KR102327197B1 - Composition for preventing or treating neuropathic pain comprising extracts of herbal mixture - Google Patents

Abstract

An embodiment of the present invention provides a pharmaceutical composition for the treatment or prevention of neuropathic pain containing a mixed extract of Astragalus, Angelica, Peony, Chunkyung, Doin, Safflower, Sokdan, Tokhwal and Wooseul as an active ingredient.

Description

Pharmaceutical composition for preventing or treating neuropathic pain comprising extracts of herbal mixtures TECHNICAL FIELD

The present invention relates to a pharmaceutical composition for the treatment or prevention of neuropathic pain comprising an herbal medicine mixture extract.

Pain refers to an unpleasant feeling caused by a strong external stimulus or damage to the body. In the case of acute pain, it occurs within minutes to hours, the cause is relatively clear and the intensity is severe, and is caused by disease, inflammatory response, or tissue damage. Chronic pain can last for weeks to years, the cause of the pain is often unclear, and includes musculoskeletal pain such as arthritis, rheumatism, peripheral neuropathy, and back pain.

Neuropathic pain (neuropathic pain) is one of the most severe pain among various types of pain, is pain caused by damage or functional abnormality of the nervous system, and has a chronic long-lasting characteristic.

Neuropathic pain is caused by certain diseases such as cancer, diabetes, AIDS, unspecified risk factors such as old age, depression, nicotine addiction, obesity, and stress, and physical damage to peripheral nerves. Acute or chronic pain is caused by abnormal activation of sensory nerve pathways. Neuropathic patients complain of various types of symptoms such as spontaneous pain, paresthesiasis, dysesthesiasis, hyperalgesia, hyperpathia, and allodynia. It is accompanied by several concomitant diseases such as sleep disorders, emotional disorders such as depression, and deterioration of social adaptability, which causes serious deterioration in quality of life.

Currently, physical methods such as spinal nerve surgical route block and electrical stimulation are mainly used as palliative treatment methods for pain, and antidepressants, anticonvulsants, selective serotonin reuptake inhibitors, narcotic analgesics, and local anesthetics are used. However, most of these treatments do not provide satisfactory pain control, and there is a high demand for the development of new treatments due to concerns about the risk of surgical treatment, resistance to drug treatment, and side effects.

The key targets for the treatment of neuropathic diseases are axonal regeneration, anti-inflammatory, and pain relief. Neuropathic disease is caused by damage to the peripheral and central nervous systems, and pain relief is the main goal of treatment because it is a disease in which pain occurs acutely or chronically due to abnormal activation of pain sensory nerve pathways due to nerve damage.

In addition, for the fundamental treatment of neuropathic diseases, not only pain relief but also nerve regeneration should ultimately be achieved. In the case of the central nervous system, it is known that the regeneration of damaged nerve cells is difficult, but in the peripheral nerves, since the axonal nerve cells begin to regenerate at the end of the peripheral nerves, it is known that the recovery is relatively possible. However, in the human body, the length of the axon to the cell body and target organ of nerve cells is very long compared to that of small animals, and the natural metabolic process and recovery rate are very slow because the probability of the disease increases in the elderly due to the nature of the neuropathic disease. Therefore, the input of a therapeutic agent capable of promoting nerve regeneration is urgently required.

Herbal medicines are traditionally used for the treatment and prevention of diseases, and most of them are of plant origin, and are based on a complex prescription of herbal ingredients. Therefore, complex effects can be induced, and the possibility of developing an effective drug that can replace many synthetic drugs currently in use is very high due to low tolerance and side effects. Accordingly, the development of therapeutic agents for the treatment or prevention of neuropathic pain using herbal preparations such as natural products has been steadily continued, and the present inventors have also completed the present invention to develop more effective herbal medicine therapeutics.

Korean Patent Publication No. 10-2014-0130599

One object of the present invention is to provide a pharmaceutical composition for the treatment or prevention of neuropathic pain comprising a mixed extract of herbal medicines as an active ingredient, and a pharmaceutical preparation for the treatment or prevention of neuropathic pain comprising the same.

Another object of the present invention is to provide a food composition for improving neuropathic pain comprising a mixed extract of herbal medicines as an active ingredient and a health functional food containing the same.

Another object of the present invention is to provide an anti-inflammatory pharmaceutical composition or a pharmaceutical composition for nerve terminal regeneration comprising a mixed extract of herbal medicines as an active ingredient.

One aspect of the present invention provides a pharmaceutical composition for the treatment or prevention of neuropathic pain containing a mixed extract of astragalus, angelica, peony, cheongung, doin, safflower, sokdan, dokhwal and wooseul as an active ingredient.

