KR101491492B1 - Extraction method of Citrus hassaku pericarp for increasing anti-inflammation activity - Google Patents

Abstract

The present invention relates to a pharmaceutical composition comprising citrus hassaku ) skin. The present invention also provides a pharmaceutical composition or functional food composition for improving, treating or preventing inflammation, which comprises as an active ingredient, an extract of Echinochloa crus-galli extract having enhanced anti-inflammatory activity extracted according to this extraction method and the Echinochloa crus-root extract.

Description

Extraction method of citrus hassaku pericarp for increasing anti-inflammatory activity [

The present invention relates to the use of citrus phytophthora ( Citrus) hassaku ) skin. The present invention also relates to an extract of Parmesan crassaceae extract having enhanced antiinflammatory activity extracted according to the above extraction method, and a pharmaceutical composition and / or food composition for promoting antiinflammatory activity containing the same.

Inflammatory responses are a series of immune responses that necessarily occur by activated immune cells. When the immune cells are exposed to foreign substances such as microorganisms including bacteria, viruses and foreign substances in the living body, the immune cells are activated and the activated immune cells accelerate the inflammation reaction. When the inflammatory reaction by lipopolysaccharide (LPS), which is a bacterial inflammation inducer, occurs, various inflammatory factors (pro-inflammatory mediators) are produced. The inflammatory factors include inducible nitric oxide synthase (iNOS) the nitric oxide produced by the like (NO, nitric oxide) and cyclooxygenase (COX-2, cyclooxygenase) prostaglandin _{E 2 (PGE 2, prostaglandin E} 2) produced by the.

NO is a biologically active molecule with high reactivity and is produced from L-arginine by nitric oxide synthase (NOS). NO is involved in neurotransmission, vascular relaxation and cell-mediated immune responses, particularly when the macrophage is stimulated with lipopolysaccharide (LPS) and interferon-γ (IFN-γ), inducible nitric oxide synthase (iNOS) Resulting in a large amount of NO. The large amount of NO produced in this way serves as an inflammatory mediator.

PGE ₂ is a major inflammatory mediator and is involved in the inflammatory response by stimulating macrophages such as cytokines, tumor necrosis factor-α (TNF-α), and lipopolysaccharide (LPS) ), Resulting in excessive production when cyclooxygenase-2 (COX-2) is expressed. PGE ₂ may increase vascular permeability and cause heat, swelling and pain in inflamed areas. PGE ₂ is inhibited by non-steroidal anti-inflammatory drugs (NSAIDs). It is used for antipyretic, analgesic and anti-inflammatory effects. It is an anti-inflammatory agent and is used for the treatment of muscle skeletal diseases such as rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. Is used.

There has been much effort to develop a pharmaceutical composition having an antiinflammatory effect by inhibiting the production of NO and PGE ₂ , and a lot of studies have been made on a pharmaceutical composition for treating or preventing inflammation including a natural plant active ingredient have.

On the other hand, Citrus hassaku is a species belonging to Citrus ( Citrus ). Such Jeju native native citrus fruits have shown efficacy in the prevention and treatment of various diseases. The citrus fruits used in Korea account for 30% of the total fruit, 20-25% of them are consumed for processing, and a large amount of citrus fruits occur as by-products in the processing process.

There are many physiologically active substances in citrus such as flavonoids, carotenoids, coumarins, phenylpropanoids and limonoids, and there are many physiologically active substances such as naringin ) And hesperidin were higher than those of pulp and the total dietary fiber content was also higher in the perilla than the pulp. A variety of physiological functions such as abundant carotenoids, bioflavonoids or terpenes in citrus peels have been reported, such as prevention of hypertension, lowering of LDL cholesterol in the blood, enhancement of HDL cholesterol content, and prevention and improvement of circulatory diseases. The contents of flavonoids, antioxidants, vitamins, and dietary fiber were the highest among the whole citrus fruits, peel and flesh of three citrus samples, and antioxidant activity and weight loss were also reported.

For example, the Korean Journal of Cancer Research (Vol. 16, No. 2, pp. 25-34) disclosed the effect of the extract of native citrus phlox peel on inhibition of inflammatory mediators in RAW264.7 macrophages activated with LPS , Korean Patent Registration No. 10-0770746 discloses a citrus-derived novirretin having anti-inflammatory activity and a method for separating and purifying the same.

