CN103153312B - 用于预防性治疗和治疗性治疗疱疹感染的吡罗昔康 - Google Patents
用于预防性治疗和治疗性治疗疱疹感染的吡罗昔康 Download PDFInfo
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- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
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- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
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- 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
- A61P31/12—Antivirals
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Abstract
本发明涉及用于预防性和治疗性治疗病毒感染的试剂,所述病毒感染特别是来自疱疹病毒家族的那些,所述试剂包含载体物质中的吡罗昔康。
Description
本发明涉及用于预防性和治疗性治疗病毒感染的试剂,所述病毒感染大致是疱疹感染,特别是单纯疱疹。
长期以来,对人和动物中的病毒感染的治疗一直是种挑战,原因是活性成分的数量受到限制。对于疱疹科的病毒也同样如此。
疱疹病毒家族(疱疹病毒)包括具有双链DNA的大量病毒。很常见的是HSV1和HSV2型的单纯疱疹病毒以及水痘-带状疱疹-病毒VZV。它们都导致疼痛的感染,其表现为体表炎症。疱疹病毒在人体中长时间存活,从而其总是导致疾病重复爆发,带有部分加重的疾病现象。
单纯疱疹感染主要在***区出现,并且表现为黏膜和嘴唇的起疱和损伤。水痘-带状疱疹-感染在儿童时期大多表现为水痘形式,而在成年时期大多表现为带状疱疹。后者导致脊神经区域中,大致在腰部、胸部以及脸部区域中的疼痛性疹。带状疱疹感染伴随发热、厌食、四肢疼痛和起疹区域的疼痛。
针对疱疹病毒已开发了一系列试剂,但是所述试剂基本上都仅适于缓和症状,但是对疾病进程仅发挥轻微影响。大多数情况下,它们仅轻微缩短疾病持续时间。大量使用的活性成分是阿昔洛韦。
原则上目前需要试剂,用其可以有效抑制病毒感染特别是疱疹感染。
EP 1457202A2中描述了用所谓非类固醇抗炎剂(NSAIDs)来治疗疱疹感染的用途。尽管在所述申请中列举了大量NSAIDs,仅描述了所述各类中的两种代表双氯芬酸和酮咯酸的效力,并且仅双氯芬酸有可靠数据进行证明。根据所述描述,双氯芬酸在局部应用中适用于减轻疾病进程;平均5天后实现对损伤的治疗。这显然是对持续10天的正常感染持续时间的缩短,但是对于患者来说人不够令人满意。
现在令人惊讶地发现,属于NSAIDs类的活性成分吡罗昔康适于预防性和治疗性地治疗病毒感染。吡罗昔康对一系列病毒引起的疾病比如说Η1Ν1型流感病毒造成的流感具有阳性影响,并且特别适于预防以及快速治疗疱疹感染,比如HSV1和HSV2型的那些,特别是唇疱疹。吡罗昔康,4-羟基-2-甲基-N-吡啶-2-基-2H-1,2-苯并噻嗪-3-甲酰胺-1,1-二氧化碳,是COX-抑制剂并且可以用作抗风湿药。
相应地,本发明涉及前述领域的试剂,其包含在适当载体物质中的吡罗昔康。
根据本发明的试剂包含吡罗昔康,其量优选为0.1至10重量%,优选0.1至5,特别优选0.5至5重量%。它可以进行局部、口服和胃肠道给药。
优选地,在***区感染(通常称为唇疱疹)的情况下,使用根据本发明的试剂。在此,其涉及单纯疱疹-病毒HSV1和HSV2的感染。同样地,还产生针对带状疱疹VZV的效力。在全部这些感染中,都形成体表疼痛性疹。
本发明试剂通常局部给药,特别是以霜剂、软膏剂、凝胶或酊剂形式局部给药。它们包含常用的载体物质,也即在医药领域惯用的用于霜剂、软膏剂、凝胶和酊剂的配制剂的常用载体物质。
此外,同样可以以片剂形式、作为粉末、输注液或注射液给药。
一般来说,将试剂应用于患者1至5次,每天1至2次。对于大多数患者来说,一次应用即可称为成功。
据频繁罹患单纯疱疹感染的众多患者报告在紧张情况下的预防性应用可以预防起疹,所述紧张情况通常导致形成疱疹。
试验报告1
借助市场上的活性成分含量为0.5重量%的吡罗昔康凝胶,在42名受试者上测试根据本发明的试剂,得到下文列出的结果:
在42名受试者中,26名使用试剂1次,而16名受试者使用试剂达5次。
在42名受试者中,15名在一天之内就确认了改善(包括预防疾病爆发),21名在1至3天确认了改善,而2名在4至10天确认了改善。41名受试者认为相容性良好,而1名受试者认为一般。1名受试者指出,本发明试剂没有帮助。
吡罗昔康的效力本身即是令人惊讶的。该活性成分原先设计为抗风湿药,化学正确地称为4-羟基-2-甲基-N(2-吡啶基)-2H-1,2-苯并噻嗪-3-甲酰胺-1,1-二氧化碳,其在很大程度上作为止痛剂给药。它在化学上完全不同于上文描述的NSAIDs双氯芬酸和酮咯酸,从而基于其化学结构无法推演出对疱疹病毒且特别是对单纯疱疹/唇疱疹的抗病毒效果。与双氯芬酸和酮咯酸相反,其适于预防起疹。
试验报告2
在筛选测试中,根据标准方法,在感染HSV1型疱疹病毒的培养物上测试具有0.4%活性成分含量的包含吡罗昔康的凝胶。最初log CD50-值为2.50,最初病毒滴度为7.00。在1、5和60分钟作用时间之后,病毒滴度(log10 TCID50/ml)为小于2.50,其对应于大于99.99%的病毒数减少。