According to an embodiment of the present invention, the mixed extract is astragalus 15% to 80% by weight, Angelica 3% to 15% by weight, Peony 2 to 12% by weight, Chungung 1% to 10% by weight, Doin 1 weight % to 10% by weight, safflower 1% to 10% by weight, quick cut 3% to 20% by weight, poisonous activity 2% to 10% by weight, and hyssop 2% to 10% by weight It can be an extract extracted by mixing have.

According to an embodiment of the present invention, the mixed extract is 1: 0.05-0.6: 0.03-0.45: 0.025-0.03: 0.025-0.03: It may be an extract extracted by mixing in a weight ratio of 0.025-0.03: 0.06-0.8: 0.03-0.4: 0.03-0.4.

According to an embodiment of the present invention, the mixed extract may be extracted using any one selected from the group consisting of water, alcohol, ethylene glycol, ethyl ether, and combinations thereof as an extraction solvent.

According to an embodiment of the present invention, the neuropathic pain may be peripheral neuropathic pain and/or central neuropathic pain.

According to an embodiment of the present invention, the neuropathic pain may be pain caused by sciatic nerve cut or reconnection after sciatic nerve cut.

According to an embodiment of the present invention, the treatment or prevention of the neuropathic pain may be achieved through regeneration of nerve endings.

Another aspect of the present invention provides a pharmaceutical preparation for treating or preventing neuropathic pain, comprising the pharmaceutical composition for treating or preventing neuropathic pain.

Another aspect of the present invention provides a food composition for alleviating neuropathic pain containing a mixed extract of astragalus, angelica, peony, cheongung, doin, safflower, sokdan, dokhwal and wooseul as an active ingredient.

Another aspect of the present invention provides a health functional food comprising a food composition for improving the neuropathic pain.

Another aspect of the present invention provides an anti-inflammatory pharmaceutical composition containing a mixed extract of astragalus, angelica, peony, cheongung, doin, safflower, sokdan, dokhwal and wooseul as an active ingredient.

Another aspect of the present invention contains a mixed extract of astragalus, angelica, peony, cheongung, doin, safflower, sokdan, dokhwal and wooseul as an active ingredient, for regeneration of nerve endings through an increase in the number of nerves and axons of peripheral nerves A pharmaceutical composition is provided.

The pharmaceutical composition according to an embodiment of the present invention has no toxicity, exhibits anti-inflammatory and nerve ending regeneration effects, and has confirmed an excellent effect in treating or preventing neuropathic pain caused by nerve damage, so it is an active ingredient It can be used as a pharmaceutical composition for the treatment and prevention of neuropathic pain comprising

It should be understood that the effects of the present invention are not limited to the above-described effects, and include all effects that can be inferred from the configuration of the invention described in the detailed description or claims of the present invention.

1 shows the analgesic effect of each composition in a mouse model of an herbal medicine mixture extract according to an embodiment of the present invention.
Figure 2 shows the analgesic effect of each concentration in the mouse model of the herbal medicine mixture extract according to an embodiment of the present invention.
Figure 3 shows the analgesic effect in a mouse model when the herbal medicine mixed extract according to an embodiment of the present invention is administered in the form of acupuncture.
Figure 4 shows the anti-inflammatory effect in Raw 264.7 cells of the herbal medicine mixed extract according to an embodiment of the present invention.
Figure 5 shows the pain behavior evaluation results in rats of the herbal medicine mixture extract according to an embodiment of the present invention.
Figure 6 shows the nerve ending regeneration effect in rats of the herbal medicine mixture extract according to an embodiment of the present invention.

Hereinafter, the present invention will be described with reference to the accompanying drawings. However, the present invention may be embodied in several different forms, and thus is not limited to the embodiments described herein.

The terms used herein are used only to describe specific embodiments, and are not intended to limit the present invention. The singular expression includes the plural expression unless the context clearly dictates otherwise. In the present specification, terms such as "comprise" or "have" are intended to designate the existence of features, numbers, steps, operations, components, parts, or combinations thereof, described in the specification, unless specifically stated to the contrary. However, it is to be understood that this does not preclude the possibility of the presence or addition of one or more other features or numbers, steps, operations, components, parts, or combinations thereof.

One aspect of the present invention provides a pharmaceutical composition for the treatment or prevention of neuropathic pain containing a mixed extract of astragalus, angelica, peony, cheongung, doin, safflower, sokdan, dokhwal and wooseul as an active ingredient.

