CN102548547B - 在治疗各种疾病中最佳使用的n,n’-二氨基二苯砜的可溶性药物制剂 - Google Patents
在治疗各种疾病中最佳使用的n,n’-二氨基二苯砜的可溶性药物制剂 Download PDFInfo
- Publication number
- CN102548547B CN102548547B CN200980158985.8A CN200980158985A CN102548547B CN 102548547 B CN102548547 B CN 102548547B CN 200980158985 A CN200980158985 A CN 200980158985A CN 102548547 B CN102548547 B CN 102548547B
- Authority
- CN
- China
- Prior art keywords
- dadps
- solution
- diaminodiphenyl sulphone
- soluble pharmaceutical
- medicine
- 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.)
- Active
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
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
- A61K31/10—Sulfides; Sulfoxides; Sulfones
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
-
- 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
- A61K31/13—Amines
- A61K31/145—Amines having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Anesthesiology (AREA)
- Psychology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明目的是证实是可制备N,N’-二氨基二苯砜的可溶性药物制剂,其用于开发制备针对下述疾病的理想药物,所述疾病选自脑梗死、癫痫、外伤性脊髓损伤、颅脑外伤、麻风病、卡氏肺孢子虫感染以及任何需要化合物快速和完全吸收的病症。作为本申请的代表性实例,评价溶解N,N’-二氨基二苯砜作为大鼠急性脑梗死模型中的神经保护剂。在研究中,N,N’-二氨基二苯砜显示出对脑损伤的有效抑制作用,并且在动物身上没有显示出不良反应。报告还显示以此方式制备的可溶性药物形式在口服给药30分钟后以及在静脉内途径立即产生峰血液水平。
Description
技术领域
本发明涉及药物生产工业、更具体地涉及针对各种疾病制备药物的工业。
背景技术
麻风病和卡氏肺孢子虫(pneurmocystis carinii)感染的化学疗法是用N,N’-二氨基二苯砜药丸的给药来进行的。N,N’-二氨基二苯砜在溶液中的药物制剂作为药物引起了技术问题,这是由于在水介质中N,N’-二氨基二苯砜的低溶解度,因此,在本发明中,使用与在人类药物安全使用相容的共溶剂,新制剂以允许高达200mg砜/3mL的增溶作用呈现。
已经被报道以90%的比例使用表面活性剂化合物吐温-80[Helton DR,Osborne DW,Pierson SK,Buonarati MH,Bethem RA.,Pharmacokinetic profiles in rats after intravenous,oral,or dermal administration of dapsone,Drug Metabolism and Disposition 28:925-929(2000)]的N,N’-二氨基二苯砜解决方案,但存在严重的缺点,即在溶解砜的必需浓度吐温-80是有毒化合物,其被排除用于人类。
本发明目的在于实现N,N’-二氨基二苯砜的水溶性混合物,以在无意识的人中可能应用它,从而使活性分子快速被吸收,并且允许通过任意全身途径(包括所有肠的和肠胃外的途径)以溶液的形式作为用于治疗给药的药物安全应用于人。
N,N’-二氨基二苯砜是目前用于麻风病的化学疗法和针对卡氏肺孢子虫肺炎的预防的药物。最近,N,N’-二氨基二苯砜(氨苯砜)已经显示出作为神经保护及抗癫痫药物的其它用途,其需要对无意识的患 者频繁给药,这使得固体药物制剂的给药是不可能的。这些氨苯砜的新应用已被授予专利权(专利No.MX 246.892,专利No.MX 264.912)并且可溶形式更适合于这种应用,因为比起固体制剂的速度,在治疗中需要更快的药物吸收。
发明内容
本发明描述了用于治疗用途的产品,所述产品基于在与其人类医药用途相容的溶剂混合物中溶解N,N’-二氨基二苯砜。N,N’-二氨基二苯砜用新应用来使用,所述应用需要对无意识的患者频繁给药,因此,目前使用的药物的固体制剂是不适用的。
在寻找溶解N,N’-二氨基二苯砜的选择时,发现乙醇、丙二醇、糖原质(glycofurol)、苯甲醇及水与各种各种添加剂,例如增稠剂、稳定剂和/或调味剂的混合物允许获得稳定的产品,所述产品优选适合通过任意肠的或肠胃外的途径来给药。由N,N’-二氨基二苯砜合成获得溶液,化合物的分子式如下所示:
在所有情况下,使用USP-级别的溶剂和试剂,其不合热原。
溶解试验是在容积10mL至5L的玻璃瓶或是不锈钢容器里进行,放置200mg的N,N’-二氨基二苯砜/3mL共溶剂混合物。所述N,N’-二氨基二苯砜的溶解是通过强烈震摇之后容器得目测来确定的。
这个单一算法用于测定溶解N,N’-二氨基二苯砜所需的乙醇、丙二醇、糖原质、苯甲醇和水的混合物的最佳比例。
对于N,N’-二氨基二苯砜溶液的稳定实验,使用10mL容积的玻璃瓶,并用煤气灯进行密封。
