WO2001030410A1 - Utilisation medicale - Google Patents

Utilisation medicale Download PDF

Info

Publication number
WO2001030410A1
WO2001030410A1 PCT/GB2000/004154 GB0004154W WO0130410A1 WO 2001030410 A1 WO2001030410 A1 WO 2001030410A1 GB 0004154 W GB0004154 W GB 0004154W WO 0130410 A1 WO0130410 A1 WO 0130410A1
Authority
WO
WIPO (PCT)
Prior art keywords
bonding material
tissue bonding
sheet
poly
albumin
Prior art date
Application number
PCT/GB2000/004154
Other languages
English (en)
Inventor
Peter Edwardson
Jose Velada
Original Assignee
Tissuemed Ltd.
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 Tissuemed Ltd. filed Critical Tissuemed Ltd.
Priority to AU10436/01A priority Critical patent/AU1043601A/en
Publication of WO2001030410A1 publication Critical patent/WO2001030410A1/fr
Priority to DK01976497T priority patent/DK1328300T3/da
Priority to PCT/GB2001/004682 priority patent/WO2002034304A1/fr
Priority to CA002422786A priority patent/CA2422786A1/fr
Priority to AT01976497T priority patent/ATE286408T1/de
Priority to JP2002537355A priority patent/JP2004512314A/ja
Priority to AU2001295765A priority patent/AU2001295765B2/en
Priority to ES01976497T priority patent/ES2236314T3/es
Priority to EP01976497A priority patent/EP1328300B1/fr
Priority to AU9576501A priority patent/AU9576501A/xx
Priority to US10/399,315 priority patent/US20040049187A1/en
Priority to DE60108258T priority patent/DE60108258T2/de

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/043—Proteins; Polypeptides; Degradation products thereof
    • A61L31/047—Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/043—Proteins; Polypeptides; Degradation products thereof

