U.S. patent application number 11/872459 was filed with the patent office on 2008-04-17 for oligosaccharide aldonic acids and their topical use.
Invention is credited to Eugene J. Van Scott, Ruey J. Yu.
Application Number | 20080090772 11/872459 |
Document ID | / |
Family ID | 32962883 |
Filed Date | 2008-04-17 |
United States Patent
Application |
20080090772 |
Kind Code |
A1 |
Yu; Ruey J. ; et
al. |
April 17, 2008 |
Oligosaccharide Aldonic Acids and Their Topical Use
Abstract
Compositions comprising oligosaccharide aldonic acids are useful
for general care, as well as for treatment and prevention, of
various cosmetic conditions and dermatological disorders, including
those associated with intrinsic and/or extrinsic aging, as well as
with changes or damage caused by extrinsic factors; general care,
as well as treatment and prevention of diseases and conditions, of
the oral, and vaginal mucosa; for general oral care, as well as
treatment and prevention of oral and gum diseases; and for wound
healing of the skin. Compositions comprising oligosaccharide
aldonic acids 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) |
Correspondence
Address: |
GOODWIN PROCTER LLP
901 NEW YORK AVENUE, N.W.
WASHINGTON
DC
20001
US
|
Family ID: |
32962883 |
Appl. No.: |
11/872459 |
Filed: |
October 15, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10811998 |
Mar 30, 2004 |
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11872459 |
Oct 15, 2007 |
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09987023 |
Nov 13, 2001 |
6740327 |
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10811998 |
Mar 30, 2004 |
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09487228 |
Jan 19, 2000 |
6335023 |
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09987023 |
Nov 13, 2001 |
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60141264 |
Jun 30, 1999 |
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Current U.S.
Class: |
514/25 ; 514/165;
514/396; 514/458; 514/564; 514/680 |
Current CPC
Class: |
A61K 8/0212 20130101;
A61K 31/715 20130101; A61Q 11/00 20130101; A61K 31/122 20130101;
A61P 17/02 20180101; A61Q 19/02 20130101; A61K 31/355 20130101;
A61Q 19/08 20130101; A61P 31/00 20180101; A61K 31/4164 20130101;
A61Q 19/00 20130101; A61K 8/60 20130101; A61Q 5/02 20130101; A61K
31/7004 20130101; A61K 8/042 20130101; A61P 29/00 20180101; A61K
31/198 20130101; A61K 31/60 20130101; A61P 19/06 20180101; A61P
17/00 20180101; A61Q 19/007 20130101 |
Class at
Publication: |
514/025 ;
514/165; 514/396; 514/458; 514/564; 514/680 |
International
Class: |
A61K 31/7004 20060101
A61K031/7004; A61K 31/122 20060101 A61K031/122; A61K 31/198
20060101 A61K031/198; A61K 31/355 20060101 A61K031/355; A61Q 19/00
20060101 A61Q019/00; A61P 17/00 20060101 A61P017/00; A61K 31/4164
20060101 A61K031/4164; A61K 31/60 20060101 A61K031/60 |
Claims
1. A method for the general care, treatment, or prevention of
cosmetic conditions or dermatological disorders comprising
topically applying a composition comprising a therapeutically
effective amount of at least one aldobionic acid selected from the
group consisting cellobionic acid, gentiobionic acid,
isolactobionic acid, isomaltobionic acid, kojibionic acid,
laminarabionic acid, maltobionic acid, melibionic acid,
nigerobionic acid, rutinobionic acid, and sophorobionic acid, and
as free acid, ester, salt, lactone, stereoisomeric,
non-stereoisomeric, saturated or unsaturated, straight or branched
chain, or cyclic forms thereof.
2. The method of claim 1, wherein said aldobionic acid is
maltobionic acid.
3. The method of claim 1, wherein said cosmetic conditions or
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; and those
indications which include dryness or looseness 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; rosacea;
pseudofolliculitis barbae; eczema; psoriasis; itchy scalp and skin;
pruritus; warts; herpes; age spots; lentigines; melasmas; blemished
skin; hyperkeratoses; hyperpigmented skin; uneven skin tone;
redness; 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; and fragility and splitting of
nail and hair.
4. The method of claim 1, wherein said composition further
comprises a topically active agent.
5. The method of claim 4, wherein said topically active 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;
antihyperkeratotic agents; antiperspirants; antipsoriatic agents;
antirosacea agents; antieczema 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;
humectants; hormones; amino acids; dipeptides; tripeptides;
oligopeptides; polypeptides; retinoids; topical cardiovascular
agents; hydroxyacids, ketoacids and related compounds; phenyl alpha
acyloxyalkanoic acids and derivatives thereof; and
N-acetyl-aldosamines, N-acetylamino acids and related N-acetyl
compounds.
6. The method of claim 4, wherein said topically active agent is
selected from the group consisting of aclovate, acyclovir,
acetylsalicylic acid, adapalene, albuterol, aluminum acetate,
aluminum chloride, aluminum hydroxide, aluminum chlorohydroxide,
amantadine, aminacrine, p-aminobenzoic acid, .gamma.-aminobutanoic
acid, aminocaproic acid, aminosalicylic acid, amitriptyline,
anserine, anthralin, ascorbic acid, ascoryl palimate, atropine,
azelaic acid, bacitracin, bemegride, beclomethasone dipropionate,
benzocaine, benzophenone, benzoyl peroxide, betamethasone
dipropionate, betamethasone valerate, brompheniramine, bupivacaine,
butoconazole, calcipotriene, camphor, capsaicin, carbamide
peroxide, carnosine, chitosan, chlorhexidine, chloroxylenol,
chlorpheniramine, ciclopirox, clemastine, clindamycin, clioquinol,
clobetasol propionate, clotrimazole, coal tar, cromolyn,
crotamiton, cycloserine, dehydroepiandrosterone, desoximetasone,
dexamethasone, diphenhydramine, doxypin, doxylamine, dyclonine,
econazole, erythromycin, estradiol, ethinyl estradiol,
fluocinonide, fluocinolone acetonide, 5-fluorouracil, glutathione,
griseofulvin, guaifenesin, haloprogin, hexylresorcinol,
homocarnosine, homosalate, hydrocortisone, hydrocortisone
21-acetate, hydrocortisone 17-valerate, hydrocortisone 17-butyrate,
hydrogen peroxide, hydroquinone, hydroquinone monoether,
hydroxyzine, ibuprofen, ichthammol, imiquimod, indomethacin,
ketoconazole, ketoprofen, kojic acid, lidocaine, meclizine,
meclocycline, menthol, mepivacaine, methyl nicotinate, methyl
salicylate, metronidazole, miconazole, minocycline, minoxidil,
monobenzone, mupirocin, naftifine, naproxen, neomycin, nystatin,
octyl methoxycinnamate, octyl salicylate, ophidine, ornithine,
oxybenzone, oxiconazole, oxymetazoline, padimate O, permethrin,
pheniramine, phenol, phenylephrine, phenylpropanolamine, piperonyl
butoxide, podophyllin, podofilox, povidone iodine, polymyxins,
pramoxine, prilocaine, procaine, promethazine propionate,
propranolol, pseudoephedrine, pyrethrin, pyrilamine, resorcinol,
retinal, 13-cis retinoic acid, retinoic acid, retinol, retinyl
acetate, retinyl palmitate, salicylamide, salicylic acid, selenium
sulfide, shale tar, sulconazole, sulfur, sulfadiazine, tazarotene,
terbinafine, terconazole, tetracaine, tetracycline,
tetrahydrozoline, thymol, tioconazole, tolnaftate, triamcinolone
diacetate, triamcinolone acetonide, triamcinolone hexacetonide,
triclosan, triprolidine, undecylenic acid, urea, vitamin E acetate,
wood tar, zinc pyrithione, glycolic acid, lactic acid,
methyllacetic acid, 4-hydroxy-mandelic acid, mandelic acid,
gluconolactone, N-acetyl-glucosamine, N-acetyl-proline, phenyl
2-acetoxyethanoic acid and diphenyl 2-acetoxyethanoic acid.
7. The method of claim 1, wherein said composition further
comprises an inorganic or organic alkali, or amphoteric
substance.
8. The method of claim 7, wherein said inorganic alkali is selected
from the group consisting of ammonium hydroxide, ammonium
phosphate, ammonium carbonate, ammonium bicarbonate, sodium
hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate,
sodium phosphate, and alkalis formed from potassium, calcium,
magnesium, strontium, aluminum, zinc, and lithium.
9. The method of claim 7, wherein said organic alkali is selected
from the group consisting of organic amines, hydroxylamines,
imines, guanidines, amine oxides, alkanolamines, alkoxylated
amines, alkylamido alkylamines, polyamines, amino acid esters,
amino acid amides, aminosaccharides, aminoalditols, aminocyclitols,
fattyamines, and imidazolines.
10. The method of claim 7, wherein said organic alkali is selected
from the group consisting of diethanolamine, triethanolamine,
isopropanolamine, diisopropanolamine, triisopropanolamine,
aminobutanol, aminoethyl propanediol, aminomethyl propanol,
aminomethyl propanediol, isopropylamine, dimethylaminoethanol,
diethylaminoethanol, methylethanolamine, diisopropylamine,
dipropylenetriamine, glucamine, N-methylglucamine, morpholine,
tromethamine, cocamines, soyamines, oleamines, stearamines,
quaterniums, creatinine, glycine ethyl ester, arginine ethyl ester,
lysine methyl ester, proline ethyl ester, citrulline benzyl ester,
glycinamide, argininamide, prolinamide, lysinamide, glucosamines
and glucosylamines, other glycosamines and glycosylamines,
aminoinositols, chitosan, stearamidoethyl diethylamine,
stearamidopropyl dimethylamine, stearamidoethyl diethanolamine, and
quaternary ammonium hydroxide.
11. The method of claim 7, wherein said amphoteric substance is
selected from the group consisting of amino acids, peptides,
polypeptides, proteins and related compounds.
12. The method of claim 7, wherein said amphoteric substance is
selected from the group consisting of glycine, arginine, lysine,
cysteine, proline, glutamine, histidine, asparagine, tyrosine,
ornithine, citrulline, creatine, creatinine, and tryptophan.
13. A method for the general care, treatment, or prevention of
diseases or conditions of the oral, vaginal or anal mucosa or for
treating skin wounds, comprising topically applying a composition
comprising a therapeutically effective amount of at least one
aldobionic acid selected from the group consisting of cellobionic
acid, gentiobionic acid, isolactobionic acid, isomaltobionic acid,
kojibionic acid, lactobionic acid, laminarabionic acid, maltobionic
acid, melibionic acid, nigerobionic acid, rutinobionic acid, and
sophorobionic acid, and as free acid, ester, salt, lactone,
stereoisomeric, non-stereoisomeric, saturated or unsaturated,
straight or branched chain, or cyclic forms thereof.
14. The method of claim 13, wherein said aldobionic acid is
lactobionic acid.
15. The method of claim 13, wherein said aldobionic acid is
maltobionic acid.
16. The method of claim 13, wherein said skin wounds are selected
from the group consisting of skin cuts, tears, lacerations, burns,
and punctures.
17. The method of claim 13, wherein said composition further
comprises a topically active agent.
18. The method of claim 17, wherein said topically active agent is
selected from the group consisting of local analgesics and
anesthetics; antibacterials; antiyeast agents; antifungal agents;
antiviral agents; antidermatitis agents; antihistamine agents;
antipruritic agents; antiinflammatory agents; vitamins;
corticosteroids; hormones; retinoids; antioxidants;
N-acetyl-aldosamines, N-acetylamino acids and related N-acetyl
compounds.
