Pharmaceutical composition for treating insomnia and method of obtaining

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical composition for treating insomnia. Said composition includes root of Polygonum multiflorum and/or its extracts, seeds of Ziziphus spinosa and/or its extracts, mulberry fruit and/or its extracts, Ganoderma and/or its extracts, lily bulb and/or its extracts, Anemarrhena rhizome and/or its extracts, root of Salvia miltiorrhiza and/or its extracts, chrysanthemum flower and/or its extracts, Poria and/or its extracts and Albizia flower and/or its extracts. Invention also relates to application of said composition.

EFFECT: claimed invention provides sedative and soporific effect, contributes to memory stimulation.

17 cl, 6 tbl, 14 ex

 

The technical field to which the invention relates

The present invention belongs to the field of Chinese herbal medicines, relates to a pharmaceutical composition and process for its preparation, and mentioned pharmaceutical composition contains the root of Polygonum multiflorum and/or its extracts, the seed of the jujube spiny and/or its extracts and the fruit of the mulberry and/or its extracts is used in the treatment of insomnia.

The prior art of the present invention

Insomnia is not a satisfactory status with respect to the quality and quantity of sleep, which lasts for quite a long time. Insomnia is clinically common and frequently occurring disease, and its clinical symptoms are difficulty in falling asleep, ready to Wake up from sleep, inability to fall asleep again after waking up too early awakening in the morning, disturbed sleep, inability to sleep throughout the night, shallow sleep or the loss of the feeling of sleep, and may be accompanied by drowsiness. In addition, insomnia can result in discomfort after waking up, fatigue, reduced efficiency of mental activity or obstacle to social functions. It is assumed that approximately 20% of people aged 20 suffer from sleep disturbance; is the number of vozraste� to 50% at age 55 and up to 90% at 80 years of age. As shown by the latest statistics, more than 42.5 per cent of China's population suffer from sleep disorders to varying degrees; the incidence of insomnia reaches 10% -20%. Results for "Sanofi-Aventis Sleep Survey" conducted by the Branch Society of Psychiatry, the Chinese Medical Association in 2002, showed that 25.9 per cent of people consider themselves to be suffering from sleep disturbance, which began 2 years (median) ago. It should be noted that, in accordance with Athenian scale perfect sleep quality do not have to 45.4% of people, of which 28% refers to insomnia, and 17.4% relates to possible insomnia (Xiaohong ZHANG, China Medical Tribune, October 10, 2002, issue 831).

In recent years, with the continuous improvement of living standards and increasing social oppression of competition, especially of hard work and study, the incidence of this disease increases, which seriously affects quality of life, work and study patients and has adverse effects on work, study and social communication. 45% of road accidents are linked to sleep loss, 50% of occupational injuries associated with lack of sleep, and the risk of an accident for a person suffering from chronic insomnia, 4.5 times higher than for a healthy person (Da JING, China Medical Tribune, March 20, 2003, issue 853).

With the increased pace of life and increased work pressure is observed more patient�in insomnia, and there is an increasingly urgent need for effective prevention and treatment of this disease. Recent studies demonstrate that the effectiveness of sedatives alone is low, especially when toxic and side effects of chemically synthesized drugs have become increasingly apparent, and the dependence of the human body, a symptom of withdrawal symptoms and symptom impact caused widespread concern practitioners and patients.

Traditional Chinese medicine has a long history in the treatment of insomnia. Based on holistic concepts and differentiation and treatment of syndromes, the effectiveness of traditional Chinese medicine in the treatment of insomnia is undeniable and long lasting with proper security, satisfactory to the commitment of patients. Therefore, people are trying to prevent and cure insomnia, under the guidance of theory of traditional Chinese medicine, and a request for the treatment of insomnia with the help of medicines derived from natural traditional Chinese materia medica, also increases.

Summary of the invention

In one aspect, the present invention provides a pharmaceutical composition containing the root of Polygonum multiflorum and/or its extracts, the seed of the jujube spiny and/or its extracts and the fruit of Shelkovo�s and/or its extracts.

In some embodiments, the pharmaceutical composition of the present invention further comprises the Ganoderma and/or its extracts, Lily bulb and/or its extracts, rhizome of anemarrhena and/or its extracts, root of Salvia mnogokratnogo and/or its extracts, chrysanthemum flower and/or its extracts and sea o and/or its extracts.

In some embodiments, the pharmaceutical composition of the present invention further comprises a flower albitius and/or its extracts.

In some embodiments, each referred to independently extract is an extract of the solvent. The said solvent can be any suitable solvent, for example water, ethanol, aqueous ethanol, supercritical carbon dioxide or any mixture.

In some embodiments, the mentioned pharmaceutical composition is prepared from medicinal raw materials with the following relationship weight parts: root of Polygonum multiflorum 150-270, the seed of the jujube spiny 145-275 and the fruit of the mulberry 160-255.

In some embodiments, the mentioned pharmaceutical composition is prepared from medicinal raw materials with the following relationship weight parts: root of Polygonum multiflorum 150-270, the seed of the jujube spiny 145-275, the fruit of the mulberry 160-255, Ganoderma 80-135, onion�Vita Lily 75-160, the rhizome of anemarrhena 50-110, root sage mnogokratnogo 120-200, chrysanthemum flower 45-120 and the sea o 75-145.

In some embodiments, the mentioned pharmaceutical composition is prepared from medicinal raw materials with the following relationship weight parts: root of Polygonum multiflorum 150-270, the seed of the jujube spiny 145-275, the fruit of the mulberry 160-255, Ganoderma 80-135, bulb lilies 75-160, rhizome of anemarrhena 50-110, root sage mnogokratnogo 120-200, chrysanthemum flower 45-120, the sea o 75-145 and flower albitius 165-288.

In some embodiments, the relationship of parts by weight of medicinal raw materials are: root of Polygonum multiflorum 158, the seed of the jujube spiny 270, the fruit of the mulberry 165, Ganoderma 135, Lily bulb 80, the rhizome of anemarrhena 110, the root of Salvia mnogokratnogo 125, chrysanthemum flower 118, the sea o 80 and flower albitius 280.

In some embodiments, the relationship of parts by weight of medicinal raw materials are: root of Polygonum multiflorum 265, the seed of the jujube spiny 147, mulberry fruit 250, Ganoderma 81, Lily bulb 158, rhizome of anemarrhena 55, Clary wort mnogokratnogo 188, 50 chrysanthemum flower, the sea o 145 and flower albitius 170.

In some embodiments, the relationship of parts by weight of medicinal raw materials are: root of Polygonum multiflorum 225, the seed of the jujube spiny 163, the fruit of the mulberry 220 Ganoderma 83, bulb lilies 113, rhizome of anemarrhena 50, Clary wort mnogokratnogo 190, chrysanthemum flower 45, 113 and the sea o flower albitius 178.

In some embodiments, the relationship of parts by weight of medicinal raw materials are: root of Polygonum multiflorum 165, the seed of the jujube spiny 228, the fruit of the mulberry 173, Ganoderma 110, Lily bulb 75, rhizome of anemarrhena 75, Clary wort mnogokratnogo 150, chrysanthemum flower 78, 78 and the sea o flower albitius 218.

In some embodiments, the relationship of parts by weight of medicinal raw materials are: root of Polygonum multiflorum 200, the seed of the jujube spiny 200, the fruit of the mulberry 200, Ganoderma 100, bulb lilies 100, rhizome of anemarrhena 66,7, root sage mnogokratnogo 166,7, chrysanthemum flower 66,7, the sea o 100 and flower albitius 200.

In some embodiments, each gram of the pharmaceutical composition contains not less than 0.5 mg, preferably not less than 1.0 mg, more preferably not less than 1.5 mg 2,3,5,4'-tetrahydroxyphenyl-2-O-β-D-glucoside (mainly derived from the root of Polygonum multiflorum or extracts) on a dry weight of the pharmaceutical composition.

In some embodiments, a dosage form of the pharmaceutical composition is a capsule, tablet, powder, oral liquid, soft capsule, pill,�, ASTA, syrup, suppository, gel, spray or an injection.

In some embodiments, a method of producing a pharmaceutical composition comprises obtaining an extract of one or more species of medicinal raw materials individually or together.

In some embodiments, a method of producing a pharmaceutical composition comprises: weighting of medicinal raw materials in accordance with the weight relationship of the parts to soak for 20-40 minutes by adding water, infusion over 30-40 minutes after boiling, filtering and again insistence within 25-30 minutes after adding water and boiling, filtering and combining the two filtrates.

In some embodiments, a method of obtaining a pharmaceutical composition comprising the following steps:

(a) obtaining alcoholic extract of the root of Polygonum multiflorum, rhizomes of anemarrhena and the seed of the jujube spiny;

(b) obtaining an aqueous extract of the fruit of the mulberry, parii, Ganoderma, root sage mnogokratnogo, flower albitius and chrysanthemum flower;

c) obtaining a powder of the bulb of Lily;

(d) application of alcoholic extract of stage (a), an aqueous extract of stage b) and a powder of the bulb of Lily stage c) as the active ingredients of the pharmaceutical composition.

In some embodiments, is capable of� obtain the pharmaceutical composition includes the following stages:

(a) the root of Polygonum multiflorum, rhizome of anemarrhena and the seed of the jujube spiny weighed in accordance with the relationship of parts by weight, add 6-12 times the amount of 30% -70% ethanol; carry out heating to reflux for 1 to 3 times during the 1-3 hours each time; the extract was filtered, pooled, and the ethanol recovered under reduced pressure and concentrated to a relative density of 1.10-1.15 times as determined at 60°C, to obtain an alcohol extract;

(b) the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and the chrysanthemum flower is weighed in accordance with the relationship of parts by weight, add 10-15-fold amount of water to be extracted, from 1 to 3 times for 1-3 hours each time; the extract was filtered, pooled and concentrated to a relative density of approximately 1,10-1,15, determined at 60°C, to obtain an aqueous extract;

c) the bulb of Lily weighed in accordance with the ratio of parts by weight and ground into a powder 100 mesh Lily bulbs;

(d) ethanolic extract stage (a), an aqueous extract of stage b) and a powder of the bulb of Lily stage c) are used as active ingredients of pharmaceutical compositions.

The active ingredients can be obtained in the required dosage forms together with optional�and pharmaceutical excipients.

Dosage form pharmaceutical composition according to the present invention may constitute any suitable dosage form, e.g. capsule, tablet, powder, oral liquid, soft capsule, pill, tincture, syrup, suppository, gel, spray or an injection.

