KR20190126565A - A composition for improving, preventing and treating of pain containing oriental medicine herbs oil extract as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for alleviating, preventing or treating pain. The present invention is able to alleviate, prevent or treat pain caused by one or more kinds selected from a group consisting of somatic pain, visceral pain, inflammatory pain, dysfunction pain, idiopathic pain, superficial pain, deep pain, migraine, and cancer pain by containing fat-soluble fraction extract such as a fir fat-soluble fraction extract, Aralia cordata Thunb fat-soluble fraction extract, upper limb fat-soluble fraction extract, and peppermint fat-soluble fraction extract as active ingredients. Moreover, the present invention can be taken in the form of food since the composition has no toxicity.

Description

A composition for improving, preventing and treating of pain containing oriental medicine herbs oil extract as an active ingredient}

The present invention relates to a composition which can contain the herbal extract fat-soluble fraction extract as an active ingredient to improve, prevent or treat pain relief.

Currently, as painkillers, anti-inflammatory drugs such as aspirin and tylenol make up the mainstream, and in case of severe pain, morphine drugs are mostly used.

Recently, a new pain inhibitor is being developed. Javelin Pharmaceuticals, a developer specializing in pain medications, is an intranasal morphine spray that is a narcotic analgesic, a nasal analgesic that has an analgesic effect comparable to intravenous morphine in the treatment of pain after severe surgery. 'Rylomine' was developed.

In addition, the painkiller `` Prialt '', developed by Irish pharmaceutical company Elan from sea snail poison, was first marketed in the UK.

Inflammatory processes, on the other hand, cause swelling and pain with a series of complex biochemical and cellular events that are activated in response to the presence of foreign material or tissue damage. The inflammatory process is a defense against foreign pathogens, but it can cause pain even in the absence of irritation of toxic substances. The local inflammatory response releases proinflammatory cytokinin, upregulates cyclooxygenase-2 to synthesize prostaglandins, sensitizing primary afferent neurons, and thereby surrounding nerve cells It activates nerve immunity by making it sensitive.

Thus, ultimately, thermal or mechanical hypersensitivity occurs. When such an inflammatory reaction occurs, pain is involved, which is called inflammatory pain.

In addition to the inflammatory pain, as the society ages, patients with degenerative arthritis and back pain-related diseases tend to increase every year, but existing opiates such as morphine are limited in use due to narcotic action to the general public, so the demand for pain relief is much higher in the future. It is expected to increase further.

In addition, the development of painkillers for pain that does not respond to existing painkillers is greatly required, and the narcotic and serious side effects of the conventional opiate-like agents, which are known to have relatively high analgesic effects, cannot be easily used by general patients. Therefore, there is no need for side effects and development of natural resources having analgesic efficacy.

Republic of Korea Patent No. 1784591 Republic of Korea Patent Publication No. 2017-0099105

An object of the present invention is to provide a pharmaceutical composition for pain relief, prevention or treatment containing fat soluble fraction extract, including fir fat soluble fraction extract, active fat soluble fraction extract, upper limb soluble fraction extract and peppermint fat soluble fraction extract as an active ingredient. .

In addition, another object of the present invention to provide a health functional food for the relief, prevention or improvement of pain containing the fat-soluble fraction mixed extract as an active ingredient.

In addition, another object of the present invention to provide a fragrance composition for alleviating, preventing or treating pain containing the fat-soluble fraction mixed extract as an active ingredient.

In addition, another object of the present invention to provide a cosmetic composition for the relief, prevention or improvement of pain containing the fat-soluble fraction mixed extract as an active ingredient.

The pharmaceutical composition for pain relief, prevention or treatment of the present invention for achieving the above object is a fat-soluble fraction mixed extract comprising a fir fat-soluble fraction extract, a lively fat-soluble fraction extract, upper limb-fat-soluble fraction extract and peppermint fat-soluble fraction extract as an active ingredient. It may contain.

Each of the fat-soluble fraction extract may be a fat-soluble fraction extract extracted by supercritical extraction or steam distillation extraction.

The solvent in the supercritical extraction may be carbon dioxide.

