CA1115211A

CA1115211A - Treatment of dry skin

Info

Publication number: CA1115211A
Application number: CA286,278A
Authority: CA
Inventors: Eugene J. Van Scott; Ruey J. Yu
Original assignee: Individual
Current assignee: Individual
Priority date: 1976-09-07
Filing date: 1977-09-07
Publication date: 1981-12-29
Also published as: CY1245A; GB1589224A; PH13782A; FR2363326A1; DE2740349C2; JPS5396329A; SG27584G; KE3401A; DE2740349A1; BE858404A; FR2363326B1; ZA775363B; MY8500566A; PT67007A; FR2422398B1; AU519802B2; AU2858377A; PT67007B; HK46285A; FR2422398A1

Abstract

ABSTRACT

This invention relates to a treatment for skin disorders characterized by cracking, flaking or scaling of hands, feet or the body commonly known as "dry skin", and specifically to compounds which have been found to be effective when topically applied to prevent as well as heal the skin lesions associated with these conditions in humans. The symptoms of dry skin in humans may be alleviated by the topical administration of a therapeutically effective amount of a composition comprising the reaction product of A) at least one reactant selected from the group consisting of citric acid, glycolic acid, glucuronic acid, galacturonic acid, glucuronolactone, gluconolactone, ?-hydroxybutyric acid, ?-hydroxyisobutyric acid, lactic acid, malic acid, mandelic acid, mucic acid, pyruvic acid, methyl pyruvate, ethyl pyruvate, .beta.-phenyllactic acid, .beta.-phenylpyruvic acid, saccharic acid, tartaric acid, tartronic acid, and .beta.-hydroxybutyric acid, and B) a base selected from the group consisting of ammonium hydroxide, an organic primary, secondary, or tertiary alkylamine, alkanol amine, diamine, dialkylamine, dialknnol-amine, alkylalkanol amine, trialkylamine, trialkanol amine, dialkyl alkanol amine, or alkyl dialkanolamine wherein the alkyl or alkanol substituent has from 1 to 8 carbon atoms; in a pharmaceutically acceptable vehicle.

Description

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This invention relates to a treatment for skin disorders characterized by cracking, flaking or scal:ing of hands, reet or t~le body commonly known as "dry skin", and speci~ically to compounds which have been found to be e~fective when topically applied to prevent as well as heal the skin lesions associated with these conditions in humans.
Se~ere "dry skin" conditions known as ichthyosis are hereditary disorders. T~le term ichthyosis alludes to a ~ish scale-like appearance o:~ the human skin. Ichthyosis, characterized by a "dr~y skin" appearance, is usually detected durlng the early years o~ child~lood. Small~ fine scales with a "pasted-on" appearance are found most prominently on the trunk and upper extremities. Larger, more ad~lerent scales are present on the legs. Only a small number of the population are a~fected by this hereditary disorder.
In contrast to ichthyosis, mild to rnoderate "dry skin"
conditions are quite common among -the populatlon. rm ese common "dry skin" conditions are specially pronounced during the f`all and winter seasons, when environmental humidity is comparatively low, '~hey are characterized by fissures, chaps, cracks or flakes of the skin on hands, ~ace, neck and legs.
Conventional treatments f`or all kinds of dry skin condltions primarily involve the -topical application of oils or oil preparations~ and hydrating emollients, In addition~
ointments containing salicylic acid, urea, glycerol, propylene glycol, sorbitol or vitamin A have been used. Prior treatments~ ~lowever~ have not been universally .successful, and have, in many cases, been unable to promote healing to cause a complete remission of the symptoms. Because the .
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mechanisms involved in causing dry skin are not known, treatment has usually resulted in a temporary remission or healing of the flaky or scaly lesions. .
We have now discovered that "dry skin" conditions ~ :
may be successfully prevented or treated with the acid, amide or ammonium salt of ~- or ~-hydroxyacids or ~-keto acids and esters thereof.
. ,..~ . .
We have discovered that the symptoms of dry skin in humans may be alleviated by topical application of a ~herapeutically effective amount of a composition :
comprising a mixture of at least two members selected from the group of citric acid, glycolic acid, glucuronic acid, galacturonic acid, glucuronolactone, gluconolactone, .: .
a-hydroxybutyric acid, ~-hydroxyisobutyric acidt lactic acid, :.
malic acid, mandelic acid, mucic acid, pyruvic acid, methyl :
pyruvate, ethyl pyruvate, ~-phenyllactic acid, ~-phenylpyruvic acid, saccharic acidr tartaric acid, tartronic acid, and ~-hydroxybutyric acid, and a pharmaceutically acceptable carrier.
We have further discovered that the symptons . .
20 of dry skin in humans may be allevia~ed by the topical .
administration o~ a t~erapeutically effective amount of a composition comprising the reaction product of A) at least one reactant selected from the group consisting o~ citric acid, glycolic acid, glucuronic acid, galacturonic acid, glucuronolactone, gluconolactone, ~-hydroxyburyric acid, hydroxyisobutyric acid, lactic acid, malic acid, mandelic acid, mucic acid, py~vic acid, methyl pyruvate, ethyl , pyruvate3 3-phenyllactic ~cid, ~-p~enylpyruvic acid, ~ saccharic acid, tartaric acid, tartronlc a.cid, ~nd ~-hydroxy-30 butyric acid, and B) a b;~se selected from tie group consisting o~ ammoniui~ hydroxide, an organic primary, secondary, or tertiary alkylaminc, ~lk~nol amine, diamine, dialkylamine,

