WO2018008973A1

WO2018008973A1 - Composition comprising forsythiae fructus extract as effective ingredient for preventing, ameliorating or treating peripheral neuropathy

Info

Publication number: WO2018008973A1
Application number: PCT/KR2017/007168
Authority: WO
Inventors: 방옥선; 김노수; 김진희; 이진무; 이유진; 김영아
Original assignee: 한국 한의학 연구원
Priority date: 2016-07-06
Filing date: 2017-07-05
Publication date: 2018-01-11
Also published as: KR101732483B1

Abstract

The present invention relates to a composition comprising a Forsythiae Fructus extract as an effective ingredient for preventing, ameliorating or treating peripheral neuropathy, particularly chemotherapy-induced peripheral neuropathy (CIPN). In detail, a Forsythiae Fructus extract of the present invention relieves the neurotoxicity and neurite growth suppression induced by anticancer agents, and effectively reduces sensitivity to increased pain stimuli in animal models with chemotherapy-induced peripheral neuropathy while not affecting the inherent cytotoxicity of anticancer agents in human cancer cell lines.

Description

Composition for the prevention, improvement or treatment of peripheral neuropathy containing poncho extract as an active ingredient

The present invention relates to a composition for the prevention, improvement or treatment of peripheral neuropathy (peripheral neuropathy) containing a Forsythiae Fructus extract as an active ingredient.

Peripheral neuropathy is caused by a disease that directly damages or affects nerve tissue. Depending on the type of nerve tissue affected, sensory neuropathy and motor neuropathy neuropathy) and autonomic neuropathy. In sensory neuropathy, sensation of touch and tremor, sensation of temperature change, tingling or burning pain, and allodynia in the skin are experienced. Motor neuropathy is accompanied by loss of balance and muscle weakness.In autonomic neuropathy, the ability to control the bladder is weakened depending on the organs affected by the nerve, resulting in incontinence or abnormal blood pressure and heart rate. Induced (RA Hughes, 2002, BMJ, v324, pp466-469; JM Torpy et al., 2010, JAMA, v303, p1556).

Various factors have been suggested as a cause of peripheral neuropathy. Genetic disorders, metabolic and endocrine system diseases, inflammatory diseases, vitamin deficiency, and anticancer drugs administered during cancer treatment are known to cause the onset. Among these, chemotherapy-induced peripheral neuropathy (CIPN) caused by chemotherapy should reduce the dose of chemotherapy given to the patient depending on the severity of symptoms or, in severe cases, stop chemotherapy itself. It has a very negative side effect. It is known that about one third of patients receiving chemotherapy experience CIPN, and one third of patients experiencing CIPN are permanently damaged (A. Bhagra, RD Rao, 2007, Curr). Oncol Rep, v9, pp 290-299). CIPN-related symptoms include numbness, tingling, burning, cold and pain in the fingers and toes, and loss of feel and strength (T. Armstrong et al., 2005) , Oncol Nurs Forum, v32, pp305-311; C. Visovsky et al., 2008, Clin J Oncol Nurs, v12, pp243-247).

Anticancer agents known to cause CIPN include platinum, taxane, vinca alkaloids, bortezomib or thalidomide, and the incidence of CIPN depends on the type and dose of anticancer agent used. And 20-75%, depending on the duration of administration (G. Cavaletti et al., 2011, Curr Treat Options Neurol, v13, pp180-190). Currently, the mechanism of neurotoxicity caused by anticancer drugs is not exactly known. However, it is assumed that the mechanisms by which anticancer drugs act on general cancer cells and the mechanisms on peripheral nervous system cells are similar to each other. It is known that anticancer agents administered to patients accumulate not only in cancer tissues but also in the peripheral nervous system, and the accumulation of such anticancer agents eventually causes neurotoxicity and cause CIPN.

