U.S. patent number RE44,302 [Application Number 12/722,170] was granted by the patent office on 2013-06-18 for n-acetyl aldosamines, n-acetylamino acids and related n-acetyl compounds and their topical use.
The grantee listed for this patent is Eugene J. Van Scott, Ruey J. Yu. Invention is credited to Eugene J. Van Scott, Ruey J. Yu.
United States Patent |
RE44,302 |
Yu , et al. |
June 18, 2013 |
N-acetyl aldosamines, N-acetylamino acids and related N-acetyl
compounds and their topical use
Abstract
Compositions comprising N-acetyl-aldosamines, N-acetylamino
acids, and related N-acetyl compounds are useful to alleviate or
improve various cosmetic conditions and dermatological disorders,
including changes or damage to skin, nail and hair associated with
intrinsic aging and/or extrinsic aging, as well as changes or
damage caused by extrinsic factors. N-acetyl-aldosamines,
N-acetylamino acids, and related N-acetyl composition may further
comprise a cosmetic, pharmaceutical or other topical agent to
enhance or create synergetic effects.
Inventors: |
Yu; Ruey J. (Chalfont, PA),
Van Scott; Eugene J. (Abington, PA) |
Applicant: |
Name |
City |
State |
Country |
Type |
Yu; Ruey J.
Van Scott; Eugene J. |
Chalfont
Abington |
PA
PA |
US
US |
|
|
Family
ID: |
22852222 |
Appl.
No.: |
12/722,170 |
Filed: |
March 11, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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12536209 |
Aug 5, 2009 |
Re. 42902 |
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11590898 |
Nov 1, 2006 |
Re. 41339 |
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Reissue of: |
09227213 |
Jan 8, 1999 |
6159485 |
Dec 12, 2000 |
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Current U.S.
Class: |
424/401; 514/847;
514/557; 514/574; 514/554; 514/844 |
Current CPC
Class: |
A61K
31/401 (20130101); A61Q 19/02 (20130101); A61K
31/405 (20130101); A61Q 3/00 (20130101); A61K
45/06 (20130101); A61K 9/06 (20130101); A61P
17/06 (20180101); A61Q 5/00 (20130101); A61K
8/447 (20130101); A61Q 19/007 (20130101); A61K
8/44 (20130101); A61K 8/4913 (20130101); A61P
17/00 (20180101); A61K 31/4045 (20130101); A61P
17/04 (20180101); A61K 31/7008 (20130101); A61K
31/198 (20130101); A61P 43/00 (20180101); A61Q
19/00 (20130101); A61K 8/60 (20130101); A61K
9/0014 (20130101); A61P 17/10 (20180101); A61P
31/10 (20180101); A61Q 5/006 (20130101); A61P
17/02 (20180101); A61P 29/00 (20180101); A61Q
19/08 (20130101); A61K 31/198 (20130101); A61K
2300/00 (20130101); A61K 31/401 (20130101); A61K
2300/00 (20130101); A61K 31/4045 (20130101); A61K
2300/00 (20130101); A61K 31/405 (20130101); A61K
2300/00 (20130101); A61K 31/7008 (20130101); A61K
2300/00 (20130101); A61Q 5/02 (20130101); Y10S
514/844 (20130101); Y10S 514/847 (20130101); A61Q
19/008 (20130101) |
Current International
Class: |
A61K
8/02 (20060101) |
Field of
Search: |
;424/401
;514/554,557,574,844,847 |
References Cited
[Referenced By]
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WO |
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May 1997 |
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WO |
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98/52576 |
|
Nov 1998 |
|
WO |
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Primary Examiner: Soroush; Ali
Attorney, Agent or Firm: Pillsbury Winthrop Shaw Pittman
LLP
Parent Case Text
.Iadd.Notice: This is a continuation reissue application of
continuation reissue application Ser. No. 12/536,209 filed Aug. 5,
2009, now Reissue U.S. Pat. No. Re. 42,902, which is a continuation
reissue application of reissue application Ser. No. 11/590,898
filed Nov. 1, 2006, now Reissue U.S. Pat. No. Re. 41,339, which is
a reissue application of U.S. Pat. No. 6,159,485. .Iaddend.
Claims
We claim:
.[.1. A composition comprising (A) a pharmaceutically acceptable
vehicle for topical treatment of cosmetic conditions or
dermatological disorders and (B) a therapeutically effective amount
of at least one compound selected from the group consisting of
N-acetyl aldosamines, N-acetylamino acids, and isomeric or
nonisomeric, free acid, salt, lactone, amide, or ester forms
thereof, wherein said N-acetyl aldosamine has the formula:
##STR00003## wherein n is an integer; R.sub.1 is selected from the
group consisting of CHO, CONH.sub.2, and COOR.sub.3; R.sub.2 is
selected from the group consisting of H, I, F, Cl, Br, and an
alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated,
straight or branched chain or cyclic form having 1 to 19 carbon
atoms; R.sub.3 is selected from the group consisting of H and an
alkyl, aralkyl, or aryl group having from 1 to 9 carbon atoms,
wherein said N-acetylamino acid or isomeric or nonisomeric, free
acid, salt, lactone, amide, or ester form thereof is at least one
member selected from the group consisting of N-acetyl-glycine,
N-acetyl-alanine, N-acetyl-valine, N-acetyl-leucine,
N-acetyl-isoleucine, N-acetyl-serine, N-acetyl-threonine,
N-acetyl-tyrosine, N-acetyl-methionine, N-acetyl-aspartic acid,
N-acetyl-asparagine, N-acetyl-glutamine, N-acetyl-arginine,
N-acetyl-lysine, N-acetyl-histidine, N-acetyl-phenylalanine,
N-acetyl-tyrosine, N-acetyl-tryptophan, N-acetyl-.beta.-alanine,
N-acetyl-taurine, N-acetyl-r-aminobutanoic acid,
N-acetyl-hydroxyproline, N-acetyl-canavanine,
N-acetyl-hydroxylysine, N-acetyl-cycloserine,
N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline,
N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline,
N-acetyl-ethionine, N-acetyl-methoxinine,
N-acetyl-.beta.-aminoisobutanoic acid, N-acetyl-homocysteine,
N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine,
N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine
(N-acetyl-serotonin), N-acetyltryptamine, N-acetyl-ornithine,
N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa,
N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine,
N-acetyl-3,5,3'-triiodothyronine, N-acetyl-thyroxine,
N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine,
N-acetyl-homocystine, and isomeric or nonisomeric, free acid, salt,
lactone, amide, or ester forms thereof, and N-acetyl-glutamic acid
and isomeric or nonisomeric, free acid, lactone, amide, or ester
forms thereof..].
.[.2. The composition of claim 1, wherein said N-acetyl aldosamine
or isomeric or nonisomeric, free acid, salt, lactone, amide, or
ester form thereof is at least one member selected from the group
consisting of N-acetyl-glycerosamine, N-acetyl-erythrosamine,
N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl-arabinosamine,
N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine,
N-acetyl-altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine,
N-acetyl-gulosamine, N-acetyl-idosamine, N-acetyl-galactosamine,
N-acetyl-talosamine, N-acetyl-glucoheptosamine,
N-acetyl-galactoheptosamine, N-acetyl-mannoheptosamine,
N-acetyllactosamine, N-acetylmuramic acid, N-acetylneuramine,
N-acetylneuramin Lactose, N-acetyl-glyceraminic acid,
N-acetyl-erythrosaminic acid, N-acetyl-threosaminic acid,
N-acetyl-ribosaminic acid, N-acetyl-arabinosaminic acid,
N-acetyl-xylosaminic acid, N-acetyl-lyxosaminic acid,
N-acetyl-allosaminic acid, N-acetyl-altrosaminic acid,
N-acetyl-glucosaminic acid, N-acetyl-mannosaminic acid,
N-acetyl-gulosaminic acid, N-acetyl-idosaminic acid,
N-acetyl-galactosaminic acid, N-acetyl-talosaminic acid,
N-acetyl-heptoglucosaminic acid, N-acetyl-heptogalactosaminic acid,
N-acetyl-heptomannosaminic acid, N-acetyl-N-acetylneuraminic acid,
and isomeric or nonisomeric, free acid, salt, lactone, amide, or
ester forms thereof..].
.[.3. The composition of claim 1, wherein said cosmetic conditions
and dermatological disorders are selected from the group consisting
of disturbed keratinization, defective syntheses of dermal
components, and changes associated with aging of skin, nail and
hair, conditions and disorders which include dryness or loose of
skin, nail and hair, xerosis, ichthyosis, palmar hyerperkeratoses,
plantar hyperkeratoses, uneven and rough surfaces of skin, nail and
hair, dandruff, Darier's disease, lichen simplex chronicus,
keratoses, acne, pseudofolliculitis barbae, eczema, psoriasis,
pruritus, warts, herpes, age spots, lentigines, melasmas, blemished
skin, hyperkeratoses, hyperpigmented skin, abnormal or diminished
syntheses of collagen, glycosaminoglycans, proteoglycans and
elastin as well as diminished levels of such components in the
dermis, stretch marks, skin lines, fine lines, wrinkles, thinning
of skin, nail plate and hair, skin thickening due to elastosis of
photoaging, loss or reduction of skin, nail and hair resiliency,
elasticity and recoilability, lack of skin, nail and hair
lubricants and luster, dull and older-looking skin, nails and hair,
and fragility and splitting of nails and hair..].
.[.4. A composition comprising: (A) a pharmaceutically acceptable
vehicle for topical treatment of cosmetic conditions or
dermatological disorders, (B) a therapeutically effective amount of
at least one compound selected from the group consisting of
N-acetyl aldosamines, N-acetylamino acids, and isomeric or
nonisomeric, free acid, salt, lactone, amide, or ester forms
thereof, wherein said N-acetyl aldosamine has the formula:
##STR00004## wherein n is an integer; R.sub.1 is selected from the
group consisting of CHO, CONH.sub.2, and COOR.sub.3; R.sub.2 is
selected from the group consisting of H, I, F, Cl, Br, and an
alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated,
straight or branched chain or cyclic form having 1 to 19 carbon
atoms; R.sub.3 is selected from the group consisting of H and an
alkyl, aralkyl, or aryl group having from 1 to 9 carbon atoms,
wherein said N-acetylamino acid has the formula: ##STR00005##
wherein R.sub.1 is H or an alkyl or aralkyl group having 1 to 14
carbon atoms; n is an integer; R.sub.2 is OH, NH.sub.2 or OR.sub.3;
and R.sub.3 is an alkyl, aralkyl or aryl group having 1 to 9 carbon
atoms which may be saturated or unsaturated, straight or branched
chain or cyclic form; H attached to a carbon atom may be
substituted by I, F, Cl, Br or an alkoxyl group having 1 to 9
carbons; and R.sub.1 may carry OH, SH, SCH.sub.3, COOH, NH.sub.2,
CONH.sub.2, guanidine or heterocyclic group, and wherein said
N-acetylamino acid is not N-acetylcysteine or a derivative thereof,
and (C) a cosmetic, pharmaceutical or other topical agent..].
.[.5. The composition of claim 4, wherein said N-acetyl aldosamine
or isomeric or nonisomeric, free acid, salt, lactone, amide, or
ester form thereof is at least one member selected from the group
consisting of N-acetyl-glycerosamine, N-acetyl-erythrosamine,
N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl-arabinosamine,
N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine,
N-acetyl-altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine,
N-acetyl-gulosamine, N-acetyl-idosamine, N-acetyl-galactosamine,
N-acetyl-talosamine, N-acetyl-glucoheptosamine,
N-acetyl-galactoheptosamine, N-acetyl-mannoheptosamine,
N-acetyllactosamine, N-acetylmuramic acid, N-acetylneuramine,
N-acetylneuramin Lactose, N-acetyl-glyceraminic acid,
N-acetyl-erythrosaminic acid, N-acetyl-threosaminic acid,
N-acetyl-ribosaminic acid, N-acetyl-arabinosaminic acid,
N-acetyl-xylosaminic acid, N-acetyl-lyxosaminic acid,
N-acetyl-allosaminic acid, N-acetyl-altrosaminic acid,
N-acetyl-glucosaminic acid; N-acetyl-mannosaminic acid,
N-acetyl-gulosaminic acid, N-acetyl-idosaminic acid,
N-acetyl-galactosaminic acid, N-acetyl-talosaminic acid,
N-acetyl-heptoglucosaminic acid, N-acetyl-heptogalactosaminic acid,
N-acetyl-heptomannosaminic acid, N-acetyl-N-acetylneuraminic acid,
and isomeric or nonisomeric, free acid, salt, lactone, amide, or
ester forms thereof..].