Definitions

  • This invention relates to a novel use of tissue bonding material, in particular to the use of such material for the prevention or inhibition of the formation of undesired connective tissue following surgery.
  • Post-surgical adhesion the formation of undesired connective tissue between adjacent tissues, is a serious problem which can give rise to major post-surgical complications. It is a particular problem in bowel surgery where it can cause, for instance, twisting of the bowel which may then necessitate further surgical intervention. Clearly, it would be beneficial for the occurrence of such adhesion to be avoided.
  • tissue bonding material as an adhesive to bond tissues together after surgery or to repair wounds, eg in place of suturing or the like, is known.
  • tissue bonding material commonly comprises proteinaceous material which is applied to the tissues to be joined and then subjected to curing by the action of heat or light. This causes the material to crosslink to itself and to the tissues, thereby creating a bond.
  • a method for the prevention or inhibition of post-surgical adhesion comprises coating one or more tissues exposed in a surgical procedure with a tissue bonding material, and causing or allowing that material to cure.
  • tissue bonding material in the manufacture of a composition for the prevention or inhibition of post-surgical adhesion.
  • tissue bonding material is meant a material which when applied to body tissues is capable of binding to those tissues and of causing the tissues to adhere to each other. The mechanism of such adhesion will normally involve curing by which the tissue bonding material molecules covalently bond to each other (cross- linking) and to the tissues.
  • the tissue bonding material will most commonly be a crosslinkable proteinaceous or other peptide material.
  • the material may be selected from natural and synthetic peptides, enzymatically cleaved or shortened variants thereof and crosslinked derivatives thereof, as well as mixtures of any of the above. Included among the peptides are structural proteins and serum proteins. Examples of proteins are albumin, ⁇ -globulins, ⁇ -globulins, ⁇ -globulins, transthyretin, collagen, elastin and fibronectin and coagulation factors including fibrinogen, fibrin and thrombin.
  • the invention more specifically provides the use of such materials in the prevention or inhibition of post-surgical adhesion, and in the manufacture of a composition for that purpose.
  • the tissue bonding material may be formulated in any suitable form for application to the tissues which are to be protected from post-surgical adhesion.
  • the formulation may be a liquid or low viscosity gel which may be applied by spraying or any other suitable means of application. A certain degree of viscosity may be desirable in order to aid retention of the material at the locus to which it is applied.
  • the material may therefore be thixotropic such that it is readily dispensed, eg from a spray pump or other applicator, but is viscous when not subjected to shear force.
  • Viscosity-modifying components which may be incorporated into the composition include hyaluronic acid and salts thereof such as sodium hyaluronate, hydroxypropylmethylcellulose, polyethylene glycol, glycerine, dextrans, honey, sodium chondroitin sulphate and mixtures thereof.
  • Formulations in the form of liquids or gels may be prepared by mixing the various components in appropriate proportions.
  • the tissue bonding material may for example be dispersed or dissolved in water, together with any additional components such as viscosity-modifying agents.
  • the liquid or gel formulation most preferably also comprises a plasticiser to confer sufficient flexibility on the formulation after curing.
  • plasticisers include polyalcohols, eg glycerol, sorbitol etc.
  • the tissue bonding material may alternatively be incorporated into a flexible sheet which can be applied to the tissue and then cured, or allowed to cure, such that it bonds to the tissue.
  • a sheet of this kind may be formed with a degree of flexibility to suit the application for which it is intended, eg by the incorporation of suitable additives and/or controlling the degree of cross-linking.
  • Such a sheet may comprise a single layer of the tissue bonding material.
  • a carrier layer may be provided.
  • Suitable materials for the carrier layer are biocompatible materials, eg polybutyrate, polysaccharides, polytetrafluoroethylene, polyesters, glycoproteins, polymer composites, collagen (including cross-linked collagen), pericardium, ethacrylate, polyurethane and derivatives thereof.
  • Other materials include absorbable and non-absorbable suture materials, eg polypropylene, polyglactin, polylactic acid, polyglycolic acid, polydioxanone and polyglyconate.
  • the sheet formulation preferably further comprises a plasticiser in order to ensure that the sheet has sufficient flexibility, even after polymerisation or cross-linking.
  • plasticisers include polyalcohols, eg glycerol, sorbitol etc.
  • the sheet preferably also comprises a synthetic structural polymer to confer strength and elasticity on the sheet.
  • Suitable such polymers include water-soluble thermoplastic polymers, in particular selected from the group consisting of poly(vinyl alcohol), poly(ethylene glycol), poly(vinyl pyrrolidone), poly(acrylic acid), poly(acrylamide), copolymers of methylvinyl ether with maleic anhydride in the anhydride, acid, ester or mixed salt form, and similar materials.
  • a relatively small proportion of surfactant, most preferably a non-ionic surfactant will generally be incorporated into the sheet, though normally to facilitate manufacture (prevention of foaming etc) rather than to confer any beneficial property on the finished product.
