MXPA98001863A

MXPA98001863A - Microemuls

Info

Publication number: MXPA98001863A
Application number: MXPA/A/1998/001863A
Authority: MX
Inventors: Bauer Kurt; Neuber Clarissa; Schmid Axel; Manfred Volker Karl
Original assignee: F Hoffmannla Roche Ag
Priority date: 1997-03-17
Filing date: 1998-03-09
Publication date: 1999-02-24

Abstract

The present invention relates to a microemulsion of the oil-in-water type, which contains at least one polyglycerol ester as an emulsifier and at least one lipophilic substance as an internal phase. The emulsifier contains a triglycerol ester of a mono-fatty acid and the lipophilic substance is one of the group of carotenoids, especially elá-carotene, vitamins A, D, E and K and their derivatives and polyunsaturated fatty acids.

Description

MICROEMULSION FIELD OF THE INVENTION The invention relates to a microemulsion of the oil-in-water type, which contains at least one ester of polyglycerol as an emulsifier and at least one lipophilic substance as an internal phase.

BACKGROUND OF THE INVENTION Certain substances, which can be used for the preparation of a microemulsion, lead to microemulsions which can be used without hesitation in food products or in the pharmaceutical or cosmetic field for humans. For example, in the pharmaceutical field, the emulsions have been prepared using surfactant emulsifiers containing polyoxyethylene radicals in the hydrophilic part of the chain. With the aid of these surfactants, even fat-soluble substances, for example vitamins or active pharmaceutical substances, can be solubilized in water to give a clear emulsion. However, these emulsifiers can be harmful to health. Its use in food products is consequently prohibited, mainly because these surfactants REF .: 26881 contain monomeric radicals that are potentially carcinogenic.

Patent GB 2 222 770 discloses microemulsions possessing esters of a sugar as emulsifiers, which contain, as essential emulsifiers, polyoxyethylenes of small olea, which, however, are toxic.

In addition, by US Pat. No. 5,045,337, a water-in-oil microemulsion system with polyglycerol mono-diglycerol esters as emulsifiers for the formulation of hydrophilic vitamins, and flavorings is known for the food field.

US patent 4,835,002 discloses oil-in-water microemulsion with polyglycerol esters for the formulation of edible lipophilic oils, oils that impart flavor or oils for flavor, which are proposed for the food field.

DESCRIPTION OF THE INVENTION The present invention relates to a microemulsion of the oil-in-water type, which contains at least polyglycerol ester as an emulsifier and, at least, a lipophilic substance as an internal phase, which can optionally be dissolved in water.

The microemulsion is characterized in that the emulsifier contains at least one triglycerol ester of monohydric acid and the lipophilic substance is selected from the group of carotenoids, especially β-carotene, vitamins A, D, E and K and their derivatives and polyunsaturated fatty acids such as, for example, aranquidonic acid, eicosapentaenoic acid and docosahexaenoic acid.

Derivatives of vitamins are, for example, vitamin A acetate, vitamin A palmitate, vitamin E acetate and the like. With the name of vitamin E, synthetic or natural tocopherols are included.

With this microemulsion it is possible to solubilize the lipophilic substances mentioned above in any amount of water, without changing the microscopic appearance of the microemulsion or without breaking the microemulsion.

The emulsifiers used are non-toxic and therefore these microemulsions can be used in food products. They can also be used in the pharmaceutical field. Cosmetic formulations are equally possible.

The preferred triglycerol monohydric acid esters are triglycerol monolaurate, triglycerol monocaproate or triglycerol monocaprylate, especially triglycerol monolaurate or triglycerol monocaprylate.

The microemulsions can be prepared with or without a coemulsifier. The preferred coemulsifiers are ethanol, propylene glycol, transcutol, polyethylene glycols, polyglycerols, monoglycerides or lecithin, especially transcutol, monoglycerides or lecithin, with lecithin being the most especially preferred.

In addition, the microemulsion may also contain at least one carrier oil. The lipophilic substance dissolves at least in part in the carrier oil, which increases the final content of lipophilic substance in the finished microemulsion. The support oil is preferably orange oil, palm oil, a triglyceride, squalane, squalene, limonene, isopropyl myristate or isopropyl palmitate, especially orange oil, squalane or limomeno, preferably orange oil.

The microemulsion contains, as a vitamin, especially tocopherol and / or vitamin A, especially vitamin A palmitate. As a carotenoid, the microemulsion preferably contains 11-trans-β-carotene, 9-cis-β-carotene, 13-cis -ß-carotene, apocarotenal, astaxanthin, canthaxanthin, crocetin or lycopene. A β-carotene is especially preferred.

Preferably, the amount of lipophilic substance, for example tocopherol, is 1-20% by weight, the amount of emulsifier is 10-99% by weight and the amount of coemulsifier (when present) is 1-89% by weight, the ratio of emulsifier to coemulsifier being preferably 50: 50% by weight.

