CA1079896A - Hydrophilic random interpolymer compositions and method for making same - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

Hydrocolloidal dispersions of random interpolymer compositions that have a capacity for absorbing water in amounts of from 10 to 125 times their own weight or greater and are also bacteriostatic are prepared by the polymerization in aqueous medium of a mixture of monomers comprising (1) up to about 90% by weight of an ester of an .alpha.,.beta.-olefinically unsaturated carboxylic acid and a monohydric or polyhydric alcohol having a terminal quarternary ammonium group and (2) at least one .alpha.,.beta.-olefinically unsaturated comonomer in the presence of a crosslinking agent comprising a difunctional monomer de-rived from an .alpha.,.beta.-olefinically unsaturated carboxylic acid. The interpolymer compositions can be used for binding or coating nonwoven fabrics including paper to improve water absorbency, or cast into a structurally self-supporting film. A water dispersion of the inter-polymer can also be formed into a gel, which can be shaped into useful articles or alternatively dried and pulverized into bacteriostatic hydrophilic particles.

Description

~079~6 BACKGROUND OF T~IE INVENTION
1. Field of the Invention This invention relates to novel compositions which are random interpolymers of a terminally quaternized derivative of acrylic acid with an ~ olefinically unsaturated comonomer polymerizable therewith, and to their preparation by polymer-ization in an aqueous medium. More particularly, this invention relates to hydrophilic interpolymer compositions having novel - bacteriostatic properties which, in conjunction with their high water ad~orbency, makes them especially suitable for applications where the combination of such water adsorbency with control of bacterial growth is desired.

2. Description of the Prior Art ; There has long been a need for polymers which can be prepared by polymerization in aqueous systems and which can be cast as self-supporting films having a large water adsorbent capacity. There has also been a need for such compositions that are bacteriostatic and can therefore control the growth of bacteria on surfaces which they contact. Some polymeric compo-sitions, such as polyvinyl alcohol and cellophane, are excellent film formers yet are unable to adsorb water in appreciable amounts. Other materials, exemplified by the so-called HXDRON*
, polymers, are more water adsorbent than the above films, but cannot be converted to flexible films from aqueous dispersions, Such materials, if they are to be converted into films, must be polymerized in non-aqueous organic solvents which are termed "syrups", as disclosed in U.S. Patent No. 3,520,949 dated July 21, 1970, inventors Ihomas H. Shepherd and Francis E. Gould, as-signors to National Patent Development Corporation. Likewise, * Trade Mark ,~ ..

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10~9896 these polymers lack bacteriostatic properties. When the above prior art compositions are bacteriostatic, they are rendered so by the inclusion of an additional substance, which is not an integral part of the polymer.
SUMMARY OF THE_INVENTION
~he present invention provides-a random interpolymer that is bacteriostatic, i8 capable of adsorbing large multiples of its own weight of water, and can be prepared by polymeriza-tion in an aqueous polymerization medium. More particularly, the bacteriostatic random interpolymers of this invention ex-hibit the properties of having a water adsorbing capacity of from about 10 to about 125 times their own weight or greater.
In accordance with one aspect of the invention, the random interpolymers are provided in the form of an aqueous colloidal dispersion or suspension which can be converted into a gel, or a dry powder, which find uses as highly adsorbent thickening agents. In addition, articles can be coated with the interpolymers to give them a lubricious coating such, for example, as medical instruments and devices which are to be ; 20 inserted into body openings e.g., proctoscopes and the like.
In accordance with ano~her aspect of the invention, the random interpolymers may be prepared initially in the form of a gel. In either event, the gelled material, when in a high-ly cross-linked form, can be cut and shaped into various ~truc-tures such as contact len~es where the bacteriostatic pro-~, ~

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10'~9~3~6 J&J 7g6 perties of the interpolymer material can be advantageously , employed.

Further, the aqueous colloidal dispersion can be cast into a self-supporting, transparent, conformable film which is particularly useful as a wound dressing since it is highly conforming to wound surfaces, and provides an occlusive bacteriostatic dressing. As set forth in Hinman, C. D., and Maibach, H. I. : Effect Of Air Exposure and Occlusion On Experimental Human Skin Wounds, Nature 200:377, 1963, an~
Winter, G. D. & Scales, J. T.: Effect Of Air Drying & Dressings On The Surface Of A Wound, Nature 197:91, 1963, it has been shown that the healing of superficial wounds can be enhanced by providing an occlusive dressing. But under such dressings - bacteria often can proliferate. However, dressings prepared ~rom the interpolymers of this in~ention are not only occ]u~ive, but also, because of their bacteriostatic ' propert~es, help prevent the proli~eration of bacteria.
.j In accordance with yet another aspect of this invention, the random interpolymers of the invention are prepared by the polymerization in aqueous medium of (A) a mixture of monomers comprising (1) up to about 90% by weight of an ester of an a,~-olefinically unsaturated carboxylic acid and a monohydric 10~79896 :
J&J 796 .
or polyhydric alcohol ha~ing a terminal quaternary ammonium group ~nd (2) at lea~t one a,~-ole~inic~lly unsaturated co-monomer, in the presence of (B) a cross-linking agent com-prising a difunctional monomer derived from an ~,~-ole~inical-ly unsaturated carboxylic acid DESCRIPTION OF THE PREFERRED EMBODIMENTS

