TW201726125A - Oral composition - Google Patents

Abstract

Provided is a composition for preventing or suppressing blurred eyesight, said composition containing citrulline or a salt thereof as an active ingredient.

Description

Oral composition

The present invention and citrulline or a salt thereof as an active ingredient prevent or inhibit turbidity of crystal crystals by high crystal crystal protection in vivo, thereby preventing or inhibiting symptoms caused by turbidity of crystal crystals, in detail, vision The composition of the ambiguity is related.

Due to advances in medical technology, cataracts have become diseases that are treated with surgery. However, the results of cataract observations will gradually increase with age from the age of 50, and reach 67-83% at the age of 80. Together with glaucoma and diabetic retinopathy, they are still the top reasons for the decline in vision during a lifetime. .

A cataract is a state in which the transparency of the crystal formed by the crystal crystals is irreversibly lost and the vision is hindered. As a factor of these age-related crystal pressures, in addition to the participation of oxidative stress caused by active oxygenates (ROS), there are reports of the involvement of hereditary factors. That is, the denaturation of the crystal protein will progress due to an increase in oxidative stress with aging and external stimuli such as ultraviolet rays, and the visual function will be hindered, making people's QOL (Quality of Life; The quality of life is remarkably lowered (Non-Patent Documents 1 and 2).

At present, there is no other way to cure cataracts than to remove turbid crystals and insert them into artificial crystals. Eye drops are very common as drugs used in drug therapy for cataracts. However, the administration of eye drops is irreversible for reversing the opacity of the lens caused by cataract to a transparent state, or improving the visual acuity caused by opacity of the crystal. It is expected to be able to slightly delay the progress and extend until the surgery (Non-Patent Documents 1 and 2).

In view of such a status quo, if an oral preparation having a high crystal crystal protection effect which can be easily taken up is provided, the visual function of the person can be maintained healthy and normal, and the QOL of the person can be improved.

L-citrulline is not used as a synthetic raw material for proteins in vivo, but is one of amino acids present in a free state. It plays an important role in maintaining vascular function as a precursor of L-arginine in the body and as a constituent element of the NO cycle associated with the supply of nitric oxide (NO), which has a vasodilating action. In response to the administration of citrulline, anti-arteriosclerosis, blood flow promoting effect, vascular endothelial function-improving effect, and retinal arteriolar expansion have been reported through the administration of vasodilator NO (Non-Patent Documents 3 and 4, 5) L-citrulline is mainly used as a functional material acting on the cardiovascular system through NO production. Further, in Europe, it is used as a pharmaceutical for anti-fatigue in the form of L-citrulline-malate. In addition, L-citrulline has a report of improving muscle protein metabolism (Non-Patent Document 6).

However, to date, for L-citrulline as an amino acid It is still unknown to reach the crystal structure after harvesting, inhibit the oxidative degeneration of the crystal protein and delay the progression of cataract.

[Previous Technical Literature] [Non-patent literature]

[Non-Patent Document 1] Japanese Society of Cataracts, (2014) 26, 13-19.

[Non-Patent Document 2] Japanese Society of Cataracts, (2014) 26, 5-12.

[Non-Patent Document 3] Proceedings of the National Academy of Sciences of the United States of America, (2005) 102, 13681-13686.

[Non-Patent Document 4] Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry, (2013) 13, 214-220.

[Non-Patent Document 5] Journal of Pharmacological Sciences, (2015) 127, 419-423.

[Non-Patent Document 6] American Journal of Physiology - Endocrinology and Metabolism, (2006) 291, 582-586.

The present invention has a problem of preventing or suppressing symptoms associated with progression of cataract, or preventing or suppressing symptoms associated with aging of a crystal lens, for example, a blurred field of vision due to turbidity of a crystal lens and a state of sputum.

In order to solve the above problems, the inventors of the present invention have conducted intensive studies on the action of an amino acid which has not been known for its action on crystal crystals, and have found that the administration of L-citrulline has an effect of effectively retarding the progress of crystal turbidity, and further It has been found that L-citrulline is excellent in in vivo migration of the crystal by oral administration, and exhibits a high crystal turbidity suppressing effect, and the present invention has been completed.

