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WO1996023532A1 - Medical and surgical adhesive composition and process for its preparation - Google Patents

Medical and surgical adhesive composition and process for its preparation

Info

Publication number
WO1996023532A1
WO1996023532A1 PCT/IB1996/000210 IB9600210W WO9623532A1 WO 1996023532 A1 WO1996023532 A1 WO 1996023532A1 IB 9600210 W IB9600210 W IB 9600210W WO 9623532 A1 WO9623532 A1 WO 9623532A1
Authority
WO
Grant status
Application
Patent type
Prior art keywords
weight
adhesive
composition
sulfolane
methacryloxy
Prior art date
Application number
PCT/IB1996/000210
Other languages
French (fr)
Inventor
Gennadiy Viktorovich Leplyanin
Original Assignee
Saybrook Trading Limited
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

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L24/00Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/04Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
    • A61L24/06Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds

Abstract

A medical and surgical adhesive composition is described which provides an increased elasticity of the adhesive film and which is free of side effects, comprising 2-ethyl cyanoacrylate, butyl acrylate and 3-methacryloxy sulfolane.

Description

DESCRIPTION

MEDICAL AND SURGICAL ADHESIVE COMPOSITION AND PROCESS FOR ITS PREPARATION

The present invention relates to medical and surgical adhesives and particularly to medical and surgical adhesive compositions comprising 2-ethyl cyanoacrylate

It is known that conventional medical and surgical adhesives are synthesized starting from derivatives of 2-cyanoacrylιc acid They show remarkable adhesive properties, forming a strong film which is easily adsorbed by the human organism The most important feature of derivatives of cyanoacrylic acid (particularly esters) is their capacity of polymerizing in a wet environment at body temperature in a few seconds Derivatives of 2-cyanoacrylιc acid are therefore used in order to glue tissues in surgical operations on kidneys, pancreas, liver, cholecyst, ureters and bile ducts, in cardiovascular and thoracic surgery, in ophthalmology, in order to glue muscles, subcutaneous tissue, epidermis and cutaneous injuries, in plastic surgery of cross ligaments in the knee articulations, in obstetrics, in gynaecology and so on

A disadvantage of derivatives of cyanoacrylic acid is a remarkable and, in some cases, acute inflammatory reaction of the glued tissues In the first 24 hours after the glueing of said tissues, e g with 2-ethyl cyanoacrylate, an acute segmental reaction appears around the adhesive film with manifestations of different levels according to the different tissues In bony tissues said reaction is weak and disappears within a week, whereas on vasal walls it dicreases at the end of the second week and on the walls of carotid and ureters it continues for a month The most acute inflammation has been observed in the muscular tissues

In order to reduce inflammatory reactions caused by derivatives of 2-cyanoacrylιc acid it was used a mixture of antibiotics and other anti-inflammatory agents However, the choice is quite limited, and such a mixture does not completely solve the problem Furthermore, hydroxyl, ammo and amido groups contained m most anti-inflammatory drugs produce a quick polimeπzation of compositions, with a consequent quick decadence

A further disadvantage of cyanoacrylates is represented by the inadequate elasticity and by the fragility of the final film, which tends to crack just after its formation Accordingly, it is an object of the present invention to provide a medical and surgical adhesive which overcomes the above mentioned disadvantages, has a simple use and is resistant in time

It was surprisingly found that if 2-ethyl cyanoacrylate is combined with two particular compounds, the resulting adhesive is characterized by the following advantages: absence of cutaneous inflammation, absence of flesh inflammation and of enteral walls inflammation by glueing enteral loops without torsions or perforations; by applying enteral anastomoses with a stitch reinforcement; by sealing enteral anastomoses made with suture thread, with a gap between the stitches increased till 10 mm.

Furthermore, it has been observed an increase in the elasticity of the adhesive film (till reaching the cutaneous elasticity) which guarantees the suture strength. The finally resulting film, furthermore, does not crack and does not modifies its features for 10-15 days. The present invention provides a new medical and surgical adhesive composition comprising: a) 65-90% by weight of 2-ethyl cyanoacrylate b) 5-17.5% by weight of 3-methacryloxy sulfolane c) 5-17.5% by weight of butyl acrylate, wherein the percentages are based on the total weight of the composition .