There ha~ now been dlscovered a novel compositlon com-prising a random interpolymer derived ~rom the polymeri.zation : of a mixture o~ monomer~ comprising: (A) (1) from about :10 10 to about 9~0 by welght of said mixture of a flrst monomer which is an e~ter of an a,~-olefinically unsaturated : carboxylic acid and a monohydric or polyhydric alcohol havlng ~ terminal quaternary ammonium group and (2), cor-- respondingly, ~rom about 90 to about 10~ by weight of said 1~ mixture of at least one ~,~-olefinlcally unsaturated co-monomer capable of being dispersed in aqueous media, in the presence of (B) at least 0.02~ by weight, based on the weight of sald mixture, o~ a cross-llnklng agent com-prising a difunctlonal monomer which i8 capable of being : -dispersed or dissolved in aqueous media and is an ester : .
or amide o~ an a,~-oleiinically unsaturated carboxylic . . :
, . . .
acid; sald comonomer (2) comprising (a) at least 10~ by welght of sald mlxture o~ monomers of an acld comonomer, or (b) at least 20% by weight of said mixture of monomers o~ an amlde comonomer, or (c) at least lO~o by weight of sa~d mixture of monomers of a comblnatlon o~ acid and amide co-".

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J&J 79 -- monomers, said combination containing at least 5% by weight of said mixture of an acid monomer. .-The esters of an a,~-olefinically unsaturated carboxylic acid and a monohydric or polyhydric alcohol having a terminal ~ .
quaternary ammonium group which may be suitably employed in this invention include those having the structure:

H2C-f~ ORl- I (R2) 3 R O X

wherein R is selected from the group consisting of hydrogen and Cl to C4 alkyl; Rl is selected from the group consisting . .
of Cl to C4 alkylene and hydroxy substituted Cl to C4 alkylene;
each R2 is selected from the group consisting of Cl to C4 alkyl; and X represents an anion of an acid sufficiently acidic to form a salt with amino nitrogen, for example Cl-, Br , I , and CH3S04-. Such esters are exemplified by 2-, methacryloyloxyethyltrimethylammonium methyl sulfate and ~ ~-:hs 2-hydroxy-3-methacryloyloxypropyltrimethylammonium chloride, ¦ the latter being preferred.
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! Difunctional monomers suitable for use as a crosslinking agent in accordance with this invention include the esters and amides of a,~-olefinically unsaturated acids selected from the :. ~ . ...

~079896 J&J 796 group consisting of the compounds defined by structural formulas I, II and III below:

I H2C C - C - O -~R3~0]n- Cl - C = CH2 R O O R

wherein R is hydrogen or Cl to C4 alkyl; R3 is Cl to C6 alkylene; and n is an integer from 1 to 3;
H H
II H2C _ C - ICl - N - R3- N - IC - C - CH2 R O O R

wherein R is hydrogen or Cl to C4 alkyl; and R3 is Cl to C6 alkylene; and III H2C = tC - ICl - N - Y
R O
wherein R is hydrogen or Cl to C4 alkyl; and Y is selected from the group consisting of - CHOH and R O R :

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1 0 7 9 89 6 J&J 796 wherein R4 is selected from the group consisting of hydrogen and Cl to C5 alkyl; and each R5 is selected from the group consisting of hydrogen and -CH20H, provided, however, that at least one R5 is -CH20H.

S Examples of such difunctional monomers include ethylene glycol dimethacrylate and diacrylate, diethyleneglycol di-, .
methacrylate and diacrylate, triethyleneglycol dimethacrylate and diacrylate, 1,3-propanediol dimethacrylate and diacrylate, . 2,2-dimethylpropanediol diacrylate, tripropylene glycol di-methacrylate and diacrylate, 1,3-butylene glycol dimethacxylate :~ and diacrylate, N,N'-propylenebisacrylamide, N,N'-methylenebis-~ .
; acrylamide; N-l-alkylol amides of a,~-olefinically unsaturated carboxylic acid, which amides have from 4 to 8 carbon atoms, j exemplified by N-methanol acrylamide, N-l-ethanolacrylamide, :
N-l-propanolacrylamide, N-methanolmethacrylamide, N-l-ethanol- :
I methacrylamide and hydroxymethyl diacetone acrylamide (available i from Lubrizol Corporation). The preferred difunctional monomer : is N,N'-methylenebisacrylamide. :
' :

The olefinically unsaturated monomers that are suitable -~
for employment as comonomers in the random interpolymers of this invention include a,~-olefinically unsaturated monomers .
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1079896 J&J 7g6 .:
such as the vinyl monomers, as well as a,~-olefinically un-saturated carboxylic acids of from 3 to 6 carbon atoms and the lower alkyl esters and amides thereof, 2-(Cl-C4) alkyl sub-stituted acrylic and crotonic acids and esters and amides there-of, and N-substituted~amides of the above acids. Examples of suitable ~,~-olefinically unsaturated ~onomers include sodium vinyl sulfate, vinyl acetate, methyl vinyl ether, vinyl chloride, crotonic acid, crotonamide, acrylic acid, methyl acrylate, methyl crotonate, ethyl acrylate, ethyl crotonate, methacrylic acid, 2-ethylacrylic acid, 2-methylcrotonic acid, butyl methacrylate, ethyl methacrylate, ethyl 2-methylcrotonate, - acrylamide, methacrylamide, 2-ethylcrotonamide, 2-ethylacryl~de., N-isopropyl acrylamide, diacetone acrylamide, N-t-butyl acrylamide, ; N-2-ethanol acrylamide, N-3-propanol acrylamide and N-methyl :15 methacrylamide. Of these, the preferred comonomers are acrylic and methacrylic acids, acrylamide and methacrylamide.