In order to obtain the above-mentioned dosage forms, during the preparation of these dosage forms can be added pharmaceutically acceptable excipients, such as filler, a disintegrant, a moving substance, fluidizer agent, binder, sweetener, flavoring agent, preservative and the like. Fillers include starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose and the like. Leavening agents include starch, pregelatinized starch, microcrystalline cellulose, carboxymethylcel sodium, cross-linked polyvinylpyrrolidone, hydroxypropyl cellulose with a low degree of substitution, cross-linked carboxymethylcellulose sodium and the like. Sliding substances include magnesium stearate, sodium dodecyl sulfate, talc powder, silica and the like. Suspendresume tools include polyvinylpyrrolidone, microcrystalline cellulose, �agarose, agar, methylcellulose, and the like. Binders include starch suspension, polyvinylpyrrolidone, methylcellulose and the like. The sweeteners include saccharin sodium, aspartame, sucrose, sodium cyclamate, glycyrrhetic acid and the like. Fragrances include sweetener and various essences. Preservatives include the parabens, benzoic acid, sodium benzoate, sorbic acid and their salts, benzalkonium bromide, chlorhexidine acetate, eucalyptus oil and the like.

Pharmaceutical composition according to the present invention can be obtained in various ways. Such techniques are well known to those skilled in the art and described in various technical documents for reference you can read Remington's Pharmaceutical Manual, etc. These methods include ordinary methods of preparation, such as mixing, dissolving, emulsifying, suspending, etc.

A method of producing tablets with a pharmaceutical composition according to the present invention comprises the following steps:

(a) selected and peeled the root of Polygonum multiflorum, rhizome of anemarrhena and coarsely crushed seed of the jujube spiny weighed in accordance with the relationship, add 6-12 times the amount of 30% -70% ethanol; OSU�estlat the reflux from 1 to 3 times for extraction within 1-3 hours each time; the extract was filtered, pooled, and the ethanol recovered under reduced pressure and concentrated to a relative density of 1.10-1.15 times as determined at 60°C, to obtain an alcoholic extract, ready-to-use;

(b) selected and peeled the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and the chrysanthemum flower is weighed in accordance with the relationship, add 10-15-fold amount of water to be extracted, from 1 to 3 times for 1-3 hours each time; the extract was filtered, pooled, and concentrated to a relative density of approximately 1,10-1,15, determined at 60°C, to obtain an aqueous extract, ready-to-use;

(c) selected and peeled onion Lily weighed in accordance with the relations and ground into a powder 100 mesh, ready to use;

(d) ethanolic extract obtained in stage (a), an aqueous extract of stage b) and finely divided powder of the bulb of Lily, obtained in stage c), is subjected to dry granulation; after the classification of the granules is added the appropriate auxiliary substances; carry out mixing, tabletting and coating of the shell.

A method of producing tablets with a pharmaceutical composition according to the present invention preferably comprises the following steps:

p> (a) selected and peeled the root of Polygonum multiflorum, rhizome of anemarrhena and coarsely crushed seed of the jujube spiny weighed in accordance with the relationship, and add 60% ethanol; exercise reflux twice for extraction, and the first time you add a 10-fold quantity and Astrovirus for 2 hours and the second time add 8 times the normal amount and Astrovirus for 1 hours; the extract was filtered, pooled, and the ethanol recovered under reduced pressure and concentrated to a relative density of 1.10-1.15 times as determined at 60°C, in order to obtain an alcoholic extract, ready-to-use;

(b) selected and peeled the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and the chrysanthemum flower is weighed in accordance with the relationship, add 11-fold amount of water to be extracted, twice for 1.5 hours each time; the extract was filtered, pooled, and concentrated to a relative density of approximately 1,10-1,15, determined at 60°C, to obtain an aqueous extract, ready-to-use;

(c) selected and peeled onion Lily weighed in accordance with the relations and ground into a powder 100 mesh, ready to use;

(d) finely divided powder of the bulb of Lily, are� at the stage (c), add in the capacity for ingredients spray dryer granulator, ethanolic extract of step a) and aqueous extract of stage (b) sbryzgivayut granulating by spraying; after the classification of the granules is added 0.5% of magnesium stearate; carry out mixing, tabletting and coating of the shell.

A method of producing a decoction of the pharmaceutical composition in accordance with the present invention includes: root of Polygonum multiflorum, the seed of spiny jujube, mulberry fruit, Ganoderma, Lily bulb, rhizome of anemarrhena, root sage mnogokratnogo, chrysanthemum flower, and sea o flower albitius weighed in accordance with the relations and put into the boiler; add water for the first time at 3-5 cm above the upper surface of the drug; medicinal raw materials are soaked for 20-40 minutes, insist for 30-40 minutes after boiling and filtered; add water again at 1-3 cm above the upper surface of the product; medicinal raw materials are infused for 25-30 minutes after boiling, filter and merge two filtrate.

A method of producing a wet pill with pharmaceutical composition according to the present invention includes:

(a) selected and peeled the root of Polygonum multiflorum, rhizome of anemarrhena and coarsely crushed seed of the jujube spiny weighed in accordance with the ratio of�mi, add 6-12 times the amount of 30% -70% ethanol; carry out heating to reflux for 1 to 3 times for extraction within 1-3 hours each time; the extract was filtered, pooled, and the ethanol recovered under reduced pressure, concentrated and dried at 60-80°C and pulverized, to obtain a dry ethanolic extract, ready-to-use;

(b) selected and peeled the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and the chrysanthemum flower is weighed in accordance with the relationship, add 10-15-fold amount of water to be extracted, from 1 to 3 times for 1-3 hours each time; the extract was filtered, pooled, concentrated and dried at 60-80°C and pulverized to obtain dry aqueous extract, ready-to-use;

(c) selected and peeled onion Lily weighed in accordance with the relations and ground into a powder 100 mesh, ready to use;

from a dry alcoholic extract obtained in stage (a), dry aqueous extract of stage b) and finely divided powder of the bulb of Lily, obtained in stage c), together make sugar plum.

All of capsules, powder, oral liquid, soft capsules, pills, tincture, syrup, suppository, gel, spray, and injection of the pharmaceutical composition in accordance with the infusion�them by the invention can be obtained from medicinal raw materials for the pharmaceutical composition in accordance with the present invention, or active ingredients of pharmaceutical compositions in accordance with the present invention in accordance with conventional pharmaceutical methods.

Pharmaceutical composition in accordance with the present invention it is possible to introduce various animals, including mammals, especially humans. For animals or people who need the introduction of pharmaceutical compositions in accordance with the present invention, the dosage may be determined by health practitioners in accordance with the condition of the subject, including, for example, the severity of the disease, General health, body weight, patient age, and the like. Pharmaceutical composition in accordance with the present invention it is possible to introduce a variety of appropriate ways, including, for example, oral, intravenous, subcutaneous, transdermal and topical administration, etc. Frequency of administration of the pharmaceutical compositions according to the present invention can be determined by various factors, including, for example, the specific disease being treated, the overall health of the subject, etc. Usually for men the dosage of the pharmaceutical composition in accordance with the present invention is 14-20 g / day based on the total weight of medicinal raw materials, and can be taken once a day or divided into 2-4 doses per day, preferably of 16.8 g per day divided in 3 doses per day.

The terms used in anastasimatarion, I have the normal meaning in the field of traditional Chinese medicine.

The root of Polygonum multiflorum: POLYGONI MULTIFLORI RADIX. It is a dry root tuber of Polygonum multiflorum Thunb. It is mined in autumn and winter, when the leaves dry up; both ends cut off; his clean and large tubers are cut into pieces; and then dried.

The processed root of Polygonum multiflorum (POLYGONI MULTIFLORI RADIX PRAEPARATA) is a processed product of the root of Polygonum multiflorum. Take a mug or pieces of the root of Polygonum multiflorum and evenly mixed with the juice giacintova beans and brewing method is carried out (Annex II D Chinese Pharmacopoeia, edition 2010) in an appropriate non-ferrous containers, as long as the juice does not boil, or carry out a method of steaming (Annex II D Chinese Pharmacopoeia, edition 2010), and treated with steam alone or treated with steam after uniform mixing with juice giacintova beans to brown on all sides, dried in the sun to incomplete drying, then cut into circles, and again dried. For every 100 kg of circles (pieces) of the root of Polygonum multiflorum use 10 kg giacintova beans. The method of extracting the juice giacintova beans: take 10 kg giacintova beans and add appropriate amount of water; boil for 4 hours, to obtain PR�about 15 kg of juice, and add extra water to the remainder of the beans and boil for 3 hours, to obtain about 10 kg of juice; juice combine and get about 25 kg of juice giacintova beans.

The seed of the jujube spiny: ZIZIPHI SPINOSAE SEMEN. It is a dried ripe seed of Ziziphus jujuba Mill var. spinosa (Bunge) Hu ex H. FChou, which is a plant of the buckthorn family. The ripe fruit is collected in late autumn and early winter, remove the pulp and shell (endocarp) and dried in the sun.

Baked at stirring the seed of the jujube spiny: take the cleaned seed of the jujube spiny and baked in accordance with a simple way to bake while stirring (Annex II D Chinese Pharmacopoeia, edition 2010), so it has increased in volume and gained a slightly darker color. Crushed into pieces before use.

The fruit of the mulberry: FRUCTUS MORI. It is a dried fruit-spike Morus alba L., which is a plant of the mulberry family. The raw material is collected from April to June, when the fruits turn red, and dried in the sun or dried after a quick steaming.

Ganoderma: GANODERMA. It is a dried sporophore Ganoderma lucidum (Leyss. ex Fr.) Karst. or Ganoderma sinense Zhao, Xu et Zhang (family polyporaceae). The raw material is collected all year; remove foreign material adhering wood dust, sand or the lower layer of nourishing CRE�professional of the substrate; dried in the shade or in an oven at 40-50°C.

The bulb of a Lily: BULBUS LILII. It is a dried fleshy scaly leaf of Lilium lancifolium Thunb., Lilium brownii FE. Brown var. viridulum Baker or Lilium pumilum DC, which are plants of the family Liliaceae. The raw material is collected in autumn and washed, and scaly leaves removed, groomed for a moment in boiling water and dried.

The rhizome of anemarrhena: RHIZOMA ANEMARRHENAE. It is a dried rhizome of Anemarrhena asphodeloides Bge., which is a plant of the family Liliaceae. The raw material is collected in autumn or winter, remove fibrous roots and soil, dried in the sun, what is known as "Maozhimu"; or remove the outer fabric and dried in the sun.

The root of Salvia mnogokratnogo: SALVIAE MILTIORRHIZAE RADIX ET RHIZOMA. It is a dried root and rhizome of Salvia miltiorrhiza Bge., which is a plant of the family Lamiaceae. The raw material is collected in spring or autumn, remove soil and dry.

Chrysanthemum flower: FLOS CHRYSANTHEMI. It is a dried head Chrysanthemum morifolium Ramat., which is a plant of the family Asteraceae. Raw materials collected in batches from September to November when flowering, dried in the shade or by baking or dried in the sun after treatment with smoke and steam. It belongs to the "Boju", "Chuju", "Gongju" and "Hangju" in accordance with different places of production and variations in processing methods.

