KR20230174698A - Pharmaceutical composition for the treatment of pain containing hemp seed oil as an active ingredient - Google Patents

Abstract

The present invention provides a pharmaceutical composition for treating pain containing hemp seed oil as an active ingredient, which has no side effects and can effectively suppress pain caused in the body as well as quickly treat the cause of pain.

Description

Pharmaceutical composition for the treatment of pain containing hemp seed oil as an active ingredient}

The present invention relates to a pharmaceutical composition for treating pain, and more specifically, to a pharmaceutical composition for treating pain containing hemp seed oil as an active ingredient.

Hemp is an annual plant belonging to the Samaceae family that has been used by mankind. Its origin is Central Asia. Its scientific name is ‘ Cannabis sativa ’, and in English-speaking countries it is called ‘Cannabis’ or ‘hemp’ after the genus name. It is also called '(Hemp)' and in Korea it is commonly called 'hemp', and clothes made of hemp are called hemp clothes or sackcloth. People are reluctant to use cannabis because it is associated with hallucinogenic effects, but hemp seed oil is an oil extracted by cold-pressing hemp seeds and does not contain the hallucinogenic ingredient (delta-9-tetrahydrocannabinol, THC). Cannabis, which has powerful inflammation treatment effects, is approved for use for medical purposes in many countries and is also used as health functional foods, beverages, and cosmetics. Legally approved hemp is made by removing the hallucinogenic THC component from hemp seeds and extracting only the cannabinoid (CBD), which is effective in treating diseases. It is known to not cause hallucinations and is not addictive. Currently, there are about 50 countries that allow the use of cannabis to treat diseases, and in most states in the U.S., Canada, Europe, and Japan, hemp oil, hemp seed oil, hemp seed oil, and hemp seeds containing cannabinoids are easily available. Even in Korea, hemp seed oil (hemp seed oil), which is allowed to be imported as food, is being distributed. Meanwhile, hemp has been found to have various effects in addition to treating inflammation, so the hemp oil industry is expected to grow significantly globally in the future. The World Health Organization (WHO) verified at the 40th Drug Dependency Expert Committee that the cannabinoid component of cannabis is effective in treating 17 diseases, including Alzheimer's dementia, Parkinson's disease, epilepsy, cancer, depression, multiple sclerosis, and diabetes complications. . In this regard, Republic of Korea Patent Publication No. 2011-0122961 discloses a composition for preventing and treating arthritis containing hemp seed extract.

However, the extract is a composition for treating arthritis that contains hemp seed extract as an active ingredient, and research on painkillers using hemp seed oil as an active ingredient is still an unexplored field.

The present invention is intended to solve various problems including the problems described above, and is a pain treatment containing hemp seed oil as an active ingredient, which has no side effects and can effectively suppress pain caused in the body as well as quickly treat the cause of pain. The purpose is to provide a pharmaceutical composition for use. However, these tasks are illustrative and do not limit the scope of the present invention.

According to one aspect of the present invention, a pharmaceutical composition for treating pain containing hemp seed oil as an active ingredient is provided.

According to another aspect of the present invention, a method for alleviating or treating pain is provided, comprising administering the pharmaceutical composition for treating pain.

According to another aspect of the present invention, a local anesthetic containing hemp seed oil as an active ingredient is provided.

As described above, the pharmaceutical composition for treating pain containing hemp seed oil as an active ingredient of the present invention not only has an analgesic effect that effectively suppresses various pains occurring in the human body, but also has the effect of quickly treating the cause of pain, thereby providing pain treatment. It can be used as a treatment for Of course, the scope of the present invention is not limited by this effect.

Figure 1 is a photograph showing the appearance of acupuncture needles (diameter 0.2 mm, top) and acupuncture needles (diameter 1 mm, bottom) that can be used together when injecting the pharmaceutical composition for treating pain of the present invention into the affected area.
Figure 2 is a photograph showing the shapes of various types of acupuncture needles recorded in Oriental medicine books.
Figure 3 is a graph showing the results of analyzing the change in flinching frequency of experimental animal mice according to administration of the pharmaceutical composition for treating pain of the present invention.
Figure 4 is a graph showing the results of analyzing the change in flinching frequency by stage (early and late) in experimental animal mice according to administration of the pharmaceutical composition for treating pain of the present invention.
Figure 5 is a graph showing the results of analyzing the change in Licking time of experimental animal mice according to administration of the pharmaceutical composition for treating pain of the present invention.
Figure 6 is a graph showing the results of analyzing the change in licking time at each stage (early and late) in experimental animal mice according to administration of the pharmaceutical composition for treating pain of the present invention.

Definition of Terms:

The term "Hemp seed oil (Cannabis Sativa Seed Oil)" used in this document refers to oil extracted from hemp seeds by cold pressing after removing the hallucinogenic ingredient (THC, tetrahydrocannabinol). do. Hemp seeds are rich in nutrients and are included in the '6 Superfood Seeds' selected by TIME magazine. They are especially rich in polyunsaturated fatty acids such as linolenic acid. Additionally, it contains 9 essential amino acids and various minerals and vitamins. Hemp seed oil is also called hemp seed oil, hemp seed oil, hemp seed oil, hemp seed oil, and hemp seed oil. In the present invention, the produced hemp seed oil was named KOC (Korea canabis oil).

Detailed Description of the Invention:

According to one aspect of the present invention, a pharmaceutical composition for treating pain containing hemp seed oil as an active ingredient is provided.

In the pharmaceutical composition, the composition may have a formulation for external use on the skin or a formulation for subcutaneous injection, and the formulation for external use on the skin may be a powder, gel, ointment, cream, liquid, herbal acupuncture, microneedle patch, transdermal patch, or aerosol formulation. You can.

In the pharmaceutical composition, the pain may be nociceptive pain, psychogenic pain, somatic pain, inflammatory pain, or pathological pain. Pain includes neuropathic pain, cancer pain, chemotherapy-related pain, postoperative pain, trigeminal neuralgia pain, idiopathic pain, and diabetic neuropathic pain. Pain may be selected from the group consisting of diabetic neuropathic pain, migraine, arthralgia, and neuralgia.

The term "nociceptive pain" is used to include all pain caused by noxious stimuli that threaten or actually damage body tissues, such as cuts, bruises, fractures ( This includes, without limitation, pain caused by bone fracture, crush injury, burn, and similar wounds. Pain receptors (nociceptors) for tissue damage are mostly located in the skin, musculoskeletal system, or internal organs. Additionally, the term “somatic pain” is used to refer to pain occurring in bones, joints, muscles, skin, or connective tissue. The “inflammatory pain” includes pain associated with active inflammation, which may be caused by trauma, surgery, infection, and autoimmune disease.

The term “neuropathic pain” is used herein to refer to pain resulting from sensory input from abnormal processing by the peripheral or central nervous system that occurs as a result of a disorder of the peripheral or central nervous system.

According to another aspect of the present invention, a method for alleviating or treating pain is provided, comprising administering the pharmaceutical composition for treating pain.

According to another aspect of the present invention, a local anesthetic containing hemp seed oil as an active ingredient is provided.

The pharmaceutical composition for treating pain of the present invention may further include a carrier for external application to the skin. The carrier for external application to the skin includes water, stearic acid, glycerin, ceramide, hyaluronic acid, surfactant (e.g., Tween20, Tween60), One or more selected from the group consisting of preservatives, antioxidants, stabilizers, diluents, pH adjusters, fragrances, and dispersants may be included.

The pharmaceutical composition for treating pain of the present invention may be 1 mg/g to 900 mg/g based on the total weight of the composition. For example, the total content of the active ingredient is 1 mg/g or more, 25 mg/g or more, 50 mg/g or more, 60 mg/g or more, 70 mg/g or more, 80 mg/g or more, 90 mg/g or more, based on the total weight of the composition. It may be more than mg/g, more than 100 mg/g, or more than 110 mg/g.