19. The method of claim 17, wherein said topically active agent is
selected from the group consisting of benzocaine, clotrimazole,
ketoconazole, miconazole, griseofulvin, econazole, metronidazole,
hydroxyzine, diphenhydramine, phenylephrine, pramoxine, lidocaine,
procaine, mepivacaine, erythromycin, tetracycline, clindamycin,
meclocycline, 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, crotamiton, propranolol, promethazine, salicylic acid,
vitamin E, vitamin E acetate, mandelic acid, gluconolactone,
N-acetyl-glucosamine, N-acetyl-proline.
20. A method for the general care, treatment, or prevention of
cosmetic conditions or dermatological disorders comprising
topically applying a composition comprising a therapeutically
effective amount of lactobionic acid as free acid, ester, salt,
partial salt, lactone, stereoisomeric, non-stereoisomeric,
saturated or unsaturated, straight or branched chain, or cyclic
form thereof, wherein the cosmetic condition or dermatological
disorder is selected from the group of indications consisting of
dryness or looseness 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; rosacea; pseudofolliculitis barbae;
eczema; psoriasis; pruritus; warts; herpes, hyperkeratoses; stretch
marks; thinning of nail plate and hair; fragility and splitting of
nail and hair; wound-healing and treatment of skin wounds; general
care as well as treatment and prevention of diseases and conditions
of oral, gum, vaginal and anal mucosa.
21. The method of claim 20, wherein the cosmetic condition or
dermatological disorder is selected from the group of indications
consisting of dry skin, acne, rosacea, eczema, and
pseudofolliculitis barbae.
22. The method of claim 20, wherein the composition further
comprises a topically active agent selected from the group
consisting of local analgesics and anesthetics; antiyeast agents;
antifungal agents; antiviral agents; antidandruff agents;
antidermatitis agents; antihistamine agents; antipruritic agents;
antiemetics; antimotion sickness agents; antiinflammatory agents;
antihyperkeratotic agents; antiperspirants; antipsoriatic agents;
antiseborrheic agents; vitamins; corticosteroids; tanning agents;
hormones; amino acids; dipeptides; tripeptides; oligopeptides;
polypeptides; retinoids; wound healing agents; oral, vaginal and
anal care or treatment agents; and gum disease treatment or care
agents.
23. The method of claim 20, wherein the composition further
comprises a topically active agent is selected from the group
consisting of aclovate, acyclovir, adapalene, albuterol, aluminum
acetate, aluminum chloride, aluminum hydroxide, aluminum
chlorohydroxide, amantadine, aminacrine, .gamma.-aminobutanoic
acid, aminocaproic acid, amitriptyline, anserine, anthralin,
ascorbic acid, ascoryl palmitate, atropine, azelaic acid,
bacitracin, bemegride, beclomethasone dipropionate, benzocaine,
betamethasone dipropionate, betamethasone valerate,
brompheniramine, bupivacaine, butoconazole, calcipotriene, camphor,
capsaicin, carbamide peroxide, carnosine, chitosan, chlorhexidine,
chloroxylenol, chlorpheniramine, ciclopirox, clemastine,
clioquinol, clobetasol propionate, clotrimazole, coal tar,
cromolyn, crotamiton, cycloserine, dehydroepiandrosterone,
desoximetasone, dexamethasone, diphenhydramine, doxypin,
doxylamine, dyclonine, econazole, estradiol, ethinyl estradiol,
fluocinonide, fluocinolone acetonide, 5-fluorouracil, glutathione,
griseofulvin, guaifenesin, haloprogin, hexylresorcinol,
homocarnosine, hydrocortisone, hydrocortisone 21-acetate,
hydrocortisone 17-valerate, hydrocortisone 17-butyrate, hydrogen
peroxide, hydroxyzine, ibuprofen, ichthammol, imiquimod,
indomethacin, ketoconazole, ketoprofen, lidocaine, meclizine,
menthol, mepivacaine, methyl nicotinate, miconazole, minocycline,
minoxidil, mupirocin, naftifine, naproxen, neomycin, nystatin,
ophidine, ornithine, oxiconazole, oxymetazoline, permethrin,
pheniramine, phenol, phenylephrine, phenylpropanolamine, piperonyl
butoxide, podophyllin, podofilox, povidone iodine, polymyxins,
pramoxine, prilocaine, procaine, promethazine propionate,
propranolol, pseudoephedrine, pyrethrin, pyrilamine, resorcinol,
retinol, retinyl acetate, retinyl palmitate, salicylamide, selenium
sulfide, shale tar, sulconazole, sulfur, sulfadiazine, tazarotene,
terbinafine, terconazole, tetracaine, tetrahydrozoline, thymol,
tioconazole, tolnaftate, triamcinolone diacetate, triamcinolone
acetonide, triamcinolone hexacetonide, triclosan, triprolidine,
undecylenic acid, urea, vitamin E acetate, wood tar, and zinc
pyrithione.
24. The method of claim 20, wherein the general care or treatment
is for prevention and/or treatment against stinging or irritations
of skin caused by chemicals, procedures, chemical peels, or other
means.
25. A method of forming a gel matrix on the skin, hair, nail or
mucosa for the purpose of protection and other attributes
comprising topically applying a composition comprising at least one
aldobionic acid selected from the group consisting of cellobionic
acid, gentiobionic acid, isolactobionic acid, isomaltobionic acid,
kojibionic acid, lactobionic acid, laminarabionic acid, maltobionic
acid, melibionic acid, nigerobionic acid, rutinobionic acid, and
sophorobionic acid, and as free acid, ester, salt, lactone,
stereoisomeric, non-stereoisomeric, saturated or unsaturated,
straight or branched chain, or cyclic forms thereof; wherein a gel
matrix is formed on the skin, hair, nail or mucosa.
26. The method of claim 25, wherein said aldobionic acid is
lactobionic acid.
27. The method of claim 25, wherein said aldobionic acid is
maltobionic acid.
28. A method for the general care of skin comprising topically
applying a composition comprising a therapeutically effective
amount of lactobionic acid, as free acid, ester, salt, partial
salt, lactone, saturated or unsaturated, stereoisomeric or
non-stercoisomeric, straight or branched chain, or cyclic form
thereof, wherein the general care improves skin texture and pores,
flakiness and redness; makes skin soft, smooth, fresh, balanced,
visibly clear, even-toned and brighter; or increases skin fullness
and plumpness.
29. A method for the general care of skin comprising topically
applying a composition comprising a therapeutically effective
amount of maltobionic acid, as free acid, ester, salt, partial
salt, lactone, saturated or unsaturated, stereoisomeric or
non-stereoisomeric, straight or branched chain, or cyclic form
thereof, wherein the general care improves skin texture and pores,
flakiness and redness; makes skin soft, smooth, fresh, balanced,
visibly clear, even-toned and brighter; or increases skin fullness
and plumpness.
30. A method for the preventative care or treatment of skin
comprising topically applying a composition comprising a
therapeutically effective amount of lactobionic acid, as free acid,
ester, salt, partial salt, lactone, saturated or unsaturated,
stereoisomeric or non-stereoisomeric, straight or branched chain,
or cyclic form thereof, wherein the preventive care or treatment is
for damages caused by laser treatment or procedure, electromagnetic
radiation, or ionizing radiation such as alpha rays, beta rays,
X-rays, and gamma rays.
31. A method for the preventative care or treatment of skin
comprising topically applying a composition comprising a
therapeutically effective amount of maltobionic acid, as free acid,
ester, salt, partial salt, lactone, saturated or unsaturated,
stereoisomeric or non-stereoisomeric, straight or branched chain,
or cyclic form thereof, wherein the preventive care or treatment is
for damages caused by laser treatment or procedure, electromagnetic
radiation, or ionizing radiation such as alpha rays, beta rays,
X-rays, and gamma rays.
32. The method of claim 1, wherein the general care is for
prevention and/or treatment against stinging or irritations of skin
caused by chemicals, procedures or other means.
Description
[0001] This application is a divisional application and claims the
benefit of U.S. application Ser. No. 10/811,998, filed Mar. 30,
2004, which is a continuation of U.S. application Ser. No.
09/987,023, filed Nov. 13, 2001, now U.S. Pat. No. 6,740,327, which
is a continuation of U.S. application Ser. No. 09/487,228, filed
Jan. 19, 2000, now U.S. Pat. No. 6,335,023, which claims priority
from U.S. provisional application Ser. No. 60/141,264, filed Jun.
30, 1999.
FIELD OF THE INVENTION
[0002] This application relates to compositions comprising
oligosaccharide aldonic acids and related compounds, and their use
for cosmetic and dermatological indications, reducing and soothing
mucosa and skin erythema, inflammation or reaction caused by
internal or external factors, wound healing, and care of skin,
hair, nail, and oral and vaginal mucosa, including the use for
changes associated with intrinsic and extrinsic aging, and changes
or damage caused by extrinsic factors such as sunlight, radiation,
air pollution, wind, cold, heat, dampness, chemicals, smoke, and
cigarette smoking.
BRIEF DESCRIPTION OF THE PRIOR ART
[0003] In our U.S. patent application Ser. No. 06/945,680, filed
Dec. 23, 1986, entitled "Additives Enhancing Topical Actions of
Therapeutic Agents," and related applications, issuing, inter alia,
as U.S. Pat. Nos. 5,665,776, 5,389,677, and 5,422,370, we described
and claimed compositions for and methods of enhancing the
therapeutic effect of a cosmetic or pharmaceutical agent by using a
hydroxyacid in combination with the agent. The generic structure of
hydroxymonocarboxylic acids disclosed may appear similar to the one
described herein for oligosaccharaide aldonic acids. The location
of the R.sub.2 molecule is a notable difference. This application
disclosed that "when n=0 and m=1 or more, the hydroxymonocarboxylic
acid is also called aldonic acid. The name comes from a
carbohydrate, aldose, which may be oxidized to aldonic acid by the
oxidation of the aldehyde group in aldose to the carboxylic group."
The application, however, does not disclose or suggest that a
carbohydrate may be chemically linked to an aldonic acid. Thus,
this application does not disclose or suggest oligosaccharide
aldonic acids.
[0004] In our related U.S. patent application Ser. No. 07/683,437,
filed Apr. 10, 1991, entitled "Compositions Comprising
2-Hydroxycarboxylic Acids and Related Compounds, and Methods for
Alleviating the Signs of Dermatological Aging," and related
applications, and issuing, inter alia, as U.S. Pat. Nos. 5,547,988,
5,554,597, and 5,561,158, we described and claimed the use of
topical compositions containing a 2-hydroxycarboxylic acid or
related compound for use in alleviating or improving the signs of
aging, including the signs caused by intrinsic and extrinsic aging
or extrinsic factors, of the skin, hair and nails. Among the many
compounds disclosed in this application, lactobionic acid, an
oligosaccharide aldonic acid, is listed as a useful related
compound.
[0005] We have now discovered that oligosaccharide aldonic acids
and related compounds, as a group, provide numerous benefits in the
treatment and prevention of various cosmetic conditions and
dermatological disorders, including those associated with intrinsic
and extrinsic aging, as well as changes and damage caused by
extrinsic factors. Oligosaccharide aldonic acids and related
compounds also provide numerous benefits in the treatment of skin
wounds; reducing or soothing erythema, inflammation or irritation;
general care, as well as treatment and prevention of diseases and
conditions, of the nasal, oral and vaginal mucosa; and general oral
care and treatment and prevention of oral and gum diseases.
