Patent Application
20240399330
The present invention concerns the technical field of methods for the manufacture of core-membrane capsules.
It concerns in particular the methods for the manufacture of core-membrane capsules, by interfacial polymerization technique.
The production of microcapsules from di- and polyisocyanates, and diethylene triamine (DETA), currently constitutes a method of choice for encapsulation manufacturers.
However, for reasons of toxicity, more drastic restrictions on the use of diisocyanates are being considered, which could extend to oligomers and polyisocyanates. Indeed, these molecules would be the cause of asthma in exposed workers.
There is therefore a need for new reactive molecules for the implementation of encapsulation techniques.
In order to remedy the aforementioned drawback of the state of the art, the present invention proposes to implement molecules with azlactone functionality as crosslinking agent in encapsulation methods by interfacial polymerization.
More particularly, according to the invention, a method is proposed for the manufacture of core-membrane capsules, which manufacturing method comprises the following successive steps:
The present invention thus proposes new reactive molecules, for the implementation of encapsulation techniques, advantageously as an alternative to compounds from the isocyanate family.
Other non-limiting and advantageous characteristics of the product/method in accordance with the invention, taken individually or in all technically possible combinations, are as follows:
in which R3 represents an aliphatic, linear or branched hydrocarbon group, comprising from 1 to 30, preferably from 1 to 20, carbon atoms which can be interrupted by one or more oxygen or sulfur atoms,
R1 and R2 independently represent a (C1-C10)alkyl group, a (C3-C6) cycloalkyl group, an aryl group, an aryl (C1-C10)alkyl group, or a heterocyclic group, and
The present invention also concerns core-membrane capsules, resulting from a method according to the invention, including a polyamide membrane.
The core-membrane capsules advantageously have a diameter ranging from 50 nm to 5 mm, preferably from 5 to 100 μm.
Of course, the different characteristics, variants and embodiments of the invention can be associated with each other in various combinations as long as they are not incompatible or exclusive of each other.
The present invention thus concerns a method for manufacturing core-membrane capsules.
Such a manufacturing method is still commonly referred to as an encapsulation method or microencapsulation method.
By «encapsulation» or «microencapsulation», is meant in particular the method by which a product (advantageously liquid) is enclosed in a capsule.
By «capsules» is meant in particular particles (advantageously spherical) which are made up of a membrane (advantageously rigid) containing a core (advantageously liquid), and which thus constitute a reservoir system.
A capsule according to the invention constitutes a solid particle comprising a core (content), advantageously liquid, which is surrounded by a membrane (solid).
The term «membrane» means, according to the invention, a continuous wall (advantageously seamless) around the (advantageously liquid) encapsulated core.
Preferably, the membrane isolates and protects the core from the external environment and/or allows control of its release in a selected environment.
According to the invention, the membrane comprises a polyamide polymer.
A polyamide (PA) is a polymer containing amide functions.
Generally, the manufacturing method according to the invention uses reactive molecules carrying azlactone functions, in combination with reactive molecules carrying amine functions, to generate the polyamide polymer membrane by an interfacial polymerization reaction.
The azlactone function actually exhibits reactivity with the amine functions. The reaction of the amine function with the carbon carrying the ester function of the azlactone function cycle leading to the opening of this cycle.
This reaction leads to the creation of the amide bond, an example of which is illustrated in the following synthesis reaction (V) between an amine function and an azlactone type function:
According to the invention, this reaction is taken advantage of in the context of the present invention, in encapsulation in order to form the polyamide membrane which envelops the core of the capsules.
According to the invention, the capsules are advantageously obtained by a manufacturing method comprising the following successive steps:
The two immiscible solutions, described in more detail below, are selected from:
Generally, an azlactone group is also referred to as an oxazolone group.
Preferably, said at least two azlactone groups of the first reactive molecule each correspond to general formula (I)
Such an azlactone group of general formula (I) according to the invention advantageously constitutes a derivative of a 5-(4H) oxazolone or 2-oxazolin-5-one group.
Such a group is further described in document FR-2 997 082 or document FR-3 054 235.
In this general formula (I), R1 and R2 independently represent a (C1-C10)alkyl group, a (C3-C6) cycloalkyl group, an aryl group, an aryl (C1-C10)alkyl group, or a heterocyclic group.