使用可溶的配方在110℃的高温釜中对玻璃瓶进行消毒。
附图说明
图1说明x轴代表以天计的时间,y轴表示DDS浓度。
图2显示其中产生脑梗死,且仅应用药物媒介物的大鼠脑组织切片。
图3显示其中产生脑梗死,且静脉内应用溶液的大鼠脑组织切片。
图4显示其中产生脑梗死,且应用口服溶液的大鼠脑组织切片。
图5显示应用口服制剂时的血浆浓度分布曲线图。
图6显示静脉内应用制剂时的血浆浓度分布曲线图。
发明详述
N,N’-二氨基二苯砜的合成
N,N’-二氨基二苯砜可以通过不同的方式进行合成,但是下述合成途径作为示例提供。
这个合成通过两个步骤进行:
1.60g的乙酰苯胺放入锥形瓶,然后用火慢慢加热直到固体完全融化。产生的粘性液体用一瓶冰块冷却,以保证固化物保留在锥形瓶的底部。165ml的氯代硫酸加入另一个部分,没有从冰浴中取出。随后,锥形瓶从冰里取出,小心地混合,并且允许反应10分钟,最后反应混合物再次加热直到剩下的乙酰苯胺全部溶化,允许它再反应10分钟。允许产物冷却然后慢慢倒入加了冰和水的容器内,过滤沉淀物并用冷水洗涤。沉淀物收集起来,在氯仿中溶解,然后用水提取三次,收集氯仿相,其放置在冰浴中,沉淀纯化的亚硫酰氯(报告的中间产物的熔点:149℃)。
2.将123.6g无水的硝基苯放入玻璃反应器中,加入89.2g氯化铝慢慢加热;然后,向热混合物加入41.3g亚硫酰氯,在140-145℃的温度加热反应混合物,再慢慢加入13g乙酰苯胺,保持反应温度两小时。在这个时间段的末期,将反应的产物倒入104ml经盐酸酸化的水中,然后沉淀深色晶体,并用稀释的乙酸进行结晶。这些晶体用5N 盐酸回流30分钟,然后中和反应混合物后,沉淀出白色的晶体(粗DDS),然后再用乙醇重结晶。
合成化合物的化学特征
为了确定合成化合物的可靠性,获得了它们的熔点,亚硫酰氯的反应中间体产物的熔点为151-153℃,DDS的熔点172-175℃。
对于中间产物和DDS,这些化合物所报告的熔点分别是149℃、175-176℃。
进行本发明的优选方式
以对于N,N’-二氨基二苯砜溶液变化的比例的乙醇、丙二醇、糖原质、苯甲醇及水制备针对下述各种疾病的药物的用途,所述疾病例如脑梗死、癫痫、外伤性脊髓损伤、脑颅损伤、脑出血、动脉瘤引起的蛛网膜下腔出血、麻风病、卡氏肺孢子虫感染以及任何需要化合物快速和完全吸收的病症,所述药物通过任意全身途径给药。
可以按照每次0.2mg/kg至12mg/kg的剂量给药,并且可经常在1至7天的时间段按需要重复。
实施例1.溶解用于给药的N,N’-二氨基二苯砜作为通过任意肠的或肠胃外途径给药的溶液。
将50mg至500g的N,N’-二氨基二苯砜称重并放入试管内。加入含有2.9体积的丙二醇、1.25体积的乙醇和0.85体积的水的5体积混合物。震摇试管直到N,N’-二氨基二苯砜完全溶解。
把获得的溶液转移至玻璃杯,密封并通过高压釜消毒。
为了确定N,N’-二氨基二苯砜是否完全溶解以及消毒步骤是否引起的可感知的N,N’-二氨基二苯砜降解,通过紫外线光检测,用高分辨率液相色谱分析N,N’-二氨基二苯砜溶液。
评估N,N’-二氨基二苯砜的可溶性制剂对神经系统保护的影响
为了评估氨苯砜的可溶性制剂的神经保护能力,在大鼠脑缺血的模型中测试它的影响。在这个模型中,大鼠的永久性脑缺血是由于大脑中动脉的永久堵塞造成,如下所述:
通过颈动脉引入官腔内缝线,会导致动物选择性的永久性脑缺血。所有的动物在外科手术时都持续的进行麻醉,通过面罩使用1.5%的氟烷。动物被仰卧地放置,固定和刮剃颈前区,从而在胸骨柄中线位置切开至胸骨舌骨肌区域并且延伸至其侧缘,在该位置识别在深层胸锁乳突肌和颈筋膜浅层的内侧缘,其影响暴露二腹肌腹部流(belly flow)下面或内部的颈总动脉。
已进行舌下环的颈总动脉锐剥离。识别颈外动脉杈、颈动脉及其枕骨和甲状腺分支,而后两者由8-0单丝打结,用电凝技术在后分割颈内动脉切开一段约5mm的长度,此时,翼腭动脉可被识别。植入微芯片,或者,其被6-0的单丝打结。在移动该支流通过这些动脉的支流后,使用3-0尼龙单丝于朝向颈内动脉的方向引入,通过颈外动脉残余部分,其位于从分叉处17mm的长度。伤口愈合,动物可以饮用水和食物来恢复。就一切情况来看,局部缺血可以通过肉眼以及线的位置来观察出。
评估N,N’-二氨基二苯砜的可溶性制剂在大鼠中的神经保护影响
从大鼠脑制成系列组织切片,使用苏木素和曙红进行染色以确定损伤位置。用新药物形式处理的动物的神经保护影响的代表性结果和媒介物的影响,在图2中显示。
图2显示相对于用媒介物处理的动物,N,N’-二氨基二苯砜新可溶性形式处理的动物中损伤区域显著降低。
N,N’-二氨基二苯砜的可溶性药物制剂在健康志愿者中的药代动力学特征
N,N’-二氨基二苯砜(DDS)的可溶性形式通过口服(图3)以及静脉内(图4)以溶液给予至18名健康人类志愿者,并且N,N’-二氨基二苯砜的血浆浓度在不同时间测定。图3和图4显示分析结果。
计算每只老鼠的药代动力学特征曲线下面积,通过口服形式得到的平均生物利用度超过92%,而通过静脉内途径的曲线下面积为100%的生物利用度。结果显示可溶得口服形式在消化道最佳的吸收。平均在半小时内获得口服形式的最大浓度,而在文献报道表明,对于 固体形式而言,达到最大血浆浓度的时间为2至3小时(Breen GA,Brocavich JM,Etzel JV,Shah V,Schaefer P,Forlenza S.,Evaluation of effects of altered gastric pH on absorption of dapsone in healthy volunteers,Antimicrobial Agents and Chemotherapy 1994 Sep;38(9):2227-2229)。
Claims (5)
1.一种在a)乙醇、b)丙二醇、c)糖原质、d)苯甲醇和e)水的混合物中的、用于治疗目的的N,N’-二氨基二苯砜溶液,其中所述混合物含有:
a)乙醇25%;
b)丙二醇58%;
c)苯甲醇1%;
d)糖原质5%;和
e)水11%。
2.权利要求1的溶液,其中所述溶液含有在0.2mg/kg至12mg/kg药物的给药剂量的量。
3.根据权利要求1至2中任一项的溶液在制备治疗选自下述疾病的药物中的用途,所述疾病选自脑梗死、癫痫、外伤性脊髓损伤、颅脑外伤、脑出血、麻风病和卡氏肺孢子虫感染,所述药物通过任意全身途径给药。
4.根据权利要求3的用途,所述药物的剂量在5-300mg/天。
5.根据权利要求3或4的用途,其中每24小时重复给药。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MX/A/2009/004635 | 2009-04-29 | ||
MX2009004635A MX2009004635A (es) | 2009-04-29 | 2009-04-29 | Formas farmaceúticas solubles de la n,n´-diamino-difenilsulfona para su uso óptimo en el tratamiento de diversas enfermedades. |
MXMX/A/2009/004635 | 2009-04-29 | ||
PCT/MX2009/000105 WO2010126349A1 (es) | 2009-04-29 | 2009-10-05 | Formas farmacéuticas solubles de la n, n'-diaminodifenilsulfona para uso óptimo en el tratamiento de diversas enfermedades |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102548547A CN102548547A (zh) | 2012-07-04 |
CN102548547B true CN102548547B (zh) | 2014-10-15 |
Family
ID=43032353
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200980158985.8A Active CN102548547B (zh) | 2009-04-29 | 2009-10-05 | 在治疗各种疾病中最佳使用的n,n’-二氨基二苯砜的可溶性药物制剂 |
Country Status (12)
Country | Link |
---|---|
US (1) | US8680156B2 (zh) |
EP (1) | EP2425829B1 (zh) |
JP (1) | JP5671010B2 (zh) |
KR (1) | KR101631945B1 (zh) |
CN (1) | CN102548547B (zh) |
BR (1) | BRPI0925000B8 (zh) |
CA (1) | CA2760017C (zh) |
CO (1) | CO6470840A2 (zh) |
HK (1) | HK1172568A1 (zh) |
MX (1) | MX2009004635A (zh) |
RU (1) | RU2538658C2 (zh) |
WO (1) | WO2010126349A1 (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101875705B1 (ko) * | 2011-12-07 | 2018-07-06 | 삼성전자주식회사 | 디아미노디페닐술폰을 포함하는 근육 소모 관련 질환의 예방 또는 치료용 약학적 조성물 |
KR20160047318A (ko) * | 2014-10-22 | 2016-05-02 | 삼성전자주식회사 | 다프손을 포함하는, 개체의 부위에서 혈관신생을 자극시키기 위한 조성물 및 그의 용도 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060204526A1 (en) * | 2003-08-13 | 2006-09-14 | Lathrop Robert W | Emulsive composition containing Dapsone |
CN1852749A (zh) * | 2003-07-22 | 2006-10-25 | 大都会自治大学 | 氨苯砜作为神经保护剂在脑中风中的应用 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5721242A (en) * | 1993-06-17 | 1998-02-24 | Hoffmann-La Roche Inc. | Antibiotic combination |
RU2200550C2 (ru) * | 1999-10-29 | 2003-03-20 | Научно-исследовательская лаборатория иммунохимиотерапии лепры и иммунотропных средств с клиникой и опытно-экспериментальным производством | Новые лекарственные формы димоцифона в терапии лепры, зудящих и аллергодерматозов, герпетиформного дерматита дюринга |
UA80393C2 (uk) * | 2000-12-07 | 2007-09-25 | Алтана Фарма Аг | Фармацевтична композиція, яка містить інгібітор фде 4, диспергований в матриці |
