JP4504063B2 - Sleep improvement medicine - Google Patents

Description

  The present invention relates to a novel sleep improving drug containing an antihistamine and a specific herbal medicine.

  Many people are suffering from insomnia due to stress society and poor environment. According to a survey result that 80% of modern people have insomnia, it is said that more than 1 out of 5 Japanese people suffer from insomnia.

  For such insomnia, drugs with antihistamines as active ingredients relieve temporary insomnia that does not require over-the-counter drugs or prescriptions in the United States, the United Kingdom, Germany, Canada, and other Western countries. It is used as a sleep improving drug.

  By the way, even if you say insomnia, depending on the condition, you may have trouble falling asleep (even if you go to sleep and go into a futon, you can't sleep well), a deep sleep disorder (even if you intend to have plenty of sleep time, you feel a good night's sleep) Do not wake up), awakening in the middle (awake many times in the night, then it is difficult to fall asleep again), early awakening (wakes up early in the morning and still wants to sleep, but cannot sleep) There are various types. For such various types of insomnia patients, an antihistamine alone may not provide a sufficient effect as a sleep improver.

  On the other hand, hypnotic sedatives and herbal medicines such as herbal extracts are also used as over-the-counter drugs. However, these need to be taken between meals two to three times a day, so the dosage is complicated and poor compliance, it is difficult to fully exert the effect, it may take a long time to manifest the effect, it is busy It was difficult to use to improve the temporary insomnia of modern people.

It has been proposed that the hypnotic / sedative action is enhanced by using diphenhydramine hydrochloride or chlorpheniramine maleate, which is an antihistamine, and an extract of Western Chabodiadia (Patent Document 1). In addition, a hypnotic composition in which diphenhydramine hydrochloride and valerian (valerian) and / or acid soy sauce are used in combination has been proposed (Patent Document 2). However, western chabodia is effective in lowering blood pressure and is difficult to use for patients with low blood pressure. On the other hand, long-term use of valerian has headaches, palpitation and muscle spasms, and acidulose has rare side effects of gastrointestinal diseases. Therefore, a safer and more effective sleep-improving drug has been desired. Furthermore, combining these herbal medicines, which are considered to have a sedative effect, and antihistamines such as diphenhydramine into a sleep-improving drug raises doubts about the safety as an over-the-counter drug.
JP-A-4-36243 Japanese Patent Laid-Open No. 10-17482

  Therefore, the present invention is superior in safety as an over-the-counter drug, and more patients can use the hypnotic action of antihistamines, and many modern people such as “bad sleep” and “slow sleep” The purpose is to provide a sleep-improving drug that can relieve the temporary insomnia that is held once a day by taking before sleeping and ensure a comfortable sleep.

  As a result of intensive studies in view of these circumstances, the present inventors have found that the above-mentioned problems can be solved by blending a specific herbal medicine with an antihistamine, and have completed the present invention.

  That is, the present invention is selected from the group consisting of antihistamines, fishing rattan hops, hops, carrots, oats, mistletoe, licorice, camellia, nematodes, mothers, celestial stars, peony skin, potentilla, chamomile, birch and linden. The present invention provides a sleep-improving drug characterized by blending one or more herbal medicines.

  The sleep-improving drug of the present invention, in which a specific herbal medicine is blended with an antihistamine, is superior in that it has a high sleep-improving effect and does not cause side effects due to components contained in the sleep-improving drug.

  The antihistamine used in the present invention is not particularly limited as long as it has an anti-H1 histamine action, but anti-H1 histamine such as ethanolamine, phenothiazine, piperazine, piperidine, propylamine and the like can be used. .

