US 2694669 A
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STABHJZED SELENIUM DISULFIDE THERAPEUTIC SHAMPOO Maynard M. Baldwin and Amps P. Young, Jr., Columbus,
Ohio, assignors, by mesne assignments, to Abbott Laboratories, North Chicago, Illa-a corporation of Illinois No Drawing.- Application January7, 1953, Serial No. 330,174
I 12 Claims. (Cl. 167-87) This invention relates to therapeutically useful stable compositions containing active selenium disulfide, and to a method for preparing said stabilized formulations.
This application is a continuation-in-part of our copending application Serial No. 39,196, filed July 16, 1948, and now abandoned.
Selenium disulfide has greatpotential therapeutic. and fungicidal value, and in the active form it is the product obtained by processes such as those described in U; S. Letters Patent Nos. 1,860,154 and 1,860,336 to B. W. Nordlander; It is, however, notuseful by itselfincompositions for biological purposes; because the: disulfide: is not wet readily,.as.intimate association of. moisture: isirequired for: the full realization of. its-: activity; Ittis, there? fore, necessary to! incorporate thedisulfide with a hydrophilic. material, such: as bentonite. Although it would appear that selenium disulfideand'bentonite downot. form a true chemical compound, it is believedthat this. association is more; than. an intimate mixture:v For convenience, these' solid, hydrophilic,-. selenium disulfide: com.-. positionsare designated as. sesols,-f andamethod for. ac.-
complishing this association is-described in'B-..:W.' Nord-- landers U. S. Letters Patent. No.1,86.0,-3.20.
Thus,,sesols are of. value. as: the active. constituents in" suspensions, pastes,,oin tments, shampoos, .andthe like, for treating abnormal sk1n.=:conditions,-,and; in the form" of dusts and suspensions. for controlling fungus diseases of plants. Sesol compositions are particularly effective for controlling. dandruff.
When formulated in .theusual aqueous media,- ;.however, it has been found that the sesol is adversely affected on extended. storage under normal temperature conditions,. and, also, onexposureto elevated temperatures-and" light. These" adverse-effects 'areevidenced by" a marked color change*of-the-sesol,- accompanied by a decrease" in its effectivenessin treatingabnormal skinconditions-and: fungi, increase in'-thediffieulty of removal; by washing;
from the scalp-and absorptive -materia1 and the appear-. ance of skin irritating effects.
It is an objectof-this-invention to--provide-a method for stabilizing sesolsin aqueous-media so that they can be. maintained in a suitable active state during adverse exposure conditions.
It is another object-of this invention to provide acom= position of matter containingsesol which has'beeni stabilized.
It is a further object of this inventionto provide a method for. producing formulations having stabilized sesol therein.
It has now been found that sesols in contact .with-aque ousmedia can be stabilized by the addition of sufficien'tv water soluble, acidic material'to the sesol-compositions:
to render the resulting compositions acidic. Over a long period of time under temperature conditions these acidic, sesol compositions maintain their characteristic yelloworange color and their therapeutic properties.
It has also been found that selenium disulfide-is exceptionally good as a treatment foriscalp, disorders such as dandruif. We have now discovered a. composition 'containing selenium disulfide which may be readily. removed.
from the scalp after thetreatment in order that. it'does.
not discolor the hair or cause irritation of'the skin. Inpreparing such a shampoo, we have found'thatitis necessary to employ a detergent-along with the aqueous hydrophilic selenium disulfidev suspension. .The detergent serves the purpose ofremoving ,the selenium disulfidesuspension from the scalpand hair following .the treat- States Patent" Patented Nov. 16,. 1954 ment therewith; and effectively"preventsaany irritationwhich might develop from prolonged contact-of "selenium disulfide with the skin.
The term detergent is used herein in its ordinary sense to mean a cleansing agentwhich is capable of removing foreignuparticles along with: washing::.v The'eXactInature of the detergent 'will" be disclosed in; greater detail= in the examples-butit is-sufiicientttoz note at'- this time. that-all compatability and. resultantinstability. intthe selenium di sulfide and the color change,- or. lack-thereof, may bede-z termined easily by one skilled in the art by subjecting formulations to the stability'test described in the examples.
