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Multi-kinase inhibitors of VEGF and tgf[beta] and uses thereof

A mammalian, angiogenesis technology, applied in medical formulations containing active ingredients, anti-inflammatory agents, non-central analgesics, etc., can solve problems such as unsatisfactory treatment strategies, complex pathophysiology, and incomplete understanding.

Pending Publication Date: 2021-05-25
AIVIVA BIOPHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] As the pathophysiology of these diseases is complex and not fully understood, available therapeutic strategies are often unsatisfactory

Method used

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  • Multi-kinase inhibitors of VEGF and tgf[beta] and uses thereof
  • Multi-kinase inhibitors of VEGF and tgf[beta] and uses thereof
  • Multi-kinase inhibitors of VEGF and tgf[beta] and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0201] The preparation of the pharmaceutical compositions described herein can be carried out according to generally accepted methods for the preparation of pharmaceutical formulations. See, eg, Remington's Pharmaceutical Sciences, 18th Edition (1990), edited by E.W. Martin, Mack Publishing Co., PA. Liquid forms for administration by injection include aqueous solutions, aqueous or oily suspensions, emulsions, microbeads, and the like. Creams or ointments may include aqueous solutions, aqueous or oily suspensions, emulsions, microbeads and the like. Suitable excipients may include solvents and / or co-solvents; solubilizers, wetting agents, suspending agents, emulsifying or thickening agents; chelating agents; antioxidants and reducing agents; antimicrobial preservatives; pH regulators; fillers; protective agents; tonicity regulators; Dosage forms can be stored or reconstituted as liquids for use.

[0202] Some embodiments include kits comprising: a compound described herein, ...

Embodiment 1

[0204] Example 1. Some multikinase inhibitors reduce skin inflammation in mice following LL-37 challenge.

[0205] Recent studies have shown a link between rosacea triggers (including Demodex folliculorum, UV radiation, stress, etc.) and the induced cellular and tissue responses. It has been proposed that the pathogenesis of the disease involves an altered innate immune response (Yamasaki, K and Gallo, R., J Dermatol Sci., 55:77-81, 2009).

[0206] Triggering the innate immune system often results in a controlled increase of cytokines and antimicrobial peptides (such as cathelicidins) in the skin. Some forms of antimicrobial peptides have both pro-inflammatory and vasoactive properties. Individuals with rosacea not only express high levels of antimicrobial peptides, but also produce forms of antimicrobial peptides that promote leukocyte chemotaxis, angiogenesis, and expression of extracellular matrix components. It has been shown that injecting these peptides into the skin o...

Embodiment 2

[0215] Example 2. Some multikinase inhibitors reduce skin TGFb1 levels after trauma-induced inflammation in minipigs.

[0216] The aim of this study was to evaluate the local effects of axitinib, nintedanib, sorafenib, and lenvatinib when administered via intradermal injection into the dorsal skin along a linear incision in minipigs. A linear incision wound is made to initiate inflammation and wound healing processes in the skin. After dosing, the mammals were observed for 9 days after dosing to assess the level of TGFb1 expression in the skin.

[0217] Three male Gottingen mice were injected via intradermal injection along the edge of each linear incision wound site (a wound on the back perpendicular to the spine, approximately 3 cm long and 3 cm from the spine) in each mammal. Batch once. Each incision wound received approximately 16 mg of test compound once intradermally along both sides of the linear wound.

[0218] One 4mm dermal punch biopsy of each incisional wound ...

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Abstract

A pharmaceutical composition for prevention or treatment of a disease or disorder characterized by chronic inflammation, associated with angiogenesis and fibrosis. The pharmaceutical composition includes a multi-target inhibitor, multi-phase modulator, or multi-kinase inhibitor, such as axitinib, nintedanib, pirfenidone, riociguat, sorafenib, sunitinib, lenvatinib, regorafenib, ponatinib, or pazopanib.

Description

technical field [0001] The present disclosure relates to methods of preventing and treating diseases or conditions characterized by chronic inflammation associated with angiogenesis and fibrosis, such as psoriasis, rosacea, erythema multiforme, bullous Pemphigus, Hereditary Hemorrhagic Telangiectasia, Rheumatoid Arthritis, Atopic Dermatitis, and Skin Wound Healing. Background technique [0002] Chronic inflammation associated with angiogenesis and fibrosis is a feature of many diseases such as psoriasis, rheumatoid arthritis and rosacea. While these broad pathologies are contributing factors, the underlying causes of these disorders are often unclear. [0003] For example, the cause of rosacea, which is characterized by facial redness, dilated blood vessels, papules, pustules, and swelling on the skin of the face, remains unknown. It is well known that episodic symptoms of flushing and redness may play a role in the development of rosacea, whatever the trigger. [0004] S...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4439G01N33/574
CPCA61K31/4439A61K31/496A61K31/4418A61K31/506A61K31/44A61K31/404A61K31/5025G01N33/5082A61K31/47A61K31/4412A61P29/00A61P43/00A61P17/00A61P13/08A61P27/02A61P17/06A61P35/00A61P19/04A61P15/00A61K31/501
Inventor 杰拉尔德·伍德罗·德弗里斯汤丹霞
Owner AIVIVA BIOPHARMA INC
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