CN1935227A - Medicine composition for improving sleep - Google Patents

Abstract

The present invention provides a medicine composition for improving sleep. Said medicine composition includes the following several portions: antihistamine; one or two kinds of Chinese medicinal materials selected from uncariae uncis cum ramulus, humulus lupulus, ginseng radix, avena sativa, viscum album, glycyrrhizae radix, poria, cnidii rhizome, anemarrhenae rhizome, arisaematis tuber, moutan cortex, potentilla anserine, camomile, piper methysticum and tilia spp.; perfume component; compound selected from vitamin and/or mineral substance; and any one component selected from melatonin compounds.

Description

Improve the pharmaceutical compositions of sleep

Technical field

The present invention relates to a kind of pharmaceutical compositions of improvement sleep of novelty, contain antihistaminic and specific composition.

Background technology

Because social pressure and environment are bad, many people have the worry of insomnia.Through the investigation modern 8 one-tenth experiences that insomnia is arranged are arranged approximately, it is said in the middle of per 5 Japaneses, to have more than 1 and just perplexed by the mistake eye.

For so insomnia, with the medicament of antihistamine (antihistamine) medicine as effective ingredient, in American-European countries such as the U.S., Britain, Germany, Canada much less, also be utilized as general with medicine or improvement sleep pharmaceutical compositions that needn't the prescription list, in order to reduce the transient insomnia symptom in Japan.

But, insomnia is according to its state, have sleeping obstacle (sleepy but go to bed also not sleep well, have difficulty in going to sleep), the obstacle of sleeping soundly is (even sleep fully, do not have the sensation of sleeping soundly yet), wake up midway and (repeatedly wake up at night, promptly can't fall asleep afterwards) or wake up in advance (wake up morning very early, afterwards sleepy but can't fall asleep) etc. form miscellaneous.For insomniac miscellaneous like this, when having only antihistaminic, fail to obtain effect of sufficient as improvement sleep pharmaceutical compositions.

On the other hand, the hypnosis town tranquilizer of crude drug extract and Chinese medicine also are utilized and generally use medicine.But, because these must 1 day 2 to 3 times take between two meal meals, so owing to take the trouble poor compliance, be very difficult to bring into play fully effect, and must just can manifest for a long time, busy modern in order to improve temporary slight insomnia, is to use the thing of inconvenience.

Again, document illustration is arranged with the hydrochloric acid hexichol peace bright (diphenhydramineydrochloride) of antihistaminic or also with the extract of maleic acid chlorobenzene and passiflora edulis (passiflora edulis), increase hypnosis, sedation (with reference to patent documentation 1).Again, a kind of improvement of document illustration sleep pharmaceutical compositions is arranged, and with Diphenylammonium chloride. bright (diphenhydramine hydrochloride) and radix valerianae (valerian root) and/or Ziziphi Spinosae (with reference to patent documentation 2).But Xi Panlian makes the effect of blood pressure drops also strong, and hypotensive patient can't use.On the other hand, can have a headache during the life-time service radix valerianae, palpitate quickly, crick etc., again, sour sour jujube has the side effect of Alimentary disease occasionally, therefore wishes to have a kind of good improvement sleep pharmaceutical compositions with safer effect.And, allocate the bright antihistaminics such as (diphenhydramine) of strong crude drug of these sedation effects and hexichol peace and make the pharmaceutical compositions that improves sleep, also queried as general safety with medicine.

And, have document illustration with the Santalum album quintessence oil as the per os SLEEP AGENT (with reference to patent documentation 3) of effective ingredient and with the per os SLEEP AGENT (with reference to patent documentation 4) of Garden lavender (lavender oil) quintessence oil as effective ingredient, these derived essential oils are not easy to be improved fully sleeper effect for the mistake eye patient of above-mentioned form of all kinds separately.

Again; known melatonin melatonin (N-acetyl group-5-methoxyl group three tryptophan) is to take the pinus as main synthetic neural hormone; in comprising human mammalian body, whole day (also promptly 24 hours) is being secreted the melatonin melatonin regularly usually.Light is the main synchronizer of whole day rule or seasonal rule, and the melatonin melatonin is had synchronizer as the biological rule of day-night cycle by identification.Again, known melatonin melatonin has and promotes the recovery (with reference to non-patent literature 1) that the time difference is blunt and can cause sleepiness (with reference to non-patent literature 2).

Utilization about the melatonin melatonin, document illustration is arranged and with melatonin melatonin and clothianadin (clonidine) (with reference to patent documentation 5), separately give melatonin melatonin (with reference to patent documentation 6), give serotonine acid (with reference to patent documentation 7) as hypnotic separately, but its effect is insufficient.Again, document illustration is also arranged and with the derivant of melatonin melatonin and benzene phenodiazine flat (benzodiazepine) as hypnotic, have side effect such as dizzy, dysmnesia, transient insomnia, dependency and produce uneasiness but be to use the benzene phenodiazine to equal (benzodiazepine) derivant.

[patent documentation 1] spy opens flat 4-36243 communique

[patent documentation 2] spy opens flat 10-17482 communique

[patent documentation 3] spy opens flat 10-25245 communique

[patent documentation 4] spy opens flat 10-25246 communique

[patent documentation 5] spy opens flat 11-171767 communique

[patent documentation 6] spy opens flat 8-502259 communique

[patent documentation 7] spy opens the 2003-81829 communique

[patent documentation 8] spy opens flat 5-155769 communique

[non-patent literature 1] Arendt J waits the people, Ergonomics, and (1987) 30, p.1379-1393.

[non-patent literature 2] Waldhauser F waits the people, Psychopharmacology, (1990); 100 (2): p.222-226.

Summary of the invention

Therefore, the present invention is a problem so that a kind of pharmaceutical compositions that improves sleep to be provided, as generally having excellent safety with medicine, can allow more patients utilize the syngignoscism of antihistaminic, can alleviate by once taking the previous day of sleeping that what is called " has difficulty in going to sleep ", transient insomnia symptom that many moderns entertained such as " can't be sunk into sleep ", guarantee comfortable sleep.

The inventor is in view of above situation, and the result of wholwe-hearted research self-criticism finds can solve above-mentioned problem by allocate special component in antihistaminic, finishes the present invention thus.

Also promptly, the present invention is a kind of pharmaceutical compositions that improves sleep, it is characterized by, the allotment antihistaminic be selected from following (a) to (d) group in any composition form:

(a) be selected from by uncariae uncis cure ramulus (Uncariae Uncis Cum Ramulus), Flos lupuli (Flos Humuli Lupuli) (Humuluslupulus), Radix Ginseng (Ginseng Radix), Herba bromi japonici (Avena sativa), the West slack parasitism (viscumalbum), Radix Glycyrrhizae (Glycyrrhizae Radix), Poria (Poria), Rhizoma Chuanxiong (Cnidii Rhizoma), the Rhizoma Anemarrhenae (Anemarrhenae Rhizoma), Rhizoma Arisaematis (Arisaematis Tuber), Cortex Moutan (MoutanCortex), Herba Potentillae Discoloris (Potentilla anserine L), Chamomile (camomile), piper methysticum (Pipermethysticum), and bodhi tree (Tilia spp.) etc. is formed the crude drug more than a kind or 2 kinds among the group;

(b) flavor component;

(c) be selected from by vitamins and/or mineral mineral form group in chemical compound; And

(d) be selected from melatonin melatonin (melatonin) chemical compound;

Any composition forms among the group.

The present invention that the allotment special component forms in antihistaminic improves the pharmaceutical compositions of sleep, is a kind of good pharmaceutical compositions that improves the sleeper effect height and can not produce the side effect that is caused by the pharmaceutical compositions composition that contains the improvement sleep.

Description of drawings

Fig. 1 imports result's diagram of test for the sleep of test example 2;

Fig. 2 imports result's diagram of test for the sleep of test example 4; With

Fig. 3 imports result's diagram of test for the sleep of test example 7.

The specific embodiment

Antihistaminic used in the present invention is if having anti-H ₁The histamine effect gets final product, and is not particularly limited, and wherein can use anti-H such as ethanolamines, phenothiazine (phenothiazine) class, piperazine (piperazine) class, piperidines (piperidine) class, propylamine class ₁The histamine medicine.

Anti-like this H ₁The concrete example of the preferred example of histamine medicine, ethanolamine can have been enumerated hexichol peace bright (diphenhydramine), decapryn (doxylamine), chlorine fiber crops Sa Ting (clemastine), diphenylpyraline (diphenylpyraline), carbinoxamine (carbinoxamine); Phenothiazine (phenothiazine) class has promethazine (promethazine), mequitazine (mequitazine), alimemazine (alimiemazine), adanton (isothipendyl); Piperazine (piperazine) has hydroxyzine (hydroxyzine), curosajin (homochlorcyclizine); Piperidines (piperidine) has hydroxyzine (hydroxyzine), Cyproheptadine (cyproheptadine); The propylamine class has chlorphenamine (chlorpheniramine), triprolidine (triprolidine), brompheniramine (brompheniramine) etc.These anti-H ₁The histamine medicine may be used singly or in combination of two or more.Again, hexichol peace bright (diphenhydramine), decapryn (doxylamine), chlorine fiber crops Sa Ting (clemastine), diphenylpyraline (diphenylpyraline), carbinoxamine ethanolamine such as (carbinoxamine) are arranged is anti-H to adducible preferred embodiment ₁The histamine medicine.These ethanolamine are anti-H ₁Serve as that the spy is good to use hexichol peace bright (diphenhydramine), decapryn (doxylamine) in the histamine medicine.

These antihistaminics can directly use free alkali, but also can be the acid-addition salts of hydrochloric acid, citric acid, succinic acid, salicylic acid, diphenyl disulfonic acid, tartaric acid, tannic acid, tea chloric acid, lauryl sulfate, sulphuric acid, pamoic acid, uncommon benzoic acid (hibenzic acid), maleic acid etc.

For example, when using hexichol peace bright (diphenhydramine) as antihistaminic, preferable acid-addition salts is adducible that hydrochloric acid hexichol peace is bright, citric acid hexichol peace is bright, tannic acid hexichol An Ming etc., and wherein special good acid-addition salts is adducible to have hydrochloric acid hexichol peace bright.The preferable acid-addition salts of decapryn (doxylamine) has the preferable acid-addition salts of decapryn succinage, chlorine fiber crops Sa Ting (clemastine) to have the preferable acid-addition salts of fumaric acid chlorine fiber crops Sa Ting, diphenylpyraline (diphenylpyraline) to have the preferable acid-addition salts of benzene chloric acid diphenylpyraline, diphenylpyraline hydrochloride, carbinoxamine (carbinoxamine) that the maleic acid carbinoxamine is arranged.

In the present invention, in order to obtain the dosage of the necessary antihistaminic of sleeper effect, different because of various antihistamine, again, different because of free alkali or the kind of its addition salts, so can't lump together, wherein the adult is good with about 10～200 milligrams at every turn.

For example, use hydrochloric acid hexichol peace is bright or citric acid hexichol peace is bright as anti-H ₁During the histamine medicine, each dosage of being grown up is good with the 25-75 milligram, serves as special good with 50 milligrams.When using decapryn succinage, each dosage of being grown up is good with 12.5～50 milligrams, serves as special good with 25 milligrams.When using chlorine fiber crops Sa Ting (clemastine), each dosage of being grown up is good with 1～2 milligram, when using diphenylpyraline (diphenylpyraline), each dosage of being grown up is good with 1～12 milligram, use the maleic acid carbinoxamine, each dosage of being grown up is good with 4～12 milligrams.

The pharmaceutical compositions of improvement sleep of the present invention is terrible above-mentioned sleeper effect, at least a composition that is selected from the aforementioned composition (a) to (b) of allotment in anti-group of medicine of necessary amount.