The fir fat soluble fraction extract, venom fat soluble fraction extract, upper limb soluble fraction extract and peppermint fat soluble fraction extract may be mixed in a weight ratio of 1: 0.3-1: 0.1-0.8: 0.3-1.

The pain consists of somatic pain, visceral pain, inflammatory pain, dysfunction pain, idiopathic pain, superficial pain, deep pain, migraine and cancer pain. It may be at least one selected from.

In addition, the health functional food for pain relief, prevention or improvement of the present invention for achieving the above another object is a fat-soluble fraction mixed extract comprising a fir fat-soluble fraction extract, a poisonous fat-soluble fraction extract, upper limb fat-soluble fraction extract and peppermint fat-soluble fraction extract Can be contained as an active ingredient.

In addition, the fragrance composition for pain relief, prophylaxis or treatment of the present invention for achieving the above another object is a fat-soluble fraction mixed extract comprising a fir fat-soluble fraction extract, a poisonous fat-soluble fraction extract, upper limb fat-soluble fraction extract and peppermint fat-soluble fraction extract Can be contained as an active ingredient.

In addition, the cosmetic composition for pain relief, prevention or improvement of the present invention for achieving the above another object is a fat-soluble fraction mixed extract comprising a fir fat-soluble fraction extract, a poisonous fat-soluble fraction extract, upper lipo-lipid fraction extract and peppermint fat-soluble fraction extract Can be contained as an active ingredient.

Compositions capable of improving, preventing or treating pain containing fat soluble fraction mixed extracts including fir fat soluble fraction extract, active fat soluble fraction extract, upper limb soluble fraction extract and peppermint fat soluble fraction extract as active ingredients are not toxic, 1 selected from the group consisting of somatic pain, visceral pain, inflammatory pain, dysfunction pain, idiopathic pain, superficial pain, deep pain, migraine and cancer pain It is very effective in improving, preventing, or treating pain of more than one species and is effective in preparing competitive food compositions and pharmaceutical compositions.

1 is a graph measuring the weight support index (WBI) for five groups of mice of the present invention.
Figure 2 is a graph measuring the avoidance response threshold (PWT) for five groups of mice of the present invention.

The present invention relates to a composition which can contain the herbal extract fat-soluble fraction extract as an active ingredient to improve, prevent or treat pain relief.

The composition of the present invention may be inhaled or applied to the skin as a fragrance, or may be used in various ways such as oral or parenteral administration and ingestion as a food.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.

The composition which can improve, prevent or treat the pain relief of the present invention contains a fat-soluble fraction mixed extract including a fir fat-soluble fraction extract, an active fat-soluble fraction extract, an upper limb-soluble fraction extract, and a peppermint fat-soluble fraction extract as an active ingredient.

The firs are evergreen needle-leaved large tall trees of pineaceae, growing about 30-40 m in height, and the present invention uses fir leaves.

The poisonous (獨 活) early spring young edible edible, fall leaves in the fall and cover the soil so that the young sprout grows long, roots are medicinal in muscle pain, paraplegia, headache, paralysis of the half body is used. In the present invention, the root of poison is used.

The upper limbs (桑枝) as a medicinal herbs dried mulberry (Morrus alba L.) of the mulberry family, it is used for branch action, antibacterial action, bowel movement inhibiting action, blood pressure lowering action.

The said mint is menthol as a main component, and this menthol can be used for a coating agent, an analgesic agent, an exciter agent, a dry agent, an insect repellent, etc.

The fir fat soluble fraction extract, active fat soluble fraction extract, upper limb soluble fraction extract and mint fat soluble fraction extract is a weight ratio of 1: 0.3-1: 0.1-0.8: 0.3-1, preferably 1: 0.5-0.9: 0.4-0.7: Mix in a weight ratio of 0.5-0.9. When the weight ratio of the active fat soluble fraction extract, upper limb soluble fraction extract and peppermint fat soluble fraction extract based on the fir fat soluble fraction extract is lower than the lower limit, the effect on pain may be significantly lowered, and when the upper limit is exceeded, the preference of flavor is lowered. And rashes when applied to the skin.

