EP0848619A1 - Orthopaedic bandages - Google Patents

Abstract

The present invention provides an orthopaedic casting bandage comprising a suitable substrate carrying a water curable organo-oxy functionalised resin where the resin comprises a prepolymer containing ionic centres.

Description

ORTHOPAEDIC BANDAGES

In particular this invention relates to casting and splinting materials based on synthetic resins which, upon contact with water will cross-link and harden to form a weight bearing support for a limb or body portion and to such resins which on contact with water will cross-link and harden.

Resin based splinting and casting materials find wide use in the immobilisation of limbs, for example the fixation of fractured bones, immobilisation of injured joints and for the support of ligaments and muscles where it is necessary to encase the limb in a partially or completely surrounding rigid form or cast.

There are several major considerations for a casting or splinting material. A suitable material should be easily handleable, with a reasonable setting time to allow sufficient time in the case of casting bandages to mould the bandage about the limb and it should be flexible and free of offensive chemicals which may affect the patient or practitioner applying the material. In addition it is desirable that during the forming of the cast the material does not generate an uncomfortable exothermic reaction and that it sets within a relatively short time under mild conditions.

Splinting and casting materials comprising water activated synthetic polymers in which a cross-linkable prepolymer resin system is coated onto a suitable substrate are well known. The most favoured and commercially developed systems are those based on prepolymers which contain isocyanate functional groups and which in the presence of cold water will cross-link to form urea bridges. The resin systems usually also contain a catalyst to speed up the cross-linking reaction and so that a weight bearing cast may be formed in as shorter time as possible consistent with requirements for moulding and shaping the splint.

The isocyanate cross linking reaction is usually an exothermic reaction. In meeting the working requirements for such resin systems the resin chemistry has to be carefully controlled so as to allow the resins to cure in a period of time which is acceptably short and yet not cure under conditions in which so much heat is evolved that the applied cast is uncomfortable to the wearer.

A disadvantage of such systems is the relatively high exotherm generated on curing and that there is a perceived health hazard with the use of orthopaedic bandages comprising isocyanate functionalised prepolymers. It is thus desirable to make suitable splinting materials without utilising isocyanate functionalised prepolymers and thus considerable care has to be taken in both the preparation of the splinting or casting material and in its use to ensure that all the isocyanate functionalities are fully reacted.

In US Patent No. 4411262 (von Bonin et al) there are disclosed splinting and casting materials comprising substrates impregnated or coated with a reactive one component system, wherein inter alia the system includes organic compounds with molecular weights greater than 10,000, comprising reactive groups which may be alkoxysilane groups. It is taught that the organic compounds themselves were produced by an isocyanate functionalised reaction and thus any perceived health risk associated with isocyanate functionalised resins is not entirely removed without ensuring that the resins are fully reacted.

US Patent No. 5,423,735 also describes materials of this type, where the water reactive resin is an alkoxysilane functionalised polyurethane/polyurea resin, produced by reacting isocyanate functionalised precursors. Such resins potentially have the same problems which may be associated with other prior resins produced from isocyanate functionalised precursors.

The present invention seeks to provide an improved orthopaedic casting bandage with a one component resin system which completely avoids the use of free isocyanate groups as the water activated reactive groups, thus eliminating any health hazard which may be associated with the use of materials containing free isocyanate groups. We have found that use of resins comprising ionic linkages avoids the use of isocyanate functionalised prepolymers.

