Fine and Uniform Methyl Vinyl Ether-Maleic Acid Inorganic Salt Copolymers and Their Use in Oral Care and Pharmaceutical Applications

Abstract

The invention relates to fine and uniform copolymer powders of partial mixed metal salts of lower alkyl vinyl ether-maleic acid copolymers having a defined particle size distribution. In particular; it relates to powders that are suitably used in the areas of oral care and pharmaceuticals and to methods for preparing the powders. Provided is a composition of powders of partial mixed metal salts of lower alkyl vinyl ether-maleic acid copolymers having: (i) a Dv50 of less than or equal to 25 microns; a Dv90 of less than or equal to 50 microns; and (ii) a particle uniformity reflected by a Dv90/Dv10 ratio of less than or equal to 10.

Claims

1. A composition of powders of partial mixed metal salts of lower alkyl vinyl ether-maleic acid copolymers having: (i) a median particle size by volume (Dv50) of less than or equal to 25 microns; a maximum particle diameter below which 90% of the sample volume exists (Dv90) of less than or equal to 50 microns; and (ii) a particle uniformity reflected by a ratio between the maximum particle diameter below which 90% of the sample volume exists and the maximum particle diameter below which 10% of the sample volume exists (Dv90/Dv10 ratio) of less than or equal to 10, preferably wherein the Dv90/Dv10 ratio is less than or equal to 6.

2. The composition of claim 1, having a Dv50 of less than 15 microns, a Dv90 of less than 25 microns and a Dv90/Dv10 ratio of less than 6.

3. The composition of claim 1, in which the oversize fraction equal to or less than 1% by volume is not greater than 75 microns.

4. The composition of claim 1, wherein from about 10 to about 90 mole % of the carboxylic units in the polymer are converted to a mixture of metal salts.

5. The composition of claim 4 wherein the metal salt is selected from the group consisting of sodium, calcium, strontium, zinc, magnesium, iron and potassium.

6. The composition of claim 5, wherein the partial mixed metal salts are sodium and calcium salts.

7. The composition of claim 5, wherein the partial mixed metal salts are calcium and zinc salts.

8. The composition of claim 1 wherein said alkyl vinyl ether-maleic acid copolymers are of the general Formula I ##STR00003## wherein R is C.sub.1 to C.sub.4 alkyl group, and the carboxylic acid functionality being a mixture of free acid and 10-90 mole % cationic salt function.

9. The composition of claim 8, wherein said C1-C4 alkyl vinyl ether is methyl vinyl ether.

10. The composition of claim 9 wherein the copolymer has a 5% aqueous solution viscosity of greater than 60 cps.

11. A personal care, oral care, health care or pharmaceutical product comprising the composition of powders of claim 1.

12. An oral care product of claim 11 being a denture adhesive.

13. The denture adhesive of claim 12, comprising partial calcium and sodium mixed salt of methyl vinyl ether-maleic acid copolymer.

14. The denture adhesive of claim 13, that contains 10-60 weight percent of the calcium and sodium mixed salt of methyl vinyl ether-maleic acid copolymer.

15. The denture adhesive of claim 12 that uses the partial calcium and zinc mixed salt of methyl vinyl ether-maleic acid copolymer.

16. A health care product of claim 11 being a wound dressing.

17. A health care product of claim 11, being a mucosal adhesive or bioadhesive.

18. A method of producing a composition of powders of claim 1 comprising the steps of: (i) copolymerizing the lower alkyl vinyl ether with maleic anhydride in a suitable solvent; (ii) hydrolyzing the resultant maleic anhydride copolymer and reacting with metal cations either in the form of a base or a salt or an oxide in an aqueous medium to give the partial mixed metal salt; (iii) drying the mixed metal salt copolymer and (iv) milling the mixed metal salt copolymer to obtain particles.

19. The method of claim 18, wherein the milling is performed by jet-milling.

20. The method of claim 18, wherein the copolymer is mixed with at least one co-ingredient prior to drying or milling and then milled together to give the final powder product.

