CH620337A5 - Process for the preparation of nonmedicinal compositions resistant to degradation caused by the action of microorganisms - Google Patents

Description

The present invention relates to a process for the preparation of compositions, excluding medicaments, resistant to degradation caused by the action of microorganisms, as well as to the compositions obtained by this process.

The content of Swiss patents Nos. 616658 and 595338 of the same holder is included here for reference.

A first object of this invention therefore consists in a process for the preparation of compositions, excluding drugs, resistant to degradation caused by the action of microorganisms, characterized in that it is mixed with a composition basic at least one compound represented by formula (I),

R — X — CH = CH — COOY

(I)

Wherein R is alkyl having 1 to 20 carbon atoms or alkenyl having 2 to 20 carbon atoms, X is S, SO, SO2, and Y is hydrogen, an alkali metal, an alkaline earth metal , NH4, an alkyl having from 1 to 20 carbon atoms, an alkenyl having from 2 to 20 carbon atoms, a radical obtained by elimination of a hydroxyl group from a polyhydric alcohol or a glycerol acetal which may have an ether bond resulting from intramolecular or intermolecular dehydration or an oxyethylene containing from 1 to 20 units or an oxypropylene containing from 1 to 20 units terminated by an alkyl group having from 1 to 20 carbon atoms, in an appropriate amount to prevent or delay the multiplication of microorganisms in this composition. A second object of this invention consists of the compositions obtained by the above method.

The present inventors have often used different kinds of antimicrobial agents known as sterilants, antifungals or antiseptics, but many problems have been encountered in the current applications thereof. Most of the commonly available antimicrobial compounds have been developed for the best use of their antimicrobial activities, but it has often been found that these antimicrobial compounds, which were expected to have a wide range of uses in the initial state of their development, have proven to be unsuitable for practical use as applied to different new systems or compositions.

45 For example, to overcome microbial contamination in cosmetics or other household products, no account was taken of the physico-chemical properties of the systems or products with which these stabilizers were to be mixed. Generally, the degree of antimicrobial activity of the compound was first tested by adding, for example, benzoic acid, antimicrobial products of aromatic phenolic type such as salicylic acid or alkaline salts of that -this, esters of p-hydroxybenzoic acid, p-isopropyl-o-methyl-phenol or o-phenylphenol, or so-called inverted soaps such as an alkylbenzyldimethylammonium halide, then to tests of long-term stability and compatibility of this compound with the system. However, these tests involve the same examinations for different kinds of compounds, and this requires a relatively long time. It has moreover often been found that only 60 few compounds are effective in a specific system. In addition, if two or more different types of systems are applied, the same test procedure must be repeated two or more times, this requiring a great loss of time and work for the tests and thus constituting an obstacle to the development of programs. 65 commercial products. In addition, since existing antimicrobial compounds have been used for a long time in a wide field of application, resistant bacteria quickly appeared one after the other, so that it

620,337

There is now a very difficult problem of controlling microbial contamination in production facilities.

Thus, the development of new compounds having excellent microbial activity, as well as the physicochemical properties which make them acceptable for use as a base for different compositions, has proved necessary.

The various inventors have found that the compounds of formula (I) exhibit significant antimicrobial activities as well as excellent physicochemical properties which make them acceptable for use as an ingredient in a basic mixture of different compositions. It has also been found that the compounds of formula (I) have the following important effects: when they are added to compositions in amounts of less than 50 ppm, they are capable of retarding the growth of Gram positive bacteria such as Staphylococcus aureus or Bacillus subtilis, which are typical microbes causing different microbial disorders in the living environment; when added to compositions in amounts less than 500 ppm, they are capable of preventing the growth of Gram negative bacteria, such as Escherichia coli, Proteus vulgaris or Pseudomonas aeruginosa as well as putrefactive bacteria; and, when added to compositions in amounts greater than 500 ppm, they are capable of inhibiting the growth of certain genera of fungi such as Penicillium, Aspergillus or Rhizopus. They also have a very high preventive effect against yeasts such as Candida which can cause Candidiasis.

In the definition of Y of formula (I), the polyhydric alcohol which may have an ether bond resulting from an intramolecular or intermolecular dehydration comprises in particular ethylene glycol, propylene glycol, glycerin, erythritol, xylitol, pentaerythritol , sorbitol and mannitol, as well as diglycerin, dipentaerythritol, xylitan, sorbitan, mannitan, and polyoxyalkylene glycols having 2 to 20 units of ethylene oxide or propylene oxide.

The compounds of formula (I) include in particular the following representative examples:

1. P-alkylsulfenylacrylic acids n-Cl2H25 - S - CH = CH - COOH (mp = 92-94 ° C)

2. ß-alkylsulfinylacrylic acids

O

II

n-C12H25— S — CH = CH — COOH (PF = 62-65 ° C)

3. ß-alkylsulfonylacrylic acids

O

II

n-C12H25- S - CH = CH - COOH (mp = 105-108 ° C)

II

O

4. Alkyl esters of P-alkylsulfenylacrylic acids n-C12H25 —S — CH = CH - COOCH3 (mp = 48-50 ° C)

5. Alkyl esters of ß-alkylsulfinylacrylic acids

O

II

n-Ci2H25— S-CH = CH-COOCH3 (PF = 55-58 ° C)

6. Alkyl esters of ß-alkylsulfonylacrylic acid

O

II

n-C12H25- S-CH = CH-COOCH3 (PF = 85-88 ° C)

II

O

7. Methylcarbitylesters of ß-alkylsulfenylacrylic acids n-Ct 2H25 - S — CH = CH — COOCH2CH2OCH2CH2och3 (n ° 1,5210)

8. Methylcarbitylesters of ß-alkylsulfinylacrylic acids

O

II

n-C! 2H25 - S - CH = CH - COOCH2CH2OCH2CH2OCH3 5 (nê0 1,5120)

9. Methylcarbitylesters of ß-alkylsulfonylacrylic acids

O

11

n-C12H25 - S - CH = CH - COOCH2CH2OCH2CH2OCH3

10 II

O

(ng 1,5210)

