JP7220838B2 - oral composition - Google Patents

Description

The present invention contains citrulline or a salt thereof as an active ingredient, and prevents or suppresses lens opacification through a higher protective effect of the lens in vivo. It relates to a composition that prevents or suppresses haziness.

With advances in medical technology, cataract has become a disease treated by surgery. However, cataract findings gradually increase with age from around the age of 50, reaching 67 to 83% in the 80s, and together with glaucoma and diabetic retinopathy, it is still one of the leading causes of vision loss over a lifetime. .

Cataract is a condition in which vision is obstructed due to irreversible loss of transparency due to aggregation of lens-constituting proteins. It has been reported that oxidative stress caused by reactive oxygen species (ROS) as well as genetic factors are involved in lens stress associated with aging. That is, due to the increase in oxidative stress associated with aging and external stimuli such as ultraviolet rays, denaturation of lens proteins progresses, which impairs visual function and lowers people's QOL (Quality of Life). significantly reduced (Non-Patent Documents 1 and 2).

At present, there is no cure for cataract other than surgical treatment in which the opacified lens is removed and an intraocular lens is inserted. Eye drops are commonly used in drug therapy for cataracts, and the administration of eye drops reversibly restores the opacity of the lens caused by cataracts to a clear state and improves the deterioration of vision due to opacity of the lens. It is performed in hopes of delaying the progression and extending the time until surgery (Non-Patent Documents 1 and 2).
In view of the current situation, if an easily ingestible oral preparation having a high lens-protective effect could be provided, it would be possible to keep people's visual function healthy and improve their QOL.

L-citrulline is a type of amino acid that exists in a free state without being used as a raw material for protein synthesis in vivo. In the body, it plays an important role in maintaining vascular function as an L-arginine precursor and as a component of the NO cycle involved in the supply of nitric oxide (NO), which has a vasodilating effect. So far, administration of L-citrulline has been reported to have antiarteriosclerotic effects, blood flow promotion effects, vascular endothelial function improvement effects, and retinal arteriole dilation effects mediated by NO production, which is a vasodilator (non Patent Documents 3, 4, 5), L-citrulline is used as a functional material that mainly acts on the cardiovascular system via NO production. In Europe, it is used in the form of L-citrulline-malate as an anti-fatigue drug. Furthermore, there is also a report that L-citrulline has an effect of improving muscle protein metabolism (Non-Patent Document 6).

However, it has not been known at all that the amino acid L-citrulline reaches the lens tissue after ingestion, inhibits oxidative denaturation of lens protein, and delays the progression of cataract.

Journal of the Japanese Cataract Society, (2014) 26, 13-19. Journal of the Japanese Cataract Society, (2014) 26, 5-12. Proceedings of the National Academy of Sciences of the United States of America, (2005) 102, 13681-13686. Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry, (2013) 13, 214-220. Journal of Pharmacological Sciences, (2015) 127, 419-423. American Journal of Physiology - Endocrinology and Metabolism, (2006) 291, 582-586.

An object of the present invention is to prevent or suppress symptoms associated with the development of cataracts, or to prevent or suppress subjective symptoms associated with aging of the lens, such as blurred or blurred vision due to opacification of the lens.

In order to solve the above problems, the present inventors have conducted sincere studies on the action of amino acids, whose action on the lens was previously unknown, and found that the administration of L-citrulline effectively retards the progress of opacification of the lens. Furthermore, L-citrulline is very excellent in the transferability into the lens by oral administration, and it was found that it exhibits a high lens opacity suppressing effect, leading to the completion of the present invention.