In one embodiment, the pharmaceutical composition for treating pain according to the present invention may be a medicine or a pharmaceutical supplement. Specifically, it may be a general drug or quasi-drug.

The administration route of the pharmaceutical composition for treating pain of the present invention can be administered through various oral or parenteral routes as long as it can reach the target tissue, specifically, oral, rectal, topical, intravenous, intraperitoneal, and intramuscular. It can be administered in conventional ways, such as intraarterially, transdermally, intranasally, inhalation, etc.

It is obvious to those skilled in the art that the appropriate total daily usage amount of the pharmaceutical composition administered in the method of the present invention can be determined within the scope of sound medical judgment. The specific therapeutically effective amount for a specific subject includes the type and degree of response to be achieved, the patient's age, weight, general health, gender and diet, administration time, administration route and secretion rate of the composition, treatment period, and specific composition. It is desirable to apply it differently depending on various factors, including drugs used or used simultaneously, and similar factors well known in the medical field.

The pharmaceutical composition of the present invention can be prepared in any formulation commonly prepared in the art (e.g., Remington's Pharmaceutical Science, latest edition; Mack Publishing Company, Easton PA), and the form of the formulation is not particularly limited. , preferably an external preparation. The external preparations of the present invention include sheets, liquid coating agents, sprays, lotions, creams, patches, powders, penetrating pads, sprays, gels including hydrogels, pasta agents, liniment agents, ointments, aerosols, powders, and suspensions. Common forms of external preparations such as medications, microneedles, herbal acupuncture, and transdermal absorbents may be included. These formulations are described in Remington's Pharmaceutical Science, 15th Edition, 1975, Mack Publishing Company, Easton, Pennsylvania 18042 (Chapter 87: Blaug, Seymour), a generally known text in all pharmaceutical chemistry.

As an example of the present invention, the pharmaceutical composition for treating pain can be applied directly to the skin. Any dressing that is commercially available or commonly known can be used. Examples of commercially available dressings include Compeel, Duoderm, Tagaderm, and Opsite.

In the pharmaceutical composition for treating pain of the present invention, acceptable carriers in pharmaceutical or cosmetic terms vary depending on the formulation, but include hydrocarbons such as petrolatum, liquid paraffin, and gelled hydrocarbons (aka plastibase); Animal and vegetable oils such as medium-chain fatty acid triglycerides, pork fat, hard fat, and cocoa fat; higher fatty alcohols and fatty acids and their esters such as cetanol, stearyl alcohol, stearic acid, and isopropyl palmitate; Water-soluble bases such as macrogol (polyethylene glycol), 1,3-butylene glycol, glycerol, gelatin, white sugar, and sugar alcohol; Emulsifiers such as glycerin fatty acid ester, polyoxyl stearate, and polyoxyethylene hydrogenated castor oil; Adhesives such as acrylic acid ester and sodium alginate; Propellants such as liquefied petroleum gas and carbon dioxide; Preservatives such as paraoxybenzoic acid esters are included, and the external preparation of the present invention can be prepared using these by a conventional method. In addition to these, stabilizers, flavorings, colorants, pH adjusters, diluents, surfactants, preservatives, antioxidants, etc. may be added as needed. The topical agent of the present invention can be applied to a local wound by a conventional method.

As an example of the present invention, the pharmaceutical composition for treating pain according to the present invention may be formulated in the form of a liquid coating agent by mixing hemp seed oil and physiological saline according to an embodiment of the present invention at a constant volume ratio. As an example of the present invention, the pharmaceutical composition according to the present invention can be formulated in the form of an ointment by mixing hemp seed oil and a water-soluble ointment base according to the above-described embodiment of the present invention and adding physiological saline to the mixture. However, the amount of the pharmaceutical composition of the present invention is determined in light of various related factors such as administration route, subject's age, gender, body weight, number of treatments, treatment time, dosage form, patient's condition, type of adjuvant, etc., so the effective amount is It should not be construed as limiting the scope of the present invention in any respect.

The dosage of the active ingredient of the pharmaceutical composition of the present invention can be determined depending on the severity of the disease, the age of the patient, etc., but is generally in the range of 0.005 ㎍/kg to 100 mg/kg, preferably 0.02 ㎍/kg to 100 mg/kg. The range is 5 mg/kg. However, since the dosage of the pharmaceutical composition of the present invention is determined in light of various related factors such as the route of administration, the patient's age, gender, weight, and patient's severity, the dosage is not intended to limit the scope of the present invention in any respect. It should not be understood.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat the disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type of patient's disease, severity, activity of the drug, and the drug. It can be determined based on factors including sensitivity to, time of administration, route of administration and excretion rate, duration of treatment, concurrently used drugs, and other factors well known in the field of medicine. The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect with the minimum amount without side effects, and this can be easily determined by a person skilled in the art. Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the patient's age, gender, condition, body weight, absorption of the active ingredient in the body, inactivation rate and excretion rate, type of disease, and concomitant drug. In general, 1 to 500 mg per kg of body weight can be administered daily or every other day, or divided into 1 to 3 times per day. However, since it may increase or decrease depending on the route of administration, gender, weight, age, etc., the above dosage does not limit the scope of the present invention in any way.

For effective pain treatment, it can be manufactured as a herbal acupuncture needle or microneedle through which a drug is injected transdermally containing the pharmaceutical composition of the present invention. Since the delivery of bioactive substances using a microneedle array is accomplished through the skin, not through the biological circulatory system such as blood vessels or lymphatic vessels, each microneedle included in the microneedle array must be able to penetrate the skin. The microneedle must have sufficient mechanical strength to penetrate the skin, and preferably causes less pain. In order to reduce pain as much as possible, it is advantageous to shorten the skin application time of the microneedle, and the active ingredient is released within a few seconds. It must be able to be delivered quickly. If the skin is open for a long time, it takes longer for the wound to heal, which increases the risk of infection. Additionally, the length of the part of the microneedle inserted into the skin must be appropriate to avoid touching the nerves in the dermis and causing pain. In addition, it is made of biocompatible and biodegradable materials such as hyaluronic acid, enabling excellent sharpness despite low strength. The aspect ratio can be freely selected and excellent sharpness can be maintained at any aspect ratio, making it possible to maintain good sharpness on the skin. Pain and skin damage should be minimized during penetration.

When applied to the skin, the microneedle may be composed of i) a single-layer needle portion that pierces the skin and penetrates into the skin, and ii) one or more layers (auxiliary layers) on the opposite side of the tip of the needle portion. It may be composed of a multi-layered structure. The auxiliary layer may be a layer located on the opposite side of the tip end of the needle unit and form part of the needle unit, or may be a layer to which one or more needle units can be attached separately from the needle unit. In the case of the above-mentioned type of microneedle, when the microneedle is applied to the skin, the auxiliary layer can also penetrate the skin, but in the microneedle type, only the needle portion penetrates the skin and the auxiliary layer is applied in contact with the skin. There is a difference.

In addition, for effective pain treatment, it can be manufactured as a skin-attached patch containing the pharmaceutical composition for treating pain of the present invention. The patch includes an impermeable support layer at the top, a pressure-sensitive adhesive layer located at the bottom of the support layer, and A drug layer attached to the lower part of the pressure-sensitive adhesive layer and containing the active ingredient therein, a release layer attached to the lower part of the pressure-sensitive adhesive layer and peeled off during use; And it can be manufactured including a release film layer that protects the skin contact portion of the drug layer.

The pharmaceutical composition for treating pain of the present invention is injected intradermally, subcutaneously, intramuscularly, intravenously, or intraarterially using a syringe. Specifically, the injection may be a subcutaneous injection, but is not limited thereto. The syringe can be used without limitation as well as a general syringe capable of administering a drug solution through a needle, as well as any syringe used to subcutaneously administer the composition of the present invention. The subcutaneous tissue is the part between muscles and bones beneath the dermal layer, and contains adipocytes containing a large amount of fat, which gives softness and contour to the human body and can be used as energy. It also means that arteries and lymph fluid are circulating.