The 3-methacryloxy sulfolane acts as an anti-inflammatory agent wich avoids the onset of inflammations in the tissues, therewith favouring their quick cicatrization. If its content is less than 5% by weight, the tissue irritation is not completely avoided, whereas if it is more than 17.5% said irritation lasts longer. A preferred amount of 3-methacryloxy sulfolane is comprised between 7.5 and 12.5% by weight, based on the total weight of the composition. A more preferred amount is 10% by weight.

Analogously, the use of butyl acrylate allows to increase the elasticity of the adhesive film. In fact it has been found that its insertion in the composition allows the film not to crack, not to break, not to cause a tissue retraction (the film elasticity reaches a value corresponding to the skin elasticity) and to remain without changes for 10-15 days. The adhesive presents excellent features and resorbs in 30-45 days. If the amount of butyl acrilate is less than 5% a retraction of the glued tissues and a film fragmentation are observed. A preferred amount of butyl acrylate is comprised between 7.5 and 12.5% by weight, based on the total weight of the composition. A more preferred amount is 10% by weight.

A preferred composition to be used as a medical and surgical adhesive comprises therefore: a) 75-85% by weight of 2-ethyl cyanoacrylate, b) 7.5-12.5% by weight of 3-methacryIoxy sulfolane and c) 7.5-12.5% by weight of butyl acrylate, wherein the percentages are based on the total weight of the composition.

The obtained adhesive presents a high stability. This feature allows its conservation for two years after its production, if it is kept at a temperature not higher than 4°C. - j -

A further object of the present invention is to provide a process for the preparation of the aforesaid medical and surgical adhesive, comprising the mixing of the three components under controlled conditions (temperature and humidity) and their continuous stirring till obtaining an adhesive product which can be stored for a further use.

In particular, 3-methacryloxy sulfolane is mixed with butyl acrylate till complete dissolution, at a temperature of 18-20 °C and at air relative humidity comprised between

50 and 60%. Afterwards, the resulting solution is dissolved in 2-ethyl cyanoacrylate.

For preparing 3-methacryloxy sulfolane. methacrylic acid and 3-oxy sulfolane are reacted at a temperature of 60-70 °C, at low pressure, with a suitable solvent, preferably toluene or benzene, distilling the formed water. It is optionally advisable to add an acid catalyst, in particular sulfuric acid or para-toluensulfonic acid (0.5-1%). In order to prevent a mixture polimerization. hydrochinone can be used. e.g. in an amount of 0.5% referring to the mixture total weight. 3-methacryloxy sulfolane precipitates in the form of a beige or white powder. Melting point 40 °C, total yield 80%.

The present invention is further described in the following examples.

Example 1

10% by weight of 3-methacryloxy sulfolane (thereafter referred to as SAK) is mixed with 10% by weight of butyl acrylate (therafter referred to as BAK) till complete dissolution, at room temperature (18-20°C) and with a relative humidity of 50-60%

The resulting solution is dissolved in 80% by weight of 2-ethyl cyanoacrylate (thereafter referred to as ECAC). The mixture is continuously stirred till obtaining an adhesive composition which does not crack when it is applied in the form of a thin film, and whose elasticity corresponds to the one of the skin. The adhesive resorbs in 40 days.

Example 2

Example 1 is repeated varying the amounts of the components as follows:

ECAC 85% by weight,

SAK 7.5% by weight, BAK 7.5% by weight.

The use of the adhesive does not cause inflammations, but a light cutaneous flush which disappears after 2-3 hours. The film does not crack for 15 days, and the elasticity corresponds to the one of the skin. Example 3 Example 1 is repeated, varying the amounts of the components as follows:

ECAC 75% by weight, SAK 12.5% by weight, BAK 12.5% by weight. The resulting film is elastic and does not crack for 16 days. No tissue inflammation was observed The adhesive was used for glueing skin and flesh injuries, as well as for the suture of anastomoses and in gut operations Test results

45 tests were performed, which were divided as follows a) 15 tests concerning the glueing of enteral loops without torsions or perforations, b) 15 tests concerning the applying of enteral anastomoses with the adhesive reinforced by stitches, c) 15 tests concerning the suture of enteral anastomoses, increasing the gap between the stitches till 10 mm or more in order to reduce the injury of the enteral wall Glueing the injured wall, the tissues to be glued are put together and smeared with a thin layer of adhesive The flaps of the injury are pressed for 2-3 minutes in order to strengthen the sutures In said lapse of time the adhesive acts on the joined flaps, thus favouπng a perfect adhesion The adhesive film is elastic and does not break for 10-15 days No tissue inflammations have been observed, and the adhesive resorbs in 30-45 days

