JPS6156016B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION It is known that certain lipids have the property of forming a mesomorphic phase (a state intermediate between crystal and liquid) in the presence of water. Some of these lipids that form the mesomorph phase swell in the aqueous phase and form multilayers, especially globules consisting of a bilayer with a thickness of about 30 to 100 Å (these globules are dispersed in the aqueous phase). ) has already been described. [Especially the Journal of Molecular Biology (J.
The article by Bangham, Standish, and Watkins, published in Mol. Biol., 13, 238 (1965) is a useful reference. ] Until now, the formation of lipid globules with a concentric structure requires the use of lipids with ionic hydrophilic and lipophilic groups, and it has not been possible to form lipid globules with an already known method of forming globules. could only obtain spherules with an average diameter of less than 1000 Å. The method for obtaining such globules consists in preparing a dispersion containing in the dispersed phase a lipid compound with globule-forming ability and treating this dispersion with ultrasound. The method for preparing the dispersion before undergoing the above-mentioned ultrasonic treatment is to first evaporate the lipids to be dispersed to form a thin film on the inner wall of the container, and second to separate the thus covered inner wall from the dispersion. There is a method of contacting the continuous phase and thirdly stirring them (so as to obtain a dispersion to be subjected to ultrasonic treatment). Another method of obtaining a pre-sonication dispersion is described in French patent application no. Next, the mixture is heated gently and vigorously shaken to stir. The spherules thus obtained, which consist of concentric layers with a maximum diameter of about 1000 Å, are generally called liposomes.

It has been suggested that liposomes can be used to entrap an aqueous phase containing an active substance into the aqueous part surrounded by the two lipid layers, and to protect the entrained active substance from external conditions. Already proposed [especially the paper by Sessa Weismann described in Journal of Lipid Research (J.Lipid Res. 9310 (1968)) and Nature Vol. 235 (1972)] The paper by Magee and Miller is helpful. Since liposomes can be of any size up to 1000 Å, the permeability of the liposome to the human body can be varied and the anchorage point of the liposome can be chosen, especially by the charge on the outer surface of the liposome [Biochem J.
(1971), 124P.58P], there are many possible uses in the pharmaceutical field. However, in the field of cosmetics, the use of globules less than 1000 Å in diameter poses a risk of penetrating through the skin. At least for use in the cosmetics field,
It is clearly desirable to obtain globules consisting of concentric lipid layers with diameters greater than 1000 Å.

Furthermore, currently known methods for obtaining liposomes incorporating active substances in concentric lipid layers have important drawbacks. First, the active substance contained in the continuous phase of the dispersion before sonication is incorporated into the lipid layer of the liposome in only a very small amount (into which the continuous phase of the dispersion is only incorporated in a very small amount). This is understood because it has been found to be rare). In order to isolate liposomes that have been loaded, it is necessary to pass the dispersion, which has already been subjected to ultrasonication, through a Sephadex separation column. In that case, the liposome dispersion is extremely diluted.

On the one hand, it is practically difficult to obtain a dispersion containing a high concentration of liposomes using conventionally known methods; on the other hand, only a very small amount of the active substance is incorporated into the liposomes, and the active substance is lost during elution from the separation column. The cost of the active substance incorporated into the liposomes is high, as this cannot be easily recovered. Therefore, it is desirable to establish a method for producing globules with concentric layers, which can produce a dispersion containing a high concentration of globules, and which reduces the loss of substances incorporated into the globule layers. ing.

After all, in the liposome production methods disclosed to date, only lipids within a strictly limited range can be used. In the prior art described above, phospholipids, lipids having both hydrophilic and lipophilic ionic groups, or unsaturated fatty acids are used.

