JP2008127303A - Agent for ameliorating functional disorder of exocrine gland, and food and drink for ameliorating functional disorder - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a preparation in an oral administration shape, effective for treatment, amelioration or prevention of various symptoms related to the function of exocrine gland, and to provide a food and drink. <P>SOLUTION: The agent for ameliorating the functional disorder of the exocrine gland, and the food and drink comprise astaxanthin and/or an ester thereof as an active ingredient. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an exocrine gland dysfunction improving agent and a food for improving dysfunction for treating, improving or preventing various symptoms associated with a decrease in body fluid due to exocrine gland dysfunction, such as dry eye and dry mouse. .

  Dry eye is also called dry eye or xerophthalmia, and is a disease in which the surface of the eyeball, that is, the keratoconjunctiva, is damaged due to quantitative and / or qualitative abnormalities of tears. Dry eyes caused by the rapid increase in VDT work (video screen terminal work) accompanying the recent OA and the drying of the indoor environment due to air conditioning and the like are increasing. There are also dry eyes due to diseases such as autoimmune abnormalities such as Sjogren's syndrome, dry keratoconjunctivitis, Steven-Jenson syndrome, and eyelid marginal inflammation. It is said that there are over 8 million dry eye patients, including potential patients, in Japan, and the increase in dry eye is a social problem.

  In recent years, an increasing number of patients have dry mouth called dry mice. Patients with dry mice may experience symptoms such as difficulty in chewing and swallowing and difficulty in pronunciation as well as difficulty in tooth decay due to a decrease in saliva volume. Dry mice are caused by side effects of drugs as well as hypertension, Sjogren's syndrome, diabetes, and salivary glanditis.

  Regarding the exocrine gland dysfunction that causes these dry eyes, dry mice, etc., if the cause is a pathological abnormality, it is necessary to first treat the cause disease and improve the environment. Agents are generally well known.

Astaxanthin is a kind of carotenoid pigment that improves lens thickness regulation dysfunction caused by ciliary fatigue, optic nerve fatigue, etc. (see Patent Document 1), and a method used to treat retinal damage or retinal disease (patent) Reference 2) has been reported. In addition, food and drink having the action of preventing astaxanthin and / or its edible ester, or preventing the progression of cataracts or suppressing the progression thereof, suppresses the onset or progression of cataracts, together with visual impairment due to cataracts It has also been reported that it can suppress monocular compound eyes, eye strain and halation that occur simultaneously (see Patent Document 3), visual performance improvement effect in a dark place (see Patent Document 4), and the like. However, it is not known that astaxanthin or an ester thereof acts to improve dysfunction of the exocrine glands.
Japanese Patent No. 3778509 US Pat. No. 5,527,533 JP-A-10-276721 JP 2005-516049 gazette

  For example, eye drops are conventionally used as a measure against dry eye, but many people dislike the use of eye drops, and the effects of preservatives contained in eye drops on the human body have also been pointed out. Yes. In addition, in order to reduce the secretion of body fluid from the exocrine glands, oral ingestion of eye drops or water may be adopted as an alternative to body fluid, but this is only symptomatic treatment. Therefore, an object of the present invention is to provide a preparation and a food and drink that are effective in treating, improving or preventing various symptoms related to the function of the exocrine gland and can be provided in an oral form.

  As a result of earnest search for a compound that is effective for various symptoms related to the function of the exocrine gland and is excellent in safety, the present inventors have improved the secretion ability of the exocrine gland astaxanthin and its esters. As a result, the present invention has been completed.

That is, the present invention
(1) an exocrine gland dysfunction improving agent comprising astaxanthin and / or an ester thereof as an active ingredient,
(2) The exocrine gland dysfunction improving agent according to (1), wherein the exocrine gland is a lacrimal gland and / or a salivary gland,
(3) Food and drink for improving dysfunction of exocrine glands, containing astaxanthin and / or its ester as an active ingredient,
(4) The food and drink for improving dysfunction of the exocrine gland according to (3), wherein the exocrine gland is a lacrimal gland and / or a salivary gland,
(5) Food and drink for improving dysfunction of exocrine gland according to (4), which is a functional food,
About.

  The exocrine gland dysfunction-improving agent and food for improving dysfunction containing the astaxanthin and / or ester thereof of the present invention as an active ingredient have an excellent effect of improving a decrease in the secretion ability of the exocrine gland.