The astragalus (herb medicine name: Astragali radix, scientific name: Astragalus membranaceus Bunge) is used as a herbal medicine by drying the roots. The astragalus is bogi-seungyang (補滯升阳), high pyo-ji-han (固表止汗), dihydrogen bell (利水消腫), saengjinyanghyeol (生津養血), haengchetongbi (行滯通痺), takdok drainage (固表止汗), It has the effects of 托毒排膿, yeomchangsaenggi (斂瘡生肌), qi depletion power (斂瘡生肌), qi depletion sugar, medium qi qi qi (中民便), catabolism (久瀉脫肛). ), disfigured blood loss (便血崩漏), pyoheojahan (表虛auto汗), paralysis of water (气虛水腫), heat-resisting scald (內熱消渴), blood hypothalamus (血虛萎黃), hemiplegia (半虛萎黃), hemiplegia It is known to be used to treat bitter mackerel (痺痛麻木), ongjeonanggue (癰疽難潰), and mouth sores (久潰不斂).

The Angelica gigantis radix (scientific name: Angelica gigas Nakai) is used as a herbal medicine by drying its roots. The above-mentioned Angelica has the effects of blood, blood and blood circulation, regrowth pain, and intestinal pain.不調), transpulmonary pain (经閉痛经), cold abdominal pain (虛寒腹痛), customs and customs pain (wind and customs pain), vaginal tissue damage (跌撲損傷), intestinal constipation (腸疽瘡瘍) used

腹痛), 질박손상(跌撲損傷), 옹종창양(癰腫瘡瘍)을 치료하는 데 사용된다. The peony (Cervical name: Paeoniae radix, scientific name: Paeonia lactiflora) is used as a herbal medicine by drying the roots. The above peony has the effects of blue fever and yanghyeol, and pain in living fish, so it is effective for heat-injected young blood, warm poisonous spots, and haemorrhagic and bloody blood. , purulent pain (目赤腫痛), liver and intestinal pain (肝鬱脇痛), transpulmonary pain (目赤腫痛), abdominal pain (

腹痛), vaginal loss (跌撲損傷), is used to treat swelling and swelling (癰腫瘡瘍).

腹痛), 두통(頭痛), 풍습비통(風濕痛)을 치료하는 데 사용된다. The cheongung (crude name: Cnidii rhizoma, scientific name: Cnidium officinale Makino) is used as a herbal medicine by drying the roots. The above-mentioned cheongung has the effects of circulating blood circulation, geopungjitong (祛钲腫痛), thoracic nasal heart pain (胸心痛), thoracic gangrene pain (胸脇刺痛), vaginal thrombosis (跌撲腫痛), menstruation. Relief (月经不調), transpulmonary pain (经閉痛經), jingha abdominal pain

It is used to treat 腹痛), headache (頭痛), and customs pain (頭痛).

), 폐옹장옹(肺癰腸癰), 질박손상(跌撲損傷), 장조변비(腸燥便秘), 해수기천(咳嗽氣喘)을 치료하는 데 사용된다. The doin (herb medicine name: Persicae semen, scientific name: Prunus persica Batsch) is used as a herbal medicine by drying mature seeds. The above-mentioned Taoin has the effects of Hal-hyeol Geoeo(活血祛瘀), Yunjang Tongbyeon(潤腸通便), Jihaepyeongcheon(止咳平喘),

), pulmonary insufficiency (肺癰腸癰), vaginal failure (跌撲損傷), intestinal constipation (腸燥便秘), and seawater effusion (咳嗽气喘).

), 흉비심통(胸心痛), 어체복통(瘀滯腹痛), 흉협자통(胸脇刺痛), 질박손상(跌撲損傷), 창양종통(瘡瘍腫痛)을 치료하는 데 사용된다. The safflower (crude name: Carthami flos, scientific name: Carthamus tinctorius L.) is dried and used as a herbal medicine. Said safflower has the effects of safflower pain relief (活血通经) and pain in living and fisheries (散瘀止痛), so it is effective for safflower (痛痛), bad luck (惡露不行), and jinghabi (惡露不行).

), chest pain, abdominal pain, abdominal pain

In the above-mentioned rapid stage (Chemical name: Dipsaci Radix, scientific name: Dipsacus asperoides C. Y. Cheng et T. M. Ai), the roots are dried and used as herbal medicines. The above-mentioned rapid end has the effect of interpolation kidney, ganglion bone, sokjeolsang, and roof rudder, and liver kidney deficiency, yoseulsanyeon ), customs pain, vaginal bruises, root fractures, bulging fistulas, and haemorrhoids.