The object of the present invention is to provide a highly concentrated aqueous dispersion of globules with a diameter of around 1000 Å. The globules have a high uptake of active substance. As used herein, the term "incorporation" refers to the entrapment of an aqueous phase within a capsule formed by lipid globules. The dispersion according to the present invention is produced by a novel method discovered by the present inventor. The novel method can be applied to ionic or non-ionic lipids, and therefore can also contain non-ionic lipid compounds among the lipids with globule-forming properties, and the aqueous phase to be incorporated. This is a method to obtain a dispersion of globules consisting of surrounding molecular layers. The above method uses at least one water-dispersible compound having the general formula X-Y, where X is an ionic or non-ionic hydrophilic group and Y is a lipophilic group. The liquid lipid to be incorporated into the globules is brought into contact with the aqueous phase that is to be incorporated into the globules, and the lipophilicity/hydrophilicity ratio of the lipid is such that the lipid forms a thin film (lamellar) in the aqueous phase that is to be incorporated into the lipid. ) to form a phase, stir it to completely mix the two to obtain a thin film phase, then add a larger amount of dispersion medium than the amount of the obtained thin film phase, and stir it vigorously for about 15 minutes. 3
It is characterized by shaking for hours.

The weight ratio of the aqueous phase brought into contact with the lipid to the weight of the lipid forming the thin film phase is approximately 0.1.
~3, the aqueous phase incorporated is probably water or an aqueous solution of the active substance, and the continuous phase (dispersion medium) of the added dispersion relative to the weight of the dispersed film phase.
the weight ratio of from about 2 to about 100, the dispersion medium and the aqueous phase incorporated are isotonic, the dispersion medium is advantageously an aqueous solution, and the final step of the process, stirring, is by shaking. Perform with a stirrer at room temperature or slightly higher temperature if the lipid is solid at room temperature, and apply ultrasonication to the globule dispersion if you want to obtain globules with an average diameter of 1000 Å or less. It is preferable to carry out this method in such a way that

As the lipid forming the thin film phase, one type of lipid may be used alone or a mixture of several types may be used. The lipids that can be used are those with lipophilic carbon chains of 12 to 30 carbon atoms, saturated or unsaturated, branched or straight chain. Particularly suitable are those with oleyl, lanolyl, tetradecyl, hexadecyl, isostearyl, lauryl or alkyl phenyl chains. When forming a thin film phase with a lipid having a nonionic hydrophilic group, use polyoxyethylene, polyglycerol, oxyethylenated polyol ester or non-oxyethylenated polyol ester as the hydrophilic group, e.g. polyoxyethylenated It is advantageous to use sorbitol esters that have been prepared.

The incorporated aqueous phase can contain active substances of all kinds, but in particular active substances which have advantageous pharmaceutical or food or cosmetic properties. Substances with advantageous cosmetic properties include substances used for skin and hair care, such as humectants such as glycerin, sorbitol, pentaerythritol, inositol, pyrrolidone carboxylic acid and their salts, synthetic tanning agents such as dioxyacetone, erythrulose, γ- such as glyceraldehyde and tartaric aldehyde
Dialdehydes (these substances can sometimes be used with pigments), water-soluble sunscreens, antiperspirants, deodorants, astringents, cooling agents, hair nourishing agents, healing agents, keratolytic agents, hair removal agents. agents, lotions, animal or plant tissue extracts, such as proteins, polysaccharides and amniotic fluid, water-soluble colorants, anti-dandruff agents, anti-seborrheic agents, oxidizing agents (bleaching agents) such as hydrogen peroxide, ring-forming agents. Examples include thioglycolic acid or its salts. Pharmaceutically active substances include vitamins, hormones, enzymes such as dismutase peroxide, vaccines, anti-inflammatory agents such as hydrocortisone, antibiotics and fungicides.

It is obvious that a lipid that can stably take up the aqueous phase should be selected depending on the active substance contained in the aqueous phase. In order for the lipids forming the thin film phase to provide stability to the globules, sufficient interaction between the lipid chains that line up and form the layer of the globules, that is, the bond between the layers must be strong. It is necessary that there be a Van der Waals force acting between the chains. Lipids with the characteristics indicated in the general definition of the method above meet this condition. The lipids that can be used in the above method according to the invention belong to the water-in-oil emulsifiers.