21. The method of claim 20, wherein the co-ingredients include one or more of carboxymethylcellulose and its sodium salt, polyvinylpyrrolidone, alginates, polyacrylic acid based copolymers, polymethacrylate based copolymers, poly(ethylene oxide), silicon dioxide, natural gums, cellulose derivatives, saccharide derivatives, synthetic polymers or mixtures thereof.

22. A personal care, oral care, health care or pharmaceutical product comprising the composition of powders obtained by the method according to claim 18.

Description

LEGEND TO THE FIGURES

[0042] FIG. 1: Tensile tests run at 37 C. for various PVM/MA-Ca/Na partial mixed salts having varying particle sizes. For details, see example 1.

[0043] FIG. 2: Particle size plot for PVM/MA-Ca/Na partial mixed salt of invention. For details, see example 2.

[0044] FIG. 3: Particle size plot for Gantrez MS-955 (commercial product). For details, see example 2.

[0045] FIG. 4: Adhesive testing comparison at 37 C. of PVM/MA-Ca/Na of the invention and Gantrez MS-955. For details, see example 2.

[0046] FIG. 5: Comparison of PVM/MA-Ca/Na of the invention and Gantrez MS-955 adhesion values at varying hydration times at 37 C. For details, see example 2.

[0047] FIG. 6: Transmittance Spectra FTIR comparison of PVM/MA-Ca/Na Invention and Gantrez MS-955. For details, see example 2.

EXPERIMENTAL SECTION

Example 1: The Effect of Particle Size on Hydration Rates and Adhesion Values

[0048] A batch of methyl vinyl ether-maleic acid partial calcium/sodium mixed salt (PVM/MA-Ca/Na) was prepared using polymerization techniques well known in the art. The resultant viscous solution was dried and the powder milled in a conventional impact mill. The resultant fine powder was then divided into five particle size regimes by sieving techniques. The following table 1 gives an overview of the resultant particle size fractions.

TABLE-US-00001 TABLE 1 Particle size PVM/MA-Ca/Na fraction 1 <15 microns Particle size PVM/MA-Ca/Na fraction 2 15-25 microns Particle size PVM/MA-Ca/Na fraction 3 25-55 microns Particle size PVM/MA-Ca/Na fraction 4 55-105 microns Particle size PVM/MA-Ca/Na fraction 5 105-300 microns

[0049] One gram of each of the above PVM/MA-Ca/Na fractions was quickly dispersed in 4 g distilled water and placed between two polymethylmethacrylate testing plates and placed in a tensile test machine at 37 C. The testing conditions were used to mimic the oral cavity. The resultant adhesion tests for the various powder sizes are summarized in FIG. 1.

[0050] As shown in FIG. 1, the particle size of the PVM/MA-Ca/Na copolymer has a drastic effect on the hydration rate of the particles and the formation of the resultant continuous structure. What is interesting to note is that the uniformity of the adhesion buildup also seems to be improved as compared to the larger particle size curves (i.e. the curves are more smooth).

[0051] It should also be pointed out that the maximum adhesion level of about 116 N is the same for all particles size fractions.

[0052] The following table 2 summarizes the time needed to reach maximum adhesion for the various sized PVM/MA-Ca/Na particles.

TABLE-US-00002 TABLE 2 PVM/MA-Ca/Na particle Hydratation time Hydratation rate size (m) (min) (N/min) <15 1 116.34 15~25 2.75 59.93 25~55 8 22.36 55~105 30 5.54 105~300 69 2.41

[0053] It is clear that hydratation of particles of about 50 microns or less occurs quickly and uniformly. Though the higher particle size materials eventually reach a similar adhesion maximum of about 116 N, the process takes much longer. In the case of denture adhesives, this is undesirable because the denture can dislodge with chewing, negatively effecting the adhesives strength and long-term durability.

