WO2014187783A1

WO2014187783A1 - Use of an isolated collagen-containing sheet material for producing a flat anti-adhesion barrier

Info

Publication number: WO2014187783A1
Application number: PCT/EP2014/060258
Authority: WO
Inventors: Ludwig Baumgartner
Original assignee: Ludwig Baumgartner
Priority date: 2013-05-21
Filing date: 2014-05-19
Publication date: 2014-11-27
Also published as: DE102013008969A1

Abstract

The invention relates to the use of an isolated collagen-containing sheet material for producing a flat anti-adhesion barrier.

Description

Use of an isolated collagen-containing sheet for

Production of a two-dimensional adhesion barrier

The present invention relates to the use of an isolated

collagen-containing sheet for the production of a flat

Adhesion barrier.

Adhesions or adhesions, medically also called adhesions, form between organs or body tissues, which are normally not connected. Adhesions usually arise as a result of

Damage (lesions) of tissue in the course of a surgical procedure or after inflammation.

Adhesion may be preceded by inflammation as part of or immediately after surgery, with adhesion resulting from disruption of the healing process or lack of oxygen during surgery.

Adhesions can also form when foreign bodies are attached to the

Surgery site remain and form a focal point of inflammation. For example, sebum on surgical gloves or remnants necessary to suture the wound, or remnants of a surgical adhesive remaining in the wound, may be responsible for the formation of an inflammatory focus which subsequently results in the formation of adhesions. Essentially, adhesions consist of connective tissue and are partially permeated by well-perfused fibers.

In addition to surgical adhesions, postoperative adhesions may also be due to introduced plastic or biological tissue materials used to reinforce or replace body tissue.

Adhesions can be the cause of many complaints postoperatively, affecting the function of affected organs or parts of the body.

For example, in dura mater repairs with bioresorbable replacement tissues, adhesions to the brain may occur or, in operations of tendon ruptures, adhesions of the repaired tendon may interfere with the tendon

surrounding body tissues occur. In abdominal hernias, for example, adhesions may occur in the intestinal area. When using plastic nets it can lead to serious adhesions.

A resulting adhesion can only be treated by an operative separation of the adhesion (adhesiolysis). Because of the high rate of reformation of adhesions after adhesiolysis, the success of this treatment is low.

The prevention of adhesions is therefore at the forefront of surgical procedures.

Effective liquid adhesion barriers, such as Ringer's lactate solution or a 4% icodextrin solution, are known in the art. These solutions are used as an interoperative irrigation fluid and as a postoperative instillate in, for example, gynecological or visceral surgery. For example, DE 10 2004 027 363 A1 describes the use of an equine collagen foil comprising a non-naturally occurring biomatrix of equine collagen fibrils for the manufacture of a medicament for the repair and regeneration of dura mater tissue in a mammal.

Furthermore, WO 2004/096086 A1 discloses surgical surface inserts for preventing tissue layer adhesions in surgical areas which comprise at least one layer of a thin, bioresorbable, smooth foil and a stabilization layer connected to the foil layer in the form of a reinforcing mesh made of plastic material, which contains a metal-containing, body-compatible continuous coating of the plastic threads is provided include.

The bioresorbable film comprises polylactate and is said to prevent adhesions during the postoperative period.

The surface insert described in WO 2004/096086 A1 obtains sufficient stability for permanent retention in the body only through the reinforcing net.

There is therefore a need for a two-dimensional adhesion barrier which has a sufficient barrier effect. In addition, the support structure of the surface adhesion barrier should be flexible, strong and liquid-tight, for example, to be used as Dura mater replacement.

In addition, the support structure of the two-dimensional adhesion barrier after its surgical use should be partially, preferably completely,

Be bioabsorbable, wherein the support structure of the surface adhesion barrier is partially, preferably completely, converted into endogenous tissue. The surface adhesion barrier should maintain its barrier properties after conversion of the support structure into the body's own tissue. The object of the present invention is achieved by the use of an isolated collagen-containing sheet for producing a two-dimensional adhesion barrier, wherein the isolated collagen-containing sheet is provided with at least one, preferably sheet-like, metal and / or plastic-containing coating.

