JP7027786B2 - Oral treatment for myofascial pain - Google Patents

Description

The present invention relates to an oral therapeutic agent having a high alleviating effect and a healing effect for myofascial pain.

Non-steroidal anti-inflammatory drugs (NSAIDs) are pain-relieving by inhibiting the activity of cyclooxygenase-2 (COX-2), which is responsible for the production of prostaglandin (PG), a pain-enhancing substance that increases due to inflammation and tissue damage. , Exhibits anti-inflammatory effect. Therefore, it is known that NSAIDs are effective for COX-related pain caused by inflammation and tissue damage, but are less effective for pain in which the contribution of COX and PG is low, such as cancer pain and neuropathic pain. For such pain, analgesics having an action mechanism different from that of COX, such as opioid receptors, various Nas involved in pain, and Ca channels, are used.

In recent years, it has been shown that there are various pain pathways for low back pain. Low back pain is roughly classified into specific low back pain and non-specific low back pain according to its pathological condition. Specific low back pain, which accounts for 15% of all low back pain, is considered to be low back pain associated with underlying diseases such as fractures, inflammation, nerve compression, and tumors, and among these low back pains, NSAIDs may be effective for low back pain accompanied by inflammation. On the other hand, non-specific low back pain, which is said to account for 85% of all low back pain, includes muscles, facet joints, intervertebral discs, etc. as the main causative tissues.

Myalgia, which is one of the causes of non-specific low back pain, is caused by muscle pain that does not depend on the physical load on the muscle such as bacterial or viral infection, and muscle that is triggered by the physical load on the muscle such as bruise or sprain. It can be roughly divided into pain. Furthermore, these myalgias can be classified according to the presence or absence of inflammation or damage to muscle tissue. Myalgia caused by bruising and sprains during infection and exercise is mainly pain accompanied by inflammation and tissue damage, and NSAIDs are effective for such pain mainly due to inflammation and tissue damage because COX and PG are largely involved. , Generally, NSAIDs are used for the purpose of pain relief.

Special Table 2009-501700 Gazette

Pain Clinic, 38: 645-654, 2017

On the other hand, myofascial pain, which is one of the myalgias, is a myalgia caused by a physical load on the muscle, but unlike the above-mentioned myalgia, it is a cord-like induration, a muscle induration, a tender point, and a trigger point. Diagnosis is based on concomitant symptoms such as the presence or absence of myalgia and limited range of motion, and these are important clinical findings. There are various hypotheses about the mechanism of myofascial pain, but a vicious cycle in which muscle contraction triggered by overload on the muscle and acetylcholine activity increased by decreased muscle blood flow / ischemia induce further muscle contraction. Has been proposed. In this respect, myofascial pain is different from the above-mentioned mere muscle damage or inflammation caused by infection or bruising. In recent years, animal models have been developed to elucidate the mechanism of myofascial pain, and histological and biochemical studies have become possible for the first time. Histological studies using animal models have revealed that muscles at the onset of myofascial pain are not associated with inflammation or significant muscle tissue damage. Furthermore, in the muscle / fascial pain model, it has been reported that the NSAIDs celecoxib (CXB), zaltoprofen, and ketoprofen have no analgesic effect even when administered after the onset of pain, and NSAIDs have been reported to have no analgesic effect. It was thought that membranous pain had no analgesic effect. In fact, recent biochemical studies have reported that the main cause of myofascial pain is not COX-2 or PG, which are the targets of NSAIDs, but functional changes in nerve growth factors and ion channels. It has been shown that the condition is completely different from conventional inflammation and injury.

As described above, since NSAIDs such as pathological conditions and CXB are ineffective, it is conventionally considered that NSAIDs are not effective for myo-muscular pain, and acetylsalicylic acid (ASP: aspirin (registered trademark)). , NSAIDs such as ibuprofen (IBP) and loxoprofen sodium hydrate (LOX), and the effects of acetaminophen (APAP) on myo-muscular pain were also unknown. Currently, in the medical field, based on the above clinical findings, nerve block therapy by trigger point injection, in which a local anesthetic is administered to the trigger point site using an injection needle, is widely used. However, this method is invasive and has problems such as damage and inflammation of tissues such as muscles and skin due to insertion, and infection associated therewith. Under these circumstances, it has been desired to develop an oral therapeutic agent having a higher reducing effect and healing effect for myofascial pain.

The present inventor created an animal model reflecting the pathophysiology of myofascial pain, and investigated an active ingredient having a high healing effect on myofascial pain. As a result, it was found that acetaminophen (APAP) and specific non-steroidal anti-inflammatory drugs (NSAIDs) show a high healing effect on myofascial pain. In particular, administration of celecoxib (CXB), which is one of the non-steroidal anti-inflammatory drugs (NSAIDs), does not show an analgesic effect by administration of CXB after the onset of pain, whereas APAP, ASP, IBP, and LOX are after the onset of pain. It was found that an analgesic effect was observed even with the administration of celecoxib, and the present invention was completed.

