JP2023110365A - Cationic vesicle and composition thereof - Google Patents

Abstract

To provide a vesicle composition that has adsorptivity to skin and hair, can include various components, and is stable and suitable for blending in cosmetic products, and a method for stabilizing a vesicle composition.SOLUTION: The present invention provides a novel cationic vesicle comprising a gemini surfactant, a method for stabilizing a cationic vesicle by adding the gemini surfactant, a cationic vesicle including a cosmetic active ingredient, and their use in cosmetics.SELECTED DRAWING: None

Description

The present invention relates to novel formulation technology. In particular, the present invention relates to cationic vesicles containing gemini surfactants, methods for producing the same, use of such cationic vesicles as cosmetics, and cationization by introducing gemini surfactants into vesicle membranes. It relates to a method for stabilizing vesicles.

A vesicle is a vesicle enclosed by a double membrane formed by self-association of amphipathic molecules. In particular, vesicles made of a phospholipid bilayer membrane similar to cell membranes are called liposomes. Various substances can be encapsulated in vesicles (liposomes). Liposomes can be used for intracellular delivery of substances encapsulated therein, and are being researched and developed as carriers in drug delivery technology (DDS: drug delivery system).

Cosmetics using technology similar to DDS using liposomes are advertised under names such as nanocosmetics and nanocapsules. Japanese Patent No. 5623076 (Patent Document 1) describes a vesicle composition using lysophospholipids and an external preparation for skin comprising the vesicle-dispersed composition. Japanese Patent Laid-Open No. 2012-206948 (Patent Document 2) describes a liposome composition that is stable even in an acidic range, and cosmetics and external preparations for skin containing the composition. JP-A-2007-176820 and JP-A-2007-176821 (Patent Documents 3 and 4) disclose that a powdery phospholipid composition that can be dispersed in an aqueous medium to obtain stable liposomes can be used to prepare cosmetics. Are listed.

Compositions that are used by topical application such as cosmetics have been devised to improve the permeation of active ingredients into cells.
Cationization is the process of making a substance positively charged. Since the skin is negatively charged, it tends to absorb positive substances.

In Japanese Patent No. 4950419 and Japanese Patent No. 5220546 (Patent Documents 5 and 6), ingredients are devised to promote intracellular permeation of substances into skin or hair cells for the purpose of use in cosmetics. liposomes have been described.

Japanese Patent Application Laid-Open No. 2006-35036 (Patent Document 7) discloses oil-based drug-containing particles in which an oil-based drug is included in a water-soluble solid matrix in the form of oil droplets, and which further includes an emulsified substance exhibiting cationic properties in water. is described.

Japanese National Publication of International Patent Application No. 2014-516030 (or WO2012/156109, Patent Document 8) describes a lipophilic UV filter substance encapsulated in a vesicle having a positive surface charge for topical application to the skin or hair as a UV protective material. Are listed.

Japanese Patent Laid-Open No. 2016-108285 (Patent Document 9) describes a cationized vesicle encapsulating a mineral as an active ingredient of cosmetics. As a substance for cationization, cationized hyaluronic acid, which is highly adsorbable to skin and hair, is preferred.

WO2019-111415 (Patent Document 10) discloses a cationized vesicle for use by adding to cosmetics, cationized with a cationized polymer containing 2-methacryloyloxyethylphosphorylcholine and a cation monomer, wherein the cationized polymer Cationic vesicles are described in which the proportion of cationic monomers is greater than 50%.

A gemini-type surfactant is a surfactant having a gemini-type (twin-type) structure in which amphipathic molecules of one hydrophobic chain and one hydrophilic group are linked via a spacer at or near the hydrophilic group. (Fig. 1). It is believed that having two hydrophobic groups and two hydrophilic groups in the molecule makes it more effective than general surfactants. For example, gemini-type surfactants have a high surface-active action, and because of their high activity, they bring about the advantage of reducing the environmental load due to the use of a small amount. Gemini-type surfactants that have been put into practical use as raw materials for cosmetics include Pellicer ^{(registered trademark)} with an amino acid spacer (manufactured by Asahi Kasei Finechem Corp.) and Vinoveil ^{(registered trademark)} with a phosphorylcholine-like group as a spacer (Japan). Oil Co., Ltd.) and the like are known.

JP 2008-255109 (Patent Document 11) discloses (a) sodium lysine dilauroyl glutamate (Pellicer ^{(registered trademark)} ), (b) cholesterol and/or phytosterol, (c) monostearyl glycerin ether, (d) di A stable vesicle composition containing propylene glycol and (e) water, and an external preparation for skin containing the vesicle composition are disclosed.