10. Glyceryl esters of ß-alkylsu ^ nylacrylic acids' OH

I

n-Ci 2H2S - S - CH - CH - COOCH2 - CH - CH2OH (n ° n ° 1.5098)

11. Glyceryl esters of ß-alkylsulfinylacrylic acids

O

oh n-C12H25 - S - CH = CH - COOCH2 - CH - CH2OH (n ° 1,5120)

25 12. Glyceryl esters of ß-alkylsulfonylacrylic acids

O OH

II I

n-Ci 2H25 - S - CH = CH - COOCH2 - CH - CH2 - OH

II °

(no 1.5092)

13. Glycerylacetals of P-alkylsulfenylacrylic acids

H3C CH3 3 v

35 o o n-C12H25-S-CH = CH-COOCH2 J [

(Mp = 45-47 ° C)

40 14. Glyceryl acetals of ß-alkylsulfinylacrylic acids

O

n-C12H25— S — CH = CH —COOCH2 J_ (ng ° 1,5068)

h3c ^ ch3 o o h3o ch3 o o

15. Glycerylacetals of ß-alkylsulfonylacrylic acids O

50 11

50 n-C12H25— S-CH = CH-COOCH2

11

(ng ° 1,5214) O

55 16. Polyoxyethylene-P-alkylsuFenylacrylic acid esters n-C12H25 - S - CH = CH - C00 (CH2CH20) 15H (n £ ° 1,5230)

17. Polyoxyethylene-P-alkylsulfinylacrylic acid esters

60 O

n-C12H14— S-CH = CH-COO (CH2CH2O) 15H (n £ 0 1.5121)

18. Polyoxyethylene-P-alkylsulfonylacrylic acid esters

65 O

II

n-C12H25- S-CH = CH-C00 (CH2CH20) 15H (n ^ 0 1.5189)

O

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19. Sorbitylesters of ß-alkylsulfenylacrylic acids n-C „H -S-CH = CH-C00-CH„ ld do 2

(Mp = 43-46 ° C)

20. Sorbitylesters of ß-alkylsulfinylacrylic acids

0

i n-C, „H0 -S-CH = CH-C00-CH„ 1 d do d

(Mp = 33-35 ° C)

HO / d [\) H

OH

21. Sorbitylesters of ß-alkylsulfonylacrylic acids

0

n "C12H25 ~ S ~ CH = CH" C00 "CH2 ° H0 /

(no £ 1.5026)

These compounds of formula (I) can be prepared, for example, in the following manner.

a) By reaction of a mercaptan represented by the general formula (II):

RSH (II)

in which R is as defined above with an acetylenemonocarboxylic acid in aqueous alkaline solution, so as to obtain a compound of formula (I) in which X is S and Y is hydrogen, an alkali metal, an alkaline earth metal or NH * .

b) By reaction of the aliphatic acid obtained in step a) or of its halide with an alcohol in the presence of an acid or basic catalyst so as to obtain a compound of formula (I) in which X is S and Y is an alkyl or an alkenyl having from 1 to 20 carbon atoms, a radical obtained by elimination of a hydroxyl group from a polyhydric alcohol or an acetylated glycerin which can have an ether bond resulting from an intramolecular or intermolecular dehydration, or an oxy-ethylene (1 to 20 units) or an oxypropylene (1 to 20 units)

terminated by an alkyl group having 1 to 20 carbon atoms.

c) By oxidation of the compounds obtained in steps a) and b) with an inorganic or organic peroxide such as sodium meta-periodate, hydrogen peroxide, perbenzoic acid, m-chloroperbenzoic acid, peracetic acid or the like, so as to obtain a compound of formula (I) in which X is SO or SO2.

The compounds of formula (I) used in the process according to the invention have excellent microbial activity as well as the physicochemical properties required for use as an ingredient in a basic mixture used for the preparation of cosmetics, detergents or the like synthetic organic products, such as different kinds of creams, lotions, shampoos and rinse lotions.

The compounds of formula (I) vary with regard to their antimicrobial activity according to their structure. When X in formula (I) is modified, R and Y being kept constant, the compounds such as those mentioned in Tables 1,2,3 and 8 are obtained, whereas, if R is modified by keeping Y constant, compounds obtained in Tables 4 and 6 are obtained, and if Y is modified by maintaining constant R and X, the compounds mentioned in Tables 5 and 7 are obtained. Thus, the antimicrobial activity of the compounds of formula (I) varies according to the specific substituents chosen for R, X and Y. On the other hand, since the physicochemical properties, particularly the compatibility, of these compounds vary according to the specific substituents chosen for R, X and Y, it is possible to choose them appropriately and use a material that is most suitable for a particular application system. This is the most important feature of the compounds used in this invention, and which distinguishes them from other traditional antimicrobial agents.

The characteristics of the compounds of formula (I) mentioned above under the numbers I to 21 are as follows.

Compounds 1 to 3 have the physicochemical properties required for cream bases. The more particularly preferred compounds are those in which R is an alkyl having from 12 to 14 carbon atoms. These compounds are therefore suitable for use as an antiseptic in day creams, beauty creams and lotions. They also have good compatibility with mixed systems which are composed essentially of an aliphatic acid. The alkali metal salts of compounds 1 and 2 have physicochemical properties analogous to those of the fatty acid sodium salts which are base materials for soaps, so that these compounds are suitable for use as an antiseptic in systems where a fatty sodium salt or an anionic surfactant is used as an emulsifier, such as, for example, machining oils of the emulsion type.

Compounds 4 to 6 vary in their properties depending on the number of carbon atoms in the alkyl group (R). Among these compounds, the short alkyl chain compounds (Cj to C5) have properties analogous to those of isopropyl myristate, isopropyl palmitate, butyl stearate and the like, which are traditional ingredients of cosmetic products, and therefore these compounds are suitable for use as an anti-septic and provide an additional function as basic fatty materials for different kinds of creams, shampoos and lotions for rinsing. On the other hand, compounds with a long alkyl chain (C6 to C20) are waxy materials, and can be used as antiseptics in emulsion type waxes and the like.

