GB2506692A - Further methods and compounds for reducing allergic reactions to hair dyes - Google Patents

Abstract

Conventional commercial hair dyes form potent allergens and may also have irritant properties. If they were not already well established in the market and the side effects tolerated by consumers they would likely be deemed unsafe for use. Disclosed are compounds, compositions, formulations and methods for reducing, avoiding or eliminating allergic contact dermatitis reactions to conventional commercial hair dyes that comprise an acid buffering system. The said buffering system may be used in a pre- or post-treatment before or after application of the hair dye.

Description

Further methods and coinnounds for reditinQ a1leric reactions to hair dv.

The invention relates to compounds, compositions, formulations and methods for avoiding; eliminating or reducing i.e. inhibiting the induction and/or decreasing the severity and/or frequency of elicitation of allergic reactions to hair dyes.

Hair dyeing products include compounds, compositions formulations and methods for colourin& tinting or highlighting the hair.

Existing hair dye products often contain potent allergens and may also have irritant propcrtics. If these hair dye products were not already well established in the market they may well bc deemed too harmfbl for use by hairdressers or consumers. Normally an individual only becomes sensitised after one or more usually several exposures to hair dyes.

Hence, hair dyes which are initially well tolerated may, after fbrther use, cause an allergic reaction.

The frequency of allergic reactions to hair dyes has not been measured with great precision in the general population, but it is common (McFadden JP. (2008). Allergy and consumer products; what constitutes an epidemic? Contact Dermatitis 59:325-326; and Thyssen JP and White JML. (2008) Epidemiological data on consumer allergy to p-phenylenediamine.

Contact Dermatitis 59, 327-343).

For example, in Thailand, measurement of paraphenylenediamine (PPD) skin contact allergy, a key indicator for hair dye allergy, in their general population would suggest that more than a million adults have this problem (Baskcttcr D A et al, (2006) The impact of exposure variables on the induction of skin sensitization. Contact Dermatitis, 55, 178-185). Estimates from Europe indicate a similar prevalence.

A classical description of hair dye contact allergy was provided by Cronin E. (1980) Contact Dermatitis Churchill Livingstonc, Edinburgh, pp 120-122 "dermatitis may begin within a few hours of the dyc being used or may appear the following day. The severity of the eczema varies considerably. There may be intense oedema of the face, particularly of the eyes, with exudation of the scalp; erythema and swelling may extend down the neck onto the upper chest and upper arms, and can even bccome gcncraliscd." Less frequently, hair dye allergy may cause swelling of the eyes as the main symptom, and the individual may fail to connect their symptoms with hair dyeing. Occasionally there is nothing more than a mild allergic reaction around the scalp margin, but further exposure to the hair dye may cause these mild symptoms to become more severe. "The severity of PPD reactions ranges from mild erythema at the hairline or ears to swelling of the eyelids and face, accompanied by an acute vesicular eruption in the scalp that requires prompt medical attention." (Rictschcl RL and Fowler JF. (2008) Hair colouring preparations. Fisher's Contact Dermatitis, BC Decker, Hamilton, 6th edition, pp3 03-304).

The present invention is based on the realisation that scnsitisation and consequent elicitation of allergy to hair dyes is predominantly mediated through the non-hair bearing skin adjacent to the scalp. This is because the dose per unit area of allergen contacting the skin adjacent to the scalp is significantly higher on the non-hair bearing skin than on the hair bearing scalp where the extensive surface area of hair will absorb much of the dye chemical(s). Dose per unit area is the single most important factor determining skin sensitisation and elicitation (Friedmann PS. The relationships between exposure dose and response in induction and elicitation of contact hypersensitivity in humans. Br J Dermatol 2007; 157 (6): 1093-1102.