Non-Patent Document 1 discloses that 2-(Dimethyldocosylammonio)ethyl octadecyl ethyl phosphate (DOEP, Vinoveil ^{(registered trademark)} -BS-100P) is combined with a cationic compound for the purpose of improving hair adsorption performance and hair care effect. is described.

Gemini-type surfactants are attracting attention in various fields as next-generation surfactants, but there are no examples of their application to cationized vesicles.

Patent No. 5623076 "Vesicle composition and skin preparation for external use" JP-A-2012-206948 "Liposomal composition, and cosmetics, external skin preparations and methods for producing the same" JP-A-2007-176820 "Powder Phospholipid Composition" JP 2007-176821 "Powder Phospholipid Composition" Japanese Patent No. 4950419 "Liposomes Containing Cationic Polymers That Promote Intracellular Penetration" Patent No. 5220546 "Hydrated lamellar phases or liposomes containing aliphatic monoamines or cationic polymers that promote intracellular penetration, and cosmetic or pharmaceutical compositions containing the same" Japanese Unexamined Patent Publication No. 2006-35036 "Oil-based drug-containing particles" Japanese National Publication of International Patent Application No. 2014-516030 "Charge donor for vesicle carrier system of UV protective agent used for skin or hair" JP 2016-108285 "cationized vesicle and composition thereof" WO2019-111415 (Patent No. 6735426) "Cationized vesicle and composition thereof" Japanese Unexamined Patent Application Publication No. 2008-255109 "Vesicle composition and external preparation for skin containing the vesicle composition"

Journal of Japanese Cosmetic Science Society Vol.38, No.1, pp.9-14 (2014)

Cationized vesicles are easily adsorbed to the skin, and when used encapsulating active cosmetic ingredients, they can efficiently deliver the ingredients to the skin, making them an excellent composition for cosmetic materials. It is an object of the present invention to provide highly stabilized cationic vesicles.

The present inventors have extensively studied materials for producing stable cationized vesicles. Then, they found that the stability of cationized vesicles was improved by using a novel gemini-type surfactant, and completed the present invention.

That is, the present invention relates to novel compounds that are gemini-type surfactants suitable as raw materials for cosmetics. Such compounds are referred to as “compounds of the invention” or “gemini surfactants of the invention” or “2C ₁₂ -3”.

The structure of the gemini-type surfactant of the present invention is shown below.

The compound represented by the above formula is referred to herein as "2C ₁₂ -3". 2C ₁₂ -3 is a compound in which two alkyl chains (C ₁₂ H ₂₅ ), which are hydrophobic moieties, are linked by a quaternary ammonium, which is a hydrophilic moieties.

The present invention also relates to a method for producing cationized vesicles using the above gemini surfactant. The present invention also relates to a method for stabilizing cationized vesicles by using gemini-type surfactants. Furthermore, the present invention provides a cationic vesicle for use as an additive in cosmetics, the cationic vesicle containing a gemini surfactant. Such cationized vesicles are sometimes referred to as "cationized vesicles of the present invention".

The present invention also relates to an active ingredient-encapsulating cationized vesicle in which a cosmetic active ingredient is retained in the cationized vesicle. The active ingredient may be either a hydrophilic substance or a lipophilic substance, regardless of its charged state.

A wide variety of active ingredients can be retained in the cationized vesicles of the present invention. Examples include minerals, amino acids, vitamins and other whitening ingredients, anti-glycation ingredients, antioxidant ingredients, anti-wrinkle ingredients, anti-blemish ingredients, and the like.

The present invention also relates to the cationized vesicle having a Z potential of +20 mV or higher.
The present invention also relates to the active ingredient-encapsulating cationized vesicle having a Z-potential of +20 mV or higher.

The invention also relates to said lyophilized cationic vesicles.
The present invention also relates to a lyophilized cationized vesicle encapsulating an active ingredient.

The present invention also relates to cosmetics containing the cationized vesicles, the cationized vesicles encapsulating an active ingredient, or the freeze-dried cationized vesicles or cationized vesicles encapsulating an active ingredient.

The cosmetics may further contain substances derived from natural products.
The cosmetics can contain one or more active ingredient-encapsulating cationized vesicles.

The present invention also provides a topical cosmetic having adsorptivity to skin and hair, wherein the cationized vesicle, the active ingredient-encapsulating cationized vesicle, or the freeze-dried cationized vesicle Alternatively, it relates to a cosmetic characterized by containing a cationic vesicle encapsulating an active ingredient.