The microemulsion can be used especially in food products, in pharmaceutical preparations and in cosmetics.

The microemulsion according to the invention is especially suitable for emulsions of which the lipophilic substances mentioned above need to be solubilized as pharmaceutically active lipophilic substances. For example, tocopherol is especially useful as a lipid.

The microemulsion can be diluted or miscible in water in any proportion. A pharmaceutically convenient dilution of the microemulsion contains for example 90% by weight of water. In this formulation, 0.1-2% by weight of tocopherol would be present.

The rate of formation of the microemulsion depends on the speed at which the individual components dissolve. When, for example, ointment-type emulsifiers are used, such as for example triglycerol monolaurate, the speed at which these emulsifiers dissolve can be accelerated by slight agitation and possible heating at approximately 40-45 ° C. A magnetic stirrer is suitable for this purpose. However, a different agitator or any heating system can be used. The formulation is terminated when a clear isotropic liquid has been formed from the individual components. This happens after a few minutes.

The formulations may additionally contain flavors, colorants and / or thickeners, when their use requires it. If the content of polyglycerol esters amounts to less than 3-5%, the formulation can be further preserved with conventional preservatives.

Other characteristics and details will be evident from the following examples.

EXAMPLE 1 5 g of tocopherol were weighed together with 30 g of triglycerol monolaurate as well as 65 g of demineralized water and dissolved at 45-50 ° C, with stirring. A clear isotropic emulsion was obtained which was stable between 4 ° C and 45 ° C: It could be dissolved with any amount of water.

EXAMPLE 2 1 g of tocopherol was stirred with 4.5 g of triglycerol monolaurate and 4.5 g of ethanol. A clear yellow emulsion was obtained at room temperature. It could dissolve with any amount of water without breaking.

EXAMPLE 3 1 g of tocopherol was stirred at room temperature with 4.5 g of triglycerol monolaurate and 4.5 g of propylene glycol. A viscous yellow solution was obtained.

The resulting microemulsion could be dissolved with more than 100 ml of water without breaking the microemulsion.

EXAMPLE 4 2.5 g of tocopherol and 7.5 g of triglycerol monocaprylate were stirred at room temperature using a magnetic stirrer until a clear, base microemulsion was obtained. This base can be diluted with water and then form microemulsions of the o / w type.

EXAMPLE 5 0.6 g of phytomenadione (vitamin Kl), 2.35 g of lecithin (co-emulsifier) and 7.05 g of triglycerol monocaprylate were stirred at room temperature using a magnetic stirrer until a clear, base microemulsion was obtained. This base could be dissolved with water and then form microemulsions of the o / w type.

EXAMPLE 6 1 g of tocopherol was stirred at room temperature with 9 g of triglycerol monocaproate. The resulting yellow, clear microemulsion was miscible with water in any proportion without the emulsion breaking.

EXAMPLE 7 1.6 g of orange oil (carrier oil) were weighed together with 3.0 g of triglycerol monolaurate (emulsifier) and 5.4 g of demineralised water and dissolved in a few minutes with stirring. A transparent yellow base microemulsion was obtained. 37 mg of the β-apo-8'-carotenic acid ethyl ester was added to this base microemulsion. The carotenoid was dissolved in the microemulsion base in the interval of a few hours, stirring. A clear, red microemulsion was obtained, which was miscible in any amount of water.

EXAMPLE 8 1.6 g of orange oil (carrier oil) were weighed together with 3.0 g of triglycerol monolaurate (emulsifier) and 5.4 g of demineralized water and dissolved in the course of a few minutes, with stirring. 31 mg of β-apo-8'-carotenal was added to this base microemulsion. The carotenoid was dissolved in the microemulsion base in the interval of a few hours, stirring. A clear, red microemulsion was obtained, which was miscible with any amount of water.

EXAMPLE 9 1.6 g of orange oil (carrier oil) were weighed together with 3.0 g of triglycerol monolaurate (emulsifier) and 5.4 g of demineralized water and dissolved in the course of a few minutes, with stirring. 0.3 mg of astaxanthin was added to this base microemulsion. The carotenoid was dissolved in the microemulsion base in the interval of a few hours, stirring. A clear orange microemulsion was obtained, which was miscible with any amount of water.

EXAMPLE 10 1.6 g of orange oil (carrier oil) were weighed together with 3.0 g of triglycerol monolaurate (emulsifier) and 5.4 g of demineralized water and dissolved in the space of a few minutes, with stirring. 1 mg of canthaxanthin was added to this base microemulsion. The carotenoid was dissolved in the base microemulsion in the interval of a few hours, stirring. A clear, orange microemulsion was obtained, which was miscible in any amount of water.

