Description:
The present invention is concerned with soap, shampoo and shave lotion formulations for use in contact with the human body, which formulations will kill or prevent the growth of microorganisms associated with the human body such as various pathogenic bacteria. These high antiseptic formulations are secured by utilizing in conjunction with soaps, shampoos and shave lotions a relatively small amount of 1,3-aliphatic diol and/or its mono- or diester. The diols and diol esters of the present invention function to provide antibacterial characteristics to specialized soaps, shampoos, shaving lotions and the like and replace materials such as hexachlorophene.
There exists a great demand for soap and shampoo formulations which have bacteriostatic properties. Conventionally, this quality is imparted to soap and shampoo formulations by the utilization of three major components, namely, hexachlorophene, tribromosalicylanilide (TBS) and trichlorocarbanilide (TCC). While these formulations are satisfactory, the formulations of the present invention are superior since they are effective against both gram negative and against gram positive bacteria, and also are completely nontoxic to humans. As a result, they may be used at higher levels in soap products than many of the current bacteriostats, if desired. They may also be used safely where children may obtain access to the soap or shampoo or as a cleansing agent for workers in the food industry where contact with food is likely.
The antibacterial soap formulations of the present invention, in general, utilize a conventional soap. Generally, these soaps are a salt of a carboxylic acid containing about 10 to 22 carbon atoms. The familiar soaps consist principally of the sodium salts of fatty acids containing 12 to 18 carbon atoms. These are most commonly made by saponifying natural fats and oils with sodium hydroxide. However, many other alkalies and other carboxylic acids, in addition to the fatty acids, are combined to form soap.
It is generally convenient to divide the various soaps into two broad classes, according to the nature of the cation. The water-soluble soaps are salts of sodium, potassium, ammonia and amines, such as triethanolamine, isopropanolamine and morpholine. The metallic soaps are salts of such cations as aluminum, calcium, magnesium, barium, lithium, zinc, lead, cobalt and copper. The water-soluble soaps are soluble in water and many organic solvents. They are used for all washing operations which employ soap, for the preparation of oil-in-water emulsions, and for suspending solid particles in water.
The most important carboxylic acids used in soap making are the naturally-occurring fatty acids containing about 12 to 18 carbon atoms. These are straight-chain acids with an even number of carbon atoms. The saturated members of this series are lauric acid (12 carbons), myristic acid (14 carbons), palmitic acid (16 carbons), and stearic acid (18 carbons). The important unsaturated fatty acids contain 18 carbon atoms. They are oleic acid (1 double bond), linoleic acid (2 double bonds), linolenic acid (3 double bonds), and ricinoleic acid (1 double bond and 1 hydroxy group). These fatty acids are found in fats and oils as esters of glycerin, that is, as a triglyceride. The predominant fatty acid constituents of the common fats and oils used in soap making are as follows: coconut oil--lauric and myristic; palm oil--oleic and palmitic; beef tallow--oleic, palmitic and stearic; lard--oleic, palmitic, stearic and linoleic; cottonseed oil--linoleic, oleic and palmitic; castor oil--ricinoleic. In addition to the fatty acids, naphthenic acids, rosin and tall oil are used in soap making. Rosin is predominantly abietic acid. Tall oil is principally oleic acid.
Lather-type shaving creams with which the present invention is concerned are predominantly potassium stearate with lesser amounts of sodium stearate and sodium and potassium coconut soaps. The major requirement is a close-knit foam with sufficient rigidity to support the beard. This is characteristic of stearate soap foams. The potassium soap is used for improved water solubility. The pressurized, or aerosol-type, shaving creams contain triethanolamine stearate with a lesser amount of triethanolamine coconut soap. Again, a stearate-type lather is required. The triethanolamine soaps are used because they are more water soluble than even the potassium soaps.
Soap shampoos of the present invention are generally about 15 to 20 percent potassium coconut in water. This soap gives a clear solution at this concentration and higher. The sodium soaps are less soluble and the triethanolamine soaps increase cost.
Scrub soaps, sold for janitor supplies, are generally potassium of low-grade oils such as soya or olive-oil foots. The major considerations are cost and high water solubility. Frequently, tall oil soaps are employed. In general, soaps of rosin and the unsaturated fatty acids are very water soluble, and the foam is loose and watery. Detergency is satisfactory at room temperature, but less than that of tallow soap at elevated temperatures.
