JP6242581B2 - Method for producing reverse vesicle composition - Google Patents

Description

  The present invention relates to a method for producing a reverse vesicle composition, and a skin external preparation using the reverse vesicle composition produced by the production method.

The technology of microencapsulating active ingredients and applying them inside and outside the living body is expected to be applied in the pharmaceutical and food fields as well as in the cosmetics field because of the advantages such as the effectiveness of the active ingredients in the capsules. Has been.
As a microencapsulation technique in the cosmetics field, a vesicle having a phospholipid such as lecithin as a bilayer component is conventionally known.
Conventionally, vesicles using lecithin were mainly water-dispersed vesicles in which the hydrophilic groups of phospholipids were oriented outward and dispersed in an aqueous phase.
On the other hand, the following are known as reverse vesicles in which the hydrophobic group of the amphiphile is oriented outward.
Patent Document 1 describes a reverse vesicle using a sucrose fatty acid ester. It also describes forming a water-in-oil emulsion by the three-phase emulsification method using the reverse vesicle as an emulsifier.
Patent Document 2 describes a reverse vesicle composition using sphingosines.

Non-Patent Document 1 describes the formation of reverse vesicles containing lecithin, and it is reported that specific lecithins form reverse vesicles in cyclohexane.
On the other hand, Non-Patent Document 2 shows that a lecithin having a carbon chain different from the above does not form a coexisting phase of an oil and a lamella phase necessary for forming a reverse vesicle in the same oil agent.

The conventional reverse vesicle described above has been manufactured by mixing the lamellar phase and the oil agent, which are constituents of the reverse vesicle, by applying physical stirring force by hand stirring or ultrasonic irradiation (the above-mentioned patent documents, (See non-patent literature.)
In the conventional method for forming a reverse vesicle, the dispersion of the lamella phase into the oil can be performed with a weak stirring force as the flexibility of the lamella phase increases. It is reported that it is important to swell with an oil component (Non-patent Document 3).

JP 2010-104946 A JP 2009-62365 A

S. Tung et al., Journal of the American Chemical Society, 2008, Vol.130, No. 27, pp.8813-8817 Langmuir, 2004, vol. 20, pp. 619-631 Langmuir, 1994, vol. 10, pp. 4006-4011

However, in the conventional method, when a large molecular weight oil agent is used, the oil agent cannot enter between the layers of the bilayer film, so that the lamellar phase becomes rigid and it is difficult to obtain a fine reverse vesicle. In particular, when trying to obtain a reverse vesicle using a relatively large molecular weight oil that can be used safely in cosmetics and the like, it is necessary to give a large stirring force, which is also a problem in terms of production efficiency. there were.

  The present invention is intended to solve the above-described problems, and an object of the present invention is to provide a novel method for producing a reverse vesicle composition. In particular, an object of the present invention is to provide a production method that facilitates the formation of a reverse vesicle composition as compared with the conventional method when using an oil agent having a large molecular weight.

The present invention for solving the above problems
Dissolving a bilayer component in a volatile solvent to obtain a first isotropic solution;
Mixing the first isotropic solution with an oil to obtain a second isotropic solution;
Volatilizing the volatile solvent in the second isotropic solution;
A volatilization step of forming a reverse vesicle of the bilayer component by volatilization of a volatile solvent;
Is a method for producing a reverse vesicle composition.
In this way, the bilayer component is dissolved in a volatile solvent to form an isotropic solution, then mixed with an oil agent, and then the volatile solvent is volatilized, so that the lamellar is removed from the isotropic solution. A reverse vesicle composition can be obtained by causing a phase transition to.
According to the method for producing a reverse vesicle composition of the present invention, a reverse vesicle composition can be produced even in a system in which a bilayer component is difficult to disperse in an oil agent by physical stirring, for example, a system using an oil agent having a high molecular weight. It becomes possible to do.
In particular, an inverse vesicle composition containing fine inverse vesicles can be easily produced.

In a preferred embodiment of the present invention, the volatile solvent is selected from alcohols, hydrocarbons, aromatics, ketones, ethers, esters, volatile silicone oils, and isoparaffins.
By using the above as a volatile solvent, when it is assumed that the manufactured reverse vesicle composition is used for an external preparation for skin such as cosmetics, its safety can be improved.

In a preferred embodiment of the present invention, the oil agent is selected from silicone oil, hydrocarbon oil, ester oil, natural animal and vegetable oil, and fluorine oil.
By using these oil agents, when it is assumed that the manufactured reverse vesicle composition is used for an external preparation for skin such as cosmetics, its safety can be improved.

