JP2000229815A - Liposomes and their use - Google Patents

Abstract

(57) [Problem] To provide a liposome having a small particle size. SOLUTION: The half-value width of the ¹⁷ O-NMR signal is 9
Obtained by subjecting water at 0 Hz or lower, a target substance, and an amphipathic compound to an ultrahigh-pressure homogenizer treatment. Since a composition containing a drug, cosmetics, a hair restorer or a hair restorer in the liposome has an excellent affinity for the tissue, the drug, a moisturizing component, a hair restorer, or a hair restorer can easily adhere to and enter the tissue. High efficacy can be expected in combination with sustained release.
In particular, when water having a half width of 60 Hz or less is used, since it has an ability to disperse fats and oils 1.5 times or more of ordinary water, a larger amount of medicine, cosmetics, hair restorer or Since the hair restorer can be maintained, a higher effect can be expected.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a liposome having a small particle size, a method for producing the liposome, and a composition containing the liposome. More specifically, the present invention relates to a liposome obtained by mixing water having a half-width of a specific ¹⁷ O-NMR signal, a target substance, and a phospholipid, the average particle diameter of which is determined using normal water. Liposomes smaller than the average particle size of the liposomes produced by the method.

[0002]

2. Description of the Related Art Generally, a liposome is a closed vesicle composed of a monolayer or a plurality of layers of a lipid obtained by mixing a phospholipid and water, and various substances are added to an inner aqueous layer or a lipid layer. Its usefulness is great because it can be retained. For example, a liposome enclosing a drug is used in a drug delivery system (DDS). In this case, the smaller the particle size of the liposome, the larger the specific surface area even at the same concentration, and the greater the affinity with the tissue, which is advantageous.

[0003] The technology for producing liposomes is rapidly advancing, and liposomes having a small particle size are being produced. However, the conventional techniques for reducing liposomes are related to physical methods and are almost in a state of completion. However, at present, no attempt has been made to reduce the particle size by focusing on the constituents of the liposome.

[0004]

[SUMMARY OF THE INVENTION Therefore, the present inventors have found that components constituting the liposome in order to reduce the particle size of the liposomes, result of our intensive studies with particular attention to the water, the specific ¹⁷ O- The present inventors have found that the average particle size of liposomes obtained using water having a half-width of the NMR signal is significantly lower than that obtained using ordinary water, and arrived at the present invention.

[0005]

The present invention provides a ¹⁷ O-NM.
A liposome having a small particle diameter obtained by mixing water having a half width of an R signal of 90 Hz or less, a target substance, and an amphipathic compound, wherein the average particle diameter of the liposome is determined using ordinary water. It relates to liposomes smaller than the average particle size of the liposomes produced.

[0006] In a preferred embodiment, the amphiphilic compound is a phospholipid, and in a further preferred embodiment, the phospholipid is lecithin.

The present invention also relates to a method for producing a liposome having a fine particle diameter, which comprises a step of mixing water having a half-width of ¹⁷ O-NMR signal of 90 Hz or less, a target component and an amphiphilic compound.

[0008] In a preferred embodiment, the water ¹⁷
The half width of the O-NMR signal is 60 Hz or less.

In a preferred embodiment, the water is water obtained by magnetizing pure water.

[0010] In a preferred embodiment, the amphiphilic compound is a phospholipid, and in a further preferred embodiment, the phospholipid is lecithin.

Further, the present invention relates to a composition containing liposomes having a small particle diameter obtained by mixing water having a half-width of ¹⁷ O-NMR signal of 90 Hz or less, a target substance and an amphiphilic compound.

[0012] In a preferred embodiment, the amphipathic compound is a phospholipid, and in a further preferred embodiment, the phospholipid is lecithin.

[0013] In a preferred embodiment, the target substance is a drug, a cosmetic, a hair restorer or a hair restorer, and the composition is a pharmaceutical composition, a cosmetic composition, a hair restorer or a hair restorer.

In a further preferred embodiment, the cosmetic composition is a cosmetic cream, a lotion, an emulsion, a serum,
It is a foundation, shampoo, rinse, treatment or hair styling.

