WO2000045804A2 - Prevention de la formation d'abces - Google Patents

Prevention de la formation d'abces Download PDF

Info

Publication number
WO2000045804A2
WO2000045804A2 PCT/US2000/002988 US0002988W WO0045804A2 WO 2000045804 A2 WO2000045804 A2 WO 2000045804A2 US 0002988 W US0002988 W US 0002988W WO 0045804 A2 WO0045804 A2 WO 0045804A2
Authority
WO
WIPO (PCT)
Prior art keywords
solution
hyaluronic acid
surgery
surgical procedure
patient
Prior art date
Application number
PCT/US2000/002988
Other languages
English (en)
Other versions
WO2000045804A3 (fr
Inventor
James W. Burns
Eugene Skrabut
Harry Van Goor
Michel M. P. J. Reijnen
Original Assignee
Genzyme Corporation
University Hospital Nijmegen
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Genzyme Corporation, University Hospital Nijmegen filed Critical Genzyme Corporation
Priority to AU33566/00A priority Critical patent/AU3356600A/en
Priority to EP00911708A priority patent/EP1148886A2/fr
Priority to CA002361572A priority patent/CA2361572A1/fr
Priority to JP2000596924A priority patent/JP2002536323A/ja
Publication of WO2000045804A2 publication Critical patent/WO2000045804A2/fr
Publication of WO2000045804A3 publication Critical patent/WO2000045804A3/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/717—Celluloses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • This invention relates to the use of dilute solutions of polyanionic polysaccharides for the treatment of a subject in order to prevent or reduce the likelihood of abscess formation.
  • the polyanionic polysaccharide solution is applied to the tissue surfaces which are exposed during a surgical procedure performed on the subject.
  • the numbers in parenthesis, as used herein, designate references which are listed and described in detail in the "Reference" section immediately preceding the claims.
  • polyanionic polysaccharide also as used herein, is intended to designate polymeric polysaccharides and their derivatives containing anionic groups at physiological pH. These include, but are not limited to, hyaluronic acid (“HA”), carboxymethyl cellulose (“CMC”), derivatives of HA, crosslinked HA, derivatives of CMC, crosslinked CMC, chondroitin sulphates, derivatives of chondroitin sulphates, crosslinked chondroitin sulphates or mixtures thereof. See U.S. Patent No. 4,582,865; U.S. Patent No. 4,937,270; and U.S.
  • HA hyaluronic acid
  • CMC carboxymethyl cellulose
  • Routine abdominal surgery can result in bacterial contamination in the intra-abdominal area of the body which is exposed during surgery. Depending on the type of bacteria encountered, this type of contamination can result in intra-abdominal sepsis and abscess formation. Abscesses, if left untreated, may cause fever, prolonged hospitalization, and possibly mortality.
  • Intra-abdominal infections may also result from a perforated bowel or appendicitis (secondary peritonitis). Patients suffering from these conditions generally undergo laparotomy to eliminate the infectious focus, accompanied by debridement and intra-operative lavage.
  • Intra-abdominal infection is typically accompanied by fibrin deposition in the abdominal cavity. This fibrin deposition may lead to both adhesion formation and abscess formation. Both adhesion formation and abscess formation have significant clinical relevance.
  • Intra-abdominal abscesses are a significant cause of morbidity and mortality in patients with generalized peritonitis. Adhesions are the main cause of intestinal obstruction in the developed world. Furthermore, adhesions are responsible for 15% to 20% of cases of infertility, and are associated with chronic abdominal and pelvic pain (1, 2, 3).
  • Various pharmaceutical agents have been investigated for use in the prevention of adhesions. Such agents include dextran, corticosteroids, phosphatidyl choline, phospholipase inhibitors, non-steroidal anti-inflammatory drugs, heparin and tissue plasminogen activator
  • tPA thrombospasmodic acid
  • Those pharmaceutical agents which have been shown to interfere with coagulation (the formation of fibrin) and fibrinolysis (the dissolution of fibrin) include, respectively, heparin and tPA, both of which have also been studied for the prevention of intra-abdominal abscess formation.
  • relevant clinical experience with such agents is limited, largely due to the fear of bleeding complications.
  • hyaluronic acid solutions to prevent the formation of post-surgical adhesions in a non-infectious environment is well known (8, 9, 10, 16, 17). Recently, modified versions of hyaluronic acid have been shown to be successful in preventing post- surgical adhesions in both experimental and clinical studies (5 to 1 1). It is believed that hyaluronic acid solutions can reduce postoperative peritoneal adhesions by reducing serosal trauma by precoating the peritoneal surfaces, which would otherwise become damaged during surgery or trauma (39). A similar benefit could be derived by coating the tissues following trauma. As a consequence, peritoneal surfaces do not adhere to each other by fibrinous deposits, and may heal without adhesion formation.