  In the present invention, the bimolecular component is not particularly limited. For example, when the obtained reverse vesicle composition is applied as a cosmetic component, lecithin and / or a nonionic surfactant are preferably mentioned.

  In one embodiment of the present invention, the first isotropic solution may contain water that is not more than 1 times the content of the bilayer component.

In one form of the present invention, the second isotropic solution is a two-phase solution in which particles of the first isotropic solution are dispersed in the oil.
Depending on the volatile solvent, the volatile solvent and the oil may form one phase or two phases. In the latter case, the particles of the first isotropic solution are dispersed in the oil. By doing so, a reverse vesicle can be manufactured.

  In a preferred form of the invention, the volatile solvent is volatilized under reduced pressure.

  The present invention also relates to a method for producing an external preparation for skin, comprising mixing the reverse vesicle composition produced by the production method described above with other components.

By using the method for producing a reverse vesicle composition of the present invention, it is possible to easily produce a reverse vesicle as compared with a conventional method for producing a reverse vesicle.
In particular, when a reverse vesicle composition is produced using an oil agent having a large molecular weight, it is not necessary to use a physical stirring force as compared with the case of using a conventional method, and productivity is improved in industrial production. It becomes possible. In addition, even when components or the like that have conventionally been difficult to form fine reverse vesicles are used, a reverse vesicle composition containing fine reverse vesicles can be produced relatively easily.

It is a schematic process drawing which shows the manufacturing method of the reverse vesicle composition of this invention. The phase state in each step is also shown.

Hereinafter, an embodiment for carrying out the present invention will be described in detail with reference to FIG.
<1> Step of Obtaining First Isotropic Solution In the production method of the present invention, first, the bilayer membrane component 1 is dissolved in the volatile solvent 2 to obtain the first isotropic solution 3.
The bilayer component indicates a component of the bilayer that constitutes the reverse vesicle.
As a component of such a bilayer membrane, any amphiphilic substance is not particularly limited, and any of an ionic surfactant and a nonionic surfactant can be used. Preferably, lecithin which is an amphoteric surfactant is used. Nonionic surfactants can also be preferably used. For example, silicone surfactants, polyoxyethylene alkyl ethers, sucrose fatty acid esters, sphingosines, fatty acids and the like can be preferably used.
The production method of the present invention is effective when lecithin is used which has a rigid bimolecular film and is difficult to form reverse vesicles by conventional physical agitation. In consideration of using the inverse vesicle composition produced by the production method of the present invention for cosmetics and the like, lecithin and a nonionic surfactant are preferably used from the viewpoint of safety.

Lecithin extracted from living bodies of plants, animals and microorganisms and purified as desired may be used, or synthesized. Preferably, plant-derived lecithin such as soybean, corn, peanut, rapeseed, and wheat, or animal-derived lecithin such as egg yolk can be used.
The lecithin in the present invention includes phosphatidylcholine, phosphatidic acid, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylserine, bisphosphatidic acid, diphosphatidylglycerol (cardiolipin) and the like.
In the present invention, “lecithin” also includes hydrogenated lecithin, enzymatically decomposed lecithin, enzymatically decomposed hydrogenated lecithin, lysolecithin and the like.

  The number of carbon atoms of the fatty acid constituting the hydrophobic group portion of lecithin is not particularly limited. For example, those having 8 to 20 carbon atoms, preferably 16 to 18 carbon atoms can be mainly used. The fatty acid may be saturated or unsaturated. The fatty acid may be linear or branched.

In the present invention, lecithin can be used in the form of a single kind of the above-mentioned compound or in the form of a mixture of the above-mentioned plural kinds of phospholipids.
The composition of lecithin is preferably composed mainly of phosphatidylcholine, for example, 20% by mass or more, and preferably 50% by mass or more is phosphatidylcholine.
A commercially available lecithin can be used without particular limitation.

When lecithin is mainly used, it can be combined with other auxiliary surfactants (nonionic surfactants, ionic surfactants).
In this case, it is preferable that lecithin accounts for 60% by mass or more, more preferably 80% by mass or more, among the bilayer components forming the reverse vesicle.

Examples of the volatile solvent for dissolving the above-described bilayer component include alcohols such as methanol, ethanol, propanol, and isopropanol, hydrocarbons such as pentane, hexane, and cyclopentane, aromatics such as benzene, acetone, and the like. And volatile silicone oils such as ketones, ethers, esters and decamethylpentasiloxane, fluorocarbons, isoparaffins and the like.
Of these, ethanol, propanol, acetone and the like are preferably used.

