Additives enhancing topical actions of therapeutic agents

Abstract

Composition and method for enhancing therapeutic effects of topically applied agents are disclosed. The cosmetic or therapeutic composition may include one or more of cosmetic or pharmaceutical agents present in a total amount of from 0.01 to 40 percent and one or more of hydroxycarboxylic acids or related compounds present in a total amount of from 0.01 to 99 percent by weight of the total composition. The cosmetic and pharmaceutical agents may include but not limited to age spots, wrinkles and keratoses removing agents; vitamins; aloes; sun screens; tanning, depigmenting and shampooing agents; antiyeasts; antifungal, antibacterial and antiviral agents; topical bronchial dilators and topical cardiovascular agents; hormonal agents; vasodilators; retinoids and other dermatological agents. The hydroxycarboxylic acids and related compounds include organic alpha and beta hydroxycarboxylic acids, alpha and beta ketocarboxylic acids and salts thereof. Topical application of the cosmetic or therapeutic composition has been found to achieve a substantial increase in cosmetic or therapeutic effect of the active ingredient in humans and domesticated animals.

What is claimed is:  
     
         1 . A method for enhancing the therapeutic effect of a composition comprising a cosmetic or pharmaceutical agent in a pharmaceutically acceptable vehicle for topical application to the skin of humans or animals comprising: 
 admixing with said composition an enhancing effective amount of at least one member selected from the group consisting of hydroxycarboxylic acid and related ketocarboxylic acid and ester, lactone or salt forms thereof.    
     
     
         2 . The method of    claim 1    wherein said cosmetic or pharmaceutical agent is a member selected from the group consisting of age spots, wrinkles and keratoses removing agents; analgesics, anesthetics, antiacne agents, antibacterials, antiyeasts, antifungals, antivirals; antiburn, antidandruff, antidermatitis, antipruritic, antiperspirant, antiinflammatory, antiaging, antihyperkeratolytic, antidryskin, antipsoriasis, antiseborrhea, astringent agents; skin softeners and emollients; coal tar, bath oils, sulfur, rinse conditioners; hair growth and hair removing agents; keratolytics, moisturizers, powders, shampoos, skin bleaches, skin protectants, soaps, cleansers, sunscreens, wart removers, vitamins, tanning agents; topical antihistamins, hormones, retinoids, vasodilators, bronchial dilators, topical cardiovasculars and dermatologicals.  
     
     
         3 . The method of    claim 1    wherein said cosmetic or pharmaceutical agent is a member selected from the group consisted of: aloe; 9-aminoacridine; PABA and its esters, acyclovir, amphotericins; benzoyl peroxide; clindamycin, chloramphenicol; clotrimazole, candicidin; cromolyn, clindamycin, crotamiton, coal tar; doxycycline; dipyridamole, dioxybenzone, diazoxide, diphenylhydantoin; ephedrine, erythromycin; fluorouracil, flucytosine; gentamicin, griseofulvin, gramicidin; halothane, hydroquinone and its monomethyl and benzyl ethers; haloprogin, hydralazine; idoxuridine, kanamycin, ketoconazole, lidocaine, miconazole, metronidazole, minoxidil, minocycline, meclocycline, metronidazole, nitroglycerine, nystatin, neomycin, oxybenzone, oxytetracycline, procaine, polymyxins, povidone-iodine, phenytoin, prazosin, retinoic acid and other retinoids, spironolactone, sulfonamides, sulfacytosine, spectinomycin, sulfamethoxazole, sulfisoxazoles, sulfamethizole, salicylic acid, selenium sulfide, sulfer, theophylline, tobramycin, tetracycline, tolnaftate, trimethoprin, troleandomycin, vitamins, vancomycin and zinc pyrithione.  
     
