TITLE: Aqueous dispersions of polymers cross-linked with metallic ions
European Patent EP0413418
 B1

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 (130 Knorr Road, Monroe, CT, 06468, US)
Ramirez, Jose E. (15 Fox Court, Trumbull, CT, 06611, US)

APPLICATION NUMBER: EP19900306515
PUBLICATION DATE: 09/11/1996
FILING DATE: 06/14/1990

ASSIGNEE: IMAGINATIVE RESEARCH ASSOCIATES INC. (416 Bunnell Street, Bridgeport,
Connecticut, 06607, US)
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

DOMESTIC PATENT REFERENCES:
EP0022624 Process for setting a polychloroprene-latex.
EP0061701 A solid entrapped emollient-moisturizer composition and the
 use thereof.

FOREIGN REFERENCES:
FR1545403A
FR2211474A
3493550 PLASTICIZED ASSOCIATED POLYMERS
3734874

OTHER REFERENCES:
EP-A 78 559
Attorney, Agent or Firm:
Froud, Clive (Elkington and Fife Prospect House 8 Pembroke Road,
Sevenoaks, Kent, TN13 1XR, GB)

CLAIMS:
1. 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.
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%; 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.
3. 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.
4. A composition as claimed in any of claims 1 to 3 wherein the
humectant is selected from propylene glycol, glycerine or combinations
thereof.
5. 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:
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:
Propylene Glycol 28.0
Mineral oil10.0
PJ7.0
Polysorbate 201.0
Zinc gluconate2.0
Water31.7
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.
Propylene Glycol  28.00
Petroleum Jelly15.00
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 gluconate2
Water49
Ex. 4
Eastman AQ 55S polymer 25.5
Propylene glycol 34.0
Zinc gluconate2.0
Water38.5
Ex. 5
Eastman AQ 55S polymer 20.3
Propylene glycol 18.0
Zinc gluconate2.0
Water59.7
Ex. 6
Eastman AQ 55S polymer 23.3
Propylene glycol 10.0
Zinc gluconate2.0
Water64.8
Ex. 7
Eastman AQ 55S polymer 21
Propylene glycol 28
Zinc gluconate2
Water49
Ex. 8
Eastman AQ 55S polymer 24
Propylene glycol 32
Zinc gluconate2
Water42
Ex. 9
Eastman AQ 55S polymer 27
Propylene glycol 36
Zinc gluconate2
Water35
Ex. 10
Eastman AQ 55S polymer 23.2
Zinc gluconate2.0
Water74.8
Ex. 11
Eastman AQ 55S polymer 23.2
Magnesium chloride  0.5
Water76.3
Ex. 12
Eastman AQ 55S polymer 24
Glycerine  32
Zinc gluconate2
Water42
Ex. 13
Eastman AQ 55S polymer 24.0
Propylene glycol 32.0
Magnesium chloride  0.3
Water43.7
Ex. 14
Eastman AQ 29S polymer 15.0
Eastman AQ 55S polymer 5.4
Propylene glycol 27.2
Mineral oil10.0
Polysorbate 202.0
Zinc gluconate3.0
Water37.4
Ex. 15
Eastman AQ 55S polymer 20.3
Propylene glycol 28.0
Mineral oil10.0
Petroleum jelly  7.0
Polysorbate 201.0
Zinc gluconate2.0
Water31.7
Ex. 16
Eastman AQ 55S polymer 20.3
Propylene glycol 28.0
Mineral oil10.0
Petroleum jelly  7.0
Polysorbate 201.0
Zinc gluconate1.5
Water32.2
Ex. 17
Eastman AQ 55S polymer 18.0
Propylene glycol 24.0
Petroleum jelly  17.0
Polysorbate 201.0
Zinc gluconate2.0
Water38.0
Ex. 18
Eastman AQ 55S polymer 21.0
Propylene glycol 28.0
Petroleum jelly  17.0
Zinc gluconate2.0
Water32.0
Ex. 19
Eastman AQ 55S polymer 21.0
Propylene glycol 28.0
Petroleum jelly  16.0
Salicylic acid2.0
Zinc gluconate2.0
Water31.0
Ex. 20
Eastman AQ 55S polymer 20.7
Propylene glycol 27.6
Petroleum jelly  15.0
Benzoyl peroxide 2.0
Glycerine  2.0
Zinc gluconate2.0
Water30.7
Ex. 21
Eastman AQ 55S polymer 21.0
Propylene glycol 28.0
Petroleum jelly  15.0
Polysorbate 201.0
Superabsorbant polymer 1.0
Zinc gluconate1.0
Water33.0