KR102318032B1 - Composition for prevention and alleviation of inflammation and neuropathic pain - Google Patents

Abstract

The present invention relates to a composition for preventing and alleviating inflammation and neuropathic pain. The composition for preventing and alleviating inflammation and neuropathic pain according to an embodiment of the present invention contains an extract of nipa palm (Nypa fruticans Wurmb) and inhibits TNF-α, TRPV1 and COX2, thereby causing neuropathy with anti-inflammatory activity. It can exhibit the effect of preventing and alleviating pain.

Description

Composition for preventing and alleviating inflammation and neuropathic pain

The present invention relates to a composition for preventing and alleviating inflammation and neuropathic pain. More specifically, it contains an extract of nipa palm (Nypa fruticans Wurmb), and inhibits TNF-α, TRPV1 and COX2, thereby exhibiting anti-inflammatory activity and preventing and alleviating neuropathic pain showing the prevention and improvement effect of neuropathic pain to the composition. In addition, as a composition based on a natural product, there is provided a composition for preventing and alleviating neuropathic pain without the problem of side effects due to long-term use.

Neuropathic pain generally refers to sensory abnormalities such as sensory disturbances, hyperalgesia and allodynia. In addition, chronic neuropathic pain may be induced by inflammation or trauma of the central and peripheral nervous system, and may cause the pain to persist.

Neuropathic pain is distinct from acute nociceptive pain, which is characterized by distinct nervous and sensory features that are therapeutically unresponsive to standard treatment for nociceptive pain, usually damage that directly or indirectly affects the peripheral and central nervous systems. or from pathogenesis. In addition, in the case of the facial region controlled by the trigeminal nerve, inflammatory or neuropathic pain may be induced by various external stimuli.

Patients with such neuropathic pain often take an immobile posture to minimize pain, so their mobility is reduced. In particular, the majority of about 70% of patients with spinal cord injury cause neuropathic pain within a few months after the injury and ultimately develop into chronic neuropathic pain that lasts for a long time. Moreover, neuropathic pain not only threatens the quality of life of the patient because it is accompanied by psychological stress such as sleep disturbance, anxiety, and depression as well as the pain itself, but also costs a lot of treatment cost, which extends beyond the patient and family to serious social and social problems. It is emerging as an economic problem.

Examples of such neuropathic pain inhibitors include anticonvulsants such as gabapentin and pregabalin that act on calcium channels; anticonvulsants, such as carbamazepine, which act on sodium channels; Serotonin Norepinephrine Reuptake Inhibitor (SNRI) class antidepressants; and opiates, which are recommended only for emergencies, are being used clinically. These are used in combination in most cases, but since all of the drugs in each class have similar side effects, the side effects may worsen depending on the patient due to this combination, but there is a problem that the therapeutic effect is low. Since neuropathic pain inhibitors are usually administered to patients for a long period of time, the most ideal prophylaxis and treatment for neuropathic pain should be those that have low toxicity and can be administered orally. In addition, despite the development of various analgesics or analgesic methods to date, it has been reported that 75% of patients with neuropathic pain still experience severe pain. The development of pain suppressants, therapeutics and foods is required.

On the other hand, the transient receptor potential (TRP) ion channel has been attracting attention in the field of pain research since Caterina et al. reported a vanilloid receptor in 1997. Among many TRP ion channels, the TRP ion channel, which is related to pain, is an ion channel that responds to a temperature stimulus and an ion channel that responds to a mechanical stimulus. TRPV1 (transient receptor potential vanilloid 1) and TRPA1 (transient receptor potential ankyrin 1) applies to TRPV1 is a TRP ion channel activated by thermal stimulation and plays an important role in neuropathic pain as an important signal integrator of nociceptors. Capsaicin, the main ingredient that makes chili peppers spicy, causes pain by activating the TRPV1 receptor. TRPV1 is present in the membranes of neurons that sense pain and temperature. When capsaicin is administered locally or systemically, it is known that it shows a strong irritant at first but shows a continuous analgesic action, so many capsaicin derivatives have been synthesized, and development as an analgesic has been attempted. TRPV1 activator is known to be involved in inflammatory response as well as pain treatment, so a study on natural food-derived TRPV1 activator will be helpful for various diseases and preventive effects.

(Patent Document 1) KR 10-2012-1132040 B1

The present invention is to provide an anti-inflammatory composition comprising a nipa palm extract.

The present invention is to provide a composition for preventing and alleviating neuropathic pain comprising a nipa palm extract.

