JP2005272342A - Antidepressive or antianxiety pharmaceutical composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a pharmaceutical composition which improves stress-induced neurologic symptoms, especially depression and anxiety. <P>SOLUTION: The antidepressive or antianxiety pharmaceutical composition is prepared by compounding (a) at least two species selected from the group consisting of Valeriana fauriei, Angelica acutiloba and Viscum album and (b) at least one species selected from the group consisting of Passiflora caerulea, Humulus lupulus, Uncaria rynchophylla and Daucus carota. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to an antidepressant or anxiolytic pharmaceutical composition, and more particularly to a novel pharmaceutical composition effective for suppressing or improving psychiatric symptoms caused by stress or the like, particularly depression and anxiety symptoms.

Stress causes brain excitement and causes depression, generalized anxiety disorder, and (primary) insomnia. The treatments include tricyclic antidepressants and benzodiazepines. There are many occasions where psychiatric drugs are used, but attention should be paid to suicide attempts and dependence.
Treatment with herbal medicine has been widely used for a long time for mild patients who do not use antidepressants and anxiolytics and for menopausal symptoms where symptoms appear temporarily. It is known that valerian has a sedative action, and is a herbal medicine that is widely used for the purpose of hypnosis and sedation. For example, in addition to valerian, a combination of passiflora (passiflora), hops, lizard (carfly) and carrots, "sedation of tension, excitement, irritability, and relief of head strain and fatigue fatigue associated with the above There is also a report (Non-patent Document 1) that an anti-stress action (a suppressive action on the amount of spontaneous exercise that increases due to stress load) is recognized.
Fundamentals and Clinical Practice 26 (9): 3903-3905, 1992

  An object of the present invention is to provide a novel pharmaceutical composition effective in suppressing and improving psychiatric symptoms caused by stress and the like, particularly depression and anxiety symptoms.

As a result of various studies to achieve the above object, the present inventors have found that a novel combination of specific herbal medicines is effective in suppressing or improving mental symptoms such as depression and anxiety. The invention has been completed.
That is, the present invention
(1) (a) at least two selected from the group consisting of valerian, pearl and mistletoe, and (b) at least one selected from the group consisting of passiflora (passiflora), hops, scorpion (butterfly) and carrot An antidepressant or anxiolytic pharmaceutical composition characterized by comprising
(2) The pharmaceutical composition according to the above (1), wherein the group (a) is valerian and toki, and the group (b) is passiflora (passiflora),
(3) A pharmaceutical composition according to the above (1), comprising a combination of valerian, toki, passiflora (passiflora), hops, scallop (butterfly) and carrot,
(4) The pharmaceutical composition according to the above (1) 1, which comprises blending valerian, toki, mistletoe, passiflora (passiflora), hops and scorpion (butterfly),
(5) The pharmaceutical composition according to the above (1), comprising valerian persimmon, mistletoe, passiflora (passiflora), hops, scabbard (butterfly) and carrot,
(6) Provided is a pharmaceutical composition according to the above (1), which is prepared by blending valerian grass, mistletoe, passiflora (passiflora), hops and ragweed (butterfly).

  (A) at least two kinds selected from the group consisting of valerian, cypress and mistletoe, and (b) at least one selected from the group consisting of passiflora (passiflora), hops, scabbard (carfly) and carrot Pharmaceutical compositions formulated and having antidepressant or anxiolytic effects are not yet known and are novel. According to the present invention, a novel specific combination of herbal medicines of the groups (a) and (b) can provide a pharmaceutical composition effective for the suppression and improvement of mental symptoms such as depression and anxiety.

Embodiments of the present invention will be described below.
As the valerian, for example, a dry powder, extract or extract powder of roots and rhizomes of valerian or related plants (eg, Valeriana) can be used. The blending amount is about 0.01 to 20 g, preferably about 0.1 to 10 g in terms of crude drug powder or extracted drug substance.

  As the touki, for example, any form of dried powder, extract or extract powder of the roots of toki or its related plants (other aceae plants) can be used. The blending amount is about 0.01 to 20 g, preferably about 0.1 to 10 g in terms of crude drug powder or extracted drug substance.

  Mistletoe is known as a herbal medicine having a hypnotic action and a blood pressure-lowering action. For example, it can be used in the form of any of its branches, leaf tops, stems, dry leaves, extracts or extract powders. The blending amount is about 0.01 to 20 g, preferably about 0.1 to 10 g in terms of crude drug powder or extracted drug substance.

  As the passiflora (passiflora), for example, any form of dried stem, root, extract or extract powder can be used. The blending amount is about 0.01 to 20 g, preferably about 0.1 to 10 g in terms of crude drug powder or extracted drug substance.