     
         4 . The method of    claim 1    wherein said hydroxycarboxylic acid is hydroxymonocarboxylic acid having the following chemical structural formula:  
       R 1 (CR 2 OH) m (CH 2 ) n COOH  
       wherein 
 R 1 , R 2 =H, alkyl, aralkyl or aryl group of saturated or unsaturated, straight or branched chain or cyclic form, having 1 to 25 carbon atoms.  
 m=1,2,3,4,5,6,7,8 or 9  
 n=0 or a numerical number up to 23  
 present as free acid, lactone or salt form, and as optically active or inactive isomer such as D, L, and DL forms; the hydrogen atom attached to the carbon atom may be substituted by a nonfunctional F, Cl, Br, I, or S atom or a lower alkyl or alkoxy saturated or unsaturated radical, having 1 to 9 carbon atoms.  
 
     
     
         5 . The method of    claim 4    wherein said hydroxymonocarboxylic acid is a member selected from the group consisted of 2-hydroxyacetic acid; 2-hydroxypropanoic acid; 2-methyl 2-hydroxypropanoic acid; 2-hydroxybutanoic acid; phenyl 2-hydroxyacetic acid; phenyl 2-methyl 2-hydroxyacetic acid; 3-phenyl 2-hydroxypropanoic acid; 2,3-dihydroxypropanoic acid; 2,3,4-trihydroxybutanoic acid; 2,3,4,5-tetrahydroxypentanoic acid; 2,3,4,5,6-pentahydroxyhexanoic acid; 2-hydroxydodecanoic acid; 2,3,4,5,6,7-hexahydroxyheptanoic acid; diphenyl 2-hydroxyacetic acid; 4-hydroxymandelic acid; 4-chloromandelic acid; 3-hydroxybutanoic acid; 4-hydroxybutanoic acid; 2-hydroxyhexanoic acid; 5-hydroxydodecanoic acid; 12-hydroxydodecanoic acid; 10-hydroxydecanoic acid; 16-hydroxyhexadecanoic acid; 2-hydroxy-3-methylbutanoic acid; 2-hydroxy-4-methylpentanoic acid; 3-hydroxy-4-methoxymandelic acid; 4-hydroxy-3-methoxymandelic acid; 2-hydroxy-2-methylbutanoic acid; 3-(2-hydroxyphenyl) lactic acid; 3-(4-hydroxyphenyl) lactic acid; hexahydromandelic acid; 3-hydroxy-3-methylpentanoic acid; 4-hydroxydecanoic acid; 5-hydroxydecanoic acid; aleuritic acid.  
     
     
         6 . The method of    claim 4    wherein said hydroxymonocarboxylic acid is a member derived from an amino acid by substituting the amino group with a hydroxy group.  
     
     
         7 . The method of    claim 4    wherein said lactone is an intermolecular or intramolecular lactone including linear acid polymer, ribonolactone, gluconolactone, galactonolactone, gulonolactone and mannonolactone.  
     
     
         8 . The method of    claim 1    wherein said compound is a keto or hydroxyketomonocarboxylic acid selected from the group consisting of pyruvic acid, hydroxypyruvic acid, hydroxypyruvic acid phosphate, methyl pyruvate, ethyl pyruvate, propyl pyruvate, isopropyl pyruvate, phenyl pyruvic acid, methyl phenyl pyruvate, ethyl phenyl pyruvate, propyl phenyl pyruvate; formyl formic acid, methyl formyl formate, ethyl formyl formate, propyl formyl formate, benzoyl formic acid, methyl benzoyl formate, ethyl benzoyl formate, propyl benzoyl formate, 4-hydroxybenzoyl formic acid, 4-hydroxyphenyl pyruvic acid, and 2-hydroxyphenyl pyruvic acid.  
     
     
         9 . The method of    claim 1    wherein said compound is a hydroxydicarboxylic acid having the following chemical structural formula:  
                 
 
       wherein  
       m=1,2,3,4,5,6,7,8, or 9  
       n=0 or a numerical number up to 23  
       present as free acid, lactone or salt form, and as optically active or inactive D, L, and meso isomer; hydrogen atom attached to the carbon atom may be substituted by a nonfunctional F, Cl, Br, I, or S atom or a lower alkyl or alkoxy saturated or unsaturated radical, having 1 to 9 carbon atoms.  
     
