COMPOSITION

Abstract
Antimicrobial composition comprising a lactam and a hydrotrope. Antimicrobial additive composition containing a lactam and a hydrotrope.
Description

The present invention relates to an improved antimicrobial composition comprising a lactam.


WO 2007/085042 and WO 2004/016588 disclose lactams for antimicrobial benefit.


Despite the prior art there remains a need for improved antimicrobial compositions.


Accordingly, and in a first aspect of the present invention there is provided an antimicrobial composition comprising a lactam and a hydrotrope preferably wherein the lactam is of formula (I) or (II):




embedded image


In a second aspect, there is provided an antimicrobial additive composition containing a lactam and a hydrotrope.


Preferably the anti-microbial composition and additive 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 third aspect of the invention there is provided an antimicrobial composition comprising an antimicrobial additive composition of the second aspect.


In a fourth aspect there is provided a method for making an antimicrobial composition comprising the steps:


(i) directly mixing a lactam with a hydrotrope to form an antimicrobial additive composition


(ii) mixing the antimicrobial additive composition of (i) with an aqueous carrier.


In a fifth aspect there is provided a method for making an antimicrobial additive composition comprising the step of directly mixing a hydrotrope with a lactam.


In a sixth aspect, the present invention provides the use of an antimicrobial composition according to the first and third aspect or an antimicrobial additive composition according to the second aspect for preventing or disrupting microbial growth.


Preferably the antimicrobial additive composition and the method of making said additive composition is substantially free of further components.


The term “substantially free” as used herein shall be understood to mean relatively little to no amount of any content. Preferably the antimicrobial contains less than 1 wt. % more preferably less than 0.1 wt. % of further components.


Preferably the aqueous carrier is suitable for use as a carrier for a home or personal care product. Preferred personal care products include shampoos, hair conditioners, deodorants, skin cleansing compositions and oral care products such as toothpastes and mouthwashes. Preferred home care products are for example a hard surface cleaner or laundry composition.


The antimicrobial additive composition according to the invention can be used as an antimicrobial raw material where it would be diluted in a further composition or the composition may be a consumer product the application of which is intended to provide antimicrobial effect to a substrate or even as a preservative when added to a consumer composition.


Preferably the lactam is of formula (I) or (II):




embedded image


Preferably the lactam is of formula (I) or (II) wherein:


R1 and R2 are each independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, aryl and aralalkyl; and


R3 is selected from hydrogen, hydroxyl, alkyl, cycloalkyl, alkoxy, oxoalkyl, alkenyl, heterocyclyl, heteroaryl, cycloalkyl, aryl, aralalkyl and —C(O)CR6=CH2;


R4 and R5 are independently selected from hydrogen, aryl, heterocyclyl, heteroaryl, and arylalkyl; and


R6 is selected from hydrogen and methyl; and


R7 is selected from hydrogen and —C(O)CR6=CH2; and


Preferably, at least one of R4 and R5 is hydrogen; and


Preferably, at least one of R1 and R2 is selected from hetercyclyl, heteroaryl, aryl and arylalkyl; and


Preferably, R1 is hydrogen. Preferably, R3 is hydrogen. Preferably, R4 is hydrogen. Preferably, R5 is hydrogen. Preferably, R6 is hydrogen; and


Preferably, R2 is aryl or aralalkyl. More preferably, R2 comprises a halogen substituted phenyl group.


Preferably, the hydrotrope is selected from monopropylene glycol, dimethylsulphoxide, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene derivatives of castor oil and ethanol.


Preferably, the hydroptrope is present at from 0.001 to 25% wt. of the composition.


Preferred lactams are:

  • 5-methylene-4-(4′-bromophenyl)-dihydroprrol-2-one (Ref. 295)
  • 5-methylene-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref. 310)
  • 5-methylene-4-phenyl-1H-pyrrol-2(5H)-one (Ref. unsubstituted)
  • methyl 2-(3-(4-fluorophenyl)-2-methylene-5-oxo-2,5-dihydro-1H-pyrrol-1-yl) (Ref. 309)
  • 3-Bromo-4-hexyl-5-(bromomethylene)-2(5H)-furanone (Ref. 113)
  • 4-(4-Trifluoromethyl)phenyl)-2(5H)-furanone (Ref. 265)
  • 5-Hydroxy-5-methyl-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref. 313)
  • 5-(Thiophenyl-3-methylene)furan-(2H)-one (Ref. 350)