WO2009108147A1 (en) | 2008-02-27 | 2009-09-03 | Qlt Usa, Inc. | Dapsone to treat rosascea |
-
2009
- 2009-04-29 MX MX2009004635A patent/MX2009004635A/es active IP Right Grant
- 2009-10-05 US US13/266,892 patent/US8680156B2/en active Active - Reinstated
- 2009-10-05 WO PCT/MX2009/000105 patent/WO2010126349A1/es active Application Filing
- 2009-10-05 CA CA2760017A patent/CA2760017C/en active Active
- 2009-10-05 JP JP2012508413A patent/JP5671010B2/ja active Active
- 2009-10-05 RU RU2011145768/15A patent/RU2538658C2/ru active
- 2009-10-05 KR KR1020117028275A patent/KR101631945B1/ko active IP Right Grant
- 2009-10-05 BR BRPI0925000A patent/BRPI0925000B8/pt active IP Right Grant
- 2009-10-05 CN CN200980158985.8A patent/CN102548547B/zh active Active
- 2009-10-05 EP EP09844101.7A patent/EP2425829B1/en active Active
-
2011
- 2011-11-29 CO CO11164315A patent/CO6470840A2/es active IP Right Grant
-
2012
- 2012-12-28 HK HK12113527.1A patent/HK1172568A1/zh unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1852749A (zh) * | 2003-07-22 | 2006-10-25 | 大都会自治大学 | 氨苯砜作为神经保护剂在脑中风中的应用 |
US20060204526A1 (en) * | 2003-08-13 | 2006-09-14 | Lathrop Robert W | Emulsive composition containing Dapsone |
Non-Patent Citations (8)
Title |
---|
An injection solution of dapsone;FRENCH T M;《LEPROSY REVIEW》;19681231;第39卷(第3期);171 * |
Bioequivalence of a propylene glycol-based liquid dapsone preparation and dapsone tablets;M.MIROCHNICK et al;《Am J Health-Syst Pharm》;20001001;第57卷;1775-1777 * |
FRENCH T M.An injection solution of dapsone.《LEPROSY REVIEW》.1968,第39卷(第3期),171. |
M.C.NAHATA et al.Stability of dapsone in two oral liquid dasage forms.《The Annals of Pharmacotherapy》.2000,第34卷848-850. |
M.MIROCHNICK et al.Bioequivalence of a propylene glycol-based liquid dapsone preparation and dapsone tablets.《Am J Health-Syst Pharm》.2000,第57卷1775-1777. |
Mirochnick et al.Pharmacokinetics of dapsone in children.《J.Pediatrics》.1993,第122卷(第5期),806-809. |
Pharmacokinetics of dapsone in children;Mirochnick et al;《J.Pediatrics》;19931231;第122卷(第5期);806-809 * |
Stability of dapsone in two oral liquid dasage forms;M.C.NAHATA et al;《The Annals of Pharmacotherapy》;20000831;第34卷;848-850 * |
Also Published As
Publication number | Publication date |
---|---|
CA2760017A1 (en) | 2010-11-04 |
RU2538658C2 (ru) | 2015-01-10 |
EP2425829B1 (en) | 2015-07-22 |
HK1172568A1 (zh) | 2013-04-26 |
CO6470840A2 (es) | 2012-06-29 |
BRPI0925000B8 (pt) | 2021-05-25 |
RU2011145768A (ru) | 2013-06-10 |
CA2760017C (en) | 2016-02-23 |
