WO1991014716A1

WO1991014716A1 - Copolymers of maleic anhydride and acrylic acid useful in denture adhesives

Info

Publication number: WO1991014716A1
Application number: PCT/US1991/001455
Authority: WO
Inventors: Mohammed Tazi; Robert B. Login; Krystyna Plochocka; Rama K. Haldar; Balgopal Gangadharan; William E. Prosise
Original assignee: Isp Investments Inc.
Priority date: 1990-03-29
Filing date: 1991-03-04
Publication date: 1991-10-03
Also published as: EP0521934A4; AU640474B2; JPH07500357A; EP0521934A1; CA2079322A1; AU7486491A

Abstract

Slurry copolymerization of maleic anhydride with (meth)acrylic acid and, optionally, with C1-C4 alkyl vinyl ether in a cosolvent system of cyclohexane and ethyl acetate yields a pumpable slurry, from which uniform, fine, white powders having a predetermined weight average molecular weight of about 10,000 to one million, preferably about 30,000 to 400,000 are obtained. The copolymers are useful in a denture adhesive composition which is a mixed partial salt of the copolymer.

Description

COPOLYMERS OF MALEIC ANHYDRIDE AND ACRYLIC ACID USE_FUL IN DENTURE ADHESIVES

The prior art has not been entirely successful in providing copolymers of maleic anhydride and acrylic acid as (1) a pumpable slurry of the copoly er in a non-toxic solvent; (2) without requiring an excessive degree of agitation/ (3) from which predetermined high molecular weight copolymers can be readily obtained; (4) in the form of uniform, fine white powders; (5) having substantially no residual monomers; (6) in a process that does not require a protective colloid; (7) wherein the solvent can be easily recycled; and which copolymers can be used effectively in denture adhesive compositions.

Accordingly, the slurry polymerization process of the present invention provides uniform, fine white copolymer powders of maleic anhydride and acrylic acid or methacrylic acid from the copolymerization of predetermined amounts of maleic anhydride and acrylic acid or methacrylic acid in a cosolvent system comprising ethyl acetate and an aliphatic or cycloaliphatic hydrocarbon. The copolymer powders of the invention are particularly useful in denture adhesive compositions.

In the process of the invention, from about 10 to 70 mole percent, preferably 20 to 60 mole percent, of maleic anhydride, and 30 to 90 mole percent, preferably 20 to 80 mole percent by weight, of acrylic acid or methacrylic acid, optionally, with up to about 25 mole percent of a C- -C^ alkyl vinyl ether, preferably methyl vinyl ether, is copolymerized in the cosolvent system of the invention, in the presence of a polymerization initiator, under suitable temperatures and reaction time conditions. The sequence of addition of these monomers further assures that the polymerization mixture remains in a slurry form in the cosolvent system of the invention at all times during the reaction.

The cosolvent system of the invention comprises about 5 to 80 percent by weight of ethyl acetate and about 20 to 95 percent by weight of an aliphatic or cycloaliphatic hydrocarbon having a boiling point of at least 10°C. above the reaction temperature. Suitable aliphatic and cycloaliphatic hydrocarbons for use herein include hexane, heptane, octane, cyclohexane and the like. Cyclohexane is preferred. Most preferably, the cosolvent system of the invention comprises about 10 to 75 percent by weight of ethyl acetate and about 25 to 90 percent by weight of the aliphatic or cycloaliphatic hydrocarbon. Most preferably, the cosolvent system comprises about 25 percent by weight of ethyl acetate and about 75 percent by weight of cyclohexane.

The cosolvent system of the invention has a synergistic effect on the polymerization as compared to each solvent alone. Particularly, ethyl acetate itself is unsuitable solvent for the polymerization because the copolymer is soluble in this solvent. Furthermore, the molecular weight of the copolymer produced in ethyl acetate is very low, and semi-solids product is produced. Similarly, cyclohexane alone is unsuitable because it produces insoluble precipitates which are not readily pumpable. Furthermore, polymer powders isolated from cyclohexane are nonunifor and contains aggregated particles. In contrast, a cosolvent system of ethyl acetate and cyclohexane provides a pumpable slurry of the copolymer without requiring excessive agitation or a protective colloid. In addition, this cosolvent system can remove any trace of residual maleic anhydride monomer from the copolymer product. The use of predetermined ratios of each solvent in the cosolvent will provide copolymers having varying molecular weights. Consequently, the amount of ethyl acetate included in the cosolvent system of the invention must be carefully controlled because ethyl acetate has the effect of reducing the molecular weight of the copolymer and of solubilizing the copolymer. For example, the use of 66 percent by weight ethyl acetate in the cosolvent system will produce a polymer having a weight average molecular weight of about 30,000, while the use of 10 percent by weight ethyl acetate will produce a copolymer with a weight average molecular weight of about 400,000, under similar reaction conditions.