Potassium of potash soaps, which are also called soft soaps, are customarily made by the semiboiling process. The fat and alkali solutions are heated together until saponification is completed. Potash soaps are not salted out. If sodium chloride were added, it would lead to the formation of sodium soap and potassium chloride. Consequently, semiboiled soaps retain all the glycerin produced in the saponification process.
Toilet soaps are based on saponified natural fats, synthetic detergents, or both. In soap bars, tallow is by far the most widely used raw material, followed by coconut oil. Other common raw materials are palm, olive, peanut, and palm kernel oils. ASTM specifications require a minimum water-free soap content of62- 83 percent and a maximum free alkali (plus alkaline salt) content of 2.3 percent. A respective formulation is:
Sodium soaps-a 87.0% Moisture-b 12.0 Perfume 0.9 Preservative-c 0.1 100.0% a 15-25% coconut oil, 75-85% tallow b Personal Ivory has about 20% water c Stannous chloride stannic chloride, or EDTA.
In deodorant soaps a small percentage of bacteriostat is added, such as 0.5 percent hexachlorophene plus 0.5 percent TCC (3,4,4'-trichlorocarbanilide); 0.5 percent Diaphene (di- and tribromosalicylanilide); or 0.6 percent each TCC, fluoromethyl TCC, and Diaphene.
Detergent bars are made with synthetic detergents only or in combination with soaps. Some typical formulations are:
Combination bar Dry basis-a ______________________________________ Soap 70.0% Sodium coconut alcohol sulfate 20.0 Coco monoglyceride sulfonate 10.0 100.0% TCC 0.6-b Diaphene 0.6-b Perfume 0.8-b a -- All bars have 8-10% water b -- Percent of base formulation ______________________________________ Detergent bar Dry basis-a Igepon A 70.0% Stearic acid 30.0 100.0% Perfume 0.8-b a -- All bars have 8-10% water b -- Percent of base formulation. ______________________________________
Some soaps contain a color stabilizer such as stearic-hydrazide, in concentration of 0.025-0.05 percent.
Suitable shampoos are available in many types and forms which lend themselves to classification according to their physical appearance, or in some instances according to their special ingredients or properties. There are liquid clear shampoos, liquid cream or cream lotion shampoos, cream paste shampoos, egg shampoos, herbal shampoos, dry shampoos, liquid dry shampoos, color shampoos and aerosol shampoos. In addition, one of several of these types may be based on special raw materials, or have special additives that would make a given product an antiseptic or anntidandruff shampoo, or that would render it particularly suitable for use on infants and young children, and hence permit it to be called a baby shampoo.
The present invention includes shaving lotions. Shaving lotions are offered as either preshave or aftershave. Preshave preparations may be of two types: (1) Those intended primarily to soften the beard usually have a wetting agent as the active ingredient, in a base of alcohol, water, and glycerin, perfumed and tinted. (2) Alcohol solutions to be applied before using an electric razor act like strong astringents, which contract the skin, making the hairs stand up straight. Aftershave lotions are usually similar in composition to astringent lotions, with a higher percentage of alcohol, which serves to cool the skin and to counteract any irritation. The alcohol also acts as a mild antiseptic to aid against infection.
Aftershave lotions consist of a solution of perfume in water and alcohol. The alcohol content ranges between 50 and 70 percent, with the perfume content ranging between 0.5 and 1.5 percent, depending upon the amount of alcohol used.
Additional materials are frequently incorporated, such as:
1. Humectant--up to 3 percent of glycerin, propylene glycol or sorbitol solution.
2. Saccharin--to overcome bitter taste of alcohol denaturant.
3. Menthol--cooling and anesthetic.
The amount of diol or diol ester utilized as an antibacterial ingredient is in the range from about 0.05 to 5.0 percent by weight, preferably in the range from about 0.1 to 0.5 percent by weight based upon the weight of the total composition.
The 1,3-diol contains from about 4 to 15 carbon atoms in the diol chain, preferably from 6 to 10 carbon atoms in the diol chain. Very desirable diols for utilization in the present invention are 1,3-heptanediol, 1,3-octanediol and 1,3-nonanediol. If a mono- or diester be utilized, the number of carbon atoms in the diol chain is in the range from about 4 to 15, preferably in the range from 4 to 10 . The number of carbon atoms in the ester group may vary in the range from about 2 to 15, preferably from about 3 to 10. Particularly desirable diol esters are 1,3-octanediol-1-monopropionate and 1,3-butanediol-1-monooctanoate.