  Preferred examples of such anti-H1 histamine drugs include diphenhydramine, doxylamine, clemastine, diphenylpyralin, carbinoxamine, etc. for ethanolamines, promethazine, mequitazine, alimemazine, isotipezil, etc. for phenothiazines, Examples of hydroxyzine, homochlorocyclidine, etc. include piperidine, hydroxyzine, cyproheptadine, etc., and propylamine, chlorpheniramine, triprolidine, brompheniramine and the like. These anti-H1 histamine drugs may be used alone or in combination of two or more. More preferable specific examples include ethanolamine anti-H1 histamine drugs such as diphenhydramine, doxylamine, clemastine, diphenylpyralin and carbinoxamine. Among these ethanolamine anti-H1 histamine drugs, it is particularly preferable to use diphenhydramine or doxylamine.

  These antihistamines may be used as they are as the free base, but hydrochloric acid, citric acid, succinic acid, salicylic acid, diphenyldisulfonic acid, tartaric acid, tannic acid, theocric acid, lauryl sulfuric acid, sulfuric acid, pamoic acid, hibenzic acid, maleic acid, etc. It may be an acid addition salt.

  For example, preferred acid addition salts when diphenhydramine is used as an antihistamine include diphenhydramine hydrochloride, diphenhydramine citrate, and diphenhydramine tannate, and particularly preferred acid addition salts include diphenhydramine hydrochloride. The preferred acid addition salt of doxylamine is doxylamine succinate, the preferred acid addition salt of clemastine is clemastine fumarate, the preferred acid addition salt of diphenylpyraline is diphenylpyraline teocrate, diphenylpyraline hydrochloride, the preferred acid of carbinoxamine An example of the addition salt is carbinoxamine maleate.

  In the present invention, the dose of the antihistamine necessary for obtaining the sleep effect varies depending on each antihistamine, and also varies depending on the type of the free base or its acid addition salt. Although it cannot be said, it is preferable to be about 10 to 200 mg per adult.

  For example, when diphenhydramine hydrochloride or diphenhydramine citrate is used as the anti-H1 histamine drug, the dose per adult is preferably 25 to 75 mg, particularly preferably 50 mg. When doxylamine succinate is used, the dose per adult is preferably 12.5 to 50 mg, particularly preferably 25 mg. When clemastine is used, the dose per adult is preferably 1-2 mg, and when diphenylpyralin is used, the dose per adult is preferably 1-12 mg. When carbinoxamine maleate is used, the dose per adult is preferably 4 to 12 mg.

  The sleep-improving drug of the present invention includes, in the above-mentioned amount of antihistamine necessary for obtaining a sleeping effect, fishing rattan, hops, carrots, oats, mistletoe, licorice, camellia, senkyu, acquaintance, Tennansei, What is necessary is just to mix | blend 1 type, or 2 or more types of crude drugs chosen from the group which consists of peony skin, potentilla, chamomile, hippopotamus, and linden. Among these herbal medicines, it is particularly preferable to add fishing rattan and / or hops. These crude drugs will be described below.

  Among the above herbal medicines, Uncariae Uncis Cum Ramulus is a thorn such as Rubiaceae, and contains alkaloids such as lincophylline, corinoxein, isolincofilin, hirustatin, nicotinic acid and the like.

  Hops (Humulus lupulus) is the fruit head of the genus Humurus, which is another name of the genus Cyprus, volatile oils such as humulene, humulone, lupron, bitter components such as lupurin containing valeric acid, flavonoids, phenolic tannins, estrogen-like substances, asbaragins Etc.

  Carrots (Ginseng Radix) are roots obtained by removing fine roots of the rotaceae ginseng or lightly boiled, and contain triterpenoid saponins, ginsenosides, acetylene compounds, panaxanes, sesquiterpenes, and the like. In the present invention, roots of Siberian carrot (Ezocogi) may be used.

  The oat (Avena sativa) contains saponins, alkaloids, sterols, flavonoids, salicylic acid, starch, protein, vitamin B, calcium, silicon, iron, manganese, zinc, and other minerals.

  Mistletoe (Viscum album) is a branch, treetop, stem and leaf of mistletoe belonging to the mistletoe family, and contains glycoproteins, polypeptides (viscotoxins), flavonoids, caffeic acid and other acids, lignans, acetylcholine, etc. To do.