This realisation explains thc hithcrto unexplained clinical observations of reactions to hair dyes. Reactions at skin sites adjacent to the scalp, such as facial swelling and inflanmiation, arc more prevalent and severe than scalp-related symptoms. As a result eases of hair dye allergy can easily be mistaken for angioedema (facial swelling from for example an ingested allergen, such as peanut) (Søsted H, Agner T Andersen KB and Menne T. (2002) 55 eases of allergic reactions to hair dye: a descriptivc, consumcr complaint-based study. Contact Dermatitis, 47: 299-303).

Hairdressers are at particular risk of developing allergic reactions to hair dyes on their hands as a result of repeated exposure to hair dyeing products in the course of their work. Hair dye process depends upon the oxidation of aromatic amines under alkaline conditions (M Dolinsky, C Wilson, H Wisneski, FX Deniers. Oxidation products of p-phenylenediamine in hair dyes Oxidation products of p-phenylenediamine in hair dyes J Soc Cosmetic Chemists 196 19: 411-422).

The prescnt invention aims to reduce, avoid or eliminate both the induction (sensitisation) of contact allergy and/or the elicitation of allergic contact dermatitis in individuals exposed to hair dye products.

In a first aspect the invention relates to a method of reducing induction of contact allergy or reducing elicitation of allergic contact derniatitis ot in or on the skin in response to hair dye comprising applying an acid buffering system to the sldn.

In another aspect the invention relates to a method wherein the acid buffering system is applied to the skin of the scalp margin.

In another aspect the invention relates to a method wherein the acid buffering system is selected froni citric acid/sodium phosphate, citric acid/sodium citrate, acetic acid/ sodium acetate, cihanoic acid/sodium ethanoate, carbonic acid/sodium carbonate, phthalic acid/potassium hydrogen phthalate, glycine/hydrochioric acid, ascorbic acid/sodium ascorbatc.

In another aspect the invention relates to a method wherein the acid in the acid buffering system is selected from: 2-aminobutanol, acetic acid, acetyl mandelic acid, adipic acid, alstonia scholaris bark extract, aluminum glycinate, aluminum lactate, aluminum triformate, aminoethyl propanediol, aminomethyl propanediol, aminomethyl propanol, aminopropancdio I, ammonia, ammonium acetate, ammonium bicarbonate, animonium carbamate, ammonium carbonate, ammonium chloride, ammonium glycolate, ammonium hydroxide, ammonium lactate, ammonium molybdate, ammonium nitrate, ammonium phosphate, ammonium thiocyanate, ammonium vanadate, ascorbic acid, azelaic acid, babassu acid, bakuhan, benzilic acid, bis-hydroxyethyl tromethamine, bismuth citrate, boric acid, butyl diethanolamine, calcium carbonate, calcium citrate, calcium dihydrogen phosphate, calcium glycinate, calcium hydroxide, calcium lactatc,calciuni oxide, calcium phosphate, citric acid, clay minerals, copper glycinate, diammonium citrate, diammonium phosphate, dibutyl ethanolamine, diethyl ethanolamine,dimethyl isopropanolamine, dimethyl mea, dioleoyl edetolmonium methosulfate, dioleyl phosphate, dipotassium phosphate, dipropylenetriamine, disodium ffimarate, disodiurn phosphatc, disodium pyrophosphate, disodium tartratc, ethanolamine, ethanolamine HC1, ethyl ethanolamine, ftmaric acid, galacturonic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutaric acid, glycine, glycolic acid, glyoxylic acid, guanidine carbonate, guanidine HC1, hydrobromic acid, hydrochloric acid, hydroxyectoin, hydroxyethylpiperazine ethane sulfonic acid, imidazole, isobutyric acid, isopropanolamine, isopropylamine, lactic acid, lactobionie acid, lauryl p-cresol ketoxime, lithium carbonate, lithium hydroxide, magnesium acetate, magnesium carbonate hydroxide, magnesium glycinate, magnesium hydroxide, magnesium lactate, magnesium oxide, maleic acid, malic acid, malonic acid, maltobionic acid, mea-borate, metaphosphoric acid, methylethanolamine, monosodium citrate, mudstone powder, paecilomyces japonica/grape/cucumber juice extract ferment filtrate, pentapotassium triphosphate, pentasodium triphosphate, phenolsulfonphthalein, phenyl mercuric borate, phosphonobutanetricarboxylic acid, phosphoric acid, phosphorus pentoxide, potassium bicarbonate, potassium biphthalate, potassium borate, potassium carbonate, potassium citrate, potassium hydroxide, potassium lactate, potassium magnesium aspartate, potassium oxide, potassium phosphate, potassium sodium tartrate, potassium tartrate, propane tricarboxylic acid, quinic acid, ribonic acid, sebacic acid, sh-decapeptide-7, sodium acetate, sodium aluminate, sodium aluminum lactate, sodium arachidate, sodium aspartate, sodium bicarbonate, sodium bisulfate, sodium borate, sodium butoxyethoxy acetate, sodium calcium boron phosphate, sodium calcium copper phosphate, sodium calcium zinc phosphate, sodium carbonate, sodium citrate, sodium esylate, sodium formate, sodium ftmarate, sodium glycolate, sodium humate, sodium hydroxide, sodium lactate, sodium metaphosphate, sodium metasilicate, sodium oxide, sodium phosphate, sodium scsquicarbonatc, sodium silicatc, sodium succinatc, sodium trimctaphosphatc, strontium hydroxide, succinic acid, sulfuric acid, tartaric acid, taurine, tea-diricinoleate/ipdi copolymer, tea-hydroiodide, tea-sulfate, tetrahydroxyethyl ethylenediamine, tetrapotassium pyrophosphate, tetrasodium pyrophosphate, triethanolamine, triisopropanolamine, trisodium phosphate, trisodium sulfosuccinate, triticuni vulgare protein, triticuni vulgare seed extract, tromcthaminc, urea, uric acid, zinc carbonate hydroxide, zinc glycinate, zinc hexametaphosphate, and zinc magnesium aspartate.