[0015] In a more preferred embodiment, the shampoo, rinse, treatment or hair styling contains a hair restoration component and / or a hair restoration component.

In a preferred embodiment, the pharmaceutical composition is a composition suitable for oral administration, mucosal application, body surface application, and intravascular or tissue administration.

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION ¹⁷ O-N used in the present invention
Water having a half width of the MR signal (hereinafter sometimes simply referred to as a half width) of 90 Hz or less can be obtained by reducing the cluster of water. Water forms a molecular group by an electric force (hydrogen bond between oxygen and hydrogen) that acts between molecules of two hydrogens and one oxygen. A cluster refers to this molecular group of water. The degree of formation of water clusters can be measured by the half-width of the ¹⁷ O-NMR signal, and the smaller the half-width, the smaller the cluster. Therefore, the half width of water of the present invention is preferably as small as possible, more preferably 75 Hz or less, and further preferably 60 Hz or less.

Water having a half-value width of 90 Hz or less of ¹⁷ O-NMR signal used in the present invention is obtained by treating pure water, purified water, tap water, ion-exchanged water and the like as described in the Japanese Pharmacopoeia by magnetic line treatment, weak current. Treatment, electric field treatment, ceramic plate treatment, far infrared treatment, high frequency (electromagnetic wave) treatment, mechanical treatment, ultrasonic treatment, electromotive force treatment, laser beam treatment, or natural ore treatment, singly or in combination. Can be

The water used is preferably purified water, ion-exchanged water or pure water, and most preferably pure water. Note that pure water refers to water that is close to pure water obtained by desalting ordinary water and has a specific resistance of about 50 Ω · cm or more in electrical resistance. Including ultrapure water.

The water obtained by clustering pure water is
Not only does the half width become 60 Hz or less, but also it has the ability to disperse fats and oils 1.5 times or more in ordinary water. It is also excellent in that it can hold a target substance such as a drug and a hair-growing component.

A processing method for reducing the half width of water to 90 Hz or less will be briefly described below by taking a magnetic field line processing method as an example. The line of magnetic force processing is usually performed by passing water at a fixed flow rate or higher through a gap between magnets (magnet devices) having a magnetic field strength of about 0.07 T (Tesla: 10,000 Gauss) or more. The treatment is preferably performed with a line of magnetic force of 0.3 T or more. In particular, 1.2T or more is preferable. A magnetic field line treatment apparatus and a method for producing magnetic field line treated water are described in, for example, Japanese Patent Application Laid-Open No. 8-1970064.

The weak current treatment is performed by flowing water into the gap between the non-insulated internal electrode and the external electrode and passing a weak current of several tens of milliamps.

The electric field treatment is performed by applying a DC or AC voltage of 1,000 volts or more to the water in the water tank. In order to increase the electric conductivity, for example, charcoal or the like can be immersed.

The wavelength of the ceramic plate treatment is 6 to 14 μm.
In this method, a ceramic plate made of a material emitting far infrared rays is immersed in a water tank.

The far-infrared treatment includes a method of passing through a ceramic filter that emits far-infrared rays, and a method of applying the output from a far-infrared heater to water. The method of passing through a ceramic filter is almost the same as that of the ceramic plate processing.

The high frequency (electromagnetic wave) processing is a method in which a higher frequency than ultrasonic waves is applied to water. Microwave processing such as a microwave oven is applicable.

The mechanical treatment is a method of rotating water at high speed.

The ultrasonic treatment is a method of applying ultrasonic waves having a frequency of about 20 to 40 KHz to water. Either a high output used for cleaning jewelry or glass utensils or a low output which promotes aging of sake can be used.

The electromotive force treatment is a method in which water flows between different kinds of conductive materials, and the clusters of water are reduced by the difference in ionization voltage.

[0030] Natural ore treatment is a method of passing clusters of natural ore layers at a suitable pressure through water to reduce clusters.

The laser beam treatment can be performed using various media that emit a laser beam. For example, a gas laser (H2O from 109.8 nm to deuterated chloroform (CDC1
3) (1990.75 μm), a liquid laser or a solid laser (YAG laser, glass laser, ruby laser, etc.) is irradiated to treat water.