The method according to the invention makes it possible to form globules with non-ionic lipid compounds, thereby making it possible to form new structures capable of incorporating active substances that can be used in the pharmaceutical, food and cosmetic fields. . When it is desired to obtain globules with no charge on the outer surface, it is effective to construct the globules with a nonionic compound.

The present invention consists of an organized molecular layer of a lipid compound and an aqueous phase incorporated therein.
A dispersion of 50,000 Å globules, in which the lipid compound has lipophilic chains, can be dispersed in water, and has sufficient affinity to swell and form a thin film phase in the aqueous phase to be incorporated into the globules. having an oily/hydrophilic ratio, (a) straight chain or branched chain, each of the following formulas R-(OCH ₂ CHOHCH ₂ -) _o OH and (In this formula, n is an integer from 1 to 6, and R is a straight or branched saturated or unsaturated aliphatic chain having 12 to 30 carbon atoms, a hydrocarbon residue of lanolin alcohol, or a long chain. α of
-2-hydroxyalkyl residues of diols), (b) polyoxyethylenated aliphatic alcohols, (c) oxyethylenated or non-oxyethylenated polyol esters, especially poly The present invention relates to a novel industrial product as a globule dispersion, which is a non-ionic amphiphilic compound selected from the group consisting of oxyethylated sorbitol esters and (d) natural or synthetic glycolipids such as cerebrosides.

The continuous phase of the dispersion surrounding the globules is an aqueous phase, and the aqueous phase entrained in the globules is an aqueous solution of the active substance and is preferably isotonic with the continuous phase of the dispersion.

Various additives can be added to the nonionic lipid compound to change the permeability of the globule or the charge on the surface of the globule. Additives that may be optionally added in this way include long-chain alcohols and diols, sterols such as cholesterol, long-chain amines and their quaternary ammonium derivatives, dioxyalkylamines, polyoxyethylated aliphatic amines. , long-chain amino alcohol esters and their salts and quaternary ammonium derivatives, phosphoric acid esters of aliphatic alcohols such as sodium dicetyl phosphate, alkyl sulfates such as sodium cetyl sulfate, certain polymers such as polypeptides and proteins. I can do it.

The incorporated aqueous phase is an aqueous solution of the active substance;
the active substance is a cosmetically active substance;
The continuous phase of the dispersion is an aqueous phase, the ratio of the weight of the globules to the weight of the continuous phase of the dispersion being approximately 0.01 to 0.5, the continuous phase of the dispersion being advantageously incorporated into the globules. It is preferably isotonic with the aqueous phase in which it is present.

The active substances that can be incorporated into the globules in the dispersion defined above are very diverse and correspond to the active substances previously indicated for carrying out the above-mentioned method according to the invention. ing. This composition can be used in many fields, but especially in the pharmaceutical and cosmetic fields.

Aqueous dispersions containing large diameter globules are particularly valuable in the cosmetics field. This is because using larger diameter globules reduces the risk of the formulation passing through the skin.

It is worth noting that in cosmetics the use of aqueous dispersions according to the invention containing nonionic lipid compounds is very advantageous over the use of the well-known emulsions. In fact, if one wishes to use formulations containing both lipid and water, amphiphilic emulsifiers must be used to increase the stability of the dispersion in order to stabilize the emulsion. It is known that certain emulsifiers exhibit relatively strong irritating effects when applied to the skin. Through research related to the present invention, it has been found that due to the chemical structure of the emulsifier, this effect of the emulsifier is highly dependent on the form in which the emulsifier is applied. This fact shows that 42% perhydrosqualene, 8% emulsifier and water
A water-in-oil emulsion consisting of 50% emulsifier exhibits strong stinging properties, whereas an aqueous dispersion containing 8% of the same emulsifier exhibits negligibly weak stinging properties, and perhydrosqualene is absolutely It becomes clear from the fact that it is harmless. The conclusion is that stinging is caused by the simultaneous action of the emulsifier and the oil phase. The use of the aqueous dispersion according to the invention makes it unnecessary to use an emulsifier and an oil at the same time. This is an important advance in the field of cosmetics.