According to the performed tests it is possible to state that an adhesive composition according to the present invention shows a complete absence of cutaneous inflammations, of flesh inflammation and of enteral walls inflammation by glueing enteral loops, without torsions or perforations No evident inflammatory reactions were observed by applying enteral anastomoses with a stitch reinforcement and by sealing enteral anastomoses made with suture thread, with a gap between the stitches increased till 10 mm Finally, it is obtained an increased elasticity of the adhesive film (till reaching the skin elasticity) which guarantees the suture strength The film does not crack and does not modify its features for 10-15 days If methacrylic acid and 3-oxysulfolene-4 are reacted as described for the preparation of 3-methacryloxy sulfolane, 3-methacryloxysulfolene-4 is obtained which can be used in the composition of the adhesive as an alternative to sulfolane

Claims

1. A medical and surgical adhesive composition comprising: a) 65-90% by weight of 2-ethyl cyanoacrylate, b) 5-17.5% by weight of 3-methacryloxy sulfolane, c) 5-17.5% by weight of butyl acrylate, the percentages being based on the total weight of the composition
2. A composition according to claim 1 comprising: a) 75-85% by weight of 2-ethyl cyanoacrylate, b) 7.5-12.5% by weight of 3-methacryloxy sulfolane and c) 7.5-12.5% by weight of butyl acrylate, the percentages being based on the total weight of the composition.
3. A composition according to claim 1 or claim 2 whrein the 3-methacryloxy sulfolane is replaced by 3-methacryloxysulfolene-4.
4 A process for the production of an adhesive composition to be used in medical and surgical field, characterized in that:
(a) 5-17.5% by weight of 3-methacryloxy sulfolane is mixed with 5-17.5% by weight of butyl acrylate till complete dissolution, at a temperature of 18-20 °C and at air relative humidity comprised between 50 and 60%, (b) the resulting solution is dissolved in 65-90% by weight of 2-ethyl cyanoacrylate, wherein the percentages are based on the total weight of the composition. 5. A process according to claim 4, wherein:
(a) 7.5-12.5% by weight of 3-methacryloxy sulfolane is mixed with 7.5-12.
5% by weight of butyl acrylate till complete dissolution, at a temperature of 18-20 °C and at air relative humidity comprised between 50 and 60%,
(b) the resulting solution is dissolved in 75-85% by weight of 2-ethyl cyanoacrylate, wherein the percentages are based on the total weight of the composition.
6. A process according to claim 4 or claim 5, wherein the 3-methacryloxy sulfolane is replaced by 3-methacryloxysulfolene-4.
7. Use of 3-methacryloxy sulfolane for the production of an adhesive composition to be used in medical and surgical field.
8. Use of 3-methacryloxy sulfolane for the production of a medical and surgical adhesive composition having anti-inflammatory properties.
PCT/IB1996/000210 1995-01-31 1996-01-30 Medical and surgical adhesive composition and process for its preparation WO1996023532A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
ITFI95A000017 1995-01-31
ITFI950017 1995-01-31

Publications (1)

Publication Number Publication Date
WO1996023532A1 true true WO1996023532A1 (en) 1996-08-08

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Family Applications (1)

Application Number Title Priority Date Filing Date
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Country Link
WO (1) WO1996023532A1 (en)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5684042A (en) * 1997-01-10 1997-11-04 Medlogic Global Corporation Cyanoacrylate compositions comprising an antimicrobial agent
US5730994A (en) * 1997-01-10 1998-03-24 Medlogic Global Corporation Methods for draping surgical incision sites
US6090397A (en) * 1997-11-03 2000-07-18 Medlogic Global Corporation Kits containing cyanoacrylate compositions comprising an antimicrobial agent
US6214332B1 (en) 1997-01-10 2001-04-10 Medlogic Global Corporation Methods for closing suturable wounds by use of cyanoacrylate ester compositions comprising an antimicrobial agent
US6475502B1 (en) 1997-11-03 2002-11-05 Flowers Park Ltd. Kits containing cyanoacrylate compositions comprising an antimicrobial agent
US6833196B1 (en) * 2002-06-24 2004-12-21 Henkel Corporation Acrylic-toughened cyanoacrylate compositions
US8865792B2 (en) * 2011-08-11 2014-10-21 Elena Leplyanina Medical glue and method of its production
US8864741B2 (en) 2008-05-19 2014-10-21 Jean-Pierre Lilley Varicose vein treatment
US8980947B2 (en) 2007-06-25 2015-03-17 Adhezion Biomedical, Llc Curing accelerator and method of making
US9018254B2 (en) 2007-06-25 2015-04-28 Adhezion Biomedical, Llc Cyanoacrylate tissue adhesives with desirable permeability and tensile strength
US9254133B2 (en) 2008-10-31 2016-02-09 Adhezion Biomedical, Llc Sterilized liquid compositions of cyanoacrylate monomer mixtures
US9309019B2 (en) 2010-05-21 2016-04-12 Adhezion Biomedical, Llc Low dose gamma sterilization of liquid adhesives
US9421297B2 (en) 2014-04-02 2016-08-23 Adhezion Biomedical, Llc Sterilized compositions of cyanoacrylate monomers and naphthoquinone 2,3-oxides
US9878041B2 (en) 2007-11-14 2018-01-30 Adhezion Biomedical, Llc Cyanoacrylate tissue adhesives