  Licorice (Glycyrrhizae Radix) is the root and stron of leguminous licorice or other related plants, including terpene saponins such as glycyrrhizic acid, flavonoids such as isoflavones, liquirutin, isoliquiltin, and formonetin, polysaccharides, sterols, coumarins, asparagine, etc. contains.

  Poria is a pine sclerotia of the pine moss family, and contains β-pachyman, β-pachymase, pachylic acid and the like.

  Senkyu (Cnidii Rhizoma) is a boiled rhizome of the celery family, and usually contains kunidylide, neokunidiland, kunidinium lactone, ligustide, kunidinic acid, sedanonic acid and the like.

  The mother (Anemarrhenae Rhizoma) is a rhizome of the lily family, and contains triterpenoids and saponins such as timosaponin and salsasapogenin, xanthone compound, vitamins such as nicotinic acid and pantothenic acid.

  The Tenansei (Arisaematis Tuber) is a tuber excluding the cork layer of the potato family, Myrtennanshou or other related genera, and contains saponins, starches, amino acids, oxalic acid, formic acid, and the like.

  Peony bark (Moutan Cortex) is the root bark of the button family button and contains monoterpene glycosides, phenols, tannins, sucrose and the like.

  Potentilla anserina L. is a whole plant of the rosaceae Yostulkinbai and contains ellagitaninin, flavonoids, choline, bitterness and the like.

As chamomile, either German chamomile or Roman chamomile may be used. Among them, Jatricia recutita (Matricaria recutita L.) is a flower part of the family Asteraceae, camomile, volatile oils such as proazulene, farnesine, α-bisabolol, spiroether, flavonoids such as antemidin, luteolin and rutin. , Bitter glycosides such as antemic acid, coumarin, and tannin. In addition, Roman chamomile (Antbemis
nobolis) is a flower part of the asteraceae Roman Camille, which contains volatile oils such as tiglic acid ester, angelic acid ester and camazulene, sesquiterpene lactone, flavonoid, coumarin and phenolic acid.

  Hippopotamus (Piper methysticum) is the root of Pepperaceae Kawakawa, which contains a resin containing Kawalactone, including Kawaine, and piperdin alkaloids such as Pipermethicine.

  Linden (Tilia spp.) Is a lime flower such as the lindenaceae linden, scallop and bonito, and contains flavonoids such as quercetin and kaempferol, caffeic acid, tannin, volatile oil and the like.

  In the present invention, the herbal medicine may be used as it is, or an extract such as a dry extract, flow extract, soft extract, tincture or essential oil may be used. Furthermore, the doses of these herbal medicines vary depending on each herbal medicine and cannot be generally stated, but are approximately 0.5 mg to 100 g in terms of dry weight of crude drug per adult. It should be noted that this dose may not be such an amount that these herbal medicines are generally capable of exhibiting conventionally known effects, such as a hypnotic effect or a sedative effect, and is preferred.

  For example, the compounding amount when using a fish rattan as a crude drug is usually in the range of 0.05 to 8 g, preferably 0.1 to 6 g in terms of dry weight of the crude drug as a dose per adult. Yes, more preferably from 0.15 to 4 g. This amount is usually in the range of about 4 to 800 mg, preferably about 8 to 600 mg, and more preferably about 12 to 450 mg in the extract, for example, as a dry extract.

  The compounding amount when using hops is usually in the range of 5 mg to 4 g, preferably 10 mg to 3 g, more preferably 20 mg to 2 g in terms of dry weight of the active pharmaceutical ingredient, as a dose per adult. . In the extract, for example, as a dry extract, it is usually in the range of about 0.25 to 480 mg, preferably about 0.5 to 360 mg, more preferably about 1 to 240 mg. Usually, it is in the range of about 0.005 to 4 mL, preferably about 0.01 to 3 mL, and more preferably about 0.02 to 2 mL.

