JP6771853B2 - Vitamin B6 containing composition - Google Patents

Description

The present invention relates to a composition containing at least one compound selected from the group consisting of vitamin B6 and salts thereof (hereinafter, collectively referred to as "vitamin B6 compound"), and a plant extract. The present invention also relates to a method for photostabilizing a vitamin B6 compound in a composition containing a vitamin B6 compound and a plant extract.

Vitamin B6 includes pyridoxine, pyridoxal and pyridoxamine. Vitamin B6 is a component involved in protein metabolism as a coenzyme of amino acid decarboxylase and transaminase in the living body, and is widely used as a medicine and hair growth for physical fatigue, eye fatigue, and nutritional supplementation during pregnancy. It is used in medicines, health foods, etc.

Vitamin B6 decomposes over time when exposed to light and should be stored in the dark. For this reason, various compositions in which vitamin B6 is stabilized have been studied conventionally. For example, an eye drop containing flavin adenine dinucleotide, pyridoxine and a specific antioxidant (Patent Document 1), an eye drop containing pyridoxine hydrochloride and berberine chloride (Patent Document 2), vitamin B6, oxymethazoline or a salt thereof. , And an eye drop containing a boric acid buffer (Patent Document 3) is known.

On the other hand, in order to stably hold a preparation containing a pharmacologically active substance that is unstable to light, a light-shielding material (brown container, aluminum container, etc.) is used as the packaging material for containing the preparation, or ultraviolet rays are used for the container. Light-shielding means such as kneading or painting an absorbent are adopted, and in the distribution process, light-shielding means such as putting a container filled with a preparation in a paper box are adopted.

However, in products manufactured by a manufacturing process that cannot use containers or packaging materials, the active ingredient is easily decomposed by light. In addition, for example, the hair restorer is transparent or translucent so that the amount and remaining amount can be confirmed in consideration of the convenience of the user because of the product characteristics that it is used continuously for a long period of one to several months every day. A container is used. For this reason, these products are stored in a dark place or in a paper box in an effort to maintain the photostability of the active ingredient. In addition, with respect to a container coated with an ultraviolet absorber, while the transparency of the container can be maintained to some extent, it is not possible to completely block light, the light stability of the active ingredient is insufficient, and the manufacturing cost of the container becomes high. There was a problem such as. In addition, such a light-shielding means using a packaging material has a problem that light stability in the manufacturing process cannot be guaranteed. Further, since the user may not use the light-shielding paper box after opening the product, the conventional light-shielding method is not always an effective method. Further, depending on the product, it is not realistic to use the preparation only under shading, and the preparation is taken out of the container and used for the application site such as scalp, skin and mucous membrane. Therefore, there is a problem that the active ingredient is exposed to light and the active ingredient is easily decomposed at the application site.

Therefore, in order to fully utilize the excellent action of vitamin B6 in various preparations and products, it is required to improve the stability of vitamin B6 against light without limiting the amount of vitamin B6 to be blended and the target of application. There is.

Japanese Unexamined Patent Publication No. 8-104636 Japanese Unexamined Patent Publication No. 2001-48780 Japanese Unexamined Patent Publication No. 2006-151969

An object of the present invention is to provide a composition containing a vitamin B6 compound having improved stability of the vitamin B6 compound against light.

Another object of the present invention is to provide a method for photostabilizing a vitamin B6 compound in a composition containing a vitamin B6 compound and a plant extract.

The present inventor has conducted various studies to solve the above problems, and found that chlorophyll contained in a plant extract reduces the photostability of vitamin B6. Conventionally, chlorophyll is known as a substance involved in photosynthesis in plants, blue-green algae, algae, etc., but it is known that co-blending with chlorophyll affects the photostability of other components such as vitamin B6. It wasn't done.

The present invention has been studied diligently based on these findings, and has been completed by finding that the concentration of chlorophyll, which affects the photostability of the vitamin B6 compound, is 0.15 ppm or more. Including.

Item 1. A composition containing at least one compound selected from the group consisting of vitamin B6 and salts thereof, and a plant extract, wherein the content of chlorophyll in the composition is less than 0.15 ppm. object.

Item 2. The plant extract contains at least one compound selected from the group consisting of vitamin B6 and salts thereof, and the compound is contained in the plant extract or is contained in the plant extract. Item 2. The composition according to Item 1, which is a mixture of a compound and at least one compound selected from the group consisting of foreign vitamin B6 and salts thereof.

Item 3. The plant extract does not contain at least one compound selected from the group consisting of vitamin B6 and salts thereof, and at least one compound selected from the group consisting of vitamin B6 and salts thereof is included in the composition. Item 2. The composition according to Item 1, which is an external composition.

Item 4. Item 3. The composition according to any one of Items 1 to 3, wherein the chlorophyll is at least one chlorophyll selected from the group consisting of chlorophyll a and chlorophyll b.

Item 5. Item 8. The composition according to any one of Items 1 to 4, wherein at least one compound selected from the group consisting of vitamin B6 and salts thereof is pyridoxine hydrochloride.

Item 6. Item 2. The composition according to any one of Items 1 to 5, wherein the plant extract is an extract extracted from a plant body of a green plant.

Item 7. Item 2. The composition according to any one of Items 1 to 6, which is a hair restorer, an eye drop, a nasal drop, an eye wash, a nasal wash, or a contact lens agent.

Item 8. A method for photostabilizing the above compounds in a composition comprising at least one compound selected from the group consisting of vitamin B6 and salts thereof, and a plant extract.
A photostabilization method characterized in that the content of chlorophyll in the composition is less than 0.15 ppm.

The composition containing the vitamin B6 compound of the present invention has improved stability of the vitamin B6 compound to light.

Further, by using the method of the present invention, the stability of the vitamin B6 compound to light can be improved in the composition containing the vitamin B6 compound and the plant extract.

The composition of the present invention contains a vitamin B6 compound and a plant extract, and the content of chlorophyll in the composition is less than 0.15 ppm.

(1) Composition
(1-1) Vitamin B6 compound Vitamin B6 compound means vitamin B6 or a salt thereof. Here, as vitamin B6, for example, pyridoxine, pyridoxal, and pyridoxamine can be mentioned. Examples of these salts include, but are not limited to, hydrochlorides, sulfates, nitrates, hydrobromic acids, phosphates and the like. Pyridoxine hydrochloride is preferably used as a vitamin B6 compound because it has an excellent effect of improving eye strain. These vitamin B6 compounds may be used alone or in any combination of two or more.