  • Hyaluronic acid is a biocompatible, non-toxic, high molecular weight polyanionic polysaccharide consisting of repeating units of alternating N-acetyl-glucosamine and D- glucuronic acid.
  • Hyaluronic acid is found in all tissues and body fluids of vertebrates (12).
  • Hyaluronic acid is known to have a stabilizing effect on extracellular matrices.
  • hyaluronic acid has been shown to interact with cell surfaces to modify cell behavior.
  • Carboxymethyl cellulose a polyanionic polysaccharide, is a derivatized form of cellulose in which the glucosidic hydroxyl groups have been carboxymethylated, rendering the polymer water soluble.
  • Carboxymethyl cellulose is used in food products (it is currently listed in the CFR as Generally Recognized As Safe (“GRAS”)), and as a moisturizing agent in topical eye products.
  • GRAS Generally Recognized As Safe
  • Sepracoat® has not been previously assessed in an infectious environment, nor has their influence on intra-abdominal abscess formation been studied in any detail. It is an objective of this invention to make such an assessment with respect to polyanionic polysaccharide compositions, and to utilize the results to provide a method of preventing or reducing the formation of abscesses.
  • a dilute solution of a polyanionic polysaccharide is effective in preventing or reducing the formation of abscesses which may result from a surgical procedure performed on a subject with established peritonitis.
  • the dilute polyanionic polysaccharide solution is a 0.2% to 2.0% by weight solution which is applied to tissue surfaces at the site of the surgical procedure which have been exposed as a result of surgery. This can be accomplished by applying the polyanionic polysaccharide solution to the tissue surfaces either prior to, during or immediately following surgery.
  • the polyanionic polysaccharide solution can be applied to the tissue surfaces at any time after the tissue has been exposed, it is preferable to apply it to the tissue surfaces following surgery so as not to interfere with the surgical procedure.
  • the polyanionic polysaccharide solution can, for instance, be used as an intra-operative lavage solution following surgical elimination of the infectious site and debridement of the surrounding tissue.
  • the lavage solution can be left in the abdomen prior to closure which may serve to prevent residual infection or abscess formation.
  • the solution can be supplied to the patient, to treat residual infection, by using a surgical drain, by intraperitoneal injection, by an indwelling catheter, or by using a similar device which may be present in the patient as a result of the surgical procedure.
  • the solution can also be supplied by means of a dialysis port, if available.
  • the method of this invention can be used when abdominal surgery is performed on a human patient.
  • This method has been found to be effective in preventing or ameliorating abscesses due to the activity of the following bacteria: Bacteroides fragilis, Proteus sp., Escherichia coli, coliform gram negative bacteria, anaerobe gram negative rod bacteria, Enterococci and Staphylococci.
  • Figure 1 is a graph showing the relative severity of adhesions for one and three weeks following cecal ligation and puncture. In the graph, the points represent the level of adhesions in individual animals, and the bars indicate median adhesion levels.
  • Figure 2 is a diagram showing the pathway for adhesion and abscess formation in the cecal ligation and puncture model, and possible methods of action of hyaluronic acid and carboxymethyl cellulose.
  • the polyanionic polysaccharide solution is a Sepracoat® hyaluronic acid solution (a 0.4% by weight solution) or carboxymethyl cellulose solution (a ⁇ 2% by weight solution).
  • Chemically modified versions of HA and CMC can also be used in the practice of this invention.
  • Derivatized versions are prepared by reacting the HA or CMC with an activating agent, such as a carbodiimide.
  • Crosslinked versions of HA and CMC are prepared by reacting the HA or CMC with a suitable crosslinking agent, such as divinyl sulfone.
  • the amount of polyanionic polysaccharide solution used in the method of this invention should be sufficient to evenly coat the surfaces of the affected tissue. It is preferred to use an overabundance of polyanionic polysaccharide solution as compared to an inadequate amount. It is believed that the use of an overabundance of polyanionic polysaccharide solution may have a "floating" effect on intra-abdominal organs, which may also result in the prevention of adhesions. In contrast, the use of large amounts of a saline solution does not have a measurable influence on adhesion and abscess formation. This result is consistent given the substantial difference in viscosity and the absorption ability between, for instance, hyaluronic acid and saline solutions.
  • Hyaluronic acid in the abdominal cavity is believed to be absorbed by the diaphragmatic stomata in a manner similar to peritoneal fluid.
  • the hyaluronic acid is biocompatible and is subsequently degraded in the same manner as endogenous hyaluronic acid, mainly in the lymph and blood, but also in the liver (33). Saline, however, is absorbed by the whole peritoneum.
