KR20070013378A - A pharmaceutical composition comprising the extract of gardenia for treating or preventing depression disease - Google Patents

Abstract

A pharmaceutical composition for treating or preventing depression disease comprising the extract of gardenia(Gardenia Jasminoides for. grandiflora) is provided to suppress activity of MAO(monoamine oxidase) without affecting internal organs influenced by sympathetic amine and serotonin. The pharmaceutical composition for treating or preventing depression disease comprises the extract of gardenia(Gardenia Jasminoides for. grandiflora) as an effective ingredient, wherein the gardenia(Gardenia Jasminoides for. grandiflora) extract is prepared by extracting gardenia(Gardenia Jasminoides for. grandiflora) with water of C1-C4 lower alcohol such as methanol, ethanol and butanol; the amount of gardenia(Gardenia Jasminoides for. grandiflora) extract is 0.1-50 wt.% based on the total weight of the composition; the composition is formulated as powder, granule, tablet, capsule, suspension, emulsion, syrup or aerosol; and the dosage of the gardenia(Gardenia Jasminoides for. grandiflora) extract is 0.0001-100 mg/kg per day.

Description

A pharmaceutical composition comprising the extract of gardenia for treating or preventing depression disease}

Figure 1 shows the change in MAO activity of rats orally administered Gardenia extract of the present invention,

Figure 2 shows the serotonin concentration change in the brain of rats orally administered the gardenia extract of the present invention.

The present invention relates to a pharmaceutical composition for the prevention and treatment of depression disease comprising gardenia extract.

In the central nervous system, serotonin (5-hydroxytryptamine, 5-HT) functions as a neurotransmitter or neuromodulator that regulates many physiological functions such as cognition, diet, sleep, sexual behavior, aggressiveness, and mood. In addition to these physiological functions, various disorders of mental and behavioral disorders such as anger, mental illness, and depression are known to be caused by serotonin imbalance in the nervous system.

Depression, also known as a `` cold of mind, '' is a common mental illness that 10-20% of all adults may experience. Depression or sad feelings are common in everyday life. Morbid depression can affect one's personal and social life, as sad or depressed feelings affect not only the mood but also the body and thoughts. It is a disease that leads to suicide attempts when severely caught up in disability, isolation, sense of guilt, guilt, and suicidal thoughts.

Therefore, inhibitors that inhibit the activity of MAO, an enzyme that uses serotonin as a substrate, have traditionally been used as drugs for treating depression.

MAO (monoamine oxidase) is widely present in mitochondria in animal tissues such as the central nervous system and peripheral tissues, and is an enzyme that controls the metabolism of neurotransmitters and hormonal amines. It catalyzes the oxidative deamination of amine compounds to break down hormonal amines derived from neurotransmitters and food and gut bacteria.

[Formula 1]

MAO mainly uses catecholamines and indolealkylamines or derivatives thereof as endogenous substrates, and A-type oxidative deamination of serotonin, norepinephrine and epinephrine depending on substrate specificity. It can be divided into B-type catalyzing the oxidation of benzylamine, phenethylamine.

The monoamine oxidase inhibitors (MAOIs) are typically depression (Youdim MB, Finberg JP, and Tipton, KF. Handbook of Experimental Pharmacology. 90/1 , pp119-192, 1988; Sambamoorthi U, et al., Med Care . 41 ( 1) , pp 180-94, 2003) and hypertension (Laux G, Philipp M, Kohnen R. Lancet. 11 ; 347 (9011): 1330, 1996), migraine (Silberstein SD, Curr Med Res Opin . 17 Suppl 1: s87 -93, 2001) and have been used as drugs to treat Parkinson's disease (Danisi F., Geriatrics . 57 (3) , pp46-50, 2002; Ahlskog JE. Neurology . 60 (3) , pp381- ) . 9, 2003), as well as other causes of panic symptoms (Sheehan DV., J Clin. Psychiatry. , 63 Suppl 14, pp17-21, 2002), as drugs for treating attention deficit and impulsive hyperactivity in children. (Spencer TJ, et al., J Clin Psychiatry . 63 Suppl 12, pp 16-22, 2002).