JP2012525379A (ja) | 2012-10-22 |
MX2009004635A (es) | 2010-10-29 |
JP5671010B2 (ja) | 2015-02-18 |
US8680156B2 (en) | 2014-03-25 |
EP2425829A1 (en) | 2012-03-07 |
BRPI0925000B1 (pt) | 2020-08-18 |
US20120157541A1 (en) | 2012-06-21 |
CN102548547A (zh) | 2012-07-04 |
KR20150124460A (ko) | 2015-11-06 |
EP2425829A4 (en) | 2012-10-17 |
WO2010126349A1 (es) | 2010-11-04 |
KR101631945B1 (ko) | 2016-06-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
TW201217343A (en) | Meglumine salt of 6-fluoro-3-hydroxy-2-pyrazinecarboxamide | |
US20230302008A1 (en) | Methods of administering intravenous meloxicam in a bolus dose | |
CN102548547B (zh) | 在治疗各种疾病中最佳使用的n,n’-二氨基二苯砜的可溶性药物制剂 | |
US20040254244A1 (en) | Agent for prophylaxis or treatment of inflammatory bowel diseases | |
JP2005505609A (ja) | 唯一の共同溶剤としてプロピレングリコールを含んでいる使用準備ができているパラセタモール注射溶液 | |
CA2572167A1 (en) | Quinolone-containing medicinal composition | |
AU2013346775B2 (en) | Medicinal lozenge based on ibuprofen sodium dihydrate | |
JP2012525379A5 (zh) | ||
CN102718693B (zh) | 一种卡络磺钠化合物及其组合物 | |
ES2423866B1 (es) | Composición farmaceútica de ibuprofeno y tramadol para inyección | |
ES2287713T3 (es) | Uso de la dapsona como neuroprotector en el infarto cerebral. | |
EP4243797A1 (en) | Rapidly infusing platform and compositions for therapeutic treatment in humans | |
JP2001519395A (ja) | カルバマゼピンまたはその誘導体を含む非経口製剤 | |
WO2023109513A1 (zh) | 爱地那非或其盐在制备预防或治疗缺血性脑损伤的药物中的应用 | |
US11672761B2 (en) | Rapidly infusing platform and compositions for therapeutic treatment in humans | |
ES2410230B1 (es) | Composición farmacéutica para el tratamiento de las enfermedades cerebrovasculares. | |
CN105481725B (zh) | L-精氨酸苯乙酸盐的晶型及其制备方法 | |
CA2367040A1 (en) | Pharmaceutical compositions comprising a pyrimidine derivative and cyclodextrin | |
Vijay et al. | Successful surgical management of black stone chip foreign body in a golden retriever dog | |
Mwembo et al. | Enhanced recovery after elective visceral surgery in countries with limited resources: our experience at the centre médical diamant of Lubumbashi (CMDL)/Democratic Republic of the Congo | |
US20170044212A1 (en) | Compound for treating sequelae of ischemic cerebral stroke | |
Gruden et al. | Massive rectal bleeding distant from a blunt car trauma | |
Walker et al. | The Stability of Sodium Phenobarbitone in Aqueous Solution | |
CN105188671A (zh) | 用于口服和胃肠外给药的稳定的氯吡格雷游离碱药物组合物 |
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 | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1172568 Country of ref document: HK |