! In a preferred embodiment of this invention, the mixture of monomers comprises from about 10 to about 80% by weight of said I mixture of said a,~-olefinically unsaturated carboxylic acid ;20 ester of a monohydric or polyhydric alcohol having a terminal , .
~; quaternary ammonium group; and at least about 20% by weight of the mixture of an olefinically unsaturated comonomer, from : about 5 to about 35% by weight of the mixture (total monomers '~ ', - 8 - .
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.' . ' '', . ' ' ', , ' , .' ~079~96 J~J 796 in the prepolymer blend - excluding the crosslinking agent) comprising a comonomer selected from the group consisting of acrylic acid and methacrylic acid (acrylic acid being most preferred), and from about 10 to about 85% by weight of the mixture comprising acrylamide, or methacrylamide (acrylamide being most preferred). Clearly the total amount of the monomers employed will be 100% and therefore if an amount equal to or approaching the maximum of one particular monomer is employed, than the relative amounts of the remaining monomers must be reduced accordingly. The amount of di-functional monomer crosslinking agent employed in this pre-ferred embodiment is from about 0.02 to about 5%, based on the weight of the mixture, from about 0.05 to about 1% being ; particularly preferred. Generally, when the intended end use ;15 of the random interpolymer is as a film, the amount of cross-linking agent will not exceed 0.5% although this may vary depending on the particular crosslinking agent, as welL as the composition of the monomer mixture. The selection of a suitable concentration of crosslinking agent (as well as monomer mixture) to meet a particular end use requirement is, however, well within the skill of the art.
.1, The random interpolymers of this invention are prepared, in accordance with another embodiment of this invention, by . . .
` - g _ 1079896 - J&J 796 the free radical polymerization of the above monomers in an aqueous medium using any suitable free radical initiator, including high energy irradiation as well as photochemical and chemical means.

- 5 Suitable chemical initiators are any of those which are commonly known in the art to effect the polymerization of acrylic monomers and which are dispersible or soluble in aqueous medium. Such initiators are capable of generating a sufficient number of free radicals to propagate the polymeri-. . .
; 10 zation reaction, and include water soluble persulfated salts such as sodium, potassium, and ammonium persulfate; t-butyl peroxypivalate; the peroxycarbonate salts; hydrogen peroxide;
and water soluble oxidation and reduction couples such as the combination of a water soluble persulfate and a water soluble , 15 bisulfite.

`i In particular, there is preferred the use of the water soluble persulfates, especially ammonium persulfate, and such "redox" pairs as those comprising water soluble persulfates as the oxidant and ammonium bisulfite as the reductant.
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0~79 89 6 J&J 796 These initiators are typically employed in a quantity ranging from about 0.2 to about 2 parts by weight per hundred parts of total monomers (phm). The pre~erred initiators and :~
especially ammonium persulfate are employed in amounts of ` 5 from 0.5 to 1 phm.

As used herein, the term "aqueous medium" is meant to include water, as well as a fluid comprising water, and one or more water-miscible organic solvents. In general, the aqueous medium may comprise water alone, especially deionized water, 10 and may further comprise, in instances where it is desirable to increase the tolerance of the aqueous medium for various ; monomers otherwise poorly dispersible in water at their higher levels within the foregoing description so as to achieve homogeneous polymerization, a water-miscible solvent, e.g.
methanol, ethanol, isopropanol, N,N-dimethylformamide, N,N-j dimethylacetamide and acetonitrile. The amount of this in-;l cluded organic solvent can be from 0 to about 60% by weight, based on the weight of the aqueous medium, and, in preferred embodiments, is from 0 to about 15% by weight.
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The amount of aqueous medium employed should ~ sufficient to achieve a uniform solution of the monomers. Generally, ` this amount of aqueous medium will be in the range of 9 to ,,: , .

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1079896 J&J 796 20 times by weight of aqueous medium based on the total weight of the monomers. In general, if larger quantities of aqueous medium are employed, the polymerization reaction proceeds less rapidly, and there is the further disadvantage of having an additional quantity of aqueous medium which must eventually be removed.

Generally, the order of addition is immaterial when admixing the monomers and aqueous medium. However, in those instances where a monomer is insoluble or poorly soluble in water and is only sparingly soluble in the aqueous medium, such monomer is preferably first dissolved in the water-miscible organic solvent and the resulting solution is then added to the aqueous medium.