  • Suitable surfactants include block copolymers of ethylene oxide and propylene oxide, such as those sold under the trade mark Pluronic ® by BASF.
  • the sheet may be manufactured by mixing the different components in aqueous solution as follows:
  • tissue-bonding material 5 - 80%, more preferably 10 - 60 %, and most preferably 15 to 40%.
  • structural polymer 0.01 - 20%, more preferably 1 - 10% , and most preferably 2 - 8%.
  • surfactant 0.001 - 10%, more preferably 0.01 - 5%, and most preferably 0.1
  • plasticiser 0.01 - 60%, more preferably 1 - 50%, and most preferably 10 -
  • the sheet may be prepared by casting the above solution into a suitable non-stick mould (e.g. of PTFE), and allowing it to set through evaporation.
  • a suitable non-stick mould e.g. of PTFE
  • the casting process used to achieve the desired thickness of the sheet may involve pouring, manual spreading or spraying of the component solutions.
  • the sheet according to the invention may be 20 - 200 ⁇ m in thickness, and typically approximately 100 ⁇ m in thickness.
  • the sheet will typically contain between 10% and 50% water by weight, and most preferably between 20% and 40%.
  • the sheet may be partially or totally hydrated with a suitable aqueous medium at or following implantation (eg a body fluid or saline solution).
  • a suitable aqueous medium eg a body fluid or saline solution.
  • the preferred tissue bonding material for use in the present invention is a soluble protein which is not part of the clotting cascade. Porcine albumin or porcine pericardium or any abundant non-thrombogenic protein, ie excluding collagen, may be used. Genetically or chemically modified versions of such proteins may also be suitable.
  • formulations for use in the method of the invention are formulations comprising albumin.
  • Mammalian albumin is preferred, particularly porcine albumin.
  • the formulation most preferably further comprises glycerol as plasticiser.
  • the tissue bonding material may, or may not, contain a thermochromic compound (which undergoes a colour change on the application of heat) and/or a photochromic compound (which undergoes a colour change on the application of light).
  • the material may include a chromophore, such as methylene blue, which will change colour when the end point (when light activated) has been reached, as described in WO 96/22797.
  • a visual colour change may provide the user with an indication that sufficient energy has been applied to ensure that curing of the tissue bonding material has occurred.
  • the resultant colour change ensures that the material will absorb no further radiant energy. This provides protection against excess energy input.
  • a light activated chromophore If a light activated chromophore is present it provides the user, ie normally a surgeon or veterinary surgeon, with means to determine whether or not adequate energy has been provided in the desired area, thereby preventing thermal damage as a result of the application of excessive energy.
  • curing may be brought about using a chemical activator such as a crosslinking agent, eg hexamethylenediisocyanate, which may be applied by spraying or wetting. In some circumstances the tissue bonding material may cure spontaneously. However, it is generally preferred that curing be brought about by the application of heat or, or most preferably, light.
  • a chemical activator such as a crosslinking agent, eg hexamethylenediisocyanate
  • composition was made up by dissolving/dispersing the albumin, methylene blue and glycerol in the water for injection.
  • the resulting viscous solution can be applied to exposed tissues by spraying, and cured by the application of laser or polychromatic light. On completion of curing the colour changes from blue to colourless.
  • porcine albumin (Sigma) was dissolved in 2.5ml water for injection (Phoenix Pharmaceuticals pH 7.7) and 0.5ml of 1% w/v methylene blue for injection. To this solution, 0.585g D-sorbitol was added and dissolved. Heating of this solution in a thermostatted water bath at 59°C increases the film rehydration time from 50 seconds (if left at room temperature) to 140 seconds. This solution was left to cool for 30 minutes and then cast on a level PTFE-coated surface. The film was left to dry at room temperature for 20 hours.
  • Example 3 Sheet Formulation
  • porcine albumin (Sigma) was dissolved in 4.5ml of water for injection (Phoenix Pharmaceuticals, pH 7.7) and 0.5ml of 1% w/v methylene blue for injection. To this solution, 0.5 glycerol was added and dissolved. This solution was then cast on a level PTFE-coated surface. The film was left to dry at room temperature for 20 hours.
  • porcine albumin 1.51g of porcine albumin, 0.1g of 80% hydrolysed polyvinyl alcohol, 1.42g of glycerol and 0.01 g of Pluronic 25R2 were dissolved in 2.02g of water for injection. 0.1 ml of this solution was poured onto a level PTFE surface, and spread to a thickness of approximately 50 ⁇ m. The solution was heated to 120°C for 10 minutes to evaporate off water and allowed to cool.
  • porcine albumin 0.5g of 80% hydrolysed polyvinyl alcohol, 3.00g of glycerol and 0.02g of Pluronic 25R2 were dissolved in 3.53g of water for injection. 0.1 ml of this solution was poured onto a level PTFE surface, and spread to approximately 30 ⁇ m thick. The sheet was heated at 120°C for 20 minutes and allowed to cool.
  • Example 6 Sheet Formulation 9.00g of porcine albumin, 1.53g of 80% hydrolysed polyvinyl alcohol, 8.98g of glycerol and 0.06g of Pluronic 25R2 were dissolved in 10.56g of water for injection. 0.3 ml of this solution was poured onto a level PTFE surface, and spread to a thickness of approximately 50 ⁇ m, and left at room temperature for 1 hour.