.[.6. The composition of claim 4 wherein said N-acetylamino acid or
isomeric or nonisomeric, free acid, salt, lactone, amide, or ester
form thereof is at least one member selected from the group
consisting of N-acetyl-glycine, N-acetyl-alanine, N-acetyl-valine,
N-acetyl-leucine, N-acetyl-isoleucine, N-acetyl-serine,
N-acetyl-threonine, N-acetyl-tyrosine, N-acetyl-methionine,
N-acetyl-aspartic acid, N-acetyl-asparagine, N-acetyl-glutamic
acid, N-acetyl-glutamine, N-acetyl-arginine, N-acetyl-lysine,
N-acetyl-histidine, N-acetyl-phenylalanine, N-acetyl-tyrosine,
N-acetyl-tryptophan, N-acetyl-proline, N-acetyl-.beta.-alanine,
N-acetyl-taurine, N-acetyl-r-aminobutanoic acid,
N-acetyl-hydroxyproline, N-acetyl-canavanine,
N-acetyl-hydroxylysine, N-acetyl-cycloserine,
N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline,
N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline,
N-acetyl-ethionine, N-acetyl-methoxinine,
N-acetyl-.beta.-aminoisobutanoic acid, N-acetyl-homocysteine,
N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine,
N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine
(N-acetylserotonin), N-acetyltryptamine, N-acetyl-ornithine,
N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa,
N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine,
N-acetyl-3,5,3'-triiodothyronine, N-acetyl-thyroxine,
N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine,
N-acetyl-homocystine, and or isomeric or nonisomeric, free acid,
salt, lactone, amide, or ester forms thereof..].
.[.7. The composition of claim 4, wherein said cosmetic conditions
and dermatological disorders are selected from the group consisting
of disturbed keratinization, defective syntheses of dermal
components, and changes associated with aging of skin, nail and
hair, conditions and disorders which include dryness or loose of
skin, nail and hair, xerosis, ichthyosis, palmar hyerperkeratoses,
plantar hyperkeratoses, uneven and rough surfaces of skin, nail and
hair, dandruff, Darier's disease, lichen simplex chronicus,
keratoses, acne, pseudofolliculitis barbae, eczema, psoriasis,
pruritus, warts, herpes, age spots, lentigines, melasmas, blemished
skin, hyperkeratoses, hyperpigmented skin, abnormal or diminished
syntheses of collagen, glycosaminoglycans, proteoglycans and
elastin as well as diminished levels of such components in the
dermis, stretch marks, skin lines, fine lines, wrinkles, thinning
of skin, nail plate and hair, skin thickening due to elastosis of
photoaging, loss or reduction of skin, nail and hair resiliency,
elasticity and recoilability, lack of skin, nail and hair
lubricants and luster, dull and older-looking skin, nails and hair,
and fragility and splitting of nails and hair..].
.[.8. The composition of claim 4, wherein said cosmetic,
pharmaceutical, or other topical agent is selected from the group
consisting of agents that improve or eradicate age spots, keratoses
and wrinkles, local analgesics and anesthetics, antiacne agents,
antibacterials, antiyeast agents, antifungal agents, antiviral
agents, antidandruff agents, antidermatitis agents, antihistamine
agents, antipruritic agents, antiemetics, antimotion sickness
agents, antiinflammatory agents, antihyperkeratolytic agents,
antiperspirants, antipsoriatic agents, antiseborrheic agents, hair
conditioners and hair treatment agents, antiaging and antiwrinkle
agents, sunblock and sunscreen agents, skin lightening agents,
depigmenting agents, vitamins, corticosteroids, tanning agents,
hormones, retinoids, and topical cardiovascular agents..].
.[.9. The composition of claim 8, wherein said cosmetic,
pharmaceutical, or other topical agent is selected from the group
consisting of clotrimazole, ketoconazole, miconazole, griseofulvin,
econazole, metronidazole, hydroxyzine, diphenhydramine, pramoxine,
lidocaine, procaine, mepivacaine, monobenzone, erythromycin,
tetracycline, clindamycin, meclocycline, hydroquinone, hydroquinone
monoether, minocycline, naproxen, ibuprofen, theophylline,
cromolyn, albuterol, retinol, retinyl acetate, retinyl palmitate,
retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone
21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate,
betamethasone valerate, betamethasone dipropionate, triamcinolone
acetonide, fluocinonide, clobetasol propionate, benzoyl peroxide,
crotamiton, propranolol, promethazine, salicylic acid, vitamin E
and vitamin E acetate..].
.[.10. A composition comprising (A) a pharmaceutically acceptable
vehicle for topical treatment of cosmetic conditions or
dermatological disorders and (B) at least 1% by total weight of the
composition of at least one compound selected from the group
consisting of N-acetyl aldosamines, N-acetylamino acids, and
isomeric or nonisomeric, free acid, salt, lactone, amide, or ester
forms thereof, wherein said N-acetyl aldosamine has the formula:
##STR00006## wherein n is an integer; R.sub.1 is selected from the
group consisting of CHO, CONH.sub.2, and COOR.sub.3; R.sub.2 is
selected from the group consisting of H, I, F, Cl, Br, and an
alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated,
straight or branched chain or cyclic form having 1 to 19 carbon
atoms; R.sub.3 is selected from the group consisting of H and an
alkyl, aralkyl, or aryl group having from 1 to 9 carbon atoms,
wherein said N-acetylamino acid or isomeric or nonisomeric, free
acid, salt, lactone, amide, or ester form thereof is at least one
member selected from the group consisting of N-acetyl-glycine,
N-acetyl-alanine, N-acetyl-valine, N-acetyl-leucine,
N-acetyl-isoleucine, N-acetyl-serine, N-acetyl-threonine,
N-acetyl-tyrosine, N-acetyl-methionine, N-acetyl-aspartic acid,
N-acetyl-asparagine, N-acetyl-glutamine, N-acetyl-arginine,
N-acetyl-lysine, N-acetyl-histidine, N-acetyl-phenylalanine,
N-acetyl-tyrosine, N-acetyl-tryptophan, N-acetyl-proline,
N-acetyl-.beta.-alanine, N-acetyl-taurine, N-acetyl-r-aminobutanoic
acid, N-acetyl-hydroxyproline, N-acetyl-canavanine,
N-acetyl-hydroxylysine, N-acetyl-cycloserine,
N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline,
N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline,
N-acetyl-ethionine, N-acetyl-methoxinine,
N-acetyl-.beta.-aminoisobutanoic acid, N-acetyl-homocysteine,
N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine,
N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine
(N-acetylserotonin), N-acetyltryptamine, N-acetyl-ornithine,
N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa,
N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine,
N-acetyl-3,5,3'-triiodothyronine, N-acetyl-thyroxine,
N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine,
N-acetyl-homocystine, and isomeric or nonisomeric, free acid, salt,
lactone, amide, or ester forms thereof, and N-acetyl glutamic acid
and isomeric or nonisomeric, free acid, lactone, amide, or ester
forms thereof..].
.[.11. A composition comprising: (A) a pharmaceutically acceptable
vehicle for topical treatment of cosmetic conditions or
dermatological disorders, (B) at least 1% by total weight of the
composition of at least one compound selected from the group
consisting of N-acetyl aldosamines, N-acetylamino acids, and
isomeric or nonisomeric, free acid, salt, lactone, amide, or ester
forms thereof, wherein said N-acetyl aldosamine has the formula:
##STR00007## wherein n is an integer; R.sub.1 is selected from the
group consisting of CHO, CONH.sub.2, and COOR.sub.3; R.sub.2 is
selected from the group consisting of H, I, F, Cl, Br, and an
alkyl, alkoxyl, aralkyl or aryl group of saturated or unsaturated,
straight or branched chain or cyclic form having 1 to 19 carbon
atoms; R.sub.3 is selected from the group consisting of H and an
alkyl, aralkyl, or aryl group having from 1 to 9 carbon atoms,
wherein said N-acetylamino acid is N-acetyl-proline or has the
formula: ##STR00008## wherein R.sub.1 is H or an alkyl or aralkyl
group having 1 to 14 carbon atoms; n is an integer; R.sub.2 is OH,
NH.sub.2 or OR.sub.3; and R.sub.3 is an alkyl, aralkyl or aryl
group having 1 to 9 carbon atoms which may be saturated or
unsaturated, straight or branched chain or cyclic form; H attached
to a carbon atom may be substituted by I, F, Cl, Br or an alkoxyl
group having 1 to 9 carbons; and R.sub.1 may carry OH, SH,
SCH.sub.3, COOH, NH.sub.2, CONH.sub.2, guanidine or heterocyclic
group, and wherein said N-acetylamino acid is not N-acetylcysteine
or a derivative thereof, and (C) a cosmetic, pharmaceutical or
other topical agent..].
.[.12. A method for treating cosmetic conditions and dermatological
disorders comprising topically applying a composition comprising
(A) a pharmaceutically acceptable vehicle for topical treatment of
cosmetic conditions or dermatological disorders and (B) a
therapeutically effective amount of a composition comprising at
least one compound selected from the group consisting of N-acetyl
aldosamines, N-acetylamino acids and isomeric or nonisomeric, free
acid, salt, lactone, amide, or ester forms thereof, wherein said
N-acetyl aldosamine has the formula: ##STR00009## wherein n is an
integer; R.sub.1 is selected from the group consisting of CHO,
CONH.sub.2, and COOR.sub.3; R.sub.2 is selected from the group
consisting of H, I, F, Cl, Br, and an alkyl, alkoxyl, aralkyl or
aryl group of saturated or unsaturated, straight or branched chain
or cyclic form having 1 to 19 carbon atoms; R.sub.3 is selected
from the group consisting of H and an alkyl, aralkyl or aryl group
having from 1 to 9 carbon atoms, and wherein said N-acetylamino
acid or isomeric or nonisomeric, free acid, salt, lactone, amide,
or ester form thereof is at least one member selected from the
group consisting of N-acetyl-glycine, N-acetyl-alanine,
N-acetyl-valine, N-acetyl-leucine, N-acetyl-isoleucine,
N-acetyl-serine, N-acetyl-threonine, N-acetyl-tyrosine,
N-acetyl-cysteine, N-acetyl-methionine, N-acetyl-aspartic acid,
N-acetyl-asparagine, N-acetyl-glutamine, N-acetyl-arginine,
N-acetyl-lysine, N-acetyl-histidine, N-acetyl-phenylalanine,
N-acetyl-tyrosine, N-acetyl-tryptophan, N-acetyl-proline,
N-acetyl-.beta.-alanine, N-acetyl-taurine, N-acetyl-r-aminobutanoic
acid, N-acetyl-hydroxyproline, N-acetyl-canavanine,
N-acetyl-hydroxylysine, N-acetyl-cycloserine,
N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline,
N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline,
N-acetyl-ethionine, N-acetyl-methoxinine,
N-acetyl-.beta.-aminoisobutanoic acid, N-acetyl-homocysteine,
N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine,
N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine
(N-acetylserotonin), N-acetyltryptamine, N-acetyl-ornithine,
N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa,
N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine,
N-acetyl-3,5,3'-triiodothyronine, N-acetyl-thyroxine,
N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine,
N-acetyl-homocystine, and isomeric or nonisomeric, free acid, salt
lactone, amide, or ester forms thereof, and N-acetyl-glutamic acid
and isomeric or nonisomeric, free acid, lactone, amide, or ester
forms thereof..].
.[.13. The method of claim 12, wherein said N-acetyl aldosamine or
isomeric or nonisomeric, free acid, salt, lactone, amide, or ester
form thereof is at least one member selected from the group
consisting of N-acetyl-glycerosamine, N-acetyl-erythrosamine,
N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl-arabinosamine,
N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine,
N-acetyl-altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine,
N-acetyl-gulosamine, N-acetyl-idosamine, N-acetyl-galactosamine,
N-acetyl-talosamine, N-acetyl-glucoheptosamine,
N-acetyl-galactoheptosamine, N-acetyl-mannoheptosamine,
N-acetyllactosamine, N-acetylmuramic acid, N-acetylneuramine,
N-acetylneuramin Lactose, N-acetyl-glyceraminic acid,
N-acetyl-erythrosaminic acid, N-acetyl-threosaminic acid,
N-acetyl-ribosaminic acid, N-acetyl-arabinosaminic acid,
N-acetyl-xylosaminic acid, N-acetyl-lyxosaminic acid,
N-acetyl-allosaminic acid, N-acetyl-altrosaminic acid,
N-acetyl-glucosaminic acid, N-acetyl-mannosaminic acid,
N-acetyl-gulosaminic acid, N-acetyl-idosaminic acid,
N-acetyl-galactosaminic acid, N-acetyl-talosaminic acid,
N-acetyl-heptoglucosaminic acid, N-acetyl-heptogalactosaminic acid,
N-acetyl-heptomannosaminic acid, N-acetyl-N-acetylneuraminic acid,
and isomeric or nonisomeric, free acid, salt, lactone, amide, or
ester forms thereof..].