     
         10 . The method of    claim 9    wherein said hydroxydicarboxylic acid is a member selected from the group consisted of 2-hydroxypropanedioic acid; 2-hydroxybutanedioic acid; erythraric acid; threaric acid; arabiraric acid; ribaric acid; xylaric acid; lyxaric acid; glucaric acid; galactaric acid; mannaric acid; gularic acid; allaric acid; altraric acid; idaric acid; talaric acid; 2-hydroxy-2-methylbutanedioic acid.  
     
     
         11 . The method of    claim 9    wherein said hydroxydicarboxylic acid is a member derived from an amino acid by substituting the amino group with a hydroxy group.  
     
     
         12 . The method of    claim 9    wherein said lactone is an intermolecular or intra molecular lactone including saccharic acid, 1,4-lactone.  
     
     
         13 . A method for enhancing the therapeutic effect of a composition comprising a cosmetic or pharmaceutical agent in a pharmaceutically acceptable vehicle for topical application to the skin of humans or animals comprising: 
 admixing with said composition an enhancing effective amount of at least one member selected from the group consisting of    Hydroxycarboxylic acid of    R(OH) m (COOH) n      Wherein m,n=1,2,3,4,5,6,7,8 or 9    R=H, alkyl, aralkyl or aryl group of saturated or unsaturated, straight or branched chain or cyclic form, having 1 to 25 carbon atoms.    citric acid, isocitric acid, agaricic acid, quinic acid, citramalic acid, glucuronic acid, glucuronolactone, galacturonic acid, galacturonolactone, uronic acids, uronolactones, ascorbic acid, dihydroascorbic acid, dihydroxytartaric acid, 1-hydroxy-1-cyclopropanecarboxylic acid, 2-hydroxyhexanedial, 5-hydroxylysine, 3-hydroxy-2-aminopentanoic acid, 4-hydroxy-3-pentenoic acid, tropic acid, 4-hydroxy-2, 2-diphenylbutanoic acid, and 3-hydroxy-3-methylglutaric acid and ester, lactone or salt forms thereof, and as an optically active or inactive D, L, DL or meso isomer; the hydrogen atom attached to the carbon atom may be substituted by a nonfunctional F, Cl, Br, I or S atom or a lower alkyl or alkoxy saturated or unsaturated radical having 1. to 9 carbon atoms.    
     
     
         14 . The method of    claim 13    wherein the lactone is an inter or intramolecular lactone.  
     
     
         15 . A therapeutic composition effective against skin conditions and disorders comprising an effective amount of at least one compound selected from the group consisting of: 
 Citramalic acid, Diphenyl 2-hydroxyacetic acid (benzilic acid), 2-phenyl 3-hydroxypropanoic acid (tropic acid), aleuritic acid, ribonic acid, ribonoloactone, 2,3,4-trihydroxybutanoic -acid, 2,3,4,5-tetrahydroxypentanoic acid, 2,3,4,5,6-pentahydroxyhexanoic acid, 2-hydroxylauric acid, 2,3,4,5,6,7-hexahydrokyheptanoic acid, 4-hydroxymandelic acid, 4-chloromandelic acid, 2-hydroxy-3-methylbutanoic acid, 2-hydroxy-4-methylpentanoic acid, 3-hydroxy-4-methoxymandelic acid, 4-hydroxy-3-methoxymandelic acid, 3-(3-hyroxphenyl) lactic acid, 3-(4-hydroxyphenyl) lactic acid, hexahydromandelic acid, 3-hydroxy-3-methylpentanoic acid, 1-hydroxy-1-cyclopropane carboxylic acid, 4-hydroxybutanoic acid, 2-hydroxyhexanoic acid, 5-hydroxylauric acid, 12-hydroxylauric acid, 10-hydroxydecanoic acid, 16-hydroxyhexadecanoic acid, 4-hydroxydecanoic acid, 5-hydroxydecanoic acid, and 4-hydroxy-2, 2-diphenylbutanoic acid. as a free acid or salt form in a pharmaceutically or cosmetically acceptable vehicle.    
     