  The content of the bilayer component in the first isotropic solution may be in a range where the bilayer component is sufficiently dissolved. For example, the content of the bilayer component can be 10 to 90% by mass. This is because when the amount is less than 10% by mass, the volatilization time of the volatile solvent may become long, and when it exceeds 90% by mass, the solution becomes viscous and may be difficult to dissolve.

Further, the first isotropic solution may contain water.
Since the production method of the present invention is intended to form an inverted vesicle without relying on conventional physical agitation, the presence of water is not necessary for the purpose of assisting dispersion by physical agitation, but rather there is little water. It can be said that it is useful in the system.
However, in the formation of inverted vesicles by volatilization of the volatile solvent, the presence of water may assist the formation of a bilayer.
From these viewpoints, the present invention may contain water having a mass of 1 or less that of the bilayer membrane component. In this case, the bilayer component can be mixed with water and mixed with a volatile solvent (FIG. 1 (a)). Of course, a bilayer component, water, and a volatile solvent may be mixed.

In the present invention, the bilayer membrane component 1 is dissolved in the volatile solvent 2 to prepare a first isotropic solution 3. This preparation can be performed by ordinary mixing and stirring.
The first isotropic solution 3 obtained by dissolving the bilayer membrane component 1 in the volatile solvent 2 is in a state where the bilayer membrane component 1 is monodispersed in the volatile solvent 2 or in the volatile solvent 2. In this state, aggregates such as reverse micelles of the bilayer membrane component 1 are formed (FIG. 1B).
Such an isotropic solution has a high fluidity and is easy to mix with a subsequent oil agent.

<2> Step of Obtaining Second Isotropic Solution In the production method of the present invention, subsequently, the first isotropic solution 3 obtained above is mixed with the oil agent 4 to obtain a second isotropic solution. Get 5.

  The oil agent is not particularly limited as long as it can be mixed with the first isotropic solution, but a liquid oil agent at 25 ° C. can be preferably used. Examples of the oil used in the present invention include silicone oil, hydrocarbon oil, ester oil, natural animal and vegetable oil, and fluorine oil.

Examples of silicone oil include organopolysiloxanes such as dimethylpolysiloxane, methylphenylpolysiloxane, dimethylsiloxane / methylphenylsiloxane copolymer, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, etc. Examples thereof include cyclic siloxane.
Among these, the cyclic siloxane described above is preferably used.

  Hydrocarbon oils include chain and cyclic hydrocarbons such as α-olefin oligomers, light isoparaffins, light liquid isoparaffins, squalane, liquid paraffin, liquid isoparaffins, hydrogenated isobutene, isooctane, decane, isododecane, isohexadecane, Polybutene etc. are mentioned.

  Ester oils include dioctyl succinate, diisobutyl adipate, dioctyl adipate, di (2-heptylundecyl) adipate, diisopropyl sebacate, dioctyl sebacate, dibutyl octyl sebacate, diisostearyl malate, triethyl citrate , Ethylene glycol dioctanoate, neopentyl glycol dioctanoate, propylene glycol dicaprate, neopentyl glycol dicaprate, trimethylolpropane trioctanoate, trimethylolpropane triisostearate, pentaerythritol tetraoleate, ethyl acetate, butyl acetate, amyl acetate Octyldodecyl neopentanoate, cetyl octanoate, isononyl isononanoate, isotridecyl isononanoate, dimethyloctanoate hex Rudecyl, ethyl laurate, hexyl laurate, isopropyl myristate, myristyl myristate, isocetyl myristate, octyldodecyl myristate, isopropyl palmitate, octyl palmitate, cetyl palmitate, isocetyl palmitate, isostearyl palmitate, stearic acid Butyl, hexyldecyl stearate, isopropyl isostearate, isocetyl isostearate, decyl oleate, oleyl oleate, octyldodecyl oleate, ethyl linoleate, isopropyl linoleate, cetyl lactate, myristyl lactate, cholesteryl hydroxystearate, dioctyl lauroyl glutamate Examples include dodecyl, lauroyl sarcosine isopropyl, and ethylhexyl methoxycinnamate. It is.

  Examples of natural animal and vegetable oils include avocado oil, almond oil, olive oil, wheat germ oil, safflower oil, jojoba oil, macadamia nut oil, cottonseed oil, and coconut oil.

