KR20210132974A - Composition for Prophylaxis or Treatment of Prostatic Diseases or Hair Loss Comprising Scaphechinus mirabilis - Google Patents

Abstract

The present invention relates to a composition for preventing or treating/alleviating symptoms of prostatic disease or hair loss, which can be administered for a long period of time without concerns about side effects or drug resistance of conventional treatments as a component derived from a natural product. More particularly, the present invention relates to a composition for preventing or treating/alleviating symptoms of prostatic disease or hair loss containing a Clypeaster japonicas extract as an active component.

Description

Composition for preventing or treating prostate disease or hair loss containing lotus leaf sea urchin extract {Composition for Prophylaxis or Treatment of Prostatic Diseases or Hair Loss Comprising Scaphechinus mirabilis}

The present invention relates to a composition for preventing or treating/improving symptoms of prostate disease or hair loss, which is a component derived from a natural product and can be administered for a long time without concerns about side effects or drug resistance of conventional therapeutic agents.

The prostate is an accessory gonad composed of glandular tissue and fibromuscular tissue that produces and secretes semen. Prostate fluid produced in the prostate is made in the testis and supplies nutrients to the moved sperm, and it helps the sperm to move actively by maintaining the liquid state so that the ejaculated semen does not harden. Representative prostate-related diseases include benign prostatic hyperplasia, prostate cancer, and prostatitis.

Benign prostatic hyperplasia (BPH) is one of the most common diseases in adult men. do. The number of BPH patients in Korea increased from about 970,000 in 2013 to 1.13 million in 2016, and is expected to reach 1.46 million by 2020. BPH, which was considered a geriatric disease, has recently been increasing among young people as well. did.

In general, the size of the prostate in adults is about 20 g. However, when the prostate enlarges to an abnormal size and grows to an abnormal size of 40 to 400 g, it compresses the nearby urinary tract and urinates more than 8 times a day, nocturia, strong and sudden urination. Bladder storage symptoms such as unbearable urgency when urinating while feeling urgency, delayed urine output only when moxibustion is required to urinate, interrupted urine flow in which the flow of urine is interrupted, and a phenomenon that requires force during urination symptoms will appear. Patients with benign prostatic hyperplasia do not need surgical treatment unless there is urinary tract obstruction or other complications, but about 50% of patients need treatment by the age of 80. In addition, some of the patients with benign prostatic hyperplasia are related to prostate cancer, and although it is not a fatal disease in itself, it is emerging as an important medical problem in the current society that is entering a super-aging society in that it lowers the quality of life.

The treatment method for benign prostatic hyperplasia was mostly surgery in the early days, but from the late 80s, it has been rapidly changed to drug administration. However, conventional drugs used for the treatment of benign prostatic hyperplasia exhibit many side effects and have limitations in their efficacy, so it is necessary to develop a new therapeutic agent that does not induce side effects or drug resistance and has excellent therapeutic effects.

Prostate cancer is the most common cancer among male cancers in the West and shows a high incidence, and the frequency is also rapidly increasing in Korea. The treatment of prostate cancer differs depending on the stage of the disease. In the case of local cancer, treatment is aimed at the fundamental treatment, but in the case of metastatic cancer, systemic treatment is performed. For the treatment of focal prostate cancer, standby therapy, radical prostatectomy, and radiation therapy can be selected in consideration of the patient's age, health, sexual function, tumor stage and differentiation, and patient preference. Metastatic prostate cancer can be treated with hormone therapy or chemotherapy.

Prostatitis is a disease in which the prostate is inflamed, and it is so common that about 50% of adult men experience symptoms at least once in their lifetime. In the case of urinary tract infection, bacteria are most often transmitted directly through the urethra, and in addition, it can also be caused by disorders of the excretion of prostatic fluid, urinary reflux into the prostate, and transmission of inflammation such as hemorrhoids or colitis.

