US 3236733 A
Description (OCR text may contain errors)
United States Patent 3 236 733 METHOD or coMBAiTriNG DANDRUFF WITH PYRIDINETHKONES METAL SALTS DETERGENT COMPOSITIONS Kenneth S. Karsten, Westport, and Wilbur S. Taylor,
Norwalk, Conn, and John J. Parran, Springfield T ownship, Hamilton County, Ohio; said Karsten and said Taylor assignors to R. T. Vanderbilt Company, Inc.,
New York, N.Y., a corporation of New York, and said Parran assignor to The Procter & Gamble Company,
Cincinnati, Ohio, a corporation of Ohio No Drawing. Original application Sept. 5, 1963, Ser. No.
306,684. Divided and this application Apr. 1, 1965,
Ser. No. 444,858
12 Claims. (Cl. 16737) The present invention is a divisional application of application Serial No. 306,684, filed September 5, 1963. Application Serial No. 306,684 is a continuation-impart of application Serial No. 85,005, filed January 26, 1961, and now abandoned. Application Serial No. 85,005 is a continuation-impart of copendin-g application Serial No. 741,- 994, filed June 16, 1958, and now abandoned.
The present invention relates to a novel shampoo composition possessing remarkable anti-dandrufi' effectiveness. The invention also relates to germicidal detergent compo'si. tions. The compositions contemplated by this invention depend upon the presence of 1-hydroXy-2-pyridinethione, salts and esters thereof, and related compounds such as 2,2'-dithiopyridine-1,1-dioxide.
Dandruff is a common affliction most usually associated with the human scalp area. It is recognized that skin normally 'sloughs off the skin surfaces of the human body. On most areas of the body, the skin which is sloughed off is normally washed away at frequent intervals so that the slough-ing-off process is not noticeable. On the scalp, which is not normally washed as often as other parts of the body, the sloughed-off skin tends to accumulate. This skin together with the natural oils exuded by the scalp form a suitable environment for the growth of bacteria, and in fact certain bacteria are known to be associated with a dandruff condition.
The presence of bacteria in a dandruff condition suggests than an obvious cure is to treat the afflicted area with an agent which is capable of killing the bacteria. Heretofore, this obvious cure has not been successful although some oi the most powerful .bacteriostats have been used. Accordingly, it is believed that factors other than bacteriostatic activity are needed in order to provide an effective dandruff cure. Thus, sulfur is recognized as having a beneficial effect which is far greater than other materials which are tar more potent germicides. The particular properties of sulfur which render it helpful in combatting dandruff are not known.
It has become increasingly desirable to improve the bacteniostatic effect of detergent compositions. The term detergent is intended to denote soap and non-soap surface active agents. Many compounds are known that have germicidal or bacteriostatic properties against specific micro-organisms or groups thereof, but such property is generally destroyed or seriously impaired when the compound is incorporated into detergent compositions.
The retention of germicidal properties by a compound after inclusion in a detergent composition is only one of the necessary or desirable properties the compound must have to be considered as a desirable additive to the detergent composition designed for application to the human body. It is extremely important that the compound exhibit substantivity, i.e., the property of remaining on the skin and retaining germicidal activity over a period of time after washing and rinsing of the skin.
Other properties that are not concerned with the germicidal properties directly are, however, important as far as commercial use of the detergent composition by the general public is concerned. These include the following properties of a detergent bar, powder, liquid, etc. after inclusion of the specific compound:
(1) Initial whiteness (2) Color stability under sunlight exposure (3) Color stability under aging (4) Absence of discoloration by copper in stamping dies (5) Non-irritating to skin (6) No unpleasant odor Accordingly, it is an object of this invention to provide a shampoo composition including a material which is an effective anti-dandruff agent.
It is another object of this invention to provide a shampoo composition containing an active amount of l-hydroxy-Z-pyridinethione, salts :and esters thereof or related compounds.
It is ,a further object of this invention to provide a detergent composition which exhibits substantive germicidal properties and has a prolonged effect in maintaining skin germs and bacteria :at a reduced level.
It has been discovered that l-hydroXy-2-pyridinethione, salts and esters thereof, and related compounds have a totally unexpected effectiveness when used to treat the human scalp and other areas which are subject to dandruff condition. This anti-dandruff effect is all the more remarkable because it is not predictable on the basis of bacteriostatic activity. There are factors, unknown at present, which require that an effective anti-dandrufi? agent be more than simply an effective bacteriostat.