In the present specification, the term “liposome” refers to a broad concept including liposomes prepared using so-called natural phospholipids and vesicles formed using an amphipathic compound.

The amphipathic compound used for producing the liposome is a compound having a hydrophilic group and a hydrophobic group in one molecule. For example, anionic vesicle-forming surfactants, amphoteric vesicle-forming surfactants, and non-ionic vesicle-forming surfactants described on pages 19-26 of "Development Technology of Functional Surfactants" (CMC (1998)). Vesicle-forming surfactants and natural vesicle-forming surfactants.

Among these, natural vesicle-forming surfactants are preferred from the viewpoint of safety and the like. As the natural vesicle-forming surfactant, glycerides, glycolipids, amino acids, steroids and phospholipids are preferably used.

[0035] Phospholipids are most preferably used. Examples of the phospholipid include lecithin (phosphatidylcholine), phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, diphosphatidylglycerol, phosphatidic acid, sphingomyelin and the like. Compositions containing these phospholipids are also preferably used.

The liposome membrane, particularly lecithin membrane, may contain cholesterol as a reinforcing and stabilizing component.

The liposome of the present invention is generally prepared by adding an appropriate amount of the target substance to water having a half width of 90 Hz or less in an amount of about 0.01.
% To about 20% by weight, preferably about 0.1% to about 5% by weight of an amphipathic compound, mixed and dispersed, and then treated with a high-pressure homogenizer, an ultra-high-pressure homogenizer or the like. Can be

Since it is preferable that the liposome is as small as possible, an ultrahigh pressure homogenizer is suitably used.
For example, a microfluidizer (Mizuho Industry Co., Ltd.)
Is used to produce fine liposomes.

Usually, a multi-layered liposome is obtained, but it can be converted into a mono-layered liposome by further sonication. Thus, the liposomes of the present invention include monolayer and multi-layer liposomes.

The liposome of the present invention has a half width of 90 Hz.
The average particle size is smaller than when the above water is used. In particular, when water having a half width of 60 Hz or less is used, the average particle size becomes about 1/2. Accordingly, the specific surface area is increased even at the same concentration as compared with conventional liposomes made of water, so that the reactivity is increased, and when applied to a living body, the affinity for tissue is increased. Therefore, the liposome of the present invention is used in any field where a surfactant is used.

The target substance which can be contained in the liposome of the present invention is preferably a drug, cosmetic, hair restorer, hair restorer, or the like. And pharmaceuticals, cosmetics,
The hair restorer or the liposome containing the hair restorer is mixed with a substance suitable as each composition to obtain a pharmaceutical composition, a cosmetic composition, a hair restorer composition, and a hair restorer composition.

Pharmaceutical compositions include oral administration (gastrointestinal tract), mucosal application (eye, oral mucosa, throat, nasal cavity, bronchial
Lung, intestine, lower body cavity), body surface application (skin, body cavity / trauma surface)
And compositions adapted for intravascular or intravenous (intravenous, intramuscular, and subcutaneous) administration and application forms.

When these compositions are administered or applied, for example, by oral administration, injection, or the like, the liposomes are absorbed into the body more quickly because they have a smaller particle size than conventional liposomes, and can be used as a target organ or target. A high concentration of drug can be transmitted around the tissue, and a high pharmacological effect can be expected in combination with sustained release. In particular, when water having a half width of 60 Hz or less is used, as described above, since it has the ability to disperse fats and oils 1.5 times or more in normal water,
Since a larger amount of drug can be held, a higher pharmacological effect can be expected.

The dosage forms suitable for oral administration include powders, granules, oral tablets, capsules, pills, elixirs, syrups, limonades, fragrances, emulsions, suspensions, infusions, decoctions, An internal tincture, an extract and a fluid extract may be mentioned.

