CN1105563A - 抗菌组合物 - Google Patents

抗菌组合物 Download PDF

Info

Publication number
CN1105563A
CN1105563A CN94107507A CN94107507A CN1105563A CN 1105563 A CN1105563 A CN 1105563A CN 94107507 A CN94107507 A CN 94107507A CN 94107507 A CN94107507 A CN 94107507A CN 1105563 A CN1105563 A CN 1105563A
Authority
CN
China
Prior art keywords
dapsone
aminometradine
preparation
infectious disease
actinomycetes
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN94107507A
Other languages
English (en)
Other versions
CN1054745C (zh
Inventor
I·康皮斯
R·特恩
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
F Hoffmann La Roche AG
Original Assignee
F Hoffmann La Roche AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG
Publication of CN1105563A publication Critical patent/CN1105563A/zh
Application granted granted Critical
Publication of CN1054745C publication Critical patent/CN1054745C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Epidemiology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

一种含有氨嘧啶和氨苯砜的药用制剂，它可用于 治疗因分支杆菌、放线菌和弓形体病病原体所引起的 传染病。

Description

本发明涉及抗菌活性组合制剂，该制剂包含2，4-二氨基-5-[3，5-二乙氧基-4-（吡咯-1-基）苄基]嘧啶（氨嘧啶）和4，4＇-二氨基-二苯砜（氨苯砜）。本发明还涉及氨嘧啶和氨苯砜的用途，它们可作为活性物质用于药物制剂的制备以治疗因分支杆菌、放线菌、特别是诺卡菌和弓形体病病原体引起的传染病，以及含氨嘧啶和氨苯砜的商品包装，其中的药品说明书涉及联合用药以治疗因分支杆菌、放线菌、特别是诺卡菌和弓形体病病原体引起的传染病的方法。
二氨基苄基嘧啶的使用，包括氨嘧啶和氨苯砜或抗菌活性磺胺任意组合的使用，能对抗因真菌卡氏肺囊虫引起的传染病，可从专利公告WO9208461中得知。我们惊奇的发现，氨嘧啶和氨苯砜的组合适用于治疗因分支杆菌、特别是M.marinum、M.smegmatis、M.avivm和M.leprac;和弓形体病病原体，特别是兔弓形虫;和放线菌，特别是诺卡菌引起的传染病。
活性物质可单独或以组合制剂的形式同时或以一定间隔给药，优选同时给药。
活性物质可于直肠内、肠道外或局部给药。片剂、胶囊、糖衣丸、糖浆、混悬液、溶液和栓剂等适用于肠内给药。输注或注射溶液适用于肠道外给药。
活性物质给药剂量按照使用方式和使用途径以及病人的需要而不同。
活性物质可以氨嘧啶：氨苯砜比率为1∶100到100∶1（重量）用于控制上述命名的传染病或病原体。治疗因分支杆菌引起的传染病优选氨嘧啶：氨苯砜比率为1∶1到1∶5（重量）。治疗因弓形体病病原体引起的传染病优选1∶2到2∶1的比率。若是诺卡菌传染病优选氨嘧啶：氨苯砜比率为4∶1到1∶1（重量）。
若是口服给药，活性物质的剂量一般等于每天每公斤体重0.5到50毫克，对于氨嘧啶优选每天每公斤体重0.5-3毫克，对于氨苯砜优选每天每公斤体重0.5-2毫克。
若是片剂形式，活性物质的量例如为每片片剂中有20-200毫克的氨嘧啶和20-100毫克的氨苯砜。
制剂可含有惰性或药用活性添加剂。例如片剂或颗粒剂可含有一系列粘合剂、填充剂、载体或稀释剂。液体制剂可以无菌水溶性溶液的形式存在。除了活性物质之外，胶囊中足可含有填充剂或增稠剂。此外，还可以有调味添加剂和常用保鲜剂、稳定剂、保湿剂和乳化剂以及用来改变渗透压的盐、缓冲剂和其它添加剂。
上述提到的载体和稀释剂可包含有机或无机的物质，例如水、明胶、乳糖、淀粉、硬脂酸镁、滑石、阿拉伯树胶、聚亚烷基二醇等等。前提是用于制剂制备的所有辅助剂都是无毒的。
对于局部给药，活性物质一般以软膏、药酒、霜剂、溶液、洗剂、喷洒剂、悬浮液等形式使用。优选软膏、霜剂和溶液。用作局部给药的这些制剂可通过作为活性成份的过程产品和无毒、惰性固体或液体载体混合而制得。该载体适用于局部治疗并且常用于这类制剂。
一般约0.1-5%，优选0.3-2%的溶液和约0.1-5%，优选0.3-2%的软膏或霜剂适用于局部给药。
若需要，抗氧剂例如生育酚、N-甲基-γ-生育胺和叔丁基-羟基茴香醚或叔丁基-羟基甲苯可与制剂混合。
本发明中的组合制剂的活性可从下表所给的数据中显示出来。
表1和表2显示了单独的和组合的活性物质在体内对各种分支杆菌和放线菌的最小抑制浓度（MIC）和FIC（部分抑制浓度）的活性。FIC可表示协同效应的大小（参见J.Bio，.Chem.1954.298，477）。FIC指数越小，则协同效应越大。
表3显示了M.lufu培养物的抑制百分率，该培养物为测试抗麻风药剂公认的标样，得到了单独的活性物质和它们的组合物给药的确定浓度。
表4和5显示了诺卡菌和弓形菌传染病在体内的活性。用病原体RH兔弓形虫10000个菌落单位腹膜内给药传染实验动物。传染后24小时将所示活性物质的剂量通过除鲠器每隔一天施入动物体内，用14天。“治愈”代表动物大脑中未发现囊肿。
Figure 941075079_IMG1
Figure 941075079_IMG2
Figure 941075079_IMG3
表5
体内抗弓形体病活性
Figure 941075079_IMG4
本发明的活性物质组合例如可用于治疗诺卡菌、放线菌、和分支杆菌。该分支杆菌因放线菌例如以色到放线菌、A.naeslundii等、brasiliensis诺卡菌、N.asteroides等和链霉菌例如madurae链霉菌。S.someliensis、S.pelletieri、Madarella    mycetomi而引起;还可治疗因分支杆菌引起的综合传染病，特别是因对病人免疫系统有破坏功能的M.avivm和M.intracellulave引起的一般性传染病;和治疗麻风和大脑弓形体病。
下面是一个典型剂量配方的例子：
片剂：
氨苯砜        100毫克
氨嘧啶        200
PRIMOJEL（淀粉衍生物）        6
Povidone    K30（聚乙烯吡咯烷酮）        8
硬脂酸镁        6