According to the present invention, the term «(C1-C10) alkyl» represents a saturated, linear or branched, hydrocarbon group, having from 1 to 10 carbon atoms, advantageously from 1 to 5 carbon atoms. By way of example, mention may be made of the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, neopentyl, isopentyl, tert-pentyl, hexyl, isohexyl, heptyl, octyl, nonyl and decyl groups.
A «(C3-C6) cycloalkyl group» represents a saturated, cyclic hydrocarbon group having 3 to 6 carbon atoms.
The term «aryl» represents a mono- or bicyclic aromatic hydrocarbon group comprising 6 to 10 carbon atoms. As an example, mention may be made of the phenyl and naphthyl groups.
By the term «aryl (C1-C10) alkyl», is meant an alkyl group having from 1 to 10 carbon atoms, advantageously from 1 to 5 carbon atoms as defined above and containing an aryl group as defined above.
The term «heterocyclic group» represents any saturated or unsaturated heterocycle, comprising from 3 to 7 carbon atoms and containing one to 3 heteroatoms selected from the group consisting of oxygen, nitrogen or sulfur. Mention may be made, for example, of piperidinyl, pyrrolidinyl, piperazinyl, pyridyl, piridinyl, imidazolyl, furyl, morpholinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, and thiazolyl groups.
Preferably, the groups R1 and R2 represent a methyl group.
More preferably, the first reactive molecule is selected from:
According to the «monomer» embodiment, the first reactive molecule is advantageously a bis-azlactone including two terminal azlactone groups which are connected by a hydrocarbon group, which can be interrupted by one or more oxygen or sulfur atoms.
Said hydrocarbon group advantageously consists of an aliphatic, linear or branched, hydrocarbon group, comprising from 1 to 30, preferably from 1 to 20, carbon atoms which can be interrupted by one or more oxygen or sulfur atoms.
In other words, the first reactive molecule of the bis-azlactone type advantageously corresponds to the following general formula (VI).
in which R1 and R2 are identical to general formula (I), and
R4 represents an aliphatic, linear or branched, hydrocarbon group, comprising from 1 to 30, preferably from 1 to 20, carbon atoms which can be interrupted by one or more oxygen or sulfur atoms.
Such a first «monomeric» reactive molecule advantageously corresponds to the following formula (II):
or the following formula (VII):
in which X represents S, O, CH2
and R represents an aliphatic, linear or branched, hydrocarbon group, comprising from 1 to 20 carbon atoms which can be interrupted by one or more oxygen or sulfur atoms.
According to the «polymer» embodiment, the polyazlactone type polymers advantageously meet the following criteria:
The polymers advantageously have a dispersity from 1 to 6, preferably ranging from 2 to 6 for a polymer or ranging from 1 to 2 for a combination of polymers.
Preferably, the first solution contains:
The polyazlactone type polymers are advantageously selected from:
By «copolymer» is preferably meant a copolymer with a homogeneous structure, more preferably random or periodic.
According to the «homopolymer» embodiment, the first reactive molecule advantageously corresponds to the following general formula (III):
in which R1 and R2 are identical to general formula (I),
R3 represents an aliphatic, linear or branched hydrocarbon group, comprising from 1 to 30, preferably from 1 to 20, carbon atoms which can be interrupted by one or more oxygen or sulfur atoms,
R1 and R2 independently represent a (C1-C10) alkyl group, a (C3-C6) cycloalkyl group, an aryl group, an aryl (C1-C10) alkyl group, or a heterocyclic group, and
n represents an integer from 20 to 70.
In this «polymer» embodiment, the first reactive molecule advantageously corresponds to the following general formula (IV):
in which n advantageously represents an integer from 20 to 70.
Such a molecule is also called poly (2-vinyl-4,4-dimethylazlactone) (PVDM).
Still according to the invention, the first solution advantageously consists of a lipophilic solution comprising a hydrophobic solvent, for example selected from benzyl benzoate, mineral oil, vegetable oil.
Moreover, the second reactive molecule is advantageously selected from:
By «chitosan», is advantageously expect the polysaccharide composed of the random distribution of D-glucosamine bonded in β-(1-4) (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit). It is produced by chemical (in an alkaline medium) or enzymatic deacetylation of chitin, the component of the exoskeleton of arthropods (crustaceans) or the endoskeleton of cephalopods (squid, etc.) or even of the wall of mushrooms. The chitosan advantageously has a degree of acetylation (DA) (percentage of acetylated units relative to the number of total units) less than 50%.
