ALLANTOIN-CONTAINING SKIN CREAM

CREME POUR LA PEAU CONTENANT DE L'ALLANTOINE

English Abstract

An allantoin-containing skin cream composition can comprise allantoin and at
least one anionic or nonionic emulsifier that is substantially hydrophilic and
is soluble in water. The pH of the composition is in a range of from about 3.0
to about 6.0; preferably, the pH of the composition is from about 5.0 to about
6Ø The composition can further comprise an acidic anionic polymer. A
preferred acidic anionic polymer is a carboxypolymethylene polymer. The
composition can further comprise a carbohydrate polymer such as
galactoarabinan, polygalactose or polyarabinose. The composition can
additionally comprise other ingredients such as herbal extracts, an
antioxidant component, an emollient component, a chelator, a solvent
component, or a preservative component. The composition is useful as a skin
protectant.

French Abstract

L'invention concerne une composition pour la peau sous forme de crème, contenant de l'allantoïne et au moins un émulsifiant anionique ou non ionique sensiblement hydrophile et hydrosoluble. Le pH de la composition est situé entre 3 et 6, mais de préférence entre 5 et 6. La composition peut en outre comporter un polymère anionique acide. Un polymère anionique acide préféré est un polymère carboxypolyméthylène. La composition peut en outre comporter un polymère glucidique, tel que le galactoarabinan, le polygalactose ou le polyarabinose. La composition peut également comprendre d'autres ingrédients, tels que des extraits d'herbes, un composant anti-oxydant, un composant émollient, un chélateur, un solvant ou un conservateur. La composition permet de protéger la peau.

Claims

I claim:
1. A composition comprising an oil-in-water emulsion comprising:
(a) allantoin; and
(b) at least one anionic or nonionic emulsifier that is substantially
hydrophilic and is soluble in water;
wherein the pH of the composition is in a range of from about 3.0 to about
6Ø
2. The composition of claim 1 wherein the pH of the composition is in.cndot.a
range of from about 5.0 to about 6Ø
3. The composition of claim 1 where the at least one anionic or nonionic
emulsifier is selected from the group consisting of:
(a) an acidic anionic polymer;
(b) an anionic emulsifier selected from the group consisting of sodium
lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, sodium
dodecylbenzenesulfonate, and sodium lauryl sarcosinate;
(c) a nonionic emulsifier that is an ethoxylated ether or an ethoxylated
ester whose chain length ranges from 8 to 22 carbon atoms;
(d) glyceryl stearate;
(e) cetyl alcohol;
(f) stearic acid;
(g) sodium stearoyl lactylate;
(h) sodium isostearoyl lactylate;
(i) triethanolamine;
(j) a polyethylene glycol ether of cetearyl alcohol wherein the number of
polyethylene glycol moieties in the ether is from 6 to 40; and
(k) beeswax.
4. The composition of claim 1 further comprising a carbohydrate polymer
selected from the group consisting of galactoarabinan, polygalactose, and
polyarabinose.
5. The composition of claim 4 wherein the carbohydrate polymer is
galactoarabinan.


6. A composition comprising an oil-in-water emulsion comprising:
(a) allantoin; and
(b) an emulsifier system comprising:
(i) an acidic anionic polymer; and
(ii) a polyethylene glycol ester of stearic acid;
wherein the pH of the composition is from about 3.0 to about 6Ø
7. The composition of claim 6 wherein the pH of the composition is from
about 5.0 to about 6Ø
8. The composition of claim 6 wherein the acidic anionic polymer is a
carboxypolymethylene polymer.
9. The composition of claim 6 further comprising a carbohydrate
polymer.
10. The composition of claim 9 wherein the carbohydrate polymer is
selected from the group consisting of galactoaxabinan, polygalactose, and
polyarabinose.
11. The composition of claim 10 wherein the carbohydrate polymer is
galactoarabinan.
12. The composition of claim 6 wherein the composition further comprises
at least one of:
(a) an emollient component comprising at least one emollient selected
from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and
cod liver oil;
(b) butylated hydroxytoluene;
(c) a solvent component comprising at least one solvent selected from the
group consisting of propylene glycol, glycerin, and butylene glycol; and
(d) a preservative component comprising at least one preservative selected
from the group consisting of methylparaben, propylparaben, and diazolidinyl
urea.
13. The composition of claim 7 wherein the composition comprises:
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(a) from about 50.0% to about 90.0% of water;
(b) from about 0.30% to about 3.0% of a.carboxypolymethylene polymer;
(c) from about 2.0% to about 9.0% of propylene glycol;
(d) from about 0.25% to about 2.5% of PEG-100 stearate;
(e) from about 5.0% to about 15.0% of lanolin oil;
(f) from about 1.0% to about 8.0% of cetyl alcohol;
(g) from about 0.5% to about 6.0% of stearyl alcohol;
(h) from about 1.0% to about 7.0% of cod liver oil;
(i) from about 0.10% to about 1.0% of butylated hydroxytoluene;
(j) from about 0.10% to about 0.50% of methylparaben;
(k) from about 0.10% to about 0.50% of propylparaben;
(1) from about 0.05% to about 0.25% of diazolidinyl urea;
(m) from about 0.50% to about 2.0% of allantoin;
(n) from about 0.05% to about 0.50% of fragrance; and
(o) from about 0.05% to about 3.0% of triethanolamine.
14. The composition of claim 13 wherein the composition comprises:
(a) from about 60.0% to about 85.0% of water;
(b) from about 0.50% to about 2.0% of a carboxypolymethylene polymer;
(c) from about 4.0% to about 7.0% of propylene glycol;
(d) from about 0.50% to about 2.0% of PEG-100 stearate;
(e) from about 8.0% to about 12.0% of lanolin oil;
(f) from about 2.0% to about 7.0% of cetyl alcohol;
(g) from about 0.75% to about 5.0% of stearyl alcohol;
(h) from about 1.0% to about 4.0% of cod liver oil;
(i) from about 0.20% to about 0.80% of butylated hydroxytoluene;
(j) from about 0.15% to about 0.40% of methylparaben;
(k) from about 0.15% to about 0.45% of propylparaben;
(1) from about 0.10% to about 0.20% of diazolidinyl urea;
(m) from about 1.0% to about 2.0% of allantoin;
(n) from about 0.10% to about 0.40% of fragrance; and
(o) from about 0.20% to about 2.0% of triethanolamine.
15. The composition of claim 14 wherein the composition comprises:
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(a) about 69.95% of water;
(b) about 0.85% of a carboxypolymethylene polymer;
(c) about 5.70% of propylene glycol;
(d) about 2.0% of PEG-100 stearate;
(e) about 10.60% of lanolin oil;
(f) about 4.20% of cetyl alcohol;
(g) about 1.50% of stearyl alcohol;
(h) about 2.00% of cod liver oil;
(i) about 0.50% of butylated hydroxytoluene;
(j) about 0.30% of methylparaben;
(k) about 0.25% of propylparaben;
(l) about 0.15% of diazolidinyl urea;
(m) about 1.50% of allantoin;
(n) about 0.20% of fragrance; and
(o) about 0.80% of triethanolamine.
16. A composition comprising an oil-in-water emulsion comprising:
(a) allantoin; and
(b) an emulsifier system comprising:
(i) an acidic anionic polymer; and
(ii) an anionic emulsifier that is substantially hydrophilic and is soluble
in water, the pH of the composition being adjusted to a range of from about
3.0 to about 6Ø
17. The composition of claim 16 wherein the pH of the composition is
from about 5.0 to about 6Ø
18. The composition of claim 16 wherein the anionic emulsifier is selected
from the group consisting of sodium lauryl sulfate, sodium laureth sulfate,
sodium oleyl
succinate, sodium dodecylbenzenesulfonate, and sodium lauryl sarcosinate.
19. The composition of claim 18 wherein the anionic emulsifier is sodium
lauryl sulfate.
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20. The composition of claim 16 wherein the acidic anionic polymer is
carboxypolymethylene.

21. The composition of claim 16 further comprising a carbohydrate
polymer selected from the group consisting of galactoarabinan, polygalactose,
and
polyarabinose.

22. The composition of claim 21 wherein the carbohydrate polymer is
galactoarabinan.

23. A composition comprising an oil-in-water emulsion comprising:
(a) allantoin;
(b) an emulsifier system comprising an acidic anionic polymer; and
(c) a base to adjust the pH of the composition to a value in a range from
about
3.0 to about 5.5.

24. The composition of claim 23 wherein the pH is in a range from about
5.0 to about 5.5.

25. The composition of claim 23 wherein the acidic anionic polymer is
carboxypolymethylene.

26. The composition of claim 23 wherein the base is an inorganic base.

27. The composition of claim 23 wherein the base is an organic base.

28. The composition of claim 27 wherein the base is triethanolamine.

29. The composition of claim 23 wherein the composition further
comprises at least one of:
(a) an emollient component comprising at least one emollient selected
from the group consisting of lanolin oil, cetyl alcohol, and cod liver oil;
(b) butylated hydroxytoluene;



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(c) a solvent component comprising at least one solvent selected from the
group consisting of propylene glycol, glycerin, and butylene glycol; and
(d) a preservative component comprising at least one preservative selected
from the group consisting of methylparaben and propylparaben.

30. The composition of claim 24 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 0.40% to about 3.0% of a carboxypolymethylene polymer;
(c) from about 2.0% to about 9.0% of propylene glycol;
(d) from about 5.0% to about 15.0% of lanolin oil;
(e) from about 1.0% to about 8.0% of cetyl alcohol;
(f) from about 1.0% to about 7.0% of cod liver oil;
(g) from about 0.10% to about 1.0% of butylated hydroxytoluene;
(h) from about 0.10% to about 0.50% of methylparaben;
(i) from about 0.10% to about 0.50% of propylparaben;
(j) from about 0.50% to about 2.0% of allantoin;
(k) from about 0.05% to about 0.50% of fragrance; and
(1) from about 0.05% to about 3.0% of triethanolamine.

31. The composition of claim 30 wherein the composition comprises:
(a) from about 60.0% to about 80.0% of water;
(b) from about 0.54% to about 2.0% of a carboxypolymethylene polymer;
(c) from about 4.0% to about 7.0% of propylene glycol;
(d) from about 8.0% to about 12.0% of lanolin oil;
(e) from about 2.0% to about 7.0% of cetyl alcohol;
(f) from about 1.0% to about 4.0% of cod liver oil;
(g) from about 0.30% to about 0.80% of butylated hydroxytoluene;
(h) from about 0.15% to about 0.40% of methylparaben;
(i) from about 0.15% to about 0.40% of propylparaben;
(j) from about 1.0% to about 2.0% of allantoin;
(k) from about 0.10% to about 0.40% of fragrance; and
(l) from about 0.20% to about 3.0% of triethanolamine.

32. The composition of claim 31 wherein the composition comprises:


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(a) about 73.55% of water;
(b) about 1.00% of a carboxypolymethylene polymer;
(c) about 5.70% of propylene glycol;
(d) about 12.0% of lanolin oil;
(e) about 3.00% of cetyl alcohol;
(f) about 2.00% of cod liver oil;
(g) about 0.50% of butylated hydroxytoluene;
(h) about 0.30% of methylparaben;
(i) about 0.25% of propylparaben;
(j) about 1.50% of allantoin;
(k) about 0.20% of fragrance; and
(l) about 0.80% of triethanolamine.

33. A composition comprising an oil-in-water emulsion comprising:
(a) allantoin;
(b) an emulsifier system comprising:
(i) an acidic anionic polymer; and
(ii) a nonionic emulsifier that is an ethoxylated ether or an ethoxylated
ester whose carbon chain length ranges from 8 to 22 carbon atoms, wherein the
pH of the
composition is from about 3.0 to about 6Ø

34. The composition of claim 33 wherein the pH of the composition is
from about 5.0 to about 6Ø

35. The composition of claim 33 wherein the acidic anionic polymer is
carboxypolymethylene.

36. The composition of claim 33 further comprising a carbohydrate
polymer selected from the group consisting of galactoarabinan, polygalactose,
and
polyarabinose.

37. The composition of claim 36 wherein the carbohydrate polymer is
galactoarabinan.



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38. The composition of claim 33 wherein the emulsifier system further
comprises glyceryl stearate.

39. The composition of claim 33 further comprising at least one of
(a) an emollient component comprising at least one emollient selected
from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and
cod liver oil;
(b) butylated hydroxytoluene;
(c) a solvent component comprising at least one solvent selected from the
group consisting of glycerin, propylene glycol, and butylene glycol; and
(d) a preservative component comprising at least one preservative selected
from the group consisting of methylparaben, propylparaben, and diazolidinyl
urea.

40. A composition comprising an oil-in-water emulsion comprising:
(a) allantoin;
(b) an emulsifier system comprising:
(1) cetyl alcohol; and
(2) stearic acid;
wherein the pH of the composition is adjusted to a value in the range of from
about 3.0 to
about 6Ø

41. The composition of claim 40 wherein the pH is from about 5.0 to about
5.8.

42. The composition of claim 40 wherein the composition further
comprises triethanolamine to adjust the pH.

43. The composition of claim 40 wherein the composition further
comprises at least one of:
(a) a solvent component comprising at least one solvent selected from the
group consisting of propylene glycol, glycerin, and butylene glycol;
(b) an emollient component comprising at least one emollient selected
from the group consisting of lanolin oil and cod liver oil;
(c) butylated hydroxytoluene; and



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(d) a preservative component comprising at least one preservative selected
from the group consisting of methylparaben and propylparaben.

44. The composition of claim 41 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 2.0% to about 9.0% of propylene glycol;
(c) from about 0.20% to about 4.0% of triethanolamine;
(d) from about 5.0% to about 15.0% of lanolin oil;
(e) from about 1.0% to about 7.0% of cetyl alcohol;
(f) from about 0.50% to about 5.0% of stearic acid;
(g) from about 1.0% to about 7.0% of cod liver oil;
(h) from about 0.10% to about 1.0% of butylated hydroxytoluene;
(i) from about 0.10% to about 0.50% of methylparaben;
(j) from about 0.10% to about 0.50% of propylparaben;
(k) from about 0.50% to about 2.0% of allantoin; and
(l) from about 0.05% to about 0.50% of fragrance.

