Composition for preventing or treating benign prostatic hyperplasia comprising rangooncreeper fruit extract

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating benign prostatic hyperplasia, comprising a quisqualis indica extract as an active ingredient. According to the present invention, by exhibiting effects of reducing prostate weight, reducing DHT, which is a prostate hyperplasia inducing factor, and reducing prostate epithelial cell hyperplasia, the Rangoon creeper fruit extract of the present invention can be advantageously used for treating and preventing prostate hyperplasia.

Description

[0001] This application is a divisional application of a patent application with application number 201680029207.9, application date May 3, 2016, and invention name “Composition containing Quisqualis extract for preventing or treating prostate hyperplasia”. Technical Field

[0002] The present invention relates to a pharmaceutical composition for preventing or treating prostate hyperplasia, comprising a quisqualis juncea extract as an active ingredient. Background Art

[0003] Benign prostatic hyperplasia (BPH) is a male disease with a sharp increase in the incidence rate among Korean men over 50 years old, and in recent years, the number of patients with BPH in Korea has increased sharply with a growth rate of more than 20% per year. In terms of the disease, the cause is the excessive growth of smooth muscle cells and epithelial cells in the transitional zone of the prostate, and various urinary disorders caused by bladder obstruction occur. One mechanism of known prostatic hyperplasia is related to testosterone and dihydrotestosterone (DHT), which are male hormones.

[0004] Meanwhile, in the drugs for treating prostatic hyperplasia, 5-α reductase inhibitors show anti-androgenic activity by selectively inhibiting the production of dihydrotestosterone and not affecting testosterone with androgenic activity, and reduce the enlarged prostate, without the side effects that occur in anticancer hormone drugs, so it is recognized as a drug for safe and etiological treatment of urinary system disorders. Therefore, currently, as drugs for treating prostatic hyperplasia, compounds such as finasteride (Proxcar, Merck) are commercially available and used to inhibit the production of dihydrotestosterone in tissues by inhibiting the activity of 5-α reductase (U.S. Patent Publication No. 4,377,584, U.S. Patent Publication No. 4,760,071, Korean Patent Publication No. 2004-0016559).

[0005] Quisqualis is native to India and grows in southern China and tropical regions. Legend has it that a man named Guo Shijun in a certain place in China cured many children's diseases with this medicine alone, so later medical practitioners named it Quisqualis. Quisqualis has mild properties, sweet taste, and contains quisqualic acid, trigonelline, pyridine and fatty oil as active ingredients. It is used to expel roundworms, and the percentage is about 70%. In addition, it is also used to expel pinworms, but its effect is lower than that of expelling roundworms, and although its effect is weak, it also plays a stomachic role. This medicine is less toxic, does not cause any harm to the body, and because of its sweet taste, it is considered to be good for children to eat (Encyclopedia of Korean Ethnic Culture).

[0006] However, the therapeutic effect of Quisqualis juncea extract on prostatic hyperplasia has not been mentioned or disclosed in any literature reported so far.

[0007] In the process of the inventor's continuous research and development of natural drug substances with the effect of inhibiting prostatic hyperplasia, it was found that the extract of Quisqualis juncea has a good effect in improving prostatic hyperplasia, and the present invention was completed. The fact discovered by the inventor is unprecedented in the reports related to the therapeutic effect of prostatic hyperplasia so far. Summary of the invention

[0008] Technical issues

[0009] Therefore, the present invention aims to provide a pharmaceutical composition for preventing or treating prostate hyperplasia comprising a Quisqualis juncea extract, which as a natural medicine has the effects of reducing prostate weight, DHT and epithelial hyperplasia in prostate hyperplasia.

[0010] Another object of the present invention is to provide a composition comprising the above extract.

[0011] Technical Solution

[0012] According to one aspect of the present invention, the present invention provides a pharmaceutical composition for preventing or treating prostatic hyperplasia, comprising a Quisqualis juncea extract as an active ingredient.

[0013] In the present invention, the Quisqualis cretacea extract includes all extracts prepared from the whole plant or a part of the plant by conventional plant extraction methods known in the art. Preferably, the Quisqualis cretacea extract is a crude extract, an extract soluble in a polar solvent, or an extract soluble in a non-polar solvent.

