TITLE: AQUEOUS DISPERSIONS OF POLYMERS CROSS-LINKED WITH METALLIC IONS
European Patent Application EP0413418 A3

ABSTRACT:
Abstract of EP0413418
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.

INVENTORS:
Vishnupad, Mohan
Ramirez, Jose E.

APPLICATION NUMBER: EP19900306515
PUBLICATION DATE: 11/27/1991
FILING DATE: 06/14/1990

ASSIGNEE: IMAGINATIVE RESEARCH ASSOCIATES INC.
INTERNATIONAL CLASSES: A61K8/02; A61K8/27; A61K8/85; A61K9/70; A61Q19/00; C08J3/24; C08K3/00;
C08K3/22; C08K5/098; (IPC1-7): C08J3/24; C08K3/00; C08K5/09
EUROPEAN CLASSES: A61K8/02F; A61K8/27; A61K8/85; A61Q19/00; C08J3/24; C08K3/00P2;
C08K3/00P2+L67/00; C08K3/00S; C08K5/098+L67/00

CLAIMS:
1. 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.
2. 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%, 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.
3. A cross-linked 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, zinc oxide, titanium dioxide
and magnesium acetate.
4. 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.

DESCRIPTION:
AQUEOUS DISPERSIONS OF POLYESTER AND POLYESTERAMIDES CROSS-LINKED WITH
METALLIC IONS AND CASTS MADE THEREFROM
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 can also contain humectants
and/or 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.
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: EMI2.1 wherein "A" is an
aromatic dicarboxylic acid moiety some of which have sodiofulfo
(-SO3<-> , 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/or 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 casts of this invention comprise water dissipatable polyester or
polyesteramide in an amount from 18 to 30%, by weight, water in an
amount from 67 to 80% humectants in an amount from 0.01 to 40%, by
weight, and a source of multivalent metal ions for cross-linking
purposes in an amount from 0.01 to 5%. Casts of this invention can also
be formulated using emollient oils in an amount from 0.01 to 25%, by
weight, based on the total weight of the composition, water
dissipatable polyester in an amount from 18-30%, by weight, water in an
amount from 67-80%, by weight, based on the total weight of the
composition, and a source of multivalent metallic ions in an amount
from 0.01 to 5% based on the total weight of the composition.
Optionally the composition also contains fragrance oils, medical agents
or color.
Cross-linked clear casts of the present invention comprise (a) a water
dissipatable polyester polymer in an amount from 18 30%, by weight,
based on the total weight of the composition; (b) water in an amount
from 67-80%, by weight, based on the total weight of the composition;
(c) a source of multivalent metallic ions in an amount of 0.1-5%, by
weight, based on the total weight of the composition; (d) humectant
such as propylene glycol, glycerine in an amount from 0.1-40%, by
weight, based on the total weight of the composition.
The cross-linked cast of the present invention can also be in the form
of an opaque emulsion system. Such emulsion cast of the present
invention comprise (a) a water dissipatable polymer in an amount from
18 to 30%, by weight, based on the total weight of the composition; (b)
water in an amount from 67 to 80%, by weight, based on the total weight
of the composition; (c) emollient oils in an amount from 0.1 to 25%, by
weight, based on the total weight of the composition; (d) a source of
multivalent metallic ions in an amount from 0.1 to 5%, by weight, based
on the total weight of the composition; (e) humectants in an amount
from 0.01 to 40%, by weight, based on the total weight of the
composition; (f) any suitable oil-in-water emulsifier in an amount from
0.01 to 5%, by weight, based on the total weight of the composition.
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 multivalent metal ions
used to cross-link the polymers in this invention include magnesium
chloride, zinc acetate, zinc gluconate, zinc oxide, titanium dioxide
and magnesium acetate. The preferred sources of multivalent metal ions
are water soluble and include 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 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
multivalent metallic ions can be achieved with or without the
additional 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,
insect repellents, sun screens and like chemicals.
The following examples illustrate how the cross-linked casts of this

invention may be formed. EXAMPLE 1
A clear cross-linked cast was produced having the following
composition:
Columns=2> Eastman AQ 55S Polymer24.0 Zinc Gluconate (USP)2.0 Propylene
Glycol34.0 Water42.0
The cross-linked cast of Example 1 was prepared by placing the
appropriate amounts of water and propylene glycol into a suitable
container and heating the mixture to 80 DEG C. The appropriate amount
of polymer was gradually added with a high shear mixing to dissolve the
solids. When all the solids were added, high shear mixing is continued,
until a clear, straw colored, thick gel was produced. The gel was then
cooled to room temperature and an appropriate amount of zinc gluconate
aqueous solution added by high shear mixing until cross-linking
occurred. The liquid was poured into a mold of desirable shape to
produce a cast of hydrogel. The metallic cross-linking can be done
either at room temperature or at elevated temperatures depending on the

