JP2015110526A - Gingival protective agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pharmaceutical composition which maintains the health of periodontal tissue because the maintenance of tissues supporting gingiva, gum, and teeth is important to prevent various influences, such as cerebrovascular disease and cardiac disease by toxins produced from oral bacteria, teeth has not only masticatory function of foods but various functions such as prevention of nutritional biases, disuse inhibition of cranial muscles, and the maintenance of brain activity by mastication.SOLUTION: The invention provides compositions for medicament application which contain as an active ingredient one or more kinds selected from astaxanthin, and/or fatty acid ester of astaxanthin, and maintain/prevent gingiva by inhibiting/preventing apoptosis of gingival cells.

Description

  [Technical Field] The present invention relates to a pharmaceutical product that protects gingival tissue and suppresses the decrease of attached gingiva and gingival tissue by using astaxanthin and / or fatty acid ester of astaxanthin as an active ingredient to suppress apoptosis of gingival cells.

  Periodontal tissue is a general term for tissues around the teeth that support the function of the tooth, and is composed of the periodontal ligament, cementum, gingiva, and alveolar bone. Among them, the gingiva is the main supporting structure of teeth. It is. About half of the reasons why Japanese lose their teeth are due to loss of attached gingiva as an initial symptom followed by destruction of the periodontal ligament and alveolar bone.

  One of the main cells constituting periodontium is gingival fibroblasts. Its function is to produce extracellular matrix such as collagen fibers and at the same time produce proteolytic enzymes such as matrix metalloprotease (MMP), and constant connective tissue of gingiva and periodontium by extracellular matrix degradation and phagocytosis It is maintenance of sex. In recent years, it has been pointed out that gingival fibroblasts highly express osteoprotegerin, a bone resorption inhibitor, and control osteoclast formation. Thus, gingival fibroblasts play a central role in maintaining good health of periodontal tissue in the gingiva, so to avoid the destruction of periodontal tissue leading to tooth loss, It is important to prevent and protect the loss of its initial pathology, gingiva and gingival fibroblasts.

  Various substances present in the oral cavity can affect periodontal tissue cells and cause damage to the periodontal tissue. For example, it is known that uptake of nicotine by smoking such as tobacco inhibits cell growth of periodontal tissue cells and suppresses the formation of extracellular matrix. Furthermore, the periodontal tissue is constantly stimulated by periodontal pathogens such as Porphyromonas gingivalis, and the cells of the stimulated periodontal tissue produce inflammatory cytokines, and teeth due to local inflammation of the periodontal tissue. Not only does it destroy surrounding tissues, but it also causes systemic chronic inflammatory conditions via blood. MAPK cascades p-38, ERK, and JNK are known as intracellular signaling pathways involved in the production of inflammatory cytokines in human fibroblasts, and their activation protects against stimuli such as periodontal pathogens As a mechanism, it promotes cell death (apoptosis) in cells.

The generation of active oxygen is also an important factor in the damage of periodontal tissues. Reactive oxygen is generated in the process of smoking, inflammation and infection as described above, and can damage periodontal tissue. Cells have an antioxidant mechanism against active oxygen generated in the body, produce glutathione, a water-soluble antioxidant, and produce enzymes that respond to oxidative stress, such as superoxide dismutase and catalase. It is expressed. Heat shock protein 32 (heme oxygenase-1) is expressed in response to stresses such as active oxygen and inflammatory cytokines, decomposes heme, a prosthetic molecule of heme protein, and has antioxidative and inflammatory properties of heme degradation products It plays an important role in cell protection during stress loading through functions such as cytokine production suppression.

  To date, the effective ingredients for preventing and improving periodontal tissue include β-glucan, mevalonic acid, polyphenol, magnesium chloride, betel nut (licanthus), licorice (licorice), nutmeg (meat), mastic (yenka), and yakumoso There are many known extracts such as (beneficial herb), antibacterial components such as elemol, vetiverol and patchouli alcohol.