Another object of the present invention is to provide a composition for neuropathic pain and alleviation derived from a natural product capable of alleviating neuropathic pain with anti-inflammatory activity.

Another object of the present invention is to provide a composition for neuropathic pain and treatment that is free from side effects and can be used periodically or for a long period of time.

In order to achieve the above object, the composition for preventing and alleviating inflammation and neuropathic pain according to an embodiment of the present invention includes a nipa palm (Nypa fruticans Wurmb) extract and inhibits TNF-α, TRPV1 and COX2.

The neuropathic pain may be a disease selected from the group consisting of nerve damage, neuropathy, central neuropathic pain, and peripheral neuropathic pain.

In the composition for preventing and alleviating inflammation and neuropathic pain, the nipa palm extract may be a nipa palm flower stalk extract.

In the composition for preventing and alleviating inflammation and neuropathic pain, the extract may be extracted using an extraction solvent selected from the group consisting _{of water, C 1} to C _{6 lower alcohols, and mixtures thereof.}

The composition for preventing and alleviating inflammation and neuropathic pain is Cephalotaxus koreana Nakai extract, Sceptridium ternatum (Thunb.) Lyon) extract, Saururus chinensis (Lour.) Baill.) extract, It may further include a natural extract selected from the group consisting of Celastrus orbiculatus extract and mixtures thereof.

General food according to another embodiment of the present invention may include a composition for preventing and alleviating inflammation and neuropathic pain.

Functional food according to another embodiment of the present invention may include a composition for preventing and alleviating inflammation and neuropathic pain.

The skin external preparation according to another embodiment of the present invention may include a composition for preventing and alleviating inflammation and neuropathic pain.

The pharmaceutical according to another embodiment of the present invention may include a composition for preventing and alleviating inflammation and neuropathic pain.

Hereinafter, the present invention will be described in more detail.

The composition for preventing and alleviating inflammation and neuropathic pain according to an embodiment of the present invention includes an extract of nipa palm (Nypa fruticans Wurmb) and inhibits TNF-α, TRPV1 and COX2.

As used herein, the term 'extract' has the meaning commonly used as a crude extract in the sugar leaf system as described above, but in a broad sense also includes a fraction obtained by additionally fractionating the extract. That is, the extract includes not only those obtained by using the above-described extraction solvent, but also those obtained by additionally applying a purification process thereto. For example, a fraction obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (prepared for separation according to size, charge, hydrophobicity or affinity), etc. The fraction obtained through the purification method is also included in the extract of the present invention.

The extract used in the present invention may be prepared in a powder state by an additional process such as distillation under reduced pressure and freeze-drying or spray-drying.

As used herein, the term “neuropathic pain” refers to any pain resulting from dysfunction of one or more lesions, central nervous system and peripheral nervous system.

The composition for neuropathic pain and treatment according to an embodiment of the present invention includes an extract of Nypa fruticans Wurmb as an active ingredient.

Nipa palm (Nypa fruticans Wurmb), also called sea bamboo shoot, is a plant belonging to the family Alanaceae, and is cultivated in freshwater or salty beaches of estuaries in Southeast Asia such as Myanmar, Indonesia, and the Philippines. Hae bamboo shoots means 'bamboo shoots from the sea', and the name was given because the appearance of young shoots resembles Korean bamboo shoots. On the other hand, nipa palm is a plant that has been traditionally used for tooth inflammation, and has recently been imported into Korea. According to previous studies, it has been reported that it contains a large amount of phenolic acid and flavonoids, and thus the antioxidant effect and cholesterol suppression effect are superior. 100g of sea bamboo shoots contain 6,040mg of polyphenol, which is 43 times that of 6-year-old red ginseng, 22 times that of blueberry, and 41 times that of chwinamul. It is reported that sea bamboo shoots mainly contain chlorogenic acid, protocatechuic acid, and kaempferol. is not being done In addition, the research results related to pain are very scarce, and in particular, there is little evidence of its effectiveness in the occurrence and prevention of sciatica such as neuropathic pain.

The neuropathic pain may be a disease selected from the group consisting of nerve damage, neuropathy, central neuropathic pain, and peripheral neuropathic pain.