Claims (7)
1.吡罗昔康用于制备预防性和治疗性治疗单纯疱疹病毒引起的病毒感染的抗病毒试剂的用途,其中所述吡罗昔康被包含在载体物质中,并且其中所述试剂具有抵抗单纯疱疹病毒的抗病毒活性。
2.根据权利要求1的用途,其特征在于所述试剂中吡罗昔康的含量为0.1至10重量%。
3.根据权利要求2的用途,其特征在于所述试剂中吡罗昔康的含量为1至5重量%。
4.根据权利要求1-3中任一项的用途,其中所述病毒感染是唇疱疹的感染。
5.根据权利要求1-3中任一项的用途,其中所述试剂为用于局部给药的试剂。
6.根据权利要求5的用途,其中所述试剂为霜剂、软膏剂、酊剂或凝胶的形式。
7.根据权利要求1至3中任一项的用途,其中所述试剂用于输注或者注射。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102010014290A DE102010014290A1 (de) | 2010-04-08 | 2010-04-08 | Mittel zur prophylaktischen und therapeutischen Behandlung von Herpes-Infektionen |
DE102010014290.5 | 2010-04-08 | ||
PCT/EP2011/001704 WO2011124366A1 (de) | 2010-04-08 | 2011-04-06 | Piroxicam zur prophylaktischen und therapeutischen behandlung von herpes - infektionen |
Publications (2)
Publication Number | Publication Date |
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CN103153312A CN103153312A (zh) | 2013-06-12 |
CN103153312B true CN103153312B (zh) | 2015-07-22 |
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CN201180021384.XA Active CN103153312B (zh) | 2010-04-08 | 2011-04-06 | 用于预防性治疗和治疗性治疗疱疹感染的吡罗昔康 |
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Country | Link |
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US (2) | US20130190301A1 (zh) |
EP (1) | EP2374461B1 (zh) |
JP (1) | JP6158077B6 (zh) |
CN (1) | CN103153312B (zh) |
CA (1) | CA2795334C (zh) |
DE (1) | DE102010014290A1 (zh) |
DK (1) | DK2374461T3 (zh) |
ES (1) | ES2612584T3 (zh) |
PL (1) | PL2374461T3 (zh) |
RU (1) | RU2555765C2 (zh) |
WO (1) | WO2011124366A1 (zh) |
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Publication number | Priority date | Publication date | Assignee | Title |
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DE102010014290A1 (de) * | 2010-04-08 | 2011-10-13 | Hans Otto Meyer zu Spelbrink | Mittel zur prophylaktischen und therapeutischen Behandlung von Herpes-Infektionen |
DE102013003756A1 (de) | 2013-03-06 | 2014-09-11 | DeaValorum UG (haftungsbeschränkt) | Piroxicam zur prophylaktischen und therapeutischen Behandlung von CMV-Infektionen |
DE102013014787A1 (de) | 2013-09-09 | 2015-03-12 | Dauphine UG (haftungsbeschränkt) | Mittel zur prophylaktischen und therapeutischen Behandlung von EHV-Infektionen |
