KR102073796B1 - Composition for preventing or treating pain comprising extracts from Combretum farinosum Kunth as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for preventing or treating pain containing Combretum farinosum Kunth extract and / or fractions thereof as an active ingredient, wherein the composition is a composition derived from natural products having excellent pain prevention effect but no toxicity and side effects. More securely.

Description

Composition for preventing or treating pain comprising extracts from Combretum farinosum Kunth as an active ingredient

The present invention relates to a composition for preventing or treating pain containing Combretum farinosum Kunth extract and / or fractions thereof as an active ingredient.

Human pain can be classified into acute pain and chronic pain. According to the International Pain Research Association, pain is defined as "unpleasant sensory and emotional experience with actual or potential tissue damage." have.

Acute pain is pain caused by invasive irritation caused by tissue damage caused by disease or trauma. Pain in childbirth, postoperative pain, pain after tissue damage, etc. are usually lost within 3 to 6 months. It is effectively treated by drugs (narcotics, NSAIDs). However, chronic pain is caused by nerve damage and subsequent changes in the nervous system due to various unclear causes, and lasts longer than the healing period of the cause of the disease or injury. In addition, the boundary of the pain area is unclear, persistent dull and deep pain, lasting more than 6 months, the effectiveness of narcotic analgesics or nonsteroidal anti-inflammatory drugs is limited. For example, there are migraine headaches, rheumatic pains, diabetic pains, and cancer pains, which can drastically reduce the quality of life of the patient, and can involve depression and the like.

On the other hand, conventional painkillers for treating pain can be divided into two types. One is narcotic analgesics such as morphine, and codeine and dihydrocodeine are widely used. The other is asteroid (non-steroidal anti-inflammatory drugs) and aspirin (NSAIDS). aspirin, ibuprofen, and indomethacin.

Recently, new pain inhibitors have been developed overseas, such as pain relief developer Javelin Pharmaceuticals' intranasal morphine spray `` Rylomine '', which is administered intravenously in the treatment of moderate to severe postoperative pain in later phase 2 clinical trials. Roots, which have comparable analgesic effects to morphine, have developed narcotic analgesics. In China, the Shanghai Xinglong Baotech Pharmaceutical Co., Ltd. has established the stomach and Iotech Pharmaceutical Co., Ltd. for pain caused by stomach and intestine, breast, lung, and kidney-related cancers. He has developed a new drug, Achilles. In addition, the new analgesic 'Prialt', extracted from sea snail venom, was developed by Irish pharmaceutical company Elan for the first time in the UK.

In Korea, the German pharmaceutical company Schwarz Perm, which has developed capsaicin antagonists, signed a joint research and licensing agreement in February 2004. There have been no cases of developing or attempting pain medications using extracts and / or fractions thereof.

As the society ages, as well as chronic malignant neoplastic pain, the number of patients with degenerative arthritis and low back pain is increasing every year, but existing opiates such as morphine are limited to the general public due to narcotic action. It is considered that the demand for pain relief is expected to be much higher in future. In addition, it is time to develop a painkiller for pain that does not respond to existing painkillers.

However, there are many reports of pain patients who do not respond to existing narcotic and non-narcotic analgesics, and conventional opioids, which are known to have relatively high analgesic effects, have been reported by general patients due to narcotic and serious side effects. The situation is not comfortable to use.

To date, as analgesics, acetaminophen, aspirin, and the like have been mainly used, but they have to be administered to adults at high doses of about 1 to 4 g per day, which causes problems such as gastrointestinal disorders, allergies, and liver toxicity. Therefore, there is a need for the development of a composition for preventing or treating pain derived from nature having no side effects and toxicity and excellent analgesic effect.

The present inventors have confirmed that the C. farinosum extract and / or fractions thereof have a pain prevention or treatment effect, and completed the present invention.

The present invention is to solve the above problems, to provide a composition for preventing or treating pain containing C. farinosum extract and / or fractions thereof as an active ingredient.

In order to achieve the above object, the present invention provides a composition for preventing or treating pain containing C. farinosum extract and / or fractions thereof as an active ingredient.

The composition for preventing or treating pain of the present invention can be applied to general chronic pain. Specifically, the pain may be pain, neuropathic pain, complex pain, or cancer pain, but is not limited thereto. For example, postoperative pain, post-traumatic pain, delivery pain, arthritis pain, diabetic neuropathic pain, shingles neuralgia, trigeminal neuralgia, pain after spinal surgery, spinal stenosis, carpal tunnel syndrome, all 2 due to cancer Secondary pain, and the neuropathic pain may be neuropathic pain (CIPN) caused by an anticancer agent.