Each fat-soluble fraction extract of the present invention can be extracted by supercritical extraction or steam distillation extraction.

The supercritical extraction method obtains a fat-soluble fraction extract of each of the firs, venom, upper limbs and mints under supercritical conditions at a pressure of 300 to 400 bar and a temperature of 40 to 60 ° C. The solvent is not particularly limited as long as it can obtain a fir fat soluble fraction extract, a poisonous fat soluble fraction extract, an upper limb soluble fraction extract, and a peppermint fat soluble fraction extract, but for high extraction efficiency and excellent efficacy on pain, it is critical to use carbon dioxide using carbon dioxide. It is preferable to extract in the state (critical temperature of carbon dioxide: 31 degreeC, critical pressure: 74 bar).

In addition, the supercritical extraction conditions are different for high extraction efficiency and pain resistance for each material, specifically, the fir extracts are supercritical at a pressure of 340 to 360 bar and a temperature of 52 to 54 ° C .; The venom is extracted at a pressure of 350 to 370 bar and a supercritical state at a temperature of 49 to 53 ° C; The upper limb is extracted in a supercritical state at a pressure of 340 to 360 bar and a temperature of 49 to 52 ° C; The mint is preferably extracted in a supercritical state at a pressure of 350 to 370 bar and a temperature of 46 to 51 ° C.

When the pressure during the supercritical extraction is less than the lower limit, the fat-soluble fraction may be hardly extracted from the herbal medicine, and when the upper limit is exceeded, the odor may disappear. In addition, when the supercritical extraction temperature is less than the lower limit, the extraction efficiency may be low, and when the upper limit is exceeded, the efficacy for pain may be lowered.

In addition, the steam distillation extraction method is based on the principle of volatilizing, quenching and concentrating the essential oil components on the surface or tissue of the herbal medicine with water vapor, pressure of 10 to 30 bar, temperature of 100 to 120 ℃ and 7 to 9 hours Obtain a fat-soluble fraction extract of each of the firs, venom, upper limbs and mints in the time state of.

At this time, the water vapor distillation extraction conditions are different for high extraction efficiency and pain resistance for each material, specifically, the fir is extracted at a pressure of 13 to 14 bar, 113 to 115 ℃ temperature and 7.5 to 8.5 hours; The venom was extracted at a pressure of 13 to 15 bar, a temperature of 118 to 120 ° C. and 7 to 8 hours; The upper liquor was extracted at a pressure of 14 to 16 bar, a temperature of 112 to 114 ° C. and 7 to 8 hours; The mint is preferably extracted at a pressure of 15 to 17 bar, a temperature of 115 to 117 ° C and 7 to 8 hours.

When the water vapor distillation extraction is less than the lower limit, the fat-soluble fraction may be hardly extracted from the herbal medicine, and when the upper limit is exceeded, the odor may disappear. In addition, the extraction efficiency may be low when the temperature of the steam distillation extraction is less than the lower limit, it may be lower the efficacy for pain rather than the upper limit. In addition, when the time of the steam distillation extraction is less than the lower limit, the fat-soluble fraction may be hardly extracted from the herbal medicine, and when the upper limit is exceeded, the odor may be altered.

The supercritical extraction method (yield: 0.4 to 5%) or the steam distillation extraction method (yield: 0.2 to 5%) of the present invention has better fragrance and extraction efficiency compared to other extraction methods such as compression and solvent dialysis. High and have better efficacy against pain. The yields of the compression method and the solvent dialysis method are 0.001 to 0.01%, respectively.

The 'extraction efficiency' refers to the amount of fir fat soluble fraction extract, active fat soluble fraction extract, upper limb soluble fraction extract and peppermint fat soluble fraction extract.

The composition of the present invention can be adsorbed to the carrier to release the fragrance and composition slowly for a long time, the carrier is preferably wrinkled porous silica particles, in order to further adsorb the volatile organic compounds contained in the composition of the present invention Preference is given to using porous silica particles whose surfaces are modified with silanol groups, amine groups or epoxy groups.

