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Nrti therapies

A product, polymer technology, applied in the direction of drug delivery, powder delivery, antiviral agents, etc., can solve problems such as the route of administration or the frequency of dosing intervals that are rarely discussed

Pending Publication Date: 2021-10-01
UNIV OF LIVERPOOL +1
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Recently reported pegylated proteins 18 , pegylated drugs (maraviroc) 19 and polymer - zidovudine 20 Conjugates are intended to target the route of infection within the systemic circulation, but route of administration or frequency of dosing intervals is rarely discussed, and actual drug release is not targeted by these systems

Method used

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Embodiment Construction

[0038] Figure 1 shows NRTIs (TFV, FTC, 3TC, and EFdA) with multiple functional groups that undergo a step-growth polymerization strategy.

[0039] The present invention offers several novel solutions, including three synthetic strategies (Fig. 1) that exploit the reactivity of NRTIs in polymerization, such as: 1) Reaction of A-B type NRTI monomers with complementary linkers (Strategy 1 ); 2) A 2 Prodrug monomer and B 2 Reaction of the Linker (Strategy 2); and 3) A 2 pendant prodrug monomer with B 2 Linker Reaction (Strategy 3).

[0040] Therefore, a key innovative aspect of the present invention is the use of a "prodrug polymer" (POP) approach, which utilizes NRTI prodrug strategies to address a key need of LA NRTI regimens. These NRTI prodrug strategies enable the synthesis of biodegradable NRTI POP structures. Materials with specific polymer structures are used to create polymer constructs, which are physically assembled implementations of polymer structures (nanopartic...

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Abstract

Polymer-of-prodrug (POP) materials enable new nucleoside reverse transcriptase inhibitor (NRTI) therapy strategies. The materials are prodrugs of NRTIs in the form of polymers. Suitable materials include products which are polymeric NRTI delivery systems comprising polymeric materials which are capable of degradation after administration to release NRTIs or NRTI prodrugs which themselves are capable of metabolism to the parent NRTIs. The NRTIs may optionally be selected from tenofovir (TFV), emtricitabine (FTC), lamivudine (3TC) and MK-8591 (EFdA). The invention facilitates long-acting (LA) regimens. Constructs of the materials may be in the form of injectable compositions or implants.

Description

technical field [0001] The present invention relates to prodrugs of nucleoside reverse transcriptase inhibitors (NRTIs) and their polymeric delivery systems. Background technique [0002] Antiretroviral therapy (ART) involves the long-term co-administration of several drug classes to simultaneously act on multiple HIV viral targets, maximizing suppression of viral replication and minimizing the emergence of drug resistance. UNAIDS statistics show that in 2015, an estimated 37 million people worldwide were infected with HIV (including 1.8 million children), and 1.1 million AIDS-related deaths occurred in 2015 alone. Some 35 million people have died and 78 million have been infected since the outbreak began. In recent years 1 , access to ART has increased to approximately 17 million patients, and to date, six classes of antiretroviral drugs (ARVs) are available: nucleoside / nucleotide reverse transcriptase inhibitors (NRTIs); non-nucleoside reverse transcriptase inhibitors (N...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/55A61K47/59A61K47/60A61K47/69A61P31/18
CPCA61K47/55A61K47/59A61K47/60A61K47/6921A61P31/18
Inventor 安德鲁·欧文史蒂文·兰纳德费伊·赫恩刘聪阿尼卡·沙基勒梅甘·内亚里卡伦·弗里·迈耶斯卡尔蒂克·滕贝尔尼科尔劳伦·班巴格斯蒂芬妮·亨里克兹
Owner UNIV OF LIVERPOOL
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