Recently, stimulants of hypersomnia (Annane D, et al., Cochrane Database Syst Rev. , (4): CD003218, 2002) have been used to treat speechlessness (Berger I, et al., Isr Med Assoc J. 4 (12) , pp1135-7, 2002), as a drug to help quit smoking (Fowler JS, et al., Neurotoxicology . 24 (1) , pp75-82, 2003; Berlin I, et al., Addiction. 97 (10) , pp1347- 54., 2002; Vessicchio JC, et al., J. Clin.Psychiatry., 3 (7) , pp594-5, 2002). In addition, the function of new MAOIs is being studied, and new functions of MAOIs have been reported as potent candidates for treating Alzheimer's disease (Sterling J, et al., J Med Chem. 21 ; 45 (24), pp5260-). 79, 2002) Pharmacotherapy for the eradication of Helicobacter pylori in duodenal ulcer patients (Silva FM, et al., Rev Hosp Clin Fac Med Sao Paulo. 57 (5) , pp205-8, 2002; Queiroz DM, et al., J. Clin. Gastroenterol., 35 (4) , pp315-20, 2002; Treiber G, et al., Helicobacter ., 7 (4) , pp225-31, 2002) (Brown BR. HIV Clin. , 14 (3) 1, pp5-8, 2002), modulating the effects of drugs treating alcoholic patients (Wing MK. Chemico-Biological Interactions, 130-132 pp919-930, 2001) It has also been applied to drug therapy to overcome social anxiety disorders (Stein DJ, et al., Int. Clin. Psychopharmacol ., 17 (4) , pp161-70, 2002). Psychomotor stimulant effects, Bergman J, Yasar S, Winger G., Psychopharmacology (Berl) .159 (1) , pp21-30, 2001), memory enhancing activity of MAO inhibitors activity (Nowakowska E, et al., J. Physiol. Pharmacol. , 52 , pp863-73, 2001).

However, SSIRs (selective serotonin reuptake inhibitors) drugs, which are most commonly prescribed as antidepressants, are single-action mechanism antidepressants that regulate the uptake of the neurotransmitter serotonin. MAIOs or tricyclic antidepressants (TCAs) due to substrate selectivity There is a more stable and resistant advantage, but it is pointed out that some patients do not show an effect as an antidepressant due to safety due to selectivity for serotonin. As a result, recently, a new dual-action antidepressant agent that inhibits the absorption of serotonin and norepinephrine is attracting new attention.

The serotonin-norepinephrine reuptake inhibitors (SNRIs) antidepressant drugs have the advantages of improving the side effects of early multi-action antidepressants, having the stability and resistance of SSRIs, and exhibiting rapid effects. It is known. However, the research is still in its infancy, and thus, there is an urgent need for continuous research on antidepressants with low side effects.

On the other hand, MAOIs inhibit the activity of MAO and at the same time affect the organs affected by sympathetic amines and serotonin, and there is a problem that interferes with the hepatic metabolism of many drugs by inhibiting the action of other enzymes. In addition, excessive central stimulation may cause tremors, insomnia, excessive sweating, excitement, hypomania, positional hypotension, dizziness, headaches, and so on.

Gardenia jasminoides (Rubiaceae) Gardenia jasminoides for. grandiflora ] was harvested when the fruit matured and became yellowish yellow in September-November and dried. Flavonoids, iridoid glycosides, and carotenoids have been reported.

In addition, it is known to be used in folk remedies, antipyretic, biliary, hemostatic, anticancer, sedative, blood pressure lowering.

Other, Hypoglycemic activity (Miura T, Nishiyama Y, Ichimaru M, Moriyasu M, Kato A., Biol Pharm Bull., 1996 Jan; 19 (1) : 160-161), anti-tumor effect (Peng CH, Huang CN, Wang CJ., Curr Cancer Drug Targets. 2005 Jun; 5 (4) : 299-305), anti-angiogenic activity (Koo HJ, Lee S, Shin KH, Kim BC, Lim CJ, Park EH. Planta Med., 2004 May; 70 (5) : 467-9), Antithrombotic effect (Suzuki Y, Kondo K, Ikeda Y, Umemura K., Planta Med., 2001 Dec; 67 (9) : 807-10), Antioxidant activity (Pham TQ , Cormier F, Farnworth E, Tong VH, Van Calsteren MR., J Agric Food Chem. , 2000 May; 48 (5) : 1455-1461), have been reported using gardenia extract and components isolated from gardenia.

