Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
2001-01-26
2002-09-10
Azpuru, Carlos (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S443000, C424S447000
Reexamination Certificate
active
06447798
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to bioadhesive compositions, particularly wound dressings comprising hydrogel compositions having bioadhesive properties.
BACKGROUND
One form of wound dressing commonly used comprises a perforated carrier material and a layer of hydrophilic coating which lies against the wound or sore. U.S. Pat. No. 5,352,508 (Cheong) discloses a net dressing in which the net is encapsulated by a hydrophilic tacky resin and wherein the resin encapsulated on the net leaves the majority of the apertures in the net substrate unoccluded. The hydrophilic tacky resin used as the coating is said to be a polymerised hydrogel.
An important feature for a wound dressing is that it should not adhere to the wound. This is in order that it is allowed to heal and to prevent damage to the wound on removal of the dressing. At the same time the wound dressing needs to adhere strongly to normal skin to prevent the wound dressing from coming off. Whilst it has been appreciated in the past that these features are important, there has been no understanding of how to achieve them in a hydrogel system.
It is an object of this invention to provide hydrogel skin adhesives possessing controlled and predictable adhesive properties which may be readily varied to suit different uses and, in the case of wound dressings or similar devices, different configurations or applications. It is also an object of the invention to provide such hydrogel skin adhesives which in addition may possess superior adhesion characteristics as compared to those commonly associated with bioadhesive hydrogels.
SUMMARY OF THE INVENTION
The performance of hydrogels as adhesives is related to the surface energetics of the adhesive and of the adherend (for example mammalian skin) and to the viscoelastic response of the bulk adhesive. The requirement that the adhesive wets the adherend to maximise the work of adhesion is well known. This requirement is generally met when the adhesive has a similar or lower surface energy to the adherend. The viscoelastic properties, in particular the elastic or storage modulus (G′) and the viscosity modulus (G″) are important. They are measured by dynamic mechanical testing at different rad/s. Their values at low rad/s (approximately 0.01 to Irad/s) and high rad/s (100 to 1000 rad/s) has been related to the wetting/creep behaviour and peel/quick stick properties respectively. The choice, assembly and processing of the ingredients of the hydrogel adhesive are usually targetted at making a material with a balance of properties suitable for pressure sensitive adhesive applications. A balance between the quantities and nature of polymer, plasticiser and the degree of crosslinking/entanglement has to be achieved.
Whilst the presence of glycerol or other polyhydric alcohols in other reported formulations has been quoted to provide humectant properties to the hydrogel, it has been found that the most important parameter to preventing water loss is the activity of the water within the hydrogel which in turn depends on the nature and proportions of the other components and manner of processing.
Water activity in the hydrogel adhesive is primarily dependent on the water content and the nature of the polymeric components and the way in which they are processed. Water activity has been shown to have a better correlation with the growth of bacteria and moulds than water content. It has been found that organisms struggle to grow at water activities less than 0.8. Enzyme activity has also been reported to decrease significantly below activity of 0.8. Some wound dressings currently available not only have high water contents but also high water activity, greater than 0.99. Although these materials are sterilised, on opening the pack they may become subject to encouraging microbial growth. Water activity has also been found to influence the adhesivity of the hydrogel adhesive in that at water activities above about 0.75, they become less adhesive. A bioadhesive composition having a suitable balance of the characteristics discussed above has now surprisingly been found.
According to the invention there is provided a water unstable bioadhesive composition characterised in that it has:
(i) a water activity of from 0.4 to 0.9;
(ii) an elastic modulus at 1 rad/s of from 700 to 15,000 Pa;
(iii) an elastic modulus at 100 rad/s of from 2000 to 40,000 Pa;
(iv) a viscous modulus at 1 rad/s of from 400 to 14,000 Pa;
(v) a viscous modulus at 100 rad/s of from 1000 to 35,000 Pa;
wherein the viscous modulus is less than the elastic modulus in the frequency range of from 1 to 100 rad/s. Preferably the surface energetics of the composition is from 25 to 40 dynes.
Examination of the rheological properties of the compositions have been successfully used to characterise and differentiate adhesive behaviour. Typically the elastic modulus (G′) and the viscous modulus (G″) are measured over a range of 0.01-100 rad/s at a given temperature. For skin applications the appropriate temperature is 37° C. The moduli at low rad/s values relate to the initial bonding of the adhesive to skin and the higher to the changes in moduli values associated with de-bonding. Methods of measuring G′ and G″ are well known; for example a Rheometric Scientific RS-5 rheometer could be used.
The water activity of the composition can be measured using impedance methods with devices such as the Rotronic AWVC (manufactured by Rotronic). The activity of water may also be determined by placing the composition in environments of controlled humidity and temperature and measuring the changes in weight. The relative humidity (RH) at which the composition does not change weight corresponds to the activity of water in the gel (RH/100). The use of saturated salt solutions to provide the appropriate environmental conditions is well known. All compositions directly exposed to relative humidities less than that corresponding to the activity of water will be thermodynamically allowed to lose water. Exposure to greater relative humidities and the composition will gain weight.
The bioadhesive composition preferably comprises an aqueous plasticiser, a copolymer of a hydrophilic unsaturated water-soluble first monomer and a hydrophilic unsaturated water-soluble second monomer and a cross-linking agent, the first monomer having a tendency preferentially to enhance the bioadhesive properties of the composition.
Preferably the first monomer has a tendency also to enhance the mechanical strength of the composition according to the invention and/or the second monomer has a tendency preferentially to increase the water activity of the composition.
The bioadhesive composition is preferably obtainable by polymerising an aqueous reactive mixture comprising the said first monomer, the said second monomer and a crosslinking agent.
According to the invention, there is further provided a wound dressing which comprises a carrier material and the bioadhesive composition according to the invention. The carrier material is either encapsulated or coated by either of the bioadhesive compositions. Preferably it is coated, particularly on only one side.
According to the invention there is also provided a process for the preparation of a wound dressing according to the invention which process comprises either:
(a) coating or encapsulating a carrier material with an aqueous reaction mixture comprising the said first monomer, the said second monomer and a crosslinking agent, and curing the coating on the material; or
(b) coating a carrier material with the bioadhesive composition according to the invention.
In preferred embodiments the first and second monomers will be acrylate based monomers selected for their ability to polymerise rapidly in water and having substantially the same molecular weight whereby in a mixture of the two the relative proportions may be varied without significantly altering the molar characteristics of the composition.
The first monomer is preferably a compound of formula
wherein R
1
is an optionally substituted hydr
Munro Hugh Semple
Yasin Mohammed
Azpuru Carlos
First Water Limited
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