The neuropathic pain includes a disease selected from the group consisting of nerve damage, neuropathy, central neuropathic pain, and peripheral neuropathic pain. In the case of neuropathic pain, it is caused by a change in the function or structure of a nerve, and sometimes the afferent circuit is blocked or not. The central neuropathic pain appears in the thalamus syndrome and spinal cord injury during stroke, and the function of controlling the peripheral nervous system is lost and appears as uninhibited hyperactivity of Ad or C- afferent nerve fibers. Pain caused by peripheral neuropathy includes pain caused by neuroma, phantom limb pain, burning pain, and pain related to the sympathetic nervous system. Peripheral nerves originate from the brain and spinal cord and have a wide range of functions that connect different parts of the body. Injuries or diseases of the peripheral nervous system can be caused by damage to the nerve itself, the spinal cord, and the nerve nucleus, of which 60-70% are often caused by lesions of the peripheral nerve itself. Currently, traumatic peripheral nerve injuries due to traffic accidents and industrial accidents are increasing, and the pain that occurs when the peripheral nerve is compressed is caused by internal deformation of the nervous system, causing continuous pain. In addition, the peripheral nerve is a tissue that is very susceptible to compression, and the degree of damage that appears at this time is closely related to the degree of pressure of the type of nerve tissue involved and the time the pressure is applied. One of the nerve injuries that can be caused by such nerve compression is a compression injury. It is usually caused by mechanical compression of the sciatic nerve causing pain and abnormal sensations along with innervation, resulting in severe muscle deterioration and muscle atrophy.

The composition includes those that inhibit TRPV1 (transient receptor potential vanilloid 1) to exhibit anti-nociceptive and nerve regeneration effects.

TRPV1 (transient receptor potential vanilloid 1), known as a non-selective cation channel, is activated by capsaicin, which is the main ingredient of hot pepper, heat (>43°), acid (>PH 6), etc. It is one of the multiphase nociceptors involved. TRPV1 expression is increased when tissue damage occurs, which is sensitized and plays an important role in conducting inflammatory noxious sensations. The damaged tissue releases inflammatory substances such as bradykinin, serotonin, substance P and CGRP (calcitonin gene-reated peptide), prostaglandin, and histamine from the vascular endothelial cells of the site. The substance sensitizes primary sensory nerve cells and collects surrounding immune cells to the damaged area. Through a series of processes, it leads to the release of more inflammatory substances. Formalin and capsaicin are drugs that are widely used in pain models, respectively, and cause harmful behavioral reactions (pain reactions) after injection into the hind legs, lips, whiskers and temporomandibular joints of experimental animals. In addition, it is known that TRPV1 is activated by inflammatory mediators, Nerve Growth Factor, Bradykinin, etc. released from the inflammatory site caused by the injection of these drugs.

Accordingly, the present invention confirmed the effect of the TRPV1 channel activated by capsaicin injected into the facial part of rats on the change in the size of formalin-induced inflammatory pain, and the nipa palm extract relieved inflammatory or neuropathic pain through inhibition of TRPV1. It was confirmed that the effect was shown.

The present invention includes a nipa palm extract as an active ingredient, to provide a composition that exhibits an excellent effect in alleviating inflammatory or neuropathic pain through inhibition of TRPV1.

However, compared to the case of using only the nipa palm extract, when used as a complex extract mixed with natural extracts, it may exhibit a more excellent effect in alleviating inflammatory or neuropathic pain through inhibition of TRPV1.

In the composition for preventing and alleviating inflammation and neuropathic pain, the nipa palm extract may be a nipa palm flower stalk extract.

When the nipa palm flower stalk extract is used, the anti-inflammatory activity may be excellent, and the effect of preventing and soothing neuropathic pain may be excellent.

In the composition for preventing and alleviating inflammation and neuropathic pain, the extract may be extracted using an extraction solvent selected from the group consisting of water, C1 to C6 lower alcohols, and mixtures thereof.

The composition for preventing and alleviating inflammation and neuropathic pain is Cephalotaxus koreana Nakai extract, Sceptridium ternatum (Thunb.) Lyon) extract, Saururus chinensis (Lour.) Baill.) extract, It may further include a natural extract selected from the group consisting of Celastrus orbiculatus extract and mixtures thereof.

The Gabija tree (Cephalotaxus koreana Nakai) is an evergreen shrub that grows in a mountain valley or forest and reaches a height of 3 m. The leaves are linear, arranged in two rows, the tip is sharply pointed, the front side is green, and the main veins are distinct. Flowers are bivalent, blooming in April, male flowers are spherical, and female flowers are hung in one place by two. The fruit is round and ripens in red in August to September of the next year, and the seeds are long oval and brown.

