CA2019224A1 - Microcapsules containing watersoluble amphiphilic substances - Google Patents
Microcapsules containing watersoluble amphiphilic substancesInfo
- Publication number
- CA2019224A1 CA2019224A1 CA002019224A CA2019224A CA2019224A1 CA 2019224 A1 CA2019224 A1 CA 2019224A1 CA 002019224 A CA002019224 A CA 002019224A CA 2019224 A CA2019224 A CA 2019224A CA 2019224 A1 CA2019224 A1 CA 2019224A1
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- Prior art keywords
- watersoluble
- microcapsules
- organic phase
- substance
- process according
- Prior art date
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Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
- B01J13/16—Interfacial polymerisation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Chemical Or Physical Treatment Of Fibers (AREA)
- Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)
- Paper (AREA)
- Detergent Compositions (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
The present invention relates to microcapsules containing watersolubles amphiphilic substances and to the process of producing them by interfacial polymerization or polycondensation, as well as to their uses.
The present invention relates to microcapsules containing watersolubles amphiphilic substances and to the process of producing them by interfacial polymerization or polycondensation, as well as to their uses.
Description
2 ~ 2 ~ `
The pre~ent invention relate3 to microcap~ules containing water~oluble amphiphilic substances and to a process enabling their production.
Microcapsules are particles of ~pherical shape, who~e size range~ between 1 and 1250~ , constituted by a qupport material, containing the encapsulated sub~tance. According to the structure of the ~upport material, two type~ of microcapsules are to be distinguished:
- microcapqules of ~he reservoir type of which the support material i~ a solid envelope, of variable thicknes~ containing the ~ubstance to be encap~ulated, - microcap~ule~ of the matrix type also known as microqpheres in which the ~upport material i~ a continuou~ network, in which the ~ubstance to be encapsulated is dispersed.
In the sense of the pre~ent invention, the term microcapsule encompasse~ both microcapsules of matrix type and microcapsule~ of reservoir type.
The support material limit~ exchanges between the encap~ulated ~ubstance and the outer medium~ whlch ha~
the effect of protecting ~aid sub~tance, and of permitting its incorporation in products into which it `, , .~ .,. ' ` ,:': ; : ,' , . : . , . :, . . ~ .
. . -- . . .
2 ~ J 2 ~
would not have been po~sible to incorporate it ln the free ~ate. In addition, the u~e of micro-encap~ulated ~ub~tance~ enable~ the release of the latter to be controlled at a different moment - the substance i~ then relea~ed by destruction of the wall of the microcapsule - or by ~preading it over time -the ~ub~tance is relea~ed by gradual diffu~ion through the ~all -.
Many sub~tance~ may be encapsulated: they may be chemical products ~uch a~ medicament~ or pesticides, or macromolecules ~uch a~ enzymes and also living cell~.
Microcapsules are used in many field~ ~uch as pharmacy, bio-indu~try, co~metic~, the farm produce indu~try, the paper indu~try, etc...
Example~ of u~es of microencap~ulation are described in detail in the article of C. DUBERNET and J P BE~OIT which appeared in "L'Actualite Chimique" ;
(Deccmber l986).
One of the proces~e~ used to encap~ula~e liquid ~ubstances i~ microencapsulation by interfacial polycondensation. Interfacial polycondensation i~ a polymeri~ation reaction which i~ produced at the interface of two immiscible llquid~, of which at lea~t one of the two contains a suitable polyfunctional reagene. In the case where this reaction occur~
without the formation of byproducts, it i~ al80 called interfacial polymeri~ation. This reaction may be carried out in an emul~ion, at the interface between the two pha~es. In thi~ ca~e, it re~ultY ln the formation of re~ervoir microcap~ules, if the oligomer~
formed at the start of the reaction are insoluble in : the disper~ed phase, and mstrlx microcapsuleY if the 2 ~ 2 2 ~
oligomers are soluble in the disper~ed pha~e.
Thi~ proces~ which has been de~cribed, for example, in French patent 1 427 085 and, more recently in the publication of R ARSHADY, /J~
MICROENCAPSULATION 1989, Vol. 6 Nl/, as well a3 in the publication of C DUBERNET and J BENOI~ ment-Joned above9 enable~ the preparation of capsules who~e wall is formed of polyamide, polyurethane, polyurea, polyester, etc Belgian patent 796 746 describe~ also a proce~s for producing, from an oil/water emulsion microcapsule3 who~e wall is formed of polyurea9 by polymeri~ation of an isocyanate, present in the organic phase. French patent 2 548 046 describes a process based on the same principle, for the encapsulation of watersoluble substances, from a water/oil 2mulsion.
The~e processe~ are ~uitable for encap3ulation of many hydrophilic or lipophilic substance~. ~owever, they do not enable the encap~ulation of water~oluble amphiphilic ~ub~tance~ ~uch a~ 5 for example, the quaternary ammoniums.
Now quaternary ammoniums are used among other thing~ for their antiseptic properties. For example, benzalkonium chloride is used ln topical application~, as a bactericide and fungicide. Its action on the HIV
viru~ has also been demon~trated. ~owe~er, the ` quaternary ammonium~ are incompatible with many ~ub~tances, particularly anionic substances such as soap~. In addltion, they are commonly used in solution, which doe~ not permit associatlng them conveniently with a ~olid ~upport. It would therefore be partlcularly advantageous to encap~ulate them.
2~224 However, this encap3ulation po~es specific problem~ ~hich had not been re~olved until now.