The sea o: PORIA. It is a dried sclerotium of fungi Porta cocos (Schw.) Wolf, (family polyporaceae). The raw material is collected mainly from July to September, remove the soil, put on the wetted surface, then spread on a dry surface. Repeat several times, until there will be no folds and is evaporated inland water, then dried in the shade, this is known as "Fulingge"; or fresh sclerotia is cut and dried in the shade in accordance with the cut parts, what is known as "Fulingpian" and "Fulingkuai".

Flower albitius: FLOS ALBIZIAE. It is a dried inflorescence Albizia julibrissin Durazz, which is a legume. Collect them Sunny days in summer, when the flower blooms, and dried in the sun without delay.

Traditional Chinese material medica of the present invention may be replaced by a traditional Chinese material medica of the same or similar efficiency, and all these material medica can be recycled in accordance with the "National processing standards for traditional Chinese material medica" or "Dictionary of Traditional Chinese Medicine". For example, the root of Polygonum multiflorum you can replace processed by the root of Polygonum multiflorum, and the seed of the jujube spiny, you can substitute baked at stirring the seed of the jujube spiny; although efficiency after replacement may be higher than that of the original medicinal plants, all of them with�allegat the scope of the present invention.

In another aspect the present invention provides the use of pharmaceutical compositions for the treatment of symptoms of insomnia, amnesia, dizziness, fatigue and/or pain and weakness in loin and knees, etc.

In another aspect of the present invention also provides a pharmaceutical composition for sedation, hypnosis, stimulate memory, reduce fatigue and/or pain relief.

In another aspect of the present invention also provides a method of treating insomnia which comprises administering the pharmaceutical composition to a patient with insomnia.

Functions and indications for the use of pharmaceutical compositions in accordance with the present invention are filling the cells of the kidneys and the health of the brain, nourishment for the heart to calm the spirit, and it is used for insomnia, which is caused by deficiency of the heart and kidneys, and symptoms which include sleep disturbance, such as difficulty falling asleep, shallow sleep, night waking, excessive dreaming, etc., accompanied by amnesia, dizziness, palpitations, fatigue, soreness and weakness in lower back and knees.

The present invention is made by Professor WU Yiling repeated practice on the basis of theoretical research tradi�ion Chinese medicine in the treatment of insomnia in combination with clinical results. Clinically observed that the symptoms of insomnia, such as amnesia, dizziness, palpitations, fatigue, soreness and weakness in loin and knees, etc., caused by deficiency of heart and kidney, can effectively be improved.

Detailed embodiments of the present invention

The following examples are offered for illustrative purposes only of obtaining the pharmaceutical composition in accordance with the present invention, but they do not limit in any way the scope of the present invention.

Example 1: Obtaining tablets with a pharmaceutical composition according to the present invention (also known as a tablet Anshen Jiannao)

Pharmaceutical raw material: root of Polygonum multiflorum 200 g; the seed of the jujube spiny 200 g; mulberry fruit 200 g; Ganoderma 100 g; Lily bulb 100 g; rhizome of anemarrhena 66,7 g; the root of Salvia mnogokratnogo 166,7 g; chrysanthemum flower 66,7 g; the sea o 100 g; and the flower of albizia 200 g

Method of obtaining:

(a) selected and purified the root of Polygonum multiflorum, rhizome of anemarrhena and coarsely crushed seed of the jujube spiny weighed in accordance with the relationship, was added 60% ethanol; was heated to reflux, in order to extract, twice, the first time added a 10-fold amount of ethanol and extracted for 2 hours and the second time to�alali 8-fold amount of ethanol and extracted for 1 hour; the extract was filtered, pooled, and ethanol regenerates under reduced pressure and concentrated to a relative density of 1.10-1.15 times as determined at 60°C, to obtain an alcoholic extract, ready-to-use;

(b) selected and peeled the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and chrysanthemum flower weighed in accordance with the relationship, added 11-fold amount of water to be extracted, twice for 1.5 hours each time; the extract was filtered, pooled and concentrated to a relative density of approximately 1,10-1,15, determined at 60°C, to obtain an aqueous extract, ready-to-use;

(c) selected and peeled onion Lily weighed in accordance with the relations and crushed into powder 100 mesh, ready to use;

(d) finely divided powder of the bulb of Lily, obtained in stage c), was added into the container for the ingredients of a spray dryer granulator, an alcoholic extract obtained in stage (a), and an aqueous extract phase (b) sbrasyvali granulating by spraying; after the classification of the granules was added 0.5% of magnesium stearate; was carried out by mixing, tabletting and coating of the shell, in order to get 975 pills mentioned tablets (0.4 g per tablet).

Example 2:obtain the capsules with a pharmaceutical composition according to the present invention

Pharmaceutical raw material: root of Polygonum multiflorum 158 g; the seed of the jujube spiny 270g; the fruit of the mulberry 165 g; Ganoderma 135 g; Lily bulb 80 g; rhizome of anemarrhena 110 g; root of Salvia mnogokratnogo 125 g; chrysanthemum flower 118 g; the sea o 80 g; and the flower of albizia 280.

Method of obtaining:

(a) selected and purified the root of Polygonum multiflorum, rhizome of anemarrhena and coarsely crushed seed of the jujube spiny weighed in accordance with the relationship, was added 6-fold amount of 30% ethanol was heated to reflux, in order to extract, 3 times for 3 hours each time; the extract was filtered, pooled, and ethanol regenerates under reduced pressure and concentrated to a relative density of 1.10-1.15 times as determined at 60°C, to obtain an alcoholic extract, ready-to-use;

(b) selected and peeled the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and chrysanthemum flower weighed in accordance with the relationship, added 10-fold amount of water to extract, 3 times for 3 hours each time; the extract was filtered and combined, and the ethanol was regenerated under reduced pressure and concentrated to a relative density of approximately 1,10-1,15, determined at 60°C, to the floor�'it aqueous extract, ready-to-use;

(c) selected and peeled onion Lily weighed in accordance with the relations and crushed into powder 100 mesh, ready to use;

(d) ethanolic extract obtained in stage (a), an aqueous extract of stage b) and finely divided powder of the bulb of Lily, obtained in stage c), were subjected to dry granulation; after the classification of the granules was added the appropriate excipients; evenly mixed and filled in capsules to obtain 983 capsules (0.42 g per capsule).

Example 3: preparation of powder pharmaceutical composition according to the present invention

Pharmaceutical raw material: root of Polygonum multiflorum 265 g; the seed of the jujube spiny 147 g; mulberry fruit 250 g; Ganoderma 81 g; Lily bulb 158 g; rhizome of anemarrhena 55 g; root of Salvia mnogokratnogo 188 g; chrysanthemum flower 50 g; the sea o 145 g and the flower albitius 170 g.

Method of obtaining:

(a) selected and purified the root of Polygonum multiflorum, rhizome of anemarrhena and coarsely crushed seed of the jujube spiny weighed in accordance with the relationship, added 12-fold amount of 70% ethanol was heated to reflux, in order to extract, 2 times for 2 hours each time; the extract was filtered and combined, and the ethanol was regenerated under reduced pressure, and the observed concentration�was demonstrated to the relative density, 1.10-1.15 times as determined at 60°C, to obtain an alcoholic extract, ready-to-use;

(b) selected and peeled the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and chrysanthemum flower weighed in accordance with the relationship, added 15-fold amount of water to be extracted, 2 times for 2 hours each time; the extract was filtered, pooled and concentrated to a relative density of approximately 1,10-1,15, determined at 60°C, to obtain an aqueous extract, ready-to-use;

(c) selected and peeled onion Lily weighed in accordance with the relations and crushed into powder 100 mesh, ready to use;

(d) ethanolic extract obtained in stage (a), an aqueous extract of stage b) and finely divided powder of the bulb of Lily, obtained in stage c), were subjected to dry grinding, to obtain 400 g of powder, which were allotted to 2 g per package.

Example 4: Obtaining oral liquid pharmaceutical composition according to the present invention

Pharmaceutical raw material: root of Polygonum multiflorum 225 g; the seed of the jujube spiny 163 g; the fruit of the mulberry 220 g; Ganoderma 83 g; bulb lilies 113 g; rhizome of anemarrhena 50 g; the root of Salvia mnogokratnogo 190 g; chrysanthemum flower 45 g; the sea o 113 g and totocalcio 178

Method of obtaining:

(a) selected and purified the root of Polygonum multiflorum, rhizome of anemarrhena and coarsely crushed seed of the jujube spiny weighed in accordance with the relationship, added 10-fold amount of 50% ethanol was heated to reflux, in order to extract, for 3 hours; the extract was filtered, and ethanol was regenerated under reduced pressure and concentrated to a relative density of 1.10-1.15 times as determined at 60°C, to obtain an alcoholic extract, ready-to-use;

(b) selected and peeled the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and chrysanthemum flower weighed in accordance with the relationship, added 12-fold amount of water to be extracted, for 3 hours; the extract was filtered and concentrated to a relative density of approximately 1,10-1,15, determined at 60°C, to obtain an aqueous extract, ready-to-use;

(c) selected and peeled onion Lily weighed in accordance with the relations and crushed into powder 100 mesh, ready to use;

(d) of alcoholic extract of step (a), an aqueous extract of stage b) and finely divided powder of the bulb of Lily, obtained in stage c), received oral solution in the corresponding�AI with conventional methods (Chunlin CAO, Pharmaceutics of Traditional Chinese Medicine, Shanghai Science & Technology Press, 1st edition in November 1986, 8th edition in October 1993: a method of producing an oral solution, p. 477-488), in order to get a 10000 ml oral solution, which was divided into a 10 ml container.

Example 5: Obtaining soft capsules with pharmaceutical composition according to the present invention

Pharmaceutical raw material: root of Polygonum multiflorum 225 g; the seed of the jujube spiny 163 g; the fruit of the mulberry 220 g; Ganoderma 83 g; bulb lilies 113 g; rhizome of anemarrhena 50 g; the root of Salvia mnogokratnogo 190 g; chrysanthemum flower 45 g; the sea o 113 g and the flower albitius 178

Method of obtaining:

(a) selected and purified the root of Polygonum multiflorum, rhizome of anemarrhena and coarsely crushed seed of the jujube spiny weighed in accordance with the relationship, added 12-fold amount of 70% ethanol was heated to reflux, in order to extract, for 1.5 hours; the extract was filtered, pooled, and ethanol regenerates under reduced pressure and concentrated to a relative density of 1.10-1.15 times as determined at 60°C, to obtain an alcoholic extract, ready-to-use;

(b) selected and peeled the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and the chrysanthemum flower in�velivoli in accordance with the relationship added 15-fold amount of water to extract, 3 times for 1 hour each time; the extract was filtered and concentrated to a relative density of approximately 1,10-1,15, determined at 60°C, to obtain an aqueous extract, ready-to-use;

(c) selected and peeled onion Lily weighed in accordance with the relations and crushed into powder 100 mesh, ready to use;

(d) of alcoholic extract of step (a), an aqueous extract of stage b) and finely divided powder of the bulb of Lily, obtained in stage c), obtained soft capsule in accordance with conventional methods (Chunlin CAO, Pharmaceutics of Traditional Chinese Medicine, Shanghai Science & Technology Press, 1st edition in November 1986, 8th edition in October 1993: a method of producing soft capsule, pp. 232-235), in order to obtain 980 softgels (0.6 g per capsule).