In the mentioned component, adducible uncariae uncis cure ramulus (Uncariae Uncis CumRamulus), Flos lupuli (Flos Humuli Lupuli) (Humulus lupulus), Radix Ginseng (Ginseng Radix), Herba bromi japonici (Avenasativa), the West of being selected from of composition (a)

Parasitic (viscum album), Radix Glycyrrhizae (Glycyrrhizae Radix), Poria (Poria), Rhizoma Chuanxiong (Cnidii Rhizoma), the Rhizoma Anemarrhenae (Anemarrhenae Rhizoma), Rhizoma Arisaematis (ArisaematisTuber), Cortex Moutan (Moutan Cortex), Herba Potentillae Discoloris (Potentilla anserine L), Chamomile (camomile), piper methysticum (Piper methysticum) and bodhi tree (Tilia spp.) etc. are formed the crude drug more than a kind or 2 kinds among the group.In these crude drugs, serve as special good with allotment uncariae uncis cure ramulus and/or Flos lupuli (Flos Humuli Lupuli).

In the middle of the mentioned component of crude drug (a), uncariae uncis cure ramulus (Uncariae Uncis Cum Ramulus) is the thorn of Rubiaceae Ramulus Uncariae Cum Uncis etc., contains Ramulus Uncariae cum Uncis alkali (rhynchophylline), corynoxeine (corynoxeine), isorhynchophylline (isorhynchophylline), diformazan and spends emerald green alkali alkaloids such as (hirsutin), niacin etc.

Flos lupuli (Flos Humuli Lupuli) (Humulus lupulus) contains humulene volatile oil such as (humulene) .beta.-bitter acid (humulone), leuprorelin (lupron), the bitter principles such as .beta.-bitter acid that contain valeric acid (valerium acid), flavone (flavonid), oestrogen (estrogen) similar substance, asparagine (aspargine) etc. for the another name that Moraceae hothouse flower grass belongs to is the fruit ear of Western hothouse flower grass.

The root of Radix Ginseng (Ginseng Radix) after for the radicula of the Radix Ginseng of removing Araliaceae, or, contain triterpene compounds (triterpenoid), plant soap matter (sapoinins), ginseng saponin, acetylide, polysaccharide body (panakisan), sesquiterpene (sesquiterpenes) etc. with its thing that soaked with warm water a little.The present invention can use the root of Siberian ginseng (slender acanthopanax Radix Ginseng).

Herba bromi japonici (Avena sative) is avenaceous seed of rice section or stem, contains mineral mineral such as plant soap matter (saponin), alkaloid (alkaloid), stearyl alcohol, flavone, salicylic acid, starch, protein, vitamin B, calcium, silicon, ferrum, manganese, zinc.

The West

Parasitic (Viscum album) is the West of Loranthaceae (loranthaceae) Loranthus Parasitic the branch and leaf tip, stem, leaf contain glycoprotein, the polyamines acid that contracts (polypeptide) (viscotoxin (viscotoxin)), flavone, caffeine and other acid, lignan (lignan), acetylcholine (acetylcholine) etc.

Radix Glycyrrhizae (Glycyrrhizae Radix) is Radix Glycyrrhizae or the root of other congener and the grass blade of pulse family, contains triterpene (triterpene), plant soap, soybean isoflavone element (isoflavone), the golden yellow ketone in Leech Shandong (transliteration), the golden yellow ketone in different Leech Shandong (transliteration), Fu Ermo Endothelium corneum flavone flavone such as (transliteration) (flavonoid), polysaccharide (polysaccharide), stearyl alcohol, coumarin (coumarin), asparagine (asparagines) of glycyrrhetinic acid (glycyrrhetinic acid) etc. etc.

Poria (Poria) is the sclerotium of the fungus Poria (poria cosos) of polypor (polypores) section, contains β-pachyman (pachyman), β-pachymaran, pachymic acid etc.

Rhizoma Chuanxiong (Cnidii Rhizoma) is generally spends (apiaceae) section Rhizoma Chuanxiong rhizome with the thing that warm water soaked umbrella shape, contains cnidium lactone (cnidilide), new cnidium lactone (neocnidilide), Rhizoma Chuanxiong ester (cnidinum lactone), ligustilide (ligustilide), cnidium acid (cnidium acid) etc.

The Rhizoma Anemarrhenae (Anemarrhenae Rhizoma) is a Liliaceae Rhizoma Anemarrhenae rhizome, contains Rhizoma Anemarrhenae soap (timosaponin), Sa Ersa soap triterpenes such as (sarsasapogenin) compounds, plant soap matter, oxygen benzophenone (xanthone) ligand, niacin, pantothenic acid vitamin classes such as (pantothenic acid) etc.

Rhizoma Arisaematis (Arisaematis Tuber) contains plant soap matter, starch, amino acid, oxalic acid, formic acid etc. for removing the Arisaema heterophyllum B1. (Arisaemaheterophyllum Bume) or the tuber of the suberin lamella of other congener of Fructus Colocasiae Esculentae section.

Cortex Moutan (Moutan Cortex) is the root bark of the Paeonia suffruticosa of Paeoniaceae, contains loose alkene oil (monoterpene) glycocide, phenols, tannin class, sucrose etc.

Herba Potentillae Discoloris (Potentilla anserine L.) is the herb of rosaceous Herba Potentillae Discoloris, contains leaf and draws note tannin (transliteration), flavone, gallbladder element (choline), amaroid etc.

Chamomile (camomile) can be used in spending any of Flos Chrysanthemi and Anthemis nobilis.Wherein, Flos Chrysanthemi (Matricaria recutita L.) is the colored portion of the another name Flos Chrysanthemi of Compositae, contains quintessence oil, farnesene (farnesene), α-Bisabolol (the bitterness glucoside of the flavone of α-bisabolol), spiral shell ether volatile oil such as (spiro ether), anthemidine (anthemidine), luteolin (luteolin), rutin etc., anthemic acid etc., coumarin (coumarin), tannin etc.Again, Anthemis nobilis flower (Antbemis nobolis) is the colored portion of Compositae Anthemis nobilis, contains Flos Chrysanthemi ester (tiglic acid ester), angelate (angelicaacid ester), chamazulene (chamazulene), sesquiterpene lactone (sesquiterpene lactone), flavone, coumarin, phenolic acid, piper methysticum lactone etc.

Piper methysticum (Piper methysticum) is the root of Piperaceae piper methysticum, and it contains piper methysticum lactone (containing kawain (kawain)), beautiful this hot alkaloid such as (transliteration) Fructus Piperis in ground of Fructus Piperis etc. to contain resin.

Bodhi tree (Tilia spp.) is the flower of Tiliaceae the West tilia, lobule Hibiscus syriacus (Tilia cordata), Tilia platyphyllos tilias such as (Tilia plyatyphyllos), contains flavone, caffeine acid, tannin, the volatilization wet goods of Quercetin (guercetin) and kaempferol (kaempferol) etc.

In the present invention, above-mentioned crude drug can directly use dried powder as composition (a), and the extract that also can use dry extract, mobile extract, soft extract, alcoholic solution, quintessence oil etc. is as composition (a).And, the dosage of these compositions (a), different because of various crude drugs, though cannot treat different things as the same, wherein be grown up 1 approximately is that to be converted into the dry thing of crude drug in whole be between 0.5 milligram～100 grams at every turn.Again, though the amount that dosage is not known usually these crude drugs can bring into play for example hypnotic effect of effect or sedation effect also can, so be preferable.

Allotment amount when for example using uncariae uncis cure ramulus as the crude drug of composition (a), each dosage of being grown up usually, is the scope of 0.05～8 gram when being scaled the dry thing of crude drug in whole, with 0.1～6 gram for good, with 0.15～4 gram for better.When extract, dry extract for example, this amount is generally the scope about 4～800 milligrams, with about 8～600 milligrams be good, with about 12～450 milligrams for better.

Allotment amount when using Flos lupuli (Flos Humuli Lupuli) as composition (a), each dosage of being grown up, common, be the scopes of 5 milligrams～4 grams when being scaled crude drug in whole drying thing,, restrain to better for good with 10 milligrams～3 grams with 20 milligrams～2.When it is extract, dry extract for example, this amount is generally the scope about 0.25～480 milligram, with about 0.5～360 milligram is good, with about 1～240 milligram for better, when flowing extract, be generally the scope about 0.005～4 milliliter, with about 0.01～3 milliliter be good, with about 0.02～2 milliliter for better.

Allotment amount when using Radix Ginseng, each dosage of being grown up, common, be the scopes of 0.5 milligram～10 grams when being scaled crude drug in whole drying thing,, restrain to better for good with 1 milligram～6 grams with 1.5 milligrams～3.When extract, for example dry extract or soft extract, this amount is generally the scope about 0.02～2700 milligram, with about 0.4～1600 milligram is good, with about 0.06～800 milligram for better, when flowing extract, be generally the scope about 0.005～10 milliliter, with about 0.001～6 milliliter be good, with about 0.0015～3 milliliter for better.

Allotment amount when using Herba bromi japonici, each dosage of being grown up, common, be the scope of 0.001～100 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.01～20 gram with 0.1～4.During extract, dry extract for example, this amount is generally the scope about 0.05～26000 milligram, with about 0.5～5200 milligram be good, with about 5～1040 milligrams for better.

Use the West

Allotment amount when parasitic, each dosage of being grown up, common, be the scope of 0.004～4 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.01～2 gram with 0.02～1.During extract, dry extract for example, this amount is generally the scope about 1～200 milligram, with about 2.5～100 milligrams be good, with about 5～50 milligrams for better.

Allotment amount when using Radix Glycyrrhizae, each dosage of being grown up, common, be the scope of 0.01～5 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.05～3 gram with 0.1～1.5.During extract, dry extract for example, this amount is generally the scope about 2～1500 milligrams, with about 10～900 milligrams is good, with about 20～450 milligrams for better, during soft extract, be generally the scope about 2.5～1250 milligrams, with about 12.5～750 milligrams be good, with about 25～375 milligrams for better.

Allotment amount when using Poria, each dosage of being grown up, common, be the scope of 0.01～9 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.05～6 gram with 0.1～3.During extract, for example dry extract or soft extract, this amount is generally the scope about 0.3～300 milligram, with about 1.5～200 milligrams is good, with about 3～100 milligrams for better, when flowing extract, be generally the scope about 0.01～9 milliliter, with about 0.05～6 milliliter be good, with about 0.1～3 milliliter for better.

Allotment amount when using Rhizoma Chuanxiong, each dosage of being grown up, common, be the scope of 0.01～3 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.05～2 gram with 0.1～1.When extract, dry extract for example, this amount is generally the scope about 0.15～800 milligram, with about 1.5～500 milligrams is good, with about 3～250 milligrams for better, when flowing extract, be generally the scope about 0.01～3 milliliter, with about 0.05～2 milliliter be good, with about 0.1～1 milliliter for better.

Allotment amount when using the Rhizoma Anemarrhenae, each dosage of being grown up, common, be the scope of 0.001～8 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.01～4 gram with 0.03～2.When extract, dry extract for example, this amount is generally the scope about 0.05～2000 milligram, with about 0.5～1000 milligram be good, with about 1.5～500 milligrams for better.

Allotment amount when using Rhizoma Arisaematis, each dosage of being grown up, common, be the scope of 0.001～6 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.005～3 gram with 0.01～2.When extract, dry extract for example, this amount is generally the scope about 0.05～1600 milligram, with about 0.3～800 milligram be good, with about 0.6～520 milligram for better.

Allotment amount when using Cortex Moutan, each dosage of being grown up, common, be the scope of 0.005～8 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.01～4 gram with 0.02～2.When extract, dry extract for example, this amount is generally the scope about 0.3～2000 milligram, with about 0.6～1000 milligram be good, with about 1～500 milligram for better.

Allotment amount when using Herba Potentillae Discoloris, each dosage of being grown up, common, be the scope of 0.005～6 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.01～4 gram with 0.03～2.When extract, dry extract for example, this amount is generally the scope about 0.3～1500 milligram, with about 0.6～1000 milligram be good, with about 2～500 milligrams for better.

Allotment amount when using Chamomile, each dosage of being grown up, common, be the scope of 0.001～20 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.005～15 gram with 0.01～10.During extract, dry extract for example, this amount is generally the scope about 0.05～5000 milligram, with about 0.3～4000 milligram be good, with about 0.6～2000 milligram for better.

Allotment amount when using piper methysticum, each dosage of being grown up, common, be the scope of 0.001～9 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.005～6 gram with 0.01～3.When extract, dry extract for example, this amount is generally the scope about 0.05～2400 milligram, with about 0.3～1600 milligram be good, with about 0.6～800 milligram for better.