Since prostate diseases such as prostate cancer, prostatic hyperplasia, and prostatitis are related to androgens, which are male hormones, treatment and prevention effects or alleviation of symptoms can be obtained by anti-androgen drugs that inhibit the expression of androgen receptors. . Anti-androgen drugs are drugs for symptom improvement rather than therapeutic drugs, and most of them recur when the drug is stopped. . Prostate-specific antigen inhibitors that suppress the expression of prostate-specific antigens and 5-alpha reductase inhibitors that inhibit the synthesis of the male hormone dihydrotestosterone are also effective in preventing, treating, and improving symptoms of the prostate disease. have. However, these drugs must be taken for at least 6 months to know whether they respond or not, and 5-alpha reductase inhibitors are known to increase the risk, especially when administered to high-grade prostate cancer patients. Accordingly, there is a demand for the development of a safer composition for preventing and treating/improving symptoms of prostate disease that can replace these drugs. For this purpose, the present inventors have studied a composition for preventing and treating/improving symptoms of prostate disease derived from natural products, and have been patented as Nos. 10-1652073, 10-1662514, 10-1688018, and 10-1733477. .

Testosterone also affects hair loss. Testosterone is converted to dihydrotestosterone (DHT) by the steroid 5-alpha reductase. DHT excessively secreted after puberty acts as the main cause of excessive sebum production in sebum cells, causing hair loss. That is, it is known that DHT binds to the androgen receptor of the hair follicle and delays protein synthesis, thereby shortening the growth period of the hair follicle and causing hair loss. Accordingly, Patent Registration No. 10-0882780 and Patent Registration No. 10-1485164, etc. apply the properties of anti-androgen drugs or 5-alpha reductase inhibitors to the prevention and treatment of hair loss along with prostate disease.

On the other hand, the lotus leaf sea urchin ( Scaphechinus mirabilis ) is a marine invertebrate belonging to the genus lotus leaf sea urchin in the phylum Lotus leaf sea urchin. The body is tray-shaped and has a flower pattern like a lotus leaf, and it is distributed in Jumunjin, Samcheok, Yeongil Bay, Busan, Namhae, Japan and northern China in Korea. Although the lotus leaf sea urchin is an animal of the sea urchin family, it is not used for food because the testes or ovaries, which are edible parts, are not greatly developed. However, few studies have been conducted on the physiological activity of lotus leaf sea urchin.

Registered Patent No. 10-1652073 Registered Patent No. 10-1662514 Registered Patent No. 10-1688018 Registered Patent No. 10-1733477 Registered Patent No. 10-0882780 Registered Patent No. 10-1485164

An object of the present invention is to provide a novel composition derived from a natural product effective for preventing and treating/improving symptoms of prostate disease or hair loss in order to solve the problems of the prior art as described above.

Another object of the present invention is to reveal the efficacy of domestic natural resources and to provide new uses thereof.

The present invention for achieving the above object relates to a pharmaceutical composition for preventing or treating prostate disease or hair loss containing a lotus leaf sea urchin extract as an active ingredient.

In the present invention, prostate disease and hair loss are diseases related to male hormone, and by inhibiting the expression of androgen receptor (AR), prostate specific antigen (PSA) and / or 5-alpha reductase, the effect of preventing or treating / improving symptoms disease that may be present. Specific examples of the prostate disease include, but are not limited to, prostate cancer, benign prostatic hyperplasia, and prostatitis. The lotus leaf sea urchin extract effectively inhibits the expression of androgen receptor, prostate-specific antigen and 5-alpha reductase in a concentration-dependent manner in the expression measurement of androgen receptor, prostate-specific antigen and 5-alpha reductase in vitro using LNCap cells, thereby preventing prostate disease and It has been shown to be effective in preventing or treating hair loss.