[0006] We have further discovered that oligosaccharide aldonic
acids possess unexpected physicochemical properties, including
binding with water and the formation of a gel matrix with water. In
addition, the oligosaccharaide aldonic acids disclosed herein are
antioxidant substances. Moreover, beneficial effects from an
oligosaccharaide aldonic acid within the skin, nail and hair are
expected to include those provided by glycosaminoglycans (GAGs).
This is due to similarities in the basic chemical structure of
oligosaccharaide aldonic acids and GAGs, and the fact that they
both form a gel matrix with water. Exemplary beneficial effects and
functions of GAGs inside the skin includes (i) binding with
polycations and cations, such as sodium and potassium ions, to
enhance water retention, and (ii) specific interaction with
collagen, elastin, fibronectin, laminin and other proteins to
stabilize the turgor of the skin.
SUMMARY OF THE INVENTION
[0007] Accordingly, it is an object of this invention to provide
methods and compositions which are useful in the treatment and
prevention of certain cosmetic conditions and dermatological
disorders, promote wound healing, and are useful for general care
of skin, hair, nail, oral and vaginal mucosa, and oral and gum
diseases.
[0008] We have now discovered that oligosaccharide aldonic acids
have protective as well as healing effects for skin, hair, nail;
oral, nasal and vaginal mucosa. The oligosaccharide aldonic acids
include glycerbionic acids, erythrobionic acids, threobionic acids,
ribobionic acids, arabinobionic acids, xylobionic acids, lyxobionic
acids, allobionic acids, altrobionic acids, glucobionic acids,
mannobionic acids, gulobionic acids, idobionic acids, galactobionic
acids, talobionic acids, alloheptobionic acids, altroheptobionic
acids, glucoheptobionic acids, mannoheptobionic acids,
guloheptobionic acids, idoheptobionic acids, galactoheptobionic
acids and taloheptobionic acids.
[0009] Compositions comprising oligosaccharide aldonic acids are
beneficial and effective for general care, reducing and soothing
mucosa and skin erythema, inflammation or reaction caused by
internal or external factors, treatment and healing of skin, hair,
nail; nasal, oral and vaginal mucosa including treatment, healing
and prevention of cosmetic conditions and dermatological
indications as well as cosmetic and clinical signs of changes
associated with intrinsic aging, or the damages caused by extrinsic
factors as sunlight, radiations, air pollution, wind, cold,
dampness, heat, chemicals, smoke, and cigarette smoking.
[0010] General care, reducing and soothing mucosa and skin
erythema, inflammation or iritation caused by internal or external
factors, treatment and healing of skin, hair, nail; nasal, oral and
vaginal mucosa, and treatment, healing and prevention of cosmetic
conditions and dermatological indications as well as cosmetic and
clinical signs of changes associated with intrinsic aging, or the
damages caused by extrinsic factors as sunlight, radiations, air
pollution, wind, cold, dampness, heat, chemicals, smoke, and
cigarette smoking may include blemished, irritated, inflammed,
unhealthy, damaged or abnormal mucosa, skin, hair, nail, nostril,
ear canal or vaginal conditions; oral or gum disease; disturbed
keratinization; defective syntheses or repair of dermal components,
and changes associated with intrinsic and extrinsic aging of skin,
nail and hair. Those conditions and indications include dryness of
the 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; pruritus;
warts; herpes; age spots; lentigines; melasmas; blemished skin;
mottled 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; cellulite; 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.
[0011] Oligosaccharide aldonic acids are also beneficial for wound
healing of skin; irritated or inflammed mucosa or skin; for skin
lightening; for cleansing of skin, hair and nail; for conditioning
of skin and nail; for protection from extrinsic factors; for
mouthwashes; for use as antioxidant agent, toner, cleanser,
moisturizer, emollient, protectant, foundation makeup, beauty
masks, face powders, rouge, cover up, lipsticks, eye makeup,
dentifrices, mouthwashes, suntan preparation, soap preparation, and
other topical preparations.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0012] 1. Oligosaccharaide Aldonic Acids and Related Compounds
[0013] An oligosaccharide aldonic acid may be defined as an aldonic
acid having a carbohydrate chemically linked to the aldonic acid.
The total number of carbohydrate monomers including the aldonic
acid itself ranges from 2 to 10. The aldonic acid may be described
as an oxidized form of a carbohydrate. For example, gluconic acid
may be obtained from glucose through an oxidation of the aldehyde
group to a carboxylic group. Although an oligosaccharide aldonic
acid may consist of one to ten aldonic acid units, preferred
compounds contain one aldonic acid unit and one to nine
carbohydrate monomers. When the total number of the carbohydrate
monomers including the aldonic acid itself are 2, 3, 4, 5, 6, 7, 8,
9 and 10, these oligosaccharide aldonic acids may be respectively
called aldobionic acid, aldotrionic acid, aldotetraonic acid,
aldopentaonic acid, aldohexaonic acid, aldoheptaonic acid,
aldooctaonic acid, aldononaonic acid and aldodecaonic acid. The
most preferred is aldobionic acid. If the name of a precursor
oligosaccharide is known, such name may be utilized as a prefix.
For example, lactobionic acid is derived from lactose, maltobionic
acid from maltose, cellobionic acid from cellobiose, isomaltobionic
acid from isomaltose, gentiobionic acid from gentiobiose and
laminarabionic acid from laminarabiose. Alternatively, the name of
a specific aldonic acid may also be used such as glycerbionic acid,
erythrobionic acid, xylobionic acid, mannobionic acid and
glucoheptabionic acid.
[0014] The smallest aldonic acid having three carbon atoms is
glyceric acid, which is obtained from glyceraldehyde. A
carbohydrate having one to nine monomers may be chemically linked
to one of the two hydroxyl groups at 2nd or 3rd carbon position of
glyceric acid to form an oligosaccharide aldonic acid. When one
carbohydrate monomer is linked to glyceric acid the compound may be
called glycerbionic acid.
[0015] Erythronic acid and threonic acid, which have four carbon
atoms, may be obtained respectively from erythrose and threose
through an oxidation process. A carbohydrate having one to nine
monomers may be chemically linked to one of the three hydroxyl
groups at 2nd, 3rd or 4th carbon position of the aldonic acid. When
one carbohydrate monomer is attached to the aldonic acid the
resulting compound may be called erythrobionic acid or threobionic
acid.
[0016] Ribonic acid, arabinoic acid, xylonic acid and lyxonic acid,
which have five carbon atoms, may be obtained respectively from
ribose, arabinose, xylose and lyxose through an oxidation process.
A carbohydrate having one to nine monomers may be chemically linked
to one of the four hydroxyl groups at 2nd, 3rd, 4th or 5th carbon
position of the aldonic acid. When one carbohydrate monomer is
attached to the aldonic acid, the resulting compound may be called
ribobionic acid, arabinobionic acid, xylobionic acid or lyxobionic
acid.
[0017] Allonic acid, altronic acid, gluconic acid, mannonic acid,
gulonic acid, idonic acid, galactonic acid and talonic acid, which
have six carbon atoms, may be obtained respectively from allose,
altrose, glucose, mannose, gulose, idose, galactose and talose
through oxidation. A carbohydrate having one to nine monomers may
be chemically linked to one of the five hydroxyl groups at 2nd,
3rd, 4th, 5th or 6th carbon position of the aldonic acid. When one
carbohydrate monomer is attached to the aldonic acid, the resulting
compound may be called allobionic acid, altrobionic acid,
glucobionic acid, mannobionic acid, gulobionic acid, idobionic
acid, galactobionic acid or talobionic acid.
[0018] Alloheptonic acid, altroheptonic acid, glucoheptonic acid,
mannoheptonic acid, guloheptonic acid, idoheptonic acid,
galactoheptonic acid and taloheptonic acid, which have seven carbon
atoms, may be obtained respectively from alloheptose, altroheptose,
glucoheptose, mannoheptose, guloheptose, idoheptose, galactoheptose
and taloheptose through oxidation. A carbohydrate having one to
nine monomers may be chemically linked to one of the six hydroxyl
groups at 2nd, 3rd, 4th, 5th, 6th or 7th carbon position of the
aldonic acid. When one carbohydrate monomer is attached to the
aldonic acid, the resulting compound may be called alloheptobionic
acid, altroheptobionic acid, glucoheptobionic acid,
mannoheptobionic acid, guloheptobionic acid, idoheptobionic acid,
galactoheptobionic acid or taloheptobionic acid.
[0019] A common carbohydrate monomer such as glucose contains an
aldehyde group (first carbon position) and five hydroxyl groups,
whereas fructose contains a keto group (at second carbon position)
and five hydroxyl groups. Many carbohydrate monomers form a five
(furanoside) or six (pyranoside) member ring between the aldehyde
or keto group and one of the hydroxyl groups at 4th or 5th carbon
position of the molecule. A newly formed hydroxyl group (anomeric
hydroxyl) at the original functional group has two isomers: alpha
or beta anomer, depending on down or up of the hydroxyl position. A
disaccharide is usually formed from two monosaccharides
(carbohydrate monomers) by eliminating one mole of water between
two anomeric hydroxyl groups (non-reducing disaccharide) or between
one anomeric hydroxyl of the second monomer and one of the hydroxyl
in the first monomer (reducing disaccharide). A non-reducing
disaccharide such as sucrose formed from fructose and glucose can
not be oxidized to an aldonic acid, whereas a reducing disaccharide
such as maltose formed from two glucose molecules can be oxidized
to maltobionic acid. Oligosaccharides containing three to ten
monomers may be formed in the same manner as in that of
disaccharides. As an alternative example, tetrasaccharides may also
be formed from two disaccharides.
[0020] Since the chemical link between two carbohydrate monomers
can be at different carbon positions, numerous different
oligosaccharides may be formed. The same is true for
oligosaccharide aldonic acids. For example, the disaccharides
maltose and cellobiose are both formed from two glucose molecules
linked between the anomeric hydroxyl of the second glucose and the
hydroxyl at the 4.sup.th carbon position of the first glucose
molecule. The only difference is that maltose is an alpha anomer
and cellobiose is a beta anomer. The same is true when these two
disaccharides are oxidized to aldonic acids. The only difference
between maltobionic acid and cellobionic acid is that the former is
an alpha and the latter is a beta anomer.
[0021] Many disaccharides which may be converted to bionic acids
include glycerbioses, erythrobioses, threobioses, ribobioses,
arabinobioses, xylobioses, lyxobioses, allobioses, altrobioses,
glucobioses, mannobioses, gulobioses, idobioses, galactobioses,
talobioses, alloheptobioses, altroheptobioses, glucoheptobioses,
mannoheptobioses, guloheptobioses, idoheptobioses,
galactoheptobioses, taloheptobioses, maltose, isomaltose, lactose,
cellobiose, gentiobiose, laminaribiose, kojibiose, melibiose,
nigerose, rutinose and sophorose. Bionic acids may be obtained from
these disaccharides by an oxidation process with hypoiodite,
bromine water or enzyme.