As suitable detergents we may mention the anionic detergents of the alkylaryl' sulfonafte type such as Nacconol NRSF and Sa'ntomerse D, and alcohol sulfate detergents such as sodium lauryl sulfate and-triethanolaminelauryl" sulfate; We have also found that*the"alky1 phosphate saltsare suitable anionic detergentsfor the purposesiofthis invention; As cationic detergents whichwe havefound satisfactory may-be listedthesulfosuccinamate detergents" such as n-octadecyl' disoditim' sulfosuccinamate and the corresponding tetrasodium' sulfosuccin'a'mate. These ma.-
terials are marketed by American Cyanamid under the" As compatible detergentswe havetrade-name Aerosol. found. the fatty amines of the type represented by Alkamine S. J. (marketed by Amalgamated Chemical Company). Wehave also found that the 'hexitol oleates such asanhydrohexitol partial oleate marketed under the name Arlacel-A (Atlas Powder Company) are suitable nonionic detergents.
Considering the detergents in another way we have found that foaming. or lathering detergents are particu+- larly suitable for this invention-since they combine bothdetergency and good foaming properties which assist 'in' removing the selenium disulfide from the skin. The .volu
minous foam-or lather produced bythese'detergents-isalso important from a consumer acceptance'stan'dpoint; In this class may be placed'the alkyl aryl sulfonates' and the alcohol sulfates. While ahigh degree of foaming or lathering is to be regarded favorably it should be rememberedrthatfoam is notsnecessa'rilyan index ofdetergency and t a suitable shampoo I can: be prepared "by" using:
a detergent which-gives: a'smallv volumeiof foam or no foam at'alL, The anhydrohexitol partial oleates, theisul-' fated fatty amines, n-octadecyl sodium"sulfosuccinalnates; and alkyl phosphate salts give-fair to poor foams but are.
excellent detergents? .andwash:away.'easily" from the skin ancl haintaking with them theselenium disulfide suspension. These'poor- 'to fair foamingtdetergentszmay:berused in conjunction with an auxiliary foam producing material such as the inorganic phosphate salts, the modified polyoxyethyleneresters, long-chain amides, cellulose derivatives; and=sequestering agents. They may also be used in conjunction with foaming or lathering' detergents.
Suitable water soluble acidic materials for stabilizing these sesol suspensions are inorganic and organic acids, or their acid salts, or mixtures of these acids with their acid salts. Examples ofthese acidic materials'are hydrochloric, sulfuric, phosphoric, -acetic,--propionic, lactic'g citric, tartaric, andsuccinic acids; and monosodium phos.-.- phate, sodium citrate, and sodium 'tartrate acid salts; The solid acids and their acid-salts may beadded to-the= sesol mixture as solids or liquids'solutions, although'it' facilitates matters to add them in solution. 7
Excellent results have been obtained by adding suflicient acidic materials to the aqueousmedia to obtain a pH of between. about 2 and 6.6.. In other words-the pH of the system must be on the acidside; butn'eed not be highly acidic. .It.wi1l be'.noted from the following examples that the stability of the selenium disulfide suspension depends to a certain extent upon the pH of the aqueous suspension. At any rate, pHs on the alkaline side should be avoided, because the shelf life of the commercial products will be adversely effected.
The following examples will serve to illustrate the invention with more particularity:
Example 1 Suspensions of a sesol were prepared by mixing the sesol with an aqueous solution of an alkyl-aryl sulfonate surface-active or wetting agent, the resulting suspension having a pH of about 8. One suspension showed marked color changes after only 18 hours at 60 C., in a constant temperature bath, without the addition of any acidic materials. Another suspension but with sufficient citric acid added to bring the pH down to 3.3, showed no appreciable color change during a period of over 650 hours at 60 C.
Example 2 A suspension of a sesol was prepared by mixing the sesol with an aqueous solution of an alkyl-aryl sulfonate surface-active or wetting agent containing one per cent mono-sodium phosphate as the only acidic material added. The resulting suspension had a pH value of above 5 and it changed color appreciably after 48 hours at 60 C.
Example 3 Suspensions of a sesol were made in water and found to have a pH of 8 or above. The pH values of the sesol suspensions were then adjusted by the addition of citric acid to provide suspensions having different pH values. These suspensions were next subjected to a temperature of 60 C. in a constant temperature bath for extended period of time. Stability of the selenium disulfide in the sesol was indicated by persistance of the characteristic yelloworange color of the sesol. The following results were Suspensions of a sesol were prepared by mixing the sesol with an aqueous solution of an alkyl-aryl sulfonate surface-active or wetting agent containing a small amount of monosodium phosphate, the resulting suspension having a pH of above 5. The pH of these suspensions were then adjusted by the additions of various amounts of citric acid solution. As before, the suspensions were placed in a 60 C. constant temperature bath, and their color stability was observed. The following results were obtained:
Approx. No. of Hours at 60 C. Without Appreciable Color Change Adjusted pH of Composition Example 5 An experiment similar to that of Example 4 was performed with suspensions that contained various amounts of acetic acid in place of the citric acid. The following results were obtained:
Adjusted pH of Composition Example 6 Approx. No. of Hours at 60 C. Without Appreclable Color Change Adjusted pH of Composition The above examples clearly point out that an aqueous, sesol suspension in water, or water to which has been added only a wetting agent, shows a marked color change after 18 hours. If the suspension contained a wetting agent and also an acid salt, the color did not change for 48 hours. Where an acid alone was used in the sesol suspension, the color did not change for over 360 hours, and if the suspension contained an acid and a wetting agent, the color did not change for over 650 hours. The maximum observed period, over 4400 hours, was shown where the sesol suspension contained an acid, an acid salt, and a wetting agent. It will be understood that, while the acid salt plus the acid provide good stabilization, an acid by itself also effects good stabilization. Excellent results were obtained where the suspension contained, in addition to the acid, an acid salt and a wetting agent.
