WO2011084025A2 - Hexane extract - Google Patents

Abstract

The present invention provides compositions for treating and relieving insomnia which include hexane extracts such as borneol, stacte, benzoin, coco grass, and wood flavor mixture. The hexane extracts prolong sleep, exhibit depressant activity of monoamineoxidases, and are effective in treating and/or relieving insomnia.

Description

 【Specification】

 [Name of invention]

 Nucleic Acid Extract

 Technical Field

 The present invention relates to a nucleic acid extract, and more particularly, to a nucleic acid extract and a composition comprising the same, which are effective in alleviating and / or improving insomnia due to excellent sleep prolonging effect and monoamine oxidase inhibitory effect.

 Background Art

 Insomnia means difficulty sleeping, at least one month, or wakes up more than three times a week, even if you fall asleep, and causes sleep deprivation during the day.

Sleep disorder is a symptom frequently occurring in modern people due to various causes, breaking the rhythm of life and causing huge disruption to social activities. Insomnia is closely related to the social activities of modern people, with the expectation that social problems and occupational factors account for 15¾-20¾. According to a recent survey, 73.4% of Koreans have experienced insomnia (Korea Institute for Health and Social Affairs, March 2000) and about 8% of patients with sleep disorders needing treatment (Korea Sleep Society, August 2000). ). As a modern sedative for treating or preventing insomnia, barbiturate-based drugs were introduced as an effective medicine for anxiety treatment in the early 1900's, but the treatment index has a low stability problem. Not solving it. have. In 1957, benzodiazepine-based drugs such as chlordiazepoxide were developed and started to be used as sedatives, and many derivatives have been developed as sedatives. These drugs are comparatively safe and have an anti-anxiety effect that alleviates anxiety symptoms, but they are also used as anticonvulsants, sedative sleeping pills, and muscle relaxants. Problems remain to be resolved, such as motor disorders, movement disorders, withdrawal of convulsions, enhanced central nervous system suppression when used with alcohol or barbiturate, and rarely cause anxiety symptoms and hostility. It can also cause side effects, such as an ideal sedative (J. Clin. Psych i at. 42, 1981, MA Schuckit, Current therapeutic opt i ons in the management of anxiety, pp. 15-24). Buspirone, an azaspirodecanedione-based drug that has been developed since the 1970s, does not bind to the benzodiazepine receptor, unlike other antianxiety agents. Although it does not directly affect the high GABA (Y-aminobutyric acid) nervous system and acts on dopamine and serotonin receptors in the hippocampus, it is known to have fewer side effects such as dyskinesia than the existing benzodiazepines. Is delayed two or three weeks, and there is a possibility of side effects on the dopamine system, which is also not an ideal neurostabilizer (Mental Medicine 15, 1990, Hwang, Kwang-min, Kwon Jun-su, Lee Bu-young, A comparative study of buspyron and diazepam on the body, pp. 87-93). In addition, Ambien (Monsanto), which currently occupies 80% of the US sleeping pill market, is reported to have a long-term sleep effect (8 hours), resulting in a sleepy condition even after waking up in the morning (Nihon Shinkei). Seishin Yakurigaku Zasshi 20 (3), 2000, M. Uchiumi, S. Isawa, M. Suzuki, M. Murasaki, The effects of Zolpidem and zopi clone on daytime sleepiness and psychomotor performance, pp. 123--130).

 <5> In oriental medicine, which has developed around relationships that cannot be separated from the body and mind in the past, medical treatments for blows, excitement, tension, and anxiety have been found in herbal medicines. There is a growing interest in research on fragrance therapy.

 <6> Therapies using fragrances have a long history in both East and West, and especially in the East, since they have been systematically organized in the fifty-two wards of the nation's era, there have been various methods of using drugs and flowers. Natural fragrances have been used to prevent and cure diseases, to restore the mind and body, and to treat cheongeumbang (千金 要 方) and "Donggibobogam" in Dongdong, fragrance therapy. Recently, it has been known that a combination medicinal extract containing nine kinds of medicinal herbs is effective in promoting sleep and suppression of cramps (Korean Patent No. 0523452, Pharmaceutical composition for the treatment and prevention of insomnia and cramps containing medicinal herbs) Drug development is needed.