.[.14. The method of claim 12, wherein said cosmetic conditions and
dermatological disorders are selected from the group consisting of
disturbed keratinization, defective syntheses of dermal components,
and changes associated with aging of skin, nail and hair,
conditions and disorders which include dryness or loose of skin,
nail and hair, xerosis, ichthyosis, palmar hyerperkeratoses,
plantar hyperkeratoses, uneven and rough surfaces of skin, nail and
hair, dandruff, Darier's disease, lichen simplex chronicus,
keratoses, acne, pseudofolliculitis barbae, eczema, psoriasis,
pruritus, warts, herpes, age spots, lentigines, melasmas, blemished
skin, hyperkeratoses, hyperpigmented skin, abnormal or diminished
syntheses of collagen, glycosaminoglycans, proteoglycans and
elastin as well as diminished levels of such components in the
dermis, stretch marks, skin lines, fine lines, wrinkles, thinning
of skin, nail plate and hair, skin thickening due to elastosis of
photoaging, loss or reduction of skin, nail and hair resiliency,
elasticity and recoilability, lack of skin, nail and hair
lubricants and luster, dull and older-looking skin, nails and hair,
and fragility and splitting of nails and hair..].
.[.15. A method for treating cosmetic conditions and dermatological
disorders comprising topically applying a composition comprising:
(A) a pharmaceutically acceptable vehicle for topical treatment of
cosmetic conditions or dermatological disorders, (B) a
therapeutically effective amount of at least one compound selected
from the group consisting of N-acetyl aldosamines, N-acetylamino
acids, and isomeric or nonisomeric, free acid, salt, lactone,
amide, or ester forms thereof, wherein said N-acetyl aldosamine has
the formula: ##STR00010## wherein n is an integer; R.sub.1 is
selected from the group consisting of CHO, CONH.sub.2, and
COOR.sub.3; R.sub.2 is selected from the group consisting of H, I,
F, Cl, Br, and an alkyl, alkoxyl, aralkyl or aryl group of
saturated or unsaturated, straight or branched chain or cyclic form
having 1 to 19 carbon atoms; R.sub.2 is selected from the group
consisting of H and an alkyl, aralkyl, or aryl group having from 1
to 9 carbon atoms, wherein said N-acetylamino acid is
N-acetyl-proline or has the formula: ##STR00011## wherein R.sub.1
is H or an alkyl or aralkyl group having 1 to 14 carbon atoms; n is
an integer; R.sub.2 is OH, NH.sub.2 or OR.sub.3; and R.sub.3 is an
alkyl, aralkyl or aryl group having 1 to 9 carbon atoms which may
be saturated or unsaturated, straight or branched chain or cyclic
form; H attached to a carbon atom may be substituted by I, F, Cl,
Br or an alkoxyl group having 1 to 9 carbons; and R.sub.1 may carry
OH, SH, SCH.sub.3, COOH, NH.sub.2, CONH.sub.2, guanidine or
heterocyclic group, and wherein said N-acetylamino acid is not
N-acetylcysteine or a derivative thereof, and (C) a cosmetic,
pharmaceutical or other topical agent..].
.[.16. The method of claim 15, wherein said N-acetyl aldosamine or
isomeric or nonisomeric, free acid, salt, lactone, amide, or ester
form thereof is at least one member selected from the group
consisting of N-acetyl-glycerosamine,N-acetyl-erythrosamine,
N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl-arabinosamine,
N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine,
N-acetyl-altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine,
N-acetyl-gulosamine, N-acetyl-idosamine, N-acetyl-galactosamine,
N-acetyl-talosamine, N-acetyl-glucoheptosamine,
N-acetyl-galactoheptosamine, N-acetyl-mannoheptosamine,
N-acetyllactosamine, N-acetylmuramic acid, N-acetylneuramine,
N-acetylneuramin Lactose, N-acetyl-glyceraminic acid,
N-acetyl-erythrosaminic acid, N-acetyl-threosaminic acid,
N-acetyl-ribosaminic acid, N-acetyl-arabinosaminic acid,
N-acetyl-xylosaminic acid, N-acetyl-lyxosaminic acid,
N-acetyl-allosaminic acid, N-acetyl-altrosaminic acid,
N-acetyl-glucosaminic acid, N-acetyl-mannosaminic acid,
N-acetyl-gulosaminic acid, N-acetyl-idosaminic acid,
N-acetyl-galactosaminic acid, N-acetyl-talosaminic acid,
N-acetyl-heptoglucosaminic acid, N-acetyl-heptogalactosaminic acid,
N-acetyl-heptomannosaminic acid, N-acetyl-N-acetylneuraminic acid,
and isomeric or nonisomeric, free acid, salt, lactone, amide, or
ester forms thereof..].
.[.17. The method of claim 15, wherein said N-acetylamino acid or
isomeric or nonisomeric, free acid, salt, lactone, amide, or ester
form thereof is at least one member selected from the group
consisting of N-acetyl-glycine, N-acetyl-alanine, N-acetyl-valine,
N-acetyl-leucine, N-acetyl-isoleucine, N-acetyl-serine,
N-acetyl-threonine, N-acetyl-tyrosine, N-acetyl-methionine,
N-acetyl-aspartic acid, N-acetyl-asparagine, N-acetyl-glutamic
acid, N-acetyl-glutamine, N-acetyl-arginine, N-acetyl-lysine,
N-acetyl-histidine, N-acetyl-phenylalanine, N-acetyl-tyrosine,
N-acetyl-tryptophan, N-acetyl-proline, N-acetyl-.beta.-alanine,
N-acetyl-taurine, N-acetyl-r-aminobutanoic acid,
N-acetyl-hydroxyproline, N-acetyl-canavanine,
N-acetyl-hydroxylysine, N-acetyl-cycloserine,
N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline,
N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline,
N-acetyl-ethionine, N-acetyl-methoxinine,
N-acetyl-.beta.-aminoisobutanoic acid, N-acetyl-homocysteine,
N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine,
N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine
(N-acetylserotonin), N-acetyltryptamine, N-acetyl-ornithine,
N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa,
N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine,
N-acetyl-3,5,3'-triiodothyronine, N-acetyl-thyroxine,
N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine,
N-acetyl-homocystine, and isomeric or nonisomeric, free acid, salt,
lactone, amide, or ester forms thereof..].
.[.18. The method of claim 15, wherein said cosmetic conditions and
dermatological disorders are selected from the groups consisting of
disturbed keratinization, defective syntheses of dermal components,
and changes associated with aging of skin, nail and hair,
conditions and disorders which include dryness or loose of skin,
nail and hair, xerosis, ichthyosis, palmar hyerperkeratoses,
plantar hyperkeratoses, uneven and rough surfaces of skin, nail and
hair, dandruff, Darier's disease, lichen simplex chronicus,
keratoses, acne, pseudofolliculitis barbae, eczema, psoriasis,
pruritus, warts, herpes, age spots, lentigines, melasmas, blemished
skin, hyperkeratoses, hyperpigmented skin, abnormal or diminished
syntheses of collagen, glycosaminoglycans, proteoglycans and
elastin as well as diminished levels of such components in the
dermis, stretch marks, skin lines, fine lines, wrinkles, thinning
of skin, nail plate and hair, skin thickening due to elastosis of
photoaging, loss or reduction of skin, nail and hair resiliency,
elasticity and recoilability, lack of skin, nail and hair
lubricants and luster, dull and older-looking skin, nails and hair,
and fragility and splitting of nails and hair..].
.[.19. The method of claim 15, wherein said cosmetic,
pharmaceutical, or other topical agent is selected from the group
consisting of agents that improve or eradicate age spots, keratoses
and wrinkles, local analgesics and anesthetics, antiacne agents,
antibacterials, antiyeast agents, antifungal agents, antiviral
agents, antidandruff agents, antidermatitis agents, antihistamine
agents, antipruritic agents, antiemetics, antimotion sickness
agents, antiinflammatory agents, antihyperkeratolytic agents,
antiperspirants, antipsoriatic agents, antiseborrheic agents, hair
conditioners and hair treatment agents, antiaging and antiwrinkle
agents, sunblock and sunscreen agents, skin lightening agents,
depigmenting agents, vitamins, corticosteroids, tanning agents,
hormones, retinoids, and topical cardiovascular agents..].
.[.20. The method of claim 19, wherein said cosmetic,
pharmaceutical, or other topical agent is selected from the group
consisting of clotrimazole, ketoconazole, miconazole, griseofulvin,
econazole, metronidazole, hydroxyzine, diphenhydramine, pramoxine,
lidocaine, procaine, mepivacaine, monobenzone, erythromycin,
tetracycline, clindamycin, meclocycline, hydroquinone, hydroquinone
monoether, minocycline, naproxen, ibuprofen, theophylline,
cromolyn, albuterol, retinol, retinyl acetate, retinyl palmitate,
retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone
21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate,
betamethasone valerate, betamethasone dipropionate, triamcinolone
acetonide, fluocinonide, clobetasol propionate, benzoyl peroxide,
crotamiton, propranolol, promethazine, salicylic acid, vitamin E,
and vitamin E acetate..].
.Iadd.21. A method for treating dermal conditions comprising
topically applying a water-containing composition comprising (A) a
cosmetically acceptable vehicle and (B) a therapeutically effective
amount of N-acetyl-glucosamine, wherein the composition does not
contain glucuronic acid, or vitamin E, wherein the conditions are
selected from the group consisting of defective syntheses of dermal
components, conditions and disorders selected from abnormal or
diminished syntheses of collagen and elastin, diminished levels of
collagen and elastin, and skin thickening due to elastosis of
photoaging. .Iaddend.
.Iadd.22. The method of claim 21, wherein the condition is
diminished levels of collagen. .Iaddend.
.Iadd.23. The method of claim 21, wherein the condition is abnormal
or diminished synthesis of collagen. .Iaddend.
.Iadd.24. The method of claim 21, wherein the condition is
diminished levels of elastin. .Iaddend.
.Iadd.25. The method of claim 21, wherein the condition is abnormal
or diminished synthesis of elastin. .Iaddend.
.Iadd.26. The method of claim 21, wherein the composition further
comprises other topical agents selected from the group consisting
of agents that improve or eradicate age spots, keratoses, local
analgesics and anesthetics, antiacne agents, antiyeast agents,
antidermatitis agents, antihistamine agents, antipruritic agents,
antiemetics, antimotion sickness agents, antiinflammatory agents,
antihyperkeratotic agents, antiperspirants, antipsoriatic agents,
antiseborrheic agents, hair conditioners and hair treatment agents,
antiaging and antiwrinkle agents, sunblock and sunscreen agents,
skin lightening agents, depigmenting agents, vitamins,
corticosteroids, tanning agents, hormones, retinoids, and topical
cardiovascular agents. .Iaddend.
.Iadd.27. The method of claim 26, wherein the topical agent is
selected from the group consisting of hydroxyzine, diphenhydramine,
pramoxine, lidocaine, procaine, mepivacaine, monobenzone,
hydroquinone, hydroquinone monoether, naproxen, ibuprofen,
theophylline, cromolyn, albuterol, retinol, retinyl acetate,
retinyl palmitate, retinoic acid, 13-cis retinoic acid,
hydrocortisone, hydrocortisone 21-acetate, hydrocortisone
17-valerate, hydrocortisone 17-butyrate, betamethasone valerate,
betamethasone dipropionate, triamcinolone acetonide, fluocinonide,
clobetasol propionate, benzoyl peroxide, crotamiton, propranolol,
promethazine, and salicylic acid. .Iaddend.
.Iadd.28. The method of claim 26, wherein the topical agent is a
vitamin. .Iaddend.
.Iadd.29. The method of claim 28, wherein the vitamin is vitamin
B.sub.3, niacinamide. .Iaddend.
.Iadd.30. The method of claim 29, wherein the composition comprises
N-acetyl-glucosamine and niacinamide, and the conditions are
selected from the group consisting of diminished levels of collagen
and elastin, and skin thickening due to elastosis of photoaging.
.Iaddend.
