CN1100931A - 病毒感染的治疗 - Google Patents
病毒感染的治疗 Download PDFInfo
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- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
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- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
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Abstract
通过给与不饱和脂肪酸,尤其是其锂盐,杀灭体
内病毒感染细胞来治疗病毒感染、尤其是逆转录病毒
感染、特别是由HIV类病毒引起的感染的方法。
Description
本发明涉及病毒感染的治疗,尤其是逆转录病毒感染的治疗,更具体地讲,涉及HIV感染和AIDS的治疗。
病毒感染是常见的,而一些病毒感染如HIV感染严重且正在增加。尽管已做了大量的研究工作,现有治疗病毒感染的方法,即试图干扰病毒的复制和转录的方法相对受到限制,所以迫切需要新的技术。我们已经找到治疗病毒感染的方法,其目的是杀灭已被病毒感染的细胞,并因而毁掉病毒繁殖的场所。当体内只是有限部分的任何种类的正常细胞被病毒感染时,这种治疗病毒感染的新方法特别适用。它适用于只有少部分免疫***细胞(淋巴细胞)在任何时候被HIV病毒感染的HIV感染。
有充分的证据,如本申请人在EP-A-0524796上所提供的证据表明:被HIV感染的患者的某些必需脂肪酸(EFAs)的水平下降。所以,在治疗HIV感染的病人时,建议单独或联合使用EFAs,尽管没有见到选择性破坏感染病毒的细胞的公开结果。有12种天然存在EFAs,它们是n-6和n-3EFAs,如图1所示。在EP-A-0524796中,引起特别注意的是GLA、DGLA、AA、EPA和DHA。除了上述EFAs以外,其它不饱和脂肪酸如十八碳四烯酸和columbinic acid也具有治疗作用。
本申请人以前已注意到当EFAs经静脉注射给药时,使用其锂盐的优点,例如,公开在欧洲申请第0585057号和第0585058号上的内容。该锂盐是相对水溶性的,所以,可将其加到普通水性静脉注射(IV)液中,使其给药变得简单。此外,因为至少相当大量的锂离子为非身体所原有的,所以锂离子可被用于容易地且迅速地监测输液速度。
现在我们已经发现:不饱和脂肪酸,尤其是其锂盐,对病毒感染的淋巴细胞有独特的作用。HIV感染的淋巴细胞在生理可耐受的锂盐浓度下被杀死,而未被感染的淋巴细胞可幸免。这就提供了这样一种可能性:从体内清除病毒感染细胞,而留下未被损害的正常细胞,因而,与仅减慢病毒繁殖的速度相反,而实际上是治愈病毒感染。已经使用GLA、花生四烯酸盐和二十碳五烯酸盐做了试验,但据认为:至少12种n-6和n-3EFAs可能具相似的作用,其它不饱和脂肪酸如:十八碳四烯酸和columbinic acid及实际上一般具两个或两个以上不饱和度的不饱和脂肪酸也有类似的作用。但是,GLA、其直接代谢产物DGLA、EPA和DHA是优选的,因为当使用时它们对于正常组织安全。
在一系列实验中,将H9正常人淋巴细胞和被HIV菌株慢性感染的H9RF细胞在加有GLA-锂盐的条件下培养,其中的GLA-锂盐浓度分别为0、10、15和20μg/ml。将该细胞培养四天,在第3和第4天使用锥虫兰排除法计数死细胞百分比。其结果见图2,并归纳如下:
1.在无锂-GLA的情况下,两个细胞群都显示:在四天末,死细胞为10-20%。
2.所有浓度的锂-GLA对未感染的H9细胞的作用效果均类似,即在四天末,死细胞为10-20%。因此,锂-GLA对未感染的细胞无毒性作用。
3.相反,被HIV感染的H9RF细胞随着锂-GLA浓度增加,其死亡率逐渐增加。在20μg/ml浓度组,四天中,90%以上的H9RF细胞被杀死。
所以,这些实验证明:在不伤害正常细胞的锂-GLA剂量下,杀死HIV感染细胞,以便清除感染源是可能的。这可能也适用于其它逆转录病毒感染和其它普通病毒感染。
所以,就最广泛的意义而言,本发明涉及通过给与不饱和脂肪酸,尤其是其锂盐,来杀死病毒感染的细胞,以治疗AIDS和HIV感染、其它逆转录病毒感染和普通病毒感染的方法,也相应涉及不饱和脂肪酸,尤其是EFAs,最好是它们的锂盐在制备通过杀灭感染病毒的细胞来治疗AIDS和HIV感染或其它逆转录病毒感染和普通病毒感染的药物方面的用途。
优选的给药途径是静脉内注射,但是,其它给药途径如:口服或其它非肠道给药途径,若合适也可以使用。每日剂量可为1mg-100g/天,以500mg-30g/天为佳,1g-15g/天为最好。
按见于欧洲申请第0585057号和0585058号上的方法,能维持不饱和脂肪酸水平在最高安全血药水平上是重要的,该方法为:
(a)静脉注射给与脂肪酸的方法,利用该方法,给与以锂盐形式的脂肪酸或一定比例脂肪酸,并定期监测血浆中锂的浓度以避免溶血,最好长期保持锂浓度不高于0.7毫摩尔,并且,最好在最初24-48小时内保持锂浓度不高于0.4-0.5毫摩尔,而当只有一定比例的脂肪酸是以锂盐形式给药时,则为所述浓度的相应的比例。
(b)静脉注射给与脂肪酸的方法,利用该方法,在输注脂肪酸前,皮下或静脉注射1000-20000IU最好是3000-10000IU的肝素或相当抗凝剂量的类似肝素的蛋白质或肽,或者将12-100IU、最好是10-20IU/ml肝素或相当抗凝剂量的类似肝素的蛋白质或肽加到含脂肪酸的输液中,或者,将给患者预先注射肝素和往输液中加入肝素这两种方法结合使用。
本发明用下列实施例进一步举例说明。
实施例
下列制剂用于杀灭体内感染细胞,以治疗AIDS或HIV或其它逆转录病毒感染或普通病毒感染。
1.含锂-GLA或锂-DGLA 1g-5g供静脉注射给药的小瓶装溶液,所述小瓶装溶液是用10%-20%乙醇制成的浓度为10%-20%的溶液,每日使用1-2瓶,通过加入等渗盐水中缓慢静脉输注给药。
2.同1中的小瓶,但含GLA或DGLA的钠盐或任何其它溶解度适合的GLA和DGLA衍生物。
3.同1或2中的小瓶,但含任何其它EFA或其它合适的不饱和脂肪酸的同类衍生物,或者含单独一种所述酸,或者含两种或更多种所述酸的混合物。
4.如上所述的EFAs或其它适合的不饱和脂肪酸本身或其衍生物的胶囊剂、片剂、锭剂、drogues或任何其它象这样适宜口服的剂型,每给药剂量单位为0.5g-1.5g的脂肪酸,每日总量为3g-15g。