Compounds 7 to 9 are estercarbitol compounds having a rather hydrophilic nature. These compounds, as well as the monoglyceride compounds 10 to 12, have an emulsifying power and can be used as antimicrobial agents for cosmetic creams, lotions, etc. They also have emulsifying compatibility with fats and fatty oils and are therefore most suitable for use as an antiseptic in such products. Compounds 13 to 15 have substantially the same properties as compounds 7 to 12 which have just been described.

Compounds 16 to 18 have a surfactant activity analogous to that of polyoxyethylene fatty acid esters which are typical nonionic surfactants and, therefore, they can be used in a wide field of use ranging from cosmetics to 55 and from household products to various synthetic products.

Compounds 19 to 21 are analogous to sorbitan fatty acid esters which are typical nonionic surfactants and therefore are suitable for use in emulsion systems such as creams, lotions, etc., where esters of m sorbitan fatty acid are usually used.

While the current typical applications of the compounds of formula (I) have been described in general, it will be understood that they can also be used widely for the purposes of preventing the putrefaction of other emulsions or solutions. 65 The proportion of mixture of the compounds of formula (I) with respect to a particular application system varies significantly depending on the purpose desired for this composition, that is to say if only the antimicrobial or antiseptic effect is sought. or if the compound

5

620,337

of formula (I) must produce both the action of a base material and the effect of an antimicrobial agent.

When only the antimicrobial activity is desired for the compounds of formula (I), it is preferred to use those in which R is an alkyl or an alkenyl having from 1 to 8 carbon atoms, preferably from 2 to 8 and better still from 4 to 8, in an amount corresponding approximately to 0.05 to 5% by weight.

On the other hand, when the compounds of formula (I) are used to act as a base material and to provide an antimicrobial effect in the application system, it is preferred to use those in which R is an alkyl or an alkenyl having 6 to 20 carbon atoms, preferably 6 to 18 and better still 8 to 16, in an amount corresponding approximately to 1 to 25% by weight.

However, the quantity of compounds of formula (I) used in a specific application can vary according to the nature of this system, according to the purpose of the use and according to the degree of the action expected as a base material and according to the effect. expected as an antimicrobial agent and, therefore, such amounts can be appropriately changed depending on the conditions encountered.

The compounds of formula (I) can therefore be incorporated into the compositions mentioned below by way of example.

A. A liquid detergent which essentially consists of 10 to 50% by weight, preferably 15 to 30%, of one or more surfactants chosen from anionic surfactants, nonionic surfactants and zwitterionic surfactants, 1 to 15% by weight, preferably 3 to 10% of a stabilizer, the remainder consisting of water. As an anionic surfactant, alkali metal salts and alkanolamine salts can be used, for example alkylbenzene sulfonate having an alkyl group of 10 to 16 carbon atoms, an alkane sulfonate having 10 to 20 carbon atoms carbon, an alkyl sulfate having 10 to 20 carbon atoms and a polyoxyethylene alkyl ether sulfate having an alkyl group of 10 to 20 carbon atoms and 1 to 20 units of ethylene oxide. As a nonionic surfactant, it is possible to use a polyoxyethylene alkyl ether having an alkyl of 10 to 20 carbon atoms and 5 to 20 ethylene oxide units, a polyoxyethylene alkylphenyl ether having an alkyl of 8 to 12 carbon atoms and from 5 to 20 units of ethylene oxide, and a fatty acid alkylolamide derived from a fatty acid having from 10 to 20 carbon atoms. As zwitterionic surfactant, betaine, sulfobetaine, an imidazol type surfactant having a long chain alkyl group of 10 to 20 carbon atoms, can be used. As stabilizer, it is possible to use, for example, lower alcohols having from 1 to 4 carbon atoms such as ethanol and propanol, and glycols such as ethylene glycol and propylene glycol, urea and aromatic sulfonates such than toluene sulfonate and xylene sulfonate.

B. An oil-in-water emulsion which can be used in particular as an oily machining composition which essentially consists of 85 to 95% by weight of liquid paraffin and 5 to 15% by weight of one or more organic surfactants chosen from anionic surfactants and nonionic surfactants as defined above.

C. A cosmetic composition which essentially consists of 10 to 70% by weight, preferably 15 to 50%, of an oily or fatty constituent chosen from liquid paraffin and vegetable oils such as olive oil, beaver, lanolin alcohol, lanolin ester and fatty acid ester, in 3 to 40% by weight, preferably 10 to 30%, of one or more organic surfactants chosen from anionic surfactants such as acid salts fatty (soaps) alkyl sulfates having 10 to 20 carbon atoms and polyoxyethylene alkyl ether sulfates having alkyl of 10 to 20 carbon atoms and 1 to 10 ethylene oxide units, and the tensio non-ionic active agents such as a polyoxyethylene alkyl ether having from 10 to 20 carbon atoms and from 1 to 10 ethylene oxide units, a fatty acid monoglyceride and an ester of sorbitol fatty acid and in 10 to 50% by weight of water, preferably 15 to 40%.

D. A shampoo composition which essentially consists of 5 to 35% by weight, preferably 8 to 20%, of anionic surfactant chosen from metal alkyl salts and alkanolamine salts of alkylbenzene sulfonate having a alkyl of 10 to 16 carbon atoms, those of alkyl sulfates having an alkyl of 5 10 to 20 carbon atoms, those of alkane sulfonates having 10 to 20 carbon atoms, those of α-olefin sulfonates having from 10 to 20 carbon atoms and those of polyoxyethylene alkyl ether sulfates having from 10 to 20 carbon atoms and from 1 to 10 ethylene oxide units, and optionally containing a nonionic surfactant, a surfactant zwitterionic, an oily and fatty constituent, a stabilizer and a chelating agent.

The antimicrobial effect of the compounds of formula (I) used in the process according to the invention generally increases in the order —S—, - SO 2 - and - SO - for X; however, this effect may vary in reverse order, more particularly with respect to mold fungi.

This invention will now be described with reference to the following illustrative examples.