  • a 0.4% by weight solution of hyaluronic acid can also be compared and contrasted with the use of a methylhydroxypropylcellulose gel and a liquefied Seprafilm® hyaluronic acid/carboxymethyl cellulose bioresorbable membrane. It has recently been shown that a methylhydroxypropylcellulose gel did not reduce adhesion and abscess formation in rats with intra-abdominal infections (30). Moreover, the Seprafilm® bioresorbable membrane, which liquefies after approximately 24 hours under normal conditions, did not seem to reduce adhesion and abscess formation. The lack of effectiveness of the Seprafilm® membrane in comparison to the Sepracoat® solution is somewhat surprising.
  • Seprafilm® The failure of Seprafilm® to reduce adhesions in an infectious environment is, however, in accordance with the findings of Medina et al. in a rabbit model of incomplete colon anastomosis (34). These results may indicate that the Sepracoat® solution is unique in its ability to prevent or reduce adhesions. It should be noted that the Seprafilm® bioresorbable membrane was only placed at the site of the surgery, i.e., the cecum resection site and under the midline incision, whereas the peritoneal injury was more generalized (18). Thus, the Seprafilm® therapy is essentially local compared to the use of the Sepracoat® solution which is more generalized. This may be due to adhesion and abscess formation in other parts of the abdominal cavity when Seprafilm® is used. However, abscess formation was noted at the sites where the Seprafilm® was located.
  • the Seprafilm® membrane may have acted as a foreign substance which, in the presence of bacteria, increases the inflammatory reaction.
  • Carboxymethyl cellulose a component of
  • Seprafilm® has been reported to reduce adhesion formation in two animal models (16, 35).
  • hyaluronic acid has been suggested that the use of hyaluronic acid decreases inflammation, interferes with fibrin formation, and accelerates the healing of peritoneal tissue. This is illustrated diagrammatically in Figure 2 (19,20,21). Inflammation is considered pivotal in adhesion and abscess formation (18,22,23,24).
  • Hyaluronic acid has been reported to inhibit the release of proteases from peritoneal leukocytes, the release of oxygen radicals from macrophages, and the scavenging of free oxygen radicals (19,25,26). Macrophages carry a hyaluronate-CD44 receptor on their membrane which is known to modulate cytokine response (27,28).
  • Hyaluronic acid is known to accelerate the healing of various tissues, including the peritoneum, without excessive growth of connective tissue (20,21). Stimulation of mesothelial recovery also seems to protect against adhesion formation (31,32). Such a mechanism of action seems unlikely since hyaluronic acid solution disappears from the abdominal cavity within 24 hours after use, before peritoneal healing takes place.
  • the animals were fasted for 12 hours before the first operation.
  • rats On the first day (day 0), rats were weighed and anaesthetized with a fluothane (Zeneca, Cheshire, United Kingdom) -nitrous oxide-oxygen mixture.
  • the abdomen of the animal was shaved and disinfected with 70% alcohol.
  • the cecum was dissected without damaging the vascularization, and was filled backwards with feces. Thereafter, the cecum was ligated just distal of the ileocecal valve, with a 3.0 polyglactin suture (Vicryl®, Ethicon.
  • Seprafilm® is a membrane formed from hyaluronic acid and carboxymethyl cellulose, and Sepracoat® is a 0.4% hyaluronic acid solution.
  • PBS phosphate buffered saline
  • Adhesions were scored in a blinded manner by one observer according to Zuhlke, whereby grade zero means no adhesions and grade 4 means firm, extensive adhesions. Grade 4 adhesions are only dissectable with sharp instruments and organ damage almost is unavoidable (15). The sites of the adhesions scored, were the midline, the upper abdomen (liver), the area between bowel loops, the parietal peritoneum and the omentum.
  • abscesses were noted and their size was taken. An abscess was defined as a walled-off collection containing purulent material. Samples were taken from the abscesses for microbiological examination. Bacterial cultures
  • Bacterial cultures taken at the day of cecal resection revealed a mixed aerobic and anaerobic flora of Proteus sp., Escherichia coli, coliforme gram negatives, anaerobe gram r o negative rods, Enterococci and Staphylococci in concentrations of 10 -10 colony forming units/ml (cfu/ml).
  • a similar flora was found in cultures of abscesses present at day seven.
  • the predominant bacteria found in abscesses at day 21 were Proteus sp. and E. coli.
  • the concentrations tended to be lower than those at day seven.
  • Diamond MP Reduction of adhesions after uterine myomectomy by Seprafilm membrane (HAL-F): a blinded, randomized, multicenter clinical study. Fertil Steril.
  • Seprafilm An absorbable adhesion barrier: An incisional hernia model in rats. Am.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Materials For Medical Uses (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Apparatus For Disinfection Or Sterilisation (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • External Artificial Organs (AREA)