  As a close technology, a gum gum health maintenance agent comprising at least one extract selected from litchi, red ginger, dokudami, buckwheat, gymnema, banaba, neem, artichoke, olive, rice, walnut, haematococcus algae and matatabi ( Patent document 1) is a method for promoting oral health in animals, wherein oral health promoting amount of at least one antioxidant (vitamin C, vitamin E, vitamin A, lipoic acid, astaxanthin, beta-carotene, L-carnitine, coenzyme Q10, glutathione, lycopene, lutein, N-acetylcysteine, soybean isoflavone, S-adenosylmethionine, taurine, tocotrienol, spinach, tomato, citrus fruit, grape, carrot, broccoli, green tea, ginkgo, Corn gluten meal, rice , Algae, curcumin, marine oil, fruits, vegetables, yeast, carotenoids, flavonoids, which method comprises to feed compositions containing polyphenols) (Patent Document 2) are known.

JP 2009-263332 A Special table 2008-525475

  Provide a gingival protective agent with abundant dietary experience, no ingestion restrictions or side effects, long action time after ingestion and natural ingredients.

  As a result of intensive studies to achieve the above object, the present inventors have found that astaxanthin and / or fatty acid esters of astaxanthin are extremely effective in improving and preventing gingival loss by suppressing apoptosis of gingival cells. The headline and the present invention were completed.

  Reduction of gingiva can be improved or prevented by using astaxanthin and / or a pharmaceutical comprising astaxanthin fatty acid ester as an active ingredient orally or as an oral solvent.

The effect | action of the cell viability improvement of the astaxanthin in the gingival cell of Table 1 is shown. The inhibitory effect of astaxanthin on the activation of apoptosis-related factors in Table 2 is shown. The action of promoting the expression of astaxanthin on the apoptosis inhibitory factors in Table 3 is shown. The action mechanism of astaxanthin in which HPS32 is involved in the stress response MAP kinase pathway obtained from the examples is shown.

The pharmaceutical product of the present invention can take the form of oral administration or oral preparation.
As an oral ingestion form, it can take the form normally used with a pharmaceutical, such as a tablet, a soft capsule, a hard capsule, a granule, a powder, a gel, or a liquid. When taken orally, astaxanthin is absorbed in the digestive tract, reaches the gingival cells through the blood, and suppresses apoptosis. Astaxanthin has a long duration of 24 hours in blood, which is half as long as it has a long duration of medicinal action, and can act effectively even when oral bacteria are active, such as at night.

  The oral preparation can take the form of a commonly used oral preparation, and can be in various forms such as solid, solid, liquid, liquid, gel, paste, and gum. Specifically, it can be prepared into various dosage forms such as a tongue-wash tablet, a mouth coating, a toothpaste, a liquid toothpaste, a liquid toothpaste, a toothpaste such as a moistened toothpaste, a mouthwash, and a mouthwash.

  Astaxanthin in the present invention means free astaxanthin. The ester form of fatty acid of astaxanthin means a monoester form and / or a diester form. Unless otherwise specified, astaxanthin means a free form and an ester of a fatty acid.

  Examples of fatty acid esters of astaxanthin include esters esterified with lower or higher saturated fatty acids or lower or higher unsaturated fatty acids. Specific examples of the lower or higher saturated fatty acid or the lower or higher unsaturated fatty acid include acetic acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, palmitooleic acid, hebutadecanoic acid, elaidic acid, ricinoleic acid, and betrothelin. Acid, vaccenic acid, eleostearic acid, punicic acid, ricinic acid, parinaric acid, gadoric acid, 5-eicosenoic acid, 5-docosenoic acid, cetoleic acid, erucic acid, 5,13-docosadienoic acid, ceracholic acid, decenoic acid , Steric acid, dodecenoic acid, oleic acid, stearic acid, eicosapentaenoic acid, docosahexaenoic acid, linoleic acid, linolenic acid, arachidonic acid and the like. Examples of carotenoid diesters include diesters esterified with the same or different fatty acids selected from the group consisting of the above fatty acids.

  As the origin of astaxanthin / astaxanthin fatty acid ester, those derived from natural products or those obtained by synthesis can be used. Examples of those derived from natural products include microalgae such as Haematococcus, yeasts such as Phaffia, crustacean shells such as shrimp, krill and crabs, craniopod viscera such as squid and octopus, various seafood Skins and fins, petals of Adonis genus plants such as Natsuzaki Fukujusou, α-proteobacteria such as Paracoccus sp. N81106, Brevundimonas sp. SD212, Erythrobacter sp. PC6, actinomycetes such as Gordonia sp. KANMONKAZ-1129, Schizochytriuym Examples thereof include those obtained from Labyrinthulas (particularly Yabetaceae) such as sp. KH105 and astaxanthin-producing genetically modified organisms. Astaxanthin-containing extracts of Haematococcus algae, Phaffia yeast and bacteria are preferable because of easy removal of impurities and astaxanthin productivity, and extraction methods such as acetone, ethanol and supercritical (including subcritical) carbon dioxide are preferred. Organic solvents are preferred.