  Examples of the fluorine oil include perfluoro oils.

  The mixing ratio of the first isotropic solution and the oil agent can be set such that the content of the bilayer component in the manufactured reverse vesicle composition is 0.1 to 10% by mass. .

By mixing the first isotropic solution 3 and the oil agent 4, an isotropic solution (second isotropic solution) 5 in which the bilayer membrane component 1 is dispersed in the oil agent 4 can be obtained.
Here, the form of dispersion of the bilayer membrane component in the oil agent varies depending on the solubility of the volatile solvent used in the oil agent.
(1) When the volatile solvent 2 is soluble in the oil agent 4, the first isotropic solution 3 is compatible with the oil agent to form a one-phase solution. That is, the bilayer component 1 contained in the first isotropic solution 3 is present in a monodispersed state or a state in which aggregates such as reverse micelles are formed in the one-phase solutions 2 and 4. (FIG. 1 (c)).
(2) On the other hand, when the volatile solvent 2 is insoluble or hardly soluble in the oil agent 4, the first isotropic solution 3 is not compatible with the oil agent 4 and forms a two-phase solution. That is, the particles 31 of the first isotropic solution 3 are dispersed in the continuous phase of the oil agent 4 (FIG. 1D). As shown in FIG. 1 (d2), the particles 31 are in a state where the bilayer component 1 is monodispersed in the volatile solvent 2, or an aggregate such as a reverse micelle of the bilayer component 1 in the volatile solvent 2. It is in the state which formed.
This state can be easily formed by a normal shaking or stirring operation in the mixing step.
In addition, when using a combination of a component that is hardly soluble in the oil agent and a component that is soluble in the oil agent as the bilayer component, the component that is insoluble in the oil agent is dissolved in a volatile solvent, and the component that is soluble in the oil agent It is also possible to dissolve these in an oil and mix them.

<3> Step of volatilizing volatile solvent In the production method of the present invention, subsequently, the volatile solvent 2 is volatilized from the second isotropic solution 5 obtained by the above operation.
Volatilization of the volatile solvent can be performed by vaporizing the volatile solvent by reducing the pressure by a conventional method. Moreover, it is possible to carry out by heating a liquid mixture to the temperature which a volatile solvent vaporizes. Volatilization is preferably performed under reduced pressure. Moreover, when heating, it heats below the temperature which can maintain a lamellar phase (reverse vesicle), ie, below the temperature which does not phase-transform.
When the above-mentioned second isotropic solution forms two phases, the first isotropic solution is sufficiently dispersed in the oil by shaking or stirring, and then this step is entered. Is preferred.
It is also preferable to apply a stirring force during volatilization from the viewpoint of forming fine reverse vesicles.

  As described above, by volatilizing the volatile solvent 2, the second isotropic solution 5 is phase-transduced, and the inverse vesicle composition 8 in which the inverse vesicle 7 is dispersed in the oil agent 4 can be obtained (FIG. 1). (E)). The state of the formed reverse vesicle may be a single layer or a multilayer. Confirmation that the reverse vesicle is formed can be confirmed, for example, by performing microscopic observation under polarized light.

The particle size of the reverse vesicle in the reverse vesicle composition produced in this manner is, for example, 200 μm or less, 20 μm in a more preferable form, and 2 μm or less in a more preferable form immediately after the production. There is an advantage that the smaller the particle size, the less likely it is to settle in the dispersion. However, the particle size of the inverse vesicle does not particularly affect the stability of the inverse vesicle itself.
The particle size of the inverse vesicle can be measured by a dynamic light scattering method or a laser diffraction method.

  The reverse vesicle composition of the present invention may contain other optional components such as preservatives, thickeners, and fragrances as long as the formation of the reverse vesicles is not hindered.

It is also possible to recover the reverse vesicle from the reverse vesicle composition produced as described above. In addition, the collection | recovery here contains the concept of concentration.
As the method, in the reverse vesicle composition, after the reverse vesicle is precipitated, the supernatant is removed.

The reverse vesicle composition produced by the production method of the present invention can be used as a raw material for an external preparation for skin. Of course, the reverse vesicle composition produced by such a method can be used as a skin external preparation as it is.
Examples of the external preparation for skin include pharmaceuticals and cosmetics, and it is particularly preferable to use cosmetics.
For example, the reverse vesicle composition can be used as a skin external preparation in the form of lotion or oil as it is or with optional components added. Moreover, the reverse vesicle composition can be used as a skin external preparation in the form of a lotion or cream by mixing with other components and emulsifying as necessary. Moreover, it can also be set as a powder type cosmetic by mixing the said reverse vesicle composition with the raw material powder of cosmetics.