  The compounding amount when using carrots is usually in the range of 0.5 mg to 10 g, preferably 1 mg to 6 g, more preferably 1.5 mg as a dose per adult, as a dose per adult. ~ 3g. This amount is usually in the range of about 0.02 to 2700 mg, preferably about 0.01 to 1600 mg, and more preferably about 0.06 to 800 mg as an extract, for example, as a dry extract or a soft extract. The flow extract is usually in the range of about 0.0005 to 10 mL, preferably about 0.001 to 6 mL, and more preferably about 0.0015 to 3 mL.

  The compounding amount when using auto is usually in the range of 0.001 to 100 g, preferably 0.01 to 20 g, more preferably 0, as a dose per adult, in terms of dry weight of the active ingredient. .1-4g. In the extract, for example, as a dry extract, it is usually in the range of about 0.05 to 26000 mg, preferably about 0.5 to 5200 mg, and more preferably about 5 to 1040 mg.

  The compounding amount when using mistletoe is usually in the range of 0.004 to 4 g, preferably 0.01 to 2 g, more preferably as the dose per adult, in terms of dry weight of the active ingredient. 0.02 to 1 g. In the extract, this amount is usually in the range of about 1 to 200 mg, preferably about 2.5 to 100 mg, and more preferably about 5 to 50 mg, for example, as a dry extract.

  The amount of licorice used is usually in the range of 0.01 to 5 g, preferably 0.05 to 3 g, more preferably 0, as a dose per adult, as a dose per adult. 0.1 to 1.5 g. In the extract, this amount is usually in the range of about 2 to 1500 mg, preferably about 10 to 900 mg, more preferably about 20 to 450 mg as a dry extract, and usually about 2.5 to about 2.5 mg as a soft extract. It is in the range of about ˜1250 mg, preferably about 12.5 to 750 mg, and more preferably about 25 to 375 mg.

  The compounding amount when using acupuncture is usually in the range of 0.01 to 9 g, preferably 0.05 to 6 g, more preferably 0, as a dose per adult, in terms of dry weight of the active ingredient. 0.1 to 3 g. This amount is usually in the range of about 0.3 to 300 mg, preferably about 1.5 to 200 mg, more preferably about 3 to 100 mg in the extract, for example, as a dry extract or a soft extract. The flow extract is usually in the range of about 0.01 to 9 mL, preferably about 0.05 to 6 mL, and more preferably about 0.1 to 3 mL.

  The compounding amount when using Senkyu is usually in the range of 0.01 to 3 g, preferably 0.05 to 2 g, more preferably 0, in terms of dry weight of the active ingredient as the dose per adult. .1 to 1 g. This amount is usually in the range of about 0.15 to 800 mg, preferably about 1.5 to 500 mg, more preferably about 3 to 250 mg as a dry extract, for example, as a dry extract. Usually, it is in the range of about 0.01 to 3 mL, preferably about 0.05 to 2 mL, and more preferably about 0.1 to 1 mL.

  The compounding amount in the case of using the mother is usually in the range of 0.001 to 8 g, preferably 0.01 to 4 g, more preferably as the dose per adult, in terms of dry bulk drug substance. 0.03 to 2 g. In the extract, this amount is usually in the range of about 0.05 to 2000 mg, preferably about 0.5 to 1000 mg, more preferably about 1.5 to 500 mg, for example, as a dry extract.

  In the case of using Tennantoshi, the compounding amount per adult is usually in the range of 0.001 to 6 g, preferably 0.005 to 3 g, more preferably 0 in terms of dry weight of the active ingredient. 0.01 to 2 g. This amount is usually in the range of about 0.05 to 1600 mg, preferably about 0.3 to 800 mg, and more preferably about 0.6 to 520 mg in the extract, for example, as a dry extract.

  The compounding amount when using peony skin is usually in the range of 0.005 to 8 g, preferably 0.01 to 4 g, more preferably as the dose per adult, in terms of dry weight of the active ingredient. 0.02 to 2 g. This amount is usually in the range of about 0.3 to 2000 mg, preferably about 0.6 to 1000 mg, and more preferably about 1 to 500 mg in the extract, for example, as a dry extract.