. , .:
In general, the temperature at which the polymerization is carried out is limited only by the stirrability of the reaction mixture. Thus, at too high a reaction temperature, the viscosity of the reaction mixture rapidly increases to ; a point where the reaction mixture is too viscous to be stirred and the reaction is then difficult to control and must be terminated. The polymerization rate, however, depends both upon the polymerization initiator employed and the temperature at which the reaction is run.

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. .,: , : : :. -J&J 796 In the preferred embodiment of this invention in which ammonium persulfate is used as the initiator, the reaction is suitably conducted at a temperature range of about 55 to 75C.
Preferably, when less than 60% by weight of the monomer S mixture is a terminally quaternized monomer, the reaction temperature should not exceed about 68C. It is also preferred that the time at the elevated temperature be limited to about 20 to 45 minutes, so as to limit the viscosity of the reaction mixture (at the reaction temperature) to no more than about

3,000 centipoise. After the reaction has proceeded for this period, it is preferred to rapidly cool the reaction mixture to below 30C. It has been found that when the duration at elevated temperature is thus limited, a random interpolymer is produced that will remain as a stable (uniform) hydro-colloidal dispersion, having a viscosity at 25C. of from ~- about 40 to about 10,000 centipoise, for a period of from 1 to 24 months or longer at room temperature.

~' Once the polymerization reaction has proceeded to the point where the random interpolymerized product exists as a gel rather than a hydrocolloidal dispersion, smooth films can no longer be cast. A~ter the hydrocolloidal dispersion has formed a gel, the gelled random interpolymer may be dried and pulverized into a powder. In this powder form, .: :

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~0~9896 J&J 796 it does retain its highly hydrophilic and bacteriostatic properties, but cannot be readily redispersed in water as a colloidal dispersion.

Of course, a dry product or a gel may be preferred for various applications. In such instances the hydrocolloidal dispersion of random interpolymer can be converted into a - gel by storing at elevated temperatures, e.g. 30 - 40C., for ~rom one to eight weeks. If desired, this gel can be used as is or dried and pulverized into a powder as discussed above. Alternatively, the hydrocolloidal dispersion can be dried directly by well-known means, for example drum drying or spray drying, to form substantially dry hydrophilic particles of the interpolymer.

. , .

` In a less preferred alternative method, the interpolymers can be prepared by the quaternization of corresponding inter-~, polymers prepared with monomer having the free amino group instead o.f the quaternary monomer, using well-known techniques. One dis~
advantage of this procedure, particularly for medical or other end uses where the ultimate product may contact people or 2a animals, is that incomplete quaternization may leave some ; ~ free amino groups in the end product, and these tend to be ~ irritating and cause undesirable side effects.
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~079896 J&J 796 The interpolymers of this invention are useful in the form of a hydrocolloidal dispersion, as a film, as a gel and in the form of particles prepared by the pulverization of the dried interpolymer. The particulate form can be used as a thickening agent in the so-called "water base" paints, or interspersed within a fibrous material, for example, paper products or other woven or nonwoven fabric materials (used, for example, as towels, disposable diapers and the like) where its combination of water adsorbency and antibacterial properties can be employed to special advantage. The hydro-colloidal dispersion itself can be used Per se in impreg-nating and coating operations for direct application to an article. Examples of such uses include the application ~, of a hydrophilic lubricious coating to a medical instrument that is intended for insertion into a body opening such, for example, as a disposable rectal thermometer, or to the surfaces of latex gloves used by physicians in carrying out physical examinations of such body cavities, ç The interpolymers are especially useful when cast into a tough, integral film. As a film, the interpolymers are particularly well-suited for covering minor wounds such as cuts, scratches, and other irritated skin areas where a dressing is indicated.

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1079896 J&J 796 The interpolymers have been shown to have in vitro bacteriostatic properties, and in vivo studies on intact skin have also established such activity. Thus, the cast films prepared from these interpolymers are well-suited as occlusive dressings for minor wounds such as cuts, scratches, and irri-tated areas.

: To cast a film of the interpolymer of this invention, an aqueous dispersion of the interpolymer, preferably a dis-persion of the interpolymer in the aqueous polymerization medium,is disposed on a smooth, non-adherent surface such as polyethylene, polytetrafluoroethylene or silicone-treated surfaces.
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The films can be cast in a variety of thicknesses. The details for film casting are well-known in the art, and such well-known procedures can be advantageously employed in preparing the interpolymer films of this invention. When a film is to be prepared from the interpolymers of this -invention, increased film flexibility can be achieved by including in the polymeric dispersion prior to casting from 5 to 40% by weight of a plasticizer such for example as glycerol, carbitol or methyl carbitol, glycerol being pre-lerred.