Example 6: obtain the pills with pharmaceutical composition according to the present invention

Pharmaceutical raw material: root of Polygonum multiflorum 165 g; the seed of the jujube spiny 228 g; the fruit of the mulberry 173 g; Ganoderma 110 g; Lily bulb 75 g; rhizome of anemarrhena 75 g; root of Salvia mnogokratnogo 150 g; chrysanthemum flower 78 g, 78 g sea o & flower albitius 218.

Method of obtaining:

(a) selected and purified the root of Polygonum multiflorum, rhizome of anemarrhena and coarsely and�melcene the seed of the jujube spiny weighed in accordance with the relationship added 8 times the amount of 40% ethanol was heated to reflux, in order to extract, twice for 2 hours each time; the extract was filtered, pooled, and ethanol regenerates under reduced pressure and concentrated to a relative density of 1.10-1.15 times as determined at 60°C, to obtain an alcoholic extract, ready-to-use;

(b) selected and peeled the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and chrysanthemum flower weighed in accordance with the relationship, added 12-fold amount of water to be extracted, twice for 1.5 hours each time; the extract was filtered and concentrated to a relative density of approximately 1,10-1,15, determined at 60°C, to obtain an aqueous extract, ready-to-use;

(c) selected and peeled onion Lily weighed in accordance with the relations and crushed into powder 100 mesh, ready to use;

(d) of alcoholic extract of step (a), an aqueous extract of stage b) and finely divided powder of the bulb of Lily, obtained in stage c), received the pills in accordance with conventional methods (Chunlin CAO, Pharmaceutics of Traditional Chinese Medicine, Shanghai Science & Technology Press, 1st edition in November 1986, 8th edition in October 1993: a method of producing the pills,pp. 248-280), to obtain 900 drops (0.5 g per pill).

Example 7: Obtaining the infusion of the pharmaceutical composition in accordance with the present invention

Pharmaceutical raw material: root of Polygonum multiflorum 158 g; the seed of the jujube spiny 270g; the fruit of the mulberry 165 g; Ganoderma 135 g; Lily bulb 80 g; rhizome of anemarrhena 110 g; root of Salvia mnogokratnogo 125 g; chrysanthemum flower 118 g; the sea o 80 g and flower albitius 280.

Method of obtaining:

(a) selected and purified the root of Polygonum multiflorum, rhizome of anemarrhena and coarsely crushed seed of the jujube spiny weighed in accordance with the relationship, added 11-fold amount of 60% ethanol was heated to reflux, in order to extract, 3 times for 1 hour each time; the extract was filtered, pooled, and ethanol regenerates under reduced pressure and concentrated to a relative density of 1.10-1.15 times as determined at 60°C, to obtain an alcoholic extract, ready-to-use;

(b) selected and peeled the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and chrysanthemum flower weighed in accordance with the relationship, added a 14-fold amount of water to extract, 3 times for 1.5 hours each time; the extract was filtered and concentrated to a relative consideration�Noi density, approximately 1,10-1,15, determined at 60°C, to obtain an aqueous extract, ready-to-use;

(c) selected and peeled onion Lily weighed in accordance with the relations and crushed into powder 100 mesh, ready to use;

(d) of alcoholic extract of step (a), an aqueous extract of stage b) and finely divided powder of the bulb of Lily, obtained in stage c), received the infusion in accordance with conventional methods (Chunlin CAO, Pharmaceutics of Traditional Chinese Medicine, Shanghai Science & Technology Press, 1st edition in November 1986, 8th edition in October 1993: method of infusion, pp. 163-165), in order to get a 10000 ml infusion, which was divided into a 10 ml container.

Example 8: obtain a syrup with the pharmaceutical composition according to the present invention

Pharmaceutical raw material: root of Polygonum multiflorum 265 g; the seed of the jujube spiny 147 g; mulberry fruit 250 g; Ganoderma 81 g; Lily bulb 158 g; rhizome of anemarrhena 55 g; root of Salvia mnogokratnogo 188 g; chrysanthemum flower 50 g; the sea o 145 g and the flower albitius 170 g.

Method: in 10000 ml of syrup were obtained in accordance with conventional methods (Chunlin CAO, Pharmaceutics of Traditional Chinese Medicine, Shanghai Science & Technology Press, 1st edition in November 1986, 8th edition in October 1993: a method of producing syrup, pp. 166-170), and distributed on a 10 ml container.

Prima� 9: obtaining a suppository with the pharmaceutical composition according to the present invention

Pharmaceutical raw material: root of Polygonum multiflorum 158 g; the seed of the jujube spiny 270g; the fruit of the mulberry 165 g; Ganoderma 135 g; Lily bulb 80 g; rhizome of anemarrhena 110 g; root of Salvia mnogokratnogo 125 g; chrysanthemum flower 118 g; the sea o 80 g; flower albitius 280.

Method of obtaining: 500 suppositories were obtained in accordance with conventional methods (Chunlin CAO, Pharmaceutics of Traditional Chinese Medicine, Shanghai Science & Technology Press, 1st edition in November 1986, 8th edition in October 1993: a method of producing suppositories, pp. 352-361), 0.5 g per suppository.

Example 10: preparation of a gel and the pharmaceutical composition according to the present invention

Pharmaceutical raw material: root of Polygonum multiflorum 225 g; the seed of the jujube spiny 163 g; the fruit of the mulberry 220 g; Ganoderma 83 g; bulb lilies 113 g; rhizome of anemarrhena 50 g; the root of Salvia mnogokratnogo 190 g; chrysanthemum flower 45 g; the sea o 113 g and the flower albitius 178

Method: in 3000 g of the gel obtained in accordance with conventional methods (Chunlin CAO, Pharmaceutics of Traditional Chinese Medicine, Shanghai Science & Technology Press, 1st edition in November 1986, 8th edition in October 1993: a method of obtaining a gel, p. 349-350) and distributed to 10 g per container.

Example 11: obtain a spray with the pharmaceutical composition according to the present invention

Pharmaceutical raw material: root of Polygonum multiflorum 225 g; the seed of the jujube calucag� 163 g; the fruit of the mulberry 220 g; Ganoderma 83 g; bulb lilies 113 g; rhizome of anemarrhena 50 g; the root of Salvia mnogokratnogo 190 g; chrysanthemum flower 45 g; the sea o 113 g and the flower albitius 178

Method: in 10000 ml of the spray were obtained in accordance with conventional methods (Chunlin CAO, Pharmaceutics of Traditional Chinese Medicine, Shanghai Science & Technology Press, 1st edition in November 1986, 8th edition in October 1993: a method of producing spray, p. 454-466) and distributed to 100 ml per container.

Example 12: getting the injection solution pharmaceutical composition according to the present invention

Pharmaceutical raw material: root of Polygonum multiflorum 165 g; the seed of the jujube spiny 228 g; the fruit of the mulberry 173 g; Ganoderma 110 g; Lily bulb 75 g; rhizome of anemarrhena 75 g; root of Salvia mnogokratnogo 150 g; chrysanthemum flower 78 g, 78 g sea o & flower albitius 218.

Method: in 1000 injection were obtained in accordance with conventional methods (Chunlin CAO, Pharmaceutics of Traditional Chinese Medicine, Shanghai Science & Technology Press, 1st edition in November 1986, 8th edition in October 1993: a method of producing an injectable solution, page 364-4193), 5 ml of a container.

Example 13: Getting broth pharmaceutical compositions according to the present invention

Pharmaceutical raw materials: same as in example 1.

Method of obtaining:

The root of Polygonum multiflorum, the seed of spiny jujube, the fruit of Shelkovo�s, the Ganoderma, Lily bulb, rhizome of anemarrhena, root sage mnogokratnogo, chrysanthemum flower, and sea o flower albitius weighed in accordance with the relationship and was put into the boiler; water was added the first time at 3-5 cm above the upper surface of the medicinal raw materials were soaked for 30 minutes and insisted for 35 minutes after boiling and filtered; again water was added at 1-3 cm above the upper surface of medicinal raw materials; insisted for 30 minutes after boiling, filtered and combined two of the filtrate, to obtain 200 doses, 500 ml per dose.

Example 14: Getting wet pills with pharmaceutical composition according to the present invention

Pharmaceutical raw materials: same as in example 1.

Method of obtaining:

(a) selected and purified the root of Polygonum multiflorum, rhizome of anemarrhena and coarsely crushed seed of the jujube spiny weighed in accordance with the relationship, was added 8-fold amount of 60% ethanol was heated to reflux, in order to extract, twice for 2 hours each time; the extract was filtered, pooled, and ethanol regenerates under reduced pressure, concentrated and dried at 75°C and crushed to obtain a dry ethanolic extract, ready-to-use;

(b) selected and peeled the fruit she�cavity, the sea o, Ganoderma, root sage mnogokratnogo, flower albitius and chrysanthemum flower weighed in accordance with the relationship, added 12-fold amount of water to be extracted, twice for 1 hour each time; the extract was filtered, pooled, concentrated and dried at 75°C and crushed to obtain a dry aqueous extract (yield of dry extract was 20%), ready-to-use;

(c) selected and peeled onion Lily weighed in accordance with the relations and crushed into powder 100 mesh, ready to use;

(d) from a dry alcoholic extract obtained in stage (a), dry aqueous extract of stage b) and finely divided powder of the bulb of Lily, obtained in stage c), together have produced pills and received 1 kg of wet bean, which was divided into 100 g per package.

Pharmacological test

To confirm the activity of the pharmaceutical compositions according to the present invention in the treatment of insomnia, the tablets obtained according to the method of example 1 (hereinafter referred to as a pharmaceutical preparation in accordance with the present invention) was used in order to implement the following pharmacological test.

1. Sedation pharmaceutical preparation according to the present invention

1.1 Experimental materials

1.1.1 Experimental animals

90 healthy male Kunming mice pure breed (body weight 18-22 g) were purchased from the laboratory animal Center of Hebei province (license number: SCXK (JI) 2003-1-003, certificate number: DK0409-0040) and contained in the Laboratory of pharmacology in Yiling Research Institute under illumination for 12 hours per day, a temperature of 20-23°C and relative humidity of 40-60%. Mice were placed in a cage for 6 mice in a cage. Mice were fed a complete granulated food offered by the laboratory animal Center of Hebei province, and provided the mice with sufficient drinking water. Mice were acclimated for 3 days.

