KR102507928B1 - Composition for preventing or treating nasal polyp comprising extract of sargassum horneri - Google Patents

Abstract

The present invention provides a composition for preventing or treating nasal polyps disease, a composition for preventing the recurrence of nasal polyposis, and a composition for preventing or treating sinusitis disease containing an extract of Sargassum horneri as an active ingredient.
The oleaginous capricorn extract has excellent anti-inflammatory activity and anti-fibrotic activity, and thus can effectively prevent, improve, or treat diseases such as nasal polyps or accompanying sinusitis, and is also helpful in preventing recurrence after nasal polyposis treatment.

Description

Composition for preventing or treating nasal polyposis disease containing an extract of thoracic capitis as an active ingredient

The present invention relates to a composition for the prevention or treatment of nasal polyposis disease, containing an extract of capitula thorax as an active ingredient.

Nasal polyp or nasal polyp is a protrusion of a structure that secretes mucus inside the nose, and is a benign edematous mucous membrane caused by the recurrence and gradual development of local edema of the nasal or sinus mucosa. It is known that the nasal polyposis mucosa is mostly composed of respiratory epithelium, and the submucosa shows severe edema, and a large number of inflammatory cells, especially eosinophils, infiltrate the fibrotic tissue.

Although the exact cause of nasal polyps is not known to date, it is a chronic inflammatory disease that often recurs despite various treatment methods. Nasal polyps form and grow by the interaction of inflammatory cells due to infection or non-infectious inflammation. The influx of eosinophils is promoted by various inflammatory mediators secreted from mast cells, and tissue damage occurs by various chemical mediators secreted from eosinophils, further worsening and progressing to edema.

Nasal polyps are known to be more common in people with asthma or rhinitis, where the mucous membranes around the nose and throat are inflamed. Symptoms of nasal polyps develop gradually over several months, and the severity of symptoms is determined by the number and size of polyps. If the size of the nasal polyp is small, there are no special symptoms, but as the size gradually increases, various symptoms may appear. The main symptoms of nasal polyps include continuous mucus secretion from the nose, nasal congestion due to polyps, and dulled sense of smell. Some complain of obstructive nasal sound, and in very severe cases, anatomical changes may occur and the bridge of the nose may widen.

The purpose of treatment of nasal polyps is to eliminate symptoms caused by nasal polyps, restore the function of the nasal cavity as a respiratory airway by removing nasal polyps, and induce drainage and ventilation of the sinuses. In addition, the goal of treatment is to restore the sense of smell and prevent the recurrence of nasal polyps. Treatment of nasal polyps can be broadly divided into drug therapy and surgical therapy. Currently, the use of steroids as pharmacotherapy is known to be effective in treating nasal polyps. In order to relieve runny nose and nasal congestion, there is a drug therapy to reduce the polyp by spraying a steroid into the nose or directly injecting a steroid into the polyp, and in the case of a large polyp, it is removed surgically, which is called polypectomy. Nasal polyps are often accompanied by chronic sinusitis rather than alone.

Sargassum horneri is a yellow-brown seaweed of the brown algae family Sargassum horneri, which is widely distributed on the coast of Korea, and has a length of about 3 to 5 m. The flat root is in the shape of a tray, and a cylindrical stem comes out from the center and branches out, and the middle and upper part of the stem are cylindrical and smooth, but there are thorns at the bottom and branches. The leaves are long elliptical or line-shaped, and the edge is split into pinnates. It grows on rocks at the upper part of the upper sublittoral belt and floats on the water at low tide. It is mainly used as feed or food, but the effect of oxen cap on nasal polyp disease has not been reported so far.

Republic of Korea Patent Registration No. 10-1026528 (2011.04.01. Notice)

An object of the present invention is to provide a composition for preventing or treating nasal polyps containing a natural product having excellent anti-inflammatory activity and anti-fibrotic activity.

In order to achieve the above object, the present invention provides a pharmaceutical composition or a health functional food composition for preventing or treating nasal polyp disease, containing an extract of Sargassum horneri as an active ingredient.

The present invention provides a pharmaceutical composition for preventing the recurrence of nasal polyps and a health functional food composition containing an extract of Sargassum horneri as an active ingredient.

In addition, the present invention provides a pharmaceutical composition and a health functional food composition for preventing or treating sinusitis disease containing an extract of Sargassum horneri as an active ingredient.