20

Example 1:

Active groups and growth inhibiting effect of Gram positive bacteria

The compounds were tested according to a test method on a mixed agar plate in order to determine the concentration of the compound in the culture medium required to inhibit the growth of different kinds of bacteria.

The test was carried out by first placing 1 ml of a solution of specified concentration of each test compound on a petri dish, then adding 19 ml of a dissolved normal agar culture medium thereto and stirring the mixture. uniformly and cooling until solidification. Then a loop of platinum of a bacterial solution containing 1,000,000 bacterial cells per milliliter is spread over the surface of this medium, then the bacteria are cultured in a chamber at constant temperature (30 ° C.) for 48 h, then the concentration. The minimum growth inhibition for each of the compounds in the culture medium was determined by observing the growth conditions of the bacteria.

The results obtained are presented in table 1. In this table, the sign + indicates that the bacteria grow normally 4o and consequently that no effect of inhibition of the test compounds was observed; the + sign indicates that the bacteria are growing a little, and that an effect of inhibiting moderate growth has been observed; and the sign - indicates that no growth of bacteria is observed and therefore a perfect growth inhibiting effect has been observed.

Table 1

Compounds tested n-Cj 2H25 - S - CH = CH - COOH O

Minimum concentration for growth inhibition (ppm)

Staphylo- Bacillus coccus aureus subtilis 500 100 50 500 100 50

n-C12H25- S — CH = CH —COOH ------

O

il n-C12H25— S — CH = CH — COOH - + + _- +

II

60 O

COONa

(Control) 4- -f- - (- + + +

ho- <t Vco2c2h5

(Control)

+ + ±

+

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6

Example 2: Table 2 (continued)

Active groups and growth inhibiting effect on bacteria - - -

Gram positive Compounds tested Minimum concentration

The tests were carried out in the same manner as in For the inhibition of Example 1, and the results obtained are presented in Table 2. Growth

(ppm)

Table 2

COONa

+ + + +

Tested compounds Minimum concentration io / r \ _on (Control) +

for inhibition of I ''

growth nk

(PPm) y.

Staphylo- Bacillus HO- <f \ -C02C2H5

coccus aureus subtilis is \ - / (Control) - + + ± + + 500 100 50 500 100 50

n-C14H29 —S-CH = CH — cooch3- ± + + + +

O 11

n-Ci4H29 - S-CH = CH-COOCH3 - - - - - - 20 Example 3:

O Active group and inhibition effect on the growth of bacteria n-C14H29-S-CH = CH-COOCH3 --- + + + Gram negative

[| The following tests were carried out according to the

O ^ Example 1, and the results obtained are presented in Table 3.

Table 3

Compounds tested Minimum concentration for growth inhibition (ppm)

Escherichia coli Proteus vulgaris Pseudomonas aeruginosa

500 100 50 500 100 50 500 100 50 n-C4H9-S-CH = CH-COOCH3 + + + + + + + + +

O

II

n-C4H9- S-CH = CH-COOCH3 - - - - - - - + +

O

II

n-C4H9- S-CH = CH-COOCH3 - - + - - + + + +

O

COONa

S -OH (Control) + + + + + + + + + +

H ° - \ 7 — C02C2H5 (Control) + + + - + + + + + +

Example 4:

Languor of the alkyl chain and inhibitory effect on the growth of bacteria

The tests were carried out according to the procedure of Example 1, and the results obtained are presented in Table 4.

(Table at the top of the next page)

7,620,337

Table 4

Compounds tested Minimum concentration for growth inhibition (ppm)

^ Staphylococcus Bacillus subtilis Escherichia Proteus vulgaris Pseudomonas

R— S —CH = CH — COOCH3 aureus coli aeruginosa

„500 100 50 500 100 50 500 100 50 500 100 50 500 100 50

n-CH3

+

+

+

+

+

+

+

+

+

+

+

+

-

-

+

n-C2H5

+

4-

+

±

+

+

±

+

+

±

+

+

-

±

+

n-C3H7

-

+

+

-

+

+

-

+

+

-

+

+

-

+

+

n-C4H9

-

-

-

-

-

-

-

-

-

-

-

-

-

+

+

n-CsHn

-

-

-

-

-

-

-

+

+

-

-

-

+

+

+

n-C6H13

-

-

-

-

-

-

-

+

+

-

-

-

±

+

+

n-CsHi7

-

-

-

-

-

-

±

+

+

-

+

+

+

+

+

n-CioH21

-

-

-

-

-

-

+

+

+

-

+

+

+

+

+

n-Ci2H25

-

-

-

-

-

-

-

±

+

±

+

+

+

+

+

n-Ci4H29

-

-

-

-

-

-

+

+

+

+

+

+

+

+

+

n-Ci6H33

-

-

-

-

-

-

+

+

+

+

+

+

+

+

+

n-Ci8H37

-

±

-

-

+

+

+

+

+

+

+

+

+

+

Sodium salicylate (control)

•

+

+

+

+

+

+

+

+

+

+

+

+

+

+

P-hydroxy acid ester

benzoic (control)

-

+

+

±

+

+

+

+

+

-

+

+

+

+

+

Example 5

Tests were carried out in the same manner as that described in Example 1, and the results obtained are presented in Table 5.

Table 5

Compounds tested Minimum concentration for growth inhibition (ppm)

Staphylo- Bacillus Escherichia Proteus Pseudomonas coccus subtilis coli vulgaris aeruginosa aureus

500 100 50 500 100 50 500 100 50 500 100 50 500 100 50

O

II

n-C4H9— S — CH = CH — COOH - + + - + ++ - + - ++ + ++ + +

O

II

n-C4H9 S - CH — CH — COONa - 4- 4- ++ + 4- + 4-4- 4- -1- 4- +

O

II

n-C4H9- S — CH = CH — COOCH3 +

O

II

n-C4H9 - S-CH = CH-C00 (CH2CH20) 2CH3 +

O OH

II I

n-C4H9— S — CH = CH —COOCH2CHCH2OH +

O

i '0

n-C .Hg-S-CH ^ CH-COOCH ^ - ^ +

O OH

n-C4H9— S — CH = CH — COO (CH2CH2O) i0H _____--- + - + + ± + +

Cf'3XCH3

I! OO n-C4Hg-S-CH = CH-COOCH2-J '+

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8

Table 5 (continued)