[0022] In accordance with the present invention, the generic
structure of oligosaccharide aldonic acids may be represented as
follows: R.sub.1(CHOR.sub.2).sub.m(CH.sub.2).sub.nCOOR.sub.3
wherein:
[0023] R.sub.1 and R.sub.3 are independently H or an alkyl, aralkyl
or aryl group of saturated or unsaturated, straight or branched
chain or cyclic form, having 1 to 25 carbon atoms;
[0024] m is 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11;
[0025] n is 0, 1, 2 3, 4, 5, 6, 7, 8, or 9;
[0026] R.sub.2 is independently selected from H or any carbohydrate
having from 1 to 9 monomers in each (CHOR.sub.2), and at least one
R.sub.2 is a carbohydrate. For example, when m=5, one of the five
R.sub.2 may be a carbohydrate and the remaining four R.sub.2 may be
H;
[0027] H attached to carbon atom may be substituted by I, F, Cl,
Br, NH.sub.2, NHCOCH.sub.3, SH, or alkyl, alkoxyl, aralkyl or aryl
group of saturated or unsaturated, straight or branched chain or
cyclic form, having from 1 to 9 carbon atoms;
[0028] R.sub.1, R.sub.2, OR.sub.2 or H may carry or be substituted
with CHO, COOH, sulfate, phosphate, nitrate, or lower alkoxyl
having from 1 to 5 carbon atoms;
[0029] H of the OH group may be substituted by an acyl group having
from 2 to 25 carbon atoms, such as acetyl (CH.sub.3CO), propanoyl
(CH.sub.3CH.sub.2CO), octanoyl [CH.sub.3(CH.sub.2).sub.6CO],
octadecanoyl [CH.sub.3(CH.sub.2).sub.16CO], eicosanoyl
[CH.sub.3(CH.sub.2).sub.18CO], tetraeicosanoyl
[CH.sub.3(CH.sub.2).sub.22CO] or benzoyl (C.sub.6H.sub.5CO)
group.
[0030] Oligosaccharide aldonic acids according to the present
invention may be present as isomeric D, L, DL or any other isomeric
or non-isomeric form, saturated or unsaturated, straight or
branched chain or cyclic form, free acid, ester, lactone, salt or
partial salt form with organic or inorganic alkali.
[0031] The preferred oligosaccharide aldonic acids contain 2 to 6
carbohydrate monomers, and more preferred ones contain 2 to 3
carbohydrate monomers, and the most preferred oligosaccharide
aldonic acids contain two carbohydrate monomers. The most preferred
oligosaccharide aldonic acids may be called bionic acids which
contain two carbohydrate monomers. In the bionic acid, the chemical
link between the two carbohydrate monomers can be at any carbon
position. The preferred link is between the anomeric carbon of the
second monomer chemically bond to any position other than the first
carbon position of the first monomer. In addition, two anomeric
isomers such as alpha and beta isomers can be formed when the
second monomer is linked to the first monomer, and therefore
numerous different bionic acids may exist. For example, glucobionic
acids include maltobionic acid and cellobionic acid.
[0032] As an example, chemical structures of some oligosaccharaide
aldonic acids are depicted below: ##STR1##
[0033] Oligosaccharide aldonic acid lactones are usually obtained
from their aldonic acids by eliminating one mole of water through
intramolecular cyclization between the carboxyl group and one of
the hydroxyl groups. Common lactones consist of five or six member
rings.
[0034] Examples of lactone form include lactobionolactone,
maltobionolactone, isomaltobionolactone, cellobionolactone,
chitobionolactone, gentiobionolactone, glucobionolactone,
galactobionolactone, mannobionolactone, ribobionolactone,
kojibionolactone, xylobionolactone, arabinobionolactone,
nigerobionolactone, laminarabinobionolactone, maltotrionolactone,
isomaltotrionolactone, chitotrionolactone, cellotrionolactone,
gentiotrionolactone, maltotetraonolactone, cellotetraonolactone and
chitotetraonolactone.
[0035] Examples of ester form include methyl lactobionate, ethyl
lactobionate, propyl lactobionate, benzyl lactobionate, methyl
maltobionate, ethyl maltobionate, propyl maltobionate, benzyl
maltobionate, methyl cellobionate, ethyl cellobionate, propyl
cellobionate and benzyl cellobionate.
[0036] Examples of acyl form include acetyl lactobionic acid,
acetyl maltobionic acid and acetyl cellobionic acid.
[0037] Examples of both acyl and ester form include acetyl
lactobionic acid methyl, ethyl or propyl ester; acetyl maltobionic
acid methyl, ethyl or propyl ester; acetyl cellobionic acid methyl,
ethyl or propyl ester.
[0038] On one embodiment of the inventions, the group of
oligosaccharide aldonic acids and related compounds according to
the invention are the group of compounds discussed herein, but
excluding lactobionic acid. In another embodiment of the invention
the group of oligosaccharide aldonic acids and related compounds
according to the invention are the group of compounds discussed
herein, but excluding lactobionic acid and salts, lactones, and
thereof.
[0039] Oligosaccharide aldonic acids may be classified into groups
according the number of carbohydrate monomers such as aldobionic
acid, aldotrionic acid, aldotetraonic acid, aldopentaonic acid,
aldohexaonic acid, aldoheptaonic acid, aldooctaonic acid,
aldononaonic acid and aldodecaonic acid. The preferred groups are
aldobionic acid up to aldohexaonic acid, with more preferred groups
of aldobionic acid up to aldotetraonic acid, and with most
preferred groups being aldobionic acid and aldotrionic acid.
[0040] Many different aldobionic acids and aldotrionic acids exist
due to various carbohydrate monomers and different linking
positions between two monomers. For example, even in the smallest
molecule of glycerbionic acid (six carbon atoms) formed from
glyceraldehyde (second monomer) and glyceric acid, there are two
different glycerbionic acids; linking at 2nd or 3rd carbon position
of the glyceric acid. Glycerbionic acids also include various
second monomers linked to glyceric acid at the 2nd or 3rd carbon
position. The second monomers include erythrose, threose, ribose,
arabinose, xylose, lyxose, allose, altrose, glucose, mannose,
gulose, idose, galactose, talose, 6-deoxymannose,
2-deoxyaminoglucose and fucose. Some representative oligosaccharide
aldonic acids include the following:
[0041] (i) Aldobionic Acids (Bionic Acids)
[0042] These bionic acids consist of one carbohydrate monomer
linked to an aldonic acid, and include glycerbionic acids,
erythrobionic acids, threobionic acids, ribobionic acids,
arabinobionic acids, xylobionic acids, lyxobionic acids, allobionic
acids, altrobionic acids, glucobionic acids, mannobionic acids,
gulobionic acids, idobionic acids, galactobionic acids, talobionic
acids, alloheptobionic acids, altroheptobionic acids,
glucoheptobionic acids, mannoheptobionic acids, guloheptobionic
acids, idoheptobionic acids, galactoheptobionic acids,
taloheptobionic acids, chitobionic acids, hyalobiouronic acids,
hyalourobionic acids, chondrosines, chondrosinbionic acids,
cellobiouronic acids, and cellourobionic acids.
[0043] As an example, glucobionic acids include lactobionic acid,
isolactobionic acid, maltobionic acid, isomaltobionic acid,
cellobionic acid, gentiobionic acid and laminarabionic acid. All
these bionic acids are formed from the same or a different
carbohydrate monomer linked to gluconic acid through a different or
the same position. Other individually named bionic acids include
melibionic acid, nigerobionic acid, rutinobionic acid,
sophorobionic acid and kojibionic acid.
[0044] (ii) Aldotrionic Acids (Trionic Acids)
[0045] These trionic acids consist of two carbohydrate monomers
linked jointly or separately to an aldonic acid, and include
glycertrionic acids, erythrotrionic acids, threotrionic acids,
ribotrionic acids, arabinotrionic acids, xylotrionic acids,
lyxotrionic acids, allotrionic acids, altrotrionic acids,
glucotrionic acids, mannotrionic acids, gulotrionic acids,
idotrionic acids, galactotrionic acids, talotrionic acids,
alloheptotrionic acids, altroheptotrionic acids, glucoheptotrionic
acids, mannoheptotrionic acids, guloheptotrionic acids,
idoheptotrionic acids, galactoheptotrionic acids, taloheptotrionic
acids, chitotrionic acids, hyalotriouronic acids, hyalourotrionic
acids, chondrosintrionic acids, cellotriouronic acids and
cellourotrionic acids.
[0046] (iii) Other Oligosaccharide Aldonic Acids and Related
Compounds
[0047] Aldonic acids with higher molecular weight may consist of
three to nine carbohydrate monomers linked jointly or separately to
an aldonic acid, and include aldotetraonic acids, aldopentaonic
acids, aldohexaonic acids, aldoheptaonic acids, aldooctaonic acids,
aldononaonic acids and aldodecaonic acids. Miscellaneous or related
aldonic acids include those which are not readily represented or
included in the above generic structure, or which have additional
functional groups in the molecules, such as a carbohydrate linked
to an uronic acid, which may or may not be represented by the above
generic structure. A sulfate, phosphate, nitrate group, amino,
acetamino group etc. may be substituted at H or OH similar to that
of chitin, chitosan, hyaluronic acid, chodroitin sulfate, heparin,
etc. to form substituted oligosaccharide aldonic acids.
[0048] 2. Topical Uses of Oligosaccharide Aldonic Acids and Related
Compounds
[0049] (i) Oligosaccharide Aldonic Acids and Related Compounds
[0050] Compositions comprising an oligosaccharide aldonic acid or
related compound described herein have numerous beneficial effects
and a broad range of uses. These compositions can comprise one or
more than one oligosaccharide aldonic acid or related compound.
[0051] According to one aspect of the invention, these compositions
may be used for general care; moisturizing; dry skin; reducing
irritation or inflammation of or soothing skin and mucosa or
treatment or prevention of skin or mucosa irritation or
inflammation caused by external factors, such as chemicals; skin
smoothing and itchy skin; as well as for treatment and prevention,
of various cosmetic conditions and dermatological disorders,
including those associated with intrinsic and/or extrinsic aging,
as well as with changes or damage caused by extrinsic factors. 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 such as sunlight,
radiations, air pollution, wind, cold, dampness, heat, chemicals,
smoke, and cigarette smoking. In addition, the compositions of the
present invention may be used to treat skin wounds, for example in
aiding the healing of skin cuts, tears, lacerations, burns,
punctures, and other wounds.
[0052] According to another aspect of the invention, these
compositions may be used for general care, as well as treatment and
prevention of diseases and conditions, of the oral, nasal and
vaginal mucosa. For example, the compositions may be used for care
and treatment of blemished, unhealthy, damaged, irritated, or
abnormal oral, nasal or vaginal mucosa, and gum diseases.
[0053] According to still another aspect of the invention, these
composition may be used for general oral care, as well as treatment
and prevention of oral and gum diseases.
[0054] 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.
[0055] With increasing age and exposure of 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.
[0056] 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.
[0057] Additionally, small blood vessels become thin walled,
dilated and often ruptured. Vascular supply thereby becomes
compromised.
[0058] 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.
[0059] 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.
[0060] Topical application to the skin, hair or nails of a
composition of the present invention is beneficial for various
cosmetic conditions and dermatological 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; irritation; dermatoses; eczema;
psoriasis; itchy scalp and skin; pruritus; warts; herpes; age
spots; lentigines; melasmas; blemished skin; mottled 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.
[0061] (ii) Combination Compositions
[0062] In addition, compositions comprising one or more than one
oligosaccharide aldonic acid or related compound may also be
incorporated into a composition comprising a cosmetic,
pharmaceutical or other topical agent to enhance or create
synergetic effects.
[0063] In accordance with this aspect of the invention, the
compositions of the present invention may contain one or more
oligosaccharide aldonic acids or related compounds to magnify the
therapeutic effect of an unrelated cosmetic or pharmaceutical
agent. At least one compound selected from the group consisting of
oligosaccharide aldonic acids and related compounds may be
incorporated into composition containing a cosmetic or
pharmaceutical agent for any of the uses described above. It has
been found that such incorporation results in magnified therapeutic
efficacies which are not simply additive effects.
[0064] 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 oligosaccaride aldonic acids and related
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 an
oligosaccharide aldonic acid and/or related compound is
incorporated into a composition containing a pharmaceutical agent,
one of the following two consequences may arise:
[0065] (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 the oligosaccharide aldonic acid and/or
related 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 oligosaccharide aldonic acid
and/or related compound. Nor does the oligosaccharide aldonic acid
and/or related 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.
