US20180228151A1

US20180228151A1 - Encapsulated lactams

Info

Publication number: US20180228151A1
Application number: US15/750,893
Authority: US
Inventors: Christopher FIDGE; Stephen Golding; Paul Damien Price; David William Thornthwaite
Original assignee: Conopco Inc
Current assignee: Conopco Inc
Priority date: 2015-08-20
Filing date: 2016-07-25
Publication date: 2018-08-16
Also published as: ZA201800842B; CN108024939A; BR112018003173B1; EP3337452A1; WO2017029070A1; BR112018003173A2; US10918107B2; EP3337452B1; US20200128826A1

Abstract

Encapsulated lactams suitable for use in compositions and compositions comprising encapsulated lactams. The compositions may be useful as antimicrobial, anti-biofilm and bacteriostatic compositions. Methods of encapsulating lactams.

Description

This application claims priority from EP 15181842.4 filed 20 Aug. 2015 which is incorporated by reference for all purposes.
The present invention relates to encapsulated lactams. The encapsulated lactams are suitable for use in compositions, for example, in antimicrobial, anti-biofilm and bacteriostatic compositions. The invention further relates to methods of encapsulating lactams.
WO 2007/085042 and WO 2004/016588 disclose lactams for antimicrobial benefit and steps towards their synthesis. WO2014/118240 discloses antimicrobial compositions comprising a lactam and a hydrotope. US2011/0059144 relates to methods of improving the aesthetics of personal care compositions by encapsulating hydrophobic actives in a polyurea shell.
However, use of these lactams is limited by compatibility with certain formulations.
The present invention relates to encapsulated lactams. The encapsulation of the lactams permits greater flexibility of formulation as the encapsulation may permit use of the lactams in higher pH formulations and/or improve their solubility. In some cases, the encapsulation facilitates control and triggered release of lactams.
More specifically, the present invention relates to encapsulated lactams as described in WO 2007/085042 and WO 2004/016588, the contents of which, and in particular the lactam structures explicitly drawn out therein, are incorporated by reference.
For example, in a first aspect, the present invention relates to an encapsulated lactam of formula (I) or (II):
wherein:
R₁and R₂are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl; and
R₃is selected from hydrogen, hydroxyl, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, cycloalkyl, aryl, aralalkyl and —C(O)CR₆═CH2;
R₄and R₅are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl; and
R₆is selected from hydrogen and methyl; and
R₇is selected from hydrogen and —C(O)CR₆═CH₂; and
Preferably, at least one of R₄and R₅is hydrogen.
It will be appreciated that, where appropriate groups may be optionally substituted.
Optional substituents may include halogens, C_1-4alkyl, C_1-4haloalkyl (for example, CF₃) and C_1-4alkoxy.
Alkyls may, for example, be C_1-2alkyls, such as C_1-6alkyls. Aryls may, for example, be C_6-10aryls, for example, phenyls.
Preferably, at least one of R₁and R₂is selected from heterocyclyl, heteroaryl, aryl and arylalkyl.
Preferably, R₁is hydrogen. Preferably, R₃is hydrogen. Preferably, R₄is hydrogen.
Preferably, R₅is hydrogen. Preferably, R₆is hydrogen. Preferably, R₇is hydrogen.
Preferably, R₂is aryl or aralalkyl. More preferably, R₂is a phenyl group or a substituted phenyl group, for example, a mono-substituted phenyl group. Substitution may be ortho, meta, or para. Preferably, it is para. Preferred substituents include halogen and methyl. For example, and without limitation, R₂may be selected from phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl and 4-methylphenyl.
Accordingly, in a first aspect, the present invention may provide an encapsulated lactam wherein the lactam is a lactam of Formula Ia or Formula IIa:
wherein R is H, halogen (preferably, F, Cl, or Br), or C_1-4alkyl (preferably methyl).
In some embodiments, the encapsulated lactam is a lactam of formula Ia. In some embodiments, the encapsulated lactam is a lactam of formula IIa.
Importantly, lactams of formula Ia have been found to be unstable in high pH7 conditions (high pH refers to a pH of at least 7). Encapsulation improves stability in these conditions, permitting the lactams to be used in a wider variety of compositions.
Preferred lactams may include:
Suitably, the encapsulated lactam is a polymer encapsulated lactam.
The encapsulated lactam may be encapsulated in a polymer selected from a poly urea polymer, a melamine-formaldehyde copolymer; a urea formaldehyde copolymer and mixtures thereof.
The inventors have surprising found that lactams as described herein inhibit free radical polymerisation.
Accordingly, suitably the polymer is a condensation polymer.