In another aspect the invention relates to a method wherein the skin is pre-treated with the acid buffering system prior to the application of the hair dye.

In another aspect the invention relates to a method wherein the skin is post-treated with the acid buffering system after the application of the hair dye.

In another aspect the invention relates to a method wherein the pre or post-treatnicnt is confined to non-scalp skin.

In another aspect the invention relates to a composition for reducing induction of contact allergy or reducing elicitation of allergic contact dermatitis of skin to hair dye comprising an acid buffering system.

In another aspect the invention relates to a composition wherein the acid buffering system is selected from citric acid/sodium phosphate, citric acid/sodium citrate, acetic acid/ sodium acetate, ethanoic acid/sodium ethanoate, carbonic acid/sodium carbonate, phthalic acid/potassium hydrogen phthalate, glycine/hydrochioric acid, ascorbic acid/sodium ascorbatc.

In another aspect the invcntion relates to a composition wherein thc acid in thc acid buffering system is selected from: 2-aminobutanol, acctic acid, acctyl mandelic acid, adipic acid, alstonia scholaris bark extract, aluminum glycinate, aluminum lactate, aluminum triformate, aminoethyl propanediol, aminomethyl propanediol, aminomethyl propanol, aminopropancdio I, ammonia, ammonium acctate, animonium bicarbonate, anhmonium carbamate, ammonium carbonate, ammonium chloride, ammonium glycolate, ammonium hydroxide, ammonium lactate, ammonium molybdate, ammonium nitrate, ammonium phosphate, animonium thiocyanatc, ammonium vanadatc, ascorbic acid, azelaic acid, babassu acid, bakuhan, benzilic acid, bis-hydroxyethyl tromethamine, bismuth citratc, boric acid, butyl diethanolamine, calcium carbonate, calcium citratc, calcium dihydrogen phosphate, calcium glycinate, calcium hydroxide, calcium lactate,calcium oxide, calcium phosphate, citric acid, clay minerals, copper glycinate, diammonium citrate, diammonium phosphate, dibutyl ethano lamine, diethyl ethanolamine,dimethyl iso propanolamine, dimethyl mea, dioleoyl edetolmonium methosulfate, dioleyl phosphate, dipotassium phosphate, dipropylenetriamine, disodium frimarate, disodium phosphate, disodium pyrophosphate, disodium tartrate, ethanolamine, ethanolaminc HCI, ethyl ethanolaniine, ifimaric acid, galacturonic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutaric acid, glycine, glycolic acid, glyoxylic acid, guanidine carbonate, guanidine HCI, hydrobromic acid, hydrochloric acid, hydroxyectoin, hydroxyethylpiperazinc ethane sulfonic acid, imidazole, isobutyrie acid, isopropanolamine, isopropylamine, lactic acid, lactobionie acid, lauryl p-cresol ketoxime, lithium carbonate, lithium hydroxide, magnesium acetate, magnesium carbonate hydroxide, magnesium glycinate, magnesium hydroxide, magnesium lactate, magnesium oxide, maleic acid, malie acid, malonic acid, maltobionic acid, mea-borate, metaphosphoric acid, methylethanolamine, monosodium citrate, mudstone powder, paecilomyces japonicaigrape/eucumber juice extract ferment