Hemp seed oil (hemp seed oil) of the present invention is an oil obtained by cold pressing from hemp seeds and contains essential fatty acids, vitamins A, D, E, minerals, omega 3, and omega 6, excluding fish oil. It is the only oil that supplies omega 3 and omega 6. It contains more essential fatty acids than any other vegetable oil, has a perfect 3:1 omega-6:omega-3 ratio, and contains natural antioxidant vitamin E and sterols that block the absorption of cholesterol. In addition, it is rich in alpha-linolenic acid (ALA) and gamma-linoleic acid, which not only plays an excellent role in moisturizing and softening the skin, but is also rich in minerals such as phosphorus, potassium, magnesium, sulfur, calcium, iron, and zinc. I'm doing it. Hemp seed oil lowers cholesterol levels, treats vascular inflammation, and purifies the blood, thereby reducing high blood pressure, heart disease, and stroke. In particular, when used on the skin, it has excellent moisturizing, anti-aging, and skin regenerative effects. When used on atopic skin, it can relieve itching and maximize the moisturizing, antibacterial, and anti-inflammatory effects.

The composition for topical skin application containing hemp seed oil as an active ingredient according to an embodiment of the present invention is a very innovative medicine that avoids continuous administration of painkillers by blocking the fundamental cause of pain rather than simply providing analgesic action. It is expected to be a new drug that can pioneer a new paradigm in pain treatment.

A pharmaceutical composition for treating pain containing hemp seed oil of the present invention as an active ingredient can be prepared in the form of herbal medicine (KCO, Korea canabis oil) and administered to pain patients. Due to its strong inflammation treatment effect, when injected into the painful area, you can see the powerful pain-relieving effect and the effect of healing inflammation. It can be used as a treatment for chronic pain diseases in the body's muscle and joint system, various arthritis and disc diseases, and its analgesic effect has been confirmed to be about 60-70% of that of lidocaine due to its additional strong analgesic effect. The difference from anesthetics such as lidocaine is that anesthetics cause pain relief but have no effect on healing pain or inflammation. However, the composition for treating pain containing hemp seed oil as an active ingredient of the present invention has an analgesic effect and a strong inflammation healing effect during herbal acupuncture treatment. In general, the analgesic effect of lidocaine disappears about 2 hours after injection, but the herbal acupuncture continues its analgesic and anti-inflammatory effect even after 2 hours, promoting healing of the affected area.

KCO herbal acupuncture treatment containing the hemp seed oil composition of the present invention causes significant pain even when injected into the affected area using thick needles of 0.5 mm or more, rather than the thin needles with a diameter of 0.2 to 0.3 mm commonly used in general local oriental medicine clinics. I don't lose. In oriental medicine, the thicker the needle, the better the treatment effect, but due to the tendency of the times to be more sensitive to pain, the thickness of the needle has become thinner to reduce pain, and as a result, the pain treatment effect of acupuncture has become somewhat weaker. The most effective oriental medicine treatment is not oriental acupuncture using thick needles since ancient times, but a more powerful treatment called acupuncture or dochim. A typical modern acupuncture needle has a diameter of about 0.2 to 0.3 mm, but a thicker acupuncture needle is about 0.5 mm, and a Chinese acupuncture needle is at least 0.5 mm in diameter and often exceeds 0.7 mm. Acupuncture needles with chisel-like tips appear in many historical records in Oriental medicine books (Figure 2). This is not because there is a lack of technology to round the tip of the needle into a needle-like shape, but because the tip is made like a chisel and is used to treat inflammatory tissue in the human body through microdissection. When applied with acupressure, it has a much more powerful effect than regular acupuncture or thick acupuncture. However, because the pain is severe, modern medical settings are reluctant to use it. Currently, in the Chinese oriental medicine world, acupuncture or acupuncture treatment is highly effective in treating pain, and it is known as acupuncture and acupuncture as an independent genre of medicine. However, because acupuncture involves a lot of pain, Chinese Oriental medicine doctors often first inject a small amount of anesthetic such as lidocaine before performing the procedure. Chinese Oriental medicine doctors legally use anesthetics regardless of whether they are Oriental or Western medicine, but in Korea, they use anesthetics legally. Oriental medicine doctors are legally prohibited from using anesthetics. Therefore, although the Korean oriental medicine community is aware of the excellent clinical effects of acupuncture, it is unable to actively use it in clinical settings due to pain. Therefore, if the pain is severe or the patient wants quick treatment, the pain treatment pharmaceutical composition of the present invention is injected into the affected area and acupuncture is performed in parallel to maximize the effect through the inflammation healing action that heals the pain itself and the powerful analgesic action. You can. The pharmaceutical composition for treating pain of the present invention has the technical feature of quickly relieving pain diseases including arthritis, spinal disc, etc. in various parts of the body and other painful areas by injecting it into the area of pain, and promoting recovery by healing inflammation. there is. Additionally, the composition of the present invention can be injected in the form of a herbal medicine into a painful area, such as an acupuncture point in the painful area, to relieve pain and heal inflammation in acute and chronic arthritis, degenerative diseases, and rheumatic diseases. In addition, by utilizing the strong analgesic effect, the effect after injection of the composition is excellent, but the treatment effect can be increased through traditional acupuncture treatment, which causes pain during the procedure, and needle therapy, which injects the medicine into the body.

In order to confirm the pain relieving effect of the therapeutic composition of the present invention, the present inventors administered formalin to mice to create a pain model. After formalin was injected into rats, which were experimental animals, the composition was administered and observed for 60 minutes, and the behavioral responses of the rats were monitored and quantified during the early and late stages. For quantification, the number of flinching behaviors (Flinching No.) and the sole licking time (Licking Time) were measured every 5 minutes. As a result, G3, G4, and G5 injected with the therapeutic composition of the present invention compared to the G2 negative control group. The number of flinchings in the experimental group decreased, and in the step-by-step analysis, it was confirmed that the number of flinchings in the G3, G4, and G5 experimental groups significantly decreased in the later stages. Additionally, as a result of measuring licking (licking time), compared to the G2 negative control group, the licking of the G3, G4, and G5 experimental groups significantly decreased from 25 minutes, and also significantly decreased at 30, 35, 40, and 50 minutes.

As a result of comparing the frequency of flinching behavior and the time of licking the soles of the subjects administered the composition, both pain reduction indicators decreased in the later stage. Currently, Lidocaine, a local anesthetic, is a treatment for pain-related diseases and is used locally as an injection or topical agent to relax muscles and relieve pain. Since a comparative analysis with the commonly used lidocaine analgesic was not conducted, the difference in efficacy could not be confirmed. However, as a result of comparison with the references below, the pain response decreased in a similar manner to the result of administering 0.04 mL of 1% lidocaine. It can be confirmed that the test substance derived from natural products is effective in relieving pain (Song, SO., et al., Effect of preventive infiltration of Lidocaine on pain response in rat Formalin test., Journal of the Korean Society of Anesthesiology. ., 29, 790-797, 1995, Dubuisson, D. et al., Pain, 4, 161-174, 1977). Therefore, the pharmaceutical composition for treating pain containing hemp seed oil as an active ingredient of the present invention can be used as a medicinal material for treating or alleviating various symptoms that cause pain.