However, although various active studies have been reported as described above, few reports have been made on blood pressure regulation, neurostable effects, dementia treatment or antidepressant effects of gardenia.

 Accordingly, the present inventors have studied the present invention by confirming the superior inhibitory activity of MAO of the Gardenia jasminoides extract of the present invention while studying the activity of inhibiting MAO using its serotonin as a substrate and its active ingredients in consideration of the advantages and disadvantages of existing antidepressants. Completed.

An object of the present invention is to provide a pharmaceutical composition for the treatment and prevention of depression, including gardenia extracts having an effect of inhibiting the activity of MAO.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of depression containing the gardenia extract and non-polar solvent soluble extract as an active ingredient.

The extract includes water and C ₁ to C ₄ lower alcohols such as methanol, ethanol, butanol and the like, and a mixture thereof, an extract available in an aqueous methanol solution.

Hereinafter, the present invention will be described in detail.

Gardenia extract of the present invention can be obtained as follows.

After collecting, drying and pulverizing the gardenia of the present invention, a volume of water up to about 2 to 10 times, preferably about 5 to 8 times the weight of the gardenia sample and C ₁ to C, such as methanol, ethanol, butanol, and the like Polar solvent of C ₄ lower alcohol or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, preferably 3 times at 90 to 100 ° C. for 3 hours with reflux cooling by adding 80% aqueous methanol solution After repeated heating and extraction, and filtered through cotton wool, the filtrate can be lyophilized again by ethanol extract obtained by concentrating under reduced pressure on a water bath of 30 to 50 ℃ to obtain a gardenia extract.

The present invention provides a pharmaceutical composition for the prevention and treatment of depression disease containing the gardenia extract obtained by the above method as an active ingredient.

In addition, the gardenia extract has been used as a medicinal herb extracts of the present invention also have no problems such as toxicity and side effects, so can be used with confidence even during prolonged administration for the purpose of prevention.

The pharmaceutical composition for preventing and treating depressive diseases according to the present invention comprises 0.1 to 50% by weight of the extract based on the total weight of the composition.

The pharmaceutical composition comprising the extract of the present invention may further comprise suitable tints, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

Pharmaceutical dosage forms of the extracts of the present invention may be used in the form of their pharmaceutically acceptable salts, or may be used alone or in combination with other pharmaceutically active compounds, as well as in any suitable collection.

Pharmaceutical compositions comprising extracts according to the invention, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Can be formulated and used. Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, aceitol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may contain at least one excipient such as starch, calcium carbonate and sucrose in the extract. Or lactose, gelatin, or the like is mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the preferred effect, the extract of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.

The present invention provides a health functional food comprising the extract and a food acceptable food supplement additive exhibiting a prophylactic effect of depression disease.

Examples of the food to which the gardenia extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.

It may also be added to foods or beverages for the purpose of preventing depressive diseases. At this time, the amount of the extract in the food or beverage may be added in 0.01 to 15% by weight of the total food weight, the health beverage composition may be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 ml. have.

The health functional beverage composition of the present invention is not particularly limited to other ingredients in addition to containing the extract as an essential ingredient in the indicated ratio, and may contain additional ingredients such as various flavoring agents or natural carbohydrates as in general beverages. . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a flavoring agent other than the above-mentioned, a natural flavoring agent, taumartin, a stevia extract, for example, rebaudioside A, glycyrrhizin, etc .; And synthetic flavoring agents such as saccharin, aspartame and the like. The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition to the above, the extract of the present invention has various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, coloring and neutralizing agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective properties Colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the extracts of the present invention may contain flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. At this time, the ratio of the additive is not very important but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

Hereinafter, the present invention will be described in more detail based on the following Examples and Experimental Examples.