The lotus leaf sea urchin extract can be prepared using any one of the methods used for natural product extraction in the art by using the lotus leaf sea urchin as it is, dried, frozen, or cooked through pre-heat treatment. For example, the lotus leaf sea urchin extract can be prepared by extracting at 10 to 100° C. using one or a mixture of two or more of C1 to C4 lower alcohol and water. When the extraction temperature is too low, the extraction efficiency is lowered, and when the temperature of the extraction process is too high, the activity of the active material may be reduced, so it was more preferable to extract at a temperature of 30 to 80°C. Extraction may be accomplished by simply immersing in a solvent, but it may be extracted by using ultrasonic waves or heating and stirring as in the following examples to increase extraction efficiency within a short time. In addition, the lotus leaf sea urchin sample may be extracted by pulverizing or grinding it into small pieces so that the extraction can be more efficient. The amount of the solvent in the extraction may be used in a volume ratio of 2 to 50 times that of the lotus leaf sea urchin sample. Since the extraction efficiency increases as the amount of the solvent increases, it is not a problem to use more than 50 times the solvent, but it is preferable that the amount of the solvent is 50 times or less in consideration of the efficiency or economic feasibility of the process. In addition, in order to increase extraction efficiency while using the same amount of solvent, it is more preferable to increase the number of extractions.

In order to use the composition of the present invention as a prophylactic or therapeutic agent, tablets, capsules, tablets, capsules, by itself or by mixing with a pharmaceutically acceptable carrier, excipient, diluent, etc. by a method known in the pharmaceutical field; It can be formulated as a preparation for oral administration such as troches, solutions, suspensions, ointments, etc., or preparations for parenteral administration, such as injections, drops, and external preparations, and can be used as a treatment and prevention agent for prostate disease or hair loss. The dosage of the active ingredient according to the present invention depends on the absorption of the active ingredient in the body, the form of the preparation, the route of administration, the age and weight of the subject to be treated, the type of specific disease or pathological condition to be treated, and the severity of the disease or pathology, etc. It may be appropriately selected according to the judgment of the prescriber, and the administration may be administered once a day or divided into several administrations. A typical dosage is 0.001 mg/kg·day to 10 g/kg·day.

In addition, the present invention provides a health functional food composition for preventing or improving symptoms of prostate disease or hair loss comprising a lotus leaf sea urchin extract as an active ingredient. The lotus leaf sea urchin extract may be added to the health functional food of the present invention in an amount of preferably 0.01 to 100% by weight. The health functional food of the present invention includes the form of tablets, capsules, pills or liquids, and the like, and the food to which the composition of the present invention can be added includes, for example, various foods, beverages, gum, tea, and vitamin complexes. , health functional foods, etc.

In addition, the present invention provides a cosmetic composition for preventing or improving symptoms of hair loss comprising a lotus leaf sea urchin extract as an active ingredient. The cosmetic composition of the present invention may include conventional adjuvants and/or carriers such as stabilizers, solubilizers, pigments, and fragrances. The cosmetic composition may be prepared in any formulation conventionally prepared in the art, for example, may be formulated as a solution, suspension, paste, gel, oil, essence, spray, etc., but is not limited thereto. Specific examples of cosmetics to which the composition of the present invention can be added include shampoo, conditioner, treatment, colorant, hair cream, and hair pack.

As described above, the composition of the present invention is effective in preventing or treating/improving symptoms of prostate disease or hair loss due to its excellent inhibitory effect on the expression of androgen receptor, prostate-specific antigen, and 5-alpha reductase. Therefore, pharmaceutical compositions, health functional food compositions and cosmetics It can be usefully used as a composition.

In addition, the present invention can suggest a new utilization method by providing a useful use of domestic natural resources.

1 is a western blot image showing that the lotus leaf sea urchin extract exhibits AR, PSA and 5-alpha reductase expression inhibitory effects.
Figure 2 is a graph showing that the lotus leaf sea urchin extract exhibits an AR expression inhibitory effect.
3 is a graph showing that the lotus leaf sea urchin extract exhibits an inhibitory effect on PSA expression.
4 is a graph showing that the lotus leaf sea urchin extract exhibits an inhibitory effect on 5-alpha reductase expression.

Hereinafter, the present invention will be described in more detail with reference to the accompanying examples. However, these embodiments are merely examples for easily explaining the content and scope of the technical idea of the present invention, and thereby the technical scope of the present invention is not limited or changed. It will be natural for those skilled in the art that various modifications and changes can be made within the scope of the technical spirit of the present invention based on these examples.