  The present invention is an exocrine gland dysfunction improving agent containing astaxanthin and / or an ester thereof as an active ingredient. Astaxanthin and its ester used as an active ingredient in the present invention may be those derived from natural products or chemically synthesized products, and these can be used alone or in an appropriate mixture.

  Natural sources include crustacean shells and eggs [Kuhn et al., Angew. Chem., 51, 465 (1938) or Ber., 71, 1879 (1938)], organs [Kuhn et al., Ber., 72 , 1879 (1939)], petals of Fukujusaku and Kinso (Seybold et al., Nature, 184, 1714 (1959)), skins of various seafood (Matsuno, Carotenoids Chemistry and Biology, Plenum Press, p. 59, 1989), eggs [Miki et al., Comp. Biochem. Physiol., 71B, 7 (1982)], Antarctic krill [Yamaguchi et al., Bull. Japan. Soc. Sci. Fish., 49, 1411 (1983), Green algae Hematococcus [Renstroem et al. Phytochemistry, 20, 2561 (1981)], red yeast Phaffia [Andrewes et al., Phytochemistry, 15, 1003 (1976)], marine bacterium Agrobacterium aurantiacum [Yokoyama et al., Biosci, Biotech. Biochem., 58, 1842 (1994) ] Is known. When using the thing derived from a natural product, the extract from these or a crude extract can be used. For example, red yeast faffia, green algae hematococcus, marine bacteria and the like are cultured in an appropriate medium and extracted from the culture, or those extracted from Antarctic krill and the like. These extracts may be in the form of an extract extracted with an organic solvent, preferably ethanol or acetone, or may be a product obtained by appropriately purifying the extract as necessary.

  Astaxanthin has been determined in its chemical structure [Andrewes et al., Acta Chem. Scand., B28, 730 (1974)] and an organic synthesis method has been established [Widmer et al., Helv. Chem. Acta, 64 2405 (1981) and Mayer et al., Helv. Chem. Acta, 64, 2405 (1981)], are also readily available as chemically synthesized products.

  For reference, examples of a method of cultivating red yeast Phaffia (Phaffia rhodozyma) in an appropriate medium and obtaining an extract from the culture, and a method of purifying astaxanthin and / or an ester thereof are given below.

  The medium used when producing astaxanthin and its esters using red yeast Phaffia rhodozyma may be either liquid or solid, but usually, shaking culture or aeration and agitation culture in a liquid medium is effective. It is. The medium may be any medium as long as red yeast grows and accumulates astaxanthin and / or an ester thereof. That is, examples of the carbon source include sugars such as glucose and lactose, glycerin, starch, and organic acids, and examples of the nitrogen source include protein hydrolysates such as peptone and casamino acid, meat extract, yeast extract, and soybean meal. Amino acids, ammonium salts, nitrates and other various nitrogen compounds are used. As the inorganic salt, various phosphates, sulfates, and sodium chloride may be added, and various vitamins, minerals, nucleic acid-related compounds, etc. may be added to promote the growth of bacterial cells.

  In culturing, it is desirable not to directly perform main culture but to inoculate a culture medium obtained by performing small-scale preculture in advance on the main culture medium. It is preferable to appropriately select and adjust the temperature, period, liquidity, etc. during the cultivation so that the amount of astaxanthin and / or its ester accumulated is maximized. The culture may be performed at about 30 ° C. for 3 to 7 days, and the liquidity of the medium should be kept at pH 4.0 to 9.5.

  As a result of such culture, astaxanthin and / or its ester is produced and accumulated in the cells. Therefore, when a liquid medium is used, the culture is once filtered or centrifuged to recover the cells and washed several times with water. The cells obtained in this manner are crushed using a physical method and then dried. Various methods can be selected for the separation and purification of the target compound from the dried cells based on the chemical properties of astaxanthin and / or its ester. That is, extraction and dissolution with various highly polar organic solvents are selected, but cell extraction using ethanol or acetone is preferable. The amount of solvent is usually preferably 3 to 5 times the amount of dry cells, and it is sufficient to repeat extraction by stirring for several hours at room temperature 2 to 3 times. The extracts are then combined and concentrated under reduced pressure at 40 ° C. or lower to obtain an oily crude extract containing astaxanthin and / or its ester. Astaxanthin and / or its ester contained in this extract vary depending on various conditions such as the solvent used, but is usually about 1 to 10%.