In accordance with the present invention there is provided an orthopaedic casting bandage as herein defined comprising a flexible substrate carrying a water curable organo-oxy functionalised resin system, characterised in that the resin system comprises at least a prepolymer of the general formula (I)

Where

i) ®, θ are charges of opposite polarities, ii) A®, Bθ are charged groups of opposite polarities and may be^NH⁺, -CC(O)O^', >NH⁺ ₂, -NH⁺ _3l iii) X comprises a water hydrolysable organo-oxy group based on Ci to Cio hydrocarbon group, iv) R⁷ is H, halide, X, alkyl, aryl based on Ci to Cio hydrocarbon group, v) q, m = 1 to 3 and n + p + m = 3, vi) R¹, R², R³, R⁴, R⁵, R⁶ may be the same or different, substituted or unsubstituted, branched, linear and may be groups based on the following Ci to C₂o, alkyl, aryl, cycloalkyl, heteroalkyl, heterocycloalkyl all of which may be optionally interrupted by -O-, -S-, -NH-, -N<, -C(O)-, >Si<, A®, Bθ, vii) further R¹, R³, R⁴, R⁵, R⁶ may be H, halide, polymeric, viii) where M is from the group comprising Si, Al, Se, Sn, B, Ti. When R¹, R³, R⁴, R⁵ and/or R⁶ comprise polymeric groups the total molecular weight of the prepolymer is preferably not greater than 40,000 more preferably not greater than 30,000.

Aptly R⁴, R⁶ may be polymeric with pendant

ΘB(R¹ _n)(R³p)(R²MR⁷ _3-,,X _q)_m groups.

The resins employed in the present invention comprise an organo-oxy hydrolysable group. Aptly the organo-oxy hydrolysable group is defined as from the group comprising alkoxy [-OR], acyloxy [-OC(O)R] and cyclic alkoxy derivatives based on Ci to Cio hydrocarbon group.

Preferably the water hydrolysable organo-oxy group is an ethoxy group.

Preferably M is silicon.

During the water curing reaction of the resin the organo-oxy groups are hydrolysed to form hydroxy groups which condense together.

As used herein water curable means that the resin system is capable of hardening to a rigid or semi-rigid structure on exposure to water.

The reaction may be exemplified by the following formulae illustrating the hydrolysis of an alkoxy silane functionalised resin to give a siloxane [-Si-O-Si-] cross-linked polymer: OR OR i) Resin Si— OR ⁺ H₂0 →" Resin -Si— OH + ROH

I I

OR OR

OR OR O

2 Resin ^■ -Si— OH -»- Resin- -Si— O— Si— -Resin + H,0

I I I

OR OR OR

OR OR ii) Resin -Si— OR + Resin -Si— OH

I I

OR OR

OR OR

Resin- -Si— — Si— -Resin + ROH OR OR

until all or most of the SiOR have reacted to give a cross-linked system.

The resin of the invention may be precured by the addition of water to cross-link a small percentage of the available silane groups. The advantage gained would be an increase in molecular weight, leading to an increase in viscosity.

In a preferred embodiment the resins of the invention may be made by the reaction of carboxylic acid terminated precursors with amine containing a water hydrolysable organo-oxy group or vice versa where the carboxylic acid terminated precursor contains a water hydrolysable organo-oxy group, to produce a salt complex of the following general structures: R— COO H₃N — R

R

R— COO H₂N R^'

R

where a salt complex is defined as a resin containing ionic linkages.

Precursors are defined as groups based on C₁-C₁₀0 hydrocarbon groups, suitably comprising reagents which herein are utilised to prepare the prepolymer of the present invention.

In a further embodiment the resins of the invention may be made by the reaction of a precursor having pendant ionic moieties with an oppositely charged precursor having in addition at least a water hydrolysable organo-oxy group.

The resins of the invention may be made by neutralising the oppositely charged precursors in a range of ratios, for example 1 : 1 ratio up to a 1 : 10 ratio, preferably a 1 : 1 ratio to a 1 :5 ratio.

Neutralising can be defined as the reaction of oppositely charged groups to form a salt complex with an overall neutral charge.

Ionic groups that are not neutralised as described above may be capped with for example hydrophilic polymeric moieties such as Jeffamines (polyether amines), and/or polyols or they may be left as charged groups. These resins represent a single component system where the hydrolysable organo-oxy group is ionically bound to the resin rather than covalently bound as in the more conventional water curable resins.