  The compounding amount in the case of using potentilla is usually in the range of 0.005 to 6 g, preferably 0.01 to 4 g, more preferably 0, as a dose per adult, in terms of dry bulk drug substance. 0.03 to 2 g. This amount is usually in the range of about 0.3 to 1500 mg, preferably about 0.6 to 1000 mg, more preferably about 2 to 500 mg in the extract, for example, as a dry extract.

  The amount of chamomile to be used is usually in the range of 0.001 to 20 g, preferably 0.005 to 15 g, more preferably 0 as a dose per adult, as a dose per adult. 0.01 to 10 g. In the extract, this amount is usually in the range of about 0.05 to 5000 mg, preferably about 0.3 to 4000 mg, more preferably about 0.6 to 2000 mg, for example, as a dry extract.

  The compounding amount in the case of using kava kaba is usually in the range of 0.001 to 9 g, preferably 0.005 to 6 g, more preferably 0, as a dose per adult, as a dose per adult. 0.01 to 3 g. This amount is usually in the range of about 0.05 to 2400 mg, preferably about 0.3 to 1600 mg, and more preferably about 0.6 to 800 mg in the extract, for example, as a dry extract.

  The amount of lindane used is usually in the range of 0.001 to 20 g, preferably 0.005 to 15 g, more preferably 0, as a dose per adult, in terms of dosage per adult. 0.01 to 10 g. In the extract, this amount is usually in the range of about 0.05 to 5000 mg, preferably about 0.3 to 4000 mg, more preferably about 0.6 to 2000 mg, for example, as a dry extract.

  The sleep-improving drug of the present invention can be produced by a conventional method except that it contains the doses of the above anti-H1 histamine drug and herbal medicine per adult. Moreover, in these manufacture, a well-known formulation additive etc. can be mixed as needed.

  Known formulation additives include excipients, bases, binders, disintegrants, disintegration aids, lubricants, fluidizing agents, coating agents, plasticizers, antifoaming agents, dragees, skins, gloss Agent, foaming agent, moisture-proofing agent, surfactant, solubilizer, buffering agent, solubilizer, solubilizer, solvent, stabilizer, emulsifier, suspending agent, dispersant, antioxidant, filler, viscosity Examples include thickeners, thickeners, pH adjusters, preservatives, preservatives, sweeteners, flavoring agents, refreshing agents, flavoring agents / fragrances, fragrances, and coloring agents.

  The dosage form of the sleep-improving drug of the present invention is not particularly limited as long as it is an internal preparation. For example, tablets, caplets, hard capsules, soft capsules, orally disintegrating tablets, chewable tablets, granules, fine granules Oral solid preparations such as preparations, internal liquid preparations such as dry syrups and syrups, and the like, particularly preferably internal preparations.

  The sleep-improving drug of the present invention thus obtained can improve sleep disorders such as falling asleep, deep sleep disorder, arousal during sleep and early awakening by taking once a day before going to bed.

  Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.

Example 1
tablet:
Granules for tableting using 200 g of diphenhydramine hydrochloride, 90 g of fish rattan extract, 354 g of lactose, 100 g of corn starch, 302 g of crystalline cellulose, 20 g of croscarmellose sodium, 24 g of polyvinylpyrrolidone and 10 g of light anhydrous silicic acid. Got. 990 g of this granule for tableting was mixed with 9 g of talc and 9 g of magnesium stearate and then tableted to obtain 3300 uncoated tablets having a diameter of 9 mm, a thickness of 4.5 mm and a tablet weight of 280 mg.

Example 2
tablet:
Granulation by a conventional method using 200 g of diphenhydramine hydrochloride, 60 g of hop extract, 384 g of lactose, 100 g of corn starch, 302 g of crystalline cellulose, 20 g of croscarmellose sodium, 24 g of polyvinylpyrrolidone, and 10 g of light anhydrous silicic acid to obtain granules for tableting It was. 990 g of this granule for tableting was mixed with 9 g of talc and 9 g of magnesium stearate and then tableted to obtain 3300 uncoated tablets having a diameter of 9 mm, a thickness of 4.5 mm and a tablet weight of 280 mg.