[0014] After grinding the Quisqualis chinensis material of the present invention, an extraction method such as hot water extraction, cold extraction, reflux extraction or ultrasonic extraction can be used, preferably hot water extraction, and extraction is carried out using a polar solvent at 20 to 120° C., preferably at 30 to 80° C., for about 1 to about 72 hours, preferably 2 to 12 hours, and then reduced pressure filtration and concentration are carried out to obtain the Quisqualis chinensis extract of the present invention, wherein the polar solvent is selected from water, ethanol, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably water or a mixed solvent of water and ethanol and more preferably water or a mixed solvent of 1 to 30% (volume / volume) water and ethanol, and the volume of the polar solvent is equivalent to about 1 to 100 times, preferably about 2 to 20 times the weight of the sample.

[0015] In a preferred embodiment of the present invention, it was found that the Quisqualis juncea extract has the effect of reducing prostate weight, DHT as a factor causing prostate hyperplasia, and prostate epithelial hyperplasia, and is therefore effective in treating and preventing prostate hyperplasia.

[0016] Therefore, the present invention provides a pharmaceutical composition for preventing or treating prostatic hyperplasia comprising a Quisqualis juncea extract as an active ingredient.

[0017] Furthermore, since the Quisqualis Creeper extract is a drug that has been consumed or used as a herbal medicine for a long time, the extract of the present invention extracted therefrom also has no problems of toxicity and side effects.

[0018] The pharmaceutical composition for preventing or treating prostate hyperplasia comprising the extract of the present invention may contain the extract in an amount of 0.1 to 50% by weight based on the total weight of the composition.

[0019] The pharmaceutical composition comprising the extract of the present invention may further comprise appropriate carriers, excipients and diluents commonly used in preparing pharmaceutical compositions.

[0020] The pharmaceutical dosage form of the extract of the present invention may also be used in the form of its pharmaceutically acceptable salt, and may be used alone or in combination with other pharmaceutically active compounds, and may be used as a suitable mixture.

[0021] The pharmaceutical composition comprising extract according to the present invention can be formulated into oral dosage form, external preparation, suppository and sterilized injection to use respectively by conventional method, and oral dosage form is for example powder, granule, tablet, capsule, suspension, emulsion, syrup and aerosol etc.The carrier, excipient and diluent that can be included in the composition comprising extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talcum, magnesium stearate and mineral oil.When preparing, use conventional diluent or excipient, for example filler, extender, adhesive, wetting agent, disintegrant and surfactant, prepare pharmaceutical composition. Solid preparations for oral administration include tablets, pills, powders, granules and capsules, and such solid preparations are prepared by mixing the extract with at least one excipient (e.g. starch, calcium carbonate, sucrose or lactose). In addition, in addition to excipients, lubricants such as magnesium stearate and talc can also be used. Liquid preparations for oral administration can include suspensions, solutions, emulsions and syrups, and can include commonly used single diluents such as water, liquid paraffin and various excipients such as wetting agents, sweeteners, flavorings and preservatives. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations and suppositories. For non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils (e.g. olive oil) and injectable esters (e.g. glycolate) can be used. For suppository bases, Witepsol, Macrogol, Tween 61, cocoa butter, laurin fat and glycerin gelatin can be used.

[0022] The preferred dosage of the extract of the present invention varies according to the patient's condition and body weight, the extent of the disease, the type of drug, and the route and period of administration, but can be appropriately selected by those skilled in the art. However, for the preferred effect, the extract of the present invention is preferably administered at a dosage of 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. It can be administered once a day or in multiple doses. The dosage does not limit the scope of the present invention in any aspect.

[0023] The extract of the present invention can be administered by various routes. All predictable methods of administration can be used, and the extract can be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, epidural or intracerebroventricular injection routes.

[0024] According to another embodiment of the present invention, the present invention provides a product for preventing or improving prostate hyperplasia comprising Quisqualis juncea extract as an active ingredient.