The origin of this vitamin B6 compound is not particularly limited. For example, it may be derived from a synthetic substance or a natural product such as a plant. Vitamin B6 compounds are commercially available.

The vitamin B6 compound contained in the composition of the present invention may be an endogenous vitamin B6 compound contained in the plant extract blended in the composition at the same time, and the vitamin B6 compound of the present invention may be separately contained from the plant extract. It may be external to the composition (foreign vitamin B6 compound) or both of these (endogenous + exogenous vitamin B6 compound).

The ratio of the vitamin B6 compound in the composition of the present invention is not particularly limited as long as the action and effect of the vitamin B6 compound can be obtained. Here, the action and effect of the vitamin B6 compound is to help the energy production from the protein and maintain the health of the skin and mucous membrane, improve skin diseases such as seborrheic dermatitis, eczema, acne, and rough skin, skin cell activation action, fluff and the like. Examples include improvement of itching, improvement of erythema caused by ultraviolet rays, anti-allergic effect, improvement of physical fatigue, improvement of eye fatigue and the like. Therefore, the blending amount thereof depends on the use of the composition of the present invention (for example, skin preparations such as hair restorers and cosmetics, eye drops, nasal drops, eye wash agents, nasal wash agents or contact lens agents). Is appropriately prepared. The general ratio of the vitamin B6 compound is usually about 0.0001 to 1% by weight, preferably about 0.02 to 0.5% by weight, and particularly preferably about 0.05 to 0.2% by weight.
In the case of hair restorer, it is usually about 0.02 to 0.5% by weight, preferably about 0.05 to 0.2% by weight; in the case of cosmetics, it is usually about 0.0001 to 5% by weight, preferably about 0.05 to 0.2% by weight; eye drops or dots. In the case of nasal medicine, it is usually about 0.005 to 0.2% by weight, preferably about 0.01 to 0.1% by weight; in the case of eye wash or nasal medicine, it is usually about 0.0005 to 0.02% by weight, preferably about 0.001 to 0.01% by weight; contact lens. In the case of a preparation, usually about 0.0005 to 1% by weight, preferably about 0.001 to 0.01% by weight can be exemplified.

(1-2) Chlorophyll The composition of the present invention is characterized by having a chlorophyll content of less than 0.15 ppm.

Chlorophyll, also known as chlorophyll, is a porphyrin-based pigment contained in plants and is a chemical substance involved in photosynthesis.

Chlorophyll contained in plants mainly includes chlorophyll a and b.

Therefore, the amount of chlorophyll contained in the composition means the total amount when a plurality of kinds of chlorophyll are contained, and the amount of the blended chlorophyll when only one of them is contained.

The content of chlorophyll in the composition is preferably less than about 0.1 ppm, particularly preferably less than about 0.05 ppm. In addition, the composition of the present invention may contain chlorophyll as long as the effects of the present invention are not impaired, and may contain about 0.001 ppm of chlorophyll.

(1-3) Plant extract and its preparation method The plant extracts targeted by the present invention include those that do not contain vitamin B6 compounds (plant extracts that do not contain vitamin B6 compounds) and those that contain vitamin B6 compounds (vitamin B6 compounds). Contains both plant extracts).

The plant extract targeted by the present invention is an extract (soft extract or dry extract) obtained by leaching a plant body into an extraction solvent (water, ethanol, etc.) and then concentrating the liquid, as described later. Therefore, it does not refer to the chemical substance (isolated) itself extracted from the plant.

From the viewpoint that the effect of the present invention is remarkably exhibited, the plant extract is preferably a plant extract extracted from the plant body of a green plant. Green plants are a group of strains characterized by having a typical green vegetative body by having chlorophyll (chlorophyll a and / or b) involved in photosynthesis.

As plants, specifically, aloe, sage, asenyaku, amacha, amachaduru, altea, ginkgo, irakusa, iller, echinashi, sage, sage, dead-nettle, Dutch sage, olive, oyster, carnauba palm, kiri, kumazasa, chrysanthemum indicum. , Clematis, Kwa, Magwa, Unshu Mikan, Daidai, Yakumosou, Ginger, Button, Swertia japonica, Taiso, Daidai, Yuzu, Houttuynia cordata, Peppermint, Hikiokoshi, Kanzo, Stevia, Clara, Getto, Kouki, Kocha, Hop, Kousuihakka, Seiyo Yadorigi, Seiyootogiri, Salvia, Fukitanpopo, Sugina, Mannen, Seiyounokogirisou, Mitsugashiwa, Shirakaba, Arnica, Kamitsure, Tachijakousou, Zeniaoi, Wheat, Kujin, Ogon, Shikon, Kouka, Chouji, Satoukibi , Watermelon, White dead-nettle, Japanese dead-nettle, Japanese mint, Sage, Cha, Tsubokusa, Tencha, Parsley, Houttuynia cordata, Hamamelis, Parietaria, Banjiro, Hechima, Biwa, Grape, Beech, Funori, Mayorana, Maronie, Murayakoenji, Melissa Peach, moyashi, eucalyptus, carrot, oyster carrot, scratches, teuchigurumi, bodaiju, rosemary, yomogi, rafuma, lettuce, uikyo, peppermint, gennoshoko, gaiyou, candelilla, sage, celery, garlic, akebi, honeybee, etc. Can be done. All of these plants are green plants.

Among the above-mentioned plants, a plant extract extracted from at least one plant selected from the group consisting of aloe, amacha, kiri, mulberry, magwa, taiso, and houttuynia cordata is preferable.

Among the plant extracts, as the plant extract containing a vitamin B6 compound, a plant extract extracted from the leaves or stems of at least one plant selected from the group consisting of ashitaba, finharisou, parsley, lettuce, celery and garlic is preferable. ..

