CN-122028942-A - Gel for treating fistulae and related methods

Abstract

The present disclosure includes kits, compositions, and methods that may be used in medical procedures, such as treating fistulae or other target sites in a subject. In some examples, the kit may comprise a dry particulate mixture, a first pharmaceutically acceptable buffer solution having a pH ranging from about 3 to about 5, and a second pharmaceutically acceptable buffer solution having a pH ranging from about 9 to about 11. The dry particle mixture may comprise a plurality of polyethylene glycol particles and a plurality of collagen particles.

Inventors

• Robert Kugelan
• Mark Rooney
• Patrick Newgold
• Edward Joseph Devlin
• JOHN MURPHY
• Megan Crobuck
• Dalah Odonowan
• CONOR O'SULLIVAN

Assignees

• 波士顿科学国际有限公司

Dates

Publication Date

20260512

Application Date

20240816

Priority Date

20230818

Claims (15)

1. 1. A kit for treating a fistula, the kit comprising: A dry particulate mixture comprising: A plurality of polyethylene glycol particles, and A plurality of collagen particles; A first pharmaceutically acceptable buffer solution having a pH in the range of about 3 to about 5, and A second pharmaceutically acceptable buffer solution having a pH in the range of about 9 to about 11.
2. 2. The kit of claim 1, wherein the first pharmaceutically acceptable buffer solution comprises at least one crosslinker, optionally wherein the crosslinker comprises trilysine acetate, N- (3-dimethylaminopropyl) -N' -ethylcarbodiimide hydrochloride, or N-hydroxysuccinimide.
3. 3. The kit of claim 1 or 2, further comprising instructions for combining the dry particulate mixture with the first and second pharmaceutically acceptable buffer solutions to form a gel for administration to a fistula.
4. 4. The kit of any one of the preceding claims, wherein the weight ratio of the plurality of polyethylene glycol particles to the plurality of collagen particles in the dry particle mixture is in the range of about 8:1 to about 6:1.
5. 5. The kit of any one of the preceding claims, wherein the plurality of collagen particles has an average particle size ranging from about 300 μιη to about 500 μιη.
6. 6. The kit of any one of the preceding claims, wherein the plurality of polyethylene glycol particles comprise a chemically modified polyethylene glycol, such as a polyethylene glycol polymer comprising one or more functional groups selected from carboxylic acid groups, ester groups, amine groups, or combinations thereof, optionally wherein the one or more functional groups comprise succinimide groups.
7. 7. The kit of any one of the preceding claims, wherein the first or second pharmaceutically acceptable buffer solution comprises a radio-opaque material.
8. 8. The kit of any one of the preceding claims, wherein the first or second pharmaceutically acceptable buffer solution comprises an antibacterial agent.
9. 9. The kit of any one of the preceding claims, further comprising: Double-barrel syringe, and Instructions for combining the dry particulate mixture with the first pharmaceutically acceptable buffer solution to form a slurry, introducing the slurry into a first barrel of the syringe, and introducing the second pharmaceutically acceptable buffer solution into a second barrel of the syringe.
10. 10. Use of a kit according to any one of the preceding claims in the treatment of a fistula in a subject.
11. 11. The use of claim 10, wherein the fistula is a fistula of the gastrointestinal tract of the subject.
12. 12. The use of claim 10 or 11, wherein the dry particulate mixture is combined with the first pharmaceutically acceptable buffer solution to form a slurry, and the slurry is combined with the second pharmaceutically acceptable buffer solution to form a gel.
13. 13. The use of claim 12, wherein the slurry is combined with the second pharmaceutically acceptable buffer solution at the fistula tract to form a gel.
14. 14. The use of claim 12 or 13, wherein the gel is formed within 30 seconds, such as within 20 seconds, after mixing the slurry with the second pharmaceutically acceptable buffer.
15. 15. A method of making the kit of any one of claims 1-9, the method comprising: preparing a collagen scaffold, optionally wherein the average pore size of the collagen scaffold ranges from about 100 μm to about 200 μm; Grinding the collagen scaffold to obtain the plurality of collagen particles; Combining the plurality of collagen particles with the plurality of polyethylene glycol particles to obtain the dry particle mixture, and Packaging the dry particulate mixture with the first pharmaceutically acceptable buffer solution and the second pharmaceutically acceptable buffer solution.