Preferred embodiments of the present invention are set out in dependent claims 2 to 11.

According to the invention, the term adhesion barrier is understood to mean a barrier which forms the formation of adhesions, also known as adhesions or adhesions, between organs and surrounding body tissue on the one hand and an insert introduced during a surgical procedure on the other hand partially, preferably completely, in the postoperative

Healing prevented.

An isolated collagen-containing sheet used according to the invention preferably remains at the point of attachment after a surgical procedure, where it provides separation of organs and surrounding body tissues after surgery.

When using an isolated collagen-containing sheet according to the invention, the infiltration of connective tissue cells between organs and surrounding endogenous tissues is reduced, preferably prevented, by the at least one, preferably sheet-like, metal- and / or plastic-containing coating.

By reducing, preferably preventing, the infiltration of

Connective tissue cells by the at least one metal and / or plastic-containing coating is prevented formation of adhesions. In a preferred embodiment, the isolated is collagen-containing

Fabrics bioresorbable after introduction into the surgical area.

Bioresorbable in the context of the invention is understood to mean that the isolated collagen-containing fabric is partially, preferably completely, converted into endogenous tissue after introduction into the surgical area.

The transformation of the isolated collagen - containing fabric into

the body's own tissue takes place through the immigration of

Connective tissue cells in the collagen-containing sheet, wherein after

Conversion of the isolated collagen-containing sheet remains at least one, preferably flat, metal and / or plastic-containing coating in the body and the barrier property is maintained.

Preferably, the collagen-containing sheet is therefore not completely enveloped with the at least one metal and / or plastic-containing coating.

Preferably, the infiltration of connective tissue cells into the isolated collagen-containing sheet occurs over areas of the isolated collagen-containing sheet that does not have a metal and / or plastic-containing coating, for example edge portions and / or cut edges of the isolated collagen-containing sheet.

In a preferred embodiment, the at least one, preferably one, metal and / or plastic-containing coating on one side on the collagen-containing sheet, preferably flat, arranged.

The at least one, preferably one, metal- and / or plastic-containing coating is preferably arranged directly on the collagen-containing sheet, preferably flat. Preferably, two metal and / or plastic-containing coatings are arranged on one side of the collagen-containing sheet. For example, a plastic-containing coating and a metal-containing coating can be arranged successively, preferably flat, on the collagen-containing sheet. Alternatively, two metal-containing coatings, which preferably have a different composition, or two plastic-containing coatings, preferably a different

Having composition, successively on the collagen-containing

Be arranged sheet.

In a further preferred embodiment, the at least one, preferably two, metal and / or plastic-containing coating (s) is (are) arranged on both sides of the collagen-containing sheet. Preferably, the at least one, preferably two, metal and / or plastic-containing coating (s) are (are) on opposite sides of the collagen-containing

Plane arranged.

Preferably, at least one, preferably one, metal-containing

Coating arranged on one side of the collagen-containing sheet and at least one, preferably one, plastic-containing coating on another, preferably opposite, side of the collagen-containing

Plane arranged. Alternatively, two metal-containing coatings or two plastic-containing coatings are two, preferably

opposite side of the collagen-containing sheet arranged.

In a preferred embodiment, the at least one metal- and / or plastic-containing coating is flat, preferably full-surface, arranged on the isolated collagen-containing sheet. Preferably, the at least one metal and / or plastic-containing coating is a

continuous layer, which is more preferably liquid-tight. By a flat, preferably full-surface, arrangement of the at least one metal and / or plastic-containing coating on the collagen-containing sheet, the infiltration of connective tissue cells between organs and surrounding endogenous tissues, which are separated by the at least one metal and / or plastic-containing coating, largely , preferably completely, while preventing migration of connective tissue cells into the isolated collagen-containing sheet, such as uncoated areas of the isolated collagen-containing sheet. As a result, the isolated collagen-containing fabric can be converted into endogenous tissue, while the at least one metal- and / or plastic-containing coating continues to act as an adhesion barrier.

Alternatively, the at least one metal- and / or plastic-containing coating is arranged overlapping on the isolated collagen-containing sheet. Preferably, the at least one metal and / or plastic-containing

Coating and the collagen-containing sheet connected by overlapping ends.