The fat-soluble fraction extract prepared as described above may be used as the extract itself or powdered for convenient use. The drying method performed to powder the extract may be lyophilization, cold air drying or natural drying, but it is preferable to use a lyophilization method in order to obtain powder without deterioration of ingredients.

On the other hand, the term 'containing as an active ingredient' herein means containing an amount sufficient to achieve the efficacy or activity of the fat-soluble fraction extract. In one example, the fat-soluble fraction extract is used at a concentration of 10 to 1500 mg / kg, preferably 100 to 1000 mg / kg. Since the fat-soluble fraction extract has no side effects on the human body even when it is excessively administered as a natural product, the upper limit of the amount of the fat-soluble fraction extract included in the composition of the present invention can be performed by those skilled in the art by selecting within an appropriate range.

The pharmaceutical composition of the present invention may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant may include excipients, disintegrants, sweeteners, binders, coatings, swelling agents, lubricants, Lubricants, flavors and the like can be used.

The pharmaceutical composition may be preferably formulated into a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers in addition to the active ingredient described above for administration.

Formulation forms of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, nontoxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders include but are not limited to natural and synthetic gums such as starch, gelatin, glucose or beta-lactose, corn sweeteners, acacia, trackercance or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.

Acceptable pharmaceutical carriers in compositions formulated in liquid solutions are sterile and physiologically compatible, including saline, sterile water, Ringer's solution, buffered saline, albumin injectable solutions, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers and bacteriostatic agents may be added as necessary. Diluents, dispersants, surfactants, binders and lubricants may also be added in addition to formulate into injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.

Furthermore, the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA can be formulated according to each disease or component according to the appropriate method in the art.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, or the like. .

Suitable dosages of the pharmaceutical compositions of the invention vary depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, condition of food, time of administration, route of administration, rate of excretion and response to reaction, Usually a skilled practitioner can easily determine and prescribe a dosage effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dose of the pharmaceutical composition of the present invention is 0.001-10 g / kg.

The pharmaceutical compositions of the present invention may be prepared in unit dosage form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Or may be prepared by incorporation into a multi-dose container. In this case, the formulation may be in the form of a solution, suspension or emulsion in an oil or an aqueous medium, or may be in the form of extracts, powders, granules, tablets or capsules, and may further include a dispersant or stabilizer.

The present invention also provides a food composition for alleviating, improving, preventing or treating pain containing the fat-soluble fraction extract as an active ingredient.

The food composition according to the present invention may be formulated in the same manner as the pharmaceutical composition, used as a functional food, or added to various foods. Examples of the food to which the composition of the present invention may be added include beverages, alcoholic beverages, confectionary, diet bars, dairy products, meat, chocolates, pizza, ramen noodles, other noodles, gums, ice creams, vitamin complexes, and health supplements. Etc.

The food composition of the present invention may include not only fat-soluble fraction extracts as active ingredients, but also components commonly added in food preparation, and include, for example, proteins, carbohydrates, fats, nutrients, seasonings, and flavoring agents. . Examples of the above carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As the flavoring agent, natural flavoring agents (tauumatin, stevia extract (for example rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared with a drink and a beverage, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts may be further included in addition to the fat-soluble fraction extract of the present invention. .

The present invention provides a health functional food comprising a food composition for alleviating, improving, preventing or treating pain including the fat-soluble fraction extract as an active ingredient. Health functional food is a food prepared by adding fat-soluble fraction extract to food materials such as beverages, teas, spices, gums, confectionery, or by encapsulating, powdering, and suspension. This means, unlike general medicines, there is no side effect that can occur when taking long-term use of medicines as food raw materials. The health functional food of the present invention thus obtained is very useful because it can be consumed on a daily basis. The amount of the fat-soluble fraction extract in such a dietary supplement can not be uniformly defined depending on the kind of the dietary supplement, but may be added within a range that does not impair the original taste of the food. 0.01 to 50% by weight, preferably 0.1 to 20% by weight. In addition, in the case of a health functional food in the form of pills, granules, tablets or capsules, it is usually added in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the dietary supplement of the present invention may be in the form of pills, tablets, capsules or beverages.