The poison vital (Cervical name: Araliae Continentalis Radix, scientific name: Aralia continentalis Kitagawa) is used as a herbal medicine by drying the roots. The poisonous activity has the effects of dehumidifying large winds and coughing and coughing, so it is effective for cold and cold rain, urinary tract pain, noise stomach wind headache, wind and cold sore throat, It is used to treat headaches.

)을 치료하는 데 사용된다. The hyssop (crude name: Achyranthis radix, scientific name: Achyranthes bidentata Bl.) is used as a herbal medicine by drying the roots. The hyssop has the effects of verb pain, interpolation kidney, gangrene bone, diuretic pain, and blood flow. ), pain, colic, musculoskeletal weakness, hydrocephalus, headache, vertigo, sore throat口瘡), hemoptysis (吐血), flesh blood (

) is used to treat

The mixed extract is Astragalus 15 wt% to 80 wt%, Angelica 3 wt% to 15 wt%, Peony 2 to 12 wt%, Chungung 1 wt% to 10 wt%, Doin 1 wt% to 10 wt%, Safflower 1 wt% % to 10% by weight, quick cut 3% to 20% by weight, poisonous activity 2% to 10% by weight, and hyssop 2% to 10% by weight, for example, Astragalus 20% to 78% by weight, Angelica 3.5 wt% to 13.5 wt%, peony 2.5 to 10 wt%, cheongung 1.5 wt% to 7 wt%, doin 1.5 wt% to 7 wt%, safflower 1.5 wt% to 7 wt%, short cut 5 wt% to 18 wt%, It may be an extract extracted by mixing in an amount of 2.5 wt% to 9 wt% of poison ivy and 2.5 wt% to 9 wt% of hyssop.

The mixed extract contains the Astragalus, Angelica, Peony, Chungung, Doin, Safflower, Sokdan, Sokhwal and Wooseul 1: 0.05-0.6: 0.03-0.45: 0.025-0.03: 0.025-0.03: 0.025-0.03: 0.06-0.8: 0.03 -0.4: It may be an extract extracted by mixing in a weight ratio of 0.03-0.4, for example, 1: 0.3: 0.225: 0.15: 0.15: 0.15: 0.4: 0.2: 0.2.

Based on the weight of the astragalus, when the content of at least one of angelicae, peony, cheongung, doin, safflower, sokdan, poison hyal and hyssul is less than the lower limit or exceeds the upper limit, the effect of pain relief and nerve ending regeneration is achieved by using each component alone It may be lower than when you use it. In addition, when using the astragalus, angelica, peony, cheongung, doin, safflower, sokdan, poisonous bow or wooseul alone, compared to using the astragalus, angelicae, peony, cheongung, doin, safflower, sokdan, poisonous bow and wooseul together It may show low efficacy.

The extraction solvent of the mixed extract may be any one selected from the group consisting of water, alcohol, ethylene glycol, ethyl ether, and combinations thereof, for example, water, but is not limited thereto.

The term “neuropathic pain” used in the present invention may be peripheral neuropathic pain and/or central neuropathic pain, for example, pain caused by peripheral nerve damage. Specifically, the neuropathic pain may be pain caused by sciatic nerve cut or reconnection after sciatic nerve cut.

The pain may be inflammatory pain of peripheral nerves or muscles, blood vessels, ligaments, connective tissues, and the like. In addition, the pain includes physical pain, psychogenic pain, hyperalgesia, headache, back pain, pelvic pain, myofascial pain, migraine, vascular pain, arthritis pain, diabetic pain, cancer-derived pain, visceral pain, fibromyalgia, post-operative pain, phantom pain , trigeminal neuralgia, diabetic neuropathy, sciatica, but is not limited thereto.

The treatment or prevention of the neuropathic pain can be achieved primarily through the regeneration of nerve endings through an increase in the nerve density and axon number of peripheral nerves. That is, the primary target of pain is peripheral nerve fibers (Aδ and c-fiber). Although there are various mechanisms of excitatory signaling of nerve fibers that cause pathology, changes in action potentials due to abnormal regulation of pain receptors (e.g., TRPV channel nociceptors, various types of inflammatory cytokine receptors) at the site of injury play an important role in the first place. Therefore, observing the expression of inflammatory cytokines (eg, TNF-α, IL-1β, IL-6, etc.) and finding a method for regulating these factors can also be a method for the treatment of chronic neuropathic pain. .