1.1.2 Experimental drug

Pharmaceutical preparation according to the present invention (tablet of example 1) is equivalent 3,47 grams of medicinal raw materials on g, and the dosage for humans is 17.0 g of medicinal raw materials per day, i.e., 0.28 g crude drugs / kg body weight (standard body weight of 60 kg). It is obtained from a suspension with 0.5% CMC-Na and store it at 4°C. In pharmacological experiments, the term "herbal medicine" refers to the aforementioned "pharmaceutical raw materials" or "materia medica", and the number of "medicinal herbs" refers to the converted amount "material medica".

Anshenbunao Ye: It is derived from deer antlers, processed root gorchakovskogo, herb of Epimedium, rhizomes of ginger (dried ginger), jujube fruit, and vitamin B1; functions and indications: improvement of the brain and calming the spirit, the product of the essence and strengthening of the bone marrow, replenishing qi and blood meal; and it is usually used for neurasthenia, insomnia, amnesia, dizziness, fatigue; it produces JILIN AODONG YANBIAN PHARMACEUTICAL CO., LTD, registration number: Z22022453 (SFDA); a clinical dosage for adults: 20 ml per day; no party: 040269.

Tablet estazolam, benzodiazepine anxiolytic, can cause inhibition of various parts of the Central nervous system; clinical manifestations may range from mild sedation to hypnosis and coma and even at higher dosages used. It offers Shijiazhuang Pharmaceutical Group Co., LTD; registration number: H13020974 (SFDA); the content of active substance: 1 mg; a clinical dosage for adults: 2-4 mg every time for hypnosis and 1-2 mg each time to soothe, 3 times a day; no party: 040101.

1.1.3 Experimental equipment

The unit for measuring the locomotor activity of mice (camera to measure locomotor activity, software to measure locomotor activity) was purchased from Beijing Shuolin Xueyuan Science and Technology Co., LTD.

Electronic analytical balance AB204-N purchased from Mettler-Toledo Instruments (Shanghai) Co., Ltd.

1.2. Ek�experimental method

1.2.1 Principles for determining dosage

In this experiment, for the pharmaceutical product in accordance with the present invention have been defined groups 5.6 g crude drugs / kg, 2.8 g crude drugs / kg and 1.4 g crude drugs / kg, which is equivalent to 20, 10 and 5 times the clinical dose for humans (0.28 g crude drugs / kg), respectively. A group of 13 ml/kg Anshenbunao Ye and a group of 2.67 mg/kg estazolama determined in accordance with the results of preliminary experiments. Mice were divided into 6 groups according to the above definition the dosage as shown in table 1.

Table 1
The impact of pharmaceutical product in accordance with the present invention on locomotor activity of mice
GroupDosingThe number of animalsThe equivalent ratio of clinical dosage (ratio)
The control group is empty-12-
The group Anshenbunao Ye13 ml/kg 1239
The group estazolama2,67 mg/kg1227
Pharmaceutical preparation according to the present invention5.6 g crude drugs / kg1220
2.8 g crude drugs / kg1210
1.4 g crude drugs / kg125

1.2.2 Method of administration

Enter the concentration of the pharmaceutical preparation according to the present invention was 0.08 g dry powder per ml, 0.04 g of dry powder per ml and 0.02 g of dry powder per ml, respectively; the input concentration for the group Anshenbunao Ye were $ 0.65 ml concentrated liquid in ml, and injected concentration estazolama was 0.13 mg/ml 0.2 ml per 10 g was administered via gavage daily, which corresponds to clinically recommended oral route, for 7 consecutive days, and estazolam entered only once on the seventh day.

1.2.3 Experimental period of 7 days.

1.2.4 detection Indicators and methods detector.�of

Mice were trained once in the morning, afternoon and evening on day 1 for every times, mice were acclimated for 5 minutes after each training, and recorded the number of cases of locomotor activity for 10 minutes. 72 mouse with an average amount equal to 150-250 times in 10 minutes was selected to participate in the experiment. The number of cases of locomotor activity was determined 1 hour after the last injection, mice were acclimated for 5 minutes, and then recorded the number of cases of locomotor activity for 10 minutes.

1.2.5 Statistical method: it is Used one way ANOVA using statistical software spss11.5.

1.3 Experimental results

The number of cases of locomotor activity of mice in groups Anshenbunao Ye and estazolama decreased compared with group blank control (P<0.01 or P<0,05). Compared with the control group is empty the number of cases of locomotor activity of mice in groups a pharmaceutical preparation in accordance with the present invention at doses of 5.6 g crude drugs / kg and 2.8 g crude drugs / kg significantly decreased (P<0,05), and the level of inhibition was of 27.5% and 23.4% respectively. For group 1.4 g crude drugs / kg the number of cases of locomotor activity of mice had the tendency to decrease, � the level of inhibition was 9.7%. The results are shown in table 2.

23,4
Table 2
The impact of pharmaceutical product in accordance with the present invention on the number of cases of locomotor activity of mice (x±s, n=12)
GroupDosingThe number of cases of locomotor activity (10 min)The level of inhibition (%)
The control group is empty240,3±30,1
The group Anshenbunao Ye13 ml/kg159,7±34,2**of 33.5
The group estazolamato 2.76 mg/kg174,0±58,9*27,5
Group pharmaceutical preparation according to the present invention5.6 g crude drugs / kgto 173.3±50,1*27,8
2.8 g crude drugs / kg184,0±55,2*
1.4 g crude drugs / kg216,8±72,69,7
Note: *P<0,05, **P<0.01, compared with the control group is empty

1.4 Conclusion

Pharmaceutical preparation according to the present invention can reduce the number of cases of locomotor activity in mice, which confirms that the pharmaceutical preparation in accordance with the present invention has a sedative effect.

2. Sedative effect of the pharmaceutical preparation in accordance with the present invention

2.1 Experimental materials

2.1.1 Experimental animals

72 healthy male Kunming mice pure breed (body weight 18-22 g) were purchased from the laboratory animal Center of Hebei province (license number: SCXK (JI) 2003-1-003, certificate number: DK0409-0016). They were kept in the Laboratory of pharmacology in Yiling Research Institute under illumination for 12 hours per day, a temperature of 20-23°C and relative humidity of 40-60%. Mice were placed in a cage for 6 mice in a cage. Complete granulated food for mice was proposed by the laboratory animal Center of Hebei province, and the mice were provided with sufficient drinking water. Mice were acclimated for 3 days.

2.1.2 Experimental drug

Pharmaceutical�ticheskii the drug in accordance with the present invention is equivalent 3,47 g crude drugs per g of dry powder, and dosage for humans is 17.0 g of medicinal raw materials per day, i.e., 0.28 g crude drugs / kg body weight (standard body weight of 60 kg). It offers Shijiazhuang Yiling Pharmaceutical co., LTD (batch No. 20040201). It is obtained from a suspension with 0.5% CMC-Na and store it at 4°C.

Anshenbunao Ye: It is derived from deer antlers, processed root of Polygonum multiflorum, a herb of Epimedium, rhizomes of ginger (dried ginger), jujube fruit, and vitamin B1; functions and indications: improvement of the brain and calming the spirit, the product of the essence and strengthening of the bone marrow, replenishing qi and blood meal; and it is usually used for neurasthenia, insomnia, amnesia, dizziness, fatigue; it produces JILIN AODONG YANBIAN PHARMACEUTICAL CO., LTD, registration number: Z22022453 (SFDA); a clinical dosage for adults: 20 ml per day; no party: 040269.

Tablet estazolam, benzodiazepine anxiolytic, can cause inhibition of various parts of the Central nervous system; clinical manifestations may range from mild sedation to hypnosis and coma and even at higher dosages used. It offers Shijiazhuang Pharmaceutical Group Co., LTD; registration number: H13020974 (SFDA); the content of active substance: 1 mg; a clinical dosage for adults: 2-4 mg every time for hypnosis and 1-2 mg each time to soothe, 3 times a day; no party: 040101.

2.1.3 Exp�experimental reagent

Pentobarbital sodium, the proposed Sinopharm (Group) Shanghai Chemical Reagent Co., Ltd, part number: F20030816.

2.2 Experimental method

2.2.1 Principles for determining dosage

In this experiment, for the pharmaceutical product in accordance with the present invention have been defined groups 5.6 g crude drugs / kg, 2.8 g crude drugs / kg and 1.4 g crude drugs / kg, which is equivalent to 20, 10 and 5 times the clinical dose for humans (0.28 g crude drugs / kg), respectively. A group of 13 ml/kg Anshenbunao Ye and a group of 2.67 mg/kg estazolama determined in accordance with the results of preliminary experiments. Mice were divided into 6 groups according to the above definition the dosage as shown in table 3.

Table 3
The impact of pharmaceutical product in accordance with the present invention on the sleep time induced by pentobarbital sodium in mice
GroupDosageThe number of animalsThe equivalent ratio of clinical dosage (ratio)
The control group is empty- 12-
The group Anshenbunao syrup13 ml/kg1239
The group estazolama2,67 mg/kg1227
Group pharmaceutical preparation according to the present invention5.6 g crude drugs / kg1220
2.8 g crude drugs /kg1210
1.4 g crude drugs /kg125

2.2.2 Method of administration

Enter the concentration of the pharmaceutical preparation according to the present invention was 0.08 g dry powder per ml, 0.04 g of dry powder per ml and 0.02 g of dry powder per ml, respectively; the input concentration for the group Anshenbunao Ye were $ 0.65 ml concentrated liquid in ml, and injected concentration estazolama was 0.13 mg/ml 0.2 ml per 10 g was administered via gavage daily, which corresponds to clinically recommended oral route, within 7 days FR�d, and estazolam entered only once on the seventh day.

2.2.3 Method of creating an animal model

1 hour after the last injection in each group were injected with 45 mg/kg of pentobarbital sodium by intraperitoneal injection.

2.2.4 Experimental period of 7 days.

2.2.5 detection Indicators and detection methods

For these experiments refer to the "Methodology on Pharmacology of Experiment" (3rd edition). Intraperitoneal dose of pentobarbital sodium, and sleep in 100% of mice did not lead to excessively long sleep time, determined in preliminary experiments, equal to 45 mg/kg 1 hour after the last injection in each group were injected with 45 mg/kg of pentobarbital sodium by intraperitoneal injection and were recorded sleep time of mice (the period of time from the disappearance of the rectifier reflex to recovery rectifier reflex).

2.2.6 Statistical method: Used a t-test using statistical software spss11.5.

2.3 Experimental results

The sleep time of mice in the group estazolama increased compared with the control group model (P<0.01). The sleep time of mice in groups a pharmaceutical preparation in accordance with the present invention at doses of 5.6 g crude drugs / kg and 2.8 grams of medicinal raw material of� per kg increased compared with the control group model (P< the 0.05 or 0.01). The results are shown in table 4.