.Iadd.31. The method of claim 30, wherein the condition is
diminished levels of collagen. .Iaddend.
.Iadd.32. A method for treating dermal conditions comprising
topically applying a water-containing composition consisting
essentially of (A) a cosmetically acceptable vehicle; (B) a
therapeutically effective amount of N-acetyl-glucosamine; and
optionally (C) a topical agent, wherein the conditions are selected
from the group consisting of defective syntheses of dermal
components, conditions and disorders selected from abnormal or
diminished syntheses of collagen and elastin, diminished levels of
collagen and elastin, and skin thickening due to elastosis of
photoaging. .Iaddend.
.Iadd.33. The method as claimed in claim 32, wherein the topical
agent is selected from the group consisting of local analgesics and
anesthetics, antiacne agents, antiyeast agents, antidermatitis
agents, antihistamine agents, antipruritic agents, antiemetics,
antimotion sickness agents, antiinflammatory agents,
antihyperkeratotic agents, antiperspirants, antipsoriatic agents,
antiseborrheic agents, antiaging and antiwrinkle agents, sunblock
and sunscreen agents, skin lightening agents, depigmenting agents,
vitamins, corticosteroids, tanning agents, hormones, retinoids, and
topical cardiovascular agents. .Iaddend.
.Iadd.34. The method of claim 33, wherein the topical agent is
selected from the group consisting of hydroxyzine, diphenhydramine,
pramoxine, lidocaine, procaine, mepivacaine, monobenzone,
hydroquinone, hydroquinone monoether, naproxen, ibuprofen,
theophylline, cromolyn, albuterol, retinol, retinyl acetate,
retinyl palmitate, retinoic acid, 13-cis retinoic acid,
hydrocortisone, hydrocortisone 21-acetate, hydrocortisone
17-valerate, hydrocortisone 17-butyrate, betamethasone valerate,
betamethasone dipropionate, triamcinolone acetonide, fluocinonide,
clobetasol propionate, benzoyl peroxide, crotamiton, propranolol,
promethazine, and salicylic acid. .Iaddend.
.Iadd.35. The method of claim 33, wherein the topical agent is a
vitamin. .Iaddend.
.Iadd.36. The method of claim 35, wherein the vitamin is vitamin
B.sub.3, niacinamide. .Iaddend.
.Iadd.37. The method of claim 36, wherein the composition comprises
N-acetyl-glucosamine and niacinamide, and the conditions are
selected from the group consisting of diminished levels of collagen
and elastin, and skin thickening due to elastosis of photoaging.
.Iaddend.
.Iadd.38. The method of claim 37, wherein the condition is
diminished levels of collagen. .Iaddend.
.Iadd.39. The method of claim 32, wherein the topical agent is one
or more topical agents selected from the group consisting of
sunblock and sunscreen agents, and vitamins. .Iaddend.
Description
FIELD OF THE INVENTION
This application relates to topical compositions containing
N-acetyl-aldosamines, N-acetylamino acids, and related N-acetyl
compounds, and their use in alleviating or improving various
cosmetic conditions and dermatological disorders including signs of
aging, changes or damage to skin, nail and hair associated with
intrinsic aging and/or extrinsic aging, as well as changes or
damage caused by extrinsic factors such as sunlight, radiation, air
pollution, wind, cold, heat, dampness, chemicals, smoke, and
cigarette smoking; and for certain skin disorders associated with
or due to itching and/or inflammation.
BRIEF DESCRIPTION OF THE PRIOR ART
In our U.S. Pat. No. 5,091,171 we described and claimed preventive
as well as therapeutic treatment to alleviate cosmetic conditions
and symptoms of dermatologic disorders with amphoteric compositions
containing alpha hydroxyacids, alpha ketoacids, polymeric forms of
hydroxyacids, and related compounds or. In our U.S. Pat. No.
5,547,988, and related patents, we described the use of topical
compositions comprising a 2-hydroxycarboxylic acid or related
compound to alleviate or improve signs of skin, nail and hair
changes associated with intrinsic or extrinsic aging. In our U.S.
Pat. No. 5,385,938, and related patents, we described preventive
and therapeutic treatment to alleviate cosmetic conditions and
symptoms of dermatologic disorders with amphoteric compositions
containing alpha hydroxy acids, alpha ketoacids, polymeric forms of
hydroxy acids, and related compounds or. In our U.S. Pat. No.
5,258,391 entitled "Phenyl Alpha Acyloxyalkanoic Acids, Derivatives
and Their Therapeutic Use" we described and claimed the use of
topical compositions containing phenyl alpha acyloxyalkanoic acids
and derivatives to enhance the keratization of nails, skin, lips
and other mucous membranes. In our U.S. Pat. No. 5,665,776 entitled
"Additives Enhancing Topical Actions of Therapeutic Agents" we
described and claimed the use of hydroxycarboxylic acids or related
compounds to increase the cosmetic or therapeutic effect of
cosmetic or pharmaceutical agents. In our U.S. Pat. No. 5,641,475
we described and claimed the use of topical compositions containing
a bioactive cosmetic, dermatologic or preservative agent and aryl
2-acetoxyethanoic acid effective as a synergist or amplifier. In
our U.S. Pat. No. 5,643,949 also entitled "Phenyl Alpha
Acyloxyalkanoic Acids, Derivatives and Their Therapeutic Use" we
described and claimed the use of topical compositions containing a
cosmetic or dermatologic drug for topical administration to nails,
skin and lips and an amount of a phenyl alpha acyloxyalkanoic acid
or derivatives effective to enhance the cosmetic or therapeutic
effect of the dermatologic drug. In U.S. Pat. No. 4,603,146 to
Albert M. Kligman, disclosure is made of the use of vitamin A
(tretionoin) to reduced and prevent epithelial growths and aid the
skin in regaining and maintaining firmness, turgor and
elasticity.
In a report entitled "Topical Tretinoin for Photoaged Skin" by
Kligman et al., J. American Academy of Dermatology, Vol. 15, pages
836-859, 886-887 (1986), daily topical application of 0.05%
tretinoin (also known as all-transretinoic acid) in a cream has
been found to improve photodamaged skin. In another report entitled
"Topical Tretinoin Improves Photoaged Skin: A Double-blind
Vehicle-controlled Study" by Weiss et al., J. American Medical
Association, Vol. 259 pages 527-532 (1988), daily topical
application of 0.1% tretinoin as compared to vehicle alone
application for 16 weeks has been shown to improve photoaged skin.
One side-effect has been a dermatitis encountered by 92% of the
patients participating in this study. The dermatitis was
characterized by a patchy erythema, localized swelling, dry skin,
and mild scaling. Patients complained about burning, tingling, or
pruritus. In yet another report entitled "Topical Tretinoin in the
Treatment of Aging Skin" by Weiss et al., J. American Academy of
Dermatology Vol. 19, pages 169-175 (1988), topical application of
0.1% tretinoin cream for 8 to 12 months has been found to improve
clinical signs of aging skin. The side effects have been burning
sensation in the eyes and mild skin irritations.
In PCT Application No. PCT/US96/16534, filed Oct. 16, 1996,
entitled "Topical Compositions Containing N-Acetylcysteine and Odor
Masking Materials," topical compositions comprising from 0.01% to
50% of N-acetylcysteine or a derivative of N-acetylcysteine, from
0.01% to 0.5% of an odor masking material, and a topical carrier
are disclosed to improve the appearance of skin.
N-Acetylcysteine is N-acetylated cysteine which is a thiol
containing amino acid, also called
.alpha.-acetamido-.beta.-mercaptopropanoic acid. Topical
compositions containing N-acetylcysteine have been claimed to
improve physical appearance of the skin including cosmetic
wrinkles. N-acetylcysteine contains a free thiol group, thus, is
known as an antioxidant. The affect of N-acetylcysteine is claimed
to be due to its antioxidant property. N-Acetylcysteine, as an
antioxidant substance, also has been indicated as protective
against pulmonary oxygen toxicity (Eur. Respir. J. 2, 116-126,
1989).
N-acetylcysteine, however, is also associated with a number of
significant drawbacks. N-acetylcysteine is known to degrade under
ordinary storage conditions and result in a malodorous smell. The
malodor is suggested to be caused by the release of thiol compounds
and hydrogen sulfide upon degradation. Thus, topical compositions
containing N-acetylcysteine have little or no commercial use due to
the strong malodor of N-acetylcysteine.
PCT/US96/16534 claimed that the malodor could be masked by addition
of certain perfume chemicals at concentrations ranging from 0.01 to
0.5% by weight. The perfume chemicals include aromatic esters,
aliphatic esters, aromatic alcohol, aliphatic alcohols, aliphatic
ketones, aromatic aldehydes, aliphatic aldehydes, aromatic ethers
and aliphatic ethers. Because the malodorous thiol compounds and
hydrogen sulfide have not been chemically neutralized or destroyed,
however, the transient masking effect is not a satisfactory
solution for most consumers, and therefore is not a viable approach
for commercialization of N-acetylcysteine in cosmetic industry.
We have now discovered that N-aldosamines, N-acetylated amino acids
and related compounds are topically effective for various cosmetic
conditions and dermatological indications including the signs of
skin, nail and hair changes associated with intrinsic and/or
extrinsic aging. The N-acetylated amino acids and related compounds
do not necessarily contain thiol groups and are not necessarily
antioxidants.
SUMMARY OF THE INVENTION
Accordingly, it is an object of this invention to provide methods
and compositions which can alleviate various cosmetic conditions
and dermatological disorders including the signs of skin, nail and
hair changes associated with intrinsic and/or extrinsic aging and
extrinsic factors, and other skin conditions associated with or due
to itching and/ or inflamation, including pruritus.
We have now discovered that N-acetyl aldosamines, N-acetylamino
acids and related N-acetyl compounds have unexpected properties.
Topical applications of compositions comprising N-acetyl
aldosamines, N-acetylamino acids and related N-acetyl compounds
have been found to improve cosmetic conditions and dermatological
disorders including cosmetic as well as clinical signs of changes
in skin, nails and hair associated with intrinsic and/or extrinsic
aging, or the damages caused by extrinsic factors such as sunlight,
radiation, air pollution, wind, cold, dampness, heat, chemicals,
smoke, and cigarette smoking.
The signs of skin changes associated with intrinsic and/or
extrinsic aging and the skin damages caused by extrinsic factors
include thinning of skin; fragile skin; deepening of skin lines and
fine lines; wrinkles, including fine and course wrinkles;
blemishes; atrophy; pigmented spots, blotches and mottles, nodules
and mottled skin; pre-cancerous lesions; elastotic changes
characterized by leathery, lusterless, uneven, coarse, rough, dry
and/or yellowish skin; loss of skin elasticity and recoilability;
loss of skin lubricating substances; changes in qualities and
quantities of glycosaminoglycans and proteoglycans and collagen and
elastic fibers; solar elastosis; decrease in collagen fibers;
diminution in the number and diameter of elasitic fibers in the
papillary dermis; atrophy; stretch marks; reduction in subcutaneous
adipose tissue; deposition of abnormal elastic materials in the
dermis leading to thickening of the dermis; older-looking skin; and
telangiectatic skin.
The signs of nails and hair changes associated with intrinsic aging
and the damages caused by extrinsic factors include thinning,
fragility, splitting, lack of luster, uneven surface, and loss of
flexibility and elasticity.
In accordance with the objects of the invention, a composition
comprising at least one compound selected from the group consisting
of N-acetyl aldosamines, N-acetylamino acids and related compounds,
present in a therapeutically effective amount and in a
pharmaceutically acceptable vehicle for topical treatment of
cosmetic conditions or dermatological disorders is provided. In one
embodiment of the invention, the composition further comprises a
cosmetic, pharmaceutical, or other topical agent.
Also in accordance with the objects of the invention, a method for
treating cosmetic conditions and dermatological disorders
comprising topically applying a therapeutically effective amount of
a composition comprising at least one compound selected from the
group consisting of N-acetyl aldosamines, N-acetylamino acids and
related compounds, in a pharmaceutically acceptable vehicle is
provided. In one embodiment of the invention, the method comprises
topically applying a therapeutically effective amount of a
composition comprising at least one compound selected from the
group consisting of N-acetyl aldosamines, N-acetylamino acids and
related compounds, and at least one cosmetic, pharmaceutical, or
other topical agent, in a pharmaceutically acceptable vehicle.