Allotment amount when using bodhi tree, each dosage of being grown up, common, be the scope of 0.001～20 gram when being scaled crude drug in whole drying thing,, restrain to better for good with 0.005～15 gram with 0.01～10.When extract, dry extract for example, this amount is generally the scope about 0.05～5000 milligram, with about 0.3～4000 milligram be good, with about 0.6～2000 milligram for better.

On the other hand, the composition of flavor component of the present invention (b) if containing the composition with sedation gets final product, is not particularly limited.Flavor component with sedation used in the present invention, adducible is that carbohydrate is formed wantonly flavor component more than a kind or 2 kinds among the group by being selected from by esters, ethers, aldehydes, ketone, Coumarins, nitrogen-containing compound, alkene.

Be suitable as the thing of composition (b) use, esters has linalyl acetate, geranyl acetate, borneol acetate, acetic acid-α-terpenoid, acetic acid-4-terpenoid, neryl acetate, myrtenyl acetate, acetic acid hay alkane-4-base ester, lavandulyl acetate, citronellyl acetate, acetic acid clove tree ester, benzyl acetate, acetic acid method mud alkane ester, acetass such as the interior osmanthus of acetic acid ester, neryl propionate, propionic esters such as citronellyl propionate, Methyl Salicylate, willow acid esters such as willow acid benzyl ester, citronellyl formate, formic acid esters such as geranyl formate, the isopropylformic acid. norbornene ester, citronellyl isobutyrate, isobutyl isobutyrate, isopropylformic acid .-isobutyrates such as 2-methyl butyl ester, 2-methyl acetic acid-2-methyl butyl ester, 2-methyl acetic acid esters such as 2-methyl acetic acid isobutyl ester, isobutyl angelate, Isoamyl angelate., angelic acid-β-angelates such as Liu ester, Flos Matricariae chamomillae acid esters such as anthemic acid isobutene. ester, cinnamic acid esters such as methyl cinnamate, benzoate such as benzyl benzoate etc. are wherein with linalyl acetate, geranyl acetate is special good.

Be suitable as the flavor component of composition (b), wherein ethers is adducible methylchavicol, anise ether, safrole, 1-ally-3,4-methy-lene dioxy benzene, parsley apiole, elemicin myristicin, methyleugenol, methyl isoeugenol, asarone, acetic acid, tetramethoxy allyl benzene, methyl paracresol, methyl thyme camphor, a methyl myrtenol etc., wherein is special good with the methylchavicol.

And, be suitable as the flavor component of composition (b), wherein aldehydes is adducible hydrocinnamicaldehydes such as sesquialter fennel olefine aldehydr, cinnamic aldehyde, benzaldehyde, willow aldehyde, anisaldehyde such as monoterpene olefine aldehydrs such as citral, citronellal, capraldehyde, the hendecanal, lauric aldehyde, decenal, octanal, cumal, aldehyde C-9, myrthenal, phellandral, Camphora olefine aldehydr, farnesal, α-eucalyptus globulus olefine aldehydr, β-eucalyptus globulus olefine aldehydr etc., serves as special good with monoterpene olefine aldehydr, sesquialter fennel olefine aldehydr etc. wherein.

And, be suitable as the flavor component of composition (b), wherein ketone adducible have pinocamphone, isopinccamphone, α-absinthol, β-absinthol, Ketone, menthone, isomenthone, verbenone, fenchone, l-menthone, d-menthone, piperitenone, pinocarvone, cryptone etc. are reined in alkane ketone, Pu, wherein with pinocamphone,

Alkane ketone, ketone is reined at the Pu, menthone, verbenone, the l-menthone, the d-menthone, pinocarvones etc. are good, Coumarins has coumarin, E)-7-Geranoxycoumarin, ayapanin, apiolin (celerin), Limettin, coumarins such as osthol, Radix Angelicae Dahuricae element (anelicine), the bergamot element, bergapten, bergaptol, furocoumarins such as Isoarborinol methyl ether., pyrans such as cardine and coumarin etc., wherein with coumarin, pyrans and coumarin are special good, nitrogenate has S-methyl sulfur benzoic acid, sulfuration book lotus, to menthone-8-mercaptan etc., wherein with S-methyl sulfur benzoic acid, the sulfuration Herba Menthae is special good.

And, be suitable as the flavor component of composition (b), wherein the terpenes carbohydrate is adducible Roripa alkene, australene, nopinene, α-fenchene, paracymene (p-cymene), myrcene, sabinene, γ-terpinene, the terpin diene, monoterpene such as camphene, β-caryophyllene, β-sesquialter fenchene, sesquiterpenes such as santalene, chamazulene azulene such as (chamazulene), β-olive alkene, farnesene, α-Patchoulene, β-Patchoulene, two terpenes such as γ-Patchoulene, wherein with hesperidene, australene, β-caryophyllene, sesquiterpene, Flos Matricariae chamomillae is not, β-olive alkene, α-Patchoulene is special good, and terpenol has linalool, geraniol, menthol, α-Folium Symplocoris Caudatae alcohol;

Two terpenols such as sesquiterpene alcoholses such as monoterpenol such as alcohol, citronellol, α-santalol, cedrenol, catechol, sclareol serve as special good with linalool, geraniol, α-santalol, sclareol etc. wherein.

Composition of the present invention (b) above-claimed cpd alone or in combination uses, wherein with the form of the dried powder of the crude drug that contains these or medical herbs plants such as (herb), extract, quintessence oil, extraction oil, extract etc. or with the form that changes flavor agent, aromatic, adds pastil, spice of the extract that contains these crude drugs or medical herbs plants such as (herb), it is good being added on the pharmaceutical compositions that improves sleep.

On concrete, the composition (b) that contains the good esters of a large amount of spies, can use the dried powder, extraction powder, quintessence oil, extraction oil, extract of plants such as Garden lavender, Anthemis nobilis, Salvia Sclare L., orange blossom, Folium citri sinensis, Martin Herba Cymbopogonis Citrari, Fructus Citri Sarcodactylis etc., the composition (b) that contains the good ethers of a large amount of spies can use the dried powder, extraction powder, quintessence oil, extraction oil, extract etc. of plant separately such as Folium Perillae, tarragon.Again, the composition (b) that contains the good aldehydes of a large amount of spies, can use lemon-balm (melissa), lemon grass (Cymbopogon citratus), lemon scented gum, Herba Cymbopogonis Citrari, coriander, Citrus, tangerine, the dried powder of plants such as orange blossom, the extraction powder, quintessence oil, extraction oil, extract etc., the composition (b) that contains the good ketone of a large amount of spies, can use Hyssopus offcinalis L. (hyssop), Salvia japonica Thunb., Herba Artemisiae Scopariae, Herba Phtheirospermi Japonici, Herba Rosmarini Officinalis, Garden lavender, Lavandula hybrida, Herba Menthae similar plants (pennyroyal), Herba Menthae (pepper mint), Herba Menthae (corn mint), Fructus Foeniculi, Fructus Foeniculi, Mentha viridis L, Apium graveolens, Fructus anethi, Eucalyptus, the dried powder of plants such as Anthemis nobilis, the extraction powder, quintessence oil, extraction oil, extract etc., contain the composition (b) of the good Coumarins of a large amount of spies, can use Fructus Citri Sarcodactylis, Fructus Citri Limoniae, grapefruit, Herba Apii graveolentis, Radix Angelicae Sinensis, tilia, xylocinnamomum, the Cortex Cinnamomi Acacia farnesiana Willd., tarragons etc. are the dried powder of plant separately, the extraction powder, quintessence oil, extraction oil, extract etc.And, the composition (b) that contains the good nitrogen-containing compound of a large amount of spies, can use niaouli (niaouli), the dried powder of plants such as Herba Menthae, the extraction powder, quintessence oil, extraction oil, extract etc., the composition (b) that contains the good terpenic series carbohydrate of a large amount of spies, can use orange blossom, Folium citri sinensis, Citrus pericarp (Pericarpium Citri junoris), grapefruit, tangerine, Fructus Citri Sarcodactylis, tilia, citruss such as Fructus Citri grandis, Cacumen Platycladi, Fructus Rhodomyrti, Herba Rosmarini Officinalis, Herba thymi vulgaris, Fructus anethi, pinaster, the clothing orchid, black pepper, Fructus Piperis, Herba leucadis ciliatae, Garden lavender, Rhizoma Zingiberis Recens, German Chamomile, myrrh, the dried powder of plants such as Herba Pogostemonis, the extraction powder, quintessence oil, extraction oil, extract etc., contain the composition (b) of the good terpenol of a large amount of spies, can make and enumerate Lavandula hybrida respectively, Herba thymi vulgaris, orange blossom, Garden lavender, sweet Fructus Citri tangerinae, lemon grass (Cymbopogon citratus), the clothing orchid, flower stork grass, fragrant Radix Salviae Miltiorrhizae, Martin Herba Cymbopogonis Citrari, sandalwood, the dried powder of plants such as Flos Rosae Rugosae, the extraction powder, quintessence oil, extraction oil, extract etc.

And, what contain special good composition (b) changes the flavor agent, aromatic, add pastil, the basic hyle of spice, the adducible Garden lavender that Folium Perillae section is arranged, the fan is grass repeatedly, fragrant Radix Salviae Miltiorrhizae, Martin Herba Cymbopogonis Citrari, cattle rattan grass, Herba leucadis ciliatae, Herba Ocimi (Herba Ocimi Pilosi), Salvia japonica Thunb., Herba Menthae (pennyroyal), Herba Menthae (pepper mint), Herba Menthae (spearmint), hundred li grass (thyme), savoury (savory), greenweed thorn stamen chapter (Herba Pogostemonis) etc., the tangerine of Citrus section, Orange Blossom, grapefruit, citrus plant (citrus), mandarin orange, Folium citri sinensis, Fructus Citri Sarcodactylis etc., the Flos Matricariae chamomillae of Compositae, Artemisia (tarragon) (tarragon), Flos Chrysanthemi etc., the lemon grass (Cymbopogon citratus) of rice section, Fructus Fragariae Ananssae, Martin Herba Cymbopogonis Citrari etc., the Eucalyptus of Fructus Rhodomyrti (myrtaceae) section, niaouli, Fructus Rhodomyrti, the Fructus Foeniculi of Herba Oenanthes Javanicae section (fennel), Fructus cari carvi (Apium graveolens), Herba Apii graveolentis, angelica, the Cortex Cinnamomi of Lignum cinnamomi camphorae section, bay (bay tree), Lignum cinnamomi camphorae etc., the Chinese juniper wood of Chinese juniper Ochnaceae etc., the pinaster of pinaster section (pine) etc., the Fructus Piperis of Piperaceae (pepper) etc., the Rhizoma Zingiberis Recens of Zingiberaceae (ginger) etc., the sandalwood of Lignum Santali Albi Ochnaceae (Lignum Santali Albi) etc., the myrrh of Burseraceae etc., the clothing orchid of sweetsop section etc., the Herba Erodii of stormy waves grass section, rosaceous Flos Rosae Multiflorae (Flos Rosae Rugosae) etc.Te Jia is the Herba Ocimi (Herba Ocimi Pilosi), Salvia japonica Thunb., Herba Menthae (pennyroyal), Herba Menthae (pepper mint), Herba Menthae (spearmint), hundred li grass (thyme), savoury (savory), greenweed thorn stamen chapter (Herba Pogostemonis) of above-mentioned Folium Perillae section etc., and the tangerine of Citrus section, Orange Blossom, grapefruit, citrus plant (citrus), Folium citri sinensis, Citrus, Fructus Citri grandis, Fructus Citri Limoniae, tilia, Fructus Citri Sarcodactylis etc. are as above-mentioned basic hyle.

Also can adopt the form of microcapsule or microencapsulation to add these compositions (b) again.

The pharmaceutical compositions of improvement sleep of the present invention, the addition of composition (b) is according to using anti-H ₁The kind of the kind of histamine medicine and amount, use composition (b) and difference, for example with the form of above-mentioned dried powder, extraction powder, quintessence oil, extraction oil, extract, or as changing flavor agent, aromatic, adding pastil, spice and when adding, 0.001～30 weight % with the pharmaceutical compositions full weight amount of improving sleep is good, with 0.005～10 weight % is preferable, with 0.01～5 weight % for better.