Clinical tests were performed which show the remarkable anti-dandrutf properties of the compositions of this invention. Four shampoo compositions were selected for the clinical tests. Two of the shampoo compositions contained 2.0% by weight, of the zinc salt of 1-hydroxy-2- pyridinethione. These two compositions embodied different detergent bases. The third shampoo composition is a control which has the same detergent base as one of the above two compositions. The fourth shampoo composition is a commercial paste shampoo containing a known bacteriostat (2,2-.thiobis (4,6-dichlorophenol)) and colloidal sulfur. The above four shampoo compositions are set forth in Table I below, with the shampoo compositions identified as #1, #2, #3 and #4, respectively.
TABLE I Shampoo compositions Code Letter #1 #3 Sulfated coconut fatty alcoholSodium salt Sodium stearate Sodium alkyl glyceryl ether sulfonate L Sodium acyl sarcosinate 2 Sodium sulfate Sodium chloride Trisodium phosphate Diethanolamide of coconut fatty acids Acetylated lanolin Phenyl mercuric acct e 3 Perfume 1-Hydroxy-2-pyridinethionc, no Water (Make up balance).
pH 2,2-thiobis(4,6-dichl0rophenol) Colloidal sulfur 1 Alkyl radicals derived from fatty alcohol, 25.3% from coconut and 3% from tallow.
2 Acyl radicals derived from coconut fatty acids. 3 3 5% solution in oleic acid in #1 and #2. 4 Maxlmum particle diameter10 microns.
The clinical test was conducted by first selecting 260 volunteers to shampoo their hair with their regular shampoo exactly one week before reporting to determine their initial dandruff grading. The grading was done by skilled graders who parted the hair over the complete scalp area sectionally to expose the entire scalp for visual examination. Grades from 10 to were assigned to each subject examined, according to the following scale:
10 Excellent, no scaling Good, slight scaling 2 Fair, some scaling 2 Moderate, moderate scaling 3 Poor, heavy scaling Very poor, heavy incrustations, erythema Only those receiving an initial grade of 6 or lower were retained for actual testing of the instant shampoo. They were given one of the four shampoos, told to shampoo at least twice a week for the first two weeks and to use no shampoo during the third week, after which they were graded. Then they were told to use their same designated shampoo at their pleasure for the fourth and fifth weeks and to use no shampoo during the sixth week, after which they were again graded for dandruff and also asked to rate their own dandruff condition on the trained graders scale. Neither the grader nor the subjects knew the identity of or distinction between the shampoos. The results of the tests by mean grades are summarized in Table II 2 Averaged scores rounded oft to one decimal place.
Careful analysis of this data shows accumulative change in average dandruff scores for each of the shampoos containing the zinc salt of 1-hydroxy-2-pyridinethione is significantly better than the other two shampoo compositions for both the 3-week and 6-week periods. Moreover, the subjects were able to observe the anti-dandruff effectiveness of the new shampoos relative to the control shampoos. It is thus clear that a detergent composition containing the zinc salt of 1-hydroxy-2-pyridinethione has a remarkable anti-dandruff efficacy which is not shown by the control which has the same detergent base. More importantly, shampoo composition #4 which contains a known baeteriostat has shown no improvement. Thus, the mere inclusion of a bacteriostat in a detergent composition does not assure that such composition will be effective in combatting dandruff. Certain other functions apparen ly m st be provid d o imp rt an i-dandruff propv respectively, contain 10 to 20 carbon atoms.
erties. These properties are inherent in the pyridinethione compositions of this invention.
The anti-dandruff shampoo compositions of this invention contain from about /4% to about 5% of the active material (1-hydroxy-2-pyridinethione compounds), preferably 1 /2% to 3%, in an aqueous detergent base. The compositions contain from about 5% to about 60% of a detergent. The detergent can be anionic, amphoteric, or cationic, although anionic organic detergent compounds are preferred, since they appear to provide the greatest anti-dandruff effectiveness when the shampoo compositions of this invention are used.
