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Composition and methods used during Anti-hiv treatment

a technology of composition and treatment, applied in the field of antihiv composition and treatment of hiv-infected patients, can solve the problems of perinatal lethality in mice, modification of the assembly of proteins in the nuclear envelope, and disruption of its functioning

Inactive Publication Date: 2011-02-24
UNIV DAIX MARSEILLE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes an anti-HIV composition and processes for treating HIV-infected patients. The invention is particularly useful for treating side effects caused by certain anti-HIV treatments, such as premature aging and lipodystrophy. The invention is also useful for treating HIV-infected patients who have developed resistance to certain treatments. The patent text describes the use of an anti-HIV composition that targets the HIV protease and the HIV reverse-transcriptase. The invention is also about a process for treating HIV-infected patients using the anti-HIV composition. The patent text references the use of a specific anti-HIV composition that targets the HIV protease and the HIV reverse-transcriptase. The invention is also about a process for treating HIV-infected patients using the anti-HIV composition.

Problems solved by technology

Indeed, a lamin B1 deficiency causes perinatal lethality in mice.
A number of mutations of the LMNA gene notably modify the assembly of proteins in the nuclear envelope and disrupt its functioning.
These morphological abnormalities are followed by functional alterations, and end by causing cell death.
The skin is rigid and taut, and gives way in places, causing, for example, tears at the armpits or the neck.
The latter, including myocardial infarction or atherosclerosis, are often the cause of death.
Cell nuclei in patients aging “normally” can have bulges characteristic of a laminopathy caused by accidental splicing events, which lead to abnormal cell functions and probably at least partially responsible for their aging.
The results are promising in vitro, but this is “gene” therapy, and the development of a drug based on this approach is extremely long and complicated, with all of the inconveniences associated with OAS vectorization in order to obtain an in vivo effect.
Finally, FTIs are specific to only one of the protein prenylation pathways, and cannot be envisaged as general post-translational prenylation inhibitors.
Whether they are genetic or acquired, these abnormalities in the nuclear matrix result in genomic instability and cell aging (Mehta et al., 2007; Oberdoerffer and Sinclair, 2007).
Abnormalities in lamin A cause a reduction in telomerase activity, resulting in accelerated telomere shortening.

Method used

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  • Composition and methods used during Anti-hiv treatment
  • Composition and methods used during Anti-hiv treatment
  • Composition and methods used during Anti-hiv treatment

Examples

Experimental program
Comparison scheme
Effect test

example 1

Additive Effect of the Association of a Hydrosoluble Hydroxymethylglutaryl-Coenzyme A (HMG-CoA) Reductase Inhibitor (a Hydrosoluble Statin: Pravastatin) and a Farnesyl-Pyrophosphate Synthase Inhibitor (an Aminobiphosphonate: Zoledronate) on Normal and Progeroid Cell Cultures

A. Protocols

A.1 Cells and Cell Culture

[0212]The cell lines are either control fibroblasts AG16409 from the Coriell Institute or fibroblasts from biopsies of patients with restrictive dermopathy. They are cultivated at 37° C. under 5% CO2 in room P2.

The usual complete culture medium is:[0213]RPMI (Invitrogen) complemented with[0214]Fetal bovine serum 20% (Invitrogen)[0215]L-Glutamine 200 mM (Invitrogen)[0216]Mixture of Penicillin / Streptomycin / Fungizone 1× (Stock 100×, Cambrex)

A.2 Cell Harvesting

[0217]The harvesting of cells is performed by trypsinization as follows (protocol for a large flask, 75 cm2, BD Falcon):[0218]The medium is suctioned;[0219]The cells are washed with 10 ml of PBS 1× (Invitrogen);[0220]5 ml o...

example 2

Effect of a Composition According to the Invention Including a Hydrosoluble Hydroxymethylglutaryl-Coenzyme A (HMG-CoA) Reductase Inhibitor and a Farnesyl-Pyrophosphate Synthase Inhibitor on the Division of Aged Human Fibroblasts and on Young Human Fibroblasts