     
         16 . The composition of    claim 15    wherein said skin conditions and disorders include dry skin, dandruff, keratoses, age spots, warts, acne, oily skin, eczema, psoriasis, wrinkles, inflammatory and pruritic skin, and disturbed keratinization.  
     
     
         17 . A method for alleviating the symptoms of skin conditions and disorders comprising the topical application of a therapeutic effective amount of at least one compound selected from the group consisting of: 
 Diphenyl 2-hydroxyacetic acid (benzilic acid), 2-phenyl 3-hydroxypropanoic acid (tropic acid), aleuritic acid, ribonic acid, ribonoloactone, 2,3,4-trihydroxybutanoic acid, 2,3,4,5-tetrahydroxypentanoic acid, 2,3,4,5,6-pentahydroxyhexanoic acid, 2-hydroxylauric acid, 2,3,4,5,6,7-hexahydroxyheptanoic acid, 4-hydroxymandelic acid, 4-chloromandelic acid, 2-hydroxy-3-methylbutanoic acid, 2-hydroxy-4-methylpentanoic acid, 3-hydroxy-4-methoxymandelic acid, 4-hydroxy-3-methoxymandelic acid, 3-(2-hydroxphenyl) lactic acid, citramalic acid, 3-(4-hydroxyphenyl) lactic acid, hexahydromandelic acid, 3-hydroxy-3-methylpentanoic acid, 1-hydroxy-1-cyclopropane carboxylic acid, 4-hydroxybutanoic acid, 2-hydroxyhexanoic acid, hydroxylauric acid, 12-hydroxylauric acid, 10-hydroxydecanoic acid, 16-hydroxyhexadecanoic acid, 4-hydroxydecanoic acid, 5-hydroxydecanoic acid, and 4-hydroxy-2, 2-diphenylbutanoic acid as a free acid or salt form in a pharmaceutically or cosmetically acceptable vehicle.    
     
     
         18 . The method of    claim 17    wherein said skin conditions and disorders include dry skin, dandruff, keratoses, age spots, wrinkles, warts, acne, oily skin, eczema, psoriasis, inflammatory and pruritic skin, and disturbed keratinization.  
     
     
         19 . An enhanced therapeutic composition effective against skin conditions and disorders comprising an effective amount of at least one member selected from the group consisting of hydroquinone and hydroquinone monoether including monomethyl and monobenzyl ether and an enhancing effective amount of at least one member selected from the group consisting of hydroxycarboxylic acids and related ketocarboxylic acids, and ester, lactone or salt form thereof, in a pharmaceutically acceptable vehicle for topical application to skin of human or animal body.  
     
     
         20 . The composition of    claim 19    wherein said skin conditions and disorders include keratoses, age spots, wrinkles, brownish spots, melasma, lentigines and other pigmented skin spots.  
     
     
         21 . The composition of    claim 19    wherein said acids and related compounds include glycolic acid, benzilic acid, tropic acid, lactic acid, malic acid, citric acid, isocitric acid, citramalic acid, tartronic acid, tartaric acid, gluconic acid, galactonic acid, alpha hydroxyisobutyric acid, phenyllactic acid, mandelic acid, atrolactic acid, gluconolactone, galactonolactone, ribonic acid, ribonolactone, pantoic acid, pantolactone, pantothenic acid, alpha hydroxybutyric acid, Beta hydroxybutyric acid, quinic acid, pyruvic acid, phenyl pyruvic acid, methyl pyruvate, ethyl pyruvate, ascorbic acid, benzoyl formic acid,. methyl benzoyl formate, and ethyl benzoyl formate.  
     
     
         22 . A method for enhancing therapeutic effects a composition of hydroquinone or its monoether derivative in a pharmaceutically acceptable vehicle comprising admixing therewith an enhancing effective amount of at least one member selected from the group consisting of hydroxycarboxylic acids and related ketocarboxylic acids, and ester, lactone or salt forms thereof.  
     
