EP0692957A1

EP0692957A1 - Multiple w/o/w emulsion preparation process

Info

Publication number: EP0692957A1
Application number: EP94913085A
Authority: EP
Inventors: Catherine Le Hen-Ferrenbach; Isabelle Terrisse; Armelle Magnet; Monique Seiller; Francis Puisieux; Jean-Louis Grossiord
Original assignee: Henkel AG and Co KGaA
Current assignee: Henkel AG and Co KGaA
Priority date: 1993-04-07
Filing date: 1994-03-30
Publication date: 1996-01-24
Also published as: DE4311445C1; US5714154A; JPH08508202A; WO1994022414A1

Abstract

In order to prepare multiple W/O/W emulsions, a mixture of an easily biodegradable oily body and of an aqueous emulsifyer (I) from the group of the glycerine- and/or oligo- or polyglycerine fatty acid esters is first transformed under strong shearing conditions into a W/O pre-emulsion, then is further treated under weak shearing conditions with an aqueous emulsifyer (II) from the group of the addition products of ethylene oxide onto fatty alcohols and/or sterols, and if required with fatty alcohols. These products are suitable for preparing cosmetic and pharmaceutical products.

Description

Process for the production of multiple / O / W inputs

Field of the Invention

The invention relates to a process for the preparation of multiple W / O / W emulsions, in which a W / O pre-emulsion is first prepared from water, an oil body and an emulsifier I under strong shear, and these are then washed under black cher shear treated with an aqueous emulsifier II, multiple W / O / W emulsions obtainable by this process and the use of these multiple W / O / W emulsions for the production of cosmetic and pharmaceutical products.

State of the art

Multiple emulsions are emulsions of emulsions. Depending on the production, a distinction is made between multiple water / oil / water (W / O / W) and oil / water / oil (0 / W / O) emulsions. The most important application of multiple emulsions is to process active ingredients that are otherwise not miscible or ready for assembly in a recipe. Another advantage is that the active ingredients can be released in a controlled manner over a longer period of time. Multiple emul Sions are therefore particularly important for the production of cosmetic and pharmaceutical products rCosm.Toil.105. 65 (1990)].

A particularly elegant process for the production of multiple emulsions is described by S.Matsumoto in J.Coll.Interf.Sei 57, 353 (1976): According to this, a pre-emulsion is first prepared at elevated temperature and with strong shear, which is then introduced into the aqueous solution of a hydrophilic emulsifier at ambient temperature and under low shear. Sorbitan monoleate and polyethylene glycol derivative are used as the emulsifier pair.

It is also known from the extensive state of the art that monoglycerides, sorbitan esters, polysorbates and highly ethoxylated fatty alcohols can in principle be considered as hydrophilic emulsifiers for the production of multiple emulsions. Here is representative of the publications in Phar. Acta.Helv. j> 6, 343 (1991), and by Seiller and Luca in Bull.Tech./Gattefosse Rep. .80., 27 (1987), S.T.P. Phar a 4_, 679 (1988) and In .J.Cosme .Sei. 13, 1 (1991).

W / O / W emulsions are also known from Yakugaku Zasshi 112, 73 (1992), which contain glycerol trifatty acid esters as oil bodies and hydrophilic polymers, such as gelatin, as stabilizing agents. The use of albumin and polyacrylates as stabilizers for the water phase and nonionic surfactants for the oil phase is known from J. Controlled Release. 3, 279 (1986). However, such formulations have proven to be insufficiently stable in storage, in particular in the case of temperature fluctuations. A particular problem in the production of multiple emulsions is therefore the selection of suitable pairs of emulsifiers, which ensure adequate thermal stability even after prolonged storage. Another disadvantage is that mineral oils are usually used as oil bodies, which show an unfavorable biodegradability.

The object of the invention was therefore to develop a new method for producing multiple W / O / W emulsions which is free from the disadvantages described.

