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Treatment and prevention of diseases mediated by microorganisms via drug-mediated manipulation of the eicosanoid balance

A technology of microorganisms and antimicrobial agents, applied in the direction of resistance to vector-borne diseases, drug combinations, drug delivery, etc., can solve problems such as development, disease recurrence, drug resistance, etc.

Inactive Publication Date: 2014-06-04
UNITED STATES OF AMERICA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Discontinuation of treatment or use of inadequate dose strengths may result in relapse of disease or development of resistance in patients

Method used

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  • Treatment and prevention of diseases mediated by microorganisms via drug-mediated manipulation of the eicosanoid balance
  • Treatment and prevention of diseases mediated by microorganisms via drug-mediated manipulation of the eicosanoid balance
  • Treatment and prevention of diseases mediated by microorganisms via drug-mediated manipulation of the eicosanoid balance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] This example demonstrates the effect of co-administration of zileuton and PGE2 on C57BL6 mice infected with M. tuberculosis and simultaneously treated with poly-ICLC.

[0086] Four groups of five C57BL / 6 mice ("B6 mice") were used in this study. All four groups were exposed to M. tuberculosis at levels of 100-150 colony forming units via the intranasal aerosol route. A control group of five mice received no further treatment. The comparison group was treated twice weekly via intranasal administration of poly-ICLC, which is polyinosine-polycytidylic acid condensed with poly-L-lysine and carboxymethylcellulose (Oncovir Inc. , Washington, DC). A comparison group of five mice received no further treatment. Five mice in the test group were administered with zileuton (administered at a concentration of 6 mg / mL in drinking water), PGE2 (administered intranasally at a concentration of 6 μg / 30 μL in phosphate-buffered saline per mouse, twice a week) ) and poly-ICLC treatment...

Embodiment 2

[0092] Two groups of five IL-1a / bDKO- / - (IL-1α / β double knockout) mice and a group of five C57BL / 6 mice were used in this study. C57BL / 6 mice were used as controls.

[0093] All three groups were exposed to levels of 100-150 colony forming units of M. tuberculosis via the intranasal aerosol route. Five IL-1a / bDKO- / - mice in the test group and C57BL / 6 mice in the control group were treated with zileuton (administered at a concentration of 6 mg / mL in drinking water) and PGE2 (in phosphate A concentration of 6 μg / 30 μL in saline buffered saline administered intranasally twice a week) for treatment. The IL-1a / bDKO- / - mice in the comparison group were not treated with zileuton and PGE2.

[0094] At 40 days post-infection, no IL-1a / b DKO- / - mice of the comparison group survived. One of the five IL-la / bDKO- / - mice in the test group died on day 40, and the remaining four mice survived more than 40 days but less than about 65 days. All C57BL / 6 mice in the control group survived for...

Embodiment 3

[0098] C57BL6 were infected by aerosol route with 200 CFU of Mtb and poly-ICLC were administered twice weekly. As a control, a group of mice was treated with PBS and not poly-ICLC. The second group of mice received no further treatment. A third group of mice was further treated with PGE2. The fourth group of mice was further treated with PGE2 and zileuton. A fifth group of mice was further treated with zileuton alone.

[0099] After a period of time, the colony forming units ("CFU") in the lungs of each group of mice were determined and the results are graphically shown in Figure 5 middle.

[0100] as in Figure 5 From the results plotted in it is clear that the control group has about 7.4log 10 CFU. Mtb-infected poly-ICLC-treated mice had approximately 8.9 log 10 CFU. Mtb-infected poly-ICLC treated mice further treated with PGE2 had approximately 9.2 log 10 CFU. Mtb-infected poly-ICLC treated mice further treated with PGE2 had approximately 8.9 log 10 CFU. Mtb-i...

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Abstract

The invention provides a method of enhancing the efficacy of antibiotic treatment of tuberculosis, trypanosomiasis, leprosy, and leishmaniasis involving co-administering to a mammal undergoing antibiotic treatment therapeutically effective amounts of a first compound that is an inhibitor of 5-lipoxygenase and optionally a second compound that is a product of the cyclooxygenase pathways. The invention also provides a pharmaceutical composition comprising an antibiotic, an inhibitor of 5-lipoxygenase, and a product of the cyclooxygenase pathways.

Description

[0001] Cross References to Related Applications [0002] This patent application claims the benefit of US Provisional Patent Application No. 61 / 515,229, filed August 4, 2011, and US Provisional Patent Application No. 61 / 515,237, filed August 4, 2011, which are incorporated by reference. Background of the invention [0003] It is known that diseases such as tuberculosis, trypanosomiasis, leprosy and leishmaniasis are caused by microorganisms. These diseases result in the death and disfigurement of the patient. Tuberculosis, for example, remains the leading cause of death. There are approximately 8 million active cases of tuberculosis each year, with 3 million deaths each year attributed to it. An estimated 1.7 billion people carry latent Mycobacterium tuberculosis infection. [0004] Currently, treatment of tuberculosis consists of the combined administration of four first-line drugs: isoniazid, rifampicin, ethambutol and pyrazine Pyrazinamide, administered alone as a singl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/381A61K31/404A61K31/41A61K31/47A61K31/5575A61K31/63A61K45/06A61P31/06A61P31/08A61P33/02
CPCA61K31/404A61K31/47A61K31/145A61K45/06A61K9/0043A61K31/417A61K31/41A61K31/5575A61K31/381A61K31/63A61P31/06A61P31/08A61P33/02Y02A50/30A61K2300/00
Inventor 卡特里娜·迈尔-巴伯布鲁诺·德·贝泽里尔·安德拉德艾伦·谢尔丹尼尔·里奥·巴伯
Owner UNITED STATES OF AMERICA
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