When a plant extract containing no vitamin B6 compound is used in the preparation of the composition of the present invention, the plant extract is used in combination with the above-mentioned vitamin B6 compound. That is, in this case, the composition of the present invention contains a plant extract containing no vitamin B6 compound and an exogenous vitamin B6 compound. On the other hand, when a plant extract containing a vitamin B6 compound is used in the preparation of the composition of the present invention, the plant extract containing the vitamin B6 compound may be used as it is without adding the above-mentioned vitamin B6 compound. It may also be used in combination with a vitamin B6 compound. That is, in this case, the composition of the present invention contains a vitamin B6 compound-containing plant extract (contains an endogenous vitamin B6 compound and does not contain an exogenous vitamin B6 compound), or a vitamin B6 compound-containing plant extract and a foreign substance. Contains sex vitamin B6 compounds.

The ratio of the plant extract to be blended in the composition of the present invention is not particularly limited as long as the effect of the plant extract can be obtained. Here, as the action and effect of the plant extract, a moisturizing effect can be mentioned, although it varies depending on the type of plant. Therefore, the blending amount thereof depends on the use of the composition of the present invention (for example, skin preparations such as hair restorers and cosmetics, eye drops, nasal drops, eye wash agents, nasal wash agents or contact lens agents). Is appropriately prepared.

As a general ratio of the plant extract, for example, about 0.00001 to 5% by weight, preferably about 0.0001 to 1% by weight, particularly preferably about 0.005 to 0.1% by weight in terms of dry matter weight can be mentioned. In the case of a hair restorer, it is usually about 0.00001 to 5% by weight, preferably about 0.0001 to 1% by weight; in the case of an eye drop or a nasal drop, it is usually about 0.00001 to 1% by weight, preferably about 0.0001 to 0.1% by weight; In the case of an eye wash or a nasal wash, it is usually about 0.00001 to 1% by weight, preferably about 0.0001 to 0.1% by weight; in the case of a contact lens preparation, it is usually about 0.00001 to 1% by weight, preferably 0.0001 to 0.1% by weight. The degree can be mentioned.

When a plant extract containing a vitamin B6 compound is used as the plant extract, it is preferable to adjust the blending ratio of the plant extract in consideration of the ratio (lower limit and upper limit) of the vitamin B6 compound in the composition.

As the raw material of the plant extract, the whole plant may be used as it is, or a part of the plant may be used.

Since chlorophyll is usually contained mainly in the leaves and stems of plants, the plant extract should be a plant extract extracted from the entire plant including the leaves and stems from the viewpoint of fully exerting the effects of the present invention. Is preferable, and more preferably, it is a plant extract extracted from leaves and / or stems.

Hereinafter, all or part of the plant is collectively referred to as "plant body".

For extraction, the raw state (undried), dried (dried), or frozen (frozen) of the plant (all or part of the plant, for example, leaves, stems, roots, etc.) Things) can be used. Further, it is also possible to use a undried, dried or frozen plant body that has been crushed to an appropriate size and pulverized.

Examples of the method for producing a plant extract include, but are not limited to, a method of combining an extraction step and a separation step, and a method of further combining a fractionation step with the above method.

The extraction step is a step of extracting necessary components as an extract from a plant using an extraction solvent, and the extraction method and extraction conditions are not particularly limited.

The type of the extraction solvent is not particularly limited, and examples thereof include water, an organic solvent, and a mixed solvent thereof. Examples of the above water include water at all temperatures such as cold water, normal temperature water, hot water, hot water and steam, and may be sterilized, ion exchanged, osmoregulated or buffered. The organic solvent is preferably a hydrophilic organic solvent, for example, a monohydric alcohol having 1 to 5 carbon atoms (ethanol, methanol, propanol, isopropanol, etc.), a polyhydric alcohol having 2 to 5 carbon atoms (glycerin, isopropylene glycol, etc.). Propylene glycol and 1,3-butylene glycol, etc.), esters (methyl acetate, etc.), ketones (acetone, etc.) and the like can be used. Only one kind of these hydrophilic organic solvents may be used, or two or more kinds may be used in combination. In the present invention, it is preferable to use at least one extraction solvent selected from the group consisting of water, ethanol, 1,3-butylene glycol and a mixture thereof from the viewpoint of safety and extraction efficiency of the active ingredient.

When a mixed solution of water and 1,3-butylene glycol is used as the extraction solvent, the content of 1,3-butylene glycol in the mixed solution is preferably about 0.1 to 70% by weight, preferably about 5 to 60% by weight. More preferably, about 10 to 50% by weight is further preferable.

When a mixed solution of water and ethanol is used as the extraction solvent, the content of ethanol in the mixed solution is preferably about 0.1 to 99.5% by weight, more preferably about 5 to 95% by weight, and about 50 to 95% by weight. Is more preferable, and about 60 to 90% by weight is most preferable.

Extraction methods include immersion extraction, stirring extraction, reflux extraction, shaking extraction and ultrasonic extraction, and extraction conditions include room temperature extraction, heat extraction (also referred to as warm extraction), pressure extraction, and supercritical extraction. Etc., but it is preferably room temperature or heat extraction. The extraction time is not particularly limited. Further, the pH may be adjusted. The above extraction operation may be performed once, or may be performed by repeating the extraction of the extraction residue obtained after the extraction operation a plurality of times. Further, before and after the extraction step, a treatment such as filtration may be performed as necessary.

The separation step is a solid-liquid method for separating the insoluble matter which is the extraction residue and the extract from the extract obtained above. For example, centrifugation, filter press, filtration (pressurization, normal pressure), chromatography. Examples thereof include a method of extraction and separation using an adsorbent / absorbent such as a graph. The extract separated from the extract may be used as it is, or may be further purified by fractionation or the like.

The fractionation step is a method of fractionating, purifying and concentrating necessary components from the extract obtained above. Methods used in the fractionation step include chromatography, dialysis, molecular sieving, and vacuum concentration using activated carbon, anion exchange resin, cation exchange resin, silica gel, polystyrene-based resin that adsorbs aromatic compounds, etc. as carriers. Methods such as freeze-drying can be mentioned, but the method is not limited thereto. Further, after this step, if necessary, a step of collecting the supernatant by centrifugation or the like may be performed.

Before and after each of the above steps, treatment such as filtration may be performed as necessary. For filtration, gauze, a filtration filter, a commercially available filter, or the like can be used. In addition, sterilization treatment or the like can be performed as needed.