The quaternary ammoniums being watersoluble, it 1~
neces~ary to encapsulate them, to obtaln a stable emulsion of the water in oil type. Now the quaternary ammoniums and more generally, watersoluble amphiphilic sub~tance~ favour emulsions of the oil in water type, `` and destabilise emulsions of the water/oil type. In addition, it i~ known tha~ the quaternary ammoniums interfere with the interfacial polymerisation reaction. Thus, for example McGINITY et alO/J.
Pharm., 70, 372 (1981)/ and ARS~ADY / J.
Microencapsulation, 6, 18-23, 1989/, con~ider that it is not pos~ible to obtain microcap~ules in the presence of quaternary ammonium.
Now the inventors have developed a proces~ which, surprisingly, enables the production of microcapsules containing watersoluble amphiphilic sub~ances, including quaternary ammonium~.
It is accordingly an object of the present invention to provide microcapsules, characteri~ed in that they contain at least one watersoluble amphiphilic substance.
According to a preferred embodiment of these ; 25 microcapsule~, the water~oluble amphiphilic substance is a cationic substance, in particular a quaternary : ammonium.
According to a particularly advantageous modality ~` of this embodiment, the water~oluble amphiphilic substance i~ benzalkonium chlorlde.
According to another preferred embodiment of the3e microcapsules the water~oluble amphiphilic substance is a non-ionic ~ubstance, in particular a water ~ .
": :
.
2~ ~2~
soluble polyoxyethylene derivative~
According to a partlcularly advantageou3 modalit~
of ~hi~ embodiment the watersoluble amphiphilic substance is a nonoxynol whose average number of - 5 ethylene oxide unit~ per molecule i~ greater than 6.
According to a particularly advantageous modality of this embodiment the watersoluble amphiphilic substance is an octoxynol whose average number of ethylene oxide units per molecule is greater than 6.
According to another preferred embodiment of the pre~ent invention, the watersoluble amphiphilic ~ubstance i~ an anionic sllbstance, in particular a ~odium alkyl sulfate.
According to a particularly advantageou~ modality of thls embodiment the water~oluble amphiphilic sub3tance is ~odium lauryl ~ulfate, According to another preferred embodiment of the pre~ent invention9 the wall of the microcapsules is constituted essentially of polyurea. It can al~o be constituted of any other polymer resulting from a polymerisation or interfacial polyconden~ation reaction, such a3 for example polyamide polyester3 or polyurethanes.
It is in addition another object of the pre~ent invention to provide a proce3s of encapsulation of watersoluble amphiphilic substances, by polycondensation or by interfacial polymerisation, which compri~e~ a first step of production of an emulsion of an aqueous phase containing the ~ubstance to be encapsulated in an organic phase, and a second step of formation of microcapsules by polymerisation of one or ~everal polyfunctional reagents, which proces~ is characterized in that the aqueou~ phase . - .......... . .
~ a ~
`:
containing the amphiphilic ~ub~tance to be encapsulated i~ emulsified in the presence of a -- suitable emul~ifying agent, in an organic pha~e containing a~ lea~ one component taken from the group con~ti~uted by aliphatic, alicyclic or aromatic hydrocarbons, halogenated or not, and triglyceride~
According to a preferred embodiment of the proce~
~- according to the pre~ent invention, the HLB
(hydrophile lipophile balance) of the emulsiEier i9 le~ than 7. An ELB le~s than 7 can be obtained by using as the emul~ifier either a ~urface active agent, or ~everal surface active agents po~sibly as~ociated with agents lowering the HLB, such a~ carboxylic acid ~alts, like for example sodium or lithium acetate or formate.
According to an advantageou~ modallty of this embodiment, the emulsifier i~ a copolymer of modified non-ionic polyester type, of HLB compri~ing between 5 ~` and 7.
According to another advantageous modality of thi~
embodiment, the emul~ifier i~ con~tituted by a mixture 9 in solution in the organic phase, of a poly~iloxane (for example the polysiloxane 3225C) and a ~orbitan ester (for example Span 85).
According to yet another advantageous modality of thi~ embodiment, the emul~ifier i~ con~tituted by an association of Polyqorbate 80, in sQlution in the aqueou~ pha~e, and a ~orbitan ester (for example Span 85), in ~olution in the organic phase.
According to another preferred embodiment of the proces~ according to the present invention, the `~ organic pha~e contain~ a mixture of triglycerides.
According to another embodiment of the process ": '`
.
~2 ~
accoridng to the present invention, the one or more `~ triglycerides contained in the organic pha~e is/are one or more triglyceride(s) of C8 to Cl~ fatty acids.
According to yet another embodiment of the process according to the present invention, the organic phase is con~tituted by a chloroform/cyclohexane mixture.
According to yet another embodiment of the proce~s according to the pre~ent invention, the organic phase contains xylene or toluene.
10The process of encap~ulation according to the pre~ent invention may also be employed in an organic pha~e con~tituted exclu~ively by triglycerides.
Applicants have in addition ob~erved that by varying the re~pective proportions of hydrocarbons and of triglycerides, it is possible ~o obtain capsule~ of ; variable strength, which can hence be adapted to various uses.
~- According to a preferred embodiment of the process according to the pre~ent invention, the organic pha~e is a hydrocarbon/triglyceride mixture which contains between 10 and 50%, by weight, of hydrocarbons.
The majority of polyfunctional reagents customarily used in the interfacial polymerisation proce~ses may be used in the proce~s according to the psesent invention, for the formation of the wall~ of the microcap~ule~.
For example diisocyanates may be u~ed to obtain microcap~ules of which the wall i3 e~sentially constituted of polyurea.
The microcapsules according to the present invention may generally be u~ed in all applications of microcap~ules. Without being limiting they may be incorporated in liquid~, pastes, creams, soaps, paints ':
' t'`
i`' .
