KR102151401B1 - Composition for preventing or treating pain comprising extracts from Jasminum microcalyx Hance as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for preventing or treating pain containing a Jasmin ( Jasminum microcalyx Hance) extract and/or a fraction thereof as an active ingredient, and the composition is a composition derived from a natural product having excellent pain prevention effect and no toxicity and side effects. , It can be applied more safely to pain treatment.

Description

Composition for preventing or treating pain containing jasmine extract as an active ingredient {Composition for preventing or treating pain comprising extracts from Jasminum microcalyx Hance as an active ingredient}

The present invention relates to a composition for preventing or treating pain containing jasmine ( Jasminum microcalyx Hance) extract and/or a fraction thereof as an active ingredient.

Pain felt by humans can be largely divided into acute pain and chronic pain, and according to the International Institute of Pain Research, pain is defined as "an unpleasant sensory and emotional experience with actual or potential tissue damage." have.

Acute pain is pain caused by invasive stimulation caused by tissue damage caused by disease or trauma, and includes childbirth pain, pain after surgery, pain after tissue damage, etc., and usually disappears within 3 to 6 months. It is effectively treated with drugs (narcotics, nonsteroidal anti-inflammatory drugs). However, chronic pain is caused by nerve damage and changes in the nervous system due to various unclear causes, and lasts longer than the healing period of the disease or injury that caused it. In addition, the boundaries of the pain area are unclear, and the pain is constantly dull and deep, lasts for more than 6 months, and the effects of narcotic analgesics and nonsteroidal anti-inflammatory drugs are limited. For example, there are migraine, rheumatic pain, diabetic pain, and cancer pain, and these pains rapidly deteriorate the patient's quality of life and may accompany depression and the like.

On the other hand, conventional pain relievers that treat pain can be largely divided into two types. One is narcotic analgesics such as morphine, and codeine and dihydrocodeine are widely used, and the other is aspirin as a non-steroidal anti-inflammatory drug (NSAIDS). aspirin), ibuprofen, and indomethacin are representative.

As a new pain suppressant developed recently, Javelin Pharmaceuticals, an intranasal morphine spray, called Rylomine, an intranasal morphine spray, is administered intravenously for the treatment of moderate to severe postoperative pain in late phase 2 clinical trials overseas. A narcotic pain reliever was developed that has the same analgesic effect as morphine, and in China, Shanghai Xinglong Baotech Pharmaceutical Co., Ltd. developed stomach and Eotech Pharmaceutical Co., Ltd. for pain caused by cancers related to gastric intestine, breast, lung and kidney. It has developed a new drug'Achilles' that is effective. In addition,'Prialt', a new pain reliever extracted from sea snail venom, was first marketed in the UK as a pain reliever developed by Elan, an Irish pharmaceutical company.

In Korea, a capsaicin antagonist was developed, and in February 2004, Schwarz Pharma, a German multinational pharmaceutical company, recognized its value and signed a joint research and license agreement, but to date, Jasminum microcalyx Hance (hereinafter,'J Microcalyx') has not been developed or attempted as a pain medication using extracts and/or fractions thereof.

As society ages, patients with chronic malignant tumor pain as well as degenerative arthritis and low back pain-related diseases are on an increasing trend every year, but conventional opiates such as morphine are limited in use due to drug action in the general population, and pain itself is a disease. It is believed that the demand for pain relievers is expected to increase even more in the future as the interest in this is higher than ever and spreading. In addition, it is the time when the development of pain relievers for pain that does not respond to existing pain relievers is greatly required.

However, many patients with pain who do not respond to existing narcotic and non-narcotic analgesics have been reported, and conventional opioids, which are known to have relatively high analgesic effects, are common patients due to narcotic and serious side effects. It is a situation that cannot be used comfortably.

Until now, acetaminophen, aspirin, and the like have been mainly used as analgesics, but these have to be administered to adults at a high dose of about 1 to 4 g per day, and side effects such as gastrointestinal disorders, allergies, and liver toxicity have been problematic. Therefore, it is required to develop a composition for preventing or treating pain derived from nature, which has no side effects and toxicity, and has excellent analgesic effect.

Accordingly, the present inventors confirmed that the jasmine (J. microcalyx) extract and/or a fraction thereof is effective in preventing or treating pain, and completed the present invention.

The present invention is to solve the above-described problem, to provide a composition for preventing or treating pain containing a jasmine (J. microcalyx) extract and/or a fraction thereof as an active ingredient.