That is, the present invention is as follows.

[1] A composition for preventing or inhibiting blurred vision, which comprises citrulline or a salt thereof as an active ingredient.

[2] The composition of [1], wherein the blurred vision is blurred vision due to opacity of the crystal.

[3] The composition of [2], wherein the blurred vision caused by opacity of the crystal is blurred vision caused by cataract.

[4] The composition of [1] or [2], which is excluded as an agricultural product or a processed product thereof.

[5] The composition of any one of [1], [2], and [4], which is a food.

[6] The composition of any one of [1] to [4], which is a feed.

[7] The composition of any one of [1] to [3], which is a pharmaceutical product.

[8] A method for preventing or suppressing blurring of vision, comprising: ingesting L-citrulline or a substance thereof for preventing or inhibiting blurring of vision of a subject animal in an intended purpose of preventing or suppressing blurred vision; The steps of salt.

[9] Use of citrulline or a salt thereof for preventing or inhibiting vision blurring.

According to the present invention, it is possible to prevent or suppress symptoms associated with cataract progression caused by aging or diabetes, which have been considered to be difficult for drug therapy by oral ingestion of the composition of the present invention.

Further, according to the present invention, it is possible to prevent or suppress the self-conscious symptoms caused by cataract caused by aging of the crystal crystal by daily ingestion of the composition of the present invention, for example, a blurred field of vision caused by turbidity of the crystal, and a state of sputum.

[Fig. 1] Fig. 1 shows a cataract score (mean ± standard deviation) in a cataract progression model. The horizontal axis shows the passage (week) of streptomycin (65 mg/kg) intravenously administered to Wistar male rats and 5% glucose water as drinking water from the date of onset of diabetes. The figure shows the control group, the diabetic (DM) group, and the DM+Cit group (0.5, 1 or 2 g/kg body weight/day) of the DM group treated with L-citrulline.

[Fig. 2] Fig. 2 shows the turbid area ratio (mean ± standard deviation) of the central portion of the crystal in the cataract progression model. The horizontal axis shows the passage (week) of streptomycin (65 mg/kg) intravenously administered to Wistar male rats and 5% glucose water as drinking water from the date of onset of diabetes. The figure shows the control group, diabetes (DM) Group, DM+Cit population of DM group (0.5, 1 or 2 g/kg body weight/day) was treated with L-citrulline.

[Fig. 3] Fig. 3 is a graph showing the L-citrulline concentration (mean ± standard deviation) in the crystal of the ninth week of onset of diabetes in the cataract progression model. The figure shows the control group, the diabetic (DM) group, and the DM+Cit group (0.5, 1 or 2 g/kg body weight/day) of the DM group treated with L-citrulline.

The present invention relates to a composition for preventing or inhibiting blurred vision containing L-citrulline or a salt thereof as an active ingredient (hereinafter sometimes referred to simply as "the composition of the present invention").

The term "visual blurring" in the present invention means that all or part of the field of view cannot be seen clearly or ambiguously.

Examples of "obscured vision" include turbidity of the crystal lens, excessive use of the eyes, dryness of the eyes, damage to the cornea, and diseases.

The term "cloudy turbidity" means a state in which avascular tissue is transparent and the opacity of the crystal is white, yellow or brown.

Examples of diseases that cause "eyesight blur" include cataracts, dry eye syndrome, glaucoma, uveitis, presbyopia (decreased focus adjustment function due to age), macular degeneration, and diabetic retinopathy.

The composition of the present invention is suitable for use in vision blur due to turbidity of crystal crystals, and is suitable for blurring of vision caused by cataract.

As a disease that causes cataract, diabetes, ectopic Sexual dermatitis, rubella, eye injuries, uveitis, radiation, steroids, etc. In addition, cataracts may occur almost universally due to aging. The composition of the present invention is particularly suitable for use in a cataract caused by diabetes and aging.

