Aqueous dispersions of polymers cross-linked with metallic ions

Abstract: A composition which is a cross-linked aqueous dispersion characterised in that it comprises: a water-dissipatable polymer in an amount of from 18 to 30%, by weight, based on the total weight of the composition; water in an amount of from 67 to 30%, by weight, based on the total weight of the composition; a source of multivalent metallic ions in an amount of from 0.1 to 5%, by weight, based on the total weight of the composition; and a humectant in an amount of from 0.1 to 40%, by weight, based on the total weight of the composition is disclosed. Such may be in the form of an emulsion which may additionally comprise: one or more emollient oils in an amount of from 0.1 to 25%, by weight, based on the total weight of the composition; and an emulsifier in an amount of from 0.01 to 5%, by weight, based on the total weight of the composition. Such compositions may be used in the production of cross-linked casts.

Description: This invention relates generally to cross-linking an aqueous dispersion of polyester or polyesteramide with the water soluble multivalent metallic ions. The aqueous dispersion of polyester or polyesteramides containing ether and sulfonate groups contain also humectants and optionally emollients which when cross-linked with metallic ions and poured into any desirable shaped mold form a clear or opaque cast of therapeutic functional nature. This invention also relates to the process of cross-linking the polyester or polyesteramide aqueous dispersion with metallic ions. Many compositions used for skin treatment contain emollients or humectants in lotion, cream or gel form. Such products are applied by evenly spreading the product on the skin. Upon loss of water, the product dries providing humectants and emollients to the epidermis. Water soluble gels that form protective films of various types are known. For example, U.S. Patent No. 4,393,048 discloses a water soluble hydrogel of alkali metal alginate and glycerine that dries to a non-toxic, pliable protective film. U.S. Patent No. 3,949,742 discloses a transparent medical dressing which performs as a synthetic film over skin wounds. Water soluble polyesters, for example U.S. Patent 4,502,976, are used to form cross-linked bioerodible hydrogels. The hydrogels, suitable for carrying water soluble therapeutic macromolecules and for implantation in living mammals, are produced by a complex polymerization process without using water soluble metallic ions. US Patent No 3,879,168 to Franklin discloses a surgical dressing made of partially soluble alginic materials in the form of gauze or wool characterized by a pH of 4 to 7 and a calcium content of 2-6% by weight comprised of a laminate of a thin layer of non-porous segmented polyurethane sewn to foam. U.S. Patent Nos. 3,734,874, 4,233,196, 4,335,220, 4,304,900, 4,304,901, and 4,300,580 describe water-dissipatable, meltable polyesters that are useful as adhesives, coating materials, films, packaging materials and other products that can be dissolved, dispersed or otherwise dissipated in water or aqueous solutions. These polyesters, however, are not cross-linked using metallic ions and cast into shapes to entrap water, humectants and/or emollients within the hardened cast. There may also be mentioned EP-A-78559 relating to aqueous copolyester dispersions suitable for the subbing of polyester film without use of organic solvents, and EP-A-61701, which concerns solid, entrapped emollients-moisturizer compositions. As explained in a technical publication from Eastman, the water dispersability of the AQ polymer is largely attributed to the presence of ionic substituents attached to the polymer chain. A simplified representation of the polymer is shown below: wherein "A" is an aromatic dicarboxylic acid moiety some of which have sodiosulfo (-SO 3 - , Na + ) substituents, "G" is an aliphatic or cycloaliphatic glycol residue and "OH" is a hydroxy end group. It is the sodio sulfo group which impart the water dispersability to the polymer. To cross-link with multivalent metallic ions and obtain the moldable shapes of this invention, the multivalent metal salts must be added and mixed according to the teaching of this invention. Departing from this process results in non-compatible mixtures of non-commercial properties. Eastman technical publications teach the synthesis and preferred methods for cross-linking water dispersible polyesters and polyesteramides with other resins through high temperature curing process and subsequent drying of the cured resins, but specifically warn against the use of the heavy metal salts included in this invention as being not compatible with the polymers used in this invention. It is therefore an object of the present invention to provide novel cross-linked