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Aqueous Suspensions of TMC278

a technology of tmc278 and suspension, which is applied in the field of pharmaceutical compositions, can solve the problems of resistance, no currently available drug therapy is capable of completely eradicating hiv, and emergence of resistant mutants, so as to prevent hiv infection, prevent hiv infection, and prevent the effect of hiv infection

Inactive Publication Date: 2015-01-08
JANSSEN SCI IRELAND UC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about a pharmaceutical composition that can be injected into the body for the treatment and prevention of HIV infection. The composition contains a therapeutically effective amount of a drug called TMC278, which is suspended in micro- or nanoparticles made of a surface modifier. The composition is administered through an aqueous carrier and can be given intermittently at a time interval of one week to one year or one week to two years. The invention also includes a method for preventing HIV infection in individuals who are at risk of being infected. The pharmaceutical composition can be used for the long-term treatment and prevention of HIV infection.

Problems solved by technology

The treatment of Human Immunodeficiency Virus (HIV) infection, known as cause of the acquired immunodeficiency syndrome (AIDS), remains a major medical challenge.
Although effective in suppressing HIV, each of these drugs, when used alone, is confronted with the emergence of resistant mutants.
However, none of the currently available drug therapies is capable of completely eradicating HIV.
Even HAART can face the emergence of resistance, often due to non-adherence and non-persistence with antiretroviral therapy.
A high pill burden is undesirable for many reasons, such as the frequency of intake, often combined with the inconvenience of having to swallow large dosage forms, as well as the need to store and transport a large number or volume of pills.
A high pill burden increases the risk of patients not taking their entire dose, thereby failing to comply with the prescribed dosage regimen.
As well as reducing the effectiveness of the treatment, this also leads to the emergence of viral resistance.
The problems associated with a high pill burden are prominent in anti-HIV therapy where a patient must take a large number of different anti-HIV agents.
HIV can never completely be eradicated so that persons infected with HIV pose a continuous risk of infecting others.
Despite these measures there is always an imminent risk of individuals being in contact with HIV infected persons of becoming infected.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of Nanosuspensions

[0111]Glass bottles of 250 ml and ZrO2 beads, used as the milling media, were sterilized in an autoclave. Five grams of drug substance were put into the 250 ml glass bottle as well as a solution of 1.25 g PLURONIC™ F108 in 60 ml of water for injection. Three hundred grams of ZrO2-beads with an average particle size of 500 μm were added. The bottle was placed on a roller mill. The suspension was micronized at 100 rpm during 72 hours. At the end of the milling process the concentrated nanosuspension was removed with a syringe and filled into vials. The resulting formulation is Formulation 1 in the following table. Determination of the concentration was done by HPLC / UV. A dilution was made to a final concentration of 25 mg / ml of TMC278. The resulting suspension was shielded from light.

[0112]Using similar procedures, Formulations 2, 3 and 4 were prepared. These were titrated with sodium hydroxide 1N solution to a pH of about 7. In formulations 2, 3 and 4 th...

example 2

Kinetic Study

[0113]The present study demonstrates that an injectable formulation of nanonised TMC278 or its HCl-salt results in stable blood plasma levels during a prolonged period of time. This study compares the plasma kinetics of TMC278 base and hydrochloric salt after single intramuscular (IM) or subcutaneous injection of a nanosuspension (Formula 1 of the previous example) at 5 mg / kg in male beagle dogs.

[0114]Six healthy male beagle dogs with body weights ranging from 8 to 16 kg at the start of the study, were used. Each dog was identified by an ear tattoo number. Two dogs were dosed intramuscularly (IM) in the left and right m. biceps femoris (treatment group A). Two dogs were dosed IM with TMC278.HCl (treatment group B). Two dogs were dosed subcutaneously (SC) in the left and right thoracal region. The injection volume was 2×0.1 ml / kg in all treatment groups. A 20 G needle was used.

[0115]Blood samples of 3 ml were taken from the left jugular vein from all dogs on day 0 at 0 h...

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Abstract

This invention concerns pharmaceutical compositions for administration via intramuscular or subcutaneous injection, comprising micro- or nanoparticles of the NNRTI compound TMC278, suspended in an aqueous pharmaceutically acceptable carrier, and the use of such pharmaceutical compositions in the treatment and prophylaxis of HIV infection.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001]This application is a divisional of U.S. application Ser. No. 12 / 305276, filed 17 Dec. 2008, currently pending, which is a national stage application of International Patent Application Number PCT / EP2007 / 056230, filed 22 Jun. 2007, which claims priority to European Patent Application Number 06115398.0, filed 23 Jun. 2006. The entire contents of each of the aforementioned applications are incorporated herein by reference in their entireties.FIELD OF THE INVENTION [0002]This invention concerns pharmaceutical compositions for administration via intramuscular or subcutaneous injection, comprising micro- or nanoparticles of the NNRTI compound TMC278, suspended in an aqueous pharmaceutically acceptable carrier, and the use of such pharmaceutical compositions in the treatment and prophylaxis of HIV infection.BACKGROUND OF THE INVENTION[0003]The treatment of Human Immunodeficiency Virus (HIV) infection, known as cause of the acquired immunodefic...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/10A61K9/14A61K31/505
CPCA61K47/10A61K9/14A61K31/505A61K9/0019A61K9/145A61K9/146A61K31/00A61P31/00A61P31/12A61P31/18A61K9/10A61K47/34
Inventor BAERT, LIEVEN ELVIRE COLETTEDRIES, WILLIE ALBERT MARIA CARLOSCHUELLER, LAURENT BRUNOFRANCOIS, MARC KAREL JOZEFVAN REMOORTERE, PETER JOZEF MARIA
Owner JANSSEN SCI IRELAND UC