. ` ~ , g ~iJ 2 ~
and varnishe~ or solid material~ such a~ paper~, textile~, ~ponges, materlal~ bas2d on polymer~, in partlcular ela~tomers.
In the accompanying drawings:
Figure 1 qhow~ the appearance of the cap~ule~
obtained; and Figure 2 ~hows the percentage of residual water ln the microcap~ule~ a~ a function of the tlme of pre3ervation .
The present in~vention will be better under~tood by means of the additional de~cription whi~h follow~, which refer~ to examples of the preparation of microcapsule~ following the proce~s according to the invention.
.
A) ORGANIC PHASE
15g of diphenylmethane diisocyanate and 6g of A 60 are disolved in 608 Of xylene, 140g of mygliol 812 were then added. (The A 60 [ICI Laboratories] i9 a non-ionic ~urfactant; it i~ a modified polyester.
Mygliol 812 i~ a mixture of triglyceride~ of ~aturated and fractionated fatty acid~ of COCO, with C8 - CLo chain length).
, : B) AQUEOUS PHASE
"` 0.3g of benzalkonium chloride are disolved in 30ml ~`~ of water.
The aqueou~ pha~e i~ emul~ified in the organic phase by mean~ of a high power microvortex for 1 to 2 minutes. ~he emulsion so prepared i~ placed with .
. i;
!
' `` `
' ~` .
2 ~
_9 _ gentle stirring (blade, 300rpm) for the duration of the reac~ion ~8 to 10h). ~he mlcrocapsules obtained are recovered after decantation. They are then washed wi~h cyclohexane then dried at ambiant temperature.
45g of microcapsules of size comprised between 30 and 50~m are thu~ obtained The amount of encap~ulated - benzalkonium chloride i~ determined by ~PLC according to the following ~echnique: a predetermined amount of microcapsules disolved in 5ml of Dimethyl formamide.
5ml of water are added to the solution to re-precipitate the polymer. The resulting suspension undergoes centrifugation a~ 35~000 rpm or lh30. The supernatant after passage over a filter of 0.2~m i~
determined by HPLC according to the following operational modalities: 30 1 of specimen are analysed by passage over a NOVAPACK CN (WATERS) column with a mobile phase compo ed for 60% of acetonitrile and 40%
of an acetate buffer, at a flow rate of 2ml/min. The detection of the peak corre~ponding to the benzalkonium chloride i9 done at 254nm. The encapsulation yield of the benzalkonium chloride, determined according to thl~ method is 40%.
Figure 1 ~hows the appearance of the cap~ules obtained, observed with the ~weep electron ~icro~cope.
A) ORGANIC PHASE
15g of diphenylmethane dii~ocyanate and 12g of A
60 are disolved in 40g of xylene to which are then i 30 added 240g of MYGLIOL 812.
.
.
`~
.
!
`
`~ '; '' ' ' , ~'`" .
`
B) AQUEOUS PHASE
3g of benzalkonium chloride are disolved in 30ml of water. The re~t of the procedure i~ identical with that described in Example 1.
40g of microcap3ule~ of a ~lze comprised between 50 and 70~m are recoveredO The encap3ulation yield i~
60% namely 46mg of benzalkonium chloride per lg of cap~ule3 .
.
A) ORGANIC PHASE
7g of diphenylmethanedii30cyanate and 4g of A 60 are disolved in 30g of toluene. 170g of MIGLYOL 840 are added to the solution.
B) AQUEOUS PHASE
0.3g of benzalXonium chloride are di~olved in 30ml of water.
The re~t of the procedure is identical with that de~cribed in Example l. l3g of microcap~ule~ ar~
recovered.
;~ 25 A) ORGANIC PHASE
15g of diphenylmethane diisocyanate and 7.5g of Span 85 are di~solved in 30g of xylene, to which are added 170g of MIGLYOL 812.
.
`"`:
":
.
, B) AQUEOUS PHASE
2,5g of Tween 80 and 0.3g of benzalkonium chloride are di3~01ved in 30ml of water. The whole is emulsified in the preceding mixture~
The re3t of the procedure is identical with that descrlbed in Example 1. 18g of microcap~ule~ are recovered.
.
A) ORGANIC PHASE
lOg of diphenylmethanediisocyanate and 5g of A60 are dissolved in 40g of xylene, to which are added 160g of MIGLYOL 812.
B) AQUEOUS PHASE
lg of sodium laurylsulfate are dissolved in 30ml of water.
The rest of the procedure is identical ~ith that described in Example 1. The microcap~ule~ have an average size of 10~.
A) ORGANIC P~ASE
15g of diphenylmethanediisocyanate and 7g of A60 sre dis~olved in 200g of xylene.
`:
" B) AQUEOUS PHASE
3g of Triton X 100 are dis~olved in 30g of water.
" 30 The re3t of the procedure is identical with that described in Example 1. The ~ize of the microcapsules ,~
~" obtained varie~ between 10 and 50~ .
` ~
., :
.
.
" ' ' A) ORGANIC PHASE
15g of diphenylmethane diisocyanate, 5g of poly~iloxane 3225C (DOW CORNING) and 5g of Span 85 are di~olved in 200g of xylene.
B) AQUEOUS PHASE
3g of Nonoxynol 9 are dis~olved in 30ml of water.
The re~t of the procedure i~ identical ~ith that ` 10 de~cribed in Example 1.
EXAMPLE B
A) ORGANIC PHASE
lOg of diphenylmethane diisocyanate and 5g of A
60 are dissolved in 200g of a cyclohexane/chloroform mixture in a ratio 4/1.