Description of the invention

The invention relates to a method for producing multiple W / O / W emulsions, in which

a) first a mixture of an oil body and a lipophilic emulsifier I from the group of glycerol and / or oligo- or polyglycerol fatty acid esters is processed under strong shear to give a W / O pre-emulsion A and

b) these are then further treated under weak shear with an aqueous emulsifier II from the group consisting of the adducts of ethylene oxide with fatty alcohols and / or sterol and, if appropriate, fatty alcohols.

Surprisingly, it was found that the multiple W / O / W emulsions obtainable by the process according to the invention ions are stable in storage for a long time even when the temperature fluctuates significantly. The invention includes the finding that by selecting the specified oil bodies and dispensing with polymeric stabilizers, multiple emulsions of a biodegradability which is significantly improved compared to the prior art can be provided.

Oil body

Dialkylcyclohexanes and dialkyl ethers are suitable as oil bodies for the preparation of the multiple W / O / W emulsions according to the invention.

The dialkylcyclohexanes are known substances that can be obtained by relevant processes in preparative organic chemistry. An example of their preparation is, for example, subjecting dialkyl aromatics (ortho / meta / para-xylene) from the BTX fraction of the petroleum to a catalytic hydrogenation.

The dialkylcyclohexanes in question follow the formula (I)

Ri-CR ² (I)

in which R ¹ and R ² independently of one another are alkyl radicals having 1 to 12 carbon atoms and C is a cyclohexyl radical. Typical examples are dimethylcyclohexane, diethylcyclohexane, methylethylcyclohexane, dipropylcyclohexane, Di-n-butylcyclohexane, di-tert-butylcyclohexane, di-2-ethylhexylcyclohexane and in particular di-n-octylcylohexane.

Dialkyl ethers are to be understood as meaning compounds of the formula (II)

R3_O_R4 (II)

in which R ^ and R ^{4 are} independently alkyl radicals having 6 to 22 carbon atoms.

These are also known substances that can be obtained by the relevant methods of preparative organic chemistry. Processes for their preparation, for example by condensation of fatty alcohols in the presence of p-toluenesulfonic acid, are known, for example, from Bull.Soc. Chim.France, 333 (1949), DE-Al 40 39 950 (Hoechst) and DE-Al 41 03 489 (Henkel) are known. From an application point of view, symmetrical dialkyl ethers are preferred which have 6 to 12 carbon atoms in the alkyl radicals. Dialkyl ethers of the formula (II), in which R 1 and R ^{4 are} octyl and / or 2-ethylhexyl radicals, have a particularly rapid emulsifying capacity. The particularly preferred dialkyl ethers for the purposes of the invention are thus di-n-octyl ether and di-2-ethylhexyl ether.

The oil bodies can be used in amounts of 10 to 30, preferably 15 to 25,% by weight, based on the pre-emulsion A. Emulsifier I

Suitable emulsifiers I are glycerol and / or oligo- or polyglycerol esters. Typical examples are technical mono- and / or diesters of glycerol with fatty acids having 12 to 22 carbon atoms, such as, for example, glycerol monolaurate, glycerol monopalmitate, glycerol onostearate, glycerol mono isostearate, glycerol monooleate and glycerol mono-henate. Further typical examples are mono- and / or di-esters of oligo- or polyglycerol mixtures (degree of self-condensation 2 to 20, preferably 2 to 10) of said fatty acids with 12 to 22 carbon atoms, such as polyglycerol -di-isostearate or polyglycerol-di-oleate. It has proven to be particularly advantageous to use mixtures of glycerol and oligo- or polyglycerol esters, for example consisting of glycerol monooleate and triglycerol di-isostearate (mixing ratio, for example 80:20 parts by weight). The emulsifiers I can be used in amounts of 1 to 10, preferably 1 to 4,% by weight, based on the pre-emulsion A.