     
         23 . The method of    claim 22    wherein said hydroxyacids and related compounds include glycolic acid, benzilic acid, tropic acid, lactic acid, malic acid, citric acid, isocitric acid, citramalic acid, tartronic acid, tartaric acid, gluconic acid, galactonic acid, alpha hydroxyisobutyric acid, phenyllactic acids mandelic acid, atrolactic acid, gluconolactone, galactonolactone, ribonic acid, ribonolactone, pantoic acid, pantolactone, pantothenic acid, alpha hydroxybutyric acid, beta hydroxybutyric acid, quinic acid, pyruvic acid, phenyl pyruvic acid, methyl pyruvate, ethyl pyruvate, ascorbic acid, benzoyl formic acid, methyl benzoyl formate, ethyl benzoyl formate.  
     
     
         24 . A method for preventing hair loss and/or enhancing hair growth comprising the topical application of a combination composition consisting of minoxidil or dipyridamole and an enhancing effective amount of at least one member selected from the group consisting of hydroxycarboxylic acids and related ketocarboxylic acids, and ester, lactone or salt forms thereof pharmaceutically acceptable vehicle for topical application to skin of human or animal body.  
     
     
         25 . The method of    claim 24    wherein said hydroxycarboxylic acid or related compound is a member selected from the group consisted of lactic acid, glycolic acid, glucuronic acid, gluconolactone, gluconic acid, 2-methyl 2-hydroxypropanoic acid, mandelic acid, tropical acid, benzilic acid, malic acid, tartaric acid, citric acid, tartronic acid, pyruvic acid, methyl pyruvate, ethyl pyruvate, saccharic acid, isocitric acid, agaricic acid, citramalic acid, aleuritic acid, mucic acid, galaturonic acid, phenyllactic acid, benzoylformic acid, atrolactic acid, galactonic acid, ascorbic acid, dihydroascorbic acid, pantoyllactone, gulonic acid, gulonolactone, pantoic acid, ribonic acid, ribonolactone, 3-hydroxybutanoic acid, 4-hydroxymandelic acid,-2-hydroxy-3-methylbutanoic acid, 3-hydroxy-4-methoxymandelic acid, 4-hydroxy-3-methoxymandelic acid, 4-chloromandelic acid, 2-hydroxy-4-methylpentanoic acid, 2-hydroxy-2-methylbutanoic acid, 3-(2-hydroxyphenyl) lactic acid, 3-(4-hydroxyphenyl) lactic acid and hexahydromandelic acid.  
     
     
         26 . A therapeutic composition useful in preventing hairloss and/or enhancing hairgrowth comprising a combination composition consisting of an effective amount of minoxidil or dipyridamole and an enhancing effective amount of at least one member selected from the group consisting of hydroxycarboxylic acids and related ketocarboxylic acids, and ester, lactone or salt forms thereof pharmaceutically acceptable vehicle for topical application to skin of human or animal body.  
     
     
         27 . The composition of    claim 26    wherein said hydroxycarboxylic acid or related compound is a member selected from the group consisted of lactic acid, glycolic acid, glucuronic acid, gluconolactone, gluconic acid, 2-methyl 2-hydroxypropanoic acid, mandelic acid, tropic acid, benzilic acid, malic acid, tartaric acid, citric acid, tartronic acid, pyruvic acid, methyl pyruvate, ethyl pyruvate, saccharic acid, isocitric acid, agaricic acid, citramalic acid, aleuritic acid, mucic acid, galacturonic acid, phenyllactic acid, benzoylformic acid, atrolactic acid, galactonic acid, ascorbic acid, dihydroascorbic acid, pantoyllactone, gulonic acid, gulonolactone, pantoic acid, ribonic acid, ribonolactone, 3-hydroxybutanoic acid, 4-hydroxymandelic acid, 2-hydroxy-3-methylbutanoic acid, 3-hydroxy-4-methoxymandelic acid, 4-hydroxy-3-methoxymandelic acid, 4-chloromandelic acid, 2-hydroxy-4-methylpentanoic acid, 2-hydroxy-2-methylbutanoic acid, 3-(2-hydroxyphenyl) lactic acid, 3-(4-hydroxyphenyl) lactic acid and hexahydromandelic acid.  
     