  As a method for producing astaxanthin / ester from Haematococcus algae, supercritical extraction / subcritical extraction using carbon dioxide is preferable. As an extraction method, one from which the initial extract is removed is more preferable because impurities can be removed. By adding medium chain fatty acids having 8 to 10 carbon atoms to these extracts, it is possible to reduce the influence of glycerin esters and other components in the extracts. Moreover, the viscosity of the oil of an extract is reduced and the process to a formulation form becomes easy.

  The amount of astaxanthin in the oral dosage form according to the present invention is an astaxanthin free form equivalent amount, and 0.001 to 1 mg, preferably 0.001 to 0.5 mg, more preferably 0.001 to 0.5 mg per kg body weight per day for adults. It can mix | blend so that the intake of 01-0.2 mg is possible. It can be set as the form divided | segmented so that it can take in multiple times so that these intakes are possible in one day. The dosage varies depending on the age, weight, symptom level, and dosage form of the person being administered.

  The compounding amount of astaxanthin in the oral administration form in the present invention is 0.01 to 10% (mass%, the same applies hereinafter), preferably 0.01 to 5% of the entire composition.

The feature of the present invention is to suppress gingival cell-specific apoptosis caused by astaxanthin. The cause of apoptosis and the inhibitor of apoptosis vary depending on each organ in the living body. In periodontal tissues, periodontal pathogens such as Porphyromonas gingivalis produce toxins such as liposaccharide, thereby stimulating gingival cell sites and causing apoptosis of gingival cells. As shown in Example 1 of the present invention, astaxanthin has two action points- (1) suppresses the action of the caspase3 series by suppressing apoptosis-inducing factors such as Bad and Bax, and (2) HSP32, HO-2, etc. It is thought that the apoptosis of the Ask series is suppressed by activating the apoptosis inhibitory factor. Up to now, astaxanthin has been focused on the antioxidant action due to its extremely high antioxidant action, but in the present invention, a novel apoptotic factor controlling action of astaxanthin was found.
HSP32 (HO-1) is a protein whose expression is induced by heat, oxidative stress, inflammatory cytokines, and the like. HSP32 has various physiological activities collectively called cytoprotection, such as anti-oxidation and inflammation, and is known to protect cells from oxidative stress.

  In order to assist the effect of the present invention, a substance having an assist effect can be added. For example, vitamins A; carotenoids (excluding xanthophyll); vitamins B; vitamins C; vitamins D, vitamins E; tocotrienols; glutathione and derivatives thereof and salts thereof; lignans, catechins, anthocyanins, tannins, Polyphenols such as rutin, chlorogenic acid, ellagic acid, coumarin, curcumin; linoleic acid, α- or γ-linolenic acid, arachidonic acid, eicosapentaenoic acid, sardine acid, docosahexaenoic acid and their derivatives and salts thereof; collagen, elastin , Fibronectin, keratin proteins and their derivatives and hydrolysates; alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine Amino acids such as syn, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, ornithine and derivatives of amino acids such as carnosine and salts thereof and peptides; glycolic acid, lactic acid, malic acid, citric acid, Α-Hydroxy acids such as salicylic acid and their derivatives and salts thereof; serum deproteinization, spleen, placenta, chicken crown, royal jelly, yeast, lactic acid bacteria, bifidobacteria, ganoderma, carrot, assembly, rosemary, oak, garlic, hinokitiol , Cephalanthin, aloe, salvia, arnica, chamomile, birch, hypericum, eucalyptus, mukuroji, sempukuka, keiketou, sunpens, sohakuhi, touki, ibukitorano, clara, hawthorn, shirayuri, ho Natural products such as Pu, Neubara, Yokuinin, Dokudami, Seaweed, Natto, Lemongrass, Hibiscus, and their extracts; Adenylic acid derivatives such as adenosine triphosphate, adenosine diphosphate, adenosine monophosphate; iron, vanadium, Minerals such as molybdenum, manganese, copper, potassium, magnesium, calcium, zinc, selenium, iodine; monosaccharides such as mannitol, xylitol, glucosamine; hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin, keratan sulfate, glycogen Polysaccharides such as deoxyribonucleic acid and ribonucleic acid; other glycyrrhizic acid, guanine, mucin, ubiquinone, α-lipoic acid, octacosanol, allicin, alliin, raspberry ketone, capsieye , Honey, royal jelly, etc. capsaicin, and may be selected from the group consisting of a mixture thereof alone or in combination. These components are generally blended in an amount of 0.01 to 90% by weight, preferably 0.1 to 50% by weight, based on the total amount of the pharmaceutical, and can be used in combination of one or more.