Table 4
The impact of pharmaceutical product in accordance with the present invention on the sleep time induced by pentobarbital sodium in mice (x±s, n=12)
GroupDosageSleep time (min)
The monitoring group model26,64±18,50
The group Anshenbunao Ye13 ml/kg21,60±11,01
The group estazolamato 2.76 mg/kg72,89±to 18.01**
The group's pharmaceutical product according to the present invention5.6 g crude drugs / kg41,55±of 14.28*
2.8 g crude drugs /kg57,90±17,04**
1.4 g crude drugs /kgof 25.75±16,69
Note: *P<0,05, **P<0.01, compared with control group� model

2.4 Conclusion

Pharmaceutical preparation according to the present invention has the effect of increasing the sleep time induced by pentobarbital sodium in mice.

3. Stimulating the memory of the impact of the pharmaceutical preparation according to the present invention

3.1 Experimental materials

3.1.1 Experimental animals

72 healthy male Kunming mice pure breed (body weight 18-22 g) were purchased from the laboratory animal Center of Hebei province (license number: SCXK (JI) 2003-1-003, certificate number: DK0409-0016). They were kept in the Laboratory of pharmacology in Yiling Research Institute under illumination for 12 hours per day, a temperature of 20-23°C and relative humidity of 40-60%. Mice were placed in a cage for 6 mice in a cage. Granulated food for mice was proposed by the laboratory animal Center of Hebei province, and the mice were provided with sufficient drinking water. Mice were acclimated for 3 days.

3.1.2 Experimental drug

Pharmaceutical preparation according to the present invention was offered by Shijiazhuang Yiling Pharmaceutical co., LTD, batch No. 20040201. It is obtained from a suspension with 0.5% CMC-Na and store it at 4°C.

HABOYIN (tablet huperzine A). Huperzine a is a highly selective reversible inhibitor of acetylcholinesterase. It produces Henan Zhulinzhongsheng Pharmaceutical Co., Ltd. Ryougi�registration No.: HI0940156 (SFDA); the content of active substance: 0.05 mg per tablet; part number: 050201.

An injection of scopolamine hydrobromide, registration No.: H31021519 (SFDA), Shanghai Hefeng Pharmaceutical Co., Ltd.; part number: 4A18003. The content of active substance: 0.3 mg.

3.1.3 Experimental equipment: water maze with program management SMG-2, manufactured at the Institute of Materia Medica Chinese Academy of medical Sciences.

3.2 Experimental method

3.2.1 Principles for determining dosage

In this experiment, for the pharmaceutical product in accordance with the present invention have been defined groups 5.6 g crude drugs / kg, 2.8 g crude drugs / kg and 1.4 g crude drugs / kg, which is equivalent to 20, 10 and 5 times the clinical dose for humans (0.28 g crude drugs / kg), respectively. Group blank control models and 0.4 mg/kg huperzine A defined additionally. Mice were divided into 6 groups according to the above definition the dosage as shown in table 5.

Table 5
The impact of pharmaceutical product in accordance with the present invention a violation of restore memory mice caused by Skopin
GroupDosageThe number of animalsThe equivalent ratio of clinical dosage (ratio)
The control group is empty-12-
The monitoring group model-12-
The group huperzine A0.4 mg/kg12-
Group pharmaceutical preparation according to the present invention5.6 g crude drugs / kg1220
2.8 g crude drugs / kg1210
1.4 g crude drugs / kg125

3.2.2 Method of administration

Enter the concentration of the pharmaceutical preparation according to the present invention was 0.08 g dry powder per ml, 0.04 g of dry powder per ml and 0.02 g of dry powder per ml, respectively, � input concentration in the group huperzine A was 0.02 mg/ml. 0.2 ml per 10 g was administered via gavage daily, which corresponds to clinically recommended oral route, for 14 consecutive days.

3.2.3 Method of creating an animal model

After 30 minutes after injection on day 14 was administered 2 mg/kg of scopolamine hydrobromide by intraperitoneal injection, excluding the control group is empty, to create a model of a violation of recover memory.

3.2.4 Experimental period: 14 days.

3.2.5 Indicators of detection and the detection methods

Mice were subjected to training (water temperature 24-26°C, water depth 10 cm). During training, the mouse was initially placed on the platform for 10 seconds, so she knew about the existence of this safety zone, then the mouse was placed next to the platform, to allow her self to climb the stairs to discover way out. All training is divided into 5 days: point A on the 9th day, a point on the 10th day, the dot on the 11th day, the point S on the 12th day and the point S on the 13th day, mice were trained once a day, every day, every workout was 2 minutes, and the animal was sent to the side of the platform with the help of a glass rod in case of delay. At the beginning of the voyage, the mouse head was turned toward the wall start point. After training was completed for the point S, from mice required that they were able� to swim to the platform in 2 minutes otherwise they were excluded. After 30 minutes after injection on day 14 was administered 2 mg/kg of scopolamine hydrobromide by intraperitoneal injection, excluding the control group is empty, to create a model of a violation of memory reconstruction. The study was conducted after 30 minutes of simulation. Mouse began to sail from point S, and recorded the number of errors (the number of inputs to a standstill) and latent period (the time period that he occupied the voyage from point S to the platform).

3.2.6 Statistical method: Used a nonparametric test using statistical software spss11.5.

3.3 Experimental results

The latent period when sailing in mice in the model group was increased compared with group blank control (P<0.01). The latent period when sailing in mice in groups huperzine A decreased compared with model group (P<0.01). The latent period in the group of pharmaceutical preparation in accordance with the present invention in a dosage of 5.6 g crude drugs / kg decreased (P<0,05). The results are shown in table 6.

Table 6
The impact of pharmaceutical product in accordance with the present invention a violation in�of Stanovlenie memory of mice caused by Skopin (x±s, n=12)
GroupDosageThe number of errors (time)The latent period (sec.)
The control group is empty11,58±7,9454,50±37,61
The monitoring group model21,08±13,13109,3*19,7 ΔΔ
The group huperzine A0.4 mg/kgequal to 16.83±14,2163,33±44,30**
The group's pharmaceutical product according to the present invention5.6 g crude drugs / kg18,83±11,6879,67±40,96*
2.8 g crude drugs /kg17,83±13.56 MHz67,75±50,67
1.4 g crude drugs /kg23,67±13,4992,92±34,29
Note: ΔΔP<0.01, compared with group blank control;
*P<0,05, **P<0.01, compared with group�ow control model

3.4 Conclusion

Pharmaceutical preparation according to the present invention has the effect of improvements in violation of memory caused by Skopin, in mice.

In addition, in a mouse model of disorders memory loss caused by Skopin, the latent period when sailing in a group of pharmaceutical preparation in accordance with the present invention in a dosage of 5.6 g crude drugs / kg decreased. In addition, in a mouse model of acquired dysmnesia caused by Skopin, the latent period when swimming in groups of a pharmaceutical preparation in accordance with the present invention at doses of 5.6 g crude drugs / kg and 2.8 g crude drugs / kg decreased. These results indicate that the pharmaceutical preparation in accordance with the present invention has the effect of improving memory.

In the experiment with the sailing of mice swimming in a group of pharmaceutical preparation in accordance with the present invention in a dosage of 5.6 g crude drugs / kg increased, and swimming in groups of a pharmaceutical preparation in accordance with the present invention at doses of 2.8 g crude drugs / kg and 1.4 g crude drugs / kg tended to increase by 25.5% and 11.3% respectively. In experiments with Roterdam time of rotarod � groups pharmaceutical preparation according to the present invention at doses of 5.6 g, 2.8 g and 1.4 g crude drugs / kg tended to increase 93.6%, to 55.9% and 3.0% respectively. These results indicate that the pharmaceutical preparation in accordance with the present invention has the effect of reducing fatigue to some extent.

In the experiment on torsion latent period of torsion in mice in the group of pharmaceutical preparation in accordance with the present invention in a dosage of 5.6 g crude drugs / kg increased, and the number of turns decreased. In the experiment with hot plate pain threshold of mice in the group of pharmaceutical preparation in accordance with the present invention at a dosage of 2.8 medicinal raw materials per kg increased. These results indicate that the pharmaceutical preparation in accordance with the present invention has the effect of pain relief.

In conclusion, the pharmaceutical preparation in accordance with the present invention has the effects of sedation, hypnosis, stimulate memory, reduce fatigue and ease pain. Clinically recommended dosage of the pharmaceutical compositions according to the present invention is 17.0 grams of medicinal raw materials per day (the standard weight of 60 kg), and when tested in the toxicity of the pharmaceutical composition in accordance with the present invention were not observed� acute toxic reactions in mice at the maximum dosage 166,80 g crude drugs / kg; and did not observe noticeable toxic response in rats when administered via gavage to 5.6, and 11.2 and 22.4 g crude drugs / kg for 3 consecutive months, and therefore, such a composition can be recommended for clinical use.

1. Pharmaceutical composition for the treatment of insomnia, which contains the root of Polygonum multiflorum and/or its extracts, the seed of the jujube spiny and/or its extracts, the fruit of the mulberry and/or its extracts, Ganoderma and/or its extracts, Lily bulb and/or its extracts, rhizome of anemarrhena and/or its extracts, root of Salvia mnogokratnogo and/or its extracts, chrysanthemum flower and/or its extracts, sea o and/or its extracts and flower albitius and/or its extracts.

2. Pharmaceutical composition according to claim 1, containing extracts obtained with the use of a solvent, such as water, ethanol, aqueous ethanol, supercritical carbon dioxide, or any mixture.

3. Pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is prepared from medicinal raw materials with the following relationship weight parts: root of Polygonum multiflorum 150-270, the seed of the jujube spiny 145-275, the fruit of the mulberry 160-255, Ganoderma 80-135, bulb lilies 75-160, rhizome of anemarrhena 50-110, root sage mnogokratnogo 120-200, chrysanthemum flower 45-120, the sea o 75-145 and flower albitius 165-288.

4. Pharmaceutical�viteska composition according to claim 1, in which the relationship of parts by weight of medicinal raw materials are: root of Polygonum multiflorum 158, the seed of the jujube spiny 270, the fruit of the mulberry 165, Ganoderma 135, Lily bulb 80, the rhizome of anemarrhena 110, the root of Salvia mnogokratnogo 125, chrysanthemum flower 118, the sea o 80 and flower albitius 280.

5. Pharmaceutical composition according to claim 1, in which the relationship of parts by weight of medicinal raw materials are: root of Polygonum multiflorum 265, the seed of the jujube spiny 147, mulberry fruit 250, Ganoderma 81, Lily bulb 158, rhizome of anemarrhena 55, Clary wort mnogokratnogo 188, 50 chrysanthemum flower, the sea o 145 and flower albitius 170.

6. Pharmaceutical composition according to claim 1, in which the relationship of parts by weight of medicinal raw materials are: root of Polygonum multiflorum 225, the seed of the jujube spiny 163, the fruit of the mulberry 220, Ganoderma 83, bulb lilies 113, rhizome of anemarrhena 50, Clary wort mnogokratnogo 190, chrysanthemum flower 45, 113 and the sea o flower albitius 178.