Example 7 A preferred composition of selenium disulfide for use as a shampoo is represented by the following formula:
Per cent w./v. Composition of equal parts of selenium sulfide The bentonite is wetted with water and the alkyl aryl sulfonate is added and dissolved with stirring. Then glyceryl monoricinoleate and monosodium phosphate are similarly added and stirred in. After the solution has become uniform the selenium sulfide-bentonite powder is added in small amounts and stirring is continued until a uniform suspension is obtained. Then citric acid is added in a quantity sufiicient to adjust the pH of the composition to about 4.5. The perfume is added and stirred in and water is added to bring up to volume. This product has a shelf life in excess of one year.
Example 8 The formulation shown in Example 7 is repeated substituting 17% weight by volume of sodium lauryl sulfate for the alkyl aryl sulfonate. The product obtained by this formulation washed away from the skin and hair very readily and produced large quantities of lather. The product is quite satisfactory as a shampoo. Upon aging for one month at 40 C. the product showed no color change.
Example 9 The formulation shown in Example 7 is repeated substituting 17% weight by volume of triethanolamine lauryl sulfate, technical, in place of the alkyl aryl sulfonate. This formulation was also a very satisfactory shampoo anagram:
and was readily washed: away: with the formation of large quantities of lather and. foam. The product was subjectedto: agingfor onemonfn at; 40? C. andnmchange in color was observed.
Example The formulation shown in Example 7 is repeated using an alkyl phosphate salt such as TLF 548 E Powder (Du Pont) or MPD 1936 B (Du Pont) in place of the alkyl aryl sulfonate in similar quantities. The pH of a suspension was adjusted to about 6.6 and the materlal was subjected to testing as a shampoo. A medium quantity of foam was obtained and the product washed away very readily from skin and hair. It appeared to have excellent properties as a detergent. The product passed the aging test of one month at 40 C. without color change.
Example 11 The formulation shown in Example 7 was repeated substituting an acid phosphate intermediate of an alkyl phosphate salt (MPD 2005 Du Pont) for the alkyl aryl sulfonate. Here again a good shampoo was obtained which produced a medium amount of foam and seemed to have excellent washing properties. The pH of the suspension was adjusted to 2.5. This product also meets the aging test of one month at 40 C. without color change.
Example 12 Example 13 The formulation shown in Example 7 was repeated substituting n-octadecyl tetrasodium (1-2-dicarboxyethyl sulfosuccinamate) for the alkyl aryl sulfonate. Here again only a fair amount of foam or lather was produced upon testing of the product, but the material was quite satisfactory as a detergent and was easy to wash away. This detergent is a cationic detergent. The shampoo met the test of one month at 40 C. without color change.
Example 14 The formulation shown in Example 7 was repeated using a non-ionic detergent as represented by the sulfated fatty amine, Alkamine S. I. (Amalgamated Chemical Company), in place of alkyl aryl sulfonate. A fair amount of foam or lather was produced, but the material was an excellent detergent and the shampoo washed away easily taking with it all of the selenium disulfide suspension. This shampoo met the aging test of one month at 40 C. without color change.
Example 15 The formulation shown in Example 7 was repeated using the non-ionic anhydrohexitol partial oleates (Arlacel AAtlas Powder Company) as detergent in place of the alkyl aryl sulfonate. In this instance only a small amount of foam was produced by the shampoo, but the shampoo showed excellent detergent properties and washed away easily taking with it the suspension of selenium disulfide. This material also passed the aging test of one month at 40 C. without color change.