Anionic detergents include both the soap and non-soap detergents. Examples of suitable soaps are the sodium, potassium, ammonium and alkanolammonium salts of higher fatty acids c o e. Particularly useful are the sodium and potassium salts of the mixtures of fatty acids derived from coconut oil and tallow. Examples of anionic non-soap detergents are alkyl glyceryl ether sulfonates, alkyl sulfates, alkyl monoglyceride sulfates or sulfonates, alkyl polyethoxy ether sulfates, acyl sarcosinates, acyl esters of isethionates, acyl N-methyl taurides, alkyl benzene sulfanates, and alkyl phenol polyethoxy sulfonates. In these compounds the alkyl and acyl groups, They are used in the form of water-soluble salts, the sodium, potassium, ammonium and alkanolammonium salts, for example. Specific examples are sodium lauryl sulfate, potassium N-methyl lauroyl tauride; and triethanolamine dodecyl benzene sulfonate.
Suitable examples of cationic detergents are dilauryldimethyl ammonium chloride, diisobutyl phenoxy ethoxy ethyl dimethylbenzyl ammonium chloride, cetyl trimethyl ammonium bromide, N-cetyl pyridinium bromide and benzethonium chloride, which are classed as quaternary ammonium salts.
Suitable examples of amphoteric detergents are alkyl beta-imino dipropionates, and alkyl beta-amino propionates, wherein the alkyl group contains 10 to 20 carbon atoms, and basic quaternary ammonium compounds derived from 2-alkyl-substituted imidazoline.
Shampoo formulations can, of course, contain any of the usual shampoo additives such as color, perfume, thickeners, solvents, opacifiers, suds builders, conditioning agents, preservatives, buffers, and anti-static agents.
In view of the fact that shampoo formulation needs a small particle size in a dispersed medium, it has been found desirable to take a wet filter cake of about 50% of the zinc salt of l-hydroxy-2-pyridinethione, add 2% of Darvan 1 (sodium polyalkyl aryl sulfonate) and 0.3% of CMC-70 (medium viscosity sodium carboxymethyl cellulose) and then grind it in a pebble mill for about fifteen hours. The Darvan adds a charge to the individual particles which prevents subsequent coalescing and the CMC slows the settling, or after settling, aids the quick redispersion of the solution by mere stirring.
It has been discovered that l-hydroxy-2-pyridinethione compounds when incorporated in detergent compositions retain their bacteriostatic properties and are skin substantive. The use of detergent compositions embodying l-hydroxy-2-pyridinethione compounds retard the growth of body germs and bacteria for much longer periods than the detergent bases.
The specific precedures used to test the properties hereinbefore enumerated are described here in some detail, as there are no established procedures yet widely adopted in the art. The particular pyridinethione compound was blended at various concentrations with detergents which are anionic, cationic, nonionic, amphoteric and mixtures thereof, specific compositions thereof being set forth in Table III. A
TABLE in Code Letter Percent Detergent Compositions Cashmere Bouquet Potassium Oleate Ultrawet K (Anionic) Aerosol OS (Anionic)- Aerosol AY (Anionic) Carboxymethyl cellulose- Tween 80 (nonionic) Brij 35 (nonionic) Pluronie F-68 (nonionic) Sterox AJ (nonionic) Paraffin Intracol 0A (Cationic) Antaron FC-34 (amphoteric) 40 Mixed phosphates 60 60 60 60 Key to Table III:
The first five soaps listed are well known proprietary soaps without germicidal agents composed of a mixture of alkali metal salts of fatty acids, the general composition of Lux and Ivory being as follows:
Potassium oleate is a liquid soap formed from 11 parts H 0, 1 part KOH, 4 parts glycerin and 4 parts red oil (oleic acid).
Ultrawet K is a sodium salt of sulfonated Cm petroleum hydrocarbons.
Aerosol OS is a sodium alkyl naphthalene sulfonate. Aerosol AY" is diarnyl sodium sulfosuccinate. Tween 80 is a polyoxyethylene sorbitan monooleate. Brij 35 is a polyoxyethylene lauryl ether.
Pluronic F-68 is a condensate of ethylene oxide with a hydrocarbon base formed by condensing propylene oxide with propylene glycol.
Sterox AJ is a polyoxyethylene ether.
Intracol 0A is a long chain fatty acid amide containing several amine groups.
Antaron FC-34 is a complex fatty amide compound.