In order to achieve the above object, the present invention provides a composition for preventing or treating pain containing a jasmine (J. microcalyx) extract and/or a fraction thereof as an active ingredient.

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

The composition containing the jasmine (J. microcalyx) 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 and no toxicity and side effects, so it can be applied more safely to the treatment of pain.

1 is a component analysis test result using thin layer chromatography (TLC) of J. microcalyx extract according to an embodiment of the present invention.
Figure 2 is a component analysis test results using high performance liquid chromatography (HPLC) J. microcalyx extract according to an embodiment of the present invention.
3 is a result of a formalin pain test (Formalin test) showing the analgesic efficacy of J. microcalyx extract according to an embodiment of the present invention.
4 to 6 are J. microcalyx extract according to an embodiment of the present invention The allodynia test showing analgesic efficacy in the monosodium urate pain model, the Chemotherapy-induced peripheral neuropathy pain model, and the Diabetic Neuropathy pain model, which is well known as a pain model due to gout (Von -frey test) result.

Hereinafter, the present invention will be described in detail so that those skilled in the art can easily implement the present invention.

J. microcalyx is a kind of genus of Jasminum, is an evergreen shrub and consists of 200 species in addition to J. microcalyx. Its main origin is in the tropical or subtropical regions of Asia and Africa. Currently, China and India are representative Asian countries producing jasmine.

Several types of jasmine flowers have a strong scent, and are mainly used as ingredients for flavoring and tea. However, among these species of jasmine commonly used are Jasminum grandiflorum L. and Jasminum officinale L. known as common jasminum, and there are about 5 horticultural species with yellow flowers. Except for all of them, they have no or no fragrance. Thus, J. microcalyx and other species are grown primarily in gardens as ornamental shrubs as perfumes. Shrubs are usually scattered up to 5 m, branches have almost no hairs, and leaves are 3.5-9Х1.5-4.5 cm wide ovate, oval, lanceolate, sharp at the end, round bottom, and cut.

Known effects of jasmine include skin care, labor promotion, disinfection, uterine tonic, pain, soothing, choiyu, aphrodisiac, pain, and anti-depressant soothing nerves. Accordingly, studies on skin cosmetic compositions or depression drug compositions containing jasmine have been mainly made in the prior art.

On the other hand, there is no case of developing or attempting a pain agent using J. microcalyx extract and/or its fractions yet, but in the present invention, it was confirmed that J. microcalyx extract and/or its fractions have excellent effects in preventing or treating pain. And completed this study.

J. microcalyx 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 J. microcalyx and/or a fraction thereof as an active ingredient.

In the present invention, the term “extract” refers to an active ingredient isolated from a natural product, and herein refers to a material isolated from the J. microcalyx.

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

In one embodiment of the present invention, the extract may be an ethanol extract obtained by extracting J. microcalyx (#129) 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 a conventional method for preparing a plant extract, preferably a heated extraction method, a pressurized extraction method, a reflux extraction method, a warm needle extraction method, a solvent extraction method, an ultrasonic grinding extraction method, and the like, preferably a solvent extraction method. However, it is not limited thereto.

In the present invention, the term “fraction” refers to a fraction of the active ingredient of the extract, and here, it means a portion obtained by separating the J. microcalyx extract into several pieces through 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 to perform separation according to polarity. When using silica gel chromatography, the solvent used includes various solvents commonly used in gel chromatography, and may preferably be a mixed solvent of a polar solvent and a non-polar solvent. For example, it may be any one selected from the group consisting of a mixed solution of chloroform (CHCl3) 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 a fraction thereof extracted as described above may be concentrated or the solvent may be removed by performing a filtration under reduced pressure or further concentration and/or freeze drying. Accordingly, the extract in the present invention is used in the sense of including a dried product dried by a conventional method and a concentrate concentrated by a conventional method.

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

Example 1. Preparation of J. microcalyx extract

Jasminum microcalyx Hance (J. microcalyx, #129) was prepared by washing and drying. 10 L of 30% ethanol was added to 1 kg of prepared J. microcalyx, extracted for 3 hours at 60° C., and filtered to obtain a J. microcalyx extract. The extract obtained by repeating the above extraction process twice was concentrated under reduced pressure at a temperature of 45° C. or lower, and then freeze-dried to obtain a powdery J. microcalyx extract (130 g, 13%).