[0066] (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 an
oligosaccharide aldonic acid and/or related compound. From the
point of positive effect, the oligosaccharide aldonic acid and/or
related 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.
[0067] From the point of negative effect, an oligosaccharide
aldonic acid or related 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.
[0068] At present we do not know the exact mechanism involved in
the synergistic effect or unexpected increase in therapeutic effect
of a cosmetic or dermatological agent by an oligosaccharide aldonic
acid. The following are relevant observations.
[0069] (1) Not Due to Enhanced Penetration.
[0070] The enhanced and substantial increase in therapeutic effects
of a cosmetic or dermatological agent incorporated with an
oligosaccharide aldonic acid is not simply due to an increased
penetration of the topical agent into the skin, nor due to a simple
addition or combination effects.
[0071] (2) Re-Activation from Therapeutic Non-Responsiveness.
[0072] Tachyphylaxis or so-called "drug resistance" is frequently
encountered with corticosteroid or other drug therapy for topical
treatment of psoriasis, eczema etc. On continued topical use, many
patients develop tachyphylaxis to corticosteroids, and the lesions
very often do not respond any more to topically applied
corticosteroid compositions, even under occlusive dressings to
enhance penetration. The exact nature of such resistance to the
drug is not known. One of the proposed hypotheses is that the
available level of receptor molecule(s) for corticosteroids in the
skin is diminished or exhausted completely due to continued daily
use of the drugs. However, it is not known whether the receptor
level is really low or the active site of the receptor molecule is
covered-up by an inhibitor.
[0073] When tachyphylaxis is encountered from corticosteroid alone
therapy, incorporation of an oligosaccharide aldonic acid into the
corticosteroid composition would eradicate the drug resistance. If
desired, the composition containing an oligosaccharide aldonic acid
alone may be applied alternatively with the corticosteroid
therapy.
[0074] (3) Eradication of Rebound Worsening.
[0075] One well-known side effect associated with continued use of
certain drugs, such as corticosteroids, is a rebound worsening of
the disease if the treatment is discontinued. The mechanism of
worsening is not known. It has been speculated that the
antiinflammatory property of corticosteroids is to suppress the
immunological expression of the disease. The disease process is not
eradicated nor substantially modified, but is only held-up like
river water is held-up by a dam. Discontinuation of the therapy is
like removing the dam.
[0076] To prevent rebound worsening encountered with
corticosteroids is to incorporate an oligosaccharide aldonic acid
into the composition containing a corticosteroid, or to use the
oligosaccharide aldonic acid alternately with the
corticosteroid.
[0077] (4) Prevention or Eradication of Side-Effects.
[0078] Other well-known side effects associated with continued
topical use of a corticosteroid are thinning and atrophy of the
skin. To prevent or eliminate such side effects, an oligosaccharide
aldonic acid may be incorporated into the composition containing a
corticosteroid, or may be used alternately with the
corticosteroid.
[0079] We have found that, in most cases, therapeutic effects of
cosmetic and pharmaceutical agents are amplified when an
oligosaccharide aldonic acid or related compound is incorporated
into the composition, i.e., consequence (b) above is observed.
[0080] The cosmetic and pharmaceutical agents which may be actuated
by oligosaccharide aldonic acids and related compounds 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; antimotionsickness 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;
coiticosteroids; tanning agents; humectants; hormones; retinoids;
gum disease or oral care agents; topical cardiovascular agents;
corn, callus and wart removing agents; dipilating agents; and other
dermatologicals.
[0081] Some examples of cosmetic and pharmaceutical agents are
aclovate, acyclovir, acetylsalicylic acid, adapalene, albuterol,
aluminum acetate, aluminum chloride, aluminum hydroxide, aluminum
chlorohydroxide, amantadine, aminacrine, aminobenzoic acid (PABA),
aminocaproic acid, aminosalicylic acid, amitriptyline, anthralin,
ascorbic acid, ascoryl palimate, atropine, azelaic acid,
bacitracin, bemegride, beclomethasone dipropionate, benzophenone,
benzoyl peroxide, betamethasone dipropionate, betamethasone
valerate, brompheniramine, bupivacaine, butoconazole,
calcipotriene, camphor, capsaicin, carbamide peroxide, chitosan,
chlorhexidine, chloroxylenol, chlorpheniramine, ciclopirox,
clemastine, clindamycin, clioquinol, clobetasol propionate,
clotrimazole, coal tar, cromolyn, crotamiton, cycloserine,
dehydroepiandrosterone, desoximetasone, dexamethasone,
diphenhydramine, doxypin, doxylamine, dyclonine, econazole,
erythromycin, estradiol, ethinyl estradiol, fluocinonide,
fluocinolone acetonide, 5-fluorouracil, griseofulvin, guaifenesin,
haloprogin, hexylresorcinol, homosalate, hydrocortisone,
hydrocortisone 21-acetate, hydrocortisone 17-valerate,
hydrocortisone 17-butyrate, hydrogen peroxide, hydroquinone,
hydroquinone monoether, hydroxyzine, ibuprofen, ichthammol,
imiquimod, indomethacin, ketoconazole, ketoprofen, kojic acid,
lidocaine, meclizine, meclocycline, menthol, mepivacaine, methyl
nicotinate, methyl salicylate, metronidazole, miconazole,
minocycline, minoxidil, monobenzone, mupirocin, naftifine,
naproxen, neomycin, nystatin, octyl methoxycinnamate, octyl
salicylate, oxybenzone, oxiconazole, oxymetazoline, padimate O,
permethrin, pheniramine, phenol, phenylephrine,
phenylpropanolamine, piperonyl butoxide, podophyllin, podofilox,
povidone iodine, pramoxine, prilocaine, procaine, promethazine
propionate, propranolol, pseudoephedrine, pyrethrin, pyrilamine,
resorcinol, retinal, 13-cis retinoic acid, retinoic acid, retinol,
retinyl acetate, retinyl palmitate, salicylamide, salicylic acid,
selenium sulfide, shale tar, sulconazole, sulfur, sulfadiazine,
tazarotene, terbinafine, terconazole, tetracaine, tetracycline,
tetrahydrozoline, thymol, tioconazole, tolnaftate, triamcinolone
diacetate, triamcinolone acetonide, triamcinolone hexacetonide,
triclosan, triprolidine, undecylenic acid, urea, vitamin E acetate,
wood tar, and zinc pyrithione.
[0082] Another example of cosmetic or other agents that may be
combined with one or more oligosaccharide aldonic acids and related
compounds include hydroxyacids, ketoacids and related compounds.
Examples of hydroxy acids include hydroxymonocarboxylic acids,
hydroxydicarboxylic acids, 2-hydroxycarboxylic acids, other
hydroxycarboxylic acids, 2-ketocarboxylic 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, methyllacetic acid, tartaric acid,
citric acid, glucuronic acid, ribonic acid, gluconolactone,
ribonolactone, gycolyl glycollate, lactyl lactate, trilactic acid
and polylactic acid.
[0083] Yet another example of cosmetic or other agents that may be
combined with one or more oligosaccharide aldonic acids or related
compounds include phenyl alpha acyloxyalkanoic acids and
derivatives thereof. These compounds may exist in a free acid, 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.
[0084] Still another example of cosmetic or other agents that may
be combined with one or more oligosaccharide aldonic acids or
related compounds include N-acetyl-aldosamines, N-acetylamino acids
and related N-acetyl compounds. These compounds may exist in a free
acid, lactone or salt form, or as stereoisomers. See, for example,
U.S. patent application Ser. No. 09/227,213, filed Jan. 8, 1999,
now U.S. Pat. No. 6,159,485. Representative example of such
compounds include N-acetyl-glucosamine and N-acetyl-proline.
[0085] When the compositions according to the present invention are
used for general care, moisturizing, dry skin, skin smoothing and
itchy skin, as well as for treatment and prevention, of various
cosmetic conditions and dermatological disorders, including those
associated with intrinsic and/or extrinsic aging, as well as with
changes or damage caused by extrinsic factors, examples of suitable
cosmetic or other agents that may be combined with one or more
oligosaccharide aldonic acids or related compounds include:
hydroxyacids, ketoacids and related compounds; phenyl alpha
acyloxyalkanoic acids and derivatives thereof N-acetyl-aldosamines,
N-acetylamino acids and related N-acetyl compounds; 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; antimotionsickness agents; antiinflammatory
agents; antihyperkeratolytic agents; antiperspirants; antipsoriatic
agents; antiseborrheic agents; astringents; cleansing 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; topical cardiovascular agents; corn, callus
and wart removing agents; and other dermatologicals.
[0086] Some examples of cosmetic and pharmaceutical agents are
aclovate, acyclovir, acetylsalicylic acid, adapalene, albuterol,
aluminum acetate, aluminum chloride, aluminum hydroxide, aluminum
chlorohydroxide, amantadine, aminacrine, aminobenzoic acid (PABA),
aminocaproic acid, aminosalicylic acid, amitriptyline, anthralin,
ascorbic acid, ascoryl palimate, atropine, azelaic acid,
bacitracin, bemegride, beclomethasone dipropionate, benzophenone,
benzoyl peroxide, betamethasone dipropionate, betamethasone
valerate, brompheniramine, bupivacaine, butoconazole,
calcipotriene, camphor, capsaicin, carbamide peroxide, chitosan,
chlorhexidine, chloroxylenol, chlorpheniramine, ciclopirox,
clemastine, clindamycin, clioquinol, clobetasol propionate,
clotrimazole, coal tar, cromolyn, crotamiton, cycloserine,
dehydroepiandrosterone, desoximetasone, dexamethasone,
diphenhydramine, doxypin, doxylamine, dyclonine, econazole,
erythromycin, estradiol, ethinyl estradiol, fluocinonide,
fluocinolone acetonide, 5-fluorouracil, griseofulvin, guaifenesin,
haloprogin, hexylresorcinol, homosalate, hydrocortisone,
hydrocortisone 21-acetate, hydrocortisone 17-valerate,
hydrocortisone 17-butyrate, hydrogen peroxide, hydroquinone,
hydroquinone monoether, hydroxyzine, ibuprofen, ichthammol,
imiquimod, indomethacin, ketoconazole, ketoprofen, kojic acid,
lidocaine, meclizine, meclocycline, menthol, mepivacaine, methyl
nicotinate, methyl salicylate, metronidazole, miconazole,
minocycline, minoxidil, monobenzone, mupirocin, naftifine,
naproxen, neomycin, nystatin, octyl methoxycinnamate, octyl
salicylate, oxybenzone, oxiconazole, oxymetazoline, padimate O,
permethrin, pheniramine, phenol, phenylephrine,
phenylpropanolamine, piperonyl butoxide, podophyllin, podofilox,
povidone iodine, pramoxine, prilocaine, procaine, promethazine
propionate, propranolol, pseudoephedrine, pyrethrin, pyrilamine,
resorcinol, retinal, 13-cis retinoic acid, retinoic acid, retinol,
retinyl acetate, retinyl palmitate, salicylamide, salicylic acid,
selenium sulfide, shale tar, sulconazole, sulfur, sulfadiazine,
tazarotene, terbinafine, terconazole, tetracaine, tetracycline,
tetrahydrozoline, thymol, tioconazole, tolnaftate, triamcinolone
diacetate, triamcinolone acetonide, triamcinolone hexacetonide,
triclosan, triprolidine, undecylenic acid, urea, vitamin E acetate,
wood tar, and zinc pyrithione. Other examples of suitable cosmetic
and pharmaceutical agents are well known to those of skill in the
art.