filtrate, pentapotassium triphosphate, pentasodium triphosphate, phenolsulfonphthalein, phenyl mercuric borate, phosphonobutanetricarboxylic acid, phosphoric acid, phosphorus pentoxide, potassium bicarbonate, potassium biphthalate, potassium borate, potassium carbonate, potassium citrate, potassium hydroxide, potassium lactate, potassium magnesium aspartate, potassium oxide, potassium phosphate, potassium sodium tartrate, potassium tartrate, propane tricarboxylic acid, quinic acid, ribonic acid, sebacie acid, sh-deeapeptide-7, sodium acetate, sodium aluminate, sodium aluminum lactate, sodium arachidate, sodium aspartate, sodium bicarbonate, sodium bisulfate, sodium borate, sodium butoxyethoxy acetate, sodium calcium boron phosphate, sodium calcium copper phosphate, sodium calcium zinc phosphate, sodium carbonate, sodium citrate, sodium esylate, sodium formate, sodium ifimarate, sodium glycolate, sodium humate, sodium hydroxide, sodium lactate, sodium metaphosphate, sodium metasilicate, sodium oxide, sodium phosphate, sodium sesquiearbonate, sodium silicate, sodium succinate, sodium trimetaphosphate, strontium hydroxide, suecinie acid, sulifiric acid, tartaric acid, taurine, tea-diricinoleate/ipdi copolymer, tea-hydroiodide, tea-sulfate, tetrahydroxyethyl ethylenediamine, tetrapotassium pyrophosphate, tctrasodium pyrophosphate, triethanolamine, triisopropanolamine, trisodium phosphate, trisodium sulfosuccinate, triticum vulgare protein, triticum vulgare seed extract, tromethamine, urea, uric acid, zinc carbonate hydroxide, zinc glycinate, zinc hexamctaphosphate, and zinc magnesium aspartate.

Detailed Description:

Commercial hair dyes for application to/by consumers contain a mixture of organic chemicals which, when exposed to an oxidation system in alkaline conditions, undergo a variety of coupling reactions to form the coloured chemicals required to generate the wide range of shades desired by consumers.

An undesirable consequence of the generation of a number of chemically reactive intermediates is that these can, during the formation of the coloured chemicals, combined with skin proteins, rendering them "foreign" and thus activating the immune system into the production of an allergic reaction i.e. a cell mediated, Type IV hypersensitivity.

Allergic contact dermatitis arises during the elicitation phase (clinical reaction in someone already sensitised or made allergic). An active sensitisation phase (induction) is required before an allergic rcsponse can be elicited. Typically an individual only becomes scnsitised to an allergenic hair dye following repeated exposures. The number of exposures required for sensitisation to occur is highly variable, the frequency of hair dyeing may mean a period of many months or years precedes the acquisition of sensitisation. Many individuals will never become sensitised. The precise chemical nature of the reactive intermediates produced by oxidation and which of these causes allergy is the subject of continuing study. However, it is clear that primary agents are oxidation products of aromatic amines such as PPD.