The Eumjigwol is a perennial plant that grows in sunny forests or grass as Sceptridium ternatum (Thunb.) Lyon, and its thick fleshy roots spread in all directions. The leaf is divided into two and becomes a nutritive leaf and a filamentous leaf. The leaf stalk has a long petiole and is split into three and has sawteeth on the edge. The sporangia is longer than the leaf, and the upper part is split long, and the sporangia hangs on the branch.

The three Baekcho (Saururus chinensis (Lour.) Baill.) is a perennial plant that grows in wetlands and has a height of 50 to 100 cm and a white rhizome. The leaves are alternate and have a sharp tip, the lower part is heart-shaped, and the edge is flat. Flowers are bisexual, blooming in white from June to August, and inflorescences are opposite to leaves. The fruit is round and has 3 to 5 threads, and there is one seed in each thread.

The composition for preventing and treating neuropathic pain is used in addition to the nipa palm (Nypa fruticans Wurmb) extract, and further includes a natural extract selected from the group consisting of a birch tree extract, Eumjigwol extract, ginseng extract and mixtures thereof. , when used as a complex extract, when used as the composition for the prevention and treatment of neuropathic pain, it can exhibit a more excellent effect.

Preferably, the composition of the present invention includes a nipa palm extract, and with respect to 100 parts by weight of the nipa palm extract, 40 to 60 parts by weight of the Gabija tree extract, 40 to 60 parts by weight of the Eumjigwol extract and 40 to 60 parts by weight of the extract may be included.

When used as a complex extract within the above range, the effect of preventing and treating neuropathic pain is further increased due to the complex action between each component. The extract includes extraction using an extraction solvent selected from the group consisting of water, C ₁ to C _{6 lower alcohols, and mixtures thereof.}

Specifically, pulverizing a natural product to prepare a nipa palm extract; leaching the pulverized product using an organic solvent; drying the sample after leaching; re-leaching the dried sample using an organic solvent; drying the sample after leaching; leaching with water; And including the step of leaching, it is possible to obtain a natural extract.

The natural extract extracted using the organic solvent may further include the step of performing fractionation using an organic solvent.

The method for preparing the extract may be a conventional extraction method in the art, such as an ultrasonic extraction method, a leaching method, and a reflux extraction method. Specifically, it may be an extract obtained by extracting a natural product from which foreign substances have been removed by washing and drying with water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof, and may be an extract extracted by sequentially applying the solvents to the sample.

The reflux extraction method is water, based on 100 mL of an alcohol having 1 to 6 carbon atoms, 10 to 30 g of a pulverized product of a natural product, a reflux time of 1 to 3 hours, and 50 to 100% alcohol or water having 1 to 6 carbon atoms. More specifically, based on 100 ml of an alcohol having 1 to 6 carbon atoms or 100 ml of water, 10 to 20 g of a pulverized product of a natural product, a reflux time of 1 to 2 hours, and 70 to 90% of an alcohol or water having 1 to 4 carbon atoms.

The leaching method is performed at 15 to 30° C. for 24 to 72 hours, and water or 50 to 100% alcohol having 1 to 6 carbon atoms is used as an extraction solvent. More specifically, the process is carried out at 20 to 25° C. for 30 to 54 hours, and the extraction solvent is water or 70 to 80% alcohol having 1 to 6 carbon atoms.

In the ultrasonic extraction method, the reaction is carried out at 30 to 50° C. for 0.5 to 2.5 hours, and the extraction solvent is water or 50 to 100% alcohol having 1 to 6 carbon atoms. Specifically, extraction is performed at 40 to 50° C. for 1 to 2.5 hours, and the extraction solvent is water or 70 to 80% alcohol having 1 to 6 carbon atoms.

Preferably, the solvent may be a mixture of water and ethanol in an amount of 1: 10 to 1:1 by volume. In the case of the above solvent, the active ingredient having an anti-inflammatory and sedative effect on neuropathic pain contained in nipa palm can be effectively obtained, which may be advantageous in enhancing the effect targeted by the present invention.

The extraction solvent may be used in an amount of 2 to 50 times, more specifically, 2 to 20 times, based on the weight of the sample. For extraction, the sample may be left for 1 to 72 hours for leaching in the extraction solvent, and more specifically, for 24 to 48 hours.

After extraction, the extract may be fractionated by sequentially applying a fresh fractionation solvent. The fractionation solvent used for fractionation is any one or more selected from the group consisting of water, hexane, butanol, ethyl acetic acid, ethyl acetate, methylene chloride and mixtures thereof, preferably ethyl acetate or methylene chloride.