That is, the present invention is as follows.
[1] A composition for preventing or suppressing blurred vision, containing citrulline or a salt thereof as an active ingredient.
[2] The composition of [1], wherein the blurred vision is caused by opacification of the lens.
[3] The composition of [2], wherein the blurred vision caused by opacification of the lens is blurred vision caused by cataract.
[4] The composition according to [1] or [2], except for agricultural and marine products or processed products thereof.
[5] The composition according to any one of [1], [2] and [4], which is a food.
[6] The composition according to any one of [1] to [4], which is a feed.
[7] The composition according to any one of [1] to [3], which is a pharmaceutical.
[8] A method for preventing or suppressing blurred vision in a subject animal intended to prevent or suppress blurred vision necessary for preventing or suppressing blurred vision in the subject animal. A method comprising ingesting an amount of L-citrulline or a salt thereof.

INDUSTRIAL APPLICABILITY According to the present invention, symptoms associated with progression of cataract due to aging or diabetes, which have been considered difficult to treat with drugs, can be prevented or suppressed by oral ingestion of the composition of the present invention.
Further, according to the present invention, subjective symptoms associated with cataract due to aging of the lens, such as blurred vision due to opacity of the lens, can be prevented or suppressed by daily ingestion of the composition of the present invention. can.

FIG. 1 shows cataract scores (mean±standard error) in the cataract progression model. The horizontal axis indicates the time (weeks) from the day when streptozotocin (65 mg/kg) was intravenously administered to male Wistar rats and 5% glucose water was given as drinking water to develop diabetes. The figure shows a control group, a diabetes (DM) group, and a DM+Cit group (0.5, 1 or 2 g/kg body weight/day) in which the DM group was treated with L-citrulline. FIG. 2 shows the opacity area ratio (mean±standard error) of the central part of the lens in the cataract progression model. The horizontal axis indicates the time (weeks) from the day when streptozotocin (65 mg/kg) was intravenously administered to male Wistar rats and 5% glucose water was given as drinking water to develop diabetes. The figure shows a control group, a diabetes (DM) group, and a DM+Cit group (0.5, 1 or 2 g/kg body weight/day) in which the DM group was treated with L-citrulline. FIG. 3 shows the L-citrulline concentration (mean±standard error) in the lens of the cataract progression model at 9 weeks after the onset of diabetes. The figure shows a control group, a diabetes (DM) group, and a DM+Cit group (0.5, 1 or 2 g/kg body weight/day) in which the DM group was treated with L-citrulline.

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

In the present invention, "blurry vision" refers to blurring or blurring of the whole or a part of vision.
Causes of "blurry vision" include lens opacification, overuse of the eye, dryness of the eye, and damage or disease of the cornea.
“Lens opacification” refers to a condition in which the avascular tissue and transparent lens is white, yellow, or brown.
Diseases that cause "blurry vision" include cataract, dry eye, glaucoma, uveitis, presbyopia (deterioration of focus control function due to aging), macular degeneration, diabetic retinopathy, and the like.
The composition of the present invention is preferably used for blurred vision caused by opacification of the lens, and preferably used for blurred vision caused by cataract.
Diseases that cause cataracts include diabetes, atopic dermatitis, rubella, eye injuries, uveitis, radiation, drugs such as steroids, and the like. In addition, cataracts can almost universally occur due to aging. Among others, the composition of the present invention is preferably used for diabetes and age-related cataracts.
The prevention of "blurring of the eyes" means to prevent the occurrence of blurring of the eyes in advance. In addition, suppression of "blurred eyes" means maintaining normal vision, and is a concept that includes improvement and treatment of "blurred eyes".

A composition containing L-citrulline or a salt thereof as an active ingredient can also prevent or suppress symptoms caused by opacification of the lens.
Symptoms caused by opacification of the lens include blurred vision (poor vision, foggy vision), asthenopia, photophobia (feeling dazzling light), decreased visual acuity, double vision (monocular diplopia), day blindness, floaters and the like. Among others, the composition of the present invention is preferably used for blurred vision.
The prevention of symptoms caused by "opacity of the lens" means to prevent the symptoms from occurring in advance. In addition, suppression of symptoms caused by "opacity of the lens" is a concept that includes delaying and improving the occurrence and progress of the symptoms, and means maintaining normal vision.
A composition containing L-citrulline or a salt thereof as an active ingredient can prevent or suppress cataracts.
Prevention of cataract means to prevent in advance so that cataract does not occur. In addition, the concept of suppressing cataract includes delaying, treating, and improving the onset and progress of cataract.