The present invention also provides the use of a fat-soluble fraction extract for the manufacture of a medicament or food for the relief, amelioration, prevention or treatment of pain. As described above, the fat-soluble fraction extract may be used for the purpose of alleviating, improving, preventing or treating pain caused by side effects of chemotherapy.

The present invention also provides a method for alleviating, ameliorating, preventing or treating pain comprising administering to a mammal an effective amount of an oil soluble fraction extract.

As used herein, the term "mammal" refers to a mammal that is the subject of treatment, observation or experiment, preferably human.

As used herein, the term “effective amount” means an amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human, as contemplated by a researcher, veterinarian, doctor or other clinician, Amounts that induce alleviation of the symptoms of the disease or disorder. It will be apparent to those skilled in the art that the effective amount and frequency of administration for the active ingredients of the present invention will vary depending on the desired effect. Therefore, the optimal dosage to be administered can be readily determined by one skilled in the art and includes the type of disease, the severity of the disease, the amount of active ingredients and other ingredients contained in the composition, the type of formulation, and the age, weight, general health of the patient. It may be adjusted according to various factors including the condition, sex and diet, time of administration, route of administration and the rate of secretion of the composition, the duration of treatment, and the drugs used simultaneously. In the prophylactic, therapeutic or ameliorating method of the present invention, in adults, when the fat-soluble fraction extract is administered once to several times a day, it is preferable to administer at a dose of 0.001 g / kg to 10 g / kg.

The composition comprising the fat-soluble fraction extract as an active ingredient in the treatment method of the present invention may be administered in a conventional manner through oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, intraocular or intradermal routes. Can be administered.

Hereinafter, preferred examples are provided to aid the understanding of the present invention, but the following examples are merely for exemplifying the present invention, and it will be apparent to those skilled in the art that various changes and modifications can be made within the scope and spirit of the present invention. It is natural that such variations and modifications fall within the scope of the appended claims.

Preparation Example 1 Using Steam Distillation Extraction

Fir, venom, upper limb and peppermint were dried to 5% water content, and the extracts were obtained by steam distillation extraction, respectively.

In order to efficiently extract the natural essential oil using the steam distillation extraction method, pressure, temperature conditions and extraction time are very important, extraction was performed by different sample conditions to obtain a high yield.

[Equation 1]

division Pressure (bar) Temperature (℃) Hours (hr) yield(%) fir 13-14 113-115 7.5-8.5 4.90 Poisonous 13-15 118-120 7-8 0.34 Upper limb 14-16 112-114 7-8 0.27 mint 15-17 115-117 7-8 0.54

Production Example  2. Supercritical  Extraction method

After firing, poisonous, upper limbs and peppermint were dried to 5% moisture content, they were placed in a supercritical extractor (ILSHIN Auto, Korea) using a recycling method of supercritical carbon dioxide, and then injected with carbon dioxide to obtain a fat-soluble fraction extract under supercritical conditions. Extraction was measured (%). At this time, the flow rate of carbon dioxide is 30 g / min.

division Pressure (bar) Temperature (℃) Hours (hr) yield(%) fir 340-360 52-54 8-8.5 2.43 Poisonous 350-370 49-53 7-9.5 0.47 Upper limb 340-360 49-52 8.5-9.5 3.70 mint 350-370 46-51 8-9.5 4.51

As shown in Tables 1 and 2, it was confirmed that the yields of the fat-soluble fraction extracts extracted by firing, poisonous, upper limbs and peppermint each by supercritical extraction were higher than the yields of the fat-soluble fractions extracted by steam distillation extraction.

Thus, the experiment was performed using the fat-soluble fraction extract extracted by the supercritical extraction method.

Example 1 fat soluble fraction mixed extract

The fir fat soluble fraction extract, the active fat soluble fraction extract, the upper limb soluble fraction extract, and the peppermint fat soluble fraction extract extracted by supercritical extraction were mixed in a weight ratio of 1: 0.83: 0.66: 0.83.