  Furthermore, impurities from this crude extract using hexane or other low-polar organic solvents, gel filtration, ion exchange chromatography using various ion exchangers, adsorption chromatography using silica gel, cyanopropyl, alumina, etc. as a carrier, etc. Astaxanthin and / or its ester are isolated by a combination of these means. However, methods other than these can be used as appropriate as long as the characteristics of astaxanthin and / or its ester can be used effectively.

  Moreover, as a method for obtaining a krill extract containing astaxanthin and / or an ester thereof, JP-A-60-4558 discloses a krill organism or a dried product thereof such as acetone, n-hexane, and ethyl acetate. After neutralizing the pH of the solvent extract that has been immersed in an organic solvent and eluted the pigment, lipase or alkali is added to decompose fatty acids and other contaminants, and this is subjected to supercritical gas extraction or molecular distillation. Or a method for producing a yellow-red orange pigment astaxanthin, which is characterized by washing with a dilute alkali. JP-A-61-281159 discloses that a crude dye solution extracted from a dried krill with an organic solvent such as acetone or n-hexane is selectively hydrogenated with an unsaturated lipid other than the dye. After the addition, lipase is added to hydrolyze the lipid, the free fatty acid is removed by urea addition and / or molecular distillation, and if necessary, further concentrated and purified by column chromatography. A method for producing astaxanthin is disclosed. In addition, Eiji Yamashita: Food and Development vol.27 No.3 (Vol.409) p38-40 (1992), high-performance liquid chromatography (HPLC) should be performed on organic solvent extracts or supercritical extracts of krill. Can separate astaxanthin diester, monoester and free astaxanthin, JP-A-5-155536 can remove triglycerides and polar lipids by HPLC, and can dramatically increase the dye concentration, In addition, substances that cause marine product-specific odors are also removed, and adsorbents that serve as stationary phases to be packed in columns include, for example, silica gel, silicic acid, activated alumina, and low-polar solvents that serve as mobile phases include, for example, n-hexane, cyclohexane, petroleum ether, etc., and polar solvents such as acetone, ethyl acetate In order to purify the pigment, first, low-polar lipids such as triglycerides are eluted with n-hexane, and then the content of acetone in n-hexane is increased (the acetone content is about 0.1 to 20%). (Range of acetone / n-hexane) and elution recovery of the dye. In the present invention, astaxanthin extracted by any method and its ester can be used.

  The ester of astaxanthin used in the present invention is an ester with any edible or pharmaceutical acceptable fatty acid, for example, saturated fatty acids such as palmitic acid and stearic acid, or oleic acid, linoleic acid, α-linolenic acid, γ -Esters of unsaturated fatty acids such as linolenic acid, bishomo-γ-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, etc., both of which are monoesters bonded to astaxanthin and diesters bonded to two Can be used in the present invention.

  Astaxanthin and its esters are known to be highly safe compounds with no observed mutagenicity.

  The exocrine gland dysfunction-improving agent according to the present invention refers to a substance or composition having an effect of treating, improving or preventing dysfunction including exocrine gland hypofunction, and various symptoms associated with exocrine gland dysfunction It contributes to the treatment, improvement or prevention. The agent for improving dysfunction of the exocrine gland according to the present invention can act to promote secretion of fluid from the exocrine gland and to activate the exocrine gland. The exocrine glands targeted by the agent for improving dysfunction of the exocrine gland of the present invention include the lacrimal gland, salivary gland, parotid gland, submandibular gland, sublingual gland, small oral salivary gland (lip gland, tongue gland, palatal gland, cheek) Gland), meibomian glands, and pancreatic β cells.

  Dry eye that is one of the symptoms associated with dysfunction of the exocrine glands is dry eye such as lacrimation, xerophthalmia, hypoxia, Sjogren's syndrome, dry keratoconjunctivitis, Steven-Jenson syndrome, eyelid margin inflammation , Dry eye associated with pemphigoid, blepharitis, allergic conjunctivitis. The exocrine gland dysfunction-improving agent according to the present invention is not only for dry eye, but also for the purpose of relieving symptoms called so-called fatigued eyes and itchy eyes by increasing lacrimation and protecting the eyes after surgery. Widely usable.