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dialkanolamine, alkylalkanol amineJ trial~ylamine, trialkanol amine, dialkyl alkanol amine, or alkyl di.alkanolamine wherein the alkyl or alkanol substituent has from 1 to 8 carbon atoms;
in a pharmaceutically acceptable ve~licle.
In a preferred embodiment of t~li.S invention, we provide a method of alleviating the symptoms of dry skin in humans by the topical application of a. composition comprising the reactant product of A) at least one reactant selected from the group consisting of citric acid, glycolic acid, glucuronic '.

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Z~, acid, galacturonic acid, glucuronolactone, gluconolactone, ~-hydroxybutyric a.cid, ~-hydroxyisobut;yric.acid, lactic acid, malic acid, manlelic acid~ mucic acid, pyruvic acid, methyl pyruvateJ ethyl pyruvate, ~-phenyllact;ic acid, ~-phenyl-pyruvic acld, saccharic acid~ tartaric acid, tartronic acid, and ~-hydroxybutyric acid and B) a base selected from the group consisting o~ ammonium hydroxide, methylamine, ethylamine, monoethanolamine, monoisopropanolamine, ethylenediamine, 1,2-diaminopropane, dimethylarnine~ diethylamine, diethanolamine, diisopropanolamine, N-methylethanolamine~ N-ethylethanolamine, triethylamine, triethanolamine~ N-methyldiethanolamine, and tri.lsopropylamine in a pharmaceutically acceptable vehicle.
It has been established through tests on humans having "dry skin" conditions that topical application of a lotion, cream or ointment containing from 1 to 20 percent of the reaction product described above and preferably from 2 to 10 percent thereof, is therapeutically effective, when applied on a regular basis, to cause, within about one to two weeks, a return of -the .a~fected areas to a normal skin condition. If two or more reaction products are used ln a composition o~ the invention, the total concentration of the products i.s preferred not to exceed 10 percent by weight of the composition. It has also been found in humans having frequent occurrence of cracking or flaking skin that topical application o~ the afore-mentioned composition of the present invention is e~ectiveJ
when applied on a regular basis, in preventing development of dry skin lesions.
Accordingly, this invention provldes a cosmetic composition containing at least one of the reaction products described above which when topically applied wi.l1 :reliably prevent the development o~ dry skin c.onditions.

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This invention further provides a medicinal composition containing at least one of the reaction products defined above which when topically applied will substantially allevia.te the symptoms o~ dr~ skin.
This invention still further provides a method for treating dry skin with the composition of the reaction product defined above in a pha.rmaceutically a.cceptable vehicle.
Generally3 the composition of this invention should have a pH of between 3.5 and 7.5.
In a pre~erred embodiment of the invention the pharmaceutically acceptable vehicle is at least one member of the group consisti.ng Or water, ethanol and propylene glycol present therein in a concentration o~ up to 99~, 7~0 and 30~, respectively.
m e invention also provides a safé and ef~icient method ~or treating the symptoms of dry skin through regular topical application of a medici.nal composition which will promote ~ealing within about one to two weeks.
Additionally, this invention provides a method for ~ormulating a cosmetic as wel.l as medicinal composi-tion in lotion, cream or ointment which when topically applied at least daily to skin areas prone to lesions of cracking~ flaking or scaling will prevent the development of dry skin or result in a restora-tion of normal healthy skin condition.
, PREPARATION OF THE THERAPEUTIC COMPOSITIONS
.
Previously, in treatment of extremel~ dry skin conditions such as ichthyosis~ ~- or ~~hydroxyacids or ~-keto-acids were prepared in a composition containing 5 to 10 percent S2~