The most preferred lactams are:

  • 5-methylene-4-(4′-bromophenyl)-dihydroprrol-2-one (Ref. 295)
  • 5-methylene-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref. 310)
  • 5-methylene-4-phenyl-1H-pyrrol-2(5H)-one (Ref. unsubstituted)
  • methyl 2-(3-(4-fluorophenyl)-2-methylene-5-oxo-2,5-dihydro-1H-pyrrol-1-yl) (Ref. 309)


Preferably, the hydrotrope is selected from monopropylene glycol, dimethylsulphoxide, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene derivatives of castor oil and ethanol.


Preferably, the polyoxyethylene sorbitan fatty ester is a monoester selected from monolaurate, monopalmitate, monostearate and monooleate.


Preferably, the polyoxyethylene sorbitan fatty ester comprises from 5 to 80 oxyethylene units, more preferably from 10 to 45 and most preferably 20. Examples include Polysorbates 20, 40, 60 and 80.


The most preferred polyoxyethylene sorbitan fatty ester is Polysorbate 20.


Preferably, the polyoxyethylene derivative of castor oil comprises from 10 to 50 oxyethylene units, more preferably from 30 to 45 and most preferably 40. Examples include PEG-20, 40 and 60 hydrogenated castor oil.


The most preferred polyoxyethylene derivative of castor oil is PEG-40 hydrogenated castor oil.


Preferably, the composition is a home care or personal care product.


Preferred personal care products include shampoos, hair conditioners, deodorants, skin cleansing compositions and oral care products such as toothpastes and mouthwashes. Preferred home care products include a hard surface cleaner or laundry composition.


Lactams

Suitable lactams are disclosed in WO 2007/085042 and WO 2004/016588 the contents of which with particular regard to the manufacture of lactams and from WO 2007/085042 the manufacture of acrylate polymers with certain lactams associated thereto, is incorporated by reference.


For example:




embedded image


embedded image


embedded image







EXAMPLE 1

The following data illustrates the antimicrobial efficacy of a laundry composition (hereinafter ‘base composition’) comprising a lactam (Ref. 295 and Ref. Unsubstituted) and a hydroptrope (monopropylene glycol) but only where hydroptrope is mixed with lactam before adding to the remainder of the composition. The test samples were as follows:


A lactam and hydroptrope only


B lactam added directly to base formulation (which contains MPG)—no pre-mixing prior to addition


C lactam pre-mixed with hydrotrope and then added to base formulation


D hydrotrope only added to base formulation


Base Formulation















%
%

Amount


activity
required
Component
in 100 g


















100
45.87
Demin Water
39.05


100
4.13
Glycerol
4.13


100
7.43
Mono Propylene Glycol (with or
7.43




without lactam according to BDC




above)


47
2.12
NaOH
4.51


100
2.10
Triethanolamine (TEA)
2.10


100
16.59
Primary Alcohol Ethoxylate (7EO)
16.59


68
0.10
Optical Brightener
0.15


50
0.81
Citric Acid
1.62


97.1
11.06
LAS Acid
11.39


100
3.10
Fatty Acid
3.10


70
5.53
SLES 3EO
7.90


32
0.41
Diethylenetriamine penta(methylene
1.28




phosphonic acid)


100
0.75
Liquid Protease
0.75



100.00









Test samples were diluted in sterile water to achieve a 11.5 ppm level of lactam. Dilute solution (80 μl) was added to a S. epidermidis suspension (20 μl) of bacteria at a concentration of 8 logs in a microplate. Growth media (100 μl tryptone soya broth) was added to each well of the microplate and incubated for 20 hours. Bacterial respiration was measured every 30 minutes and the results were:


A—lactam+hydrotrope only (respiration of surviving bacteria detected ˜4-5 h)


B—lactam added directly to base formulation (which contains MPG)—no pre-mixing prior to addition (respiration of surviving bacteria detected 4-5 hrs)


C—lactam pre-mixed with hydrotrope and then added to base formulation (respiration of surviving bacteria not detected—20 hrs is max detection time)


D—hydrotrope added to base formulation (respiration of surviving bacteria detected 3-4 hrs).


The results are shown in FIG. 1.