To date, there is no standard treatment approved by the US FDA for the treatment of CIPN. Clinically, anticonvulsants such as gabapentin or antidepressants such as amitriptyline have been used to alleviate the symptoms of CIPN. However, large-scale clinical trials of CIPN have not been proven effective. In addition, these drugs have side effects such as dizziness and drowsiness, and have a disadvantage in that high dose administration is impossible due to a low safety margin. Therefore, due to the lack of medical care of CIPN, there is an urgent need to develop new materials for safer and more effective CIPN treatment and prevention. Since CIPN is a disease with multiple mechanisms, it is considered appropriate to develop a multi-target-based material, and medicinal plants or natural materials, which have been used traditionally, may be treated as important starting materials from the viewpoint of this material development strategy.

Meanwhile, Forsythia Fructus refers to the dried fruit of the ash of Forsythia viridissima Lindley or Forsythia suspensa Vahl, which is used as a medicinal herb in Japan, but in China It is known to use only dried fruit of Dangari forsythia without using. Yeon-kyo is the name that fruit is formed in a room similar to lotus, and it rises long among various grasses. Or, if a seed is split, a piece and a piece are similar to feathers, so it is known that it is called a bridge using a kite that means 'to touch' and a bridge that means 'feather'. This drug has a peculiar smell, its bitter taste, and a little cold.

The drug has the effect of lowering and detoxifying the fever, eliminating wind and fever, and causing boils and cuts to swell, swell, or loosen the swelling. Therefore, the fever can be lowered early in the fever to reduce the fever and mental confusion, or can be used to boil, lymphadenitis, and sore throat. In ideology, it is a medicine that can be used by Soyangin. As a pharmacological action, antibacterial action, anti-inflammatory action, blood pressure drop, hemostatic action, liver treatment action, antipyretic effect, clay, diuretic action have been reported. The main chemicals include forsythol, sterol compounds, saponins, and oleanolic acids. Appearance is oval or long oval granules, with pointed ends and fruit stems at the base. The outer surface is light brown or dark brown with scattered light gray small ridges and two vertical grooves. The well-done splits along the longitudinal groove and the end is twisted. The inside of the split rind is yellowish brown with a septum in the middle. Seeds have elongated oval wings.

Korean Patent Publication No. 2016-0062303 discloses a composition for the prophylaxis or treatment of an immune disease containing a duct extract, and Korean Patent Publication No. 2009-0047501 contributes to the treatment of neuropathy induced by chemotherapy. It is disclosed with respect to the method and pharmaceutical preparations, Korean Patent Publication No. 2014-0123444 discloses a pharmaceutical composition and health functional food for the prevention or treatment of cancer comprising a natural product extract as an active ingredient, There is no disclosure regarding a composition for preventing, improving or treating peripheral neuropathy containing the extract as an active ingredient.

The present invention is derived from the above requirements, the present invention provides a composition for preventing, ameliorating or treating peripheral neuropathy containing a duct extract as an active ingredient. The present invention reduces pain response by administering the duct extract to an animal model in which peripheral neuropathy was induced by the administration of oxaliplatin, and inhibited neuronal toxicity and neurite growth by oxaliplatin as the duct extract was treated in nerve cells. The present invention was completed by confirming that the mitigatory extract did not affect the cytotoxicity of lung cancer and colorectal cancer cell lines by oxaliplatin.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of peripheral neuropathy (peripheral neuropathy) containing a duct extract as an active ingredient.

In addition, the present invention provides an anticancer adjuvant containing the duct extract as an active ingredient.

In addition, the present invention provides a health functional food composition for the prevention or improvement of peripheral neuropathy (peripheral neuropathy) containing a duct extract as an active ingredient.

The present invention relates to a composition for the prevention, improvement or treatment of peripheral neuropathy (peripheral neuropathy), in particular, chemotherapy-induced peripheral neuropathy caused by an anticancer agent, containing as a active ingredient extract, specifically Yeongyo extract of the present invention does not affect the intrinsic cytotoxic effects of anticancer agents in human cancer cell lines, and at the same time mitigates neuronal cytotoxicity and neurite growth inhibition by anticancer agents, and increased pain in animal models of anticancer drug induced peripheral neuropathy. The effect is to effectively reduce the sensitivity to stimulation.