 [Detailed Description of the Invention]

 [Technical problem]

 Therefore, the problem to be solved by the present invention is to provide a nucleic acid extract and a composition comprising the same that is effective for insomnia relief and / or improvement.

 Technical Solution

 The present invention provides nucleic acid extracts of cedar, scented scent, benzoic, scented, and cedar complexes.

<9> The Dragon Brain (Ryong 腦 ， B0ME0LUM) was published in the Korean Pharmacopoeia Herbal Medicine (WC) Standard Collection (2007) It is also called ice floe, Borneo 1, etc., and it is obtained by steam distillation of poly resin or stem and branches from the trunk of Dryobalanops aromatica Gaertner (Dr. incense and Dipterocarpaceae). It is a white crystal.

<ιο> The STYRAX LIQUIDES is listed in the Korean Pharmacopoeia Herbal Medicines (2007) collection, also called succinate oil, etc., which is called scented liquid liquefied liquida bar. oriental is Mi 1 ler (American Hamamel idaceae).

 <π> BENZOIN is contained in the Korean Pharmacopoeia (9th Amendment),

 It is also called Benzoinum, and this drug is known as Benzoinum Styrax benzoin Dryander or Styrax tonkinensis Craib ex Hart. Resin obtained from (Styracaceae).

 <12> Cyperus Rhizome is contained in the Korean Pharmacopoeia (9th Amendment) and is also called Cyperi Rhizoma, which is the root of the root of Cyperus rotundus Linne (Cyperaceae). Will be removed.

 <13> The Mok-hyang (木香, AUCKLANDIAE RADIX) is stored in the Korean herbal medicine (Herbal Medicine) standard collection, this drug is called Mokyang (木香) Aucldandia lappa Decne. (Chrysanthemum Compositae) is the root.

 The cedar, scented scent, benzoin, hyangbuja, and cedar may be collected from nature or purchased on the market.

 <15> Among the above mixtures are not limited to the cedar, scented scent, Benzoin, hyangbuja, and neck fragrance is not limited to this, 50 to 200 parts by weight, 50 to 200 parts by weight of benzoin, 50-200 parts by weight of fragrant scent against 100 parts by weight of the brain It may be a ratio of 50 to 200 parts by weight of neck, preferably 100 parts by weight of scented aroma, 100 parts by weight of benzoin, 100 parts by weight of fragrance and 100 parts by weight of cedar.

<16> The nucleic acid extracts are camphor, camphor, alpha- _copaene , beta- _{elemen ᅤ cyperene} , beta- _celinene , alpha- _selenene , delta-cardinene, 9, 10-dehydroisotransporter pollen 8 , 9-dehydroiso ventolene, alpha-cyferon, benzylbenzoate, benzylcinnamate, and methyldihydroisofimarate.

 The nucleic acid extract may be administered in a conventional manner, but preferably, by inhalation, the nucleic acid extract may have a rapid effect without the objection of the subject and avoid side effects.

The nucleic acid extract of the present invention may be formulated further including excipients, carriers, and / or diluents, and preferably pharmaceutically acceptable excipients, carriers and / or It can be formulated using a diluent or the like. The composition of the present invention may be administered in a conventional formulation, and may be preferably formulated in a formulation such as an inhalant. Preferred examples of the unit Brother lactose (乳糖), and the preferable example of the support is dextran, and preferred examples of _yae the diluent ethanol.

 In addition, the present invention provides a composition for improving insomnia and / or alleviation comprising the nucleic acid extract of the present invention. The improvement means that the symptoms of insomnia are better and the alleviation means that the symptoms of insomnia are prevented from becoming worse. The nucleic acid extract is an active ingredient or active ingredient included in the composition.

 <20> The composition of the present invention is preferably a fragrance composition or a pharmaceutical composition. The pharmaceutical composition may include a pharmaceutically acceptable carrier and the like, and the fragrance composition may be prepared by including a carrier and the like which are allowed in the preparation of the fragrance. The fragrance is meant to include fragrances, fragrances, perfume oils and the like. The pharmaceutical composition may be for the treatment and / or prophylaxis of insomnia, the treatment and / or prevention of insomnia may be by monoamine oxidase inhibition, may be due to insomnia improvement and / or alleviation.