Bacteriostatic activity per so was tested by taking plugs of the blended solid compositions (liquid compositions were placed in peni-cups) and placing them on separate nutrient agar plates inoculated with Bacillus subtilis (found in soil and decomposing organic material), Staphylococcus aureus (found on the human skin) and Salmonella typhosa (cause of typhoid fever). These three bacteria are conventionally used in in vitro testing for activity and substantivity. The plates were incubated for 24 hours at about 37 C. and then the diameter of the zone of no bacterial growth around each plug was measured in millimeters (diameter of plug or peni-cup excluded) and recorded.
Substantivity was measured by soaking untanned calfskin buttons in an 8% aqueous solution of the test soap, then repeatedly rinsing the buttons in distilled water, and subsequently placing the buttons on nutrient agar plates inoculated with the same bacteria as noted above. Thereafter, the procedure is the same as following for bacterioitatic activity per se. The results are reported in Table TABLE IV Bacteriostatic activity and substantivity Inhib. Zone-Diameter (mm.)
Additive cent Soap Soap Plug Calfskin SAT A None (ControL.
TABLE IVCntinued 4 4 100 111585 00 4 m T 1 m m k 11 05 5 590 77 0 964 0 43 t 0 w 1 m 1 1 5 31A I O-B 0729 7 o m s mmrn n mm m mm m mmwm m n 1 111 am1t1 r11 1 bum 2t m e 222066 4212 624 0 404 00 65540 00 8606 50 19 49.210176121068566444 38 6 Z r 1 640t 6 1 76 0 6 8 140 7 U7 4 21 5 356699 1106254 59 6 b D A 2lsaw2 wmzwmnwmmwww2l%3m2 1%233%2w. mmmmllm%3%32m%2%%22222222222222% 21 2 .1 1 a 1 0 n 622040500105 00 8 428002200316428246 7420056526443008326095 462641 6 p a "w GHIJKLMBBCOOODEFGGGGHIJKLMBOCGGGGcHIJKLMnccoocooococcocoocoooccoo0 00 C 7 77 777 7 7 5 0 1111111 Qll LQOW 11111110 1L0 0 1111111111 IIQQQQQQQQQQQQQQQLLLLL LL L M0 P m m n u u Tm. n. n i n 1 r e .1 9 n 1n d d .1 .HO n .n m n gse .nb m 6 0 V. 0 m V. "e m m1 m V P 1 p M ma .1 iia l 1 YD u .5 m H n g t t m u nmn w u 1 m mw n C n .a a m mama w miwwm m n A w zlsem l bbaldmdo t 1 t y 1 1 i 1 y y y y y y P rrrrr u r u urrr rr m 222222 0 0 0 22222 22 2 9nd d d. a: a es at fi hts I: 111111 1 11111 11 1 u 0 N 2 0 n 9 draining for seconds. Thereafter, the left hand was uncovered, the right hand was covered with a neoprene activity and substantivity. Samples number 33 and 5 hand Applied Microglove, and the washing procedure repeated using unmedi cated, i.e., control soap. Thus the left hand serves as an unmedicated soap-washed control for the test soap-washed were further tested in a modification of the split-use washing test described by Quinn et al biology 2, 2024 (1954). In the modified test, first the right hand.
ed and the left hand covered The hands of each subject were washed three times each Then both hands were soaped day and bacterial counts made on the wash water used for 20 seconds by briskly rubbing the moistened medicated test bar with a small amount of wash water held in the cupped hands, the lather being worked up as far as the in the second washing on the third and fifth days of the test. The control or unmedicated soap is used for the washings at which bacterial counts are made so that none wrist for seconds, followed by rinsing the hands for of the test compound is present in the wash water to 20 seconds while immersed in the Wash water and then 75 influence the results. Aliquots of the wash water in which 9 each hand is washed were added to nutrient agar pour plates within one minute after completion of washing. The plates were incubated for 48 hours at 37 C., the bacterial colonies counted and the results calculated for the entire wash water. The results are summarized in 10 weeks, a very severe test, while the C (Ivory) soaps were tested after the normal two weeks aging at 125 F. as described for Table VI. Bacteriostatic activity and substantivity were then determined by the same methods described and reported in Table IV. Table VII shows 5 Table V. the post-aging results of these tests.