A cosolvent system comprising ethyl acetate and cyclohexane is particularly advantageous because their boiling points are very close (76°C. and 80°C, respectively) , which enables the cosolvent system to be recycled easily by distillation. Mixtures of solvents with boiling points far apart are not favored because they would become enriched in the lower boiling solvent upon recycle distillation.

The boiling points of the solvents used herein usually are at least 10°, and preferably 20° or more, above the operating polymerization temperature, (preferably about 65°C). This difference helps to moderate the effect of the exothermic polymerization reaction upon the solvent and obviates the need for a pressurized reactor.

The total monomer content in the cosolvent system of the invention usually is about 10 to 30 percent by weight, preferably about 20 to 25 percent by weight. In this concentration, the slurry remains pumpable under ordinary agitation of reactants at a reaction temperature between about 50° to 150°C. The polymerization initiator for the process herein preferably is selected from peroxy esters, such as t-butylperoxy pivalate or t-amylperoxy pivalate, or dialkyl peroxides, such as di-decanoyl peroxide, although other initiators known in the art for free radical polymerization may be used as well.

In operation of the polymerization process of the invention, a solution comprising maleic anhydride reactant, initiator and cosolvent is precharged in a suitable reactor, and acrylic acid or methacrylic acid is fed continuously into the precharged solution, which is maintained at about 60° to 80°C, over a period of about 0.3 to 10 hours. The optional alkyl vinyl ether monomer is added after the acrylic acid reactant has been added. The polymerization mixture then is held at the reaction temperatures for an additional 15 to 90 minutes following completion of addition of all monomers. Several initiator boosters can be introduced during or after feeding of comonomers.

The invention will now be described with reference to the following specific working examples.

EXAMPLE 1

COPOLYMERIZATION OF ACRYLIC ACID AND MALEIC ACID IN ETHYL ACETATE-CYCLOHEXANE COSOLVENT

A 1-liter resin kettle was equipped with a stirrer, reflux condenser, N inlet tube and an inlet closed with a rubber septum for introduction of initiator. The kettle was charged with 49.0 g. (0.50 mole) of maleic anhydride (MA) , 275 g. (75 wt. %) of ethyl acetate (EA) and 92 g. (25 wt. %) of cyclohexane (CH) . Agitation of the mixture was begun and the system was purged by bubbling in N₂ for 30 minutes, during which time maleic anhydride dissolved completely. The reaction mixture was then warmed to 65°C. and 0.3 ml of Lupersol 11 (Pennwalt) was injected through the septum to initiate polymerization. Simultaneously, dropwise addition of 73.0 g. (1.0 mole) of acrylic acid (AA) was begun and continued over a period of 3 hours. Lupersol 11 was added at a rate of 0.3 ml of initiator for each 30 minutes of AA addition during this period. After completion of all additions, the resulting mixture was maintained at 65°C. for 2 hours.

After 15 minutes the reaction mixture became whitish, and, thereafter, a uniformly thick, creamy slurry was formed which was pumped out of the kettle into a filtration unit. There the slurry was filtered and the polymer product was dried for about 12 hours at 65°C. in a forced air oven. The polymer product was a uniform, fine white powder, having a weight average molecular weight (as determined by GPC) of about 47,000. A sample of 1 g. of the polymer dissolved in 5 ml acetone was treated with triphenyl phosphine and it indicated that the conversion of maleic anhydride into polymer was complete.

EXAMPLES 2-11

The procedure of Example 1 was followed to provide copolymers of varying compositions and molecular weights. The results of Examples 1-11 are shown in Table 1 below. In Examples 9 and 10 therein, a third monomer, either butyl vinyl ether or methyl vinyl ether, was introduced after addition of acrylic acid was completed. TABLE 1

Weight Average

Monomers Solvent Molecular Wt,

Ex. No. AA MA Other EA CH Initiator** Temp. Mw

(mole %) ( t %) (% by wt) (°C) (X 10^)

1 66 33 75 25 L-ll 0.3 65 47 2 66 33 25 75 L-ll 0.4 65 145 3 50 50 25 75 L-ll 0.4 65 79 4 57 43 50 50 L-ll 3.2 65 19 5 57 43 25 75 L-ll 0.8 65 59 6 57 43 25 75 Dec-F 0.4 75 202 I σ, 7 57 43 25 75 L-PMS 0.4 75 110 I 8 80 20 10 90 L-ll; 0.25 65 310

BVE*

45 33 22 50 50 L-ll; 3.2 65 16 MVE*

10 67 17 16 10 90 L-ll; 0.4 60 337 11 80 20 - 100 L-ll; 0.0 65 345

* BVE - butyl vinyl ether; * MVE - methyl vinyl ether

** L-ll - t-butyl perpivalate, L-PMS - t-butyl peroctoate, Dec-F - decanoyl peroxide

COMPARATIVE EXAMPLES 12-16

The procedure of Example 1 was followed using different solvents. The following results were obtained and are shown in Table 2 below. It is seen therein that single solvents, including ethyl acetate, cyclohexane, toluene, t-methyl butyl ether and xylene, produced nonuniform slurries and polymer powders, which were difficult to process and much less advantageous products than those made in the cosolvent system of the present invention.