The composition containing C. farinosum extract and / or fractions thereof according to the present invention as an active ingredient is a composition derived from a natural product having excellent pain treatment effect but no toxicity and side effects, and thus can be more safely applied to pain treatment.

1 is a component analysis test results using thin layer chromatography (TLC) of C. farinosum extract according to an embodiment of the present invention.
Figure 2 is a component analysis test results using high performance liquid chromatography (HPLC) of C. farinosum extract according to an embodiment of the present invention.
3 is a formalin test result showing the analgesic efficacy of C. farinosum extract according to an embodiment of the present invention.
4 to 6 is a C. farinosum extract according to an embodiment of the present invention Von test for pain relief in the monosodium urate pain model, a well-known pain model due to gout, the chemotherapy-induced peripheral neuropathy pain model, and the diabetic neuropathy pain model. -frey test) result.

Hereinafter, the present invention will be described in detail so that a person skilled in the art can easily carry out the present invention.

C. farinosum is a tropical American plant known as 'orange flame vine', a species of bush willow that grows from Mexico to northern Argentina. C. farinosum is a giant shrub that grows up to 3 m (9.8 ft) without special support and up to 11 m (36 ft) when supported. Its stems have a stripe with a cylindrical shape, and the leaves are 6 to 16 cm long and 3 to 8 cm wide. Or ovate, leaf's upper side is dark green, and underside is yellowish. Petiole 0.5-2.2cm long, hairless, with greyish, pointed stalks. Flowers bloom between February and May, which vary in color from green to yellow to orange to red over time, but are most often seen in red. Fruits are 17-27mm Х10-19mm, reddish in color, and the hairline has the form of gray felt scales that frequently inhabit the base and inflorescence.

On the other hand, there has been no case of developing or attempting a pain agent using the C. farinosum extract and / or fractions thereof, but in the present invention, C. farinosum extract and / or fractions thereof have an excellent effect in preventing or treating pain. Confirmed and completed this study.

C. farinosum used in the present invention is not particularly limited in its form, and the composition of the present invention is characterized in that it contains an extract obtained from C. farinosum and / or a fraction thereof as an active ingredient.

As used herein, the term “extract” refers to an active ingredient isolated from natural products, and here refers to a material isolated from C. farinosum.

The C. farinosum extract may be obtained by a conventional C. farinosum extraction method using at least one solvent selected from the group consisting of water and C ₁ to C ₄ linear or branched alcohols or mixtures thereof.

In one embodiment of the present invention, the extract may be an ethanol extract obtained by extracting C. farinosum (# 116) with 30 to 80% (v / v) ethanol in order to achieve an effective pain prevention or treatment effect .

The extract may be prepared according to the conventional method for producing a plant extract, preferably by a warm extraction method, pressure extraction method, reflux extraction method, warm extraction method, solvent extraction method, ultrasonic grinding extraction method, etc., preferably solvent extraction method It may be by, but is not limited to.

As used herein, the term "fraction" refers to a fraction obtained by fractionating the active ingredient of the extract, wherein the C. farinosum extract is separated into several pieces by chromatography.

The chromatography may be any one capable of performing separation of fractions according to size, ions, charge (polarity), hydrophobicity or affinity, but is preferably silica gel chromatography performing separation according to polarity. When using silica gel chromatography, the solvent used includes various solvents conventionally used for gel chromatography, and may preferably be a mixed solvent of a polar solvent and a nonpolar solvent. For example, it may be any one selected from the group consisting of a mixed solution of chloroform (CHCl 3) and methanol, a mixed solution of n-hexane and ethyl acetate, and a mixed solution of ethyl acetate and methanol. Preferably, it may be a mixed solution of n-hexane and ethyl acetate or ethyl acetate and methanol.

In addition, the extract and / or fractions thereof extracted as described above may then be concentrated or removed from the solvent by performing a reduced pressure filtration process or by further concentrating and / or lyophilizing. Thus, the extract in the present invention is used in the sense that it includes a dried product dried in a conventional manner and a concentrate concentrated in a conventional manner.

Hereinafter, a composition for preventing or treating pain containing the extract and / or a fraction thereof obtained from C. farinosum of the present invention as an active ingredient and a method for preparing the same will be described in detail with reference to various examples below.

Example 1. Preparation of C. farinosum extract

Combretum farinosum Kunth (C. farinosum, # 116) was prepared by washing and drying. 10 L of 30% ethanol was added to 1 kg of prepared C. farinosum and extracted at 60 ° C. for 3 hours, followed by filtration to obtain C. farinosum extract. The extract obtained by repeating the above extraction process twice was concentrated under reduced pressure at a temperature of 45 ° C. or lower, followed by freeze drying to obtain a powdery C. farinosum extract (120 g, 12%).

