Antimicrobial preservative system and method comprising a formaldehyde substituted hydantoin

• US 5,037,843 A
• Filed: 03/05/1990
• Issued: 08/06/1991
• Est. Priority Date: 03/05/1990
• Status: Expired due to Term

• Current Assignee: Rhodia Operations (Solvac SA)
• Original Assignee: Mcintyre Group, Ltd.
• Inventors: Schoenberg, Thomas G.
• Primary Examiner(s): Hollrah, Glennon H.
• Assistant Examiner(s): Hollinden, Gary
• Application Number:
  US07/488,654
• Time in Patent Office: 519 Days
• Field of Search: 514/392, 514/389, 514/738, 514/544, 514/696, 514/693, 514/512, 548/308, 548/312
• US Class Current: 514/389
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 43/50 1,3-Diazoles; Hydrogenated 1,3-diazoles
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 2800/31 Anhydrous
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 8/4946 Imidazoles or their condensed derivatives, e.g. benzimidazoles
• CPC Class Codes: A61Q 17/005 Antimicrobial preparations

Abstract

A method of preparing an antimicrobial preservative system in a substantially anhydrous liquid form is disclosed. The antimicrobial preservative system inhibits or retards microbial growth when an effective antimicrobial amount is subsequently added to a medium capable of supporting undesirable microbial growth. More particularly, the preservative system comprises a condensation product of a 5,5-disubstituted hydantoin and formaldehyde prepared in the presence of a substantially anhydrous, water-miscible, solvent and an alkalizing agent. Also disclosed is a cold-stable, substantially anhydrous liquid preservative system comprising 1,3-dimethylol-5,5-dimethylhydantoin alone or in combination with an effective antimicrobial amount of at least one paraben preservative prepared by an embodiment of the disclosed method.

Claims

1. A cold stable antimicrobial preservative system in substantially anhydrous liquid form which is dissolvable in an antimicrobially effective amount in a medium capable of supporting microbial growth comprising:

(a) as an active preservative, a condensation product of formaldehyde and a 5,5-disubstituted hydantoin wherein each such substituent group on the hydantoin ring is independently selected from the group consisting of phenyl and lower alkyl containing 1 to about 6 carbon atoms, said condensation product having a methylol functional group attached to one or both nitrogen atoms on the hydantoin ring;

(b) a substantially anhydrous, water-miscible solvent selected from the group consisting of polyhydroxy alcohols having about 3 to about 6 carbon atoms per molecule, alkylene carbonates having about 2 to about 3 carbon atoms in the alkylene radical thereof per molecule, and mixtures thereof; and

(c) sufficient alkalizing agent to provide a pH between about 6 and about 9 when one part by weight of said liquid preservative system is diluted with about 9 to about 19 parts by weight of deionized water.

2. The antimicrobial preservative system of claim 1 further containing at least one paraben preservative.

3. The antimicrobial preservative system of claim 1 having a free formaldehyde content below about 2 weight percent.

4. The antimicrobial preservative system of claim 1 wherein said solvent is a polyhydroxy alcohol selected from the group consisting of propylene glycol, glycerine, butylene glycol, hexylene glycol and mixtures thereof.

5. The antimicrobial preservative system of claim 1 wherein said solvent is an alkylene carbonate selected from the group consisting of ethylene carbonate, propylene carbonate and mixtures thereof.

6. The antimicrobial preservative system of claim 1 where each said substituent group is an alkyl group and both said alkyl groups are identical.

7. The antimicrobial preservative system of claim 1 wherein said condensation produce comprises 1,3-dimethylol-5,5-dimethylhydantoin.

8. The antimicrobial preservative system of claim 1 wherein said solvent is propylene glycol and said alkalizing agent is an alkali metal hydroxide.

9. The antimicrobial preservative system of claim 8 wherein said condensation product is 1,3-dimethylol-5,5-dimethylhydantoin present at a concentration of about 40 to about 75 weight percent on a total system weight basis and said system has a diluted pH of about 6.5 to about 8.5.

10. The antimicrobial preservative system of claim 8 further containing dissolved therein at least one paraben preservative selected from the group consisting of phenyl esters of parahydroxybenzoic acid, alkyl esters of parahydroxybenzoic acid containing 1 to about 10 carbon atoms in the alkyl group, and derivatives and mixtures thereof.

11. The antimicrobial preservative system of claim 10 wherein said paraben preservative is methylparaben.

12. A preservative system of claim 7 that is incorporated in an amount in the range of about 0.01 weight percent to about 1 weight percent into a personal care product.

13. A preservative system of claim 7 that is incorporated in an amount in the range of about 0.01 weight percent to about 1 weight percent into a household product.

14. A preservative system of claim 7 that is incorporated in an amount in the range of about 0.01 weight percent to about 1 weight percent into an industrial product.

15. An aqueous medium capable of supporting microbial growth containing the preservative system of claim 1 in an effective antimicrobial amount.

16. An aqueous medium capable of supporting microbial growth containing the preservative system of claim 2 in an effective antimicrobial amount.