The pharmaceutical composition according to an embodiment of the present invention is non-toxic, and has excellent anti-inflammatory and nerve regeneration effects, and based on this, it can exhibit excellent analgesic efficacy for pain caused by nerve damage.

As used herein, the term “contained as an active ingredient” means including the herbal medicine mixed extract according to an embodiment of the present invention in an amount sufficient to achieve a predetermined efficacy or activity. The herbal medicine mixture extract may be administered in a pharmaceutically effective amount, and the effective dose level may be determined according to the type and age of the individual, sex, sensitivity to drugs, treatment period, drugs used at the same time, and other medical factors.

The pharmaceutical composition according to an embodiment of the present invention may be administered as an individual therapeutic agent or may be administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with existing therapeutic agents.

The daily dosage of the pharmaceutical composition may be 0.01 g/kg to 100 g/kg, for example, 0.01 g/kg to 10 g/kg, for example, 0.2 g/kg to 4 g/kg, It can be administered once or several times a day, but considering the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, severity of disease, etc., there is no side effect and the maximum effect can be obtained. The amount can be easily determined by a person skilled in the art.

The pharmaceutical composition may be administered by various routes such as oral, subcutaneous, intraperitoneal, intrapulmonary, intranasal, intramuscular, intravenous and arterial.

Another aspect of the present invention provides a pharmaceutical preparation for treating or preventing neuropathic pain, comprising the pharmaceutical composition for treating or preventing neuropathic pain.

The pharmaceutical composition for the treatment or prevention of neuropathic pain comprising the herbal medicine mixture extract according to an embodiment of the present invention as an active ingredient includes a pharmaceutically acceptable carrier, excipient and/or diluent in addition to the active ingredient described above. can be formulated.

The pharmaceutical preparation may be formulated in the form of oral dosage forms such as powders, granules, tablets, coated tablets, capsules, suspensions, emulsions, syrups, suppositories, aerosols, external preparations, suppositories, or injections, but is not limited thereto. .

The pharmaceutical formulation may include one or more excipients, for example, starch, lactose, gelatin, sucrose; slush; preservatives; air freshener; It may be prepared by further mixing a sweetener or the like.

Another aspect of the present invention provides a food composition for alleviating neuropathic pain containing a mixed extract of astragalus, angelica, peony, cheongung, doin, safflower, sokdan, dokhwal and wooseul as an active ingredient. In addition, another aspect of the present invention provides a health functional food comprising the food composition for improving the neuropathic pain.

As used herein, the term “health functional food” refers to food manufactured and processed using raw materials or ingredients having useful functions in the human body. Here, 'functionality' refers to intake for the purpose of obtaining useful effects for health purposes such as regulating nutrients for the structure and function of the human body or physiological action.

The food composition may be formulated in the same manner as the pharmaceutical composition and used as a health functional food, and may be added to various foods.

The health functional food containing the food composition may be in the form of beverages, alcohol, sweets, chocolate, other noodles, gum, ice cream, vitamin complexes, health functional foods, and the like. The health functional food may further contain other nutrients, vitamins, electrolytes, flavoring agents, flavoring agents, coloring agents, stabilizers, preservatives, and the like.

Another aspect of the present invention is an anti-inflammatory pharmaceutical composition containing a mixed extract of Astragalus, Angelica, Peony, Chunkyung, Doin, Safflower, Sokdan, Tokhwal and Wooseul as an active ingredient, or the anti-inflammatory pharmaceutical composition comprising the Provides anti-inflammatory pharmaceutical preparations.

Another aspect of the present invention provides a pharmaceutical composition for nerve terminal regeneration or a pharmaceutical preparation for nerve regeneration containing a mixed extract of astragalus, angelica, peony, cheongung, doin, safflower, sokdan, dokhwal and wooseul as an active ingredient.

Another aspect of the present invention provides a method for preparing a mixed extract of Astragalus, Angelica, Peony, Cheongung, Doin, Safflower, Sokdan, Dokhwal and Wooseul.

The method for producing a mixed extract of Astragalus, Angelica, Peony, Chungung, Doin, Safflower, Sokdan, Poison Hal and Wooseul is (i) a herbal medicine mixture by mixing Astragalus, Angelica, Peony, Chunkyung, Doin, Safflower, Sokdan, Toxin and Wooseul. preparing a; and (ii) extracting the herbal medicine mixture using an extraction solvent.

First, it includes the step of preparing a mixture of herbal medicines by mixing Hwanggi, Angelica, Peony, Cheongung, Doin, Safflower, Sokdan, Dokhwal and Wooseul.