Abstract

L'invention concerne un procédé relatif à la prévention ou à la réduction de la gravité de la formation d'un abcès chez l'homme, qui consiste à utiliser une solution diluée de polysaccharide polyanionique, et de préférence une solution d'acide hyaluronique ou de carboxyméthylcellulose, en application au tissu sur le site d'une procédure chirurgicale.
PCT/US2000/002988 1999-02-04 2000-02-04 Prevention de la formation d'abces WO2000045804A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AU33566/00A AU3356600A (en) 1999-02-04 2000-02-04 Prevention of abscess formation
EP00911708A EP1148886A2 (fr) 1999-02-04 2000-02-04 Prevention de la formation d'abces
CA002361572A CA2361572A1 (fr) 1999-02-04 2000-02-04 Prevention de la formation d'abces
JP2000596924A JP2002536323A (ja) 1999-02-04 2000-02-04 膿瘍形成の予防

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US11870799P 1999-02-04 1999-02-04
US60/118,707 1999-02-04

Publications (2)

Publication Number Publication Date
WO2000045804A2 true WO2000045804A2 (fr) 2000-08-10
WO2000045804A3 WO2000045804A3 (fr) 2001-03-08

Family

ID=22380260

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/002988 WO2000045804A2 (fr) 1999-02-04 2000-02-04 Prevention de la formation d'abces

Country Status (5)

Country Link
EP (1) EP1148886A2 (fr)
JP (1) JP2002536323A (fr)
AU (1) AU3356600A (fr)
CA (1) CA2361572A1 (fr)
WO (1) WO2000045804A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1205183A2 (fr) * 2000-11-13 2002-05-15 Michio Hayashi Composition antimicrobique contenant de l'acétate de cellulose
US7238677B2 (en) 2003-03-28 2007-07-03 Kimberly-Clark Worldwide, Inc. Prevention of urogenital infections
US7700819B2 (en) 2001-02-16 2010-04-20 Kci Licensing, Inc. Biocompatible wound dressing
US7763769B2 (en) 2001-02-16 2010-07-27 Kci Licensing, Inc. Biocompatible wound dressing
RU2486892C1 (ru) * 2011-11-25 2013-07-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального обучения "Хакасский государственный университет им. Н.Ф. Катанова" (ФГБОУ ВПО "ХГУ им. Н.Ф.Катанова") Способ лимфотропной терапии при ортодентальных абсцессах у кроликов

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1911769B1 (fr) * 2005-08-04 2013-10-30 Teijin Limited Dérivé de cellulose

