Reducing post-operative adhesion formation with intraperitoneal glutamine

a technology of intraperitoneal glutamine and post-operative adhesion, which is applied in the direction of dipeptide ingredients, biocide, plant growth regulators, etc., can solve the problems of increasing so as to reduce post-operative adhesion formation and reduce the risk of adhesion formation

Inactive Publication Date: 2010-10-14
ADETHERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0016]In another aspect, this invention provides use of a glutamine source for reducing post-operative adhesion formation.
[0017]In another aspect, this invention provides use of a glutamine source in the manufacture of a medicament for intraperitoneal administration to reduce post-operative adhesion formation.

Problems solved by technology

However, it is extremely common after abdominal and pelvic operations and remains a source of considerable morbidity.
Use of both absorbable polyglycolic acid meshes and non-absorbable polypropylene meshes as reinforcing materials in surgery is associated with a high incidence of adhesion formation [6a, 6b].
Most of the existing methods inhibit one of these categories and yet have limited success.
A decrease in extracellular glutamine impairs the function of macrophages and other immune cells, resulting in increased protein degradation from skeletal muscle [20].

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0030]70 plus male Wistar rats (over 350 g each) were assessed histologically on post-operative days 1, 3, 5, 7, 10, 30, and at about 6 weeks. The rats were randomly distributed based on the mode of treatment, type of sutures and presence or absence of hemorrhage during surgery. Initially, there were three surgery groups (alanyl-glutamine treatment, saline, no treatment) plus a control (no surgery). A fifth group using L-glutamine instead of alanyl-glutamine was included after preliminary results were obtained.

[0031]The rats were anaesthetized with halothane / Ketamine. Open surgery involving a midline sub-umbilical incision and a modified cecal puncture with pulstring to prevent soilage after abdominal closure was done. The procedure involved some fecal extrusion, mimicking clinical scenarios of iatrogenic / traumatic perforations of the bowel. Alanyl-glutamine [Degussa; Coubevoie, France] (0.3 g / kg-1.5 g / kg); saline (5 ml); or L-glutamine [Wiler; PCCA] (1.5 g / kg) was instilled into th...

example 2

[0041]Previous studies show a high incidence of adhesion formation when surgical mesh is employed as a reinforcing material [6a, 6b]. We repeated trials as described in Example 1, inserting Marlex™ mesh during the procedure on the surgical groups. Comparable results to that described in Example 1 were obtained between days 1-42.

[0042]Severity of adhesions was assessed at day 90 using the adhesion score of Zuhlke, et al. [54]. This scoring procedure has been described in the literature for assessment of other potential treatments for adhesions [55]. At day 90, the adhesion score in animals treated with alanyl-glutamine was 0-1 (no adhesion or flimsy adhesion), comparable to the virgin abdomens of the control group. This differs from previous measurements of adhesions using polypropylene mesh which reported up to about 90% adhesion formation [6a].

example 3

[0043]Adhesions tend to recur once in place. We examined the effect of alanyl-glutamine treatment on such secondary adhesions. The modified caecal perforation with pulstring closure procedure described in Example 1 was performed on 9 Sprague-Dawley rats. These were divided into 5 groups, each group receiving a different form of mesh (INTERCEED™; PROCEED™; BARD™ composite; prolene; and a mesh which was allowed to be “infected” by repeated re-opening of the wound). The surgical procedure with mesh implacement was performed without application of a glutamine source. Six months after initial surgery, a laparotomy was performed on each rat then adhesiolysis followed by installation of alanyl-glutamine. Three weeks later the rats were assessed for recurrence of adhesions and scored according to Zuhlke, et al. [54] and no secondary adhesions were seen.

[0044]Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of under...

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Abstract

Intraperitoneal administration of glutamine reduces post-operative adhesion formation.

Description

BACKGROUND OF THE INVENTION[0001]Adhesions are abnormal deposits of fibrous tissue that form within the peritoneal cavity. Abdominal adhesions are a common cause of small bowel obstruction and female infertility [1-3]. Adhesion formation occurs after any surgical procedure. However, it is extremely common after abdominal and pelvic operations and remains a source of considerable morbidity. The incidence ranges from about 67%-93% after general surgical abdominal operations and up to about 97% after open gynecologic pelvic procedures [4, 5]. In clinical and autopsy studies of patients who had prior laparotomy, the incidence of intra-abdominal adhesions was about 70-90% [6]. Use of both absorbable polyglycolic acid meshes and non-absorbable polypropylene meshes as reinforcing materials in surgery is associated with a high incidence of adhesion formation [6a, 6b].[0002]Factors associated with the formation of post-surgical adhesions include trauma, thermal injury, infection, ischemia an...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/70A61K38/05A61K31/198A61P41/00
CPCA61K9/0019A61K9/0024A61K9/12A61K38/05A61K31/198A61L31/16A61L2300/214A61L2300/25A61L31/047A61P17/02A61P41/00A61L31/10A61L31/145A61L31/148A61L2300/252A61L2300/412A61L2300/424
Inventor OBAYAN, ADEBOLA O.E.
Owner ADETHERAPEUTICS
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