  The pharmaceutical product containing the gingival protective agent of the present invention may contain appropriate amounts of various additives used for the production of general preparations. Examples of such additives include excipients, binders, acidulants, foaming agents, artificial sweeteners, fragrances, lubricants, colorants, stabilizers, pH adjusters, and surfactants. Excipients include, for example, corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, pregelatinized starch, porous starch, and other sugars, lactose, sucrose, glucose and other sugars, mannitol, xylitol, Examples thereof include sugar alcohols such as erythritol, sorbitol, maltitol, magnesium aluminate metasilicate, hydrotalcite, anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate, and light anhydrous silicic acid. Examples of the binder include hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gum arabic powder, gelatin, and pullulan. Examples of the disintegrant include starch, agar, carmellose calcium, sodium carboxymethyl starch, croscarmellose sodium, crospovidone, crystalline cellulose, and F-MELT (trademark, manufactured by Fuji Chemical Industry Co., Ltd.). Examples of sour agents include citric acid, tartaric acid, malic acid, ascorbic acid and the like. Examples of the foaming agent include sodium bicarbonate and sodium carbonate. Examples of the sweetener include saccharin sodium, dipotassium glycyrrhizin, aspartame, stevia and thaumatin. Examples of the fragrances include lemon oil, orange oil, menthol and the like. Examples of the lubricant include magnesium stearate, sucrose fatty acid ester, polyethylene glycol, talc, stearic acid, and sodium stearyl fumarate. Examples of the colorant include edible pigments such as edible yellow No. 5, edible red No. 2, and edible blue No. 2, edible lake pigments, and iron sesquioxide. Examples of the stabilizer include sodium edetate, tocopherol, cyclodextrin and the like. Examples of the pH adjuster include citrate, phosphate, carbonate, tartrate, fumarate, acetate, amino acid salt and the like. Examples of the surfactant include polysorbate 80, methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, polyoxyethylene sorbitan monolaurate, gum arabic, and powdered tragacanth. In order to improve the absorption and formulation of astaxanthin and tocotrienol, it can be in a powder state.

  For syrups, drinks, suspensions, eye drops, injections and other liquids, active ingredients are adjusted to pH, buffers, solubilizers, suspensions, etc., as required, tonicity agents, stabilizers, antiseptics It can be formulated by a conventional method in the presence of an agent. Examples of the suspending agent include polysorbate 80, methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, polyoxyethylene sorbitan monolaurate, gum arabic, and powdered tragacanth. Examples of the solubilizer include polysorbate 80, hydrogenated polyoxyethylene castor oil, nicotinamide, polyoxyethylene sorbitan monolaurate, macrogol, and castor oil fatty acid ethyl ester. Examples of the stabilizer include sodium sulfite and sodium metasulfite. Examples of the preservative include methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, sorbic acid, phenol, cresol, chlorocresol and the like.

The pharmaceutical of this invention can be mix | blended with food and drink, and can be ingested as the form of food and drink.
As food and drink, it can be added to supplements, functional health foods, special-purpose foods, health foods, general foods, and beverages. Foods are preferred and can be ingested in the same form as the aforementioned pharmaceuticals, solid dosage forms such as tablets, intraoral quick disintegrating tablets, capsules, granules, fine granules, and liquid dosage forms such as syrups and suspensions. Among ingredients used in the above pharmaceutical preparations, those that can be used in foods can be selected, in addition to milk protein, soy protein, egg albumin protein, etc., or egg white oligopeptide, soy hydrolyzate that is a degradation product thereof, A mixture of amino acids alone can also be used in combination. In addition, when provided in the form of a drink, nutritional additives such as amino acids, vitamins and minerals, sweeteners, spices, fragrances, and pigments may be added to improve the nutritional balance and flavor during intake. Good. The form of the food or drink of the present invention is not limited to these.