45. The composition of claim 44 wherein the composition comprises:
(a) from about 60.0% to about 85.0% of water;
(b) from about 4.0% to about 7.0% of propylene glycol;
(c) from about 0.50% to about 3.0% of triethanolamine;
(d) from about 8.0% to about 12.0% of lanolin oil;
(e) fxom about 2.0% to about 6.0% of cetyl alcohol;
(fj from about 1.0% to about 4.0% of stearic acid;
(g) from about 1.50% to about 5.0% of cod liver oil;
(h) from about 0.20% to about 0.80% of butylated hydroxytoluene;
(i) frorn about 0.15% to about 0.40% of methylparaben;
(j) from about 0.15% to about 0.40% of propylparaben;
(k) from about 1.0% to about 2.0% of allantoin; and
(l) from about 0.10% to about 0.40% of fragrance.

46. The composition of claim 45 wherein the composition comprises:
(a) about 71.70% of water;
(b) about 5.70% of propylene glycol;



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(c) about 1.25% of triethanolamine;
(d) about 10.60% of lanolin oil;
(e) about 3.50% of cetyl alcohol;
(f) about 2.50% of stearic acid;
(g) about 5.0% of cod liver oil;
(h) about 0.50% of butylated hydroxytoluene;
(i) about 0.30% of methylparaben;
(j) about 0.25% of propylparaben;
(k) about 1.50% of allantoin; and
(l) about 0.20% of fragrance.

47. A composition comprising an oil-in-water emulsion comprising:
(a) allantoin;
(b) an emulsifier system comprising:
(i) sodium stearoyl lactylate;
(ii) sodium isostearoyl lactylate;
(iii) optionally, triethanolamine;
(iv) optionally, at least one nonionic emulsifier selected from the
group consisting of a nonionic emulsifier that is an ethoxylated ether or an
ethoxylated ester
whose carbon chain length ranges from 8 to 22 carbon atoms; and
(c) an acid to adjust the pH to a range of from about 3.0 to about 6Ø

48. The composition of claim 47 wherein the pH is from about 5.0 to about
5.8.

49. The composition of claim 47 wherein the acid is citric acid.

50. The composition of claim 47 further comprising at least one of:
(a) a solvent component comprising at least one solvent selected from the
group consisting of propylene glycol, butylene glycol, and glycerin;
(b) an emollient component comprising at least one emollient selected
from the group consisting of lanolin oil, cetyl alcohol, and cod liver oil;
(c) butylated hydroxytoluene;
(d) tetrasodium EDTA; and


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(e) a preservative component comprising at least one preservative selected
from the group consisting of methylparaben and propylparaben.

51. The composition of claim 48 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 2.0% to about 9.0% of propylene glycol;
(c) from about 0.05% to about 0.5% of citric acid;
(d) from about 0.30% to about 3.0% of sodium stearoyl lactylate;
(e) from about 0.05% to about 1.0% of sodium isostearoyl lactylate;
(f) from about 0.05% to about 0.25% of tetrasodium EDTA;
(g) from about 5.0% to about 15.0% of lanolin oil;
(h) from about 1.0% to about 8.0% of cetyl alcohol;
(i) from about 1.0% to about 7.0% of cod liver oil;
(j) from about 0.10% to about 1.0% of butylated hydroxytoluene;
(k) from about 0.10% to about 0.50% of methylparaben;
(l) from about 0.10% to about 0.50% of propylparaben;
(m) from about 0.50% to about 2.0% of allantoin; and
(n) from about 0.05% to about 0.50% of fragrance.

52. The composition of claim 51 wherein the composition comprises:
(a) from about 60.0% to about 80.0% of water;
(b) from about 4.0% to about 7.0% of propylene glycol;
(c) from about 0.10% to about 0.40% of citric acid;
(d) from about 0.50% to about 2.5% of sodium stearoyl lactylate;
(e) from about 0.10% to about 0.70% of sodium isostearoyl lactylate;
(f) from about 0.10% to about 0.20% of tetrasodium EDTA;
(g) from about 8.0% to about 12.0% of lanolin oil;
(h) from about 2.0% to about 7.0% of cetyl alcohol;
(i) from about 1.0% to about 4.0% of cod liver oil;
(j) from about 0.20% to about 0.80% of butylated hydroxytoluene;
(k) from about 0.15% to about 0.40% of methylparaben;
(l) from about 0.15% to about 0.40% of propylparaben;
(m) from about 1.0% to about 2.0% of allantoin; and
(n) from about 0.10% to about 0.40% of fragrance.



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53. The composition of claim 52 wherein the composition comprises:
(a) about 73.42% of water;
(b) about 5.70% of propylene glycol;
(c) about 0.18% of citric acid;
(d) about 1.04% of sodium stearoyl lactylate;
(e) about 0.25% of sodium isostearoyl lactylate;
(f) about 0.15% of tetrasodium EDTA;
(g) about 15.0% of lanolin oil;
(h) about 3.80% of cetyl alcohol;
(i) about 2.00% of cod liver oil;
(j) about 0.50% of butylated hydroxytoluene;
(k) about 0.30% of methylparaben;
(l) about 0.25% of propylparaben;
(m) about 1.50% of allantoin; and
(n) about 0.20% of fragrance.

54. A composition comprising an oil-in-water emulsion comprising:
(a) allantoin; and
(b) an emulsifier system comprising at least one polyethyleneglycol ether of
cetearyl alcohol, wherein the number of polyethylene glycol moieties in the
polyethyleneglycol ether of cetearyl alcohol is from 6 to 40; and
(c) an acid to adjust the pH of the composition to a range of from about 3.0
to
about 6Ø

55. The composition of claim 54 wherein the pH is from about 5.0 to about
5.8.

56. The composition of claim 54 wherein the acid is citric acid.

57. The composition of claim 54 further comprising at least one of:
(a) a solvent component comprising at least one solvent selected from the
group consisting of propylene glycol, butylene glycol, and glycerin;



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(b) an emollient component comprising at least one emollient selected
from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and
cod liver oil;
(c) butylated hydroxytoluene;
(d) tetrasodium EDTA; and
(e) a preservative component comprising at least one preservative selected
from the group consisting of methylparaben, propylparaben, and diazolidinyl
urea.

58. The composition of claim 54 wherein the emulsifier system comprises
ceteareth-25 and ceteareth-6.

59. The composition of claim 55 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 2.0% to about 9.0% of propylene glycol;
(c) from about 0.05% to about 0.50% of tetrasodium EDTA;
(d) from about 0.50% to about 4.0% of ceteareth-25;
(e) from about 0.04% to about 0.40% of citric acid;
(f) from about 5.0% to about 15.0% of lanolin oil;
(g) from about 3.0% to about 10.0% of cetyl alcohol;
(h) from about 1.0% to about 5.0% of stearyl alcohol;
(i) from about 0.50% to about 4.0% of ceteareth-6;
(j) from about 1.0% to about 7.0% of cod liver oil;
(k) from about 0.1 % to about 1.0% of butylated hydroxytoluene;
(l) from about 0.10% to about 0.50% of methylparaben;
(m) from about 0.10% to about 0.50% of propylparaben;
(n) from about 0.05% to about 0.50% of diazolidinyl urea;
(o) from about 0.50% to about 2.0% of allantoin; and
(p) from about 0.05% to about 0.50% of fragrance.

60. The composition of claim 59 wherein the composition comprises:
(a) from about 55.0% to about 75.0% of water;
(b) from about 4.2% to about 7.0% of propylene glycol;
(c) from about 0.10% to about 0.30% of tetrasodium EDTA;
(d) from about 2.0% to about 3.5% of ceteareth-25;
(e) from about 0.10% to about 0.30% of citric acid;



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(f) from about 8.0% to about 12.0% of lanolin oil;
(g) from about 3.5% to about 7.5% of cetyl alcohol;
(h) from about 2.0% to about 4.0% of stearyl alcohol;
(i) from about 1.0% to about 3.0% of ceteareth-6;
(j) from about 1.0% to about 4.0% of cod liver oil;
(k) from about 0.20% to about 0.80% of butylated hydroxytoluene;
(l) from about 0.15% to about 0.40% of methylparaben;
(m) from about 0.15% to about 0.40% of propylparaben;
(n) from about 0.10% to about 0.30% of diazolidinyl urea;
(o) from about 1.0% to about 2.0% of allantoin; and
(p) from about 0.10% to about 0.30% of fragrance.

61. The composition of claim 60 wherein the composition comprises:
(a) about 66.33% of water;
(b) about 5.70% of propylene glycol;
(c) about 0.15% of tetrasodium EDTA;
(d) about 2.60% of ceteareth-25;
(e) about 0.12% of citric acid;
(f) about 10.60% of lanolin oil;
(g) about 4:30% of cetyl alcohol;
(h) about 3.50% of stearyl alcohol;
(i) about 1.80% of ceteareth-6;
(j) about 2.00% of cod liver oil;
(k) about 0.50% of butylated hydroxytoluene;
(l) about 0.30% of methylparaben;
(m) about 0.25% of propylparaben;
(n) about 0.15% of diazolidinyl urea;
(o) about 1.50% of allantoin; and
(p) about 0.20% of fragrance.

62. A composition comprising an oil-in-water emulsion comprising:
(a) allantoin;
(b) an emulsifier system comprising:
(i) a polyethylene glycol ester of stearic acid; and



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(ii) glyceryl stearate; and
(c) an acid to adjust the pH of the composition to a range of from about 3,0
to
about 6Ø
63. The composition of claim 62 wherein the pH is from about 5.0 to about
5.8.
64. The composition of claim 62 wherein the number of ethylene glycol
moieties in the polyethylene glycol ester of stearic acid is from 25 to 100.
65. The composition of claim 64 wherein the polyethylene glycol ester of
stearic acid is PEG-100 stearate.
66. The composition of claim 62 wherein the acid is citric acid.
67. The composition of claim 62 wherein the composition further
comprises at least one of:
(a) a solvent component comprising at least one solvent selected from the
group consisting of propylene glycol, butylene glycol, and glycerin;
(b) an emollient component comprising at least one emollient selected
from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and
cod liver oil;
(c) - butylated hydroxytoluene;
(d) tetrasodium EDTA; and
(e) a preservative component comprising at least one preservative selected
from the group consisting of methylparaben, propylparaben, and diazolidinyl
urea.
68. The composition of claim 63 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 2.0% to about 9.0% of propylene glycol;
(c) from about 0.05% to about 0.50% of tetrasodium EDTA;
(d) from about 0.04% to about 0.40% of citric acid;
(e) from about 1.0% to about 5.0% of PEG-100 stearate;
(f) from about 5.0% to about 15.0% of lanolin oil;
(g) from about 2.0% to about 10.0% of cetyl alcohol;
74


(h) from about 1.0% to about 4.0% of stearyl alcohol;
(i) from about 1.0% to about 5.0% of glyceryl stearate;
(j) from about 1.0% to about 7.0% of cod liver oil;
(k) from about 0.10% to about 1.0% of butylated hydroxytoluene;
(l) from about 0.10% to about 0.50% of methylparaben;
(m) from about 0.10% to about 0.50% of propylparaben;
(n) from about 0.05% to about 0.50% of diazolidinyl urea;
(o) from about 0.50% to about 2.0% of allantoin; and
(p) from about 0.05% to about 0.50% of fragrance.
69. The composition of claim 68 wherein the composition comprises:
(a) from about 55.0% to about 80.0% of water;
(b) from about 4.0% to about 7.0% of propylene glycol;
(c) from about 0.10% to about 0.30% of tetrasodium EDTA;
(d) from about 0.10% to about 0.30% of citric acid;
(e) from about 1.50% to about 3.0% of PEG-100 stearate;
(f) from about 8.0% to about 12.0% of lanolin oil;
(g) from about 2.5% to about 7.5% of cetyl alcohol;
(h) from about 1.0% to about 3.5% of stearyl alcohol;
(i) from about 2.0% to about 4.0% of glyceryl stearate;
(j) from about 1.0% to about 4.0% of cod liver oil;
(k) from about 0.20% to about 0.80% of butylated hydroxytoluene;
(l) from about 0.15% to about 0.40% of methylparaben;
(m) from about 0.15% to about 0.40% of propylparaben;
(n) from about 0.10% to about 0.30% of diazolidinyl urea;
(o) from about 1.0% to about 2.0% of allantoin; and
(p) from about 0.10% to about 0.40% of fragrance.
70. The composition of claim 69 wherein the composition comprises:
(a) about 67.86% of water;
(b) about 5.70% of propylene glycol;
(c) about 0.15% of tetrasodium EDTA;
(d) about 0.14% of citric acid;
(e) about 2.60% of PEG-100 stearate;
75


(f) about 10.60% of lanolin oil;
(g) about 3.00% of cetyl alcohol;
(h) about 2.50% of stearyl alcohol;
(i) about 2.50% of glyceryl stearate;
(j) about 2.00% of cod liver oil;
(k) about 0.50% of butylated hydroxytoluene;
(l) about 0.30% of methylparaben;
(m) about 0.25% propylparaben;
(n) about 0.20% of diazolidinyl urea;
(o) about 1.50% of allantoin; and
(p) about 0.20% of fragrance.
71. A composition comprising an oil-in-water emulsion comprising:
(a) allantoin;
(b) a carbohydrate polymer; and
(c) an emulsifier system comprising:
(1) beeswax; and
(2) an anionic emulsifier that is substantially hydrophilic and is
soluble in water;
wherein the pH of the composition is in a range from about 3.0 to about 6Ø
72. The composition of claim 71 wherein the pH of the composition is in a
range of from about 5.0 to about 6Ø
73. The composition of claim 71 wherein the carbohydrate polymer is
selected from the group consisting of galactoarabinan, polygalactose, and
polyarabinose.
74. The composition of claim 73 wherein the carbohydrate polymer is
galactoarabinan.
75. The composition of claim 71 wherein the anionic emulsifier that is
substantially hydrophilic and soluble in water is selected from the group
consisting of sodium
lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, sodium
dodecylbenzenesulfonate, and sodium lauryl sarcosinate.
76