Hereinafter, the present invention will be described in more detail through examples. However, the present invention is not limited to the embodiments disclosed below, but can be implemented in various different forms. The examples below make the disclosure of the present invention complete, and provide those of ordinary skill in the art with the scope of the invention. It is provided to provide complete information.

hemp seed oil

Hemp seed oil used in the present invention was prepared by cold-pressing hemp seeds with the husk removed from hemp seeds, filtering the oil through a micro filter, and then sterilizing it.

liniment manufacturing

A liniment for pain treatment was prepared using the hemp seed oil prepared above. Specifically, 1 L of hemp seed oil was mixed with 2.0 ml of glycol, 1.0 g of EDTA, 2.0 g of hyaluronic acid, 3.0 ml of ethanol, 2.0 g of glycerin, and 2.0 ml of 1,2-hexanediol, and 1.5 ml of PEG-7 olive oil ester. , was prepared by stirring a mixture of 30 g of carbomer and 3 g of triethanolamine for 2 hours.

Example 1: Herbal medicine effect experiment

In order to further confirm the pain improvement effect of the pharmaceutical composition for treating pain of the present invention, the present inventors selected 10 patients who visited the hospital and administered the composition 5 to 14 times in the form of herbal acupuncture to the relevant pain area using a 1cc syringe. (0.05 to 0.2 cc) It was confirmed whether the patient's pain was improved. Patients with severe pain were treated with the above-mentioned herbal acupuncture treatment followed by the procedure using acupuncture as shown in Figure 1.

As a result, the patient's pain was reduced when herbal acupuncture treatment using the composition of the present invention was performed alone or in combination with acupuncture treatment, and when the procedure was repeated more than 5 times, there were no symptoms or the pain was significantly reduced. The results of the pain improvement effect after the patient's procedure are summarized in Tables 1 to 10 below.

dictionary
Date of first visit 2022.05.07. statement about pain Difficulty bending the waist. My back is bent.
Severe pain in the 4th and 5th lumbar vertebrae and severe pulling up to the crook of the lower leg. Patient specific information 68-year-old woman, severe spinal stenosis and disc symptoms, but unable to rest due to working a lot at the market










Composition administration 1 time - administration date
statement about pain 2022.05.07.
Back pain. Back bending due to pain in the 4th and 5th lumbar vertebrae below the waist.
Pain relief after procedure 2nd dose - administration day
statement about pain 2022.05.11. Right side neck~shoulder pain
Left back and buttock pain. After the previous treatment, the tightness in the crook of my left calf was reduced.
Pain decreases from 10 at first to about 3 or 4 3 times - administration day
statement about pain 2022.05.14.
Yesterday, I overexerted myself at work and my back pain returned to an 8 out of 10. 4th time - administration day
statement about pain 2022.05.18.
Shoulder pain - difficult to straighten, excessive pain while working a lot, about 9 out of 10
Back pain - improved, more pain on the right side. Left leg pulling improved.
Pain is about 7 out of 10. 5 times - administration day
statement about pain 2022.05.21.
When I get tired, my back hurts and I bend over. Leg pulling symptoms are improving
Back pain is good, but it hurts if you overdo it. Pain is about 5 or 6 out of 10. 6th dose - administration day
statement about pain 2022.05.23.
Back pain hurts the most when lifting objects and often pain when walking, but it has improved from 10 to 4. 7th time - administration day
statement about pain 2022.05.25.
Pain greatly improved. If you lean back, the pain and leg pulling will disappear. It hurts when I work, but when I don't, the pain goes away.
Pain: 3 to 4 out of 10

after death

Statement of Effect Patients suffering from long-standing back pain due to heavy labor and chronic pain with a bent back due to spinal stenosis are improved by the pain-relieving and inflammation-healing effects of KCO herbal acupuncture and the pain-healing action of acupuncture. In addition, although it has an excellent pain healing effect, acupuncture, which causes a lot of pain during the procedure, is administered after pain relief with KDO herbal acupuncture, which greatly enhances the effect and reduces the patient's pain.

dictionary
Date of first visit 2021.04.30 statement about pain Interstitial cystitis occurred after treatment for thyroid cancer. Bladder pain. Difficulty holding it in. I received urological treatment for a long time, but they said there was no solution. Patient specific information 48-year-old woman, urologist diagnosed that there is no further treatment











composition
administration 1 time - administration date
statement about pain 2021.04.30.
Pain in the lower abdomen, bladder pain, anal pain, difficulty urinating, nocturia, and frequent urination. 2nd dose - administration day
statement about pain 2021.05.03.
Feeling of slight improvement after treatment of perineal and bladder pain areas. Pain improved by 9 out of 10 at first. 3 times - administration day
statement about pain 2021.05.21.
Bladder pain and frequent urination are gradually improving. Pain improved from 10 to 7-8 4th time - administration day
statement about pain 2021.06.02.
Abdominal pain and bladder pain are improving, but it is difficult. 5 times - administration day
statement about pain 2021.06.25.
Abdominal pain and bladder pain are improving. Pain has improved by 3 to 4 out of 10. 6th dose - administration day
statement about pain 2021.07.09.
I had severe insomnia, but I started sleeping well, and my abdominal pain and bladder pain improved by 2 to 3 out of 10. 7th time - administration day
statement about pain 2021.07.26.
Bladder pain remains at 4 out of 10 8th - administration day
statement about pain 2021.08.09.
Bladder pain and abdominal pain improved from 10 to 2-3. 9th dose - administration day
statement about pain 2021.09.06.
Bladder pain and abdominal pain are less, but coccydynia is present. Pain improved by 2 to 3 out of 10 10 times - administration day
statement about pain 2021.10.12.
Analgia appears Pain improved by 2 to 3 out of 10 11th - administration day
statement about pain 2021.11.17.
Pain improved a lot. Started hiking. Pain improved by 1 to 2 out of 10. 12th dose - administration day
statement about pain 2021.12.01.
Almost no pain, but feeling slightly uncomfortable 13th - administration day
statement about pain 2022.02.21.
There is almost no pain, just a tingling sensation in the lower abdomen. 14th - administration day
statement about pain 2022.04.04.
disappearance of symptoms
after death
Statement of Effect Patients suffering from unexplained interstitial cystitis pain who had no treatment in the urology department were treated with the powerful analgesic and inflammation-removing effects of KCO herbal acupuncture and acupuncture.

dictionary Date of first visit 2022.05.-16 statement about pain The back pain is so severe that it is difficult to tolerate. I received treatment for a long time while working at the hospital, but there was no improvement. Patient specific information 54-year-old female, pain in the quadratus lumborum region, lumbar vertebrae 4 and 5, pain in the gluteus maximus on both hips




composition
administration 1 time - administration date
statement about pain 2022.05.16.
The pain is so severe that it is difficult to bear, to the point of asking for help.
After the treatment, the pain was relieved and I was able to walk out. 2nd dose - administration day
statement about pain 2022.05.17.
The pain decreases from 10 at first to about 5 or 6. 3 times - administration day
statement about pain 2022.05.18.
Now that I'm a little better, I work a lot at home. My condition is down today. Pain feels like a 6 out of 10 4th time - administration day
statement about pain 2022.05.20.
I did something wrong at work, but I worked. Pain improved, reduced from 10 to 5. 5 times - administration day
statement about pain 2022.05.21
Pain greatly improved, decreased from 10 to 3

after death

Statement of Effect Back pain so severe that it is difficult to bear is quickly healed and improved through KCO herbal acupuncture and acupuncture treatment. In addition, the pain-relieving effect is excellent, but acupuncture, which causes a lot of pain during the procedure, is performed after pain relief with KDO herbal acupuncture, which greatly enhances the effect and reduces the patient's pain.