The advantage conferred to resins of the invention with their ionic nature is that the wetting out characteristics of said resins are improved, where wetting out is defined as the ability of the resin to take up water, which in turn affects the rate the resins react with water.

Additionally, it was observed that these resins exhibit a reduced tack on activation with water thus making a casting bandage comprising such a resin easier to apply and mould to a limb.

Furthermore the preferred resin formulation is free of isocyanate moieties to avoid the perceived health hazards thereof.

The organo-oxy hydrolysis reaction may be catalysed.

Suitable catalysts may be from the group comprising organotin salts, methane sulphonic acid (MSA), phosphoric acids,

1 ,5-diazabicyclo[4.3.0]non-5-ene (DBN),

1 ,8-diazabicyclo[5.4.0]undec-7-ene (DBU), potassium fluoride, bismorpholino dialkyl ethers and p-toluene sulphonic acid.

Preferably potassium fluoride is used as a catalyst.

The catalyst or mixture of catalysts may be present in an amount of about 0 to 20% w/w and preferably 0 to 5% w/w, and most preferably 0 to 2% w/w of the resin. Aptly if present, the catalyst should comprise at least 0.05% w/w of the resin.

Preferred formulations according to the present invention can include effective amounts of a variety of additives conventional in the art. These additives may comprise fillers, pigments, fragrances, surfactants lubricants, or mixtures thereof. Effective amounts are amounts sufficient to provide the benefits of the additive.

Suitably powdered fillers include but are not limited to talc, calcium carbonate, fumed silica sold under the trade name CAB-O-SIL™, alumina and fibrous reinforcing fillers such as wollastonites (calcium metasilicate), to impart desirable viscosity and handling characteristics.

The fillers may be present as single chemical species or as mixtures and, when used, are aptly present in an amount of up to 50% w/w, preferably up to 20% w/w and aptly at least 1.0% w/w of the resin.

Although the splinting and casting material of the present invention is described in terms of "an orthopaedic casting bandage", the term is also intended to embrace splints, supports and braces, where such splints, supports and braces do not necessarily surround the whole limb or other body portion.

The resin system used in the bandages of the invention according to the invention may be carried on any substrate suitable for a casting, splinting or bracing material.

The resin system employed in the invention may be coated, laminated, sprayed or impregnated onto a suitable substrate using conventional methods in the art. Aptly the bandages of the invention are prepared by nip-coating the resin system on to the substrate.

The viscosity of the resin system is preferably suitable for application to a substrate. Furthermore the viscosity is preferably such that the resin system remains in place on and within the substrate, while in storage and during curing. Aptly the resin systems of the invention have viscosities from 1 ,000 to 100,000 mPas^'1, more preferably from 40,000 to 60,000 mPas^"1.

A preferred substrate is a flexible fabric carrier which may be a woven, knitted or non woven fabric which can carry enough of the resin system of the invention to ensure that the resultant cast has adequate strength. The substrate should be sufficiently porous to allow water to come into contact with the carried system when the formed bandage is immersed in water. The substrate may be in the form of tapes, bandages, sheets or other conventional forms, apt for preparing orthopaedic casting bandages, splinting materials or braces.

Suitable materials for forming the substrate include polyester, nylon, polypropylene, polyamides, polyolefins and glass fibre or mixtures thereof. Examples of such substrates are disclosed in Patent Nos. US 4,427,002, US 4,627,424 and EP 326,285.

Aptly the substrate may be a mesh having openings through it to enable the water to penetrate into the rolled bandage to contact all parts of the resin system. The openings will permit circulation of air and aid evaporation of moisture from the skin beneath the cured cast.

Preferably the mesh is of a loose weave or knit so as to allow at least partial impregnation as well as coating by the resin system.

The amount of resin carried by the substrate may vary depending on the intrinsic properties of the resin system and should be sufficient to ensure that the resultant cast has adequate strength.

Suitable amounts range from 30 to 80% w/w of the resin system which is calculated using the equation:

weight of (substrate + resin) - weight of (substrate) x 100% weight of (substrate + resin) Preferably 40 to 70% w/w and most preferably 50 to 65% w/w of the resin system are used.

