KR20230138973A - An analgesic formula comprising fingerroot and milk thistle - Google Patents

Abstract

The present invention relates to a composition for suppressing pain containing a blend of finger root and milk thistle as an active ingredient. More specifically, the present invention contains a blend of finger root and milk thistle as an active ingredient to prevent pain. , to provide a composition for improvement or treatment.

Description

An analgesic formula comprising fingerroot and milk thistle to relieve pain

The present invention relates to a pain-suppressing combination of fingerroot and milk thistle.

Pain includes acute pain, subacute pain, recurrent pain, persistent cancer pain, chronic pain, and chronic pain syndrome. The mechanism of pain known to date is an unpleasant sensation felt by stimulating the cerebral cortex and system areas through afferent nerve pathways from nociceptors to nerve fibers. Substances related to pain include prostaglandin, leukotriene, and thromboxane, which are produced by cyclooxygenase and lipoxygenase using arachidonic acid as a substrate. In addition, there are serotonin, catecholamine, protons, histamine, and potassium ions.

Pain treatment includes pharmacological treatment (analgesics, non-narcotic analgesics, non-steroidal anti-inflammatory drugs, antidepressants), injection treatment (mainly local injections into muscle pain areas), physical therapy (cold treatment, heat treatment, high voltage direct current). There are electrotherapy, transcutaneous electrical nerve stimulation therapy, exercise therapy, ultrasound therapy, iontophoresis, and phonophoresis), but these treatment methods usually have side effects, are resistant to repeated treatments, and the effects are often temporary, so in reality, It is difficult to expect appropriate and perfect treatment.

Pain felt by humans can be broadly divided into acute pain and chronic pain. According to the International Association for the Study of Pain, pain is defined as “an unpleasant sensory and emotional experience accompanied by actual or potential tissue damage.” there is.

Acute pain is pain caused by nociceptive stimulation caused by tissue damage due to disease or trauma, and includes pain after childbirth, pain after surgery, pain after tissue damage, etc. It generally disappears within 3 to 6 months and can be caused by various symptoms. It is effectively treated with drugs (narcotic analgesics, non-steroidal anti-inflammatory drugs). However, chronic pain is caused by nerve damage and subsequent changes in the nervous system due to various unclear causes, and it lasts longer than the healing period of the causing disease or damage. In addition, the boundaries of the pain area are unclear, the pain is persistently dull and deep, lasts for more than 6 months, and the effect of narcotic analgesics or non-steroidal anti-inflammatory drugs is limited. For example, there are migraines, rheumatic pain, diabetic pain, and cancer pain, and such pain can drastically reduce the patient's quality of life and be accompanied by depression.

Meanwhile, existing painkillers that treat pain can be broadly divided into two types. One is narcotic analgesics such as morphine, and codeine and dihydrocodeine are widely used, and the other is non-steroidal anti-inflammatory drugs (NSAIDS). Representative examples include aspirin, ibuprofen, and indomethacin.

As a recently developed new pain suppressant, Rylomine, an intranasal morphine spray from overseas pain treatment specialist developer Javelin Pharmaceuticals, has been used in combination with intravenous morphine for the treatment of moderate to severe postoperative pain in late phase 2 clinical trials. A root narcotic analgesic that has comparable analgesic effects has been developed, and in China, Shanghai Xinglong Biotech Pharmaceutical Company has developed a new drug, 'Achilles,' which is effective for pain caused by cancer related to the stomach, intestines, breast, lung, kidney, etc. ' has been developed. In addition, 'Prialt', a new painkiller extracted from sea snail venom, was developed by Irish pharmaceutical company Elan and was first marketed in the UK.

Capsaicin antagonist was developed in Korea, and in February 2004, Schwarz Pharma, a German multinational pharmaceutical company, recognized its value and signed a joint research and licensing agreement.

As society ages, as well as chronic malignant pain, the number of related diseases such as degenerative arthritis and back pain is increasing every year. However, the use of existing opiates such as morphine is limited due to their narcotic effect in the general public, and the pain itself is It is considered a disease, and as interest in it is spreading more than ever, the demand for pain relievers is expected to increase even more in the future. In addition, there is a great need for the development of analgesics for pain that does not respond to existing analgesics.