[0054] In addition, denture adhesive formulations are usually a mixture of adhesive polymers. It is essential that the various polymer ingredients hydrate at similar rates in order that the hydrated gelatinous mass forms uniformly to obtain maximum adhesion properties. Adhesive components that hydrate at vastly different rates result in defects in the formation of the continuous gelatinous mass/film. These defects act as weak points in the hydrating structure resulting in inferior adhesion properties, which limits the maximum adhesion obtained and adhesion durability of the formulation.

Example 2: Comparison Studies of Invention and Existing Commercial Product

[0055] A large-scale batch of PVM/MA-Ca/Na copolymer was produced, dried and jet-milled to give the fine particle size dimensions outlined in this invention. This material was compared to the commercial PVM/MA-Ca/Na copolymer, Gantrez MS-955 manufactured by Ashland Inc. and used as a base ingredient in many denture adhesive formulations.

[0056] Particle size measurements were conducted on both powders using a Malvern Mastersizer 3000 particle size analyzer. The resultant particle size plots for the PVM/MA-Ca/Na of the invention and Gantrez MS-955 are shown in FIGS. 2 and 3, respectively. The following table 3 is a summary of the particle size values for the two polymer materials.

TABLE-US-00003 TABLE 3 Maximum Dv10.sup.1 Dv50.sup.2 Dv90.sup.3 Dv90/Dv10 particle Polymer (m) (m) (m) ratio size (m) PVM/MA- 4.4 8.0 13.5 3.1 25 Ca/Na invention Gantrez 12.0 41.1 86.3 7.2 250 MS-955 .sup.1The maximum particle size diameter below which 10% of the sample volume exists .sup.2The maximum particle size diameter below which 50% of the sample volume exists also called median particle size by volume .sup.3The maximum particle size diameter below which 90% of the sample volume exists

[0057] The two powders were formulated as 20% solids in purified water and allowed to completely hydrate. Once hydrated, 4 g of each hydrated mass was placed between two polymethylmethacrylate testing plates and placed in a tensile test machine and submerged in artificial saliva at 37 C. The adhesion test was then conducted at various time periods mimicking the oral cavity and the effect of chewing. The results are shown in FIG. 4.

[0058] As can be seen from the graph, the adhesion profile for the PVM/MA-Ca/Na invention product shows significantly improved maximum adhesion and longevity of adhesion as compared to the commercial Gantrez MS-955 product. The ultra-fine and uniform particle distribution of the invention show a vastly superior adhesion profile that is especially desirable for denture adhesive applications.

[0059] The two products were then compared by a second adhesion test conducted in the same manner as earlier, but the adhesion measurements were taken at various hydration times. These results are shown in FIG. 5.

[0060] As can be seen from FIG. 5, the fine particle PVM/MA-Ca/Na invention shows significantly improved adhesion values at short hydration times as compared to the commercial Gantrez MS-955. The fine powder of the invention hydrates readily and uniformly generating a continuous adhesive matrix that quickly generates the desired adhesion values. This is especially important for applications in which the powder should generate an adhesive matrix within a short time period such as is the case with denture adhesives.

[0061] Table 4 summarizes various particles size details for multiple batches of PVM/MA-Ca/Na of the invention. Batches 1-4 of the PVM/MA-Ca/Na materials possessed similar adhesion profiles to batch 1, which was the original material of the invention identified in FIG. 4.

TABLE-US-00004 TABLE 4 PVM/MA-Ca/Na Dv10 Dv50 Dv90 Dv90/Dv10 invention (m) (m) (m) ratio Batch 1 4.4 8.0 13.5 3.1 Batch 2 2.5 7.0 12.8 5.1 Batch 3 2.1 6.7 12.7 6.0 Batch 4 1.3 4.3 12.0 9.2

[0062] In order to rule out the possibility that the differences in adhesion profiles was not due to a difference in the chemical composition of the polymers, the two polymer powders were compared by FTIR analysis as shown in FIG. 6. As can be seen in the FTIR spectrograms of the individual polymers, the individual spectrograms are almost identical which indicates that the two polymers are of similar chemical composition.