Example 3
tablet:
Granulation by conventional methods using 200 g of diphenhydramine hydrochloride, 60 g of carrot extract, 304 g of lactose, 100 g of corn starch, 382 g of crystalline cellulose, 20 g of croscarmellose sodium, 24 g of polyvinylpyrrolidone and 10 g of light anhydrous silicic acid to obtain granules for tableting It was. 990 g of this granule for tableting was mixed with 9 g of talc and 9 g of magnesium stearate and then tableted to obtain 3300 uncoated tablets having a diameter of 9 mm, a thickness of 4.5 mm and a tablet weight of 280 mg.

Example 4
tablet:
Granulated by a conventional method using 200 g of diphenhydramine hydrochloride, 60 g of fish rattan extract, 40 g of hop extract, 344 g of lactose, 100 g of corn starch, 302 g of crystalline cellulose, 20 g of croscarmellose sodium, 24 g of polyvinylpyrrolidone, and 10 g of light anhydrous silicic acid, Granules for tableting were obtained. 990 g of this granule for tableting was mixed with 9 g of talc and 9 g of magnesium stearate and then tableted to obtain 3300 uncoated tablets having a diameter of 9 mm, a thickness of 4.5 mm and a tablet weight of 280 mg.

Example 5
tablet:
Using ordinary methods using 200 g of diphenhydramine hydrochloride, 60 g of fish rattan extract, 40 g of hop extract, 40 g of carrot extract, 304 g of lactose, 100 g of corn starch, 302 g of crystalline cellulose, 20 g of croscarmellose sodium, 24 g of polyvinylpyrrolidone, and 10 g of light anhydrous silicic acid. Granulation was performed to obtain granules for tableting. 990 g of this granule for tableting was mixed with 9 g of talc and 9 g of magnesium stearate and then tableted to obtain 3300 uncoated tablets having a diameter of 9 mm, a thickness of 4.5 mm and a tablet weight of 280 mg.

Example 6
tablet:
Granulation for tableting was obtained using 100 g of diphenhydramine hydrochloride, 120 g of mistletoe extract, 350 g of lactose, 358 g of crystalline cellulose, 20 g of croscarmellose sodium, 48 g of light anhydrous silicic acid, and 24 g of hydroxypropylcellulose. After mixing 918 g of these granules with 9 g of magnesium stearate and 9 g of talc, they were tableted to obtain 3400 uncoated tablets having a diameter of 9 mm, a thickness of 4.2 mm, and a tablet weight of 260 mg.

Example 7
tablet:
Granulation for tableting was obtained using 100 g of diphenhydramine hydrochloride, 60 g of Ezoukogi extract, 350 g of lactose, 418 g of crystalline cellulose, 20 g of croscarmellose sodium, 48 g of light anhydrous silicic acid, and 24 g of hydroxypropylcellulose. After mixing 918 g of these granules with 9 g of magnesium stearate and 9 g of talc, they were tableted to obtain 3400 uncoated tablets having a diameter of 9 mm, a thickness of 4.2 mm, and a tablet weight of 260 mg.

Example 8
tablet:
Granulation for tableting was obtained using 100 g of diphenhydramine hydrochloride, 60 g of oat powder, 350 g of lactose, 418 g of crystalline cellulose, 20 g of croscarmellose sodium, 48 g of light anhydrous silicic acid, and 24 g of hydroxypropylcellulose. After mixing 918 g of these granules with 9 g of magnesium stearate and 9 g of talc, they were tableted to obtain 3400 uncoated tablets having a diameter of 9 mm, a thickness of 4.2 mm, and a tablet weight of 260 mg.

Example 9
tablet:
Granules for tableting were obtained by granulation by a conventional method using 100 g of diphenhydramine hydrochloride, 60 g of potentilla extract, 350 g of lactose, 418 g of crystalline cellulose, 20 g of croscarmellose sodium, 48 g of light anhydrous silicic acid, and 24 g of hydroxypropylcellulose. After mixing 918 g of these granules with 9 g of magnesium stearate and 9 g of talc, they were tableted to obtain 3400 uncoated tablets having a diameter of 9 mm, a thickness of 4.2 mm, and a tablet weight of 260 mg.