For example, use the bright or bright anti-H of citric acid hexichol peace of hydrochloric acid hexichol peace as composition (b) ₁During the histamine medicine, composition (b) use be selected from Folium Perillae section, the Citrus section more than a kind or 2 kinds look into thing as the source, basis change flavor agent, aromatic, when adding pastil or spice, with respect to anti-H ₁During histamine medicine 100 weight portions, for good, be preferable with 0.05～600 weight portion with the composition (b) that adds 0.01～1800 weight portion, with 0.1～300 weight portion for better.

Allotment amount when particularly composition (b) uses from flavor component that Garden lavender obtains is with respect to anti-H ₁Histamine medicine 100 weight portions, with 0.1～50 weight portion is good, with 0.2～25 weight portion is preferable, composition (b) is use when Herba Rosmarini Officinalis obtains, with 0.1～50 weight portion is good, with 0.2～25 weight portion be preferable with 0.2～25 weight portion for better, allotment amount when composition (b) uses from the flavor component that citrus obtains, with 0.1～100 weight portion is good, with 0.2～50 weight portion for better, composition (b) uses when Fructus Citri Sarcodactylis obtains, and is good with 0.1～50 weight portion, with 0.2～25 weight portion for better.

Again, preferable thing in vitamins of (c) of the present invention composition and the mineral mineral, adducible have vitamin C, vitamin B group, calcium, a magnesium etc., can use a kind or mix that these vitaminss and mineral mineral use more than 2 kinds.

Wherein vitamin C is adducible bad hematic acid such as ascorbic acid, sodium ascorbate, anti-bad blood calcium and a slaine thereof etc.

Again, the vitamin B group is adducible a thiamine (thiamine), thiamine hydrochloride, thiamine mononitrate, curing thiamine mononitrate (nitric acid thiamine disulfide), thiamine disulfide, thiamine two (palmityl) sulfuric acid, hydrochloric acid two (cetylamine), fursultiamine hydrochloride (fursultiamine), fursultiamine, eight thiamine, commetamin (cycothiamine), two isobutyl group thiamine (bisibuthiamine), bisbentiamine (bisbentiamine), prosulthiamine (prosultiamine), benfotiamine (benfotiamine), cocarboxylase, the vitamin B of two ylmethyl thiamine etc. ₁And salt with and the vitamin B of derivant, riboflavin (riboflavin), Riboflavin butyrate, Riboflavin Sodium Phosphate, flavin adenine dinucleotide etc. ₂And salt with and the vitamin B of derivant, pyridoxol, 2-methyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine., pyridoxamine, pyridoxin phosphate, pyridoxal 5-phosphate, phosphopyridoxamine etc. ₆And salt with and the vitamin B of derivant, cobalamine, cyano group cobalamine, Hydroxycobalamin, acetic acid Hydroxycobalamin, mecobalamin (mecobalamine) etc. ₁₂And salt with and derivant, niacin amide, six niacin mesoinositols, meglin, nicotinic acid and salt with and the pantothenic acid of derivant, calcium pantothenate, sodium pantothenate, pantothenic acid alcohol, pantethin (pantethine) etc. and salt thereof with and the orotic acid of derivant, biotin (biotin), folic acid, orotic acid, oropur, Magnesium Orotate, choline orotate etc. and salt thereof with and derivant, vitamin B ₁₅(pangamic acid), Pangamic acid, calcium salt (vitamin B ₁₅Calcium; Pangamic acid calcium salt) vitamin B ₁₅And salt with and the thioctic acid of derivant, thioctic acid (lipoic acid), lipoic acid polyacrylamide etc. and salt thereof with and derivant, para amidocyanogen benzoic Acid (PABA) and salt thereof with and the inositol of derivant, inositol, six niacin mesoinositols etc. and salt thereof with and the choline of derivant, choline, choline orotate, choline bitartrate etc. and salt thereof with and the vitamin of derivant etc. and vitamins like working substance.Among these vitamin Bs group to be selected from by vitamin B ₁, vitamin B ₆, vitamin B ₁₂And be good more than a kind or 2 kinds among these salt and these derivants composition group.

And, calcium is adducible have calcium gluconate, calcium hydrogen phosphate, calcium phosphate dibasic anhydrous, calcium glycerophosphate, calcium lactate, Shen fall calcium carbonate, calcium chloride, calcium carbonate, calcium hydroxide, calcium lactate, calcium gluconate, calcium citrate, L-Radix Asparagi amino acid calcium, L-bran amic acid calcium, calcium glycerophosphate, 5 '-ribose nuclear calcium, calcium sulfate, tricalcium phosphate, calcium propionate, dalcium biphosphate, calcium dihydric pyrophosphate, carboxymethylcellulose calcium, CSL, calcium oxide etc.

Again, magnesium can be enumerated magnesium silicate, magnesium oxide, magnesium carbonate, magnesium hydroxide, silicic acid magnesium aluminate, aluminum magnesium hydroxide, silicic acid aluminic acid, aluminium hydroxide-carbonic acid acid magnesium combination drying gel, shallow lake, the common Shen product of magnesium hydroxide-aluminium potassium sulfate, shallow lake, the common Shen product of aluminium hydroxide-calcium carbonate-magnesium carbonate etc.

The allotment amount of the composition (c) of the pharmaceutical compositions of improvement sleep of the present invention because different according to its kind, cannot treat different things as the same, wherein in order to increase anti-H ₁Histamine medicine hypnotic effect, each dosage of being grown up are approximately between 0.1 μ g～3.9g, if get final product measuring.

On concrete, the each dosage of for example ascorbic adult is generally between 5～3000 milligrams, be good with 25～2000 milligrams, with 50～500 milligrams for better, if when the pharmaceutical compositions that the allotment improvement is slept, get final product to measuring.

Again, and different, each dosage is about between 0.1 μ g～1.5g vitamin B group's allotment amount according to vitamin B group's kind, if get final product measuring.In more detail, each dosage of being grown up is generally between 0.1～500 milligram, is good with 0.5～200 milligram, with 1～100 milligram for better, if to get final product to measuring the allotment amount that decides in the pharmaceutical compositions that improves sleep.Vitamin B ₂The each dosage of adult, be generally between 0.5～180 milligram, be good with 1～90 milligram, with 2～45 milligrams for better.Vitamin B ₆The each dosage of adult, be generally between 1～500 milligram, be good with 1～200 milligram, with 5～100 milligrams for better.Vitamin B ₁₂The each dosage of adult, be generally between 0.0001～15 milligram, be good with 0.0005～3 milligram, with 0.001～1.5 milligram for better.The dosage that the adult of nicotinic acid is each is generally between 0.1～1000 milligram, is good with 1～800 milligram, with 12～400 milligrams for better.The dosage that the adult of pantothenic acid is each is generally between 0.1～120 milligram, is good with 1～60 milligram, with 5～30 milligrams for better.The dosage that the adult of biotin is each is generally between 0.001～10 milligram, is good with 0.005～1 milligram, with 0.01～0.5 milligram for better.The dosage that the adult of folic acid is each is generally between 0.01～100 milligram, is good with 0.05～20 milligram, with 0.1～10 milligram for better.The dosage that the adult of orotic acid is each is generally between 1～500 milligram, is good with 5～200 milligrams, with 10～1000 milligrams for better.Vitamin B ₁₅(pangamicacid) dosage that adult is each is generally between 0.0001～1 milligram, is good with 0.0005～0.5 milligram, with 0.001～0.1 milligram for better.The each dosage of adult of thioctic acid (lipoic acid) is generally between 0.1～500 milligram, is good with 1～200 milligram, with 2～100 milligrams for better.The dosage that the adult of para amidocyanogen benzoic Acid is each is generally between 1～1500 milligram, is good with 2～1000 milligrams, with 10～500 milligrams for better.The dosage that the adult of inositol is each is generally between 1～800 milligram, is good with 5～400 milligrams, with 10～200 milligrams for better.The dosage that the adult of choline is each is generally between 1～1500 milligram, is good with 2～1000 milligrams, with 10～500 milligrams for better.Therefore, when using above-mentioned listed vitamins, if when allotment improves the pharmaceutical compositions of sleep, get final product to measuring.

On the other hand, when the mineral mineral uses calcium, for increasing anti-H ₁The hypnotic effect of histamine medicine, each dosage of being grown up, usually, calcium is below 2500 milligrams, be good with 2～600 milligrams, with 5～300 milligrams for better, if when the pharmaceutical compositions that the allotment improvement is slept, get final product to measuring.

Again, when the mineral mineral uses magnesium, for increasing anti-H ₁The hypnotic effect of histamine medicine, each dosage of being grown up, usually, magnesium is below 700 milligrams, be good with 1～320 milligram, with 2～160 milligrams for better, if when the pharmaceutical compositions that the allotment improvement is slept, get final product to measuring.

At this moment, anti-H ₁The usage ratio of histamine medicine and composition (c), different according to the kind of employed thing, usually, with respect to anti-H ₁Histamine medicine 100 weight portions, composition (c) is good about with 0.0002～6000 weight portion.With 0.002～1000 weight portion serves as special good.

And the employed melatonin melatonin of composition of the present invention (d) by absorbed or absorb the back metabolism by live body, can be reached the chemical compound of the short effect effect of melatonin melatonin.On concrete, composition (d) is adducible melatonin melatonin deriv, three tryptophan, 5-hydroxyl three tryptophan, paddy Li Foniya (griffonia), Brassica oleracea L.var.capitata (kale) etc. such as natural or synthetic melatonin melatonin, 2-iodine melatonin melatonin, 2-chlorine melatonin melatonin, 2-bromine melatonin melatonin, 6-chlorine melatonin melatonin, 6-hydroxyl melatonin melatonin.In these melatonin melatonin chemical compounds, serve as special good to use melatonin melatonin, 5-hydroxyl three tryptophan, three tryptophan again.

The allotment amount of the composition (d) of the pharmaceutical compositions of improvement sleep of the present invention, each dosage of being grown up is generally between 0.01～1500 milligram.In more detail, composition (d) is the allotment amount when using the melatonin melatonin, and each dosage of being grown up is generally between 0.01～20 milligram, is good with 0.05～10 milligram, with 0.1～3 milligram for better.Again, allotment amount when composition (d) uses 5-hydroxyl three tryptophan, each dosage of being grown up is generally between 0.1～200 milligram, is good with 1～150 milligram, with 10～100 milligrams for better, allotment amount when using three tryptophan, each dosage of being grown up is generally between 0.1～1500 milligram, with 1～1000 milligram is good, with 10～500 milligrams for better.

Again, in the composition (d) of hypnosis compositions of the present invention and the allotment amount of antihistaminic, different according to the kind of using composition (d) and antihistaminic, usually with respect to antihistaminic 100 weight portions, if allotment composition (d) gets final product when being 0.02～3000 weight portion left and right sides, with 0.1～1000 weight portion is good, with 0.2～200 weight portion for better.

The pharmaceutical compositions of improvement of the present invention sleep is except with above-mentioned anti-H ₁More than a kind or a kind of histamine medicine and composition (a) to (d) beyond allocating in the mode of each dosage of being grown up, can use the well-established law manufacturing.

Well-known formulation additives, adducible have an excipient, base, bonding agent, disintegrating agent, the disintegrate accessory agent, lubricant, flowing agent, varnish, plasticizer, defoamer, the sugar-coat agent, the gloss agent, foaming agent, damp proof compound, interfacial agent, but solvation, buffer agent, lytic agent, the dissolving adjuvant, solvent, the stabilization agent, emulsifying agent, suspending agent, dispersant, antioxidant, filler, sticky dose, glutinous thickening agent, pH adjusts agent, antiseptic, preservative agent, sweeting agent, change the flavor agent, refrigerantization agent, add pastil, spice, aromatic, coloring agent etc.

Again, the agent shape of the pharmaceutical compositions of improvement sleep of the present invention, have no particular limits during oral preparations, wherein for example can be the mixture for internal use etc. of solid preparation for oral administration, dry syrup, syrups etc. such as tablet, capsule, hard capsule, soft capsule, intraoral disintegration tablet, chewable tablet, granule, granula subtilis, serve as special good with solid preparation for oral administration wherein.Again, composition (a) to (d) all can be added with the form of rapid release portion, or also can or all add and continue by suction wherein a part long-time with the form of slow release portion.