In a further preferred embodiment, the isolated collagen-containing fabric is provided with only one metal and / or plastic-containing, preferably metal- or plastic-containing, coating which is flat,

preferably over the entire surface, is arranged on the isolated collagen-containing sheet. Preferably, the one metal and / or plastic-containing coating is a continuous coating, which is more preferred

is liquid-tight.

In another preferred embodiment, the isolated collagen-containing sheet is an avital autogenous tissue or web, an avital allograft or tissue web, an avian xenogeneic tissue or web, a collagen sheet, or a collagen mesh. Biological tissues, such as pericardium, preferably have properties such as flexibility, strength and leak-tightness.

By processing into an avital, bioresorbable tissue or

Woven fabric is due to the individual process steps removal of all non-collagen components, such as fat. Through these process steps, however, a loosening of the fiber structure continues, so that thereby a more or less porous fabric is formed.

The autogenous tissue or tissue network, allogenic tissue or tissue network or xenogeneic tissue or tissue network used may be provided, for example, by methods known in the art. Preferably, a method described in WO 01/13718 A1 or WO 2009/140980 A1, the contents of which are hereby incorporated by reference, is an avital allograft tissue or tissue network used in the present invention, an avian xenogeneic tissue or tissue web or an avital autogenous tissue or tissue network provided.

In contrast to a woven fabric, a woven mesh has a net-like structure which, for example, can be made by introducing holes into an avital,

Bioresorbable tissue is obtained.

A suitable avital, bioresorbable tissue or tissue mesh can be obtained commercially, for example, from Tutogen Medical GmbH (Neunkirchen a.Br., DE).

Preferably, by suitable process steps, a destruction of tissue cells, a washing out of cellular and extracellular components and a removal and / or inactivation of prions, bacteria and / or viruses from the autogenous tissue, allogenic tissue or xenogeneic tissue to obtain an avital isolated collagen-containing sheet. Suitable tissues preferably include dura mater, dermis, fascia lata, temporal fascia or pericardium. Depending on the origin of the corresponding tissue is autogenous, allogenic or xenogeneic tissue, preferably before the application of at least one metal and / or

plastic-containing coating is provided as avitales, bioresorbable tissue.

The remaining collagen structure of the avital autogenous tissue or

Tissue network, avital allogeneic tissue or tissue network or avital xenogeneic tissue or tissue network can serve as a guide rail for building new, endogenous tissue after introduction into the body.

Alternatively, the isolated collagen-containing sheet is a collagen sheet or a collagen mesh.

Suitable methods for producing a collagen foil or a collagen mesh used according to the invention are known in the art. Preferably, a method described in DE 10 2004 027 363 A1 provides a collagen foil or collagen mesh used in the present invention, preferably from horse or bovine tendons.

Preferably, a collagen foil has substantially no pores. In contrast, a collagen network has a large pore structure consisting essentially of collagen.

In a further preferred embodiment, the at least one metal- and / or plastic-containing coating is porous, wherein the at least one metal- and / or plastic-containing coating has pores having a pore size of less than 150 nm, preferably less than 100 nm.

By choosing suitable coating parameters, such as

Coating time in the vapor deposition, the thickness and the Porosity of at least one metal and / or plastic-containing coating can be adjusted.

Connective tissue cells have a size of about 150 to 300 nm.

By using at least one metal and / or plastic-containing

Coating, the migration of connective tissue cells through the at least one metal- and / or plastic-containing coating is effectively prevented if the at least one metal- and / or plastic-containing coating is non-porous or any pores present have a size of less than 150 nm, preferably less than 100 nm.

More preferably, the at least one metal and / or plastic-containing coating is non-porous throughout, preferably liquid-tight.

In a further preferred embodiment, a surface of the isolated collagen-containing sheet is pretreated to close or reduce any existing pores in the isolated collagen-containing sheet. Preferably, the pre-treatment reduces the size of existing pores, more preferably to a size of less than 150 nm, preferably less than 100 nm.

Furthermore, possibly existing unevenness of the surface of the isolated collagen-containing sheet by the pretreatment

be compensated.

Preferably, the at least one metal and / or plastic-containing coating is then applied to the pretreated surface of the isolated collagen-containing sheet.