It is worth noting the fact that various auxiliaries, such as opacifiers, gelling agents, fragrances, perfumes and colorants, can be added to the globules of the invention in order to improve the appearance and organoleptic effect.

Generally speaking, the advantage of the dispersion according to the invention is that it is possible to introduce hydrophilic substances into an environment that is necessarily lipophilic. Under these conditions, the globules absorb substances that can change the substances in the aqueous phase by enveloping them, such as oxidizing agents, digestive fluids and other substances in the aqueous phase. It can be concluded that the substance in the aqueous phase is protected from compounds that are reactive against it. By varying the size and charge of the globules, the permeability and/or fixation of the active substance in the aqueous phase can be varied. The action of the active substance in the aqueous phase can also be varied (delayed action). Moreover, since these active substances are coated, the organoleptic effects, especially the taste, can be eliminated or significantly altered.
The lipids that can be used in this preparation have beneficial properties of their own, such as imparting softening, lubricity and gloss.

EXAMPLES Next, the present invention will be specifically explained using Examples, but the present invention is not limited thereto.

Example 1 In a 50 ml round bottom flask, 500 mg of sorbitol oxyethylene triolate (Tween 85 from ICI Atlas) oxyethylated with 20 moles of ethylene oxide and 0.7 M
Contact with 0.335 ml of sorbitol solution to homogenize the mixture. This operation is carried out at room temperature.

Then 3 ml of an aqueous solution containing 1% of a substance known under the trade name Carbopol 934 (polyacrylic acid cross-linked with polyallylsucrose, sold by Goodrich) is added. Place the flask on a shaker;
Stir vigorously for 1 hour.

The resulting dispersion is gel-like. The diameter of the globules is 1 micron or more.

Example 2 In a 50 ml round bottom flask, oleyl alcohol (Brij, a product of ICI Atlas) was oxyethylated with 10 moles of ethylene oxide.
96] and 250 mg of oleyl alcohol oxyethylated with 2 moles of ethylene oxide [Brij 92, a product of ICI Atlas Co., Ltd.] were thoroughly mixed, and the resulting mixture was brought into contact with 1 ml of 0.5 M glycerin solution. Equalize. The operation is carried out at room temperature.

Then 20ml of 0.245M (NaC,KC) solution
Add. Agitate the flask on a shaker for 1 hour.

The resulting dispersion is fluid and milky. The diameter of the pellets is approximately 1 micron.

Example 3 In a 50 ml round bottom flask, the general formula (In this formula, R is the alkyl group of the alcohol of hydrous lanolin, and the statistical average value of is 3). Equalize. Experiments are performed at room temperature.

Then add 4 ml of water. shake the flask
Stir vigorously for 30 minutes.

The resulting dispersion is milky. The diameter of the small ball is 1
It is more than a micron.

Example 4 In a 50 ml round bottom flask, the general formula (In this formula, R is a tetradecyl group and n is 2) 500 mg of the substance represented by and a 0.4M sorbitol solution
0.75ml and mix to homogenize. The experiment is
Perform at 40℃.

Then add 4 ml of water. shake the flask
Stir vigorously for 30 minutes.

The dispersion obtained after sonication is transparent. The diameter of the globules is less than 1 micron.

Example 5 In a 50 ml round bottom flask, the general formula (In this formula, R is a hexadecyl group and n is 2.) 500 mg of a substance represented by the following formula is brought into contact with 0.335 ml of a 0.3M cysteine hydrochloride solution, and the mixture is homogenized by mixing. Experiments are conducted at 55°C.

Then 4.1ml of 0.145M (NaC,KC) solution
Add. Stir the flask vigorously on a shaker for 3 hours.