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10~9896 J.~J 796 The ~ollowing examples will further serve to illustrate the preparation and use o~ the interpolymers of this inven-tlon.
Example I
A 5-liter ~ulti-neck flask, equipped with a nitrogen inlet, mechanical stirrer, thermometer, reflux condenser and an addition funne~ was charged with the fol]owing reagents:
2-hydroxy-3-methacryloyloxypropyl-trimethylammonium chloride, Sipomer Q-l, Alcolac Chemical Corporation 108 g ~crylic acid 24 g Acrylamide 108 g N,N'-methylenebisacrylamide 0 12 g Water ~7oo g ~fter purging the system wlth nitrogen ~or 100 minutes, the contents were heated until the temperature reached 55C, Then a solution o~ ammonium persulfate, (2.4 g ) in 10 ml, o~ water was added, When the temperature reached 68, flnd the viscosity o~ the reaction mixture became such that the stirrer began to labor, then 240.0 g o~ methanol were added over a 10 min. period anA the reaction mixture cooled The colloidal dispersion obtained had a solids content o~
; 7,76%, equivalent to 100% conversion. A ~ilm is obtained by drying down, in a polyethylene lined tray having a surface area o~ about 40 cm2 and containing a piece o~
~auze or simllar fabric to act as a reinforcement, 200 g o~ the above dispersion to whlch is added 5 g. of glycerol, at 100F ~or 48 hours. A weighed sample of the film is . .
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placed in 150 g of deionized water for 24 hours. The - -mixture is then Qtrained through 40 mesh screening.

Example II

A 5-liter, multi-necked flask, equipped with a nitrogen ; 5 inlet, mechanical stirrer, thermometer and reflux condenser was charged with the following reagents:
2-hydroxy-3-methacryloyloxypropyl-trimethylammonium chloride 126 g.
Acrylamide 126 g ; 10 N,N'-Methylenebisacrylamide 0.14 g.
Acrylic acid 28 g.
Methanol 280 g.
Water 3175 g.
The system was purged with nitrogen for approximately 60 minutes. The reaction mixture wa~ then heated until the , ~e temperature reached 55C. At this time a solution of 1.4 g.
of ammonium persulfate in 25 ml. o~ water was added. When the temper~ture reached 63.5C, heating was discontinued, l and the te~perature was maintained between 63 and 64C
-~20 for 10 minutes, The reaction mixture was cooled to 24.5C
and filtered air was bubbled through the ~tirred reaction mixture for 2 hours. The colloidal dispersion so obtained had a solids content of 7.37% and a viscosity of 80 cP.
~¦ A film was obtained by drying down, in a polyethylene lined ~5 tray having a surface area of about 40 cm2, and containing a piece o~ gauze or similar fabric to act as a reinforce~
ment, 200 g. of the above dispersion to which was added ., . ~ '~

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1079896 J&J 796 5 g. of glycerol, at 100 F for 4~ hours. A weighed sample of the ~ilm was placed in 150 g. of deionized water for 24 hours. The mixture was then strained through 40 mesh screening and the amount of water ad~orbed calculated.
For this polymer there was adsorbed 35.5 g. of H20 per g.
of hydrocolloid.

Example III

Using the polymerization procedure described in Examples I or II, the monomers listed in the following table were polymerized under the conditions and with the results indicated to give colloidal dispersions of inter-polymers in accordance with the present invention. The amount of ingredients in the table is in grams.

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~79896 J~J 796 Example IV

An aqueous dispersion of the interpolymer prepared from 12 g. of acrylic acid, 54 g of acrylamide, o.o6 g. Or N,N'-methylenebisacrylamide and 54 g. of 2-hydroxy-3-methacryloyloxy-propyltr~methylarnmonium chloride in 1520 g. of water and 120 g. of methanol was prepared using 1.2 g. ar~nonium per-sulfate as the initiator The polyrnerization was carried out at 55 to 63C for 0.8 hours. The resulting hydro-colloidal dispersion had a solids content of 6.4~ and a vlscosity of 193 cP. 4.3 g of glycerol plasticlzer were added to ~00 g. of the dispersion and the interpolymer cast as films having thicknesses in the range 20 to 30 mils.
From these films hydrocolloiflal film dressln~s were prepared in the following manner. A 3x3 inch, 1/16 inch thick polyester urethanefoam was coated on one side thereof with a pressure sensitlve adhesive A 2-1/4 x 2-1/4 inch portion o~ the film prepared as described above was affixed to the center area of the coated side of the foarn by means of the pressure sensitive adhesive, leaving a 3/8 inch border about the perimeter of the foam to serve as a mesns for flttaching the h~drocolloidal ~ilm dressing to the desired skln are~.

Example V

To illustrate the irl vitro bacteriostatic pro~erties of the hydrocolloid film against specific organisrns, 2cm x ~cm portions o~ a film of Example IV, without any L oam . .
~ -22-1079~96 J~J 79 backing, were placed in the center of test plates containing a 10 ml base layer of nutrient agar overlaid wlth 4 ml agar containing approximately 2,000,000 viable cells of test organism per ml. The plates were then incubated for 24 hours at 3~C. The average zone of inhibition of triplicate trials is set forth below.
Staph aureus 2 3mm (from the edge of the dressing) Staph, epi-dermidis 3 mm (~rom the edge o~ the dressing) 0 Similar acti~ity can be demonstrated against Ps aeroginosa, K. pneumoniae, and E. coli Por films produced with 2-hydroxy-3-methacryloyloxypropyltrimethylammonlum chloride Exam~le VI
Hydrocolloid fllm dressings of Example IV were attached to a human subject's skin and occluded with Saran film.
After 48 hours the dressings were removed, and a sample taken by washing the treated area with 1.5 milliliters of physiological saline in a 28 millimeter diameter cylinder.
0 The area was gently scraped for 30 seconds with a sterile pipette. One milliliter of the wash solution was trans- -ferred to a tube containing 9 milliliters of peptone w~ter.
These suspensions, and dilutions made from them, were plated in Brain Heart Infusion Agar. After incubation for 48 hours, colonies on the plates were counted and the numbers of bacteria per square centimeter of skin calcu-lated~