Example 10
tablet:
Granulation for tableting was obtained using 100 g of diphenhydramine hydrochloride, 30 g of koji extract, 380 g of lactose, 418 g of crystalline cellulose, 20 g of croscarmellose sodium, 48 g of light anhydrous silicic acid, and 24 g of hydroxypropylcellulose. After mixing 918 g of these granules with 9 g of magnesium stearate and 9 g of talc, they were tableted to obtain 3400 uncoated tablets with a diameter of 9 mm, a thickness of 4.2 mm, and a tablet weight of 260 mg.

Example 11
tablet:
Granules for tableting were obtained by granulating in an ordinary manner using 100 g of diphenhydramine hydrochloride, 60 g of dried senkyu extract, 370 g of lactose, 398 g of crystalline cellulose, 20 g of croscarmellose sodium, 48 g of light anhydrous silicic acid, and 24 g of hydroxypropylcellulose. After mixing 918 g of these granules with 9 g of magnesium stearate and 9 g of talc, they were tableted to obtain 3400 uncoated tablets having a diameter of 9 mm, a thickness of 4.2 mm, and a tablet weight of 260 mg.

Example 12
tablet:
Granules for tableting were obtained using 100 g of diphenhydramine hydrochloride, 30 g of chamomile powder, 380 g of lactose, 418 g of crystalline cellulose, 20 g of croscarmellose sodium, 48 g of light anhydrous silicic acid, and 24 g of hydroxypropylcellulose to obtain granules for tableting. After mixing 918 g of these granules with 9 g of magnesium stearate and 9 g of talc, they were tableted to obtain 3400 uncoated tablets having a diameter of 9 mm, a thickness of 4.2 mm, and a tablet weight of 260 mg.

Example 13
tablet:
100 g diphenhydramine hydrochloride, 80 g mistletoe extract, 40 g spruce extract, 40 g auto powder, 40 g potentilla extract, 20 g ginseng extract, 40 g dried cucumber extract, 20 g chamomile powder, 250 g lactose, 298 g crystalline cellulose, 20 g croscarmellose sodium, light Granulation was carried out by a conventional method using 48 g of anhydrous silicic acid and 24 g of hydroxypropyl cellulose to obtain granules for tableting. After mixing 918 g of these granules with 9 g of magnesium stearate and 9 g of talc, they were tableted to obtain 3400 uncoated tablets having a diameter of 9 mm, a thickness of 4.2 mm, and a tablet weight of 260 mg.

Example 14
Granules:
50 g diphenhydramine hydrochloride, 60 g hop extract, 150 g licorice extract, 5 g wisdom extract, 30 g Tennan star extract, 200 g peony skin extract, 240 g birch powder, 50 g linden powder, 650 g mannitol, 520 g potato starch, 5 g hydroxypropylcellulose and light anhydrous silicic acid Granules were prepared in a conventional manner using 20 g and 20 g of fragrance, and packaged so as to be 2 g per package, thereby obtaining 900 packaged granules.

Example 15
Capsule:
200 g diphenhydramine hydrochloride, 80 g fishing rod extract, 60 g hop extract, 150 g crystalline cellulose, 140 g lactose, 150 g corn starch, 10 g light anhydrous silicic acid and 10 g magnesium stearate to produce a mixed powder, per capsule The capsule was filled into hard capsules (size 2) to 200 mg to obtain 3800 capsules.

Comparative Example 1
Capsule:
200 g of diphenhydramine hydrochloride, 220 g of crystalline cellulose, 210 g of lactose, 150 g of corn starch, 10 g of light anhydrous silicic acid and 10 g of magnesium stearate are mixed to prepare a mixed powder. Hard capsules (size 2) No.) to obtain 3800 comparative capsules.