The plant extract obtained by the above method may be used as it is in a liquid form, but it can also be pulverized by a drying step such as spray drying, vacuum drying, or freeze drying.

As described above, the composition of the present invention is characterized by having a chlorophyll content of less than 0.15 ppm. Since the chlorophyll is usually derived from a plant extract, it is preferable to remove or reduce the amount of chlorophyll when preparing the plant extract. Such treatment includes an extraction method using various extraction solvents (water, ethanol, 1,3-butylene glycol, a mixture thereof, etc.), a fractionation method using a carrier (activated carbon, etc.), centrifugation, filter pressing, etc. An extraction separation method using filtration and the like can be mentioned.

The content of chlorophyll contained in the plant extract can be measured by an absorptiometry using a spectrophotometer, a high performance liquid chromatography method, an extraction isolation method, a derivative conversion method or the like.

(1-4) Other Ingredients The composition of the present invention further comprises, if necessary, other ingredients commonly used in the art, as long as the pharmacological action and stability of the vitamin B6 compound and the plant extract are not impaired. It can be contained. However, this does not apply if it overlaps with the contained components already described. Such other components include, for example, solvents, decongestant components, eye-regulating components, anti-inflammatory components, astringent components, antihistamine components, anti-allergic components, vitamins, amino acids, antibacterial components, bactericidal components, sugars, etc. Examples thereof include polysaccharides and derivatives thereof, cellulose and derivatives thereof, water-soluble polymers, local anesthetic components, steroid components, glaucoma treatment components, and cataract treatment components. Other preferable components in the present invention include, for example, the following.

Solvent: Examples of the solvent include water, alcohols, ethers, or mixtures thereof. Examples of alcohols include at least one selected from the group consisting of polyhydric alcohols and lower alcohols.

Polyhydric alcohols include propylene glycol, glycerin, diglycerin, triglycerin, ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propanediol, dipropanediol, tripropanediol, butanediol, dibutanediol, pentanediol, Examples thereof include pentantriol, hexanediol, cyclohexanetriol, pentaerythritol, trimethylolpropane, sorbitol and mannitol. Examples of the lower alcohol include methanol, ethanol, propanol, isopropanol, butanol, isobutanol, amyl alcohol, isoamyl alcohol and the like. Among them, propylene glycol, glycerin, ethanol and the like are preferable as alcohols from the viewpoint of safety and stability of vitamin B6 compound and plant extract.

The total content of alcohols in the composition of the present invention is not particularly limited depending on the type of polyhydric alcohol or lower alcohol, but is preferably about 40% by weight or less, and preferably about 30% by weight or less. More preferably, it is about 20% by weight or less.

Congestion-removing ingredients: for example, α-adrenaline agonists, specifically epinephrine, ephedrine hydrochloride, ephedrine hydrochloride, oxymethazoline hydrochloride, tetrahydrozoline hydrochloride, tetrahydrozoline nitrate, naphazoline hydrochloride, naphazoline nitrate, phenyleffrin hydrochloride, methylephedrine hydrochloride, hydrogen tartrate. Ephedrine and the like can be mentioned. These may be d-form, l-form or dl-form.

Ocular muscle regulator component: Examples thereof include cholinesterase inhibitors having an active center similar to acetylcholine, specifically, quaternary ammonium compounds such as neostigmine methylsulfate, and pharmacologically acceptable salts thereof.

Anti-inflammatory or astringent ingredients: for example, zinc sulphate, zinc lactate, allantin, ε-aminocaproic acid, indomethacin, lysozyme chloride, silver nitrate, pranoprofen, dipotassium glycyrrhizinate, diclofenac sodium, bromfenac sodium, berberine chloride, Examples thereof include berberine sulfate and methyl salicylate.

Vitamins: For example, at least one vitamin selected from the group consisting of vitamin A, vitamin B (other than the above vitamin B6 compounds), vitamin C, vitamin D, vitamin E, and other vitamins. Can be contained. Examples of vitamin A species include retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene and pharmacologically acceptable salts thereof. Examples of vitamin Bs include thiamine, thiamine disulfide, disetiamine, octothiamine, sicothiamine, bisibuchiamine, bisbenchamine, prosulfiamine, benfothamine, fursulfiamine, riboflavin, flavin adenine dinucleotide, hydroxocobalamin, etc. Cyanicobalamine, methylcobalamin, deoxyadenocobalamine, folic acid, tetrahydrofolic acid, dihydrofolic acid, nicotinic acid, nicotinic acid amide, nicotinic alcohol, pantothenic acid, pantenol, biotin, choline, inositol and their pharmacologically acceptable Examples include salts. Examples of vitamin Cs include ascorbic acid and its derivatives, erythorbic acid and its derivatives, and pharmacologically acceptable salts thereof. Examples of vitamin Ds include ergocalciferol, choleciferol, hydroxycholecalciferol, dihydroxycholecalciferol, dihydrotachysterol and pharmacologically acceptable salts thereof. Examples of vitamin Es include tocopherol and its derivatives, ubiquinone derivatives and pharmacologically acceptable salts thereof. Examples of other vitamins include carnitine, ferulic acid, γ-oryzanol, orotic acid, rutin, eriocitrin, hesperidin and pharmacologically acceptable salts thereof.

Amino acids: Examples thereof include aminoethyl sulfonic acid (taurine), glutamic acid, creatinine, sodium glutamate, sodium chondroitin sulfate and the like. These may be d-form, l-form or dl-form.

Antibacterial or bactericidal ingredients: for example, aminodeoxycanamycin sulfate, kanamycin sulfate, gentamycin sulfate, erythromycin sulfate, streptomycin sulfate, tobramycin, micronomycin sulfate, alkylpolyaminoethylglycine, chloramphenicol, tetracycline hydrochloride, oxytetracycline hydrochloride , Ofloxacin, norfloxacin, levofloxacin, romefloxacin hydrochloride, sulbenicin sodium, cefmenoxime hydrochloride, benzylpenicillin potassium, berberine sulfate, berberine chloride, sodium colistin metasulfonate, erythromycin, erythromycin lactobionate, kitasamycin, spiramycin, fradiomycin sulfate Polymyxin, dibecasin, amikacin, amikacin sulfate, acyclovir, iododeoxycytidine, idoxuridine, cyclositidine, citocin arabinoside, trifluorotimidine, bromodeoxyuridine, polyvinyl alcohol iodine, iodine, amhotericin B, isoconazole, econazole , Chloramphenicol, Nystatin, Pimalysin, Fluorocitosine, Myconazole and the like.