The present invention also includes applying the cationic vesicles, the active ingredient-encapsulating cationized vesicles, or cosmetics containing the freeze-dried cationized vesicles or active ingredient-encapsulating cationized vesicles to the skin or hair. , relating to a method of cosmetic surgery. The beauty treatment method may be performed at a salon or at home.

The cationized vesicle of the present invention has excellent skin permeability and skin permeability, and is suitable for blending in functional cosmetics. In addition, the cationized vesicle of the present invention is more stable than conventionally known cationized vesicles because it suppresses aggregation/precipitation and an increase in particle size that leads to them, and has improved stability over time, such as no change in surface charge. ing. In addition, the cationized vesicle of the present invention has a higher concentration of substances that can be encapsulated than conventionally known vesicles, and the substances that can be encapsulated are diversified. Furthermore, the cationized vesicle of the present invention has improved compatibility with compounding raw materials, and can be applied to various dosage forms.

INDUSTRIAL APPLICABILITY The present invention can contribute to the provision of a wide variety of cosmetics that are excellent in adsorption, penetration, and persistence.

Schematic representation of gemini-type surfactants, phospholipids, and common surfactants. Electron microscope image of cationized vesicles of the present invention.

1. Vesicles Vesicles are formed by the association of amphipathic molecules in water as spherical structures closed by bilayer membranes with hydrophobic tails inward and hydrophilic heads outward.

Single lamellar vesicles (SLVs), also called "unilamellar vesicles", are spherical vesicles composed of one lipid bilayer membrane.
A vesicle having a structure in which double membranes are laminated in multiple layers is called a multilamellar vesicle (MLV). MLVs, also called "multilamellar vesicles", are composed of multiple concentrically arranged lipid bilayer membranes.

There are many amphiphilic molecules that can form vesicles, especially those made from phospholipids called liposomes. A vesicle is a general term for vesicles composed of phospholipids and surfactants. Liposomes are like capsules that have the same membrane as skin cells, and have excellent biocompatibility.

Phospholipid membranes are composed of phospholipids derived from egg yolk or soybean, glycerophospholipids, or cyclic phosphatidic acid, and are originally negatively charged. Phospholipids may also be synthesized or commercially available.

Furthermore, cholesterol and phospholipids can be combined for the purpose of adjusting the hardness and permeability of a lipid bilayer membrane composed of phospholipids.
A vesicle can be prepared by a conventional manufacturing method generally known as a liposome manufacturing method.

Known techniques for producing liposomes include the method of Bangham (J. Mol. Biol., 13, 238 (1965)) or a modified method thereof, vortex treatment, ultrasonic treatment (Biochem. Biophys. Res. Commun., 94, 1367 (1980)), ethanol injection method (J. Cell. Biol., 66, 621 (1975)), French press method (FEBS Lett., 99, 210 (1979)), ether injection method (NY Acad. Sci., 308, 250 (1978)), cholic acid (surfactant) method (Biochim. Biophys. Acta, 455, 322 (1976)), calcium fusion method (Biochim. Biophys. Acta, 394, 483 (1978)), the freeze-thaw method (Arch.Biochem.Biophys., 212, 186 (1981)), the reverse phase evaporation method (Proc. NAS USA, 75, 4194 (1978)), the method using a glass filter ( Third US-Japan Symposium on Drug Delivery System (1995)), emulsification using a high-pressure homogenizer, methods using commercially available kits such as Cortsome ^{(registered trademark)} , and methods using other commercially available manufacturing equipment.

The cationized vesicles of the present invention may be either unilamellar vesicles or multilamellar vesicles. In one aspect, the cationic vesicles of the invention are unilamellar vesicles. In one aspect, the cationic vesicles of the invention are multilamellar vesicles.

Both MLVs and SLVs are referred to herein without distinction as "cationized vesicles" of the present invention. In addition, cationized MLV is sometimes abbreviated as "CMLV" and cationized SLV is abbreviated as "CSLV".

2. Cationized Vesicles Containing a Gemini-Type Surfactant The cationized vesicles of the present invention are prepared using the gemini-type surfactant "2C ₁₂ -3" and a cationized polymer, as well as the general raw materials for preparing liposomes described above. , can be prepared using known manufacturing methods.

Examples of raw materials for preparing the cationic vesicles of the present invention, other than gemini-type surfactants and cationic polymers, include phospholipids, cholesterol, and aqueous solvents. Furthermore, the cationized vesicles of the present invention can contain any ingredient that can be used in cosmetics.