There is no published article or patent to disclose the anti-inflammatory effect and the anti-inflammatory effect contained in the parasitoid, and in particular, the disclosed document on the extraction method of parasitic skin which can maximize the anti-inflammatory effect Not yet reported.

It is very useful if large quantities of citrus fruits occur as by-products each year and the anti-inflammatory effects of these by-products can be increased as much as possible.

Accordingly, the technical problem to be solved by the present invention is to provide a method of extracting parachute skin having an anti-inflammatory activity-enhancing effect by identifying the conditions for extracting parachute skin optimized to enhance anti-inflammatory activity.

The present invention also provides an extract of Echinochloa crus-galli which has been enhanced by the anti - inflammatory activity extracted according to the Echinochloa crus extract method.

In addition, the present invention provides a pharmaceutical composition or food composition for promoting anti-inflammatory activity comprising the extract of Echinococcus epidermidis as an active ingredient.

In order to accomplish the above object, the present invention provides a method of extracting parchment skin from an aqueous ethanol solution having an ethanol concentration of 25 to 60% by volume as an extraction solvent at an extraction temperature of 30 to 45 ° C for 2 to 6 hours The present invention provides a method for extracting parchment skin for promoting anti-inflammatory activity.

The invention is based on NO production, and PGE ₂ production amount to determine the anti-inflammatory effect than any other extract derived as a condition an extract made from extraction process according to a result of testing a variety of conditions for increasing the anti-inflammatory effect of the extract in the present invention is similar to It is based on the fact that it exhibits a remarkably excellent effect in the test.

That is, the inventors of the present invention have found that, by using an ethanol aqueous solution having a concentration of ethanol of 25 to 60% by volume as an extraction solvent and extracting conditions at an extraction temperature of 30 to 45 DEG C and an extraction time of 2 to 6 hours, The present inventors have confirmed that the extract is highly effective in promoting anti-inflammatory activity and completed the present invention.

It is preferable to use a powdery sample obtained by sufficiently lyophilizing and crushing the parchment scales used in the present invention.

The concentration of ethanol in the aqueous ethanol solution, which is an extraction solvent used in the method of extracting pericarp of the present invention, is preferably 25 to 60% by volume, more preferably 30 to 55% by volume.

In the method of extracting the parchment of the present invention, the extraction temperature is preferably in the range of 30 to 45 ° C, more preferably 30 to 41 ° C.

In the method of extracting pericarp of the present invention, the extraction time is preferably 2 to 6 hours, more preferably 3 to 5 hours.

The present invention also provides a phytochemical extract having enhanced antiinflammatory activity extracted according to the above extraction method, and provides a pharmaceutical composition or functional food composition for promoting antiinflammatory activity containing the phytophthora phloem extract as an active ingredient.

Examples of the functional food in which the Echinochloans crassulosa extract of the present invention can be used include beverage, gum, tea, vitamin complex, health supplement, bread, confectionery, candy, etc. However, But is not limited thereto.

That is, the composition for treating or preventing inflammation produced under the extraction conditions according to the present invention can be manufactured in the form of medicines and functional foods. Such medicaments and functional foods may include pharmaceutically or pharmacologically acceptable excipients or additives. The compositions of the present invention may be administered alone or in admixture with any convenient vehicle, excipient, or the like, and such dosage forms may be single-dose or multiple-dose formulations.

The pharmaceutical or functional food containing the composition of the present invention may be a solid preparation or a liquid preparation. Solid preparations include, but are not limited to, powders, granules, tablets, capsules, suppositories, and the like. Solid form preparations may include, but are not limited to, excipients, flavoring agents, binders, preservatives, disintegrants, lubricants, fillers, and the like. Examples of the liquid preparation include water, a solution such as a solution of propylene glycol, a suspension, an emulsion, and the like, but not limited thereto, and it can be prepared by adding a suitable coloring agent, a flavoring agent, a stabilizer, a tackifying agent and the like.

For example, the acid can be prepared by simple mixing of the phytate extract, which is an active ingredient of the present invention, with a pharmacologically acceptable excipient such as lactose, starch and microcrystalline cellulose. The granular preparation may be prepared by mixing the phytopathic peel extract of the present invention with a suitable pharmaceutically acceptable excipient and a suitable pharmaceutically acceptable binder such as polyvinylpyrrolidone or hydroxypropylcellulose and then mixing the mixture with water or a solvent such as ethanol or isopropanol Wet granulation method or dry granulation method using compressive force. Further, the tablet may be prepared by mixing the above granule with a suitable pharmaceutically acceptable salt such as magnesium stearate and then tableting it using a tablet machine.