Example 16 A composition was prepared as represented by the following formula:
Per cent w./v. Composition of equal parts of selenium sulfide and bentonite 5.0 Bentonite 4.0 Glyceryl monoricinoleate 1.0 Citric acid 0.2-0.5 Perfume 0.5 Anhydrohexitol partial oleate 13.0 Monobasic sodium phosphate 2.0 Water q. s. to 100 In this formulation: a: detergent wasi employecl' which produced only a relatively small quantity of:-' foam or lather in itself. The detergent was, however, quite suitable forremoving the: suspension: of selenium disulfide from the hairtand-ysealp. In--order.to enhance the foaming qualities and thereby produce a product which would havecgreater consumer acceptance, an auxiliary foaming agent, monosodium phosphate wasadded.
The stabilizedsesol in-aqueous media may be used in the manufacture of liquid, paste, and oil-in-water emulsion shampoos, and in liquids, pastes, and ointments having remarkable skin treating properties. The stabilized sesol composition may be incorporated in the shampoo base, or the sesol may be added to the shampoo base and then stabilized. This later method has been used to produce a shampoo which maintained its yellow-orange color at 60 C. over 4400 hours.
In summary it will be appreciated that this invention discloses a very easy method for stabilizing sesols in aqueous media. The term aqueous media, as used herein, is understood to include emulsions, pastes and other sesol compositions of varying viscosity in which water forms an integral part. The use of well-known, economically obtained acids permits the ready production of formulations containing sesol which have long shelflife. Such formulations maintain their characteristic yellow-orange color for extended periods of time as well as their useful therapeutic and fungicidal qualities. Thus, this stabilization of the sesol formulations greatly enhances their commercial value, saleability, and widespread employment.
1. A shampoo composition comprising an alkyl-aryl sulfonate, an aqueous suspension of activated stabilized hydrophilic selenium disulfide and sufficient of an acidic substance to adjust the pH between about 3 and about 5.
A shampoo composition comprising an alkyl-aryl sulfonate, an aqueous suspension of activated stabilized hydrophilic selenium disulfide and sufiicient of an acid to adjust the pH between about 3 and about 5.
3. A shampoo composition comprising an alkyl-aryl sulfonate, an aqueous suspension of activated stabilized hydrophilic selenium disulfide and sufficient of an acid salt to buffer the pH between about 3 and about 5.
4. A shampoo composition comprising an alkyl-aryl sulfonate, an aqueous suspension of activated stabilized hydrophilic selenium disulfide and sufiicient of an acid salt and an acid to buffer the pH between about 3 and about 5.
5. A shampoo composition comprising an alkyl-aryl sulfonate, an aqueous suspension of activated stabilized hydrophilic selenium disulfide composed of selenium disulfide and bentonite and sufiicient of an acidic substance to adjust the pH between about 3 and about 5.
6. A shampoo composition comprising an alkyl-aryl sulfonate, an aqueous suspension of activated stabilized hydrophilic selenium disulfide composed of selenium disulfide and bentonite and suflicient of an acid to adjust the pH between about 3 and about 5.
7. A shampoo composition comprising an alkyl-aryl sulfonate, an aqueous suspension of activated stabilized hydrophilic selenium disulfide composed of selenium disulfide and bentonite and suificient of an acid salt to buffer the pH between about 3 and about 5.
8. A shampoo composition comprising an alkyl-aryl sulfonate an aqueous suspension of activated stabilized hydrophilic selenium disulfide'containing selenium disulfide and bentonite and sufficient of an acid salt and an acid to buffer the pH between about 3 and about 5.
9. A shampoo composition comprising a stable aqueous suspension of activated stabilized hydrophilic selenium disulfide, suflicient of an acidic substance to adjust the pH between about 2 and about 6.6, and a detergent.
10. A shampoo composition comprising a stable aqueous suspenslon of activated stabilized hydrophilic selenium disulfide, sufiicient of an acidic substance to ad ust the pH between about 2 and about 6.6, and a lathering detergent.
11. A shampoo composition comprising a stable aqueous suspenslon of activated stabilized hydrophilic selenlum disulfide, suflicient of an acidic substance to ad ust the pH between about 2 and about 6.6, a detergent, and a foam producing material.
12. A shampoo composition comprising a stable aqueous suspension of activated stabilized hydrophilic selenium disulfide, sufiicient of an acidic substance to adjust the pH between abmZ 2 and about 6.6, and an OTHER 'RE FERENCES alcohol sulfate detergent Cataline: Journal American Pharmaceutical Assm, References Cited in the file of this patent Prac. Pharm. Edition, November 1946, pp. 484 to 489.
UNITED STATES PATENTS 5 Number Name Date 1,860,320 Nordlander May 24, 1932 2,149,249 Nitsche Feb. 28, 1939