Experimental Example 1. Component analysis test using thin layer chromatography (TLC)

In order to confirm the distribution of components of the C. farinosum extract obtained in Example 1, TLC (Thin layer chromatography, silicagel 60 (Merk Co. USA) F254 precoated using) the extract in methanol at 190 mg / ml concentration After dissolving, 5 ul was dropped and developed in a developing solvent (hexane: ethyl acetate = 4: 1,4: 2,4: 3, 3: 4, 2: 4, 1: 4). After the development, the color development of sulfuric acid was observed after shooting with UV (254 nm, 366 nm), which is shown in FIG. 1.

As a result of the analysis, as shown in Figure 1, the components having a polar dominant, it can be seen that also contains some non-polar material.

Experimental Example 2 Component Analysis Test Using High Performance Liquid Chromatography (HPLC)

In order to confirm the component distribution of the C. farinosum extract obtained in Example 1, it was analyzed by HPLC (high performance liquid chromatography).

Analysis was performed using column Agilent Eclips SB-C18 (4.5 uM, 4.5 * 150 mm id) flow rate 0.7 mL / min, mobile phase water (0.1% Formic acid) (A) and methanol (B) for 0 min A: B = 95: 5, 40 min A: B = 0: 100, 43 min A: B = 0: 100, 45 min A: B = 95: 5, 50 min A: B = 95: 5, UV 280 nm , Peak was confirmed by detection at 254 nm. The results are shown in FIG.

As a result, as shown in Figure 2, the C. farinosum extract obtained in Example 1 shows a simple form in 280 nm detection chromatography, a large amount of a substance having a certain degree of mesopolarity at 254 nm You can check.

Experimental Example 3. Evaluation of analgesic efficacy: formalin test

In order to evaluate the analgesic efficacy of the C. farinosum extract obtained in Example 1, after administering the extract to the mice, a formalin test was performed, and the results are shown in FIG. 3.

Specifically, 30 minutes after oral administration of the extract to the mouse, the experiment was conducted by administering 5% Formalin to the left foot of the mouse, in which the same test was used in mice that were not administered the extract as a control.

As a result, as shown in Figure 3, the significant analgesic effect of the C. farinosum extract in the 2nd phase can be confirmed.

Experimental Example 4. Evaluation of analgesic efficacy: Von-frey test

C. farinosum extract obtained in Example 1 was evaluated for analgesic efficacy using various pain models.

After administration of the extract to each mouse, a sciatic nerve injury was performed after a Von-frey test for mechanical stimulation (Von-frey test), the results are shown in Figures 4 to 6 below.

In the measuring method, the mouse was placed in an acrylic box installed on a wire mesh test bench for at least 60 minutes, and the continuous reaction was evaluated by the up-down method using Von Frey Filament. Specifically, the filament was vertically contacted with the sole of the left affected leg of the mouse and maintained for 5 to 6 seconds, so that the mouse exhibited a rapid avoidance reaction or immediately jumped or licked the sole while removing hairs. Stimulation of the Von Frey Filament resulted in a weak filament if positive, and a strong filament if no positive response. At this time, the same test was used using the mice not administered the extract as a control.

As a result, as shown in Figures 4 to 6, the C. farinosum extract according to the present invention is a monosodium urate pain model, Chemotherapy-induced peripheral neuropathy (an anticancer drug-induced neuropathy), which is well known as a pain model due to gout Dose-dependent pain relief in both pain and diabetic neuropathy pain models can be seen, especially in diabetic neuropathy.

So far I looked at the center of the preferred embodiment for the present invention. Those skilled in the art will appreciate that the present invention can be implemented in a modified form without departing from the essential features of the present invention.

Claims (8)

C. C is extracted for 2 to 4 hours at 50 to 70 ℃ by adding at least one solvent selected from the group consisting of water, C ₁ to C ₄ linear or branched alcohol, and mixtures thereof to C. farinosum ( Combretum farinosum Kunth) For preventing or treating pain containing C. farinosum fraction, which is separated by chromatography, using a solvent in which the farinosum extract is mixed in a volume ratio of hexane: ethyl acetate = 4 to 1: 1-4 as a developing solvent. Pharmaceutical compositions.
delete delete delete delete The method of claim 1,
The pain is any one or more chronic pain selected from the group consisting of nociceptive pain, neuropathic pain, mixed pain and cancer pain, for the prevention or treatment of pain Pharmaceutical compositions.
The method of claim 6,
The neuropathic pain is neuropathic pain (CIPN) by an anticancer agent, pain prevention or treatment pharmaceutical composition.
A pharmaceutical formulation comprising the composition of claim 1.

Images