The resulting dispersion is substantially transparent at 55°C. The diameter of the pellets is approximately 2 microns. When the dispersion is gradually cooled to room temperature, an opaque white gel is obtained.

Diluting the aliquoted dispersion at 55° C. with an isotonic or non-isotonic solution containing a thickener, such as a rubber or polymer, results in a slightly opaque solution. Select the dilution rate depending on the desired state of the solution.

Example 6 A 50 ml round bottom flask is placed in a water bath at 55°C, in which the general formula (In this formula, R is a hexadecyl group and n is 2) 500 mg of the substance represented by and 100 mg of 0.3M methionine solution
ml and mix to homogenize. 55 experiments
Perform at ℃.

Stir the flask vigorously on a shaker for 3 hours at 55°C.

The resulting dispersion is clear. The diameter of the pellets is approximately 1 micron. A white gel is obtained upon cooling to room temperature.

Example 7 In a 50 ml round bottom flask, the general formula (In this formula, R is an alkyl group of isostearyl alcohol, and the statistical average value of n is 2.) 500 mg of the substance represented by the following formula is brought into contact with 5 ml of water and mixed to homogenize. Experiments are conducted at room temperature.

Stir the flask vigorously on a shaker for 4 hours.
The resulting dispersion is milky. The diameter of the small sphere is approximately 5
It is micron.

The dispersion may be subjected to ultrasonication to reduce the size of the globules.

Example 8 In a 50 ml round bottom flask, the general formula (In this formula, R is an alkyl group of oleyl alcohol, and n is 2.) 83.2 mg (200 μ-mol) of a substance represented by the following formula is dissolved in 2 ml of a mixed solvent of chloroform and methanol at a mixing ratio of 2:1. The solvent is evaporated using a rotary evaporator and then vacuumed for 1 hour using a vane pump to remove any remaining traces of solvent.

This lipid is contacted with 10 ml of 0.3M glucose solution. Stir the flask vigorously on a shaker for 4 hours. Experiments are conducted at room temperature.

The dispersion is sonicated for 20 minutes to reduce the diameter of the globules to less than 0.5 microns. The dispersion is then filtered through a column of Sephadex G50 gel swollen with a 0.145M (NaC, KC) solution. The resulting solution has a slight bluish tinge.

Example 9 In a 50 ml round bottom flask, the general formula (In this formula, R is the alkyl group of isostearyl alcohol, and is 2) 58 mg of a substance represented by the general formula (In this formula, R is the alkyl group of isostearyl alcohol and is 6.) Mix well with 58 mg of the substance represented by
Contact with 10 ml of 1M glucose solution.

Experiments are conducted at room temperature. 4. Shake the flask with a shaker.
Stir vigorously for an hour.

The dispersion obtained is very well dispersed.
The diameter of the pellets is approximately 1 micron. The dispersion may be sonicated for 30 minutes to reduce the diameter of the globules to less than 0.5 microns.

Even if the diameter of the small spheres contained is 1 micron or more, or even if the diameter is 0.5 micron or less,
Filter through a Sephadex G50 gel column swollen with a 0.475M (NaC, KC) solution.

Example 10 In a 50 ml round bottom flask, 500 mg of monolauryl ether of tetraethylene glycol and 0.4 ml of a 0.3 M glucose solution are brought into contact and mixed to homogenize. Experiments are conducted at room temperature.

Then 5 ml of a solution of 0.145M (NaC, KC)
Add.

Agitate the flask vigorously for 15 minutes on a shaker.

The resulting dispersion is clear. The diameter of the pellets is approximately 1 micron.

Example 11 In a 50 ml round bottom flask, the general formula (In this formula, R is a hexadecyl group,
(The statistical average value of is 3.) 500 mg of the substance represented by is brought into contact with 0.5 ml of a solution containing 50 mg of Croteine C (a protein with a molecular weight of about 10,000, manufactured by Croda) per ml.

Homogenize this mixture. Experiments are conducted at 60°C.
Then add 4 ml of a 0.145M (NaC, KC) solution.