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~079896 .: J&J 796 ~ .
' As shown in the Table below, the dressings of thi.s .Ln-~ention inhlbited bacterial growth on intact skin o.f all o~
10 sub~ects, TABLE
Bacteria per cm2 recovered ~rom treated and control sites Saran Film Saran Film Occluded Occluded *Dialyzed Hydrocolloid Hydrocollold Saran Film Skin Sub~ect Film Dressing Film DresQing Control Control 46xlO~ 79x103 14x105 19x102 13X102 62 50x105 22 3 ~ 13 8 22x105 17

4 ~ 13 802 21x105 74 ~i 5 768 29xlo2 34x104 43 6 142 24 97x104 l4g 7 89 12 84x104 14 8 29xlo2 34x105 106 9 17x103 74xlo2 48x104 36 : ~ 10 l8xlo2 46X102 31x104 70 -~ *Dialyzed hydrocolloid ~ilm was cast ~rom ; hydrocolloid dlspersion that had been sub-Jected to dialysis to remove any impurities (e.g. unreacted monomer) that may have been i present.
Example VII
..
The volar aspect o~ the left forearm o~ a human ..
volunteer was shaved and then prepped with a 70~ ethanol , swab. Three super~icial incisions 15 mm. long and approxi-.) mately 300 microns deep were made with a sterile scalpel (blade No. 11).
The incisions were then dressed with sterile hydro-colloid film with ~oam backing descrlbed in Example IV.

1079~96 The control portions of the wounds were biopsied once to yield information at 1, 2 and 3 days post wounding. The biopsies are small, elliptical samples obtained after infiltration of these areas with ca. 0.3 - 0.4 cc of 2% lidocaine hydrochloride. The fresh tissue was quick-frozen for cryotomy (Slee HR Cryostat).
Eight micron thick sections were cut, fixed in Wolman's solution and stained with hematoxylin and eosin.
Gross observations of the incisions reveal that a moderate scab formation is present on day 1 and this decreases slightly by the third day. mere is no apparent infection, hemorrhage, edema or excessive tenderness. A slight amount of dried serosanguinous exudate is present on the film when removed from the wound.
From the standpoint of histology, day 1 reveals slight inflammation and the wound wa~ re-epithelialized. A fibrin network i9 present below the hyperplastic epidermis. Differ-entiation of the epidermis starts at that time.
; By day 2, a slight perivascular inflammatory response .~ i9 seen in a re-epithelialized wound. A few fibroblasts can be seen in the perivascular areas. The epidermis has a hyper-plastic appearance and is differentiated. A few necrotic cells are present in the lifting scab. A dermal fibrin net-work is present.
By the third day a moderate polymorphonuclear inflam-matory response is seen. The wound, as before, is re-epithelialized and hyperplastic. No fibroplasia are noticed. A fibrin network is seen in the dermis and the .-, ., ~:

. ~ . . , ' .

~079896 J&J 79~
, , .
- stratum granulosum is prësent. A lifting scab is seen and contains only a few necrotic cells.
These studles reveal a well-healed wound by day 2.
This is equivalent to saran dressed wounds of the same age, In addition to preventing free evaporatlon ~rom wound tis-sues, the foam hydrocolloid dressing probably stabllize~
the wound mechanically, i.e., reducing shear ~orces, This might also be the reason the wound is re-epithelialized and differentiated by day 2. No evidence of any primary irrita 0 tion or damage to tis~ue is observed.
Example VIII
Cantharidin induced blister wounds were dressed with (a) a sample o~ hydrocolloid film as prepared in Example IV, (b) another sample of the same hydrocolloid film occluded "j wlth Saran fllm and (c) a Saran film occluded control. The Saran ~ilm drecsings were a~fixed by means o~ 6urgical tape.
After the dressings were in place for 48 hours, the wounds, together with a skin control, were sampled ~or bacterial growth. Sampllng was done by washing the treated area with j3 2,5 milliliters physiological saline in a 12.7 mm. diameter ; cylinder. The area was not scraped as with intact skin, `
Saline was agitated in the cylinder by swl~hing a pipette back and ~orth for 60 seconds. One ml. of the wash solution was then transferred to a tube contalning 9 ml. of peptone water. These suspensions and dilutions made from them were ;` plated in Brain Heart Infusion Agar. A~ter incubation for 48 hours, colonies on the plates were counted and the numbers ~; o~ ~acteria per square centimeter of skin calculated.
~ j ;
.~. .-- ~.
.~' .