After obtaining the extract or fraction, a method such as concentration or freeze-drying may be additionally used.

Functional food according to another embodiment of the present invention may include the composition for preventing and treating neuropathic pain.

The composition for preventing and treating neuropathic pain of the present invention contains an extract of nipa palm (Nypa fruticans Wurmb), and when it is intended to be used as a functional food composition due to a unique off-flavor of seaweed, there is a problem of poor preference. Similarly, even in the case of a complex extract in which the nipa palm extract is mixed with a natural extract, due to the unique taste and aroma of the natural extract mixed with the unique odor of seaweed, when provided as a functional food composition, a problem of poor preference occurs.

In order to prevent this problem, more preferably, in the present invention, in order to improve palatability, an extract of Pachysandra terminalis and an extract of Siraitia grosvenorii may be further included.

The guardian reef (Pachysandra terminalis) grows in the shade of a tree, and the main stem is straight and the end is green, and there is fine hairs at first, but it gradually disappears. Grows to around 30cm in height. The leaves are alternate phyllotaxis, but gather at the top and run like an upside-down egg, with sawtooths on the top. There are fine hairs on the veins of the leaf surface, and the lower part becomes narrower to become a petiole. In addition, flowers bloom in April or May, are white, and hang on the inflorescence. Female flowers hang a little on the lower part of the ear, and male flowers hang on the upper part a lot. The calyx is divided into 4 and there are no petals. There are 3 to 5 stamens, and the style is divided into two and folded. The fruit is a drupe, egg-shaped, and has no hair on the outside. Distributed in Korea, Japan, Sakhalin Island, and China.

Siraitia grosvenorii (Siraitia grosvenorii) is a herbaceous perennial plant in the gourd family, native to China and Thailand. The fruits and leaves of the loquat family are used as medicines in oriental medicine. It is a plant that is difficult to cultivate artificially due to difficult cultivation conditions as it lives in soil with good drainage and humus.

By additionally including the Suhocho extract and Nahanfruit extract, it is possible to provide a functional food composition with excellent palatability by neutralizing the peculiar odor of seaweed and the unique taste and flavor of the natural extract.

Preferably, the composition of the present invention is based on 100 parts by weight of the nipa palm extract, 40 to 60 parts by weight of the Gabija tree extract, 40 to 60 parts by weight of the Eumjigwol extract, 40 to 60 parts by weight of the trifolium extract, 20 to 30 parts by weight of the Suho extract It may be included in an amount of 30 to 50 parts by weight of parts and leprosy extract. When used as a complex extract within the above range, it exhibits an excellent effect in preventing and treating neuropathic pain, and at the same time makes it possible to provide a functional food composition with excellent taste.

General food according to another embodiment of the present invention may include a composition for preventing and alleviating inflammation and neuropathic pain. Tea according to another embodiment of the present invention refers to a general food as a palatable food, and the tea may include a composition for preventing and alleviating inflammation and neuropathic pain.

Functional food according to another embodiment of the present invention may include a composition for preventing and alleviating inflammation and neuropathic pain.

"Functional food" as defined herein means a food manufactured and processed using raw materials or ingredients useful for the human body according to Act No. 6727 of the Functional Food Act, and "functionality" refers to the structure and It refers to intake for the purpose of obtaining useful effects for health purposes such as regulating nutrients for function or physiological effects.

When the extract according to the present invention is used as a food additive, the extract may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages and vitamin complexes, and it includes all health foods in the ordinary sense.

The skin external preparation according to another embodiment of the present invention may include the composition for preventing and treating neuropathic pain.

The pharmaceutical according to another embodiment of the present invention may include the composition for preventing and treating neuropathic pain.

The preferred dosage of the extract of the present invention varies depending on the condition and weight of the patient, the degree of disease, the drug form, the route and duration of administration, but may be appropriately selected by those skilled in the art. However, for a desirable effect, the extract is preferably administered at 0.01 mg/kg to 10 g/kg per day, preferably at 1 mg/kg to 1 g/kg. Administration may be administered once a day, or may be administered in several divided doses. Therefore, the above dosage does not limit the scope of the present invention in any way.

The present invention provides an anti-inflammatory composition comprising a nipa palm extract.

The present invention provides a composition for preventing and alleviating neuropathic pain comprising an extract of nipa palm.

In the case of the composition for preventing and alleviating inflammation and neuropathic pain according to the present invention, an extract derived from a natural product is used to effectively relieve neuropathic pain, and there is no problem of side effects. Can be used for a long time.