<Test Example>

Animal experiment

190-220 g of Sprague-Dawley rats (Central Lab. Animal Inc., Korea, Male) were used for the experiment. It was raised in a polycarbonate cage (280W X 420D X 180H mm), supplied with sufficient feed and water, and controlled for 12 hours of day and night with appropriate artificial light (day from 7:00 am). And maintained a constant temperature (20 ~ 24 ℃) and humidity (40 ~ 60%). They spent a week looking to adapt to the changed environment, maintaining a sleep cycle and confirming abnormal behavior.

For the experiment, degenerative arthritis was induced by a single dose of 5 mg of MIA (Monosodium iodoacetate, 60 mg / ml) in the rat hind limb joints except the normal group.

The experimental animals were selected only healthy animals with constant weight change, and the normal group administered physiological saline by random placement method, the negative control group administered olive oil 1 day after MIA, and the extract of Example 1 1 day after MIA. One sample administration group, one day after MIA administration, was divided into a positive control group administered with aspirin, and 6 animals were used in each experimental group.

At this time, the olive oil, the extract of Example 1 and aspirin were forcibly administered once a day from the start of administration using a disposable syringe within 21 stomachs for 3 weeks.

The extract of Example 1 was dissolved in saline at the following concentrations (100, 400 mg / kg) and orally administered 10 ml / kg.

5 groups of mice

Normal group: 6 saline solution administered 3 weeks_1 mg / kg / day

Negative control: 6 animals at 3 weeks olive oil 1 day after MIA_1 mg / kg / day

Example 1 (100): 6 extracts of Example 1 1 day after MIA administration_100 mg / kg

Example 1 (400): 6 extracts of Example 1 1 day after MIA administration_400 mg / kg

Positive control group: 6 animals aspirin 3 weeks after 1 day of MIA_150 mg / kg / day

The aspirin dose is a value obtained by calculating a dose applied to a test animal based on the highest dose of 1500 mg / kg administered to arthritis.

Experimental Example 1. Pain Test_Weight (weight bearing index)

WBI was measured on day 3, 7, 14 and 21 after administration of the test substance, and measured using a static weight bearing test device (SWB-TOUCH-R, Bioseb, Boulogne, France). Animals were placed in an inclined acrylic chamber and the hind limbs were placed on separate pressure sensors, and the force carried on each hind limb was measured three times for 5 seconds, using the following [Equation 2]. The more painful the test, the less the legs, the less weight they carry.

[Equation 2]

1 is a graph measuring the weight support index (WBI) for the five groups of mice of the present invention, Table 3 is a numerical value of the graph of FIG.

division 3day 7 day 14 day 21 day Normal 49.4 49.6 49.4 51.1 Negative control 28.0 33.6 39.8 40.9 Example 1 (100) 29.3 40.3 44.9 46.4 Example 1 (400) 34.2 39.1 46.4 48.0 Positive control 35.5 40.1 47.2 49.1

As shown in Table 3 and FIG. 1, the fat-soluble fraction mixed extract prepared according to Example 1 of the present invention showed a high level compared to the negative control, and showed similar values to the normal group and the positive control group. It was.

It was confirmed that the arthritis pain was severe enough to be similar to the negative control group up to 3 days in the group administered with 100 mg / kg of the fat-soluble fraction mixed extract of Example 1, but arthritis pain improved from 7 days.

In addition, the group administered with 400 mg / kg of the fat-soluble fraction mixed extract of Example 1 was confirmed that arthritis pain improves continuously from 3 days.

Experimental Example 2. Pain test_PawT (paw withdrawal threshold)

The avoidance response threshold (PWT) was measured 3, 7, 14, and 21 days after administration of the test substance, and an analgesy meter (Ugo Basile Srl, VA, Italy) was used to assess the pressure on the affected leg. ) Was measured. The animal's hind paw was placed on the lumbar spine and the pedal slowly increased pressure on the lumbar spine and the pressure measured by the animal trying to escape the leg from the instrument. The more sensitive you are to pain, the lower the pressure to escape your legs.