N-Acetyl aldosamines, N-acetylamino acids and related N-acetyl
compounds which are useful for topical treatment of skin, nail and
hair changes associated with intrinsic and/or extrinsic aging and
extrinsic factors include, inter alia, N-acetyl-aldosamines which
are derivatives of aminosugars and include N-acetyl-ribosamine,
N-acetyl-arabinosamine, N-acetyl-glucosamine,
N-acetyl-galactosamine and N-acetyl-mannosamine, and N-acetylamino
acids which are N-acetyl derivatives of amino acids and include
N-acetyl-glycine, N-acetyl-proline, N-acetyl-lysine,
N-acetyl-arginine and N-acetyl-tryptophan.
Additional objects and advantages of the invention will be set
forth in part in the description that follows, and in part will be
obvious from the description, or may be learned by practice of the
invention. The objects and the advantages of this invention may be
realized and obtained by means of the compositions and methods
particularly pointed out in the appended claims.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
1. N-Acetyl-aldosamines, N-Acetylamino Acids and Related N-Acetyl
Compounds
(i) N-Acetyl-aldosamines
One aspect of the present invention pertains to compositions
comprising N-acetyl-aldosamines and related compounds.
N-acetyl-aldosamines are N-acetylated aminosugars in which the
acetylamino group is preferably located at position 2 of the carbon
chain. In accordance with the present invention, the generic
structure or formula of N-acetyl-aldosamines which are topically
beneficial for various cosmetic and dermatologic indications may be
represented as follows:
##STR00001## where n is an integer, preferably 1-19; R.sub.1 is
selected from the group consisting of CHO, CONH.sub.2, and
COOR.sub.3; R.sub.2 is selected from the group consisting of H, l,
F, Cl, Br, and an alkyl, alkoxyl, aralkyl or aryl group of
saturated or unsaturated, isomeric or non-isomeric, straight or
branched chain or cyclic form, having 1 to 19 carbon atoms; and
R.sup.3 is selected from the group consisting of H, an alkyl,
aralkyl or aryl group having 1 to 9 carbon atoms.
N-Acetyl-aldosamines may be present as saturated or unsaturated,
isomeric or non-isomeric, straight or branched chain or cyclic
form. A typical cyclic form of an N-acetyl-aldosamine is a five
member ring (furanose form) or a six member ring (pyranose
form).
The following are some representative N-acetyl-aldosamines and
related compounds: N-acetyl-glycerosamine, N-acetyl-erythrosamine,
N-acetyl-threosamine, N-acetyl-ribosamine, N-acetyl-arabinosamine,
N-acetyl-xylosamine, N-acetyl-lyxosamine, N-acetyl-allosamine,
N-acetyl-altrosamine, N-acetyl-glucosamine, N-acetyl-mannosamine,
N-acetyl-gulosamine, N-acetyl-idosamine, N-acetyl-galactosamine,
N-acetyl-talosamine, N-acetyl-glucoheptosamine,
N-acetyl-galactoheptosamine, N-acetyl-mannoheptosamine,
N-acetyllactosamine, N-acetylmuramic acid, N-acetylneuramine,
N-acetylneuramin Lactose, N-acetyl-glyceraminic acid,
N-acetyl-erythrosaminic acid, N-acetyl-threosaminic acid,
N-acetyl-ribosaminic acid, N-acetyl-arabinosaminic acid,
N-acetyl-xylosaminic acid, N-acetyl-lyxosaminic acid,
N-acetyl-allosaminic acid, N-acetyl-altrosaminic acid,
N-acetyl-glucosaminic acid, N-acetyl-mannosaminic acid,
N-acetyl-gulosaminic acid, N-acetyl-idosaminic acid,
N-acetyl-galactosaminic acid, N-acetyl-talosaminic acid,
N-acetyl-heptoglucosaminic acid, N-acetyl-heptogalactosaminic acid,
N-acetyl-heptomannosaminic acid, and N-acetyl-N-acetylneuraminic.
The amides and esters of the foregoing acid compounds also are
contemplated by the present invention. Examples of five and six
member ring forms are 2-acetamido-2-deoxy-D-ribofuranoside,
2-acetamido-2-deoxy-D-ribopyranoside,
2-acetamido-2-deoxy-D-glucofuranoside,
2-acetamido-2-deoxy-D-glucopyranoside,
2-acetamido-2-deoxy-D-galactofuranoside and
2-acetamido-2-deoxy-D-galactopyranoside.
(ii) N-Acetylamino Acids
Another aspect of the invention pertains to compositions comprising
N-acetylamino acids and related compounds. N-acetylamino acids are
N-acetyl derivatives of amino acids. In accordance with the present
invention, the generic structure or formula of N-acetylamino acids
and related compounds which are topically beneficial for various
cosmetic and dermatologic indications may be represented as
follows:
##STR00002## where R.sub.1 is H, or an alkyl or aralkyl group
having 1 to 14 carbon atoms; n is an integer, preferably from 0 to
5; R.sub.2 is OH, NH.sub.2 or OR.sub.3; and R.sub.3 is an alkyl,
aralkyl or aryl group having 1 to 9 carbon atoms; the alkyl,
aralkyl or aryl group may be saturated or unsaturated, isomeric or
non-isomeric, straight or branched chain or cyclic form; and in
addition R.sub.1 may carry OH, SH, SCH.sub.3, COOH,
NH.sub.2CONH.sub.2, guanidine or heterocyclic group; the H attached
to a carbon atom may be substituted by I, F, Cl, Br or alkoxyl
group having 1 to 9 carbons. N-Acetylamino acids may be present as
isomeric or non-isomeric, as a free acid, salt, lactone, amide or
ester form.
The following are some representative N-acetylamino acids and
related compounds: N-acetyl-glycine, N-acetyl-alanine,
N-acetyl-valine, N-acetyl-leucine, N-acetyl-isoleucine,
N-acetyl-serine, N-acetyl-threonine, N-acetyl-tyrosine,
N-acetyl-cysteine, N-acetyl-methionine, N-acetyl-aspartic acid,
N-acetyl-asparagine, N-acetyl-glutamic acid, N-acetyl-glutamine,
N-acetyl-arginine, N-acetyl-lysine, N-acetyl-histidine,
N-acetyl-phenylalanine, N-acetyl-tyrosine, N-acetyl-tryptophan,
N-acetyl-proline, N-acetyl-.beta.-alanine, N-acetyl-taurine,
N-acetyl-r-aminobutanoic acid, N-acetyl-hydroxyproline,
N-acetyl-canavanine, N-acetyl-hydroxylysine, N-acetyl-cycloserine,
N-acetyl-homoarginine, N-acetyl-norleucine, N-acetyl-norvaline,
N-acetyl-homoserine, N-acetyl-methylserine, N-acetyl-hydroxyvaline,
N-acetylethionine, N-acetyl-methoxinine,
N-acetyl-.beta.-aminoisobutanoic acid, N-acetyl-homocysteine,
N-acetyl-cysteine sulfinic acid, N-acetyl-homophenylalanine,
N-acetyl-homotryptophan, N-acetyl-5-hydroxytryptamine
(N-acetylserotonin), N-acetyltryptamine, N-acetyl-ornithine,
N-acetyl-citrulline, N-acetyl-argininosuccinic acid, N-acetyl-dopa,
N-acetyl-3-iodotyrosine, N-acetyl-3,5-diiodotyrosine,
N-acetyl-3,5,3'-triiodothyronine, N-acetyl-thyroxine,
N-acetyl-creatine, N-acetyl-creatinine, N-acetyl-cystine and
N-acetyl-homocystine.
The above N-acetylamino acids and related N-acetyl compounds may be
present as a free acid, salt, lactone, amide or ester form.
Examples of these compounds include N-acetyl-cysteine ammonium
salt, N-acetyl-homocysteine thiolactone, N-acetyl-L-cystine methyl
ester, N-acetyl-L-tryosinamide, N-acetyl-L-tryosine ethyl ester,
N-acetyl-serine amide, N-acetylglycine methyl ester,
N-acetylglycinamide, and N-acetyl-tryptophan methyl, ethyl, propyl
or isopropyl esters.
The related N-acetyl compounds may also include dimers and
oligomers formed from N-acetylamino acids with 2 to 5 monomer
units. Examples include N-acetylglycylglycine and its amide and
esters, N-acetylglycyl-leucine its amide and esters,
N-acetylglycyltryptophan, N-acetylglycylglutamic acid and its amide
and esters, N-acetyltryosyl-phenylalanine and its amide and esters,
N-acetylglycyllysine and its amide and esters,
N-acetylleucyl-glycine and its amide and esters,
N-acetylglycyl-glycyl-glycine and its amide and esters,
N-acetylglycyl-lysyl-hydroxyproline and its amide and esters.
A preferred group N-Acetylamino acids and related compounds are the
group of compounds represented by the generic structure or formula
above, but excluding N-acetylcysteine and derivatives of
N-acetylcysteine. N-acetylcysteine is known to degrade under
ordinary storage conditions and result in a malodorous smell. The
malodor is suggested to be caused by the release of thiol compounds
and hydrogen sulfide upon degradation. Because N-acetylcysteine and
its derivatives are malodorous, they are less preferred for use in
the present invention.
2. Topical Uses of N-Acetyl-aldosamines, N-Acetylamino Acids and
Related N-Acetyl Compounds
(i) N-Acetyl-aldosamines, N-Acetylamino Acids and Related N-Acetyl
Compounds
Compositions comprising the N-acetyl-aldosamine, N-acetylamino acid
or related N-acetyl compounds described herein are topically
beneficial for various cosmetic conditions and dermatologic
disorders, including those associated with intrinsic and/or
extrinsic aging, as well as with changes or damage caused by
extrinsic factors. These compositions can comprise one or more than
one N-acetylaldosamine, N-acetylamino acid or related N-acetyl
compound. In a preferred embodiment, the compositions may be used
for skin, hair and nail changes associated with intrinsic and/or
extrinsic aging, and changes or damage caused by extrinsic
factors.
With respect to age associated skin changes, the underlying bases
of these changes is described in U.S. Pat. No. 4,603,146 (Kligman).
In particular, the underlying causes of skin changes associated
with aging can be more easily understood in view of the following
summary of the changes in the epidermis and dermis as aging
progresses.
With increasing age and exposure of a human to sun and other
environmental traumas, cells divide at a slower rate (decreased
capacity to renew themselves). They show marked irregularities in
size, shape and staining properties; orderliness (polarity) from
below to above is lost. The thickness of the epidermis decreases
(atrophy). The horny layer which comprises the barrier against
water loss and penetration of chemicals becomes abnormal due to the
shedding (exfoliation) of cells in large group or clusters instead
of as individual cells, resulting in roughness, scaling and
dryness. There is loss of the orderly transformation of living
epithelial cells into cornified dead cells which are shed at the
surface, that is, differentiation is impaired. Aberrant
differentiation results in numerous foci of abnormal epithelial
growths or tumors, the most frequent and important of which are
actinic keratoses. After many years these can transform into frank
skin cancers called basal cell and squamous cell cancers. Pigment
producing cells (melanocytes) can also become altered forming flat,
dark growths (lentigo melanoma) which may progress to malignant
melanoms.
The cells which make the fibers of the dermis become smaller and
sparser with increasing age, usually in sun-damaged facial skin.
There is a great loss of collagen fibers resulting in looseness and
easy stretchability of the skin; elastic fibers become abnormal so
that the skin does not promptly snap back after being stretched.
Since the fibrous components comprise more than 90% of the bulk of
skin of which 95% is collagen, the degradation of these fibers,
especially collagen, is mainly responsible for wrinkling, laxness
and loss of elasticity.
Additionally, small blood vessels become thin walled, dilated and
often ruptured. Vascular supply thereby becomes compromised.
The signs of nail and hair changes associated with intrinsic aging
and the damages caused by extrinsic factors include thinning of
hair and nail plate; lack of lubricants and luster, and uneven
surface of hair and nails; fragility and splitting of hair and
nails; and reduction of flexibility, resiliency, and elasticity of
hair and nails.
The conventional management of signs of aging skin has been the use
of cosmetics, as well as medical procedures such as phenol,
trichloroacetic acid, and other chemical peels, and plastic
surgery, etc. Such medical procedures are costly and risky with
serious side effects, and the treatments alter only the cosmetic
appearance of the skin, without any significant modifications of
the underlying aging process.