1 is a ratio of cells forming neurites when treated with increasing concentrations of GF extracts of the present invention (WEFF) sequentially in PC-12 cells induced with nerve growth factor (NGF) (A ) And a graph showing the sum of the lengths of the grown neurites (B) and the effect of the neurites growing under a microscope (C).

a: PC-12 cells treated with (+) NGF, nerve growth factor (100 ng / ml);

b: PC-12 cells treated with (+) NGF + Oxal (200nM) + V, nerve growth factor (100ng / ml), oxaliplatin (200nM) and PBS as vehicle;

c: PC-12 cells treated with (+) NGF + Oxal + WEFF (12.5 μg / ml), nerve growth factor (100 ng / ml), oxaliplatin (200 nM) and soft water extract (12.5 μg / ml);

d: PC-12 cells treated with (+) NGF + Oxal + WEFF (25 μg / ml), nerve growth factor (100 ng / ml), oxaliplatin (200 nM) and soft water extract (25 μg / ml);

e: PC-12 cells treated with (+) NGF + Oxal + WEFF (50 μg / ml), nerve growth factor (100 ng / ml), oxaliplatin (200 nM) and soft water extract (50 μg / ml); And

f: PC-12 cells treated with (+) NGF + Oxal + WEFF (100 μg / ml), nerve growth factor (100 ng / ml), oxaliplatin (200 nM), and soft water extract (100 μg / ml),

*** means that there is a statistically significant difference ( p <0.001) compared to the (+) NGF treatment group (a), and #, ## or ### compared to the NGF + Oxal + V treatment group (b) This means that there is a significant difference (#, p <0.05;##, p <0.01;###, p <0.001).

Figure 2 shows that after the induction of neuronal differentiation of PC-12 cells using nerve growth factors, the treatment of oxaliplatin induced the toxicity of neurons and the duct extract of the present invention protects neurons. ** indicates that the toxicity of neurons was statistically significant by treatment with oxaliplatin as compared to PC-12 cells ((-) Oxal + (-) WEFF) not treated with oxaliplatin, p <0.01 , ## means that when treated with ductile water extract of the present invention compared to the control treated with oxaliplatin and vehicle (PBS), there is a statistically significant neuroprotective effect of reducing the toxicity of neurons, p < 0.01.

Figure 3 is injected once a week, 10 times / total (20 mg / kg) intraperitoneal injection of 10 mg / kg oxaliplatin to induce peripheral neuropathic pain in the mouse model (C57BL / 6), pontoon water extract (WEFF) is a graph showing the weight change measured by daily oral administration.

4 is a result of confirming the change in the pain response rate according to administration of oxaliplatin to C57BL / 6 mice to induce peripheral neuropathy and administration of ductal water extract of the present invention.

** and *** indicate a statistically significant increase in pain response in animal models administered oxaliplatin compared to normal, ** is p <0.01, and *** is p <0.001. In the experiment, the test was performed with von Frey filament with 0.4g (A) and 0.16g (B) bending force.

##, ### indicates that the oxaliplatin administered group compared to the oxaliplatin + vehicle (0.5% CMC solution) administration group, and the response to pain in the group administered the ductal water extract of the present invention statistically significantly reduced ## is p <0.01 and ### means p <0.001.

Figure 5 is a result confirming the relative viability of the lung cancer cell lines (A549, A) and colon cancer cell lines (HCT116, B) treated with the ductile water extract of the present invention in combination with oxaliplatin.

The present invention relates to a pharmaceutical composition for the prevention or treatment of peripheral neuropathy (peripheral neuropathy) containing a duct extract as an active ingredient.

The duct bridge extract is preferably extracted with water, a lower alcohol of C ₁ ~ C ₄ or a mixture thereof as a solvent, the lower alcohol is preferably methanol or ethanol. The duct bridge extract is preferably prepared by a manufacturing method including the following steps, but is not limited thereto.

1) extracting by adding an extraction solvent to the bridge;

2) filtering the extract of step 1); And

3) drying the filtered extract of step 2) under reduced pressure.

In the above method, the bridge of step 1) can be used without limitation, such as grown or commercially available.