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991004058A2 (fr) * 1989-09-21 1991-04-04 Norpharmco Inc. Traitement de maladies et d'etats pathologiques
US5700787A (en) * 1994-09-02 1997-12-23 Brigham & Women's Hospital, Inc. Capsular polysaccharide immunomodulator

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09208476A (ja) * 1996-01-26 1997-08-12 Takada Seiyaku Kk 腹腔内投与用医薬組成物

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991004058A2 (fr) * 1989-09-21 1991-04-04 Norpharmco Inc. Traitement de maladies et d'etats pathologiques
US5700787A (en) * 1994-09-02 1997-12-23 Brigham & Women's Hospital, Inc. Capsular polysaccharide immunomodulator

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
BURNS, J.W. ET AL: "Prevention of tissue injury and postsurgical adhesions by precoating tissues with hyaluronic acid solutions" JOURNAL OF SURGICAL RESEARCH, vol. 59, no. 6, - 1995 pages 644-652, XP000952895 cited in the application *
DATABASE EMBASE [Online] ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL; AN: 1994166185, XP002151239 & NARAMA, I. ET AL: "26-week chronic toxicity study and 5-week recovery test of high molecular weight sodium hyaluronate (NRD101) in rats by intraperitoneal administration" JAPANESE PHARMACOLOGY AND THERAPEUTICS, vol. 22, no. SUPPL. 3, 1994, pages 93-134, *
FOSCHI, D. ET AL: "Hyaluronic acid prevents oxygen free-radical damage to granulation tissue: a study in rats" INTERNATIONAL JOURNAL OF TISSUE REACTIONS, vol. 12, no. 6, 1990, pages 333-339, XP000953074 *
MUELLER, P.O.E. ET AL: "Intraperitoneal use of sodium carboxymethylcellulose in horses undergoing exploratory celiotomy" VETERINARY SURGERY, vol. 24, no. 2, 1995, pages 112-117, XP000953146 *
ONDERDONK, A.B. ET AL: "Immunomodulatory effects of derivatized hyaluronic acid-carboxymethylcellulose gels (DHA) in an animal model for intraabdominal sepsis" ABSTRACTS OF THE 99TH GENERAL MEETING OF THE AMERICAN SOCIETY FOR MICROBIOLOGY, vol. 99, 1 June 1999 (1999-06-01), page 11 XP000953083 *
PATENT ABSTRACTS OF JAPAN vol. 1997, no. 12 (C, 25 December 1997 (1997-12-25) & JP 09 208476 A (TAKADA SEIYAKU KK), 12 August 1997 (1997-08-12) *
PECK, L.S. ET AL: "Evaluation of CMC and HA solutions for adhesiolysis" JOURNAL OF INVESTIGATIVE SURGERY, vol. 8, 1995, pages 337-348, XP000953093 *
REIJNEN, M.M. ET AL: "Prevention of intraabdominal abscesses and adhesions using a hyaluronic acid solution in a rat peritonitis model" ARCHIVES OF SURGERY, vol. 134, no. 9, September 1999 (1999-09), pages 997-1001, XP000952881 cited in the application *
TZIANABOS, A.O. ET AL: "Structure and function of Bacteroides fragilis capsular polysaccharides: Relationship to induction and prevention of abscesses" CLINICL INFECTIOUS DISEASES, vol. 20, no. suppl. 2, 1995, pages S132-S140, XP000952888 *
YAACOBI, Y. ET AL: "Prevention of postoperative abdominal adhesions by tissue precoating with polymer solutions" JOURNAL OF SURGICAL RESEARCH, vol. 55, no. 4, October 1993 (1993-10), pages 422-426, XP000952885 cited in the application *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1205183A2 (fr) * 2000-11-13 2002-05-15 Michio Hayashi Composition antimicrobique contenant de l'acétate de cellulose
EP1205183A3 (fr) * 2000-11-13 2002-11-06 Michio Hayashi Composition antimicrobique contenant de l'acétate de cellulose
US6669903B2 (en) 2000-11-13 2003-12-30 Michio Hayashi Bactericidal or bacteriostatic method
US7700819B2 (en) 2001-02-16 2010-04-20 Kci Licensing, Inc. Biocompatible wound dressing
US7763769B2 (en) 2001-02-16 2010-07-27 Kci Licensing, Inc. Biocompatible wound dressing
US8084664B2 (en) 2001-02-16 2011-12-27 Kci Licensing, Inc. Biocompatible wound dressing
US8163974B2 (en) 2001-02-16 2012-04-24 Kci Licensing, Inc. Biocompatible wound dressing
US8735644B2 (en) 2001-02-16 2014-05-27 Kci Licensing, Inc. Biocompatible wound dressing
US7238677B2 (en) 2003-03-28 2007-07-03 Kimberly-Clark Worldwide, Inc. Prevention of urogenital infections
RU2486892C1 (ru) * 2011-11-25 2013-07-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального обучения "Хакасский государственный университет им. Н.Ф. Катанова" (ФГБОУ ВПО "ХГУ им. Н.Ф.Катанова") Способ лимфотропной терапии при ортодентальных абсцессах у кроликов