In the middle of the pharmaceutical compositions of above-mentioned improvement sleep of the present invention, special good scheme is adducible following thing.

(1) each form of administration of the pharmaceutical compositions of improvement sleep contains 50 milligrams of hydrochloric acid hexichol peaces bright and 12～450 milligrams of uncariae uncis cure ramulus extracts and/or 1～240 milligram of hops extract.

(2) each form of administration of the pharmaceutical compositions of improvement sleep contains 50 milligrams of bright and 0.1～12.5 milligram of flavor component, 0.1～12.5 milligram of flavor component and 0.1～25 milligram of flavor component or 0.1～12.4 milligram of flavor components that obtain from Fructus Citri Sarcodactylis that obtained by citrus that obtain from Herba Rosmarini Officinalis that obtained by Garden lavender of hydrochloric acid hexichol peace.

(3) improve each form of administration of the pharmaceutical compositions of sleep, contain 50 milligrams of hydrochloric acid hexichol peaces bright with 50～500 milligrams of vitamin Cs, 1～100 milligram of vitamin B ₁, 5～100 milligrams of vitamin Bs ₆, 0.001～1.5 milligram of vitamin B ₁₂And 5～300 milligrams of calcium and/or 2～160 milligrams of magnesium.

(4) each form of administration of the pharmaceutical compositions of improvement sleep contains 50 milligrams of hydrochloric acid hexichol peaces bright and 0.1～3 milligram of melatonin melatonin, 10～100 milligrams of 5-hydroxyl three tryptophan or 10～500 milligram of three tryptophan.

The pharmaceutical compositions of so resulting improvement sleep of the present invention can have various dosage regimens, is good with the thing of taking form once before going to bed every day wherein.And, take once by before going to bed every day, can improve sleeping obstacle, the obstacle of sleeping soundly, sleep disorder such as wake up, wake up in advance midway.

The pharmaceutical compositions of improvement sleep of the present invention, composition (a) is to the anti-H of enhancing of composition (d) ₁The actuation gear of the hypnotic effect of histamine medicine still has not clear part though have, and when wherein allocating composition (c), can followingly think deeply.Also promptly, can think that the vitamin B group has stable spirit and neural effect, this is relevant with the enhancing hypnotic effect.Again, vitamin C has the effect that promotes hormone secretion, and calcium has the effect that pair effect effects on neural system is obtained loosening, and for the neural excitation that stimulation causes, magnesium has quelling effect etc., is associated with the enhancing of hypnotic effect separately.

[embodiment]

Below enumerate embodiment, illustrate in greater detail the present invention, but the present invention is not subjected to any restriction of embodiment.

Embodiment 1

Tablet:

Use that 200 gram hydrochloric acid hexichol peaces are bright, 90 gram uncariae uncis cure ramulus extracts, 3 54 gram lactose, 100 gram corn starchs, 302 gram crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium (croscarmellose sodium), 24 gram polyethylene Pyrrolizidine alkane ketone, 10 gram light anhydrous silicic acid, granulate by well-established law, obtain the tabletting granule.After 990 this tablettings of gram are restrained magnesium stearate and mix with granule and 9 gram Pulvis Talci, 9, carry out tabletting, 4.5 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3300 is 280 milligrams plain sheet.

Embodiment 2

Tablet:

Use that 200 gram hydrochloric acid hexichol peaces are bright, 60 gram hops extract, 384 gram lactose, 100 gram corn starchs, 302 gram crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 24 gram polyethylene Pyrrolizidine ketone alkane ketone, 10 gram light anhydrous silicic acid, granulate by well-established law, obtain the tabletting granule.After 990 this tablettings of gram are restrained magnesium stearate and mix with granule and 9 gram Pulvis Talci, 9, carry out tabletting, 4.5 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3300 is 280 milligrams plain sheet.

Embodiment 3

Tablet:

Use that 200 gram hydrochloric acid hexichol peaces are bright, 60 gram Radix Ginseng extracts, 304 gram lactose, 100 gram corn starchs, 382 gram crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 24 gram polyethylene Pyrrolizidine ketone alkane ketone, 10 gram light anhydrous silicic acid, granulate by well-established law, obtain the tabletting granule.After 990 this tablettings of gram are restrained magnesium stearate and mix with granule and 9 gram Pulvis Talci, 9, carry out tabletting, 4.5 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3300 is 280 milligrams plain sheet.

Embodiment 4

Tablet:

Use that 200 gram hydrochloric acid hexichol peaces are bright, 60 gram uncariae uncis cure ramulus extracts, 40 gram hops extract, 344 gram lactose, 100 gram corn starchs, 302 gram crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 24 gram polyethylene Pyrrolizidine ketone alkane ketone, 10 gram light anhydrous silicic acid, granulate by well-established law, obtain the tabletting granule.After 990 this tablettings of gram are restrained magnesium stearate and mix with granule and 9 gram Pulvis Talci, 9, carry out tabletting, 4.5 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3300 is 280 milligrams plain sheet.

Embodiment 5

Tablet:

Use that 200 gram hydrochloric acid hexichol peaces are bright, 60 gram uncariae uncis cure ramulus extracts, 40 gram hops extract, 40 gram Radix Ginseng extracts, 304 gram lactose, 100 gram corn starchs, 302 gram crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 24 gram polyethylene Pyrrolizidine ketone alkane ketone, 10 gram light anhydrous silicic acid, granulate by well-established law, obtain the tabletting granule.After 990 this tablettings of gram are restrained magnesium stearate and mix with granule and 9 gram Pulvis Talci, 9, carry out tabletting, 4.5 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3300 is 280 milligrams plain sheet.

Embodiment 6

Tablet:

Use bright, the 120 gram the West of 100 gram hydrochloric acid hexichol peaces

Parasitic, 350 gram lactose, 358 restrain crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl celluloses, granulate by well-established law, obtain the tabletting granule.After 918 this tablettings of gram are restrained Pulvis Talci and mix with granule and 9 gram magnesium stearate, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3400 is 260 milligrams plain sheet.

Embodiment 7

Tablet:

Use 100 gram hydrochloric acid hexichol peaces are bright, 120 gram slender acanthopanax Radix Ginseng (ezoukogi) extracts, 350 restrain lactose, 418 and restrain crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl celluloses, granulate by well-established law, obtain the tabletting granule.After 918 this tablettings of gram are restrained Pulvis Talci and mix with granule and 9 gram magnesium stearate, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3400 is 260 milligrams plain sheet.

Embodiment 8

Tablet:

Use 100 gram hydrochloric acid hexichol peaces are bright, 60 gram Herba bromi japonici extracts, 350 restrain lactose, 418 and restrain crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl celluloses, by the well-established law granulation, obtain the tabletting granule.After 918 this tablettings of gram are restrained Pulvis Talci and mix with granule and 9 gram magnesium stearate, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3400 is 260 milligrams plain sheet.

Embodiment 9

Tablet:

Use 100 gram hydrochloric acid hexichol peaces are bright, 60 gram Herba Potentillae Discoloris extracts, 350 restrain lactose, 418 and restrain crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl celluloses, by the well-established law granulation, obtain the tabletting granule.After 918 this tablettings of gram are restrained Pulvis Talci and mix with granule and 9 gram magnesium stearate, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3400 is 260 milligrams plain sheet.

Embodiment 10

Tablet:

Use 100 gram hydrochloric acid hexichol peaces are bright, 30 gram tuckahoe extracts, 380 restrain lactose, 418 and restrain crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl celluloses, by the well-established law granulation, obtain the tabletting granule.After 918 this tablettings of gram are restrained Pulvis Talci and mix with granule and 9 gram magnesium stearate, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3400 is 260 milligrams plain sheet.

Embodiment 11

Tablet:

Use 100 gram hydrochloric acid hexichol peaces are bright, 60 gram Rhizoma Chuanxiong dry extracts, 370 restrain lactose, 398 and restrain crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl celluloses, by the well-established law granulation, obtain the tabletting granule.After 918 this tablettings of gram are restrained Pulvis Talci and mix with granule and 9 gram magnesium stearate, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3400 is 260 milligrams plain sheet.

Embodiment 12

Tablet:

Use 100 gram hydrochloric acid hexichol peaces are bright, 30 gram Chamomile powder, 380 restrain lactose, 418 and restrain crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl celluloses, by the well-established law granulation, obtain the tabletting granule.After 918 this tablettings of gram are restrained Pulvis Talci and mix with granule and 9 gram magnesium stearate, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3400 is 260 milligrams plain sheet.

Embodiment 13

Tablet:

Use bright, the 80 gram the West of 100 gram hydrochloric acid hexichol peaces

Parasitic extract, 40 gram slender acanthopanax Radix Ginseng extracts, 40 gram Herba bromi japonici powder, 40 gram Herba Potentillae Discoloris, 20 gram tuckahoe extracts, 40 gram Rhizoma Chuanxiong dry extracts, 20 gram Chamomile powder, 250 gram lactose, 298 gram crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl celluloses, granulate by well-established law, obtain the tabletting granule.After 918 this tablettings of gram are restrained Pulvis Talci and mix with granule and 9 gram magnesium stearate, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3400 is 260 milligrams plain sheet.

Embodiment 14

Granule:

Use that 50 gram hydrochloric acid hexichol peaces are bright, 60 gram hops extract, 150 gram Radix Glycyrrhizae extracts, 5 gram Rhizoma Anemarrhenae extracts, 30 gram Rhizoma Arisaematis powder, 200 gram Cortex Moutan extracts, 240 gram slips Fructus Piperis extracts, 50 crin pellet (lindane) powder, 650 gram mannitols (mannitol), 520 KEMA tinkling of pieces of jade sweet potato starch, 5 gram hydroxy propyl celluloses and 20 gram light anhydrous silicic acid, 20 gram spice, make granule by well-established law, be packetized into every bag 2 grams, obtain subpackage granule 900 bags.

Embodiment 15

Capsule:

Uniform mixing 200 gram hydrochloric acid hexichol peace is bright, 80 gram uncariae uncis cure ramulus extracts, 60 gram hops extract, 150 gram crystalline celluloses, 140 gram lactose, 150 gram corn starchs, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 seed lac wafers.

Comparative example 1

Capsule:

Uniform mixing 200 gram hydrochloric acid hexichol peaces are bright, 220 gram crystalline celluloses, 210 restrain lactose, 150 gram corn starchs, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 relatively capsules.

Comparative example 2

Capsule:

Uniform mixing 80 gram uncariae uncis cure ramulus extracts, 60 gram hops extract, 250 gram crystalline celluloses, 240 gram lactose, 150 gram corn starchs, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 relatively capsules.

Test example 1

The hypnosis test:

With embodiment 15, comparative example 1 and comparative example 2 resulting capsule colloids, with adult's 11 objects by name with slight sleeplessness tendency, please they between ten days, the precontract of going to bed was taken a seed lac wafer in 30 minutes, test sleeping obstacle (sleepy but go to bed also not sleep well, have difficulty in going to sleep), the obstacle of sleeping soundly is (even sleep fully, do not have the sensation of sleeping soundly yet), wake up midway and (repeatedly wake up at night, promptly can't fall asleep afterwards) or wake up in advance (wake up morning very early, afterwards sleepy but can't fall asleep) pharmacy effect.Evaluation is divided into well, good slightly, no change, 5 stages such as poor slightly, poor.The result of sleeping obstacle, the obstacle of sleeping soundly, the improvement rate (%) of waking up midway, wakeing up in advance, improvement rate as shown in table 1.