PPD is a well recognized and common cause of allergic contact dermatitis. It is the primary agent used for the diagnosis of hair dye allergy. Here it is used as an indicative example of oxidative hair dye allergy.

To act as contact allergens, organic chemicals must form covalent bonds with skin proteins.

It has been suggested that oxidation of PPD to the highly reactive chemical 1,4-benzoquinone is the probable explanation for the allergenicity. It has also been speculated that the oxidation of PPD to its trimer (known as Bandrowski's base) may account for the allergenicity of PPD. The clinical evidence in support of cither of thcse hypothcses is limited.

Alternatively, the oxidative formation of the benzoquinonediimine intermediate froni PPD, which produces a very unstable and highly reactive chemical species, which would be anticipated to be highly allergenic in vivo, has been proposed. Whatever the underlying mechanism responsible for the allergenicity of aromatic hair dye chemicals it is notable that all of the currently proposed models involve oxidation.

The present invention relies on this realization and provides methods, and compositions for reducing or eliminating the allergenicity of aroniatic hair dye chemicals by inhibiting their oxidation to allergenic intermediates through preventing the alkaline conditions required for these oxidation reactions.

It also relies on the realisation that induction and elicitation of allergic contact dermatitis to hair dye chemicals occurs primarily through the non-hair bearing skin surrounding the scalp.

Preferably, the compositions for inhibiting oxidation are applied to the skin prior to the application of the hair-dye in a pre-treatment and/or post-treatment step. More preferably the compositions for inhibiting oxidation of aromatic hair dye chemicals are applied only to areas wherc the allergic reactions are most pronounced, such as the skin around the scalp margins, on the face and on the neck By avoiding applying the pre-treatment to the scalp there is also less risk that the inhibition of oxidation of aromatic hair dye chemicals will interfere with the desired hair colouring process.

Claims (10)