The bandages of the invention may be used to form a hardened cast by wetting and shaping the wet material around a body member or part thereof and allowing the bandage to cure.

Upon curing the resin system generally becomes bonded, physically or chemically to the substrate.

Aptly wetting is achieved by immersing the bandage in water, and removing any excess water, for example, by squeezing the bandage several times before application to the body member.

When removed from the water the bandage can be readily wrapped about the limb which is to be immobilised and wherein the limb is preferably protected with a conventional underlying stockinette or padding.

An alternative method for forming a cast or splint comprises applying the bandage of the invention material to the body member to be immobilised followed by spraying the bandage with water.

The curing reaction of the resin system should be sufficiently slow to allow the bandage of the invention to be positioned and shaped before the bandage becomes unworkable. Suitable working times are aptly 1 to 6 minutes more aptly 2 minutes to 4 minutes. The curing reaction of the resin system should, however, be sufficiently fast to permit the formed cast or splint to become supportive and load-bearing as soon as possible after completion of working. Aptly the bandage will set and become supportive between 5 and 30 minutes, more aptly within 15 minutes and particularly in the case of a cast, will aptly become load-bearing within 60 minutes, more aptly after 10 minutes. The resin systems employed in the present invention possess the further advantage in that the curing reaction is only slightly exothermic thus causing no harm or discomfort to the patient.

The cast may be readily removed by conventional means such as by cutting with a convention vibrating sawtooth disc.

The orthopaedic casting bandage of the invention should be protected during storage from water and moisture vapour to prevent a premature setting taking place. The bandage can be conventionally packaged in heat sealed pouches such as metal foil polyethylene laminate pouches.

The invention will now be described by way of the following examples only and it should be understood that normal precautions for excluding moisture during chemical reactions were employed.

Preparation of hydrophilic alkoxy silane terminated resins Examples 1. 2 and 3

The amounts and reagents used are specified in Table 1.

Table 1

Example 1 : Method

A polyamic acid derivative of Jeffamine EDR-148 with maleic anhydride was reacted with a silane (3-APTMS) in a 100% solids reaction by mixing the reagents in a dry reaction vessel, at room temperature, which was subsequently purged with nitrogen, sealed and left for 10 hours.

Examples 2 & 3 were prepared as described for Example 1.

Examples 4 and 5

The reagents and amounts used are specified in Table 2.

Table 2

Reagents (molecular weight) Example 4 Example 5

Adipic acid (146.16) 10g _

A-H70 (341.34) 46.4g 57.3g

Dichloromethane _ 50cm³

Carbon tetrachloride 100cm³ _

Butanetetracarboxylicacid (234.16) . 10g

Example 4: Method

A round bottom flask 250cm³ was charged with adipic acid and an organic solvent (carbon tetrachloride) to give a suspension. The suspension was stirred with nitrogen at room temperature and subsequently a silane (A-1170) was added, upon which a moderate exotherm was observed. The suspension was stirred until a homogenous mixture was formed before the organic solvent was removed by rotary evaporation, to yield a viscous Iiquid.

Example 5 was prepared as described for Example 4.

Preparation of coated bandages

Resins as prepared in Examples 1 to 5 were coated onto dry glass fibre bandages by passing the substrate through the resin system followed by passing the coated bandage through a nip roller, adjusted to a suitable pressure for obtaining a coating weight of 50- 60% w/w coating. The resins were optionally mixed with fillers such as Cabo-Sil M5 to improve handling and coating properties. A suitable substrate was a glass fibre bandage.

The coated bandage was activated with water by immersion in cold water and squeezing sufficiently to wet the coated bandage. Preferably the bandage is only squeezed once in cold water before application to a mandrel representing a limb.

