Compositions and methods for promoting hemostasis and other physiological activities

Patent metadata

Field	Value
Publication number	US-9364513-B2
Application number	US-19967008-A
Country	US
Kind code	B2
Filing date	Aug 27, 2008
Priority date	Apr 25, 2005
Publication date	Jun 14, 2016
Grant date	Jun 14, 2016

Abstract

Compositions that include nanoscale structured materials or precursors thereof (e.g., self-assembling peptides) are described. The compositions can include other substances (e.g., a vasoconstrictor). Also described are methods for using the compositions to promote hemostasis, to protect the skin or wounds from contamination, to decontaminate a site upon removal of previously applied compositions that provided a protective coating, and to inhibit the movement of bodily substances other than blood. The compositions are also useful in isolating tissue, removing tissue, preserving tissue (for, e.g., subsequent transplantation or reattachment), and as bulking, stabilizing or hydrating agents. Medical devices that include the compositions (e.g., a stent or catheter), bandages or other wound dressings, sutures, and kits that include the compositions are also described.

First claim

What is claimed is:

1. A method for inhibiting the flow of a bodily fluid from a surgical incision or wound site on or in an animal, comprising:
applying a composition comprising self-assembling peptides to an exposed surface of a surgical incision or wound site on or in the animal,
wherein the self-assembling peptides consist of a sequence of from 8 to 16 amino acid residues conforming to one or more of Formulas I-IV:
((Xaa neu -Xaa + ) x (Xaa neu -Xaa − ) y ) n   (I)

((Xaa neu -Xaa − ) x (Xaa neu -Xaa + ) y ) n   (II)

((Xaa + -Xaa neu ) x (Xaa − -Xaa neu ) y ) n   (III)

((Xaa − -Xaa neu ) x (Xaa + -Xaa neu ) y ) n   (IV)

wherein Xaa neu represents alanine or leucine; Xaa + represents arginine or lysine; Xaa − represents aspartic acid or glutamic acid; x and y are integers having a value of 1 or 2, or 4, independently; and n is an integer having a value of 1-4,
wherein the composition is a solution or a solid,
wherein the concentration of self-assembling peptides in the solution is between 1.0% weight to volume and 4.0% weight to volume, inclusive,
wherein the composition has a concentration of ions less than 5 mM and
wherein the self-assembling peptides are in a concentration effective to form a macroscopic structure upon contacting a concentration of ions greater than 5 mM at the surgical incision or wound site that prevents passage of the bodily fluid from the surgical incision or wound site through the structure.

2. A method as in claim 1 , wherein the structure provides an optically transparent environment on or within the surgical incision or wound site of the animal.

3. A method as in claim 1 , wherein irrigation of the surgical incision or wound site of the animal with saline is not performed prior to, during, and/or after creation of the surgical incision or the wound site.

4. A method as in claim 1 , wherein the surgical incision or wound site of the animal is within or adjacent to a blood vessel, tissue, urogenital area, lung, dura, intestines, stomach, heart, biliary tract, urinary tract, esophagus, brain, spinal cord, gastrointestinal tract, liver, muscle, artery, vein, nervous system, eye, ear, nose, mouth, pharynx, respiratory system, cardiovascular system, digestive system, urinary system, reproductive system, musculoskeletal system, integument, or site of anastomosis.

5. A method as in claim 1 , wherein the composition further comprises a coloring agent.

6. A method as in claim 1 , wherein the composition is applied to a surgical incision through which an endoscope, laparoscope, or catheter passes, prior to and/or after the surgical incision is created.

7. A method for inhibiting the flow of blood from a surgical incision or wound site on or in an animal, comprising:
applying a solid composition and an aqueous solution to an exposed surface of a surgical incision or wound site of an animal, where the bodily fluid is flowing from the surgical incision or wound site of the animal, or to an exposed surface of the animal followed by creating a surgical incision at the exposed surface to which the solid composition and the aqueous solution were applied,
wherein the solid composition comprises an effective concentration of self-assembling peptides consisting of the amino acid sequence RADARADARADARADA (SEQ ID NO:1) and has a concentration of ions less than 5 mM, and the aqueous solution, when combined with the composition, dissolves or hydrates the composition,
wherein the dissolved or hydrated composition has a concentration of self-assembling peptides between 1.0% weight to volume and 4.0% weight to volume,
wherein the dissolved or hydrated composition upon contacting a concentration of ions greater than 5 mM at the site of application forms a macroscopic structure at the surgical incision or wound site that prevents passage of bodily fluid from the surgical incision or wound site through the structure.

8. A method as in claim 7 , wherein the solid composition and the aqueous solution are provided in a kit with instructions for use and, optionally, means for application.

9. A method as in claim 1 , wherein the concentration of self-assembling peptides in the solution is between 1% (10 mg/ml) and 3.0% (30 mg/ml), inclusive.

10. A method as in claim 1 , wherein the concentration of self-assembling peptides in the solution is between 2% (20 mg/ml) and 3.0% (30 mg/ml), inclusive.

11. A method as in claim 1 , wherein, prior to application of the composition, the surgical incision of the animal is created or the wound site of the animal is provided.

12. A method as in claim 1 , wherein, after application of the composition, the surgical incision of the animal is created.

13. A method as in claim 7 , wherein the concentration of self-assembling peptides is effective to form a macroscopic structure that reduces the amount of time required to achieve hemostasis by between 75% and 100% relative to amount of the time required to achieve hemostasis when iced saline is applied to the surgical incision site or wound site of the animal.

14. A method as in claim 1 , wherein the self-assembling peptides comprise the amino acid sequence RADARADARADARADA (SEQ ID NO: 1).

Assignees

• Ellis-Behnke Rutledge
• Zhang Shuguang
• Schneider Gerald
• So Kwok-Fai
• Tay David
• Liang Yu-Xiang
• Maasachusetts Inst Of Technology
• Versitech Ltd

Inventors

• Ellis-Behnke Rutledge
• Zhang Shuguang
• Schneider Gerald
• So Kwok-Fai
• Tay David
• Liang Yu-Xiang

Classifications

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P9/14

  Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers · CPC title

• A61P41/00

  Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• A61K38/10

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title