TABLE V Split-use hand washing test Three Day Results Five Day Results No. Subject Bacteria Count Bacteria Count (Millions) Percent (Millions) Percent Decrease Decrease On Right On Right Left Right Left Right V 2. 75 0. 48 82. 5 2. 12 0. 186 91. 2 W 2. 0. 84 61. 8 2. 15 0. 88. 4 X 2. 11 0. 47 77. 7 3. 33 0. 17 94. 9 Y 2. 94 1.93 34. 4 4. 32 0. 37 91. 4 Z 3.86 0.423 89.0
1 See Table IV.
From the results reported in Table V, it will be noted that the bacteriostatic activity and substantivity of the pyridinethione compounds can be demonstrated in an actual hand washing technique. Various other desirable properties of the same soap-pyridinethione compound mixtures of Table IV are reported in Table VI.
The initial whiteness is reported both after mixing of the pyr-idinethione compounds with the soap and after the soap bar had been formed in the conventional brass die.
The sunlight color stability was tested by breaking a soap bar in two and exposing one portion in an east window for two weeks, rotating it one-quarter turn daily.
The heat aging color stability was tested by placing a sample bar in a closed glass jar within an oven at 125 F. for two weeks which is presumed to be approximately equivalent to one year shelf storage.
The tests reported in Table VI are of the same numbered samples of Table IV but all the samples of Table IV were not tested here.
TAB-LE VI Color changes due to aging TABLE VII Bacteriostatic activity and sn'bstantivity after heat aging 1 See Table IV. R TrGrowth touching button in one place.
No. Initial Blend Initial Bar Heat Aged Sunlight Aged 1. White. White Slightly oil-white. Slightly oil-white. 2 dn do rlo D0, 15 Off-white- Off-white Brown Brown. 16. White White. Off-White- Cream.
' Off-white Light brown Light brown.
White. White White. dn rlo D Blue-black sheen on .do- D0.
surface only. Blue-black Butt Bufi.
sheen on surface only. 2
1 See Table IV.
2 This slight surface sheen, caused evidently by contact with the brass bar-forming die, was removed before the oven and sunlight aging tests.
It will be noted that samples 29 and 33 (zinc salt of 1-hydroxy-2-pyridinethione) gave excellent results in the color tests and, in fact, slightly better than the control bars containing no bacter-iostatic agent. Samples 48 and 50 (2,2'-dithiopyridine-1,l-dioxide) were also fairly good except for the surface sheen on the initial bar, a feature which might be overcome by changing the bar-forming conditions or dies.
The soaps showing the more desirable results in the color tests were subjected to bacteriostatic and substantivity tests after heat aging in an attempt to determine the extent of loss of bacteriostatic effect, if any, during heat aging. The B (LUX) soaps were aged for six After the aging tests, these samples retained their bacteriostatic activity and substantivity.
Detergent compositions N, O, P and Q were dry granular formulations of heavy-duty laundry type to which were added for separate test 1% by weight of zinc, sodium, disulfide and cetyl ammonium derivatives of the 1-hydroxy-2-pyridinethione. It was found that fabrics washed with these formulations had drastic reductions in bacteria count relative to fabrics washed in the same formulation without the active agent and further that this reduction was partly maintained after rinsing. Fabrics laundered in this manner would be particularly useful for wear or use that contacts the skin, or where large numbers of bacteria are encountered such as hospital and diaper laundries.
No skin irritation has been noted with any of the pyridinethione compounds tested.
The pyridinethione compounds do not impart odors to a detergent composition. This is a property highly desirable to both the manufacturer and the user of the detergent.
Not only do the pyridinethione compounds have exelement germicidal and substantive properites, which are maintained after prolonged aging, but these compounds also give excellent results in the various color tests which are so important in offering soap to the consumer market. As will be noted, many of the compounds stay white through the heat aging and sunlight aging tests and the others have only slight discoloration.
The specific examples reported in the tables have included 0.07 to by weight of the pyridinethione compounds in the detergent composition (based on solids) in order that specific comparisons could be made with the various compounds and also with various controls and prior art compounds. However, it will be obvious that a wider range of pyridinethione compounds can be used and we have found from 0.01 to to be generally a satisfactory range although this should not be a limiting feature of our invention.