5.如上所述的EFAs或其它适合的不饱和脂肪酸本身或其衍生物的油剂、泡沫剂、whips、奶油冻,颗粒剂、粉剂或任何其它这样的适宜口服的剂型,每给药剂量单位为0.5g-1.5g的脂肪酸,每日总量为3g-15g。
6.软膏、乳膏、洗剂、油剂、洗发剂或任何其它适合局部用药的剂型,它们含适宜浓度的任何EFAs或其它适宜的不饱和脂肪酸或它们的衍生物,浓度为例如0.1-10重量%的脂肪酸,常规每日用量为如3g-15g脂肪酸。
Claims (6)
1、治疗AIDS和HIV感染的方法,它包括通过给AIDS和HIV感染患者使用有效量的一种或多种不饱和脂肪酸本身或其衍生物,尤其是锂盐来杀灭病毒感染的细胞;所述不饱和脂肪酸或其衍生物尤其是指12种n-6和n-3EFAs,特别是GLA或DGLA或EPA或DHA。
2、按权利要求1的方法,其中,脂肪酸或各脂肪酸的每日所用量为1mg-100g,以500mg-30g为佳,1g-15g更好,最好是静脉注射给药。
3、按权利要求1提出的方法治疗除HIV感染外的逆转录病毒感染的方法。
4、按权利要求1提出方法治疗任何病毒感染的方法。
5、一种或多种不饱和脂肪酸,尤其是它们的锂盐,在制备药物方面的用途,所述药物供通过杀灭体内病毒感染细胞来治疗AIDS和HIV感染、或其它逆转录病毒感染、或普通病毒感染。
6、12种n-6和n-3EFAs特别是GLA或DGLA或EPA或DHA的如权利要求5的用途。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
TW83103554A TW251235B (en) | 1994-03-03 | 1994-04-21 | Treatment of viral infections |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9304746.2 | 1993-03-09 | ||
GB939304746A GB9304746D0 (en) | 1993-03-09 | 1993-03-09 | Treatment of viral infections |
Publications (1)
Publication Number | Publication Date |
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CN1100931A true CN1100931A (zh) | 1995-04-05 |
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ID=10731687
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN94102459A Pending CN1100931A (zh) | 1993-03-09 | 1994-03-09 | 病毒感染的治疗 |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP0615752A1 (zh) |
JP (1) | JPH072663A (zh) |
KR (1) | KR940021056A (zh) |
CN (1) | CN1100931A (zh) |
AU (1) | AU5758594A (zh) |
CA (1) | CA2117214A1 (zh) |
GB (1) | GB9304746D0 (zh) |
NO (1) | NO940810L (zh) |
NZ (1) | NZ260052A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110339187A (zh) * | 2019-07-30 | 2019-10-18 | 中国医学科学院病原生物学研究所 | 缓解寨卡病毒感染相关的新生儿小头症的药物 |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU5000796A (en) * | 1996-01-05 | 1997-08-01 | CESA, Clean Energy SA | Process for the deactivation of hiv and other viruses |
US6576636B2 (en) | 1996-05-22 | 2003-06-10 | Protarga, Inc. | Method of treating a liver disorder with fatty acid-antiviral agent conjugates |
US5795909A (en) | 1996-05-22 | 1998-08-18 | Neuromedica, Inc. | DHA-pharmaceutical agent conjugates of taxanes |
WO1999026958A1 (en) * | 1997-11-25 | 1999-06-03 | Protarga, Inc. | Nucleoside analog compositions and uses thereof |
DE19836339B4 (de) | 1998-08-11 | 2011-12-22 | N.V. Nutricia | Kohlenhydratmischung |
US7235583B1 (en) | 1999-03-09 | 2007-06-26 | Luitpold Pharmaceuticals, Inc., | Fatty acid-anticancer conjugates and uses thereof |
AUPR030800A0 (en) * | 2000-09-22 | 2000-10-12 | Pharmalink International Limited | Immunomodulatory preparation |
WO2002076402A2 (en) | 2001-03-23 | 2002-10-03 | Protarga, Inc. | Fatty amine drug conjugates |
ATE556706T1 (de) | 2001-03-23 | 2012-05-15 | Luitpold Pharm Inc | Fettalkohol-arzneimittel-konjugate |