  As the hop, for example, a dry powder, an extract, or an extract powder of the unfertilized female flower (carp) can be used. The blending amount is about 0.01 to 20 g, preferably about 0.1 to 10 g in terms of crude drug powder or extracted drug substance.

  For example, the stalk of the side branch of the vine and the dry powder of the part of the stalk, the extract or the extract powder can be used as the scab. The blending amount is about 0.01 to 20 g, preferably about 0.1 to 10 g in terms of crude drug powder or extracted drug substance.

  As the carrot, for example, a dry powder, extract or extract powder in the form of ginseng root can be used. The blending amount is about 0.01 to 20 g, preferably about 0.1 to 10 g in terms of crude drug powder or extracted drug substance.

The pharmaceutical composition of the present invention includes (a) at least two kinds selected from the group consisting of valerian, toki and mistletoe, and (b) a group consisting of passiflora (passiflora), hops, scabbard (butterfly) and carrot And at least one selected from the above.
As the herbal medicines in group (a), valerian and toki are preferable, and as the herbal medicine in group (b), passiflora (passiflora) is preferable.
Specific examples of combinations include valerian, eucalyptus, passiflora (passiflora), hops, lizards (butterfly) and carrots; Examples include combinations of valerian, mistletoe, passiflora (passiflora), hops, lizard (butterfly) and carrots; and valerian, mistletoe, passiflora (passiflora), hops and lizard (butterfly).
The specific blending amount can be appropriately selected from a range in which the dose normally employed in the above range can be achieved for each herbal medicine, and the amount ratio between the herbal medicines is not particularly limited.

  The herbal powder and extract components used in the present invention have been used medicinally as a simple or traditional Chinese medicine, and the herbal powder or extract components obtained according to conventional methods can be used as they are. As the form of the crude drug powder or the extracted component, a normal commercially available product or a processed product thereof can be used. As the crude drug powder, for example, it may be used as a dry product in the form of a powder (fine powder) obtained by further finely pulverizing a dry chopped product. In addition, the form of the extracted component from the herbal medicine is not particularly limited, and any form such as dry extract, extract powder, soft extract, flow extract, ethanol or tincture containing ethanol and water can be used. Preferably, an extraction component having a high degree of freedom in formulation, for example, a dry extract powder is used. As the extraction solvent, for example, water, a hydrophilic solvent or a mixture thereof is often used. Examples of the hydrophilic solvent include alcohols such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, s-butanol and t-butanol (preferably having 1 to 3 carbon atoms such as methanol, ethanol, propanol and isopropanol). Water-soluble alcohol, more preferably ethanol); cellosolves such as methyl cellosolve and ethyl cellosolve; ketones such as acetone; ethers such as dioxane and tetrahydrofuran; pyridine, morpholine, acetonitrile, N, N-dimethylformaldehyde, dimethyl Examples thereof include nitrogen-containing solvents such as acetamide and N-methylpyrrolidone. These hydrophilic solvents may be used alone or as a mixed solvent of two or more.

  The dosage form and dosage form of the pharmaceutical composition of the present invention are not particularly limited. For example, the above-mentioned fine granules or granules in a powder, fine granules, granules, pills, tablets, capsules, etc. Can be formulated into various preparations for oral or parenteral administration, such as solid preparations such as capsules filled with a liquid; suspensions, emulsions, syrups and other semi-solid preparations such as jelly preparations. In particular, solid preparations for oral administration such as tablets, granules and capsules are preferred. These preparations use pharmacologically acceptable fillers, extenders, binders, disintegrants, surfactants, lubricants, diluents, excipients that are usually used as necessary. It can be prepared by a conventional method. Moreover, you may use a solubilizing agent, a buffering agent, a preservative, a solubilizer, a fragrance | flavor, a coloring agent, a corrigent, etc. as needed.

The pharmaceutical composition of the present invention is effective in suppressing or improving psychiatric symptoms caused by stress and the like, particularly depression and anxiety symptoms, in mammals such as humans. Alternatively, the desired effect can be obtained by parenteral administration.
EXAMPLES The present invention will be described in more detail below with reference to examples and test examples, but the present invention is not limited to these examples.

According to formulations A to D shown in Table 1 below, commercially available herbal extract powders were mixed according to a conventional method to obtain a powdery pharmaceutical composition of the present invention.

