Lactam solubility

Abstract

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

Claims

1. A composition comprising a lactam and 0.5% wt. to 20% wt of a non-ionic surfactant, wherein the lactam is ##STR00009## and the non-ionic surfactant is a C.sub.12-C.sub.15 alcohol ethyoxylate with 6.5-7.6 moles of ethylene oxide to alcohol.

2. The composition of claim 1, wherein the composition comprises less than 2% wt. non-ionic surfactant.

3. The composition of claim 1, wherein the composition comprises between 5% to 15% wt. of the C.sub.12-C.sub.15 alcohol ethyoxylate with 6.5-7.6 moles of ethylene oxide to alcohol.

4. The composition of claim 1, wherein the composition comprises 5% to 11% wt. of the C.sub.12-C.sub.15 alcohol ethyoxylate with 6.5-7.6 moles of ethylene oxide to alcohol.

5. The composition of claim 1, wherein the composition comprises 9% to 11% wt. of the C.sub.12-C.sub.15 alcohol ethyoxylate with 6.5-7.6 moles of ethylene oxide to alcohol.

6. The composition of claim 1, wherein the composition comprises 4% to 7% wt. of the C.sub.12-C.sub.15 alcohol ethyoxylate with 6.5-7.6 moles of ethylene oxide to alcohol.

7. The composition of claim 1, wherein the ratio of lactam to non-ionic surfactant is from 1:0.5 to 1:1.

8. The composition of claim 1, wherein the ratio of lactam to non-ionic surfactant is from 1:1 to 1:10.

9. The composition of claim 1, wherein the ratio of lactam to non-ionic surfactant is from 1:10 to 1:100.

10. The composition of claim 1, wherein the ratio of lactam to non-ionic surfactant is from 1:1 to 1:1000.

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) Non-Ionic Surfactant

(3) For the purposes of this disclosure, non-ionic surfactant shall be defined as amphiphilic molecules with a molecular weight of less than about 10,000, unless otherwise noted, which are substantially free of any functional groups that exhibit a net charge at the normal wash pH of 6-11.

(4) Any type of non-ionic surfactant may be used, although preferred materials are further discussed below. Highly preferred are fatty acid alkoxylates, especially ethoxylates, having a C.sub.8-35 alkyl or alkenyl chain, preferably a C.sub.8-30 alkyl or alkenyl chain, more preferably a C.sub.10-24 alkyl or alkenyl chain chain, especially a C.sub.10-18 alkyl or alkenyl chain, alkyl groups may be preferred, and having preferably 3 to 25, more preferred 5 to 15 ethylene oxide groups, for example, Neodol surfactants, available from Shell (The Hague, The Netherlands); ethylene oxide/propylene oxide block polymers which may have molecular weight from 1,000 to 30,000, for example, Pluronic from BASF (Ludwigshafen, Germany); and alkylphenol ethoxylates, for example Triton X-100, available from Dow Chemical (Midland, Mich., USA).

(5) Other non-ionic surfactants may be preferred. These include condensates of alkanolamines with fatty acids, such as cocamide DEA, polyol-fatty acid esters, such as the Span series available from Uniqema (Gouda, The Netherlands), ethoxylated polyol-fatty acid esters, such as the Tween series available from Uniqema (Gouda, The Netherlands), alkylpolyglucosides, such as the APG line available from Cognis (Dusseldorf, Germany) and n-alkylpyrrolidones, such as the Surfadone series of products marketed by ISP (Wayne, N.J., USA).

(6) For example, the non-ionic surfactant may be a non-ionic surfactant of comprising an esterified sorbitan, such as a non-ionic surfactant of formula (III):

(7) ##STR00008##

(8) wherein w+x+y+z is 0 to 20, and n is alkyl or alkenyl. For example w+x+y+z may be 0, as in the Span series available from Uniqema; and Alk may be C.sub.8-35, for example, C.sub.10-24, especially C.sub.10-18. For example, in Span monopalmitate, Alk is C.sub.15 alkyl, while in Span 20, Alk is C.sub.11 alkyl.