Abstract

L'invention concerne l'utilisation de matières qui lient des tissus, par exemple des matières par l'intermédiaire desquelles des tissus corporels peuvent adhérer ensemble, afin de prévenir la formation non souhaitée de tissu conjonctif entre des tissus adjacents suite à une opération chirurgicale (adhésion post chirurgicale). La matière qui lie les tissus est, de préférence, une protéine ou similaire, par excellence l'albumine, et est préparée comme un liquide ou un gel, ou comme une feuille flexible qui peut être appliquée aux tissus et entraîner leur guérison.
PCT/GB2000/004154 1999-10-28 2000-10-27 Utilisation medicale WO2001030410A1 (fr)

Priority Applications (12)

Application Number Priority Date Filing Date Title
AU10436/01A AU1043601A (en) 1999-10-28 2000-10-27 Medical use
DE60108258T DE60108258T2 (de) 2000-10-23 2001-10-22 Selbstklebende, hydratierbare matrix für therapeutische anwendungen
AT01976497T ATE286408T1 (de) 2000-10-23 2001-10-22 Selbstklebende, hydratierbare matrix für therapeutische anwendungen
PCT/GB2001/004682 WO2002034304A1 (fr) 2000-10-23 2001-10-22 Matrice hydratable auto-adhesive a usage therapeutique topique
CA002422786A CA2422786A1 (fr) 2000-10-23 2001-10-22 Matrice hydratable auto-adhesive a usage therapeutique topique
DK01976497T DK1328300T3 (da) 2000-10-23 2001-10-22 Selvklæbende hydratiserbar matrix til topisk terapeutisk anvendelse
JP2002537355A JP2004512314A (ja) 2000-10-23 2001-10-22 局所的な治療に用いられる粘着性の水和可能なマトリックス
AU2001295765A AU2001295765B2 (en) 2000-10-23 2001-10-22 Self-adhesive hydratable matrix for topical therapeutic use
ES01976497T ES2236314T3 (es) 2000-10-23 2001-10-22 Maatriz autoadhesiva hidratable para uso terapeutico topico.
EP01976497A EP1328300B1 (fr) 2000-10-23 2001-10-22 Matrice hydratable auto-adhesive a usage therapeutique topique
AU9576501A AU9576501A (en) 2000-10-23 2001-10-22 Self-adhesive hydratable matrix for topical therapeutic use
US10/399,315 US20040049187A1 (en) 2000-10-23 2001-10-22 Self-adhesive hydratable matrix for topical therapeutic use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9925379.1 1999-10-28
GBGB9925379.1A GB9925379D0 (en) 1999-10-28 1999-10-28 Medical use

Publications (1)

Publication Number Publication Date
WO2001030410A1 true WO2001030410A1 (fr) 2001-05-03

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2000/004154 WO2001030410A1 (fr) 1999-10-28 2000-10-27 Utilisation medicale

Country Status (3)

Country Link
AU (1) AU1043601A (fr)
GB (1) GB9925379D0 (fr)
WO (1) WO2001030410A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004087227A1 (fr) * 2003-04-04 2004-10-14 Tissuemed Limited Formulations pour adhesifs tissulaires
US7373375B2 (en) 2000-09-29 2008-05-13 Sony Corporation Information management system using agents
EP2269662A1 (fr) * 2009-06-30 2011-01-05 Karl Storz Endoskop Produktions GmbH Procédé et soudure destinés à l'assemblage interposé de deux surfaces
CN107249651A (zh) * 2015-02-27 2017-10-13 大日精化工业株式会社 医疗用材料和防粘连材料
CN113440644A (zh) * 2021-06-10 2021-09-28 广东省科学院健康医学研究所 一种弹性白蛋白胶粘剂及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996022797A1 (fr) * 1995-01-27 1996-08-01 Tissuemed Limited Amelioration de l'activation d'adhesifs 'biologiques' pour tissus, agents liants et agents de scellement faisant appel a des chromophores a 'couleur changeante'
WO1997029715A1 (fr) * 1996-02-20 1997-08-21 Fusion Medical Technologies, Inc. Compositions et procedes permettant de fermer les tissus et de prevenir les adherences postoperatoires
US5791352A (en) * 1996-06-19 1998-08-11 Fusion Medical Technologies, Inc. Methods and compositions for inhibiting tissue adhesion

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996022797A1 (fr) * 1995-01-27 1996-08-01 Tissuemed Limited Amelioration de l'activation d'adhesifs 'biologiques' pour tissus, agents liants et agents de scellement faisant appel a des chromophores a 'couleur changeante'
WO1997029715A1 (fr) * 1996-02-20 1997-08-21 Fusion Medical Technologies, Inc. Compositions et procedes permettant de fermer les tissus et de prevenir les adherences postoperatoires
US5791352A (en) * 1996-06-19 1998-08-11 Fusion Medical Technologies, Inc. Methods and compositions for inhibiting tissue adhesion

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7373375B2 (en) 2000-09-29 2008-05-13 Sony Corporation Information management system using agents
WO2004087227A1 (fr) * 2003-04-04 2004-10-14 Tissuemed Limited Formulations pour adhesifs tissulaires
EP2269662A1 (fr) * 2009-06-30 2011-01-05 Karl Storz Endoskop Produktions GmbH Procédé et soudure destinés à l'assemblage interposé de deux surfaces
US20110100545A1 (en) * 2009-06-30 2011-05-05 Beat Krattiger Method and solder for form-fitted joining of two surfaces
US8641856B2 (en) 2009-06-30 2014-02-04 Storz Endoskop Produktions Gmbh Method and solder for form-fitted joining of two surfaces
CN107249651A (zh) * 2015-02-27 2017-10-13 大日精化工业株式会社 医疗用材料和防粘连材料
CN113440644A (zh) * 2021-06-10 2021-09-28 广东省科学院健康医学研究所 一种弹性白蛋白胶粘剂及其制备方法
CN113440644B (zh) * 2021-06-10 2023-01-17 广东省科学院健康医学研究所 一种弹性白蛋白胶粘剂及其制备方法

Also Published As

Publication number Publication date
AU1043601A (en) 2001-05-08
GB9925379D0 (en) 1999-12-29

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