polyester polymers with humectants and optionally emollients by using water soluble metallic ions. A further object of the present invention is to provide a convenient process of cross-linking the humectant and emollients with the polyester polymer in the presence of water soluble metallic ions. A further object of this invention is to provide such casted patches containing water soluble medicaments and oil soluble medicaments. Such patches can be used as controlled release transdermal delivery patches. It has been found that the objectives of this invention may be realized by forming a cast containing humectants and/or emollient oils, water, water dissipatable polyesters, and by cross-linking with water soluble multivalent metal ions. Such compositions when poured into a mold harden without pressure and have utility in wound treatment, skin treatment and controlled release drug and fragrance patches. The present invention provides a composition which is a cross-linked aqueous dispersion obtainable by mixing: a water-dissipatable ether and sulphonate group-containing polyester or polyesteramide in an amount of from 18 to 30%; water in an amount of from 30 to 80%; and a humectant in an amount of from 0.1 to 40%; and then crosslinking the polyester or polyesteramide by adding a source of water-soluble multivalent metallic ions in an amount of from 0.1 to 5%, the percentages being by weight, based on the total weight of the composition. Optionally the composition also contains fragrance oils, medical agents or color. Such a composition can also be in the form of a cross-linked emulsion, and may additionally comprise: one or more emollient oils in an amount of from 0.1 to 25%; and an emulsifier in an amount of from 0.01 to 5%; the percentages being by weight, based on the total weight of the composition. The present invention further provides a method of producing a cross-linked cast characterised in that it comprises: (a) forming such a composition; and (b) pouring the composition into a mold whereby there is obtained a cross-linked cast. Polymers useful in the present invention must be capable of cross-linking with water soluble metal ions, and, when poured in liquid form into a mold hardening without pressure to form a cast of any desirable shape. Polymers suitable for use in this invention include the water-dissipatable polyester and polyesteramides described in U.S. Patent No. 3,734,874 to Kibler, et al., U.S. Patent No. 4,233,196 to Sublet and U.S. Patent No. 4,304,901 to O'Neill, et al. A preferred water dissipatable polyester is commercially available on Eastman AQ 55S polymers. Examples of organic and inorganic sources of the water-soluble multivalent metal ions used to cross-link the polymers in this invention include magnesium chloride, zinc acetate, zinc gluconate, and magnesium acetate. The preferred sources of multivalent metal ions are zinc gluconate and magnesium chloride. In forming the clear cross-linked casts of this invention, water by itself or in combination with humectant such as propylene glycol and glycerine may be used. In forming cross-linked, opaque emulsion casts of this invention any emollient oil may be used. Emollients useful in this invention include hydrocarbon oils and semi-solid hydrocarbons, lanolin and derivatives, silicone oils and esters commonly used in the cosmetic and dermatological fields. The cross-linking of polymer containing emulsion systems by means of water-soluble multivalent metallic ions can be achieved with or without the additional oil-in-water emulsifiers. The selection of an appropriate emulsifier for a given system is within the purview of one skilled in the art. Optionally, a wide variety of agents may be incorporated into the compositions of this invention for a variety of purposes. For example, medicaments such as benzoyl peroxide, methyl nicolinate, salicylic acid, benzocaine and menthol can be cast into desirable shapes for therapeutic use. The cross-linked hydrogels and emulsions can be cast into any desirable shape and used for various purposes. For example, casts in the form of face masks may be used for treating dry skin. Casts in the form of patches or pads may be used to cover burns and wounds for soothing and comforting the inflamed area, or for delivering active medicaments to the damaged skin as a controlled release, transdermal patch. Both the clear and opaque emollient casts may also contain fragrance, colour insect repellents and sun screens. The following examples illustrate how the cross-linked casts of this invention may be formed. EXAMPLE 1 An emulsion crosslinked cast was produced having the following composition: Eastman AQ 55S Polymer 20.3 Propylene Glycol 28.0 Mineral oil 10.0 PJ 7.0 Polysorbate 20 1.0 Zinc gluconate 2.0 Water 31.7 The cross-linked emulsion casts were formed by placing