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

In order to confirm the distribution of constituents of the J. microcalyx extract obtained in Example 1, fractionation was performed by chromatography.
After dissolving the extract in methanol at a concentration of 190 mg/ml in thin layer chromatography (TLC, using silica gel 60 (Merk Co. USA) F254 pre-coated), 5 ul was added dropwise to develop a solvent (normal-hexane:ethyl acetate= 4:1,4:2,4:3, 3:4, 2:4, 1:4). After development and photographing with UV (254 nm, 366 nm), the coloration of sulfuric acid was observed, which is illustrated in FIG. 1.

As a result of the analysis, as shown in FIG. 1, it can be confirmed that components having non-polarity are mainly composed and some polar substances are also included.

Experimental Example 2. Component analysis test using high performance liquid chromatography (HPLC)

In order to confirm the distribution of constituents of the J. microcalyx extract obtained in Example 1, it was analyzed using high performance liquid chromatography (HPLC).

Analysis was performed using a column Agilent Eclips SB-C18 (4.5uM, 4.5 * 150 mm id) flow rate 0.7 mL/min, mobile phase water (0.1% Formic acid) (A) and methanol (B) for 0 minutes A:B= 95:5, 40 minutes A:B=0:100, 43 minutes A:B=0:100, 45 minutes A:B=95:5, 50 minutes A:B=95:5, and UV 280 nm , Detected at 254 nm and confirmed the peak. The results are shown in FIG. 2.

As a result of the analysis, as shown in FIG. 2, in the case of the J. microcalyx extract obtained in Example 1, it showed a simple form in 280 nm detection chromatography, and at 254 nm, a large amount of substances having a certain degree of intermediate polarity existed. I can confirm.

Experimental Example 3. Analgesic efficacy evaluation: Formalin pain test (Formalin test)

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

Specifically, 30 minutes after oral administration of the extract to the mouse, 5% Formalin was administered to the left foot of the mouse to conduct the experiment, and at this time, the same test was performed using mice to which the extract was not administered as a control.

As a result, as shown in Figure 3, it can be confirmed the significant analgesic efficacy of the J. microcalyx extract in the 2nd phase.

Experimental Example 4. Analgesic efficacy evaluation: allodynia test (Von-frey test)

The J. microcalyx extract obtained in Example 1 was evaluated for analgesic efficacy using various pain models.

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

In the measurement method, the mouse was placed in an acrylic box installed on a wire mesh experiment table and acclimated for more than 60 minutes, and then a continuous reaction was evaluated by the Up-Down method using Von Frey Filament. Specifically, the filament was in vertical contact with the left affected foot of the mouse and maintained for 5 to 6 seconds so that the mouse showed a rapid avoidance reaction, or immediately flinching while removing the hairs or licking the sole of the foot was considered as positive. If Von Frey Filament was stimulated and positive reaction was found, it was stimulated with weak filament, and if there was no positive reaction, it was analyzed by stimulation with strong filament. At this time, the same test was performed using mice to which the extract was not administered as a control.

As a result, as shown in FIGS. 4 to 6, the J. microcalyx extract according to the present invention is a monosodium urate pain model well known as a pain model due to gout, Chemotherapy-induced peripheral neuropathy (neuropathy caused by anticancer drugs). ) In both the pain model and the Diabetic Neuropathy (diabetic neuropathy) pain model, a dose-dependent pain relief effect can be confirmed, and in particular, it can be seen that it is more effective for pain caused by diabetic neuropathy.

So far, the present invention has been looked at around its preferred embodiments. Those of ordinary skill in the art to which the present invention pertains will be able to understand that the present invention can be implemented in a modified form without departing from the essential characteristics of the present invention.

Claims (8)

A pharmaceutical composition for preventing or treating pain, containing an extract extracted for 2 to 4 hours at 50 to 70° C. by adding ethanol to Jasmin (Jasminum microcalyx Hance) as an active ingredient.
delete The method of claim 1,
A pharmaceutical composition for preventing or treating pain, containing a fraction separated by chromatography using a solvent mixed with the jasmine extract in a volume ratio of hexane:ethyl acetate = 4 to 1:1 to 4 as a developing solvent as an active ingredient .
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 preventing or treating pain Pharmaceutical composition.
The method of claim 6,
The neuropathic pain is neuropathic pain (CIPN) caused by an anticancer agent, a pharmaceutical composition for preventing or treating pain.
A pharmaceutical formulation comprising the composition of claim 1.

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