Sugars: Examples thereof include monosaccharides and disaccharides, specifically glucose, trehalose, lactose, fructose and the like.

Polysaccharides or derivatives thereof: Examples thereof include sodium hyaluronate, sodium chondroitin sulfate and the like.

Cellulose or its derivatives or salts thereof: Examples thereof include sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose and the like.

Water-soluble polymers other than those mentioned above: Examples thereof include polyvinyl alcohol (completely or partially saponified), polyvinylpyrrolidone, dextrin, polyethylene glycol and the like.

Local anesthetic components: for example, lidocaine, oxybuprocaine, dibucaine, procaine, ethyl aminobenzoate, meprilcine, and salts thereof.

Steroid components: Examples include hydrocortisone, prednisolone, and salts thereof.

Glaucoma therapeutic components: For example, levobunolol, timolol, and salts thereof.

Cataract therapeutic component: For example, pyrenoxin and the like can be mentioned.

The content ratio of these components in the composition is appropriately determined according to the type of the preparation, the type of the contained components, and the like. For example, it is about 0.0001 to 50% by weight, preferably about 0.0001 to 25% by weight, more preferably about 0.001 to 10% by weight, based on the whole preparation.

In addition, the aqueous solution of the present invention may further contain additives usually used in the art, if necessary, as long as the pharmacological action and stability of the vitamin B6 compound and the plant extract are not impaired. However, this does not apply if it overlaps with the contained components already described. Such components include, for example, preservatives, bactericides or antibacterial agents, thickeners, solubilizers or solubilizers, pH regulators, isotonic agents, fragrances, refreshing agents, chelating agents, buffering agents. , Stabilizers, substrates and the like. Preferred additives in the present invention include, for example, the following additives.

Preservatives, bactericides or antibacterial agents: for example, alkyldiaminoethylglycine hydrochloride, sodium benzoate, ethanol, chlorobutanol, sorbic acid, potassium sorbate, sodium dehydroacetate, methyl paraoxybenzoate, ethyl paraoxybenzoate, paraoxybenzoic acid Examples thereof include propyl, butyl paraoxybenzoate, oxyquinoline sulfate, phenethyl alcohol, benzyl alcohol, biguanide compound, acrinol and the like.

Thickeners: For example, sodium carboxymethyl cellulose, dextran, polyethylene glycol, carboxyvinyl polymer, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, polyvinyl alcohol (complete or partially saponified), polyvinylpyrrolidone, macrogol, sodium chondroitin sulfate, etc. Can be mentioned.

Solubilizer or solubilizer: For example, glycine-type amphoteric surfactant such as alkyldiaminoethylglycine, alkyl ether carboxylate, sulfonate such as sodium tetradecene sulfonate, alkyl sulfate such as sodium lauryl sulfate, N. -N-acyl taurine salt such as cocoyl methyl taurine sodium, POE alkyl ether phosphate such as POE (10) sodium lauryl ether phosphate and its salt, N-acyl amino acid salt such as lauroyl methyl alanine sodium, POE (3) lauryl Examples thereof include POE alkyl ether sulfate such as sodium ether sulfate and anionic surfactants such as α-olefin sulfonate. Specifically, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monooleate, polyoxyethylene (20) sorbitan tristearate, polyoxyethylene (20) ) Sorbitane oleate, polyoxyl 40 stearate, sucrose stearate, decaglyceryl monostearate, lauryl glucoside, macrogol 4000. The numbers in parentheses indicate the number of additional moles.

Examples of the cationic surfactant include quaternary ammonium compounds and biguanide compounds. Examples of the quaternary ammonium compound include cetylpyridinium chloride hydrate, decalinium chloride, benzethonium chloride, benzalconium chloride, alkyldimethylammonium chloride, alkyltrimethylammonium chloride, methylbenzethonium chloride, and lauroylcolamino. Examples include formylmethylpyridinium chloride. Examples of the biguanide compound include chlorhexidine or a salt thereof, and preferably chlorhexidine gluconate, chlorhexidine hydrochloride and the like.

pH adjusters: Examples thereof include hydrochloric acid, aminoethyl sulfonic acid, epsilon-aminocaproic acid, acetic acid, sodium hydroxide, sodium hydrogen carbonate, sodium carbonate, triethanolamine, monoethanolamine and the like.

Isotonic agents: for example, sodium hydrogen sulfite, sodium sulfite, potassium chloride, calcium chloride, sodium chloride, magnesium chloride, potassium acetate, sodium acetate, sodium hydrogen carbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, glycerin, propylene glycol And so on.

Fragrances or refreshing agents: For example, terpenes (specifically, anethole, eugenol, camphor, geraniol, cineole, borneol, menthol, limonene, ryuno, etc. These may be d-form, l-form or dl-form. ) Essential oils (specifically, camphor oil, cool mint oil, kehi oil, spear mint oil, sardine water, sardine oil, peppermint oil, bergamot oil, eucalyptol oil, rose oil, etc.) and the like can be mentioned.

Chelating agent: Examples thereof include ascorbic acid, tetrasodium edetate, sodium edetate, citric acid and the like.

Buffering agents: Examples thereof include citric acid, sodium citrate, acetic acid, potassium acetate, sodium acetate, sodium hydrogen carbonate, sodium carbonate, boric acid, borax and the like.

Stabilizers: Examples thereof include cyclodextrin, dibutylhydroxytoluene, tromethamole, tocopherol, sodium metabisulfite, monoethanolamine, aluminum monostearate and the like.

Bases: Examples include octyldodecanol, olive oil, sesame oil, titanium oxide, potassium bromide, soybean oil, camellia oil, corn oil, rapeseed oil, paraffin, castor oil, plastibase, lacquer oil, lanolin, petrolatum and the like.

(1-6) Osmotic pressure and pH of the composition
The composition of the present invention can be adjusted to an osmotic pressure ratio within a range acceptable to the living body, if necessary. The osmotic pressure ratio to the physiological saline solution is usually about 0.3 to 4, preferably about 0.5 to 2, and more preferably about 0.5 to 1.4. The osmotic pressure ratio can be adjusted by appropriately using a buffer, an isotonic agent, salts and the like in addition to the pH adjuster.

