Composition preventing tissue adhesion and preparation method thereof

Inventors

Choi, Jin-SukLee, Young-WooLee, Yun-geeKim, Jun-hoLee, Jin-ho

Assignees

GENEWEL CO LtdInstitute for Industry Academia Cooperation of Hannam University

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Publication Number

US-9095643-B2

Patent

Publication Date

2015-08-04

Expiration Date


Abstract

Provided is a composition preventing tissue adhesion and a method for preparing the same, and, more particularly, a composition preventing tissue adhesion which further contains a drug selectively inhibiting inflammatory response and a method for preparing the composition, in which the composition is produced through a chemical reaction by adding a cross-linking agent to an aqueous solution which contains a block copolymer containing a polyethyleneoxide block having the ability to suppress tissue adhesion, and a polymer with 10,000 to 1,000,000 g/mol of molecular weight which can be mixed with the copolymer; the composition is characterized in that the difference of viscosity, absorbance of visible rays region, and stability between the upper and lower liquid layers are within 10% when centrifuging the composition; and also the method for preparing the composition enhances cross-linking homogenization and viscosity stability through simultaneous spraying and stirring methods without a reaction retardant.

Core Innovation

A composition preventing tissue adhesion is provided as a combination of a first aqueous solution and a second aqueous solution. The first aqueous solution comprises 1 to 50 wt% of a block copolymer having 1,000 to 500,000 g/mol molecular weight and comprising a polyethyleneoxide block, and 0.1 to 4 wt% of a polymer of 10,000 to 1,000,000 g/mol molecular weight capable of being mixed with the block copolymer. The second aqueous solution comprises 0.01 to 2 wt% of a cross-linking agent.

The cross-linking agent is selected from acetate or halide compounds including one or more cations selected from Mg2+, Mn2+, Ca2+, Cu2+, Sr2+, Ba2+, Fe2+, and Co2+; chitosan; glutaraldehyde; formalin; poly-L-lysine; dopamine; and amino acids including isoleucine, phenylalanine, leucine, threonine, lysine, tryptophan, methionine, valine, histidine, alanine, arginine, asparagine, aspartate, cysteine, glutamine, glutamate, glycine, proline, serine and tyrosine. The second aqueous solution is added into the first aqueous solution at a spraying rate of 10 to 100 ml/min.

The composition requires that a difference of viscosity between the upper and lower liquid layers is within 10% when centrifuging for 3 minutes at 3,000 rpm and 25°C. In related aspects, both difference of viscosity and difference of absorbance under 400 to 750 nm wavelength of visible rays region between the upper and lower liquid layers are within 10% when centrifuging under the same conditions.

Claims Coverage

The document provides two independent claims, covering a composition preventing tissue adhesion and a method for preparing the same. Across these independent claims, three inventive features are identified: the two-aqueous-solution formulation, the listed cross-linking agent selection, and the spray-rate addition with layer uniformity criteria.

Two-aqueous-solution tissue-adhesion-preventing composition

A composition preventing tissue adhesion is formulated as a combination of a first aqueous solution and a second aqueous solution, where the first aqueous solution contains a polyethyleneoxide-containing block copolymer and a polymer capable of being mixed with the block copolymer, and the second aqueous solution contains a cross-linking agent.

Listed cross-linking agent selection

The cross-linking agent is one or more selected from acetate or halide compounds including one or more cations selected from Mg2+, Mn2+, Ca2+, Cu2+, Sr2+, Ba2+, Fe2+, and Co2+; chitosan; glutaraldehyde; formalin; poly-L-lysine; dopamine; and isoleucine, phenylalanine, leucine, threonine, lysine, tryptophan, methionine, valine, histidine, alanine, arginine, asparagine, aspartate, cysteine, glutamine, glutamate, glycine, proline, serine and tyrosine.

Spray-rate addition with layer uniformity criterion

The second aqueous solution is added into the first aqueous solution at a spraying rate of 10 to 100 ml/min, and the composition is characterized such that a difference of viscosity between the upper and lower liquid layers is within 10% when centrifuging for 3 minutes at 3,000 rpm and 25°C. In the method, both difference of viscosity and difference of absorbance under 400 to 750 nm wavelength of visible rays region between the upper and lower liquid layers are within 10% under the same centrifugation conditions.

Overall, the independent claims cover a tissue-adhesion-preventing composition with a two-aqueous-solution formulation, a listed cross-linking agent, and spray-rate addition that yields within-10% upper/lower layer uniformity by viscosity, and by both viscosity and visible 400 to 750 nm absorbance in the method.

Stated Advantages

Not explicitly described in patent.

Documented Applications

Not explicitly described in patent.

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