Claims (6)

1、一种药用制剂，它包含氨嘧啶和氨苯砜及常用的药用载体。
2、权利要求1的制剂，它所包含的氨嘧啶和氨苯砜的重量比率为1∶100到100∶1。
3、权利要求1的制剂，它所包含的氨嘧啶和氨苯砜的重量比率为1∶1到1∶5。
4、氨嘧啶和氨苯砜用于制备药物制剂以治疗因分支杆菌、放线菌、特别是诺卡菌和弓形体病病原体引起的传染病。
5、一种商品包装，它包含将氨嘧啶和氨苯砜结合使用治疗因分支杆菌、放线菌、特别是诺卡菌和弓形体病病原体引起的传染病的说明。
6、上文所描述的发明。
CN94107507A 1993-06-17 1994-06-16 抗菌组合物 Expired - Fee Related CN1054745C (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CH1801/1993 1993-06-17
CH1801/93 1993-06-17
CH180193 1993-06-17

Publications (2)

Publication Number Publication Date
CN1105563A true CN1105563A (zh) 1995-07-26
CN1054745C CN1054745C (zh) 2000-07-26

Family

ID=4218921

Family Applications (1)

Application Number Title Priority Date Filing Date
CN94107507A Expired - Fee Related CN1054745C (zh) 1993-06-17 1994-06-16 抗菌组合物

Country Status (13)

Country Link
US (1) US5721242A (zh)
EP (1) EP0629403B1 (zh)
JP (1) JP2650852B2 (zh)
CN (1) CN1054745C (zh)
AT (1) ATE170751T1 (zh)
AU (1) AU685449B2 (zh)
CA (1) CA2125121A1 (zh)
DE (1) DE59406863D1 (zh)
DK (1) DK0629403T3 (zh)
ES (1) ES2122085T3 (zh)
MY (1) MY110998A (zh)
NZ (1) NZ260721A (zh)
RU (1) RU2136272C1 (zh)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2030129A1 (en) * 1989-11-29 1991-05-30 Thomas Saupe 1,8-napthalenedicarboximides as antidotes
DE60102461T2 (de) 2000-04-27 2005-02-24 Basilea Pharmaceutica Ag Pyrimidinyl methyl indolderivate mit antibakterieller wirkung
EP1675563A4 (en) * 2003-08-13 2009-07-15 Qlt Usa Inc EMULSION COMPOSITION WITH DAPSON
BRPI1006875B8 (pt) * 2009-01-12 2021-05-25 Intervet Int Bv composição farmacêutica, bactérias, e, uso de bactérias vivas
MX2009004635A (es) * 2009-04-29 2010-10-29 Univ Autonoma Metropolitana Formas farmaceúticas solubles de la n,n´-diamino-difenilsulfona para su uso óptimo en el tratamiento de diversas enfermedades.
RU2638926C2 (ru) * 2016-06-02 2017-12-19 федеральное государственное бюджетное образовательное учреждение высшего образования "Волгоградский государственный медицинский университет" Министерства здравоохранения Российской Федерации Противолепрозное средство, обладающее бактериостатической и бактерицидной активностью в отношении m. lufu, представляющее собой производное o-бензоиламинобензойной кислоты
JP7446594B2 (ja) * 2017-07-21 2024-03-11 学校法人東京薬科大学 好中球細胞外トラップ形成促進剤