The composition of the present invention, for example, in the liquid preparation for internal use described later, is usually preferably pH 2 to 10, more preferably pH 4 to 9, and pH 6 to 8 in terms of feeling of administration and stability of the active ingredient. If it is, it is more preferable. The composition for the outer skin is usually preferably pH 3 to 10, more preferably pH 3 to 9, and pH 4 to 8 in terms of low irritation to the skin, good usability, and stability of the active ingredient. More preferred.

In particular, in the case of mucosal application compositions such as eye drops, nasal drops, eye wash agents, nasal wash agents and contact lens agents, the pH is usually 5 to 9.5 in terms of hypoallergenicity to the mucous membrane and stability of the active ingredient. Preferably, pH 5.5 to 9 is more preferable, and pH 6 to 8 is even more preferable.

(1-7) Method for producing composition Vitamin B6 compound tends to be unstable and easily photodecomposes in a composition having a high water content. Therefore, the composition containing the vitamin B6 compound of the present invention can effectively improve the stability of the vitamin B6 compound with respect to light when it is a composition containing water (water-containing composition).

When the composition of the present invention contains water, the content of water in the composition is preferably about 5% by weight or more, more preferably about 20% by weight or more, further preferably about 50% by weight or more, and 70% by weight or more. Is particularly preferable. Further, the upper limit can be about 99.9% by weight or less, preferably about 99% by weight or less, and more preferably about 95% by weight or less.

The composition of the present invention utilizes known operations according to its use (skin preparations such as hair restorers and cosmetics, eye drops, nasal drops, eye wash agents, nasal wash agents, contact lens agents, etc.). However, it can be produced by blending and mixing each of the above-mentioned components. The blending order of each component is not particularly limited.

For example, in the case of skin preparations such as hair restorers, external analgesics and cosmetics, and ophthalmic preparations such as eye drops and eye wash, each component is first mixed, and if necessary, filtration sterilization is performed, and finally. It can be prepared by filling a container. More specifically, when the composition is a hair restorer, components such as a vitamin B6 compound and a plant extract are dissolved using distilled water or purified water and an additive to adjust the osmotic pressure and pH to a predetermined level. It can be manufactured by filtering and sterilizing in a sterile environment and aseptically filling a wash-sterilized container.

(1-8) Uses of Composition The composition of the present invention can be used, for example, in the form of internal use or external use depending on the purpose, and can be provided as a locally administered preparation for various purposes.

As an internal use form, for example, various solid preparations such as tablets, pills, capsules (soft capsules, hard capsules), powders (powder) and granules (including dry syrup), or liquids for internal use (liquids). , Suspension, syrup, jelly) and other liquid preparations.

As an external form, for example, in the case of a skin preparation, it can be used as a liquid preparation (lotion, suspension, emulsion, aerosol), ointment, cream, gel (gel), patch, etc. can do. Further, if it is an ophthalmic preparation, it can be used not only as a therapeutic preparation but also as a non-therapeutic preparation such as a contact lens preparation. Specific examples of ophthalmic preparations include eye drops (also called eye drops, including eye drops that can be used while wearing contact lenses), eyewashes (also called eyewashes, eyewashes that can be used while wearing contact lenses). , Contact lens mounting solutions, contact lens agents (cleaning solutions, preservative solutions, rinsing solutions, disinfectants, multipurpose solutions, etc.) and the like. In addition, in this specification, a contact lens also means a hard contact lens (including an oxygen permeable hard contact lens), and all types of contact lenses such as a soft contact lens.

Since the composition of the present invention has improved stability of the vitamin B6 compound to light, it is preferably applied to a preparation in which the low stability of the vitamin B6 compound to light has been regarded as a problem. .. As a preparation in which the low stability of the vitamin B6 compound to light is particularly problematic, for example, a composition containing water (water-containing composition) such as an internal liquid preparation, a skin preparation which is a liquid preparation, an eye wash agent, and a contact lens preparation. Things). This is because the vitamin B6 compound tends to be unstable and photodecomposes easily in the composition containing water.

Since the composition of the present invention has high light stability of the vitamin B6 compound, it is packaged in a form of multiple administration and is continuously used by the user, for example, an eye drop (eye drop). Agents), eye drops (eye drops), nasal drops (nasal drops), oral drugs (oropharyngeal drugs, and mouthwashes, etc.), ear drops, nasal drops (nasal drops), contact lens agents, It is also useful as a liquid internal medicine (liquid gastrointestinal medicine, liquid cold medicine, etc.), a skin external medicine (hair restorer, external pain reliever, external antipruritic, etc.), cosmetics (skin water, milky lotion, beauty liquid, etc.).

When used as a specific preparation, the composition of the present invention can improve the light stability of a vitamin B6 compound without relying on the device of the container and packaging material. The container for packaging the composition of the present invention is not particularly limited, but for example, since it may be desired to grasp the content and remaining amount of the filled composition such as an ophthalmic preparation, olefins such as polyethylene and polypropylene may be desired. A container having a translucent property made of a based resin, a polyester resin such as polyethylene terephthalate, or the like is preferably mentioned.

Conventionally, when filled in a transparent or translucent container, the vitamin B6 compound is easily exposed to light, and a composition containing a plant extract and vitamin B6 may be made into a product filled in a transparent or translucent container. , It was very difficult because the stability of vitamin B6 compound to light was reduced. However, since the composition of the present invention has improved stability of vitamin B6s to light, even if a transparent or translucent container is used as the container for packaging the composition, the composition of the present invention can be used. The effect can be exerted and the composition can be kept stable. As a transparent or translucent container, the transmittance in the visible light region is usually 10% or more, preferably 30% or more, more preferably 50% or more, and further preferably 70% or more. It is preferably 80% or more, and particularly preferably 80% or more. Further, the upper limit of the transmittance is not particularly required, but is 99% or less.

(2) Light Stabilization Method of Vitamin B6 Compound The light stabilization method of the present invention is a photostabilization method of the above compound in a composition containing a vitamin B6 compound and a plant extract, and contains chlorophyll in the composition. It is characterized in that the amount is less than 0.15 ppm.