Not only are there many reports of pain patients who do not respond to existing narcotic and non-narcotic analgesics, but also existing opioids, which are known to have relatively high analgesic effects, are suffering from narcotic properties and serious side effects, making them difficult for general patients. It is not possible to use it comfortably.

To date, acetaminophen and aspirin have been mainly used as painkillers, but these must be administered to adults in high doses of about 1 to 4 g per day, which has led to problems with side effects such as gastrointestinal disorders, allergies, and hepatotoxicity. Therefore, there is a need to develop a natural pain prevention or treatment composition that has no side effects or toxicity and has excellent analgesic effects.

Accordingly, the present inventors worked to develop a material that suppresses pain from natural products with fewer side effects, and as a result, they completed the present invention by confirming that the pain suppressing effect was significantly increased when finger root and milk thistle were combined, compared to the single substance. did.

Document 1. Republic of Korea Patent 10-2151401 Document 2. Republic of Korea Patent 10-2007758

Document 1. Escamilla, M. M. et al., 2019, Analgesic Effect of Herbal Extract. Int. J. Pharmacol. 15(5): 629-635. Document 2. Mi, B. et al., 2020, A network pharmacology study on analgesic mechanism of Yuanhu-Baizhi herb pair. BMC Compl. Med. &Therap. 20:284.

The purpose of the present invention is to provide a composition that prevents, improves, and treats pain, including finger root and milk thistle as active ingredients.

The present invention provides a composition for preventing, improving, and treating pain, including finger root and milk thistle as active ingredients.

The present inventor sought to develop a substance that can treat pain without side effects. As a result, it was discovered that a combination of finger root and milk thistle could significantly reduce pain.

The composition for preventing and treating pain of the present invention contains finger root and milk thistle as active ingredients.

Fingerroot is the rhizome of Boesenbergia rotunda , a member of the ginger family. It is used as a spice in tropical Southeast Asia and has been widely used as a traditional medicine due to its strong antibacterial and anti-inflammatory effects [ Evidence-based Complementary and Alternative Med., 2012, Article ID 473637 (2012)]. In addition, the ethanol extract of finger root and the panduratin A component isolated therefrom are low molecular weight compounds and have been reported to have anti-obesity and anti-diabetic effects [Diabetes, Obes. Metab. 13(7): 584 (2011); Int. J. Mol. Sci. 13:994 (2012)]. In the present invention, finger root was very effective in suppressing pain when combined with milk thistle.

Milk thistle ( Silybum ) plants are distributed in central and southern Europe, the Mediterranean, Russia, and Central Asia, and there are two species. Of these, only one species has been introduced and cultivated in China, and is used as a medicine. Already 2,000 years ago, the leaves of milk thistle ( Silybum marianum ) were used as a treatment for liver disease in ancient Greece. Milk thistle is widely used in Germany to treat all types of chronic liver disease, especially fatty liver caused by excessive consumption of alcoholic beverages.

Silybum marianum is listed as the official native plant of milk thistle fruit (Cardui Mariae Fructus) in the American Pharmacopoeia (28th edition) and the British Herbal Pharmacopoeia (1996).

All parts of milk thistle are edible, and the fruit (seed) contains flavonolignan, and the main components are collectively called silymarin. Pharmacological studies have shown that silymarin protects the cell membrane of hepatocytes, improves liver function, and prevents liver damage caused by various liver toxins. In addition to flavonolignans such as silymarin, milk thistle fruits contain proteins, amino acids, fats, polyunsaturated fatty acids, vitamins and trace elements.

In the present invention, finger root and milk thistle are (a) water, (b) anhydrous and hydrous lower alcohols having 1-4 carbon atoms (methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, etc.) , (c) a mixed solvent of the lower alcohol and water, (d) acetone, (e) ethyl acetate, (f) chloroform, (g) 1,3-butylene glycol, (h) hexane, or (i) diethyl It can be used by extraction with ether.

In the present invention, it is obvious to those skilled in the art that finger root and milk thistle extracts showing the same effect can be obtained even if the finger root and milk thistle are extracted using other extraction solvents as well as the above extraction solvent.

In addition, the extract of the present invention includes not only extracts using the above-described extraction solvents, but also extracts that have undergone conventional purification processes. Fractions obtained through various additional purification methods, such as separation by ultrafiltration membrane with a certain molecular weight cut-off value, separation by various chromatographs (designed for separation according to size, charge, hydrophobicity, or affinity). It is also included in the extract of the present invention.