The prevention of "obscured vision" means preventing the occurrence of blurred vision or delaying the onset of blurred vision. The suppression of "obscured vision" means maintaining a normal field of vision and also includes the concept of improvement or treatment of "visual blurring".

Further, a composition containing L-citrulline or a salt thereof as an active ingredient can prevent or inhibit the symptoms caused by turbidity of the crystal.

Symptoms caused by turbidity of crystal crystals include blurred vision (poor vision, fog vision), eye fatigue, photophobia (feeling light glare), decreased vision, viewing one object as two (monocular double vision), 昼Blind, flying mosquitoes, etc. The composition of the present invention is particularly suitable for blurring of vision used therein.

The prevention of the symptoms caused by "crystal opacity" means preventing the occurrence of this symptom in advance. The suppression of the symptoms caused by "crystal opacity" also includes the concept of delaying and improving the occurrence or progression of the symptoms, and means maintaining a normal field of vision.

Further, a composition containing L-citrulline or a salt thereof as an active ingredient can prevent or inhibit cataract.

The prevention of cataract means preventing the occurrence of cataract in advance. The so-called inhibition of cataract also includes the concept of delaying, treating, and improving the onset or progression of cataract.

As the citrulic acid used in the composition of the present invention, it can be mentioned L-citrulline, D-citrulline and DL-citrulline are preferably L-citrulline. The citrulline can be obtained by a method of chemical synthesis, a method of fermentation production, or the like. In addition, citrulline can also be obtained by purchasing a commercially available product. As a method of chemically synthesizing citrulline, for example, the method described in J. Biol. Chem., 122, 477 (1938), J. Org. Chem., 6, 410 (1941) can be mentioned.

For example, the method described in JP-A-63-075387 and JP-A-63-068091 can be cited as a method of producing L-citrulline by fermentation. Further, commercially available products can also be used for L-citrulline, D-citrulline and DL-citrulline.

Examples of the salt of L-citrulline include an acid addition salt, a metal salt, an ammonium salt, an organic ammonium salt, an organic amine addition hydrazine, an amino acid addition salt, and the like.

Examples of the acid addition salt include inorganic acid salts such as hydrochloride, sulfate, nitrate, and phosphate; acetate, maleate, fumarate, citrate, malate, and lactate. An organic acid salt of α-ketoglutarate, gluconate or octanoate.

Examples of the metal salt include alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as magnesium salts and calcium salts; aluminum salts and zinc salts.

The organic ammonium salt may, for example, be a tetramethylammonium salt or the like.

The organic amine addition salt may, for example, be a monoethanolamine salt, a diethanolamine salt, a triethanolamine salt, a morpholine salt or a piperidine salt.

Examples of the amino acid addition salt include glycinate, phenylalanine, persalt, aspartate, and glutamate.

Among the above-mentioned salts of L-citrulline, it is preferred to use citrate or malate for the purpose of the present invention, but other The salt may be used in combination of two or more kinds of salts as appropriate.

Further, the above-mentioned salt of L-citrulline can be produced and used according to a method known per se, but a commercially available product can also be used.

The composition of the present invention can be provided in a liquid form, a milk form, a gel form, a capsule form, a powder form, a granule form, a tablet form, or the like, which is generally used in the pharmaceutical art.

The content of L-citrulline in the composition of the present invention varies depending on the dosage form of the composition, but is usually 0.1% by weight to 100% by weight in terms of the amount of free L-citrulline, and 0.5% by weight. It is preferably from 80% by weight, more preferably from 1% by weight to 70% by weight.

The composition of the present invention is excluded from the aspect of agricultural aquatic products or processed products thereof. The so-called agricultural products refer to the agricultural products of agricultural production, as well as aquatic products such as fish, shellfish, seaweed and other aquatic organisms collected from the ocean, rivers, lakes, etc., which are foods or ingredients. The so-called processed products mean the use of the aforementioned agricultural products. Food or ingredients.

Therefore, the term "excluding the agricultural product or the processed product thereof" in the present invention means a composition excluding the food or the foodstuff ingested in the general diet.