[0025] In the present invention, the product is not limited to a specific type of product, and can be a health function product in terms of its function. "Health function product" refers to a product prepared or processed using raw materials or ingredients that have good functions for the human body, and "function" refers to obtaining good effects in terms of health use, such as nutritional control or physiological effects in terms of human body structure and function.

[0026] The product for preventing prostate hyperplasia according to the present invention comprises the extract in an amount of 0.01 to 95 wt%, preferably 1 to 80 wt%, based on the total weight of the composition.

[0027] In addition, in order to prevent prostate hyperplasia, health care functional products in the form of tablets, capsules, powders, granules, liquids and pills can be prepared and processed.

[0028] In addition to containing the extract of the specified amount as an essential component, the product of the present invention can also include other ingredients, without any particular limitation, and can contain many flavoring agents or natural carbohydrates as additional ingredients. The example of natural carbohydrates includes common sugar and sugar alcohol, common sugar is for example monosaccharide, such as glucose and fructose; disaccharide, such as maltose and sucrose; and polysaccharide, such as dextrin and cyclodextrin, and sugar alcohol is for example xylitol, sorbitol, erythritol, etc. For the flavoring agent different from the above, natural flavoring agent (thaumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agent (saccharin, aspartame, etc.) can be advantageously used. Based on 100ml of the composition of the present invention, the amount of natural carbohydrate is generally about 1 to 20g, and preferably about 5 to 12g.

[0029] In addition to the above, the extract of the present invention may contain various nutritional supplements, vitamins, minerals (electrolytes), flavoring agents (such as synthetic flavoring agents and natural flavoring agents), coloring agents and macroporous agents (cheese, chocolate, etc.), pectin acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, and carbonating agents used in carbonated beverages, etc.

[0030] Beneficial Effects

[0031] As described above, the Quisqualis juncea extract of the present invention can be effectively used for treating and preventing prostate hyperplasia by virtue of the effects of reducing prostate weight, DHT as a factor causing prostate hyperplasia, and prostate epithelial hyperplasia. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 Shown are changes in prostate weight in an animal model of prostate hyperplasia treated with Quisqualis cretacea extract.

[0034] Figure 2 Shown are changes in prostate DHT in an animal model of prostate hyperplasia treated with Quisqualis cretacea extract.

[0035] Figure 3 Shown are serum testosterone levels in an animal model of prostatic hyperplasia treated with Quisqualis cretacea extract.

[0036] Figure 4 Shown are histopathological changes of the prostate in an animal model of prostatic hyperplasia treated with Quisqualis juncea extract.

[0037] Figure 5 The results of toxicity evaluation in an animal model of prostatic hyperplasia treated with Quisqualis juncea extract are shown. DETAILED DESCRIPTION

[0038] Hereinafter, embodiments of the present invention will be described in detail. However, these embodiments are provided to describe the present invention in more detail, and the scope of the present invention is not limited thereto.

[0039] Example 1. Preparation of Quisqualis chinensis extract

[0040] Commercially available quince cretae chinensis was purchased and ground, and then 300 g was placed in 3 L of 70% ethanol, and ultrasonic extraction was performed 3 times within one hour using an ultrasonic extractor. The extracted solution was filtered with Whatman No. 2 (150 mm Φ) filter paper to remove insoluble materials, and concentrated under reduced pressure at 40° C. using a concentrator equipped with a condenser. In order to completely remove the solvent, 500 mL of purified water was added, and the extract concentrated under reduced pressure was suspended, and 80.51 g of extract (yield: 26.84%) was obtained using a freeze dryer.

[0041] Example 2. Animal Model

[0042] After 10-week-old male Wister rats (Central Lab. Animal Inc.) were acclimatized for one week, testosterone propionate (TP) was subcutaneously injected into the prostate hyperplasia induction group at 3 mg / kg for 4 weeks to establish a model. The Quisqualis Creeper extract prepared in Example 1 was orally administered at 150 mg / kg for 4 weeks 1 hour before TP injection, and finasteride (10 mg / kg), a 5α-reductase inhibitor for the treatment of prostate hyperplasia, was administered to the positive control group in the same manner.