The Sargassum horneri extract according to the present invention has excellent anti-inflammatory activity and fibrosis induction inhibitory effect, and can be used as a pharmaceutical composition or health functional food composition for preventing or treating diseases such as nasal polyps or accompanying sinusitis. can

The pharmaceutical composition and health functional food composition according to the present invention have fewer side effects and are safe because they use natural products such as the above-mentioned oxen cap, can more effectively prevent or treat nasal polyps or sinusitis, and prevent recurrence after nasal polyposis treatment. also helps

1 is a graph showing the change in production of nitric oxide (NO) according to the treatment of the black thrips extract according to Experimental Example 2 of the present invention.
FIG. 2 is a graph showing changes in the production of prostaglandin E ₂ (PGE ₂ ) according to the treatment of an extract of the thoracic capsular capillaries according to Experimental Example 2 of the present invention.
Figure 3 is a graph confirming the cytotoxicity of the spp.
4 is a Western blot confirming changes in the expression of fibrosis-inducing factors according to the treatment of the thorax capricorn extract according to Experimental Example 3 of the present invention.
5 is a graph showing changes in the expression of α-smooth muscle actin (α-SMA) according to the treatment of the black capsular capricorn extract according to Experimental Example 3 of the present invention.
6 is a graph showing changes in the expression of Type 1 collagen according to the treatment of the black capsular capillaries extract according to Experimental Example 3 of the present invention.
7 is a graph showing changes in the expression of fibronectin according to the treatment of the thoracic capitis extract according to Experimental Example 3 of the present invention.

Hereinafter, the present invention will be described in detail.

The present inventors completed the present invention by confirming the anti-inflammatory activity and anti-fibrotic activity of the oleaginous capricorn extract prepared using an ethanol aqueous solution as an extraction solvent.

The present invention provides a pharmaceutical composition for preventing or treating nasal polyp disease, containing an extract of Sargassum horneri as an active ingredient.

In the present specification, " Sargassum horneri ", as described above, is a yellowish-brown seaweed belonging to the brown algae plant Sargassum horneri, which is widely distributed on the coast of Korea, and is used as feed or food.

As used herein, "extract" refers to a substance obtained by extracting a component of a natural substance regardless of the extraction method, extraction solvent, extracted component, or the form of the extract. It may include all materials that can be obtained by processing or processing by the method.

The extract may be extracted according to a method commonly used in the art, for example, hot water extraction, ultrasonic extraction, filtration, reflux extraction, etc., which are performed alone or in combination of two or more methods. It can be.

In the present invention, the oxen capsular extract may be obtained by extracting the roots, stems, leaves, outposts or mixtures thereof of the spp. , ethanol, propanol, butanol, or an aqueous solution thereof may be included as the solvent, preferably 60 to 80% by weight, more preferably 70% by weight ethanol aqueous solution, but is not limited thereto.

In the present invention, the chinensis purpura extract may have excellent anti-inflammatory activity.

The extract of the thoracic capitula can effectively inhibit the production of prostaglandin E ₂ (PGE ₂ ) _. The PGE ₂ may be excessively produced by an inflammation-inducing substance such as lipopolysaccharide (LPS) or an inflammation-inducing cytokine, and the excessively produced PGE ₂ may cause problems such as tissue damage caused by an inflammatory reaction.

According to an experimental example of the present invention, the production of PGE ₂ was significantly increased in the group treated with LPS alone, but the production of PGE ₂ was decreased in a concentration-dependent manner when the group was treated with the extract of PGE 2 .

In the present invention, the thorax purpura extract may have excellent anti-fibrotic activity.

The oxen cap extract can inhibit the expression of one or more selected from fibrosis-inducing factors consisting of Type 1 collagen, fibronectin, and α-smooth muscle actin (α-SMA). there is.

According to an experimental example of the present invention, the expression of type 1 collagen, fibronectin, and α-SMA protein increased by transforming growth factor-beta (TGF-β) that promotes tissue fibrosis was found in the extract treatment showed a significant decrease.

That is, the extract of the oleaginous capricorn has excellent anti-inflammatory activity and anti-fibrotic activity, and thus can be used as a pharmaceutical composition effective for preventing or treating nasal polyp disease.

In the present specification, "nasal polyp" is a chronic inflammatory disease in which a benign edematous mucosa in the shape of a bunch of grapes originating from the middle nasal passage (middle nasal passage) protrudes into the nasal cavity, and the cause is unknown.

The present invention provides a pharmaceutical composition for preventing the recurrence of nasal polyps containing an extract of Sargassum horneri as an active ingredient.

The nasal polyp disease is an inflammatory disease with a high possibility of recurrence, but since the extract of the oleaginous capricorn has excellent anti-inflammatory activity and anti-fibrotic activity, the pharmaceutical composition containing the same is used to treat nasal polyps after surgery to remove nasal polyps. Recurrence can be prevented by inhibiting remodeling.