[0087] When the compositions according to the present invention are
used for general care, as well as treatment and prevention of
diseases and conditions, of the oral and vaginal mucosa, examples
of suitable cosmetic or other agents that may be combined with one
or more oligosaccharide aldonic acids or related compounds include:
hydroxyacids, ketoacids and related compounds; phenyl alpha
acyloxyalkanoic acids and derivatives thereof N-acetyl-aldosamines,
N-acetylamino acids and related N-acetyl compounds; local
analgesics and anesthetics; antibacterials; antiyeast agents;
antifungal agents; antiviral agents; antihistamine agents;
antipruritic agents; antiemetics; antimotion sickness agents;
antiinflammatory agents; vitamins; corticosteroids; hormones; and
gum disease or oral care agents.
[0088] Some examples of cosmetic and pharmaceutical agents are
clotrimazole, ketoconazole, miconazole, griseofulvin, econazole,
metronidazole, hydroxyzine, diphenhydramine, pramoxine, lidocaine,
procaine, mepivacaine, monobenzone, anthralin, coal tar,
benzocaine, benzoyl peroxide, 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. Other examples of suitable
cosmetic and pharmaceutical agents are well known to those of skill
in the art.
[0089] When the compositions according to the present invention are
used for general oral care, as well as treatment and prevention of
oral and gum diseases, examples of suitable cosmetic or other
agents that may be combined with one or more oligosaccharide
aldonic acids or related compounds include: hydroxyacids, ketoacids
and related compounds; phenyl alpha acyloxyalkanoic acids and
derivatives thereof N-acetyl-aldosamines, N-acetylamino acids and
related N-acetyl compounds; analgesics and anesthetics;
antibacterials; antiyeast agents; antifungal agents; antiviral
agents; antiinflammatory agents; vitamins; and other gum disease or
oral care agents.
[0090] Some examples of cosmetic and pharmaceutical agents are
triclosan, sodium flouride, zinc chloride, zinc citrate, zinc
sulfate, chlorhexidine, chlorhexidine and digluconate.
[0091] When the compositions according to the present invention are
used for treating skin wounds, for example in aiding the healing of
skin cuts, tears, lacerations, burns, punctures, and other wounds,
examples of suitable cosmetic or other agents that may be combined
with one or more oligosaccharide aldonic acids or related compounds
include: hydroxyacids, ketoacids and related compounds; phenyl
alpha acyloxyalkanoic acids and derivatives thereof
N-acetyl-aldosamines, N-acetylamino acids and related N-acetyl
compounds; analgesics and anesthetics; wound cleansers;
antibacterials; antiyeast agents; antifungal agents; antiviral
agents; antiinflammatory agents; skin lightening agents;
depigmenting agents; vitamins; burn relief agents; and
corticosteroids.
[0092] (iii) Molecular Complex and Slow-Release Compositions
[0093] A formulation containing an oligosaccharide aldonic acid
usually has a pH of below 3.0, and the composition may irritate
human skin of atopic or sensitive skin type on repeated topical
application, due to lower pH or uncontrolled release and
penetration of the acid into stratum corneum of the skin. We have
found that an oligosaccharide aldonic acid can form a buffer system
with an alkali and/or a molecular complex with a complexing agent,
and the resulting composition has the following attributes: (1)
easy and simple process in formulating, (2) raising the overall pH
of the formulation to above 3.0, (3) having a buffer system in the
composition, (4) no irritation or minimal stinging to sensitive
skin, (5) controlled or slow-release of the active ingredient into
the skin, and (6) retaining the therapeutic efficacy. The substance
used for neutralizing, partially neutralizing, salt forming,
buffering or complexing may be an inorganic or organic alkali, or
amphoteric.
[0094] An alkali is defined as a substance which shows a pH of
above 7.0 in a solution. Common inorganic alkalis include for
example ammonium hydroxide, ammonium phosphate, ammonium carbonate
or bicarbonate, sodium hydroxide, sodium carbonate, sodium
bicarbonate, sodium acetate, sodium phosphate, and the like alkalis
formed from potassium, calcium, magnesium, strontium, aluminum,
zinc, and lithium. Common organic alkalis are amines,
hydroxylamines, imines, guanidines, amine oxides, alkanolamines,
alkoxylated amines and alkylamido alkylamines, such as
diethanolamine, triethanolamine, isopropanolamine,
diisopropanolamine, triisopropanolamine, aminobutanol, aminoethyl
propanediol, aminomethyl propanol, aminomethyl propanediol,
isopropylamine, methylethanolamine, diisopropylamine,
dipropylenetriamine, glucamine, N-methylglucamine, morpholine,
tromethamine, cocamines, soyamines, oleamines, stearamines,
quaterniums and the like. The buffer system in the composition
consists of two species; namely oligosaccharide aldonic free acid
and oligosaccharide aldonate anion despite an inorganic or organic
alkali.
[0095] A molecular complexing agent with an oligosaccharide aldonic
acid may be an amphoteric or non-amphoteric substance. The mole
ratio of a complexing agent may be higher than one, however the
preferred ratio is less than one, and most preferred ratio is from
0.1 to 0.5. The amphoteric substance by definition should have both
an acidic and a basic functional groups in the molecule, and can
behave both as an acid and an alkali in a solution. Inorganic
amphoteric substances include certain metallic oxides such as
aluminum oxide and zinc oxide. However, the preferred amphoteric
system consists of an organic amphoteric substance. The molecule of
an organic amphoteric substance should consist of at least one
acidic function selected from carboxylic, phosphoric and sulfonic
groups, and at least one basic function from amino, imino and
guanido groups. Examples of organic amphoteric substances include
amino acids, peptides, polypeptides, proteins and related compounds
such as glycine, arginine, lysine, cysteine, proline, glutamine,
tryptophan, asparagine, tyrosine, ornithine, citrulline, creatine,
histidine and canavanine.
[0096] In an amphoteric system, the molecular complex consists of
several ionic species. For example, a triple ionic complex will be
formed from one mole of an oligosaccharide aldonic acid (having one
reactive group) with one mole of glycine (having two functional
groups), and a quadruple ionic complex will be formed with arginine
or lysine (having three functional groups). Due to ionic bonds and
forces between the positive charge and the negative charge of the
molecular complex ions, the release and penetration of the
oligosaccharide aldonic acid into the skin will be controlled at
moderate and optimal rate. Thus the slow-release system can reduce
or eliminate skin irritation without compromising the intended
therapeutic effects.
[0097] The non-amphoteric complexing agents are organic alkalis
which include organic amines, polyamines, hydroxylamines, imines,
guanidines, amine oxides, alkanolamines, alkoxylated amines,
alkylamido alkylamines, amino acid esters, amino acid amides,
aminosaccharides, aminoalditols, aminocyclitols, fattyamines,
imidazolines and the like which are capable of forming the
molecular complex and/or salts with oligosaccharide aldonic acids.
The molecular weight of a complexing agent may range from 50 to
10,000, however the preferred one ranges from 100 to 600. Examples
of some complexing agents include creatinine, glycine ethyl ester,
arginine ethyl ester, lysine methyl ester, proline ethyl ester,
citrulline benzyl ester, glycinamide, argininamide, prolinamide,
lysinamide, glucamine, methylglucamine, glucosamines and
glucosylamines, other glycosamines and glycosylamines,
aminoinositols, chitosan, stearamidoethyl diethylamine,
stearamidopropyl dimethylamine, stearamidoethyl diethanolamine,
quaternary ammonium hydroxide.
[0098] (iv) Antioxidant Properties
[0099] An antioxidant may be defined as a substance capable of
preventing or inhibiting oxidation. Most oligosaccharide aldonic
acids are antioxidant compounds because they possess two or more
hydroxyl groups near the carboxylic group. The antioxidant property
is readily determined by using any one of the following test
methods: prevention or retardation of air oxidation of (a)
anthralin, (b) hydroquinone, or (c) banana peel. A freshly prepared
anthralin solution or cream is bright yellow, and an air oxidized
one is brownish or black. A hydroquinone solution or cream is
colorless or white color, and an air oxidized one is brownish or
black. A freshly peeled banana peel is light yellow in color and an
oxidized one ranges in color from tan, dark tan, brown to brownish
black.
[0100] For example, in control experiments, fresh banana peels cut
into sizes of 1.times.2 cm in 50 mm plastic petri dishes containing
5 ml water at neutral or acidic pH changed in color from
white-yellowish to tan within 6 hours at room temperature, and
changed to dark tan color during the next period of 24 to 72 hours.
When fresh banana peels were placed in dishes containing 5 ml of
0.1 M lactobionic acid under the same conditions, the banana peels
remained white-yellowish for the period of 24 hours, and changed in
color to tan after 72 hours. The above test results show that
lactobionic acid is an antioxidant substance. Using anthralin and
hydroquinone test methods also confirmed that lactobionic acid is a
moderate antioxidant.
[0101] (v) Gel Matrix Formation
[0102] In contrast to an alpha hydroxyacid and polyhydroxyacid, an
oligosaccharide aldonic acid can form a gel matrix when its aqueous
solution is evaporated at room temperature. The transparent gel
obtained retains certain amount of water forming a clear gel
matrix. The amount of water retention depends on individual
oligosaccharide aldonic acid. Examples of gel matrix preparations
are provided below.
[0103] The formation of a gel matrix between an oligosaccharide
aldonic acid and water has been found to have moisturizing,
soothing, healing and slow-release effects in addition to other
various beneficial effects to skin, mucous membrane, hair and nail.
The beneficial effects from an oligosaccharaide aldonic acid within
the skin, nail and hair are expected to include those provided by
glycosaminoglycans (GAGs). This is due to similarities in the basic
chemical structure of oligosaccharaide aldonic acids and GAGs, and
the fact that they both form a gel matrix with water. Exemplary
beneficial effects and functions of GAGs inside the skin includes
(i) binding with polycations and cations, such as sodium and
potassium ions, to enhance water retention, and (ii) specific
interaction with collagen, elastin, fibronectin, laminin and other
proteins to stabilize the turgor of the skin.
[0104] 3. General Preparation of the Cosmetic and Therapeutic
Compositions
[0105] (i) General Preparation
[0106] Compositions comprising an oligosaccharide aldonic acid or
related compound of the instant invention may be formulated as
solution, gel, lotion, cream, ointment, shampoo, spray, stick,
powder, masque, mouth rinse or wash, vaginal gel or preparation, or
other form acceptable for use on skin, nail, hair, oral mucosa,
vaginal mucosa, mouth or gums.
[0107] To prepare a solution composition, at least one
oligosaccharide aldonic acid or related compound of the instant
invention is dissolved in a solution prepared from water, ethanol,
propylene glycol, butylene glycol, and/or other topically
acceptable vehicle. The concentration of a single oligosaccharide
aldonic acids or related compound or the total concentration of all
oligosaccharide aldonic acids and related compounds, where the
composition comprises more than one oligosaccharide aldonic acids
or related compounds, 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.
[0108] To prepare a topical composition in lotion, cream or
ointment form, the oligosaccharide aldonic acid or related
compounds is first dissolved in water, ethanol, propylene glycol,
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 oligosaccharide
aldonic acid or related compounds are the same as described
above.
[0109] 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,
hydroxypropylmetlhylcellulose, carbomer or ammoniated
glycyrrhizinate to a solution comprising the oligosaccharide
aldonic acid or related 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
oligosaccharide aldonic acids or related compounds is first
dissolved in water or propylene glycol, and the solution thus
obtained is mixed with a shampoo base. Concentrations of the
oligosaccharide aldonic acids or related compounds used in gel or
shampoo form are the same as described above.