The composition of the present invention can be used as a pharmaceutical for preventing or suppressing blurred vision (hereinafter sometimes referred to as "medicine of the present invention").

The pharmaceutical of the present invention contains L-citrulline or a salt thereof as an active ingredient, and may further contain any other active ingredient for treatment.

The pharmaceutical of the present invention is a mixture of an active ingredient and a carrier, and It is made by any method known in the art of pharmaceutical technology.

The administration form of the pharmaceutical of the present invention is preferably the most effective when the treatment is used, and examples thereof include oral administration or parenteral administration such as intravenous, intraperitoneal or subcutaneous administration, but It can be easily administered, so oral administration is preferred.

Examples of the administration form include a tablet, a powder, a granule, a pill, a suspension, an emulsion, an infusion/decoction, a capsule, a syrup, a liquid, an elixir, an extract, an elixir, and a flow extract. Oral preparations such as injections, injections, ointments, suppositories, etc., but oral preparations are preferred.

When formulated as an oral preparation, general additives such as excipients, binders, disintegrants, lubricants, dispersing agents, suspending agents, emulsifiers, diluents, buffers, antioxidants, preservatives, flavoring agents, and the like can be used. .

For example, tablets, powders, granules and the like which are suitable for oral administration may be added with sugars such as lactose, white sugar, glucose, sucrose, mannitol, sorbitol, starches such as potato, wheat, corn, etc.; calcium carbonate and calcium sulfate. An inorganic substance such as sodium bicarbonate or sodium chloride; an excipient such as a plant powder such as crystalline cellulose, licorice powder or gentian powder; starch, agar, gelatin powder, crystalline cellulose, sodium carboxymethyl cellulose , disintegrators such as calcium carboxymethylcellulose, calcium carbonate, sodium hydrogencarbonate, sodium alginate; lubricants such as magnesium stearate, talc, hydrogenated vegetable oil, polyethylene glycol, eucalyptus oil, etc.; polyvinyl alcohol, hydroxy A binder such as propyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, gelatin or starch paste; a surfactant such as a fatty acid ester; a plasticizer such as glycerin, and the like.

A preparation suitable for parenteral administration, such as eye drops, may be added with a pharmaceutically acceptable isotonic agent, a solubilizing agent, a stabilizer, a preservative, etc., as needed, without damaging the effects of the present invention.

Examples of the isotonic agent include propylene glycol, glycerin, sodium chloride, and potassium chloride. Examples of the co-solvent include polysorbate 80, polyoxyethylene hardened castor oil, and the like.

As a preservative, it can be converted as a conversion soap such as benzalkonium chloride, bensonin chloride or chlorhexidine gluconate; methylparaben, propylparaben or butylparaben. Examples of p-hydroxybenzoic acid esters; alcohols such as chlorobutanol, phenylethyl alcohol, and benzyl alcohol; and sodium acetate dehydrated.

Examples of the stabilizer include ethylenediaminetetraacetic acid and their pharmaceutically acceptable salts, tocopherol and derivatives thereof, sodium sulfite, and the like.

As the injection, a salt solution, a glucose solution or a carrier composed of a mixture of a salt solution and a glucose solution can be used.

In addition, such non-oral preparations may also be added with a diluent, a preservative, a fragrance, an excipient, a disintegrant, a lubricant, a binder, a surfactant, a plasticizer exemplified in the oral preparation. One or more additives.

The content of L-citrulline in the pharmaceutical product of the present invention varies depending on the dosage form of the pharmaceutical product, etc., but is usually 0.1% by weight to 100% by weight in terms of the amount of free L-citrulline, and is 0.5 weight%. More preferably, it is preferably from 1% by weight to 70% by weight.