Therefore, the present invention provides the following oral therapeutic agents.
[1]. Muscle / myocardial pain containing at least one selected from (A) acetaminophen and (B) non-steroidal anti-inflammatory drug (excluding celecoxib, zaltoprofen, ketorolac, nimesulide, and asecrofenac) as active ingredients. Oral remedy for.
[2]. The oral therapeutic agent for myofascial pain according to [1], wherein the component (B) is (b-1) loxoprofen, (b-2) acetylsalicylic acid, and (b-3) ibuprofen.
[3]. (A) The oral therapeutic agent for myofascial pain according to [1] or [2], which contains acetaminophen as an essential ingredient.
[4]. Further, (b-1) an oral therapeutic agent for myofascial pain according to [3], which contains loxoprofen.
[5]. (B-1): The muscle / fascia according to [4], wherein the compounding mass ratio of the component (A) and the component (b-1) represented by (A) is 1: 4.5 to 8.5. Oral treatment for sexual pain.
[6]. Further, (b-2) the oral therapeutic agent for myofascial pain according to [3], which contains acetylsalicylic acid.
[7]. (B-2): The muscle / fascia according to [6], wherein the compounding mass ratio of the component (A) and the component (b-2) represented by (A) is 1: 0.3 to 1.0. Oral treatment for sexual pain.
[8]. The oral therapeutic agent for myofascial pain according to any one of [1] to [7], which is taken once after the onset of myofascial pain.

According to the present invention, it is possible to provide an oral therapeutic agent for myofascial pain, which has a high alleviating effect and a healing effect for myofascial pain.

It is a graph which shows the result of the evaluation method-1 of the healing effect on myofascial pain. It is a graph which shows the result of the evaluation method-2 of the healing effect on myofascial pain.

Hereinafter, the present invention will be described in detail.
The active ingredients of the oral therapeutic agent for myo-muscular pain of the present invention are (A) acetaminophen and (B) non-steroidal anti-inflammatory drug (excluding celecoxib, zaltoprofen, ketorolac, nimesulide, and asecrophenac). ), Which can be selected from 1 or more, and can be used alone or in combination of 2 or more.

[(A) component]
Acetaminophen (N- (4-hydroxyphenyl) acetamide) Acetaminophen can also be pharmaceutically acceptable salts. These can be used alone or in combination of two or more. When the component (A) is blended, the blending amount of the component (A) is not particularly limited as long as it has a pharmacological effect on myofascial pain of the present invention and is within a range where there is no problem in manufacturing. The dose for humans is usually 65 to 1,000 mg / dose for adults, preferably 95 to 500 mg / dose, more preferably 100 to 400 mg / dose, and even more preferably 130 to 300 mg / dose. When the value is set to the lower limit or higher, the effectiveness of the present invention is sufficiently obtained, and when the value is set to the upper limit or lower, the occurrence of side effects is suppressed, and the drug is used as an oral therapeutic agent for myofascial pain that is safe for the human body. Can be done. The number of doses per day is appropriately selected from 1 to 4 times. The amount of the component (A) in the oral therapeutic agent for myofascial pain (hereinafter, may be referred to as a therapeutic agent) is the above intake amount or an optional component (physiologically active substance or additive) described later. It is appropriately selected depending on the above, but 3.0 to 70% by mass is preferable.

[(B) component]
(B) Non-steroidal anti-inflammatory drugs (NSAIDs: Non-Steroidal Anti-Inflammatory Drugs) are a general term for drugs having anti-inflammatory, analgesic, and antipyretic effects, and refer to non-steroidal anti-inflammatory drugs. The component (B) of the present invention is not particularly limited as long as it excludes celecoxib, zaltoprofen, ketorolac, nimesulide, and aceclofenac. Non-steroidal anti-inflammatory drugs other than the above include salicylic acid, acetylsalicylic acid (aspirin (registered trademark)), aspirin aluminum, salsalate (sazapyrin), salicylamide, etenzamid, sodium salicylate, ibuprofen, loxoprofen, diclofenac, ketoprofen, naproxen, etc. Flurubiprofen, pyroxicum, thiaprofenic acid, suprofen, tolmethin, aluminoprofen, benoxaprofen, benzidamine, slindac, acemethasin, progourmet tacin, amphenac, mofezolac, lornoxicam, ampyroxycam, phenoprofen, thiaprofenic acid, oxaprodin , Mephenamic acid, flufenac acid, fervinac, azapropazone, fembufen, etodrac, lofecoxib, diflunisal, zomepyrac, etc., and pharmaceutically acceptable salts can also be used. Of these, (b-1) loxoprofen, (b-2) acetylsalicylic acid, and (b-3) ibuprofen are preferable from the viewpoint of healing effect on myofascial pain.

When the component (B) is blended, the blending amount of the component (B) is not particularly limited as long as it has a pharmacological effect on myofascial pain of the present invention and is within a range where there is no problem in manufacturing. The dose to humans is usually 10 to 1,500 mg / dose for adults, preferably 15 to 1,000 mg / dose. By setting it above the lower limit, the desired efficacy can be sufficiently obtained, and by setting it below the upper limit, the occurrence of side effects is suppressed, and it is an oral therapeutic agent for myofascial pain that is safe for the human body. be able to. The number of doses per day is appropriately selected from 1 to 4 times. The blending amount of the component (B) in the therapeutic agent is appropriately selected depending on the above intake amount and optional components (physiologically active substances and additives) described later, but is preferably 0.1 to 70% by mass.