[Example]

Example 1: Preparation of lotus leaf sea urchin extract

The lotus leaf sea urchin extract was purchased from the Marine Life Resources Bank (NP20160003) and used. The preparation method of the extract is briefly as follows; The collected lotus leaf sea urchin samples were washed with water and freeze-dried, and then the samples were pulverized. 1 L of 70% EtOH was added to 100 g of the pulverized sample, followed by ultrasonic extraction for 7 hours. The extract was filtered with a filter paper to remove insoluble matter, and then the solvent was removed using a rotary vacuum concentrator. The extract from which the solvent was removed was dissolved in distilled water and then freeze-dried to obtain 4.32 g of the extract.

Example 2: Efficacy evaluation of lotus leaf sea urchin extract in LNCaP cells

The effect of the lotus leaf sea urchin extract prepared in Example 1 on the expression of prostate-specific antigen, androgen receptor and 5-alpha reductase was confirmed by the following experiment.

LNCaP cells (ATCC, USA), a male hormone-dependent human prostate cancer cell line commonly used as an experimental model for prostate disease, were plated in a 6-well plate at ^{a concentration of 5 × 10 5} cells/well and cultured at 37°C for 15 hours. . The cultured cells were treated with the lotus leaf sea urchin extract at a concentration of 10, 50, or 100 μg/ml together with 1 μM of Testosterone, and then cultured for an additional 72 hours and then harvested. As a positive control (BPH), the lotus leaf sea urchin extract was not treated and only 1 μM of Testosterone was treated, and as a control (Finasteride), 10 μM of Finasteride, a treatment for benign prostatic hyperplasia, was treated together with 1 μM of Testosterone instead of the lotus leaf sea urchin extract. The untreated group was used as a negative control group.

The cells harvested after culture were treated with RIPA buffer (50 mM Tris-HCl, pH 8.0, with 150 mM sodium chloride, 1% NP-40, 0.5% sodium deoxycholate, and 0.1% sodium dodecyl sulfate, with a protease inhibitor cocktail). and centrifuged at a speed of 12,000 rpm for 20 minutes to separate proteins. The isolated protein was quantified by BCA (Bicinchoninic acid) method.

10 μg of the quantified protein was treated on SDS-PEGE gel, electrophoresed, and then the protein was transferred to the PVDF membrane. After that, the PVDF membrane was reacted with 5% skim milk for about 1 hour to remove non-specific binding proteins on the surface, and primary antibodies AR and PSA, 5α-reductase and β-actin were each 1:1000, 1:1000, 1:1000, 1:5000 diluted and reacted for one day at 4 ℃. After that, the secondary antibody (Anti-goat; 1: 5000, Santacruz, CA, USA , Anti-Rabbit, 1:5000, Abfrontier, Seoul, Korea) was treated at room temperature for 1 hour, and the ECL kit (Amersham, UK) was Protein expression of AR, PSA and 5α-reductase was confirmed using the

1 is an electrophoresis photograph showing the Western blotting results for AR, PSA and 5-alpha reductase proteins, and FIGS. 2 to 4 are AR, PSA and 5-alpha reductase protein expression in the control group and the experimental group, respectively. The degree is shown graphically. 1 to 4, it can be confirmed that the lotus leaf sea urchin extract effectively acts on the inhibition of the expression of AR, PSA and 5-alpha reductase proteins.

Claims (6)

A pharmaceutical composition for the prevention or treatment of prostate cancer, benign prostatic hyperplasia or prostatitis, comprising a lotus leaf sea urchin extract as an active ingredient.
The method of claim 1,
The lotus leaf sea urchin extract is a pharmaceutical composition for the prevention and treatment of prostate disease, characterized in that it is extracted using one or a mixture of two or more selected from the group consisting of water and C1-C4 lower alcohols as a solvent.
A food composition for preventing or improving symptoms of prostate cancer, prostatic hyperplasia or prostatitis, characterized in that it contains a lotus leaf sea urchin extract as an active ingredient.
A pharmaceutical composition for preventing or treating hair loss containing lotus leaf sea urchin extract as an active ingredient.
A food composition for preventing or improving symptoms of hair loss containing lotus leaf sea urchin extract as an active ingredient.
A cosmetic composition for preventing or improving symptoms of hair loss containing lotus leaf sea urchin extract as an active ingredient.

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