appropriate amounts of water and propylene glycol in a suitable container and heating the mixture to 80°C. The appropriate amount of polymer was gradually added with a high shear mixing until a clear viscous liquid was produced. The polysorbate 20 was added to the clear liquid and mixing continued. The melted oil phase was then added to the aqueous phase and homogenized to form a smooth emulsion. To this emulsion the appropriate amount of aqueous solution of zinc gluconate was added with continued mixing. Pouring into a mold at appropriate viscosity formed a cast of the desired shape. The cross-linking of the emulsion can be carried out between 50°C to 70°C, as desired, for manufacturing and suitable for pouring into the molds for casting purposes. EXAMPLE 2 Water insoluble sources of multivalent metallic ions such as, for example, zinc oxide or titanium dioxide can be added to form more rigid cross-linked casts. Eastman AQ 55S Polymer 21.00 Propylene Glycol 28.00 Petroleum Jelly 15.00 Glycerol Monostearate and Polyoxyethylene stearate 1.00 Zinc Oxide 2.00 Zinc Gluconate 2.00 Microcrystalline Wax 5.00 Water 26.00 EXAMPLES 3-21 The following are additional specific examples of formulations used to produce cross-linked casts of this invention: Ex. 3 Eastman AQ 55S polymer 21 Propylene glycol 28 Zinc gluconate 2 Water 49 Ex. 4 Eastman AQ 55S polymer 25.5 Propylene glycol 34.0 Zinc gluconate 2.0 Water 38.5 Ex. 5 Eastman AQ 55S polymer 20.3 Propylene glycol 18.0 Zinc gluconate 2.0 Water 59.7 Ex. 6 Eastman AQ 55S polymer 23.3 Propylene glycol 10.0 Zinc gluconate 2.0 Water 64.8 Ex. 7 Eastman AQ 55S polymer 21 Propylene glycol 28 Zinc gluconate 2 Water 49 Ex. 8 Eastman AQ 55S polymer 24 Propylene glycol 32 Zinc gluconate 2 Water 42 Ex. 9 Eastman AQ 55S polymer 27 Propylene glycol 36 Zinc gluconate 2 Water 35 Ex. 10 Eastman AQ 55S polymer 23.2 Zinc gluconate 2.0 Water 74.8 Ex. 11 Eastman AQ 55S polymer 23.2 Magnesium chloride 0.5 Water 76.3 Ex. 12 Eastman AQ 55S polymer 24 Glycerine 32 Zinc gluconate 2 Water 42 Ex. 13 Eastman AQ 55S polymer 24.0 Propylene glycol 32.0 Magnesium chloride 0.3 Water 43.7 Ex. 14 Eastman AQ 29S polymer 15.0 Eastman AQ 55S polymer 5.4 Propylene glycol 27.2 Mineral oil 10.0 Polysorbate 20 2.0 Zinc gluconate 3.0 Water 37.4 Ex. 15 Eastman AQ 55S polymer 20.3 Propylene glycol 28.0 Mineral oil 10.0 Petroleum jelly 7.0 Polysorbate 20 1.0 Zinc gluconate 2.0 Water 31.7 Ex. 16 Eastman AQ 55S polymer 20.3 Propylene glycol 28.0 Mineral oil 10.0 Petroleum jelly 7.0 Polysorbate 20 1.0 Zinc gluconate 1.5 Water 32.2 Ex. 17 Eastman AQ 55S polymer 18.0 Propylene glycol 24.0 Petroleum jelly 17.0 Polysorbate 20 1.0 Zinc gluconate 2.0 Water 38.0 Ex. 18 Eastman AQ 55S polymer 21.0 Propylene glycol 28.0 Petroleum jelly 17.0 Zinc gluconate 2.0 Water 32.0 Ex. 19 Eastman AQ 55S polymer 21.0 Propylene glycol 28.0 Petroleum jelly 16.0 Salicylic acid 2.0 Zinc gluconate 2.0 Water 31.0 Ex. 20 Eastman AQ 55S polymer 20.7 Propylene glycol 27.6 Petroleum jelly 15.0 Benzoyl peroxide 2.0 Glycerine 2.0 Zinc gluconate 2.0 Water 30.7 Ex. 21 Eastman AQ 55S polymer 21.0 Propylene glycol 28.0 Petroleum jelly 15.0 Polysorbate 20 1.0 Superabsorbant polymer 1.0 Zinc gluconate 1.0 Water 33.0

Claims: A composition which is a cross-linked aqueous dispersion obtainable by mixing: a water-dissipatable ether and sulphonate group-containing polyester or polyesteramide in an amount of from 18 to 30%; water in an amount of from 30 to 80%; and a humectant in an amount of from 0.1 to 40%; and then crosslinking the polyester or polyesteramide by adding a source of water-soluble multivalent metallic ions in an amount of from 0.1 to 5%, the percentages being by weight, based on the total weight of the composition. A composition as claimed in claim 1 which is a cross-linked emulsion characterised in that it additionally comprises: one or more emollient oils in an amount of from 0.1 to 25%; and an emulsifier in an amount of from 0.01 to 5%; the percentages being by weight, based on the total weight of the composition. A composition as claimed in claim 1 or claim 2 wherein the source of multivalent metallic ions is selected from magnesium chloride, zinc acetate, zinc gluconate, and magnesium acetate. A composition as claimed in any of claims 1 to 3 wherein the humectant is selected from propylene glycol, glycerine or combinations thereof. A method of producing a cross-linked cast characterised in that it comprises: (a) forming a composition as claimed in any of claims 1 to 3; and (b) pouring the composition into a mold whereby there is obtained a cross-linked cast.

Inventors: RAMIREZ JOSE E, VISHNUPAD MOHAN, RAMIREZ, JOSE E., VISHNUPAD, MOHAN
Applicants: IMAGINATIVE RES ASS, IMAGINATIVE RESEARCH ASSOCIATES INC.
Application year: 1990
Main classification: C08J3
IPC codes: C08J3, C08K5, C08K3, A61K8, A61Q19