Emulsifier II

Adducts of an average of 20 to 50, preferably 20 to 30, mol of ethylene oxide with fatty alcohols having 16 to 22, preferably 16 to 13, carbon atoms are suitable as emulsifier II. Typical examples are adducts of an average of 25 to 30 mol of ethylene oxide with stearyl alcohol, isostearyl alcohol, oleyl alcohol, elaidyl alcohol, petroselinyl alcohol, linolyl alcohol, linolenyl alcohol, arachyl alcohol, Gadoleyl alcohol, behenyl alcohol and erucyl alcohol as well as their technical mixtures, such as are obtained, for example, in the high-pressure hydrogenation of native fatty acid methyl esters or aldehydes from Roelen's oxosynthesis. Addition products of an average of 25 to 30 moles of ethylene oxide with technical grade cetylstearyl alcohols are preferably used.

Addition products of an average of 10 to 40 moles of ethylene oxide with sterols of plant and / or animal origin are also suitable as further emulsifiers. The term sterols here is understood to mean steroids with 27 to 30 carbon atoms which only carry a hydroxyl group at C-3, but otherwise have no functional groups and are often incorrectly referred to as sterols [ROEMPP Chemie Lexikon, Vol. 5 , 1992, p.4302]. Typical examples are addition products of on average 10 to 40, preferably 25 to 30, moles of ethylene oxide with zoosterols, such as cholesterol, lanosterol, spongosterol or stellasterin or phystosterols, such as ergosterol, stigmasterol and sitosterol. Adducts of on average 25 to 30 moles of ethylene oxide with soyasterol are particularly preferred.

In a preferred embodiment of the invention, mixtures of addition products of an average of 20 to 50 moles of ethylene oxide with fatty alcohols with 16 to 22 carbon atoms and sterols of vegetable and / or animal origin are used. A typical example is a mixture of an adduct of an average of 30 moles of ethylene oxide with cetylstearyl alcohol and a adduct of an average of 25 moles of ethylene oxide with soybean sterol in a weight ratio of 1: 5 to 5: 1, preferably 2 : 1. Emulsifiers II can be used in amounts of 1 to 10, preferably 2.3 to 6.5,% by weight, based on the multiple W / O / W emulsion.

In a particular embodiment of the invention, fatty alcohols having 12 to 22, preferably 16 to 18 carbon atoms can be added to the emulsifier II as co-emulsifiers, which form a liquid-crystalline network in the emulsifier phase and to further improve the stability of the resulting W / O / W emulsions. Suitable fatty alcohols are, for example, technical cetyl / stearyl alcohols. The weight ratio between emulsifier II and co-emulsifier can be 1: 1 to 1: 2, preferably 1: 1.5 to 1: 1.8.

Preparation of pre-emulsion A

To produce the pre-emulsion, the oil body is placed in a stirring device and the lipophilic emulsifier I is added. The components are homogenized under strong shear, ie at a stirrer speed of 1000 to 2000, preferably 1200 to 1700 rpm. Centripetal turbines or, in particular, colloid mills can be considered as stirring devices. It has proven to be particularly advantageous to carry out the preparation of the pre-emulsion A at elevated temperature, ie at 50 to 90, preferably 70 to 80 ° C. The homogenization time is usually in the range from 5 to 40, preferably 10 to 30, minutes. For stabilization it is also recommended to use the pre-emulsion salt, preferably add magnesium sulfate in amounts of 0.5 to 2% by weight, based on the pre-emulsion.

The composition of the pre-emulsion A is therefore typically:

al) 10 to 30 (preferably 15 to 25)% by weight of oil body; a2) 1 to 10 (preferably 1 to 4)% by weight of emulsifier I; a3) 0.5 to 2 (preferably 0.5 to 1)% by weight of salt; a4) ad 100 wt .-% water.

The water content of the pre-emulsion A is usually 58 to 88.5, preferably 70 to 83% by weight.

Preparation of the multiple W / O / W emulsion

To prepare the multiple W / O / W emulsion, the pre-emulsion A is placed in a stirrer and mixed with the aqueous emulsifier II. The pre-emulsion A can be used in amounts of 50 to 90, preferably 65 to 80,% by weight, based on the multiple W / O / W emulsion. The components are homogenized under low shear, ie at a stirrer speed of 10 to 500, preferably 150 to 250 rpm. Zen tripetal turbines or, in particular, colloid mills are again suitable as stirring devices. It has proven particularly advantageous to carry out the preparation of pre-emulsion A at 20 to 60 and in particular 20 to 25 ° C. The homogenization time is usually in the range from 5 to 50, preferably 10 to 30, minutes. The composition of the multiple W / O / W emulsion is thus typically:

bl) 50 to 90 (preferably 65 to 80)% by weight of pre-emulsion b2) 1 to 10 (preferably 2 to 7)% by weight of emulsifier II b3) 0 to 5 (preferably 1 to 4)% by weight Co-emulsifier b4) ad 100 wt .-% water.

