JP7500278B2 - Oral medication to improve pupil accommodation - Google Patents

Description

The present invention relates to an oral medication for improving pupil accommodation function.

As electronic devices become more widespread, working at VDTs (visual display terminals) for long periods of time can cause various eye problems for modern people. One of the eye problems is a symptom where light is too bright when it hits the eye. One of the causes of this symptom is an inability to properly regulate the amount of light entering the eye, in other words, poor pupil adjustment.

Pupil regulation is achieved by the action of the sphincter pupillae, which is involved in pupil constriction, and the dilator pupillae, which is involved in pupil dilation. With regard to the autonomic nerves that control the movement of these muscles, there was a time when it was believed that the sphincter pupillae was controlled by the parasympathetic nerves, and the dilator pupillae was controlled by the sympathetic nerves. However, in reality, histological and electrophysiological studies have made it clear that the sphincter pupillae is also distributed by adrenergic nerves, and the dilator pupillae is also distributed by cholinergic nerves (Non-Patent Document 1). In other words, when the pupil constricts, the sphincter pupillae is also controlled by adrenergic nerves, and when the pupil dilates, the dilator pupillae is also controlled by cholinergic nerves. Thus, pupil regulation is achieved by a complex nervous reaction in which nerves that bring about opposing reactions work simultaneously, both when the pupil constricts and when the pupil dilates.

On the other hand, various ingredients have been reported to be effective in alleviating various eye symptoms. Specifically, vitamins such as vitamin B1 (Patent Document 1), vitamin B12, vitamin E, and vitamin A, astaxanthin (Non-Patent Document 2), anthocyanin (Non-Patent Document 3), black soybean husk extract (Non-Patent Document 4), and DHA (Non-Patent Document 5) are known.

Pupillary nerve mating. Neurology 2:29 (4) :357-368, 1988. J. Clin. Biochem. Nutr., 2013, 53(1),1-7. Pharmacology and Therapeutics., 2007, 35(5), 447-455. Journal of Clinical Ophthalmology, 2005, 98(11), 982-986. Invest. Ophthalmol. Vis. Sci. 2007, 48(2), 756-762.

JP 2002-302446 A

As mentioned above, pupil accommodation is based on a unique mechanism in which nerves that produce opposing responses work simultaneously during both pupil constriction and pupil dilation, so it is not known what kind of action can be applied to improve pupil accommodation.

For example, the ingredients known to be effective in relieving various eye symptoms work by improving blood flow or relaxing the ciliary body, and therefore cannot improve the pupil's accommodation function.

In addition, even if the muscles that control pupil adjustment are controlled by the autonomic nervous system, if an oral drug with a psychotropic effect is administered, such an oral drug will cause the parasympathetic nervous system to become dominant or will facilitate a smooth switch between the sympathetic and parasympathetic nervous systems, and therefore is not thought to work to improve the pupil adjustment function.

For this reason, oral medications that can improve pupil accommodation are desirable.

Therefore, the present invention aims to provide an oral medication that improves the pupil's accommodation function.

After extensive research, the inventors discovered that Keishikaryukotsuboreito has the effect of improving the pupil's accommodation function. Based on this knowledge, the present invention was completed through further research.

That is, the present invention provides the following aspects.
Item 1. An oral medication for improving pupil accommodation function, containing Keishikaryukotsu-boreito extract.
Item 2. The oral medication according to Item 1, which is used to improve miosis in a bright place.

The present invention provides an oral medication that improves pupil accommodation function.

The oral medication of the present invention contains Keishikaryukotsuboreito extract and is characterized by its use in improving pupil accommodation function. The oral medication of the present invention is described in detail below.

Keishikaryukotsuboreito extract Keishikaryukotsuboreito is preferably a Kampo prescription described in "New Guide to General Kampo Prescriptions" (supervised by Yukihiro Goda and Takashi Hakamzuka, edited by the Japan Kampo Herbal Medicine Preparation Association, published by Jiho Co., Ltd.), specifically, a mixture of herbs consisting of cinnamon bark, peony root, Chinese sage, scutellaria root, borei root, licorice, and ginger can be mentioned. Keishikaryukotsuboreito also includes the mixture of herbs (Kampo prescriptions) described in currently widely used Kampo-related letters, as stipulated in the "Basic Handling Policy for Kampo Preparations" established by the Kampo Herbal Medicine Investigation Committee.