EXAMPLE 2

The following illustrates the broad application of the invention within the realm of lactams.


The example below is from data obtained when pre-blending lactams with hydrotrope before adding to the remainder of the composition, and diluting to 11.5 ppm and 0.575 ppm in sterile water in order to assess efficacy against S. epidermidis suspension Dilute solution (80 μl) was added to a S. epidermidis suspension (20 μl) of bacteria at a concentration of 8 logs in a microplate. Growth media (100 μl tryptone soya broth) was added to each well of the microplate and incubated for 20 hours. Bacterial respiration was measured every 30 minutes. Data of the test samples were then compared to un-treated cell suspensions (sterile water added instead of test samples) and percent inhibition calculated.

















Result (inhibition of




bacterial respiration



Test
versus water control)









5-methylene-4-(2′-fluorophenyl)-
79.4%



dihydropyrrol-2-one



5-methylene-4-(4′-bromophenyl)-
82.5%



dihydroprrol-2-one



5-methylene-4-phenyl-1H-pyrrol-2(5H)-
82.5%



one










EXAMPLE 3

The aim of this example was to investigate methods of achieving solubility of 5-methylene-4-phenyl-1H-pyrrol-2(5H)-one (Ref. unsubstituted) into the following above described base formulation.


An Ultrasonic mixer was used to obtain determine solubility.


We used a Hielscher UP200S (200W) Sonic Tip on batches of 5-20 ml. We sonicated for up to 60 minutes.


















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
base @ 5%







3% in
Magnetic stirring
~25% of lactam
Clear solution with


Polysorbate
1 hour
solubilised.
a large quantity of


20

Particles visible.
particles visible


3% in PEG-
Magnetic stirring
~25% of lactam
Clear solution with


40
1 hour
solubilised.
a large quantity of


Hydrogenated

Particles visible.
particles visible


Castor Oil


3% in
Magnetic stirring
No solubility



Isopentyldiol
1 hour
observed.


3% in MMB
Magnetic stirring
No solubility




1 hour
observed.


3% in
Magnetic stirring
No solubility



Diglycerin
1 hour
observed.


3% in
Magnetic stirring
No solubility



Diglycerin
1 hour
observed.


3% in
Magnetic stirring
No solubility



Pentylene
1 hour
observed.


Glycol


3% in
Magnetic stirring
No solubility



Hexylene
1 hour
observed.


Glycol


3% in
Magnetic stirring
No solubility



Hexylene
1 hour
observed.


Glycol


3% in PEG-
Magnetic stirring
~10% of lactam
Cloudy in solution


60
1 hour
solubilised.


Hydrogenated

Particles visible.


Castor Oil


3% in
Magnetic stirring
~10% of lactam
Cloudy and gel-like


Polysorbate
1 hour, 50 C.
solubilised.
lumps in solution


60

Particles visible.


3% in
Magnetic stirring
~10% of lactam
Cloudy and gel-like


Polysorbate
1 hour
solubilised.
lumps in solution


80

Particles visible.


3% in
Magnetic stirring
~5% of lactam



Dipropylene
1 hour
solubilised


Glycol

(slight colour




change observed




showing this.




Particles visible.


3% in
Magnetic stirring
~5% of lactam
Cloudy when cooled


Sorbitan
1 hour, 50 C.
solubilised
or added to M30


Oleate

(slight colour




change observed




showing this.




Particles visible.


3% in
Magnetic stirring
~5% of lactam
Cloudy solution with


Sisterna
1 hour
solubilised
large number of


SP30-C

(slight colour
particles visible.




change observed




showing this.




Particles visible.


3% in
Magnetic stirring
~5% of lactam
Hazy solution with


Sisterna
1 hour
solubilised
large number of


SP50-C

(slight colour
particles visible.




change observed




showing this.




Particles visible.


3% in
Magnetic stirring
~5% of lactam
Cloudy solution with


Sisterna
1 hour
solubilised
large number of


SP70-C

(slight colour
particles visible.




change observed




showing this.




Particles visible.









The polysorbates and Pegylated castor oil were considered suitable enough to pursue further experimentation.


Further Evaluations with Each Candidate Solubiliser


We then tested the candidate solubilisers with 1% lactam, both with 72 hours high speed magnetic stirring (with held temperature of ˜500 in the cases of solubilisers that solidify alone at room temperature) and also 20 minutes Sonication.