[table 1]

Test medicine	Improvement rate (%)
									Sleeping obstacle		The obstacle of sleeping soundly		Wake up midway		Wake up in advance
	More than good	More than good slightly	More than good	More than good slightly	More than good	More than good slightly	More than good	More than good slightly
									Embodiment 15	45.5	81.8	36.4	81.8	18.2	72.7	27.3	72.7
Comparative example 1	18.2	63.6	9.1	54.5	9.1	45.5	18.2	45.5
									Comparative example 2	0.0	9.1	0.0	18.2	0.0	9.1	0.0	9.1

The resultant thing of embodiment 15 resulting capsule colloids and comparative example is relatively the time, sleeping obstacle, the obstacle of sleeping soundly, wake up midway, wake up in advance to improve effect good.Again, in this test example, do not observed because of taking the hydrochloric acid hexichol and pacified bright caused general side effect (dizzy, carebaria, thirsty, constipation, vomiting sense, inappetence, ophthalmic pruritus, dysuria, eruption, tired out sense) and uncariae uncis cure ramulus and the caused general side effect of Flos lupuli (Flos Humuli Lupuli) (nauseating, vomiting, inappetence).

Test example 2

Sleep imports test

It is 1 group 5 of male wister rats that animal system uses ddy.Test medicine is modulated at the thing that 1 capsule parts of suspension embodiment 15 in 500 milliliter of 0.5% sodium carboxy methyl cellulose aqueous solution, comparative example 1 or 2 resulting capsules forms respectively, 0.1 milliliter of the per 10 gram body weight oral administration of mouse.Again, control group (control) is an oral administration 0.5% a sodium carboxy methyl cellulose aqueous solution similarly.After 60 minutes, carry out the intraperitoneal administration of 80 milligrams/kilogram of hexobarbital (hexobarbital) injection at each test medicine oral administration, measure to righting reflex and disappear the needed time.With this as the sleep importing time.The sleep importing time as shown in Figure 1.

Import result of the test from sleep, when comparative example 1 resulting medicament and control group compared, the importing time of sleeping as can be seen shortened.Again, when embodiment 15 resulting medicaments also compared with control group and comparative example 2, the importing time of sleeping as can be seen shortened.On the other hand, comparative example 2 resulting medicaments are to the almost not influence of sleep importing time.Again, the resulting medicaments of embodiment 15 shorten 23.5 times of medicament that the sleep importing times are about 1.5 times of medicament of comparative example 1, are about comparative example 2.

Again, with antihistaminic be selected from uncariae uncis cure ramulus, Flos lupuli (Flos Humuli Lupuli), Radix Ginseng, Herba bromi japonici, the West respectively

The crude drug of parasitism, Radix Glycyrrhizae, Poria, Rhizoma Chuanxiong, the Rhizoma Anemarrhenae, Rhizoma Arisaematis, Cortex Moutan, Herba Potentillae Discoloris, Chamomile, piper methysticum and bodhi tree when allocating separately, carries out the result of identical test, confirms that arbitrary medicament all has the sleeper effect of improvement.

Embodiment 16

Tablet

Use 2500 gram hydrochloric acid hexichol peaces are bright, 4050 gram lactose, 2000 restrain corn starchs, 3500 and restrain crystalline celluloses, 250 gram cross-linked carboxymethyl cellulose sodium, 300 gram polyethylene Pyrrolizidine ketone alkane ketone, granulate by well-established law, obtain the tabletting granule.After 11340 this tablettings of gram are restrained magnesium stearate and mix with granule and 135 gram Fructus Citri Limoniae powder, 112.5 gram Pulvis Talci, 112.5, carry out tabletting, 4.5 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 44000 is 260 milligrams tablet.

Embodiment 17

Tablet

Use 100 gram hydrochloric acid hexichol peaces are bright, 427.4 gram crystalline celluloses, 400 restrain lactose, 20 and restrain cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl celluloses, 0.6 gram tangerine oil, by the well-established law granulation, obtain the tabletting granule.After 918 this tablettings of gram are restrained Pulvis Talci and mix with granule and 9 gram magnesium stearate and 9, carry out tabletting, 4.5 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3500 is 260 milligrams tablet.

Embodiment 18

Granule:

Use that 50 gram hydrochloric acid hexichol peaces are bright, 432 gram glycerol sugar alcohols, 470 KEMA tinkling of pieces of jade sweet potato starch, 5 gram hydroxypropyl fibers and 20 gram light anhydrous silicic acid, 20 gram Herba Menthae powders (pepper mint power), 3 gram Fructus Citri Limoniae powder, make granule by well-established law, be packetized into every bag 1 gram, obtain subpackage granule 900 bags.

Embodiment 19

Capsule:

Uniform mixing 200 gram hydrochloric acid hexichol peace is bright, 220 gram crystalline celluloses, 231 gram lactose, 100 gram corn starchs, 30 gram Fructus Foeniculi powder, 9 gram Oleum Anisi Stellati, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 seed lac wafers.

Embodiment 20

Capsule:

Uniform mixing 200 gram hydrochloric acid hexichol peace is bright, 220 gram crystalline celluloses, 240 gram lactose, 100 gram corn starchs, 8.6 gram Oleum Cinnamomis, 10.6 gram Pericarpium Citri junoris powder, 0.4 gram orange peel oil, 0.4 gram Oleum Rosae Rugosae, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 seed lac wafers.

Embodiment 21

Capsule:

Uniform mixing 200 gram hydrochloric acid hexichol peaces are bright, 239.28 gram crystalline celluloses, 240 restrain lactose, 100 gram corn starchs, 0.72 gram Essential lavender oil, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 seed lac wafers.

Embodiment 22

Tablet:

Uniform mixing 100 gram hydrochloric acid hexichol peaces are bright, 427.4 gram crystalline celluloses, 400 restrain lactose, 20 and restrain cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl cellulose sodium, 0.6 bergamot oil, granulate by well-established law, obtain the tabletting granule.After 918 this tablettings of gram are restrained Pulvis Talci and mix with granule and 9 gram magnesium stearate, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3500 is 260 milligrams plain sheet.

Embodiment 23

Tablet:

Uniform mixing 100 gram hydrochloric acid hexichol peaces are bright, 427.4 gram crystalline celluloses, 400 restrain lactose, 20 and restrain cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl cellulose sodium, 0.6 oil of rosemary, granulate by well-established law, obtain the tabletting granule.After 918 this tablettings of gram are restrained Pulvis Talci and mix with granule and 9 gram magnesium stearate, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3500 is 260 milligrams plain sheet.

Comparative example 3

Capsule:

Uniform mixing 200 gram hydrochloric acid hexichol peaces are bright, 220 gram crystalline celluloses, 260 restrain lactose, 100 gram corn starchs, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 relatively capsules.

Comparative example 4

Capsule:

339.28 gram crystalline cellulose, 340 gram lactose, 100 gram corn starchs, 0.72 gram Essential lavender oil, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 relatively capsules.

Test example 3

The hypnosis test:

With embodiment 21, comparative example 3 and comparative example 4 resulting capsule colloids, with adult's nine objects by name with slight sleeplessness tendency, please they between seven days, the precontract of going to bed was taken a seed lac wafer in 30 minutes, test sleeping obstacle (sleepy but go to bed also not sleep well, have difficulty in going to sleep), the obstacle of sleeping soundly is (even sleep fully, do not have the sensation of sleeping soundly yet), wake up midway and (repeatedly wake up at night, promptly can't fall asleep afterwards) or wake up in advance (wake up morning very early, afterwards sleepy but can't fall asleep) pharmacy effect.Evaluation is divided into well, good slightly, no change, 5 stages such as poor slightly, poor.The result of sleeping obstacle, the obstacle of sleeping soundly, the improvement rate (%) of waking up midway, wakeing up in advance, improvement rate as shown in table 2.

[table 2]

Test medicine	Improvement rate (%)
									Sleeping obstacle		The obstacle of sleeping soundly		Wake up midway		Wake up in advance
	More than good	More than good slightly	More than good	More than good slightly	More than good	More than good slightly	More than good	More than good slightly
									Embodiment 21	44.4	88.9	33.3	77.8	11.1	66.7	22.2	66.7
Comparative example 3	33.3	66.7	22.2	55.6	0.0	44.4	11.1	44.4
									Comparative example 4	0.0	11.1	0.0	0.0	0.0	11.1	0.0	0.0

Can know from table 2 and to know, the hypnosis of the present invention of allocating savory composition with solid preparation (embodiment 21) with the comparative formulations (comparative example 3) of not allocating savory composition relatively the time, sleeping obstacle, the obstacle of sleeping soundly, wake up midway, wake up in advance to improve effect good.With respect to this, confirm to have only the preparation (comparative example 4) that uses flavor component, almost do not improve sleeper effect.In the test of test example 3, do not observed because of taking the hydrochloric acid hexichol and pacified bright caused general side effect (dizzy, carebaria, thirsty, constipation, vomiting sense, inappetence, ophthalmic pruritus, dysuria, eruption, tired out sense) again.Again, because that Garden lavender is the disadvantage of side effect, habituation etc. is less, for many years by the frequent thing of use, so the present invention can be described as safe hypnosis solid preparation.

Test example 4

Sleep imports test

It is 1 group 5 of male wister rats that animal is used ddy.Test medicine is modulated at the thing that 1 capsule parts of suspension embodiment 21 in 500 milliliter of 0.5% sodium carboxy methyl cellulose aqueous solution, comparative example 3 or 4 resulting capsules forms respectively, 0.1 milliliter of the per 10 gram body weight oral administration of mouse.Again, control group (control) oral administration 0.5% sodium carboxy methyl cellulose aqueous solution similarly.After 60 minutes, carry out the intraperitoneal administration of 80 milligrams/kilogram of hexobarbital (hexobarbital) injection at each test medicine oral administration, measure to righting reflex and disappear the needed time.With this as the sleep importing time.The sleep importing time as shown in Figure 2.

Can know from the 2nd figure and to know that Garden lavender group's (comparative example 4) separately is identical with control group, comparative example 3 can know relatively the time with embodiment 21 and know, combination Garden lavender and hydrochloric acid hexichol are pacified when bright, can have a mind to the free burial ground for the destitute as can be seen to shorten the importing time of sleeping.

Other flavor component, for example use Herba Rosmarini Officinalis, the hypnosis that forms of Citrus composition, Fructus Citri Sarcodactylis such as Fructus Citri tangerinae also can access same result with solid preparation.

Embodiment 24

Tablet:

Use that 200 gram hydrochloric acid hexichol peaces are bright, 20 grams are to Beprocin, 40 gram pyridoxine hydrochlorides, 2 gram cyano group cobalamine, 304 gram lactose, 100 gram corn starchs, 310 gram crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 24 gram polyethylene Pyrrolizidine ketone alkane ketone, 10 gram light anhydrous silicic acid, granulate by well-established law, obtain the tabletting granule.After 918 this tablettings of gram are restrained magnesium stearate and mix with granule and 9 gram Pulvis Talci, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3300 is 260 milligrams tablet.

Embodiment 25

Tablet:

Use that 100 gram hydrochloric acid hexichol peaces are bright, 2 gram thiamine hydrochlorides, 1 gram cyano group cobalamine, 30 gram niacin amide, 20 gram calcium pantothenates, 10 gram Riboflavin butyrates, 100 gram ascorbic acid, 30 gram calcium gluconates, 317 gram lactose, 100 gram corn starchs, 318 gram crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid, 24 gram hydroxy propyl celluloses, granulate by well-established law, obtain the tabletting granule.After 918 this tablettings of gram are restrained magnesium stearate and mix with granule and 9 gram Pulvis Talci, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3300 is 260 milligrams tablet.

Embodiment 26

Granule:

Use that 50 gram hydrochloric acid hexichol peaces are bright, 500 gram calcium ascorbate, 20 gram thiamine hydrochlorides, 2 gram riboflavin (riboflavin), 20 gram pyridoxine hydrochlorides, 0.5 gram cyano group cobalamine, 0.4 gram folic acid, 0.5 gram biotin (biotin), the floating clear acid of 60 grams, 0.2 gram Pangamic acid, calcium salt (VITAMIN B15 calcium; Pangamic acidcalcium salt), 5 gram thioctic acid, 50 gram inositols, 25 gram hydrogen tartrate silicon, 200 gram calcium gluconates, 501.4 gram mannose calcium, 520 KEMA tinkling of pieces of jade sweet potato starch, 5 gram hydroxy propyl celluloses and 20 gram light anhydrous silicic acid, 20 gram spice, make granule by well-established law, be packetized into every bag 2 grams, obtain subpackage granule 900 bags.