  In addition, as a dry mouse that is one of the symptoms associated with the above-mentioned dysfunction of the exocrine gland, Sjogren's syndrome, hypertension, diabetes, adverse effects of radiation therapy, kidney disease, salivary gland atrophy in the elderly, salivary glanditis, salivary gland-related Examples include xerostomia caused by nervous system disorders, side effects of drugs, and temporary xerostomia of saliva during menopause in women.

  In many cases, the onset mechanism of symptoms such as dry eye and dry mouse is not specified and is difficult to specify. The exocrine gland dysfunction-improving agent of the present invention can effectively act on symptoms such as dry eye and dry mouse regardless of the onset mechanism.

  The exocrine gland dysfunction-improving agent according to the present invention may be provided in the form of a pharmaceutical or a food. When the astaxanthin derived from a natural product is contained, any of the above crude extract or purified product can be used. When these are used, since the properties of astaxanthin and its ester are oily, the active ingredient can be used as a buoyant agent by adding a compound that becomes a buoyant agent or a synergist according to a conventional method.

  When producing pharmaceuticals or foods in the present invention, astaxanthin or crude extract can be used by dissolving in ethanol and diluting with water as it is. can do. In preparing an emulsion preparation, gallic acid, L-ascorbic acid (or an ester or salt thereof), gum (eg locust bean gum, gum arabic or gelatin), and vitamin P (eg hesperidin, rutin) are used in the aqueous phase. , Flavonoids such as quercetin, catechin and thianidine, polyphenols or mixtures thereof), etc., and astaxanthin or its ester, crude extract or mixture thereof are added to the oil phase, and glycerol, glycerin fatty acid ester, sorbitan It can be easily prepared by adding and emulsifying a normal liquid oil such as fatty acid ester, sucrose fatty acid ester, dextrin or oil and fat such as rapeseed oil, soybean oil, corn oil and the like. In emulsification, mixed emulsification can be performed using a high-speed stirrer, a homogenizer, or the like.

  When the exocrine gland dysfunction-improving agent of the present invention is used as a pharmaceutical product, the pharmaceutical product is preferably in a dosage form that can be conveniently administered orally. Examples of the pharmaceutical dosage form according to the present invention include solid preparations such as capsules, tablets, powders or granules, and liquid preparations such as internal preparations or syrups.

  In the pharmaceutical product according to the present invention, astaxanthin and / or its ester as an active ingredient depending on the dosage form of the formulation, excipient, binder, disintegrant, lubricant, corrigent, stabilizer, solubilizer, etc. Any pharmaceutically acceptable additive can be added. More specifically, when the pharmaceutical product according to the present invention is a solid preparation, for example, excipients such as lactose, glucose, sucrose, and mannitol; disintegrants such as starch and sodium alginate; magnesium stearate, talc Additives such as lubricants such as polyvinyl alcohol, hydroxypropyl cellulose, gelatin; surfactants such as fatty acid esters; plasticizers such as glycerin can be included in the preparation. When the pharmaceutical product according to the present invention is a liquid preparation, for example, sugars such as sucrose, sorbit and fructose; glycols such as polyethylene glycol and propylene glycol; oils such as sesame oil, olive oil and soybean oil; p- Additives such as preservatives such as hydroxybenzoates can be included in the formulation. Moreover, in the case of a liquid formulation, the pharmaceutical agent according to the present invention may be a formulation in which astaxanthin and / or its ester as an active ingredient is dissolved at the time of use.

  The ratio of astaxanthin and / or its ester (active ingredient) contained in the pharmaceutical product according to the present invention is not particularly limited, but is usually 0.01 to 100 parts by weight, preferably 0.1 to 100 parts by weight in the preparation. It is prepared so as to be contained at a ratio of 50 parts by weight. The pharmaceutical product according to the present invention can be easily produced according to a pharmaceutically acceptable method.

  The dosage of the pharmaceutical agent according to the present invention varies depending on the route of administration, dosage form, degree of symptom of patient, age, body weight, for example, a preparation containing about 5 to 200 mg of active ingredient per capsule. Depending on the patient, the capsules can be administered in about 1 to 10 capsules per day, preferably about 1 to 6 capsules in several divided doses per day.