The amount of administration of the pharmaceutical of the present invention to humans and the number of administrations vary depending on the type of administration, the age and weight of the patient, the nature or severity of the symptoms to be treated, but usually adults (body weight 60 kg) per On the day of L-citrulline (in terms of free guar acid), it is 400mg~10g orally, 400mg~5g is preferred, 400mg~3g is better, and 500mg~2g is further. More preferably, 800mg~2g is the best way to apply once a day to several times. The amount of administration of the eye drops or the like is divided into one to several times in accordance with the amount converted based on the above-mentioned oral administration amount.

Further, regarding the administration amount of the pharmaceutical of the present invention to humans, the blood citrulline concentration can be derived from oral administration of L-citrulline to rodents (Kobayashi et al., Pharmacognosy Research, 6(4). 2014), and the relationship between blood citrulline concentration (Moinard et al., British Journal of Nutrition, 99 (4) 2008) when humans orally administered L-citrulline. That is, about 1 g of L-citrulline is orally administered to rodents per 1 kg of body weight for one day, which corresponds to about 0.8 g of L-citrulline orally administered to human adults every day. As shown in the examples described later, by orally administering 0.5 g of L-citrulline per kg of body weight per day for 9 weeks, the progression of cataract is suppressed, so that in order to prevent or suppress blurring of human vision, Adults must orally administer about 0.4 g of L-citrulline per day.

Although there are no special restrictions on the investment, it is usually 1 day to 1 year, preferably 2 weeks to 6 months, and 9 to 3 months is the best.

Further, the composition of the present invention can be used not only for humans but also for animals other than humans (hereinafter referred to as "non-human animals").

Examples of the non-human animal include animals other than humans such as mammals, birds, reptiles, amphibians, and fish.

Therefore, the pharmaceutical of the present invention can also provide a pharmaceutical for preventing or suppressing blurred vision as a non-human animal.

The administration amount of the pharmaceutical of the present invention when administered to a non-human animal varies depending on the species, age, nature or severity of the symptoms of the animal, but usually 1 hour per 1 kg body weight, and L-citrulline is used. (The amount of guaric acid converted into a free form) is calculated to be 10 mg to 5 g, and 100 mg to 2 g is preferably administered once a day to several times.

Although there are no special restrictions on the investment, it is usually 1 day to 1 year, preferably 2 weeks to 3 months.

The composition of the present invention can also provide a food for preventing or suppressing blurring of vision (hereinafter sometimes referred to as "food of the present invention"). Moreover, food additives are also included in the food of the present invention.

One aspect of the food additive of the food of the present invention (hereinafter sometimes referred to as "the food additive of the present invention") can be produced in the same manner as the pharmaceutical preparation of the present invention.

The food additive of the present invention can be processed into a form such as a powder, granules, pellets, troches, and various liquid preparations.

The food of the present invention may also be a dairy product such as a juice, a refreshing drink water, a tea, a lactic acid bacteria drink, a fermented milk, a frozen dessert, a cream, a cheese, a yogurt, a processed milk, a skim milk, a ham, a sausage, a hamburger. Fish products such as fish products, fish plates, bamboo wheels, Satsuma fried fish cakes (sweet and not spicy), egg products such as Japanese soup omelet, egg tofu, biscuits, jellies, chewing gum, candy, snacks, etc. Dim Sum, bread, noodles, pickles, smoked products, dried fish, boiled, salted, soup, tune Any type of flavoring material, such as bottled food, canned food, and sterilized bag food.

Further, the food of the present invention may be in the form of, for example, a powder, a tablet, a capsule, a tablet, a gel or the like.

In addition, the food of the present invention can provide special health foods, nutritional functional foods, functional foods such as food and drink, foods for the elderly, foods for the elderly, etc., which are used for prevention and suppression of blurred vision. Use foods, health supplements, etc.

In the food of the present invention and the food additive of the present invention, an additive generally used for foods, for example, a sweetener described in the Japanese Food Additives Association (Japan Food Additives Association), may be added. Coloring agents, preservatives, thickening stabilizers, antioxidants, color developing agents, bleaching agents, fungicides, chewing gum bases, bittering agents, enzymes, brighteners, sour agents, seasonings, emulsifiers, fortifiers, manufacturing Agents, spices, spice extracts, etc.