[0043] Statistical analysis

[0044] Statistical analysis was performed using ANOVA (analysis of variance), ##P < 0.01 and #P < 0.05 indicated significant differences compared with the normal control group (NC), and **P < 0.01 and *P < 0.05 indicated significant differences compared with the prostate hyperplasia-induced group (BPH).

[0045] Example 3. Prostate weight measurement

[0046] After the animals were sacrificed, the prostate was taken from each group (normal control group: NC, prostate hyperplasia induced group: BPH, prostate hyperplasia induced group + Quisqualis cretacea extract administration group: BPH+Quisqualis cretacea, prostate hyperplasia induced group + finasteride administration group: BPH+finasteride) and its weight was measured.

[0047] Figure 1 The figure shows the changes in prostate weight in an animal model of prostate hyperplasia treated with Quisqualis serrata extract. Figure 1 As can be seen in the results, the prostate weight in the Quisqualis Creeper extract administration group (BPH+Quisqualis Creeper) was significantly reduced compared to the prostate hyperplasia induced group (BPH) using TP. This shows an effect similar to that of finasteride currently used to treat prostate hyperplasia.

[0048] Example 4. Changes in prostate DHT

[0049] In order to measure the changes of dihydrotestosterone (DHT), which is essential for the production, growth and maintenance of the prostate, proteins were isolated from prostate tissue isolated at the time of sacrifice after 4 weeks of drug administration. The prostate was placed in RIPA buffer (20mM Tris-HCl, 150mM NaCl, 1mM Na2EDTA, 1mM EGTA, 1% NP-40, 1% sodium deoxycholate, 2.5mM sodium pyrophosphate, 1mM β-glycerophosphate, 1mM Na3VO4, 1μg / ml leupeptin; Cell-Signaling, USA) for protein extraction, and then homogenized, and the homogenate was centrifuged at 1400rpm for 15 minutes to collect the supernatant. After the concentration of the separated protein was determined using the Bio-Rad protein assay kit (Bio-Rad, USA), in order to measure the DHT content in the supernatant, the amount of DHT in the prostate was measured using an ELISA kit (Cayman, USA) that specifically responds to DHT according to the manufacturer's method. According to the quantified protein values, the measured values ​​were converted and the differences were compared by performing statistical analysis.

[0050] Figure 2 The changes of prostate DHT in an animal model of prostate hyperplasia treated with Quisqualis serrata extract are shown. Figure 2As can be seen from the results, it was found that the concentration of DHT causing prostate hyperplasia was significantly decreased in the group administered with the Quisqualis cretacea extract.

[0051] Example 5. Serum testosterone measurement

[0052] To determine the testosterone level in animals with prostatic hyperplasia, the blood separated at the end of the experiment was centrifuged at 12,000 rpm for 20 minutes, and the supernatant was collected and the serum testosterone level was measured using an ELISA kit (Cayman, USA).

[0053] Figure 3 Serum testosterone levels in an animal model of prostatic hyperplasia treated with Quisqualis serrata extract are shown. Figure 3 It can be seen that the testosterone level was significantly decreased in the group administered with the Quisqualis cretacea extract.

[0054] Example 6. Histopathological changes of the prostate

[0055] The prostate gland dissected after the experiment was fixed with 10% neutral buffered formalin for 24 hours and then embedded in paraffin. The embedded tissue was cut into 4 μm thick sections, stained with hematoxylin (Sigma-Aldrich, USA) and eosin Y (Sigma-Aldrich), mounted in mounting medium, and examined using an optical microscope.

[0056] Figure 4 The histopathological changes of the prostate in an animal model of prostatic hyperplasia treated with Quisqualis serrata extract are shown. Figure 4 It can be seen that in the prostate hyperplasia induced group, the height and number of epithelial cells were greatly increased, while a decrease in epithelial hyperplasia was observed in the group administered with the Quisqualis crenata extract.

[0057] Example 7. Serum ALT and AST Measurement

[0058] In order to evaluate the toxicity of Quisqualis juncea extract in an animal model of prostatic hyperplasia, the blood separated at the end of the experiment was centrifuged at 12000 rpm for 20 minutes, the supernatant was collected and the general hepatotoxicity indices, ALT (alanine aminotransferase) and AST (aspartate aminotransferase) levels in the serum were measured.