  In the present invention, the functional food is a food having a medicinal effect that is permitted or specified by the government or a public body. For example, a functional food such as a nutritional functional food or a food for specified health use, a special-purpose food. Etc. In addition, although a name and a rule change with situations and times, what is essentially the same is included in the present invention. This includes packages and containers that display medicinal benefits, and foods that contain explanatory documentation.

  Examples of forms of general foods, ie, foods and drinks include margarine, butter, butter sauce, cheese, fresh cream, shortening, lard, ice cream, yogurt, dairy products, sauce products, fish products, pickles, natto, boiled beans, fried beans , Tofu, mapo tofu, mixed nuts, french fries, potato chips, snacks, kakimochi, popcorn, sprinkle, chewing gum, chocolate, pudding, jelly, gummy candy, candy, drop, caramel, bread, castella, cake, donut, Biscuits, cookies, crackers, baked goods, macaroni, pasta, ramen, buckwheat, udon, salad oil, instant soup, dressing, eggs, mayonnaise, miso, etc. or carbonated drinks such as fruit juice drinks, soft drinks, sports drinks or Such as carbonated beverages, may tea, coffee, non-alcoholic or liqueur, alcoholic beverages such as medicinal liquor, such as cocoa, energy drinks, milk, be added examples of the general foods such as soy milk.

In order to describe the present invention in more detail, examples are given below, but the present invention is not limited to these examples only [human normal gingival fibroblast test]
The inventors investigated the influence of astaxanthin on the cell death (apoptosis) of normal human gingival fibroblasts caused by periodontal disease-causing bacteria Porphyromonas gingivalis, which will be described below.

[Measurement of cell viability]
Human normal gingival fibroblasts (HGF: ScienCell Research Laboratories), which are the main cells that make up human periodontal tissue, are seeded on a plate at a concentration of 1 x 105 cells / ml, and after reaching subconfluence, astaxanthin prepared in advance Was added to the medium so that the astaxanthin concentration was 10 μM. For comparison, the same amount of dimethyl sulfoxide solution containing no astaxanthin was added. After 24 hours of culture, periodontal disease-causing porphyromonas gingivalis-derived liposaccharide (hereinafter LPS) was added at a concentration of 100 μg / ml and further cultured for 24 hours, and the cell viability was measured by MTT assay. . The results are shown in Table 1 and FIG.

[Table 1]

[Detection of apoptosis-related factors]
Human gingival fibroblasts treated or not treated with astaxanthin and LPS in the same manner as described above were washed with a phosphate buffer, lysed with Lysis Buffer, and a cell lysate (Lysate) was extracted.
Using the Cytometric Bead Array (CBA) system (BD), the concentration of phosphorylated proteins ERK, p38 and JNK in lysate is reacted with fluorescent beads coated with capture antibody and lysate, and then PE detection antibody is added and flow Quantification was performed with cytometry CantoII (BD). The results are shown in Table 2 and FIG.

[Table 2]

  Furthermore, 35 types of apoptosis-related factors were simultaneously detected with the Proteome Profiler Human Apoptosis Antibody Array Kit (R & D). In other words, a membrane array spotted with diluted Lysate and apoptosis-related antibodies was reacted overnight, washed with Washing Buffer, and then chemiluminescent for the presence of apoptosis-related molecules using Biotin-labeled detection antibody and HRP-labeled streptavidin. Detected by the method. The results are shown in Table 3 and FIG.

[Table 3]

  In Table 1, in the cell group stimulated with LPS without adding astaxanthin, the cell proliferation was remarkably suppressed, but in the cell group added with astaxanthin, the cell proliferation suppression by the stimulation of LPS was significantly released, which is The cell activity was equivalent to that of the non-stimulated cell group.

  To elucidate the effects of astaxanthin on the intracellular signaling pathways associated with apoptosis, the expression of apoptosis-related factors was measured with the CBA system. The ERK pathway acts on cell proliferation and survival, and the stress-responsive MAP kinase (p38 and JNK) pathway is thought to cause cell death (apoptosis) in response to various environmental stress stimuli. As shown in Table 2, astaxanthin inhibited p38 and ERK activation induced by stimulation of LPS from Porphyromonas gingivalis. JNK was below the lower limit of detection.