The food of the present invention can be processed and produced by using a general food production method, in addition to adding L-citrulline to the food or adding them in the form of the above-mentioned food additive.

Further, in the case where the food of the present invention is a solid food such as granules, for example, fluidized bed granulation, agitation granulation, extrusion granulation, tumbling granulation, air granulation, compression molding granulation, or the like may be used. Granulation methods such as crush granulation, spray granulation, spray granulation, coating methods such as enamel coating, fluidized bed coating, dry coating, etc., expansion drying, excess water vapor method, foam pad method, a puffing method such as a microwave heating method, an extrusion granulator or an extruder Extrusion method, etc. are manufactured.

The amount of L-citrulic acid to be added to the food of the present invention is appropriately determined depending on the type of the food, the effect expected by ingesting the food, and the like, but L-citrulline (in terms of free L-melon) The amount of the amine acid is usually from 0.1% by weight to 100% by weight, preferably from 0.5% by weight to 80% by weight.

Further, the content of L-citrulline in the food additive of the present invention is set such that the content of L-citrulline in the food reaches the above range when the food additive of the present invention is added to the food.

The intake amount, the number of intakes, and the ingestion period of the food of the present invention are the same as those of the pharmaceutical product of the present invention to humans.

When the food of the present invention is provided as a health-care functional food, a special-purpose food, a health-supplemented food, or the like, the intake amount per one time calculated from the intake amount of the food of the present invention is included in the intake amount of one meal. It is better to pack or fill the food for the unit. Here, the "food packaged or filled in a unit of intake per meal" means that the food to be ingested once is packaged or filled into a container such as a bag, a box, or a bottle.

The composition of the present invention can also be used as a feed for preventing or suppressing blurred vision (hereinafter sometimes referred to as "feed of the present invention"). Further, the feed of the present invention also contains a feed additive.

An aspect of the feed additive of the present invention (hereinafter sometimes referred to as "the feed additive of the present invention") can be produced in accordance with the method for producing a pharmaceutical product of the present invention in the same manner as the food additive of the present invention. Made. The feed additive of the present invention is prepared by mixing or dissolving other feed additives as needed, and is processed into a form of, for example, a powder, a granule, a pellet, a tablet, and various liquid preparations.

The feed of the present invention is a feed for adding non-human animals by adding L-citrulline or a feed additive containing L-citrulline, and can be processed and produced using a general feed production method.

As a feed for non-human animals, any feed for non-human animals such as mammals, birds, reptiles, amphibians, and fish may be used, and examples thereof include pet feeds for dogs, cats, and hamsters, and cattle. Feed for livestock such as pigs, feed for poultry such as chicken and turkey, feed for farmed fish such as squid, squid, and squid.

Examples of the non-human animal feed which can be used in the present invention include cereals, dregs, vegetable oils, animal feeds, other feeds, and refined products.

Examples of the cereals include sorghum, wheat, barley, oats, rye, brown rice, buckwheat, corn, glutinous rice, hazelnut, corn, soybean, and the like.

Examples of the dregs include rice bran, defatted rice bran, bran, wheat germ, wheat bran, corn bran, corn germ, and the like.

Examples of the vegetable oil mites include soybean oil, linseed oil, cotton oil, peanut oil, safflower oil, coconut oil, palm oil, sesame oil, sunflower oil, rapeseed oil, kapok seed oil, mustard oil, and the like. .

As animal feed, for example, fish meal (Beiyang fishmeal, import) Fishmeal, whole fishmeal, coastal fishmeal, etc.), fish paste, meat powder, meat and bone meal, blood meal, decomposed hair, bone meal, processing by-products for livestock, feather meal, silkworm cocoons, skim milk powder, dried whey, etc.

As other feeds, for example, plant stems and leaves (苜蓿, hay, yarrow powder, locust powder, etc.), corn processing industry by-products (corn protein meal, corn protein feed, corn immersion liquid, etc.), starch processing Products (starch, etc.), sugar, fermentation industrial products (yeast, beer, malt root, wine cellar, soy sauce, etc.), agricultural production by-products (citrus processing residue, bean curd residue, coffee grounds, cocoa residue, etc.), cassava , broad beans, gum bean powder, seaweed, krill, spirulina, green algae, minerals, etc.