The aqueous solvent is not particularly limited as long as it is generally used in cosmetics, and examples thereof include purified water, hot spring water, deep-sea water, and steam-distilled water of plants. The amount of the aqueous solvent is not particularly limited, and can be appropriately determined depending on the content of other components, but is generally 5 to 95%.

Various methods including the liposome production method described above can be used as the method for producing the cationized vesicle of the present invention. For example, the cationized vesicle of the present invention can be produced by stirring and mixing the components at a temperature of about 80°C, and then gradually cooling to about room temperature to about 35°C.

Gemini-type surfactant 2C ₁₂ -3 forms vesicles with excellent stability together with other ingredients. Gemini surfactant 2C ₁₂ -3 can be produced according to the procedures described in the Examples. The production method can be modified as appropriate using knowledge and commonly used techniques well known to those skilled in the art.

The cationized vesicle of the present invention contains 0.00001 to 20% by mass, more preferably 0.0001 to 10% by mass, more preferably 0.001 to 1% by mass of the total amount of the gemini surfactant 2C ₁₂ -3 relative to the total amount of the vesicle. preferably. This is because stable vesicles may not be formed when the content is too high or too low.

The gemini-type surfactant may be in the free form or in the salt form. Salts that are commonly used in cosmetics can be used without particular limitation. Examples include alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, Preferred examples include organic amine salts such as ammonium salts, triethylamine salts, triethanolamine salts and monoethanolamine salts, and basic amino acid salts such as lysine salts and alginates.

3. Cationization Cationization is the process of making a substance positively charged. Since cationized vesicles are positively charged, they are expected to be more easily adsorbed and permeated into the skin than non-cationized vesicles. In the present invention, it is desirable to cationize the vesicles to such an extent that such effects can be obtained.

The surface charge of vesicles is evaluated as the Ζ (zeta) potential. Specifically, the cationized vesicle of the present invention preferably has a Z (zeta) potential of +20 mV or more, preferably +30 mV or more.

A cationizing molecule is used to cationize the vesicles. Generally, a cationic polymer is used as the cationic molecule. Cationized vesicles are obtained by adding a cationized molecule (cationized polymer) during vesicle preparation to cationize the vesicles.

A cationized polymer is a polymeric substance cationized by introducing a cationic group. The cationic polymer itself needs to be biocompatible, and in addition, preferably has a moisturizing effect on the skin and hair.

Examples of cationic groups are shown below.

In the above formula, R ₁ and R ₂ each independently represent an alkyl group having 1 to 3 carbon atoms, R ₃ represents an alkyl group or alkenyl group having 1 to 24 carbon atoms, and X ⁻ represents a monovalent anion. . Examples of monovalent anions represented by X ⁻ include halogen ions such as fluorine ion, bromide ion, chloride ion and iodine ion.

Examples of cationic polymers that can be used in the present invention include polymers of 2-methacryloyloxyethylphosphorylcholine (abbreviation: MPC) and specific cationic monomers. MPC is an epoch-making biocompatible material with extremely high affinity for living organisms, having both the same structure as cell membranes and a polymerizable structure.

Examples of cationic monomers that form copolymers with MPC include:
^BLEMMER® QA: (2-hydroxy-3-methacryloyloxypropyl)trimethylammonium chloride;
MOETAC: 2-(methacryloyloxy)ethyltrimethylammonium chloride;
DMAEA ^{(registered trademark)} -BQ: N,N-dimethylaminoethyl acrylate, benzyl chloride quaternary salt, and the like.

The ratio of MPC to cationic monomer in the cationic polymer and the molecular weight of the cationic polymer can vary. In the present invention, a cationized polymer having a composition produced according to Reference Examples is also preferably used.

In one embodiment, the proportion of cationic monomers in the cationic polymer is preferably 50% or greater, more preferably 55% or greater. The present inventors have confirmed that cationic vesicles can be produced even when the proportion of cationic monomer is increased to 82%. Further, the molecular weight of the cationized polymer is preferably 600,000 or more. The present inventors have confirmed that cationized vesicles can be formed even with a molecular weight of 2,000,000.

In one embodiment, a cationized polymer consisting of a copolymer of (2-hydroxy-3-methacryloyloxypropyl)trimethylammonium chloride and 2-methacryloyloxyethylphosphorylcholine is preferably used. This is a synthetic polymer consisting of the above-mentioned Blemmer QA (registered trademark) and MPC, and the component name (display name) is "Polyquaternium-64".