However, the following Examples and Experimental Examples are merely illustrative of the present invention, but the content of the present invention is not limited thereto.

Example 1 Preparation of Gardenia Extract

1-1. Gardenia extract for oral administration

After 100 g of well dried gardenia was ground and ground to powder, 800 ml of 80% ethanol solution was added thereto, and the mixture was heated and extracted three times at 100 ° C. for 6 hours while reflux cooling and then filtered through cotton wool.

The obtained filtrate was freeze-dried again 17.67 g of the ethanol extract obtained by concentrating under reduced pressure on a water bath at 40 ℃ to obtain 16 g of a powder.

 The gardenia extract obtained as described above was stored in a deep freezer at -80 ° C and dissolved in distilled water during the experiment.

1-2. Gardenia Methanol Extract

100 g of dried gardenia was ground, powdered, and 80% methanol solution was added thereto, followed by heating for 6 hours while reflux cooling on a 95 ° C water bath.

After cooling to room temperature and filtration, the foil was washed with 80% methanol solution to make the filtrate to 1000 ml, and then concentrated under reduced pressure in a 45 ℃ water bath to give 1500 mg of methanol extract.

Experimental Example 1. Reagents and Experimental Preparation

1-1. reagent

Gardenia used in the present invention was purchased from a Chinese herbal medicine wholesaler in Gyeongdong Market, Seoul, Serotonin, Benzylamine, Ion exchange resin Amberlite GC-50 used for measuring the enzyme activity is Sigma Chemical Co., St. Louis, MO , USA) product was used.

In addition, HPLC solvents were manufactured by Merk, and column chromatography and sample extraction solvents were purchased from domestic special reagents.

1-2. Laboratory animals

Sprague-Dawely male rats, 5 weeks old, are supplied from BIOGENOMICS Co., Ltd. to control lighting at a temperature of 23 ± 3 ℃, humidity of 50 ± 10%, and 12-hour cycle. Was used in the experiment after adapting for 2-4 weeks while freely supplying solid food and water.

Experimental Example 2. Measurement of activity of brain MAO-A

2-1. Enzyme source preparation

Rats were anesthetized in an ether-doped anesthesia jar, and then opened, and blood was collected from the left ventricle. The skulls were immediately dissected to extract the brain. The extracted brain was washed with 0.01 M phosphate buffered saline (PBS; pH 7), and 9 ml cold 0.25 M sucrose solution per 1 g of wet weight was added and homogenated for 1 minute with a Turrax homogenizer. .

The homogenate was centrifuged at 700 x g for 20 minutes at 4 ° C, the supernatant was taken and again centrifuged at 18,000 x g for 20 minutes, and the supernatant was discarded and the pellet was submerged in 5 ml of PBS / g. Suspension was used as an enzyme source.

2-2. Enzyme Activity Measurement

0.5 ml of the enzyme source prepared above was placed in a test tube, and 0.5 ml of 0.1 mM serotonin solution was added as a substrate solution, and then incubated for 90 minutes in a 37.5 ° C. thermostat. The reaction was stopped by heating for 3 minutes in a 95 ° C. water bath, and immediately centrifuged at 700 × g, 1.0 mL of the supernatant was poured into a previously prepared Amberlite GC-50 (H ⁺ form) column (0.6 × 4 cm). After sufficiently washing the resin with distilled water (40 ml or more), 3 ml of 4 N acetic acid solution was poured into the resin, and the eluate was received in a test tube and the absorbance was measured at 277 nm.

Separately, the correction group with the substrate solution was added to the reaction end point instead of the reaction initiation point with the experimental group. Based on the control group of each experimental group, the change in the enzyme activity according to the temperature change and the drug projection was calculated according to a predetermined formula.

Experimental Example 3 Determination of Activity of Liver MAO-B

3 -1. Enzyme source preparation

In order to fractionate the rat liver mitochondria, the rat was anesthetized in an anesthetic bottle to which ether was added, and then opened. The blood was collected from the left ventricle, and blood was immediately extracted. The extracted liver was washed with 0.01 M phosphate buffered saline (PBS; pH 7), and 9 ml cold 0.25 M sucrose solution per 1 g of wet weight was added and homogenated with a Turrax homogenizer for 1 minute. .