The herbal medicine mixture is astragalus 15% to 80% by weight, Angelica 3% to 15% by weight, Peony 2 to 12% by weight, Cheongung 1% to 10% by weight, Doin 1% to 10% by weight, Safflower 1 weight % to 10% by weight, quick cut 3% to 20% by weight, poisonous activity 2% to 10% by weight, and hyssop 2% to 10% by weight, for example, Astragalus 20% to 78% by weight, Angelica 3.5 wt% to 13.5 wt%, peony 2.5 to 10 wt%, cheongung 1.5 wt% to 7 wt%, doin 1.5 wt% to 7 wt%, safflower 1.5 wt% to 7 wt%, short cut 5 wt% to 18 wt%, It can be prepared by mixing in an amount of 2.5 wt% to 9 wt% of poison active and 2.5 wt% to 9 wt% of hyssop.

Alternatively, the herbal medicine mixture is a mixture of astragalus, angelica, peony, cheongung, daoin, safflower, sokdan, dokhwal and hyssul 1: 0.05-0.6: 0.03-0.45: 0.025-0.03: 0.025-0.03: 0.025-0.03: 0.06-0.8 : 0.03-0.4: It can be prepared by mixing in a weight ratio of 0.03-0.4, for example, 1: 0.3: 0.225: 0.15: 0.15: 0.15: 0.4: 0.2: 0.2.

Then, the manufacturing method includes extracting the herbal medicine mixture using an extraction solvent.

The extraction using the extraction solvent may be performed by extraction at room temperature or boiling water extraction using a medicinal water heater, but is not limited thereto.

The extraction solvent of the mixed extract may be any one selected from the group consisting of water, alcohol, ethylene glycol, ethyl ether, and combinations thereof, for example, water, but is not limited thereto.

The herbal medicine mixture may be provided in a weight ratio of 1: 1 to 1: 50, for example, 1: 6 to 1: 22, with the extraction solvent. When the ratio of the extraction solvent to the herbal medicine mixture is out of the above range, the active ingredient of the herbal medicine mixture may be extracted in a small amount in the extract.

The manufacturing method is filtration of the extract; concentration, eg, concentration under reduced pressure; and/or drying, for example, lyophilizing.

Example

Examples 1 to 3. Preparation of herbal medicine mixture extract

Prepared by purchasing a mixture of Astragalus root, Angelica root, Peony root, Cheongung root, Doin seed, Safflower flower, Sokdan root, Toxin root, and Hyssul root from Omni Hub (Daegu, Korea). did. The dried materials were stored at -20 °C until use.

After mixing the prepared herbal medicines in the composition shown in Table 1 below, 1 L of water was added to each mixture, and heated at 100° C. to obtain a mixed extract. Then, the mixed extract was freeze-dried under reduced pressure using a freeze dryer to prepare a mixed extract powder.

Example 1 Example 2 Example 3 Astragalus 120 g 20 g 10 g donkey 6 g 6 g 6 g peony 4.5 g 4.5 g 4.5 g celestial palace 3 g 3 g 3 g doin 3 g 3 g 3 g safflower 3 g 3 g 3 g quick conclusion 8 g 8 g 8 g solitary 4 g 4 g 4 g hyssop 4 g 4 g 4 g

Experimental Example 1. Confirmation of pain relief effect of herbal medicine mixture extract

1.1. animal model creation

First, C57BL/6 mice were bred by supplying sufficient feed and water. During breeding, 12 hours of day-night control with appropriate artificial illuminance was maintained, and the temperature was maintained at 20 to 25 °C and humidity at 40 to 60%.

After a one-week adaptation period, partial sciatic nerve ligation (PSL) was performed to induce neuropathic pain. One week after the partial sciatic nerve ligation was performed, the induction of pain was confirmed from each individual. In order to confirm the effect of partial sciatic nerve ligation, the population that underwent control surgery was prepared as a normal group.

1.2. Confirmation of pain relief effect of herbal medicine mixture extract

In order to confirm the analgesic effect of the herbal medicine mixture extract obtained in Examples 1 to 3, an animal experiment using mice was performed.

To the pain-induced mice obtained in Experimental Example 1, the herbal medicine mixture extract powder obtained in Examples 1 to 3 was dissolved in saline and orally administered at a dose of 2 g per 1 kg of the mouse body weight for 2 weeks, and the control group was treated with a drug Instead, the same dose of saline was orally administered.