1 relates to a neuropathic pain model test result of a composition according to an embodiment of the present invention.
Figure 2 relates to the neuropathic pain model test results of the composition according to an embodiment of the present invention.
Figure 3 relates to the neuropathic pain model test results of the composition according to an embodiment of the present invention.
4 is a neuropathic pain model test results of the composition according to an embodiment of the present invention.
5 is a neuropathic pain model test results of the composition according to an embodiment of the present invention.

Hereinafter, embodiments of the present invention will be described in detail so that those of ordinary skill in the art can easily carry out the present invention. However, the present invention may be embodied in many different forms and is not limited to the embodiments described herein.

[Preparation Example: Preparation of Extract]

1. Preparation of nipa palm extract

100 g of nipa palm extract in the form of dry and pulverized powder was mixed with 1 L of 80% ethanol at -20°C and extracted at room temperature for 4 hours. A filter cake was used to remove the powder component after extraction, and only the liquid component was filtered through the flask. The filtered liquid component was boiled in a water bath at 65° C. to prepare pure nipa palm extract (NF).

2. Preparation of other natural extracts

30% ethanol was added to 1 kg of dry and pulverized powdered Gabija tree extract raw material, followed by reflux extraction at 80° C. for 1 to 3 hours. The extraction was repeated twice at the same number of times and for the same time, and the obtained extract was dried under reduced pressure and then vacuum dried at 60° C. to prepare a Gabija tree extract (N2).

Eumjigwol extract (N3), Sambaekcho extract (N4), Suhocho extract (X1), and Nahanfruit extract (X2) were prepared by using the same method as the method for preparing the Gabija tree extract (N2).

3. Preparation of Complex Extracts

The nipa palm extract (NF), banyan tree extract (N2), Eumjigwol extract (N3), ginseng extract (N4), Suhocho extract (X1) and Nahan fruit extract (X2) are in the central range as shown in Table 1 below. It was mixed into a composition for preventing and treating neuropathic pain.

G1 G2 G3 G4 G5 G6 G7 G8 G9 NF 100 100 100 100 100 100 100 100 100 N2 - 30 40 60 80 30 40 60 80 N3 - 30 40 60 80 30 40 60 80 N4 - 30 40 60 80 30 40 60 80 X1 - - - - - 10 20 30 40 X2 - - - - - 30 40 50 60

(unit weight parts)

[Experimental Example 1-1: Neuropathic pain relief effect on nipa palm extract]

The Formalin experiment is a representative experimental model that can evaluate the inflammatory pain behavior response due to tissue damage and inflammatory response induced by injecting formalin subcutaneously. Capsaicin, which acts as an agonist of TRPV1, was added. In case of infusion, neuropathic pain behavioral response evaluation can be seen.

To explain the specific experimental method, the experimental animals were acclimatized for at least 10 minutes in an experimental plastic container before pain response evaluation. 25 μl of 5% formalin was injected using an insulin syringe (0.25 × 8 mm), and it was observed that consciousness was restored within a few seconds after formalin injection. First, in order to confirm the effect of the TRPV1 channel activity on the behavioral response of formalin-injected experimental animals, capsaicin injected at each concentration (0.1μg, 1μg, 10μg/10 μL) through the inserted polyethylene tube. The behavioral response to pain induced by sulcus was observed in the same manner as after formalin injection. Next, 0.1μg, 1μg/10μL capsaicin was administered to the same injection site 1 hour before formalin administration, and changes in pain behavioral response were observed for 45 minutes. As a solvent (Vehicle) of capsaicin, a mixture of 10% ethanol, 10% to 80% and 80% physiological saline was used.

As a result of pre-treatment with 0.1μg, 1μg/10μL capsaicin before formalin injection, a significant increase in pain behavioral response was observed, indicating that formalin-induced neuropathic pain in the TRPV1 channel activated by capsaicin injected into the facial area of rats. was found to have an effect on the size change of Then, for the neuropathic pain relief effect of the nipa palm extract, 500 mg/kg of nipa palm extract (NF) was treated 10 minutes before capsaicin injection, and the effect on the change of neuropathic pain behavioral response was observed. (Fig. 1)

As a result, it was found that the treatment of nipa palm extract (NF) significantly alleviated the increased pain behavioral response. It was confirmed that the TRPV1 channel increased neuropathic pain sensation by capsaicin, and that this hyperalgesia was significantly reduced by nipa palm extract (NF).