For example, the polymer may be a condensation polymer of produced from a diamine and a diisocyanate.
For example, the polymer may be or may comprise a polyurea of Formula P1:
wherein R^P1comprises a phenylene and R^P2is an alkylene.
For example, R^P1may be —CH₂-phenylene; in other words, the polymer may be derived from polymethylene polyphenyl isocyanate.
For example, R^P2may be a straight chain alkylene of formula —(CH₂)_m—. In some cases, m is an integer from 2 to 10, for example from 2 to 8, for example from 4 to 8, for example, 6 (in other words, R^P2may be hexylene).
In other words, the lactam may be encapsulated in a polymer formed from polymethylene polyphenyl isocyanate and hexamethylenediamine.
In some cases, the polymer and/or encapsulate structure is selected and/or configured to permit controlled or triggered release. For example, the encapsulate may dissolve at a pre-determined rate under certain conditions. For example, the encapsulate may release in response to a trigger. The trigger may be, for example, the presence or a certain concentration of acid, base, a salt, an enzyme; or a non-chemical trigger such as ultrasound or light.
Suitably, the lactam is encapsulated to form particles whose average diameter is from about 10 nanometers to about 1000 microns, preferably from about 50 nanometers to about 100 microns, more preferably from about 2 to about 40 microns, even more preferably from about 4 to 15 microns. A particularly preferred range is from about 5 to 10 microns, for example 6 to 7 microns. The capsule distribution can be narrow, broad or multimodal. Multimodal distributions may be composed of different types of capsule chemistries.
The encapsulation process suitably is done in a carrier oil, which may be a ketone. For example, the carrier oil may be a C_5-20alkyl ketone, for example a C_5-15alkyl ketone, for example a C_5-10alkyl ketone, for example a C_6-8alkyl ketone, such as a C₇alkyl ketone. The alkylketone may be branched or straight-chain. Preferably, it is straight chain. The oxo group of the alkyl ketone may be located at C2; in other words, the alkylketone may be an alkyl-2-one. A preferred carrier oil is 2-heptanone.
The obtained encapsulated lactam in carrier oil may be used as an additive for compositions.
Accordingly, in a second aspect the present invention relates to an additive comprising an encapsulated lactam. Suitably, the encapsulated lactam is in provided in a carrier oil. The lactam may be a lactam of Formula I or Formula II.
Accordingly, in a second aspect the present invention may provide an additive comprising an encapsulated lactam wherein the lactam is a lactam of Formula Ia or Formula IIa (wherein R is as defined herein) in a carrier oil.
Preferred lactams may be as described for the first aspect.
In some embodiments, the carrier oil is an alkylketone as described above. Preferably it is a C_5-10alkyl-2-one, most preferably it is heptan-2-one.
The encapsulated lactams are suitable for use in compositions. The composition may be, without limitation, any of a personal care composition, a homecare composition, a pharmaceutical composition, or an industrial composition such as an anti-biofilm coating or paint, for example, for use in maritime environments. The composition may also be an agricultural chemical. The compositions may be suitable for use as antimicrobial, anti-biofilm and bacteriostatic compositions. Non-limiting examples of such compositions are provided herein. The compositions may also be used as additive compositions; in other words, the composition may be combined with further ingredients such as excipients to form a composition as described above.
Accordingly, in a third aspect the present invention relates to compositions comprising an encapsulated lactam. The lactam may be a lactam of Formula I or Formula II.
Accordingly, in a third aspect the present invention may provide a composition comprising an encapsulated lactam of Formula Ia or IIa (wherein R is as defined herein).
Preferred lactams may be as described for the first aspect.
Advantageously, the composition may be a composition of pH≥7, for example ≥8, for example ≥9, for example ≥10, for example ≥11.
Preferably the composition contains 0.000001 to 50% wt. lactam, more preferably 0.001 to 50% wt. even more preferably 0.01 to 5% wt, most preferably 0.01-2%.
In a fourth aspect, the present invention relates to method of encapsulating lactams, the method comprising interfacial polycondensation. The lactam may be a lactam of Formula I or Formula II, and the options and preferences described below may apply.
Accordingly, in a fourth aspect the present invention may provide a method of encapsulating a lactam of Formula Ia or lib (wherein R is as described herein), the method comprising:

- (a) combining said lactam with a carrier oil; then
- (b) combining said lactam in carrier oil with a first polymerization agent; then
- (c) combining the product of step (b) with an aqueous solution of a stabilizer;
- (d) adding an aqueous solution comprising a second polymerization agent
- to the product of step (c) while stirring the mixture;

wherein the first and second polymerization agents form a polymer when they react with each other.
It will be appreciated that the carrier oil and aqueous solution are immiscible. The polymerization is therefore interfacial polycondensation.
The first polymerization agent may be an isocyanate. For example, it may be polymethylene polyphenyl isocyanate. The second polymerization agent may be a diamine, for example an α,ω-diamino C_2-10alkylene such as hexamethylenediamine.
Suitably, the lactam is dissolved in the carrier oil. Preferred carrier oils are described above. In other words, the product of step (a) is a solution. Suitably, the concentration of the solution is about 0.5 wt %. It may be higher. For example, it may be about 1 wt %. In some cases, the concentration of the solution is less than 5 wt %, suitably less than 3 wt %.
Suitably, step (c) includes vigorous agitation, for example homogenization. The speed may be greater than 5 k rpm, for example, greater than 10 k rpm. It may be around 15 k rpm. Suitably, the product of step (c) is an emulsion (i.e. the mixture may be emulsified).
Suitably, step (d) includes stirring, for example at up to 1000 rpm, up to 500 rpm. It may be 200-300 rpm. Step (d) may last around 1 hour.
The process may include a curing step (step (e)). For example, step (e) may comprise agitation of the product of step (d) for 1 hour, 2 hours, 3 hours, 4 hours, 5 hours. The agitation may use a bottle roller.
The stabilizer may be sulfonate, for example a naphthalene sulfonate such as an alkyl naphthalene sulfonate condensate (NSC). A commercially available example is Morwet-D425®, available from AkzoNobel® (Surface Chemistry).
It will be appreciated that options and preferences described with respect to the first aspect apply equally where possible to the other aspects, and vice versa.

FIGURES

FIG. 1 shows a simple representation of encapsulation using an interfacial polycondensation method.

FIG. 2 shows a cured emulsion comprising an encapsulated lactam according to the invention.

FIG. 3 shows a microscope picture of encapsulated particles according to the invention.

DESCRIPTION

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.

Compositions

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.
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.
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.
The composition may also be used in medical applications, for example to coat equipment including medical devices.
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 optic 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.
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.
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). The composition may be a deodorant/anti-perspirant composition. 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.
In some cases, the composition is a contact lens cleaning fluid.
The composition may be a composition suitable for use in agriculture, for example, as a soil additive (solid or liquid).
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