1. Claims: 1. A method of reducing induction of contact allergy or reducing elicitation of allergic contact dermatitis of in or on the skin in response to hair dye comprising applying an acid buffering system to the skin.
2. 2. A method as claimed in claim 1 wherein the acid buffering system is applied to the skin of the scalp margin.
3. 3. A method as claimed in claim 1 or claim 2 wherein the acid buffering system is selected from citric acid/sodium phosphate, citric acid/sodium citrate*, acetic acid! sodium acetate, cthanoic acid/sodium cthanoatc, carbonic acid/sodium carbonate, phthalic acid/potassium hydrogen phthalatc, glycine/hydrochloric acid, ascorbic acid/sodium ascorbate.
4. 4. A method as claimed in any preceding claim wherein the acid in the acid buffering system is selected from: 2-aminobutanol, acetic acid, acctyl mandelic acid, adipic acid, alstonia seholaris bark extract, aluminum glycinate, aluminum lactate, aluminum triformate, aminoethyl propanediol, aminomethyl propanediol, aminomethyl propanol, aminopropanediol, ammonia, ammonium acetate, ammonium bicarbonate, ammonium carbamate, ammonium carbonate, ammonium chloride, ammonium glycolate, ammonium hydroxide, ammonium lactate, ainmonium molybdatc, ammonium nitrate, ammonium phosphate, ammonium thiocyanate, ammonium vanadate, ascorbic acid, azelaic acid, babassu acid, bakuhan, bcnzilic acid, bis-hydroxycthyl tromcthaminc, bismuth citrate, boric acid, butyl diethanolamine, calcium carbonate, calcium citrate, calcium dihydrogen phosphate, calcium glycinate, calcium hydroxide, calcium lactate,calcium oxide, calcium phosphate, citric acid, clay minerals, copper glycinate, diammonium citrate, diammonium phosphate, dibutyl ethanolamine, diethyl ethanolamine,dimethyl isopropanolamine, dimethyl mea, dioleoyl edetolmonium methosulfate, dioleyl phosphate, dipotassium phosphate, dipropylenetriamine, disodium fumarate, disodium phosphate, disodium pyrophosphate, disodium tartrate, ethanolamine, ethanolamine HCI, ethyl ethanolamine, fumaric acid, galacturonic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutaric acid, glycine, glycolic acid, glyoxylic acid, guanidine carbonate, guanidine HCI, hydrobromic acid, hydrochloric acid, hydroxyectoin, hydroxyethylpiperazine ethane sulfonic acid, irnidazoic, isobutyric acid, isopropanolamine, isopropylamine, lactic acid, lactobionic acid, lauryl p-cresol ketoxime, lithium carbonate, lithium hydroxide, magnesium acetate, magnesium carbonate hydroxide, magnesium glycinate, magnesium hydroxide, magnesium lactate, magnesium oxide, malcic acid, malic acid, malonic acid, maltobionic acid, mea-borate, metaphosphoric acid, methylethanolamine, monosodium citrate, mudstone powder, paecilomyces japonica/grape/cucumber juice extract ferment filtrate, pentapotassium triphosphate, pentasodium triphosphate, phenolsulfonphthalein, phenyl mercuric borate, phosphonobutanetricarboxylic acid, phosphoric acid, phosphorus pentoxide, potassium bicarbonate, potassium biphthalate, potassium borate, potassium carbonate, potassium citrate, potassium hydroxide, potassium lactate, potassium magnesium aspartate, potassium oxide, potassium phosphate, potassium sodium tartrate, potassium tartrate, propane tricarboxylic acid, quinic acid, ribonic acid, sebacic acid, sh-decapeptide-7, sodium acetate, sodium aluminate, sodium aluminum lactate, sodium arachidate, sodium aspartatc, sodium bicarbonate, sodium bisulfate, sodium borate, sodium butoxyethoxy acetate, sodium calcium boron phosphate, sodium calcium copper phosphate, sodium calcium zinc phosphate, sodium carbonate, sodium citrate, sodium esylate, sodium formate, sodium fumarate, sodium glycolate, sodium humate, sodium hydroxide, sodium lactate, sodium metaphosphate, sodium metasilicate, sodium oxide, sodium phosphate, sodium sesquicarbonate, sodium silicate, sodium succinate, sodium trimetaphosphate, strontium hydroxide, succinic acid, sulfuric acid, tartaric acid, taurine, tea-diricinoleate/ipdi copolymer, tca-hydroiodidc, tea-sulfate, tctrahydroxycthyl ethylcnediamine, tetrapotassium pyrophosphate, tetrasodium pyrophosphate, triethanolamine, triisopropanolamine, trisodium phosphate, trisodium sulfosuccinatc, triticum vulgare protein, triticum vulgare seed extract, tromethamine, urea, uric acid, zinc carbonate hydroxide, zinc glycinatc, zinc hexametaphosphate, and zinc macsium aspartate.
5. 5. A method as claimed in any preceding claim wherein the skin is pre-treated with the acid buffering system prior to the application of the hair dye