B) AQUEOUS PHASE
lg of benzalkonium chloride i~ di3solved in 30ml of water.
The re~t of the procedure i~ identical ~ith that described in Example 1.
INFL~NC~ 0~ ~H~ ORG~IC PHAS~ 0~ TH~ PROP~RTI~S
OF THE MICROC~PS~L~S
, ~
A) INFLUENCE ON THE MECHANICAL PROPERTIES
Table 1 below ~hows the influence of the ~; composition of the organic pha~e on the mechanical ``` strength properties of the mlcrocapsule~ prepared from a 1% solution of benzalkonium chloride, :.
., 2~92~
ORGANIC PHASE STRENGTH
5 XYLENE 100~ 0 XYLENE 80% MYGLIOL 20~ 0 XYLENE 60~ MYGLIOL 40~ 0 XYLENE 50~ MYGLIOL 50~ 0 XYLENE 40~ MYGLIOL 60%
15 XYLENE 30% MYGLIOL 70% +~+
XYLENE 15~ MYGLIOL 85 MYGLIOL 100%
.: 20 The key to thi~ table i8 the following:
Very fragile microcap~ule~ 0 Fragile microcap~ules 25 Strong microcapsules Very strong microcapsule~ +~
. ~ .
~B) INFLUENCE ON THE WATER CONTENT OF THE
. ~ ~
MICROCAPSULES AND ITS CHANGE IN THE COURSE OF TIME
`~`The water content is evaluated by measuring the `~ weight loss on drying by heating in the oven for one ~; hour a~ 105 C.
~ ~ -~- :
;, ~ - .
.
2 2 ~
Figure 2 shows the percentage of residual water ln the microcapsule~ as a function of the time of preservation for microcapsules prepared from a 1%
- solution of benzalkonium chloride, in 3 lipid phases of different composition ~ --~ XYLENE i5% ~IYGLIOL 85~6 - ~_ XYLENE 40% MYGLIOL 60~6 ~ MYGLIOL 100%
.`
.
'';
. .
, ~ ,, :, . . . ", :
..; ;
The pre~ent invention relate3 to microcap~ules containing water~oluble amphiphilic substances and to a process enabling their production.
Microcapsules are particles of ~pherical shape, who~e size range~ between 1 and 1250~ , constituted by a qupport material, containing the encapsulated sub~tance. According to the structure of the ~upport material, two type~ of microcapsules are to be distinguished:
- microcapqules of ~he reservoir type of which the support material i~ a solid envelope, of variable thicknes~ containing the ~ubstance to be encap~ulated, - microcap~ule~ of the matrix type also known as microqpheres in which the ~upport material i~ a continuou~ network, in which the ~ubstance to be encapsulated is dispersed.
In the sense of the pre~ent invention, the term microcapsule encompasse~ both microcapsules of matrix type and microcapsule~ of reservoir type.
The support material limit~ exchanges between the encap~ulated ~ubstance and the outer medium~ whlch ha~
the effect of protecting ~aid sub~tance, and of permitting its incorporation in products into which it `, , .~ .,. ' ` ,:': ; : ,' , . : . , . :, . . ~ .
. . -- . . .
2 ~ J 2 ~
would not have been po~sible to incorporate it ln the free ~ate. In addition, the u~e of micro-encap~ulated ~ub~tance~ enable~ the release of the latter to be controlled at a different moment - the substance i~ then relea~ed by destruction of the wall of the microcapsule - or by ~preading it over time -the ~ub~tance is relea~ed by gradual diffu~ion through the ~all -.
Many sub~tance~ may be encapsulated: they may be chemical products ~uch a~ medicament~ or pesticides, or macromolecules ~uch a~ enzymes and also living cell~.
Microcapsules are used in many field~ ~uch as pharmacy, bio-indu~try, co~metic~, the farm produce indu~try, the paper indu~try, etc...
Example~ of u~es of microencap~ulation are described in detail in the article of C. DUBERNET and J P BE~OIT which appeared in "L'Actualite Chimique" ;
(Deccmber l986).
One of the proces~e~ used to encap~ula~e liquid ~ubstances i~ microencapsulation by interfacial polycondensation. Interfacial polycondensation i~ a polymeri~ation reaction which i~ produced at the interface of two immiscible llquid~, of which at lea~t one of the two contains a suitable polyfunctional reagene. In the case where this reaction occur~
without the formation of byproducts, it i~ al80 called interfacial polymeri~ation. This reaction may be carried out in an emul~ion, at the interface between the two pha~es. In thi~ ca~e, it re~ultY ln the formation of re~ervoir microcap~ules, if the oligomer~
formed at the start of the reaction are insoluble in : the disper~ed phase, and mstrlx microcapsuleY if the 2 ~ 2 2 ~
oligomers are soluble in the disper~ed pha~e.
Thi~ proces~ which has been de~cribed, for example, in French patent 1 427 085 and, more recently in the publication of R ARSHADY, /J~
MICROENCAPSULATION 1989, Vol. 6 Nl/, as well a3 in the publication of C DUBERNET and J BENOI~ ment-Joned above9 enable~ the preparation of capsules who~e wall is formed of polyamide, polyurethane, polyurea, polyester, etc Belgian patent 796 746 describe~ also a proce~s for producing, from an oil/water emulsion microcapsule3 who~e wall is formed of polyurea9 by polymeri~ation of an isocyanate, present in the organic phase. French patent 2 548 046 describes a process based on the same principle, for the encapsulation of watersoluble substances, from a water/oil 2mulsion.