Ingredients (raw materials) of cosmetics are given international names called INCI names based on the rules of "International Nomenclature of Cosmetic Ingredients". The Japanese display name corresponding to this INCI name is determined by the Japan Cosmetic Industry Association.

Regarding polyquaternium-64, visit the website of the Japan Cosmetic Industry Association (https://www.jcia.org/user/business/ingredients/namelist)
Now the following chemical formula:
It is described as being a polymer of a quaternary ammonium salt represented by "Polyquaternium-64" is a substance name generally used as a description of cosmetic ingredients regardless of the proportion of cationic monomers. In a typical commercial polyquaternium-64, the ratio of MPC/Blemmer QA® is 70/30, so the percentage of cationic monomer in the cationic polymer is 30%. However, in the present invention, the proportion of (2-hydroxy-3-methacryloyloxypropyl)trimethylammonium chloride in Polyquaternium-64 may be 50% or more, or 55% or more.

Examples of polyquaternium-64 whose composition has been changed include polyquaternium-64 (Lipidure C composition change) described in Japanese Patent No. 6735426 (Patent Document 10) and also described in Reference Example 1 of the present application (Lipidure is registered trademark).

It is desirable that the Z potential of the cationized vesicle be kept stable even when excipients are added for storage, lyophilized, and then redissolved in an aqueous solvent.
It is desirable that the Z-potential of the cationized vesicle be kept stable even during long-term storage. Specifically, when stored at room temperature (for example, 25° C.), it is desirable that the Z (zeta) potential is kept constant for 7 days or longer, preferably 4 weeks or longer, and more preferably 4 months or longer.

It is desirable that the Z potential of the cationized vesicle be kept stable even when the active ingredient is encapsulated. Specifically, the cationized vesicle encapsulating an active ingredient should have a Z (zeta) potential of +20 mV or higher, preferably +30 mV or higher.

It is desirable that the Z potential of the active ingredient-encapsulating cationized vesicle be kept stable for a long period of time even when it is blended in cosmetics. Specifically, for example, it is desirable that the cationized vesicle encapsulating an active ingredient has a Z (zeta) potential of +20 mV or higher, preferably +30 mV or higher, in water for 4 months or longer.

4. Particle size of the cationized vesicles The particle size of the cationized vesicles of the invention is between 1 and 1000 nm, preferably between 10 and 200 nm, or between 10 and 100 nm, or between 20 and 200 nm. Aggregation of vesicle particles increases the Z (zeta) average, which is the particle size. The cationized vesicle is desirably controlled so that aggregation of particles is prevented as much as possible and the particle size does not increase. This is because an increase in particle size may cause undesirable phenomena such as precipitation.

Aggregation/precipitation is likely to occur when the repulsive force between particles becomes weak when the surface charge is close to zero. Therefore, as described above, it is desirable that the Z (zeta) potential of the cationized vesicle and the active ingredient-encapsulating cationized vesicle be maintained at a positive potential above a certain level.

It is desirable that the particle size of the cationized vesicle be kept stable even when excipients are added for storage, freeze-dried, and then re-dissolved in an aqueous solvent.
It is desirable that the particle size of the cationized vesicle be kept stable even during long-term storage.

It is desirable that the particle size of the cationized vesicle be kept stable even when the active ingredient is encapsulated. Specifically, for example, the particle size of the active ingredient-encapsulating cationized vesicle is 1 to 1000 nm, preferably 10 to 200 nm, or 10 to 100 nm, or 20 to 200 nm. Furthermore, it is desirable that the particle size of the active ingredient-encapsulating cationized vesicle be kept stable for a long period of time even when it is blended in cosmetics.

5. Cationized Vesicles Encapsulating Active Ingredients Cationic vesicles encapsulating active ingredients in cosmetics can be added to cosmetics such as lotions, serums, emulsions, creams, and shampoos to efficiently deliver the ingredients to the skin. Alternatively, cationized vesicles encapsulating a cosmetic active ingredient can be directly used as cosmetics.

The substance encapsulated in the cationized vesicle is appropriately selected depending on the use of cosmetics. The active ingredient may be either a hydrophilic substance or a lipophilic substance, regardless of its charged state. A wide variety of active ingredients can be encapsulated in the cationized vesicles of the present invention. Examples include minerals, amino acids, vitamins (eg, vitamin C and its derivatives), whitening ingredients, anti-glycation ingredients, antioxidant ingredients, anti-wrinkle ingredients, anti-blemish ingredients, and the like.