Citrulline for use in the compositions of the present invention includes L-citrulline, D-citrulline and DL-citrulline, with L-citrulline being preferred. Citrulline can be obtained by a chemical synthesis method, a fermentation production method, or the like. Citrulline can also be obtained by purchasing a commercial product. Methods for chemically synthesizing citrulline include, for example, the methods described in J. Biol. Chem., 122, 477 (1938) and J. Org. Chem., 6, 410 (1941).

Methods for producing L-citrulline by fermentation include, for example, the methods described in JP-A-53-075387 and JP-A-63-068091. Commercially available L-citrulline, D-citrulline and DL-citrulline can also be used.

Salts of L-citrulline include acid addition salts, metal salts, ammonium salts, organic ammonium salts, organic amine addition salts, amino acid addition salts and the like.

Acid addition salts include inorganic acid salts such as hydrochlorides, sulfates, nitrates and phosphates, acetates, maleates, fumarates, citrates, malate, lactates, and α-ketoglutarate. , gluconate and caprylate.
Examples of metal salts include alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as magnesium salts and calcium salts, aluminum salts, zinc salts and the like.
Organic ammonium salts include tetramethylammonium salts and the like.
Organic amine addition salts include monoethanolamine salts, diethanolamine salts, triethanolamine salts, morpholine salts, piperidine salts and the like.
Amino acid addition salts include glycine salts, phenylalanine salts, lysine salts, aspartates, glutamates, and the like.

Among the above salts of L-citrulline, citrulline and malate are preferably used for the purpose of the present invention, but other salts may be used, and two or more salts may be used in appropriate combination. good too.
The salt of L-citrulline described above 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 common dosage form in the technical field of pharmaceutical science, such as liquid, emulsion, gel, capsule, powder, granule, and tablet.

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

The composition of the present invention excludes those in the form of agricultural and fishery products or processed products thereof. Agricultural and marine products refer to agricultural products produced by agriculture, and aquatic products such as seafood and seaweed collected from oceans, rivers, lakes, etc., which are used as food or ingredients, and processed products thereof. The term refers to foods or foodstuffs produced using the agricultural and fishery products.
Therefore, in the present invention, "excluding those in the form of agricultural and marine products or processed products thereof" is intended to exclude compositions in the form of foods or ingredients that are eaten in daily general meals. be.

The composition of the present invention can be provided as a medicament for preventing or suppressing blurred vision (hereinafter sometimes referred to as "the medicament of the present invention").
The medicament 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 medicament of the present invention is produced by mixing an active ingredient with a carrier and by any method well known in the technical field of pharmaceuticals.

The dosage form of the pharmaceutical of the present invention is preferably the most effective one for treatment, and oral administration or parenteral administration such as intravenous, intraperitoneal or subcutaneous administration can be mentioned. Oral administration is preferred due to its affordability.
Dosage forms for administration include tablets, powders, granules, pills, suspensions, emulsions, infusions/decoctions, capsules, syrups, liquids, elixirs, extracts, tinctures, and liquid extracts. Parenteral agents such as oral agents, injections, drip infusions, creams, and suppositories are included, and oral agents are preferably used.

When formulating an oral formulation, general additives such as excipients, binders, disintegrants, lubricants, dispersants, suspending agents, emulsifiers, diluents, buffers, antioxidants, preservatives, flavoring agents, etc. additives can be used.