[0045] Dosage forms suitable for mucosal application include eye drops or ointments for the eye, sublinguals, buccal tablets and lozenges for the oral mucosa, mouthwashes for the throat, nasal cavity Examples include sprays, aerosols and inhalants for bronchi and lungs, enemas for the intestine, and suppositories and vaginals for the lower body cavity.

As the dosage form suitable for application to the body surface, in the case of skin, ointments, plasters, liniments, lotions,
Pasta, poultice, liquid, alcoholic beverage, external tincture and the like can be mentioned. In the case of a body cavity / trauma surface, an irrigation agent and the like can be mentioned.

As dosage forms suitable for intravascular or intradermal administration, injections can be used for subcutaneous, intramuscular, intravenous, etc. and subcutaneous tissues, and implants for subcutaneous tissues.

In order to form the above-mentioned dosage form, excipients, auxiliaries, additives and the like usually used in the production of pharmaceuticals can be added.

Examples of the excipient include solvents, bases, diluents, extenders, fillers, excipients and the like.

As the auxiliary agent, a solubilizing agent, a solubilizing agent,
Buffers, tonicity agents, emulsifiers, suspending agents, dispersants, thickeners, gelling agents, hardeners, absorbents, adhesives, elasticizers, plasticizers, binders, disintegrants, lubricants , A coating agent, a sustained release agent, and a propellant.

The additives include antioxidants, preservatives, humectants, light-shielding agents, brighteners, antistatic agents, fragrances, sweeteners, flavoring agents, coloring agents, soothing agents, and soothing agents. No.

[0051] Drugs suitable for the pharmaceutical composition of the present invention include, for example, inotropic agents, vasopressors, antiarrhythmic agents, therapeutic agents for angina pectoris, vasodilators, antihypertensive agents, diuretics and antihyperlipidemic agents. Respiratory drugs, such as cardiovascular drugs, bronchodilators, respiratory stimulants, bronchial asthma treatments, antitussives and expectorants
Gastrointestinal drugs such as stomachic digestives, peptic ulcer treatments, intestinal antidiarrheals, laxatives, treatment for colitis, treatment for hemorrhoids, treatment for liver or pancreatic diseases, antidote, bile medicine, etc. Liver, pancreas,
Urinary and reproductive agents such as gallbladder and renal disease drugs, sleeping pills, sedatives, antipyretic analgesics, antiepileptics, psychotropic drugs, cerebral metabolic activators, autonomic nervous drugs, Parkinson's disease treatment Agents acting on the nervous system, such as drugs, muscle relaxants, hematopoietic agents, hemostatic agents, blood system agents such as antithrombotic agents, corticosteroids, nonsteroidal anti-inflammatory agents, anti-inflammatory enzymes, antirheumatic agents, antihistamines Drugs that act on metabolic systems such as drugs for treating inflammation and allergies, such as drugs for treating diabetes and gout, drugs for pathogenic microorganisms, drugs for sensory organs for ophthalmology, otolaryngology and dermatology, and immunosuppressants , A bone metabolism improving agent, a hormonal agent, a vitamin agent, a Chinese medicine and the like.

The dosage form of the pharmaceutical composition is formed according to the purpose by a method known to those skilled in the art.

Further, when the liposome having a small average particle size of the present invention is used in a cosmetic composition, a hair restorer composition or a hair restorer composition, the affinity of the liposome to the skin or hair tissue is increased. Components contained in the liposome, for example, moisturizing components, hair-growing components, hair-growing components, and the like can easily adhere to and enter the stratum corneum, hair, and the like, and can be expected to have a high effect in combination with sustained release. In particular, the half width is 60
When water at a frequency of less than or equal to Hz is used, as described above, since it has the ability to disperse fats and oils 1.5 times or more than ordinary water, a larger amount of cosmetics, hair restorer or hair restorer is contained in the liposome. Since it can be maintained, higher effects can be expected.

As cosmetic compositions, basic cosmetics (lotion, cream, milky lotion, serum, pack, etc.), finished cosmetics (foundation, lipstick, blusher, whitening, etc.), and shampoos, rinses, treatments as hair cosmetics Or a hairdressing agent. A shampoo, a rinse, a treatment or a hairdressing material may contain a hair-growing component or a hair-growing component.