(9) For example, w+x+y+z may be 20, as in the Tween series, also referred to polysorbates. Suitable polysorbates may include polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate), polysorbate 40 (polyoxyethylene (20) sorbitan monopalmitate), polysorbate 60 (polyoxyethylene (20) sorbitan monostearate), polysorbate 80 (polyoxyethylene (20) sorbitan monooleate).

(10) The non-ionic surfactant may be an alkyl polysaccharide, for example of formula IV:
RO(C.sub.nH.sub.2nO).sub.t(glycosyl).sub.x(IV)

(11) wherein R is selected from the group consisting of alkyl, alkylphenyl, hydroxyalkyl, hydroxyalkylphenyl, and mixtures thereof in which alkyl groups contain from about 10 to about 18, preferably from about 12 to about 14, carbon atoms; n is 0 to 3, preferably 2; t is from 0 to about 10, preferably 0; and x is from 1.3 to about 10, preferably from 1.3 to about 2.7. The glycosyl is preferably derived from glucose. To prepare these compounds, the alcohol or alkylpolyethoxy alcohol is formed first and then reacted with glucose, or a source of glucose, to form the glucoside (attachment at the 1-position). The additional glycosyl units can then be attached between their 1-position and the preceding glycosyl unit's 2-, 3-, 4- and/or 6-position, preferably predominantly the 2-position.

(12) Furthermore, non-ionic surfactants not specifically mentioned above, but within the definition, may also be used.

(13) Of course, it will be appreciated that more than one non-ionic surfactant may be used; in other words, the compositions may comprise more than one non-ionic surfactant as described herein. In this case, the amounts of non-ionic surfactant disclosed herein refer to the total amount of non-ionic surfactant.

(14) Compositions

(15) 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.

(16) 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.

(17) 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, etcsuch additives are known in the art). The composition may comprise an aqueous solvent or an organic solvent to suit purpose.

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

(19) 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.

(20) 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.

(21) 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.

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

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

(24) 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

(25) Screening of NIS

(26) The following representative example uses 4-(4-chlorophenyl)-5-methylene-pyrrol-2-one.

(27) Excess solid lactam (3 mg) was placed in a Whatman Mini Uniprep sample vial, fitted with a 0.45 um nylon filter. Water or water+additive (NIS) (500 L) was added the mixture shaken and tapped briefly to initially disperse the solid and the mixture then agitated for 48 hours using a plate shaker fitted with a vial holder. After 48 hours, the solid was removed from the system by pressing down the plunger with integral filter on the vial. This removes the solid and provides filtered solution within the inner chamber which is then ready for analysis.

(28) The level of lactam dissolved in solution was quantified using HPLC analysis. Samples were analysed on an Agilent 1200 series HPLC fitted with a Thermo Hypersil Gold C18 column (152.13 m), isocratic elution with 60/40 methanol/water (+0.1% Formic Acid), 0.4 mL/min flow rate, using a DAD detector at 285 nm. The lactam tested has a retention time of 2.8 minutes.

(29) For each additive, the absolute level of lactam in solution was measured and reported as an increase in solubility of lactam relative to water alone.

(30) 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.

(31) TABLE-US-00001 Mean Lactam Level in Solubility % Additive Solution Increase vs Additive in Water (ppm) water alone Neodol 25-7 0 2.4 1.0 0.5 116.0 48.3 1 203.2 84.7 2 390.4 162.7 5 603.3 251.4 10 612.5 255.2 20 455.6 189.8 Tween 20 0 1.7 1.0 0.5 61.6 36.9 1 118.3 70.9 2 226.5 135.8 5 518.3 310.7 10 829.6 497.3 20 1546.3 927.0 Tween 80 0 6.0 1.00 0.5 41.5 6.92 1 75.0 12.51 2 123.3 20.56 5 208.4 34.74 10 391.4 65.23 0.5 50.5 18.9 1 104.9 39.1 2 170.7 63.7 5 432.4 161.3 10 942.3 351.6 20 1490.8 556.3 0.1 15.2 5.7 0.5 42.6 15.9 1 77.5 28.9 2 139.6 52.1

(32) The inventor(s) have demonstrated that non-ionic surfactants are beneficial at increasing lactam solubility in water, in particular at lower concentrations. The best examples are Tween 20 and Neodol 25-7.
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(33) It will be appreciated that, except where expressly provided otherwise, all preferences are combinable.