Lactam solubility

Abstract

Compositions comprising lactams and biosurfactants, suitable for use as antimicrobial, anti-biofilm and bacteriostatic compositions.

Claims

1. A composition comprising a solution comprising a lactam, at least 0.1% wt. rhamnolipid, and water, wherein the lactam is a lactam of Formula Ia or Formula IIa: ##STR00004## wherein R is H, halogen, or C.sub.1-4alkyl wherein the ratio of lactam to rhamnolipid is from 1:0.5 to 1:20.

2. The composition of claim 1, wherein R is H, F, Cl, Br, or Me.

3. The composition of claim 1, wherein the lactam is selected from: ##STR00005##

4. The composition of claim 1, wherein the rhamnolipid is a mono-rhamnolipid or a di-rhamnolipid.

5. The composition of claim 1, wherein the composition comprises a surfactant and a glycolipid biosurfactant comprises 20-90% wt. of the total surfactant in the composition.

6. The composition of claim 1, wherein the composition comprises 0.01 to 5% wt. lactam.

7. The composition of claim 1, wherein the lactam is 4-(4-chlorophenyl)-5-methylene-pyrrol-2-one.

8. The composition of claim 1, wherein the composition comprises 0.1% wt. to 4% wt rhamnolipid.

9. A composition comprising a solution comprising lactam, water and at least 0.1% wt. mono-rhamnolipid or di-rhamnolipid, wherein the lactam is 4-(4-chlorophenyl)-5-methylene-pyrrol-2-one.

10. The composition of claim 9, wherein the ratio of lactam to rhamnolipid is from 1:0.5 to 1:20.

11. The composition of claim 9 comprising 0.01 to 5% wt. lactam.

12. The composition of claim 9 comprising 0.01 to 2% wt. lactam.

13. The composition of claim 9, wherein the composition comprises 0.1% wt. to 4% wt rhamnolipid.

14. A composition comprising a solution comprising 4-(4-chlorophenyl)-5-methylene-pyrrol-2-one, 0.1% wt. to 4% wt glycolipid biosurfactant and water wherein the glycolipid biosurfactant is mono-rhamnolipid and/or di-rhamnolipid, and water.

15. The composition of claim 14, wherein the composition comprises 0.01 to 5% wt. 4-(4-chlorophenyl)-5-methylene-pyrrol-2-one.

16. A composition comprising a solution comprising 0.01 to 5% wt lactam and 20-90% wt mono-rhamnolipid and/or di-rhamnolipid, wherein the lactam is 4-(4-chlorophenyl)-5-methylene-pyrrol-2-one.

17. The composition of claim 16 comprising 20-90% wt di-rhamnolipid.

18. The composition of claim 16 comprising 20-90% wt mono-rhamnolipid and di-rhamnolipid.

Description

DESCRIPTION

(1) Lactams may be obtained using methods as described in WO 2007/085042 and WO 2004/016588, which are herein incorporated by reference in their entirety.

(2) Compositions

(3) The compositions described herein may be compositions having anti-microbial activity. In some cases, the compositions are anti-bacterial. They may have bactericidal and/or bacteriostatic activity. The inventor(s) have observed desirable bacteriostatic activity. Accordingly, in some cases, the composition is a bacteriostatic composition.

(4) The compositions may also prevent and/or inhibit biofilm formation. Biofilms are formed when microorganisms stick to a surface. Biofilm extracellular polymeric substances may be formed. Biofilms (also referred to as slime) present problems in industrial environments; for example, they may form in pipes in apparatus, or industrial and agricultural structures, on solar panels, and on boat hulls and other marine structures. Biofilms may also pose a problem in domestic environments. For example, biofilms may form in domestic appliances such as washing machines. Biofilms are also present in personal care, for example, they may form on tooth surfaces.

(5) Compositions suitable for any and all of these applications are within the scope of the invention. In some cases, the composition is a paint or other coating. In such cases, the composition may further comprise a binder, optionally a pigment and optionally one or more conventional additives (for example, to modify surface tension, improve flow properties, improve the finished appearance, increase wet edge, improve pigment stability, etc—such additives are known in the art). The composition may comprise an aqueous solvent or an organic solvent to suit purpose.

(6) The composition may also be used in medical applications, for example to coat equipment including medical devices.

(7) In some cases, the composition is a pharmaceutical composition. In other words, the composition may comprise a lactam as described herein and a pharmaceutically acceptable excipient. The composition may be suitable for topical use (for example, it may be a cream or lotion), it may be suitable for ocular use (for example, it may be an used as a pharmaceutical eye drop), it may be suitable for otic use (for example, it may be used as an ear drop), it may be suitable as a mouth wash, or it may be suitable for oral administration.