The basic cosmetic may be a cosmetic in which a liposome containing an aqueous component, an oily component and / or other various components, which is usually blended as a cosmetic, is dispersed, or is blended with the liposome as a usual cosmetic. It may be a cosmetic containing various components such as an oil component, an aqueous component, and an emulsifier.

Examples of the aqueous component include a humectant, a mucous agent, an alcohol and the like.

The humectant contributes to the moisturizing of the stratum corneum, a feeling of use, and the like. Specifically, for example, glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, polyethylene glycol, polyhydric alcohol,
Sugars, amino acids and the like can be mentioned. These moisturizers
Usually it is added in an amount of less than about 20% by weight, preferably less than about 15% by weight.

The mucus (thickening agent) contributes to moisturizing properties, stability, feeling of use, etc. Specifically, for example, quince sheet (quince seed gum), tragacanth gum, pectin,
Alginates, cellulose derivatives (for example, sodium carboxymethylcellulose), acrylic acid-based polymers, veegum, polyvinyl alcohol and the like can be mentioned.

Alcohol contributes to refreshing feeling, sterilization, dissolution of the components, and the like, and examples thereof include ethanol and isopropanol.

As the oily component, any of animal and plant and mineral natural oily components and synthetic oily components can be used.

Examples of animal and plant oily components include beeswax, water wax, carnapa wax, candelillauro, cacao butter, cetyl alcohol (1-hexadecanol),
Stearic acid alkyl ester, lanolin, olive oil, camellia oil, castor oil, cottonseed oil, 9-octadecene-1-
Ole (oleyl alcohol), oleic acid, squalane and the like can be mentioned.

Examples of the mineral oil component include solid paraffin, ceresin, microcrystalline, wax, petrolatum, liquid paraffin, and silicone oil.

Examples of the synthetic oil component include synthetic ester oils and synthetic polyether oils.

The oil component may be contained, for example, in an amount of about 10 to 80% by weight. The range varies depending on the type of cosmetic, such as oiliness, weak oiliness, and neutrality, and can be determined as appropriate.

As other components, the basic cosmetics of the present invention include softeners (emollients), keratin softeners, solubilizers, buffers, various chemicals, fragrances, preservatives, dyes, anti-fading agents, ultraviolet absorbers , A sequestering agent and the like in an appropriate amount.

The softener (emollient) contributes to moisturizing and feeling of use, and includes, for example, ester oils and higher alcohols.

Examples of the keratin softener include alkalis such as potassium hydroxide and potassium carbonate.

Emulsifiers (solubilisers, surfactants) include polyoxyethylene oleyl ether, octyldodecanol, lipophilic glyceryl monostearate, self-emulsifying propylene glycol monostearate, polyoxyethylene cetyl ether, polyoxyethylene Ethylene sorbitan monolaurate and the like. Emulsifiers, such as octyldodecanol, can be added in amounts usually of about 2-8% by weight, preferably about 3-5% by weight.

Examples of the drug include an astringent such as zinc p-phenolsulfonate; a bactericide such as benzalkonium hydrochloride;
Nutrients such as vitamin and amino acid derivatives.

Examples of the buffer (pH adjusting agent) include citric acid and salts thereof.

The cosmetic creams usually include emollient cream, massage cream, cleansing cream, makeup cream, sunscreen cream, hair cream, deodorant cream, shaving cream, face cream, hand cream, body cream, etc. Although various names based on differences in functions, application sites, and the like are included, the present invention includes all of these.

Finish cosmetics (foundation, lipstick,
Liposomes are used for
In addition to the aqueous component, a pigment is included. As a pigment,
Examples thereof include organic and inorganic pigments such as iron oxide, titanium oxide, zinc oxide, talc, sericite, kaolin, aluminum or barium lake as a tar pigment, and mica titanium as a pearl pigment.

The finished cosmetic may contain components generally used for finished cosmetics, in addition to liposomes. For example, the oil component, the aqueous component, and the like can be appropriately selected and used in an appropriate amount.