[0059] Figure 5 The results of the evaluation of toxicity in an animal model of prostatic hyperplasia treated with Quisqualis serrata extract are shown. Figure 5 It can be seen that no significant changes in ALT and AST were observed in both the prostate hyperplasia induced group and the Quisqualis cretacea extract administration group compared with the normal control group.

[0060] Interpretation of results

[0061] According to the example, testosterone propionate (TP) was subcutaneously injected into white rats for 4 weeks to induce prostate hyperplasia, and Quisqualis brevis extract and finasteride for treating prostate hyperplasia were orally administered for 4 weeks. After the end of drug administration, the following changes were measured.

[0062] (1) By comparing the weights of the prostates obtained from the sacrificed rats, it was confirmed that a decrease in the prostate weight was found in the group administered with the Quisqualis cretacea extract compared with the group induced with prostate hyperplasia using TP, and this showed an effect similar to that of the group administered with finasteride for the treatment of prostate hyperplasia.

[0063] (2) Furthermore, by comparing the changes in dihydrotestosterone (DHT) that causes prostate hyperplasia after drug administration, it was confirmed that the DHT level was significantly reduced in the group administered with Quisqualis cretica extract, and that the effect was similar to that of finasteride.

[0064] (3) According to the results of histopathological analysis of the prostate, epithelial hyperplasia was reduced in the prostate hyperplasia induced group after administration of the Quisqualis juncea extract.

[0065] Therefore, the Quisqualis juncea extract of the present invention has the effect of reducing prostate weight, DHT as a factor causing prostate hyperplasia, and prostate epithelial hyperplasia, and thus can be used as a drug effective in treating prostate hyperplasia.

[0066] Preparation Example

[0067] The following provides preparation examples of the compositions of the present disclosure.

[0068] Preparation Example 1. Preparation of pharmaceutical preparations

[0069] 1-1. Preparation of powder

[0070] 2g of the extract of Example 1 of the present invention

[0071] 1g lactose

[0072] The ingredients are mixed and packed in a sealed package to prepare a powder.

[0073] 1-2. Preparation of tablets

[0074] 100 mg of the extract of Example 1 of the present invention

[0075] 100mg corn starch

[0076] 100mg lactose

[0077] 2mg magnesium stearate

[0078] After the ingredients are mixed, tablets are prepared according to a common tablet preparation method to form tablets.

[0079] 1-3. Preparation of capsules

[0080] 100 mg of the extract of Example 1 of the present invention

[0081] 100 mg corn starch

[0082] 100 mg lactose

[0083] 2mg magnesium stearate

[0084] After mixing the ingredients, gelatin capsules are filled according to a conventional capsule preparation method to prepare capsules.

[0085] The present invention has been described above with respect to preferred embodiments. It will be appreciated by those skilled in the art of the present disclosure that the present invention may be implemented in a modified form without departing from the essential features of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative rather than a restrictive perspective. The scope of the present invention is embodied in the appended claims rather than in the foregoing description, and should be interpreted as: all differences within their equivalent range are included in the present disclosure.

Claims

1. Use of a pharmaceutical composition in the preparation of an oral drug for preventing or treating prostatic hyperplasia, the pharmaceutical composition comprising a Quisqualis juncea extract as an active ingredient, in, The Quisqualis Cremaster extract is obtained by subjecting ground Quisqualis Cremaster to ultrasonic extraction followed by filtration and reduced pressure concentration.

2. The use according to claim 1, wherein the Quisqualis Creeper extract is extracted with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.

3. The use according to claim 1, wherein the Quisqualis Creeper extract has the effect of reducing prostate weight, dihydrotestosterone (DHT) as a factor causing prostate hyperplasia, and prostate epithelial hyperplasia.

4. Use of Quisqualis chinensis extract in the preparation of an oral administration product for preventing or improving prostatic hyperplasia, in, The Quisqualis Cremaster extract is obtained by subjecting ground Quisqualis Cremaster to ultrasonic extraction followed by filtration and reduced pressure concentration.

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