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DE3437232A1 (de) * | 1984-10-10 | 1986-04-17 | Mack Chem Pharm | Stabilisierte injektionsloesungen von piroxicam |
IT1216686B (it) * | 1988-04-01 | 1990-03-08 | Chiesi Farma Spa | Formulazioni farmaceutiche acquose di piroxicam e procedimento per laloro preparazione. |
IT1230922B (it) * | 1989-06-23 | 1991-11-08 | Giuseppe De Benedittis | Composizione per il trattamento della nevralgia erpetica acuta e della nevralgia post erpetica |
ES2059869T3 (es) * | 1990-04-26 | 1994-11-16 | Sagitta Arzneimittel Gmbh | Preparado farmaceutico que contiene piroxicam para uso topico. |
JP3031990B2 (ja) * | 1990-10-19 | 2000-04-10 | 同仁医薬化工株式会社 | 消炎鎮痛クリーム剤組成物 |
RU2182016C2 (ru) * | 1997-03-20 | 2002-05-10 | Панацея Биотек Лтд. | Спазмолитическая композиция, способ получения спазмолитической композиции |
DE10300222A1 (de) * | 2003-01-03 | 2004-07-15 | MedInnova Gesellschaft für medizinische Innovationen aus akademischer Forschung mbH | Verwendung von Wirksubstanzen zur Prophylaxe und/oder Therapie von Viruserkrankungen |
US7132452B2 (en) | 2003-03-10 | 2006-11-07 | Fang-Yu Lee | Topical formulation having effects on alleviating pain/inflammation caused by herpes virus infection |
DE102010014290A1 (de) * | 2010-04-08 | 2011-10-13 | Hans Otto Meyer zu Spelbrink | Mittel zur prophylaktischen und therapeutischen Behandlung von Herpes-Infektionen |
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2014
- 2014-01-29 US US14/167,676 patent/US20140148447A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
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Therapeutic effects of feldene piroxicam on herpes zoster;Yamamoto M,et al.;《Acta Dermatologica (kyoto)》;19841231;第79卷(第4期);第315-320页 * |
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JP6158077B2 (ja) | 2017-07-05 |
ES2612584T3 (es) | 2017-05-17 |
JP2013523789A (ja) | 2013-06-17 |
RU2012147474A (ru) | 2014-05-20 |
CA2795334A1 (en) | 2011-10-13 |
RU2555765C2 (ru) | 2015-07-10 |
WO2011124366A1 (de) | 2011-10-13 |
CA2795334C (en) | 2015-06-09 |
DK2374461T3 (en) | 2017-02-06 |
CN103153312A (zh) | 2013-06-12 |
US20140148447A1 (en) | 2014-05-29 |
EP2374461A1 (de) | 2011-10-12 |
DE102010014290A1 (de) | 2011-10-13 |
US20130190301A1 (en) | 2013-07-25 |
EP2374461B1 (de) | 2016-10-26 |
JP6158077B6 (ja) | 2018-08-29 |
PL2374461T3 (pl) | 2017-08-31 |
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