[0075] Cosmetic products for hair include shampoos, rinses, treatments and hair styling products. A shampoo, a rinse, a treatment or a hairdressing material may contain a hair-growing component or a hair-growing component.

The hair cosmetic composition includes, in addition to the above-described liposomes, a composition in which liposomes containing an aqueous component and / or an oil component usually contained in hair cosmetics are dispersed. It may be a composition in which various components used are dispersed.

The components to be blended include, for example, emulsifiers, conditioning agents, alcohol, dandruff agents,
Disinfectants, tonics, softeners (emollients), keratin softeners, mucous agents, chelating agents, various chemicals, fragrances, preservatives, dyes, anti-fading agents, ultraviolet absorbers, sequestering agents, etc. .

The mucous agent (thickener) contributes to moisturizing properties, stability, feeling of use, etc. Specifically, for example, quince sheet (quince seed gum), tragacanth gum, pectin,
Alginates, cellulose derivatives (for example, sodium carboxymethylcellulose), acrylic acid-based polymers, veegum, polyvinyl alcohol, and electrolytes (for example, sodium chloride, potassium chloride) and the like.

The hydrotrope contributes to improving the low-temperature stability of the hair wash and the solubility of the surfactant. For example, ethanol used as a bactericide, propylene glycol, alcohols such as glycerin also used as a humectant, polyoxyethylene sorbitan monolaurate,
Examples include nonionic solubilizers such as polyethylene glycol fatty acid esters, sodium benzenesulfonate, sodium xylenesulfonate, and urea.

Emulsifiers emulsify shampoos and contribute to imparting a luxurious, mild and creamy feel. For example, styrene polymer, polyvinyl acetate and the like can be mentioned. Magnesium stearate, ethylene glycol monostearate, ethylene glycol distearate,
Stearyl alcohol, fish scale foil, titanium mica and the like can be used as pearlescent agents.

The conditioning agent contributes to combing, improvement of stiffness, suppleness of hair, ease of cohesion, strengthening of hair and the like. For example, collagen or its hydrolyzate, amino acids, sodium 2-pyrrolidone-5-carboxylate, milk casein, egg albumin, lecithin, ceramide, chemisorbents such as panthenol (vitamin B complex), lanolin and its derivatives Derivatives, squalane, liquid paraffin, petrolatum, fatty acids, higher alcohols, esters, silicone oil and its derivatives, fats and oils (for example,
Oil-based physical adsorptive substances such as castor oil and olive oil)
Examples thereof include cationically modified cellulose ether derivatives, quaternary ammonium salts of polyvinylpyrrolidone derivatives, distearyldimethylammonium chloride polymer, and ionic adsorption type cationic polymers such as alkyl polyethyleneimine.

Alcohol contributes to a refreshing sensation, sterilization, dissolution of the components, and the like. For example, ethanol, isopropanol and the like can be mentioned.

Examples of the dandruff removing agent include, in addition to sulfur and sulfur compounds such as sulfur, selenium sulfide, tincpyridione (Zpt), menthols, triclosan halocarban, allantoin, and salicylic acid.

The humectant contributes to moisturizing the stratum corneum, feeling of use, and the like. For example, glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol,
Examples include polyethylene glycol, polyhydric alcohols, sugars, amino acids, and sorbitol.

The softener (emollient) contributes to moisturizing and feeling of use, and includes, for example, ester oils and higher alcohols.

Examples of the keratin softener include alkalis such as potassium hydroxide and potassium carbonate.

Examples of the drug include an astringent such as zinc p-phenolsulfonate; a bactericide such as benzalkonium hydrochloride;
Nutrients such as vitamin / amino acid derivatives, ultraviolet absorbers and the like.

In addition, a buffer (pH adjusting agent) is used. Examples include citric acid and its salts.

In the shampoo and treatment of the present invention, in addition to the liposome of the present invention, about 1 to 40% by weight of a surfactant, a foaming agent, and a hydrotrope (solubiliser)
Etc. may be included.

As the surfactant, any of anionic, cationic, amphoteric and nonionic surfactants can be used. Surfactants can be included in amounts of about 1-40% by weight.

