Adhesion formation is a well-known complication of many types of surgical procedures, particularly abdominal and bowel surgeries. Adhesion formation typically occurs as a result of the formation of a fibrin clot, which transforms into scar tissue connecting different tissues that are normally separated. Surgical intervention is frequently required in order to eliminate the adhesions, although the adhesions can, and often do, reappear following the surgery. The primary objective of adhesion inhibiting barriers is to interrupt the adhesion formation mechanism, which is believed to result from the diffusion of fibrinogen into the space between the tissues subject to surgical trauma, thereby causing the formation of fibrin clots in the space.
As such, post-surgical adhesions present a major healthcare problem of significant clinical and medical economic relevance. Abdominal adhesions are not only the leading cause of small bowel obstruction, but also major sources of infertility and of abdominal and pelvic pain. It has been shown that post-surgical adhesions cause at least about 20% of cases of infertility and about 40% of cases of chronic pelvic pain.
Although it is known that the incidence of post-surgical adhesions may be reduced by various improvements in surgical techniques and/or better instrumentation, adhesions cannot be prevented without adjuvant therapy, because every minute trauma may induce their formation. In view thereof, significant efforts have been made to provide effective means and treatment methods for reducing or preventing such adhesions connected with surgery. Many substances or constructs have been reported to have positive effects on surgical adhesions, such as collagen films, collagen gels, and sodium hyaluronate/carboxymethylcellulose film and fibrin glue.
In addition to acting as an adhesion barrier, a successful anti-adhesion formulation should be “biocompatible,” meaning that it has minimal to no medically unacceptable toxic or injurious effect on the biological function of the subject, and “bioabsorbable,” meaning that it can be absorbed by the tissue without a significant amount remaining in the subject as an implant device. It is to be understood that such bioabsorbable materials are broken down by the body, then the resulting products are excreted therefrom by various means, including passage in urine, feces or as carbon dioxide in the breath. Thus, the formulation should remain in the body for a sufficient period of time to be effective in separating the tissue and preventing adhesions, while being absorbed by the tissue once the danger of adhesion formation has ended, thereby minimizing any long term effects which may result from the use of an implant device.
Perforation is the second most common complication of peptic ulcer and is often associated with NSAID use especially in the elderly population. See N Zaji, “Laparoscopic Repair of Perforated Peptic Ulcers Versus Conventional Open Surgery,” Laparoscopic Hospital, New Delhi, India, July 2007. Approximately 10-20% of patients with peptic ulcers suffer perforation of the stomach or duodenum, in which a chemical peritonitis develops initially from the gastric and duodenal secretion then bacterial contamination superimposed within hours. Helicobacter pylori infection plays a central role in the genesis of peptic ulcer. See Graham, D. Y., “Treatment of peptic ulcers caused by Helicobacter pylori,” 328 N Engl J Med 349-350 (1993).
The perforation of a duodenal ulcer allows for the egress of gastric and duodenal contents into the peritoneal cavity with a resulting initial chemical peritonitis. If there is continued leakage of gastro-duodenal contents, bacterial contamination of the peritoneal cavity could occur. See A. J. Donovan, “Perforated Duodenal Ulcer An Alternative Therapeutic Plan,” 133 ARCH SURG 1166-1171, (November 1998).
U.S. Pat. No. 7,198,786 proposes a method of reducing or preventing adhesions which would form in a patient during or after surgery by administering to the wound surface of a patient a fibrinogen solution in an amount of about 0.025 ml fibrinogen/cm2 to about 0.25 ml fibrinogen/cm2 of the surface being at risk for developing adhesions. The use of fibrinogen in a preparation comprising fibrinogen at a concentration of 20 to 80 mg/ml for the reduction or prevention of post-surgical adhesion formation is also proposed.
EP 1,341,561 proposes a layered wound dressing material comprising: a wound facing hydrogel layer and a barrier layer, wherein the barrier layer comprises a pH-sensitive material that is substantially insoluble in water at 25° C. under acidic conditions, but substantially soluble in water at 25° C. under neutral or alkaline conditions. In use, the hydrogel layer absorbs and is gradually neutralized by wound exudate until its pH rises to a level that causes dissolution of the barrier layer, thereby allowing excess exudate to flow out from the hydrogen layer. Also proposed are wound dressings comprising barrier layers and methods of use of such dressings.
Despite these advances in the art, it would be desirable to provide a suitable adhesion inhibiting barrier as well as a method for reducing or preventing post-surgical adhesions in a patient. There also remains a need for a barrier for containing the gastric and duodenal contents of a perforated ulcer in order to minimize the risk of further deterioration of the compromised area.
USPTO Backgrounds
USPTO Backgrounds