Stir the flask vigorously on a shaker for approximately 3 hours.

The resulting dispersion is clear. The diameter of the pellets is approximately 1 micron. When this is slowly cooled to room temperature, an opaque white gel is obtained.

Example 12 General formula obtained by molecular distillation in a 50 ml round bottom flask (In this formula, R is the alkyl group of oleyl alcohol and n is 2) and 150 mg of cholesterol.
and general formula (In this formula, RCOO is the residue of copra, n
is an integer from 2 to 5) and 50 mg of the amine represented by the formula are mixed well, and the mixture is brought into contact with 0.5 ml of 0.3 M sorbitol solution.
Equalize. Experiments are performed at room temperature.

Then 4 ml of 0.145M (NaC, KC) solution
Add.

Stir the flask vigorously on a shaker for 4 hours.

The resulting dispersion has a protein-like sheen. The diameter of the pellets is approximately 2 microns.

Example 13 In a 50 ml round bottom flask, the general formula (In this formula, R is the alkyl group of oleyl alcohol and n is 2) 425 mg of the substance represented by the following formula (In this formula, R is an oleyl group, and the statistical average value is 1) 75 mg of amine represented by and 0.3M glucose solution
Mix with 0.5ml and homogenize. Experiments are conducted at room temperature.

Then 4 ml of 0.145M (NaC, KC) solution
Add.

Stir the flask vigorously on a shaker for 4 hours.

The resulting dispersion is opaque. The diameter of the globules is 2 microns or more.

The dispersion may be subjected to ultrasonication to reduce the size of the globules to less than 1 micron.

Example 14 In a 50 ml round bottom flask, the general formula (In this formula, R is a hexadecyl group and n is 2.) 80 mg of the substance represented by the following formula, 10 mg of cholesterol, and 10 mg of dicetyl phosphate are dissolved in 2 ml of a mixed solvent of chloroform and methanol at a mixing ratio of 2:1.

The solvent is evaporated using a rotary evaporator and then vacuumed for 1 hour using a vane pump to remove any remaining traces of solvent.

This lipid is contacted with 10 ml of 0.15 M pyroglutamic acid sodium salt solution. Place the flask in a 55°C water bath and stir vigorously for 2 hours on a shaker, then gradually cool to room temperature.

The dispersion is subjected to ultrasonic treatment for 1 hour at a temperature around room temperature. The dispersion is then filtered through a column of Cephadex G50 gel swollen with distilled water.

The dispersion obtained after sonication is fluid and transparent. The diameter of the globules is less than 1 micron.

Example 15 In a 50 ml round bottom flask, the general formula (In this formula, R is the alkyl group of the alcohol of hydrous lanolin, and the statistical average value of n is 3.) 240 mg of the substance represented by the following formula and 60 mg of cholesterol are thoroughly mixed.

0.15M Pyroglutamate Sodium Salt Solution 0.4
ml and mix to homogenize. Experiments are conducted at 45°C. Then 4.6 ml of 9% sodium chloride solution are added.

Place the flask in a 45°C water bath and stir vigorously for 2 hours using a shaker. Then gradually cool to room temperature.

The resulting dispersion is fluid and milky. The diameter of the globules is 1 micron or more.

Example 16 In a 50 ml round bottom flask, the general formula (In this formula, R is a hexadecyl group and n is 2.) 200 mg of the substance represented by the following formula, 25 mg of cholesterol, and 25 mg of dicetyl phosphate are thoroughly mixed. Add 0.3 ml of 10% tartaric aldehyde solution to the resulting mixture and homogenize. Experiments are conducted at 55°C. then
Add 4.7 ml of 0.145 M (NaC, KC) solution.

Place the flask in a 55°C water bath and shake with a shaker.
Stir vigorously for an hour. Then gradually cool to room temperature.

The resulting dispersion is a gel with a slight bluish tinge.