Preparation of the Lactam Solutions

In each case we incorporated the lactam powder into the solubilisers (at the levels indicated in the below table) using high speed stirring to avoid lumps from forming. Once the powder was added, the described mixing method (either continued high speed stirring or Ultrasonic mixing) commenced. In the cases of Sorbitan Oleate and Polysorbate-60, we applied initial heating to approx. 500 to ensure the solubilisers were fully liquid prior to commencing addition of the lactam. Both of these materials are non-flowing at room temperature. PEG-40 Hydrogenated Castor required initial heating to ˜350 to ensure complete fluidity prior to commencing.


Incorporation of the Lactam Solutions into Base


The base sample provided had a 5% ‘gap’ purposely left out as space for the lactam solution to be added. We ensured the lactam solutions were fully uniform through constant mechanical agitation (to avoid the settling of any unsolubilised lactam material) and added them to base using slow speed stirring to incorporate them without generating aeration.


Stability Testing

We conducted stability testing on all test variants that looked positive (i.e. a reasonable proportion of lactam was solubilised). We prepared samples of the test variants in clear plastic jars and placed them at various temperature conditions:

    • Ambient temperature.
    • 40 C.
    • 50 C.
    • Refrigerator.
    • High light (‘shop’ window).


The aim was to observe any difference in colour, viscosity, solubility or general physical stability. The samples were evaluated every day and compared to the ambient temperature sample to note any changes. All samples were allowed to equilibrate to ambient temperature before being evaluated.


Isopentyldiol


















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
M30 @ 5%







1% in
Magnetic stirring
No solubility



Isopentyldiol
72 hours
observed at any




stage.


1% in
20 minutes
~5% of lactam



Isopentyldiol
sonication. Temp
solubilised



reached 60-70 C.
(forced). Large




number of




particles visible.









3-Methoxy-3-methyl-1-butanol


















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
M30 @ 5%







1%
Magnetic stirring
No solubility




72 hours
observed at any




stage.


1%
20 minutes
~5% of lactam




sonication. Temp
solubilised



reached 60-70 C.
(forced). Large




number of




particles visible.









Diglycerin


















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
M30 @ 5%







1%
Magnetic stirring
No solubility




72 hours
observed at any




stage.


1%
20 minutes
No solubility




sonication. Temp
observed.



reached 60-70 C.









Pentylene Glycol


















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
M30 @ 5%







1%
Magnetic stirring
~5% of lactam




72 hours
solubilised. Large




number of




particles visible.


1%
20 minutes
~5% of lactam




sonication. Temp
solubilised. Large



reached 60-70 C.
number of




particles visible.









PEG-60 Hydrogenated Castor Oil


















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
M30 @ 5%







1%
Magnetic stirring
~25% of lactam
Cloudy in solution.



72 hours at 50 C.
solubilised.
Particles visible.




Particles visible.


1%
20 minutes
~25% of lactam
Cloudy in solution.



sonication. Temp
solubilised.
Particles visible.



reached 60-70 C.
Particles visible.









Polysorbate 60


















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
M30 @ 5%







1%
Magnetic stirring
~25% of lactam
Cloudy in solution.



72 hours at 50 C.
solubilised.
Particles visible.




Particles visible.


1%
20 minutes
~25% of lactam
Cloudy in solution.



sonication. Temp
solubilised.
Particles visible.



reached 60-70 C.
Particles visible.









Polysorbate 80


















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
M30 @ 5%







1%
Magnetic stirring
~25% of lactam
Cloudy in solution.



72 hours at 50 C.
solubilised.
Particles visible.




Particles visible.


1%
20 minutes
~25% of lactam
Cloudy in solution.



sonication. Temp
solubilised.
Particles visible.



reached 60-70 C.
Particles visible.









Sisterna SP30-C


















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
M30 @ 5%







1%
Magnetic stirring
~25% of lactam
Cloudy in solution.



72 hours at 50 C.
solubilised.
Particles visible.




Particles visible.


1%
20 minutes
~25% of lactam
Cloudy in solution.



sonication. Temp
solubilised.
Particles visible.



reached 60-70 C.
Particles visible.









Sisterna SP50-C


















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
M30 @ 5%







1%
Magnetic stirring
~25% of lactam
Cloudy in solution.