In the above method, as the extraction method of the duct bridge extract of step 1), conventional methods in the art such as filtration, hot water extraction, dipping extraction, reflux cooling extraction, and ultrasonic extraction may be used. The extraction solvent is preferably extracted by adding 2 to 40 times the volume based on the weight of the dried duct bridge. Extraction temperature is preferably 20 ~ 100 ℃ but is not limited thereto. In addition, the extraction time is preferably 0.5 to 10 hours, more preferably 1 to 4 hours, most preferably 2 hours is not limited thereto. In addition, the extraction is preferably repeated 2-3 times, but is not limited thereto.

In the above method, the decompression concentration in step 3) preferably uses a vacuum decompression concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, the drying is preferably reduced pressure drying, vacuum drying, boiling drying, spray drying or freeze drying, but is not limited thereto.

The peripheral neuropathy is preferably a chemotherapy-induced peripheral neuropathy induced by an anticancer agent, and the anticancer agent is a platinum-based, taxane-based, vinca alkaloids, bortezomib ( bortezomib) or thalidomide, including, but not limited to, all anticancer agents that are clinically, pharmacologically and biomedically available.

The platinum-based anticancer agent is preferably at least one selected from cisplatin, carboplatin, and oxaliplatin, and the taxane-based anticancer agent is preferably at least one selected from paclitaxel and docetaxel. It is not limited to this.

The pharmaceutical compositions of the present invention may be in various oral or parenteral formulations. In formulating the composition, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.

Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin. In addition to simple excipients, lubricants such as magnesium stearate, talc and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions or syrups, and include various excipients such as wetting agents, sweeteners, fragrances or preservatives, in addition to the commonly used simple diluents such as water and liquid paraffin. Can be.

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations or suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As a base of suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol, gelatin, and the like may be used.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and it is preferable to select an external skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injection method for parenteral administration. I never do that.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, the pharmaceutically effective amount means an amount sufficient to treat the disease at a reasonable benefit / risk ratio applicable to the medical treatment, and the effective dose level refers to the type, severity, drug activity, and drug of the patient. Sensitivity, time of administration, route of administration and rate of release, duration of treatment, factors including concurrent use of drugs, and other factors well known in the medical arts. The compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can achieve the maximum effect with a minimum amount without side effects, which can be readily determined by one skilled in the art.

The dosage of the composition of the present invention varies depending on the patient's weight, age, sex, health status, diet, time of administration, administration method, excretion rate and severity of the disease, the daily dosage is the amount of duct extract It is 0.01-1000 mg / kg, Preferably it is 30-500 mg / kg, More preferably, it is 50-300 mg / kg, It can be administered 1-6 times a day. However, the dosage may be increased or decreased depending on the route of administration, the severity of obesity, sex, weight, age, etc., and the above dosage does not limit the scope of the present invention in any way.

The pharmaceutical composition of the present invention is preferably used in combination with an anticancer agent, but may be used alone or in combination with methods using surgery, radiation therapy, hormonal therapy, and biological response modifiers.

In addition, the present invention relates to an anticancer adjuvant containing duct extract as an active ingredient. The anticancer adjuvant is preferably administered in combination with an anticancer agent including platinum, taxane, vinca alkaloids, bortezomib or thalidomide, and is caused by an anticancer agent. There is a characteristic that is effective in preventing or treating peripheral neuropathy.

The present invention also relates to a nutraceutical composition for the prevention or improvement of peripheral neuropathy (peripheral neuropathy) containing a duct extract as an active ingredient.

1) extracting by adding an extraction solvent to the bridge;

2) filtering the extract of step 1); And

3) drying the filtered extract of step 2) under reduced pressure.

The platinum-based anticancer agent is preferably at least one selected from cisplatin, carboplatin and oxaliplatin, and the taxane-based anticancer agent is preferably at least one selected from paclitaxel and docetaxel. It is not limited to this.

The health functional food composition may be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, and the like, but is not limited thereto and may be manufactured and processed in any form according to the law.