23. A substantially anhydrous liquid antimicrobial preservative system of claim 1 wherein said preservative comprises 1,3-dimethylol-5,5-dimethyl-hydantoin obtained by the reaction of 5,5-dimethylhydantoin with about 1 to about 3 moles of paraformaldehyde calculated as formaldehyde per mole of said 5,5-dimethylhydantoin in a substantially anhydrous medium comprising propylene glycol and sodium hydroxide.

24. A method of inhibiting or retarding microbial growth in a consumer product requiring preservation against microbial growth, the method comprising incorporating into the product an effective microbial inhibiting amount of the substantially anhydrous antimicrobial preservative system of claim 1.

25. The method of claim 24 wherein the antimicrobial preservative system comprises 1,3-dimethylol-5,5-dimethylhydantoin.

26. The method of claim 25 wherein the antimicrobial preservative system further includes at least one paraben preservative.

17. A method for preparing a substantially anhydrous liquid antimicrobial preservative composition comprising the steps of sequentially:

(a) dissolving each of paraformaldehyde and a 5,5-disubstituted hydantoin wherein each such substituent is independently selected from the group consisting of phenyl and lower alkyl containing less than 7 carbon atoms in a substantially anhydrous, water-miscible solvent selected from the group consisting of polyhydroxy alcohols each having about 3 to about 6 carbon atoms per molecule, alkylene carbonates each having about 2 to about 6 carbon atoms per molecule, and mixtures thereof, together with sufficient alkalizing agent to provide a substantially anhydrous liquid composition having a pH above about 6 when diluted with about 9 to about 19 parts by weight of deionized water;

(b) heating said liquid composition to a temperature above about 50 degrees C. to provide a heated liquid reaction mixture which is substantially visually clear;

(c) maintaining said liquid reaction mixture at said temperature and said diluted pH until reaction between said paraformaldehyde and said hydantoin is substantially complete based on a determination of the amount of free formaldehyde present in said reaction mixture, said reaction being substantially complete when the amount of said free formaldehyde is below about 2 weight percent based on total weight of said reaction mixture; and

(d) cooling and optionally filtering the so-cooled said resulting reaction mixture to provide such a substantially anhydrous liquid antimicrobial preservative composition, said preservative composition being characterized by;

(1) containing a condensation product of said paraformaldehyde and said hydantoin wherein methylol functional groups are attached to at least one of the two nitrogen atoms of the ring of said hydantoin, and

(2) having a capacity to inhibit and/or retard the growth of undesirable microorganisms when an antimicrobially effective amount thereof is subsequently included in a medium capable of supporting microbial growth.

18. The antimicrobial preservative system obtained from the method of claim 17.

19. The method of claim 17 further including the step of including at least one paraben preservative in the substantially anhydrous liquid antimicrobial preservative system after step (c) at a temperature favoring dissolution of the paraben preservative either while the reaction mixture is cooling in step (d) or in an added step (e).

20. The antimicrobial preservative system obtained from the method of claim 19.

21. The antimicrobial preservative system of claim 20 wherein the included paraben ester is selected from the group consisting of phenyl esters of parahydroxybenzoic acid, alkyl esters of parahydroxybenzoic acid having 1 to about 10 carbon atoms in the alkyl group, and derivatives thereof, used alone or in combination.

22. The antimicrobial preservative system obtained from the method of claim 17 wherein the condensation product comprises 1,3-dimethylol-5,5-dimethyl hydantoin, the solvent is a polyhydroxy alcohol selected from the group consisting of propylene glycol, glycerine, butylene glycol, and hexylene glycol, used alone or in combination and the alkalizing agent is an alkali metal hydroxide.

27. The method of claim 34 wherein said liquid composition contains 5,5-dimethylhydantoin as said hydantoin and about 1 to about 3 moles of said paraformaldehyde, calculated as formaldehyde, per mole of said 5,5-dimethylhydantoin, said solvent comprises a substantially anhydrous polyhydroxy alcohol having about 3 to about 6 carbon atoms per molecule, said temperature is in the range of about 50 degrees C. to about 110 degrees C. and said method is carried out in a sealed reaction vessel.

28. The method of claim 27, wherein said condensation product is 1,3-dimethylol-5,5-dimethylhydantoin.

29. The method of claim 28, wherein said 1,3-dimethylol-5,5-dimethylhydantoin is present at about 40 to about 75 weight percent, the polyhydroxy alcohol is propylene glycol and the alkalizing agent is sodium hydroxide.

30. An antimicrobial preservative system produced by the process of claim 34 wherein said 5,5-disubstituted hydantoin is 5,5-dimethylhydantoin, and said preservative system contains 1,3-dimethylol-5,5-dimethylhydantoin.

31. The system of claim 30 which contains about 55 to about 75 weight percent of said 1,3-dimethylol-5,5-dimethylhydantoin and has a free formaldehyde content of less than about 2 weight percent on a total system weight basis.

32. The system of claim 31 wherein said liquid composition is heated at a temperature in the range of about 60 degrees C. to about 110 degrees C.

33. The system of claim 30 further containing at least one paraben preservative.