Examples of the refined product include protein (casein, albumin, etc.), amino acid, saccharide (sucrose, glucose, etc.), minerals, vitamins, and the like.

Further, the feed of the present invention may also be used, for example, for flow layer granulation, agitation granulation, extrusion granulation, rotary granulation, air granulation, compression molding granulation, crush granulation, spray granulation, spray granulation, etc. Granulation method, coating method of sputum coating, fluidized bed coating, dry coating, etc., expansion method, excess water vapor method, foam pad method, microwave heating method, etc., extrusion granulator A solid feed such as a pellet is produced by an extrusion method such as an extruder.

The amount of L-citrulic acid added to the feed of the present invention is appropriately determined depending on the type of the feed, the effect expected by ingesting the feed, and the like, but L-citrulline (in terms of free L-melon) The amount of the amine acid is usually from 0.1% by weight to 100% by weight, preferably from 0.5% by weight to 80% by weight.

Further, the content of L-citrulline in the feed additive of the present invention is set such that the content of L-citrulline in the feed reaches the above range when the feed additive of the present invention is added to the feed.

The intake amount, the number of intakes, and the ingestion period of the feed of the present invention are the same as those for non-human animals in the pharmaceutical preparation.

The composition of the pharmaceutical, food, and feed of the present invention described above exhibits an excellent preventive or inhibitory effect on blurred vision.

Therefore, the composition of the present invention is suitable for a person who is employed in an occupation of the eye, and an elderly person who complains about blurred vision with age. Furthermore, the term "elderly" as used in the present invention means a person who is generally 60 years old or older.

Further, the composition of the present invention is also suitable for predicting a pet or the like who is suffering from a cataract.

The present invention also provides a method for preventing or suppressing blurred vision of humans and non-human animals (hereinafter also referred to as "the method of the present invention").

The method of the present invention comprises the step of ingesting an amount of L-citrulline or a salt thereof in an amount required to prevent or inhibit blurred vision of the subject animal.

Target animals include human and non-human animals.

In the case of humans, the method of the present invention is not particularly limited as long as it is a subject with sensible vision, but is suitable for a person or an elderly person who is over-use of the eye.

In addition, in the case of non-human animals, it is suitable for mammals, alpaca, and cattle, pigs, sheep, goats, rabbits, etc. for feeding meat. Breeding of poultry, squid, squid, squid, etc., which are raised for meat consumption, such as horses, donkeys, camels, scorpions, etc., such as mammals for labor purposes, such as livestock, ducks, chickens, geese, turkeys, and oysters. Fish and so on.

In the method of the present invention, L-citrulline or a salt thereof is ingested by a target animal in the form of the above-described pharmaceutical, food or feed of the present invention.

The intake amount of L-citrulline or a salt thereof is determined depending on the type, age, symptom, state, and the like of the target animal, but the pharmaceutical product of the present invention can be administered to humans and non-human animals in accordance with the above-mentioned number and period of time. The same amount.

Also included in the present invention is a method for preventing or suppressing blurring of vision, and the method comprises ingesting L-guanamine in an amount required to prevent or inhibit vision blurring of a subject animal intended to prevent or suppress blurred vision. The step of an acid or a salt thereof. Definitions and amounts are as described above.

Also included in the present invention is the use of citrulline or a salt thereof for the manufacture of a preventive or inhibitor of blurred vision. Definitions and amounts are as described above.

The invention is illustrated in more detail below by way of examples, but the scope of the invention is not limited by the examples.