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Week 9208, Derwent World Patents Index; AN 92-062719, XP002003594 *
DATABASE WPI Week 9218, Derwent World Patents Index; AN 92-148365, XP002003593 *

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6214332B1 (en) 1997-01-10 2001-04-10 Medlogic Global Corporation Methods for closing suturable wounds by use of cyanoacrylate ester compositions comprising an antimicrobial agent
US5730994A (en) * 1997-01-10 1998-03-24 Medlogic Global Corporation Methods for draping surgical incision sites
US5753699A (en) * 1997-01-10 1998-05-19 Medlogic Global Corporation Methods for treating non-suturable, superficial wounds by use of cyanoacrylate ester compositions comprising an antimicrobial agent
US5762919A (en) * 1997-01-10 1998-06-09 Medlogic Global Corporation Cyanoacrylate compostions comprising an antimicrobial agent
US5783177A (en) * 1997-01-10 1998-07-21 Medlogic Global Corporation Cyanoacrylate compositions comprising an antimicrobial agent
US5807563A (en) * 1997-01-10 1998-09-15 Medlogic Global Corporation Methods for draping surgical incision sites
US5811091A (en) * 1997-01-10 1998-09-22 Medlogic Global Corporation Cyanoacrylate compostions comprising an antimicrobial agent
US5902594A (en) * 1997-01-10 1999-05-11 Medlogic Global Corporation Cyanoacrylate compositions comprising an antimicrobial agent
US6086906A (en) * 1997-01-10 2000-07-11 Medlogic Global Corporation Cyanoacrylate compositions comprising an antimicrobial agent
US5684042A (en) * 1997-01-10 1997-11-04 Medlogic Global Corporation Cyanoacrylate compositions comprising an antimicrobial agent
US6090397A (en) * 1997-11-03 2000-07-18 Medlogic Global Corporation Kits containing cyanoacrylate compositions comprising an antimicrobial agent
US6475502B1 (en) 1997-11-03 2002-11-05 Flowers Park Ltd. Kits containing cyanoacrylate compositions comprising an antimicrobial agent
US6833196B1 (en) * 2002-06-24 2004-12-21 Henkel Corporation Acrylic-toughened cyanoacrylate compositions
US8980947B2 (en) 2007-06-25 2015-03-17 Adhezion Biomedical, Llc Curing accelerator and method of making
US9018254B2 (en) 2007-06-25 2015-04-28 Adhezion Biomedical, Llc Cyanoacrylate tissue adhesives with desirable permeability and tensile strength
US9878041B2 (en) 2007-11-14 2018-01-30 Adhezion Biomedical, Llc Cyanoacrylate tissue adhesives
US8864741B2 (en) 2008-05-19 2014-10-21 Jean-Pierre Lilley Varicose vein treatment
US9254133B2 (en) 2008-10-31 2016-02-09 Adhezion Biomedical, Llc Sterilized liquid compositions of cyanoacrylate monomer mixtures
US9309019B2 (en) 2010-05-21 2016-04-12 Adhezion Biomedical, Llc Low dose gamma sterilization of liquid adhesives
US8865792B2 (en) * 2011-08-11 2014-10-21 Elena Leplyanina Medical glue and method of its production
US9421297B2 (en) 2014-04-02 2016-08-23 Adhezion Biomedical, Llc Sterilized compositions of cyanoacrylate monomers and naphthoquinone 2,3-oxides

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