Comparative Example 2
Capsule:
80g of fish rattan extract, 60g of hop extract, 250g of crystalline cellulose, 240g of lactose, 150g of corn starch, 10g of light anhydrous silicic acid and 10g of magnesium stearate to make a mixed powder so that it becomes 200mg per capsule Were filled into hard capsules (size 2) to obtain 3800 capsules.

Test example 1
Hypnosis test:
The capsules obtained in Example 15, Comparative Example 1 and Comparative Example 2 were administered to 11 adults with mild insomnia for 10 days, about 30 minutes before going to bed. Sleep: poor sleep, can't sleep well, deep sleep disorder (even if I intended to have plenty of sleep time, I don't feel a good sleep), awakening in the middle (I wake up many times in the night and then go to sleep again) ), And the effect of the drug on early arousal (wakes up early in the morning and still wants to sleep but cannot sleep). Evaluation was carried out in five stages: good, slightly good, unchanged, slightly bad, and bad. The results of the improvement rate (%) of sleep deprivation disorder, deep sleep disorder, mid-term awakening, and early awakening are shown in Table 1.

  The capsule obtained in Example 15 was superior to those obtained in Comparative Examples in improving sleep, deep sleep disorder, mid-wake and early awakening. In addition, in this test example, there were common side effects (vertigo, headache, dry mouth, constipation, nausea, loss of appetite, itchy eyes, dysuria, rash, malaise), and fishing wrinkles and hops. No common side effects based (nausea, vomiting, loss of appetite, etc.) were observed.

Test example 2
Sleep induction test:
As animals, 5 male ddy mice were used per group. Test drugs were prepared by suspending one capsule of the capsules obtained in Example 15 and Comparative Example 1 or 2 in 500 mL of 0.5% sodium carboxymethylcellulose aqueous solution, and 0.1 mL of 10 g of mouse body weight was prepared. Orally administered at a rate. Similarly, a 0.5% sodium carboxymethyl cellulose aqueous solution was orally administered to the control group (control). Sixty minutes after oral administration of each test drug, 80 mg / kg of hexobarbital injection solution was intraperitoneally administered, and the time until disappearance of the right reflex was measured. This was defined as sleep introduction time. The results of the sleep induction test are shown in FIG.

  From the results of the sleep induction test, the drug obtained in Comparative Example 1 was found to have a shorter sleep induction time than the control group. Moreover, compared with the control group and the comparative example 2, the shortening of the sleep introduction time was seen also in the medicine obtained in Example 15. On the other hand, the drug obtained in Comparative Example 2 hardly affected the sleep introduction time. The drug obtained in Example 15 shortened the sleep time by about 1.5 times that of Comparative Example 1 and about 23.5 times that of Comparative Example 2.

  In addition, an antihistamine and a herbal medicine selected from fishing rattan, hops, carrots, oats, mistletoe, licorice, camellia, nematode, nanny, celestial star, peony skin, potentilla, chamomile, birch and linden As a result of conducting the same test on the drugs, the sleep improvement effect was observed for all the drugs.

  The sleep-improving drug of the present invention has a high sleep-improving effect and is excellent without causing side effects due to components contained in the sleep-improving agent.

  Therefore, the sleep improving agent of the present invention can be used to ensure comfortable sleep.

FIG. 1 is a drawing showing the results of a sleep induction test. more than

Claims (4)

A sleep-improving drug, comprising diphenhydramine or an acid addition salt thereof, and a fishing wicker basket and hops. The dose per adult dose of diphenhydramine or an acid addition salt, sleep-improving agent of claim 1 wherein 25 to 75 mg. The sleep-improving drug according to claim 1, wherein the dose per adult of fish rattan and hops is 0.5 mg to 100 g in terms of dry weight of a crude drug. The sleep-improving drug according to any one of claims 1 to 3 , wherein the compounding amount of fishing rattan and hops with respect to 100 parts by weight of diphenhydramine or an acid addition salt thereof is 0.01 to 2000 parts by weight.

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