For example, first at least one plastic-containing coating can be applied to the isolated collagen-containing sheet to to close or reduce any existing pores in the isolated collagen-containing sheet. Subsequently, at least one further plastic-containing coating and / or at least one

metal-containing coating applied to the pretreated surface of the isolated collagen-containing sheet.

In a further preferred embodiment, the at least one metal- and / or plastic-containing coating has a thickness of more than 1 nm, preferably more than 10 nm, preferably more than 100 nm.

More preferably, the at least one metal and / or plastic-containing coating is a flexible metal and / or plastic-containing coating. In order to preferably ensure the flexibility of the metal- and / or plastic-containing coating, the metal- and / or plastic-containing coating has a thickness in the range from 1 nm to 5000 nm, preferably 10 nm to 3500 nm, more preferably 25 to 3000 nm, more preferably 50 to 2900 nm, more preferably 100 nm to 1900 nm.

In a further preferred embodiment, the at least one metal- and / or plastic-containing coating on the isolated collagen-containing

Sheet by vapor deposition, preferably by

physical vapor deposition (PVD) or chemical

Vapor Deposition (CVD) applied.

Preferably, the chemical vapor deposition is performed by means of PACVD (Plasma Activated Chemical Vapor Deposition).

A suitable method for applying at least one metal- and / or plastic-containing coating by vapor deposition is

For example, in DE 199 45 299 A1, the content of which is incorporated herein by reference. The method described in DE 199 45 299 A1 allows the application of at least one metal- and / or plastic-containing coating on the isolated collagen-containing sheet.

Preferably, by using suitable metals, preferably gold, silver, palladium, titanium or alloys, compounds or mixtures thereof, more preferably gold, silver, titanium or alloys, compounds or mixtures thereof, more preferably gold, an application on a metal-containing coating means Vapor deposition, preferably PACVD done.

By using suitable monomers, for example tetrafluoroethylene, ethylene, silicone monomers or mixtures thereof, preferably a plastic-containing coating can be applied by means of vapor deposition, preferably PACVD, which is preferably polypropylene,

Polytetrafluoroethylene, silicone or mixtures thereof.

Preferably, the at least one metal and / or plastic-containing

Coating designed as a film.

Preferably, the film has a thickness in the range from 1 nm to 3000 nm, more preferably from 20 nm to 1500 nm, more preferably from 50 nm to 500 nm.

Preferably, the film formed as at least one metal and / or plastic-containing coating on the isolated collagen-containing

Fabric by sewing, gluing, pressing or welding, more preferably by gluing, attached.

Preferably, the film formed as at least one metal and / or plastic-containing coating with the isolated collagen-containing

Glued fabrics. Preferably, the film comprising the collagen-containing sheet is prepared by using a preferably medically suitable adhesive which is more preferably selected from the group consisting of cyanoacrylate adhesive,

Fibrin glue, chitosan adhesive, dispersion adhesive or mixtures thereof, more preferably fibrin glue, chitosan glue or mixtures thereof, is selected, glued.

Preferably, the film with the collagen-containing sheet is connected over the entire surface. Alternatively, the film pointwise with the collagen-containing

Be connected.

In another preferred embodiment, they are (are) as a film

trained at least one, preferably two, metal and / or

plastic-containing coating (s) on both sides of the collagen-containing

Sheets arranged. Preferably, the ones formed as a film are (are) at least one, preferably two, metal and / or plastic-containing

Coating (s) on opposite sides of the collagenous

Plane arranged.

Preferably, at least one, preferably one, formed as a foil metal and / or plastic-containing coating on one side of the

collagen-containing sheet arranged and at least one, preferably one, plastic-containing coating on another, preferably

opposite side of the collagen-containing sheet arranged.

In a further preferred embodiment, the at least one, preferably flat, metal-containing coating is a metal layer.

Preferably, the metal layer comprises gold, silver, palladium, titanium or alloys, compounds or mixtures thereof, more preferably gold. In a further preferred embodiment, the at least one, preferably flat, plastic-containing coating is a polymer layer.

Preferably, the polymer layer comprises or consists of polypropylene, polytetrafluoroethylene, silicone or mixtures thereof, more preferably polytetrafluoroethylene.