     
         28 . A therapeutic composition useful in preventing hairloss and/or enhancing hair growth comprising an effective amount of dipyridamole in a pharmaceutically acceptable vehicle for topical application to skin of human or animal body.  
     
     
         29 . A method for preventing hairloss and/or enhancing hair growth comprising the topical application of a composition consisting of dipyridamole in a pharmaceutically acceptable vehicle for topical application to skin of human or animal body.  
     
     
         30 . A prophylactic and therapeutic composition effective against acne and for oily skin and as skin cleanser comprising an effective amount of benzilic acid in a pharmaceutically acceptable vehicle for topical application to skin of human or animal body.  
     
     
         31 . A method for preventing as well as treating acne or for oily skin as skin cleanser comprising the topical application to involved skin of a composition containing an effective amount of benzilic acid in a pharmaceutically acceptable vehicle for topical application to skin of human or animal body.  
     
     
         32 . A method for preventing as well as treating wrinkles or skin changes associated with aging of skin comprising the topical application to involved skin of a composition containing a therapeutic effective amount of at least one member selected from the group consisted of hydroxycarboxylic acids and related ketocarboxylic acids, and ester, lactone or salt forms thereof.  
     
     
         33 . The method of    claim 32    wherein said hydroxycarboxylic acids and related compounds include 2-Hydroxyacetic acid; 2-hydroxypropanoic acid; 2-methyl 2-hydroxypropanoic acid; 2-hydroxybutanoic acid; phenyl 2-hydroxyacetic acid; phenyl 2-methyl 2-hydroxyacetic acid; 3-phenyl 2-hydroxyacetic acid; 2,3-dihydroxypropanoic acid; 2,3,4-trihydroxybutanoic acid, 2,3,4,5-tetrahydroxypentanoic acid, 2,3,4,5,6-pentahydroxyhexanoic acid, 2-hydroxydodecanoic acid, 2,3,4,5,6,7-hexahydroxyheptanoic acid, diphenyl 2-hydroxyacetic acid; 4-hydroxymandelic acid; 4-chloromandelic acid; 3-hydroxybutanoic acid; 4-hydroxybutanoic acid; 2-hydroxyhexanoic acid; 5-hydroxydodecanoic acid, 12-hydroxydodecanoic acid, 10-hydroxydecanoic acid, 16-hydroxyhexadecanoic acid, 2-hydroxy-3-methylbutanoic acid; 2-hydroxy-4-methylpentanoic acid; 3-hydroxy-4-methoxymandelic acid; 4-hydroxy-3-methoxymandelic acid; 2-hydroxy-2-methylbutanoic acid; 3-(2-hydroxyphenyl) lactic acid: 3-(4-hydroxyphenyl) lactic acid; hexahydromandelic acid; 3-hydroxy-3-methylpentanoic acid; 4-hydroxydecanoic acid; 5-hydroxydecanoic acid; aleuritic acid; 2-Hydroxypropanedioic acid; 2-hydroxybutanedioic acid; erythraric acid; threaric acid; arabiraric acid; ribaric acid; xylaric acid; lyxaric acid; glucaric acid; galactaric acid; mannaric acid; gularic acid; allaric acid; altraric acid; idaric acid; talaric acid; 2-hydroxy-2-methylbutanedioic acid; 
 Citric acid, isocitric acid, agaricic acid, quinic acid, glucuronic acid, glucuronolactone, galacturonic acid, galacturonolactone, uronic acids, uronolactones, ascorbic acid, dihydroascorbic acid, dihydroxytartaric acid, tropic acid, ribonolactone, gluconolactone, galactonolactone, gulonolactone, mannonolactone, ribonic acid, gluconic acid, citramalic acid;  
 Pyruvic acid, hydroxypyruvic acid, hydroxypyruvic acid phosphate, methyl pyruvate, ethyl pyruvate, propyl pyruvate, isopropyl pyruvate; phenyl pyruvic acid, methyl phenyl pyruvate, ethyl phenyl pyruvate, propyl phenyl pyruvate; formyl formic acid, methyl formyl formate, ethyl formyl formate, propyl formyl formate, benzoyl formic acid, methyl benzoyl formate, ethyl benzoyl formate, propyl benzoyl formate, 4-hydroxybenzoyl formic acid, 4-hydroxyphenyl pyruvic acid, 2-hydroxyphenyl pyruvic acid.  
 