A. Example Objective

[0293]In this example, the evaluation of the in vitro effect of a composition according to the invention including a hydrosoluble hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor and a farnesyl-pyrophosphate synthase inhibitor on the rate of cell division (mitotic index) of fibroblasts was measured. A comparison of the effect of the composition on aged human fibroblasts with respect to young human fibroblasts was also performed. The number of active agents used in this experiment is four, and the products were used in pair combinations. The active agents used are:[0294]A1: Zolendronate[0295]A2: Alendronate[0296]B1: Pravastatin[0297]B2: Simvastatin

[0298]The specific associations that were used in...

example 3

Effect of the Association of a Hydrosoluble Hydroxymethylglutaryl-Coenzyme A (HMG-CoA) Reductase Inhibitor and a Farnesyl-Pyrophosphate Synthase Inhibitor on a Mouse Model Having a Progeroid Syndrome

[0312]The Zmpste24− / − KO mice used here are those described in the cited article of Varela & al., 2005 (49). Evidence of efficacy of the association of the two molecules (pravastatin and zoledronate) was reported in collaboration with a Spanish laboratory (C. Lopez-Otin). The efficacy is obtained at combined doses that do not have an effect when the products are used separately, demonstrating an additive effect.

[0313]The two molecules (Zoledronic acid (Zometa (registered trademark)) 100 μg / kg / day and Pravastatin 100 mg / kg / day) were diluted in PBS 1× and injected intraperitoneally, on a daily basis, in 1-month-old mice until their death. The controls are wild mice of the same range, treated with PBS 1× alone.

[0314]The survival of the treated mice was significantly improved, and was maxima...

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Abstract

This invention relates to a composition comprising an anti-HIV treatment and a treatment for side effects of said anti-HIV treatment in an HIV-infected patient. This invention is, for example, very useful in the treatment of side effects caused by certain anti-HIV treatments, for example premature aging and lipodystrophy, which can be caused by protease inhibitors or reverse transcriptase inhibitors. The composition of this invention includes at least one hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, at least one farnesyl-pyrophosphate synthase inhibitor, and at least one anti-HIV agent. One of the processes for treating an HIV-infected patient includes, in any order, the following steps: (i) administration of a mixture including at least one hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor and at least one farnesyl-pyrophosphate synthase inhibitor and (ii) administration of an anti-HIV agent, in which the administrations are concomitant, successive or alternative.

Description

RELATED APPLICATIONS[0001]The present application relates to French Patent Application No. FR 08 / 50019 filed on Jan. 3, 2008. This application also relates to French Patent Application No. FR 06 / 06097 filed on Jul. 5, 2006 and its corresponding PCT Application filed on Jul. 5, 2007 entitled “Médicament destine au traitement des maladies avec persistence et / ou accumulation de proteins prénylées” [“Drug intended for the treatment of diseases with persistence and / or accumulation of prenylated proteins”]. The entire contents of each of the above-referenced patent applications are hereby incorporated by reference.TECHNICAL FIELD[0002]The invention relates to an anti-HIV composition and processes for treating an HIV-infected patient.[0003]This invention is, for example, very useful in the treatment of side effects caused by certain anti-HIV treatments, for example premature aging and lipodystrophy, which can be caused by protease inhibitors or reverse-transcriptase inhibitors.[0004]In the...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/663A61P31/18
CPCA61K31/22A61K31/675A61K45/06A61K2300/00A61K31/427A61K31/496A61K31/366A61K31/4025A61K31/66A61K31/665A61K31/215A61P17/00A61P3/00A61P31/18A61P39/06A61P43/00
Inventor CAU, PIERREBOURGEOIS, PATRICEBONNIOL, VINCENTLEVY, NICOLAS
Owner UNIV DAIX MARSEILLE
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