The~e processe~ are ~uitable for encap3ulation of many hydrophilic or lipophilic substance~. ~owever, they do not enable the encap~ulation of water~oluble amphiphilic ~ub~tance~ ~uch a~ 5 for example, the quaternary ammoniums.
Now quaternary ammoniums are used among other thing~ for their antiseptic properties. For example, benzalkonium chloride is used ln topical application~, as a bactericide and fungicide. Its action on the HIV
viru~ has also been demon~trated. ~owe~er, the ` quaternary ammonium~ are incompatible with many ~ub~tances, particularly anionic substances such as soap~. In addltion, they are commonly used in solution, which doe~ not permit associatlng them conveniently with a ~olid ~upport. It would therefore be partlcularly advantageous to encap~ulate them.
2~224 However, this encap3ulation po~es specific problem~ ~hich had not been re~olved until now.
The quaternary ammoniums being watersoluble, it 1~
neces~ary to encapsulate them, to obtaln a stable emulsion of the water in oil type. Now the quaternary ammoniums and more generally, watersoluble amphiphilic sub~tance~ favour emulsions of the oil in water type, `` and destabilise emulsions of the water/oil type. In addition, it i~ known tha~ the quaternary ammoniums interfere with the interfacial polymerisation reaction. Thus, for example McGINITY et alO/J.
Pharm., 70, 372 (1981)/ and ARS~ADY / J.
Microencapsulation, 6, 18-23, 1989/, con~ider that it is not pos~ible to obtain microcap~ules in the presence of quaternary ammonium.
Now the inventors have developed a proces~ which, surprisingly, enables the production of microcapsules containing watersoluble amphiphilic sub~ances, including quaternary ammonium~.
It is accordingly an object of the present invention to provide microcapsules, characteri~ed in that they contain at least one watersoluble amphiphilic substance.
According to a preferred embodiment of these ; 25 microcapsule~, the water~oluble amphiphilic substance is a cationic substance, in particular a quaternary : ammonium.
According to a particularly advantageous modality ~` of this embodiment, the water~oluble amphiphilic substance i~ benzalkonium chlorlde.
According to another preferred embodiment of the3e microcapsules the water~oluble amphiphilic substance is a non-ionic ~ubstance, in particular a water ~ .
": :
.
2~ ~2~
soluble polyoxyethylene derivative~
According to a partlcularly advantageou3 modalit~
of ~hi~ embodiment the watersoluble amphiphilic substance is a nonoxynol whose average number of - 5 ethylene oxide unit~ per molecule i~ greater than 6.
According to a particularly advantageous modality of this embodiment the watersoluble amphiphilic substance is an octoxynol whose average number of ethylene oxide units per molecule is greater than 6.
According to another preferred embodiment of the pre~ent invention, the watersoluble amphiphilic ~ubstance i~ an anionic sllbstance, in particular a ~odium alkyl sulfate.
According to a particularly advantageou~ modality of thls embodiment the water~oluble amphiphilic sub3tance is ~odium lauryl ~ulfate, According to another preferred embodiment of the pre~ent invention9 the wall of the microcapsules is constituted essentially of polyurea. It can al~o be constituted of any other polymer resulting from a polymerisation or interfacial polyconden~ation reaction, such a3 for example polyamide polyester3 or polyurethanes.
It is in addition another object of the pre~ent invention to provide a proce3s of encapsulation of watersoluble amphiphilic substances, by polycondensation or by interfacial polymerisation, which compri~e~ a first step of production of an emulsion of an aqueous phase containing the ~ubstance to be encapsulated in an organic phase, and a second step of formation of microcapsules by polymerisation of one or ~everal polyfunctional reagents, which proces~ is characterized in that the aqueou~ phase . - .......... . .
~ a ~
`:
containing the amphiphilic ~ub~tance to be encapsulated i~ emulsified in the presence of a -- suitable emul~ifying agent, in an organic pha~e containing a~ lea~ one component taken from the group con~ti~uted by aliphatic, alicyclic or aromatic hydrocarbons, halogenated or not, and triglyceride~
According to a preferred embodiment of the proce~
~- according to the pre~ent invention, the HLB
(hydrophile lipophile balance) of the emulsiEier i9 le~ than 7. An ELB le~s than 7 can be obtained by using as the emul~ifier either a ~urface active agent, or ~everal surface active agents po~sibly as~ociated with agents lowering the HLB, such a~ carboxylic acid ~alts, like for example sodium or lithium acetate or formate.
According to an advantageou~ modallty of this embodiment, the emulsifier i~ a copolymer of modified non-ionic polyester type, of HLB compri~ing between 5 ~` and 7.
According to another advantageous modality of thi~
embodiment, the emul~ifier i~ con~tituted by a mixture 9 in solution in the organic phase, of a poly~iloxane (for example the polysiloxane 3225C) and a ~orbitan ester (for example Span 85).
According to yet another advantageous modality of thi~ embodiment, the emul~ifier i~ con~tituted by an association of Polyqorbate 80, in sQlution in the aqueou~ pha~e, and a ~orbitan ester (for example Span 85), in ~olution in the organic phase.
According to another preferred embodiment of the proces~ according to the present invention, the `~ organic pha~e contain~ a mixture of triglycerides.
According to another embodiment of the process ": '`
.
~2 ~
accoridng to the present invention, the one or more `~ triglycerides contained in the organic pha~e is/are one or more triglyceride(s) of C8 to Cl~ fatty acids.
According to yet another embodiment of the process according to the present invention, the organic phase is con~tituted by a chloroform/cyclohexane mixture.
According to yet another embodiment of the proce~s according to the pre~ent invention, the organic phase contains xylene or toluene.