Figure 2 is a graph measuring the avoidance response threshold (PWT) for five groups of mice of the present invention, Table 4 is a numerical value of the graph of FIG.

division 3day 7 day 14 day 21 day Normal 467.5 540.8 552.5 495.0 Negative control 148.3 244.2 166.7 186.7 Example 1 (100) 398.3 260.8 216.7 269.2 Example 1 (400) 237.5 167.5 122.5 210.8 Positive control 337.5 162.5 160.0 269.2

As shown in Table 4 and Figure 2, the fat-soluble fraction mixed extract prepared according to Example 1 of the present invention showed a high value compared to the negative control, it was confirmed that a little higher or similar to the positive control It was.

Specifically, the group administered with the fat-soluble fraction mixed extract of Example 1 at 100 mg / kg and 400 mg / kg was confirmed to improve arthritis pain until 3 days.

Hereinafter, a preparation example of a composition containing an extract of the present invention will be described, but the present invention is not intended to be limited thereto but only to be described in detail.

Formulation Example 1 Preparation of Powder

Fat-Soluble Fraction Extract in Example 1           500 mg

Lactose 100 mg

Talc 10 mg

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

Formulation Example 2 Preparation of Tablet

300 mg fat-soluble fraction extract in Example 1

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

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

Formulation Example 3 Preparation of Capsule

200 mg fat-soluble fraction extract in Example 1

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

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

Formulation Example 4 Preparation of Injection

600 mg fat-soluble fraction extract in Example 1

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

_{Na 2 HPO 4 · 12H 2 O} 26 mg

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

Formulation Example 5 Preparation of Liquid

4 g fat-soluble fraction extract in Example 1

10 g of isomerized sugar

5 g of mannitol

Purified water

After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding a proper amount of lemon flavor, and then mixing the above components, adding purified water to adjust the total to 100 g by adding purified water, and then filled in a brown bottle The solution is prepared by sterilization.

Formulation Example 6 Preparation of Granules

1,000 mg fat-soluble fraction extract in Example 1

Vitamin mixture proper amount

Vitamin A Acetate 70 mg

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

Vitamin B12 0.2 mg

Vitamin C 10 mg

Biotin 10 mg

Nicotinamide 1.7 mg

Folic acid 50 mg

Calcium Pantothenate 0.5 mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

15 mg potassium monophosphate

Dicalcium Phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is a composition which is relatively suitable for granules in a preferred embodiment, the composition ratio may be arbitrarily modified, and the above components are mixed according to a conventional granulation method and then granulated. It can be prepared and used in the manufacture of health functional food composition according to a conventional method.

Formulation Example 7 Preparation of Functional Beverage

1,000 mg fat-soluble fraction extract in Example 1

Citric Acid 1,000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 mL of purified water

After mixing the above components according to the conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated Used to prepare functional beverage compositions of the invention.

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

Formulation Example 8 Preparation of Cosmetics in Emulsion Formulation

Cosmetics of emulsion formulations such as nutrient cosmetics, creams and essences, and cosmetics of solubilized formulations such as softening cosmetics were prepared.

To the cosmetic composition was prepared in the composition shown in Table 5. The manufacturing method is as follows.

1) The mixture which mixed the raw materials of 1-9 was heated at 65-70 degreeC.

2) 10 was added to the mixture of step 1).

3) The mixture of the raw materials of 11-13 was heated to 65-70 degreeC, and completely dissolved.

4) Through step 3), the mixture of 2) was slowly added to emulsify for 2 to 3 minutes at 8,000 rpm.

5) The raw material of 14 was dissolved in a small amount of water, and then added to the mixture of step 4) and emulsified for 2 minutes.

6) 15 to 17 of the raw materials were weighed, respectively, and added to the mixture of step 5) and emulsified for 30 seconds.

7) After the emulsification of the mixture of step 6) through a degassing process to cool to 25 ~ 35 ℃ to prepare an emulsion cosmetic.