Compounds tested Minimum concentration for growth inhibition (ppm)

Staphylo- Bacillus Escherichia Proteus Pseudomonas coccus subtilis coli vulgaris aeruginosa aureus

500 100 50 500 100 50 500 100 50 500 100 50 500 100 50

COONa

OH (Control) + ++ + ++ + ++ + ++ + +

HO— ^ y — CO2C2H5 (Control) - + + - -4- + + + +

Example 6:

length of the alkyl chain and inhibitory effect on the growth of fungi and yeasts

1 ml of a solution of a compound at a specified concentration and 19 ml of a heated and dissolved Sabourand agar medium were introduced into a 9 cm diameter petri dish sterilized to dryness and, after uniform mixing, the mixture obtained was cooled and solidified in the form of a flat plate.

On this medium was spread a platinum loop of a suspension of spores of Penicillium citrinum, Aspergillus niger and Trichophyton mentagrophytes respectively, as well as a suspension of Candida albicans, according to the JIS-Z-2911 test method for fungistatic resistance. After 5 days of culture in a chamber at constant temperature (25 ° C), the growth conditions of the fungi and yeast were observed in order to determine the minimum effective concentration for inhibiting the growth of each of the compounds tested. The results obtained are presented in Table 6.

Table 6

Compounds tested Minimum concentration for growth inhibition (ppm)

O

Il Penicillium Aspergillus niger Trichophyton Candida

R— S — CH = CH — COOCH3 citrinum mentagrophytes albicans

R =

500

100

50

500

100

50

500

100

50

500

100

50

CH3

+

+

+

+

+

+

-

±

+

±

+

+

n-C2H5

-

+

+

±

+

+

-

-

+

-

+

+

n-C3H7

-

+

+

-

+

+

-

-

+

-

±

+

n-C4H9

-

+

+

-

+

+

-

-

-

-

-

-

n-CsHu

+

+

+

-

+

+

-

-

+

+

+

+

n-C6H13

-

-

+

-

+

+

-

-

-

-

+

+

n-C8H17

-

-

-

-

+

+

-

-

-

-

-

-

n-C10H21

-

-

+

±

+

+

-

-

±

-

-

-

n-C12H25

+

+

+

+

+

+

-

-

+

-

-

-

n-Ci4H29

+

+

+

+

+

+

-

±

+

-

-

±

n_Ci6H33

+

+

+

+

+

+

-

+

+

-

+

+

n-C18H37

+

+

+

+

+

+

-

+

+

+

+

+

Potassium sorbate (control)

+

+

+

+

+

+

-

+

+

+

+

+

Sodium dehydroacetate

(control)

-

+

+

+

+

+

-

+

+

-

+

+

Example 7

The effect of the test compounds for inhibiting the growth of fungi and yeasts was tested in the same way as in Example 1, and the results obtained are presented in Table 7.

(Table at the top of the next page)

9

Table 7

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Compounds tested

Minimum concentration for growth inhibition (ppm)

Penicillium Aspergillus Trichophyton Candida citrinum niger mentagrophytes albicans

500 100 50 500 100 50 500 100 50 500 100 50

n-C4H9 - S - CH = CH - COOH

-

+

+

-

+

+

+

+

+

+

O

II

n-QHg- S - CH = CH — COONa

+

+

+

+

+

+

+

+

±

+

O

j!

n-C4H9 - S-CH = CH-COOCH3

-

+

+

-

+

■

O

II

n-C4H9 - S - CH = CH - C00 (CH2CH20) 2CH3

-

+

+

-

-

+ -

-

-

±

+

O OH

He |

n-C4H9 - S-CH = CH-COOCH2CHCH2OH

-

+

-

+

-

- -

+

+

O

i! O n-C4Hg-S-CH = CH-COOCH2— ^ N

-

■

+

-

•

+ -

-

+

+

+

OH

O

I

n-C4H9 - S-CH = CH-COO (CH2CH2O) 10H

+

+

+

-

+

+

+

+

+

+

CH3 \ / CH3

O 3 ^ 3

Il O O n-C4Hg — S-CH = CH-COOCH2—! 1

+

+

+

+

+ -

+

+

Potassium sorbate (control) Sodium hydroacetate (control)

+

+ +

+ +

+ +

+ +

1 1 ++

+ +

+ + +

+ +

+ +

Example 8

0.2% by weight of the various compounds of formula (I) where 1.0% by weight of a commercial antiseptic has been mixed in a machining oil of the emulsion type (consisting of 90 parts of fluid paraffin, 8 parts of sodium dodecylbenzenesulfonate and 2 parts of a fatty acid soap) diluted with 20 times its weight of water, then a mixed solution (10s cells / ml) of three strains of Bacilli pyo-cyaneus (Pseudomonas earuginosa IFO 3898.3919 and 3924) and a strain of Colon bacilli (Escherichia coli IFO 3806) were inoculated into said solution and cultured with stirring at constant temperature (30 ° C). After a determined period of time, the number of bacteria present per milliliter of test solution was measured by the so-called dilution mixing method in order to determine the effect of the compounds for the prevention of putrefaction. The results obtained are presented in Table 8.

