Prevention of adhesions

a technology of adhesion and mmps, which is applied in the field of prevention of adhesions, can solve the problems of peritoneal environment no information currently available regarding the expression of mmps and timps, and affect the development of adhesion, so as to reduce or prevent adhesion, and diagnose the probability of adhesion formation

Inactive Publication Date: 2005-07-14
FLORIDA UNIV OF A FLORIDA +2
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  • Application Information

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Benefits of technology

[0008] It has now been discovered that an unbalanced level of MMP-1 and TIMP-1 in a human subject, high TIMP-1 expression, and the association of a major portion of MMP-1 in complex with TIMP-1 may be major contributing factors in the peritoneal environment by providing a favorable-condition for adhesion development. This discovery has lead to the development of novel methods for treating surgical adhesions, for diagnosing the probability of developing adhesion formation, and for preparing pharmaceutical formulations for reducing or preventing adhesions.

Problems solved by technology

Inhibition, interruption, or excess expression of these molecules seems to be responsible for failure in normal healing, resulting in either impairment or excess tissue formation (adhesion development).
Although the role of growth factors, cytokines, eicosanoids and serine proteinases have been investigated in relation to peritoneal wound repair and adhesion formation, there is no information currently available in respect to the expression of MMPs and TIMPs in the peritoneal environment.

Method used

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  • Prevention of adhesions
  • Prevention of adhesions
  • Prevention of adhesions

Examples

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[0025] Tissue specimens including skin, fascia, parietal peritoneum, uterus, fallopian tube, ovary, large bowel, omentum and adhesion, as well as peritoneal fluids were collected from patients (N=55) who were undergoing abdominal / pelvic surgical procedures. Peritoneal fluids were excluded if the fluids became contaminated with blood during the collection. Thus, peritoneal fluid from 15 patients were analyzed. The collection of the tissues and peritoneal fluid from these patients was approved by the Institutional Review Board from each individual institution prior to initiation of the study. All patients gave informed written consent prior to tissue collection.

[0026] The patient's pelvic findings at surgery were used to asses the type of adhesions. The extent of adhesion formation was determined and classified based on their severity as previously described. In female patients, adhesions involving only a small area, usually the tubes and ovaries, and lysed with ease were categorized...

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Abstract

Methods for the prevention of adhesion formation involve the administration of therapeutic formulations to a patient which include antibodies to TIMP-1 or TIMP-1 antisense oligonucleotides. The formulations can also include suitable carriers, such as a hyaluronic acid matrix, for optimal administration. The treatment procedure can be initiated and monitored by a diagnostic procedure which involves the detection of elevated levels of TIMP-1 in a patient.

Description

BACKGROUND OF THE INVENTION [0001] It is well established that post-operative adhesions develop in the vast majority of patients after surgery. Injury or inflammation in the peritoneal cavity produces a fibrous exudate. As a result, the serosal surfaces stick together. The fibrous exudate may be absorbed or invaded by fibroblasts to form a permanent fibrous adhesion. [0002] Removal of fibrin before it is invaded by fibroblasts prevents the formation of permanent fibrous adhesions. Removal of fibrin occurs due to the fibrinolytic activity of the peritoneal cavity. Fibrinolytic activity can vary as a result of surgery. Fibrinolytic activity is absent from a peritoneal wound during the first 48 hours after surgery. However, there is a gradual increase after this time up to 8 days when the peritoneum heals. The source of the fibinolytic activity is found in the mesothelial cells. It is postulated that the absence of definitive mesothelial cells with their associated fibrinolytic activit...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K16/38
CPCC07K16/38
Inventor CHEGINI, NASSERBURNS, JAMESDIAMOND, MICHAEL P.HOLMDAHL, LENA E.
Owner FLORIDA UNIV OF A FLORIDA
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