Negatively charged substances are generally difficult to encapsulate in vesicles and cationized vesicles. In contrast, the cationized vesicle of the present invention can contain a negatively charged substance as a cosmetic component. Examples of such cosmetic components to be encapsulated include negative ion-bearing components such as minerals, amino acids, anionic surfactants, vitamin C and its derivatives.

Examples of minerals include the deep sea water concentrate composition described in JP-A-2007-217356, the deep-sea water described in JP-A-2000-290159, and the Yunohana extract described in Japanese Patent No. 3967357. be done. The deep sea water concentrate composition, deep sea water, or dried seawater, which is a dried product thereof, or cationized vesicles encapsulating the Yunohana extract are herein referred to as "cationized vesicles encapsulating minerals."

For example, the deep sea water concentrate is a NF membrane permeate concentrate obtained by a manufacturing method comprising the following steps (1) and (2):
(1) Treating deep sea water with a nanofilter membrane that can remove more than 90% of sulfate ions, Brix is 2.8-3.6, Mg ion concentration is 300-900mg/L, Ca ion concentration is 200-600mg/L, and obtaining NF membrane permeated water having an SO ₄ ion concentration of 0 to 300 mg/L; and
(2) Concentrate the NF membrane permeated water obtained in step (1) to obtain Brix of 30.0 to 55.0, Mg ion concentration of 10,000 to 100,000 mg/L, Ca ion concentration of 4,000 to 40,000 mg/L, and SO ₄ Obtaining a NF membrane permeate concentrate having an ion concentration of 0-1,000 mg/L and Ca ion concentration:Mg ion concentration=1:0.25-1:4.

In the concentration of the NF membrane permeated water, it is preferable that the concentration is 14 to 50 times and the NF membrane permeated water concentrate is in the form of an aqueous solution without precipitates. Further, for example, the nanofilter membrane preferably has a pore size of 0.1 to 1 nm and a pressure of 0.3 to 2.0 MPa.

Further, for example, the Yunohana extract is a composition containing an ozone oxidation product of Yunohana obtained by a production method including the following steps (1) to (3):
(1) Crystallize hot spring fumaroles on blue clay at a constant temperature and humidity to obtain Yunohana,
(2) dissolving Yunohana in an aqueous solvent, and
(3) Ozonooxidize the dissolved matter to obtain an ozone-oxidized product.

The Yunohana extract contains: (1) 25-40,000 mg/L sulfate ions; (2) 5.0-8,000 mg/L trivalent iron ions; and (3) aluminum ions; divalent iron ions: 3 It is preferred that the ratio of valence iron ions is 4,900:2,000 or less. Here, it is also preferable that the ratio of divalent iron ions to 1 trivalent iron ion is 0.5 or less.

In this specification, the deep sea water concentrate composition, deep sea water, dried seawater, and Yunohana extract may be simply referred to as "minerals".
The cationized vesicle of the present invention has a higher concentration of minerals that can be encapsulated than conventional vesicles. The mineral concentration is about 0.0001% to about 5%, for example, about 0.01% to about 5%, about 2% to about 5%, about 3% to about 5%, in terms of weight percent relative to the total weight of the vesicle. can be done.

In addition, the cationized vesicle of the present invention can encapsulate various substances. In addition to the minerals described above, examples of cosmetic components to be encapsulated include vitamin C derivatives (eg, sodium ascorbyl phosphate) and the like. The vitamin C derivative can be encapsulated at a concentration of about 0.1% to about 5% in weight percent with respect to the total weight of the vesicle.

The active ingredient-encapsulating cationized vesicle is heated at a temperature of about 80°C (for example, 75 to 85°C) to encapsulate the active ingredient, cationized polymer, phospholipid, cholesterol, gemini surfactant, and optionally other cosmetic ingredients. and an aqueous solvent (purified water, hot spring water, deep sea water, steam-distilled water of plants, etc.) are stirred and mixed, and then gradually cooled to about room temperature to about 35°C. In addition, it can be produced by appropriately using a known technique as the method for producing liposomes described above. The cooled composition may be further emulsified under high pressure (eg 220MPa X 5Pass) and filtered (eg filtered through a 1.0 μm filter).