76. The composition of claim 75 wherein the anionic emulsifier that is
substantially hydrophilic and soluble in water is sodium lauryl sulfate.
77. The composition of claim 71 wherein the composition further
comprises citric acid.
78. The composition of claim 71 further comprising at least one of
(a) a solvent component comprising at least one solvent selected from the
group consisting of propylene glycol, butylene glycol, and glycerin;
(b) an emollient component comprising at least one emollient selected
from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and
cod liver oil;
(c) butylated hydroxytoluene;
(c) tetrasodium EDTA; and
(d) a preservative component comprising at least one preservative selected
from the group consisting of methylparaben and propylparaben.
79. The composition of claim 72 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 2.0% to about 9.0% of propylene glycol;
(c) from about 0.50% to about 5.0% of a 30% solution of sodium lauryl
sulfate;
(d) from about 0.05% to about 0.30% of tetrasodium EDTA;
(e) from about 1.0% to about 25.0% of galactoarabinan;
(f) from about 0.05% to about 0.25% of citric acid;
(g) from about 5.0% to about 15.0% of lanolin oil;
(h) from about 1.0% to about 8.0% of cetyl alcohol;
(i) from about 0.50% to about 6.0% of stearyl alcohol;
(j) from about 0.50% to about 5.0% of beeswax;
(k) from about 0.50% to about 15.0% of cod liver oil;
(l) from about 0.1% to about 3.0% of butylated hydroxytoluene;
(m) from about 0.10% to about 0.50% of methylparaben;
(n) from about 0.10% to about 0.50% of propylparaben;
(o) from about 0.50% to about 2.0% of allantoin; and
77



76. The composition of claim 75 wherein the anionic emulsifier that is
substantially hydrophilic and soluble in water is sodium lauryl sulfate.
77. The composition of claim 71 wherein the composition further
comprises citric acid.
78. The composition of claim 71 further comprising at least one of:
(a) a solvent component comprising at least one solvent selected from the
group consisting of propylene glycol, butylene glycol, and glycerin;
(b) an emollient component comprising at least one emollient selected
from the group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and
cod liver oil;
(c) butylated hydroxytoluene;
(c) tetrasodium EDTA; and
(d) a preservative component comprising at least one preservative selected
from the group consisting of methylparaben and propylparaben.
79. The composition of claim 72 wherein the composition comprises:
(a) from about 50.0% to about 90.0% of water;
(b) from about 2.0% to about 9.0% of propylene glycol;
(c) from about 0.50% to about 5.0% of a 30% solution of sodium lauryl
sulfate;
(d) from about 0.05% to about 0.30% of tetrasodium EDTA;
(e) from about 1.0% to about 25.0% of galactoarabinan;
(f) from about 0.05% to about 0.25% of citric acid;
(g) from about 5.0% to about 15.0% of lanolin oil;
(h) from about 1.0% to about 8.0% of cetyl alcohol;
(i) from about 0.50% to about 6.0% of stearyl alcohol;
(j) from about 0.50% to about 5.0% of beeswax;
(k) from about 0.50% to about 15.0% of cod liver oil;
(l) from about 0.1% to about 3.0% of butylated hydroxytoluene;
(m) from about 0.10% to about 0.50% of methylparaben;
(n) from about 0.10% to about 0.50% of propylparaben;
(o) from about 0.50% to about 2.0% of allantoin; and
77

Description

CA 02408689 2002-11-12
WO 01/87232 PCT/USO1/14899
ALLANTOIN-CONTAINING SHIN CREAM
by
Elliott Farber
CROSS REFERENCES
This application is a continuation-in-part application of Application Serial
No.
09/570,266, entitled "Allantoin-Containing Skin Cream," filed May 12, 2000 by
Elliott
Farber, which in turn is a continuation-in-part application of Application
Serial No.
09/360,095, entitled "Oil-in-Water Emulsion With Improved Stability," filed
July 23, 1999
by Elliott Farber. Both of these prior applications are hereby incorporated in
their entirety by
this reference.
BACKGROUND OF THE INVENTION
This invention is directed to a skin cream containing allantoin in an oil-in-
water emulsion with improved stability.
Allantoin is a commonly used ingredient in cosmetic applications, particularly
for skin creams, where it exerts a skin protective function. Many such
cosmetic compositions
and other compositions are prepared as emulsions, particularly oil-in-water
emulsions. One
emulsifier system used with such compositions is a combination of sodium
lauryl sulfate and
beeswax. Although solutions of sodium lauryl sulfate are alkaline with an
approximate pH of
9.5, the simultaneous use of beeswax with its organic acids produces a complex
and
neutralized system with a pH of about 6.8 to about 7.5. However, in such a
system with a pH
range of 6.8 to 7.5, allantoin degrades significantly with time and in
accelerated stability tests
at 40°C. Because cosmetics and other preparations designed for
application to the skin are
typically stored by users at room temperature, and room temperatures can
fluctuate with
climatic conditions, such a degree of stability is undesirable. Therefore,
there is a need for an
oil-in-water emulsified composition containing allantoin in which the
stability of allantoin is
increased.


CA 02408689 2002-11-12
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In particular, there is a need for compositions that are suitable for treating
a
number of severe and difficult-to-treat skin conditions. One of these skin
conditions is
epidermolysis bullosa. This is a severe genetic skin disorder in which the
skin breaks down
and large blisters appear. These blisters are difficult to treat by
conventional means. Other
skin diseases for which improved treatments are needed are pressure ulcers,
decubitus ulcers
or bed sores, and diabetic ulcers, as well as milia. Therefore, improved
compositions that are
suitable for treating these diseases are needed.
SUMMARY
In general, a composition according to the present invention comprises an oil-
in-water emulsion comprising:
( 1 ) allantoin; and
(2) at least one anionic or nonionic emulsifier that is substantially
hydrophilic and is soluble in water.
The pH of the composition is in a range of from about 3.0 to about 6Ø This
pH range stabilizes the allantoin and makes storage of the composition for
extended periods
practical. Preferably, the pH of the composition is in a range of from about
5.0 to about 6Ø
Typically, the at least one anionic or nonionic emulsifier is selected from
the
group consisting of:
(1) an acidic anionic polymer;
(2) an anionic emulsifier selected from the group consisting of sodium
lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, sodium
dodecylbenzenesulfonate, and sodium lauryl sarcosinate;
(3) a nonionic emulsifier that is an ethoxylated ether or an ethoxylated
ester whose chain length ranges from 8 to 22 carbon atoms;
(4) glyceryl stearate;
(5) cetyl alcohol;
(6) stearic acid;
(7) sodium stearoyl lactylate;
(8) sodium isostearoyl lactylate;
2


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(9) triethanolamine;
(10) a polyethylene glycol ether of cetearyl alcohol wherein the number of
polyethylene glycol moieties in the ether is from 6 to 40; and
(11) beeswax.
The composition can further comprise a carbohydrate polymer selected from
the group consisting of galactoarabinan, polygalactose, and polyarabinose.
Typically, the
carbohydrate polymer is galactoarabinan.
One embodiment of the present invention is a composition comprising an oil-
in-water emulsion comprising:
(1) allantoin; and
(2) an emulsifier system comprising:
(a) an acidic anionic polymer; and
(b) a polyethylene glycol ester of stearic acid.
The pH of the composition is from about 3.0 to about 6Ø Preferably, the pH
of the composition is from about 5.0 to about 6Ø
Typically, in this embodiment, the acidic anionic polymer is a
carboxypolymethylene polymer.
The composition can further comprise a carbohydrate polymer. Typically, the
carbohydrate polymer is selected from the group consisting of galactoarabinan,
polygalactose, and polyarabinose. Preferably, the carbohydrate polymer is
galactoarabinan.
Another embodiment of the present invention is a composition comprising an
oil-in-water emulsion comprising:
( 1 ) allantoin; and
(2) an emulsifier system comprising:
(a) an acidic anionic polymer; and
(b) an anionic emulsifier that is substantially hydrophilic and is soluble
in water, the pH of the composition being adjusted to a range of from about
3.0 to about 6Ø
Preferably, the pH of the composition is adjusted to a range of from about 5.0
to about 6Ø
3


CA 02408689 2002-11-12
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The anionic emulsifier can be selected from the group consisting of sodium
lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, sodium
dodecylbenzenesulfonate, and sodium lauryl sarcosinate. Preferably, the
anionic emulsifier is
sodium lauryl sulfate.
The composition can further comprise a carbohydrate polymer selected from
the group consisting of galactoarabinan, polygalactose and polyarabinose.
Preferably, the
carbohydrate polymer is galactoarabinan.
Another embodiment of the present invention is a composition comprising an
oil-in-water emulsion comprising:
(1) allantoin; .
(2) an emulsifier system comprising an acidic anionic polymer; and
(3) a base to adjust the pH of the composition to a value in a range from
about
3.0 to about 6Ø Preferably, the pH of the composition is from about 5.0 to
about 5.5.
Preferably, the acidic anionic polymer is a carboxypolymethylene polymer.
Preferably, the base is an organic base such as triethanolamine.
In another embodiment, the composition comprises an oil-in-water emulsion
comprising:
(1) allantoin;
(2) an emulsifier system comprising:
(a) an acidic anionic polymer; and
(b) a nonionic emulsifier that is an ethoxylated ether or an ethoxylated
ester whose carbon chain length ranges from 8 to 22 carbon atoms, wherein the
pH of the
composition is from about 3.0 to about 6Ø Preferably, the pH of the
composition is from
about 5.0 to about 6Ø
In this embodiment, the emulsifier system can further comprise glyceryl
stearate.
This embodiment also can include a carbohydrate polymer as described above.
4


CA 02408689 2002-11-12
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In yet another embodiment of the present invention, a composition comprising
an oil-in-water emulsion comprising:
( 1 ) allantoin;
(2) an emulsifier system comprising:
(a) sodium stearoyl lactylate;
(b) sodium isostearoyl lactylate;
(c) optionally, triethanolamine;
(d) optionally, at least one nonionic emulsifier selected from the group
consisting of a nonionic emulsifier that is an ethoxylated ether or an
ethoxylated ester whose
carbon chain length ranges from 8 to 22 carbon atoms; and
(3) an acid to adjust the pH to a range of from about 3.0 to about 6Ø
Preferably, the pH is adjusted to a range of from 5.0 to about 5.8.
Typically, the acid is citric acid.
Still another embodiment of the present invention is a composition comprising
an oil-in-water emulsion comprising:
( 1 ) allantoin; and
(2) an emulsifier system comprising at least one polyethyleneglycol ether of
cetearyl alcohol, wherein the number of polyethylene glycol moieties in the
polyethyleneglycol ether of cetearyl alcohol is from 6 to 40; and
(3) an acid to adjust the pH of the composition to a range of from about 5.0
to
about 5.8.
For this embodiment, the acid is typically also citric acid.
For this embodiment, the emulsifier system typically comprises ceteareth-25
and ceteareth-6.
Yet another embodiment of the present invention is a composition comprising
an oil-in-water emulsion comprising:
( 1 ) allantoin;
(2) an emulsifier system comprising:
5


CA 02408689 2002-11-12
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(a) a polyethylene glycol ester of stearic acid; and
(b) glyceryl stearate; and
(3) an acid to adjust the pH of the composition to a range of from about 3.0
to
about 6Ø Preferably, the pH is adjusted to a range of from about 5.0 to
about 5.8.
Typically, in this embodiment, the number of ethylene glycol moieties in the
polyethylene glycol ester of stearic acid is from 25 to 100. Preferably, the
polyethylene
glycol ester of stearic acid is PEG-100 stearate. Typically, in this
embodiment, the acid is
citric acid.
Still another embodiment of the present invention is a composition
comprising an oil-in-water emulsion comprising:
(1) allantoin;
(2) a carbohydrate polymer; and
(3) an emulsifier system comprising:
(a) beeswax; and
(b) an anionic emulsifier that is substantially hydrophilic and is
soluble in water;
wherein the pH of the composition is in a range from about 3.0 to about 6Ø
Preferably, the
pH is in the range of from about 5.0 to about 6Ø
The carbohydrate polymer in this embodiment is as described above.
Typically, the anionic emulsifier that is substantially hydrophilic and
soluble
in water is selected from the group consisting of sodium lauryl sulfate,
sodium laureth sulfate,
sodium oleyl , succinate, sodium dodecylbenzenesulfonate, and sodium lauryl
sarcosinate.
Preferably, the anionic emulsifier is sodium lauryl sulfate.
The composition can further comprise citric acid to adjust the pH.
For all of these embodiments, the composition can comprise one or more
additional ingredients as described below.
6


CA 02408689 2002-11-12
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The composition can comprise an emollient component comprising at least
one emollient selected from the group consisting of lanolin oil, cetyl
alcohol, stearyl alcohol,
and cod liver oil.
The composition can comprise an emollient such as butylated hydroxytoluene.
The composition can comprise herbal extracts such as one or more of St.
John's wort extract, witch hazel extract, chamomile extract, and arnica
extract.
The composition can comprise a preservative component comprising at least
one preservative selected from the group consisting of methylparaben,
propylparaben, and
diazolidinyl urea.
The composition can comprise a chelating agent such as tetrasodium EDTA.
The composition can comprise a solvent component comprising at least one
solvent selected from the group consisting of propylene glycol, butylene
glycol and glycerin.
Preferably, the solvent component is propylene glycol.
Ranges of compositions are disclosed for each of these embodiments.
DESCRIPTION
A composition according to the present invention comprises an oil-in-water
emulsion comprising:
(1) allantoin; and
(2) at least one anionic or nonionic emulsifier that is substantially
hydrophilic and is soluble in water.
The composition can further. include other ingredients, such as a chelating
agent to bind metal ions that might accelerate degradation of the composition.
A particularly
preferred chelating agent is EDTA. The EDTA can be added in various acid or
salt forms
7


CA 02408689 2002-11-12
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depending on the pH of the composition, such as EDTA itself, disodium EDTA, or
tetrasodium EDTA.
The pH of the composition is in a range of from about 3.0 to about 6Ø This
pH range stabilizes the allantoin and makes storage of the composition for
extended periods
practical. Preferably, the pH is in a range of from about 5.0 to about 6Ø
Typically, the at least one anionic or nonionic emulsifier is selected from
the
group consisting of
(1) an acidic anionic polymer;
(2) an anionic emulsifier selected from the group consisting of sodium
lauryl sulfate, sodium laureth sulfate, sodium oleyl succinate, sodium
dodecylbenzenesulfonate, and sodium lauryl sarcosinate;
(3) an nonionic emulsifier that is an ethoxylated ether or an ethoxylated
ester whose chain length ranges from 8 to 22 carbon atoms;
(4) glyceryl stearate;


(5) cetyl alcohol;


(6) stearic acid;


(7) sodium stearoyl lactylate;


(8) sodium isostearoyl lactylate;


(9) triethanolamine;


(10) a polyethylene glycol ether of cetearyl alcohol
wherein the number of


polyethylene glycol
moieties in the
ether is from
6 to 40; and


(11) beeswax.