One week after surgery and two weeks after drug administration, the degree of pain induction was evaluated by using a behavioral pain test (von Frey test) for each subject. Specifically, mechanical sensitivity was evaluated by measuring the paw withdrawal threshold (PWT) by applying mechanical stimulation to the plantar surface of each hind paw of the subject using von frey filaments. A constant force was applied by applying the filament having the same tip diameter of 0.8 mm to a designated area of the plantar surface. The number of responses to a total of 10 stimuli was recorded, and the duration of each stimulus was 1 second, and the interval between stimuli was about 10 to 20 seconds.

As a result of the experiment, it was observed that the pain significantly increased in all pain-induced animal models one week after the operation. In addition, as a result of conducting a behavioral pain test 2 weeks after drug administration, all of the herbal medicine mixture extracts of Examples 1 to 3 showed a significant pain relief effect, and in particular, Examples 1 and 2 showed a statistically significant analgesic effect. It could be confirmed, and Example 2 showed the most excellent effect among the three types of herbal medicine mixed extracts (FIG. 1).

Experimental Example 2. Confirmation of effective concentration of herbal medicine mixture extract

For the herbal medicine mixture extract of Example 2, which showed the best effect in Experimental Example 1, an animal experiment using mice was performed to confirm the effective concentration for the analgesic effect of the herbal medicine mixture extract.

The herbal medicine mixed extract powder obtained in Example 2 was dissolved in saline in the pain-induced mice obtained in Experimental Example 1.1. and saline was orally administered to the control group instead of the drug.

One week after surgery and two weeks after drug administration, each subject was evaluated for pain induction using a behavioral pain test.

As a result of the experiment, it was confirmed that the best pain suppression efficacy was exhibited when the herbal medicine mixture extract of Example 2 was provided at 2 g/kg (FIG. 2).

Experimental Example 3. Evaluation of analgesic effect of herbal medicine mixed extract in the form of acupuncture

An animal experiment using a mouse was performed to confirm the analgesic effect of the herbal medicine mixture extract administered in the form of acupuncture on the herbal medicine mixture extract of Example 2, which showed the best effect in Experimental Example 1.

After dissolving the herbal medicine mixture extract powder obtained in Example 2 in saline in the pain-induced mouse obtained in Experimental Example 1.1. to a concentration of 0.2 g/ml, both sides of Yangneungcheon and Hwando acupuncture points were placed in a total of 4 locations 31 Using a gauge insulin syringe (BD, USA), 20 μl of each acupuncture point in the form of acupuncture needles was administered daily for 4 days. All control groups were injected with the same dose of saline instead of the drug.

After completion of drug administration, each subject was subjected to a behavioral pain test in the same manner as described in Experimental Example 1.2. to evaluate the degree of pain.

As a result of the experiment, it was observed that the paw withdrawal threshold (PWT) significantly increased in all pain induction models one week after the operation. As a result of conducting a behavioral pain test 4 days after the acupoint injection of the drug, it was confirmed that the acupoint injection of the herbal medicine mixture extract of Example 2 showed a significant pain relief effect (FIG. 3).

Experimental Example 4. Evaluation of anti-inflammatory efficacy of herbal medicine mixture extract

Raw 264.7 cells were prepared from the Korea Cell Line Bank (Seoul, Korea). The cells were placed in high-glucose DMEM supplemented with 10% FBS and maintained at 37 °C in a humidified incubator of _{5% CO 2 .} After the cells were pre-treated with the herbal extract mixtures of Examples 1, 2 and 3 at various concentrations, LPS was treated at a concentration of 100 ng/ml for 24 hours.

For the evaluation of anti-inflammatory efficacy, the NO secreted from the cells was measured at an absorbance of 560 nm using a NO detection kit.

As a result of the experiment, all of the herbal extract mixtures of Examples 1, 2 and 3 exhibited significant anti-inflammatory efficacy compared to the LPS-treated group at a concentration of 1000 μg/ml or more. In particular, it was confirmed that the herbal medicine mixture extract of Example 2 showed the most excellent anti-inflammatory effect (FIG. 4).

Experimental Example 5. Evaluation of nerve terminal regeneration efficacy of herbal medicinal mixture extract

After the rats were anesthetized, both the proximal and distal ends of the sciatic nerve were fixed to the surrounding muscle tissue. After 1 week or 3 months had elapsed after the wound was sutured and recovered, the nerve endings were carefully removed from the tissue, and nerve splicing surgery was performed carefully using 7-0 nylon thread. Afterwards, the herbal extract mixture of Example 3 was orally administered at a concentration of 400 mg/kg daily for 14 days. In the control group, the same amount of saline was orally administered.