The extract of the present invention can be prepared in powder form by additional processes such as reduced pressure distillation and freeze-drying or spray drying.

The composition of the present invention may be provided as a pharmaceutical composition or a food composition.

When the composition of the present invention is prepared as a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the pharmaceutical composition of the present invention are those commonly used in preparation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, Includes, but is not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition to the above ingredients, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Suitable pharmaceutically acceptable carriers and agents are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention can be administered orally or parenterally, and is preferably administered orally.

The appropriate dosage of the pharmaceutical composition of the present invention is prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. It can be. The general dosage of the pharmaceutical composition of the present invention is within the range of 0.01-3,000 mg/kg per day for adults.

The pharmaceutical composition of the present invention is prepared in unit dose form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily performed by a person skilled in the art. Alternatively, it can be manufactured by placing it in a multi-capacity container. At this time, the dosage form may be in the form of a solution, suspension, syrup, emulsion, etc. in oil or aqueous medium, or in the form of extract, powder, powder, granule, tablet, capsule, etc., and may additionally contain a dispersant, stabilizer, etc. You can.

When the composition of the present invention is manufactured as a food, it includes not only finger root and milk thistle as active ingredients, but also ingredients commonly added during food production, such as proteins, carbohydrates, fats, nutrients, seasonings, and flavoring agents. The above-mentioned carbohydrates are common sugars such as monosaccharides (glucose, fructose, etc.), disaccharides (maltose, sucrose, etc.), oligosaccharides, polysaccharides (dextrin, cyclodextrin, etc.), and sugar alcohols (xylitol, sorbitol, erythritol, etc.). As a flavoring agent, natural flavoring agents [thaumatin, stevia extract (rebaudioside A), glycyrrhizin, etc.] or synthetic flavoring agents (saccharin, aspartame, etc.) can be used.

The composition for suppressing pain containing finger root and milk thistle as active ingredients of the present invention can relieve, prevent, improve, and treat pain. Therefore, the composition of the present invention can be used as a health food composition for suppressing pain and can be used as a wide range of pain suppressants.

The present invention will be described in more detail through examples below. These examples are only for illustrating the present invention in more detail, and according to the gist of the present invention, it will be obvious to those skilled in the art that the scope of the present invention is not limited by these examples. will be.

Example 1. Preparation of finger root and milk thistle samples

Finger root is from Indonesia, purchased from Donggwang General Products Co., Ltd. (1141-51, Jegi-dong, Dongdaemun-gu, Seoul), and ground to 100 mesh. Milk thistle was made into milk thistle extract powder (500 mg/g of silymarin), ( It was purchased and used from Zelzone Bio Co., Ltd. (#611, Building 1, 505 Beonyeong-ro, Gunpo-si, Gyeonggi-do).

Example 2. Measurement of pain suppression effect using experimental animals

1. Experimental method

1) Experimental animals and experimental diet

Six-week-old ICR male mice used as experimental animals were supplied by Orient Bio Co., Ltd. (322 Galmachi-ro, Jungwon-gu, Seongnam-si, Gyeonggi-do).

The experimental animals were raised in a space with a constant temperature of 22 ± 1°C, humidity of 55 ± 10%, and a 12-hour light/dark cycle, and were allowed to freely consume chow (Orient Bio) and drinking water.

The daily dosage of the sample according to Example 1 was calculated from the ratio of the recommended daily intake for humans and the average metabolic weight ( ^3/4 of body weight) of humans and mice, and then [Nutr. Res. 11, 1465 (1991)], due to the nature of animal model testing, it was quadrupled to obtain quick results. The recommended daily intake for humans was 650 mg of finger root, 250 mg of milk thistle extract powder, 900 mg of finger root and milk thistle mixture, and the average human body weight was 65 kg. Samples mixed in distilled water were administered orally twice a day for 5 days.

2) Measurement of pain suppression effect using hot plate test

This was conducted after oral administration of the sample for 5 days.