TABLE 2

Monomers

Ex. No. AA MA Solvent Initiator Temp. Appearance of

(mole %) (°C.) Slurry Polymer

12 80 20 Toluene L-ll, 0.34 60

13 80 20 Methyl- L-ll, 0.25 55 t-butyl ether

14 66 33 Cyclohexane L-ll, 0.20 60

15 57 43 Ethyl L-ll, 3.2 65 Dark red solution and acetate a sticky semi-solid

16 13 87 Xylene L-ll, 2.1 100 Red soln. Red glass, and very hard semisolid

The FIGURE is a graph of adhesive force in lbs. vs. number of cycles during Instron testing of adhesive compositions of the invention.

There is provided a denture adhesive which is a mixed partial salt of the copolymer of maleic anhydride and acrylic acid (or methacrylic acid) , optionally including a C₁-C₄ alkyl vinyl ether, having a weight average molecular weight of about 30,000 to 400,000, preferably about 50,000 to 350,000.

The copolymer suitably comprises about 10 to 70 mole percent, preferably 20 to 60 mole percent, of maleic anhydride, about 30 to 90 mole percent, preferably 40 to 80 percent, of acrylic acid (or methacrylic acid) , and 0 to 25 mole percent of a C₁-C₄ alkyl vinyl ether.

The partial mixed salts include calcium/sodium salts wherein the equivalent ratio of calcium to sodium cations may range from 2:1 to 10:1, preferably between 3:1 to 7:1, and the degree of neutralization of initial carboxyl groups is from 0.5 to 0.95, preferably from 0.7 to 0.9.

The adhesive copolymer of this invention is converted to its mixed partial salt, which preferably is employed as a dry powder having a particle size of less than 250 μ , and, more desirably, a particle size of from about 5 to about 200 μ.

Denture adhesive compositions are provided herein by incorporating dry powders of the above adhesive copolymer as mixed salts into a liquid base carrier by mixing until a homogeneous cream paste suspension or collodial dispersion is obtained, usually within a period of from about 20 minutes to about 5 hours. The resulting composition contains an effective adhesive amount of the adhesive copolymer mixed salt, generally between about 5 and about 50 wt. %, and preferably between about 10 and about 35 wt. %, of the final composition. Suitable mixed partial salts herein include the calcium/sodium mixed partial salts which are prepared by reacting the copolymer with suitable bases. Preferably the equivalent ratio of calcium cations to sodium cations in the mixed partial salts may range from 2:1 to 10:1 and most preferably is between 3:1 and 7:1 (on a mole ratio basis, the range of calcium to sodium cations is from 1:1 to 5:1, most preferably from 1.5:1 to 3.5:1). The sum total of cations in the mixed partial salt should be sufficient to give a degree of neutralization of from 0.5 to 0.95 and preferably 0.7 to 0.9 of the total initial carboxyl groups in the copolymer. In the determination of the total initial carboxyl groups in the copolymer, the anhydride radical is considered as containing 2 initial carboxyl groups.

The base carrier portion of the composition generally includes a water soluble or partially water soluble hydrophilic carrier which is capable of swelling upon exposure to moisture to form a mucilaginous mass. Such carrier materials include natural and synthetic gums, viscous liquids, gels and powders. Among those suitably employed as base carriers in the composition are karaya gum, gelatine, gum tragacanth, gum acacia, gum shiraz, algin, sodium alginate, tragacanth, methyl cellulose, a mixture of petrolatum and mineral oil, glycerine, polyvinylpyrrolidone, K-30 and K-90, carboxymethyl cellulose, ethylene oxide polymers, of which the preferred is a mixture of petrolatum and mineral oil in a ratio of 40:60-60:40.

The adhesive copolymer of the invention can be employed as the sole adhesive component in the denture adhesive composition or it can be used as a coadhesive with another adhesive material. Such adhesive additive, if present, will generally comprise about 5-20%.by weight of the composition. Suitable adhesive additives include natural or synthetic polymers such as cellulose, karaya gum, gum tragacanth, gum acacia, carboxymethyl cellulose or salt thereof, polymethacrylate, polyvinylpyrrolidone, polyvinyl acetate, or any mixture of the above.