Formulations suitable for oral administration such as tablets, powders and granules include sugars such as lactose, sucrose, glucose, sucrose, mannitol and sorbitol, starches such as potato, wheat and corn, calcium carbonate, calcium sulfate and sodium hydrogen carbonate. , inorganic substances such as sodium chloride, excipients such as crystalline cellulose, licorice powder, plant powder such as gentian powder, starch, agar, gelatin powder, crystalline cellulose, carmellose sodium, carmellose calcium, calcium carbonate, sodium hydrogen carbonate, Disintegrants such as sodium alginate, lubricants such as magnesium stearate, talc, hydrogenated vegetable oil, macrogol and silicone oil, binders such as polyvinyl alcohol, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, carmellose, gelatin and starch paste , surfactants such as fatty acid esters, plasticizers such as glycerin, and the like, can be added to form formulations.

Formulations suitable for parenteral administration, such as eye drops, may contain pharmaceutically acceptable tonicity agents, solubilizers, stabilizers, preservatives, and the like, if necessary, to the extent that they do not impair the effects of the present invention. can be added at
Isotonic agents include propylene glycol, glycerin, sodium chloride, potassium chloride and the like. Solubilizers include polysorbate 80, polyoxyethylene hydrogenated castor oil, and the like.
Preservatives include inverting soaps such as benzalkonium chloride, benzethonium chloride and chlorhexidine gluconate, parabens such as methyl parahydroxybenzoate, propyl parahydroxybenzoate and butyl parahydroxybenzoate, chlorobutanol, phenylethyl Examples include alcohols and alcohols such as benzyl alcohol, and sodium dehydroacetate.
Stabilizers include ethylenediaminetetraacetic acid and their pharmaceutically acceptable salts, tocopherol and its derivatives, sodium sulfite, and the like.
Injections can be prepared using a carrier comprising a salt solution, a glucose solution, or a mixture of a salt solution and a glucose solution.
Also in these parenteral preparations, one or more selected from diluents, preservatives, flavoring agents, excipients, disintegrants, lubricants, binders, surfactants, plasticizers, etc. exemplified in the oral preparations of additives can be added.

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

The dosage and frequency of administration of the drug of the present invention to humans vary depending on the dosage form, age and weight of the patient, the nature or severity of the symptoms to be treated, etc., but usually an adult (body weight 60 kg) per day, L- Citrulline (amount converted to free citrulline) is orally 400 mg to 10 g, preferably 400 mg to 5 g, more preferably 400 mg to 3 g, still more preferably 500 mg to 2 g, most preferably 800 mg to 2 g. Administer once to several times daily. The dose of the eye drops or the like is converted from the above oral dose and administered once or multiple times.

Regarding the oral dose of the drug of the present invention to humans, the blood citrulline concentration when L-citrulline was orally administered to rodents (Kobayashi et al., Pharmacognosy Research, 6(4) 2014), and L - It can be derived from the relationship with blood citrulline concentration when citrulline is orally administered to humans (Moinard et al., British Journal of Nutrition, 99(4) 2008). That is, oral administration of about 1 g of L-citrulline per kg body weight per day to rodents corresponds to oral administration of about 0.8 g of L-citrulline per day to humans. As shown in the examples below, oral administration of 0.5 g of L-citrulline per 1 kg of rat body weight per day for 9 weeks inhibited the progression of cataracts. It is calculated that approximately 0.4 g of L-citrulline orally administered per adult per day is required to achieve this.
The administration period is not particularly limited, but is usually 1 day to 1 year, preferably 2 weeks to 6 months, most preferably 9 weeks to 3 months.

Moreover, 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").
Non-human animals include animals other than humans, such as mammals, birds, reptiles, amphibians, and fish.

Therefore, the medicament of the present invention can also be provided as a medicament for preventing or suppressing blurred vision in non-human animals.
The dosage of the drug of the present invention when administered to non-human animals varies depending on the animal type, age, nature or severity of symptoms, etc., but is usually L-citrulline (free form) per 1 kg of body weight per day. The dose (converted to citrulline) is 10 mg to 5 g, preferably 100 mg to 2 g, once or several times a day.

The administration period is not particularly limited, but is usually 1 day to 1 year, preferably 2 weeks to 3 months.