 The dose of the nucleic acid extract or composition of the present invention may be determined according to the route of administration, the dosage form, the purpose of use, and the degree of disease of the patient. For example, the dose of l ~ 2mg / kg / day based on the nucleic acid extract may be determined. Can be administered by inhalation through the respiratory system.

 The present invention also provides a use for improving insomnia and / or alleviating insomnia, preferably for treating insomnia, and / or for preventing prophylaxis of cerebellar, scented, benzoate, scented, and cedar complex nucleic acid extracts.

In addition, the present invention provides a method for improving and / or alleviating insomnia, preferably for treating and / or preventing insomnia, comprising administering to a subject in need thereof a nucleic acid extract of cerebellar, scented, benzoate, scented, and cedar complex. To provide.

The matters mentioned in the nucleic acid extract of the present invention, the use of improving the composition of insomnia and / or alleviating agent, and the method of improving the insomnia and / or alleviating the same function as the contrary.

 The nucleic acid extract of the present invention may be prepared by a nucleic acid extraction method, specifically, selecting a medicine and determining a compounding ratio; Powdering the medicine and mixing the mixture according to a mixing ratio; Adding nucleic acid to the powder and extracting at 25 degrees Celsius; And removing the nucleic acid with a concentrator.

<26> Regarding formulation, see Remington's Pharmaceutical Science, Mack.

See methods disclosed in Publishing Company, Easton PA (latest version), and the like. All.

 The nucleic acid extract of the present invention exhibits an effect of prolonging sleep and inhibiting monoamine oxidase, and does not show side effects such as dizziness, and is effective for improving insomnia and / or alleviating insomnia.

 Advantageous Effects

 The solvent extract of the present invention and the composition comprising the same have an effect of extending sleep and inhibiting monoamine oxidase, and are effective in improving and / or alleviating insomnia.

[Brief Description of Drawings]

 1 is a diagram illustrating a graph of chromatographic analysis of Experimental Example 1. FIG.

 [Form for implementation of invention]

 Advantages and features of the present invention, and methods of accomplishing the same will be apparent from the embodiments described below in detail. However, the present invention is not limited to the embodiments disclosed below, but will be implemented in various forms, and only the embodiments are to make the disclosure of the present invention complete and have ordinary skill in the art to which the present invention belongs. It is provided to fully inform the scope of the invention, and the invention is defined only by the scope of the claims.

 Example 1 Preparation of Nucleic Acid Extract

5 kinds of medicines, ie, Cerebral Fragrance, Sohap Flavor, Benzoin, Hyangbuja and Mokyang, were used in the market (Severe Medicine, Republic of Korea, Gyeongsangbuk-do, Gyeongju). Each of these medicines minutes, and then, the powdered yongnoe 200 mg, sohaphyang 200 mg, benzoic 200 mg, elecampane 200 mg, Cyperus rotundus were combined common as the blending ratio of 200 mg into the nucleic acid one here allowed to stand for 48 hours at 25 ^° C in words It was. Shake occasionally to ensure good extraction. After filtering the nucleic acid layer, the nucleic acid was completely removed by a concentrator (Eyela NE, Japan) to prepare a nucleic acid extract.

 <33> <Comparative Example 1> Preparation of nucleic acid extract No. 0523452

 9 kinds of medicinal herbs disclosed in Korean Patent No. 0523452, namely, dragon head, mussel incense, benzoin, cedar, frankincense, incense, clove, fennel and saengbu, obtained in the market (Sacred Medicine, Republic of Korea, Gyeongsangbuk-do, Gyeongju) Except for the use, nucleic acid extracts were prepared in the same manner as in Example 1.