dictionary Date of first visit 2022.05.10 statement about pain My knees hurt a lot, I was receiving orthopedic treatment, and I had difficulty flexing while taking painkillers and anti-inflammatory medication.
Back pain - long-standing, persistent pain after surgery Patient specific information
case history 66-year-old woman. History of lumbar 4th and 5th disc surgery,







composition
administration 1st dose - day of administration Statement about pain 2022.05.10.
Knees - pain when waking up in the morning, pain when moving. Back pain - always pain when working. Acupuncture after KCO herbal acupuncture treatment on the painful area. Multiple pains relieved after the procedure. 2nd dose - statement about pain on day of administration 2022.05.11.
After knee surgery, pain decreased from 10 to 2~3.
After the back pain treatment, the pain was reduced from 10 to 3. After the previous treatment, the pain felt better when going down the stairs. 3rd dose - day of administration Statement about pain 2022.05.13.
Knee pain has improved a lot. It has improved to the point where it barely hurts at all.
Back pain - mild pain near the buttocks, improved from 10 to 2-3 4th - Administration day Statement about pain 2022.05.21.
Knees: Although it is uncomfortable when working, the usual slight pain is gone.
Back pain - some old pain near the tailbone. Pain is about 2-3 out of 10.
5th - Administration day Statement about pain 2022.05.23.
I don't feel much knee pain.
Back pain - When I work, the pain improves from 10 to 2. Episode 6 - Statement of pain on administration day 2022.05.25.
I barely feel any knee pain.
Low back pain, old pain near the tailbone, but almost improved. Pain is about 2 out of 10. Episode 7 - Statement of pain on administration day
2022.05.30.
Knee pain has almost disappeared. Back pain and nighttime pain near the tailbone have improved by 1 to 2 out of 10.

after death

Statement of Effect Stubborn and long-standing back pain after knee and spinal disc surgery is improved by the pain-relieving and inflammation-healing effects of KC0 herbal acupuncture. In addition, although it has an excellent pain healing effect, acupuncture, which causes a lot of pain during the procedure, is administered after pain relief with KDO herbal acupuncture, which greatly enhances the effect and reduces the patient's pain.

dictionary
Date of first visit 2022.05.06 statement about pain Old pain rising in right shoulder.
Pain in the medial ligament area of the knee Patient specific information 73-year-old woman, adhesive shoulder arthritis and degenerative knee arthritis








composition
administration 1 time - administration date
statement about pain 2022.05.06.
Treatment of shoulder pain and medial knee pain 2nd dose - administration day
statement about pain 2022.05.08.
After one treatment, shoulder pain is reduced and knee pain is relieved. 3 times - administration day
statement about pain 2022.05.10.
Shoulder pain has softened and pain at origin has decreased from 10 to 6.
Knee pain improved and pain level decreased from 10 to 6 at the time of admission. 4th time - administration day
statement about pain 2022.05.11.
The shoulder pain has improved, but the pain was so severe that it still hurts. Pain improved by 5 out of 10
Knee pain improved, bending and straightening became more comfortable. Pain improved by 7 out of 10 5 times - administration day
statement about pain 2022.05.17.
Shoulder pain has improved a lot. Going up is very smooth. Pain has improved to about 4 out of 10.
Knee pain: Bending and straightening becomes much more comfortable. Pain is about 6 out of 10. 6th dose - administration day
statement about pain 2022.05.18.
Much improvement in shoulders and knees
Shoulder pain improved from 10 to 3 7th time - administration day
statement about pain 2022.05
Knee pain improved by 4 out of 10
after death
Statement of Effect The effectiveness of KCO herbal acupuncture in recovering from inflammation and treating pain appears to be very high, as the adhesive shoulder arthritis and degenerative knee arthritis of the elderly, which had not healed for a long time, are improved and treated.

dictionary
Date of first visit 2022.02.19 statement about pain Pain in the left shoulder, to the point where I can't sleep, and I can't rest because I look after my grandchild when I take a break from work. Patient specific information 65-year-old woman, suffered from left adhesive shoulder arthritis for over a year. Due to circumstances, she could only come to the hospital once a week.












Composition administration 1 time - administration date
statement about pain 2022.02.19.
The pain in my left shoulder was so bad that I couldn't sleep. I continued to receive treatment, but it didn't get better.
2nd dose - administration day
statement about pain 2022.02.26.
Much improved after 1 treatment. Pain in the shoulder joint improved by 7 to 8 out of 10. 3 times - administration day
statement about pain 2022.03.05. Shoulder pain becomes lighter, pain improves by 7 out of 10 4th time - administration day
statement about pain 2022.03.26.
After the previous treatment, the treated area had redness and itchiness like an allergy symptom, so I took a 2-week break and felt better.
It's amazing that my shoulder pain is still improving. Pain improved to 6 out of 10
5 times - administration day
statement about pain 2022.04.09.
Shoulder pain is improving, but it hurts a bit after seeing the baby.
Pain is improving to 5-6 out of 10. 6th dose - administration day
statement about pain 2022.4.16.
While the pain is improving, the raising movement has improved without any major problems.
Pain improved by about 5 out of 10.
7th time - administration day
statement about pain 2022.04.23.
Shoulder pain improves to the point where it doesn't usually hurt as much if you don't overdo it just because you look at the baby.
Pain improved by 4 to 5 out of 10. 8th - administration day
statement about pain 2022.04.30.
Shoulder pain: It hurts when I work too hard. It still hurts because I can't rest. The pain is still at 4-5 out of 10.
9th dose - administration day
statement about pain 2022.05.07.
It has improved a lot. There is no pain at night. I sleep well. Pain has improved by 3 to 4 out of 10. 10 times - administration day
statement about pain
2022.05.21.
It's improved, but I still feel a bit of pain because I keep overdoing it.
Shoulder pain improved by 2 to 3 out of 10

after death

Statement of Effect In the treatment of adhesive shoulder arthritis in the elderly, which is difficult and takes a long time to treat, the pain-relieving effect of KCO herbal acupuncture, muscle and ligament damage, recovery of joint cartilage cells, and healing and recovery of arthritis through improvement of blood circulation were observed. .Also, although it has an excellent pain healing effect, acupuncture that causes a lot of pain during the procedure is performed after pain relief with KCO herbal acupuncture, thereby greatly increasing the effect and reducing the patient's pain burden.

dictionary Date of first visit 2022.05.10 statement about pain The stress of corporate work is severe. I usually have back pain, but 3 days ago, I experienced sharp pain in my lower back and legs while washing my face in the morning. Feeling like my back is being cut Patient specific information 46-year-old woman, pain in lumbar vertebrae 4 and 5, severe pain from left gluteus maximus to femur








Composition administration 1 time> Administration date
statement about pain 2022.05.10.
Difficulty sitting due to severe pain, pain somewhat relieved after treatment on the painful area 2 times> Administration date
statement about pain 2022.05.11.
After the previous treatment, pain improved from 10 to 5.
After treatment, I started to feel better when I started walking, and the boiling pain was reduced by half. 3 times> Administration date
statement about pain 2022.05.13.
My back pain has improved a lot. The painful buoy seems to be coming down to my buttocks.
Pain improved from 10 to 3 4 times> Administration date
statement about pain 2022.05.14.
Pain has improved from 10 to 3 due to constant need to stand at work. 5> Administration date
statement about pain 2022.05.21.
The pain was greatly reduced, but without treatment, the pain occurred again. It improved from 10 to 5.
6> Administration date
statement about pain 2022.05.23.
Pain in the lower back and hips decreased from 10 to 4 while improving. 7- Date of administration
statement about pain 2022.05.25.
Left hip pain and lower back are relieved. Pain decreases from 10 to 3.
after death
Statement of Effect Confirmed to improve blood circulation, remove inflammation, and promote recovery for inflammation of lumbar muscles, ligaments, and cartilage.