Embodiment 27

Capsule:

Uniform mixing 200 gram hydrochloric acid hexichol peaces are bright, 100 gram thiamine hydrochlorides, 200 restrain pyridoxine hydrochlorides, 0.5 and restrain cyano group cobalamine, 120 gram crystalline celluloses, 109.5 gram lactose, 70 gram corn starchs, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 seed lac wafers.

Embodiment 28

Coated tablets:

Use that 200 gram hydrochloric acid hexichol peaces are bright, 80 gram benfotiamines, 32 gram Riboflavin Sodium Phosphates, 80 gram phosphoric acid are trembled aldehyde, 240 gram calcium hydrogen phosphate, 240 gram calcium lactate, 360 gram crystalline celluloses, 200 gram low degree of substitution hydroxy propyl celluloses, 40 gram croscarmelloses, 424 gram lactose, 9 gram light anhydrous silicic acid, 48 gram hydroxy propyl cellulose sodium, granulate by well-established law, obtain the tabletting granule.After 1836 this tablettings of gram are restrained magnesium stearate and mix with granule and 18 gram Pulvis Talci, 18, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 7000 is 260 milligrams plain sheet.Should the element sheet to 6000, use HICOATER (FREUND industry), to these plain sheets in the mode of drying regime with 5 milligrams/sheet, spraying contains 150 gram HYDROXY PROPYL METHYLCELLULOSE 2910,10 gram Polyethylene Glycol (macrog0l), 6000,22 gram titanium oxides and the talcous 10% water system coating fluids of 18 grams, obtains coated tablets.

Embodiment 29

Coated tablets:

Use that 200 gram hydrochloric acid hexichol peaces are bright, 200 gram ascorbic acid, 40 gram calcium pantothenates, 310 gram crystalline celluloses, 240 gram lactose, 10 gram storehouse Loews Bobs pause (crospovidon; A kind of disintegrating agent), after 20 gram light anhydrous silicic acid, 10 gram Pulvis Talci, 10 gram magnesium stearate mix, obtain the tabletting granule.This tabletting is carried out tabletting with granule, and 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3600 is 260 milligrams plain sheet.Should the element sheet to 3000, use HICOATER (FREUND industry), to these plain sheets in the mode of drying regime with 10 milligrams/sheet, spraying contains 150 gram HYDROXY PROPYL METHYLCELLULOSE, 2910,10 gram polyethylene glycol 6000s, 16 gram titanium oxides and the talcous 10% water system coating fluid of 24 grams, obtains coated tablets.

Embodiment 30

Granule:

Use 100 gram hydrochloric acid hexichol peaces bright; 200 gram ascorbic acid; the bad hematic acid calcium of 200 grams; 6 gram thiamine mononitrates; 4 gram riboflavin; the 6 gram hydrochloric acid alcohol of trembling; 1 gram cyano group cobalamine; 10 gram pantothenic acid alcohol; 160 grams, six niacin mesoinositols; 940 gram mannitols; 200 gram low degree of substitution hydroxy propyl celluloses; 87 gram corn starchs; 6 gram hydroxy propyl celluloses; the soft anhydrous silicic acid of 20 grams; 20 gram aspartames (aspartame); 20 gram acesulfame potassiums (acesulfame K); 20 gram spice; granulate by well-established law; obtain the tabletting granule; be packetized into every bag 1 gram, obtain subpackage granule 1800 bags.

Embodiment 31

Granule:

Use 100 gram hydrochloric acid hexichol peaces bright; 200 gram ascorbic acid; the bad hematic acid calcium of 200 grams; 40 gram fursultiamine hydrochloride; 4 gram riboflavin; 6 gram pyridoxine hydrochlorides; 1 gram cyano group cobalamine; 200 gram phosphoglycerol; 120 gram silicic acid magnesium aluminates; 1100 gram mannitols; 240 gram low degree of substitution hydroxy propyl celluloses; 86 gram corn starchs; 7 gram hydroxy propyl celluloses; the soft anhydrous silicic acid of 24 grams; 24 gram aspartames (aspartame); 24 gram acesulfame potassiums (acesulfame K); 24 gram spice; granulate by well-established law; obtain the tabletting granule; be packetized into every bag 1.2 grams, obtain subpackage granule 1800 bags.

Comparative example 5

Capsule:

Uniform mixing 200 gram hydrochloric acid hexichol peaces are bright, 220 gram crystalline celluloses, 260 restrain lactose and 120 gram corn starchs, are mixed and made into mixed-powder equably, are filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 relatively capsules.

Comparative example 6

Capsule:

Uniform mixing 100 gram hydrochloric acid hexichol peaces are bright, 200 gram salt pyridoxols, 0.5 restrain cyano group cobalamine, 220 gram crystalline celluloses, 209.5 gram lactose, 70 gram corn starchs, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 relatively capsules.

Test example 5

The hypnosis test:

With embodiment 27, comparative example 5 and comparative example 6 resulting capsule colloids, with adult's 12 objects by name with slight sleeplessness tendency, please they between seven days, the precontract of going to bed was taken a seed lac wafer in 30 minutes, test sleeping obstacle (sleepy but go to bed also not sleep well, have difficulty in going to sleep), the obstacle of sleeping soundly is (even sleep fully, do not have the sensation of sleeping soundly yet), wake up midway and (repeatedly wake up at night, promptly can't fall asleep afterwards) or wake up in advance (wake up morning very early, afterwards sleepy but can't fall asleep) pharmacy effect.Evaluation is divided into well, good slightly, no change, 5 stages such as poor slightly, poor.The result of sleeping obstacle, the obstacle of sleeping soundly, the improvement rate (%) of waking up midway, wakeing up in advance, improvement rate as shown in table 3.

[table 3]

Test medicine	Improvement rate (%)
									Sleeping obstacle		The obstacle of sleeping soundly		Wake up midway		Wake up in advance
	More than good	More than good slightly	More than good	More than good slightly	More than good	More than good slightly	More than good	More than good slightly
									Embodiment 27	41.7	75.0	25.0	75.0	16.7	58.3	25.0	58.3
Comparative example 5	25.0	66.7	16.7	58.3	8.3	41.7	8.3	50.0
									Comparative example 6	0.0	0.0	0.0	8.3	0.0	8.3	0.0	0.0

Embodiment 32

Tablet:

Use that 200 gram hydrochloric acid hexichol peaces are bright, 6 gram melatonin melatonins (melatonin), 332 gram lactose, 100 gram corn starchs, 328 gram crystalline celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 24 gram hydroxy propyl celluloses and 10 gram light anhydrous silicic acid, after these are fully mixed, granulate by well-established law, obtain the tabletting granule.After 918 this tablettings of gram are restrained magnesium stearate and mix with granule and 9 gram Pulvis Talci, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3300 is 260 milligrams plain sheet.

Embodiment 33

Tablet:

Use that 200 gram hydrochloric acid hexichol peaces are bright, 1.2 gram melatonin melatonins (melatonin), 326.8 gram lactose, 100 gram corn starchs, 328 gram crystalline celluloses, 30 gram cross-linked carboxymethyl cellulose sodium, 24 gram polyethylene cough up pyridine ketone alkane ketone and 10 gram light anhydrous silicic acid, after these are fully mixed, granulate by well-established law, obtain the tabletting granule.After 918 this tablettings of gram are restrained magnesium stearate and mix with granule and 9 gram Pulvis Talci, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3300 is 260 milligrams plain sheet.

Embodiment 34

Tablet:

Use 100 gram hydrochloric acid hexichol peaces are bright, 200 gram 5-hydroxyls, three tryptophan, 320 restrain lactose, 298 and restrain crystalline celluloses, 30 gram cross-linked carboxymethyl cellulose sodium, 48 gram light anhydrous silicic acid and 24 gram hydroxy propyl celluloses, after these are fully mixed, granulate by well-established law, obtain the tabletting granule.After 918 this tablettings of gram are restrained magnesium stearate and mix with granule and 9 gram Pulvis Talci, 9, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3300 is 260 milligrams plain sheet.

Embodiment 35

Coated tablets:

Use that 100 gram hydrochloric acid hexichol peaces are bright, 200 gram 5-hydroxyls, three tryptophan, 30 gram pyridoxine hydrochlorides, 40 gram niacin amide, 60 gram magnesium carbonate, 120 gram lactose, 106 gram crystalline celluloses, 260 gram low degree of substitution hydroxy propyl celluloses, 60 gram cross-linked carboxymethyl cellulose sodium, 20 gram light anhydrous silicic acid and 24 gram hydroxy propyl celluloses, after these are fully mixed, granulate by well-established law, obtain the tabletting granule.After 918 these granules of gram and 9 gram magnesium stearate, 9 are restrained Pulvis Talci and mix, carry out tabletting, 4.2 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 3300 is 260 milligrams plain sheet.Should the element sheet to 3000, use HICOATER (FREUND industry), to these plain sheets in the mode of drying regime with 10 milligrams/sheet, spraying contains 10% water system coating fluid of 150 gram HYDROXY PROPYL METHYLCELLULOSE, 2910,10 gram polyethylene glycol 6000s, 16 gram titanium oxides and 24 gram Pulvis Talci, obtains coated tablets.

Embodiment 36

Two synusia agent:

Use that 200 gram hydrochloric acid hexichol peaces are bright, 118 gram lactose, 80 gram corn starchs, 168 gram crystalline celluloses, 176 gram low degree of substitution hydroxy propyl celluloses, 20 gram cross-linked carboxymethyl cellulose sodium, 20 gram hydroxy propyl celluloses and 10 gram light anhydrous silicic acid, after these are fully mixed, granulate by well-established law, obtain granule.Mix 3.6 gram Pulvis Talci and 3.6 gram magnesium stearate at 712.8 these granules of gram, carry out tabletting, obtain tabletting granule 1.Then, use 12 gram melatonin melatonins, 420 gram lactose, 120 gram HYDROXY PROPYL METHYLCELLULOSE, 80 gram fixed oils, 80 gram stearic acid and 80 gram fatty acid glycerides, after these are fully mixed, granulate, obtain granule by well-established law.Mix 7.2 gram magnesium stearate at 712.8 these granules of gram, carry out tabletting, obtain tabletting granule 2.And, carry out tabletting, making this tabletting is 100 grams with granule 1 and tabletting with granule 2 layer separately, 4.1 millimeters, the every weight of 9 millimeters of diameters, thickness that obtains 6500 is 200 milligrams two synusia agent.

Embodiment 37

Granule:

Use that 50 gram hydrochloric acid hexichol peaces are bright, 800 grams, three tryptophan, 800 gram mannitols, 105 KEMA tinkling of pieces of jade sweet potato starch, 200 gram low degree of substitution hydroxy propyl celluloses, 5 gram hydroxy propyl celluloses, the soft anhydrous silicic acid of 20 grams, and 20 gram spice, after these are fully mixed, granulate by well-established law, obtain the tabletting granule, be packetized into every bag 2 grams, obtain subpackage granule 950 bags.

Embodiment 38

Capsule:

Uniform mixing 100 gram hydrochloric acid hexichol peaces are bright, 2 gram melatonin melatonins, 200 restrain crystalline celluloses, 278 gram lactose and 200 gram corn starchs, 10 gram light anhydrous silicic acid, 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 seed lac wafers.

Embodiment 39

Capsule:

Uniform mixing 100 gram hydrochloric acid hexichol peaces are bright, 200 gram 5-hydroxyls, three tryptophan, 200 restrain crystalline celluloses, 180 gram lactose and 100 gram corn starchs, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 seed lac wafers.

Embodiment 40

Capsule:

Uniform mixing 100 gram hydrochloric acid hexichol peaces are bright, 600 grams, three tryptophan, 28 restrain crystalline celluloses, 26 gram lactose and 26 gram corn starchs, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 seed lac wafers.

Comparative example 7

Capsule:

Uniform mixing 100 gram hydrochloric acid hexichol peaces are bright, 200 gram crystalline celluloses, 280 restrain lactose and 200 gram corn starchs, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 relatively capsules.

Comparative example 8

Capsule:

Uniform mixing 2 gram melatonin melatonins, 200 gram crystalline celluloses, 378 gram lactose and 200 gram corn starchs, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 relatively capsules.

