Hydrogen sulfide releasing polymer compounds

a technology of hydrogen sulfide and polymer compounds, which is applied in the field of polymer compounds, can solve the problems of difficult administration of hydrogen sulfide, and inability to control the release of hydrogen sulfide by hydrolysis

Pending Publication Date: 2022-07-28
CROMA PHARMA GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The polysaccharide-based hydrogen sulfide releasing polymers provide a stable and controlled release of hydrogen sulfide, suitable for therapeutic applications in skin conditions, ocular diseases, and osteoarthritis, with applications as dermal fillers, intraocular implants, viscosupplements, and wound dressings, enhancing wound healing and lubrication properties.

Problems solved by technology

Being a gaseous compound, hydrogen sulfide is difficult to administer.
A major disadvantage of all compounds which release hydrogen sulfide by hydrolysis is their instability in aqueous solution.
Once these compounds are dissolved in water hydrogen sulfide is released in an uncontrollable manner.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 4

f Hydrogen Sulfide

[0132]The investigated polymer compounds according to the invention (as shown in FIGS. 1A and 1C) were analyzed for their hydrogen sulfide release properties in presence of a thiol containing component with an amperometric detection device (H2S Micro-Sensor with H2S permeable membrane; AMT Analysenmesstechnik GmbH). The H2S release was triggered by the addition of L-cysteine.

[0133]FIG. 6 depicts the results of a H2S release assay, wherein 50 mL of a 0.1% (m / m) solution of the H2S releasing chitosan derivative, which was synthesized as described in example 1, was prepared with 50 mM acetate buffer (pH 5.5). To the resulting solution, which had a pH of 5.3, 1.5 mL of a 100 mM solution of L-cysteine were added. The resulting release of H2S was monitored at room temperature.

[0134]FIG. 7 depicts the results of a H2S release assay, wherein 0.1% (m / m) of a H2S releasing hyaluronic acid derivative of example 2 (FIG. 1A) were incubated in DMEM (Dulbecco's modified eagle med...

example 6

ling Preparation—Sponge

[0138]An aqueous hydrogel solution comprising 1.5% (m / m) H2S releasing chitosan derivative with a degree of modification of about 185 mol S-acetyl moieties according to the invention is prepared. The solution is cast into 12 well cell culture plates-in an amount of 0.9 g per well) and freeze dried. The resulting lyophilisate is a sponge with a round shape and has a diameter of about 2 cm. The sponges are sealed individually in pouches. The pouches and secondary packaging material are then sterilized via gamma irradiation.

[0139]For the treatment of wounds the sterile sponges are applied on the skin wound. A few drops of a sterile buffered solution of N-acetylcysteine in a concentration of 5 mg / mL may be applied on the sponge to immediately start the release of H2S. The wound area is then covered with a secondary wound dressing with low gas permeability, such as a film consisting of polyethylene, polypropylene or polytetrafluoroethylene or a fabric or fleece tha...

example 7

tment—Topical Hydrogel

[0140]An aqueous hydrogel solution comprising 1% (m / m) H2S releasing hyaluronic acid derivative with a degree of modification of about 250 mol S-acetyl moieties according to the invention is prepared in a phosphate buffer with a physiologically acceptable pH value. The solution is then filled into single use containers (e.g. single dose polypropylene containers or glass syringes with a filling volume of about 3 mL) and sterilized with moist heat. A second composition comprising N-acetylcysteine in a physiologic buffer solution in a concentration of 10 mg / mL is also provided in a single use container. The resulting hydrogel with a low viscosity is applied on intact skin or inflamed skin areas, immediately followed by the application of approximately the same amount of the composition comprising N-acetylcysteine to the same skin area.

[0141]The treatment with the hydrogel may be preferred in case of cosmetic skin conditions or skin disease such as for treatment of...

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Abstract

The invention provides a hydrogen sulfide releasing polymer compound having a polysaccharide backbone, wherein the compound has at least two substructures, and wherein said substructures are capable of releasing hydrogen sulfide by thiol activation as well as uses thereof. Additionally, a method of treatment and prevention of a skin condition, an ocular disease or osteoarthritis is provided.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This Application is a continuation of U.S. patent application Ser. No. 16 / 348,012, filed May 7, 2019, which is a 371 of International Patent Application No. PCT / EP2017 / 078421, filed Nov. 7, 2017, which claims the benefit of European Patent Application No. 16197625.3, filed Nov. 7, 2016, which are incorporated by reference in their entireties.BACKGROUND[0002]The invention relates to hydrogen sulfide releasing polymer compounds and uses thereof.[0003]Hydrogen sulfide (H2S) is a biological signalling molecule. Its function seems to be comparable and potentially linked with the better investigated gaseous transmitter nitric oxide (NO). Hydrogen sulfide is believed to be involved in processes like angiogenesis and inflammation. H2S and / or H2S releasing compounds were shown to have an anti-inflammatory effect, inhibit apoptosis in vascular endothelial cells and cardiomyocytes, and induce vasodilatation. Being a gaseous compound, hydrogen sulfid...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K31/728A61P17/10A61P17/02A61K8/73A61K9/00A61K9/06A61K31/726A61Q19/08C08B37/08A61K31/105A61P27/02A61Q19/00A61P17/18A61P17/00A61K31/795A61P19/02C08B37/00C08B15/00
CPCA61K31/728A61K2800/91A61P17/02A61K8/735A61K8/736A61K9/0019A61K9/06A61K31/726A61Q19/08C08B37/003C08B37/0072A61K31/105A61P27/02A61Q19/00A61P17/18A61P17/00A61K31/795A61P19/02C08B37/0045C08B37/0069C08B15/00C08B37/0084A61P17/10A61K31/717A61K31/166A61K9/0021A61P17/08A61K8/731C08F251/00C08F251/02A61K31/05A61K8/73A61K8/733
InventorPRINZ, MARTINHOFFER, MARTIN
OwnerCROMA PHARMA GMBH