72 hours at 50 C.
solubilised.
Particles visible.




Particles visible.


1%
20 minutes
~25% of lactam
Cloudy in solution.



sonication. Temp
solubilised.
Particles visible.



reached 60-70 C.
Particles visible.









Sisterna SP70-C


















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
M30 @ 5%







1%
Magnetic stirring
~25% of lactam
Cloudy in solution.



72 hours at 50 C.
solubilised.
Particles visible.




Particles visible.


1%
20 minutes
~25% of lactam
Cloudy in solution.



sonication. Temp
solubilised.
Particles visible.



reached 60-70 C.
Particles visible.









Polysorbate 20




















Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
M30 @ 5%





3%
Magnetic stirring
~25% of lactam
Clear solution with



1 hour
solubilised.
a large quantity of




Particles visible.
particles visible


4.2%
Magnetic stirring.
~25% of lactam
Clear solution with



24 hours
solubilised,
a large quantity of




Particles visible.
particles visible


4.2%
Magnetic stirring.
~25% of lactam
Clear solution with



24 hours.
solubilised,
a large quantity of




Particles visible.
particles visible




Initially stirred for




2, 4 and 6 hours.




No real changed




observed during




this time (all max.




25% solubilised).


4.2%
20 minutes
~50% of lactam
Clear solution with



sonication. Temp
solubilised.
a large quantity of



reached 60-70 C.
Particles visible
particles visible


4.2%
60 minutes
~60-70% of lactam
Clear solution with



sonication. Temp
solubilised.
a large quantity of



reached 90 C.
Particles visible
particles visible


2.1%
20 minutes
~90% of lactam
Clear solution. A



sonication. Temp
solubilised. Dark
very small number



reached 60-70 C.
colour formed
of remaining





unsolubilised





lactam particles





visible


2.1%
60 minutes
90% of lactam
Clear solution with



sonication. Temp
solubilised. Some
a minute number



reached 90-100 C.
small particles
of particles visible.




visible.


4.2%
Magnetic stirring.
~25% of lactam
Clear solution with



48 hours
solubilised,
a large quantity of




Particles visible.
particles visible


2.1%
Magnetic stirring.
~50% of lactam
Clear solution with



24 hours
solubilised,
a large quantity of




Particles visible.
particles visible


2.1%
Magnetic stirring.
~75% of lactam
Clear solution with



48 hours
solubilised,
a large quantity of




Particles visible.
particles visible


2.1%
Magnetic stirring,
~50% of lactam
Clear solution with



heated to 50 C. 8
solubilised,
a large quantity of



hours.
Particles visible.
particles visible


3%
20 minutes
~50% of lactam
Clear solution with



sonication. Temp
solubilised.
a large quantity of



reached 60-70 C.
Particles visible
particles visible








Observations


% lactam in

Observations of
when added to


solvent
Mixing method
solvent solution
base @ 5%





3%
60 minutes
~60-70% of lactam
Clear solution with



sonication. Temp
solubilised.
a large quantity of



reached 90 C.
Particles visible
particles visible


1%
Magnetic stirring.
~75% of lactam
Clear solution with



24 hours
solubilised,
a few particles




Particles visible.
visible


1%
Magnetic stirring.
~95% of lactam
Clear solution with



72 hours
solubilised A few
a few particles




particles visible.
visible




After 48 hours it




was approx. 80-




85%.


2.1%
Magnetic stirring,
~75% of lactam
Clear solution with



heated to 50 C. 72
solubilised,
a large quantity of



hours.
Particles visible.
particles visible


1.5%
Magnetic stirring.
~50% of lactam
Clear solution with



48 hours
solubilised,
a large quantity of




Particles visible.
particles visible


1.5
Magnetic stirring,
~75% of lactam
Clear solution with



heated to 50 C. 72
solubilised,
a large quantity of



hours.
Particles visible.
particles visible


1.5%
20 minutes
~75% of lactam
Clear solution with



sonication. Temp
solubilised. Some
a number of



reached 60-70 C.
Particles visible
particles visible


1.5%
60 minutes
~95% of lactam
Clear solution with



sonication. Temp
solubilised.
a minute number



reached 80-90 C.
Particles visible.
of particles visible




Dark brown colour.