The amounts of each herb that makes up Keishikaryukotsuboreito include 1-4 parts by weight, preferably 1.5-3 parts by weight, of cinnamon bark; 1-4 parts by weight, preferably 1.5-3 parts by weight, of peony root; 1-4 parts by weight, preferably 1.5-3 parts by weight, of taiso stalk; 0.75-3 parts by weight, preferably 1-2 parts by weight, of rye sprouts; 0.75-3 parts by weight, preferably 1-2 parts by weight, of boraeolus root; 0.5-2 parts by weight, preferably 0.75-1.5 parts by weight, of licorice root; and 0.25-1.5 parts by weight, preferably 0.5-1 part by weight, of ginger.

Suitable examples of herbal medicine preparations used in the manufacture of Keishikaryukotsu-boreito extract for use in the present invention include 2 parts by weight of Cinnamon Bark, 2 parts by weight of Peony Root, 2 parts by weight of Taisou Root, 1.5 parts by weight of Ryukotsu Root, 1.5 parts by weight of Borei Root, 1 part by weight of Licorice Root, and 0.5 parts by weight of Shokyo Root.

The extract form of Keishikaryukotsuboreito may be either a liquid extract such as a soft extract, or a solid dry extract powder.

The liquid extract of Keishikaryukotsu-Mori-to can be obtained by subjecting the mixed herbs according to the Keishikaryukotsu-Mori-to prescription to an extraction process and concentrating the resulting extract as necessary. The dried extract powder of Keishikaryukotsu-Mori-to can be obtained by drying the liquid extract.

In the production of Keishikaryukotsubourito extract, the extraction solvent used in the extraction process is not particularly limited, and may be water or aqueous ethanol. The extraction process for Keishikaryukotsubourito is not particularly limited, and may be, for example, a method in which extraction is performed with about 5 to 10 times the total weight (converted to dry weight) of the crude drugs contained in Keishikaryukotsubourito, followed by concentrating to 1/2 the volume and removing the solids to obtain a liquid extract of Keishikaryukotsubourito. Furthermore, this liquid extract is subjected to a drying process to obtain a dried extract powder of Keishikaryukotsubourito. The drying process is not particularly limited, and may be performed by any known method, and may be, for example, a spray drying method or a method in which a suitable adsorbent (e.g., silicic anhydride, starch, etc.) is added to a soft extract with a high extract concentration to obtain an adsorbed powder.

When an extract is used as Keishikaryukotsu-Mori-to in the present invention, an extract prepared by the above-mentioned method may be used, or a commercially available product may be used. For example, Keishikaryukotsu-Mori-to dried extract-F (manufactured by Alps Pharmaceutical Co., Ltd.) is a known product as a dried extract powder of Keishikaryukotsu-Mori-to, and is also commercially available.

In the oral medication of the present invention, the content of Keishikaryukotsu-Morito extract is not particularly limited as long as the effects of the present invention are achieved, but is usually 5 to 100% by weight, preferably 10 to 90% by weight, more preferably 20 to 80% by weight, and even more preferably 30 to 60% by weight, calculated as the amount of dried extract powder of Keishikaryukotsu-Morito extract. In the present invention, the amount of dried extract powder of Keishikaryukotsu-Morito refers to the amount of the dried extract powder itself when Keishikaryukotsu-Morito is used, and refers to the amount of the residue after removing the solvent when a liquid extract of Keishikaryukotsu-Morito is used. In addition, when the dried extract powder of Keishikaryukotsu-Morito contains additives such as adsorbents added during production, the amount refers to the amount excluding the additives.

Other components The oral medicine of the present invention may be composed of Keishikaryukotsuboreito extract alone, or may contain additives and bases according to the formulation. Such additives and bases are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include excipients, binders, disintegrants, lubricants, isotonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, flavorings, fragrances, powders, thickeners, dyes, chelating agents, etc. These additives may be used alone or in combination of two or more. The content of these additives and bases is appropriately set according to the types of additives and bases used, the formulation form of the oral medicine, etc.

In addition, the oral medication of the present invention may contain other nutritional components and pharmacological components as necessary, in addition to the Keishikaryukotsuboreito extract. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzymes, sedatives, hypnotics, antihistamines, caffeine, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, vitamins, and menthols. These nutritional components and pharmacological components may be used alone or in combination of two or more. The content of these components is appropriately set depending on the type of components used, the formulation form of the oral medication, and the like.

