334A1/en not_active Abandoned
- 2010-04-05 US US13/263,017 patent/US20120289602A1/en not_active Abandoned
- 2010-04-05 ES ES10761831.6T patent/ES2633691T3/es active Active
- 2010-04-05 CA CA2757466A patent/CA2757466C/en active Active
- 2010-04-05 CN CN201080021109.3A patent/CN102421430B/zh active Active
- 2010-04-05 KR KR1020100030722A patent/KR101136513B1/ko active IP Right Grant
- 2010-04-05 WO PCT/KR2010/002070 patent/WO2010117170A2/ko active Application Filing
- 2010-04-05 EP EP10761831.6A patent/EP2417972B1/en active Active
- 2010-04-05 DK DK10761831.6T patent/DK2417972T3/en active
- 2010-04-05 JP JP2012504572A patent/JP5734953B2/ja active Active
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2016
- 2016-08-24 AU AU2016219606A patent/AU2016219606B2/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6927303B2 (en) | 2002-06-19 | 2005-08-09 | Neurotech Co., Ltd. | Tetrafluorobenzyl derivatives and pharmaceutical composition for preventing and treating acute and chronic neurodegenerative diseases in central nervous system containing the same |
Also Published As
Publication number | Publication date |
---|---|
KR101136513B1 (ko) | 2012-04-17 |
EP2417972A4 (en) | 2012-08-22 |
US20120289602A1 (en) | 2012-11-15 |
ES2633691T3 (es) | 2017-09-22 |
CA2757466C (en) | 2018-07-31 |
EP2417972A2 (en) | 2012-02-15 |
DK2417972T3 (en) | 2017-08-14 |
JP5734953B2 (ja) | 2015-06-17 |
AU2010235334A1 (en) | 2011-11-24 |
AU2016219606B2 (en) | 2018-03-15 |
WO2010117170A3 (ko) | 2011-03-10 |
CN102421430B (zh) | 2014-06-25 |
CN102421430A (zh) | 2012-04-18 |
EP2417972B1 (en) | 2017-06-14 |
KR20100111245A (ko) | 2010-10-14 |
CA2757466A1 (en) | 2010-10-14 |
JP2012522834A (ja) | 2012-09-27 |
AU2016219606A1 (en) | 2016-09-15 |
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