[Experimental Example 1-2: Heat hyperalgesia test for nipa palm extract]

To prevent tissue damage, the right hind leg of the sciatic nerve-injured rat was placed in hot water (46C), and the measurement was performed within 20 seconds and repeated 3 times at 5-minute intervals. .(measured by immersion on days 0, 3, 7, 10 and 14) Place the right hind leg of a sciatic nerve-injured rat in hot water (46C). To avoid tissue damage, measurements were taken within 20 s and repeated 3 times with an interval of 5 min.

Thermal hyperalgesia is a method of observing avoidance responses when noxious thermal stimuli stimulate nociceptors and cause pain. The avoidance response of the foot can be understood as a rapid response to painful thermal stimuli, which is a direct indicator of nociceptive threshold. Aspirin was used as a positive control. Referring to FIG. 2 , it can be confirmed that, in the heat hyperalgesia test of the aspirin group, there was a significant antialgesic inhibitory effect on days 7, 10, and 14 compared to the vehicle group. In addition, the above experiment also showed that the delay of the paw withdrawal response was delayed by a statistically significant difference (p < 0.05) in the NF, SB and NF + SB treated groups compared with the vehicle group. In addition, it was confirmed that the additive effect of NF when administered with TRPV1 antagonist when compared with TRPV1 antagonist alone or NF alone on days 3, 7, 10, and 14 was confirmed.

[Experimental Example 1-3: Analysis of inflammatory markers for nipa palm extract]

Initial investigations of TRPV1 regulation of pro-inflammatory cytokines in vivo have focused on the responsiveness of pain to promote the release of pro-inflammatory cytokines, including IL-6, TNF-α and IL-1β. TRPV1 also regulates the development and development of numerous neurological disorders by regulating inflammatory cytokines in the central nervous system (CNS). TRPV1 regulates synaptic transmission and plasticity in neurons and interacts with pro-inflammatory cytokines in the course of inflammatory neurological diseases. Therefore, the anti-inflammatory activity was evaluated by analyzing the inflammatory markers for the group treated with the nipa palm extract. The results are shown in FIG. 3 below.

[Experimental Example 1-3: Evaluation of COX2, TRPV 1 for nipa palm extract]

The activity of the Nipaya extract according to the present invention on the regulation of COX2 and TRPV 1 was evaluated and shown in FIGS. 4 and 5 below.

[Experimental Example 2: Comparison of pain test results for complex extracts]

1. Capsaicin Pain Model Test for Complex Extracts

It was confirmed that the nipa palm extract (NF) had the effect of preventing and treating neuropathic pain through the experiment of the neuropathic pain model. proceeded. On the other hand, the results are described as G1 and index for relative comparison. The degree of effect of G1 was set as index 5, and the degree of effect on G2 to 5 was described as an index of 1 to 10, and a higher score means better pain control effect.

G1 G2 G3 G4 G5 Neuropathic Pain Model 5 3 4 5 7

(Unit: Index)

Table 2 shows the results of relatively comparing the pain control effects of G2 to 5 compared to G1. Compared to G1, it was confirmed that G3 and G4 showed an equal degree of pain control effect, whereas G5 showed a relatively good pain control effect.

[Experimental Example 3: Sciatic nerve regeneration effect according to the decrease in TRPV1 expression of nipa palm extract]

1. Causes crush damage to the sciatic nerve

After induced general anesthesia by intraperitoneal injection of Ketara and Yuhan (Ketarnin hydrochloride) 15mg/100g, the hairs on both thighs were removed. implemented. After exposing the sciatic nerve and using a hemostatic forceps with a tip diameter of 1 mm 1 cm above the branch point of the tibial nerve and the common peroneal nerve, crush damage was induced for 30 seconds. It was loosely ligated with 7-0 silk to the epineurium of the damaged area to be engulfed, and the muscle and skin were sutured.

2. Evaluation of the effect of nipa palm extract on nerve regeneration

The experimental animals were divided into an experimental group (n=15) and a control group (n=15), and the experimental group was again divided into groups administered with 500 mg/kg of nipa palm extract (NF) for 1 week, 2 weeks, and 3 weeks, and 5 animals were assigned to each group. The control group was also divided into 1 week, 2 week, and 3 week saline administration groups, and 5 animals were assigned to each group. After the animals were anesthetized for each period, the sciatic nerve was cut and the tissue morphological changes were confirmed by optical and electron microscopy.