Preparation of acrylic acid copolymers for subseguent reaction with alkoxy alkylaminosilanes: Examples 6 - 14

The amounts and reagents used are specified in Table 3 below:-

Tabie 3:

EXAMPLE NO: MASS (ε) I

REAGENT 6 7 8 9 10 11 12 13 14

I. Acrylic acid 15.1 11.0 10.0 10J 10.0 10J 10.0 12.0 10.5

II. Ethyl hexyl 35.2 39.0 40.1 40.0 40.0 40J 40.0 38.0 20.1 acrylate

III. Dodecanthiol 0.5 0.56 0.5 0.5 0.5 0J3 0.26 0.38

IV. Crodamer - 5.1 0.55 2.5 1.0 - - - - UVM 25

V. Stearylmeth- - - - - - - - - 20.0 acrylate

VI. BCHPC in ethyl 1.0 IJ 0J IJ 1.0 1.0 1.0 1.0 IJ acetate (50cm³)

Example 6: Method:

A dry 700cm round bottom flask was charged with reagents I V, ethyl acetate (250cm³), fitted with a stirrer and purged with nitrogen before heating the mixture whilst stirring in a water bath at

80° C. Bis-4-t-butylcyclohexyl peroxy dicarbonate in ethylacetate

(VI) was added dropwise via a pressure equalising dropping funnel.

The conditions were then maintained for three hours after which the sample was discharged into a dry jar and sealed under nitrogen.

Examples 7-14 were prepared as described for Example 1.

Preparation of alkoxy silane terminated resins from acrylic acid copolymers prepared in Examples 6-14:

Acrylic acid copolymers, prepared as described in Examples 6- 14, were dissolved in dichloromethane by stirring overnight at room temperature and subsequently treated with Silquest A-1170 at molar ratios of 1 : 1 , 1.3: 1 , 2: 1 and 4: 1. The reaction mixtures were allowed to stand for 20 minutes and then concentrated by rotary evaporation to yield alkoxy silane functionalised resins.

Example 15 Preparation of acid terminated alkoxy silane precursorss

A dry 250cm³ round bottom flask, fitted with a stirrer and purged with nitrogen was charged with mercaptopropyltrimethoxysilane [18.3g, 0.09mol] and acrylic acid [6.7g, 0.09mol]. To this was added DBN catalyst [2.5g, 10% w/w]. The mixture was stirred while heating to 100°C for 12hrs.

A carboxylic acid terminated alkoxy silane precursor was formed and reacted with Jeffamine EDR148 [0.045mol] to give an alkoxy silane terminated resin.

Preparation of coated bandages Alkoxy silane terminated resins as prepared above in Examples 6-15 were coated onto a substrate to achieve a resin loading of approximately 65% by weight.

The coated bandages were then wound onto a mandrel representing a limb coated with a PTFE sheet, so as to form a cylinder the same width as the bandages and water activated by spraying with water for 30 seconds from a plant sprayer. Excess water was squeezed out of the casts by hand pressure and the casts were surface smoothed. The bandages set in 2-10 minutes and no exotherm was noted.

Table 4: Materials used in Examples 1-15:

Table 4

Material Supplier

3-APTMS (3-aminopropyltrimethoxysilane) Huls UK (DYNASYLAN AMMO™)

A-1170 (bis (trimethoxy silylpropyl)amine) OSI Specialities (SILQUEST™)

Jeff amine EDR 148 (polyethylene glycol diamine) Huntsman Coφoration

Acrylic acid Aldrich Chem. Co.

2-Ethylhexylacrylate Aldrich Chem. Co.

Stearyl Methacrylate Aldrich Chem. Co.

Crodamer UVM-25 (Hexanedioldiacrylate) Croda Resins

Interox BCHPC Bis-(4-t-butylcylolohexyl)peroxy Solvay Interox Ltd dicarbonate

Dodecanethiol Aldrich Chem. Co.

Ethylacetate Aldrich Chem. Co.

Methylene Chloride Merck Ltd.