As shown in Table 3, expression of heat shock protein 32 (heme oxygenase-1) (hereinafter referred to as HSP32), an anti-apoptosis-related factor, was observed in cells stimulated with LPS after addition of astaxanthin, whereas astaxanthin HSP32 expression was not observed in the cells stimulated with LPS without addition of or in the cells not stimulated with LPS.
From this, it is considered that astaxanthin promotes the expression of HSP32 in gingival fibroblasts, thereby reducing the damage given to the cells by LPS derived from Porphyromonas gingivalis and inhibiting apoptosis of gingival fibroblasts. The action of astaxanthin involving HPS32 in the stress response MAP kinase pathway is shown in FIG.
From the above, it was shown that astaxanthin has an anti-apoptotic action in gingival cells.

[Production Example 1] Tablet According to a conventional method, the following ingredients were uniformly mixed and tableted in the following composition ratio to give a tablet of 300 mg per tablet.
Asteryl powder 20F 20 parts by weight Fmelt F1 40 parts by weight Powdered cellulose 15 parts by weight Lactose 22 parts by weight Aspartame 1 part by weight Silicon dioxide 1 part by weight Sucrose fatty acid ester 1 part by weight Asteryl powder 20F [manufactured by Fuji Chemical Industry Co., Ltd.] Is a powder containing 2% by weight of astaxanthin in terms of free form.

[Formulation Example 2] Drink agent The following ingredients were blended, and water was added to 10 L according to a conventional method to prepare a drink agent.
Water-soluble astaxanthin solution 25g
Liquid sugar 1000g
DL-sodium tartrate 1g
Citric acid 10g
Vitamin C 10g
Vitamin E 20g
Purified water The remaining water-soluble astaxanthin solution (manufactured by Fuji Chemical Industry Co., Ltd.) is an aqueous solution of Haematococcus alga extract oil containing 1 wt% astaxanthin in terms of free form.

[Formulation Example 3] Mouthwash The following ingredients were blended, and water was added to 1 L according to a conventional method to prepare a mouthwash.
Water-soluble astaxanthin solution 2.5g
Sodium fluoride 0.04g
Potassium nitrate 5g
Polyoxyethylene hydrogenated castor oil 2g
Ethanol 5g
Glycerin 1g
Saccharin sodium 0.01g
Fragrance 0.2g
Methylparaben 0.3g
Sodium hydroxide appropriate amount (pH 7.5 adjustment amount)
Purified water remaining

[Formulation Example 4] Toothpaste The following ingredients were mixed, and water was added and mixed according to a conventional method to prepare a toothpaste.
Water-soluble astaxanthin solution 1 part by weight calcium hydrogen phosphate 2 parts by weight anhydrous silicic acid 8 parts by weight sodium lauryl sulfate 1 part by weight propylene glycol 3 parts by weight sodium alginate 0.3 part by weight sodium polyacrylate 0.4 part by weight 70% by weight Sorbitol 30 parts by weight Xylitol 10 parts by weight Sodium saccharin 0.01 parts by weight Fragrance 0.5 parts by weight Methylparaben 0.15 parts by weight Sodium hydroxide Appropriate amount (pH 7.1 adjusted amount)
Purified water remaining

Claims (7)

A gingival cell apoptosis inhibitor comprising astaxanthin and / or fatty acid ester of astaxanthin as an active ingredient. A gingival protective agent comprising astaxanthin and / or fatty acid ester of astaxanthin as an active ingredient. The pharmaceutical according to any one of claims 1 and 2, comprising a medium-chain fatty acid triglyceride. The pharmaceutical product according to any one of claims 1 to 3, wherein astaxanthin and / or fatty acid ester of astaxanthin is obtained by pulverizing Haematococcus algae and extracting it with carbon dioxide at a concentration of 5% or more. The pharmaceutical form according to any one of claims 1 to 4, wherein the dosage form is an oral dosage form. The pharmaceutical form according to any one of claims 1 to 4, wherein the administration form is an oral preparation. The food-drinks containing the pharmaceutical of any one of Claims 1-4.

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