As a result, the total number of myelinated nerve fibers in the experimental group administered with nipa palm extract (NF) changed to 36.0±3.4, 154.3±33.8, and 129.3±12.7 at 1, 2, and 3 weeks after administration, respectively, between 1 and 2 weeks. The total number of myelinated nerve fibers increased rapidly (p<0.01) and showed a tendency to decrease slightly at 3 weeks. The control group administered with physiological saline changed to 35.3±9.1, 74.3±9.6, and 116.0±15.1, respectively, at 1 week, 2 weeks, and 3 weeks after administration, and showed a gradual increase trend. The degenerated myelinated nerve fibers in the control group were 38.3±8.5, 40.7±15.0, and 36.3±8.5 at 1, 2 and 3 weeks, respectively. Therefore, it was found that the administration of nipa palm extract (NF) after inflicting crush damage to the sciatic nerve reduces the degenerated myelinated nerve fibers caused by crush damage and restores the myelinated nerve fibers.

1 week 2 weeks 3 weeks Experimental group administered with NF 36.0±3.4 154.3±33.8 129.3±12.7 Control group administered with physiological saline 35.3±9.1 74.3±9.6 116.0±15.1

[Experimental Example 4: Taste Test]

1. Sensory evaluation test

G1, G5 of the complex extract, and G6 to 9 of the fermented complex extract were diluted to prepare a sound note. The tea drink was tasted by 10 tasters, and the taste and aroma were expressed as an index of 1 to 10, and the average value (0.5 rounding applied) is shown in [Table 4] below. In the index, the higher the number, the higher the degree of preference.

G1 G5 G6 G7 G8 G9 taste 5.5 4.5 6 6 6 5 incense 4.5 2.5 4 5 6 4 Overall preference (average) 5.5 4 5.5 6 6.5 5

(Unit: Index)

Referring to Table 4, in the case of G1, the taste of the nipa palm extract was evaluated well, but the unique flavor of seaweed lowered the preference, and when G5 was mixed, it can be seen that the sour flavor is added and the preference is lowered. In addition, in the case of G9 mixing, it can be seen that the astringent and sour flavor is stronger, so the preference is lower. On the other hand, in the case of the complex extracts G7 and G8, it was confirmed that the preference increased while the unique flavor and taste of the nipa palm extract was neutralized.

Therefore, in the case of the complex extracts G7 and G8, it can be provided as a functional food effective for relieving neuropathic pain with a more favorable flavor and taste.

Although the preferred embodiment of the present invention has been described in detail above, the scope of the present invention is not limited thereto, and various modifications and improvements by those skilled in the art using the basic concept of the present invention as defined in the following claims are also provided. is within the scope of the

Claims (9)

Contains an extract of Nypa fruticans Wurmb,
Inhibiting TNF-α, TRPV1 and COX2
A composition for preventing or alleviating inflammation and neuropathic pain,
The composition is Gabija tree (Cephalotaxus koreana Nakai) extract, Sceptridium ternatum (Thunb.) Lyon) extract, Saururus chinensis (Lour.) Baill.) extract, Suhocho (Pachysandra terminalis) extract and Nahan ( Siraitia grosvenorii) further comprising an extract
A composition for preventing or alleviating inflammation and neuropathic pain. According to claim 1,
The neuropathic pain is central neuropathic pain or peripheral neuropathic pain.
A composition for preventing or alleviating inflammation and neuropathic pain. According to claim 1,
The nipa palm extract is a nipa palm flower stalk extract
A composition for preventing or alleviating inflammation and neuropathic pain. According to claim 1,
The extract is extracted using an extraction solvent selected from the group consisting of water, C ₁ to C _{6 lower alcohols and mixtures thereof.}
A composition for preventing or alleviating inflammation and neuropathic pain. delete Claims 1 to 4, comprising the composition for preventing or alleviating inflammation and neuropathic pain according to any one of claims 1 to 4
A general food for the prevention or relief of inflammation and neuropathic pain. Claims 1 to 4, comprising the composition for preventing or alleviating inflammation and neuropathic pain according to any one of claims 1 to 4
Functional food for preventing or alleviating inflammation and neuropathic pain. Claims 1 to 4, comprising the composition for preventing or alleviating inflammation and neuropathic pain according to any one of claims 1 to 4
An external preparation for the prevention or relief of inflammation and neuropathic pain. Claims 1 to 4, comprising the composition for preventing or alleviating inflammation and neuropathic pain according to any one of claims 1 to 4
Medicines for the prevention or relief of inflammatory and neuropathic pain.

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