- . . ~ - . :

107~8~6 J~cJ 7~36 The f`ollowing Table shows the numbers of bacteria cul-tured from the blister wounds.
TABLE
-Hydrocolloid Hydrocolloid SARANR Skin ~ ilm Film Occluded Control Control 1 23X106 58 94x105 35xlo2 2 23 23 89x104 35 3 lOxiO7 37x105 62x104 173 4 115 35 37x105 104 O 5 104 17x103 39x105 6 299 23 11x106 7 391 12 l6xlo6 37x103 8 39xlo6 23 15X106 35x102 llxlo6 llxlo6 l2xlo6 24Xlo2 ExamPle IX
A 3-liter, multinecked ~lask, equipped with a nitrogen inlet, mechanical stirrer, thermometer and reflux condenser w~s charged with the ~ollowing reagents:
2-Hydroxy-3-methacryloyloxypropyl-trlmethylammonium chloride 135 g ~ :
Acrylamide 7 5 g.
Acrylic acid 7.5 g.
N,N~-Methylenebisacrylamide o.o75 g 3 Water 1775 ~.
The system was purged with nitrogen for approximately 60 minutes. The reaction mlxture was then heated until the ~ -temperature reached 55 C. At thl~ time, a solution of am-monium persulfate (0.75 g.) in 25 ml. o~ water was added : ~.

1079896 J&J '796 , and heating continued. Heatin~ was dlscontinued when the temperature reached 65C; and the temperature was maintained between 62 and 66C for 30 minutes. The reaction mixture was then cooled rapldly to below 30C and ~iltered air then bubbled through the reaction mixture ~or 1 - 2 hour~, The colloidal disperæion so obtained had a solids content of 7,7%
and a viscosity of 140 cP. A sample of the dispersion was dried in a convection oven at 100C for 3 hours, yielding 0,6763 g, of polymer, The dried polymer was then immersed 0 in 150 g. of distilled water for 24 hrs, The mixture was stralned through 40 mesh screening and the amount of water absorbed by the polymer calculated, This interpolymer absorbed 40 g, of water per gram of polymer, When another sample was drled at 100F for 48 hours, the interpolymer showed no water absorption, When the drying was performed at 100C for 19 hours, the water absorption was 8 g, of water per g, of polymer, Example X
Using the polymerization procedure described in Example ~'1 IX, the monomers listed in the following table were poly-; merized, dried and tested under the conditions and with the results set forth in the following table, From the drying and water retention data set forth therein, it can be seen that for certain interpolymers within the scope of the present in~ention, proper selection of drying con-ditions may be necessary to achieve the desired water ,1 retention properties. The amount o~ ingredients in the table is in grams.

~ .

.s ' ~ : , ,;.

~7~896 ~ ~

J&J 796 Polymer A B C D

Acrylamide - 30 126 120 Acrylic Acid 10 - 28 30 Sipomer Q-l 1 go 120 126 150 N,N'-Methylenebis-acrylamide 0,05 0.o75 0.14 o.o6 Ammonium persulfate 0.5 0.75 1.4 1.5 Water 1200 1800 3025 3600 i o Polymerization Temp, C 55-66 55-66 55-65 55-65 % Solids 7,7 7.8 ~.3 7.6 Viscosity, cP 70 265 120 375 Absorptlon~ g.H20/g Polymer ~L5 a, Sample dried 2 2 at 100F N,R. N.R. 32.4 21,1 b, Sample drled at 100C, 3 hr. 84.9 18,3 36.6 35.1 c. Sample dried at '0 100C, 19 hr.67.3 134.6 13.4 27,8 ' ' "
1. Sipomer Q-l = 2-hydrox~-3-methacryloyloxypropyltrimethyl-ammonium chloride - Alcolac Chemical Corp, ~ 2, N.R. = no water retention .
Now, ha~ing described the novel interpolymers of this ~5 inventlon, together with their preparation and use, those -skilled in the art will have no difficulty in making changes and modificationæ which do not depart from the scope or spirlt o~ the ~nventlon,

Claims (23)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:-

1. A random interpolymer derived from the polymerization of a mixture of monomers comprising: (A) (1) from about 10 to about 90% by weight of said mixture of a first monomer which is an ester of an .alpha.,.beta.-olefinically unsaturated carboxylic acid and a monohydric or polyhydric alcohol having a terminal quaternary ammonium group and (2), cor-respondingly, from about 90 to about 10% by weight of said mixture of at least one .alpha.,.beta.-olefinically unsaturated co-monomer capable of being dispersed in aqueous media, in the presence of (B) at least 0.02% by weight, based on the weight of said mixture, of a cross-linking agent com-prising a difunctional monomer which is capable of being dispersed or dissolved in aqueous media and is an ester or amide of an .alpha.,.beta.-olefinically unsaturated carboxylic acid; said comonomer (2) comprising (a) at least 10% by weight of said mixture of monomers of an acid comonomer, or (b) at least 20% by weight of said mixture of monomers of an amide comonomer, or (c) at least 10% by weight of said mixture of monomers of a combination of acid and amide co-monomers, said combination containing at least 5% by weight of said mixture of an acid monomer.

2. The interpolymer of Claim 1 in which said first monomer is selected from the group consisting of the com-pounds having the structural formula:

wherein R is selected from the group consisting of hydrogen and C1 to C4 alkyl; R1 is selected from the group consisting of C1 to C4 alkylene and hydroxy substltuted C1 to C4 alkylene;
each R2 is selected from the group consisting of C1 to C4 alkyl, and X- represents an anion of an acid sufficiently acidic to form a salt with amino nitrogen.