It is obvious from these results that the l-hydroxy-Z- pyridinethione and its derivatives have properties which indicate their use as an ingredient of a germicidal or medicinal soap or detergent.
This invention is concerned with l-hydroxy-2-pyridinethi-one (and derivatives) which has the following structural formula in tautomeric form, the sulfur being attached to No. 2 position of the pyridine ring:
2-rnercaptopyridine l-oxide The salts and esters disclosed herein represent substitution of the corresponding cation for the hydrogen of one of the tautomeric forms. Depending, of course, on the valence of the cation involved, there may be more than one of the 1-hydroxy-2-pyridinethione rings in the com-pound. Although a number of compounds have been specifically disclose-d, it will be apparent to one skilled in the art that inorganic salts other than those tested are suitable. Further, other amine salts, quaternary arnmonium salts, and other esters are also suitable. The disulfide (2,2-dithiodipyridine-1,1-dioxide) represents the attachment of two 1-hydroxy-2-pyridinethione rings by the elimination of the two hydrogens from the sulfur atoms to give a sulfur-to-sulfur linkage. Other substituted or derived compounds of 1-hydroxy-2-pyridinethione which retain the bacteriostatic and substantive properties are considered to be within the scope of this invention.
The active pyridinethione compounds may be incorporated into liquid, bar or powder detergent compositions as desired to satisfy the particular product requirement. The detergent compositions herein are hydrophilic but the composition as a whole may include hydrophobic components, e.g., paraffin. Detergent compositions may, of course, include conventional additives such as perfume, color, emollients, binders, inert fillers, etc.
What is claimed is:
1. A method for combatting dandruff comprising the step of applying to the hair and scalp of humans a detergent composition comprising an amount of zinc pyridinethione sufficient to provide effective anti-dandruff control.
2. A method for combatting dandruff comprising the step of applying to the hair and scalp of humans a detergent composition comprising an amount of cadmium pyridinethione sufficient to provide effective antidandruff control.
3. A method for combatting dandruff comprising the step of applying to the hair and scalp of humans a detergent composition comprising an amount of tin pyridinethione sufficient to provide effective anti-dandruff control.
4. A method for combatting dandruff comprising the step of applying to the hair and scalp of humans a detergent composition comprising an amount of zirconium pyridinethione sufficient to provide effective anti-dandruff control.
5. A method for combatting dandruff comprising the step of treating the hair and scalp with a composition comprising an anionic detergent base and an amount of zinc pyridinethione sufficient to provide effective antidandruff control.
6. A method for combatting dandruff comprising the step of treating the hair and scalp with a composition comprising an anionic detergent base and an amount of cadmium pyridinethione sufficient to provide effective anti-dandruff control.
7. A method for combatting dandruff comprising the step of treating the hair and scalp with a composition comprising an anionic detergent base and an amount of tin pyridinethione sufficient to provide effective antidandruff control.
8. A method for combatting dandruff comprising the step of treating the hair and scalp with a composition comprising an anionic detergent base and an amount of zirconium pyridinethione sufficient to provide effective anti-dandruff control.
9. A method for combatting dandruff comprising the step of treating the hair and scalp with a shampoo composition comprising a detergent base and from about .25% to about 5% of zinc pyridinethione.
10. A method for combatting dandruff comprising the step of treating the hair and scalp with a shampoo composition comprising a detergent base and from about .25% to about 5% of cadmium pyridinethione.
11. A method for combatting dandruff comprising the step of treating the hair and scalp with a shampoo composition comprising a detergent base and from about .25 to about 5% of tin pyridinethione.
12. A method for combatting dandruff comprising the step of treating the hair and scalp with a shampoo composition comprising a detergent base and from about .25% to about 5% of zirconium pyridinethione.
References Cited by the Examiner UNITED STATES PATENTS 2,742,393 4/1956 Bernstein 260294.8 X 2,742,476 4/ 1956 Bernstein 260-2948 2,809,971 10/ 1957 Bernstein 260294.8 X 2,846,398 8/1958 Beaver et al. 252107 OTHER REFERENCES Elder et al.: Drug and Cosmetic Industry, vol. 77, No. 5, pp. 622-623, 714-717, 719 and 721 (November 1955).
Schimmel Briefs, No. 271, October 1957.
JULIAN S. LEVITT, Primary Examiner.