The mouse was placed on a hot pad maintained at 30°C and allowed to adapt for about 10 minutes. The mouse was placed on a hot plate maintained at a constant temperature (55 ± 1°C), and the time for licking the front or hind paws or jumping off (hot plate latency) was measured (Jones CK et al. Efficacy of duloxetine, a potent and balanced serotonergic and noradrenergic reuptake inhibitor, in inflammatory and acute pain models in rodents. J Pharmacol Exp Ther. 2005, 312(2): 726-732.). During the measurement, the mouse taking off its feet to move was excluded from the measurement, and the measurement was performed within 30 seconds (cut-off time: 30 seconds) to prevent tissue damage. When measuring the avoidance response, in the case of mice that did not respond within the time limit (30 seconds), the cut-off time (30 seconds) was recorded (Choi JH et al. Anti-inflammatory and anti-nociceptive properties of Prunus padus . J Ethnopharmacol. 2012, 144(2): 379-386).

3) Statistical processing

Measurements were analyzed using Duncan's multiple range test and expressed as mean ± SEM [SAS Institute, Inc., SAS User's Guide: Statistics, 5th ed., Cary, NC, (1985)].

2. Experiment results

The avoidance reaction time increased by 15% and 20% in the fingerroot and milk thistle groups, respectively, compared to the control group, but there was no statistically significant difference. In all combination groups of finger root and milk thistle, the avoidance reaction time significantly increased compared to the single group of finger root and milk thistle, and the rate of increase was less than that of the single group of finger root and milk thistle. The synergistic effect of pain suppression due to the combination of the two ingredients was recognized, exceeding the arithmetic sum of 35%, and the pain suppression rate was the highest at 83% in the 75:25 mixing ratio group. Through this, it was confirmed that ingestion of a combination of finger root and milk thistle had an excellent pain suppressing effect (Table 1).

Effect of oral administration of finger root, milk thistle and their combination on avoidance reaction time in hot plate test ¹ sample control group finger root milk thistle 90:10 ² 75:25 60:40 Avoidance reaction time (seconds) 3.30± ^0.27a 3.81± ^0.33a 3.95± ^0.40a 4.85± ^0.34b 6.04± ^0.41c 5.16± ^0.39b Increase rate (%) 15 20 47 83 56

¹ Mean ± SEM, 10 animals per group. Values with different superscripts in the same column are significantly different (P<0.05).

² Combination ratio of finger root and milk thistle.

Example 3. Measurement of pain suppression effect in humans

1. Test method

For the sample according to Example 1, 120 people with pain in the fingers, wrist, calf, waist, shoulder, and knee joints were selected and a pain inhibition test was performed.

The subject's pain level before and after sample intake was measured using a visual analog scale (VAS) by listing scores from 0 to 10 in the order of 'no pain' → 'extreme pain'. After correcting the results of the comparison group (placebo group) to be 0, the degree of pain suppression in each group was confirmed.

The daily dosage of the sample according to Example 1 was 650 mg of finger root, 250 mg of milk thistle extract powder, and 900 mg of a mixture of finger root and milk thistle, which were orally administered twice a day for 15 days.

Measurements were analyzed using Duncan's multiple range test and expressed as mean ± SEM [SAS Institute, Inc., SAS User's Guide: Statistics, 5th ed., Cary, NC, (1985)].

2. Test results

Compared to the control group, human joint pain decreased by 14% in the finger root group and by 11% in the milk thistle group, but there was no statistically significant difference. In all combination groups of finger root and milk thistle, pain was significantly reduced compared to the single group of finger root and milk thistle, and the pain suppression rate was 25, which is the arithmetic sum of the suppression rates of the finger root and milk thistle single group. In excess of %, the synergistic effect of pain suppression due to the combination of the two ingredients was recognized, and the pain suppression rate in the 75:25 group was the highest at 63%. Through this, it was confirmed that ingestion of a combination of finger root and milk thistle had an excellent pain suppressing effect (Table 2).

Effects of consumption of fingerroot, milk thistle, and their combinations on joint pain in humans ¹ sample finger root milk thistle 90:10 ² 75:25 60:40 Pain suppression rate (%) 14± ^5a 11± ^4a 27± ^3b 63± ^6c 35± ^7b

¹ Mean ± SEM, 20 people per group. Values with different superscripts in the same column are significantly different (P<0.05).

² Combination ratio of finger root and milk thistle.

Although specific parts of the present invention have been described in detail above, it is clear to those skilled in the art that these specific techniques are merely preferred embodiments and that the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the invention is defined by the appended claims and their equivalents.

Claims (1)

A composition for preventing, improving and treating pain containing 60 to 90% by weight of finger root and 10 to 40% of milk thistle.