As the content of the vitamin B6 compound and the plant extract contained in the composition, the content described in the item of the above composition can be adopted.

In the photostabilization method of the present invention, in a composition containing a vitamin B6 compound and a plant extract, the content of chlorophyll in the composition is set to less than 0.15 ppm, whereby the vitamin B6 compound in the composition is exposed to light. Stability can be improved. The content of chlorophyll in the composition is preferably less than about 0.1 ppm, particularly preferably less than about 0.05 ppm.

The description of other components in the composition, additives and the like is as described in the item of the above composition.

Hereinafter, the present invention will be described more clearly by way of examples. However, the present invention is not limited to such examples.

(1) Preparation of composition A plant extract was prepared using aloe (aloe seed: Candelabra aloe) as a plant body.

The ethanol extract of aloe is made by finely chopping raw aloe, drying it and pulverizing it, and adding about 10 times the amount of ethanol aqueous solution (80% by weight ethanol, 80% EtOH) to the total amount of the dried product at 70 to 90 ° C. Obtained by extraction for 2 to 3 hours in (Aloe EtOH extract). Then, activated carbon was added to remove chlorophyll to obtain an activated carbon-treated extract of aloe (aloe EtOH extract (after treatment with activated carbon)). In addition, the 1,3-butylene glycol extract of aloe is dried after finely chopping raw aloe, and about 30 times the amount of 40 wt% 1,3-butylene glycol aqueous solution is added to the total amount of the dried product at room temperature. Obtained by extracting 5 to 7 days and nights in (Aloe BG extract).

The solid content of the aloe extract was as follows.

80% EtOH extract of aloe (aloe EtOH extract in the table): 2.5% by weight (dry matter weight)
Aloe 1,3-butylene glycol extract (in the table, aloe BG extract): 1% by weight (dry matter weight)
80% EtOH extract of aloe and extract after activated carbon treatment (in the table, aloe EtOH extract (after activated carbon treatment)): 1% by weight (dry matter weight)
Using the above aloe extract, each component was dissolved in purified water to make a total amount of 100 g with the composition shown in Table 1, and a test solution of the composition was prepared.

It was confirmed that each of the above-prepared aloe extracts (aloe EtOH extract, aloe BG extract and aloe EtOH extract (after treatment with activated charcoal)) contained aloe and aloenin, which are components of aloe. Therefore, these aloe extracts are suitable plant extracts containing the active ingredient of aloe.

Citric acid and sodium citrate were used to adjust the pH of the test solution. The pH of the test solution was pH 5.5.

Pyridoxine hydrochloride (vitamin B6) was added separately from aloe extract (plant extract).

The content of chlorophyll in the test solution was measured by the following procedure by absorptiometry using a spectrophotometer. A 4 g sample was taken, 0.1 g of basic calcium carbonate was added, 5 mL of water and 40 mL of acetone were added, and then the sample was placed in an ultrasonic cleaner and centrifuged. This process was repeated twice. 50 mL of diethyl ether and 40 mL of water were added to the supernatant, mixed, allowed to stand, and the operation of removing the aqueous layer was repeated 3 times. Further, it was dehydrated and filtered through anhydrous sodium sulfate, and the volume was adjusted to 100 mL with diethyl ether. This was measured at measurement wavelengths of 660 nm and 642.5 nm using a spectrophotometer (manufactured by Hitachi, Ltd., model number U-2000), and the values were calculated according to the following formulas.

Total chlorophyll (mg / 100g) = (7.12 E ₆₆₀ + 16.8 E _642.5 ) x V x _100/1000
Chlorophyll a (mg / 100g) = (9.93 E ₆₆₀ −0.777 E _642.5 ) × V × _100/1000
Chlorophyll b (mg / 100g) = Total Chlorophyll (mg / 100g) -Chlorophyll b (mg / 100g)
E ₆₆₀ and E _{642.5 refer} to the absorbance at 660 nm and 642.5 nm, W for the sample collection amount (g), and V for the ether constant volume (mL).

In the table, EtOH indicates ethanol and BG indicates 1,3-butylene glycol.

(2) Evaluation of photostability of vitamin B6 in the composition
Photostability test method Each test solution was filled in a transparent glass bottle (capacity 200 mL) with 100 mL or 200 mL each, and these were used as test samples. Using a growth chamber (Sanyo Electric Co., Ltd., MLR-351) as a fluorescent lamp tester, the test sample was continuously irradiated with light of 10,000 lux / hour at 15 ° C for 54 hours and exposed to light of 540,000 lux hr. I let you. This light irradiation amount was set based on the average irradiation amount for about 6 months in ordinary households with reference to the "Osaka Prefecture LED Lighting Equipment Development Promotion Plan Formulation Project" report (Osaka Prefecture).

The pyridoxine hydrochloride concentration in the test sample before and after light irradiation was measured by high performance liquid chromatography. From the measured pyridoxine hydrochloride concentration of the test sample, the residual rate (%) of pyridoxine hydrochloride after light irradiation was calculated according to the following formula.

Residual rate (%) = 100 x pyridoxine hydrochloride concentration after light irradiation (% by weight)
/ Pyridoxine hydrochloride concentration (% by weight) before light irradiation
(3) Test results Tables 1 and 2 show the photostability test results.

Examples 1 to 3 containing pyridoxine hydrochloride (vitamin B6 compound) and aloe extract (plant extract) and having a chlorophyll a (chlorophyll) content of less than 0.15 ppm show the residual rate of pyridoxine hydrochloride after the photostability test. Was expensive. Specifically, in Examples 1 to 3, the residual rate of pyridoxine hydrochloride was 90% or more.

In Comparative Examples 1 to 3 having a chlorophyll a content of 0.15 ppm or more, the residual rate of pyridoxine hydrochloride decreased to 85% or less.

That is, it was found that the stability of pyridoxine hydrochloride to light can be improved by adjusting the concentration of chlorophyll a in the composition containing aloe extract to less than 0.15 ppm.

Aloe usually contains chlorophyll a and b, but the content of chlorophyll b was lower than the content of chlorophyll a, and was less than 0.05 ppm in both Examples and Comparative Examples.