The following syntheses are provided by way of illustration and exemplification, and not by way of limitation.
Encapsulation was achieved via an interfacial polycondensation method which can be represented simply as shown in FIG. 1.
The following representative example uses 4-(4-chlorophenyl)-5-methylene-pyrrol-2-one.
2-heptanone was used as the carrier (oil phase) for the lactam at a ratio of 1:199 (Lactam:Heptanone) which equates to 0.5% lactam solution. The inventor(s) have determined that the lactam is also soluble at 1%. The isocyanate was polymethylene polyphenyl isocyanate (Mn340) and the crosslinker was hexamethylenediamine (HMDA). Emulsification was carried out at a shear of 15K. The stabiliser is a commercial naphthalene sulphonate called Morwet-D425®. Morwet forms dark brown solutions so the encapsulated slurry is often buff/brown coloured.

PU Encapsulation Procedure

Preparation of Oil Phase A: 5 g (2-Heptanone:Lactam; 1:199) and 0.42 g isocyanate (PMDI, 340) were mixed in a 28 ml vial and agitated until fully dissolved.
Preparation of aqueous Phase B: 16 ml water containing 3 wt % MorwetD425 was prepared in a beaker.
Preparation of amine soln C: An aqueous HMDA solution (40%) was prepared.
Phase B was added to phase A under homogenization at 15 k rpm and then the mixture emulsified for 2 min (buff coloured emulsion obtained). Afterward, 1 ml of solution C was added dropwise into the emulsion over 1 min whilst stirring at 200-300 rpm. After 1 hour the sample slurry was placed on a bottle roller for approx. 5 hours to obtain a cured emulsion shown in FIG. 2.
As can be seen from FIG. 3, encapsulated particles were obtained.
-oOo-
It will be appreciated that, except where expressly provided otherwise, all preferences are combinable.

Claims

1. An encapsulated lactam wherein the lactam is a lactam of Formula Ia or Formula IIa:

wherein R is H, halogen, or C_1-4alkyl; characterised in that encapsulated lactam is encapsulated in a condensation polymer.

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

3. The encapsulated lactam of claim 1, wherein the lactam is selected from:

4. The encapsulated lactam of claim 1 wherein the lactam is encapsulated in a polymer selected from a poly urea polymer, a melamine-formaldehyde copolymer; a urea formaldehyde copolymer and mixtures thereof.

5. The encapsulated lactam of claim 1 wherein the lactam is encapsulated in a polymer formed from polymethylene polyphenyl isocyanate and hexamethylenediamine.

6. An additive comprising an encapsulated lactam according to claim 1 in a carrier oil.

7. The additive of claim 6, wherein the carrier oil is an alkyl ketone, optionally wherein the carrier oil is heptan-2-one.

8. A composition comprising an encapsulated lactam according to claim 1.

9. The composition of claim 8, wherein the composition contains 0.000001 to 50% wt. lactam, optionally 0.001 to 50% wt., optionally 0.01 to 5% wt, optionally 0.01-2%.

10. A method of encapsulating a lactam, wherein the lactam is a lactam of Formula Ia or Formula IIa:

wherein R is H, halogen, or C_1-4alkyl,

the method comprising:

(a) combining said lactam with a carrier oil; then

(b) combining said lactam in carrier oil with a first polymerisation agent; then

(c) combining the product of step (b) with an aqueous solution of a stabilizer;

(d) adding an aqueous solution comprising a second polymerization agent to the product of step (c) while stirring the mixture;

wherein the first and second polymerization agents form a polymer when they react with each other.

11. The method of claim 10, wherein step (a) comprises dissolving said lactam in an alkyl ketone to form a solution, optionally wherein the alkyl ketone is heptan-2-one and/or optionally wherein the concentration of the solution is less than 1% wt.

12. The method of claim 10, wherein the first polymerization agent is an isocyanate, optionally polymethylene polyphenyl isocyanate.

13. The method of claim 10, wherein the second polymerization agent is an α,ω-diamino C_2-10alkylene; optionally hexamethylenediamine.

14. The method of claim 10, wherein the method further comprising the step of agitating the product of step (d) for at least one 1 hour; optionally around 5 hours.