In a further preferred embodiment, the isolated

collagen-containing sheet a metal-containing coating, preferably metal layer on.

Preferably, the isolated collagen-containing sheet with only a metal-containing coating, preferably metal layer, equipped, the surface, preferably over the entire surface, on the isolated collagen-containing

Sheet is arranged. Preferably, the one is metal-containing

Coating, preferably metal layer, a continuous coating, which is more preferably liquid-tight.

In a further preferred embodiment, the collagen-containing sheet has a plastic-containing coating, preferably

Plastic layer, on.

Preferably, the isolated collagen-containing sheet with only one plastic-containing coating, preferably plastic layer, equipped, the surface, preferably over the entire surface, on the isolated collagen-containing

Sheet is arranged. Preferably, the one is plastic-containing

Coating, preferably plastic layer, a continuous coating, which is more preferably liquid-tight.

In a further preferred embodiment, an isolated collagen-containing sheet used according to the invention furthermore contains at least one medicinal active substance which preferably supports wound healing. Suitable medicinal agents include, for example, anti-inflammatory drugs, antibiotics or hemostatic agents.

Preferably, the at least one medicinal agent is disposed in the isolated collagen-containing sheet or at least one

medicinal agent is disposed in at least one additional storage layer on the isolated collagen-containing sheet.

Preferably, the at least one medicinal agent diffuses into the surrounding tissue at the site of attachment of the isolated collagen-containing sheet used according to the invention and preferably promotes wound healing. As a result, preferably a regeneration of the tissue is promoted after a surgical procedure.

For example, an isolated used in the invention contains

collagen-containing sheet at least one antiphlogistic, a directed against inflammation drug.

Anti-inflammatory drugs are known in the art and preferably include steroidal or non-steroidal anti-inflammatory drugs or combinations thereof.

Suitable non-steroidal anti-inflammatory drugs are, for example, non-selective cyclooxygenase (COX) 1/2 inhibitors or selective cyclooxygenase (COX) -2 inhibitors.

Suitable non-selective cyclooxygenase (COX) 1/2 inhibitors are

for example, acetylsalicylic acid, acetylsalicylic acid derivatives,

Arylpropionic acid derivatives such as ibuprofen, flurbiprofen, naproxen, ketoprofen or tiaprofenic acid, arylacetic acid derivatives such as diclofenac, indoleacetic acid derivatives such as indomethacin,

Anthranilic acid derivatives, such as flufenamic acid or Mefenamic acid, oxicams, such as piroxicam, tenoxicam or meloxicam, or pyrazolone derivatives, such as phenylbutazone.

Suitable selective cyclooxygenase (COX) -2 inhibitors are, for example, rofecoxib, lumiracoxib, valdecoxib, parecoxib, etoricoxib or celecoxib.

Suitable steroidal (steroidal) antiphlogistics are, for example

Dexamethasone, hydrocortisone or prednisolone.

By releasing the at least one anti-inflammatory agent, it is preferable to inhibit the development of inflammation and further to suppress the formation of adhesions as a result of the inflammation.

Likewise, the release of at least one antibiotic, for example gentamycin, can be isolated from an isolate used according to the invention

Collagen-containing tissue suppress the formation of inflammation by bacteria, which have, for example, come through the surgical procedure in the tissue.

An isolated collagen-containing sheet used in the present invention is preferably used in human or veterinary surgery.

Preferably, an isolated collagen-containing sheet used in the present invention may be used for tendon ruptures as the transfusion tissue

Replacement material for surgical dura mater repairs, to be used in hernia surgeries.

Preferably, an isolated collagen-containing sheet used in the invention may be used in dental surgery to prevent the onset of connective tissue cells in the newly established bone granule bed in the jaw in guided bone regeneration (GBR). Hereinafter, the invention will be illustrated by examples without being limited thereto.

Example 1 :

Bovine Dermis, size 3 x 4 cm ² , prepared, 0.6 mm thick, was coated on its surface on one side with a cyanoacrylate adhesive and with a gold foil, 24 carats, 150 nm thick, pasted, then packaged and sterilized.

