Propanediol monoacetate mononitrate

Abstract

The present invention relates to propanediol monoacetate mononitrate as well as the use thereof as antimicrobial agent, in particular for cosmetic applications.

Claims

1. Propanediol monoacetate mononitrate of formula (I) ##STR00002##

2. A method to improve preservation of a product by inhibiting microbial degradation thereof, wherein the method comprises adding an anti-microbial effective amount of 1,3-propanediol monoacetate mononitrate to the product.

3. A method to maintain skin homeostasis and/or balance skin microbiome which comprises contacting the skin with an effective amount of 1,3-propanediol monoacetate mononitrate.

4. A deodorant product which comprises 1,3-propanediol monoacetate mononitrate as a deodorant active compound.

5. An anti-acne product which comprises 1,3-propanediol monoacetate mononitrate as an anti-acne agent.

6. A method for treating skin conditions selected from the group consisting of Pityriasis versicolor, dandruff formation, seborrheic dermatitis, atopic dermatitis and psoriasis, wherein the method comprises applying to skin in need thereof an effective treatment amount of 1,3-propanediol monoacetate mononitrate.

7. A cosmetic or pharmaceutical composition comprising 1,3-propanediol monoacetate mononitrate.

8. The cosmetic or pharmaceutical composition according to claim 7, wherein the 1,3-propanediol monoacetate mononitrate is an antimicrobial agent.

9. The cosmetic or pharmaceutical composition according to claim 7, wherein the 1,3-propanediol monoacetate mononitrate is an antifungal and/or antibacterial agent.

10. The cosmetic or pharmaceutical composition according to claim 9, wherein the 1,3-propanediol monoacetate mononitrate is an agent that inhibits the growth of microbes selected from the group consisting of S. epidermis, C. xerosis, M. furfur, and P. acnes and mixtures thereof.

11. The cosmetic or pharmaceutical composition according to claim 7, wherein the 1,3-propanediol monoacetate mononitrate is present in an amount of about 0.005 to 2 wt. %, based on the total weight of the composition.

12. The cosmetic or pharmaceutical composition according to claim 7, wherein the 1,3-propanediol monoacetate mononitrate is present an amount of 0.01 to 1 wt. %, based on the total weight of the composition.

13. The cosmetic or pharmaceutical composition according to claim 7, wherein the 1,3-propanediol monoacetate mononitrate is present in an amount of 0.05 to 0.75 wt. %, based on the total weight of the composition.

14. The cosmetic or pharmaceutical composition according to claim 7, wherein the 1,3-propanediol monoacetate mononitrate is present in an amount of 0.1 to 0.5 wt. %, based on the total weight of the composition.

15. A non-therapeutic method for killing and/or inhibiting growth of microbial cells, wherein the method comprises contacting the microbial cells with an effective amount of 1,3-propanediol monoacetate mononitrate.

16. The method according to claim 15, wherein the microbial cells are fungal and/or bacterial cells.

17. A process for preparing 1,3-propanediol monoacetate mononitrate, wherein the process comprises reacting 1,3-propandiol monoacetate with nitrosulfuric acid.

18. The process according to claim 17, wherein the process is carried out in an inert organic solvent.

Description

Example 1: Preparation of Propanediol Monoacetate Mononitrate (PDMAMN)

(1) 1,3-propandiol monoacetate (PDMA) in dichloromethane (800 g/h, 40%, 2.7 mol PDMA/h) and nitrosulfuric acid (830 g/h, consisting of 2 mol sulfuric acid (98%) per mol of fuming nitric acid, 3.24 mol HNO3/h) were continuously dosed to a microreactor at 0° C. applying a residence time of 11 seconds. Then the mixture is quenched with water (4.1 kg/h) at 15° C. and further neutralised using a sodium hydroxide solution (1.14 kg/h containing 28% NaOH in water). The partially neutralised reaction mixture is collected in a flask for 120 seconds (225 g). The aqueous phase was separated and the organic phase three times washed with water (3×45 ml) and the solvent evaporated in vacuo. Yield: 99% (14.8 g; 98% purity as determined by HPLC).

Example 2 Antimicrobial Efficacy

(2) The antimicrobial efficacy of propanediol monoacetate mononitrate (PDMAMN) is assessed in analogy to the regulatory challenge test method (NF EN ISO11930). The following test solutions were tested 1. Inv 1: 400 mg PDMAMN in 1 ml PEG 400 were diluted with 40 mL physiological serum (0.85% NaCl) containing 7% Ethanol (˜1% of PDMAMN) 2. Inv 2: 200 mg PDMAMN in 1 ml PEG 400 were diluted in 40 mL physiological serum (0.85% NaCl) containing 7% Ethanol (˜0.5% of PDMAMN) 3. Inv 3: 40 mg 3-PDMAMN in 1 ml PEG 400 were diluted in 40 mL physiological serum (0.85% NaCl) containing 7% Ethanol (˜0.1% of PDMAMN) 4. Ref 1: Physiological serum (0.85% NaCl) 5. Ref 2: 1 mL PEG 400+40 mL physiological serum (0.85% NaCl) containing 7% Ethanol 6. Control: 0.5% Phenonip in physiological serum (0.85% NaCl)

(3) All test solutions were deposed in 96-deep well plates (1.6 ml/well). The wells were contaminated with the respective bacterial or the fungal strains as outlined in table 1*10.sup.5 to 1*10.sup.6 cfu/ml for the bacteria and 1*10.sup.4 to 1*10.sup.5 cfu/ml for the fungi to obtain the initial contamination as outlined in table 1, Zero. After the contamination, each well was thoroughly mixed to ensure a homogeneous distribution of the microorganism. Then each plate was incubated at 22° C. for 24 h. The counting of the (remaining) population was carried out 24 h after contamination.

(4) TABLE-US-00001 TABLE 1 Zero Inv 1 Inv 2 Inv 3 Ref 1 Ref 2 Control colony counts [cfu/ml] S. epidermidis 500000 0 0 0 500000 400000 0 (deo, gram+) C. xerosis 250000 0 0 0 250000 250000 0 (deo, gram+) M. furfur 4000 0 0 0 40000 40000 0 (dandruff, yeast) P. Acnes 100000 0 0 0 100000 100000 0 (acne, gram+)

(5) As can be seen in the table above propanediol monoacetate mononitrate exhibits an excellent antimicrobial activity, almost comparable to Phenonip™, a broad spectrum antimicrobial agent designed for preservation of a wide range of cosmetics and toiletries.