Usually the water content of the multiple W / O / W emulsion - including the water content of the pre-emulsion A - is 57 to 93, preferably 74 to 89% by weight.

Another object of the invention relates to particularly stable multi-W / O / W emulsions containing

15 to 20% by weight dioctylcyclohexane 1 to 5% by weight triglycerol di-isostearate /

Glycerol monooleate (4: 1 parts by weight) 0.5 to 2% by weight magnesium sulfate

1 to 3% by weight of cetylstearyl alcohol-30 EO adduct 0.5 to 2% by weight of sterol-25 EO adduct 1 to 4% by weight of cetyl / stearyl alcohol ad 100% by weight of water.

Industrial applicability

The multi-plen W / O / W emulsions obtainable by the process according to the invention prove to be stable even after prolonged storage and are readily biodegradable. They are suitable for picking up and controlled, time-delayed delivery of active substances that cannot otherwise be assembled.

Another object of the invention therefore relates to the use of the multiple W / O / W emulsions obtainable by the process according to the invention for the production of cosmetic and pharmaceutical products, in particular agents for hair and body cleaning and care, in which the multiple emulsions can be contained in amounts of 1 to 99, preferably 10 to 50% by weight, based on the composition.

The following examples are intended to explain the subject matter of the invention in more detail without restricting it.

Examples

I. Substances used

a) Oil body

al) Cetiol ^(R) S, Fa. Henkel KGaA, Düsseldorf / FRG

Dioctylcyclohexane a2) Cetiol ( ^R ) OE, Fa.Henkel KGaA, Düsseldorf / FRG

Di-n-octyl ether

b) Emulsifier I

bl) Dehymuls ( ^R ) B, Sidobre-Sinnova, Meaux / FR

Polyglycerol di-isostearate, degree of condensation = 5 b2) Monomuls ( ^R ) 90-O-18,

Chemische Fabrik Grünau, Illertissen / FRG Glycerin monooleate, monoglyceride content 90% by weight

c) Emulsifier II

cl) Mergital ( ^R ) E 1471, Sidobre-Sinnova, Meaux / FR

Cetylstearyl alcohol-30 EO adduct c2) Generol ( ^R ) 122 E 25, Henkel KGaA, Düsseldorf / FRG

Soyasterol-25 EO adduct Production example 1:

la) pre-emulsion A:

20 g of Cetiol ( ^R ) S and 4 g of Dehymuls ( ^R ) B were placed in a centripetal turbine and a solution of 0.7 g of magnesium sulfate in 75 ml of water was added. The reaction mixture was then homogenized at 80 ° C. and over a period of 10 min at a speed of 1500 rpm. The speed was then reduced first to 1125 and then to 750 rpm and in each case homogenized for a further 10 min.

lb) Multiple W / O / W emulsion:

77 g of the pre-emulsion A were introduced and a solution of 2.1 g Mergital ( ^R ) E 1471 and 1 g Generol ( ^R ) 122 E 25 in 20 g water was added within 40 s and at ambient temperature over a period of Homogenized for 30 min at a speed of 200 rpm.

Production example 2:

2a) pre-emulsion A:

20 g of Cetiol ( ^R ) OE and 4 g of Monomuls ( ^R ) 90-O-18 were placed in a centripetal turbine and mixed with a solution of 0.7 g of magnesium sulfate in 75 ml of water. The reaction mixture was then homogenized at 80 ° C. and over a period of 10 min at a speed of 1500 rpm. The speed was then reduced first to 1125 and then to 750 rpm and in each case homogenized for a further 10 min.

b) Multiple W / O / W emulsion:

77 g of the pre-emulsion A were introduced and a solution of 2.1 g Mergital ( ^R ) E 1471 and 1 g Generol ^(R) 122 E 25 in 20 g water was added within 40 s and at ambient temperature over a period of Homogenized for 30 min at a speed of 200 rpm.