The particular preferred diols of the present invention are 1,3-diols and correspond to the following chemical formulas: ##SPC1##
where R represents an n-alkyl group containing 6 to 12 carbon atoms. Thus, the preferred 1,3-diols must contain a minimum of six carbon atoms in the chain (R = 3). Diols with fewer carbon atoms are not as effective as antibacterial materials or additives. The preferred diols contain from seven to nine carbon atoms in the chain (R = 4 to 6).
The preferred monoesters of the present invention correspond to the following chemical formulas: ##SPC2##
where R = an n-alkyl chain of 0 to 12 carbon atoms and R 1 is an n-alkyl chain containing from 1 to 17 carbon atoms. Thus, the esters may contain from 3 to 15 carbon atoms in the diol portion of the molecule. The preferred monoesters are those which contain 4 to 10 carbon atoms in the diol portion (R = 1 to 7) of the molecule and from 3 to 10 carbon atoms (R1 = 2 to 9) in the ester portion of the molecule. Very desirable monoesters are 1,3-butanediol-1-monooctanoate and 1,3-octanediol-1-monopropionate. These monoesters may exist in two different forms. Form A is the 1-monoester form. Form B is the 3-monoester form.
Still another ester form which is useful for certain applications is the diester C. ##SPC3## where R = an n-alkyl chain of 0 to 12 carbon atoms and R 1 is an n-alkyl chain of 1 to 17 carbon atoms. The preferred diesters contain from about 4 to 8 carbon atoms in the diol portion (R = 1 to 5) and from 3 to 10 carbon atoms (R1 = 2 to 9) in the ester portions of the molecule. Although the diesters are generally not as active as the monoesters, they are useful in cases where their physical properties (e.g., their increased lipophilic character) are especially desirable.
It is essential, for both the 1,3-diols and their esters that the molecules be linear and that the hydroxy and/or carbalkoxy (ester) groups be attached to the first and third carbon atoms. It is this 1,3-difunctionality which renders these compounds especially useful because of their inherent safety for use around humans and animals.
Other suitable diols for use in the present invention are 1,3-hexanediol, 1,3-decanediol and 1,3-undecanediol.
The diol and diol esters of the present invention may be prepared by any suitable technique such as by the Reformatsky reaction followed by reduction, or by means of the Prins reaction of formaldehyde and the appropriate olefin.
In order to further illustrate the invention, various tests were carried out, the results of which are described in the following examples and tables of data. In Table I are summarized the results of toxicity measurements for a variety of dihydroxy compounds including the 1,3-diols. These studies were conducted with rats.
TABLE I ______________________________________ TOXICITY DATA FOR VARIOUS DIOLS Oral LD50 Dihydroxy Compound Compounds Dihydroxy Compound (7 days)1,2 ______________________________________ 1 1,3-butanediol 29 g/kg 2 1,3-pentanediol >20 g/kg 3 1,5-pentanediol 2 g/kg 4 1,3-hexanediol >20 g/kg 5 1,5-hexanediol >20 g/kg 6 2,5-hexanediol 2 g/kg 7 1,6-hexanediol 5 g/kg 8 1,3-heptanediol >20 g/kg 9 1,3-octanediol >20 g/kg 10 1,3-nonanediol >20 g/kg 11 1,3-decanediol >20 g/kg 12 1,3-undecanediol >20 g/kg ______________________________________ 1 Single dose in rats. 2 LD50 = lethal dose for 50% kill.
LD 50 values are a common measure of the toxicity of a compound. These LD 50 values represent the lethal dose for a 50 percent kill of the animals tested per unit weight of the animals. The higher the LD 50 value, the lower the toxicity. The data in Table I establish that the 1,3-configurations of polyalcohols are the least toxic. The LD 50 values are significantly higher in compounds possessing this structural feature. The LD 50 values given in Table I were obtained by giving test animals graded single doses of the test compounds orally and observing them for one week. The number of deaths in each group was noted and the dose required for a 50 percent kill taken as the LD 50 value. In many cases, no death occurred even at the 20 g/kg level (about as much as one can give a rat in one dose), hence the basis of the ">20" values shown in the table.