by weight of the compo~mds in a cream or ointment. The pH
of the composition was about 2 or less. In treatment of common dry skin condi-tions according to this invention, we found that the above composition with low pH could cause some skin irritation (redness and sensation of burning) on some of the sensitive subjects. It was ther~fore desirable to develop compositions which were therapeutically effective but not irritative.
In this invention we provide a method for alleviating the symptoms of dry skin in humans comprising the topical administration of a therapeutically ef~ective amount o~ a composit-lon comprising the reaction product of A) at least one reactant selected from the group consisting of citric acid~ glycolic acid, glucuronic acid, galacturonic acid, glucuronolactone, gluconolactone~ a-hydroxy-butyric acid, ~-hydroxyisobutyric acid, lactic acid, malic acid3 mandelic acid, mucic acid~ pyruvic acid~ methyl pyruvateJ ethyl pyruva-te, ~-phenyllactic acid, ~-phenylpyruvic acid, saccharic acid~ tartaric acid, tartronic acid, and ~-hydroxybutyric acid, and B) a base selected from the group consis-ting of ammonium hydroxide, an organic primary, secondary, or tertiary alkylamine, alkanol amine, diamine, dialkylamine, dialkanol-amine, alkylalkanol amine, trialkylamine, trialkanol amine, dialkyl al~anol amine, or alkyl dialkanolamine wherein the alkyl or alkanol substituent has from 1 to 8 carbon atoms;
in a pharmaceutically acceptable vehicle.
The reactlon product of the instant invention is prepared by reacting at least one member selected from the group consisting of citric acid, glycolic acid, glucuronic .

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acid) galacturonic acidJ glucuronolactone~ gluconolactone~
~-hydroxybutyric acid, a-hydroxyisobutyric acid~ lactic acid, malic acid, mandelic acid, mucic acid~ pyruvic acid, methyl pyruvate, ethyl pyruvate, ~-phenyllactic acid, ~-phenylpyruvic acid, saccharic acid) tartaric acid, tartronic acid, and ~-hydroxybutyric acid, in a solvent with a base selected ~rom the group consisting of ammonium hydroxide, an organic primary, secondary, or tertiary alkylamine, alkanol amine, diamine, dialkylamine5 dialkanolamine, alkylalkanol amine, trialkylamine, trialkanol amine, dialkyl alkanol amine, or alkyl dialkanolamine wherein the alkyl or alkanol substituent has from 1 to 8 carbon atoms.
The sol~ent used in -the reaction is one or more selected from the group of waterJ alcohol, e-ther and acetone.
The preferred solvent is water. The concentration o~ solvent used irl the reaction is from about 5 to about 30 percent.
m e reaction may be carried out at temperatures of ~rom about 0C to about 75C. It is preferred to carry out the reaction at room tempera-ture.
In a pre~erred embodiment the reaction product comprises from about 1 to about 20 percent by volume of the total composition.
In a further preferred embodiment the reaction product comprises from about 2 to about 10 percent by volume o~ the total composition, qhe compositions of the present invention include those comprising two or more than two di~ferent reaction produc-ts.
The prophylactic as well as therapeu-tic com~osi-tion may be prepared in a form of lotion~ cream or ointment. In these instances, cosmetically acceptable ingredients are : .

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incorporated into the ~ormulation, and lotions, creams or ointments are readily prepared.
m e ~ollowing are illustrative examples of ~ormu-lations o~ compositions according to this invention, Although the examples utilize only selected formulations useful according to this in~ention, it should be understood that the following examples are illustrative and not limited.
Therefore, any of the aforementioned acids3 esters and amines may be substituted according to the teachings of this invention in the following formulations~

E~AMPI,~ 1 -Glycolic acid, 5 grams was dissolved in 10 ml water and ethanolamine, 3 ml was added to partially neutralize the acidity o~ the solution. This solution was admixed with 82 grams of water-nonwashable lotion prepared ~rom mineral oil, cottonseed oil, isopropyl palmitate and water with a sur~actant such as sorbitan sesquioleate. The ingredients o:~ said lotion are present in 15:15:5:60:5 parts by weightJ respectively.
m e lotion thus prepared is stored in a plastic squeeze bottle ha~ing a nozzle attached -thereto.
; . . ' .
j~ Lactic acid, USP grade 5 ml was dissolved in 10 ml o~
water and triethanolamine, 5 ml was added to neutralize partiall~
the acidity o~ the solution. This solution was admixed with 80 grams o~ water~nonwashable lotion-prepared ~rom mineral oil, cottonseed oil and water with a surfactant such as sorbitan sesquioleate. The ingredients of said lo-tion are present in 30:15:50:5 parts by weight, respectively.