     
     
         34 . A prophylactic and therapeutic compositions comprising an effective amount of at least one member selected from the group consisted of hydroxycarboxylic acids and related ketocarboxylic acids, and ester, lactone or salt forms thereof in a pharmaceutically acceptable vehicle for topical treatment of skin wrinkles or skin changes associated with aging.  
     
     
         35 . The composition of    claim 34    wherein said hydroxycarboxylic acids and related compounds include 2-Hydroxyacetic acid; 2-hydroxypropanoic acid; 2-methyl 2-hydroxypropanoic acid; 2-hydroxybutanoic acid; phenyl 2-hydroxyacetic acid; phenyl 2-methyl 2-hydroxyacetic acid; 3-phenyl 2-hydroxyacetic acid; 2,3-dihydroxypropanoic acid; 2,3,4-trihydroxybutanoic acid, 2,3,4,5-tetrahydroxypentanoic acid, 2,3,4,5,6-pentahydroxyhexanoic acid, 2-hydroxydodecanoic acid, 2,3,4,5,6,7-hexahydroxyheptanoic acid, diphenyl 2-hydroxyacetic acid; 4-hydroxymandelic acid; 4-chloromandelic acid; 3-hydroxybutanoic acid; 4-hydroxybutanoic acid; 2-hydroxyhexanoic acid; 5-hydroxydodecanoic acid, 12-hydroxydodecanoic acid, 10-hydroxydecanoic acid, 16-hydroxyhexadecanoic acid, 2-hydroxy-3-methylbutanoic acid; 2-hydroxy-4-methylpentanoic acid; 3-hydroxy-4-methoxymandelic acid; 4-hydroxy-3-methoxymandelic acid; 2-hydroxy-2-methylbutanoic acid; 3-(2-hydroxyphenyl) lactic acid; 3-(4-hydroxyphenyl) lactic acid; hexahydromandelic acid; 3-hydroxy-3-methylpentanoic acid; 4-hydroxydecanoic acid; 5-hydroxydecanoic acid; aleuritic acid; 2-Hydroxypropanedioic acid; 2-hydroxybutanedioic acid; erythraric acid; threaric acid; arabiraric acid; ribaric acid; xylaric acid; lyxaric acid; glucaric acid; galactaric acid; mannaric acid; gularic acid; allaric acid; altraric acid; idaric acid; talaric acid; 2-hydroxy-2-methylbutanedioic acid; 
 Citric acid, isocitric acid, agaricic acid, quinic acid, glucuronic acid, glucuronolactone, galacturonic acid, galacturonolactone, uronic acids, uronolactones, ascorbic acid, dihydroascorbic acid, dihydroxytartaric acid, tropic acid, ribonolactone, gluconolactone, galactonolactone, gulonolactone, mannonolactone, ribonic acid, gluconic acid, citramalic acid;  
 Pyruvic acid, hydroxypyruvic acid, hydroxypyruvic acid phosphate, their esters; methyl pyruvate, ethyl pyruvate, propyl pyruvate, isopropyl pyruvate; phenyl pyruvic acid, its esters; methyl phenyl pyruvate, ethyl phenyl pyruvate, propyl phenyl pyruvate; formyl formic acid, its esters; methyl formyl formate, ethyl formyl formate, propyl formyl formate; benzoyl formic acid, its esters; methyl benzoyl formate, ethyl benzoyl formate, propyl benzoyl formate; 4-hydroxybenzoyl formic acid, its esters; 4-hydroxyphenyl pyruvic acid, its esters; 2-hydroxyphenyl pyruvic acid and its esters.