The toxicity data with respect to the esters are given in the following Table II. Some commercial antimicrobial agents are also shown. All are significantly more toxic (lower LD 50 values) than either the diols or the esters.
TABLE II ______________________________________ Antimicrobial Agent Oral LD 50 (Rats)1 ______________________________________ Diol Esters >20 g/kg Hexachlorophene2 (G-11) 0.104 g/kg Bithionol2 6.6 g/kg Dichlorophen (G-4)2 1.24 g/kg3 Roccal4 0.23 g/kg o-Phenylphenol4 0.14 g/kg ______________________________________ 1 LD50 = Lethal dose for 50% kill. 2 Source: Mfg. Chemist and Aerosol News, July (1969) pp 38-40. 3 Guinea pigs. 4 Handbook of Toxicology, Vol. I.
In order to further illustrate this invention and, in particular, to establish the superiority of the 1,3-diols and esters as bacteriostats and mold inhibitors, the following microbiological tests were conducted.
EXAMPLE 1
Nutrient broth was used as the basal nutrient medium for the growth of all microorganisms tested. Five ml. of nutrient broth medium (Difco Co.) were placed in 18 mm. × 150 mm. test tubes and the basal medium sterilized with steam at 15 psi for 15 minutes. After cooling, a sufficient amount of the various compounds were added to the basal medium to give the concentrations used. Normally a final concentration of 0.2, 1 and 2 percent were used.
After mixing the chemicals with nutrient broth, the tubes were inoculated with the various test microorganisms. The test microorganisms were grown 25 hours earlier in nutrient broth and 1 drop of the dense microbial suspension was added to the tubes.
The tubes containing the chemicals and microorganisms were then incubated at the optimal growth temperature reported for each microorganism tested. Either 37°C. or 30°C. was used. Growth in control tubes, as well as those containing chemicals, was observed visually. After a suitable incubation period, a small aliquot of the test solutions was streaked on an agar plate. This was done in order to confirm the visual readings of the presence of microbial growth.
The results are shown in Tables III and IV. The "minimum effective concentration" is the lowest concentration of additive which effectively prevented growth under the conditions of the test.
TABLE III __________________________________________________________________________ PRESERVATIVE ACTION AGAINST BACTERIA Minimum Inhibitor Concentration Against Compound P. aerouginosa Salmonella typhimurium E. coli __________________________________________________________________________ 1,3-Heptanediol 1% 0.5% 1% 1,3-Nonanediol 0.5% 0.2% 0 1,3-Octanediol-1-monopropionate 0 0.2% 2% 1,3-Butanedioldipropionate 0 0.2% 1% __________________________________________________________________________ Symbol: 0 = not tested.
It is apparent from the above that the effectiveness of these materials against a wide spectrum of bacteria is established by the typical data shown in Table III. Of especial interest is the result that some of the test compounds are active against Salmonella at levels as low as 0.2 percent. These tests were carried out under conditions conducive to prolific growth of the organisms. Under conditions of normal usage, the test compounds are effective at even lower levels. Salmonellae are important public health organisms. All members of the genus are considered as human pathogens.
The present additives are also very effective with respect to mold inhibition which is shown in the following Table IV.
TABLE IV __________________________________________________________________________ PRESERVATIVE ACTION AGAINST MOLDS Minimum Effective Concentration Against Trichoderma Botrytis P. roquefortii Fusarium Compound 12688* 9435* 6988* 10911* B. fulva A. niger A. flavus __________________________________________________________________________ 1,3-Pentanediol + + 2% + + + + 1,3-Heptanediol 1% 1% 0.2% 1% 0.2% 0.2% 1% 1,3-Pentanediol- 0 0 1% 0 0 1% 0 monopropionate 1,3-Octanediol- 0.2% 0.2% 0.2% 0.2% 0.2% 0.2% 0.2% monopropionate 1,3-Butanediol- 0.2% 0.2% 0.2% 1% 0.2% 0.2% 0.2% dipropionate 1,3-Butanediol- 0 0 0.2% 0 0 0.2% 0 monooctanoate 1,3-Pentanediol- 0 0 1% 0 0 0.2% 0 monooctanoate __________________________________________________________________________ Symbols: + = No effect at 2%. The lowest level tested in this experiment was 0.2%. 0 = Not tested. *All microorganism numbers -- American Type Culture Collection.