[0110] 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.
[0111] Other forms of compositions for delivery of oligosaccharide
aldonic acids and related compounds of the instant invention are
readily blended, prepared or formulated by those skilled in the
art.
[0112] (ii) Gel Matrix Preparations
[0113] In contrast to an alpha hydroxyacid and polyhydroxyacid, an
oligosaccharide aldonic acid can form a gel matrix. A gel matrix
may be formed on the skin, hair, nail or mucosa when a solution
comprising an oligosaccharide aldonic acid undergoes
evaporation.
[0114] In one example, a gel matrix can be formed when aqueous
solution comprising an oligosaccharide aldonic acid is evaporated
at room temperature. The transparent gel thus obtained retains
certain amount of water forming a clear gel matrix. The amount of
water retention depends on individual oligosaccharide aldonic acid.
For example, maltobionic acid 1 g in a beaker was dissolved in
water 1 ml, and the solution thus obtained was left at room
temperature. Fifty percent of the original water had been
evaporated at the end of 24 hours, and 57% at the end of 48 hours,
and 60% at the end of 72 hours, and no more or minimal evaporation
of water could be detected after 72 hours. A clear gel film thus
obtained contained 29% water complexed with maltobionic acid
molecules. In the same manner, lactobionic acid formed a clear gel
matrix with 14% water molecules and cellobionic acid formed a
transparent gel with 7% water molecules. The formation of a gel
matrix between an oligosaccharide aldonic acid and water has been
found to have soothing, healing and slow-release effects in
addition to other various beneficial effects to skin, mucous
membrane, hair and nail.
[0115] The following are illustrative examples of formulations and
other aspects of the present 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 oligosaccharide
aldonic acids or related compounds may be substituted according to
the teachings of this invention in the following examples.
EXAMPLE 1
[0116] A typical experiment to determine a gel matrix formation of
an oligosaccharide aldonic acid may be carried out as follows.
[0117] Maltobionic acid 1 g in a beaker of 3.6 cm diameter and 3.6
cm height was dissolved in water 1 ml, and the solution thus
obtained was left at room temperature between 20-25.degree. C. to
allow a slow evaporation of the water. Fifty percent of original
water had been evaporated at the end of 24 hours, 57% at the end of
48 hours, 60% at the end of 72 hour and 60.5% at the end of 96
Hours. A clear continuous gel film was formed at the end of 72
hours, and this was confirmed by observation under a microscope and
determination from its physical characteristics. The continuous
transparent film thus obtained consisted of 71% maltobionic acid
and 29% water by weight, and was formed as a complex gel matrix
between maltobionic acid molecules and water molecules.
[0118] Under the same conditions, a clear continuous gel film was
formed from lactobionic acid 1 g and water 1 ml. The continuous
film thus obtained consisted of 86% lactobionic acid and 14% water
by weight, and was formed as a complex gel matrix between
lactobionic acid molecules and water molecules.
[0119] Under the same experiment, a clear continuous gel film was
formed from cellobionic acid 1 g and water 1 ml. She continuous
film thus obtained consisted of 93% cellobionic acid and 7% water
by weight, and was formed as a complex gel matrix between
cellobionic acid molecules and water molecules.
[0120] Under the same conditions and experiment, gluconic acid did
not form any form of a gel matrix.
EXAMPLE 2
[0121] Antioxidant property of an oligosaccharide aldonic acid may
be determined by utilizing anthralin test method as follows.
[0122] Anthralin also known as dithranol is a yellowish powder, and
a composition containing anthralin without a suitable antioxidant
is chemically unstable even at room temperature. For example,
anthralin 0.05% in an oil-in-water cream changed in color from
yellow to gray within 24 hours at room temperature, and the cream
became brownish within 48 hours. Under anhydrous condition,
anthralin 0.05% ointment prepared from white petrolatum 2 parts and
mineral oil 1 part by weight changed in color from bright yellow to
grayish yellow within 24 hours, and the ointment became brownish
after 12 days at room temperature.
[0123] Based on the above observations, an oil-in-water cream
containing 0.4% anthralin with or without a known antioxidant was
used as a positive or vehicle control. The final concentration of a
test substance or antioxidant was 0.1 M. It was found that while
the control cream without an antioxidant changed in color from
yellow to grey within 24 hours, the positive control cream with a
known antioxidant (vitamin C or oxalic acid) and the test cream
containing lactobionic acid, maltobionic acid or cellobionic acid
did not change the color within 24 hours. These results indicated
that the bionic acids are comparably equal to vitamin C and oxalic
acid as antioxidant substances, Antioxidant property of an
oligosaccharide aldonic acid may also be determined by utilizing
hydroquinone test method as follows. Hydroquinone also known as
1,4-dihydroxybenzene is a white powder, and a composition
containing hydroquinone without a suitable antioxidant is
chemically unstable even at room temperature. For example,
hydroquinone 2% in an oil-in-water cream changed in color from
white to grey within 2 hours, and the cream became light brown
within 48 hours and dark brown after 72 hours at room temperature.
Under the same test conditions, the cream containing 2%
hydroquinone and 0.4 M concentration of a known antioxidant
(vitamin C, citric acid or N-acetylcysteine), maltobionic acid,
lactobionic acid or cellobionic did not change color even after 5
days. These results indicated that the bionic acids are comparably
equal to vitamin C, citric acid and N-acetylcysteine as antioxidant
substances.
EXAMPLE 4
[0124] Antioxidant property of an oligosaccharide aldonic acid may
also be determined by utilizing banana peel test method as
follows.
[0125] A fresh ripe banana peel cut into sizes of 2.times.2 cm has
the outer layer light yellow in color. These freshly cut banana
peels after exposed to air or immersed in an aqueous solution
without an antioxidant in 50 mm plastic petri dishes rapidly
changed in color from yellowish to tan within 3 hours, dark tan
within 24 hours and brown black after 72 hours. A test substance
including a positive control such as vitamin C, citric acid or
N-acetylcysteine was prepared as 0.1 M concentration, and each test
dish contained 5 ml test solution. Freshly cut banana peels
2.times.2 cm in sizes were immersed in 5 ml test solutions
including known antioxidants and vehicle controls with pH at 7.0
and 4.0. It was found that while the banana peels immersed in water
alone changed in color from white yellowish to tan within 4 hours,
the banana peels did not change color in the solution containing
maltobionic acid or lactobionic acid. The same results were also
found for the known antioxidant substances, vitamin C, citric acid
and N-acetylcysteine. These results indicated that the bionic acids
are antioxidant substances.
EXAMPLE 5
[0126] Typical solution compositions suitable for topical use on
hair, scalp, nail or skin, or use for wound healing, or for general
care of oral or vaginal mucosa comprising an oligosaccharide
aldonic acid may be formulated as follows.
[0127] (a) Maltobionic acid 50% aqueous solution was prepared by
dissolving maltobionic acid 50 g in 50 ml water. This solution 10 g
was mixed with a vehicle 90 ml prepared from ethanol 40 parts,
water 40 parts and propylene glycol 20 parts by volume. The
composition had pH 3.1 and contained 5% maltobionic acid.
[0128] (b) Cellobionic acid 25% aqueous solution was prepared by
dissolving cellobionic acid 25 g in 75 ml water. This solution 40 g
was mixed with a vehicle 60 ml prepared from ethanol 40 parts,
water 40 parts and propylene glycol 20 parts by volume. The
composition had pH 3.5 and contained 10% cellobionic acid.
[0129] (c) Lactobionic acid 0.5 g was dissolved in 99.5 ml solution
prepared from water 40 parts, ethanol 40 parts and propylene glycol
20 parts by volume. The composition had pH 2.6 and contained 0.5%
lactobionic acid.
[0130] A solution composition with pH 1.9 containing 10%
lactobionic acid was formulated from 10 g lactobionic acid
dissolved in water 50 ml, ethanol 20 ml and propylene glycol 20
ml.
[0131] A solution composition with pH 2.1 containing 25%
lactobionic acid was formulated from lactobionic acid 50% aqueous
solution 50 g and enough ethanol to make a total volume of 100
ml.
EXAMPLE 6
[0132] Typical shampoo compositions comprising an oligosaccharide
aldonic acid for hair, scalp or body wash may be formulated as
follows.
[0133] Maltobionic acid 50% aqueous solution 10 g was mixed
uniformly with a shampoo base 90 g. The composition had pH 2.9 and
contained 5% maltobionic acid.
[0134] Cellobionic acid 25% aqueous solution 20 g was mixed
uniformly with a shampoo base 80 g. The composition had pH 3.9 and
contained 5% cellobionic acid.
[0135] Lactobionic acid 10 g was dissolved in 20 ml water, and the
solution thus obtained was mixed uniformly with a shampoo base 70
g. The composition had pH 2.6 and contained 10% lactobionic
acid.
EXAMPLE 7
[0136] Typical cream compositions comprising an oligosaccharide
aldonic acid for cosmetic or dermatological indications, or for
general care of nail, skin or mucous membranes may be formulated as
follows.
[0137] Maltobionic acid 50% aqueous solution 50 g was mixed with an
oil-in-water base 50 g. The composition had pH 1.7 and contained
25% maltobionic acid.
[0138] Cellobionic acid 25% aqueous solution 20 g was mixed with an
oil-in-water base 80 g. The composition had pH 3.3 and contained 5%
cellobionic acid.
[0139] Lactobioic acid 2 g was dissolved in 18 ml water, and the
solution thus obtained was mixed uniformly with a cream base 80 g
or commercially available hydrophilic ointment. The white cream
thus formulated had pH 2.2 and contained 2% lactobionic acid.
[0140] A cream composition with pH 1.7 contained 10% lactobionic
acid was formulated from lactobionic acid 10 g, water 10 ml and
cream base 80 g.
[0141] A cream composition with pH 1.8 contained 18% lactobionic
acid was formulated from lactobionic acid 54% aqueous solution 33.3
g and a cream base 66.7 g.
[0142] A cream composition with pH 1.7 contained 27% lactobionic
acid was formulated from lactobionic acid 54% aqueous solution 50 g
and a cream base 50 g.
EXAMPLE 8
[0143] Typical gel compositions comprising an oligosaccharide
aldonic acid for cosmetic or dermatological indications, wound
healing, or for general care of hair, scalp, nail, skin, oral or
vaginal mucosa may be formulated as follows.
[0144] Maltobionic acid 50% aqueous solution 20 g was mixed
uniformly with a gel base 80 g. The composition had pH 2.9 and
contained 10% maltobionic acid.
[0145] Cellobionic acid 6 g was dissolved in water 18 ml, and the
solution thus obtained was mixed with a gel base 76 g. The
composition had pH 3.9 and contained 6% cellobionic acid.
[0146] Lactobionic acid 54% aqueous solution 9.3 g was mixed
uniformly with a gel base 90.7 g. The gel composition thus
formulated had pH 3.0 and contained 5% lactobionic acid.
EXAMPLE 9
[0147] Typical water-in-oil compositions comprising an
oligosaccharide aldonic acid for cosmetic or dermatological
indications, wound healing, or for general care of nail, skin, oral
or vaginal mucosa may be formulated as follows.
[0148] Maltobionic acid 50% aqueous solution 20 g was mixed
uniformly with a water-in-oil base 80 g. The water non-washable
composition thus formulated contained 10% maltobionic acid.
[0149] Cellobionic acid 25% aqueous solution 20 g was mixed
uniformly with a water-in-oil base 80 g. The water non-washable
composition thus formulated contained 5% cellobionic acid.