After completion of the experiment, motor function and pain response were evaluated. Thereafter, the rats were sacrificed to separate the sciatic nerve from the rats, rapidly frozen, and tissue sections (20 μm) were prepared using a cryosectioning machine. They were sequentially reacted with primary antibodies (anti-NF-200, Sigma) and secondary antibodies (fluorescein goat anti-mouse IgG, Life Technologies), and then attached to slides. Then, it was reacted with Hoechst33258 (2.5 μg/ml) to visualize the nuclei. The fluorescence image of the tissue was observed using a fluorescence microscope, and the degree of nerve regeneration was observed by capturing and analyzing by Adobe Photo Program.

As a result of the pain behavior experiment, it was confirmed that the motor function was significantly improved in the rats treated with the herbal medicine mixture extract of Example 3 compared to the control group provided with saline (FIG. 5A), and at the same time the pain sensation was significantly suppressed. (FIG. 5B).

In addition, as a result of tissue observation, in rats treated with the herbal medicine mixture extract of Example 3, compared to the control group provided with saline, it was confirmed that the nerve density and the number of axons increased by confirming that the damaged nerve endings are being regenerated. could be inferred (FIG. 6).

The description of the present invention described above is for illustration, and those of ordinary skill in the art to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. For example, each component described as a single type may be implemented in a dispersed form, and likewise components described as distributed may be implemented in a combined form.

The scope of the present invention is indicated by the following claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be construed as being included in the scope of the present invention.

Claims (12)

Contains as active ingredients a mixed extract of Astragalus, Angelica, Peony, Chunkyung, Doin, Safflower, Sokdan, Sokhwal and Wooseul.
The mixed extract is extracted with water as an extraction solvent, a pharmaceutical composition for the treatment or prevention of neuropathic pain. The method of claim 1,
The mixed extract is astragalus 15 wt% to 80 wt%, Angelica 3 wt% to 15 wt%, Peony 2 to 12 wt%, Chungung 1 wt% to 10 wt%, Doin 1 wt% to 10 wt%, Safflower 1 wt% Treatment of neuropathic pain, characterized in that it is an extract extracted by mixing in a content of % to 10% by weight, 3% to 20% by weight, 2% to 10% by weight of poisonous activity, and 2% to 10% by weight of hyssop or a pharmaceutical composition for prophylaxis. The method of claim 1,
The mixed extract contains Astragalus, Angelica, Peony, Chunkyung, Doin, Safflower, Sokdan, Sokhwal and Wooseul 1: 0.05-0.6: 0.03-0.45: 0.025-0.03: 0.025-0.03: 0.025-0.03: 0.06-0.8: 0.03 -0.4: A pharmaceutical composition for the treatment or prevention of neuropathic pain, characterized in that the extract is extracted by mixing in a weight ratio of 0.03-0.4. delete The method of claim 1,
The neuropathic pain is a pharmaceutical composition for the treatment or prevention of neuropathic pain, characterized in that peripheral neuropathic pain or central neuropathic pain. The method of claim 1,
The neuropathic pain is a pharmaceutical composition for the treatment or prevention of neuropathic pain, characterized in that it is pain caused by sciatic nerve cut or reconnection after sciatic nerve cut. The method of claim 1,
The treatment or prevention of neuropathic pain is a pharmaceutical composition for the treatment or prevention of neuropathic pain, characterized in that it is made through the regeneration of nerve endings through the increase in the nerve density and axon number of peripheral nerves. A pharmaceutical preparation for the treatment or prevention of neuropathic pain, comprising the pharmaceutical composition for the treatment or prevention of neuropathic pain according to any one of claims 1 to 6. Contains as active ingredients a mixed extract of Astragalus, Angelica, Peony, Chunkyung, Doin, Safflower, Sokdan, Sokhwal and Wooseul,
The mixed extract is extracted by using water as an extraction solvent, a food composition for improving neuropathic pain. A health functional food comprising the food composition for improving neuropathic pain according to claim 8. Contains as active ingredients a mixed extract of Astragalus, Angelica, Peony, Chunkyung, Doin, Safflower, Sokdan, Sokhwal and Wooseul,
The mixed extract is extracted by using water as an extraction solvent, an anti-inflammatory pharmaceutical composition. Contains as active ingredients a mixed extract of Astragalus, Angelica, Peony, Chunkyung, Doin, Safflower, Sokdan, Sokhwal and Wooseul,
The mixed extract is to be extracted using water as an extraction solvent,
A pharmaceutical composition for regeneration of nerve endings for the treatment or prevention of neuropathic pain, through an increase in nerve density and axonal number of peripheral nerves.

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