The composition can further comprise a carbohydrate polymer selected from
the group consisting of galactoarabinan, polygalactose, and polyarabinose.
Typically, the
carbohydrate polymer is galactoarabinan.
One embodiment of an improved composition containing allantoin is a
composition that comprises an oil-in-water emulsion comprising:
(1) allantoin; and
(2) an emulsifier system comprising:
(a) an acidic anionic polymer; and
8


CA 02408689 2002-11-12
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(b) a polyethylene glycol ester of stearic acid.
The pH of the composition is adjusted to a range of from about 3.0 to about
6Ø Preferably, the pH is adjusted to a range of from about 5.0 to about 6Ø
The pH is
adjusted with sodium hydroxide or other base as required.
The acidic anionic polymer is preferably a carboxypolymethylene polymer.
Such polymers are marketed under the brand names "Carbomer" and "Carbopol." A
suitable
carboxypolymethylene polymer is marketed by B.F. Goodrich under the brand name
"Carbomer." This is a slightly cross-linked polyacrylic acid that is from 1%
to 2% cross-
linked by allylsucrose or allylpentaerythritol with the polyacrylic acid. The
resulting
molecular weight range of this polymer is from about 2 x 106 daltons to about
1 x 109 daltons.
The average molecular weight of this polymer is about 4 x 106 daltons.
Preferably, the concentration of the carboxypolymethylene polymer is from
about 0.5 percent to about 2 percent of the composition.
The composition can further comprise a carbohydrate polymer. Preferably,
the carbohydrate polymer is galactoarabinan. Galactoarabinan is derived from
trees of the
genus Larix (larch) and is a hemicellulosic product easily extractable by
water in a pure form.
Galactoarabinan has been consumed by humans in common foods such as carrots,
tomatoes,
maple syrup, soybeans, and wheat flour, among others. The molecular weight of
the
galactoarabinan is about 20,000. A suitable source of galactoarabinan is
Larex, Inc (White
Bear Lake, MN). Typically, the composition contains from about 1 percent to
about 25
percent of galactoarabinan. Preferably, the composition contains from about 2
percent to
about 10 percent of the carbohydrate polymer. A
This embodiment of a composition according to the present invention can
further include other ingredients. For example, the composition can include an
emollient
component for smoothness. The emollient component can include at least one
emollient
selected from the group consisting of lanolin oil, cetyl alcohol, stearyl
alcohol, and cod liver
oil.
9


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The composition can also. include an antioxidant to prevent rancidity of
ingredients such as cod liver oil. A preferred antioxidant is butylated
hydroxytoluene (BHT).
The composition can further include a solvent component. Typically, the
solvent component can include at least one solvent selected from the group
consisting of
propylene glycol, glycerin, or butylene glycol. Preferably, the solvent
component is
propylene glycol.
The composition can further include a preservative component. The
preservative component can comprise at least one preservative selected from
the group
consisting of methylparaben, propylparaben, and diazolidinyl urea. Preferably,
the
preservative component comprises methylparaben, propylparaben, and
diazolidinyl urea.
The composition can further include fragrance. The use of fragrance is well
known in the cosmetic art and in the art of over-the-counter drug formulation,
and many
suitable fragrances are known in the art. The stability and function of the
cream is not altered
by the presence or absence of fragrance.
Optionally, this embodiment of the composition can further include herbal
extracts. The herbal extracts can include one or more of St. John's wort
extract, witch hazel
extract, chamomile extract, and arnica extract. However, these herbal extracts
are typically
omitted in this embodiment.
This embodiment of the composition can optionally further include other
components, such as proteins, humectants, other preservatives, essential oils,
other vitamins,
colorants, hydroxyacids, other plant extracts, chelators, sunscreens, sodium
hyaluronate,
lipids, fatty acids, thickeners, panthenol, and the like. The use of such
components is
conventional in the cosmetic art and in the over-the-counter drug art. Typical
sunscreens are
octyl methoxycinnamate and benzophenone-3.
The following discussion describes ranges, preferred concentrations and
optimum concentrations for preferred compositions according to this embodiment
of the
present invention with a pH range of from about 5.0 to about 6Ø


CA 02408689 2002-11-12
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Water can comprise from about 50.0% to about 90.0% of this embodiment of
the composition. Preferably, water comprises from about 60.0% to about 85.0%
of this
embodiment of the composition. An optimum concentration of water in this
embodiment of
the composition is about 69.95%.
The carboxypolymethylene polymer can comprise from about 0.30% to about
3.0% of this embodiment of the composition. Preferably, the
carboxypolymethylene polymer
comprises from about 0.50% to about 2.0% of this embodiment of the
composition. An
optimum concentration of the carboxypolymethylene polymer is about 0.85% of
this
embodiment of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of this
embodiment of the composition. Preferably, propylene glycol comprises from
about 4.0% to
about 7.0% of this embodiment of the composition. An optimum concentration of
propylene
glycol is about 5.70% of this embodiment of the composition.
PEG-100 stearate can comprise from about 0.,25% to about 2.5% of this
embodiment of the composition. Preferably, PEG-100 stearate comprises from
about 0.50%
to about 2.0% of this embodiment of the composition. An optimum concentration
of PEG-
100 stearate is about 1.50% of this embodiment of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of this embodiment
of the composition. Preferably, lanolin oil comprises from about 8.0% to about
12.0% of this
embodiment of the composition. An optimum concentration of lanolin oil is
about 10.60% of
this embodiment of the composition.
Cetyl alcohol can comprise from about 1.0% to about 8.0% of this
embodiment of the composition. A preferred concentration of cetyl alcohol is
from about
2.0% to about 7.0% of this embodiment of the composition. An optimum
concentration of
cetyl alcohol is about 4.20% of this embodiment of the composition.
Stearyl alcohol can comprise from, about 0.5% to about 6.0% of this
embodiment of the composition. A preferred concentration of stearyl alcohol is
from about
11


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0.75% to about 5.0% of this embodiment of the composition. An optimum
concentration of
stearyl alcohol is about 1.50% of this embodiment of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of this embodiment
of the composition. Preferably, cod liver oil comprises from about 1.0% to
about 4.0% of
this embodiment of the composition. An optimum concentration of cod liver oil
is about
2.00% of this embodiment of the composition.
Butylated hydroxytoluene can comprise from about 0.10% to about 1.0% of
this embodiment of the composition. Preferably, butylated hydroxytoluene
comprises from
about 0.20% to about 0.80% of this embodiment of the composition. An" optimum
concentration of butylated hydroxytoluene is about 0.50% of this embodiment of
the
composition.
Methylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. A preferred concentration of methylparaben is
from about
0.15% to about 0.40% of this embodiment of the composition. An optimum
concentration of
methylparaben is about 0.30% of this embodiment of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. Preferably, propylparaben comprises from about
0.15% to
about 0.40% of this embodiment of the composition. An optimum concentration of
propylparaben is about 0.25% of this embodiment of the composition.
Diazolidinyl urea can comprise from about 0.05% to about 0.25% of this
embodiment of the composition. Preferably, diazolidinyl urea comprises from
about 0.10%
to about 0.20% of this embodiment of the composition. An optimum concentration
of
diazolidinyl urea is about 0.15% of this embodiment of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of this embodiment
of the composition. A preferred concentration of allantoin is from about 1.0%
to about 2.0%
of this embodiment of the composition. An optimum concentration of allantoin
is about
1.50% of this embodiment of the composition.
12


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Fragrance can comprise from about 0.05% to about 0.50% of this embodiment
of the composition. Preferably, fragrance comprises from about 0.10% to about
0.40% of this
embodiment of the composition. An optimum concentration of fragrance is about
0.20% of
the composition,. As indicated above, fragrance can be omitted, and it may be
desirable to
omit fragrance in circumstances in which the composition is intended for use
on sensitive
individuals or individuals who may undergo an allergic reaction to fragrance.
Triethanolamine can comprise from about 0.05% to about 3.0% of this
embodiment of the composition to adjust the pH. A preferred concentration of
triethanolamine is from about 0.20% to about 2.0%,of this embodiment of the
composition.
An optimum concentration of triethanolamine is about 0.80% of this embodiment
of the
composition.
In another alternative embodiment of the composition, the emulsifier can be an
anionic emulsifier that is substantially hydrophilic and is soluble in water.
In this
embodiment, the anionic emulsifier replaces the polyethylene glycol ester of
stearic acid.
This embodiment further includes the acidic anionic polymer such as
carboxypolymethylene.
Optionally, but preferably, this alternative embodiment of the composition
includes the
carbohydrate polymer such as galactoarabinan.
The anionic emulsifier that is substantially hydrophilic and soluble in water
can be selected from the group consisting of sodium lauryl sulfate, sodium
laureth sulfate,
sodium oleyl succinate, sodium dodecylbenzenesulfonate, and sodium lauryl
sarcosinate. A
particularly preferred anionic emulsifier is sodium lauryl sulfate.
Commercially available preparations of sodium lauryl sulfate contain
sufficient excess sodium hydroxide so that they have a pH of about 10Ø This
sodium
hydroxide can be used to adjust the pH when the anionic emulsifier is sodium
lauryl sulfate;
in this alternative, no additional alkali may be needed. When another anionic
emulsifier is
used, additional alkali may be required to adjust the pH.
In yet another alternative embodiment of the composition, the emulsifier
system comprises the acidic anionic polymer as described above and a nonionic
emulsifier
13


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that is an ethoxylated ether or an ethoxylated ester whose carbon chain length
ranges from 8
to 22 carbon atoms.
Preferably, the acidic anionic polymer is carboxypolymethylene as described
above.
This alternative embodiment of the composition can further include glyceryl
stearate in the emulsifier system.
This embodiment of the composition has a pH from about 3.0 to 6.0, adjusted
as necessary, typically with an acid. The acid can be an organic acid, an
inorganic acid, or a
mixture of both. Preferably, the pH is from about 5.0 to about 6Ø
This embodiment of the composition can further comprise a carbohydrate
polymer such as galactoarabinan as described above.
In this embodiment of the composition, preferred organic acids include
organic acids whose carbon chain length ranges from 2 to 22 carbon atoms and
can be
monocarboxylic, dicarboxylic, or tricarboxylic acids. The acids can be
aliphatic or aromatic.
Particularly preferred organic acids include citric acid, ascorbic acid,
glycolic acid, lactic
acid, benzoic acid, and salicylic acid. A most particularly preferred organic
acid is citric
acid.
Typically, in this embodiment of the composition, the inorganic acid is a
strong acid. It can be a monoprotic, diprotic, or triprotic acid. Particularly
preferred
inorganic acids include hydrochloric acid, sulfuric acid, and phosphoric acid.
This alternative embodiment of the composition can further include other
ingredients as described above, including an emollient component, an
antioxidant, a solvent
component, a chelating agent, herbal extracts, a preservative, and fragrance.
The composition can further include other components, such as proteins,
humectants, other preservatives, essential oils, other vitamins, colorants,
hydroxyacids, other
plant extracts, sunscreens, sodium hyaluronate, lipids, fatty acids,
thickeners, panthenol, and
14


CA 02408689 2002-11-12
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the like. The use of such components is conventional in the cosmetic art and
in the over-the-
counter drug art. Typical sunscreens are octyl methoxycinnamate and
benzophenone-3.
In yet another embodiment of the composition, the emulsifier system
comprises the acidic anionic polymer described above; one example of this
acidic anionic
polymer is marketed as Carbomer. In this embodiment, the pH is adjusted with
an organic or
inorganic base to a range of from about 3.0 to about 6Ø Preferably, the pH
is adjusted to a
range of from about 5.0 to about 5.5. A preferred organic base is
triethanolamine. A
preferred inorganic base is sodium hydroxide. In general, it is preferred to
use an organic
base such as triethanolamine.
This embodiment can further comprise other ingredients. For example, this
embodiment of the invention can further comprise a solvent component.
Typically, the
solvent component comprises at least one solvent selected from the group
consisting of
propylene glycol, glycerin, or butylene glycol. Preferably, the solvent
component is
propylene glycol.
This embodiment of the invention can further comprise an emollient
component. The emollient component can comprise at least one solvent selected
from the
group consisting of lanolin oil, cetyl alcohol, and cod liver oil. Preferably,
the emollient
component comprises all of lanolin oil, cetyl alcohol, and cod liver oil.
This embodiment of the composition can also include an antioxidant. A
preferred antioxidant is butylated hydroxytoluene.
This embodiment of the invention can further. comprise a preservative
component. The preservative component can comprise at least one preservative
selected
from the group consisting of methylparaben and propylparaben. Preferably, the
preservative
component comprises both methylparaben and propylparaben.
This embodiment of the composition can further include fragrance as
described above. The stability and function of the cream are not altered by
the presence or
absence of fragrance. As indicated above, it may be desirable to omit
fragrance in some
cases.