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4515948A (en) * 1973-09-12 1985-05-07 Hoffmann-La Roche Inc. 2,4-Diamino-5-(4-amino and 4-dimethylamino-3,5-dimethoxy benzyl)pyrimidines
ATE15446T1 (de) * 1981-09-23 1985-09-15 Hoffmann La Roche Verfahren zur herstellung von sulfonamidpotentiator-l¯sungenund ein neues sulfanilamid.
US4590271A (en) * 1982-05-01 1986-05-20 Burroughs Wellcome Co. 2,4-diamino-5-(substituted)pyrimidines, useful as antimicrobials
US4587341A (en) * 1982-05-07 1986-05-06 Burroughs Wellcome Co. 2,4-diamino-5-(1,2,3,4-tetrahydro-(substituted or unsubstituted)-6-quinolylmethyl)pyrimidines, useful as antimicrobials
IE913974A1 (en) * 1990-11-14 1992-05-20 Protos Corp Specific inhibition of dihydrofolate reductase and compounds¹therefor

Also Published As

Publication number Publication date
MY110998A (en) 1999-07-31
JPH072672A (ja) 1995-01-06
RU94019991A (ru) 1996-04-27
NZ260721A (en) 1997-03-24
US5721242A (en) 1998-02-24
ES2122085T3 (es) 1998-12-16
ATE170751T1 (de) 1998-09-15
AU685449B2 (en) 1998-01-22
DE59406863D1 (de) 1998-10-15
AU6469794A (en) 1994-12-22
EP0629403A1 (de) 1994-12-21
JP2650852B2 (ja) 1997-09-10
DK0629403T3 (da) 1999-06-07
CA2125121A1 (en) 1994-12-18
EP0629403B1 (de) 1998-09-09
RU2136272C1 (ru) 1999-09-10
CN1054745C (zh) 2000-07-26

Similar Documents

Publication Publication Date Title
US4806529A (en) Tetracycline activity enhancement
US5258372A (en) Tetracycline activity enhancement using doxycycline or sancycline
WO1998030228B1 (en) Compounds and their combinations for the treatment of influenza infection
JPH08501317A (ja) 抗菌性インターフェロン誘発性医薬品
EP1200463B1 (en) Antimicrobial histone h1 compositions and methods of use thereof
KR20160145216A (ko) 바퀴벌레에서 유래한 항균 펩타이드 페리플라네타신-1 및 그의 조성물
CN1105563A (zh) 抗菌组合物
US20150025132A1 (en) Compositions and methods for inhibiting endospores using green tea polyphenols
AU777397B2 (en) Multi-dose erythropoietin formulations
CA1266000A (en) Pharmaceutical composition for treating dysentery
US6413993B1 (en) Combination preparation for treating malaria
CA1285226C (en) Compositions containing a 2,4-diamino-pyrimidine and sulphadimidine
Raimer New and emerging therapies in pediatric dermatology
JP3693377B2 (ja) 生体内で感染防御作用を有するペプチド混合物と、このペプチド混合物を含有する組成物
Chen et al. Pharmacokinetics of oxytetracycline in nile tilapia Oreodromis niloticus challenged with Streptococcus iniae and Vibrio vulnificus
CA1036939A (en) Composition for treating mycobacterioses
US20060142243A1 (en) Use of n-acetyl-d-glucosamine for preparing medicines for urogenital tract infection's treatment and prevention
JPH04506056A (ja) ペプチド組合せ組成物及びその用法
RU2103997C1 (ru) Лекарственное средство для лечения заболеваний животных микробной этиологии, способ лечения желудочно-кишечных заболеваний животных микробной этиологии и способы лечения гинекологических заболеваний коров микробной этиологии
RU2185840C1 (ru) Лекарственный препарат для профилактики и лечения инфекционных заболеваний
EP0384722B1 (en) Chemical compositions
KR960015952B1 (ko) 동물의 하리치료제 조성물 및 이를 함유하는 제제
CN115006405A (zh) 二氢杨梅素协同盐酸头孢噻呋在抗mrsa耐药菌感染的应用
CN114712355A (zh) Rhps4在制备抑制人类病原菌药物中的应用及其药物
CN115414487A (zh) 千金藤素联合大环内酯类抗生素在制备抗菌产品中的应用

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
C19 Lapse of patent right due to non-payment of the annual fee
CF01 Termination of patent right due to non-payment of annual fee