Corresponding features may be substituted in the foregoing.

In addition, the present invention provides a pharmaceutical composition for preventing or treating sinusitis disease containing an extract of Sargassum horneri as an active ingredient.

In this specification, "sinusitis (or sinusitis, sinusitis)" means that bacteria or viruses infiltrate the sinuses, which are empty spaces in the facial bones around the nose, causing inflammation. The sinuses are connected to the inside of the nose through a small hole (natural hole), through which ventilation of air and excretion of secretions in the sinus are performed. It can be divided into two types: acute and chronic. Acute sinusitis usually occurs as a late complication of a cold, and chronic sinusitis is accompanied by nasal polyp disease. many.

Since the extract of the oleaginous capricorn has excellent anti-inflammatory activity and anti-fibrotic activity, it can be used as a pharmaceutical composition effective for preventing or treating sinusitis disease.

Corresponding features may be substituted in the foregoing.

As used herein, "prevention" refers to any activity that suppresses or delays the onset of nasal polyp disease, sinusitis disease, or at least one symptom of the disease by administration of the pharmaceutical composition or health functional food composition according to the present invention. means It may also include treatment of subjects in remission of the disease to prevent or prevent relapse.

As used herein, "treatment" refers to improving or beneficially changing the symptoms, such as alleviating, reducing or disappearing at least one symptom of nasal polyp disease, sinusitis disease, or at least one symptom of the disease by administration of the pharmaceutical composition according to the present invention. means all actions.

In the present specification, "pharmaceutical composition" is a composition administered for a specific purpose, which is administered to prevent, treat, or prevent recurrence of nasal polyp disease, sinusitis disease, or at least one or more symptoms of the disease for the purpose of the present invention. means that

The pharmaceutical composition according to the present invention can be prepared according to conventional methods in the pharmaceutical field. The pharmaceutical composition may be formulated with an appropriate pharmaceutically acceptable carrier according to the formulation and, if necessary, may further contain excipients, diluents, dispersants, emulsifiers, buffers, stabilizers, binders, disintegrants, solvents, and the like. there is. The appropriate carrier and the like do not inhibit the activity and properties of the extract of the present invention, and may be selected differently depending on the dosage form and dosage form.

The pharmaceutical composition according to the present invention can be applied in any dosage form, and more specifically, it can be formulated and used in parenteral dosage forms such as oral dosage forms, external preparations, suppositories and sterile injection solutions according to conventional methods.

Among the oral dosage forms, the solid dosage form is in the form of tablets, pills, powders, granules, gels, capsules, etc., and includes at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, sorbitol, mannitol, cellulose, It can be prepared by mixing gelatin, etc., and lubricants such as magnesium stearate and talc may be included in addition to simple excipients. In addition, in the case of a capsule formulation, a liquid carrier such as fatty oil may be further included in addition to the above-mentioned materials.

Among the oral formulations, liquid formulations include suspensions, solutions for internal use, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. there is.

The parenteral formulation may include a sterilized aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a lyophilized formulation, and a suppository. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, Tween 61, cacao butter, laurin fat, glycerogeratin, and the like may be used. It is not limited thereto, and all suitable agents known in the art may be used.

In addition, calcium or vitamins may be further added to the pharmaceutical composition according to the present invention to enhance therapeutic efficacy.

In the pharmaceutical composition according to the present invention, the pharmaceutical composition may be administered in a pharmaceutically effective amount.

In the present specification, "pharmaceutically effective amount" means an amount that is sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects.

The effective dosage level of the pharmaceutical composition depends on the purpose of use, the patient's age, sex, weight and health condition, disease type, severity, drug activity, drug sensitivity, administration method, administration time, administration route and excretion rate, treatment Duration, combination, or factors including drugs used concurrently and other factors well known in the medical arts may be determined differently. For example, although not constant, generally 0.001 to 100 mg/kg, preferably 0.01 to 10 mg/kg, may be administered once or several times a day. The dosage is not intended to limit the scope of the present invention in any way.

The pharmaceutical composition according to the present invention can be administered to any animal that can develop nasal polyposis disease or sinusitis disease, and the animal includes, for example, humans and primates as well as livestock such as cattle, pigs, horses, and dogs. can include

The pharmaceutical composition according to the present invention may be administered by an appropriate administration route according to the formulation form, and may be administered through various oral or parenteral routes as long as it can reach the target tissue. The method of administration is not particularly limited, and may be administered by conventional methods such as oral, rectal or intravenous, intramuscular, skin application, intraventricular inhalation, intrauterine dural or intracerebroventricular injection. there is.