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The following discussion describes ranges, preferred concentrations and
optimum concentrations fox preferred compositions according to this embodiment
of the
present invention where the pH is from about 5.0 to about 5.5.
Water can comprise from about 50.0% to about 90.0% of this embodiment of
the composition. Preferably, water comprises from about 60.0% to about 80.0%
of this
embodiment of the composition. An optimum concentration of water is about
73.55% of this
embodiment of the composition.
The carboxypolymethylene polymer can comprise from about 0.40% to about
3.0% of this embodiment of the composition. Preferably, the
carboxypolymethylene polymer
comprises from about 0.5% to about 2.0% of this embodiment of the composition.
An
optimum concentration of the carboxypolymethylene polymer is about 1.00% of
the
composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of this
embodiment of the composition. Preferably, the propylene glycol comprises from
about
4.0% to about 7.0% of this embodiment of the composition. An optimum
concentration of
the propylene glycol is about 5.70% of this embodiment of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of this embodiment
of the composition. Preferably, lanolin oil comprises from about 8.0% to about
12.0% of this
embodiment of the composition. An optimum concentration of lanolin oil is
about 10.0% of
this embodiment of the composition.
Cetyl alcohol can comprise from about 1.0% to about 8.0% of this
embodiment of the composition. Preferably, cetyl alcohol comprises from about
2.0% to
about 7.0% of this embodiment of the composition. An optimum concentration of
cetyl
alcohol is about 3.00% of this embodiment of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of this embodiment
of the composition. Preferably, cod liver oil comprises from about 1.0% to
about 4.0% of
J6


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this embodiment of the composition. An optimum concentration of cod liver oil
is about
2.00% of this embodiment of the composition.
Butylated hydroxytoluene can comprise from about 0.10% to about 1.0% of
this embodiment of the composition. Preferably, butylated hydroxytoluene
comprises from
about 0.30% to about 0.80% of this embodiment of the composition. An optimum
concentration of butylated hydroxytoluene is about 0.50% of this embodiment of
the
composition.
Methylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. Preferably, methylparaben comprises from about
0.15% to
about 0.40% of this embodiment of the composition. An optimum concentration of
methylparaben is about 0.30% of this embodiment of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. Preferably, propylparaben comprises from about
0.15% to
about 0.40% of this embodiment of the composition. An optimum concentration of
propylparaben is about 0.25% of this embodiment of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of this embodiment
of the composition. Preferably, allantoin comprises from about 1.0% to about
2.0% of this
embodiment of the composition. An optimum concentration of allantoin is about
1.50% of
this embodiment of the composition.
Fragrance, if present, can comprise from about 0.05% to about 0.50% of this
embodiment of the composition. Preferably, if present, fragrance comprises
from about
0.10% to about 0.40% of this embodiment of the composition. An optimum
concentration of
fragrance, if present, is about 0.20% of this embodiment of the composition.
Triethanolamine, as a 95% solution, can comprise from about 0.05% to about
3.0% of this embodiment of the composition to adjust the pH to a value in the
range of from
about 5.0 to about 5.5. Preferably, triethanolamine comprises from about 0.20%
to about
2.0% of this embodiment of the composition to adjust the pH as indicated. An
optimum
17


CA 02408689 2002-11-12
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concentration of triethanolainine is about 0.80% of the composition to adjust
the pH as
indicated.
Yet another embodiment of a composition according to the present invention
is a composition comprising an oil-in-water emulsion comprising:
( 1 ) allantoin; and
(2) an emulsifier system comprising:
(a) cetyl alcohol; and
(b) stearic acid.
In this embodiment, the pH is adjusted to a range of from about 3.0 to about
6.0 by addition of a quantity of a weak organic base. Preferably, the pH is
adjusted to a range
of from about 5.0 to about 5.8. The weak organic base can be an amine-
containing base such
as ethanolamine, diethanolamine, or triethanolamine. A preferred organic base
is
triethanolamine.
This embodiment can further comprise other ingredients. For example, this
embodiment of the invention can further comprise a solvent component.
Typically, the
solvent component comprises at least one solvent selected from the group
consisting of
propylene glycol, glycerin, or butylene glycol. Preferably, the solvent
component is
propylene glycol.
This embodiment of the invention can further comprise an emollient
component. The emollient component can comprise at least one solvent selected
from the
. group consisting of lanolin oil, cetyl alcohol,. and cod liver oil.
Preferably, the emollient
component comprises all of lanolin oil, cetyl alcohol, and cod liver oil.
This embodiment of the composition can also include an antioxidant. A
preferred antioxidant is butylated hydroxytoluene.
This embodiment of the invention can further comprise a preservative
component. The preservative component can comprise at least one preservative
selected
from the group consisting of methylparaben and propylparaben. Preferably, the
preservative
component comprises both methylparaben and propylparaben.
18


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This embodiment of the composition can further include fragrance as
described above. The stability and function of the cream is not altered by the
presence or
absence of fragrance. As indicated above, it may be desirable to omit
fragrance in some
cases.
The following discussion describes ranges, preferred concentrations and
optimum concentrations for preferred compositions according to this embodiment
of the
present invention when the pH is in the range of from about 5.0 to about 5.8.
Water can comprise from about 50.0% to about 90.0% of this embodiment of
the composition. Preferably, water comprises from about 60.0% to about 85.0%
of this
embodiment of the composition. An optimum concentration of water is about
71.70% of this
embodiment of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of this
4
embodiment of the composition. Preferably, propylene glycol comprises from
about 4.0% to
about 7.0% of this embodiment of the composition. An optimum concentration of
propylene
glycol is about 5.70% of this embodiment of the composition.
Triethanolamine can comprise from about 0.2% to about 4.0% of this
embodiment of the composition. Preferably, triethanolamine comprises from
about 0.5% to
about 3.0% of this embodiment of the composition. An optimum concentration of
triethanolamine is about 1.25% of this embodiment of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of this embodiment
of the composition. Preferably, lanolin oil comprises from about 8.0% to about
12.0% of this
embodiment of the composition. An optimum concentration of lanolin oil is
about 10.60% of
this embodiment of the composition.
Cetyl alcohol can comprise from about 1.0% to about 7.0% of this
embodiment of the composition. Preferably, cetyl alcohol comprises from about
2.0% to
about 6.0% of this embodiment of the composition. An optimum concentration of
cetyl
alcohol is about 3.50% of this embodiment of the composition.
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Stearic acid can comprise from about 0.50% to about 5.0% of this embodiment
of the composition. Preferably, stearic acid comprises from about 1.0% to
about 4.0% of this
embodiment of the composition. An optimum concentration of stearic acid is
about 2.50% of
this embodiment of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of this embodiment
of the composition. Preferably, cod liver oil comprises from about 1.50% to
about 5.0% of
this embodiment of the composition. An optimum concentration of cod liver oil
is about
2.0% of this embodiment of the composition.
Butylated hydroxytoluene can comprise from about 0.1% to about 1.0% of this
embodiment of the composition. Preferably, butylated hydroxytoluene comprises
from about
0.2% to about 0.8% of this embodiment of the composition. An optimum
concentration of
butylated hydroxytoluene is about 0.50% of this embodiment of the composition.
Methylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. Preferably, methylparaben comprises from about
0.15% to
about 0.40% of this embodiment of the composition. An optimum concentration of
methylparaben is about 0.30% of this embodiment of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. Preferably, propylparaben comprises from about
0.15% to
about 0.40% of the composition. An optimum concentration of propylparaben is
about
0.25% of this embodiment of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of this embodiment
of the composition. Preferably, allantoin comprises from about 1.0% to about
2.0% of this
embodiment of the composition. An optimum concentration of allantoin is about
1.50% of
this embodiment of the composition.
If present, fragrance can comprise from about 0.05% to about 0.50% of this
embodiment of the composition. Preferably, fragrance comprises from about
0.10% to about


CA 02408689 2002-11-12
WO 01/87232 PCT/USO1/14899
0.40% of this embodiment of the composition. An optimum concentration of
fragrance is
about 0.20% of this embodiment of the composition.
Still another embodiment of a composition according to the present invention
is a composition comprising an oil-in-water emulsion comprising:
(1) allantoin; and
(2) an emulsifier system comprising:
(a) sodium stearoyl lactylate;
(b) sodium isostearoyl lactylate;
(c) optionally, triethanolamine;
(d) optionally, at least one nonionic emulsifier selected from the group
consisting of a nonionic emulsifier that is an ethoxylated ether or an
ethoxylated ester whose
carbon chain length ranges from 8 to 22 carbon atoms.
I S Sodium stearoyl lactylate is the sodium salt of the stearic acid ester of
lactyl
lactate. Sodium isostearoyl Iactylate is the sodium salt of the isostearic
acid ester of lactyl
lactate.
In this embodiment of the composition, the composition further comprises an
acid to adjust the pH to a range of from about 3.0 to about 6Ø Preferably,
the pH is adjusted
to a range of from about 5.0 to about 5.8. The acid can be an inorganic or an
organic acid as
described above. Preferably, the acid is a weak organic acid. Most preferably,
the acid is
citric acid.
This embodiment can further comprise other ingredients. For example, this
embodiment of the invention can further comprise a solvent component.
Typically, the
solvent component comprises at least one solvent selected from the group
consisting of
propylene glycol, glycerin, or butylene glycol. Preferably, the solvent
component is
propylene glycol.
This embodiment of the invention can further comprise an emollient
component. The emollient component can comprise at least one emollient
selected from the
group consisting of lanolin oil, cetyl alcohol, and cod liver oil. Preferably,
the emollient
component comprises all of lanolin oil, cetyl alcohol, and cod liver oil.
21


CA 02408689 2002-11-12
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This embodiment of the invention can further comprise a chelator component.
Preferably, the chelator component is tetrasodium ethylenediaminetetraacetic
acid.
This embodiment of the invention can further comprise a preservative
component. The preservative component can comprise at least one preservative
selected
from the group consisting of methylparaben and propylparaben. Preferably, the
preservative
component comprises both methylparaben and propylparaben.
This embodiment of the composition can also include an antioxidant. A
preferred antioxidant is butylated hydroxytoluene.
This embodiment of the composition can further include fragrance as
described above. The stability and function of the cream are not altered by
the presence or
absence of fragrance. As indicated above, it may be desirable to omit
fragrance in some
cases.
The following discussion describes ranges, preferred concentrations and
optimum concentrations for preferred compositions according to this embodiment
of the
present invention when the pH is in the range of from about 5.0 to about 5.8.
Water can comprise from about 50.0% to about 90.0% of this embodiment of
the composition. Preferably, water comprises from about 60.0% to about 80.0%
of this
embodiment of the composition. An optimum concentration of water is about
73.72% of this
embodiment of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of this
embodiment of the composition. Preferably, propylene glycol comprises from
about 4.0% to
about 7.0% of this embodiment of the composition. An optimum concentration of
propylene
glycol is about 5.70% of this embodiment of the composition.
Citric acid can comprise from about 0.05% to about 0.50% of this embodiment
of the composition. Preferably, citric acid comprises from about 0.10% to
about 0.40% of
22


CA 02408689 2002-11-12
WO 01/87232 PCT/USO1/14899
this embodiment of the composition. An optimum concentration of citric acid is
about 0.18%
of this embodiment of the composition.
Sodium stearoyl lactylate can comprise from about 0.30% to about 3.0% of
this embodiment of the composition. Preferably, sodium stearoyl lactylate
comprises from
about 0.50% to about 2.50% of this embodiment of the composition. An optimum
concentration of sodium stearoyl lactylate is about 1.00% of this embodiment
of the
composition.
Sodium isostearoyl lactylate can comprise from about 0.05% to about 1.0% of
this embodiment of the composition. Preferably, sodium isostearoyl lactylate
comprises from
about 0.10% to ' about 0.70% of this embodiment of the composition. An optimum
concentration of sodium isostearoyl lactylate is about 0.25% of this
embodiment of the
composition.
Tetrasodium EDTA can comprise from about 0.05% to about 0.25% of this
embodiment of the composition. Preferably, tetrasodium EDTA comprises from
about 0.10%
to about 0.20% of this embodiment of the composition. An optimum concentration
of
tetrasodium EDTA is about 0.15% of this embodiment of the composition.
Lanolin oil can comprise from about 5.0% to about I 5.0% of this embodiment
of the composition. Preferably, lanolin oil comprises from about 8.0% to about
12.0% of this
embodiment of the composition. An optimum concentration of lanolin oil is
about 10.60% of
this embodiment of the composition.
Cetyl alcohol can comprise from about 1.0% to about 8.0% of this
embodiment of the composition. Preferably, cetyl alcohol comprises from about
2.0% to
about 7.0% of this embodiment of the composition. An optimum concentration of
cetyl
alcohol is about 3.80% of this embodiment of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of this embodiment
of the composition. Preferably, cod liver oil comprises from about 1.0% to
about 4.0% of
this embodiment of the composition. An optimum concentration of cod liver oil
is about
2.0% of this embodiment of the composition.
23


CA 02408689 2002-11-12
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Butylated hydroxytoluene can comprise from about 0.10% to about 1.0% of
this embodiment of the composition. Preferably, butylated hydroxytoluene
comprises from
about 0.20% to about 0.80% of this embodiment of the composition. An optimum
concentration of butylated hydroxytoluene is , about 0.50% of this embodiment
of the
composition.
Methylparaben can comprise from about 0.10°lo to about 0.50% of
this
embodiment of the composition. Preferably, methylparaben comprises from about
0.15% to
about 0.40% of this embodiment of the composition. An optimum concentration of
methylparaben is about 0.30% of this embodiment of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. Preferably, propylparaben comprises from about
0.15% to
about 0.40% of the composition. An optimum concentration of propylparaben is
about
0.25% of this embodiment of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of this embodiment
of the composition. Preferably, allantoin comprises from about 1.0% to about
2.0% of this
embodiment of the composition. An optimum concentration of allantoin is about
1.50% of
this embodiment of the composition.
If present, fragrance can comprise from about 0.05% to about 0.50% of this
embodiment of the composition. Preferably, fragrance comprises from about
0.10% to about
0.40% of this embodiment of the composition. An optimum concentration of
fragrance is
about 0.20% of this embodiment of the composition.
Still another embodiment of a composition according to the present invention
is a composition comprising an oil-in-water emulsion comprising:
3 0 ( 1 ) allantoin; and
(2) an emulsifier system comprising at least one polyethyleneglycol ether of
cetearyl alcohol.
24