The composition of the present invention may be administered orally or parenterally (for example, intramuscular injection, intraperitoneal injection, intravenous injection, infusion, subcutaneous injection, implant), inhalant, nasal administration agent, , Rectal, sublingual, transdermal, topical, and the like, but is not limited thereto. May be formulated into suitable dosage unit formulations, including those conventionally used and non-toxic, pharmaceutically acceptable carriers, additives, vehicles according to the route of administration. Depot formulations that are capable of sustained release of the drug over a period of time are also within the scope of the present invention.

In order to achieve the object of the present invention, improvement of inflammation, the phytomassus extract prepared according to the method of the present invention may be administered at about 0.0001 mg / kg to about 10 g / kg daily, and about 0.001 mg / kg to about 1 g / kg is preferred. However, the dose may vary depending on the degree of purification of the Echinochloa crus-galli extract, the patient's condition (age, sex, weight, etc.), severity of the condition being treated, For convenience, the total daily dose may be divided as needed and divided into several doses throughout the day.

The present invention provides a preparation method of extracting parchment skin extract having excellent anti-inflammatory activity, that is, an extraction condition. The present invention also provides a pharmaceutical composition or functional food composition for enhancing antiinflammatory activity, which comprises as an active ingredient, an extract of Echinochloa crus-galli extract having enhanced antiinflammatory activity extracted according to this extraction method and an Echinochloa crus-galli extract.

FIG. 1 is a graph showing three-dimensional superimposition of extraction conditions with the minimum amount of NO production and extraction conditions with the minimum amount of PGE ₂ production as a function of extraction temperature, ethanol ratio and extraction time. FIG.

Hereinafter, embodiments of the present invention will be described in detail to facilitate understanding of the present invention. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.

Depending on several extraction conditions Parch pericarp  extraction

Citrus hassaku ) mature fruit was obtained from Cheju National University. The peeled peel was dried by lyophilization and pulverized.

The crushed parchment scales were extracted according to the extraction temperature as shown in Table 1, the concentration of ethanol as an extraction solvent and the extraction time.

Example No. Extraction condition ethanol(%) Extraction temperature (캜) Extraction time (hr) One 31 41 3 2 79 41 3 3 31 75 3 4 79 75 3 5 31 41 7 6 79 41 7 7 31 75 7 8 79 75 7 9 15 58 5 10 95 58 5 11 55 30 5 12 55 86 5 13 55 58 One 14 55 58 9 15 55 58 5 16 55 58 5 17 55 58 5 18 55 58 5 19 55 58 5 20 55 58 5

Yield evaluation

The total extraction yield of the samples extracted according to the extraction conditions as in Examples 1 to 20 was measured as follows. 10 mL of the extract was evaporated to dryness at 105 ° C., and the weight of the extract was measured. The extract yield (%, total extraction yield) was expressed as a percentage of the amount of raw material (dry matter) used in the extract preparation.

The yields of the extracts according to the extraction conditions in Examples 1 to 20 are shown in Table 2 below, and the yield of the 12th section extract with an ethanol concentration of 55%, an extraction temperature of 75 ° C and an extraction time of 5 hours was 51.69 ± 0.07%, and the extracts with the ethanol concentration of 95%, the extraction temperature of 53 ℃ and the extraction time of 5 hours were the lowest at 38.95 ± 0.33%.

As shown in the following Table 2, the yield was found to be increased with increasing ethanol concentration and extraction temperature, and it was found to be most influenced by extraction temperature and ethanol concentration relative to extraction solvent.

Determination of total phenolic compound content

Phenolic substances are one of the secondary metabolites widely distributed in the plant system and have various structures and molecular weights. Various phenolic compounds present in plants show antioxidant ability by hydrogen donation through hydroxyl group and resonance stabilization of phenolic ring structure.

The total polyphenol content of the extract was determined by modifying the Folin-Ciocalteau method. After adding 45 μl of 1N Folin-Ciocalteau's phenol reagent and 135 μl of 2% Na ₂ CO ₃ to 20 μl of each extract, the mixture was allowed to stand at room temperature for 2 hours and absorbance was measured at 750 nm. At this time, the total polyphenol content in the sample was determined from a calibration curve obtained using gallic acid as a standard substance.