Comparative example 9

Capsule:

Uniform mixing 300 gram 5-hydroxyls three tryptophan, 200 gram crystalline celluloses, 80 gram lactose and 200 gram corn starchs, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 relatively capsules.

Comparative example 10

Capsule:

Uniform mixing 700 grams three tryptophan, 30 gram crystalline celluloses, 20 gram lactose and 30 gram corn starchs, 10 gram light anhydrous silicic acid and 10 gram magnesium stearate, be mixed and made into mixed-powder equably, be filled in hard capsule (No. 2, size), make 200 milligrams of every capsules, obtain 3800 relatively capsules.

Test example 6

The hypnosis test:

With embodiment 40, comparative example 7 and comparative example 10 resulting capsule colloids, with adult's 17 objects by name with slight sleeplessness tendency, please they between seven days, the precontract of going to bed was taken two capsules in 30 minutes, test sleeping obstacle (sleepy but go to bed also not sleep well, have difficulty in going to sleep), the obstacle of sleeping soundly is (even sleep fully, do not have the sensation of sleeping soundly yet), wake up midway and (repeatedly wake up at night, promptly can't fall asleep afterwards) or wake up in advance (wake up morning very early, afterwards sleepy but can't fall asleep) pharmacy effect.Evaluation is divided into well, good slightly, no change, 5 stages such as poor slightly, poor.The result of sleeping obstacle, the obstacle of sleeping soundly, the improvement rate (%) of waking up midway, wakeing up in advance, improvement rate as shown in table 4.

[table 4]

Test medicine	Improvement rate (%)
									Sleeping obstacle		The obstacle of sleeping soundly		Wake up midway		Wake up in advance
	More than good	More than good slightly	More than good	More than good slightly	More than good	More than good slightly	More than good	More than good slightly
									Embodiment 40	52.9	88.2	23.5	70.6	17.6	76.5	23.5	64.7
Comparative example 7	11.8	58.8	5.9	58.8	5.9	47.1	17.6	47.1
									Comparative example 10	5.9	17.6	0.0	11.8	5.9	11.8	5.9	17.6

The resultant thing of embodiments of the invention 40 resulting capsule colloids and comparative example is relatively the time, sleeping obstacle, the obstacle of sleeping soundly, wake up midway, wake up in advance to improve effect good.

Test example 7

Sleep imports test

It is 1 group 5 of male wister rats that animal is used ddy.Test medicine is modulated at suspension embodiment 38, embodiment 39 in 250 milliliter of 0.5% sodium carboxy methyl cellulose aqueous solution, embodiment 40, comparative example 7, comparative example 8, comparative example 9, and the thing that forms of 1 capsule parts of comparative example 10 resulting capsules, 0.1 milliliter of the per 10 gram body weight oral administration of mouse respectively.Again, control group (control) oral administration 0.5% sodium carboxy methyl cellulose aqueous solution similarly.After 60 minutes, carry out the intraperitoneal administration of 80 milligrams/kilogram of hexobarbital (hexobarbital) injection at each test medicine oral administration, measure to righting reflex and disappear the needed time.With this as the sleep importing time.The sleep importing time as shown in Figure 3.

Import result of the test from sleep, when embodiment 38 resulting medicaments and control group and comparative example 7 and 8 compared, the importing time of sleeping as can be seen shortened.When embodiment 39 resulting medicaments and control group and comparative example 7 and 9 compared, the importing time of sleeping as can be seen shortened.Again, when embodiment 40 resulting medicaments and control group and comparative example 7 and 10 compared, the importing time of sleeping as can be seen shortened.Again, the resulting medicaments of embodiment 38 shorten the sleep importing times and are about 2.0 times of medicament of comparative example 7, are about 2.4 times of medicament of comparative example 8, reach 7.9 times of medicament of comparative example 10 approximately.Again, the resulting medicaments of embodiment 39 shorten the sleep importing times be about 1.5 times of medicament of comparative example 7,1.8 times of comparative example 8 resulting medicaments, reach comparative example 10 resulting medicaments 5.9 times.And the resulting medicaments of embodiment 40 shorten the sleep importing times and are about 1.3 times of medicament of comparative example 7,1.6 times of comparative example 8 resulting medicaments, also reach 5.1 of comparative example 10 resulting medicaments.

Utilize possibility on the industry

Improvement sleep pharmaceutical compositions of the present invention improves the sleeper effect height and the contained composition of improvement sleep pharmaceutical compositions side effect can not occur.

Therefore, improvement sleep pharmaceutical compositions of the present invention can be used to guarantee comfortable sleep.

Claims (24)

1. a pharmaceutical compositions that improves sleep is characterized by, and allotment comprises antihistaminic and combines with any composition that is selected from following (a) to (d):

(a) be selected from more than a kind or 2 kinds following crude drug by, comprise uncariae uncis cure ramulus (Uncariae Uncis CumRamulus), Flos lupuli (Flos Humuli Lupuli) (Humulus lupulus), Radix Ginseng (Ginseng Radix), Herba bromi japonici (Avenasativa), the West

Parasitic (viscum album), Radix Glycyrrhizae (Glycyrrhizae Radix), Poria (Poria), Rhizoma Chuanxiong (Cnidii Rhizoma), the Rhizoma Anemarrhenae (Anemarrhenae Rhizoma), Rhizoma Arisaematis (ArisaematisTuber), Cortex Moutan (Moutan Cortex), Herba Potentillae Discoloris (Potentilla anserine L), Chamomile (camomile), piper methysticum (Piper methysticum), and bodhi tree (Tilia spp.) etc. is formed the crude drug more than a kind or 2 kinds among the group;

(b) flavor component;

(c) be selected from by vitamins and/or mineral mineral form group in chemical compound; And

(d) melatonin melatonin (melatonin) chemical compound.

2. the pharmaceutical compositions of improvement sleep as claimed in claim 1, wherein antihistaminic is the anti-H of ethanolamines ₁The histamine medicine.

3. the pharmaceutical compositions of improvement sleep as claimed in claim 2, the wherein anti-H of ethanolamines ₁The histamine medicine is hexichol peace bright (diphenhydramine) or its acid-addition salts.

4. the pharmaceutical compositions of improvement as claimed in claim 3 sleep, wherein hexichol peace bright (diphenhydramine) or the each dosage of the adult of its acid-addition salts is 25～75 milligrams.

5. the pharmaceutical compositions of improvement sleep as claimed in claim 2, the wherein anti-H of ethanolamines ₁The histamine medicine is decapryn (doxylamine) or its acid-addition salts.

6. the pharmaceutical compositions of improvement as claimed in claim 5 sleep, wherein decapryn (doxylamine) or the each dosage of the adult of its acid-addition salts is 12.5～50 milligrams.

7. the pharmaceutical compositions of improvement sleep as claimed in claim 1, wherein the each dosage of adult of composition (a) is 0.5 milligram～100 grams.

8. the pharmaceutical compositions of improvement sleep as claimed in claim 1, wherein composition (a) is uncariae uncis cure ramulus (Uncariae Uncis Cum Ramulus) and/or Flos lupuli (Flos Humuli Lupuli) (Humulus lupulus).

9. as the pharmaceutical compositions of each improvement sleep in the claim 1 to 8, wherein for this antihistaminic of 100 weight portions, the allotment amount of composition (a) is 0.01～2000 weight portion.

10. as the pharmaceutical compositions of each improvement sleep in the claim 1 to 6, wherein composition (b) is the chemical compound that is selected from more than a kind or 2 kinds among the following compounds group, comprise by esters, ethers, aldehydes, ketone, Coumarins, nitrogen-containing compound, alkene class carbohydrate, enol form group in more than a kind or 2 kinds.

11. pharmaceutical compositions as the improvement sleep of each or the 10th in the claim 1 to 6, wherein composition (b) is to be selected from by following chemical compound more than a kind or 2 kinds, comprises linalyl acetate (linalylacetate), acetic acid Herba Pelargonii Graveolentis grass ester, to the allyl benzene methyl ether, monoene aldehyde, the sesquiterpene olefine aldehydr, pinocamphone (pinocamphone), thatch ketone (bornanone), pulegone (pulegone), menthone, verbenone (verbenone), l-Cuminum celery ketone (l-carvone), d-Cuminum celery ketone, pinocarvone (pinecarvone), coumarin (coumarin), Fu Kuluo coumarin (fukuro-coumarin), S-methyl-sulfur benzoic acid, to menthone-8-mercaptan (p-methone-8-thiol), hesperidene (limonene), australene (α-pinene), β-caryophyllene (β-caryophyllene), β-sesquialter Fructus Foeniculi (β-sesquiphellandrene), common milfoil (chamazulene), β-olive alkene (β-elemene), α-patchoulene (α-patchoulene), linalool (linalool), geraniol (geraniol), α-santalol (α-santalol), sclareol (sclareol) etc. form among the group more than a kind or 2 kinds.

12. as the pharmaceutical compositions of each improvement sleep in the claim 1 to 6, the 10th or 11, wherein composition (b) be dried powder, extracts powder, quintessence oil, extraction oil or extract.

13. as the pharmaceutical compositions of each improvement sleep among each or the 10th to 12 in the claim 1 to 6, wherein composition (b) is for changing distinguish the flavor of agent, aromatic, adding pastil or spice.

14. pharmaceutical compositions as each improvement sleep among each or the 10th to 13 in the claim 1 to 6, wherein composition (b) be selected from following basis source more than a kind or 2 kinds change the flavor agent, aromatic, add pastil or spice, comprise being selected from by Folium Perillae section, Citrus section, Compositae, rice section, Fructus Rhodomyrti (myrtaceae) section, Herba Oenanthes Javanicae section, Lignum cinnamomi camphorae section, the Chinese juniper Ochnaceae, Piperaceae, Zingiberaceae, the Lignum Santali Albi Ochnaceae, Burseraceae, sweetsop section, Flos Pelargonii (geranium) section, what Rosaceae was formed source, a kind of basis more than 2 kinds among the group changes the flavor agent, aromatic, add pastil or spice.

15. as the pharmaceutical compositions of each improvement sleep among each or the 10th to 14 in the claim 1 to 6, wherein the allotment amount of composition (b) accounts for 0.001～30 weight % of total composition.

16. as the pharmaceutical compositions of each improvement sleep in the claim 1 to 6, wherein composition (c) is to be selected from following chemical compound more than a kind or 2 kinds, comprise among vitamin C and the vitamin B group more than a kind or 2 kinds.

17. as the pharmaceutical compositions that the improvement of claim 16 is slept, wherein the vitamin B group is selected from following chemical compound more than a kind or 2 kinds, comprises vitamin B ₁, vitamin B ₆, vitamin B ₁₂And they salt and derivant in more than a kind or 2 kinds.

18. the pharmaceutical compositions of improvement sleep as claimed in claim 1, wherein composition (c) is calcium and/or magnesium.

19. as the pharmaceutical compositions of each improvement sleep in the claim 1 to 6, the 16th to 18, wherein with respect to the anti-H of 100 weight portions ₁The histamine medicine, the allotment amount of composition (c) is with respect to anti-H ₁Histamine medicine 100 weight portions are 0.0002～6000 weight portion.

20. the pharmaceutical compositions of improvement sleep as claimed in claim 1, wherein the each dosage of adult of composition (d) is 0.01 milligram～1500 milligrams.

21. as the pharmaceutical compositions of claim 1 or the 20th 's improvement sleep, wherein composition (d) is melatonin melatonin (malatonin), each dosage of being grown up is 0.01 milligram～20 milligrams.

22. as the pharmaceutical compositions of claim 1 or the 7th 's improvement sleep, wherein composition (d) is 5-hydroxyl three tryptophan, each dosage of being grown up is 0.1 milligram～200 milligrams.

23. as the pharmaceutical compositions of the improvement sleep of claim 1 or the 7th, wherein composition (d) is three tryptophan, each dosage of being grown up is 0.1 milligram～1500 milligrams.

24. as the pharmaceutical compositions of each improvement sleep among claim 1 or the 20th to 23, wherein with respect to the anti-H of 100 weight portions ₁The histamine medicine, the allotment amount of composition (d) is 0.02～3000 weight portion with respect to antihistaminic 100 weight portions.

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