Furtherance Emulsifier 1 Emulsifier 2 Emulsifier 3 One Stearic acid 0.3 0.3 0.3 2 Stealy alcohol 0.2 0.2 0.2 3 Glyceryl Monostearate 1.2 1.2 1.2 4 Beeswax 0.4 0.4 0.4 5 Polyoxyethylene sorbitan
Monolauric acid ester 2.2 2.2 2.2 6 Methyl paraoxybenzoate 0.1 0.1 0.1 7 Paraoxybenzoic Acid Profiles 0.05 0.05 0.05 8 Cetylethylhexanoate 5 5 5 9 Triglycerides 2 2 2 10 Cyclomethicone 3 3 3 11 Distilled water To 100 To 100 To 100 12 Concentrated glycerin 5 5 5 13 Triethanolamine 0.15 0.15 0.15 14 Polyacrylic acid polymer 0.12 0.12 0.12 15 Pigment 0.0001 0.0001 0.0001 16 incense 0.10 0.10 0.10 17 Fat-Soluble Fraction Extract of Example 1 0.0001 One 10

Formulation Example 9 Preparation of Cosmetics in Solubilized Formulations

To the cosmetic composition of the solubilizing agent type was prepared in the composition shown in Table 6. The manufacturing method is as follows.

1) Raw materials 2 to 6 were placed in raw material 1 (purified water) and dissolved using a still mixer.

2) The raw materials of 8-11 were put into the raw material of 7 (alcohol), and it melt | dissolved completely.

3) The mixture of step 2) was solubilized with slow addition to the mixture of step 1).

Furtherance Solubilized Formulation 1 Solubilized Formulation 2 Solubilized Formulation 3 One Purified water To 100 To 100 To 100 2 Concentrated glycerin 3 3 3 3 1,3-butylene glycol 2 2 2 4 EDTA-2Na 0.01 0.01 0.01 5 Pigment 0.0001 0.0002 0.0002 6 Fat-Soluble Fraction Extract of Example 1 0.1 5 5 7 Alcohol (95%) 8 8 8 8 Methyl paraoxybenzoate 0.1 0.1 0.1 9 Polyoxyethylene
Hydrogenated Ester 0.3 0.3 0.3 10 incense 0.15 0.15 0.15 11 Cyclomethicone - - 2

Claims (8)

A pharmaceutical composition for alleviating, preventing or treating pain, comprising a fat-soluble fraction mixed extract comprising an fir fat-soluble fraction extract, an active fat-soluble fraction extract, an upper-fat-soluble fraction extract, and a peppermint fat-soluble fraction extract. The pharmaceutical composition for alleviating, preventing or treating pain of claim 1, wherein each of the fat-soluble fraction extracts is a fat-soluble fraction extract extracted by a supercritical extraction method or a steam distillation extraction method. The pharmaceutical composition for alleviating, preventing or treating pain of claim 2, wherein the solvent is carbon dioxide during supercritical extraction. The method of claim 1, wherein the fir fat soluble fraction extract, active fat soluble fraction extract, upper limb soluble fraction extract and peppermint fat soluble fraction extract is characterized in that the pain is mixed in a weight ratio of 1: 0.3-1: 0.1-0.8: 0.3-1 Pharmaceutical compositions for palliative, prophylactic or therapeutic treatment. The method of claim 1, wherein the pain is somatic pain, visceral pain, inflammatory pain, dysfunction pain, idiopathic pain, superficial pain, deep pain, migraine And cancer pain, the pharmaceutical composition for alleviating, preventing or treating pain, characterized in that at least one selected from the group consisting of. A health functional food for alleviating, preventing or improving pain, comprising a fat-soluble fraction mixed extract including an fir fat-soluble fraction extract, an active fat-soluble fraction extract, an upper-fat-soluble fraction extract, and a peppermint fat-soluble fraction extract. A fragrance composition for alleviating, preventing or treating pain, comprising a fat-soluble fraction mixed extract comprising an fir fat-soluble fraction extract, an active fat-soluble fraction extract, an upper-fat-soluble fraction extract, and a peppermint fat-soluble fraction extract. A cosmetic composition for alleviating, preventing or ameliorating pain, comprising a fat-soluble fraction mixed extract including an fir fat-soluble fraction extract, a poisonous fat-soluble fraction extract, an upper-fat-soluble fraction extract, and a peppermint fat-soluble fraction extract.

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