7. Pharmaceutical composition according to claim 1, in which the relationship of parts by weight of medicinal raw materials are: root of Polygonum multiflorum 165, the seed of the jujube spiny 228, the fruit of the mulberry 173, Ganoderma 110, Lily bulb 75, rhizome of anemarrhena 75, Clary wort mnogokratnogo 150, chrysanthemum flower 78, 78 and the sea o flower albitius 218.

8. Pharmaceutical composition �about p. 1, in which the relationship of parts by weight of medicinal raw materials are: root of Polygonum multiflorum 200, the seed of the jujube spiny 200, the fruit of the mulberry 200, Ganoderma 100, bulb lilies 100, rhizome of anemarrhena 66,7, root sage mnogokratnogo 166,7, chrysanthemum flower 66,7, the sea o 100 and flower albitius 200.

9. Pharmaceutical composition according to claim 1, in which each gram of the pharmaceutical composition contains not less than 0.5 mg, preferably not less than 1.0 mg, more preferably not less than 1.5 mg 2,3,5,4'-tetrahydroxyphenyl-2-O-β-D-glucoside in terms of dry weight of the pharmaceutical composition.

10. Pharmaceutical composition according to claim 1, wherein the dosage form of the pharmaceutical composition is a capsule, tablet, powder, oral liquid, soft capsule, pill, tincture, syrup, suppository, gel, spray or an injection.

11. Pharmaceutical composition according to claim 2, where the method of obtaining the pharmaceutical composition comprises obtaining an extract of one or more species of medicinal raw materials individually or together.

12. Pharmaceutical composition according to claim 11, where the method of obtaining the pharmaceutical composition includes the weighing of drugs in accordance with weight relationship of the parts to soak for 20-40 minutes by adding �odes, insistence within 30-40 minutes after bringing to a boil, filtering and again insistence within 25-30 minutes after adding water and boiling, filtering and combining the filtrates.

13. Pharmaceutical composition according to claim 1, wherein the method of obtaining the pharmaceutical composition includes the following stages:
(a) obtaining alcoholic extract of the root of Polygonum multiflorum, rhizomes of anemarrhena and the seed of the jujube spiny;
(b) obtaining an aqueous extract of the fruit of the mulberry, parii, Ganoderma, root sage mnogokratnogo, flower albitius and chrysanthemum flower;
c) obtaining a powder of the bulb of Lily; and
(d) application stage alcoholic extract, aqueous extract of stage b) and a powder of the bulb of Lily stage) as the active ingredients of the pharmaceutical composition.

14. Pharmaceutical composition according to claim 1, wherein the method of obtaining the pharmaceutical composition includes the following stages:
(a) the root of Polygonum multiflorum, rhizome of anemarrhena and the seed of the jujube spiny weighed in accordance with the relationship of parts by weight, add 6-12 times the amount of 30% -70% ethanol; carry out heating to reflux, in order to extract, from 1 to 3 times for 1-3 hours each time; the extract was filtered, and unite for the regeneration of the ethanol under reduced pressure�m, and concentrated to a relative density of 1.10-1.15 times as determined at 60°C, to obtain an alcohol extract;
(b) the fruit of the mulberry, sea o, Ganoderma, root sage mnogokratnogo, flower albitius and the chrysanthemum flower is weighed in accordance with the relationship of parts by weight, add 10-15-fold amount of water to be extracted, from 1 to 3 times for 1-3 hours each time; the extract was filtered, pooled and concentrated to a relative density of approximately 1,10-1,15, determined at 60°C, to obtain an aqueous extract;
c) the bulb of Lily weighed in accordance with the relationship of parts by weight and ground into a powder 100 mesh Lily bulbs; and
(d) using ethanolic extract of step a), an aqueous extract of the station b) and the powder of the bulb of Lily stage) as the active ingredients of the pharmaceutical composition.

15. Use of pharmaceutical composition according to any one of claims. 1-9 for the treatment of symptoms of insomnia, amnesia, dizziness, fatigue and/or pain and weakness in the lower back and knees.

16. Use of pharmaceutical composition according to any one of claims. 1-9 for sedation, hypnosis, stimulate memory, reduce fatigue and/or pain relief.

17. A method of treating insomnia, comprising administering the pharmaceutical composition according to any one of claims. 1-9 PA�Ianto with insomnia.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of organic chemistry, namely to novel derivatives of pyrazole pyridine of formula , as well as to its tautomers, geometrical isomers, enantiomers, diastereomers, racemates and pharmaceutically acceptable salts, where G1 represents H; G2 represents -CHR1R2; R1 and R2 independently on each other are selected from H; C1C6-alkoxy-C1C6-alkyl; C1-C6-alkyl; optionally substituted phenyl; optionally substituted phenyl-C1-C6-alkyl; optionally substituted morpholine-C1-C6-alkyl; or -CHR1R2 together form a ring, selected from an optionally substituted C3-C8-cycloalkyl and substituted piperidine; G3 is selected from an optionally substituted C1C6-alkoxy -C1-C6-alkyl; C1-C6-alkyl; substituted phenyl; substituted phenyl-C1C6-alkyl; G4 is selected from a substituted acyl-C1C6-alkyl, where acyl represents a group -CO-R and R stands for H or morpholine; optionally substituted C1-C6-alkyl; optionally substituted phenyl or indene; substituted phenyl-C1-C6-alkyl; optionally substituted pyridine- or furanyl-C1C6-alkyl; morpholine- or piperidine-C1-C6-alkyl; G5 represents H; where the term "substituted" stands for the groups, substituted with 1 to 5 substituents, selected from the group, which includes a "C1-C6-alkyl," "morpholine", "C1-C6-alkylphenyl", "di-C1-C6-alkylamino", "acylamino", which stands for the group NRCOR", where R represents H and R" represents a C1-C6-alkyl, "phenyl", "fluorine-substituted phenyl", "C1-C6-alkoxy", "C1-C6-alkoxycarbonyl", "halogen". The invention also relates to a pharmaceutical composition based on the formula (I) compound and particular compounds.

EFFECT: obtained are the novel derivatives of pyrasole pyridine, useful for the treatment and/or prevention of disorders or states, associated with NADPH-oxidase.

12 cl, 3 tbl, 21 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of biochemistry, in particular to cyclic peptide, capable of inducing antibody response. Peptide consists of formula X2X3VGSNK-Z or X3VGSNKG-Z, where X2 represents E, G, Q or K, X3 represents D or N and Z represents agent, stabilising bent, present inside peptide sequence, with peptide being cyclised by covalent bonding of N-end amino acid with Z, where Z represents peptide fragment YNGK. Conjugate, containing said cyclic peptide, conjugated with immunogenic carrier molecule is also claimed. peptide and conjugate, which contains it, can be applied for production of medication or as vaccine against Alzheimer's disease. Methods of obtaining cyclic peptide and conjugate are also claimed.

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8 cl, 11 dwg, 1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula I, wherein R1 and R2 are identical or different and specified in an alkyl or alkenyl hydrocarbon chain; the R3 group values split by lipase are specified in the patient claim. R4 and R5 are independently hydrogen or C1-C7alkyl; R6 represents hydrogen or C1-C7alkyl; and R7 and R8 are independently hydrogen or C1-C7alkyl. The invention also refers to using compounds of formulas ,

which are introduced into the mammalian biological system and increase the cell concentrations of specific sn-2 substituted ethanolamine-plasmalogens.

EFFECT: compounds are applicable in treating or preventing the age-related disorders associated with high membrane cholesterol, high amyloids and low plasmalogens, such as neurodegeneration, cognitive disorder, dementia, cancer, osteoporosis, bipolar disorder and vascular diseases.

11 cl, 18 dwg, 7 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine. What is described is a transdermally absorbable formulation prepared by dissolving donepezil in an adherent plaster base, which contains a hydrophobic polymer and an absorption enhancer. The absorption enhancer represents one substance, or two or more substances specified in lauryl alcohol, triethyl citrate, isopropylmyristate, cetyl lactate, oleyl alcohol, sorbitan monooleate, polyethyleneglycol monostearate, lauromacrogol, N-methyl-2-pyrroldone and triacetin.

EFFECT: transdermally absorbable formulation can administer donepezil stably for a relatively long period of time and can provide both blood donepezil increase, and the properties of sustained release of donepezil.

4 cl, 4 dwg, 6 tbl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) and their pharmaceutically acceptable salts, wherein A is thiazolyl, oxazolyl, thienyl, furyl, imidazolyl, pyrazolyl or oxadiazolyl (structures of which are presented in cl.1 of the patent claim), R1 represents C1-6alkyl; R2 represents (i) phenyl substituted by halogen; C1-6alkyl optionally substituted by morpholine or C1-6dialkylamino; C1-6alkoxy optionally substituted by halogen; or heterocyclyl, wherein a heterocyclyl substitute is specified in morpholine; pyrazolyl optionally substituted by C1-6alkyl; piperidinyl; pyrrolidinyl; oxadiazolyl substituted by C1-6alkyl; furyl substituted by C1-6alkyl; dioxydoisothiazolidinyl; triazolyl; tetrazolyl substituted by C1-6alkyl, tridiazolyl substituted by C1-6alkyl; thiazolyl substituted by C1-6alkyl; pyridyl; or pyrazinyl; (ii) substituted or unsubstituted heterocyclyl specified in quinolinyl; pyridyl substituted by C1-6alkoxy or morpholinyl; or benzo [d] [1, 2, 3] triazolyl substituted by C1-6alkyl; R3 represents phenyl substituted by 2 or 3 substitutes specified in halogen; C1-6alkyl; C1-6alkoxy optionally substituted by halogen; hydroxy group; cyano; or -C(=O)ORa, wherein Ra represents phenyl; R4 represents hydrogen, C1-6alkyl or C1-6halogenalkyl. The invention also refers to a pharmaceutical composition containing the compounds of formula (I), a method for PDE10 inhibition, a method of treating neurological disorders, and to intermediate compounds: 2-(4-chlor-3,5-dimethoxyphenyl)furan and 4-(5-methyl-1,3,4-thiadiazol-2-yl)benzaldehyde.

EFFECT: compounds of formula (I) as PDE10 inhibitors.

39 cl, 13 ex, 2 tbl, 77 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: given invention refers to new 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole derivatives, which can be used for modulating histamine receptors in individuals or for treating neurodegenerative diseases. The above derivatives have formula , wherein R1 is specified in an alkyl, substituted alkoxy or phenyl, and aralalkyl; R2 is specified in an alkyl, C6-C14-aryl optionally substituted by 1 to 5 substitutes specified in alkoxy and alkyl; R3 is an alkyl; and R4 is an alkyl.

EFFECT: presented are the new compounds effective as histamine receptor modulators, and a based pharmaceutical composition.