Also Published As

Publication number Publication date
EP1148886A2 (fr) 2001-10-31
AU3356600A (en) 2000-08-25
CA2361572A1 (fr) 2000-08-10
WO2000045804A3 (fr) 2001-03-08
JP2002536323A (ja) 2002-10-29

Similar Documents

Publication Publication Date Title
Burns et al. A hyaluronate based gel for the prevention of postsurgical adhesions: evaluation in two animal species
Leach et al. Reduction of postsurgical adhesion formation in the rabbit uterine horn model with use of hyaluronate/carboxymethylcellulose gel
Elkins et al. Adhesion prevention by solutions of sodium carboxymethylcellulose in the rat. I.
CA2458853C (fr) Utilisation de fucanes dans le traitement des adherences, de l'arthrite et du psoriasis
AU2002325113A1 (en) Use of fucans in the treatment of adhesions, arthritis and psoriasis
Back et al. Application of hyaluronic acid/sodium alginate-based microparticles to prevent tissue adhesion in a rabbit model
Murphy et al. Use of a high-molecular-weight carboxymethylcellulose in a tissue protective solution for prevention of postoperative abdominal adhesions in ponies
DK175597B1 (da) Anvendelse af en vævsplasminogenaktivator (t-PA) til fremstilling af et præparat til anvendelse til forebyggelse af fibrinaflejring eller adhærencedannelse eller -gendannelse, topiske præparater og dispenseringsindretninger til.
EP1148886A2 (fr) Prevention de la formation d'abces
Peck et al. Topics and trends in surgical research: evaluation of CMC and HA solutions for adhesiolysis
KR20030055102A (ko) 유착방지제
Reijnen et al. Hyaluronic acid‐based agents do not affect anastomotic strength in the rat colon, in either the presence or absence of bacterial peritonitis
US8158610B2 (en) Dextrin-containing composition for preventing surgical adhesions
JP4276601B2 (ja) 外科手術上の癒着を阻止するためのデキストリンを含有する組成物
EP1001790B1 (fr) Composition destinee a la lubrification et a la separation de tissus et de membranes biologiques
US20110293691A1 (en) Multimodal adhesion barrier
van Goor MMP]. Reijnen JFGM Meis VA Postma
Durmus et al. Comparison of the effects of different concentrations of sodium carboxymethylcellulose on prevention of intraabdominal adhesions in rats
Goldberg Tissue-protective solutions and films for adhesion prevention
Akçıl et al. Composing an Adhesion Barrier Using Hyaluronic Acid and Carboxymethylcellulose to Prevent Mediastinal Adhesion
Burns et al. Hyaluronan-Based Membrane for the Prevention of Postsurgical Adhesions
Reijnen et al. Hyaluronan-based agents do not affect anastomotic strength in the rat colon, in either the
KR101349200B1 (ko) 헥소사민 화합물 또는 이의 약학적으로 허용 가능한 염을포함하는, 수술 후 유착의 예방 또는 치료용 약학 조성물

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: A3

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

WWE Wipo information: entry into national phase

Ref document number: 33566/00

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2000911708

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2361572

Country of ref document: CA

Ref country code: CA

Ref document number: 2361572

Kind code of ref document: A

Format of ref document f/p: F

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 596924

Kind code of ref document: A

Format of ref document f/p: F

WWP Wipo information: published in national office

Ref document number: 2000911708

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 2000911708

Country of ref document: EP