Generally and preferably, the reactive molecules are selected from one of the following pairs (first reactive molecule/second reactive molecule):
Still generally, at least one of said immiscible solutions, preferably said two immiscible solutions, contains a surfactant.
The presence of at least one surfactant is useful to facilitate the penetration of drops from the dispersed phase into the continuous phase.
Such a surfactant is for example selected from:
Still generally, one of said immiscible solutions, intended to form the core of said capsules, contains at least one active ingredient.
The active ingredient is advantageously selected from lipophilic active ingredients and hydrophilic active ingredients.
More preferably, said at least one active ingredient is selected from:
The immiscible solutions are then mixed to carry out the interfacial polymerization step.
By «interfacial polymerization» is meant in particular a polymerization occurring at the interface between two immiscible solutions, resulting in a polymer which is constrained at the interface.
In this context, during said interfacial polymerization step, the immiscible solutions are mixed so that:
The reactive molecules then react together by said interfacial polymerization reaction, on the surface of said droplets, to form said membrane comprising said polyamide polymer.
To obtain the dispersed/continuous phases, the mixture of immiscible solutions is advantageously selected from a dripping operation:
The mixture of immiscible solutions can also consist of an emulsification operation:
According to a preferred embodiment, during the polymerization step:
Said interfacial polymerization step is still advantageously implemented with at least one of the following conditions:
The generated core-membrane capsules are then recovered from the continuous phase and transferred to aqueous solution, or dried.
Generally and according to a preferred embodiment, said immiscible solutions are free of isocyanates, more preferably diisocyanates and/or polyisocyanates.
In other words, the reactive molecules are free of isocyanates, more preferably diisocyanates and/or polyisocyanates.
The method according to the invention makes it possible to obtain core-membrane capsules including a polyamide membrane.
Such core-membrane capsules advantageously have a diameter ranging from 50 nm to 5 mm, preferably from 5 to 100 μm.
Of course, various other modifications can be made to the invention within the scope of the appended claims.
The present invention is further illustrated in the context of the Examples below.
Solution A: a solution of 0.5 g of Marlipal 24/70 supplemented to 100 g with water was prepared. 24 g of this solution were taken and placed in a beaker. 6 g of HMDA was added. The solution was stirred for 10 min.
Solution B: 0.2 g of bis-azlactone and less than 0.05 g of hydrophobic red dye were solubilized in 0.8 g of benzyl benzoate. The solution was placed in an Eppendorf tube then placed in a water bath with magnetic stirring at a temperature of 50° C.
The bis-azlactone corresponds to the following formula (II):
Drip Solution B into Solution A
Solution B was drawn into a syringe. The syringe was then placed 3 cm above solution A. Through a cone, the drops of solution B fell into solution A. Solution A was stirred throughout for 1 hour. The capsules were then removed, washed with ethanol and redissolved in water or dried at room temperature.
The analysis is then carried out by observation using a binocular magnifying glass. The capsule membrane is visible and the average capsule diameter is 2.5 mm. The capsules could be washed and dried. The dry membrane is transparent and leaves the liquid core.
The conditions of this example 1 are further developed in table 1 below
Solution A: a solution of 1 g of hydroxypropyl methylcellulose supplemented to 100 g with water was prepared. 27 g of this solution were taken and placed in a 30 mL centrifugation tube. 3 g of DETA was added. The solution was stirred for 10 min.
Solution B: 0.2 g of PVDM and less than 0.05 g of hydrophobic red dye were solubilized in 0.8 g of benzyl benzoate. The solution was placed in an Eppendorf tube then placed in a water bath with magnetic stirring at a temperature of 50° C.
The PVDM has the following characteristics:
Solution B was drawn into a syringe. A cone was placed at the end of the syringe then plunged 0.5 cm below the surface of solution A. Through a cone, the drops of solution B slowly fall into solution A. When the dropping was completed, the tube was stirred on a rotary shaker at 20 revolution per minute for 1 h. The capsules were then removed, washed with ethanol and redissolved in water or dried at room temperature.
The analysis is then carried out by observation using a binocular magnifying glass. The capsule membrane is visible and the average diameter of the capsule is 3 mm. The capsules could be washed and dried, revealing liquid core capsules and transparent membrane.
The conditions of Example 2 are further developed in Table 2 below.
Core-membrane microcapsules were further synthesized in the combinations and conditions recalled in Table 3 below.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2109664 | Sep 2021 | FR | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/075584 | 9/14/2022 | WO |