EXAMPLE 10
[0150] Typical masque compositions comprising an oligosaccharide
aldonic acid for cosmetic or dermatological indications of nail, or
skin for example on the face, may be formulated as follows.
[0151] Maltobionic acid 50% aqueous solution 16 g was mixed
uniformly with a masque base 84 g. The masque composition thus
formulated contained 8% maltobionic acid.
[0152] Cellobionic acid 25% aqueous solution 36 g was mixed
uniformly with a masque base 64 g. The masque composition thus
formulated contained 8% cellobionic acid.
EXAMPLE 11
[0153] A typical synergetic composition comprising an
oligosaccharide aldonic acid in combination with an anti-fungal
agent for infections of nail, scalp, hair, skin, oral or vaginal
mucosa may be formulated as follows.
[0154] Lactobionic acid 10 g was dissolved in 90 ml solution
prepared from water 40 ml, ethanol 40 ml and propylene glycol 20
ml. The composition thus formulated contained 10% lactobionic acid,
and was used as a nail or scalp conditioner.
[0155] For fungal infections, lactobionic acid 10 g and
clotrimazole 2 g were dissolved in 88 ml solution prepared from
water 60 ml, ethanol 20 ml and propylene glycol 20 ml. The
synergetic composition thus formulated had pH 3.3 and contained 10%
lactobionic acid and 2% clotrimazole, and were suitable for
treatment of fungal infections of nail, scalp, hair, skin, oral or
vaginal mucosa.
EXAMPLE 12
[0156] A typical synergetic composition comprising an
oligosaccharide aldonic acid in combination with a corticosteroid
for eczema, psoriasis or other inflammatory dermatoses may be
formulated as follows.
[0157] Lactobionic acid 5 g was dissolved in 10 ml water, and
hydrocortisone 17-valerate 0.2 g was dissolved in 10 ml warm
propylene glycol. Two solutions thus prepared were added to and
mixed uniformly with 74.8 g cream base or commercially available
hydrophilic ointment. The white cream thus formulated contained 5%
lactobionic acid and 0.2% hydrocortisone 17-valerate.
EXAMPLE 13
[0158] A typical synergetic composition comprising an
oligosaccharide aldonic acid in combination with an anti-acne agent
may be formulated as follows.
[0159] Lactobionic acid 54% aqueous solution 11 g and salicylic
acid 2 g were dissolved and mixed with 87 ml solution prepared from
ethanol 70 ml and propylene glycol 30 ml. The synergetic
composition thus formulated had pH 3.1, and contained 6%
lactobionic acid and 2% salicylic acid.
EXAMPLE 14
[0160] In one of the studies related to skin changes associated
with aging, skin thickness was measured by micrometer calipers as
follows:
[0161] The skin was grasped with a 2.times.6 cm metal hinge; the
internal faces of which 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 sites were done and an average number was used for
calculation of the skin thickness.
EXAMPLE 15
[0162] A female subject, age 56, topically applied twice daily to
her left forearm for four weeks lactobionic acid 22% in a solution
prepared from water 7 parts and propylene glycol 3 parts. After
four weeks her right forearm was still loose and relatively thin,
and the skin was relatively rough and dry. In contrast, her left
forearm was more firm and plump, and the skin was smooth, soft and
not dry. 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 described in the Example. These
results indicated that lactobionic acid would be topically
effective and beneficial for various cosmetic and dermatological
indications.
EXAMPLE 16
[0163] A male subject, age 66, with chronic atopic eczema and
pruritic dry skin topically applied twice daily maltobionic acid
17% cream to itchy skin areas of eczema and dry skin lesions for
two weeks. The treated skin became smooth and less dry and itchy
within a week of topical application. The eczema lesions improved
significantly after two weeks of topical treatment with maltobionic
acid.
EXAMPLE 17
[0164] A female subject, age 59, having xerosis with flaky dry skin
condition of her forearms topically applied twice daily maltobionic
acid 5% water-in-oil cream for two weeks. After two weeks, her
forearms became smooth and soft, and the dry skin condition
disappeared completely.
EXAMPLE 18
[0165] A male subject, age 60, having two skin fissures (open cuts)
2-3 mm long at the finger tips, extending from the hyponychia,
topically applied twice daily lactobionic acid 10% oil-in-water
cream to one fissure for one week. The other fissure was treated
with a vehicle control. While the control site remained unhealed
and painful, the skin treated with the active cream healed rapidly,
and the pain disappeared after a few days of topical application.
After a week of topical treatment with the active cream, the skin
fissure healed completely while the control site remained unhealed.
This result indicated that the oligosaccharide aldonic acid would
be topically effective for promoting wound healing of the skin.
EXAMPLE 19
[0166] A typical composition comprising molecular complex of an
oligosaccharide aldonic acid in amphoteric system may be formulated
as follows.
[0167] Lactobionic acid 7.2 g (0.02 mole) was dissolved in 14.4 ml
water, and the solution containing 33.3% active ingredient had pH
1.9. L-Arginine 0.88 g (0.005 mole) was added to the solution with
stirring to form molecular complex as shown by an increase in pH of
the solution. The complexing reaction was completed as indicated by
no more increase in pH of the solution. The final pH of the
solution was 3.4, and the solution was mixed with sufficient
quantity of water-in-oil cream to make a total composition of 100 g
by weight. The water-non-washable cream thus formulated contained
molecular complex of 7.2% lactobionic acid and 0.88%
L-arginine.
EXAMPLE 20
[0168] A typical synergetic composition comprising molecular
complex of an oligosaccharide aldonic acid in combination with skin
lightening agents may be formulated as follows.
[0169] Maltobionic acid 50% aqueous solution 14.4 g was diluted
with 7.2 ml water, and the solution had pH 1.6. L-Lysine 1.16 g was
added to form molecular complex as shown by the increase of pH to
3.3. In another container, hydroquinone 2 g and kojic acid 1 g were
dissolved in warm propylene glycol 12 g, and this solution together
with the above molecular complex solution were mixed with
oil-in-water cream to make a total composition of 100 g by weight.
The synergetic cream thus formulated contained 2% hydroquinone and
1% kojic acid in molecular complex of 7.2% maltobionic acid and
1.2% L-lysine.
EXAMPLE 21
[0170] A typical synergetic composition comprising vitamin A and
vitamin E may be formulated as follows.
[0171] Cellobionic acid 3 g was dissolved in water 16 ml and
propylene glycol 4 ml, and L-arginine 0.4 g was added to the
solution with stirring to form an amphoteric complex. This complex
and retinyl acetate 2 g and tocopheryl acetate 2 g were mixed with
an oil-in-water cream to make a total composition of 100 g by
weight. The amphoteric composition thus formulated had pH 5.5, and
contained 3% cellobionic acid, 2% vitamin A and 2% vitamin E. This
composition is topical effective for various cosmetic and
dermatological indications.
EXAMPLE 22
[0172] Lactobionic acid 50% aqueous solution 10 g was diluted with
60 ml water and 10 ml propylene glycol, and the solution had pH
2.1. L-Arginine 5% solution 20 g prepared from 8 parts water and 2
parts propylene glycol by volume was added to form molecular
complex of amphoteric system as shown by the increase of pH to 3.3.
The composition thus formulated contained 5% lactobionic acid in
molecular complex with 1% L-arginine.
[0173] A male subject, age 67, having chronic gum disease of
bleeding during the tooth brushing, used the above bionic acid
complex composition twice daily as a gurgling solution with at
least one minute of contact time in oral cavity. No food or drink
was taken for the next 30 minutes. After one week of such oral
treatment with the bionic acid composition, the gum bleeding
stopped or became less noticeable during the tooth brushing. This
result suggests that the oligosaccharide aldonic acid would be
effective or beneficial for treatment of gum diseases.
EXAMPLE 23
[0174] Lactobionic acid 50% aqueous solution 10 g was uniformly
mixed with an oil-in-water base 80 g, and the cream thus obtained
had pH 2.5. L-Arginine 5% solution 10 g prepared from 8 parts water
and 2 parts propylene glycol by volume was added to form molecular
complex of amphoteric system as shown by the increase of pH to 3.1.
The composition thus formulated contained 5% lactobionic acid in
molecular complex with 0.5% L-arginine.
[0175] A female subject, age 60, having dry vaginal mucosa
topically applied the above bionic acid cream twice daily to the
affected areas of the mucosa. After one week of topical
applications, the dryness of vaginal mucosa disappeared completely
and the mucosa became smooth and moist. This result suggests that
the oligosaccharide aldonic acid would be therapeutically effective
for topical treatment of dry vaginal mucosa.
EXAMPLE 24
[0176] Lactobionic acid 54% aqueous solution 30 g was uniformly
mixed with an oil-in-water base 60 g. The cream thus prepared had
pH 2.0 and contained 18% lactobionic acid.
[0177] A male subject, age 66, having a lasting scrotum and
perineum itch after each time taking a shower topically applied the
above bionic acid cream to the affected areas of the skin. The itch
stopped immediately after topical application of the cream. This
result suggests that the oligosaccharide aldonic acid would be
therapeutically effective and beneficial for topical treatment of
senior itch or itch of unknown causes.
EXAMPLE 25
[0178] A sterile 22-gauge needle was held in the jaws of a surgical
needle holder, and two linear wounds 1 cm in length and 0.5 mm in
depth were made on alcohol-swabbed left forearm of a healthy male
subject, age 76. The wounds were swabbed dry with cotton balls. A
control solution containing 0.9% sodium chloride in distilled water
was applied to one wound, and a test solution containing 2%
lactobionic acid in distilled water was applied to the other wound.
Both wounds were covered with 3M Tegaderm tapes for five days. At
the end of one week, whereas the control wound was not
epithelialized, the test wound was healed with
re-epithelialization. The erythema disappeared from both skin sites
at the end of nine days.
[0179] These test results showed that a bionic acid was topically
effective for improving wound healing.
EXAMPLE 26
[0180] A sterile 4 mm skin biopsy punch was used to make two
circular wounds 0.5 mm in depth on alcohol-swabbed left forearm of
a healthy male subject, age 76. The wounds were swabbed dry with
cotton balls. A control solution containing 0.9% sodium chloride in
distilled water was applied to one circular wound, and a test
solution containing 2% lactobionic acid in distilled water was
applied to the other circular wound. Both wounds were covered with
3M Tegaderm tapes for five days. At the end of one week, the
control wound was not epithelialized and the test wound was healed
with re-epithelialization. The erythema disappeared from both skin
sites at the end of nine days.
[0181] These test results showed that a bionic acid was topically
effective for improving wound healing.
EXAMPLE 27
[0182] A female subject, age 60, developed contact dermatitis or
erythema on her face after topical applications of 20%
unneutralized glycolic acid cream. She applied 5% partially
neutralized lactobionic acid cream on the left side of her face and
a control cream on the right side of her face. Whereas the erythema
persisted on the right side of her face, the skin on the left side
of her face improved substantially and the erythema became less
noticeable after three topical applications of lactobionic acid
cream over the 24 hour period.
[0183] These results showed that a bionic acid was topically
effective in reducing skin irritations caused by an external
factor.
EXAMPLE 28
[0184] A male subject, age 67, with sensitive skin developed acute
erythema on his both thighs after taking hot shower using alkaline
soap. He applied 3% partially neutralized maltobionic acid cream on
his left thigh and a control cream on his right thigh. Whereas the
erythema and itch persisted on his right thigh, the erythema and
itch disappeared within a few minutes alter topical application of
maltobionic acid cream.
[0185] These results showed that a bionic acid was topically
effective in reducing skin irritations caused by an external
factor.
[0186] 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 patents or patent application, including U.S.
provisional application Ser. No. 60/141,624, and 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.
* * * * *