EXAMPLE 11 1.6 g of orange oil (carrier oil) were weighed together with 3.0 g of triglycerol monolaurate (emulsifier) and 5.4 g of demineralized water and dissolved in the course of a few minutes, with stirring. 8 mg of lycopene was added to this base microemulsion. The caroteniode was dissolved in the base microemulsion in the interval of a few hours, stirring. A clear, red microemulsion was obtained, which was miscible in any amount of water.

EXAMPLE 12 1.6 g of orange oil (carrier oil) were weighed together with 3.0 g of triglycerol monolaurate (emulsifier) and 5.4 g of demineralized water and dissolved in the range of a few minutes, stirring 2 mg of an 11-tans-ß-carotene was added to this microemulsion base, the carotenoid was dissolved in the microemulsion base in the interval of a few hours, stirring.A clear, orange-red microemulsion was obtained. It was miscible in any amount of water.

EXAMPLE 13 1.6 g of orange oil (carrier oil) were presented together with 3.0 g of triglycerol monolaurate (emulsifier) and 5.4 g of demineralized water and dissolved in the interval of a few minutes, with stirring. 30 mg of 13-cis-β-carotene was added to this base microemulsion. The carotenoid was dissolved in the base microemulsion in the interval of a few hours, stirring. A clear, red microemulsion was obtained, which was miscible in any amount of water.

EXAMPLE 14 1.6 g of orange oil (carrier oil) were weighed together with 3.0 g of triglycerol monolaurate (emulsifier) and 5.4 g of demineralized water and dissolved in the interval of a few minutes, with stirring. 90 mg of 9-cis-β-carotene was added to this base microemulsion. The carotenoid was dissolved in the base microemulsion in the interval of a few hours, stirring. A clear, red microemulsion was obtained, which was miscible in any amount of water.

EXAMPLE 15 0.6 g of vitamin A acetate and 9.4 g of triglycerol monolaurate (emulsifier) were treated with 15.0 g of demineralised water and heated at 60 ° C for about 5 minutes, stirring with a magnetic stirrer. . After cooling, a yellow microemulsion was obtained which was dilutable in any amount of water.

EXAMPLE 16 1.0 g of vitamin E acetate, 8.0 g of triglycerol monolaurate (emulsifier) and 1.0 g of Imwitor 988 (caprylic acid monodiglyceride from Hüls, co-emulsifier) were stirred at room temperature with 10 g. , 0 g of demineralized water, using a magnetic stirrer until a microemulsion is obtained. This microemulsion was dilutable in any amount of water.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Having described the invention as above, the content of the following is claimed as property.

Claims

1. A microemulsion of the oil-in-water type, characterized in that it contains at least one polyglycerol ester as an emulsifier and at least one lipophilic substance as internal phase, in which the emulsifier contains a triglycerol ester of a monohydric acid and the substance Lipophilic is one of the group of carotenoids, especially ß-carotene, vitamins A, D, E, and K and their derivatives, and polyunsaturated fatty acids.

2. The microemulsion according to claim 1, characterized in that the triglycerol ester of monohydric acid is triglycerol monolaurate, triglycerol monocaproate or triglycerol monocaprylate, especially triglycerol monolaurate or triglycerol monocaprylate.

3. The microemulsion according to claim 1 or claim 2, characterized in that it additionally contains a coemulsifier.

4. The microemulsion according to claim 3, characterized in that the coemulsifier is ethanol, propylene glycol, transcutol, a polyethylene glycol, a monoglyceride or lecithin, especially transcutol, a monoglyceride or lecithin, preferably lecithin.

5. The microemulsion according to any of claims 1 to 4, characterized in that it additionally contains at least one support oil.

6. The microemulsion according to claim 5, characterized in that the supporting oil is orange oil, palm oil, a triglyceride, squalane, squalene, limonene, isopropyl myristate or isopropyl palmitate, especially orange oil, squalane or limonene, preferably orange oil.

7. The microemulsion according to any one of claims 1 to 6, characterized in that it contains tocopherol and / or vitamin A, especially vitamin A palmitate, as a vitamin.

8. The microemulsion according to any one of claims 1 to 7, characterized in that the content of lipophilic substance, especially tocopherol, is 1-20% by weight, the emulsifier content is 10-99% by weight, and the content of co-emulsifier (when present) is 1-89% by weight, the ratio of emulsifier to co-emulsifier being preferably about 50:50% by weight.

9. The microemulsion according to any one of claims 1 to 8, characterized in that it contains as carotenoid at least one of the group of 11-trans-β-carotene, 9-cis-β-carotene, 13-cis-β-carotene, apocarotenal, astaxanthin, canthaxanthin, crocetin and lycopene, preferably at least one β-carotene.

10. The microemulsion according to any one of claims 1 to 9, characterized in that it is diluted with water.

11. The microemulsion according to any one of claims 1 to 10, characterized in that it is for use in food products, in pharmaceutical preparations and in cosmetics.

12. A food, pharmaceutical or cosmetic product, characterized in that it contains at least one microemulsion according to any one of claims 1 to 10.