Table 8

Concentration (o /. \

Compounds tested

Immediately after the start of cultivation

Antiseptic effect Duration of test 4 days after 8 days after

30 days later

0.2 0.2

0.2

n-C12H25 - S — CH = CH — COOH 385xl03

O

II

n-C12H25— S — CH —CH — COOH 473 x 103 O

II

n-C12H2J - S - CH = CH - COOH 237 x 103

II

O

308 xlO3 '148 xlO3 25 x 103

334 xlO3 133 xlO3 12xl03

53 xlO3 57 xlO3 23 xlO3

620337

10

Table 8 (continued)

Concentration (%)

Compounds tested

Antiseptic effect Duration of test

Immediately after the start of cultivation

4 days later

8 days later

30 days later

0.2

n-C12H25 —S — CH = CH - O

COONa

462 xlO3

292 xlO3

277 xlO3

74 xlO3

0.2

y n-C12H25- S — CH = CH-O

-COONa

321x103

146 xlO3

98 xlO3

oo X o

U)

0.2

n-C12H2J— S — CH = CH-O

-COONa

298 x103

215 xlO3

104x 103

122 xlO3

1.0

COONa

Ó

(control)

1203 x103

1321 x 103

1248 xlO3

1097 x103

1.0

COONa

û

(control)

938 x 103

807 xlO3

651x103

712 xlO3

0

No antiseptic added

3019 xlO3

4208 x 103

2436 xlO3

2512 xlO3

Example 9

Specimens were prepared by mixing the compounds of formula 3s (I) and commercial antiseptics at predetermined concentrations in the composition for the treatment of hair mentioned below, then these specimens were subjected to various antisepsis tests.

10% liquid paraffin

Petroleum jelly 3

Beeswax 5

Lanolin 2

Polyoxyethylenesorbitan 3 monostearate

Dye; perfume traces 45

Antiseptic (test compound) see table 9

Water remains

First, three different bacterial strains of Pseudomonas aeruginosa, Escherichia coli and Proteus vulgaris, which are typical bacteria producing microbial contamination, were 50

inoculated into the hair treatment composition which was free of any antiseptic, then inoculated also with dust and dirty materials collected from the walls, floors, machines and air of a cosmetic manufacturing facility, then the mixture was stirred continuously using an agitator so as to prepare a contaminated composition in which the bacteria exist at a rate of 10® to 107 cells per gram of mixture. This bacterial composition was inoculated at a rate of lg / 100 g of each specimen. After inoculation, each specimen was subjected to continuous agitation by means of an agitator, and a platinum loop from each specimen was collected after the passage of a specified period of time, then inoculated into a broth, which was then cultured in a constant temperature chamber (30 ° C) for 48 h. The antiseptic activity of each specimen was then determined based on the turbidity of the broth.

The results obtained are presented in Table 9; in this table 9, the sign + signifies that the growth of bacteria has taken place (no inhibition), the sign ± signifies that a bacteriostatic action of each compound has been observed (moderate inhibition), and the sign - signifies that 'bactericidal action has been observed (total inhibition).

Table 9

Compounds tested

Concen- Antiseptic effect Adaptability to the tration system Duration of the test (%) 7d 15d 30d

O

II

n-C4H9- S-CH = CHCOOCH3

O

il n-C12H25- S-CH = CHCOOCH3

0.20 0.50

0.50 1.00

+

system compatibility and no change to emulsion conditions

Same. Slightly reduced antiseptic power due to its greater solubility in seeds

II

Table 9 (continued)

620337

Compounds tested Concen- Antiseptic effect Adaptability to the tration system Test duration (%) 7 days 15 days 30 days

O OH

he I

n-C4H9- S-CH = CH-COOCH2CHCH2OH

O OH

II I

n-C12H25— S - CH = CH - COOCH2CHCH2OH

O

II

n-C4H9- S-CH = CH-C00 (CH2CH20) 5H

O

n-C12H25 - S - CH = CH - C00 (CH2CH20) i SH

n-C, r '-S-CH = CH-COOCK.

■ o - - - 2 ~ f

HO '^

O

"Ì

OK

OH

n-c ^ H ^ -s-CH ^ CH-coocr ^

0

NOT

0.20 0.50

0.50 1.00

0.20 0.50

0.50 1.00

0.20 0.50

0.50 1.00

ho y "on oh

± +

+ +

± +

+ +

+ +

Good compatibility with the system. Soluble in water, so easy to mix.

- Same

+ - Good compatibility with the system - contribution and emulsification

+ ± Good compatibility with the system + and excellent surface-active activity; good effect for adaptation to the system

+ - Good compatibility with the system; Span-like and useful in the system

+ + Good compatibility with the sys-

± - téme; analogous to Span and useful in the system. Provides better hair treatment when used in the system

HO- ^ y- C00C2H5

(control) 0.20 + + + Separate compound when the 0.40 + + ± concentration exceeds 0.3%

COONa

(control) 0.20 +++ Produces poor stability of 0.50 +++ emulsion; separation at a concentration of 0.5%

U

OH

COONa OH

n \ ì

CH,

[n-C14H29 - N — CH2— + Cl "

CH3 ~~

n-C12H25NH (CH2) 2NH (CH2) 2NHCH2COOH

(control) 0.20 0.50

(control) 0.20 0.50

(control) 0.20 0.50

(control) 0.20 0.50

+ +

+ +

+

+ +

+ +

+ +

+ +

+ Same. Separation at a concentration of 0.50%

+ Moderately soluble in water, and + therefore gives an excessively bad effect with regard to the separation of the compound and the stability of the emulsion

- Breaking of the emulsion and tendency

- at separation. Most striking at a concentration of 0.50%

-1- Properties similar to the previous + compound, although a little more moderate

620,337

12

Example 10:

Kitchen detergent n-C12H250 (CH2CH20) 15H n-C12H250 (CH2CH20) 3S03Na

CH3

I

n-C12H25 —N + —CH2COO "

I

ch3

n-C12H25 — CON (CH2CH2OH) 2 Inorganic salt Antiseptic Water

10% 5

2

1.5

see table 10 remains

The compounds of formula (I) and commercial antiseptics were mixed in predetermined proportions in the liquid detergent of the above composition to prepare specimens. A bacterial solution was inoculated into each of the specimens at a rate of 1 ml / 100 ml of liquid detergent and was cultured with stirring at a constant temperature of 30 ° C. The bacterial solution was prepared by inoculating bacteria collected from the different parts of a plant for the production of detergents in a liquid detergent without antiseptic of the composition mentioned above and by culture thereof up to a concentration of 107 cells / ml.

The antiseptic effect was judged by collecting a platinum loop from each of the specimens, inoculating it in a broth and periodically measuring its turbidity.

The results obtained are presented in table 10. In this table, the sign + indicates a propagation of bacteria (no inhibitory effect), the sign ± indicates a bacteriostatic effect of the compounds (moderate inhibition), and the sign - indicates a bactericidal effect (total inhibition).