The compositions of the invention are particularly useful for affixing dentures and can also be used in surgical procedures which require temporary displacement of tissue. As a denture adhesive, the thermal stability of the present composition, over a temperature range, which is at least sufficient to embrace all conditions encountered by living tissue, e.g. 5°-50°C., is particularly desirable. Because of their increased adhesive strength and thermal stability, the composition retains its adhesive properties over a long period of time, i.e. up to 24 hours.

The following illustrates a few representative formulations into which the adhesive copolymer can be added in effective amounts up to about 50%.

Cream Denture Adhesive Composition wt. %

Mineral Oil

Petrolatum

Sodium carboxymethyl cellulose

(adhesive additive) Colorant Flavoring Agent Material of Invention

Paste Ostomy Adhesive Composition

Mineral oil (heavy)

Glycerine

Polyvinylpyrrolidone

Carboxymethyl cellulose

Tosylate of quat. amino-N-propylpyrrolidone

Matrial of Invention

Denture Adhesive Powder Composition

Gum tragacanth 40

Gum acacia 20

Spearmint oil 0.05

Material of Invention 39.05

PREPARATION OF DENTURE ADHESIVE COMPOSITIONS

The copolymer was converted to its mixed, partial salts as follows. 25 g. of the copolymer was charged into a 250 ml round bottom, 3-necked flask together with 90 g. of isopropyl alcohol. The contents were agitated to make a slurry and 9.59 g. of calcium hydroxide was added slowly with agitation during 15 minutes. Then 2.08 g. of sodium hydroxide dissolved in 38 g. of water was added with agitation. The mixture was heated at 45°C. with agitation for 1-1/2 hours. The pH of the liquid phase was 4.89. The mixture was filtered and the precipitate was dried in a vacuum oven overnight at 65°C.

PREPARATION OF ADHESIVE COMPOSITIONS FOR INSTRON TESTING

The dry, mixed salt of the MA/AA copolymer was milled to pass through a number 60 mesh sieve (250 μ) and the resulting powder was then dispersed at a temperature of 55-65°C. , followed by cooling to 20-25°C. , into a petrolatum base using mechanical stirring. The ratio of copolymer to. base by weight was 1:2. The resulting cream dispersion was collected as the desired adhesive composition.

Adhesive compositions of the dry, mixed salt of the copolymers, and GANTREZ MS-955, which is a commercial mixed salt copolymer of maleic anhydride and methyl vinyl ether, also were prepared for testing in the same manner as described above. 2 g. samples of each of the above prepared compositions were evaluated for adhesion characteristics by Instron testing according to the following procedure:

In the first step, the upper and lower plates of the Instron apparatus were brought together to obtain a zero position. The upper plate was then raised 0.06 inch and the upper cycle limit on the Instron indicator is set at this point. The upper plate was then lowered and the lower cycle limit was set. In its lowest position, the upper plate was distanced 0.03 inch above the lower plate. With these Instron settings determined, the upper plate was then raised and 2 g. of the test sample was uniformly spread over the surface of the lower plate in a 1/16 to 1/8 inch thickness; thereafter simulated salivary fluid was applied over the sample so that it was barely covere .

The Instron crosshead was cycled between the previously set limits at a crosshead speed of 0.2 in./min. The Instron chart was set in the continuous mode at a speed of 2 in./min. to record the compression and adhesion force for each cycle, 5 to 100 cycles.

At the end of 100 cycles, the motion of the upper plate was halted and raised high enough to clean the surface before the next adhesive test.

Each recording was analyzed and the adhesional forces (lbs.) for the 1st, 5th, 10th, 20th, 40th lOOth cycles were recorded and then plotted graphically.

The results of this study are shown in the FIGURE. This data show significantly better initial stick strength and long term adhesion for adhesive formulations containing the copolymer compositions of the invention as compared to a related copolymer composition (MS-955) useful as a denture adhesive.

Claims

WHAT IS CLAIMED IS:

1. Copolymers of maleic anhydride and acrylic acid or methacrylic acid, optionally including a C₁-C₄ alkyl vinyl ether, having a predetermined weight average molecular weight of about 10,000 to one million suitable for denture adhesives made by: copolymerizing about 10 to 70 mole percent of maleic anhydride, about 30 to 90 mole percent of acrylic acid or methacrylic acid, and from 0 to 25 mole percent of a C.^-^ alkyl vinyl ether, in the presence of a free radical initiator, at about 50° to 150°C. , in a cosolvent system comprising about 5 to 80 percent by weight of ethyl acetate and about 20 to 95 percent by weight of an aliphatic or cycloaliphatic hydrocarbon having a boiling point at least 10°C. above the reaction temperature, to produce a pumpable slurry of said copolymer in said cosolvent system, and recovering the copolymer therefrom as a uniform, fine powder having substantially no residual maleic anhydride.

2. A denture adhesive composition containing the copolymer of claim 1.

3. A denture adhesive according to claim 2 which comprises a mixed, partial salt of the copolymer of claim 1.