composition. EXAMPLE 2
An emulsion crosslinked cast was produced having the following
composition:
Columns=2> Eastman AQ 55S Polymer20.3 Propylene Glycol28.0 Mineral
oil10.0 PJ7.0 Polysorbate 201.0 Zinc gluconate2.0 Water31.7
The cross-linked emulsion casts of Example 2 were formed by placing
appropriate amounts of water and propylene glycol in a suitable
container and heating the mixture to 80 DEG 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 DEG C to 70 DEG C, as desired,
for manufacturing and suitable for pouring into the molds for casting

purposes. EXAMPLE 3
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.
Columns=2> Eastman AQ 55S Polymer21.00 Propylene Glycol28.00 Petroleum
Jelly15.00 Glycerol Monostearate and Polyoxyethylene stearate1.00 Zinc
Oxide2.00 Zinc Gluconate2.00 Microcrystalline Wax5.00 Water26.00

EXAMPLES 4-24
The following are additional specific examples of formulations used to
produce cross-linked casts of this invention:
Columns=2> TITLE: Ex. 4 Eastman AQ 55S polymer21 Propylene glycol28 Zinc gluconate2 Water49 Columns=2> Title: Ex. 5 Eastman AQ 55S
polymer25.5 Propylene glycol34.0 Zinc gluconate2.0 Water38.5 Columns=2>
TITLE: Ex. 6 Eastman AQ 55S polymer20.3 Propylene glycol18.0 Zinc gluconate2.0 Water59.7 Columns=2> Title: Ex. 7 Eastman AQ 55S
polymer23.3 Propylene glycol10.0 Zinc gluconate2.0 Water64.8 Columns=2>
TITLE: Ex. 8 Eastman AQ 55S polymer21 Propylene glycol28 Zinc gluconate2
Water49
Columns=2> TITLE: Ex. 9 Eastman AQ 55S polymer24 Propylene glycol32 Zinc gluconate2 Water42 Columns=2> Title: Ex. 10 Eastman AQ 55S
polymer27 Propylene glycol36 Zinc gluconate2 Water35 Columns=2> TITLE: Ex. 11 Eastman AQ 55S polymer23.2 Zinc gluconate2.0 Water74.8
Columns=2> TITLE: Ex. 12 Eastman AQ 55S polymer23.2 Magnesium chloride0.5 Water76.3 Columns=2> Title:
Ex. 13 Eastman AQ 55S polymer24 Glycerine32 Zinc gluconate2 Water42
Columns=2> TITLE: Ex. 14 Eastman AQ 55S polymer24.0 Propylene glycol32.0 Magnesium chloride0.3 Water43.7 Columns=2> Title: Ex. 15
Eastman AQ 29S polymer15.0 Eastman AQ 55S polymer5.4 Propylene
glycol27.2 Mineral oil10.0 Polysorbate 202.0 Zinc gluconate3.0
Water37.4 Columns=2> TITLE: Ex. 16 Eastman AQ 55S polymer20.3 Propylene glycol28.0 Mineral oil10.0 Petroleum jelly7.0 Polysorbate 201.0 Zinc
gluconate2.0 Water31.7 Columns=2> TITLE: Ex. 17 Eastman AQ 55S polymer20.3 Propylene glycol28.0 Mineral oil10.0
Petroleum jelly7.0 Polysorbate 201.0 Zinc gluconate1.5 Water32.2
Columns=2> TITLE: Ex. 18 Eastman AQ 55S polymer18.0 Propylene glycol24.0 Petroleum jelly17.0 Polysorbate 201.0 Zinc gluconate2.0
Water38.0 Columns=2> TITLE: Ex. 19 Eastman AQ 55S polymer21 Propylene glycol28 Dimethicone19 Petroleum jelly9 Glycerolmonostearate and
Polyoxyethylene Stearate1 Zinc gluconate2 Water30 Columns=2> TITLE: Ex. 20 Eastman AQ 55S polymer21.0 Propylene glycol28.0 Petroleum
jelly17.0 Zinc gluconate2.0 Water32.0
Columns=2> TITLE: Ex. 21 Eastman AQ 55S polymer21.0 Propylene glycol28.0 Petroleum jelly16.0 Salicylic acid2.0 Zinc gluconate2.0
Water10.0 Columns=2> TITLE: Ex. 22 Eastman AQ 55S polymer20.7 Propylene glycol27.6 Petroleum jelly15.0 Benzoyl peroxide2.0 Glycerine2.0 Zinc
gluconate2.0 Water30.7 Columns=2> TITLE: Ex. 23 Eastman AQ 55S polymer21.0 Propylene glycol28.0 Menthol2.0 Zinc gluconate2.0 Water26.0
Columns=2> TITLE: Ex. 24 Eastman AQ 55S polymer21.0 Propylene glycol28.0 Petroleum
jelly15.0 Polysorbate 201.0 Superabsorbant polymer1.0 Zinc gluconate1.0
Water33.0