The other cosmetic ingredients include moisturizing ingredients, crude drug extracts, enzymes such as tyrosinase, superoxide dismutase, and lipase, vitamins and their derivatives such as retinol, ascorbic acid, tocopherol, pyridoxal, riboflavin, β-carotene, and chlorophyll. such as organic pigments, glycerin, sorbitol, urea, lactic acid, propylene glycol, polyethylene glycol and copolymers, moisturizing ingredients such as glucose derivatives, paraffin, stearyl alcohol, cetyl alcohol, squalane, silicone oil, stearis, etc. emollient ingredients, treatment ingredients, dandruff-suppressing ingredients, hair-restoring ingredients, hair-restoring ingredients, ultraviolet absorbers, antioxidants, fragrances, preservatives, and the like. You may use these in combination of 2 or more types as needed.

By introducing the gemini-type surfactant of the present invention into the vesicle membrane, it is possible to incorporate raw materials into cosmetics, which have been difficult to blend due to problems of compatibility. This makes it possible to apply cationized vesicles to various formulations of cosmetics.

6. Formulation of Cosmetics Cosmetics can be produced by adding one or more active ingredient-encapsulating cationized vesicles to formulations such as ordinary lotions, serums, milky lotions, creams, and shampoos. . Alternatively, it is also possible to obtain cationized vesicles encapsulating an active ingredient at the same time while preparing cosmetics.

The form of cosmetics is not particularly limited, but it is generally considered to be used by applying to the skin or hair. Topical application also includes application to the skin or hair followed by rinsing. For example, skin care cosmetics such as face wash, cleansing agent, lotion, serum, pack, massage cream, milky lotion, moisture cream, lip balm, etc. Makeup cosmetics such as foundation, white powder, lipstick, blush, eye shadow, etc. Body care cosmetics Soaps, liquid cleansers, bath additives, etc., and hair care cosmetics such as shampoos, rinses, hair treatments, hair styling agents, hair tonics, hair tonics, scalp treatments, etc. can be used. The above cosmetics may contain various cosmetic ingredients commonly used in cosmetics (oils, waxes, hydrocarbons, fatty acids, alcohols, esters, amino acids, vitamins, Surfactants, pH adjusters, preservatives, fragrances, moisturizers, powders, UV absorbers, thickeners, pigments, antioxidants, whitening agents, anti-inflammatory agents, anti-wrinkle agents, rough skin improvers, acne drugs, alkalis, chelating agents, sequestering agents, etc.) can be appropriately added.

In addition, the cosmetics of the present invention may contain substances derived from natural products. Examples of such substances include: Japanese apricot extracts described in Japanese Patent No. 4795475, such as a Japanese apricot root extract and a Japanese apricot fruit distilled water. Plum juice fermented liquid described in Patent No. 2526362. Plant-derived steam-distilled water described in JP-A-2012-116761, for example, steam distillation of one or more plants selected from passion fruit, shimatangerine, banana, atemoya, plum, tankan, lemon-lime, and ginger water. Angelica keiskei extract described in Japanese Patent No. 3544505. A seawater-derived yeast culture described in JP-A-2009-029788.

The amount of the active ingredient-encapsulating cationized vesicle to be added varies depending on the dosage form, but the active ingredient-encapsulating cationized vesicle can be contained in an amount of 0.1 to 100% by mass based on the total amount of the cosmetic, for example, 1 to 100% by mass. 50% by mass can be contained.

7. Beauty treatment method The cosmetic of the present invention can be used for makeup performed by the person himself/herself or for a beauty treatment method performed by another person such as an esthetician. The cosmetic of the present invention is preferably applied to the skin or hair, and methods of use include a method of using hands and fingers, and a method of impregnating a nonwoven fabric with the cosmetic.

8. Stabilization of cationized vesicles by gemini-type surfactant By blending the gemini-type surfactant 2C ₁₂ -3 as a vesicle component, vesicles with excellent stability are formed. In one aspect of the present invention, the gemini surfactant 2C ₁₂ -3 is added in an amount of 0.00001 to 20% by mass, more preferably 0.0001 to 10% by mass, more preferably 0.001 to 1% by mass relative to the total amount of the vesicle. A method for stabilizing cationized vesicles by By adding 2C ₁₂ -3, the particle size becomes smaller than that of conventionally known cationic vesicles, and the vesicles remain stable in that state.

EXAMPLES Hereinafter, the present invention will be specifically described with reference to Examples. It should be noted that these examples are for the purpose of explaining the present invention, and are not intended to limit the scope of the present invention.

[Example 1: Preparation of gemini surfactant]
A gemini surfactant (compound 2C ₁₂ -3) was prepared by the following procedure.
Dissolve 15.0 g of N,N,N',N'-tetramethyl-1,3-propanediamine in 100 mL of acetonitrile. It was heated to reflux for 1 hour. After evaporation of the reaction solution, the residue was washed with hexane and ethyl acetate twice each, and recrystallized with a mixed solvent of ethyl acetate and methanol to obtain a white solid cation x cation gemini surfactant 2C12-3 ( 50.0 g of molecular weight 629) was obtained.

