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Biodegradable polyesteramide used for the treatment of arthritic disorders

An arthritic, inflammatory technology in the field of biodegradable polyesteramides for the treatment of arthritic conditions

Active Publication Date: 2020-08-11
DSM IP ASSETS BV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, a disadvantage of this formulation is the hydrolytic degradation of the lactic-co-glycolic acid, releasing acidic by-products as the polymer degrades

Method used

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  • Biodegradable polyesteramide used for the treatment of arthritic disorders
  • Biodegradable polyesteramide used for the treatment of arthritic disorders
  • Biodegradable polyesteramide used for the treatment of arthritic disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0101] Fabrication of TAA-loaded PEA-III-Bz microparticles

[0102] 300 mg of PEA-III-Bz was dissolved in dichloromethane. 75 mg of TAA was added to the solution and homogenized by sonication. use The suspension was added to 20 ml of cold water containing 1 wt% poly(vinyl alcohol) under high shear. After obtaining a stable suspension, the particles were hardened for 12 hours in 100 ml of water containing 1% by weight of poly(vinyl alcohol). Excess water and surfactant were removed by rinsing and centrifugation. Finally, the particles are frozen and dried under vacuum. exist figure 1 A picture of the particles is given in . figure 2 The particle size distribution is given in .

Embodiment 2

[0104] Culture of chondrocytes in the presence of TAA-loaded PEA-III-Bz microparticles

[0105] OA chondrocytes were harvested from three human donors and cultured from total knee arthroplasty. Cells were incubated with 5 µg of microparticles produced in Example 1 in transwells. Cells and media were collected every three days and transwells were transferred to wells with freshly plated OA chondrocytes from the same donor. The amount of PGE-2 (prostaglandin-E2) produced by the cells during the incubation time was determined by ELISA.

[0106] The total duration of the experiment was 38 days.

[0107] Cells were cultured under the following conditions:

[0108] 1. Control experiment; no particles

[0109] 2. Positive control, chondrocytes stimulated by TNF-α, without granules

[0110] 3. Chondrocytes stimulated by TNF-α were incubated with 5 μg of empty PEA-III-Bz particles

[0111] 4. Chondrocytes stimulated by TNF-α were incubated with 5 μg of PEA-III-Bz particles load...

Embodiment 3

[0115] Cumulative release of fluorescein from PEA-III-Bz membranes

[0116] A proof-of-principle study has been performed employing fluorescein as a slowly released dye from the membrane.

[0117] In acute inflammation, polymorphonuclear neutrophils (PMNs) are the first type of cells to migrate to the site of inflammation, where they produce several pro-inflammatory mediators, including attracting other PMNs and other cell types (such as monocytogenes). Chemokine for nuclear cells - macrophages and lymphocytes), corresponding to chronic inflammation. Neutrophils and macrophages are two cell types known to interact with biomaterials, which may lead to their degradation. Using differentiated HL60 neutrophil-like cells, the interaction of neutrophil-like cells with biomaterials can be modeled. Neutrophils are inflammatory cell first responders that migrate to sites of inflammation and are known to have a high level of interaction with foreign bodies such as biological materia...

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Abstract

The invention relates to biodegradable polyesteramide used for the treatment of arthritic disorders. The present invention relates to a formulation sized for injection comprising a biodegradable polyesteramide co-polymer comprising at least a diol of bicyclic-1,4:3,6-dianhydrohexitol and analgesics for use in the treatment of arthritic disorders. More specific the invention relates to a formulation comprising injectable microparticle according to claim 1 wherein the polyesteramide co-polymer further comprises a diacid, a diol different from bicyclic-1,4:3, 6-dianhydrohexitol and at least two different amino-acids. The formulation is used to treat pain or inflammation in a patient comprising administering to said patient a therapeutically effective amount of the formulation once or twice ayear.

Description

[0001] This application is the application date of March 06, 2015, and the application number is "201580018254.9" (International Application No. PCT / EP2015 / 054785) of the invention patent application "Biodegradable polyester amide for the treatment of arthritis conditions" Divisional application. technical field [0002] The present invention relates to a formulation for use in the treatment of arthritic conditions comprising a preparation of injectable size comprising a biodegradable polyester amide copolymer comprising at least one bicyclic-1,4: Diol of 3,6-dianhydrohexitol (dianhydrohexitol). The invention also relates to said formulation for use in the treatment of arthritic conditions, administered as 1 or 2 injections per year. Background technique [0003] Arthritic conditions are associated with a strong inflammatory response causing pain and discomfort to the patient. Pain is associated with many medical conditions and affects millions of people. The American Pai...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/16A61K47/34A61K31/58A61P19/02A61P29/00
CPCA61K9/0024A61K9/1647A61K31/573A61L27/18A61L27/54A61L2300/41A61L2300/402A61L2400/06A61L2430/24C08L77/12A61K31/785A61P19/02A61P29/00A61K9/0019A61K9/1617C08G69/44
Inventor 延斯·克里斯托·蒂斯德特莱夫·欧拉夫·亚历山大·舒曼乔治·米霍夫朱利安·弗朗索瓦·贝拉尔德
Owner DSM IP ASSETS BV
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