The homogenate was centrifuged at 700 x g for 20 minutes at 4 ° C, the supernatant was taken and again centrifuged at 18,000 x g for 20 minutes, and the supernatant was discarded and the pellet was submerged in 5 ml of PBS / g. Suspension was used as an enzyme source.

3-2. Enzyme Activity Measurement

Enzyme activity was measured according to the method of McWeen et al. (McWeen, CM, Cohen. JR and Cohen, JD, An amine oxidase in normal human serum, J. Lab. Clin. Med. , 62 , 766-776, 1963).

0.5 ml of 4 mM benzylamine-HCl solution with 0.5 ml of enzyme source and substrate solution was added to the test tube and incubated in a 37.5 ° C. thermostat for 90 minutes, and then 0.2 ml of 60% perchloric acid solution was added to stop the reaction. After addition, the mixture was shaken and centrifuged at 700 × g for 20 minutes, and a cyclohexane layer was taken to determine absorbance at 242 nm.

The correction group and the experiment group were carried out together, and the change in enzyme activity according to the temperature change and the drug administration was calculated according to the prescribed formula based on the control group of each test group.

Experimental Example 4. Determination of MAO activity by oral administration of Gardenia extract

Six rats prepared in Experimental Example 1 were fasted 12 hours as a group, and then the gardenia extract powder obtained in Example 1-1 was used as a sample for oral administration. That is, 10 mg of lyophilized gardenia powder was dissolved in 1 ml of distilled water and fasted orally administered to the animals fasted one day before the experiment, two times 4 ml two times before the afternoon and the day before the experiment. The control group was administered 4 ml of distilled water under the same conditions, in which the amount corresponds to 0.3 g / kg per animal body weight in the dry weight of the sample, and 8 to 12 g / 60 kg in humans. (Kang, Byung-Soo et al., Herbology, Younglimsa, Seoul, Korea, 2000)

After 2 hours of oral administration, it was dissected to measure the change in activity of MAO by the method of Experimental Examples 2 to 3, and the results are shown in FIG. 1.

As can be seen in Figure 1, when comparing the enzyme activity of the control group administered distilled water instead of the gardenia extract, there is no statistically significant difference, while MAO-A was shown to increase the enzyme activity by the gardenia extract, MAO- B tended to decrease.

Experimental Example 5. Determination of Serotonin Content in the Brain by Oral Administration of Gardenia Extract

In order to measure the content of serotonin in the brain tissue extracted in Experimental Example 4, the rat was anesthetized in an anesthetic bottle to which ether was added, and then opened, and blood was collected from the left ventricle. It extracted. The extracted brain was washed with 0.01 M phosphate buffered saline (PBS; pH 7), and 9 ml cold 0.25 M sucrose solution per 1 g of wet weight was added and homogenated for 1 minute with a Turrax homogenizer. .

The homogenate was centrifuged at 700 × g for 20 minutes at 4 ° C., the supernatant was taken, and then rapidly centrifuged at 18,000 × g for 20 minutes, and then 1 ml of the supernatant was immediately stored in a freezer at −80 ° C. for analysis. 0.1 ml of 4 M potassium acetate solution (potassuium acetate; H 7.4) was added thereto, dissolved, and centrifuged for 15 minutes at 10,000 rpm at 4 ° C. 50 µl of the supernatant was taken, diluted in the same amount with HPLC buffer, filtered through an HPLC sample preparation filter, and 10 µl of the filtrate was used for analysis.

The HPLC used for analysis was manually injected using a 100 μl loop into a Hewlett-Packardd 1100 System equipped with a gradient pump and a DAD detector. The column used for analysis was Capcellpack C18 (1.0 × 250 mm), and the analytical solvent was used by mixing 20 mM KH ₂ PO / CHCN ₃ mixed solvent at a ratio of 80:20. At this time, the flow rate was 1 ml / min, the temperature of the oven was 40 ° C., the retention time was about 3.7 minutes, and the measurement wavelength was 254/360 nm.