10The process of encap~ulation according to the pre~ent invention may also be employed in an organic pha~e con~tituted exclu~ively by triglycerides.
Applicants have in addition ob~erved that by varying the re~pective proportions of hydrocarbons and of triglycerides, it is possible ~o obtain capsule~ of ; variable strength, which can hence be adapted to various uses.
~- According to a preferred embodiment of the process according to the pre~ent invention, the organic pha~e is a hydrocarbon/triglyceride mixture which contains between 10 and 50%, by weight, of hydrocarbons.
The majority of polyfunctional reagents customarily used in the interfacial polymerisation proce~ses may be used in the proce~s according to the psesent invention, for the formation of the wall~ of the microcap~ule~.
For example diisocyanates may be u~ed to obtain microcap~ules of which the wall i3 e~sentially constituted of polyurea.
The microcapsules according to the present invention may generally be u~ed in all applications of microcap~ules. Without being limiting they may be incorporated in liquid~, pastes, creams, soaps, paints ':
' t'`
i`' .
. ` ~ , g ~iJ 2 ~
and varnishe~ or solid material~ such a~ paper~, textile~, ~ponges, materlal~ bas2d on polymer~, in partlcular ela~tomers.
In the accompanying drawings:
Figure 1 qhow~ the appearance of the cap~ule~
obtained; and Figure 2 ~hows the percentage of residual water ln the microcap~ule~ a~ a function of the tlme of pre3ervation .
The present in~vention will be better under~tood by means of the additional de~cription whi~h follow~, which refer~ to examples of the preparation of microcapsule~ following the proce~s according to the invention.
.
A) ORGANIC PHASE
15g of diphenylmethane diisocyanate and 6g of A 60 are disolved in 608 Of xylene, 140g of mygliol 812 were then added. (The A 60 [ICI Laboratories] i9 a non-ionic ~urfactant; it i~ a modified polyester.
Mygliol 812 i~ a mixture of triglyceride~ of ~aturated and fractionated fatty acid~ of COCO, with C8 - CLo chain length).
, : B) AQUEOUS PHASE
"` 0.3g of benzalkonium chloride are disolved in 30ml ~`~ of water.
The aqueou~ pha~e i~ emul~ified in the organic phase by mean~ of a high power microvortex for 1 to 2 minutes. ~he emulsion so prepared i~ placed with .
. i;
!
' `` `
' ~` .
2 ~
_9 _ gentle stirring (blade, 300rpm) for the duration of the reac~ion ~8 to 10h). ~he mlcrocapsules obtained are recovered after decantation. They are then washed wi~h cyclohexane then dried at ambiant temperature.
45g of microcapsules of size comprised between 30 and 50~m are thu~ obtained The amount of encap~ulated - benzalkonium chloride i~ determined by ~PLC according to the following ~echnique: a predetermined amount of microcapsules disolved in 5ml of Dimethyl formamide.
5ml of water are added to the solution to re-precipitate the polymer. The resulting suspension undergoes centrifugation a~ 35~000 rpm or lh30. The supernatant after passage over a filter of 0.2~m i~
determined by HPLC according to the following operational modalities: 30 1 of specimen are analysed by passage over a NOVAPACK CN (WATERS) column with a mobile phase compo ed for 60% of acetonitrile and 40%
of an acetate buffer, at a flow rate of 2ml/min. The detection of the peak corre~ponding to the benzalkonium chloride i9 done at 254nm. The encapsulation yield of the benzalkonium chloride, determined according to thl~ method is 40%.
Figure 1 ~hows the appearance of the cap~ules obtained, observed with the ~weep electron ~icro~cope.
A) ORGANIC PHASE
15g of diphenylmethane dii~ocyanate and 12g of A
60 are disolved in 40g of xylene to which are then i 30 added 240g of MYGLIOL 812.
.
.
`~
.
!
`
`~ '; '' ' ' , ~'`" .
`
B) AQUEOUS PHASE
3g of benzalkonium chloride are disolved in 30ml of water. The re~t of the procedure i~ identical with that described in Example 1.
40g of microcap3ule~ of a ~lze comprised between 50 and 70~m are recoveredO The encap3ulation yield i~
60% namely 46mg of benzalkonium chloride per lg of cap~ule3 .
.
A) ORGANIC PHASE
7g of diphenylmethanedii30cyanate and 4g of A 60 are disolved in 30g of toluene. 170g of MIGLYOL 840 are added to the solution.
B) AQUEOUS PHASE
0.3g of benzalXonium chloride are di~olved in 30ml of water.
The re~t of the procedure is identical with that de~cribed in Example l. l3g of microcap~ule~ ar~
recovered.
;~ 25 A) ORGANIC PHASE
15g of diphenylmethane diisocyanate and 7.5g of Span 85 are di~solved in 30g of xylene, to which are added 170g of MIGLYOL 812.
.
`"`:
":
.
, B) AQUEOUS PHASE
2,5g of Tween 80 and 0.3g of benzalkonium chloride are di3~01ved in 30ml of water. The whole is emulsified in the preceding mixture~
The re3t of the procedure is identical with that descrlbed in Example 1. 18g of microcap~ule~ are recovered.
.
A) ORGANIC PHASE
lOg of diphenylmethanediisocyanate and 5g of A60 are dissolved in 40g of xylene, to which are added 160g of MIGLYOL 812.
B) AQUEOUS PHASE
lg of sodium laurylsulfate are dissolved in 30ml of water.
The rest of the procedure is identical ~ith that described in Example 1. The microcap~ule~ have an average size of 10~.
A) ORGANIC P~ASE
15g of diphenylmethanediisocyanate and 7g of A60 sre dis~olved in 200g of xylene.