The results of measurement of the total phenolic compound content (mg / 100g) according to the extraction conditions in Examples 1 to 20 are shown in Table 2 below. The ethanol concentration was 55%, the extraction temperature was 53 ° C, The total phenolic content of the extract of 14th time, 9 hours, was the highest at 47.16 ± 0.89 mg / g, and the extract of 9th section with 15% ethanol concentration, 53 ℃ extraction temperature and 5 hours extraction time was 35.38 ± 0.31 mg / g.

As shown in the following Table 2, the total phenolic compound content was found to increase with increasing ethanol concentration and extraction time of the extract. Total phenolic compound content was most influenced by extraction time and ethanol concentration on the extraction solvent .

As described later, the extraction conditions capable of increasing the content of the total phenolic compounds and the extraction conditions capable of enhancing the inflammatory effect were inconsistent, suggesting that the extraction conditions capable of enhancing the anti-inflammatory effect are very specific .

NO  Production amount measurement

The NO concentration was determined by measuring the nitrite concentration in the culture medium using the Griess regent. RAW 264.7 cells were plated in 96-well plates at 1 × 10 ⁵ cells / well and cultured for 24 hours. Each extract was pretreated at a concentration of 100 μg / ml and treated with lipopolysaccharide (LPS, 1 ug / mL) And cultured for 24 hours. The cell culture supernatant (100 uL) was placed in a 96-well plate, and an equal volume of Griess regent was added thereto. After reacting at room temperature for 10 minutes, the absorbance was measured at 540 nm using an ELISA microplate reader. The NO concentration in the culture medium was determined using a standard curve for the concentration of sodium nitrite.

The results of measurement of the NO production amount (%) according to the extraction conditions in each of Examples 1 to 20 were measured in the range of 63.51 to 81.70% as shown in Table 2.

As shown in Table 2 below, the amount of NO produced decreased as the concentration of the extraction solvent decreased.

PGE ₂  Production amount measurement

RAW 264.7 cells were plated in 6-well plates at a cell density of 1x10 ⁶ cells / ml and cultured in a 5% CO ₂ incubator at 37 ° C for 24 hours. After replacing the cells with fresh RPMI 1640 medium, each extract was pre-treated with 100 μg / ml of the cells, cultured for 2 hours, treated with LPS (1 μg / ml) and cultured for 24 hours. The separated and the cell culture was centrifuged for 3 minutes at 5,000 rpm the supernatant using the PGE ₂ enzyme immunoassay (EIA) kits (R & D Systems, Abington, UK) was measured both PGE _2.

The amount (%) of PGE ₂ according to the extraction conditions in each of Examples 1 to 20 was in the range of 61.92 to 81.17% as shown in Table 2 below, compared with the control stimulated only with LPS without any drug treatment.

Example No. Extraction yield (%) Total phenolic
Compound (mg / g) LPS induced
NO production (%) LPS induced
Production of PGE ₂ (%) One 45.50 41.51 63.51 61.92 2 42.33 43.89 66.09 70.69 3 49.74 36.51 77.73 74.25 4 45.96 44.54 71.56 71.08 5 46.62 40.91 69.87 70.28 6 41.94 43.65 80.01 80.55 7 50.77 37.22 76.53 78.59 8 45.92 43.47 68.88 69.62 9 47.31 35.38 73.45 73.29 10 38.95 43.53 74.05 74.82 11 45.95 41.45 64.90 63.81 12 51.69 40.49 73.35 72.31 13 46.45 43.89 71.86 73.27 14 47.04 47.16 81.70 81.17 15 48.43 42.58 72.16 72.58 16 48.29 42.82 70.97 72.17 17 47.62 43.89 71.36 71.49 18 47.68 42.88 73.05 72.31 19 48.43 43.89 72.76 71.36 20 48.06 43.59 72.76 72.72

Establish optimal extraction conditions using experimental results

Based on the experimental results shown in Table 2 above, the extraction conditions such as extraction temperature, ethanol concentration and extraction time were evaluated to minimize the NO production amount and PGE ₂ production amount for the anti-inflammatory activity enhancing effect. For reference, extraction conditions were also evaluated to optimize the yield and the content of total phenolic compounds.

In Example 1, the amount of NO-induced LPS-induced NO production was 63.51%, that of PGE ₂ was 61.92%, that of Example 11 was 64.90%, and the amount of PGE ₂ production was 63.81% ₂ production. The extraction conditions of Example 1 are ethanol concentration of 31%, extraction temperature of 41 DEG C, extraction time of 3 hours, and extraction conditions of Example 11 are ethanol concentration of 55%, extraction temperature of 30 DEG C and extraction time of 5 hours. Based on the experimental results, the range of optimal extraction conditions is as follows: the ethanol concentration is 31 to 55%, the extraction temperature is 30 to 41 ° C, and the extraction time is 3 to 5 hr (Table 3).