A reverse vesicle composition having the composition shown in Table 1 was produced by the following method.
That is, for Samples A to D, a mixture of bilayer components and water (lamellar mixture) was dissolved in a volatile solvent to prepare an intermediate solution (first isotropic solution). Subsequently, this intermediate solution was mixed with an oil agent to obtain a mixed solution. This solution formed two phases. Subsequently, this mixed solution was stirred with a vortex mixer for 1 minute to obtain a dispersion (second isotropic solution) in which the intermediate solution was dispersed in the oil, and then heated to 35 ° C. in a reduced pressure oven. Dry until volatile solvent is gone.
For sample E, a mixture of the bilayer component and water was mixed with an oil agent, and the mixed solution was stirred with a vortex mixer under the same conditions as described above.
About the obtained composition, formation of the reverse vesicle was confirmed using the polarization microscope. For those in which the formation of reverse vesicles was confirmed, ◯ was entered, and for those in which the formation of reverse vesicles was not confirmed, x was entered.

As shown in Table 1, formation of reverse vesicles was confirmed in Samples A to D using a method in which a lamella mixture was dissolved in a volatile solvent to prepare an intermediate solution and then mixed with an oil agent.
On the other hand, in the sample E using the method of directly mixing the lamella mixture with the oil agent as in the conventional case, the formation of the reverse vesicle was not confirmed.
From this, it was found that the reverse vesicle composition can be easily prepared by dissolving the bilayer component in a volatile solvent in advance, mixing it with an oil agent, and then volatilizing the volatile solvent.
In addition, in the prescription of sample E, the present inventors have confirmed that an inverted vesicle composition can be produced by applying a stronger stirring force using an ultrasonic disperser or the like. The production method of the present invention can produce a reverse vesicle composition without requiring a strong stirring force by such an ultrasonic disperser, and is useful in this respect when assuming industrial production. It can be said that there is.
Moreover, when using the oil agent with a larger molecular weight than the oil agent used in the present Example, it is thought that the manufacturing method of this invention becomes very useful.

Below, the manufacture example of skin external preparation (cosmetics) is described. A compounding quantity is shown in the mass percentage.
Example 1. Treatment oil (A) Lecithin 0.4
(A) Water 0.1
(A) Ethanol 0.2
(B) Squalane 69.4
(B) Olive oil 20
(B) Jojoba oil 10
(B) Fragrance 0.1

After the mixture of lecithin and water of group (A) was dissolved in a volatile solvent, these were mixed with the components of group (B), and this mixed solution was stirred with a vortex mixer for 1 minute. Subsequently, the volatile solvent was removed by a conventional method.
As a result, a treatment oil containing a reverse vesicle (reverse vesicle solution) was produced.

Example 2 Cream (A) Dimethicone 31.5
(A) Cyclopentasiloxane
(A) (Dimethicone / Vinyl Dimethicone) Crosspolymer 5
(A) Polyether-modified silicone 2
(A) Sorbitan sesquiisostearate 1
(A) Phenoxyethanol 0.5
(B) Water 30
(B) 1,3-butanediol 10
(C) Reverse vesicle solution 10
(C-1) Lecithin 2
(C-2) Propanol 2
(C-3) Squalane 98

A reverse vesicle solution (C) was prepared in the same manner as in Example 1 using (C-1,2,3). The components of group (A) were mixed uniformly, the components of group (B) were mixed, and an emulsion was formed using a homogenizer. Thereafter, the emulsion and (C) prepared in advance were mixed by hand stirring.
As a result, a cream containing reverse vesicles was produced.

Example 3 FIG. Sunscreen cosmetics (A) Cyclopentasiloxane 26.7
(A) Polyether-modified silicone 3
(A) 40% hydrophobized fine particle titanium oxide slurry * 15
(A) 40% hydrophobized fine particle zinc slurry * 10
* Dispersion medium: cyclopentasiloxane (B) water 30
(B) 1,3-BG 5
(B) Methylparaben 0.3
(C) Reverse vesicle solution 10
(C-1) Lecithin 0.7
(C-2) Water 0.3
(C-3) Ethanol 2.0
(C-4) Cyclopentasiloxane 99

A reverse vesicle solution (C) was prepared in the same manner as in Example 1 using (C-1 to 4) in advance. The components of group (A) were uniformly mixed by hand stirring and heated to 80 ° C. What was heated and stirred at 80 degreeC of the component of (B) group was added there, and it emulsified with the homogenizer. When the emulsion was cooled and reached 35 ° C., the emulsion and the previously prepared (C) were mixed by hand stirring.
As a result, a sunscreen cosmetic containing reverse vesicles was produced.