The pharmaceutical composition according to the present invention may be used alone for the prevention or treatment of nasal polyposis disease or sinusitis disease, and may be used in combination with surgery or other drug treatment.

The present invention provides a health functional food composition for preventing or improving nasal polyposis disease, containing Sargassum horneri extract as an active ingredient.

The extract of the thoracic thorax may be obtained by extracting the roots, stems, leaves, outposts, or mixtures thereof of the thoracic thorax with a C1 to C4 alcohol or an aqueous solution thereof as a solvent. For example, methanol, ethanol, propanol, Butanol or an aqueous solution thereof may be included as the solvent, preferably 60 to 80% by weight, more preferably 70% by weight ethanol aqueous solution, but is not limited thereto.

The oyster hat cap extract can effectively inhibit the production of prostaglandin E ₂ (PGE ₂ ), and _is effective in inhibiting type 1 collagen, fibronectin, and α-smooth muscle actin. , α-SMA) can inhibit the expression of one or more selected from fibrosis inducing factors.

That is, the extract of the oleaginous capricorn has excellent anti-inflammatory activity and anti-fibrotic activity, so it can be used as a health functional food composition effective for preventing or improving nasal polyp disease.

The present invention provides a health functional food composition for preventing the recurrence of nasal polyps containing an extract of Sargassum horneri as an active ingredient.

The nasal polyp disease is an inflammatory disease with a high possibility of recurrence, but since the oleaginous capricorn extract has excellent anti-inflammatory activity and anti-fibrotic activity, after nasal polyp removal surgery using the health functional food composition containing the same, cost reduction Recurrence can be prevented by inhibiting the remodeling of the species.

Corresponding features may be substituted in the foregoing.

In addition, the present invention provides a health functional food composition for preventing or improving sinusitis disease containing an extract of Sargassum horneri as an active ingredient.

Since the extract of the oleaginous capricorn has excellent anti-inflammatory activity and anti-fibrotic activity, it can be used as a health functional food composition effective for preventing or improving sinusitis disease.

Corresponding features may be substituted in the foregoing.

In the present specification, "improvement" means that nasal polyp disease, sinusitis disease, or at least one or more symptoms of the disease are alleviated, reduced, or eliminated by ingestion of the health functional food composition according to the present invention, or the symptoms are improved or It means any action that makes a beneficial change.

In the present specification, "health functional food" includes food manufactured and processed using raw materials or ingredients having useful functionalities for the human body according to Health Functional Food Act No. 6727, and in addition to providing nutrition, the purpose of the present invention It refers to food with high medical and medical effects processed to efficiently display biological control functions such as prevention of upper nasal polyposis disease or sinusitis disease, biological defense, immunity, and recovery.

For the purpose of preventing or improving nasal polyp disease or sinusitis disease, the health functional food according to the present invention may be prepared in the form of powder, granule, tablet, capsule, syrup or beverage. There is no limit to the form that the health functional food can take, and it can be formulated in the same way as the pharmaceutical composition and used as a functional food or added to various foods.

The health functional food may include all foods in a conventional sense. For example, beverages and various drinks, fruits and their processed foods (canned fruit, jam, etc.), fish, meat and their processed foods (ham, bacon, etc.), breads and noodles, cookies and snacks, dairy products (butter, cheese, etc.) ), etc., and may include all functional foods in a conventional sense. In addition, food used as feed for animals may also be included.

The health functional food composition according to the present invention may be prepared by further including food chemically acceptable food additives (food additives) commonly used in the art and other appropriate auxiliary components. The suitability as a food additive can be determined according to the standards and standards for the item in accordance with the general rules of the Food Additive Code and general test methods approved by the Ministry of Food and Drug Safety, unless otherwise specified. Examples of the items listed in the 'Food Additive Code' include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, kaoliang pigment, and guar gum; mixed preparations such as sodium L-glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar color preparations; and the like.

The other auxiliary ingredients include, for example, flavoring agents, natural carbohydrates, sweeteners, vitamins, electrolytes, colorants, pectic acid, alginic acid, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents, etc. may additionally contain. In particular, as the natural carbohydrate, monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol may be used. As the sweetener, natural sweeteners such as thaumatin and stevia extract or synthetic sweeteners such as saccharin and aspartame may be used.

An effective dose of the extract of the oleaginous capricorn extract contained in the health functional food according to the present invention may be appropriately adjusted according to the purpose of use, such as preventing or improving nasal polyp disease or sinusitis disease.

The health functional food composition uses food as a raw material and has the advantage of not having side effects that can occur when taking general medicines for a long time. .