2.1%
60 minutes
90% of lactam
Clear solution with



sonication. Temp
solubilised. Some
a minute number



reached 80 C.
small particles
of particles visible.




visible.









PEG-40 Hydrogenated Castor Oil


















Observations


% lactam

Observations of
when added to


in solvent
Mixing method
solvent solution
M30 @ 5%







3%
Magnetic stirring
~25% of lactam
Clear solution with



1 hour
solubilised.
a large quantity of




Particles visible.
particles visible


4.2%
Magnetic stirring.
~25% of lactam
Clear solution with



24 hours
solubilised,
a large quantity of




Particles visible.
particles visible


4.2%
Magnetic stirring.
~25% of lactam
Clear solution with



24 hours.
solubilised,
a large quantity of




Particles visible.
particles visible




Initially stirred for




2, 4 and 6 hours.




No real changed




observed during




this time (all max.




25% solubilised).


4.2%
Magnetic stirring.
~25% of lactam
Clear solution with



48 hours
solubilised,
a large quantity of




Particles visible.
particles visible


2.1%
Magnetic stirring.
~50% of lactam
Clear solution with



24 hours
solubilised,
a large quantity of




Particles visible.
particles visible


2.1%
Magnetic stirring.
~75% of lactam
Clear solution with



48 hours
solubilised,
a large quantity of




Particles visible.
particles visible


4.2%
20 minutes
50% of lactam
Clear solution with



sonication. Temp
solubilised. Large
a large number of



reached 60-70 C.
number of
particles visible




particles visible.




Very dark colour.


4.2%
60 minutes
75% of lactam
Some fragments



sonication. Temp
solubilised. Very
visible in M30,



reached 110 C.
dark colour.
suggesting partial





breakdown of





solvent.


4.2%
60 minutes
75% of lactam
Fragments



sonication. Temp
solubilised. Very
avoided due to



reached 80 C.
dark colour.
temperature





control. Clear





solution with some





small particles





visible.


2.1%
20 minutes
90% of lactam
Clear solution with



sonication. Temp
appeared to
a small number of



reached 80 C.
solubilise however
black particles




small amount of
visible




‘burnt’ spots




visible.


2.1%
60 minutes
lactam solubilised.
Some fragments



sonication. Temp
Very dark colour.
visible in M30,



reached 110 C.

suggesting partial





breakdown of





solvent.


2.1%
Magnetic stirring,
~50% of lactam
Clear solution with



heated to 50 C. 8
solubilised,
a large quantity of



hours.
Particles visible.
particles visible


3%
20 minutes
~75% of lactam
Clear solution with



sonication. Temp
solubilised.
a large quantity of



reached 60-70 C.
Particles visible
particles visible


3%
60 minutes
~75% of lactam
Clear solution with



sonication. Temp
solubilised.
a large quantity of



reached 80 C.
Particles visible
particles visible


1%
Magnetic stirring.
~75% of lactam
Clear solution with



24 hours
solubilised,
a few particles




Particles visible.
visible


1%
Magnetic stirring.
~90% of lactam
Clear solution with



72 hours
solubilised, A few
a few particles




particles
visible


1%
Magnetic stirring.
~99% of lactam
Clear solution with



72 hours with
solubilised, A tiny
a very small



temp. at 50 C.
number of
number of




particles remained
particles visible


2.1%
30 minutes
lactam appeared
Clear solution with



sonication. Temp
to solubilise
a small number of



reached 90 C.
however ‘burnt’
black particles




spots visible.
visible









Observation and Formulation Rules
Temperature and Colour Change

One of our first observations was the colour change which was visible in all successful (or partially successful) samples. We saw development of a slight amber tinge to the solution when some lactam was starting to become solubilised. This colour change progressed rapidly when samples exceeded 50 C, resulting in a dark brown colour. When the temperature reached 65C, the dark brown colour was virtually opaque*.


*This level of temperature was only tested for the Polysorbate-20 and PEG-40 Hydrogenated Castor Oil variants.


From observations throughout the project, we concluded that ˜50 C was the optimum temperature for solubilising the lactam.


Mixing Conditions

Very long periods of mechanical stirring (48-72 hours) resulted in improvements in solubilisation compared to shorter periods; however we did not find this length of mixing to be sufficient for full solubilisation. Ultrasonic mixing did prove to be far more successful and we concluded would be required for effective solubilisation, certainly with the shortlisted Polysorbate-20 and PEG-40 Hydrogenated Castor Oil candidates.