(8) In some cases, the composition is a composition suitable for use in the home (often referred to as a homecare composition) or institutions. Homecare compositions include, without limitation, cleaning products, laundry detergents, and fabric conditioners. In some cases, the composition is a homecare composition, for example a laundry liquid. The composition may therefore comprise a detergent surfactant and a builder. The composition may be a fabric conditioner (also called a fabric softener) and may comprise an antistatic agent. The composition may also be a domestic cleaning product.

(9) In some cases, the composition is a personal care composition. For example, the composition may be intended for use on the skin (for example, a cream, cleanser or serum). For example, the composition may be useful in the prevention or treatment of acne. For example, the composition may comprise one or more of dimethicone, petrolatum, a humectant such as hyaluronic acid or glycerin; and ceramide(s). In some cases, the composition is a personal care composition comprising a detergent, for example, the composition may be a face wash or shower gel or hair shampoo. The composition may be a hair treatment composition other than a shampoo. The composition may be a deodorant composition (for example, a deodorant powder, paste or liquid). The composition may be an oral care composition (such as a toothpaste or mouthwash and may include, for example, fluoride and/or flavourings.

(10) In some cases, the composition is a contact lens cleaning fluid.

(11) The composition may be a composition suitable for use in agriculture, for example, as a soil additive (solid or liquid).

(12) The composition may be a composition suitable for use in the treatment of or manufacture of glass or lens for example as an additive/treatment for solar panels.

Examples

(13) Mono and Di rhamnolipids were extracted and purified from a commercial sample of JBR425, supplied by Jeneil®, using supercritical CO.sub.2 using the following method.

(14) A commercial sample of JBR425 (ex Jeneil®) was mixed with a Celllite 454® support and transferred to a supercritical CO.sub.2 extractor. The temperature and pressure was increased to produce supercritical CO.sub.2 and residual oils and fats were removed from the extractor in a defatting step. A cosolvent, industrial methylated solvent (IMS), was then added to the remaining defatted rhamnolipid mixture on the Cellite 454® support in the presence of supercritical CO.sub.2. The co-solvent IMS was introduced at an increasing gradient from 2.5% to 10% to facilitate the separation and removal of the different mono- and di-rhamnolipid ratios.

(15) Bio-surfactant solutions at the levels shown in the results below were prepared for screening. The maximum level tested was dictated by the solubility of the surfactant in water. The following representative example uses 4-(4-chlorophenyl)-5-methylene-pyrrol-2-one.

(16) Solid lactam was weighed into Whatman® Mini Uniprep sample vials, fitted with a 0.45 μm nylon filter (2.7 to 3.3 mg per vial). 50 μL of a solvent solution was placed into each sample vial, the vial capped and shaken briefly by hand to agitate the solid, then placed on a Thermo Labsystems Wellmix® plate shaker and continuously agitated for 48 hours. After this time, the excess solid in the vial was removed using the integral filter membrane and the resultant solution analysed by HPLC to determine the level of dissolved lactam.

(17) Samples were analysed using an Agilent 1200® series HPLC fitted with a Hypersil Gold C18 column (15×2.1×3 μm), using isocratic elution with 60/40 methanol/water (+0.1% Formic Acid) at a flow rate of 0.4 mL/min, using a DAD detector at 285 nm. 4-(4-Chlorophenyl)-5-methylene-pyrrol-2-one has a retention time of ˜2.8 minutes.

(18) Each test surfactant solution was tested in triplicate and the mean value of lactam in solution calculated. Values of solubility were quoted as the improvement in aqueous solubility vs water alone (i.e. mean level of lactam dissolved in water+solvent/mean level of lactam dissolved in water) to allow comparison between screens conducted on different days.

(19) TABLE-US-00001 Mean Lactam Level in Solubility % Additive in Solution Increase vs Additive Water (ppm) water alone Mono-rhamnolipid 0 2.7 1.0 R1 0.1 10.9 4.1 0.5 39.3 14.7 1 75.3 28.1 2 149.7 55.9 4 194.8 72.7 Di-rhamnolipid R2 0 2.7 1.0 0.1 15.2 5.7 0.5 42.6 15.9 1 77.5 28.9 2 139.6 52.1

(20) The inventor(s) have demonstrated that rhamnolipid biosurfactants are beneficial at increasing lactam solubility in water, in particular at lower concentrations. The best example is R2.

(21) It will be appreciated that, except where expressly provided otherwise, all preferences are combinable.