Algae and blue-green algae also contain chlorophyll. Chlorophyll contained in algae includes chlorophyll b (some green algae), chlorophyll c (brown algae and diatoms), chlorophyll d (red algae), and chlorophyll e (unequal hair algae). Chlorophyll c is a chlorophyll contained in blue-green algae.

Therefore, instead of the plant (aloe), algae and blue-green algae were used to prepare a test solution of a composition such as an extract in the same manner as the aloe. These compositions contained pyridoxine hydrochloride (vitamin B6 compound) and extracts of algae and blue-green algae, and the content of chlorophyll was less than 0.15 ppm. Then, the photostability of vitamin B6s in the composition of these test solutions was evaluated in the same manner as in the plant body.

As a result, it was found that the residual rate of pyridoxine hydrochloride was also high in the compositions such as extracts prepared from algae and blue-green algae after the photostability test.

Based on these facts, the stability of pyridoxin hydrochloride to light is also obtained by adjusting the concentration of chlorophyll in the composition to less than 0.15 ppm in the composition containing extracts prepared from algae and blue-green algae as well as plant extracts. It turned out that it can be improved.

(3) Prescription example
Hair restorer A hair restorer (Prescription Examples 1 to 9) having a composition shown in Table 3 and having a chlorophyll content of less than 0.15 ppm was prepared. All of the hair restorers were excellent in the stability of pyridoxine hydrochloride, pyridoxal hydrochloride, and pyridoxamine dihydrochloride.

Eye drops The eye drops (Prescription Examples 10 to 18) having the composition shown in Table 4 and having a chlorophyll content of less than 0.15 ppm were prepared. All of the eye drops were excellent in the stability of pyridoxine hydrochloride.

The composition shown in nasal drops Table 5, the content of chlorophyll was prepared nasal agents that it is less than 0.15ppm (the Formulation Example 19). The nasal drop was also excellent in the stability of pyridoxine hydrochloride.

Eye wash agent An eye wash agent (Prescription Example 20) having a composition shown in Table 6 and having a chlorophyll content of less than 0.15 ppm was prepared. The eye wash also had excellent stability of pyridoxine hydrochloride.

Nasal irrigation agent A nasal irrigation agent (Prescription Example 21) having a composition shown in Table 7 and having a chlorophyll content of less than 0.15 ppm was prepared. The nasal wash also had excellent stability of pyridoxine hydrochloride.

Contact Lens Agents A contact lens agent (Prescription Example 22) having a composition shown in Table 8 and having a chlorophyll content of less than 0.15 ppm was prepared. The contact lens preparation was also excellent in the stability of pyridoxine hydrochloride.

Cream A cream having a composition shown in Table 9 and having a chlorophyll content of less than 0.15 ppm (Prescription Example 23) was prepared. The cream was also excellent in the stability of pyridoxine hydrochloride.

The composition shown in lotion Table 10, the content of chlorophyll was prepared lotion is less than 0.15ppm (the Formulation Example 24). The lotion was also excellent in the stability of pyridoxine hydrochloride.

Beauty Essence A beauty essence (Prescription Example 25) having a composition shown in Table 11 and having a chlorophyll content of less than 0.15 ppm was prepared. The beauty essence was also excellent in the stability of pyridoxine hydrochloride.

Drinks A drink (Prescription Example 26) having a composition shown in Table 12 and having a chlorophyll content of less than 0.15 ppm was prepared. The drink was also excellent in the stability of pyridoxine hydrochloride.

Claims (6)

A composition containing pyridoxine hydrochloride and a plant extract.
The content of the pyridoxine hydrochloride is 0.02 to 0.5% by weight.
The plant extract is extracted from the leaves and / or stems of at least one plant selected from the group consisting of aloe, akebi, dokudami, ashtaba, biwa, peppermint, white birch, magwa, kanzo, asenyaku and eucalyptus. And
The composition is characterized in that the content of chlorophyll in the composition is less than 0.15 ppm (provided that it is polyvalent from plants belonging to the genus Calanthe, Phaius flavus, or other Orchidaceae plants having pseudobulbs or juice. A skin external preparation, characterized by containing an alcohol or polyhydric alcohol-containing solution extract.
A hair restorer / hair restorer characterized by containing a baldness extract,
It is characterized by blending one or a combination of vitamin B6 hydrochloride, L-ascorbic acid and its derivatives, asparagine, glutamine, iris extract, carrot extract, and odorico grass extract with kohone extract. Cosmetics,
And nutritional formulations with ribose and forate, the content of which is an effective amount to support total nucleotide metabolism). The plant extract contains pyridoxine hydrochloride, and the pyridoxine hydrochloride is contained in the plant extract, or is a mixture of the substance contained in the plant extract and the exotic pyridoxine hydrochloride.
The composition according to claim 1, wherein the plant extract is extracted from aloe using at least one extraction solvent selected from water, ethanol, 1,3-butylene glycol and a mixture thereof. The composition according to claim 1, wherein the plant extract does not contain pyridoxine hydrochloride, and the pyridoxine hydrochloride is externally added to the composition. The composition according to any one of claims 1 to 3, wherein the chlorophyll is at least one chlorophyll selected from the group consisting of chlorophyll a and chlorophyll b. The composition according to any one of claims 1 to 4 , which is a hair restorer, an eye drop, a nasal drop, an eye wash, a nasal wash, or a contact lens agent. A method for photostabilizing the above compounds in a composition comprising at least one compound selected from the group consisting of vitamin B6 and salts thereof, and a plant extract.
The plant extract is extracted from leaves and / or stems.
A photostabilization method characterized in that the content of chlorophyll in the composition is less than 0.15 ppm (however, from the composition, plants belonging to the genus Calanthe, the genus Phaius flavus, and other plants belonging to the family Orchidaceae having pseudobulbs. Or a skin external preparation, which comprises a polyhydric alcohol or a polyhydric alcohol-containing solution extract from a juice.
A hair restorer / hair restorer characterized by containing a baldness extract,
It is characterized by blending one or a combination of vitamin B6 hydrochloride, L-ascorbic acid and its derivatives, asparagine, glutamine, iris extract, carrot extract, and odorico grass extract with kohone extract. Cosmetics,
And nutritional formulations with ribose and forate, the content of which is an effective amount to support total nucleotide metabolism).