The metallized, isolated collagen-containing sheet thus produced has barrier properties on the coated side and may be e.g. at

Tendon ruptures are used as a transposition tissue in hand surgery.

Example 2:

A reconstituted, xenogenic, biological material (e.g.

Achilles tendons on horseback) collagen foil with a size of 10 x 10 cm and a thickness of 0.8 mm was coated on one side by plasma with gold particles, wherein gold was deposited in a thickness of 200 nm on the collagen foil. Subsequently, the metallized

Collagen foil packaged and sterilized. The metallized thus produced

Collagen foil has barrier properties on the metal side and may be e.g. be used as a substitute material for surgical dura mater repairs.

Example 3:

A tissue made by combining a collagen suspension made from reconstituted xenogenic biological material with a polypropylene (PP) net was prepared by covering the PP mesh with a suitable amount of the collagen suspension in a dish and then placing it in a dish was subjected to guided drying. The resulting dried composite film has increased barrier properties and can be used, for example, in hernia surgery.

Example 4:

A prepared bovine pericardium, size 15 x 15 cm, was in dry

Condition on one side sprayed with a polytetrafluoroethylene (PTFE) solution and dried again in a suitable manner. The resulting superficial

plasticized collagen-containing isolated sheet has one-sided

Barrier properties and may e.g. used in hernia surgery.

Example 5:

Allogeneic avitale dermis, size 2 x 3 cm, ready-prepared, thickness 0.7 mm, was plasma-coated on one side with gold particles, with gold deposited in a layer thickness of 200 nm on the allogeneic avital dermis. Subsequently, the metallized allogeneic avital dermis was packaged and sterilized.

The metallized allogeneic aviteral dermis thus prepared may be e.g. in the

Dental surgery used to guide the rebuilding of connective tissue cells in guided bone regeneration (GBR)

To prevent bone granule bed in the jaw.

Example 6:

A prepared porcine dermis, size 15x18 cm, was dried and sprayed on the pore side with a PTFE solution to reduce the strong pore structure. After re-drying, this dermis on the treated side was coated by plasma with gold particles, with gold in one

Layer thickness of 250 nm was deposited.

The one-sided metallized porcine dermis thus produced has

Barrier properties and may e.g. used in hernia surgery.

Claims

claims

1 . Use of an isolated collagen-containing sheet for producing a laminar adhesion barrier,

characterized,

that the isolated collagen-containing sheet is provided with at least one metal and / or plastic-containing coating.

2. Use according to claim 1,

characterized,

in that the isolated collagen-containing sheet is an avital autogenous tissue or tissue web, an avital allograft tissue or web, an avian xenogeneic tissue or tissue web, a collagen foil or a collagen mesh.

3. Use according to claim 2,

characterized,

that the avital autogenous tissue, avital allogeneic tissue or avian xenogeneic tissue is the dura mater, dermis, fascia lata, temporal fascia or pericardium.

4. Use according to one of claims 1 to 3,

characterized, in that the at least one metal- and / or plastic-containing coating has a thickness of more than 1 nm, preferably from a range of 1 nm to 5000 nm.

5. Use according to one of claims 1 to 4,

characterized,

in that the at least one metal- and / or plastic-containing coating is arranged on one side or on both sides on the collagen-containing fabric.

6. Use according to one of claims 1 to 5,

characterized,

that the at least one metal and / or plastic-containing coating on the collagen-containing sheet by vapor deposition, preferably physical vapor deposition (PVD) or chemical

Vapor deposition (CVD) is applied.

7. Use according to one of claims 1 to 5,

characterized,

that the at least one metal and / or plastic-containing coating is formed as a film.

8. Use according to claim 7,

characterized,

that the film is glued to the collagen-containing sheet.

9. Use according to one of claims 1 to 8,

characterized,

in that the at least one metal-containing coating is a metal layer and preferably comprises gold, silver, palladium, titanium or alloys, compounds or mixtures thereof.

10. Use according to one of claims 1 to 8, characterized,

in that the at least one plastic-containing coating is a polymer layer and preferably comprises polypropylene, polytetrafluoroethylene, silicone or mixtures thereof.

1 1. Use according to any one of claims 1 to 10 in human or veterinary surgery.