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EX~-IPLE 3 Part A: Polyoxyethylene (20) sorbitan mono-oleate (hereina~ter ~.~een ~0)5 gm Cetyl alcohol 20 gm Part B: Water 45 ml Propylene glycol 10 ml Glycolic acid 10 gm Ethanolamine 7 ml Heat Part A to 75C and heat Part B to 75C. Add Part B slowly to Part A with agitation. Continue agitation until the mixture is congealed. m e ~rater-washable cream thus prepared has a p~
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o~ 4.7.
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EXA~IPLE 4 Part A ~een 80 5 gm Cetyl alcohol 22 gm ~-.
Part B: Water 55 ml PropyIene glycol 10 ml Lactic acid 5 ml Ethanolamine 2 ml Heat Part A to 75C and heat Part B to 75C. Add Part B slo~rly to Part A ~ith agitation, Continue agitation until the mixture is congealed. The water-washable cream thus prepared has a pH
o~ 4,5.
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EX~PL~ 5 ` Part A: ~reen 80 1~52~i Cetyl alcohol 15 gm Stearyl alcohol 5 gm Part B: ~ater 60 ml Propylene glycol 5 ml Citric acid 2 gm Lactic acid 2 ml Glycolic acid 2 gm Ethanolamine 3 ml Heat both Part A and Part B to 75C. Add Part B slowl~ to Part A with agitation, Continue agitation until the mixture is congealed, m e water-washable cream containing three active ingredients has a pH of 4.4.
. . .

EX~MPLE 6 Glycolic acidJ 7 grams was dissolved in 10 ml o~ ice . :
water and ethanolamine, 5 ml was added to neutralize partially the acldity of the solution. This solution was admixed with 78 grams o~ water-nonwashable ointment prepared from petrolatum, mineral oil, spermaceti and water with a sur~actant such as sorbitan sesquioleate. The ingredients of said ointment are present in 10:10:6:68:6 parts by weight, respectively.

' ' ~ Lactic acid, USP grade 5 ml ~ras dissolved in 10 ml of ice water and triethanolamine, 4 ml was added to neutralize - partially the acidity of the solution. This solution ~as admixed ~lith 81 grams o~ water-nonwashable ointment prepared .

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~lSZ~Ll from petrolatum~ mineral oil, isopropyl myristate, spermaceti and water with a sur~actant such as sorbitan sesquioleate.
The ingredients o~ said ointment are present in 10:10:10:6:58:6 parts by weight, respectively.

a Hydroxyisobutyric acid, 5 grams and sorbitol 2 grams were dissolved in 8 ml o~ water. mis solution was admixed wlth 85 grams o~ water-nonwashable ointment prepared ~rom petrolatum~ mineral oil, spermaceti and wa-ter with a surfactant such as sorbitan sesquioleate. The ingredients o~
said ointment are present in 10:10:6:68:6 parts by weight, respectively.

F.XA~IPLE 9 Pyruvic acid 2 ml, glycolic acid 2 grams, citric acid .
2 grams/ and lactic acid 2 ml were dissolved in 12 ml of waterO
This solution was admixed with commercially available USP grade hydrophilic ointment (80 grams) to a uniform consistency.
water-washable ointment thus prepared contained four actlve . ingredients.
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TEST RESULTS
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(A) Severe Dry Skin Ten patients with severe dry skin conditions such as ichthyosis were instructed first to wet the body b~ taking a shower and then apply a thin ~ilm of the compositions formulated according to Examples 4~ 7 or 9 on left side of the bo~y.
Other commercially available preparations such as vegetable oil or petrolatum were applied on right side of the body. ~ice daily topical application was continued for several weeks. In all the patients tested the left side of the body became less flaky and felt smoother than the right side after about a week o~ topical treatment. The roughtand flaky lesions on the left side of the body were substantially clear after ten days of treatment. The left side of the body devoid o~ any cracking, flaking or scaling usuall~ reached an improved state comparable to normal appearing skin within two to three weeks after initial treatment, Very little or no substantial improvement was seen on the right side of the body, which had been treated with vegetable oil or petrolatum alone. m erefore aPter three weeks the patients were instructed to apply the composition o~ the present invention on the right side of the body, Again, the skin on the right side of the body became normal appearing within two to three weeks.
Once a normal appearing skin was restored, it remained improved for from several weeks to several months, varying from patient to patient~ without further application o~ the ointment.
It was, however, necessary to continue the application of the ointment in order to maintain the skin free from recurrence o~
the overt disease.