The formulation form of the oral drug of the present invention is not particularly limited as long as it can be administered orally, and examples of the formulation include solid formulations such as powders, fine granules, granules (including dry syrup), tablets, pills, capsules (soft capsules, hard capsules), etc.; semi-solid formulations such as jellies; and liquid formulations such as liquids, suspensions, syrups, etc. Among these formulation forms, solid formulations are preferred from the viewpoints of the stability of the ingredients contained therein, portability, etc.

To prepare the oral medication of the present invention in the above-mentioned formulation form, the Keishikaryukotsuboreito extract, and additives, bases, and pharmacological ingredients added as necessary may be used to formulate the drug in accordance with the usual formulation methods used in the pharmaceutical field.

The oral medication of the present invention is used for the purpose of improving pupil accommodation function. The subjects who need to improve pupil accommodation function include people who feel excessive glare when exposed to bright light. That is, more specifically, the oral medication of the present invention is used for the purpose of improving miosis in bright places.

More specific examples of people who require improvement in pupil accommodation include people with presbyopia, who are prone to a decline in pupil accommodation, but people who do not have presbyopia can also be included as long as they have a decline in pupil accommodation.

Dosage and Usage: The oral drug of the present invention is administered orally. The dosage of the oral drug of the present invention is appropriately set according to the age, sex, constitution, severity of symptoms, etc. of the person to be administered. For example, the oral drug of the present invention may be administered in an amount equivalent to about 0.2 to 20 g, preferably about 0.5 to 10 g, more preferably about 1 to 5 g, and even more preferably about 1.5 to 3 g of dried extract powder per person per day, 1 to 3 times a day, preferably 2 or 3 times a day. The timing of administration is not particularly limited, and may be before, after, or between meals, but is preferably before (30 minutes before a meal) or between meals (2 hours after a meal).

The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

The raw herbs used for the preparation of Keishikaryukotsu-boreito extract powder were 2 parts by weight of cinnamon, 2 parts by weight of peony root, 2 parts by weight of taiso, 1.5 parts by weight of rheum rhizome, 1.5 parts by weight of borei, 1 part by weight of licorice, and 0.5 parts by weight of ginger, which were then chopped and extracted with 20 times the weight (210 parts by weight) of water at about 100°C for 1 hour, centrifuged to obtain an extract, which was concentrated under reduced pressure and dried using a spray dryer to obtain Keishikaryukotsu-boreito extract powder. The Keishikaryukotsu-boreito extract powder obtained was 25g per 105g of raw herb mixture. The drying using the spray dryer was performed by dropping the extract into an atomizer at a rotation speed of 10,000 rpm and supplying hot air at 150°C.

Test Example Seven subjects who felt excessive glare when exposed to bright light were given 2.3g of Keishikaryukotsuboreito extract powder per day (calculated as the amount of dried extract, given twice in a single dose before or after meals) for one week (Example 1). After a four-week non-medication period, they were given a commercially available drug known to be effective in alleviating eye symptoms (100mg vitamin B1, 60μg vitamin B12, 50mg vitamin E, 100mg hepronicate, 60mg oxoamidine powder, 300mg magnesium potassium L-aspartate, and 10mg gamma-oryzanol per day (3 tablets)) once a day for one week (Comparative Example 1).

Before and after taking the drug (Example 1 and Comparative Example 1), light was applied to the eye in a dark place, and the pupils at the time when miosis was completed were photographed using a digital single-lens camera α6000 (Sony Corporation) connected to a slit lamp BQ900 LED (Japan Focus Co., Ltd.), and the pupil diameter (mm) was measured using ImageJ and the average was calculated. The results are shown in Table 1.

As shown in Table 1, in Comparative Example 1, the pupil diameter did not shrink compared to before administration, and no miosis improvement effect in bright places was obtained, but in Example 1, the pupil diameter shrank compared to before administration, and miosis improvement effect in bright places was obtained. In other words, it was confirmed that the administration of Keishikaryukotsuboreito extract improved the pupil accommodation function. Furthermore, pupil accommodation function improved in 6 out of 7 subjects.

Furthermore, when participants were asked about the effect of the drug on improving the sensation of excessive glare when exposed to bright light before taking the drug, 86% of participants in Example 1 answered "Satisfied" or "Somewhat Satisfied" (43% answered "Satisfied"), whereas in Comparative Example 1 the figure was only 14% (0% answered "Satisfied").

Claims (1)

An oral medication containing Keishikaryukotsuboreito extract, used to improve pupillary accommodation function and to improve miosis in bright places.