  When the exocrine gland dysfunction improving agent of the present invention is used as a food or drink, its form is not limited. As the food and drink according to the present invention containing astaxanthin and / or an ester thereof, for example, confectionery such as biscuits, cookies, cakes, candy, chocolate, chewing gum, Japanese confectionery; bread, noodles, rice, tofu or processed products thereof; Fermented foods such as refined sake and medicinal liquor; seasonings such as mirin, vinegar, soy sauce, miso and dressing; livestock foods such as yogurt, ham, bacon, sausage, and mayonnaise; marine foods such as kamaboko, fried tempura, and hampen; fruit juice Examples include beverages, soft drinks, sports drinks, jelly-like drinks, alcoholic drinks, tea, coffee, cocoa and other beverages.

  The food and drink of the present invention can be processed and produced by ordinary methods by blending astaxanthin and / or an ester thereof, or a natural product containing these with raw materials of general foods. The blending concentration varies depending on the dosage form and the morphological properties of the food and drink, and is not particularly limited, but is generally preferably 0.001 to 10% by weight.

  When the food or drink of the present invention is used as a dietary supplement or functional food, the form thereof may be the same form as the above-mentioned pharmaceuticals. For example, a protein (a milk protein having a high nutritional value with a balanced amino acid as a protein source, Proteins such as soy protein and egg albumin are the most widely used, but in addition to these degradation products, egg white oligopeptides and soy hydrolysates, mixtures of amino acids alone are also used), sugars, fats, trace elements Further, it may be processed forms such as natural liquid foods, semi-digested nutritional foods and component nutritional foods, drinks, capsules, and the like containing vitamins, emulsifiers, fragrances and the like. When serving as sports drinks or nutritional drinks, nutritional additives and sweeteners such as easily digestible water-containing carbon, amino acids, vitamins, minerals, etc. are used to improve nutritional balance and improve the flavor when ingested. , Spices, fragrances, pigments and the like can also be blended.

  The form of the dietary supplement or functional food of the present invention is not limited to these, and may be the form of the above-mentioned general food or drink, but preferably in unit dosage form if possible.

  The food and drink according to the present invention may be taken when various symptoms associated with dysfunction of exocrine glands such as dry eye and dry mouse are recognized. Moreover, you may use regularly in order to prevent, improve, or reduce the various symptoms accompanying the dysfunction of an exocrine gland.

  The intake of the food and drink according to the present invention varies depending on the degree of symptoms, age, weight, etc. of the person who ingests, but for example, the intake of one dose for an adult is effective for the astaxanthin and / or ester thereof according to the present invention. The total amount of the components can be about 1-1000 mg, preferably about 5-500 mg. It is good to take this several times a day.

  Hereinafter, although an Example is described in detail, this invention is not limited to these.

(Example 1)
It has already been reported that the ability to secrete tears and saliva is reduced by irradiating the mouse head and neck. In the following, the exocrine gland dysfunction improving effect of astaxanthin was examined in vivo using this exocrine gland disorder model mouse.

Experimental animals and rearing conditions For experimental animals, five C57BL / 6 mice were used for each of the control diet group and the astaxanthin diet group. After 2 weeks of preliminary breeding, the head and neck were irradiated with 15 Gy of radiation and further breeded for 4 weeks. Breeding conditions before and after irradiation were such that the prepared feed and water were freely ingested, and room temperature was 23 ± 1 °, RH was 50 ± 5%, and the light / dark cycle was 12 hours.

A standard feed (AIN-93G manufactured by Oriental Yeast Co., Ltd.) was used for the test feed “control food”, and an oil containing 0.2% by weight of astaxanthin 5% in the above standard feed for the “astaxanthin food” (ASTALIL manufactured by Fuji Chemical Co., Ltd.) Oil 50F) was used. The feed was fed freely and given 5g / day per animal. Therefore, astaxanthin was administered to the “astaxanthin diet” administration group at 0.5 mg / animal / day (22.7 mg / kg / day).