[Example 2: Preparation of CMLV]
Cationized MLVs (CMLV) were made by high pressure emulsification from polyquaternium-64, hydrogenated lecithin, hydrogenated cyclic Na lysophosphatidate, cholesterol, aqueous solvent and gemini-type surfactant (compound 2C ₁₂ -3).

[Example 3: Effect of gemini-type surfactant on CMLV stability]
The effect on CMLV stability was investigated by varying the loading of 2C ₁₂ -3 in existing cationic vesicles.

Particle size (Z-average) and surface potential (Z-potential) on day 0, day 1, day 7 or 8, day 14, day 21 or 22, day 28 or 29 Time course measurements were taken on the eyes. (Table 1). CMLV II28 is a cationized vesicle described in Japanese Patent No. 6735426 (Patent Document 10). No. 1, 2, 3, 9 are CMLVs made by adding 2C ₁₂ -3 to CMLV II28.
Contains 0.01% of No.1 IG20 2C _12-3
No.2 Contains 0.1% of IG20 2C _12-3
No.3 Contains 0.001% of IG20 2C _12-3
Contains 1% of No.9 IK08 2C _12-3

It has been found that the use of a gemini-type surfactant provides stability over time in which no aggregation occurs and the surface charge does not change. That is, the addition of 2C ₁₂ -3 makes the particle size smaller than CMLVCMLV II28 and stabilizes in that state. In particular, No. 2 has excellent stability in a small state.

[Example 4: Observation with an electron microscope]
The cationized MLV of Example 3 (No. 2 IG20) was observed with a transmission electron microscope. An electron microscope image is shown in FIG. It was found that a spherical multi-layered structure with a particle diameter of around 100 nm was formed.

The following reference examples describe the preparation of a cationized polymer consisting of MPC and ^Blemmer® QA, a cationized polymer consisting of MPC and MOETAC, and a cationized polymer consisting of MPC and ^DMAEQ® -BQ.

[Reference Example 1: Preparation of cationized polymer]
16.6 g of MPC and 33.4 g of Blemmer ^{(registered trademark)} QA were dissolved in 200 g of water, placed in a four-necked flask, and nitrogen was blown for 30 minutes. industrial product, 0.55 g) was added and polymerized for 10 hours. The polymerization liquid was added dropwise to 5 liters of diethyl ether with stirring, and the deposited precipitate was filtered and vacuum-dried at room temperature for 48 hours to obtain 30.1 g of cationized polymer powder. As a result, a cationized polymer (polyquaternium-64) having a molecular weight of 700,000 and consisting of 45% MPC and 55% Blemmer ^{(registered trademark)} QA (MPC/cation=45/55) was obtained.

In the same manner, cationized polymers with different molecular weights and ratios of MPC and Bremmer QA, and cationized polymers with different cation monomers consisting of MPC and MOETAC or DMAEQ-BQ were obtained.

A cationized polymer (Lipidure C, MPC/cation=70/30, molecular weight 600,000) consisting of 70% MPC and 30% Blemmer ^{(registered trademark} ) QA is conventionally known commercially available polyquaternium-64.

Claims (10)

the formula below

A compound represented by A cationized vesicle containing the compound of claim 1 . 3. The cationized vesicle according to claim 2, which is a multilamellar vesicle. The cationized vesicle according to claim 2 or 3, which has a Z potential of +20 mV or more. The cationized vesicle according to any one of claims 2 to 4, which has a particle size of 20 nm to 200 nm. A cationized vesicle encapsulating an active ingredient, wherein the cationized vesicle according to claim 5 holds a cosmetic active ingredient. 7. The method according to claim 6, wherein the active ingredient is selected from the group consisting of minerals, amino acids, anionic surfactants, vitamins, whitening ingredients, anti-glycation ingredients, antioxidant ingredients, anti-wrinkle ingredients, and anti-blemish ingredients. A cationized vesicle encapsulating an active ingredient as described. A cosmetic containing one or more of the active ingredient-encapsulating cationized vesicles according to claim 7. 9. Cosmetics according to claim 8, which are skin care cosmetics, makeup cosmetics, body care cosmetics, hair care cosmetics or hair care cosmetics. A cosmetic treatment method comprising applying the cosmetic according to claim 8 to the skin or hair.