EP1597978A1 (en) | 2004-05-17 | 2005-11-23 | Nutricia N.V. | Synergism of GOS and polyfructose |
US8252769B2 (en) | 2004-06-22 | 2012-08-28 | N. V. Nutricia | Intestinal barrier integrity |
RU2429718C2 (ru) * | 2004-06-22 | 2011-09-27 | Н.В. Нютрисиа | Повышение целостности барьера у больных с вич |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8319073D0 (en) * | 1983-07-14 | 1983-08-17 | Efamol Ltd | Fatty acid compositions |
GB8320203D0 (en) * | 1983-07-27 | 1983-09-01 | Horrobin D F | Anti-viral compositions |
ES2040847T3 (es) * | 1987-04-27 | 1996-07-16 | Efamol Holdings | Un procedimiento para preparar una composicion farmaceutica que contiene una sal de litio. |
US4997851A (en) * | 1987-12-31 | 1991-03-05 | Isaacs Charles E | Antiviral and antibacterial activity of fatty acids and monoglycerides |
HU209973B (en) * | 1988-03-09 | 1995-01-30 | Biorex Kutato Fejlesztoe Kft | Process for production of antiviral and immunstimular pharmaceutical composition |
EP0400547A1 (en) * | 1989-06-02 | 1990-12-05 | Abbott Laboratories | Parenteral nutrition product |
GB8918294D0 (en) * | 1989-08-10 | 1989-09-20 | Efamol Holdings | Pharmaceutical compositions |
GB9111900D0 (en) * | 1991-06-03 | 1991-07-24 | Efamol Holdings | Fatty acid compositions |
US5604258A (en) * | 1991-06-24 | 1997-02-18 | Women's And Children's Hospital Adelaide | Methods for treating malaria and other diseases |
GB9116054D0 (en) * | 1991-07-24 | 1991-09-11 | Efamol Holdings | Preparation of fatty acid medicaments |
EP0585057A1 (en) * | 1992-08-25 | 1994-03-02 | Scotia Holdings Plc | Lithium salts of fatty acids for the treatment of viral infections and cancer |
-
1993
- 1993-03-09 GB GB939304746A patent/GB9304746D0/en active Pending
-
1994
- 1994-03-07 AU AU57585/94A patent/AU5758594A/en not_active Abandoned
- 1994-03-08 JP JP6037108A patent/JPH072663A/ja active Pending
- 1994-03-08 NZ NZ260052A patent/NZ260052A/en unknown
- 1994-03-08 CA CA002117214A patent/CA2117214A1/en not_active Abandoned
- 1994-03-08 NO NO940810A patent/NO940810L/no unknown
- 1994-03-09 CN CN94102459A patent/CN1100931A/zh active Pending
- 1994-03-09 KR KR1019940004569A patent/KR940021056A/ko not_active Application Discontinuation
- 1994-03-09 EP EP94301654A patent/EP0615752A1/en not_active Withdrawn
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110339187A (zh) * | 2019-07-30 | 2019-10-18 | 中国医学科学院病原生物学研究所 | 缓解寨卡病毒感染相关的新生儿小头症的药物 |
Also Published As
Publication number | Publication date |
---|---|
NO940810D0 (no) | 1994-03-08 |
NO940810L (no) | 1994-09-12 |
GB9304746D0 (en) | 1993-04-28 |
EP0615752A1 (en) | 1994-09-21 |
CA2117214A1 (en) | 1994-09-10 |
AU5758594A (en) | 1994-09-15 |
NZ260052A (en) | 1997-06-24 |
KR940021056A (ko) | 1994-10-17 |
JPH072663A (ja) | 1995-01-06 |
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