dictionary
Date of first visit 2022.03.12 statement about pain left ankle sprain
I received disc surgery at a hospital for back pain and it did not get better and lasted for a long time. Patient specific information 63-year-old woman, ankle sprain, back pain, long-standing lower leg calf pain














composition
administration 1 time - administration date
statement about pain 2022.03.12.
Ankle pain, back pain, throbbing pain from buttocks to calves 2nd dose - administration day
statement about pain 2022.03.14. After treatment, the lower back becomes softer and ankle pain is relieved.
Pain decreased from 10 to 8 or 9 3 times - administration day
statement about pain 2022.3.19.
Back pain has become lighter and hip pain has decreased, but it feels heavy. Numbness and tingling in my calves. The pain is decreasing, but the pain feels like an 8 out of 10. 4th time - administration day
statement about pain 2022.03.21.
Ankle pain greatly improved. Back and hip pain relieved, reduced from 10 to 7. 5 times - administration day
statement about pain 2022.03.23.
Ankle and back pain has been greatly reduced, but when I stand for a long time, there is numbness and aching pain from my back to my calves. Back pain has decreased from 10 to 5, but calf pain has decreased to 10 to 8. 6th dose - administration day
statement about pain 2022.04.01.
There is almost no pain in the ankle, but it may swell slightly if you stand for a long time.
Back pain has improved a lot, 4-5 out of 10. Calf pain is still there. 7th time - administration day
statement about pain 2022.04.04.
Ankle pain almost improved
Back pain improved by 4 out of 10 8th - administration day
statement about pain 2022.04.11.
Back pain improves to level 3 to 4. If you stand for a long time or work a lot, calf pain improves to level 10 to level 7. 9th dose - administration day
statement about pain 2022.04.26.
Back pain hurts when I work a lot, but usually gets much better, improving from 10 to 3. 10 times - administration day
statement about pain 2022.05.13.
My back pain has improved a lot, and it usually doesn't bother me that much.
Improved from 10 to 2~3
My calf is still numb, but it has improved to about 6 out of 10. 11th - administration day
statement about pain Back pain has improved to the point where I don’t normally feel it.
The numbness in my calves has improved to about 5-6 out of 10. 12th dose - administration day
statement about pain

2022.05.27.
Back pain when sitting for a long time, pain improves significantly when resting, discomfort when working a lot, pain improves by about 4

after death

Statement of Effect Chronic pain after spinal disc surgery is treated through the analgesic and inflammation treatment effects of KCO herbal acupuncture. We were able to confirm the tissue regeneration effect of herbal acupuncture on spinal muscle tissue, cartilage, and disc. In addition, although the pain healing effect is excellent, the pain is significantly reduced by performing the procedure after relieving acupuncture with KDO herbal acupuncture, which causes a lot of pain during the procedure.

dictionary Date of first visit 2022.4.1.. statement about pain After falling and getting hurt a month ago, I fractured thoracic vertebrae 9 and 11, developed a herniated disc in my lumbar spine, had difficulty sitting and standing due to severe pain, was on leave from work, and had severe numbness in my legs. So much so that I can't sleep at night. Patient specific information 38-year-old male, fractured thoracic vertebrae 9 and 11, lumbar 4th and 5th disc symptoms












Composition administration 1 time - administration date
statement about pain 2022.04.01.
Acupuncture (diameter 0.5mm*5cm) treatment is performed on painful thoracic and lumbar areas with KCO (Korea canabis oil) at one point. 0.5cc each. Acupuncture treatment is highly effective, but the shape of the acupuncture needle is different from that of an acupuncture needle. It is difficult to perform the procedure alone due to the severe pain due to its shape. When performed in parallel with KCO, the procedure is pain-free due to the analgesic effect of KCO. After treatment, pain is relieved by about 20% in the affected area. 2nd dose - administration day
statement about pain 2022.04.05.
Pain has improved. It is difficult to bend or straighten the back, but the usual pain has decreased somewhat. 3 times - administration day
statement about pain 2022.04.13.
The pain has greatly improved, and the pain is gradually getting lighter. 4th time - administration day
statement about pain 2022.04.18.
Pain is improving, difficulty sitting and standing, and numbness in the lower extremities due to lumbar disc disease are improving somewhat. At first visit, pain improved by 6 to 7 out of 10.
5 times - administration day
statement about pain 2022.04.25.
The pain is getting much easier. The initial pain has improved from 10 to 5-6. 6th dose - administration day
statement about pain 2022..05.02
Thoracic pain has eased significantly, and numbness in the lower extremities due to herniated disc has been alleviated. Pain has decreased from 10 to 5. 7th time - administration day
statement about pain 2022.05.07.
Significantly reduced pain. Pain level reduced from 10 to 3. 8th - administration day
statement about pain 2022.05.13.
Significantly reduced lower back pain, numbness in the lower extremities, and thoracic pain. Pain eased from 10 to 4. 9th dose - administration day
statement about pain 2022.05.16.
Disc numbness in lower extremities is greatly reduced. Pain is about 4 out of 10. 10 times - administration day
statement about pain 2022.05.23.
Almost all of it has healed, but the numbness in my legs, thoracic pain, and lumbar disc symptoms after driving for a long time are almost completely cured.
after death
Statement of Effect After herbal acupuncture treatment, thoracic vertebral fracture and lumbar disc symptoms were almost improved in a short period of time, and the effect of promoting healing and recovery of muscles, ligaments, cartilage and fractured tissues was confirmed.

dictionary
Date of first visit 2021.11.24 statement about pain Chronic prostatitis, stubborn discomfort in the left perineum, testicular and anal pain. Stinging pain when urinating. Patient specific information 36-year-old male, received urological treatment for several years for chronic prostatitis, but no improvement.













Composition administration 1 time - administration date
statement about pain 2021.11.24.
Chronic prostate pain, perineum, lower abdomen, and perianal pain treatment 2nd dose - administration day
statement about pain 2021.12.01.
Feeling of slight improvement after perineal surgery. 3 times - administration day
statement about pain 2021.12.07.
Perineal pain decreased from 10 to 3-4. 4th time - administration day
statement about pain 2021.12.29
Discomfort in the perineum and anus continues to improve significantly. 5 times - administration day
statement about pain 2022.01.10.
There is a tingling sensation in the perineum, but the condition is improving. 6th dose - administration day
statement about pain 2022.01.28.
There is a feeling of discomfort in the perineum, but the pain has improved by about 3 degrees. 7th time - administration day
statement about pain 2022.02.16.
There is stabbing pain in the perineum, but the pain is improving by level 3. 8th - administration day
statement about pain 2022.03.11.
There was almost no pain, but it appeared recently. 9th dose - administration day
statement about pain 2022.03.25.
Feeling of needing to urinate, symptoms fluctuating slightly 10 times - administration day
statement about pain 2022.04.16.
Symptoms Slight discomfort Initial pain: 3 to 4 out of 10 11th - administration day
statement about pain 2022.05.09.
Testicular discomfort only when driving, no symptoms other than foreign body sensation 12th dose - administration day
statement about pain 2022.05.16.
I've been having some discomfort recently for about 2 weeks. 13th - administration day
statement about pain 2022.05.23.
Symptom comfort without discomfort in the perineum, anus and testicles 14th - administration day
statement about pain
2022.05.28.
Almost no symptoms, pain improved from 10 at first to 1-2 symptoms after death True Statement of Effect KCO herbal acupuncture treats various symptoms of chronic prostatitis, which is known to be incurable, by exhibiting analgesic and inflammation healing effects.