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In polyethylene glycol ethers of cetearyl alcohol suitable for use in
compositions according to the present invention, the number of ethylene glycol
moieties can
range from 6 to 40, e.g., R(OCH2CHz~zsOH where R = CH3(CHz)16-i8~ In one
preferred
embodiment of the present invention, the emulsifier system comprises both
ceteareth-25 and
ceteareth-6, i.e., polyethylene glycol ethers of cetearyl alcohol with 25 and
6 ethylene glycol
units respectively.
In this embodiment of the composition, the composition further comprises an
acid to adjust the pH to a range of from about 3.0 to about 6Ø Preferably,
the pH is adjusted
to a range of from about 5.0 to about 5.8. The acid can be an inorganic or an
organic acid as
described above. Preferably, the acid is a weak organic acid. Most preferably,
the acid is
citric acid.
This embodiment can further comprise other ingredients. For example, this
embodiment of the invention can further comprise a solvent component.
Typically, the
solvent component comprises at least one solvent selected from the group
consisting of
propylene glycol, glycerin, or butylene glycol. Preferably, the solvent
component is
propylene glycol.
This embodiment of the invention can further comprise a chelator component.
Preferably, the chelator component is tetrasodium ethylenediaminetetraacetic
acid. ,
This embodiment of the invention can further comprise an emollient
component. The emollient component can comprise at least one emollient
selected from the
group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver
oil. Preferably,
the emollient component comprises all of lanolin oil, cetyl alcohol, stearyl
alcohol, and cod
liver oil.
This embodiment of the composition can also include an antioxidant. A
preferred antioxidant is butylated hydroxytoluene.
This embodiment of the invention can ~~.uther comprise a preservative
component. The preservative component can comprise at least one preservative
selected
from the group consisting of methylparaben, propylparaben, and diazolidinyl
urea.


CA 02408689 2002-11-12
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Preferably, the preservative component comprises all of methylparaben,
propylparaben, and
diazolidinyl urea.
This embodiment of the composition can further include fragrance as
S described above. The stability and function of the cream are not altered by
the presence or
absence of fragrance. As indicated above, it may be desirable to omit
fragrance in some
cases.
The following discussion describes ranges, preferred concentrations and
optimum concentrations for preferred compositions according to this embodiment
of the
present invention when the pH is adjusted to a range of from about 5.0 to
about 5.8.
Water can comprise from about. 50.0% to about 90.0% of this embodiment of
the composition. Preferably, water comprises from about 55.0% to about 75.0%
of this
embodiment of the composition. An optimum concentration of water is about
66.33% of this
embodiment of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of this
embodiment of the composition. Preferably, propylene glycol comprises from
about 4.2% to
about 7.0% of this embodiment of the composition. An optimum concentration of
propylene
glycol is about 5.70% of this embodiment of the composition.
Tetrasodium EDTA can comprise from about 0.05% to about 0.50% of this
embodiment of the composition. Preferably, tetrasodium EDTA comprises from
about 0.10%
to about 0.30% of this embodiment of the composition. An optimum concentration
of
tetrasodium EDTA is about 0.15% of this embodiment of the composition.
Ceteareth-25 can comprise from about 0.50% to about 4.0% of this
embodiment of the composition. Preferably, ceteareth-25 comprises from about
2.0% to
about 3.5% of this embodiment of the composition. An optimum concentration of
ceteareth-
25 is about 2.60% of this embodiment of the composition.
Citric acid can comprise from about 0.04% to about 0.40% of this embodiment
of the composition. Preferably, citric acid comprises from about 0.10% to
about 0.30% of
26


CA 02408689 2002-11-12
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this embodiment of the composition. An optimum concentration of citric acid is
about 0.12%
of this embodiment of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of this embodiment
of the composition. Preferably, lanolin oil comprises from about 8.0% to about
12.0% of this
embodiment of the composition. An optimum concentration of lanolin oil is
about 10.60% of
this embodiment of the composition.
Cetyl alcohol can comprise from about 3.0% to about 10.0% of this
embodiment of the composition. Preferably, cetyl alcohol comprises from about
3.5% to
about 7.5% of this embodiment of the composition. An optimum concentration of
cetyl
alcohol is about 4.30% of this embodiment of the composition.
Stearyl alcohol can comprise from about 1.0% to about 5.0% of this
1 S embodiment of the composition. Preferably, stearyl alcohol comprises from
about 2.0% to
about 4.0% of this embodiment of the composition. An optimum concentration of
stearyl
alcohol is about 3.50% of this embodiment of the composition.
Ceteareth-6 can comprise from about 0.5% to about 4.0% of this embodiment
of the composition. Preferably, ceteareth-6 comprises from about 1.0% to about
3.0% of this
embodiment of the composition. An optimum concentration of ceteareth-6 is
about 1.80% of
this embodiment of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of this embodiment
of the composition. Preferably, cod liver oil comprises from about 1.0% to
about 4.0% of
this embodiment of the composition. An optimum concentration of cod liver oil
is about
2.00% of this embodiment of the composition.
Butylated hydroxytoluene can comprise from about 0.10% to about 1.0% of
this embodiment of the composition. Preferably, butylated hydroxytoluene
comprises from
about 0.20% to about 0.80% of this embodiment of the composition. An optimum
concentration of butylated hydroxytoluene is about 0.50% of this embodiment of
the
composition.
27


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Methylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. Preferably, methylparaben comprises from about
0.15% to
0.40% of this embodiment of the composition. An optimum concentration of
methylparaben
is about 0.30% of this embodiment of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. Preferably, propylparaben comprises from about
0.15% to
about 0.40% of this embodiment of the composition. An optimum concentration of
propylparaben is about 0.25% of this embodiment of the composition.
Diazolidinyl urea can comprise from about 0.05% to about 0.50% of this
embodiment of the composition. Preferably, diazolidinyl urea comprises from
about 0.10%
to about 0.30% of this embodiment of the composition. An optimum concentration
of
diazolidinyl urea is about 0.15% of this embodiment of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of this embodiment
of the composition. Preferably, allantoin comprises from about 1.0% to about
2.0% of this
embodiment of the composition. An optimum concentration of allantoin is about
1.50% of
this embodiment of the composition.
If present, fragrance can comprise from about 0.05% to about 0.50% of this
embodiment of the composition. Preferably, fragrance comprises from about
0.10% to about
0.40% of this embodiment of the composition. An optimum concentration of
fragrance is
about 0.20% of this embodiment of the composition.
Yet another embodiment of a composition according to the present invention
is a composition comprising an oil-in-water emulsion comprising:
(1) allantoin; and
(2) ~an emulsifier system comprising:
(a) a polyethylene glycol ester of stearic acid; and
(b) glyceryl stearate.
Typically, the number of ethylene glycol moieties in the polyethylene glycol
ester of stearic acid is from 25 to 100. Two preferred polyethylene glycol
esters of stearic
28


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acid for use in this embodiment of compositions according to the present
invention are PEG-
40 stearate and PEG-100 stearate, with 40 and 100 "ethylene glycol moieties
respectively. A
particularly preferred polyethylene glycol ester of stearic acid is PEG-100
stearate.
In this embodiment of the composition, the composition further comprises an
acid to adjust the pH to a range of from about 3.0 to about 6Ø Preferably,
the pH is adjusted
to a range of from about 5.0 to about 5.8. The acid can be an inorganic or an
organic acid as
described above. Preferably, the acid is a weak organic acid. Most preferably,
the acid is
citric acid.
This embodiment can further comprise other ingredients. For example, this
embodiment of the invention can further comprise a solvent component.
Typically, the
solvent component is one or more of propylene glycol, glycerin, or butylene
glycol.
Preferably, the solvent component is propylene glycol.
This embodiment of the invention can further comprise a chelator component.
Preferably, the chelator component is tetrasodium ethylenediaminetetraacetic
acid.
This embodiment of the invention can further comprise an emollient
component. The emollient component can comprise at least one emollient
selected from the
group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver
oil. Preferably,
the emollient component comprises all of lanolin oil, cetyl alcohol, stearyl
alcohol, and cod
liver oil.
This embodiment of the composition can also include an antioxidant. A
preferred antioxidant is butylated hydroxytoluene.
This embodiment of the invention can further comprise a preservative
component. The preservative component can comprise at least one preservative
selected
from the group consisting of methylparaben, propylparaben, and diazolidinyl
urea.
Preferably, the preservative component comprises all of methylparaben,
propylparaben, and
diazolidinyl urea.
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This embodiment of the composition can further include fragrance as
described above. The stability and function of the cream are not altered by
the presence or
absence of fragrance. As indicated above, it may be desirable to omit
fragrance in some
cases.
The following discussion describes ranges, preferred concentrations and
optimum concentrations for preferred compositions according to this embodiment
of the
present invention when the pH is in the range of from about 5.0 to about 5.8.
Water can comprise from about 50.0% to about 90.0% of this embodiment of
the composition. Preferably, water comprises from about 55.0% to about 80.0%
of this
embodiment of the composition. An optimum concentration of water is about
67.86% of this
embodiment of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of this
embodiment of the composition. Preferably, propylene glycol comprises from
about 4.30%
to about 7.00% of this embodiment of the composition. An optimum concentration
of
propylene glycol is about 5.70% of this embodiment of the composition.
Tetrasodium EDTA can comprise from about 0.05% to about 0.50% of this
embodiment of the composition. Preferably, tetrasodium EDTA comprises from
about 0.10%
to about 0.30% of this embodiment of the composition. An optimum concentration
of
tetrasodium EDTA is about 0.15% of this embodiment of the composition.
Citric acid can comprise from about 0.04% to about 0.40% of this embodiment
of the composition. Preferably, citric acid comprises from about 0.10% to
about 0.30% of
this embodiment of the composition. An optimum concentration of citric acid is
about 0.14%
of this embodiment of the composition.
PEG-100 stearate can comprise from about 1.0% to about 5.0% of this
embodiment of the composition. Preferably, PEG-100 stearate comprises from
about 1.50%
to about 3.00% of this embodiment of the composition. An optimum concentration
of PEG-
100 stearate is about 2.60% of this embodiment of the composition.


CA 02408689 2002-11-12
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Lanolin oil can comprise from about 5.0% to about 15.0% of this embodiment
of the composition. Preferably, lanolin oil comprises from about 8.0% to about
12.0% of this
embodiment of the composition. An optimum concentration of lanolin oil is
about 10.60% of
this embodiment of the composition.
Cetyl alcohol can comprise from about 2.0% to about 10.0% of this
embodiment of the composition. Preferably, cetyl alcohol comprises from about
2.50% to
about 7.50% of this embodiment of the composition. An optimum concentration of
cetyl
alcohol is about 3.00% of this embodiment of the composition.
Stearyl alcohol can comprise from about 1.0% to about 4.0% of this
embodiment of the composition. Preferably, stearyl alcohol comprises from
about 1.0% to
about 3.5% of this embodiment of the composition. An optimum concentration of
stearyl
alcohol is about 2.50% of this embodiment of the composition.
Glyceryl stearate can comprise from about 1.0% to about 5.0% of this
embodiment of the composition. Preferably, glyceryl stearate comprises from
about 2.0% to
about 4.0% of this embodiment of the composition. An optimum concentration of
glyceryl
stearate is about 2.50% of this embodiment of the composition.
Cod liver oil can comprise from about 1.0% to about 7.0% of this embodiment
of the composition. Preferably, cod liver oil comprises from about 1.0% to
about 4.0% of
this embodiment of the composition. An optimum concentration of cod liver oil
is about
2.00% of this embodiment of the composition.
Butylated hydroxytoluene can comprise from about 0.10% to about 1.0% of
this embodiment of the composition. Preferably, butylated hydroxytoluene
comprises from
about 0.20% to about 0.80% of this embodiment of the composition. An optimum
concentration of butylated hydroxytoluene is about 0.50% of this embodiment of
the
composition.
Methylparaben can comprise from about 0.10% to about 0.50% of this .
embodiment of the composition. Preferably, methylparaben comprises from about
0.15% to
31


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0.40% of this embodiment of the composition. An optimum concentration of
methylparaben
is about 0.30% of this embodiment of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. Preferably, propylparaben comprises from about
0.15% to
about 0.40% of this embodiment of the composition. An optimum concentration of
propylparaben is about 0.25% of this embodiment of the composition.
Diazolidinyl urea can comprise from about 0.05% to about 0.50% of this
embodiment of the composition. Preferably, diazolidinyl urea comprises from
about 0.10%
to about 0.30% of this embodiment of the composition. An optimum concentration
of
diazolidinyl urea is about 0.20% of this embodiment of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of this embodiment
of the composition. Preferably, allantoin comprises from about 1.0% to about
2.0% of this
embodiment of the composition. A preferred concentration of allantoin is about
1.50% of
this embodiment of the composition.
If present, fragrance can comprise from about 0.05% to about 0.50% of this
embodiment of the composition. Preferably, fragrance comprises from about
0.10% to about
0.40% of this embodiment of the composition. An optimum concentration of
fragrance is
about 0.20% of this embodiment of the composition.
Yet another embodiment of a composition according to the present invention
is a composition comprising an oil-in-water emulsion comprising:
(1) allantoin;
(2) a carbohydrate polymer; and
(3) an emulsifier system comprising:
(a) beeswax; and
(b) an anionic emulsifier that is substantially hydrophilic and is
soluble in water.
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The carbohydrate polymer is typically selected from the group consisting of
galactoarabinan, polygalactose, and polyarabinose. Preferably, the
carbohydrate polymer is
galactoarabinan.
The anionic emulsifier that is substantially hydrophilic and soluble in water
can be selected from the group consisting of sodium lauryl sulfate, sodium
laureth sulfate,
sodium oleyl succinate, sodium dodecylbenzenesulfonate, and sodium lauryl
sarcosinate. A
particularly preferred anionic emulsifier is sodium lauryl sulfate.
The pH of the composition is adjusted to a range of between about 3.0 and
about 6.0, typically with an acid. Preferably, the pH is adjusted to a range
of from about 5.0
to about 6Ø The acid can be an inorganic or an organic acid as described
above. Preferably,
the acid is a weak organic acid. Most preferably, the acid is citric acid.
This embodiment can further comprise other ingredients. For example, this
embodiment of the invention can further comprise' a solvent component.
Typically, the
solvent component comprises at least one solvent selected from the group
consisting of
propylene glycol, glycerin, or butylene glycol. Preferably, the solvent
component is
propylene glycol.
This embodiment of the invention can further comprise a chelator component.
Preferably, the chelator component is tetrasodium ethylenediaminetetraacetic
acid.
t
This embodiment of the invention can further comprise an emollient
component. The emollient component can comprise at least one emollient
selected from the
group consisting of lanolin oil, cetyl alcohol, stearyl alcohol, and cod liver
oil. Preferably,
the emollient component comprises all of lanolin oil, cetyl alcohol, stearyl
alcohol, and cod
liver oil.
This embodiment of the composition can also include an antioxidant. A
preferred antioxidant is butylated hydroxytoluene.
This embodiment of the invention can further comprise a preservative
component. The preservative component can comprise one or more of
methylparaben or
33