Production example 3:

3a) pre-emulsion A:

20 g of Cetioi ( ^R ) S and 4 g of Dehymuls ( ^R ) B were placed in a centripetal turbine and a solution of 0.7 g of magnesium sulfate in 75 ml of water was added. The reaction mixture was then homogenized at 80 ° C. and over a period of 10 min at a speed of 1500 rpm. The speed was then reduced first to 1125 and then to 750 rpm and in each case homogenized for a further 10 min.

3b) Multiple W / O / W emulsion:

60 g of pre-emulsion A were introduced and within 40 s with a solution of 1.4 g Mergital ( ^R ) E 1471, 0.7 g Generol ( ^R) 122 E 25 and 3.52 g cetyl / stearyl alcohol added to 34.4 g of water and homogenized at 60 ° C. over a period of 30 min at a speed of 200 rpm.

Claims

1. A method for producing multiple W / O / W emulsions, in which one

a) first of all, a mixture of an oil body and a lipophilic emulsifier I from the group of glycerol and / or oligo- or polyglycerol fatty acid esters is processed under strong shear to form a W / O pre-emulsion A and

b) these are then further treated under low shear with an aqueous emulsifier II from the group of addition products of ethylene oxide with fatty alcohols and / or sterols and, if appropriate, fatty alcohols.

2. The method according to claim 1, characterized in that oil bodies selected from the group formed by dialkyl cyclohexanes and dialkyl ethers are used.

3. Process according to claims 1 and 2, characterized gekenn¬ characterized in that technical mono- and / or diesters of glycerol with fatty acids having 12 to 22 carbon atoms are used as emulsifier I.

4. Process according to claims 1 and 2, characterized gekenn¬ characterized in that technical mono- and / or diesters of oligo- or polyglycerol mixtures (own degree of self-condensation 2 to 10) with fatty acids with 12 to 22 carbon atoms are used as emulsifier I.

5. Process according to Claims 1 to 4, characterized in that addition products of an average of 20 to 50 moles of ethylene oxide with fatty alcohols having 16 to 22 carbon atoms are used as emulsifier II.

6. Process according to Claims 1 to 4, characterized in that addition products of an average of 10 to 40 moles of ethylene oxide with sterols of plant and / or animal origin are used as emulsifier II.

7. The method according to claims 1 to 6, characterized gekenn¬ characterized in that as emulsifier II mixtures of Anla¬ products of an average of 20 to 50 moles of ethylene oxide with fatty alcohols with 16 to 22 carbon atoms and sterols of vegetable and / or animal Her¬ coming in.

8. The method according to claims 1 to 7, characterized gekenn¬ characterized in that fatty alcohols having 12 to 22 carbon atoms are used as emulsifier II.

9. The method according to claims 1 to 8, characterized gekenn¬ characterized in that the oil bodies in amounts of 10 to 30 wt .-% - based on the pre-emulsion A - used.

10. The method according to claims 1 to 9, characterized gekenn¬ characterized in that the emulsifiers I in amounts of 1 to 10 wt .-% - based on the pre-emulsion A - used.

11. The method according to claims 1 to 10, characterized gekenn¬ characterized in that the pre-emulsion A in amounts of 50 to 90 wt .-% - based on the multiple W / O / W emulsion - is used.

12. The method according to claims 1 to 11, characterized gekenn¬ characterized in that the emulsifiers II in amounts of 1 to 10 wt .-% - based on the multiple W / O / W emulsion - used.

13. Containing multiple W / O / W emulsions

Glycerol monooleate, 4: 1 parts by weight 0.5 to 2 wt .-% magnesium sulfate

14. Use of multiple W / O / W emulsions according to the method according to claims 1 to 12 for the production of cosmetic and pharmaceutical products.