The composition of the present invention can also be provided as a food for preventing or suppressing blurred vision (hereinafter sometimes referred to as "the food of the present invention"). The food of the present invention also includes food additives.

A food additive, which is one aspect of the food of the present invention (hereinafter sometimes referred to as "food additive of the present invention"), can be produced by the same method as the pharmaceutical preparation of the present invention.
The food additive of the present invention can be processed and manufactured in the form of powder, granules, pellets, tablets, and various liquids, for example.

The food of the present invention includes, for example, juices, soft drinks, teas, lactic acid bacteria beverages, fermented milk, frozen desserts, butter, cheese, yogurt, processed milk, dairy products such as skimmed milk, and meat products such as ham, sausages and hamburgers. , kamaboko, bamboo rings, fish paste products such as satsumaage, dashi rolls, egg products such as egg tofu, cookies, jelly, chewing gum, candy, confectionery such as snacks, bread, noodles, pickles, smoked products, dried fish, tsukudani, It may be in any form such as salted products, soups, seasonings, etc., and may be bottled food, canned food, or retort pouch food.

Also, the food of the present invention may be in the form of powder, sheet, capsule, tablet, jelly, or the like.
Furthermore, the food of the present invention is a food for specified health use for preventing and suppressing blurred vision, a food with nutrient function claims, a food with health claims such as food and drink with function claims, a food for sick people, a food for the elderly such as food for special uses, and a health food. It can be provided as a supplementary food or the like.

The food of the present invention and the food additive of the present invention include additives generally used in food, such as sweeteners, coloring agents, preservatives, and thickening agents described in the Food Additive Labeling Handbook (Japan Food Additives Association). Viscosity stabilizers, antioxidants, color formers, bleaching agents, antifungal agents, gum bases, bittering agents, enzymes, brightening agents, acidulants, seasonings, emulsifiers, reinforcing agents, manufacturing agents, fragrances, spice extracts, etc. may be added.

The food of the present invention can be processed and manufactured by using a general food manufacturing method, except that L-citrulline is added to the food or added in the form of the above food additives. can.
In addition, when the food of the present invention is a solid food such as granules, for example, fluid bed granulation, stirring granulation, extrusion granulation, rolling granulation, airflow granulation, compression molding granulation, crushing granulation , granulation methods such as spray granulation and injection granulation, coating methods such as pan coating, fluidized bed coating and dry coating, expansion methods such as puff drying, excess steam method, foam mat method, microwave heating method, extrusion granulation It can also be produced using an extrusion method such as a machine or an extruder.

The amount of L-citrulline to be added to the food of the present invention is appropriately determined according to the type of food, the expected effects of ingestion of the food, etc. The amount added is usually 0.1% to 100% by weight, preferably 0.5% to 80% by weight.
In addition, the content of L-citrulline in the food additive of the present invention is such that when the food additive of the present invention is added to the food, the content of L-citrulline in the food is within the above range. set.

The intake amount, intake frequency, and intake period of the food of the present invention are the same as the dosage for humans of the pharmaceutical of the present invention.

When the food of the present invention is provided as a food with health claims, a food for special uses, a health supplement, or the like, the intake per meal calculated from the intake of the food of the present invention described above is It is preferably included in the food in the form of packaging or filling in units. Here, "food in the form of being packaged or filled in units of one meal intake" means that the amount of food to be taken at one time is packed or filled in a container such as a bag, box, bottle, or the like. It means that there is

The composition of the present invention can also be provided as a feed for preventing or suppressing blurred vision (hereinafter sometimes referred to as "feed of the present invention"). The feed of the present invention also includes feed additives.

A feed additive that is one aspect of the feed of the present invention (hereinafter sometimes referred to as "feed additive of the present invention") is, like the food additive of the present invention, produced according to the method for producing the pharmaceutical of the present invention. can be manufactured. The feed additive of the present invention is produced by mixing or dissolving other feed additives, if necessary, and processing and producing, for example, powders, granules, pellets, tablets, and various liquid formulations.