Example 2: Pain relief experiment

In order to confirm the effect of the composition for treating pain containing the hemp seed oil of the present invention as an active ingredient according to the formulation, a liniment containing the composition was prepared. Afterwards, 20 patients who visited an Oriental medicine clinic with back pain or joint pain in fingers, wrists, ankles, knees, toes, arms, shoulders, etc. were selected and applied a liniment prepared according to an embodiment of the present invention to the painful area. It was applied to the affected area and evaluated after 24 hours for convenience, feel, pain reduction, and feeling of use. Comparison was made using commercially available lidocaine as a control, and the evaluation scores were 5 points for very satisfactory, 4 points for satisfaction, 3 points for average, 2 points for poor, and 1 point for very poor. As a result, compared to lidocaine, a commercial product, it was found that in addition to the pain-relieving effect, there was no skin irritation at the application site and the skin improvement effect and the feeling of use were excellent. The results of the pain relief experiment are summarized in Table 11 below.

treatment effect composition lidocaine convenience 4.9 3.5 touch 4.6 3.8 reduce pain 4.8 3.3 feeling of use 4.9 3.2

Example 3: Evaluation of pain relief efficacy using a pain model

In order to confirm the pain relieving effect of the pharmaceutical composition for treating pain of the present invention, the present inventors administered 5% formalin subcutaneously to the soles of rats to induce a pain model, and then administered the composition of the present invention to induce flinching. ) The pain relieving effect of the composition was evaluated by measuring behavioral changes such as licking or licking the soles of the feet. Specifically, formalin was injected into the sole of the foot of a rat, a pain-inducing model, a pain response was induced, and the composition was administered to evaluate the degree of pain. After formalin injection, experimental animals temporarily show a two-stage pain response [Biphasic Pain Response (Early Phase & Late Phase)]. In the early phase, a rapidly occurring systemic olfactory reflex is observed due to the injection. And it is immediate pain. At this time, the animal mainly shows reflex movements such as lifting its paws, and this reaction lasts for about 5 to 10 minutes. Additionally, in the late phase, the pain is persistent, causing the animal to engage in behaviors such as bending its tail or stretching its legs, which lasts for about an hour. Generally, pain responses appear in the form of flinching, licking, biting, and shaking.

3-1: Experimental animals

The experimental animal used in the present invention, a 10-week-old male SD (Sprague-Dawley) rat, was inspected for its appearance when brought in, and its body weight was measured using an electronic scale (CP4202S, Sartorius, GER). They were managed under ad libitum feeding conditions using a feeder in a aviary with lights turned on every 12 hours and temperature and humidity (23±3°C/50±20% (RH)) maintained, and clinical symptoms were observed during the acclimatization period. In addition, body weight was measured at the end of the acclimatization period, and the animal's health status was evaluated by checking clinical symptoms and changes in body weight.

3-2: Experimental method

The present inventors classified the experimental group as shown in Table 12 below, and pain was induced in the experimental group by administering 50 μl of 5% formalin subcutaneously to the left sole of the rat. Afterwards, the G3 experimental group (L) was administered 30 ㎕ of the composition of the present invention once, the G4 experimental group (M) was administered twice, and the G5 experimental group (H) was administered three times. Meanwhile, the negative control group was not administered the composition, and the normal control group was administered 50 ㎕ of saline solution instead of formalin. Information on the experimental method is shown in Table 12 below, and the average body weight of the experimental animals is shown in Table 13 below.

Experimental conditions
classification pain inducer composition
Experiment
information
administration dosage
Number of administrations
volume density volume G1 saline solution 50㎕ Normal control group G2
5%
formalin

5%

50㎕ Negative control group G3 One 30㎕ Experimental group (L) G4 2 60㎕ Experimental group (M) G5 3 90㎕ Experimental group (H)

Average body weight of experimental animals group pain inducer composition classification average weight G1 saline solution Mean 368 SD 25 N 3 G2 5% formalin Mean 365 SD 24 N 3 G3 5% formalin
low concentration
(30㎕ x 1) Mean 364 SD 19 N 3 G4 5% formalin
medium concentration
(30㎕ x 2) Mean 358 SD 19 N 3 G5 5% formalin
high concentration
(30㎕ x 3) Mean 370 SD 23 N 3

3-3: Behavioral evaluation and analysis

After measuring the body weight of each individual on the day of administration of the composition of the present invention, one individual was transferred to an L-Cage tilted at a 45° angle and acclimatized for 10 minutes. After being placed in a correction frame and fixed, 50 ㎕ of 5% Formalin was administered subcutaneously to the sole of the left foot. After 2 minutes, the composition was injected subcutaneously into the left sole, and upon completion of administration, the subject was transferred to an L-Cage tilted at a 45° incline. After filming a video at the bottom of the L-Cage for 60 minutes, the number of flinching and licking times were recorded through the recorded video.

3-4: Statistical processing

Evaluation items were expressed as mean and standard deviation, and statistical processing between each experimental group was performed using a statistical program (GraphPad Prism, GraphPad Software, USA). The average value of each evaluation item was subjected to One-Way Analysis of Variance (ANOVA) and determined to be statistically significant if P <0.05.

Example 4: Flinching frequency analysis

To induce a mouse model of pain, the present inventors administered 50 μL of 5% formalin subcutaneously to rats, then administered the composition in the same manner 2 minutes later, and measured the number of flinching (flinching) of the rat's paws for 60 minutes for 5 minutes. Measured in units. As a result, in the normal control group, G1 (normal control group), there were an average of less than 10 reactions during the observation period, and in the negative control group, G2 (negative control group), there were 20 ± 15 reactions, 14 ± 12 reactions, and 39 ± 16 reactions at 5-minute intervals. , 28 ± 3 times, 32 ± 11 times, 88 ± 18 times, 50 ± 21 times, 57 ± 27 times, 53 ± 9 times, 16 ± 18 times, 16 ± 14 times, and 5 ± 9 times were observed. Also, in the G3 experimental group (L), 15±11 times, 23±18 times, 10±4 times, 19±3 times, 23±20 times, 49±11 times, 29±11 times, 14±8 times. , 20 ± 10 reactions, 13 ± 16 reactions, 13 ± 9 reactions, and 2 ± 3 reactions were observed, and in the G4 experimental group (M), 57 ± 13 reactions, 0 reactions, 0 reactions, 7 ± 13 reactions, Responses were 14±13 times, 61±14 times, 37±40 times, 19±17 times, 18±22 times, 0 times, 16±12 times, and 0 times, and in the G5 experimental group (H), 49±23 times, 0 times, 0 times, 13±22 times, 12±21 times, 45±41 times, 37±32 times, 27±46 times, 0 times, 8±13 times, 30±27 times, 9 There were ±16 reactions. Through the results of the G2 negative control group, it was confirmed that a typical biphasic pain response pattern was reproduced and an appropriate pain model was derived. In addition, the G3, G4, and G5 experimental groups administered the composition showed a significant decrease in the number of flinching times at 15 and 45 minutes compared to the G2 negative control group (Figure 3) (15 minutes - G2 vs G3, G4, G5: ^## P <0.01, 45 minutes - G2 vs G3, G4: ^# P <0.05, G2 vs G5: ^## P <0.01).

In addition, in the pain model induced by formalin administration, the number of flinching in each stage was summed and compared in the form of a biphasic pain response pattern (early stage and late stage), and the result was 2 ± 3 times in the G1 normal control group in the early stage; The G2 negative control group was observed 34 ± 24 times, G3 38 ± 22 times, G4 57 ± 13 times, and G5 49 ± 23 times, and there was no statistically significant difference between the G2 negative control group and the G3, G4, and G5 experimental groups. However, in the later stage, the G1 normal control group administered the composition of the present invention was 14 ± 3 times, G2 384 ± 71 times, G3 193 ± 26 times, G4 173 ± 53 times, and G5 180 ± 43 times. , the number of flinching in the G5 experimental group was found to be significantly reduced (Figure 4) (G2 vs G3, G4, G5: ^## P <0.01). The plinking frequencies are summarized in Tables 14 and 15 below.

Frequency of flinching after administration hour
(minute) G1 Normal control group G2 negative control group G3 experimental group (L) G4 experimental group (M) G5 experimental group (H) Mean SD N Mean SD N Mean SD N Mean SD N Mean SD N 5 0 3 3 20 15 3 15 11 3 57
** 13 3 49
** 23 3 10 0 0 3 14 12 3 23
* 18 3 0 0 3 0 0 3 15 One One 3 39
*** 16 3 10
## 4 3 0
## 0 3 0
## 0 3 20 6 7 3 28 3 3 19 3 3 7 13 3 13 22 3 25 0 0 3 32 11 3 23 20 3 14 13 3 12 21 3 30 One One 3 88
** 18 3 49 11 3 61* 14 3 45 41 3 35 One 2 3 50 21 3 29 11 3 37 40 3 37 32 3 40 0 0 3 57 27 3 14 8 3 19 17 3 27 46 3 45 3 5 3 53
** 9 3 20
# 10 3 18
# 22 3 0
## 0 3 50 One 2 3 16 18 3 13 16 3 0 0 3 8 13 3 55 One One 3 16 14 3 13 9 3 16 12 3 30 27 3 60 0 One 3 5 9 3 2 3 3 0 0 3 9 16 3

Comparison to control group using one-way ANOVA and Dunnett's multiple comparison test.