Topical application to the skin, hair or nails of a composition of
the present invention is beneficial for various cosmetic conditions
and dermatologic disorders including those associated with
intrinsic and/or extrinsic aging and extrinsic factors, and also
including those characterized by the foregoing changes to the skin,
hair and nails. Exemplary indications are characterized as
disturbed keratinization, defective syntheses of dermal components,
and changes associated with aging of skin, nail and hair; and those
indications which include dryness or loose of skin, nail and hair;
xerosis; ichthyosis; palmar and plantar hyperkeratoses; uneven and
rough surface of skin, nail and hair; dandruff; Darier's disease;
lichen simplex chronicus; keratoses; acne; pseudofolliculitis
barbae; eczema; psoriasis; itchy scalp and skin; pruritus; warts;
herpes; age spots; lentigines; melasmas; blemished skin;
hyperkeratoses; hyperpigmented skin; abnormal or diminished
syntheses of collagen, glycosaminoglycans, proteoglycans and
elastin as well as diminished levels of such components in the
dermis; stretch marks; skin lines; fine lines; wrinkles; thinning
of skin, nail plate and hair; skin thickening due to elastosis of
photoaging, loss or reduction of skin, nail and hair resiliency,
elasticity and recoilability; lack of skin, nail and hair
lubricants and luster; dull and older-looking skin, nail and hair;
fragility and splitting of nail and hair; and other topical
conditions and indications.
(ii) Combination Compositions
In addition, compositions comprising one or more than one
N-Acetyl-aldosamine, N-acetylamino acid and related N-acetyl
compound may also be incorporated into a composition comprising a
cosmetic, pharmaceutical or other topical agent to enhance or
create synergetic effects.
In accordance with this aspect of the invention, the compositions
of the present invention may contain one or more
N-Acetyl-aldosamine, N-acetylamino acid and related N-acetyl
compounds to magnify the therapeutic effect of an unrelated
cosmetic or pharmaceutical agent. At least one compound selected
from the group consisting of N-Acetyl-aldosamine, N-acetylamino
acid and related N-acetyl compounds may be incorporated into
composition containing a cosmetic or pharmaceutical agent for
topical treatment to improve or alleviate signs of skin, nails or
hair changes associated with intrinsic aging or the damages caused
by extrinsic factors. It has been found that such incorporation
results in magnified therapeutic efficacies which are not simply
additive effects.
Most pharmaceutical drugs produce their therapeutic effects by
first interacting with their receptors in the target tissues. Many
drug receptors are functional macromolecules such as enzymes, cell
membrane components or certain components of cells. The binding
affinity or interacting property of a drug toward its specific
receptor molecule is intimately governed by the chemical structure
of the drug. Since most pharmaceutical agents are chemically
different from N-acetyl compounds of the instant invention, the
respective receptor molecule should be different and so are the
pharmacological actions and the therapeutic effects. Under such
conditions if N-Acetyl-aldosamine, N-acetylamino acid and/or a
related N-acetyl compound is incorporated into a composition
containing a pharmaceutical agent, one of the following two
consequences may arise:
(a) No enhancement or any substantial changes in either effect. In
this case, the overall clinical effect would be a mixed effect,
i.e. the effect due to the pharmaceutical agent alone mixed with
the effect due to N-Acetyl-aldosamine, N-acetylamino acid or
related N-acetyl compound alone. Also in this case, the interaction
between the pharmaceutical agent and its receptor molecule is not
affected nor interfered by the presence of N-Acetyl-aldosamine,
N-acetylamino acid or related N-acetyl compound. Nor does the
N-Acetyl-aldosamine, N-acetylamino acid or related N-acetyl
compound assist in or enhance the binding affinity or the
interaction of the pharmaceutical agent toward its receptor
molecule. The clinical results from such combination composition
would be just the mixed effects.
(b) Amplified therapeutic action or substantial loss of therapeutic
action in either effect. In this case, the interaction between the
pharmaceutical agent and its receptor molecule is affected either
positively or negatively by the presence of a N-Acetyl-aldosamine,
N-acetylamino acid or related N-acetyl compound. From the point of
positive effect, N-Acetyl-aldosamine, N-acetylamino acid or the
related N-acetyl compound may produce an amplified effect by either
increasing the affinity of the receptor molecule toward the
pharmaceutical agent; acting as a better and more efficient
coenzyme or as an activator by disrupting barriers and removing
obstacles for better binding of the agent toward its receptor
molecule; for example, enzyme activation by removal of natural
inhibitors. In all these cases the overall clinical results would
be due to magnified therapeutic effects which are not predictable
from either effect alone.
From the point of negative effect, a N-Acetyl-aldosamine,
N-acetylamino acid or related N-acetyl compound might interfere
with or decrease the binding affinity of the pharmaceutical agent
toward its receptor molecule; i.e. acting as an competitor or
inhibitor. In such case, the overall clinical results should be due
to substantial diminishment or completely loss of therapeutic
effects, which is also unpredictable from either effect alone.
We have found that, in most cases, therapeutic effects of cosmetic
and pharmaceutical agents are amplified when a N-acetyl-aldosamine,
N-acetylamino acid or related N-acetyl compound is incorporated
into the composition, i.e., consequence (b) above is observed.
The cosmetic and pharmaceutical agents which may be actuated by
N-Acetyl-aldosamine, N-acetylamino acid or a related N-acetyl
compound include those that improve or eradicate age spots,
keratoses and wrinkles; local analgesics and anesthetics; antiacne
agents; antibacterials; antiyeast agents; antifungal agents;
antiviral agents; antidandruff agents; antidermatitis agents;
antihistamine agents; antipruritic agents; antiemetics; antimotion
sickness agents; antiinflammatory agents; antihyperkeratolytic
agents; antiperspirants; antipsoriatic agents; antiseborrheic
agents; hair conditioners and hair treatment agents; antiaging and
antiwrinkle agents; sunblock and sunscreen agents; skin lightening
agents; depigmenting agents; vitamins; corticosteroids; tanning
agents; hormones; retinoids; and other dermatologicals.
Some examples of cosmetic and pharmaceutical agents are
clotrimazole, ketoconazole, miconazole, griseoflivin, econazole,
metronidazole, hydroxyzine, diphenhydramine, pramoxine, lidocaine,
procaine, mepivacaine, monobenzone, erythromycin, tetracycline,
clindamycin, meclocycline, hydroquinone, hydroquinone monoether,
minocycline, naproxen, ibuprofen, theophylline, cromolyn,
albuterol, retinol, retinyl acetate, retinyl palmitate, retinal,
retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone
21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate,
betamethasone valerate, betamethasone dipropionate, triamcinolone
acetonide, fluocinonide, clobetasol, propionate, benzoyl peroxide,
kojic acid, crotamiton, propranolol, promethazine, salicylic acid,
vitamin E and vitamin E acetate.
Another example of cosmetic or other agents that may be combined
with one or more N-acteyl-aldosamines, N-acetylamino acids or
related N-acetyl compounds include hydroxyacids, ketoacids and
related compounds. Examples of hydroxy acids include
hydroxymonocarboxylic acids, hydroxydicarboxylic acids,
2-hydroxycarboxylic acids, other hydroxycarboxylic,
2-ketocarboxylic acids acids and related compounds. See, for
example, U.S. Pat. Nos. 5,422,370, 5,547,988, 5,470,880, and
5,385,938. The hydroxy acids may exist as a free acid, an ester, a
lactone, in salt form with an organic base or an inorganic alkali,
and as stereoisomers. Representative examples of hydroxy acids and
related compounds include glycolic acid, mandelic acid, lactic
acid, tropic acid, methyllactic acid, lactobionic acid, tartaric
acid, citric acid, glucuronic acid, ribonic acid, gluconolactone,
ribonolactone, gycolyl glycollate, lactyl lactate, trilactic acid
and polylactic acid.
Yet another example of cosmetic or other agents that may be
combined with one or more N-acteyl-aldosamines, N-acetylamino acids
or related N-acetyl compounds include phenyl alpha acyloxyalkanoic
acids and derivatives thereof. These compounds may exist in a free
acid, lactone or salt form, or as stereoisomers. See, for example,
U.S. Pat. Nos. 5,258,391 and 5,643,949. Representative example of
such compounds include diphenyl alpha acetoxyacetic acid, phenyl
alpha acetoxyacetic acid, phenyl alpha methyl alpha acetoxyacetic
acid, phenyl alpha acetoxypropanoic acid, and 2-phenyl beta
acetoxypropanoic acid.
3. General Preparation of the Cosmetic and Therapeutic
Compositions
Compositions comprising N-acetyl-aldosamine, N-acetylamino acid or
related N-acetyl compounds of the instant invention may be
formulated as solution, gel, lotion, cream, ointment, shampoo,
spray, stick, powder, masque or other form topically acceptable for
use on skin, nail and hair.
To prepare a solution composition, at least one N-acetyl compound
of the instant invention is dissolved in a solution prepared from
water, ethanol, propylene glycol, butylene glycol, diisopropyl
adipate and/or other topically acceptable vehicle. The
concentration of a single N-acetyl compound or the total
concentration of all N-acetyl compounds, where the composition
comprises more than one N-acetyl compound, may range from 0.01 to
99.9% by weight of the total composition, with preferred
concentration of from 0.1 to 50% by weight of the total composition
and with more preferred concentration of from 0.5 to 25% by weight
of the total composition. Contemplated embodiments of the instant
invention include ranges of 0.1% to 0.2%, 0.2% to 0.3%, 0.3% to
0.4%, 0.4% to 0.5%, 0.5% to 0.6%, 0.6% to 0.7%, 0.7% to 0.8%, 0.8%
to 0.9%, 0.9% to 1%, 1% to 2%, 2% to 3%, 3% to 4%, 4% to 5%, 5% to
6%, 6% to 7%, 7% to 8%, 8% to 9%, 9% to 10%, 10% to 14%, 14% to
18%, 18% to 22%, 22% to 26%, 26% to 30%, 30% to 35%, 35% to 40%,
40% to 45%, 45% to 50%, 50% to 60%, 60% to 70%, 70% to 80%, 80% n
to 90%, and 90% to 99.9% by weight of the total composition.
To prepare a topical composition in lotion, cream or ointment form,
the N-acetyl compound is first dissolved in water, ethanol,
propylene glycol, diisopropyl adipate and/or another vehicle, and
the solution thus obtained is mixed with a desired base or
pharmaceutically acceptable vehicle to make lotion, cream or
ointment. Concentrations of the N-acetyl compound are the same as
described above for the solution form.
A topical composition of the instant invention may also be
formulated in a gel or shampoo form. A typical gel composition is
formulated by the addition of a gelling agent such as chitosan,
methyl cellulose, ethyl cellulose, polyvinyl alcohol,
polyquaterniums, hydroxyethylcellulose, hydroxypropylcellulose,
hydroxypropylmethylcellulose, carbomer or ammoniated
glycyrrhizinate to a solution comprising the N-acetyl compound. The
preferred concentration of the gelling agent may range from 0.1 to
4 percent by weight of the total composition. In the preparation of
shampoo, the N-acetyl compound is first dissolved in water or
propylene glycol, and the solution thus obtained is mixed with a
shampoo base. Concentrations of the N-acetyl compound used in gel
or shampoo form are the same as described above.
To prepare a combination composition for synergetic effects, a
cosmetic, pharmaceutical or other topical agent is incorporated
into any one of the above compositions by dissolving or mixing the
agent into the formulation.
Other forms of compositions for topical delivery of N-acetyl
compound of the instant invention are readily prepared or
formulated by those skilled in the art.
The following are illustrative examples of formulations according
to this invention. Although the examples utilize only selected
compounds and formulations, it should be understood that the
following examples are illustrative and not limiting. Therefore,
any of the aforementioned N-acetyl compounds may be substituted
according to the teachings of this invention in the following
examples.
EXAMPLE 1
A typical N-acetyl-aldosamine, N-acetylamino acid or the related
acetyl compound in a cream composition may be formulated as
follows. N-Acetyl-.alpha.-D-glucosamine 10 g was dissolved in 30 ml
warm water, and the solution thus obtained was mixed uniformly with
60 g cream base or commercially available hydrophilic ointment. The
white cream thus formulated contained 10% N-acetyl-glucosamine.
N-Acetyl-glucosamine 1% or 5% cream was formulated in the same
manner except that N-acetyl-.alpha.-D-glucosamine 1 g or 5 g was
used, and was dissolved in 39 ml or 35 ml water.
EXAMPLE 2
N-Acetyl-D-mannosamine 1 g was dissolved in 20 ml warm water, and
the solution thus obtained was mixed uniformly with 79 g cream base
or commercially available hydrophilic ointment. The white cream
thus formulated contained 1% N-acetyl-mannosamine.
EXAMPLE 3
N-Acetyl-L-glutamine 0.5 g was dissolved in 20 ml water, and the
solution thus obtained was mixed uniformly with 79.5 g cream base
or commercially available hydrophilic ointment. The white cream
thus formulated contained 0.5% N-acetyl-L-glutamine.