 <Example 2> Confirmation of the effect of extending the sleep time of the nucleic acid extract

Seven mice {Dae Bio Bio Co., Ltd.} were prepared as Example 1 administration group. Example 1 The dosing group is placed in a cage in a special kennel with minimal external air. Sleep effect was measured by allowing the mice to spontaneously inhale the hexane extract aroma of Example 1 (a dose corresponding to 1.5 mg / kg / day of human standard). At this time, the inhalation time was 3 hours in the day, 3 hours in the afternoon, 6 hours in total, inhaled for 7 days. One hour after the last inhalation, 50 mg / kg of the sleeping drug pentotal sodium was dissolved in saline and intraperitoneally injected to observe how long the sleeping time was extended by the sleeping agent. Sleeping time was measured by comparing the time until the recovery of the clove reflected on the basis of the point of disappearing the righting reflex by touching the tip of the nose of the mouse.

 The control group was administered in the same manner as in Example 1 except that the nucleic acid extract of Example 1 was not administered, and the positive control group was a sedative chlor promazine hydrochloride instead of the nucleic acid extract of Example 10. Except for oral administration of mg / kg was carried out in the same manner as in Example 1 administration group. In addition, Comparative Example 1 administration group was carried out in the same manner as in Example 1 except that the nucleic acid extract of Comparative Example 1 was administered. All experimental results were statistically analyzed using the Origin (Version 7.0) program. When significance was recognized, the significance test was performed below p <0.05 level using Student's -test. The results are shown in the table below. Sleep time in the table is the mean standard error, and the rate of increase is a percentage of the control time.

 <38> [Table 1]

 * p O.Qi

 Compared with the control group, the comparative example 1 administration group was significantly (p <0.05) extended by 8.8 minutes, but the example 1 administration group was significantly (p <0.05) extended by 22.9 minutes. This indicates that the increase in the sleeping time is more than four times greater than that of the control group compared to the control group of the administration of Example 1 in comparison. From these results, it can be seen that the solvent extract of the present invention can prolong sleep time without waking up, and is effective for improving insomnia and / or alleviating insomnia. In addition, it can be seen that the sleep effect can be exhibited without side effects by a simple inhalation, regardless of methods such as oral administration and injection.

In addition, all the mice treated with Example 1 had side effects such as dizziness. Not observed.

 <Example 3> Confirmation of the monoamine oxidase inhibitory effect of the nucleic acid extract

 Monoamine oxidase is an enzyme that catalyzes the oxidative deamine reaction of monoamines (serotonin, dopamine, epinephrine, norepinephrine, etc.) to remove amino groups from molecules to form aldehydes and ammonia. . Serotonin, the substrate for this enzyme, is a neurotransmitter related to sleep. Therefore, the effects of inhibiting monoamine oxidase, which degrades serotonin, may be effective in improving sleep disorders (Jouvet, M. Biogenic amines and the states of sleep: pharmacological and neurophus io 1 ogi ca 1 studies suggest a relationship between brain serotonin and sleep.See Science 163, 32-41 (1969)).

 With varying doses of nucleic acid extracts, the effect of inhibiting monoamine oxidase activity was confirmed by an in vitro test. The enzyme source for measuring monoamine oxidase activity was prepared by the following method. That is, brain tissues were extracted from experimental animals (mouse; Dae Bio Biolink), and then washed once with a small amount of 0.32M cold sucrose solution. A 10% (w / v) homogenate was prepared from the above sucrose solution, followed by centrifugation at 1,000 × for 10 minutes to obtain a supernatant. The precipitate was washed twice with a small amount of sucrose, and then the supernatant and wash were combined and centrifuged at 12,000X for 20 minutes. The obtained pellet (mitochondrial fraction) was washed once with a sucrose solution and then used as an enzyme source. The above operation was carried out at 0 ~ 4 ° C.

 <45> About 1 mg of the pellet, 50 mM Trizma-HCl complete solution (pH 8.2) 3 i, 1 mM benzylamine 0.5 in 1 mL / of the nucleic acid extract of Example 1, respectively, 1 mg /, 2 mg / m ^ , Was dissolved in DMS0 (dimethylsulfoxide) at a concentration of 5 mg / ^. After the incubation for 30 minutes at 37 ° C, the reaction tube was immediately cooled with water. 3> zinc sulfate 1 was added here, it mixed well by vortex, and it left to stand for about 30 minutes. The supernatant from which the precipitate was removed was centrifuged for 5 minutes and absorbance was measured at 250 nm. In addition, the control test further comprises the step of stopping the enzyme reaction by heating 10¾> (w / v) homogenate made of sucrose solution at 100 ° C for 5 minutes, after which no nucleic acid extract is added. Except for the same procedure as above.