Description

Gel for treating fistulae and related methods Cross Reference to Related Applications The present application claims priority from U.S. provisional application No. 63/520,407, filed 8/18 of 2023, which is incorporated herein by reference in its entirety. Technical Field The present disclosure relates generally to gel materials for medical procedures, including endoscopic procedures. Background Gel materials are useful in many medical environments for separating tissue and/or covering injured tissue. A fistula is an abnormal connection or passage that connects two organs or vessels that are not normally connected. Fistulae may form between the intestine and the skin, between the vagina and the rectum, and at various sites within the gastrointestinal tract (e.g., stomach, intestine, colon, etc.). Adhesion to tissue and the ability to permanently close the fistula can be challenging. In addition, formulating a gel may be difficult to promote tissue repair at the target site while maintaining the bioresorbability of the gel. Disclosure of Invention The present disclosure includes kits, compositions, and methods useful for medical procedures. For example, the present disclosure includes a kit that can include a dry particulate mixture, a first pharmaceutically acceptable buffer solution having a pH ranging from about 3 to about 5, and a second pharmaceutically acceptable buffer solution having a pH ranging from about 9 to about 11. The dry particle mixture may comprise a plurality of polyethylene glycol particles and a plurality of collagen particles. The first pharmaceutically acceptable buffer solution may comprise at least one crosslinker, optionally wherein the crosslinker comprises trilysine acetate, N- (3-dimethylaminopropyl) -N' -ethylcarbodiimide hydrochloride, or N-hydroxysuccinimide. The weight ratio of the plurality of polyethylene glycol particles to the plurality of collagen particles in the dry particle mixture may be in the range of about 8:1 to about 6:1. The plurality of collagen particles may have an average particle size ranging from about 300 μm to about 500 μm. The plurality of polyethylene glycol particles may comprise a chemically modified polyethylene glycol, such as a polyethylene glycol polymer comprising one or more functional groups selected from carboxylic acid groups, ester groups, amine groups, or combinations thereof. Alternatively, the one or more functional groups may comprise a succinimide group. The first pharmaceutically acceptable buffer solution and/or the second pharmaceutically acceptable buffer solution may comprise a radio-opaque material and/or an antimicrobial agent. In some examples, the kit may further include instructions for combining the dry particulate mixture with the first and second pharmaceutically acceptable buffer solutions to form a gel for administration to the fistula tract. Additionally or alternatively, the kit may further comprise a dual barrel syringe, and instructions for combining the dry particulate mixture with the first pharmaceutically acceptable buffer solution to form a slurry, introducing the slurry into a first barrel of the syringe, and introducing the second pharmaceutically acceptable buffer solution into a second barrel of the syringe. Also disclosed herein is a use of the kit for treating a fistula in a subject, wherein the kit may be described above or elsewhere herein. The present disclosure also includes methods of making the kits described above or elsewhere herein. The method may include preparing a collagen scaffold, optionally wherein the collagen scaffold has an average pore size ranging from about 100 μm to about 200 μm, milling the collagen scaffold to obtain the plurality of collagen particles, combining the plurality of collagen particles with a plurality of polyethylene glycol particles to obtain a dry particle mixture, and packaging the dry particle mixture with the first pharmaceutically acceptable buffer solution and the second pharmaceutically acceptable buffer solution. The disclosure also includes methods of treating a subject. In some examples, the method includes combining a dry particulate mixture with a first pharmaceutically acceptable buffer solution having a pH ranging from about 3 to about 5 to form a slurry, and combining the slurry with a second pharmaceutically acceptable buffer solution having a pH ranging from about 9 to about 11 at a target site of the subject to form a gel at the target site. The dry particle mixture may comprise a plurality of polyethylene glycol particles and a plurality of collagen particles. In some examples, the method includes administering to a target site of the subject a slurry comprising a plurality of polyethylene glycol particles, a plurality of collagen particles, a first pharmaceutically acceptable buffer solution having a pH ranging from about 3 to about 5, and administering to the target site a second pharmaceutically acceptable buffer solution having a pH ranging from