Test example 1

Prescriptions A to D obtained in Example 1 for hyperemogia and anxiety behavior on elevated plus maze observed after light blockage and isolated rearing stress using olfactory bulbectomized rats, one of the models of antidepressant neurosis The improvement effect of was investigated.
(1) Preparation of olfactory bulb-excised rat Under anesthesia, the head of a Crj: Wistar rat was fixed, the scalp was incised, holes were drilled in the left and right olfactory bulb parts with a dental drill, and the tip of the oral sonde was removed. The left and right olfactory bulbs were aspirated and removed with the contacted aspirator, and then the scalp was sutured to create an olfactory bulb-extracted rat. As rats in the sham-operated group, rats were created in which holes were made in the left and right olfactory bulb regions without sucking and removing the olfactory bulb.
(2) Isolated isolation breeding Rats after excision of the olfactory bulb were reared in individual breeding spaces, with the light blocked and isolated so that the neighbors could not be seen. During this time, as a general rule, avoiding contact with animals.
(3) Specimen administration A required amount of water for injection was added to one day of Formulations A to D, suspended or dissolved, and orally administered to rats once a day for 8 days.
Since there is a limit to the number of animals that can perform olfactory bulbectomy at one time, the test was conducted in two steps as shown in Tables 2 and 3.

(4) Antidepressant effect Olfactory bulb-extracted rats after light blockage and isolation breeding stress, using rats on day 7 of sample administration, in a soundproof room before and after 2 hours of sample administration on day 7 Japanese Pharmacological Journal, 82: 267-292 on the reaction to the stick placed on the tip of the nose, the reaction when air is blown, the resistance to capture and handling, the reaction when the tail is pinched with forceps and the cry during the test , 1983, based on the method of Gomida et al., Was evaluated with a five-point score, and the total score was compared. The results are shown in FIG. 1 and FIG.
As shown in FIG. 1 and FIG. 2, in the olfactory bulb-extracted rats (vehicle control), a significant excess of emotion was observed after light blockage and isolated rearing stress compared to the sham-operated group without olfactory bulb extraction. With continuous oral administration of Formulas A, B, C and D, significant improvement (anti-depressive effect) was observed for the excess of emotion seen after light blockage and isolated rearing stress.

(5) Anti-anxiety action It consists of two elevated arms crossed in a cross shape at the center. A wall is attached to one arm except for the crossing part to make a closed arm, and the other is an open arm without a wall. An elevated cross maze painted in white was used. This maze was installed in a soundproof room, and a rat used for an antidepressant test was used the next day (8 days after sample administration). 2 hours after sample administration, placed at the central intersection of the maze, facing the open arm, the number of times to enter any arm, the stay time on any arm (seconds), the defecation on the arm, the number of urination Was observed for 5 minutes.
In the olfactory bulb-excised rats, after light blockage and isolated rearing stress, compared with the sham-operated group without olfactory bulbectomy, there was a significant difference in the following items on the elevated plus maze as an indicator of anxiety behavior .
1) Decrease in the number of times of entering each arm 2) Shortening the staying time on the open arm and prolonging the staying time on the closed arm In the prescription C, an improvement tendency was observed with respect to 2). The results are shown in FIGS.

  ADVANTAGE OF THE INVENTION According to this invention, the pharmaceutical composition effective in suppressing and improving the psychiatric symptoms resulting from stress etc., especially a depression and an anxiety symptom can be provided.

It is a graph which shows the test result of the antidepressant action about prescription A and C. It is a graph which shows the test result of the antidepressant action about prescription B and D. It is a graph which shows the frequency | count of approach to the open arm about prescription A and C in the test of an anxiolytic action. It is a graph which shows the frequency | count of approach to the closed arm about prescription A and C in the test of an anxiolytic action. It is a graph which shows the residence time on the open arm about prescription A and C in the test of an anxiolytic action. It is a graph which shows the residence time on the closed arm about prescription A and C in the test of an anxiolytic action.

Claims (6)

  (A) at least two kinds selected from the group consisting of valerian, toki and mistletoe, and (b) at least one selected from the group consisting of passiflora (passiflora), hops, lizard (carfly) and carrot An antidepressant or anxiolytic pharmaceutical composition characterized by comprising.   The pharmaceutical composition according to claim 1, wherein group (a) is valerian and toki, and group (b) is passiflora (passiflora).   The pharmaceutical composition according to claim 1, comprising valerian, toki, passiflora (passiflora), hops, scallop (butterfly) and carrot.   The pharmaceutical composition according to claim 1, comprising valerian, toki, mistletoe, passiflora (passiflora), hops and lizard (butterfly).   The pharmaceutical composition according to claim 1, comprising valerian, mistletoe, passiflora, hops, lizard and carrot. The pharmaceutical composition according to claim 1, comprising valerian, mistletoe, passiflora (passiflora), hops and lizard (butterfly).

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