The composition containing the duct extract of the present invention as an active ingredient may be added as it is to food or used together with other food or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient can be suitably determined according to the purpose of use (prevention or improvement). In general, the amount of the extract in the health food can be added to 0.1 to 90 parts by weight of the total food weight. However, in the case of long-term intake for health and hygiene or health control purposes, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.

When the health functional food composition of the present invention is used as a beverage, there is no particular limitation on other ingredients except for containing the extract as an essential ingredient in the indicated ratio, and various flavors or natural carbohydrates are added as in the general beverage. It may contain as a component. Examples of the natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tautin, stevia extract (e.g., Rebaudioside A, glycyrginine, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. Can be.

In addition, the duct extract of the present invention is a variety of nutrients, vitamins, minerals (electrolytes), flavors such as synthetic and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. In addition, the duct extract of the present invention may contain natural fruit juice and fruit flesh for the production of fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The ratio of such additives is not so important, but is generally selected in the range of 0.1 to 20 parts by weight per 100 parts by weight of duct extract.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for explaining the present invention in more detail, it is obvious to those skilled in the art that the scope of the present invention is not limited by them.

1. Preparation of Forsythiae Fructus Water Extract (WEFF)

In order to prepare the duct bridge extract of the present invention, 100 g of the dried duct bridge purchased from Gwangmyeongdang Pharmaceutical Co., Ltd. (Ulsan, South Korea) was ground to prepare a sample in powder form. 100 g of ground dry sample and 2 l of water Put into a round flask and mix. A water bath connected to a reflux extractor with a cooling tube was heated and extracted twice, once every two hours. The extracted extract was filtered under reduced pressure using a paper filter paper (Whatman No. 2) and a vacuum pump (GAST). The filtered liquid extract was concentrated under reduced pressure using a rotary evaporator (YEYELA). The concentrated extract was lyophilized and then homogenized with a mortar and pestle to obtain soft water extract (WEFF). The resulting soft water extract was placed in a sealed plastic container and stored at 4 ° C. cold storage until the experiment.

2. Culture of Cells

1) Culture of PC-12 Cells

PC-12 cells to be used in the Examples for confirming the effect of the duct extract of the present invention is a rat-derived Chromocytocytoma (Pheochromocytoma), when the neuronal growth factor (NGF) is treated to finally differentiate into neurons It is a cell line that is useful as a cell model of neurological research because of its characteristics. PC-12 cells were treated with 5% (v / v) non-heat inactivated fetal bovine serum (FBS), 10% (v / v) heat inactivated horse serum (HS), Coating with collagen type I in an incubator maintained at 37 ° C., 5% (v / v) CO ₂ using DMEM growth medium containing 100 units / ml penicillin and 100 μg / ml streptomycin Cultured in a 100 mm cell culture dish.

2) Culture of Human Lung Cancer Cell (A549) and Human Colon Cancer Cell (HCT116)

Human lung cancer cells (A549) and human colon cancer cells (HCT116) were treated at 37 ° C. using RPMI1640 growth medium containing 10% (v / v) heat inactivated FBS, 100 units / ml penicillin, 100 μg / ml streptomycin. The cells were cultured in 100 mm cell culture dishes in an incubator maintained at 5% (v / v) CO ₂ and used for later in vitro experiments.

3. Preparation of Chemotherapy-induced Peripheral Neuropathy (CIPN) Animal Model

In order to carry out an embodiment of the present invention, a animal model of chemotherapy-induced peripheral neuropathy (CIPN) induced with oxaliplatin was prepared.

Specifically, 8-10 weeks old C57BL / 6 male mice were subjected to a purification period in a cage in an animal laboratory, followed by three baseline (BL), and group separation (N = 6 mice / group). Was carried out. Subsequently, 10 mg / kg of oxaliplatin was injected into the abdominal cavity for a total of 20 mg / kg over 2 weeks to induce peripheral neuropathic pain.

4. Statistical Processing

The results obtained in the examples of the present invention were expressed as mean ± standard deviation (mean ± SD) or mean ± standard error (mean ± SE), and the statistical mean comparison between groups was T-test and ANOVA / Tukey post-hoc. The test was conducted. p values were expressed as * <0.05, ** <0.01, *** <0.001.