Examples of the anionic surfactant include, for example,
Alkyl sulfate (AS), alkyl ether sulfate (A
ES), α-olefin sulfonate (AOS), soap, glycerin monoalkyl ester monosulfate, protein / fatty acid condensate, alkyl phosphate ester salts and the like.

[0092] Cationic surfactants are also used, in particular, as the main component of hair rinses. For example, alkyl trimethyl ammonium chloride, dialkyl dimethyl ammonium chloride, alkyl dimethyl benzyl ammonium chloride and the like can be mentioned.

Examples of the zwitterionic surfactant include imidazoline type, alkyl betaine type and alkyl sulfone betaine type surfactants.

Examples of the nonionic surfactant include, for example,
Alkanolamide, amine oxide and the like can be mentioned.

The foaming agent contributes to enhancing the foaming property of the surfactant as a shampoo base material, and examples thereof include fatty acid alkanolamides, fatty acids, higher alcohols, and water-soluble polymers.

Examples of the hair restorer and the hair restorer include ethanol, female hormones, corticosteroids, vitamin B6, vitamin E, pantothenic acid and its derivatives, cantaritis tincture, capsicum tincture, ginger tincture, assembly extract, cepharanthin, hinokitiol, photosensitive Element, salicylic acid, resorcinol, menthol, antihistamine,
Glycyrrhizin, carburonium chloride, bayram, audocinin and the like can be mentioned.

The cosmetics, shampoos and / or treatments and hair stylings of the present invention are manufactured by
Known methods can be used.

[0098]

The present invention will be described below with reference to examples.
The present invention is not limited by this embodiment.

(Production example of water used in the present invention) Slit gap width 2 mm, water flow velocity about 15 m / min, magnetic field line intensity 1.2 T
, Pure water and purified water were respectively circulated for 24 hours to obtain magnetic field irradiation water. The half-value width of the magnetic-field-treated water from the obtained pure water, the magnetic-field-treated water from the purified water, and the purified water were measured using JNM EX-270 manufactured by JEOL Ltd. The half width is shown below. Magnetic line treated water from pure water 56.3 Hz Magnetic line treated water from purified water 83.7 Hz Purified water 142.4 Hz

(Reference Example: Dispersibility of Triglyceride Oleate) 43.5 mg of oleic acid triglyceride was added to each of 10 ml of water treated with magnetic field from purified water and purified water, and the mixture was shaken at 128 rpm for 5 minutes. Immediately collect 4 ml to make a sample. 0.54 ml of each sample is NM of Φ5mm
Samples were collected in an R sample tube and used as an internal standard at a concentration of 10 mM TSP-
It was added d ₄ fold aqueous 0.06 ml. The final concentration of TSP-d ₄ was then ^{the 1 H-NMR} measurement and 1 mM. In this measurement, ¹ H
Since the NMR spectrum does not require a huge ¹ H signal due to water, it was suppressed using the ¹ H-Homo Gated Decoupling (HMG) method, and 128 integrated measurements were performed. The concentration of triglyceride oleate dispersed in water is the signal strength and internal standard of the methylene group of oleate triglyceride
It was calculated from the signal intensity ratio of the methyl protons of TSP-d _4.
The measurement was performed using JNM LA-400 FT-NMR Spec from JEOL Ltd.
This was performed using a trometer.

As a result of the measurement, it was found that the relative strength of triglyceride oleate dispersed in water obtained by magnetically treating pure water was about twice that of purified water. In addition, it was also found that the magnetic field line treated water from the purified water was about 1.1 times the relative intensity of the purified water. This fact indicates that water having smaller clusters has better dispersibility of trioleic acid than purified water.