EXAMPLE 4
N-Acetyl-DL-proline 2 g was dissolved in 20 ml warm water, and the
solution thus obtained was mixed uniformly with 78 g cream base or
commercially available hydrophilic ointment. The white cream thus
formulated contained 2% N-acetyl-proline.
EXAMPLE 5
N-Acetyl-glycine 3 g was dissolved in 20 ml water, and the solution
thus obtained was mixed uniformly with 77 g cream base or
commercially available hydrophilic ointment. The white cream thus
formulated contained 3% N-acetyl-glycine.
EXAMPLE 6
N-Acetyl-L-arginine 4 g was dissolved in 20 ml water, and the
solution thus obtained was mixed uniformly with 76 g cream base or
commercially available hydrophilic ointment. The white cream thus
formulated contained 4% N-acetyl-arginine.
EXAMPLE 7
A typical N-acetyl-aldosamine, N-acetylamino acid or related
N-acetyl compound in a solution composition may be formulated as
follows. N-acetyl-.alpha.-D-glucosamine 0.5 g was dissolved in 99.5
ml solution prepared from water 40 ml, ethanol 40 ml and propylene
glycol 20 ml. The composition thus prepared contained 0.5%
N-acetyl-glucosamine. N-Acetyl-glucosamine 5% in solution form was
formulated in the same manner except that 5 g instead of 0.5 g
active ingredient was dissolved in 95 ml solution.
EXAMPLE 8
N-Acetyl-D-galactosamine 1 g was dissolved in 99 ml solution
prepared from water 40 ml, ethanol 40 ml and propylene glycol 20
ml. The composition thus prepared contained 1%
N-acetyl-galactosamine.
EXAMPLE 9
N-Acetyl-L-tyrosinamide 2 g was dissolved in 98 ml solution
prepared from water 40 ml, ethanol 40 ml and propylene glycol 20
ml. The composition thus prepared contained 2%
N-acetyl-tyrosinamide.
EXAMPLE 10
N-Acetyl-L-lysine 0.5 g was dissolved in 99.5 ml solution prepared
from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The
composition thus prepared contained 0.5% N-acetyl-lysine.
EXAMPLE 11
N-Acetyl-L-tyrosine 0.2 g was dissolved in 99.8 ml solution
prepared from water 40 ml, ethanol 40 ml and propylene glycol 20
ml. The composition thus prepared contained 0.2%
N-acetyl-tyrosine.
EXAMPLE 12
N-Acetyl-L-cysteine methyl ester 0.5 g was dissolved in 99.5 ml
solution prepared from water 40 ml, ethanol 40 ml and propylene
glycol 20 ml. The composition thus prepared contained 0.5%
N-acetyl-cysteine methyl ester.
EXAMPLE 13
N-Acetyl-L-tyrosine ethyl ester 3 g was dissolved in 97 ml solution
prepared from ethanol 80 ml and propylene glycol 20 ml. The
composition thus prepared contained 3% N-acetyl-tyrosine ethyl
ester.
EXAMPLE 14
N-acetyl-L-cysteine 2 g was dissolved in 98 ml solution prepared
from water 80 ml and propylene glycol 20 ml. The composition thus
prepared contained 2% N-acetyl-cysteine.
EXAMPLE 15
A typical combination composition comprising for example
N-acetyamino acid ester and hydrocortisone 17-valerate for eczema
and other inflammatory dermatoses may be formulated as follows.
N-Acetyl-L-tyrosine ethyl ester 3 g and hydrocortisone 17-valerate
0.4 g were dissolved in 20 ml warm propylene glycol, and the
solution thus obtained was mixed uniformly with 76.6 g cream base
or commercially available hydrophilic ointment. The white cream
thus formulated had pH 5.1, and contained 3% N-acetyl-L-tyrosine
ethyl ester and 0.4% hydrocortisone 17-valerate.
EXAMPLE 16
A typical combination composition comprising for example
N-acetylaldosamine and an anti-itch agent may be formulated as
follows.
N-Acetyl-.alpha.-D-glucosamine 2 g was dissolved in 10 ml water and
the solution was mixed with diphenhydramine 2 g in 4 ml water
containing 2 g gluconolactone. The above solution was mixed
uniformly with 80 g cream base or commercially available
hydrophilic ointment. The composition with pH 5.1 contained 2%
N-acetyl-D-glucosamine and 2% diphenhydramine.
A male subject, age 66, having an itchy lesion of lichen simplex
chronicus on his right lower leg topically applied the above cream
to the lesion. A few minutes after the topical application, the
itch disappeared completely and the skin remained free of itch for
the following 12 hours.
4. Application and Treatment Using N-Acetyl-Aldosamines,
N-Acetylamino Acids and Related N-Acetyl Compounds
The N-acetyl aldosamines, N-acetylamino acids and related N-acetyl
compositions of the present invention may be applied to any area of
the skin, hair, or nails. Exemplary areas of application include
the hands, arms, neck, legs, feet, trunk, hair shaft, nails,
including the nail plate and nail cuticle, and on and around the
face. Exemplary areas of facial application include the nose,
forehead, and areas around the eyes. The compositions may be
applied with or without occlusion. Any suitable occlusive device
may be used. In addition, it is within the knowledge of the skilled
artisan how best to apply such occlusive devices to achieve the
desired result.
The compositions of the present invention may be applied to these
areas with varying frequency and for varying duration. In this
regard, the skilled artisan will appreciate how to alter the
frequency and duration of application to achieve the desired
effect. For example, the compositions of the instant invention can
be applied at varying frequencies including on a daily basis, 1 or
more times daily, or 1 or more times weekly. When being applied on
a daily basis, the instant invention can be applied 1, 2, 3 or more
times a day. When being applied on a weekly basis the instant
invention can be applied 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or
more times a week. The duration of treatment with the compositions
of the instant invention can also vary. For example, the
compositions may be applied for 1, 2, 3, 4, 5, 6 or more weeks; or
for 1, 2, 3, 4, 5, 6 or more months. The duration of treatment may
also be continuous. Again, the skilled artisan will appreciate the
interaction between frequency and duration of use in order to
achieve and/or maintain the desired effect.
In addition, the skilled artisan will appreciate how to vary
concentrations of the instant invention in conjunction with the
frequency and duration of use to achieve the desired effect. For
example, a composition of higher concentration might be applied
with less frequency or for a shorter duration. In contrast, a
composition of a lower concentration might be applied more
frequently or for a longer duration.
TEST RESULTS
A Method of Measurement
In one of the studies related to skin changes associated with
aging, skin thickness was measured by micrometer calipers as
follows: The skin was grasped with a 2.times.6 cm metal hinge, the
internal faces of the hinge were coated with emery cloth to prevent
slippage, and manually squeezed to threshold subject discomfort.
Combined thickness of two whole-skin layers including thickness of
the two hinge leaves was measured with micrometer calipers.
Thickness of the two hinge leaves was subtracted to determine the
actual thickness of two whole-skin layers. Triplicate measurements
on treated site were done and an average number was used for
calculation of the skin thickness.
1. Xerosis and Dry Skin
A male subject, age 66, who had xerosis and dry skin on lower legs
topically applied twice daily 5% N-acetyl-glucosamine cream for one
week. After a few days of topical treatment, the skin became less
rough and scaly, and felt smooth. The dry skin returned to
normal-looking skin after one week of topical application. This
result indicated that N-acetyl-glucosamine was therapeutically
effective for topical treatment of xerosis and dry skin.
2. Acne
A female subject, age 27, who had adolescent acne with multiple
papules and pustules on her face applied topically twice daily 5%
N-acetyl-glucosamine solution. After a few days of treatment, most
lesions became less inflamed and gradually eradicated. This result
indicated that N-acetyl-glucosamine was therapeutically effective
for topical treatment of acne.
3. Effect of an N-acetyl Compound on Skin
In order to determine biological effects of a topically applied
N-acetyl compound of the instant invention, seven women and one man
of ages ranging from 58 to 81 years participated in this study.
Topical formulation for the study was N-acetyl-L-cysteine 2% in a
solution prepared from water 80 ml and propylene glycol 20 ml.
Test sites were 1 cm square sites on extensor surface of forearm, 5
cm from the antecubital crease, a grid pattern formed by Hayes Test
Chambers on Hayes adhesive strips. Each test chamber, 1 cm square,
contained a square piece of filter paper which was fully moistened
with 0.033 ml test solution.
Test chambers were impressed on the skin to leave outlines which
were marked with Sanford Sharpie permanent marker. Sites were
re-marked at each successive application of test solutions. Vehicle
control sites were on the opposite forearm. Filter paper of each
chamber was saturated with 0.033 ml solution and chambers were
fixed in place with the Hayes adhesive tape that held the test and
vehicle chambers. Chambers were removed twice weekly, and replaced
with a new adhesive strip of chambers with filter paper moistened
with test or vehicle solutions. The test was carried out for five
weeks. Punch biopsy specimens, 3 mm or 4 mm in diameter, were
secured at the end of the study, and specimens were processed and
analyzed. Measurements of several tissue characteristics were also
made.
Punch biopsy specimens obtained from test and control sites were
placed immediately into the fixative, and processed for
histochemical staining.
Epidermal thickness was measured with Micro Image Analysis System,
and the mean thickness was expressed as area of
epidermis/horizontal length. The thickness of papillary dermis
(upper dermis) was also measured.
All the skin sites treated with N-acetyl-cysteine showed an average
of 96% increase in thickness of epidermis over the control. In
addition, all the test sites showed 47-227% increase in production
of hyaluronic acid in papillary dermis over the control.
The above results indicated that N-acetyl compounds of the instant
invention would be topically beneficial for treatment of various
cosmetic or dermatologic indications including wrinkles and changes
of skin, nail and hair associated with intrinsic and extrinsic
aging.
4. Effect of N-acetyl-glucosamine on Skin
A female subject, age 74, applied topically twice daily 10%
N-acetyl-glucosamine cream to her right forearm for three weeks.
After three weeks her untreated left forearm was still loose,
relatively thin and wrinkled when lifted. In contrast, her right
forearm was more firm, smooth, plump and minimally wrinkled when
lifted. While there was no change in skin thickness of her left
forearm, her right forearm had increased 37% in skin thickness as
measured by the micrometer calipers. This result indicated that
N-acetyl-glucosamine would be therapeutically effective for topical
treatment of wrinkles and changes of skin, nail or hair associated
with aging.
5. Effect of N-acetyl-DL-homocysteine thiolactone on Skin
A male subject, age 76, applied topically twice daily 5%
N-acetyl-DL-homocysteine thiolactone cream to his right forearm for
three weeks. After three weeks his untreated left forearm was still
loose, relatively thin and wrinkled when lifted. In contrast, his
right forearm was more firm, smooth, plump and minimally wrinkled
when lifted. While there was no change in skin thickness of his
left forearm, his right forearm had increased 89% in skin thickness
as measured by the micrometer calipers. This result indicated that
N-acetyl-homocysteine thiolactone would be therapeutically
effective for topical treatment of wrinkles and changes of skin,
nail or hair associated with aging.
6. Effect of N-acetyl-L-cysteine on Skin
A female subject, age 71, applied topically twice daily 5%
N-acetyl-L-cysteine cream to her right forearm for three weeks.
After three weeks her untreated left forearm was still loose,
relatively thin and wrinkled when lifted. In contrast, her right
forearm was more firm, smooth, plump and minimally wrinkled when
lifted. While there was no change in skin thickness of her left
forearm, her right forearm had increased 14% in skin thickness as
measured by the micrometer calipers. This result indicated that
N-acetyl-cysteine would be therapeutically effective for topical
treatment of wrinkles and changes of skin, nails or hair associated
with aging.
7. Effect of N-acetyl-L-cysteine methyl ester on Skin
A female subject, age 59, applied topically twice daily 5%
N-acetyl-L-cysteine methyl ester cream to her right forearm for
three weeks. After three weeks her untreated left forearm was still
loose, relatively thin and wrinkled when lifted. In contrast, her
right forearm was more firm, smooth, plump and minimally wrinkled
when lifted. While there was no change in skin thickness of her
left forearm, her right forearm had increased 13% in skin thickness
as measured by the micrometer calipers. This result indicated that
N-acetyl-cysteine methyl ester would be therapeutically effective
for topical treatment of wrinkles and changes of skin, nails or
hair associated with aging.