Serotonin solution used for the enzyme activity of serotonin (5-TH) 10 ㎎ to 50% CH ₃ CN to prepare a stock solution dissolved in 1 ㎖, and diluted with _{50% CH 3 CN 0.1, 0.5} , 1, 5, 10 ㎕ / ㎖ Prepare the test solution to be, but all the experiments were repeated seven times to obtain the average value, the results are shown in FIG.

As shown in Figure 2, while the content of serotonin in the brain tissue of the control group is 19.2 mg / ㎖, rats orally administered with the gardenia extract of the present invention was confirmed to increase significantly compared to the control group to 22.8 mg / ㎖ Could. This is not a statistically significant change when compared to 25.7 mg / ml of the positive control group administered with 5 mg / kg of deprenyl, which is used as an antidepressant in clinical practice as an MAO inhibitor, but serotonin acts as a neurotransmitter. Considering this is a very important change.

Experimental Example 6. Measurement of in vitro MAO activity change of gardenia extract

The gardenia methanol extract obtained in Example 1-2 was dissolved in distilled water to make a 10 mg / ml solution, and this solution was used as a stock solution, but the solution was 1 (10 mg / ml), ½ (5 mg / ml), or ¼ (2.5). Mg / ml) using the diluent as the test solution, the enzyme activity was measured according to the methods of Experimental Examples 2 to 3.

As a result, the gardenia methanol extract was found to significantly inhibit the activity of MAO-A and MAO-B in vitro. In this case, the inhibitory activity against MAO-A and MAO-B of methanol extract was 49.8 and 141.8% at the mg / ml concentration, respectively. In particular, the inhibitory activity of MAO-B was remarkable.

Experimental Example 7. Statistical Processing

The experimental results were SAS statistical program, and was determined to be a significant difference when the p is less than 0.05 through the Student's t-test.

One example of the formulation of the pharmaceutical composition comprising the extract of the present invention, but the present invention is not intended to limit it, but is intended to explain in detail.

Formulation Example 1 Preparation of Powder

Gardenia Extract Powder 20mg

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation Example 2 Preparation of Tablet

Gardenia Extract Powder 10mg

100 mg corn starch

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation Example 3 Preparation of Capsule

Gardenia Extract Powder 10mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 2mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation Example 4 Preparation of Injection

Gardenia Extract Powder 10mg

Mannitol 180 mg

Sterile distilled water for injection 2794 mg

_{Na 2 HPO 4 · 12H 2 O} 26 ㎎

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation Example 5 Preparation of Liquid

Gardenia Extract Powder 10mg

10 g of isomerized sugar

5 g of mannitol

Purified water

According to the conventional method of preparing a liquid solution, each component is added and dissolved in purified water, lemon flavor is added to the appropriate amount, the above components are mixed, and then purified water is added to adjust the total amount to 100 ml, and then sterilized by filling in a brown bottle. To prepare.

Formulation Example 6 Preparation of Healthy Drink

Gardenia Extract Powder 10mg

15 g of vitamin C

100 g of vitamin E (powder)

Iron lactate 19.75 g

3.5 g of zinc oxide

Nicotinamide 3.5 g

0.2 g of vitamin A

0.25 g of vitamin B1

0.3 g of vitamin B2

Water

After mixing the above components in accordance with a conventional method for preparing a healthy beverage, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated and stored in the present invention It is used to prepare a healthy beverage composition according to.

Although the composition ratio is a composition suitable for a preferred beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

As described above, the gardenia extract and the non-polar solvent soluble extract of the present invention exhibit an antidepressant effect to alleviate depression by inhibiting the activity of MAO, so that the pharmaceutical composition for the prevention and treatment of depression disease without side effects using natural products Or as a dietary supplement.

Claims (4)

A pharmaceutical composition for the prevention and treatment of depressive diseases containing gardenia extract as an active ingredient. The method of claim 1, The gardenia extract is a pharmaceutical composition which is an extract available in water, C ₁ to C ₄ lower alcohol or a mixed solvent thereof. A health functional food comprising gardenia extract and food acceptable food additives exhibiting an effect of preventing and improving depression. The method of claim 3, Health functional foods that are healthy drinks.

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