`:
" B) AQUEOUS PHASE
3g of Triton X 100 are dis~olved in 30g of water.
" 30 The re3t of the procedure is identical with that described in Example 1. The ~ize of the microcapsules ,~
~" obtained varie~ between 10 and 50~ .
` ~
., :
.
.
" ' ' A) ORGANIC PHASE
15g of diphenylmethane diisocyanate, 5g of poly~iloxane 3225C (DOW CORNING) and 5g of Span 85 are di~olved in 200g of xylene.
B) AQUEOUS PHASE
3g of Nonoxynol 9 are dis~olved in 30ml of water.
The re~t of the procedure i~ identical ~ith that ` 10 de~cribed in Example 1.
EXAMPLE B
A) ORGANIC PHASE
lOg of diphenylmethane diisocyanate and 5g of A
60 are dissolved in 200g of a cyclohexane/chloroform mixture in a ratio 4/1.
B) AQUEOUS PHASE
lg of benzalkonium chloride i~ di3solved in 30ml of water.
The re~t of the procedure i~ identical ~ith that described in Example 1.
INFL~NC~ 0~ ~H~ ORG~IC PHAS~ 0~ TH~ PROP~RTI~S
OF THE MICROC~PS~L~S
, ~
A) INFLUENCE ON THE MECHANICAL PROPERTIES
Table 1 below ~hows the influence of the ~; composition of the organic pha~e on the mechanical ``` strength properties of the mlcrocapsule~ prepared from a 1% solution of benzalkonium chloride, :.
., 2~92~
ORGANIC PHASE STRENGTH
5 XYLENE 100~ 0 XYLENE 80% MYGLIOL 20~ 0 XYLENE 60~ MYGLIOL 40~ 0 XYLENE 50~ MYGLIOL 50~ 0 XYLENE 40~ MYGLIOL 60%
15 XYLENE 30% MYGLIOL 70% +~+
XYLENE 15~ MYGLIOL 85 MYGLIOL 100%
.: 20 The key to thi~ table i8 the following:
Very fragile microcap~ule~ 0 Fragile microcap~ules 25 Strong microcapsules Very strong microcapsule~ +~
. ~ .
~B) INFLUENCE ON THE WATER CONTENT OF THE
. ~ ~
MICROCAPSULES AND ITS CHANGE IN THE COURSE OF TIME
`~`The water content is evaluated by measuring the `~ weight loss on drying by heating in the oven for one ~; hour a~ 105 C.
~ ~ -~- :
;, ~ - .
.
2 2 ~
Figure 2 shows the percentage of residual water ln the microcapsule~ as a function of the time of preservation for microcapsules prepared from a 1%
- solution of benzalkonium chloride, in 3 lipid phases of different composition ~ --~ XYLENE i5% ~IYGLIOL 85~6 - ~_ XYLENE 40% MYGLIOL 60~6 ~ MYGLIOL 100%
.`
.
'';
. .
, ~ ,, :, . . . ", :
..; ;
Claims
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1) Microcapsules, characterized in that they contain at least one watersoluble amphiphilic substance.
2) Microcapsules according to claim 1, characterized in that the watersoluble amphiphilic substance is a cationic substance, in particular a quaternary ammonium substance.
3) Microcapsules according to claim 2, characterized in that the watersoluble amphiphilic substance is benzalkonium chloride.
4) Microcapsules according to claim 1, characterized in that the watersoluble amphiphilic substance is a non-ionic substance, in particular a watersoluble polyoxyethylene derivative.
5) Microcapsules according to claim 4, characterized in that the watersoluble amphiphilic substance is a nonoxynol whose average number of ethylene oxide units per molecule is greater than 6.
6) Microcapsules according to claim 4, characterized in that the watersoluble amphiphilic substance is an octoxynol whose average number of ethylene oxide units per molecule is greater than 6.
7) Microcapsules according to claim 1, characterized in that the watersoluble amphiphilic substances is an anionic substance, in particular a sodium alkyl sulfate.
8) Microcapsules according to claim 7, characterized in that the watersoluble amphiphilic substance is sodium lauryl sulfate.
9) Microcapsules according to claim 1, characterized in that the wall of the microcapsules is constituted essentially of polyurea.
10) Process for encapsulating watersoluble amphiphilic substances, by interfacial polycondensation or polymerization, which comprises a first step of producing an emulsion of an aqueuse phase containing the substance to be encapsulated in an organic phase, and a second step of formingmicrocapsules by polymerization of one or several polyfunctional reagents, which process is characterized in that the aqueuse phase containing the amphiphilic substance to be encapsulated is emulsified, in the presence of a suitable emulsifying agent, in an organic phase containing at least one component taken from the group constituted by, aliphatic, alicyclic, or aromatic hydrocarbons, halogenated or not, and triglycerides.
11) Process according to claim 10, characterized in that the HLB (hydrophile lipophile balance) of the emulsifying agent is less than 7.
12) Process according to claim 10, characterized in that as eemulsifying agent, there is used at least one surface-active agent, if necessary associated with an agent lowering the HLB selected from among the group comprising surface-active agents and salts in particular carboxylic acid salts of basic metals.
13) Process according to any one of claims 10 or 11, characterized in that the emulsifying agent is a copolymer of the modified non-ionic polyester type, of HLB comprised between 5 and 7.
14) Process according to any one of claims 10 or 11, characterized in that the emulsifying agent is constituted by a mixture, in solution in the organic phase, of polysiloxane and of a sorbitan ester.
15) Process according to any one of claims 10 or 11, characterized in that the emulsifying agent is constituted by the association of polysorbate 80, in solution in the aqueuse phase, and of a sorbitan ester, in solution in the organic phase.