The feed of the present invention can be processed and manufactured by adding L-citrulline or a feed additive containing L-citrulline to a feed for non-human animals and using a general feed manufacturing method. can.
As the feed for non-human animals, any feed for non-human animals such as mammals, birds, reptiles, amphibians or fish may be used. livestock feeds, poultry feeds such as chickens and turkeys, and farmed fish feeds such as tuna, sea bream and yellowtail.

Non-animal feeds that can be used in the present invention include cereals, rice brans, vegetable oil cakes, animal feeds, other feeds, refined products, and the like.

Examples of grains include milo, wheat, barley, oats, rye, brown rice, buckwheat, millet, millet, millet, corn, and soybeans.
Examples of brans include rice bran, defatted rice bran, wheat bran, wheat germ, barley bran, corn bran, corn germ and the like.
Examples of vegetable oil cakes include soybean cake, linseed cake, cottonseed cake, peanut cake, safflower cake, coconut cake, palm cake, sesame cake, sunflower cake, rapeseed cake, and kapok. Oil cake, mustard oil cake and the like can be mentioned.
Examples of animal feeds include fish meal (North Sea meal, imported meal, whole meal, coastal meal, etc.), fish soluble, meat meal, meat-and-bone meal, blood meal, decomposed hair, bone meal, livestock processing by-products, feather meal, silkworm, Skim milk powder, dried whey and the like can be mentioned.
Other feeds include plant stems and leaves (alfalfa, hay cube, alfalfa leaf meal, pseudoacacia powder, etc.), corn processing industrial by-products (corn gluten meal, corn gluten feed, corn staple liquor, etc.), processed starch products (starch, etc.). , sugar, fermented industrial products (yeast, beer lees, malt roots, alcohol lees, soy sauce lees, etc.), agricultural production by-products (citrus processed lees, tofu lees, coffee lees, cocoa lees, etc.), cassava, broad beans, guamir, seaweed, Examples include krill, spirulina, chlorella, and minerals.
Refined products include proteins (casein, albumin, etc.), amino acids, carbohydrates (sucrose, glucose, etc.), minerals, vitamins, and the like.

Further, the feed of the present invention can be prepared by, for example, fluidized bed granulation, stirring granulation, extrusion granulation, rolling granulation, airflow granulation, compression molding granulation, crushing granulation, spray granulation, injection granulation, and the like. Coating methods such as granulation method, pan coating, fluid bed coating, dry coating, puff drying, excess steam method, foam mat method, microwave heating method, etc., extrusion method such as extrusion granulator and extruder, etc. It can also be produced as a solid feed such as granules.

The amount of L-citrulline to be added to the feed of the present invention is appropriately determined according to the type of feed, the effect expected from ingestion of the feed, etc. ), it is usually added in an amount of 0.1% to 100% by weight, preferably 0.5% to 80% by weight.
In addition, the content of L-citrulline in the feed additive of the present invention is adjusted so that when the feed additive of the present invention is added to feed, the content of L-citrulline in the feed falls within the range described above. set.

The intake amount, intake frequency, and intake period of the feed of the present invention are the same as the dosage for non-human animals in pharmaceutical formulations.

The pharmaceutical, food, feed, and other compositions of the present invention described above exhibit an excellent effect of preventing or suppressing blurred vision.
Therefore, the composition of the present invention is preferably used for people in occupations that overwork their eyes and elderly people who complain of blurred vision with aging. In addition, in the present invention, the term "elderly people" generally refers to people aged 60 and over.
In addition, the composition of the present invention is preferably used for pets that are expected to have cataracts.

The present invention also provides methods for preventing or suppressing blurred vision in humans and non-human animals (hereinafter sometimes referred to as "methods of the present invention").
The method of the present invention comprises the step of allowing a subject animal intended to prevent or suppress blurred vision to ingest L-citrulline or a salt thereof in an amount necessary to prevent or suppress blurred vision in the subject animal. including.