Significance compared to G1 normal control: ^* P <0.05, ^** P <0.01, ^*** P <0.001.

Significance compared to G2 negative control: ^# P <0.05, ^## P <0.01.

Frequency of flinching by stage hour
(minute) G1 Normal control group G2 negative control group G3 experimental group (L) G4 experimental group (M) G5 experimental group (H) Mean SD N Mean SD N Mean SD N Mean SD N Mean SD N Early 2 3 3 34 24 3 38 22 3 57
* 13 3 49
* 23 3 review 14 3 3 384
*** 71 3 193
**,## 26 3 173
**,## 53 3 180
**,## 43 3

Comparison to control group using one-way ANOVA and Dunnett's multiple comparison test.

Significance compared to G1 normal control: ^* P <0.05, ^** P <0.01, ^*** P <0.001.

Significance compared to G2 negative control: ^# P <0.05, ^## P <0.01.

Example 5: Licking frequency analysis

The present inventors measured the licking action time every 5 minutes after administering the composition of the present invention to a pain mouse model. As a result, G1, the normal control group, was observed to move for an average of less than 10 seconds during the observation period, but G2 was 2 ± 3 seconds, 0 seconds, 24 ± 26 seconds, 85 ± 14 seconds, 115 ± 34 seconds, 105 ± 56 seconds, Behaviors were observed for 83 ± 45 s, 67 ± 70 s, 34 ± 48 s, 56 ± 6 s, 16 ± 17 s, and 23 ± 33 s. Additionally, G3 acted for 36 ± 33 s, 13 ± 11 s, 67 ± 60 s, 60 ± 52 s, 59 ± 31 s, 54 ± 19 s, 28 ± 48 s, 12 ± 21 s, and 3 ± 5 s. Observations were made, but there was no movement for 45 to 60 minutes. Additionally, G4 has 1±2 seconds, 1±2 seconds, 48±33 seconds, 80±34 seconds, 60±24 seconds, 59±29 seconds, 27±15 seconds, 0 seconds, 19±31 seconds, 0 seconds, 1 Movements of ±2 seconds and 4±8 seconds were observed, and for G5, movements were 7±11 seconds, 2±3 seconds, 13±22 seconds, 52±40 seconds, 71±23 seconds, 35±50 seconds, 19±18 seconds, and 5 seconds. Movement was observed for ±8 seconds and 8±14 seconds, and no movement was observed for 45 to 60 minutes. Therefore, the G3, G4, and G5 experimental groups showed a significant decrease from 25 minutes compared to the negative control group, G2, and showed a statistically significant decrease in licking time at 30 minutes, 35 minutes, 40 minutes, and 50 minutes (Figure 5) (Figure 5) 25 min - G2 vs G3, G4: # P <0.05, 30 min, 35 min - G2 vs G5: ^# P <0.05, 40 min - G2 vs G4, G5: ^# P <0.05, 50 min - G2 vs G3, G4, G5: ^### P <0.001).

In addition, as a result of analyzing the licking action time by dividing it into early and late stages, in the early stage, G1 was observed to be 0 seconds, G2 1 ± 2 seconds, G3 29 ± 41 seconds, G4 1 ± 2 seconds, and G5 5 ± 11 seconds, which was significant. did not show any difference. However, in the later stage, the licking time of the experimental group administered the composition was significantly reduced to G3 170±158 seconds, G4 179±169 seconds, and G5 122±130 seconds compared to the control group G1 6±7 seconds and G2 364±378 seconds, but G2 There was no significant difference between the negative control group and the G3, G4, and G5 experimental groups (Figure 6). The above results experimentally demonstrated the excellent pain relief effect resulting from administration of the pharmaceutical composition for treating pain of the present invention. The results are summarized in Tables 16 and 17 below.

Licking action time after administration hour
(minute) G1 Normal control group G2 negative control group G3 experimental group (L) G4 experimental group (M) G5 experimental group (H) Mean SD N Mean SD N Mean SD N Mean SD N Mean SD N 5 0 0 3 2 3 3 36
**,# 33 3 One 2 3 7 11 3 10 0 0 3 0 0 3 13
**,## 11 3 One 2 3 2 3 3 15 4 8 3 24 26 3 67
* 60 3 48 33 3 13 22 3 20 0 0 3 85
** 14 3 60
* 52 3 80
** 34 3 52 40 3 25 0 0 3 115
*** 34 3 59
**,# 31 3 60
**,# 24 3 71
*** 23 3 30 0 0 3 105
*** 56 3 54
*** 19 3 59
*** 29 3 35
***,# 50 3 35 0 0 3 83
** 45 3 28 48 3 27 15 3 19
# 18 3 40 One One 3 67
* 70 3 12 21 3 0
# 0 3 5
# 8 3 45 One 2 3 34 48 3 3 5 3 19 31 3 8 14 3 50 0 0 3 56
*** 6 3 0
### 0 3 0
### 0 3 0
### 0 3 55 0 0 3 16
* 17 3 0
# 0 3 One
# 2 3 0
# 0 3 60 0 0 3 23 33 3 0 0 3 4 8 3 0 0 3

Comparison to control group using one-way ANOVA and Dunnett's multiple comparison test.

Significance compared to G1 normal control: ^* P <0.05, ^** P <0.01, ^*** P <0.001.

Significance compared to G2 negative control: ^# P <0.05, ^## P <0.01, ^### P <0.001.

Step-by-step Licking Action Time hour
(minute) G1 Normal control group G2 negative control group G3 experimental group (L) G4 experimental group (M) G5 experimental group (H) Mean SD N Mean SD N Mean SD N Mean SD N Mean SD N Early 0 0 3 One 2 3 29 41 3 One 2 3 5 11 3 review 6 7 3 364 378 3 170 158 3 179 169 3 122 130 3

Comparison to control group using one-way ANOVA and Dunnett's multiple comparison test.

Significance compared to G1 normal control: P ≥0.05, no statistical significance

Significance compared to G2 negative control: P ≥0.05, no statistical significance

The present invention has been described with reference to the above-described embodiments, but this is merely illustrative, and those skilled in the art will understand that various modifications and equivalent other embodiments are possible therefrom. Therefore, the true technical protection scope of the present invention should be determined by the technical spirit of the attached patent claims.

Claims (7)

A pharmaceutical composition for treating pain containing hemp seed oil as an active ingredient. According to paragraph 1,
The composition is a pharmaceutical composition having a formulation for external application to the skin or a formulation for subcutaneous injection. According to paragraph 1,
The skin external formulation is a pharmaceutical composition having a powder, gel, ointment, cream, liquid, microneedle patch, herbal acupuncture, transdermal patch, or aerosol formulation. According to paragraph 1,
The pharmaceutical composition, wherein the pain is nociceptive pain, psychogenic pain, somatic pain, inflammatory pain, or pathological pain. According to paragraph 4,
The pathological pain includes neuropathic pain, cancer pain, anticancer drug pain, postoperative pain, trigeminal neuralgia pain, idiopathic pain, and diabetic nerve. A pharmaceutical composition selected from the group consisting of diabetic neuropathic pain, migraine, arthralgia and neuralgia. A method for alleviating or treating pain, comprising administering the pharmaceutical composition of any one of claims 1 to 5. A local anesthetic containing hemp seed oil as an active ingredient.