Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
2002-04-24
2003-04-22
Acquah, Samuel A. (Department: 1711)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C424S078060, C424S078070, C424S078170, C514S002600, C514S009100, C514S012200, C514S013800, C514S014800, C514S015800, C514S016700, C528S354000, C528S361000, C525S439000, C525S450000
Reexamination Certificate
active
06551610
ABSTRACT:
BACKGROUND OF THE INVENTION
In 1988, a national hospital discharge survey estimated that postoperative adhesions contributed to 282,000 hospital admissions for adhesiolytic abdominal surgery, nearly one million days of in-patient care, and 1.2 billion dollars in expenditures. It is expected that these figures have increased despite surgical and adjuvant strategies to decrease the incidence of adhesions. A recent retrospective study examined hospital re-admissions from a group of 29,790 patients who underwent abdominal or pelvic surgery in 1986. From this group, 34% were readmitted over a ten year period for disorders directly or possibly related adhesion complications. Although 58% of this cohort required only one readmission, 44% had 2 to 5 admissions. The most severe complication was a small bowel obstruction in which 64% of the patients required additional surgery. In addition, the sites of initial surgery were equally distributed among mid/hindgut, foregut, and female reproductive tract. It has been estimated that up to 54% of all intestinal obstructions are secondary to adhesions bands from prior surgery. To date, no prospective study has shown a decrease in the incidence of intestinal obstruction using adjuvants designed to reduce postoperative adhesions.
The clinical statistics noted above and other data show clearly that postoperative adhesions (POA) are significant complications in most surgical procedures. Among the most common and widely addressed types of POA are the peritoneal types, which are the leading cause of intestinal blockage or obstruction. Equally important types of POA are encountered following gynecological surgery, which can lead to infertility, chronic pain, and obstructive disorder. Pericardial POA received relatively less attention than the two aforementioned types. On the other hand, minor, but growing, interest has been directed to adhesions such as those experienced in the thorax and tendons and vertebra. Although POA can be minimized by following careful surgical techniques, several non-surgical approaches have been used with variable levels of success. Some of the non-surgical approaches to prevent POA focused on the prevention of fibrin deposition as a strategy to prevent post-surgical adhesion. These strategies included the use of anticoagulants and irrigation, and the separation of tissue surfaces using (1) Dextran® lavage in intraperitoneal procedures; (2) oxidized cellulose films, e.g., Interceed; (3) carboxymethyl cellulose solution; (4) chondroitin sulfate solutions; (5) polyvinyl pyrrolidone solutions; (6) Polyoxamer 407 solutions; and (7) Gortex films. Other approaches to prevent post-surgical adhesions have relied on the (1) removal of fibrin matrix through the use of fibrinolytics and proteolytic enzymes or tissue-type plasminogen activator.
Developing appropriate and effective therapies for inhibiting inflammation and adhesion formation is still a major challenge. While NSAIDs (non-steroidal anti-inflammatory drugs) have been shown to decrease the tissue inflammatory response and enhance fibrinolytic potential in peritoneal tissues, previous studies have shown that these drugs need to be delivered to specifically targeted areas for several days to be effective. In turn, while hyaluronic acid has demonstrated potential as a drug carrier, the concentrations and molecular weights required for biological efficacy prohibit the practical use of this compound in an injectable form. A moderately effective strategy for preventing POA in rats entailed the local administration of non-steroidal anti-inflammatory drugs, such as Tolmetin®, as part of a controlled release system (U.S. Pat. No. 4,937,254). A promising strategy for preventing POA in flexor tendons was explored by Shalaby and coworkers (U.S. Pat. Nos. 6,037,331 and 5,866,544) entailed use of a locally administered controlled release system of bioactive agents (including NSAID) in moderate viscosity gel-forming hyaluronic acid systems as a transient barrier matrix. The promising results associated with the latter strategy and availability of a novel class of liquid, absorbable gel-forming copolyesters, which have been successfully used by Shalaby and coworkers on a transient matrix for the controlled release of bioactive agents (U.S. Pat. Nos. 5,612,052 and 5,714,159) contributed to the conceptual development of the present invention.
Growing interest in developing absorbable pharmaceutical surgical products which degrade in the biologic environment to safe by-products without residual mass remaining at the application site justified the search for novel, absorbable gels. In a recent disclosure, a novel gel-former was described to be based on absorbable copolymers which, upon hydration, result in hydrogels that are stabilized by pseudo-crosslinks provided by a hydrophobic polyester component covalently linked to a hydrophilic component made of pharmaceutically acceptable polymer, such as polyoxyethylene. The polyester component is made of safe monomers, such as p-dioxanone, &egr;-caprolactone, glycolide, lactide, trimethylene carbonate, and mixtures thereof. Contrary to a related study, which describes in situ formation of biodegradable, microporous, solid implants in a living body through coagulation of a solution of a polymer in an organic solvent such as N-methyl-2-pyrrolidine, the new hydrogel-former does not require the use of solvents. Such solvents did include low molecular organic compounds that can migrate from the application site and cause cell dehydration and tissue necrosis. Equally important is the fact that previously known systems are solid implants which can elicit mechanical incompatibility and, hence, patient discomfort as compared with the new compliant, swollen, mechanically compatible hydrogels.
The use of absorbable gel-formers may very well lead to some of the most important applications of absorbable polymers in the pharmaceutical and biomedical industries. Among the inventor disclosed current activities in this area are uses of the gel-formers in (1) periodontal application of antibiotics; (2) antibiotics formulations for osteomyelitis, (3) intraocular drug delivery; (4) wound healing and hemostasis; (5) controlling the release of insulin; and (6) controlling the bioavailability of ricin A-chain.
Adhesion formation after abdominal surgery is a significant cause of post-operative morbidity. In gynecological surgery, adhesion can lead to infertility, chronic pain, and obstructive disorder. Numerous adhesion prevention adjuvants have been investigated, most of which are based on pharmacological agents or protective barriers. However, the combined effect of a transient barrier and pharmacological agent using a local controlled release system was practically unexplored. Meanwhile, analysis of the different theories on the cause and prevention of post-surgical adhesion and critical review of numerous attempts to achieve different levels of efficacy by many investigators led the present inventor to conceptualize that an ideal system for post-surgical adhesion prevention must meet a least four of the following requirements: (1) ease of application as a liquid that transforms into a three-dimensional compliant gel upon administration to a surgical site; (2) formation of a temporary barrier which exhibits barrier properties for up to 72 hours; (3) exhibiting mild adhesive properties toward traumatized tissue; (4) dissolves or disperses into a mechanically biocompatible components; (5) yielding minimum acidic by-products; (6) dissolving the bioactive agent; (7) allowing the release of a bioactive agent in two modes, an initial burst followed by additional release for up to 72 hours; and (8) the bioactive agent is (a) a non-steroidal, anti-inflammatory drug (NSAID), and/or (b) an anti-angiogenic agent, that retards or inhibits temporarily cell growth, proliferation, and neovascularization at non-toxic doses. To date, however, only up to three of these requirements have been met by any of the systems known in the prior art; this can be deduced from the following summari
Shalaby Marc
Shalaby Shalaby W.
Shalaby Waleed S. W.
Acquah Samuel A.
Gregory Leigh P.
Poly-Med, Inc.
LandOfFree
Multifaceted compositions for post-surgical adhesion prevention does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Multifaceted compositions for post-surgical adhesion prevention, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Multifaceted compositions for post-surgical adhesion prevention will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3113327