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propylparaben. Preferably, the preservative component comprises methylparaben
and
propylpaxaben.
This embodiment of the composition can further include fragrance as
described above. The stability and function of the cream are not altered by
the presence or
absence of fragrance. As indicated above, ~it may be desirable to omit
fragrance in some
cases.
The following discussion describes ranges, preferred concentrations and
optimum concentrations for preferred compositions according to this embodiment
of the
present invention when the pH is adjusted to a range of from about 5.0 to
about 6Ø
Water can comprise from about 50.0% to about 90.0% of this embodiment of
the composition. Preferably, water comprises from about 60.0% to about 80.0%
of this
embodiment of the composition. An optimum concentration of water is about
61.65% of this
embodiment of the composition.
Propylene glycol can comprise from about 2.0% to about 9.0% of this
embodiment of the composition. Preferably, propylene glycol comprises from
about 4.0% to
about 7.0% of this embodiment of the composition. An optimum concentration of
propylene
glycol is about 5.70% of this embodiment of the composition.
Sodium lauryl sulfate, as a 30% solution, can comprise from about 0.50% to
about 5.0% of this embodiment of the .composition. Preferably, sodium lauryl
sulfate, as a
30% solution, comprises from about 1.0% to about 3.0% of this embodiment of
the
composition. An optimum concentration of sodium lauryl sulfate, as a 30%
solution, is about
1.90% of this embodiment of the composition.
Tetrasodium EDTA can comprise from about 0.05% to about 0.30% of this
embodiment of the composition. Preferably, tetrasodium EDTA comprises from
about 0.10%
to about 0.20% of this embodiment of the ' composition. An optimum
concentration of
tetrasodium EDTA is about 0.15% of this embodiment of the composition.
34


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Galactoarabinan can comprise from about 1.0% to about 25.0% of this
embodiment of the composition. Preferably, galactoarabinan comprises from
about 3.0% to
about 15.0% of this embodiment of the composition. An optimum concentration of
galactoarabinan is about 5.00% of this embodiment of the composition.
Citric acid can comprise from about 0.05% to about 0.25% of this embodiment
of the composition. Preferably, citric acid comprises from about 0.10% to
about 0.20% of
this embodiment of the composition. An optimum concentration of citric acid is
about 0.15%
of this embodiment of the composition.
Lanolin oil can comprise from about 5.0% to about 15.0% of this embodiment
of the composition. Preferably, lanolin oil comprises from about 8.0% to about
12.0% of this
embodiment of the composition. An optimum concentration of lanolin oil is
about 10.60% of
this embodiment of the composition.
Cetyl alcohol can comprise from about 1.0% to about 8.0% of this
embodiment of the composition. Preferably, cetyl alcohol comprises from about
2.0% to
about 7.0% of this embodiment of the composition. An optimum concentration of
cetyl
alcohol is about 4.20% of this embodiment of the composition.
Stearyl alcohol can comprise from about 0.50% to about 6.0% of this
embodiment of the composition. Preferably, stearyl alcohol comprises from
about 1.0% to
about 4.0% of this embodiment of the composition. An optimum concentration of
stearyl
alcohol is about 2.00% of this embodiment of the composition.
Beeswax can comprise from about 0.50% to about 5.0% of this embodiment of
the composition. Preferably, beeswax comprises from about 1.0% to about 3.0%
of this
embodiment of the composition. An optimum concentration of beeswax is about
1.90% of
this embodiment of the composition.
Cod liver oil can comprise from about 0.50% to about 15.0% of this
embodiment of the composition. Preferably, cod liver oil comprises from about
1.0% to
about 10.0% of this embodiment of the composition. An optimum concentration of
cod liver
oil is about 2.00% of this embodiment of the composition.


CA 02408689 2002-11-12
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Butylated hydroxytoluene can comprise from about 0.1 % to about 3.0% of this
embodiment of the composition. Preferably, butylated hydroxytoluene comprises
from about
0.25% to about 2.50% of this embodiment of the .composition. An optimum
concentration of
butylated hydroxytoluene is about 0.50% of this embodiment of the composition.
Methylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. Preferably, methylparaben comprises from about
0.15% to
about 0.40% of this embodiment of the composition. An optimum concentration of
methylparaben is about 0.30% of this embodiment of the composition.
Propylparaben can comprise from about 0.10% to about 0.50% of this
embodiment of the composition. Preferably, propylparaben comprises from about
0.15% to
about 0.40% of this embodiment of the composition. An optimum concentration of
propylparaben is about 0.25% of this embodiment of the composition.
Allantoin can comprise from about 0.50% to about 2.0% of this embodiment
of the composition. Preferably, allantoin comprises from about 1.0% to about
2.0% of this
embodiment of the composition. An optimum concentration of allantoin is about
1.50% of
this embodiment of the composition.
If present, fragrance can comprise from about 0.05% to about 0.50% of this
embodiment of the composition. Preferably, if present, fragrance can comprise
from about
0.10% to about 0.40% of this embodiment of the composition. An optimum
concentration of
fragrance is about 0.20% of this embodiment of the composition.
Examples of particularly preferred compositions according to the present
invention are described below.
The composition is prepared by standard mixing techniques, such as are
conventional in the cosmetic art and in the art of over-the-counter drug
formulation for
blending ,lipid-soluble components and water-soluble components. These mixing
techniques
include both manual and mechanical mixing, and include homogenization mixing
and sweep
mixing. The mixing techniques to be used can be chosen by one of ordinary
skill in the art
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based on variables such as the viscosity of the components to be mixed and the
volume of
those components, as well as the relative proportion of lipid-soluble and
water-soluble
ingredients. The composition can be mixed in two or more batches, such as one
batch
containing lipid-soluble ingredients and another batch containing water-
soluble ingredients,
and the batches can then be mixed at the final stage of preparation.
The batches to be used are shown in Tables 1-11.
Compositions according to the present invention can be formulated for the
treatment of skin diseases and conditions. Among the skin diseases and
conditions for which
compositions according to the present invention can be formulated are
epidermolysis bullosa,
decubitus ulcers, pressure ulcers, diabetic ulcers, and milia. Compositions
according to the
present invention can be formulated for treatment of other skin diseases and
conditions. The
details of the composition can be varied according to the particular condition
to be treated.
For example, greater or lesser degrees of oil or lipid-soluble components can
be included;
and, in the case of compositions intended to be used on patients who may
undergo allergic
reactions, compounds that often generate allergic reactions, such as fragrance
and coloring,
can be excluded. Such details can readily be ascertained by one of ordinary
skill in the art.
The invention is illustrated by the following Examples. These Examples are
for illustrative purposes only and are not intended to limit the invention.
Example 1
Preparation of Skin Protectant Over-the-Counter Cream with pH of 7.4
(Prior Art Example)
A skin protectant over-the-counter (OTC) cream was prepared in accordance
with the formulation of Table 1.
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CA 02408689 2002-11-12
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TABLE 1
COMPOSITION OF ALLANTOIN-CONTAINING SKIN CREAM'VVITH pH OF 7.4
INGREDIENT RANGE PREFERRED OPTIMUM



Part A



Water 50.0-90.0 55.0-75.0 66.20


Sodium Lauryl Sulfate 0.50-2.50 1.00-2.50 1.90
(30%)


Propylene Glycol 2.0-9.0 3.0-6.0 5.30


Tetrasodium EDTA 0.05-0.50 O.I O-0.30 0.1 S



Part B



Lanolin Oil 5.0-15.0 8.0-12.0 10.60


Cetyl Alcohol 3.0-10.0 3.5-7.5 6.80


Stearyl Alcohol 1.0-5.0 1.0-3.0 2.00


Beeswax O.SO-2.50 1.0-2.5 1.90


Cod Liver Oil 1.0-7.0 1.0-4.0 2.00


BHT 0.10-1.00 0.20-0.80 O.SO



Part C



St. John's Wort Extract0.05-0.50 0.05-0.15 0.10


Witch Hazel Extract O.OS-0.50 0.05-0.15 0.10


Chamomile Extract 0.05-O.SO 0.05-0.15 0.10


Arnica Extract 0.05-O.SO O.OS-0.15 0.10


Methylparaben 0.10-0.50 0.15-0.40 0.30


Propylparaben 0.10-0.50 0.10-0.3 0 0.25


Allantoin 0.50-2.00 0.50-2.00 1.50


Fragrance 0.05-0.50 0.10-0.30 0.20


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The Part A ingredients were combined and heated to 175°F with
mixing. The
Part B ingredients were combined and heated to 175°F with mixing. The
Part B mixture was
then added to the Part A mixture with mixing. The resulting mixture was then
cooled to
120°F with continued mixing. The Part C ingredients were then added
with mixing. The
final emulsion was allowed to cool with continued mixing. The resulting cream
had a pH of
7.4. Samples of the cream prepared from Example 1 were used for accelerated
aging stability
studies and analyzed for their allantoin concentration after a period of time
at 40°C. The
results are shown in Table ~.
As can be seen from Table 2, the allantoin in the cream from Example 1
undergoes degradation and would not meet the specifications required for an
OTC drug.
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TABLE 2
STABILITY OF ALLANTOIN IN SKIN CREAM COMPOSITION
OF EXAMPLE 1 WITH STORAGE AT 40°C
Days at 40C Weight % Allantoin



0 1.5



30 1.4



60 1.3



90 1.2




CA 02408689 2002-11-12
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Example 2
Preparation of a Cream Containing Allantoin with Lower pH
An OTC skin cream containing allantoin was prepared using the ingredients in
Table 3 to provide a cream with a lower pH.
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TABLE 3
COMPOSITION OF ALLANTOIN-CONTAINING
SKIN CREAM WITH pH OF 5.3
INGREDIENT RANGE PREFERRED OPTIMUM



Part A



Water 50.0-90.0 55.0-75.0 68.68


Sodium Lauryl Sulfate'(30%)0.50-2.50 1.00-2.50 1.90


Propylene Glycol 2.0-9.0 3.0-6.0 5.30


Tetrasodium EDTA 0.05-0.50 0.10-0.30 0.15


Citric Acid 0.05-0.50 0.08-0.35 0.12



Part B



Lanolin Oil 5.0-1 S.0 8.0-12.0 10.60


Cetyl Alcohol 3.0-10.0 3.5-7.5 4.20


Stearyl Alcohol 1.0-5.0 1.0-3.0 2.00


Beeswax 0.50-2.50 1.0-2.5 1.90


Cod Liver Oil 1.0-7.0 1.0-4.0 2.00


BHT 0.10-1.00 0.20-0.80 0.50



Part C



St. John's Wort Extract0.05-0.50 0.05-0.15 0.10


Witch Hazel Extract 0.05-0.50 O.OS-0.15 0.10


Chamomile Extract 0.05-0.50 0.05-0.15 0.10


Arnica Extract - 0.05-O.SO 0.05-0.15 0.10


Methylparaben O. I O-0.50 O.1 S-0.40 0.30


Propylparaben 0.10-0.50 0.10-0.30 0.25


Allantoin 0. 5 0-2. 00 0.5 0-2. 00 1.5 0


Fragrance 0.05-0.50 0.10-0.30 0.20


The Part A ingredients were combined and heated to 17S°F with
mixing. The
Part B ingredients were combined and heated to 17S°F with mixing. The
Part B mixture was
added to the Part A rriixture with mixing. The resulting mixture was then
cooled to 120°F
with mixing at which time the Part C ingredients were added with mixing. The
fnal
emulsion was allowed to cool with continue mixing. The resulting cream had a
pH of 5.3.
It was found that a similar cream was produced if Part B was added to Part A
or Part A was added to Part B. However, the cream has a better appearance if
the oil phase
and water phase are homogenized under high shear after the two phases are
added to one
another.
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Samples of the cream of this example were used for accelerated aging stability
studies and analyzed for theix allantoin concentration. The results are shown
in Table 4. As
can be seen from Table 4, the allantoin is stable over time in a cream with a
pH of 5.3.
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TABLE 4
STABILITY OF ALLANTOIN IN SKIN CREAM COMPOSITION OF
EXAMPLE 2 WITH STORAGE AT 40°C
Days at 40C Weight % Allantoin



0 1.4



30 1.4



60 1.4



90 1.4


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Example 3
Preparation of Allantoin-Containing Skin Cream with Ionic Emulsifiers
An allantoin-containing skin cream with ionic emulsifiers is prepared
according to Table 5. The preparation follows the method used in Example 2,
with the
ingredients in each of Part A, Part B, and Part C being combined separately
and then Part B
being added to Part A, with Part C then being added to the combination of Part
A and Part B.
The pH is adjusted to a value in a range of from about 5.0 to about 5.8 by
neutralizing the
stearic acid with enough triethanolamine to reach this pH. Other bases can be
used instead of
triethanolamine.