By simultaneously applying a dispersion of liposomes containing tartaric aldehyde and an aqueous solution of tartaric aldehyde to the skin at the same time, the dispersion of liposomes containing tartaric aldehyde prepared so that the concentrations of both tartaric aldehydes are equal, the liposome's (1) ability to enhance color development can be achieved. and (2) the effect of the color development on increasing the fastness to cleaning performed using water and detergent can be measured.

The above embodiments are not intended to limit the invention, and all possible modifications can be made without going beyond the scope of the invention.

Claims (1)

[Claims] 1. A dispersion of globules with a diameter of approximately 100 to 50,000 Å, consisting of an organized molecular layer of a lipid compound and an aqueous phase incorporated therein, wherein the lipid compound has a lipophilic chain. , each having a lipophilicity/hydrophilicity ratio such that it can be dispersed in water and swell to form a thin film phase in the aqueous phase to be incorporated into the globules; (a) linear or branched, respectively; The following formula R-(OCH ₂ CHOHCH ₂ -) _o OH and (In this formula, n is an integer from 1 to 6, and R is a straight or branched saturated or unsaturated aliphatic chain having 12 to 30 carbon atoms, a hydrocarbon residue of lanolin alcohol, or a long chain. α of
-2-hydroxyalkyl residues of diols), (b) polyoxyethylenated aliphatic alcohols, (c) oxyethylenated or non-oxyethylenated polyol esters, especially poly The globule dispersion is a nonionic amphipathic compound selected from the group consisting of oxyethylated sorbitol esters and (d) natural or synthetic glycolipids such as cerebrosides. 2 Nonionic amphiphilic compounds include long-chain alcohols and diols, sterols such as cholesterol, long-chain amines and their quaternary ammonium derivatives, dihydroxyalkylamines, polyoxyethylated aliphatic amines, long-chain Additions selected from the group consisting of amino alcohol esters and their salts and quaternary ammonium derivatives, phosphate esters of aliphatic alcohols such as sodium dicetyl phosphate, alkyl sulfates such as sodium cetyl sulfate and certain polymers such as polypeptides and proteins. The dispersion liquid according to the above item 1, which is a combination of agents. 3. The dispersion according to item 1 or 2 above, wherein the continuous phase (dispersion medium) of the dispersion surrounding the globules is an aqueous phase. 4. Dispersion according to any of the preceding clauses, wherein the aqueous phase to be incorporated into the globules is an aqueous solution of the active substance, preferably isotonic with the continuous phase of the dispersion. 5 Humectants such as glycerin, sorbitol, pentaerythritol, inositol, pyrrolidone carboxylic acids and their salts, artificial bronzing agents such as dioxyacetone, erythrulose, glyceraldehyde and gamma-dialdehydes such as tartaric aldehyde (which is optional) (can be used with pigments), water-soluble sunburn inhibitors,
Antiperspirants, deodorants, astringents, refreshing agents, hair tonics, healing agents, keratolytic agents, depilatory agents, lotions, extracts of animal or plant tissues such as proteins, polysaccharides and amniotic fluid, water-soluble colorants , an anti-dandruff agent, an anti-seborrhea agent, an oxidizing agent such as hydrogen peroxide, and a reducing agent such as thioglycolic acid and its salts, the aqueous phase incorporated into the globules contains at least one substance selected from the group consisting of: The dispersion liquid according to any one of the preceding items 1 to 4, which contains the dispersion liquid and can be used as a cosmetic. 6. at least one substance selected from the group consisting of vitamins, hormones, enzymes such as peroxide dismutate, vaccines, anti-inflammatory agents such as hydrocortisone, antibiotics and bactericidal agents,
5. The dispersion liquid according to any one of the preceding items 1 to 4, which contains an aqueous phase incorporated into globules and can be used in the pharmaceutical or food industries. 7. The dispersion according to any one of items 1 to 6 above, which contains at least one of an opacifying agent, a gelling agent, an aromatic agent, a perfume, and a pigment.