Animal subjects include humans and non-human animals.
In the case of humans, the method of the present invention is not particularly limited as long as the subject feels blurred vision.
In the case of non-human animals, mammals raised for meat such as cattle, pigs, sheep, goats and rabbits, and mammals raised for labor such as alpacas, horses, mules, camels and donkeys. It is suitably applied to livestock, poultry raised for meat such as ducks, chickens, geese, turkeys and quails, and cultured fish such as tuna, sea bream and yellowtail.

In the method of the present invention, L-citrulline or a salt thereof is ingested by the subject animal in the form of the pharmaceutical, food, or feed of the present invention.
The intake of L-citrulline or a salt thereof is determined according to the type, age, symptoms or condition of the target animal, but in the pharmaceuticals of the present invention, the doses similar to those described above are used for humans and non-human animals. Amounts can be taken at the times and durations described above.

EXAMPLES The present invention will be described in more detail below with reference to examples, but the scope of implementation of the present invention is not limited by these examples.

Streptozotocin (65 mg/kg) was intravenously administered to 6-week-old male Wistar rats to develop diabetes, and 5% glucose water was given as drinking water to prepare ultrahyperglycemic model rats, which were used as a cataract progression model. and Experiments included a control group (n = 7) in which streptozotocin solvent was administered through the tail vein, and a diabetic (DM) group (n = 7) in which streptozotocin (65 mg/kg) was administered through the tail vein and then 5% glucose water was given as drinking water. 9), and the DM group was treated with 3 doses of L-citrulline (0.5, 1 or 2 g/kg body weight/day) as DM + Cit group (n = 5 in each group), and L-citrulline was mixed in drinking water. was administered orally for 9 weeks. Changes in the lens image were observed over time using a shadowless illumination lens observation device for small animals until 9 weeks after the formation of hypermature cataracts in the DM group. Subsequently, the cataract score by the lens opacification classification method and the degree of opacity in the central part of the lens by image analysis were quantified to evaluate the onset and progression of cataract. Furthermore, the L-citrulline concentration in the lens at 9 weeks was quantified.

The cataract score was determined from each lens image based on the criteria classified into the following 6 stages, and expressed as the average value for each group.
Score 0: No opacification Score 1: Peripheral lens opacification Score 2: Peripheral and central lens opacification (cortex) Score 3: Widespread opacification in lens cortex Score 4: Nuclear cataract Score 5: Hypermaturity Cataract

As a result, in the DM group, opacification first developed in the peripheral part of the lens, and in the third week after the onset of diabetes, opacification was also observed in the central part. Thereafter, the range of opacification of the lens expanded and the degree of opacity gradually increased, and at the 9th week, a finding that the entire lens became strongly opacified was observed.
When quantified as a cataract score, in the DM+Cit group, progression of cataract was inhibited from week 4 onwards, and significant inhibition of progression of cataract was observed from week 8 to 9 (Fig. 1).
In addition, the quantitative results of the central lens opacity showed that the DM+Cit group significantly suppressed the progress of lens opacification, as in the case of the cataract score, compared to the diabetes group (Fig. 2).
A significant increase in L-citrulline concentration in the lens at 9 weeks after the onset of diabetes was observed in all doses compared to the control group and the DM group (Fig. 3).

From this, it was clarified for the first time that administration of L-citrulline from the early stage of cataract development to the progression process increases the concentration of L-citrulline in the lens and effectively suppresses opacification of the lens. It has been shown to be an excellent cataract preventive or inhibitor.

The present invention provides a composition that is orally effective in preventing or suppressing cataracts, blurred vision resulting therefrom, or subjective symptoms associated with aging of the lens, such as blurred or blurred vision due to opacification of the lens. can be done.

Claims (3)

A composition containing citrulline or a salt thereof as an active ingredient for preventing or suppressing blurred vision caused by cataracts (excluding those in the form of agricultural and marine products or processed products thereof). 2. The composition of claim 1 , which is a food. 2. The composition of claim 1, which is a pharmaceutical.

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