From all of the trials conducted, we believe with the right Ultrasonic mixing conditions (of energy versus batch size versus controlled max. 50 C temperature), efficient solubilisation could be achieved.

Claims
  • 1. Antimicrobial additive composition containing a lactam and a hydrotrope, wherein the hydrotrope is selected from the group consisting of monopropylene glycol, dimethylsulphoxide, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene derivatives of castor oil and ethanol.
  • 2. Antimicrobial additive composition according to claim 1 wherein the additive composition is substantially free of further components.
  • 3. Antimicrobial composition comprising a lactam and a hydrotrope, wherein the hydrotrope is selected from the group consisting of monopropylene glycol, dimethylsulphoxide, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene derivatives of castor oil and ethanol.
  • 4. Antimicrobial composition comprising an antimicrobial additive composition of claim 1.
  • 5. (canceled)
  • 6. Antimicrobial composition according to claim 1 wherein the hydrotrope is present at from 0.001 to 5% wt. of the composition.
  • 7. Antimicrobial composition or additive composition according to claim 1 wherein the lactam is of formula (I) or (II):
  • 8. Antimicrobial composition or additive composition according to claim 1 wherein the lactam is selected from the group consisting of: 5-methylene-4-(4′-bromophenyl)-dihydroprrol-2-one (Ref. 295), 5-methylene-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref. 310), 5-methylene-4-phenyl-1H-pyrrol-2(5H)-one (Ref. unsubstituted), methyl 2-(3-(4-fluorophenyl)-2-methylene-5-oxo-2,5-dihydro-1H-pyrrol-1-yl) (Ref. 309), 5-methylene-4-phenyl-dihydro-pyrrol-2-one (Ref. 219), 3-Bromo-4-hexyl-5-(bromomethylene)-2(5H)-furanone (Ref. 113), 4-(4-Trifluoromethyl)phenyl)-2(5H)-furanone (Ref. 265), 5-Hydroxy-5-methyl-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref. 313), 5-(Thiophenyl-3-methylene)furan-(2H)-one (Ref. 350) and mixtures thereof.
  • 9. Antimicrobial composition or additive composition according to claim 1 wherein the lactam is selected from the group consisting of: 5-methylene-4-(4′-bromophenyl)-dihydroprrol-2-one (Ref. 295), 5-methylene-4-(2′-fluorophenyl)-dihydropyrrol-2-one (Ref. 310), 5-methylene-4-phenyl-1H-pyrrol-2(5H)-one (Ref. unsubstituted), methyl 2-(3-(4-fluorophenyl)-2-methylene-5-oxo-2,5-dihydro-1H-pyrrol-1-yl) (Ref. 309) and mixtures thereof.
  • 10. Antimicrobial composition or additive composition according to claim 1 wherein the lactam is present at from 0.001 to 50% wt. of the composition.
  • 11. Antimicrobial composition or additive composition according to claim 5 wherein the polyoxyethylene derivative of castor comprises 40 oxyethylene units.
  • 12. Antimicrobial composition or additive composition according to claim 5 wherein the polyoxyethylene sorbitan fatty ester comprises from 5 to 80 oxyethylene units.
  • 13. Antimicrobial composition or additive composition according to claim 1 which is a home or personal care composition.
  • 14. Antimicrobial composition or additive composition according to claim 13 which is selected from a shampoo, conditioner, deodorant, skin cleansing composition, antiperspirant.
  • 15. Antimicrobial composition or additive composition according to claim 13 which is selected from a laundry composition, hard surface cleaner and toilet cleaner.
  • 16. (canceled)
  • 17. Method for making an antimicrobial composition comprising the steps: (i) directly mixing a lactam with a hydrotrope to form an antimicrobial additive composition; and(ii) mixing the antimicrobial additive composition of step (i) with an aqueous carrier.
  • 18. (canceled)
  • 19. (canceled)
  • 20. Use of an antimicrobial additive composition or composition according to claim 1 for preventing or disrupting microbial growth.
  • 21. (canceled)
Priority Claims (1)
Number Date Country Kind
13153600.5 Feb 2013 EP regional
PCT Information
Filing Document Filing Date Country Kind
PCT/EP2014/051731 1/29/2014 WO 00