8. Effect of N-acetyl-L-cysteine methyl ester on Skin
A female subject, age 72, applied topically twice daily 10%
N-acetyl-L-cysteine methyl ester cream to her left forearm for
three weeks. After three weeks her untreated right forearm was
still loose, relatively thin and wrinkled when lifted. In contrast,
her left forearm was more firm, smooth, plump and minimally
wrinkled when lifted. While there was no change in skin thickness
of her right forearm, her left forearm had increased 26% in skin
thickness as measured by the micrometer calipers. This result
indicated that N-acetyl-L-cystine methylester would be
therapeutically effective for topical treatment of wrinkles and
changes of skin, nail or hair associated with aging.
9. Effect of N-acetyl-L-cysteine methyl ester on Skin
A male subject, age 76, applied topically twice daily 5%
N-acetyl-L-cysteine methyl ester cream to his left forearm for
three weeks. After three weeks his untreated right forearm was
still loose, relatively thin and wrinkled when lifted. In contrast,
his left forearm was more firm, smooth, plump and minimally
wrinkled when lifted. While there was no change in skin thickness
of his right forearm, his left forearm had increased 87% in skin
thickness as measured by the micrometer calipers. This result
indicated that N-acetyl-cysteine methyl ester would be
therapeutically effective for topical treatment of wrinkles and
changes of skin, nail or hair associated with aging.
10. Effect of N-acetyl-DL-homocysteine thiolactone on Skin
A female subject, age 59, applied topically twice daily 5%
N-acetyl-DL-homocysteine thiolactone cream to her left forearm for
three weeks. After three weeks her untreated right forearm was
still loose, relatively thin and wrinkled when lifted. In contrast,
her left forearm was more firm, smooth, plump and minimally
wrinkled when lifted. While there was no change in skin thickness
of her right forearm, her left forearm had increased 21% in skin
thickness as measured by the micrometer calipers. This result
indicated that N-acetyl-homocysteine thiolactone would be
therapeutically effective for topical treatment of wrinkles and
changes of skin, nail or hair associated with aging.
11. Effect of N-acetyl-DL-tryptophan on Skin
A female subject, age 71, applied topically twice daily 10%
N-acetyl-DL-tryptophan cream to her left forearm for three weeks.
After three weeks her untreated right forearm was still loose,
relatively thin and wrinkled when lifted. In contrast, her left
forearm was more firm, smooth, plump and minimally wrinkled when
lifted. While there was no change in skin thickness of her right
forearm, her left forearm had increased 11% in skin thickness as
measured by the micrometer calipers. This result indicated that
N-acetyl-tryptophan would be therapeutically effective for topical
treatment of wrinkles and changes of skin, nail or hair associated
with aging.
12. Effect of N-acetyl-L-tyrosine ethyl ester on Skin
A female subject, age 47, applied topically twice daily 10%
N-acetyl-L-tyrosine ethyl ester cream to her left forearm for four
weeks. After four weeks her untreated right forearm was still
loose, relatively thin and wrinkled when lifted. In contrast, her
left forearm was more firm, smooth, plump and minimally wrinkled
when lifted. While there was no change in skin thickness of her
right forearm, her left forearm had increased 11% in skin thickness
as measured by the micrometer calipers. This result indicated that
N-acetyl-L-tyrosine ethyl ester would be therapeutically effective
for topical treatment of wrinkles and changes of skin, nail or hair
associated with aging.
13. Effect of N-acetyl-DL-tryptophan on Skin
A female subject, age 56, applied topically twice daily 10%
N-acetyl-DL-tryptophan cream to her right forearm for three weeks.
After three weeks her untreated left forearm was still loose,
relatively thin and wrinkled when lifted. In contrast, her right
forearm was more firm, smooth, plump and minimally wrinkled when
lifted. While there was no change in skin thickness of her left
forearm, her right forearm had increased 21% in skin thickness as
measured by the micrometer calipers. This result indicated that
N-acetyl-tryptophan would be therapeutically effective for topical
treatment of wrinkles and changes of skin, nail or hair associated
with aging.
14. Effect of N-acetyl-L-arginine on Skin
A female subject, age 47, applied topically twice daily 10%
N-acetyl-L-arginine cream to her right forearm for four weeks.
After four weeks her untreated left forearm was still loose,
relatively thin and wrinkled when lifted. In contrast, her right
forearm was more firm, smooth, plump and minimally wrinkled when
lifted. While there was no change in skin thickness of her left
forearm, her right forearm had increased 32% in skin thickness as
measured by the micrometer calipers. This result indicated that
N-acetyl-L-arginine would be therapeutically effective for topical
treatment of wrinkles and changes of skin, nail or hair associated
with aging.
15. Effect of N-acetyl-DL-tryptophan on Skin
A female subject, age 66, applied topically twice daily 10%
N-acetyl-DL-tryptophan cream to her left forearm for five weeks.
After five weeks her untreated right forearm was still loose,
relatively thin and wrinkled when lifted. In contrast, her left
forearm was more firm, smooth, plump and minimally wrinkled when
lifted. While there was no change in skin thickness of her right
forearm, her left forearm had increased 12% in skin thickness as
measured by the micrometer calipers. This result indicated that
N-acetyl-tryptophan would be therapeutically effective for topical
treatment of wrinkles and changes of skin, nail or hair associated
with aging.
16. Effect of N-acetyl-L-tyrosine ethyl ester on Skin
A female subject, age 72, applied topically twice daily 10%
N-acetyl-L-tyrosine ethyl ester cream to her right forearm for four
weeks. After four weeks her untreated left forearm was still loose,
relatively thin and wrinkled when lifted. In contrast, her right
forearm was more firm, smooth, plump and minimally wrinkled when
lifted. While there was no change in skin thickness of her left
forearm, her right forearm had increased 34% in skin thickness as
measured by the micrometer calipers. This result indicated that
N-acetyl-tyrosine ethyl ester would be therapeutically effective
for topical treatment of wrinkles and changes of skin, nail or hair
associated with aging.
17. Effect of N-acetyl-L-arginine on Skin
A female subject, age 72, applied topically twice daily 10%
N-acetyl-L-arginine cream to her left forearm for four weeks. After
four weeks her untreated right forearm was still loose, relatively
thin and wrinkled when lifted. In contrast, her left forearm was
more firm, smooth, plump and minimally wrinkled when lifted. While
there was no change in skin thickness of her right forearm, her
left forearm had increased 22% in skin thickness as measured by the
micrometer calipers. This result indicated that N-acetyl-arginine
would be therapeutically effective for topical treatment of
wrinkles and changes of skin, nail or hair associated with
aging.
18. Effect of Combination Composition on Skin
A female subject, age 72, applied topically twice daily a
combination cream formulated from 10% each of
N-acetyl-.alpha.-D-glucosamine and gluconolactone to her right
forearm for three weeks. After three weeks her untreated left
forearm was still loose, relatively thin and wrinkled when lifted.
In contrast, her right forearm was more firm, smooth, plump and
minimally wrinkled when lifted. While there was no change in skin
thickness of her left forearm, her right forearm had increased 118%
in skin thickness as measured by the micrometer calipers. This
result indicated that N-acetyl-glucosamine in combination with
other topical agents would be topically effective for various
cosmetic and dermatologic indications including wrinkles and
changes of skin, nail and hair associated with intrinsic and
extrinsic aging.
19. Effect of N-acetylamino Acid on the Scalp
A typical composition suitable for topical use on hair, scalp, nail
and skin comprising for example N-acetylamino acid may be
formulated as follows. N-Acetyl-DL-proline 2 g was dissolved in 98
ml solution prepared from water 40 ml, ethanol 40 ml and propylene
glycol 20 ml. The composition with pH 2.7 contained 2%
N-acetyl-DL-proline. A male subject, age 66, having itchy scalp
topically applied the above composition to itchy area of scalp. A
few minutes after the topical application, scalp itch disappeared
completely and the scalp remained free of itch for the next 24
hours.
20. Effect of Combination Composition (Anti-fungal Agent) on Nail
or Scalp
A typical composition comprising for example N-acetylamino acid in
combination with an anti-fungal agent for nail or scalp infections
may be formulated as follows. N-Acetylglycine 2 g was dissolved in
98 ml solution prepared from water 40 ml, ethanol 40 ml and
propylene glycol 20 ml. The composition thus prepared contained 2%
N-acetylglycine, and was used as a nail or scalp conditioner. For
nail or scalp infections, N-acetylglycine 2 g and clotrimazole 2 g
were dissolved in 96 ml solution prepared from water 40 ml, ethanol
40 ml and propylene glycol 20 ml. The composition with pH 3.7
contained 2% N-acetylglycine and 2% clotrimazole, and were
topically effective for nail or scalp infections.
21. N-acetylamino Shampoo Composition
A typical shampoo composition comprising for example N-acetylamino
acid for hair, scalp or body wash may be formulated as follows.
N-Acetyl-L-arginine 4 g was dissolved in 20 ml water, and the
solution thus obtained was mixed uniformly with 76 g shampoo base.
The shampoo composition with pH 6.6 contained 4%
N-acetyl-L-arginine
22. Effect N-acetyl-L-lysine on an Oily Scalp
N-Acetyl-L-lysine 2 g was dissolved in a 98 ml solution prepared
from water 40 ml, ethanol 40 ml and propylene glycol 20 ml. The
composition with pH 6.5 contained 2% N-acetyl-L-lysine. A male
subject, age 66, having an oily and pruritic scalp topically
applied the above composition to the affected area of the scalp,
and the area was dried with warm air to remove excess solvents. A
few minutes after the topical application, the scalp itch
disappeared completely and the scalp remained free of itch the next
12 hours.
23. Effect of N-acetyl-DL-proline on Pruritus
A male subject, age 77, with chronic Grover's Disease (Acantholytic
Dermatosis) for approximately one year duration had complained
about excruciating pruritus on skin lesions of inflammatory papules
which did not respond well to conventional topical
anti-inflammatory agents. The subject topically applied
N-acetyl-DL-proline 5% in oil-in-water cream to the itchy lesions.
A few minutes after the topical application, the severe itch
disappeared completely and the lesions remained free of itch for
the next 12 hours.
24. Effect of N-acetyl-D-galactosamine on Urticaria
A female subject, age 72, having acute urticaria due to unknown
cause did not respond to conventional topical anti-itch
medications. The subject topically applied N-acetyl-D-galactosamine
5% in solution to skin areas of the urticarial lesions. A few
minutes after the topical application, the severe itch disappeared
completely and the skin remained free of itch for the next 24 hours
with concomitant disappearance of urticarial lesions.
25. Effect of N-acetyl-DL-proline on Itchy Skin and Dry Skin
Lesions
A female subject, age 86, with chronic nummular eczema and pruritic
dry skin topically applied N-acetyl-DL-proline 5% in solution to
itchy skin areas of eczema and dry skin lesions. A few minutes
after the topical application, the itch disappeared completely and
the lesions remained free of itch for the next 48 hours.
26. Effect of N-acetyl-DL-proline on Itchy Skin
A male subject, age 76, having axillary itch due to use of a
conventional antiperspirant topically applied N-acetyl-DL-proline
5% in solution to itchy underarm skin areas. Within a few minutes
after the topical application, the itch disappeared completely and
the skin remained free of itch for the next five days.
27. Effect of N-acetyl-L-glutamine on Pruritus
A male subject, age 77, with chronic Grover's Disease (Acantholytic
Dermatosis) for approximately one year duration had complained
about excruciating pruritus on skin lesions of inflammatory papules
which did not respond well to conventional topical
anti-inflammatory agents. The subject topically applied
N-acetyl-L-glutamine 5% in a solution prepared from water 4 parts,
ethanol 4 parts and propylene glycol 2 parts by volume. A few
minutes after the topical application, the severe itch disappeared
completely and the lesions remained free of itch for the next 24
hours.
28. Effect of N-acetyl-.alpha.-D-glucosamine on Pruritus
A male subject, age 77, with chronic Grover's Disease
(Ancantholytic Dermatosis) for approximately one year duration had
complained about excruciating pruritus on skin lesions of
inflammatory papules which did not respond well to conventional
topical anti-inflammatory agents. The subject topically applied
N-acetyl-.alpha.-D-glucosamine 5% in a solution prepared from water
4 parts, ethanol 4 parts and propylene glycol 2 parts by volume. A
few minutes after the topical application, the severe itch
disappeared completely and the lesions remained free of itch for
the next 24 hours.
The invention described herein may be embodied in other specific
forms without departing from the spirit or essential
characteristics thereof. The specific embodiments previously
described are therefore to be considered as illustrative of, and
not limiting, the scope of the invention. Additionally, the
disclosure of all publications cited above are expressly
incorporated herein by reference in their entireties to the same
extent as if each were incorporated by reference individually.
* * * * *