3. The interpolymer of Claim 2 in which said anion is halogen.

4. The interpolymer of Claim 2 in which said anion is CH3SO4-.

5. The interpolymer of Claim 2 in which the ester is 2-methylacryloyloxyethyltrimethylammonium methyl sulfate, or 2-hydroxy-3-methacryloyloxypropyltrimethylammonium chloride.

6. The interpolymer of Claim 1 in which said comonomer iq selected from the group consisting of the vinyl monomers, the .alpha.,.beta.-olefinically unsaturated carboxylic acids of from 3 to 6 carbon atoms and the lower alkyl esters and amides thereof, 2-(C1-C4) alkyl substituted acrylic and crotonic acids and esters and amides thereof, and N-substituted amides of the above acids.

7. The interpolymer of Claim 6 wherein said comonomer is selected from the group consisting of sodium vinyl sul-fate, vinyl acetate, methyl vinyl ether, vinyl chloride, crotonic acid, crotonamide, acrylic acid, methyl acrylate, methyl crotonate, ethyl acrylate, ethyl crotonate, methacrylic acid, 2-ethylacrylic acid, 2-methylcrotonic acid, butyl methacrylate, ethyl methacrylate, ethyl 2-methylcrotonate, acryl-amide, methacrylamide, 2-ethylcrotonamide, 2-ethylacrylamide, N-isopropyl acrylamide, diacetone acrylamide, N-t-butyl-acrylamide, N-2-ethanol acrylamide, N-3-propanol acrylamide and N-methyl methacrylamide.

8. The interpolymer of Claim 6 wherein said comonomer is selected from the group consisting of acrylic acid, methacrylic acid, acrylamide and methacrylamide.

9. The interpolymer of Claim 6 in which said mixture of monomers comprises from about 10 to about 80% by weight of said first monomer, from about 5 to about 35% by weight of an acld comonomer selected from the group consisting of acrylic and methacrylic acids and from about 10 to about 85 by weight of an amide comonomer selected from the group con-sisting of acrylamide and methacrylamide.

10. The interpolymer of Claim 1 in which said cross-linking agent is selected from the group consisting of the compounds defined by structural formulas I, II and III below:

I
wherein R is hydrogen or C1 to C4 alkyl; R3 is C1 to C6 alkylene; and n is an integer from 1 to 3;

II
wherein R is hydrogen or C1 to C4 alkyl; and R3 is C1 to C6 alkylene; and III wherein R i5 hydrogen or Cl to C4 alkyl; and Y s selected from the group consistlng of and wherein R4 is selected from the group consisting of hydrogen and C1 to C5 alkyl; and each R5 is selected from the group consisting of hydrogen and -CH2OH, provided, however, that at least one R5 is -CH2OH.

11. The interpolymer of Claim 10 in which the crosslink-ing agent is N,N'-methylenebisacrylamlde,

12. The interpolymer of Claim 9 wherein said crosslink-ing agent is N,N'-methylenebisacrylamide, and is present in an amount of from about 0.05 to about 1% by welght, based on the weight of the monomer mixture.

13. A process for preparing the random interpolymer of Claim 1 comprising the steps of admixing monomers comprising (A) (1) from about 10 to about 90% by weight of said mixture of a first monomer which is an ester of an .alpha.,.beta.-olefinically unsaturated carboxylic acid and a monohydric or polyhydric alcohol having a terminal quaternary ammonium group and (2), correspondingly, from about 90 to about 10% by weight of said mixture of at least one .alpha.,.beta.-olefinically unsaturated comonomer capable of being dispersed in aqueous media, in the presence of (B) at least 0.02% by weight, based on the weight of said mixture, of a cross-linking agent com-prising a difunctional monomer which is capable of being dispersed or dissolved in aqueous media and is an ester or amide of an a,.beta.-olefinIcally unsaturated carboxylic acid; said comoner (2) comprising (a) at least 10% by weight of said mixture of monomers of an acid comonomer, or (b) at least 20% by weight of said mixture of monomers of an amide comonomer, or (c) at least 10% by weight of said mixture Or monomers of a combination of acid and amide co-monomers, said combination containing at least 5% by weight of said mixture of an acid monomer; and about 9 to 20 parts by weight of aqueous medium per part of the total monomers;
and initiating reaction by means of a free radical initiator,

14, The process of Claim 13 in which the aqueous medium comprises at least 40% by weight of water and up to about 60% by weight of a water miscible organic solvent

15. The process of Claim 14 in which said water miscible solvent 18 methanol

16. The process of Claim 13 in which the free radical initiator is a chemical initiator.

17. The process of Claim 16 in which said chemical initiator comprises ammonium persulfate.

18. The process of Claim 17 in which said ammonium per-sulfate content is from about 0.5 to about l% by weight based on the weight of the monomer mixture.

19. The process of Claim 17 in which the polymerization is carried out at a temperature of from about 55°C to about 75°C.

20. The interpolymer of Claim 1 in the form of an aqueous colloidal suspension.

21. The interpolymer of Claim 1 in the form of a film.

22. The interpolymer of Claim 1 in the form of a gel.

23. The interpolymer of Claim 1 in the form of hydro-philic particles.