CA 02408689 2002-11-12
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TABLE 5
ALLANTOIN-CONTAINING SKIN CREAM WITH IONIC EMULSIFIERS
INGREDIENT RANGE PREFERRED OPTIMUM


Part A


Water 50.0 - 90.0 60.0 - 85.0 71.70


Propylene Glycol 2.0 - 9.0 4.0 - 7.0 5.70


Triethanolamine (99%)0.20 - 4.0 0.50 - 3.0 1.25


Part B


Lanolin Oil 5.0 - 15.0 8.0 - 12.0 10.60


Cetyl Alcohol 1.0 - 7.0 2.0 - 6.0 3.50


Stearic Acid 0.50 - 5.0 1.0 - 4.0 2.50


Cod Liver Oil 1.0 - 7.0 1.5 - 5.0 2.00


Butylated Hydroxytoluene0.10 - 1.0 0.20 - 0.80 0.50


Part C


Methylparaben 0.10 - 0.50 0.15 - 0.40 0.30


Propylparaben 0.10 - 0.50 0.15 - 0.40 0.25


Allantoin 0.50 - 2.0 1.0 - 2.0 1.50


Fragrance 0.05 - 0.50 0.10 - 0.40 0.20


46


CA 02408689 2002-11-12
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Example 4
Preparation of Allantoin-Containing Skin Cream with Lactylate Emulsifiers
An allantoin-containing skin cream with the emulsifiers sodium stearoyl
lactylate and sodium isostearoyl lactylate is prepared according to Table 6.
The preparation
follows the method used in Example 3. The pH is adjusted by the addition of
the appropriate
quantity of citric acid.
47


CA 02408689 2002-11-12
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TABLE 6
ALLANTOIN-CONTAINING SKIN CREAM WITH LACTYLATE EMULSIFIERS
INGREDIENT RANGE PREFERRED OPTIMUM
Part A
Water 50.0 - 90.0 60.0 - 80.0 73.42


Propylene Glycol . 2.0 - 9.0 ~ 4.0 - 7.0 5.70


Citric Acid 0.05 - 0.50 0.10 - 0.40 0.18


Sodium Stearoyl Lactylate0.30 - 3.0 0.50 - 2.50 1.00


Sodium Isostearoyl 0.05 - 1.0 0.10 - 0.70 0.25
Lactylate


Tetrasodium EDTA 0.05 - 0.25 0.10 - 0.20 0.15


Part B
Lanolin Oil 5.0 - 15.0 8.0 - 12.0 10.60


Cetyl Alcohol 1.0 - 8.0 2.0 - 7.0 3.80


Cod Liver Oil 1.0 - 7.0 1.0 - 4.0 2.00


Butylated Hydroxytoluene0.10 - 1.0 0.20 - 0.80 0.50


Part C


Methylparaben 0.10 - 0.50 0.15 - 0.40 0.30


Propylparaben 0.10 - 0.50 0.15 - 0.40 0.25


Allantoin 0.50 - 2.0 1.0 - 2.0 1.50


Fragrance 0.05 - 0.50 0.10 - 0.40 0.20


48


CA 02408689 2002-11-12
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Example 5
Preparation of Allantoin-Containi~~Skin Cream with Carbo~nolymethylene Polymer
An allantoin-containing skin cream with carboxypolymethylene polymer is
prepared according to Table 7. The preparation follows the method used in
Example 3,
except that the triethanolamine (Part D) is added last, after the combining of
Parts A, B, and
C, to avoid thickening of the emulsion. The triethanolamine is added to adjust
the pH.
49

CA 02408689 2002-11-12


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TABLE 7


ALLANTOIN-CONTAINING
SKIN CREAM WITH


CARBOXYPOLYMETHYLENE
POLYMER



INGREDIENT RANGE PREFERRED OPTIMUM


Part A


Water 50.0 - 90.0 60.0 - 80.0 73.55


Carboxypolymethylene 0.40 - 3.0 0.50 - 2.0 1.00


Polymer


Propylene Glycol 2.0 - 9.0 4.0 - 7.0 5.70


Part B


Lanolin Oil 5.0 - 15.0 8.0 - 12.0 10.00


Cetyl Alcohol 1.0 - 8.0 2.0 - 7.0 3.00


Cod Liver Oil 1.0 - 7.0 ~ 1.0 - 4.0 2.00


Butylated Hydroxytoluene0.10 - 1.0 0.20 - 0.80 0.50


Part C


Methylparaben 0.10 - 0.50 0.15 - 0:40 0.30


Propylparaben 0.10 - 0.50 0.15 - 0.40 0.25


Allantoin 0.50 - 2.0 1.0 - 2.0 1.50


Fragrance 0.05 - 0.50 0.10 - 0.40 0.20


Part D


Triethanolamine (99%)0.05 - 3.0 0.20 - 2.0 0.80





CA 02408689 2002-11-12
WO 01/87232 PCT/USO1/14899
Example 6
Pr~aration of Allantoin-Containing Skin Cream with Polyet>~lene Glycol Ethers
of Cetearyl
Alcohol
An allantoin-containing skin cream with polyethylene glycol ethers of cetearyl
alcohol is prepared according to Table 8. The preparation follows the method
used in
Example 3. The citric acid is added to adjust the pH.
51

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TABLE 8


ALLANTO1N-CONTAINING
SKIN CREAM WITH


POLYETHYLENE GLYCOL
ETHERS OF CETEARYL
ALCOHOL



INGREDIENT RANGE PREFERRED OPTIMUM


Part A


Water 50.0 - 90.0 55.0 - 75.0 66.33


Propylene Glycol 2.0 - 9.0 4.0 - 7.0 5.70


Tetrasodium EDTA 0.05 - 0.50 0.10 - 0.30 0.15


Ceteareth-25 0.50 - 4.0 2.00 - 3.50 2.60


Citric Acid 0.04 - 0.40 0.10 - 0.30 0.12


Part B


Lanolin Oil 5.0 -15.0 8.0 - 12.0 10.60


Cetyl Alcohol 3.0 -10.0 3.5 - 7.5 4.30


Stearyl Alcohol 1.0 - 5.0 2.0 - 4.0 3.50


Ceteareth-6 0.50 - 4.0 1.0 - 3.0 1.80


Cod Liver Oil 1.0 - 7.0 1.0 - 4.0 2.00


Butylated Hydroxytoluene0.10 - 1.0 0.20 - 0.80 0.50


Part C


Methylparaben 0.10 - 0.50 0.15 - 0.40 0.30


Propylparaben 0.10 - 0.50 0.15 - 0.40 0.25


Diazolidinyl Urea 0.05 - 0.50 0.10 - 0.30 0.15


Allantoin 0.50 - 2.0 1.0 - 2.0 1.50


Fragrance 0.05 - 0.50 0.10 - 0.30 0.20



52


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Example 7
Preparation of Allantoin-Containing Skin Cream with Pol~ylene Glycol Ester of
Stearic
Acid and Glycerol Stearate
An allantoin-containing skin cream with a polyethylene glycol ester of stearic
acid and glyceryl stearate is prepared according to Table 9. The preparation
follows the
method used in Example 3. The citric acid is added to adjust the pH.
53


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TABLE 9
ALLANTO1N-CONTAINING SKIN CREAM WITH
POLYETHYLENE GLYCOL ESTER OF STEARIC ACID
AND GLYCERYLSTEARATE
INGREDIENT RANGE PREFERRED OPTIMUM
Part A
Water 50.0 - 90.0 55.0 - 80.0 67.86


Propylene Glycol 2.0 - 9.0 4.3 - 7.0 5.70


Tetrasodium EDTA 0.05 - 0.50 0.10 - 0.30 0.15


Citric Acid 0.04 - 0.40 0.10 - 0.30 0.14


PEG-100 Stearate 1.0 - 5.0 1.5 - 3.0 2.60


Part B
Lanolin Oil 5.0 - 15.0 2.0 - 12.0 10.60


Cetyl Alcohol 3.0 - 10.0 2.5 - 7.5 3.0


Stearyl Alcohol 1.0 - 4.0 1.0 - 3.5 2.50


Glyceryl Stearate 1.0 - 5.0 2.0 - 4.0 2.50


Cod Liver Oil 1.0 - 7.0 1.0 - 4.0 2.00


Butylated Hydroxytoluene0.10 - 1.0 0.20 - 0.80 0.50


Part C


Methylparaben 0.10 - 0.50 0.15 - 0.40 0.30


Propylparaben 0.10 - 0.50 0.15 - 0.40 0.25


Diazolidinyl Urea 0.05 - 0.50 0.10 - 0.30 0.20


Allantoin 0.50 - 2.00 1.0 - 2.0 1.50


Fragrance 0.05 - 0.50 0.10 - 0.40 0.20


54


CA 02408689 2002-11-12
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Example 8
Preparation of Allantoin-Containing Skin Cream with Carboxynolymethvlene
Polymer and
Pol,~ylene Glycol Ester of Stearic Acid
An allantoin-containing skin cream with a caxboxypolymethylene polymer and
a polyethylene glycol ester of stearic acid is prepared according to Table 10.
The preparation
follows the method used in Example 5, with the triethanolamine (Part D) being
added last.
The triethanolamine is added to adjust the pH.


CA 02408689 2002-11-12
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TABLE 10
ALLANTOIN-CONTAINING SKIN CREAM WITH
A CARBOXYPOLYMETHYLENE POLYMER AND A
POLYETHYLENE GLYCOL ESTER OF STEARIC ACID
INGREDIENT RANGE PREFERRED OPTIMUM
Part A
Water 50.0 - 90.0 60.0 - 85.0 69.95


Carboxypolymethylene Polymer0.30 - 3.0 0.50 - 2.0 0.85


Propylene Glycol 2.0 - 9.0 4.0 - 7.0 5.70


PEG-100 Stearate 4.25 - 2.5 0.50 - 2.0 1.50


Part B
Lanolin Oil 5.0 - 15.0 8.0 - 12.0 10.60


Cetyl Alcohol 1.0 - 8.0 2.0 - 7.0 4.20


Stearyl Alcohol 0.50 - 6.0 0.75 - 5.0 1.50


Cod Liver Oil ~ 1.0 - 7.0 1.0 - 4.0 2.00


Butylated Hydroxytoluene0.10 - 1.0 0.X0 - 0.80 0.50


Part C
Methylparaben 0.10 - 0.50 0.15 - 0.40 0.30


Propylparaben 0.10 - 0.50 0.15 - 0.40 0.25


Diazolidinyl Urea 0.05 - 0.25 0.10 - 0.20 0.15


Allantoin 0.50 - 2.0 1.0 - 2.0 1.50


Fragrance 0.05 - 0.50 0.10 - 0.40 0.20


Part D
Triethanolamine (99°1°) 0.05 - 3.0 0.20 - 2.0 0.80
56


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Example 9
Preparation of Allantoin-Containing Skin Cream with Galactoarabinan, Sodium
Lauryl
Sulfate, and Beeswax
An allantoin-containing skin cream with galactoarabinan, sodium lauryl
sulfate, and beeswax is prepared according to Table 11. The preparation
follows the method
used in Example 3. The citric acid is used to adjust the pH.
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CA 02408689 2002-11-12
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TABLE 11
ALLANTO1N-CONTAINING SKIN CREAM WITH
GALACTOARABINAN, SODIUM LAURYL SULFATE,
AND BEESWAX
INGREDIENT RANGE PREFERRED OPTIMUM
Part A
Water 50.0 - 90.0 60.0 - 80.0 61.65


Propylene Glycol 2.0 - 9.0 4.0 - 7.0 5.70


Sodium Lauryl Sulfate 0.50 - 5.0 1.0 - 3.0 1.90
(30%)


Tetrasodium EDTA 0.05 - 0.30 0.10 - 0.20 0.15


Galactoarabinan 1.0 - 25.0 3.0 - 15.0 5.00


Citric Acid 0.05 - 0.25 0.10 - 0.20 0.15


Part B
Lanolin Oil 5.0 - 15.0 8.0 - 12.0 10.60


Cetyl Alcohol 1.0 - 8.0 2.0 - 7.0 4.20


Stearyl Alcohol 0.50 - 6.0 1.0 - 4.0 2.00


Beeswax 0.50 - 5.0 1.0 - 3.0 1.90


Cod Liver Oil 0.50 - 15.0 1.0 - 10.0 2.00


Butylated Hydroxytoluene0.10 - 3.0 0.25 - 2.5 0.50


Part C
Methylparaben 0.10 - 0.50 0.15 - 0.40 0.30


Propylpaxaben 0.10 - 0.50 0.15 - 0.40 0.25


Allantoin 0.50 - 2.0 1.0 - 2.0 1.50


Fragrance 0.05 - 0.50 0.10 - 0.40 ~ 0.20


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ADVANTAGES OF THE PRESENT INVENTION
The present invention provides an allantoin-containing composition that is an
oil-water emulsion using either an acidic anionic polymer and an anionic
emulsifier or an
acidic anionic polymer and a nonionic emulsifier that is an ethoxylated ether
or ethoxylated
ester. The composition can further include a carbohydrate polymer that can be
polygalactose
or polyarabinose. If an ethoxylated ether or ethoxylated ester is used, the
composition can
further comprise glyceryl stearate. The composition has improved thermal
stability. The
composition according to the present invention is useful for treatment of a
number of skin
diseases and conditions, including epidermolysis bullosa, pressure ulcers,
diabetic ulcers,
decubitus ulcers, and milia. Compositions according to the present invention
are also useful
as skin protectants even when these diseases are not present. Compositions
according to the
present invention are well tolerated and can be used with other treatments.
Although the present invention has been described in considerable detail, with
reference to certain preferred versions thereof, other versions and
embodiments are possible.
Therefore, the scope of the invention is determined by the following claims. .
59