Hereinafter, examples will be described in detail to aid understanding of the present invention. However, the following examples are merely illustrative of the contents of the present invention, but the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

<Example 1> Preparation of hoesaeng capsular extract

The hoesaeng hats were collected from Yangyang-gun, Gangwon-do, washed with tap water, and stored frozen at -80 ° C for 1 day. Freeze-preserved samples were dried for 4 days using a freeze dryer. The dry sample was pulverized using a grinder to prepare a powder form.

70% ethanol was added to the dried sample in powder form, and extraction was repeated 8 times with an ultrasonic extractor for 1 hour at room temperature. Each extraction was filtered using a filter paper, and the filtered extract was concentrated using a vacuum concentrator. The concentrated sample was dried using a lyophilizer for 4 to 5 days after freezing at -80 ° C for complete drying. The dried extract was made into a powder form and stored frozen at -80 ° C until use in experiments.

<Experimental Example 1> Confirmation of cytotoxicity of the extract of thorax

In order to evaluate the cytoprotective effect of digested hydrolysates against LPS-induced radical toxicity with RAW264.7 cells, cell viability was measured by CCK assay.

2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt (WST-1) kit for ethanol extract and LPS-treated cells After adding 10 μL (1 μg/mL) of (CCK-8) and incubating for 1 hour, the resulting formazan salt was dissolved and measured at a wavelength of 450 nm.

As a result, a survival rate of more than 80% was shown at the maximum concentration of 500 μg/mL of the ethanol extract of the black caps.

<Experimental Example 2> Confirmation of the anti-inflammatory activity of the extract

1. Confirmation of NO inhibition activity

RAW 264.7 cells were cultured in a 24-well plate, treated with ethanol extracts of 0, 200, 300, and 500μg/mL for each concentration, reacted for 30 minutes, and then treated with 1μg/mL of LPS and cultured for 24 hours. Then, 150 μL of the cell culture medium, 130 μL of distilled water, and 20 μL of a grease reagent kit were mixed, reacted at room temperature for 30 minutes, and absorbance was measured at 548 nm.

As a result, as shown in FIG. 1 , the ethanol extract of the chinensis chinensis did not significantly inhibit NO production.

2.PGE ₂ Confirmation of inhibitory activity

After processing according to the suggested method using the PGE ₂ (R&D Inc., Minneapolis, MN, USA) ELISA kit, absorbance was measured at 405 nm.

As a result, as shown in FIG. 2, although the production of PGE ₂ was significantly increased in the group treated with LPS alone compared to the control group, when the ethanol extract of PGE 2 was treated in a concentration range that did not show cytotoxicity, concentration-dependently The production of PGE ₂ was found to be reduced.

<Experimental Example 3> Confirmation of the inhibitory effect of fibrosis-inducing factor expression of thorax capella extract using non-polyposis fibroblasts (NPDFs)

1. Cytotoxicity measurement

The effect on cell viability was measured using Cell Counting Kit-8 using the principle of WST-1 assay.

As a result, as shown in FIG. 3, after pre-treatment with 30, 50, and 100 μg/mL concentrations of ethanol extracts for 1 hour, transforming growth factor-beta (TGF-β) was treated with 100 μg/mL, As a result of culturing for a period of time, the cell survival rate was greater than 80%.

2. Identification of the inhibitory effect of type 1 collagen, fibronectin, and α-SMA on the extracts from NPDFs.

Nasal polyp-derived fibroblasts (NPDFs) were seeded in a 96-well plate at 6×10 ⁴ cells/mL. Thereafter, after pre-treatment with the ethanol extract of the black capped cape, 100 μg/mL of transforming growth factor-beta (TGF-β) was treated and cultured for 24 hours. In order to measure the expression of type 1 collagen, fibronectin, and α-smooth muscle actin (α-SMA) proteins in cells, proteins were extracted and western blotting was performed. did

As a result, as shown in FIGS. 4 to 7 , it was found that the expression of type 1 collagen, fibronectin, and α-SMA protein increased by TGF-β was significantly suppressed by the ethanol extract of the oleander cap.

Having described specific parts of the present invention in detail above, it is clear to those skilled in the art that these specific descriptions are only preferred embodiments, and the scope of the present invention is not limited thereby. do. That is, the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims (10)

It contains Sargassum horneri extract as an active ingredient,
The extract induces fibrosis, characterized in that inhibiting the expression of one or more selected from the group consisting of type 1 collagen, fibronectin and α-smooth muscle actin (α-SMA) A reagent composition for factor inhibition. According to claim 1,
The hoesaeng hatban extract,
A reagent composition, characterized in that it is extracted with a C1 to C4 alcohol or an aqueous solution thereof as a solvent. delete delete delete delete delete delete delete delete

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