Example 1 Liposomes for shampoo were prepared using magnetically treated water (half width: 56.3 Hz) from pure water obtained in Production Example. As a comparative example, commercially available purified water (half width: 142.4 Hz) of the Japanese Pharmacopoeia was used. Were mixed and passed through a microfluidizer manufactured by Mizuho Industry Co., Ltd. to produce liposomes, and the particle size distribution was measured by a dynamic light scattering method using a dynamic light scattering photometer (DLS-7000) manufactured by Otsuka Electronics Co., Ltd. . The particle size distributions when using magnetic line-treated water (half width: 56.3 Hz) and purified water (half width: 142.4 Hz) were 55 nm (0.055 μm) and 112 nm (0.112 μm), respectively.
μm). The average particle size of the liposomes using magnetic field-treated water was about half that of the liposomes using purified water, and a large difference was found in the average particle size of the liposomes depending on the water used.

(Example 2: Preparation of shampoo composition containing liposome) A shampoo composition having the following composition was prepared using each of the liposome stock solutions obtained in Example 1. The unit is% by weight. Liposome stock solution 5% Sodium alkyl ether sulfate 16% Lauryl acid diethanolamide 4% Propylene glycol 2% Preservatives, dyes, fragrances Trace amount of water Remaining shampoo made with magnetically treated water compared to shampoo made with purified water The hair was moist and the usability was good.

[0104]

The average particle size of liposomes prepared using water having a half width of 90 Hz or less is smaller than the average particle size of liposomes prepared using ordinary water, and was used in pharmaceutical compositions. In such a case, the drug can be absorbed into the body faster, and a high concentration of the drug can be transmitted to the periphery of the target organ or tissue.

Also, when used in a cosmetic composition, a hair restorer composition, or a hair restorer composition, since it has excellent affinity for skin or hair tissue, for example, a moisturizing component, a hair restorer component, a hair restorer component, etc. Attached to skin stratum corneum, hair, etc.
It is easy to enter, and combined with sustained release, a high effect can be expected.

In particular, when water having a half width of 60 Hz or less is used, since it has the ability to disperse fats and oils 1.5 times or more of ordinary water, a larger amount of drugs, cosmetics, Since a hair restorer or a hair restorer can be retained, a higher effect can be expected.

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Claims (15)

[Claims] The half-value width of the ¹⁷ O-NMR signal is 90.
Hz and a liposome having a fine particle diameter obtained by mixing water, a target substance, and an amphiphilic compound, wherein the average particle diameter of the liposome is the average of liposomes produced using ordinary water. Liposomes smaller than particle size. 2. The method according to claim 1, wherein the amphiphilic compound is a phospholipid.
The liposome according to claim 1. 3. The liposome according to claim 2, wherein the phospholipid is lecithin. 4. The half-value width of a ¹⁷ O-NMR signal is 90.
A method for producing a liposome having a fine particle diameter, comprising a step of mixing water, a target component, and an amphiphilic compound at a frequency of not more than Hz. 5. The method according to claim 4, wherein the half-width of the ¹⁷ O-NMR signal of water is 60 Hz or less. 6. The method according to claim 4, wherein the water is water obtained by magnetizing pure water. 7. The method according to claim 1, wherein the amphiphilic compound is a phospholipid.
The method according to claim 4. 8. The method according to claim 7, wherein the phospholipid is lecithin. 9. The half-value width of a ¹⁷ O-NMR signal is 90.
A composition containing a liposome having a fine particle diameter obtained by mixing water at a frequency of not more than Hz, a target substance, and an amphiphilic compound. 10. The composition according to claim 9, wherein said amphiphilic compound is a phospholipid. 11. The composition according to claim 10, wherein said phospholipid is lecithin. 12. The composition according to claim 9, wherein the target substance is a drug, a cosmetic, a hair restorer or a hair restorer, and the composition is a pharmaceutical composition, a cosmetic composition, a hair restorer or a hair restorer. The composition according to Item. 13. The cosmetic composition, wherein the cosmetic composition comprises
The composition according to claim 12, which is a lotion, an emulsion, a serum, a foundation, a shampoo, a rinse, a treatment or a hairdressing agent. 14. The composition according to claim 13, wherein the shampoo, rinse, treatment or hair styling comprises a hair-growing component and / or a hair-growing component. 15. The composition according to claim 12, wherein the pharmaceutical composition is a composition suitable for an administration / application form for oral administration, mucosal application, body surface application, and intravascular or intratissue administration.