[Examples]

Streptomycin (65 mg/kg) was intravenously administered to a 6-week-old Wistar male rat to develop diabetes, and a hyperglycemic model rat was prepared by administering 5% glucose water as drinking water. Cataract progression model. The experiment was carried out with a control group (n=7) in which the tail vein was administered with streptomycin, and a tail vein was administered with streptozotocin (65 mg/kg). The DM group treated with 5% glucose water as drinking water (n=9) and DM+ treated with L-citrulline (0.5, 1 or 2 g/kg body weight/day) in three doses Cit group (n=5 for each group), L-citrulline was mixed into drinking water and orally administered for 9 weeks. The small animal was observed with water crystal clear illumination observation apparatus, and changes in the crystal image up to 9 weeks after the formation of the over-cooked cataract by the DM group were observed over time. Next, the cataract score was performed according to the crystal opacity classification method, and the turbidity of the central portion of the crystal lens was quantified by image analysis to evaluate the onset and progression of cataract. The concentration of L-citrulline in the crystal of the ninth week was further quantified.

The cataract score is determined by each of the crystal images based on the criteria divided into the following six stages, and is expressed as the average value of each group.

Score 0: no turbidity

Score 1: turbidity at the edge of the crystal

Score 2: turbidity at the edge and center of the crystal (cortex)

Score 3: a wide range of turbid diffusion in the crystal of the crystal

Score 4: Nuclear cataract

Score 5: Overripe cataract

As a result, it was observed that the DM group was initially turbid in the edge of the crystal, and turbidity was observed even in the center of the third week after the onset of diabetes. Thereafter, as the turbidity range of the crystal crystals expanded, the degree gradually increased, and it was confirmed at the 9th week that the entire turbid crystal was turbid.

The cataract score was quantified. Compared with the diabetic group, the DM+Cit group observed the progression of cataract inhibition after the 4th week, and confirmed that the progression of cataract was significantly inhibited by the 8th to 9th week (Fig. 1).

Furthermore, as a result of the turbidity measurement at the center of the crystal crystal, it was found that the DM+Cit group was extremely potent and significantly inhibited the progress of crystal opacity as compared with the diabetic group as in the cataract score (Fig. 2).

The L-citrulline concentration in the crystals at the 9th week of the onset of diabetes was confirmed to be significantly increased in all the doses relative to the Control group and the DM group (Fig. 3).

From this result, it was found for the first time that by administering L-citrulline during the progression from the early stage of cataract, the concentration of L-citrulline in the crystal is increased, and the turbidity of the crystal is effectively suppressed, showing the present invention. The composition is an excellent preventive or inhibitor of cataract.

[Industry use possibility]

According to the present invention, it is possible to provide an oral and effective composition for preventing or suppressing cataract or blurred vision caused by cataract, or a subjective symptom accompanying aging of a crystal, such as a blurred field of vision caused by turbidity of a crystal, and a state of sputum.

The present application is based on Japanese Patent Application No. 2015-191996 filed in Japan, the entire contents of which are incorporated herein.

Claims (13)

A composition for preventing or inhibiting blurred vision, which comprises citrulline or a salt thereof as an active ingredient. The composition of claim 1, wherein the blurred vision is blurred vision due to opacity of the crystal. The composition of claim 2, wherein the blurred vision caused by opacity of the crystal is blurred vision caused by the cataract. If the composition of claim 1 or 2 is excluded, it is excluded as an agricultural product or a processed product thereof. A composition according to any one of claims 1, 2 and 4, which is a food. The composition of any one of claims 1 to 4, which is a feed. The composition of any one of claims 1 to 3, which is a pharmaceutical product. A method for preventing or suppressing blurring of vision, comprising the step of ingesting an amount of L-citrulline or a salt thereof required for preventing or inhibiting blurring of vision of an animal of the subject in a subject animal intended to prevent or suppress blurring of vision . The method of claim 8, wherein the blurred vision is blurred vision due to opacity of the crystal. The method of claim 9, wherein the blurred vision caused by opacity of the crystal is blurred vision caused by the cataract. A use of citrulline or a salt thereof for the prevention or inhibition of vision blurring. As used in claim 11, wherein the blurred vision is caused by water The vision of crystal opacity is blurred. As used in claim 12, the blurred vision caused by opacity of the crystal is blurred vision due to cataract.