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(B) Common Dry Skin Human subjects with mild to moderate degrees o~ dry skin conditions, as evidenced by dry, cracking or f`laking of the skin, were instructed to apply topically the lotion, cream or ointment of the present invention formulated according to Examples 1 through 8 on the affected skin areas. Twice daily topical application was continued for a few weeks. In all the twenty-three human subJects tested the ~eeling of the skin dryness disappeared a~ter three to four days o~ topical treatment. In twenty-one human subjects tested the rough and cracked skin usually became less pronounced within a weeks time.
Generally the skin appeared normal and felt smooth after about two weeks of topical treatment.
In contrast to the severe dry skin disease the common dry skin conditions once restored to normal ~ppearing skin remained improved for some time until causes o~ dry skin, such as low h~nidity, cold weather, detergents, soaps, chemicals~ etc., recurred. On continued use it was also found that twice daily topical application of a composition of the present invention prevented the development of new dry s~in lesions.
me invention may be embodied in other specific forms without departing ~rom the spirit or esse~tial characteristics thereof. The present embodiment is) there~ore, to be considered in all respects as illubtrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes ~hich come within the meaning and range of equivalency of the claims are, there~ore~ in-tended to be embraced therein.

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Claims

C L A I M S

1. A therapeutic composition for topical administration for alleviating the symptoms of dry skin in humans comprising the reaction product of A) at least one reactant selected from the group consisting of citric acid, glycolic acid, glucuronic acid, galacturonic acid, glucuronolactone, gluconolactone, .alpha.-hydroxy-butyric acid, .alpha.-hydroxyisobutyric acid, lactic acid, malic acid, mandelic acid, mucic acid, pyruvic acid, methyl pyruvate, ethyl pyruvate, .beta.-phenyllactic acid, .beta.-phenylpyruvic acid, saccharic acid, tartaric acid, tartronic acid, and .beta.-hydroxybutyric acid, and B) a base selected from the group consisting of ammonium hydroxide, an organic primary, secondary, or tertiary alkylamine, alkanol amine, diamine, dialkylamine, dialkanolamine alkylalkanol amine, trialkylamine, trialkanol amine, dialkyl alkanol amine, or alkyl dialkanolamine wherein the alkyl or alkanol substituent has from 1 to 8 carbon atoms; in a pharmaceutically acceptable vehicle.

2. The composition of Claim 1, wherein the reaction product comprises a reactant product of A) at least one reactant selected from the group consisting of citric acid, glycolic acid, glucuronic acid, galacturonic acid, glucuronolactone, gluconolactone, .alpha.-hydroxy-butyric acid, .alpha.-hydroxyisobutyric acid, lactic acid, malic acid, mandelic acid, mucic acid, pyruvic acid, methyl pyruvate, ethyl pyruvate, .beta.-phenyllactic acid, .beta.-phenylpyruvic acid, saccharic acid, tartaric acid, tartronic acid, and .beta.-hydroxybutyric acid, and B) a base selected from the group consisting of ammonium hydroxide, methylamine, ethylamine, monoethanolamine, monoisopropanolamine, ethylenediamine, 1,2-diaminopropane, dimethylamine, diethylamine, diethanolamine, diisopropanolamine, N-methylethanolamine, N-ethylethanolamine, triethylamine, triethanolamine, N-methyldiethanolamine, and triisopropylamine.

3. The composition of Claim 2, wherein the vehicle is at least one member selected from the group consisting of water, ethanol and propylene glycol present therein in a concentration of up to 99%, 70% and 30%, respectively.

4. The composition of any of Claims 1 to 3, wherein the composition has a pH of from 3.5 to 7.5

5. The composition of any of Claims 1 to 3, wherein the reaction product is present in a concentration of from 1 up to about 20 percent by volume of the total composition.