Observation of exocrine gland dysfunction improving effect Saliva and tear volume were measured for each group of mice. FIG. 1 shows the results of measurement of saliva immediately before irradiation and 1, 2, and 4 weeks after irradiation, and FIG. 2 shows the results of tear fluid measured immediately before irradiation and after 1 and 2 weeks of irradiation. . The amount of saliva secretion is measured by administering pilocarpine intraperitoneally (1 mg / kg) under anesthesia (xylazine + ketamine) and collecting saliva with a capillary (10 μL) every minute for 15 minutes immediately after administration. The total amount (μL) for 15 minutes per (g) was displayed. For lacrimal secretion, pilocarpine was administered intraperitoneally (5 mg / kg) under anesthesia (xylazine + ketamine), and a cotton thread (zone quick) was inserted into the left eye for 15 minutes immediately after administration. It was measured by measuring the length permeated by the liquid, and expressed as a total length (mm) for 15 minutes per body weight (g).

  As can be seen in FIG. 1, regarding the secretion amount of saliva, the mice in the astaxanthin diet group suppressed the decrease due to irradiation compared to the mice in the control diet group. Furthermore, as a result of the t-test, it was confirmed that the decrease due to irradiation was significantly suppressed in the astaxanthin diet group mice as compared to the control diet group mice after 1 week and 4 weeks of irradiation. In addition, as shown in FIG. 2, regarding the secretion amount of tears, the mice in the astaxanthin diet group suppressed the decrease due to irradiation compared to the mice in the control diet group.

(Formulation Example 1: Tablet)
The following ingredients were uniformly mixed at the following composition ratio to form a tablet of 180 mg per tablet.

Astaxanthin 5% by weight
Lactose 75% by weight
Heavy magnesium oxide 20% by weight
100% by weight
(Formulation example 2: soft capsule)
A shell material composed of the following components of the soft capsule was filled with hematococcus extracted oil (containing 10% by weight of astaxanthin) by a conventional method to obtain a soft capsule having an inner volume of 100 mg.

70% gelatin
Glycerin 23% by weight
Propyl paraoxybenzoate 0.5% by weight
Water balance 100% by weight
(Formulation Example 3: Capsule)
In the shell material of the soft capsule formulation of Formulation Example 2, 50 mg of hematococcus extract oil (containing 5% by weight of astaxanthin) and 150 mg of medium chain fatty acid (Actor M-1) are filled by a conventional method, and a soft capsule with a 200 mg content per capsule An agent was obtained.

(Formulation Example 4: Drink)
The following ingredients were blended in the following weights, and water was added according to a conventional method to prepare a drink.

Astaxanthin 5g
Liquid sugar 4kg
DL-sodium tartrate 1g
Citric acid 50g
Vitamin C 50g
Vitamin E 150g
Cyclodextrin 25g
Potassium chloride 5g
Magnesium sulfate 2g
(Formulation Example 5: nourishing tonic)
The following components were blended in the following weights, and water was added according to a conventional method to prepare a liquid.

Astaxanthin ethyl ester 5g
Liquid sugar 4kg
DL-sodium tartrate 1g
Citric acid 50g
Vitamin B1 10g
Vitamin B2 10g
Vitamin B6 10g
Vitamin B12 10g
Vitamin C 50g
Vitamin E 150g
Folic acid 5g
Nicotinic acid 10g
Cyclodextrin 25g
Potassium chloride 5g
Magnesium sulfate 2g

  The exocrine gland dysfunction-improving agent of the present invention has an action to treat, ameliorate or prevent exocrine gland dysfunction. Therefore, treatment of various symptoms related to the function of exocrine gland including dry eye and dry mouse, Useful for improvement or prevention. In addition, astaxanthin and its esters used in the present invention are naturally occurring substances and have food experience, so it is easily considered that they are low in toxicity and high in safety. Therefore, the present invention is useful as a new food / beverage product, functional food and pharmaceutical product.

The amount of saliva secretion when glandular tissue is damaged by irradiation is shown. The amount of lacrimal secretion when glandular tissue is damaged by irradiation is shown.

Claims (5)

  An agent for improving dysfunction of exocrine glands containing astaxanthin and / or an ester thereof as an active ingredient.   The exocrine gland dysfunction-improving agent according to claim 1, wherein the exocrine gland is a lacrimal gland and / or a salivary gland.   A food or drink for improving dysfunction of exocrine glands, comprising astaxanthin and / or an ester thereof as an active ingredient.   The food or drink for improving dysfunction of the exocrine gland according to claim 3, wherein the exocrine gland is a lacrimal gland and / or a salivary gland. The food or drink for improving dysfunction of the exocrine gland according to claim 4, which is a functional food.

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