Example 1 Confirmation of CIPN Inhibitory Effect of Pyrophyllum Water Extract in Vitro

Example 1-1. Determination of Neuronal Growth Inhibitory Effect of Yeon-kyo Water Extract

The neurite outgrowth inhibitory effect of the water extract of Fructus of the present invention was confirmed. Specifically, the cultured PC-12 cells were uniformly inoculated in a 24 well plate coated with collagen type IV at a concentration of 1 × 10 ⁴ cells / well, and then cultured in DMEM growth medium to adhere to the bottom surface. After 24 hours, the cells were replaced with DMEM medium containing 100 ng / ml neuronal growth factor (NGF) without serum to induce the production of neurites, and treated with 200 nM oxaliplatin to induce neurotoxicity.

The prepared soft water extract (WEFF) was treated at concentrations of 12.5, 25, 50, and 100 ㎍ / ml, respectively, and after 3 days, observed with an optical microscope to analyze the ratio of neurites-produced cells and the length of neurites. It was.

As a result, as shown in Figure 1, the neurites induced by the neuronal growth factor (NGF) is reduced by oxaliplatin treatment (NGF + Oxal), the ratio of cells forming the neurites (A) and the grown neurites It was confirmed that the sum of the lengths (B) was recovered by the duct water extract (WEFF), and the inhibition of neurites growth inhibition by oxaliplatin was relieved by the duct water extract (WEFF).

Example 1-2. Confirmation of Cytotoxic Protective Effects of Yeonkyo Water Extract

The protective effect of oxaliplatin (Oxaliplatin) on the cytotoxicity of the water extract of the present invention was confirmed. Specifically, the cultured PC-12 cells were uniformly inoculated into a 96 well plate coated with collagen type IV at a concentration of 2 × 10 ³ cells / well and then cultured in DMEM growth medium to adhere to the bottom surface. After 24 hours, differentiation into neurons was induced by replacing with DMEM medium containing 100 ng / ml of neuronal growth factor (NGF) without serum to induce neurites. Four days later, 200 nM of oxaliplatin was treated to induce cytotoxicity to neurons. The prepared soft water extract (WEFF) was treated at concentrations of 25, 50, and 100 µg / ml, respectively, and after 2 days, viability of each well was measured using Ez-cytox.

As a result, as shown in Figure 2, PC12 cells induced differentiation into neurons by nerve growth factor (NGF) was reduced cell viability by oxaliplatin treatment (NGF + Oxal), duct water extract (WEFF) It was confirmed that neuronal toxicity caused by oxaliplatin is alleviated by).

Example 2 Identification of Weight Changes in Animal Models of Chemotherapy-induced Peripheral Neuropathy (CIPN)

As a result of confirming the weight change of the prepared animal model, the experimental animal group administered oxaliplatin decreased body weight compared to the normal group, and after induction of CIPN for 2 weeks, the group administered oral extract (WEFF) orally was 0.5 as vehicle. Compared with the group administered the% CMC solution, no side effects such as weight loss were seen, but rather recovered faster than the vehicle administration group (FIG. 3).

Example 3 Confirmation of ChIPtherapy-induced Peripheral Neuropathy (CIPN) Mitigation Effect of Fructus Water Extract in Vivo

By measuring mechanical hyperalgesia using an oxaliplatin-induced peripheral neuropathy animal model, the CIPN inhibitory effect of the soft water extract of the present invention was confirmed.

Specifically, 0.5% (v / v) carboxymethyl cellulose (CMC) solution as the 250 mg / kg soft water extract (WEFF) and negative control group after two weeks of pain induced in the peripheral neuropathy animal model Were administered orally 7 times a week each day. Two weeks after the pain-induced von Frey filament test, the same stimulation of 0.16 g and 0.4 g was applied to the hind paw of the mouse once a week during the administration period. Sensitivity to stimuli is expressed as the percentage of animal subjects responding to the stimulus.