6. 6. A niethod as claimed hi any preceding claim wherein the skin is post-treated with the acid buffering system after the application of the hair dye.
7. 7. A method as claimed in claim 5 or claim 6 wherein the pre or post-treatment is confined to non-scalp skin.
8. S. A composition for reducing induction of contact allergy or reducing elicitation of allergic contact demiatitis of skin to hair dye comprising an acid buffering system.
9. 9. A composition as claimed in claim S wherein the acid buffering system is selected from citric acidisodium phosphate, citric acid/sodium citrate, acetic acid/ sodium acetate, ethanoic acid/sodium ethanoate, carbonic acid/sodium carbonate, phthalic acid/potassium hydrogen phthalate, glycine/hydrochioric acid, ascorbic acid/sodium ascorbate.
10. 10. A composition as claimed in claim 9 wherein thc acid in thc acid buffering systcm is selected from: 2-aminobutanol, acctic acid, acetyl mandclic acid, adipic acid, aistonia scholaris bark extract, aluminum glycinate, aluminum lactate, aluminum triformate, aminoethyl propanediol, aminomethyl propanediol, aminomethyl propanol, aminopropancdiol, ammonia, animonium aectate, animonium bicarbonate, ammonium carbamate, ammonium carbonate, ammonium chloride, ammonium glycolate, ammonium hydroxide, ammonium lactate, aminonium molybdatc, ammonium nitrate, ammoniurn phosphate, ammonium thiocyanate, ammonium vanadate, ascorbic acid, azelaic acid, babassu acid, bakuhan, benzilic acid, bis-hydroxyethyl tromethamine, bismuth citrate, boric acid, butyl diethanolamine, calcium carbonate, calcium citrate, calcium dihydrogen phosphate, calcium glycinate, calcium hydroxide, calcium lactate,calcium oxide, calcium phosphate, citric acid, clay minerals, copper glycinate, diammonium citrate, diammonium phosphate, dibutyl ethanolamine, diethyl ethanolamine,dimethyl isopropanolamine, dimethyl mea, dioleoyl edetolmonium methosulfate, dioleyl phosphate, dipotassium phosphate, dipropylenetriamine, disodium fumarate, disodium phosphate, disodium pyrophosphate, disodium tartrate, ethanolamine, ethanolamine HC1, ethyl ethanolamine, flimaric acid, galacturonic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutaric acid, glycine, glycolic acid, glyoxylic acid, guanidine carbonate, guanidine HCI, hydrobromic acid, hydrochloric acid, hydroxyectoin, hydroxyethylpiperazine ethane sulfonic acid, imidazole, isobutyric acid, isopropanolamine, isopropylamine, lactic acid, lactobionic acid, lauryl p-cresol ketoxime, lithium carbonate, lithium hydroxide, magnesium acetate, magnesium carbonate hydroxide, magnesium glycinate, magnesium hydroxide, magnesium lactate, magnesium oxide, maleic acid, malic acid, malonic acid, maltobionic acid, mea-borate, metaphosphoric acid, methylethanolamine, monosodium citrate, mudstone powder, paecilomyces japonica/grape/cucumber juice extract ferment filtrate, pentapotassium triphosphate, pentasodium triphosphate, phenolsulfonphthalein, phenyl mercuric borate, phosphonobutanetricarboxylic acid, phosphoric acid, phosphorus pentoxide, potassium bicarbonate, potassium biphthalate, potassium borate, potassium carbonate, potassium citrate, potassium hydroxide, potassium lactate, potassium magnesium aspartate, potassium oxide, potassium phosphate, potassium sodium tartrate, potassium tartrate, propane tricarboxylic acid, quinic acid, ribonic acid, sebacic acid, sh-decapeptide-7, sodium acetate, sodium aluminate, sodium aluminum lactate, sodium arachidate, sodium aspartate, sodium bicarbonate, sodium bisulfate, sodium borate, sodium butoxyethoxy acetate, sodium calcium boron phosphate, sodium calcium copper phosphate, sodium calcium zinc phosphate, sodium carbonate, sodium citrate, sodium esylate, sodium formate, sodium fumarate, sodium glyeolate, sodium humate, sodium hydroxide, sodium lactate, sodium metaphosphate, sodium metasilicate, sodium oxide, sodium phosphate, sodium sesquiearbonate, sodium silicate, sodium succinate, sodium trimetaphosphate, strontium hydroxide, succinie acid, sulfUric acid, tartaric acid, taurine, tea-d.iricinoleate/ipdi copolymer, tea-hydroiodide, tea-sulfate, tetrahydroxyethyl ethylenediamine, tetrapotassium pyrophosphatc, tetrasodium pyrophosphate, triethanolarninc, triisopropanolamine, trisodium phosphate, trisodium sulfosuccinate, triticum vulgare protein, triticum vulgare seed extract, tromethamine, urea, uric acid, zinc carbonate hydroxide, zinc glycinate, zinc hexametaphosphate, and zinc magnesium aspartate.