16) Process according to claim 10, characterized in that the organic phase contains a mixture of triglycerides.
17) Process according to claim 10, characterized in that the one or more triglycerides contained in the organic phase is/are one or more triglycerides of C8 to C18 fatty acids.
18) Process according to claim 10, characterized in that the organic phase is constituted by a chloroform/cyclohaxane.
19) Process according to claim 10, characterized in that the organic phase contains xylene or toluene.
20) Process according to claim 10, characterized in that the organic phase is a hydrocarbon/triglyceride mixture which contains between 10 and 50%, by weight, of hydrocarbons.
21) Process according to claim 10, characterized in that in the microcapsule formation step, the polyfunctional reagent used is a diiqocyanate.
22) Liquid or semi-solid products, characterized in that they contain microcapsules according to
claim 1.
23) Papers or textiles, characterized in that they contain microcapsules according to claim 24) Polymer based products, in particular elastomers, characterized in that they contain microcapsules according to claim 1 25) Soaps, characterized in that they contain microcapsules according to claim 1 .
23) Papers or textiles, characterized in that they contain microcapsules according to claim 24) Polymer based products, in particular elastomers, characterized in that they contain microcapsules according to claim 1 25) Soaps, characterized in that they contain microcapsules according to claim 1 .
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8908777 | 1989-06-30 | ||
| FR8908777A FR2649019B1 (en) | 1989-06-30 | 1989-06-30 | MICROCAPSULES CONTAINING WATER-SOLUBLE AMPHIPHILIC SUBSTANCES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2019224A1 true CA2019224A1 (en) | 1990-12-31 |
Family
ID=9383320
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002019224A Abandoned CA2019224A1 (en) | 1989-06-30 | 1990-06-18 | Microcapsules containing watersoluble amphiphilic substances |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0407257A3 (en) |
| JP (1) | JPH03131339A (en) |
| KR (1) | KR910000129A (en) |
| CA (1) | CA2019224A1 (en) |
| DE (1) | DE407257T1 (en) |
| ES (1) | ES2020795A4 (en) |
| FR (1) | FR2649019B1 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2679777B1 (en) * | 1991-08-02 | 1993-12-03 | Hutchinson | MICROCAPSULES CONTAINING AMPHIPHILIC AND WATER-SOLUBLE SUBSTANCES, THEIR PREPARATION PROCESS AND THEIR APPLICATIONS IN SURGERY AND MEDICINE. |
| DE69324393T2 (en) * | 1992-01-22 | 1999-09-30 | Hutchinson, Paris | Antiseptic-based products and their uses |
| FR2686221B1 (en) * | 1992-01-22 | 2000-02-25 | Hutchinson | ANTISEPTIC COMPOSITIONS AND THEIR APPLICATIONS. |
| FR2691325B1 (en) * | 1992-05-21 | 1997-06-06 | Hutchinson | ANTISEPTIC COMPOSITIONS AND THEIR APPLICATIONS. |
| FR2698561B1 (en) * | 1992-11-27 | 1995-02-17 | Flamel Tech Sa | Microcapsules containing at least one active principle, application of these microcapsules in systems for instantaneous release of active principles, and coating process useful for preparing said microcapsules. |
| US5700679A (en) * | 1996-06-07 | 1997-12-23 | Novavax, Inc. | Lipid vesicles having a bilayer containing a surfactant with anti-viral and spermicidal activity |
| GB9621297D0 (en) * | 1996-10-11 | 1996-11-27 | Warwick Int Group | Micro capsules |
| US6248364B1 (en) | 1997-04-07 | 2001-06-19 | 3M Innovative Properties Company | Encapsulation process and encapsulated products |
| DE10138996A1 (en) | 2001-08-15 | 2003-02-27 | Basf Ag | Microcapsule dispersion |
| FR3023852A1 (en) * | 2014-07-21 | 2016-01-22 | Satisloh Ag | FIBROUS MEDIUM COMPRISING PARTICLES CONTAINING PARTIALLY SOLUBLE ACTIVE AGENT IN WATER, PARTICLES AND METHODS OF MAKING THE PARTICLES |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3020148A1 (en) * | 1980-05-28 | 1981-12-03 | Bayer Ag, 5090 Leverkusen | CONCENTRATED MICROCAPSULE SUSPENSIONS FOR REACTION COPY PAPERS |
| EP0048354B1 (en) * | 1980-09-22 | 1985-01-02 | Pennwalt Corporation | A marking or labeling agent |
-
1989
- 1989-06-30 FR FR8908777A patent/FR2649019B1/en not_active Expired - Fee Related
-
1990
- 1990-06-18 CA CA002019224A patent/CA2019224A1/en not_active Abandoned
- 1990-06-20 EP EP19900401742 patent/EP0407257A3/en not_active Withdrawn
- 1990-06-20 ES ES90401742T patent/ES2020795A4/en active Pending
- 1990-06-20 DE DE199090401742T patent/DE407257T1/en active Pending
- 1990-06-29 JP JP2174310A patent/JPH03131339A/en active Pending
- 1990-06-29 KR KR1019900009714A patent/KR910000129A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0407257A2 (en) | 1991-01-09 |
| JPH03131339A (en) | 1991-06-04 |
| EP0407257A3 (en) | 1992-01-08 |
| KR910000129A (en) | 1991-01-29 |
| ES2020795A4 (en) | 1991-10-01 |
| DE407257T1 (en) | 1991-05-23 |
| FR2649019B1 (en) | 1991-10-18 |
| FR2649019A1 (en) | 1991-01-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 19931220 |