Extraction condition Preferred range (optimum value) Extraction temperature (캜) 30 to 41 (35) Ethanol concentration (%) 31 to 55 (43) Extraction time (hr) 3 to 5 (4)

In Example 2, when the ethanol concentration is 79% and the optimum extraction condition is out of the range, the NO production amount is 66.09% and the PGE ₂ production amount is 70.69%. In Example 3, when the temperature is outside the optimal extraction condition range of 75 캜, the NO production amount is increased to 77.73% and the PGE ₂ production amount is increased to 74.25%. In Example 5, when the optimum extraction condition is out of the range of 7 hr, the NO production amount is increased to 69.87% and the PGE ₂ production amount is increased to 70.28%. From these facts, it can be seen that the amount of NO and PGE ₂ produced is significantly reduced within the range of optimum extraction conditions, as compared with the range.

The yield was 45.50% in Example 1 and 45.95% in Example 11, and the content of the phenolic compound was 41.41 mg / g in Example 1 and 41.45 mg / g in Example 11, And exhibits a considerable effect within the range.

Establish optimal extraction conditions by regression analysis

Regression analysis was conducted to establish optimal extraction conditions based on the extraction conditions and evaluation results used in Examples 1 to 20. For the reaction surface analysis, SAS (statistical analysis system) program was used.

The independent variables (Xi) were coded in five steps of ethanol concentration (X ₁ ), extraction temperature (X ₂ ) and extraction time (X ₃ ) of the extraction solvent at -1.68, -1, 0, 1, -1.68 4).

Independent variable sign Factor value
-1.682 -One 0 One 1.682 ethanol(%) X ₁ 15 31 55 79 95 Extraction temperature (캜) X ₂ 30 41 58 75 86 Extraction time (hr) X ₃ One 3 5 7 9

(Y ₁ ), total polyphenol content (Y ₂ ), NO production amount (Y ₃ ) and PGE ₂ production amount (Y ₄ ) as the quality factors of the extract, , Which were repeated three times and the mean value was used for regression analysis. Using the results obtained in the above Examples 1 to 20 (Table 2), the reaction surface regression analysis was carried out to obtain optimum extraction conditions, and the respective dependent parameters such as yield, total phenolic compound content, Regression equations for NO production and PGE ₂ production were obtained.

reaction Second order Polynomials R ² Significance level Total yield Y _Y = 35.357852 - 0.301439X ₁ - 0.004153X ₂ + 1.259806X ₃ - 0.003131X ₁ ² - 0.000322X ₁ X ₂ + 0.001484X ₂ ² - 0.006719X ₁ X ₃ + 0.001157X ₂ X ₃ - 0.086066X ₃ ² 0.9903 <0.0001 Total phenolic content Y _TP = 32.312353 + 0.204201X ₁ + 0.245401X ₂ - 1.138844X ₃ - 0.002459X ₁ ² + 0.003533X ₁ X ₂ - 0.004835X ₂ ² - 0.003698X ₁ X ₃ + 0.002884X ₂ X ₃ + 0.135698X ₃ ² 0.9503 0.0907 LPS induced NO production Y_NO = -7.662093 + 0.391837X_One + 2.020014X₂ + 3.515877X₃ + 0.000611X_One ² - 0.010219X_OneX₂ - 0.007047X₂ ² + 0.015833X_OneX₃- 0.111494X₂X₃ + 0.262211X₃ ² 0.9488 0.0001 LPS induced PGE ₂ production Y _P = -11.515066 + 0.605215X ₁ + 2.036909X ₂ + 2.461893X ₃ + 0.001041X ₁ ² - 0.012041X ₁ X ₂ - 0.008426X ₂ ² - 0.011198X ₁ X ₃ - 0.071424X ₂ X ₃ + 0.307473X ₃ ² 0.9594 0.0001

Table 6 shows the optimal extraction conditions and quality characteristics for each parameter.

reaction X ₁ X ₂ X ₃ Predictive response yield(%)
94.21 48.30 5.26 (min) 43.94 74.01 5.40 (max) Total phenolic compound (mg / 100 g) 19.30 62.52 4.71 (min) 65.75 52.27 8.85 (max) LPS induced NO production (%) 42.67 33.47 3.26 (min) 68.08 45.15 8.55 (max) LPS induced PGE ₂ production (%) 37.10 34.00 3.60 (min) 60.21 48.16 8.90 (max)

Response to results in yields The R ² value of the surface regression equation was 0.9903, meaning that significance was recognized at a significance level within 1% (Table 5). The predicted steady-state point was a saddle point. The extraction temperature for the sample was 74.0 ° C, the ethanol concentration for the extraction solvent was 43.9%, and the extraction time was estimated to be 52.49% at 5.4 hr.