The results are shown in the table below. The results showed a dose-dependent tendency to inhibit enzyme activity as the dose of nucleic acid extract increased. In particular, the enzyme activity was inhibited by about half at the concentration of 5.0mg / ml nucleic acid extract. <47> [Table 2]

 From the above results, the nucleic acid extract of the present invention exhibits the effect of inhibiting monoamine oxidase, thus exhibiting the effect of maintaining sleep, and consequently, it is effective in improving and / or alleviating insomnia. In addition, it can be seen that it is possible to control the degree of insomnia improvement and / or alleviation effect by adjusting the dose because it can inhibit the enzyme activity in a dose-dependent manner. As a result, it is possible to control the improvement and / or alleviation of insomnia so that side effects from excessive sleep are not generated.

 Experimental Example 1 Composition Analysis of Nucleic Acid Extracts

<5i> The components and contents of the nucleic acid extract prepared in Example 1 were analyzed by GC-MS method. GC-MS (HP 6890 series; Hewlett-Packard) was used and the column was measured using an HP capillary column (60.0 mx 250 μπι x 0.25 μιη). The gas used for the measurement is nitrogen and the measurement conditions are as follows. That is, the initial temperature is maintained at 40 ^° C for 5 minutes, then increased by 5 ^° C in 1 minute to 90 ^° C and maintained at this temperature for 5 minutes, then increased by 5 ^° C in 1 minute Raise it up to 110 ^° C and hold at this temperature for 10 minutes, then raise it by 2 ^° C in 1 minute, raise it to 230 ^° C, hold it for 5 minutes at this temperature, and finally raise it to 300 ^° C, The measurement was continued.

The chromatographic analysis result graph is shown in FIG. 1 and shows the retention time and content in the following table. The X axis of FIG. 1 represents the retention time and the y axis represents the abundance. <53> [Table 3]

 <54>

 From the above results, the nucleic acid extract of the present invention is camphor, camphor, alpha-copaene, beta-elemen, cyperene, beta-celinene, alpha-selenene, delta-cardinene, 9, 10-dehydroyi. It can be seen that it includes a communicator pollen, 8,9-dehydroisolinker pollen, alpha-cyferon, benzylbenzoate, benzylcinnamate, and methyldihydroisopimarate.

 Industrial Applicability

 The present invention provides nucleic acid extracts of cedar, scented scent, benzoic, scented, and cedar complexes. The solvent extract of the present invention exhibits the effect of prolonging sleep and producing monoamine oxidase inhibitors, and is effective in improving insomnia and / or alleviating insomnia and thus has industrial applicability.

Claims

[Range of request]  [Claim 1]  A composition for improving or alleviating insomnia, including nucleic acid extracts of cedar, scented scent, benzoate, scented, and cedar.  [Claim 2]  The composition of claim 1, wherein the mixture is 50-200 parts by weight of scented fragrance, 50-200 parts by weight of benzoate, 50-200 parts by weight of fragrant scent, and 50-200 parts by weight of cedar.  [Claim 3]  The composition according to claim 2, wherein 100 parts by weight of scented fragrance, 100 parts by weight of benzoic acid, 100 parts by weight of fragrant scent, and 100 parts by weight of scent of rice is 100 parts by weight.  [Claim 4]  The nucleic acid extract of claim 1, wherein the nucleic acid extract is camphor, camphor, alpha-copaene, beta-elemen, cyperene, beta-celinene, alpha-selenene, delta-cardinene, 9, 10-dehydroisohydride. A composition comprising a fluorine, 8, 9-dehydroisobarperolene, alpha-cyferon, benzylbenzoate, benzylcinnamate, and methyl dihydroisofimarate.  [Claim 5]  The composition according to any one of claims U to 4, wherein the composition is a fragrance composition.