Silquest A-189 (Mercaptopropyltrimethoxysilane) OSI Specialities

3-APTES (3-aminopropyltriethyoxy silane) OSI Specialities

Claims

1. An orthopaedic casting bandage comprising a flexible substrate carrying a water curable organo-oxy functionalised resin system, characterised in that the resin system comprises at least a prepolymer of the general formula (I)

Where

i) ® Θ are charges of opposite polarities ii) A®, BΘ are charged groups of opposite polarities and may be

JNH⁺, -CC(O)O-, >NH ⁺ ₂, -NH⁺ ₃, iii) X comprises a water hydrolysable organo-oxy group based on

Ci to Cio hydrocarbon group, iv) R⁷ is H, halide, X, alkyl, aryl based on Ci to C_i0 hydrocarbon group, v) q, m = 1 to 3 and n + p + m = 3, vi) R¹, R², R³, R ⁴, R⁵, R⁶ may be the same or different, substituted or unsubstituted, branched, linear and may be groups based on the following Ci to C_20l alkyl, aryl, cycloalkyl, heteroalkyl, heterocycloalkyl all of which may be optionally interrupted by -O-,

-S-, -NH-, -N< -C(O)-, >Si< A®, BΘ, vii) further R¹, R³, R⁴, R⁵, R⁶ may be H, halide, polymeric, viii) where M is from the group comprising Si, Al, Se, Sn, B, Ti.

2. A bandage according to claim 1 wherein the water hydrolysable organo-oxy group X is from the group comprising alkoxy [-OR], acyloxy [-OC(O)R], cyclic alkoxy derivatives based on Ci to Cio hydrocarbon group.

3. A bandage according to claim 1 wherein the water hydrolysable organo-oxy group is a d to C₆ hydrocarbon group.

4. A bandage according to claim 1 wherein the water hydrolysable organo-oxy group is an ethoxy group.

5. A bandage according to claim 1 wherein M is silicon.

6. A bandage according to claim 1 including a catalyst to catalyse the polymerisation reaction of the organo-oxy functionalised prepolymer with water.

7. A bandage according to claim 5 wherein said catalyst is from the group comprising: methane sulphonic acid,

1,5-diazabicyclo[4.3.0]non-5-ene,

1,8-diazabicyclo[5.4.0]undec-7-ene, ethyl titanate, p-toluene sulphonic acid, dibutyltindilaurate, potassium fluoride, or mixtures thereof.

8. A bandage according to claim 5 wherein said catalyst is present in an amount up to 20% w/w of the resin.

9. A bandage according to claim 1 including a filler.

10. A bandage according to claim 6 wherein said filler is fumed silica.

11. A bandage according to claim 1 including additions comprising pigments, fragrances, surfactants, lubricants or mixtures thereof.

12. A bandage according to claim 1 wherein the resin system is coated onto the flexible substrate.

13. A bandage according to claim 11 wherein the resin system comprises a weight of 30 to 80% w/w.

14. A bandage according to claim 1 wherein the flexible substrate is a woven, knitted or non woven fabric.

15. A bandage according to claim 13 wherein the flexible substrate comprises polyester, nylon, polypropylene, polyamides, polyolefins, glass fibre or mixtures thereof.

16. A method for applying an orthopaedic casting bandage according to claim 1 comprising wetting the bandage, shaping the bandage around a body member and allowing the resin system to cure.

17. A method for applying an orthopaedic casting bandage according to claim 1 comprising shaping the bandage around a body member and wetting said bandage by spraying with water and allowing the resin system to cure.

18. An orthopaedic splinting material comprising a flexible substrate carrying a water curable organo-oxy functionalised resin as defined in claim 1.

19. An article comprising a water curable organo-oxy functionalised resin as defined in claim 1.

20. The use of a water curable organo-oxy functionalised resin as defined in claim 1 to 5 in an orthopaedic casting bandage or splint.

21. A method for treating a fracture of a body part which comprises applying an orthopaedic casting bandage according to claim 1 to said body part and causing the bandage to set by curing the resin.