The R ² value of the regression equation for the total phenolic compound content of the extract according to the extraction conditions was 0.9503 and the predicted normal point of the total phenolic compound content was the saddle point, The maximum ethanol concentration of the solvent was estimated to be 46.60 mg / g when the extraction temperature was 52.27 ℃ and the extraction time was 8.85 hr.

In addition, R ² of the response surface regression equation for the NO production amount was 0.9488, meaning that the significance was recognized at a significance level within 5%. The NO production of LPS-stimulated cell cultures after treatment with P. parapertussis was estimated to be about 43% (42.67%), the extraction temperature was about the saddle point, At 33 ℃ (33.47 ℃) and extraction time was about 3 hr (3.26 hr), NO production was the lowest value of 59.57%.

In addition, the R ² of the response surface regression equation for the PGE ₂ production amount was 0.9594, meaning that significance was recognized at a significance level within 5%. The PGE ₂ production level of the cell culture medium stimulated with LPS after treatment with the Epsilon cutaneous extract was estimated to be about 37% (37.10%) in ethanol concentration of the extraction solvent as the saddle point, At 34 ° C (34.00 ° C) and about 4 hours (3.60 hr), PGE ₂ production was the lowest at 59.30%.

Extraction conditions in which NO and PGE ₂ production amounts calculated through regression analysis are minimized are included in the range of optimized extraction conditions obtained through practical implementation in the above Examples 1 to 20.

FIG. 1 shows a three-dimensional graph of the reaction surface in which NO and PGE ₂ production amounts are minimized with the extraction temperature, the ethanol ratio and the extraction time as parameters.

The extraction conditions in the parcthus sinensis extraction method of the present invention is an extraction method in which the anti-inflammatory effect is optimized. The present invention provides a pharmaceutical composition or a functional food composition for improving, treating or preventing inflammation, which comprises the extract of Echinochloa crus-galli extract extracted as an active ingredient according to this extraction method. It is expected that the extract of Echinochloa crus-galli extract extracted according to the present invention can greatly enhance the anti-inflammatory activity and thus can be usefully used in the art.

Claims (7)

The pericarp is extracted with an aqueous ethanol solution having an ethanol concentration of 25 to 60% (v / v) as an extraction solvent at an extraction temperature of 30 to 41 캜 for 2 to 6 hours,
Increases the content of phenolic compounds and decreases the production of nitric oxide (NO) and prostaglandin E ₂ (prostaglandin E ₂ , PGE ₂ )
Wherein the phenolic compound content is at most 46.60 mg / g, the NO production amount is at least 59.57%, and the PGE ₂ production amount is at least 59.30%, compared with the case where the extract is not treated. &Lt; / RTI &gt; The method according to claim 1, wherein the parmesan is a powdery sample obtained by lyophilization and pulverization. The process according to claim 1, wherein the concentration of ethanol is 30 to 55% (v / v). delete The process according to claim 1, wherein the extraction time is 3 to 5 hours. 6. A process for producing a polyurethane foam according to any one of claims 1 to 3 and 5,
Increases the content of phenolic compounds and decreases the production of nitric oxide (NO) and prostaglandin E ₂ (prostaglandin E ₂ , PGE ₂ )
Wherein the content of the phenolic compound is at most 46.60 mg / g, the NO production amount is at least 59.57%, and the amount of PGE ₂ is at least 59.30%, as compared with the case where the extract is not treated. As an active ingredient. 6. A process for producing a polyurethane foam according to any one of claims 1 to 3 and 5,
Increases the content of phenolic compounds and decreases the production of nitric oxide (NO) and prostaglandin E ₂ (prostaglandin E ₂ , PGE ₂ )
Wherein the content of the phenolic compound is at most 46.60 mg / g, the NO production amount is at least 59.57%, and the amount of PGE ₂ is at least 59.30%, as compared with the case where the extract is not treated. As an active ingredient.

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