Table 10

Antiseptic

Concentration (%)

Antiseptic effect

Immediately after inoculation 1 day

Test duration 5 d 15 d

30 days

O

II

n-C4H9- S — CH = CH — COOH O

II

n-C4H9 - S - CH = CH - COONa O

II

n-C4H9 - S - CH = CH - COOCH3 O

II

n-C4H9 - S - CH = CHC00 (CH2CH20) 2CH3

O

II

n-C4H9— S — CH = CHCOO (CH2CH2O) 10H

O OH

II I

n-C4H9 - S - CH = CHCOOCH2 CHCH2OH

1.5 1.5 0.2 1.0 1.0 1.0

+

+

+

+

+

+

+

+

+

+

+ +

+

+

H, C CH,

3 \ / 3

VS / \

O O O

»I I

n-C4H9-S-CH = CHCOOCH2CHCH2

O II

n-C .Hn-S-CH = CHCOOCH 4 "

2

HO

COONa

No antiseptic

O

\

OH

OH

0.5

1.0

(control) 1.0

(control) 1.0

zero

+

+

+

+

+

+

+

+

+

+

+

+

+

+

13

620,337

Glycerin Sorbitol

Example 11

A hair rinse lotion having the composition „,,

The following was prepared and subjected to the same test as that described in _ ° ^ ° X ^ e r'ene "^ aur-rester Example 10 in order to estimate the antiseptic effect of the compounds ar um 'C0 oran *

10 5 3

traces see table 11

hair rinse lotion

Water

rest

Dipalmityldimethylammonium chloride 5% Liquid paraffin 5

The results obtained are presented in Table 11.

Table 11

Antiseptic

Concen

Antiseptic effect

Adaptability to the system

tration

Duration of the test

(%)

3 d

15 d

30 days

n-C3H7 - S - CH = CH - COOCH3

0.50

+

+

-

Good compatibility

1.00

+

±

-

O

y n-C3H7 - S - CH = CH - COOCH3

0.20

-

_

-

Same

0.50

-

-

O

II

II

n-C3H7-

S - CH = CH - COOC4H9

0.20 0.50

-

Same

O

II

n-C8H17 - S - CH = CH - COOCH3

0.20

■

•

-

Same

0.50

±

-

-

O

II

n-C3H7 - S - CH = CH - COOCH3

0.20

+

+

-

Same

II

O

0.50

+

-

-

O

II

n-CgHj 7 - S - CH = CH - COOCH3

0.20

+

+

-

Same

II

O

0.50

+

+

-

O OH

II 1

n-C4H9 - S - CH = CHCOOCH2 - CHCH2OH

0.20

+

+

-

Also serves as a surfactant

0.50

+

-

-

O

II

n-C4H9 - S - CH = CHC00 (CH2CH20) 5H

0.20

+

+

-

Presents surface activity

0.50

+

activates and acts as an active ingredient

O

n-C8H17— S — CH = CHCOO (CH2CH2O) 10H

O

il n-C4Kg-S-CH = CH-COOCH2

0.20 0.50

0.20 0.50

+ + +

+ +

+ Same. Surfactant effect

- superior

- Same

CH,

[n-Ci4H29 - N — CH2 - ^ ^] + Cl (control)

CH3

0.20 + + + 0.50 + + +

n-C12H2SNH (CH2) 2NH (CH2) 2NHCH2COOH (control) 0.20 4- + +

0.50 -f + 4-

Produces separation from the system. Particularly unstable at a concentration of 0.50%

Produces white turbidity in the system

620,337

14

Table 11 (continued)

Antiseptic

Concen- Antiseptic effect tration Duration of test

(%) 3 d 15 d 30 d

Adaptability to the system

HO-

NH

-c-nh2

(control)

0.20 -

+

+

+

Produces separation of

0.50

+

+

+

cooch2ch3 system

(control)

0.20

+

+

+

Produces excess turbidity

0.50

+

+

+

sive of the system and a com-

insoluble plex

Example 12

Specimens were prepared by mixing compounds of formula (I) or commercial antiseptics in determined concentration in pastes having the following compositions.

Dough composition (A)

Polyvinyl acetate Silicon

Dibutyl phthalate

Perfume

Dye

Antiseptic

Water

Dough composition (B)

Modified starch

Polyvinyl acetate

Silicon

Perfume

Dye

Antiseptic

Water

80%

5 2

traces traces see table 12 remains

15%

20 1

traces traces see table 12 remains

Dough composition (C)

20 Modified starch Silicon Urine

Sodium paratoluenesulfonate Perfume 25 Colorant Antiseptic Water

40%

1 3

2

traces traces see table 12 remains

The bacterial solution for inoculation was prepared by inoculating dust collected from different parts of a manufacturing facility into pastes of the same composition without antiseptic and allowing them to rot. Then, this bacterial solution was inoculated at a rate of 1 g / 100 g in each specimen, then these specimens were placed in a desiccator having a humidity higher than 90% and left to stand at room temperature for 2 months. The antiseptic power of each specimen was estimated based on the change in external appearance, discoloration and odor.

The results obtained are presented in Table 12. In this table, the sign O indicates that there has been no change in any of the following characteristics: external appearance, color and odor; the sign A indicates deterioration of at least one of these characteristics; and the sign X indicates a deterioration of all these characteristics.