6. The composition of any of Claims 1 to 3, wherein the reaction product is present in a concentration of from 2 up to about 10 percent by volume of the total composition.

7. The composition of any of Cla1ms 1 to 3, wherein the composition comprises a reaction product of from about 5 to about 7 parts glycolic acid, and about 3 to about 5 parts mono-ethanolamine in about 10 parts water per 100 oarts of said vehicle.

8. The composition of any of Claims 1 to 3, wherein the composition comprises a reaction product of about 5 parts lactic acid and about 4 to about 5 parts triethanolamine in about 10 parts water per 100 parts of said vehicle.

9. The composition of any of Claims 1 to 3, wherein said composition comprises: a reaction product of about 5 parts glycolic acid and 3 parts ethanolamine in a vehicle of mineral oil, cottonseed oil, isopropyl palmitate, water, and a surfactant present in a ratio of 15:15:5:60:5 per 100 parts of said vehicle.

10. The composition of any of Claims 1 to 3, wherein said composition comprises: a reaction product of about 5 parts lactic acid and 5 parts triethanolamine in 10 parts water in a vehicle of mineral oil, cottonseed oil, water, and a surfactant present in a ratio of 30:15:50:5 per 100 parts of said vehicle.

11. The composition of any of Claims 1 to 3, wherein said composition comprises: a reaction product of 10 parts glycolic acid and 7 parts ethanolamine in 20 parts cetyl alcohol, 5 parts polyoxyethylene (20) sorbitan monooleate, 45 parts water, and 10 parts propylene glycol.

12. The composition of any of Claims 1 to 3, wherein said composition comprises: a reaction product of 5 parts lactic acid and 2 parts ethanolamine in 22 parts cetyl alcohol, 5 parts polyoxyethylene (20) sorbitan monooleate, 55 parts water, and 10 parts propylene glycol.

13. The composition of any of Claims 1 to 3, wherein said composition comprises: a reaction product of 2 parts citric acid, 2 parts lactic acid, 2 parts glycolic acid and 3 parts ethanolamine in 15 parts cetyl alcohol, 5 parts stearyl alcohol, 5 parts polyoxyethylene (20) sorbitan monooleate, 60 parts water, and 5 parts propylene glycol.

14. The composition of any of Claims 1 to 3, wherein said composition comprises: a reaction product of 7 parts glycolic acid and 5 parts ethanolamine in 10 parts water in a vehicle of petrolatum, mineral oil, spermaceti, water, and a surfactant present in a ratio of 10:10:6:68:6 parts per 100 parts of said vehicle.

15. The composition of any of Claims 1 to 3, wherein said composition comprises: a reaction product of 5 parts lactic acid and 4 parts triethanolamine in 10 parts water in a vehicle of petrolatum, mineral oil, isopropyl myristate, spermaceti, water, and a surfactant present in a ratio of 10:10:10:6:58:6 parts per 100 parts of said vehicle.

16. A composition for alleviating the symptons of dry skin in humans by topical application to involved areas of the body, comprising a therapeutically effective amount of a mixture of at least two members selected from the group of citric acid, glycolic acid, glucuronic acid, galacturonic acid, glucuronolactone, gluconolactone, ?-hydroxybutyric acid, ?-hydroxyisobutyric acid, lactic acid, malic acid, mandelic acid, mucic acid, pyruvic acid, methyl pyruvate, ethyl pyruvate, .beta.-phenyllactic acid, .beta.-phenylpyruvic acid, saccharic acid, tartaric acid, tartronic acid, and .beta.-hydroxybutyric acid, and a pharma-ceutically acceptable carrier.

17. The composition of Claim 16, wherein the mixture is present in a concentration of from 1 up to about 20 percent by volume of the total composition.

18. The composition of Claim 16, wherein the mixture is present in a concentration of from 2 up to about 10 percent by volume of the total composition.

19. The composition of Claim 16, wherein the composition comprises about 5 parts .alpha.-hydroxyisobutyric acid in 2 parts sorbitol and 8 parts water admixed with 85 parts of a pharmaceutically acceptable vehicle.

20. The composition of Claim 16, wherein the composition comprises about 2 parts pyruvic acid, 2 parts glycolic acid, 2 parts citric acidg and 2 parts lactic acid in 12 parts water, admixed with 80 parts of said vehicle.