Example 4 Emulsion type foundation (A) Cyclopentasiloxane 24.2
(A) Diphenylsiloxyphenyl trimethicone 10
(A) Polyether-modified silicone 4
(A) Ethylhexyl methoxycinnamate 5
(A) Diethylaminohydroxybenzoyl hexyl benzoate 0.5
(B) Pigment dye (titanium oxide, iron oxide) 10
(C) Organically modified bentonite 1
(D) Water 30
(D) Glycerin 10
(D) Methylparaben 0.3
(E) Reverse vesicle solution 5
(E-1) Lecithin 1.4
(E-2) Water 0.6
(E-3) Ethanol 3
(E-4) Cyclopentasiloxane 98

A reverse vesicle solution (E) was prepared in the same manner as in Example 1 using (E-1 to 4) in advance. The components of group (A) were uniformly mixed by hand stirring and heated to 80 ° C. (B) The component of (B) group is disperse | distributed with a disper to the mixture of the component of (A) group, Then, the component for (C) is disperse | distributed with a disper. Using a homogenizer, the obtained oil phase and (D) group uniformly mixed at 80 ° C. are mixed and emulsified. When the emulsion was cooled and reached 35 ° C., the emulsion and (E) prepared in advance were mixed by hand stirring.
As a result, an emulsified foundation containing a reverse vesicle was produced.

Example 5 FIG. Powder Foundation (A) Silicone-treated pigment dye (titanium oxide, iron oxide) 15
(A) Talc 29.7
(A) Mica 10
(A) Fluorine-treated sericite 10
(A) Silica 10
(A) Methyl methacrylate cross polymer 10
(A) Mica titanium 5
(A) Methylparaben 0.3
(B) Reverse vesicle solution 10
(B-1) Lecithin 3
(B-2) Water 0.3
(B-3) Acetone 1
(B-4) Polyoxyethylene alkyl ether 0.3
(B-5) Dimethicone 40
(B-6) Jojoba oil 56.4

A reverse vesicle solution (B) was prepared in the same manner as in Example 1 using (B-1 to 6) in advance. After mixing the components of (A) group and coarsely pulverizing with a pulverizer, (B) was added and mixed with a Henschel mixer. Then, it grind | pulverized again with the pulverizer, and it casted into the metal dish.
As a result, a powder foundation containing reverse vesicles was produced.

  The present invention can be applied to the production of cosmetics and foods.

Claims (7)

Dissolving a bilayer component in a volatile solvent to obtain a first isotropic solution;
Mixing the first isotropic solution with an oil to obtain a second isotropic solution;
Volatilizing the volatile solvent in the second isotropic solution;
Forming a reverse vesicle of the bilayer component by volatilization of a volatile solvent;
Only including,
The bilayer component is lecithin,
The manufacturing method of the reverse vesicle composition whose said oil agent is a liquid oil agent at 25 degreeC (however, except the form including the process of forming a reverse vesicle by physical stirring) .   The method for producing a reverse vesicle composition according to claim 1, wherein the volatile solvent is selected from alcohols, hydrocarbons, aromatics, ketones, ethers, esters, volatile silicone oils, and isoparaffins.   The method for producing a reverse vesicle composition according to any one of claims 1 and 2, wherein the oil agent is selected from silicone oil, hydrocarbon oil, ester oil, natural animal and vegetable oil, and fluorine oil. The method for producing an inverted vesicle composition according to any one of claims 1 to 3 , wherein the first isotropic solution contains water that is not more than 1 times the mass of the bilayer component. The production of the reverse vesicle composition according to any one of claims 1 to 4 , wherein the second isotropic solution is a two-phase solution in which particles of the first isotropic solution are dispersed in the oil agent. Method. The method for producing a reverse vesicle composition according to any one of claims 1 to 5 , wherein the volatile solvent is volatilized under reduced pressure. The manufacturing method of the skin external preparation containing the process of mixing the reverse vesicle composition manufactured by the manufacturing method of the reverse vesicle composition in any one of Claims 1-6 with another component.

Images