Table 12

Antiseptic

Concentration n-C4H9 - S — CH = CH = CH — COOCH3

O

II

n-C4H9 - S - CH = CH - COOCH3

OH

I

n-C4H9 - S — CH = CH — COOCH2CHCH2OH O OH

II i n-C4H9 - S - CH = chcooch2 CHCH2OH

n-C4H9 -S-CH = CHC00 (CH2CH20) 2CH3 O

0.50

0.50

0.50

0.50 0.50

Antiseptic effect

Composition of the dough

B C

O

O

O

O O

O

O

O

O O

O O

o

AT

n-C4H9 - S - CH = CHC00 (CH2CH20) 2CH3

0.50

O

o o

15

Table 12 (continued)

620,337

Antiseptic

Concentration (%)

Antiseptic effect

Composition of dough B

O

II

n-C4H9 - S - CH = CHC00 (CH2CH20) 2CH3

II

O

n-C4H9 - S - CH = CHC00 (CH2CH20) 2H O

k3cT T °

0 J

(control)

CH3CH = CHCH = CH-COOH (control)

0.50 0.50

0.50 0.50

O

o o

o

X

X

Example 13

Appropriate disinfectants have been added to industrial water respectively, this water being circulated continuously day and night in a closed circuit by means of a pump. The transparency and the odor of the water were observed periodically 3o in order to estimate the disinfecting effect of the compounds of formula (I), the transparency of the water being measured by means of a turbidimeter. The results obtained are presented in Table 13.

Palmytylbenzyldimethylammonium chloride is unsuitable for use as a disinfectant because it produces foams during circulation, while sodium hypochlorite is subject to deactivation when exposed to sunlight and, therefore, it presents the problem of the duration of its effectiveness. The compounds of formula (I) used in the process according to the invention, on the other hand, are excellent both as regards their anti-foaming property and the duration of their effectiveness.

The compounds of formula (I) have antimicrobial activity against one or more bacteria, fungi, and yeasts. They are useful in the same way as various known stabilizers, such as lower alkyl esters of p-hydroxybenzoic acid, sodium salicylate and the like. They can be used to preserve various perishable organic materials against attack and destruction by bacteria, fungi and yeasts. The materials requiring such preservation are in particular those based on carbohydrates and proteins, as well as various industrial and cosmetic compositions containing fatty substances, oils, waxes and organic surfactants. This invention is based on the discovery of the antimicrobial activity of the compounds of formula (I), as well as their compatibility with other ingredients of cosmetics, detergents and machining oil. The other ingredients of these compositions can be any traditional ingredient used in usual amounts.

Table 13

Disinfectant effects Duration of test

15 days 30 days 60 days

Properties examined

Trans- Odor Trans- Odor Trans- Odor parence parence parence

2% solution

O

II

n-CH3 —S -CH = CHC00 (CH2CH20) 5H 2% solution of

O OH

II I

n-CH3 —S -CH = CHCOOCH2CHCH2OH

Dilution disinfectant

(number of times)

100 - - -

500 - - - ±

1000 - ± - + ±

100 - - - - -

500 - - - - -

1000 + - + ±

620,337

16

Table 13 (continued)

Disinfectant

Dilution

Disinfectant effects

(number

Duration of the test

many times)

15d

30 days

60 d

Properties examined

Trans

Odour

Trans

Odour

Trans

Odour

appearance

appearance

appearance

2% solution

100

±

G

500

-

-

±

_

+

±

II

1

1000

-

+

±

+

+

n-C -: ^? - CH = CHC00-CHo f

HO ^

i

"OH

OH

2% solution

100

_

ch3

500

-

-

±

-

+

±

[n-c14h29-N-cH2 - <^ \ ycr

1000

+

+

+

+

+

+

1 \ S

CH3 (control)

2% NaOCl solution (control)

100

+

±

500

-

-

+

±

+

+

1000

±

±

+

+

+

+

R

Claims (13)

} 620,337 CLAIMS 1. Process for the preparation of compositions, excluding medicaments, resistant to the degradation caused by the action of microorganisms, characterized in that at least one compound represented by the mixture is mixed with a base composition formula (I) R — X — CH = CH — COOY (I) in which R is an alkyl containing from 1 to 20 carbon atoms, or an alkenyl containing from 2 to 20 carbon atoms, X is S, SO or SO2, and Y is hydrogen, an alkali metal, an alkaline earth metal , NH4, an alkyl containing from 1 to 20 carbon atoms, an alkenyl containing from 2 to 20 carbon atoms, a radical obtained by elimination of a hydroxyl group from a polyhydric alcohol, an acetal of glycerin, or (RiO) nR2, where Ri is ethylene or propylene, n is between 1 and 20 and R2 is hydrogen or an alkyl having 1 to 20 carbon atoms, in an amount suitable to prevent or delay the multiplication of microorganisms in said composition. 2. Method according to claim 1, characterized in that the basic composition comprises at least one substance subject to degradation by microorganisms and chosen from the group comprising carbohydrates, proteins, fatty substances, oils, waxes and organic surfactants. 3. Method according to claim 1 for the preparation of a cosmetic composition, characterized in that one adds to a liquid, a cream or a paste, at least one compound of formula (I). 4. Method according to claim 1 for the preparation of a liquid detergent, characterized in that one adds to a liquid base composition at least one compound of formula (I). 5. Method according to claim 1 for the preparation of an oil-in-water emulsion usable in particular as oil for machining, characterized in that at least one compound of formula (I) is added to a basic emulsion . 6. Method according to claim 1, characterized in that, in formula (I), R is an alkyl having from 1 to 8 carbon atoms or an alkenyl having from 2 to 8 carbon atoms, and by the fact that the amount of this compound is between 0.05 and 5% by weight relative to the total weight of the composition. 7. Method according to claim 1, characterized in that, in the compound of formula (I), R is an alkyl or an alkenyl having from 6 to 20 carbon atoms, and in that the amount of this compound is between 1 and 25% by weight relative to the total weight of the composition. 8. Method according to claim 1, characterized in that Y is a hydrogen atom. 9. Method according to claim 1, characterized in that Y is a hydrogen atom, CH3, c4h9, Na (CH2CH20) 2CH3, CH2CH-CH2OH, 14. Composition according to claim 11 in the form of an oil-in-water emulsion usable in particular as oil for machining obtained by the process according to claim 5. OH -in. 10. Method according to claim 9, characterized in that X is SO. 11. Composition obtained by the process according to claim 1. 11 / - CH., X J (D 0 _i I -CH. or (RiOJnH. 12. Cosmetic composition in liquid, cream or paste form according to claim 11, obtained by the process according to claim 3. 13. Composition according to claim 11 in the form of a liquid detergent obtained by the process according to claim 4.