As a result, as shown in FIG. 4, after administration of the soft water extract, it was confirmed that the response rate to pain was decreased.

Example 4. Confirmation of the effect of soft water extract on the cytotoxicity of oxaliplatin in human tumor cells in vitro

In tumor clinical trials, in vitro human tumors were excluded in order to rule out the possibility that chemotherapeutic water extracts could negatively affect chemotherapy outcomes with chemotherapy when the anticancer agent and ductile water extract were administered simultaneously or at intervals. In the cells, it was confirmed that the duct extracts affect the cytotoxicity of anticancer drugs.

Specifically, as described above, after culturing human lung cancer cells (A549) and human colon cancer cells (HCT116), each cell was divided into 5 x 10 ³ cells per well in a 96 well culture dish. After 24 hours, oxaliplatin (0-100 µg / ml) and soft water extract (100 µg / ml) diluted sequentially were treated simultaneously. The negative control group was treated with oxaliplatin and used a cell group treated with PBS as a vehicle instead of the soft water extract. After 72 hours of treatment, cell viability was measured using an Ez-Cytox cell viability measurement kit.

As a result, as shown in Figure 5, when treated with oxaliplatin alone, concentration-dependently inhibited the growth of A549 human lung cancer cells and HCT116 human colon cancer cells, and treated with oxaliplatin at the concentration of 100 ㎍ / ㎖ Even if it was confirmed that the water extract did not have a negative effect on the cancer cell growth inhibitory effect of oxaliplatin. Therefore, as a result, it was confirmed that the soft water extract did not affect the anticancer effect of oxaliplatin when used in combination with oxaliplatin to cancer patients.

Claims

Pharmaceutical composition for the prevention or treatment of peripheral neuropathy (peripheral neuropathy) containing a cheongyo extract as an active ingredient.
The pharmaceutical composition for preventing or treating peripheral neuropathy according to claim 1, wherein the duct extract is extracted with water, lower alcohols of C 1 to C 4 or a mixture thereof as a solvent.
The pharmaceutical composition for preventing or treating peripheral neuropathy according to claim 2, wherein the lower alcohol is methanol or ethanol.
The pharmaceutical composition for preventing or treating peripheral neuropathy according to claim 1, wherein the peripheral neuropathy is a chemotherapy-induced peripheral neuropathy induced by an anticancer agent.
The method of claim 4, wherein the anticancer agent is platinum-based, taxane-based, vinca alkaloids, bortezomib, or thalidomide, which is used for preventing or treating peripheral neuropathy. Pharmaceutical composition.
The pharmaceutical composition for preventing or treating peripheral neuropathy according to claim 5, wherein the platinum-based anticancer agent is at least one selected from cisplatin, carboplatin, and oxaliplatin.
The pharmaceutical composition for preventing or treating peripheral neuropathy according to claim 5, wherein the taxane-based anticancer agent is at least one selected from paclitaxel and docetaxel.
The pharmaceutical composition for preventing or treating peripheral neuropathy according to claim 1, further comprising an excipient or a diluent in addition to the active ingredient.
Anticancer adjuvant containing Yeongyo extract as an active ingredient.
The method of claim 9, wherein the anticancer adjuvant is used in combination with an anticancer agent including platinum, taxane, vinca alkaloids, bortezomib, or thalidomide. Anticancer supplements.
10. The anticancer adjuvant according to claim 9, which is effective for preventing or treating peripheral neuropathy induced by an anticancer agent.
Health functional food composition for the prevention or improvement of peripheral neuropathy (peripheral neuropathy) containing Yeongyo extract as an active ingredient.
The method according to claim 11, wherein, in addition to the active ingredient, a nutrient, a vitamin, an electrolyte, a flavoring agent, a coloring agent, an enhancer, a pectic acid and a salt thereof, an alkanoic acid and a salt thereof, an organic acid, a protective colloidal thickener, a pH adjuster, a stabilizer Functional food composition for the prevention or improvement of peripheral neuropathy (peripheral neuropathy), characterized in that it further comprises at least one selected from preservatives, glycerin, alcohol and carbonation agent used in carbonated drinks.