20 cl, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to new quinolin-4-one derivatives of formula (1) or to its pharmaceutically acceptable salt, wherein R1 represents: (1) hydrogen, (2) C1-C6 alkyl, (35) carbamoyl-C1-C6 alkyl optionally containing morpholinyl-C1-C6 alkyl, or (36) phosphonoxy-C1-C6 alkyl optionally containing one or two C1-C6 alkyl groups on a phosphonoxy group; R2 represents: (1) hydrogen or (2) C1-C6 alkyl; R3 represents phenyl, thienyl or furyl, wherein a phenyl ring presented by R3, can be substituted by one C1-C6 alkoxy group; R4 and R5 are bound to form a group presented by any of the following formulas: , , , , , , or a group presented by the following formula: a group optionally containing one or more substitutes specified in a group consisting of C1-C6 alkyl groups and oxogroups; R6 represents hydrogen; and R7 represents C1-C6 alkoxy group. The invention also refers to a pharmaceutical composition based on the compound of formula , to a preventive and/or therapeutic agent based on the compound of formula (1), using the compound of formula (1), a method for preparing the compound of formula , as well as to specific compounds.

EFFECT: there are prepared new quinolin-4-one derivatives effective in treating neurodegenerative diseases, diseases caused by neurological dysfunction, or diseases caused by mitochondrial dysfunction.

18 cl, 1 tbl, 257 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of structural formula (I), which possesses phosphodiesterase 10 inhibitory activity. In formula (I), R1 represents hydrogen, halogen or lower alkyl; the ring A represents optionally substituted 6-10-merous monocyclic or bicyclic heteroaryl containing 1 to 3 nitrogen atoms as heteroatoms, or a group containing a cycloaliphatic 6-merous ring condensed with the above heteroaryl, which is specified in 6-merous cycloalkane and aliphatic 6-merous heterocyclic ring containing an oxygen atom; the ring B represents optionally substituted 4-6-merous monocyclic nitrogen-containing group, which can additionally contain an oxygen atom or a 3-6-merous monocyclic hydrocarbonic group, which can be optionally saturated; R3 represents hydrogen; lower alkyl optionally substituted by a substitute specified in lower alkoxy; or lower cycloalky. The R2,Y radicals, as well as substitutes of the rings A and B are presented in the patent claim.

EFFECT: invention refers to the pharmaceutical composition containing the above compound, to a method of treating or preventing schizophrenia, anxiety disorders, drug addiction, disorders with a symptom of cognition deficiency, affective disorder or mood episode, each of which is mediated by phosphodiesterase 10 activity.

20 cl, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present group of inventions refers to medicine, namely to neurology, and concerns treating vegetative-vascular dystonia, dizziness syndrome of various origins, and kinetosis. That is ensured by administering a therapeutic agent containing an activated-potentiated form of brain-specific protein S-100 antibody and using the activated-potentiated form of endothelial NO-synthase antibodies as an additional exalting agent.

EFFECT: invention provides the effective treatment of the above pathological conditions by the synergetic effect of the ingredients of the therapeutic agent.

9 cl, 16 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: claimed group of inventions relates to medicine, namely to neurology, and deals with treatment of Alzheimer's disease. For this purpose pharmaceutical composition, which contains activated potentiated form of antibodies to brain-specific protein S-100 and activated potentiated form of antibodies to endothelial NO-synthase, is introduced.

EFFECT: introduction of claimed composition provides efficient treatment of Alzheimer's disease due to synergic neuroprotective, anti-ischemic and anxiolytic action of composition components.

9 cl, 5 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) and their pharmaceutically acceptable salts, wherein A is thiazolyl, oxazolyl, thienyl, furyl, imidazolyl, pyrazolyl or oxadiazolyl (structures of which are presented in cl.1 of the patent claim), R1 represents C1-6alkyl; R2 represents (i) phenyl substituted by halogen; C1-6alkyl optionally substituted by morpholine or C1-6dialkylamino; C1-6alkoxy optionally substituted by halogen; or heterocyclyl, wherein a heterocyclyl substitute is specified in morpholine; pyrazolyl optionally substituted by C1-6alkyl; piperidinyl; pyrrolidinyl; oxadiazolyl substituted by C1-6alkyl; furyl substituted by C1-6alkyl; dioxydoisothiazolidinyl; triazolyl; tetrazolyl substituted by C1-6alkyl, tridiazolyl substituted by C1-6alkyl; thiazolyl substituted by C1-6alkyl; pyridyl; or pyrazinyl; (ii) substituted or unsubstituted heterocyclyl specified in quinolinyl; pyridyl substituted by C1-6alkoxy or morpholinyl; or benzo [d] [1, 2, 3] triazolyl substituted by C1-6alkyl; R3 represents phenyl substituted by 2 or 3 substitutes specified in halogen; C1-6alkyl; C1-6alkoxy optionally substituted by halogen; hydroxy group; cyano; or -C(=O)ORa, wherein Ra represents phenyl; R4 represents hydrogen, C1-6alkyl or C1-6halogenalkyl. The invention also refers to a pharmaceutical composition containing the compounds of formula (I), a method for PDE10 inhibition, a method of treating neurological disorders, and to intermediate compounds: 2-(4-chlor-3,5-dimethoxyphenyl)furan and 4-(5-methyl-1,3,4-thiadiazol-2-yl)benzaldehyde.

EFFECT: compounds of formula (I) as PDE10 inhibitors.

39 cl, 13 ex, 2 tbl, 77 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, particularly to experimental pharmacology, and can be used as a method for rat sedation with an api-phytocomposition. The method for rat sedation with the api-phytocomposition involving single and daily one-week administration of a sedative agent, which is administered intragastrically through a probe in a dose of 200 mg/kg of animal's body weight, wherein the api-phytocomposition contains honey, bee-bread, lime pollen, propolis, valerian extract in a ratio of 10:2:1:1:1, and represents an aqueous suspension.

EFFECT: method described above is effective for rat sedation and causes no side effects.

1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and medicine and concerns using comenic acid potassium salt as a preventive and therapeutic antioxidant, stress- and neuroprotective agent in the amount of 2 to 8 mg per 1 kg of body weight daily on the empty stomach for 3 days.

EFFECT: agent possess high efficacy.

4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyranyl aryl methylbenzoquinazolinone compounds of formula (I), which are positive allosteric modulators of the M1 receptor and which can be used to treat diseases associated with the M1 receptor, such as Alzheimer's disease, schizophrenia, pain disorders or sleep disturbance. In formula (I) X-Y are selected from a group comprising (1) -O-CRARB-, (2) -CRARB-O-, (3) -CRARB-SRC-, (4) -CRARB-NRC- and (5) -NRC-CRARB-, where each RA and RB is a hydrogen atom, and RC is selected from a group comprising (a) hydrogen, (b) -C(=O)-C1-6alkyl, (c) -C1-6alkyl, (d) -C(=O)-CH2-C6H5, (e) -S(=O)2-C1-6 alkyl, R1 is a hydroxy group, R2 is selected from a group comprising (1) -phenyl, (2) - heteroaryl, where the phenyl or heteroaryl group R2 is optionally substituted; the rest of the values of the radicals are given in the claim.

EFFECT: obtaining novel pyranyl aryl methylbenzoquinazolinone compounds.

28 cl, 12 tbl, 37 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmacology and concerns using comenic acid sodium salt as a preventive and therapeutic antioxidant, stress and neuroprotective agent in the amount of 1 to 4 mg per 1 kg of body weight daily on the empty stomach for 3 days.

EFFECT: invention provides the high clinical effectiveness.

3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, particularly to pharmacology and pharmaceutics, and concerns a sedative agent representing glycine immobilised on detonation nanodiamond particles 2-10 nm in size, and to a method for preparing it.

EFFECT: preparing the sedative agent.

4 cl, 7 dwg, 13 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention discloses crystalline form of S-zopicone with spectrum of powder X-ray diffraction with application of Cu-Ka radiation, with characteristic peaks, expressed under conditions 20 approximately at 11.08°, approximately 12.38°, approximately 15.86°, approximately 17.88°, approximately 19.98°C and approximately 20.58°, DSC-thermogram, on which peak is observed approximately at 207.7°C, and infrared spectrum of absorption (IR) with characteristic peaks approximately at 3078 cm-1, approximately 2942-2838 cm-1, approximately 2790 cm-1, approximately 1716 cm-1, approximately 1463 cm-1, approximately 1372 cm-1 and approximately 757 cm-1.

EFFECT: claimed are: method of preparation of crystalline form of eszopiclone, pharmaceutical preparation and its application in manufacturing medication for treatment of sleep disorder.

8 cl, 8 dwg, 10 ex

FIELD: medicine.

SUBSTANCE: present group of inventions refers to medicine, namely therapy and neurology, and concerns a melatonin agonist therapy. As the above melatonin agonist, (lR-Trans)-N-[[2-(2,3-dihydro-4-benzofuranyl)cyclopropyl]methyl]propanamide is administered in effective doses that provides treating or preventing disruption of circadian rhythm or sleep disturbance.

EFFECT: invention provides treating or preventing disruption of circadian rhythm or sleep disturbance.

9 cl, 2 ex, 4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention provides new imidazo[1,2-b]pyridazine compounds covered by general structural formula (I) wherein the radicals and symbols have the values presented in the patent claim, and pharmaceutically acceptable salts thereof. The compounds of structural formula (I) are effective both for treating or preventing the diseases related to GABA receptor inhibition, anxiety, epilepsy, sleep disorders, including insomnia, and for inducing a sedative-hypnotic, anaesthetic effect, sleep and muscle relaxation.

EFFECT: there are presented methods for preparing the above compounds, and also intermediate compounds for preparing them.

21 cl, 4 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmaceutical industry, and concerns a pharmaceutical composition for sublingual or buccal administration of the active ingredients of a low to poor water-solubility. As an active ingredient, the composition contains a solution of a hormone specified in a group consisting of melatonin, oestrogens, progesterone, testosterone and dihydrotestosterone in a pharmaceutically acceptable solvent, adsorbed or absorbed on particles of a pharmaceutically acceptable carrier. The invention also concerns methods for preparing and using the above pharmaceutical composition.

EFFECT: what is presented is the new composition for sublingual or buccal administration of the active ingredients of a low to poor water-solubility.

19 cl, 4 ex, 2 tbl, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to oral hygiene preparations. An oral care composition contains a) an aqueous phase; b) stannous tin ions dissolved in the aqueous phase; c) nitrates in the aqueous phase; wherein total nitrates is that a molar amount of nitrogen measured as a nitrate in the aqueous phase makes 1.8-0.1 of the molar amount of stannous tin ions; and d) a flavouring agent. What is also presented is a method for storage and a storage container for this composition; using nitrate for stabilising oxidised stannous tin ions dissolved in the aqueous phase. What is also presented is also a version of the composition, wherein the composition is aqueous.

EFFECT: using the group of inventions stabilises oxidised stannous tin ions dissolved in the aqueous phase by the above molar ratio of nitrate and stannous tin ions.

17 cl, 2 tbl, 15 ex

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