[(B-1) component]
Loxoprofen (2- [p- [2-Oxygroupnylmethyl] Phenyl] Propionic Acid)
Loxoprofen can also use its pharmaceutically acceptable salts and may be present in the form of their hydrates, examples of which include loxoprofen sodium dihydrate (raw as water content). It corresponds to about 12% by mass in the powder of the drug). In the present invention, the amounts and ratios of loxoprofen are all converted to loxoprofen sodium dihydrate. The amount of water in the therapeutic agent includes the amount of water brought in from loxoprofen sodium dihydrate. As loxoprofen and a salt thereof, one kind alone or two or more kinds may be used as appropriate.

When the component (b-1) is blended, the blending amount of the component (b-1) is not particularly limited as long as it has a pharmacological effect on myofascial pain of the present invention and is within a range where there is no problem in manufacturing. The dose to humans is usually 10 to 150 mg / dose for adults, preferably 15 to 100 mg / dose. By setting it above the lower limit, the desired efficacy can be sufficiently obtained, and by setting it below the upper limit, the occurrence of side effects can be suppressed, and it can be used as an oral treatment for myofascial pain that is safe for the human body. can. The number of doses per day is appropriately selected from 1 to 3 times. The blending amount of the component (b-1) in the therapeutic agent is appropriately selected depending on the above intake amount and optional components (physiologically active substances and additives) described later, but is preferably 0.5 to 70% by mass.

[(B-2) component]
Acetylsalicylic acid (Aspirin®, 2-Acetoxybenzoic Acid)
As acetylsalicylic acid, its pharmaceutically acceptable salts can also be used. These can be used alone or in combination of two or more. When the component (b-2) is blended, the blending amount of the component (b-2) is not particularly limited as long as it has a pharmacological effect on myofascial pain of the present invention and is within a range where there is no problem in manufacturing. The dose to humans is usually 100 to 1,500 mg / dose for adults, more preferably 300 to 1,000 mg / dose. By setting it above the lower limit, the desired efficacy can be sufficiently obtained, and by setting it below the upper limit, the occurrence of side effects can be suppressed, and it can be used as an oral treatment for myofascial pain that is safe for the human body. can. The number of doses per day is appropriately selected from 1 to 3 times. The blending amount of the component (b-2) in the therapeutic agent is appropriately selected depending on the above intake amount and optional components (physiologically active substances and additives) described later, but is preferably 10.0 to 70% by mass.

[(B-3) component]
Ibuprofen (2- (4-isobutylphenyl) Propionic Acid)
Ibuprofen can also use its pharmaceutically acceptable salts. These can be used alone or in combination of two or more. When the component (b-3) is blended, the blending amount of the component (b-3) is not particularly limited as long as it has a pharmacological effect on myofascial pain of the present invention and is within a range where there is no problem in manufacturing. The dose to humans is usually 100 to 200 mg / dose for adults, more preferably 130 to 200 mg / dose. By setting it above the lower limit, the desired efficacy can be sufficiently obtained, and by setting it below the upper limit, the occurrence of side effects can be suppressed, and it can be used as an oral treatment for myofascial pain that is safe for the human body. can. The number of doses per day is appropriately selected from 1 to 3 times. The blending amount of the component (b-3) in the therapeutic agent is appropriately selected depending on the above intake amount and optional components (physiologically active substances and additives) described later, but is preferably 3.0 to 70% by mass.

From the viewpoint of healing effect on myofascial pain, it is preferable to use (A) acetaminophen as an essential component, and a combination of (A) component and (b-1) loxoprofen dihydrate, (A). ) And (b-2) acetylsalicylic acid have a synergistic effect and are particularly preferable.

(B-1): The compounding mass ratio of the component (A) and the component (b-1) represented by (A) is preferably 1: 4.5 to 8.5, preferably 1: 4.5 to 6. More preferred.
(B-2): The compounding mass ratio of the component (A) and the component (b-2) represented by (A) is preferably 1: 0.3 to 1.0, preferably 1: 0.5 to 0. 7 is more preferable.
By setting it to the lower limit of the above ratio or more, it becomes easy to obtain a synergistic analgesic effect on myofascial pain. On the other hand, when the ratio is not more than the upper limit of the above ratio, side effects can be suppressed and a high analgesic effect can be obtained. Further, it can be a preparation having excellent manufacturability and ingestibility (tablet size, number of doses, taste (suppression of bitterness)).

The therapeutic agent of the present invention may contain any component (physiologically active substance or additive) to be blended in the oral pharmaceutical preparation as long as the effect of the present invention is not impaired. Examples of the additive include a binder, an excipient, a disintegrant, a lubricant, a fragrance, a sweetener, an acidulant and the like. These can be used alone or in combination of two or more in appropriate amounts.

Examples of the physiologically active substance include a sedative hypnotic component (allylisopropylacetylurea, bromvaleryluurea, etc.) and an antihistamine component (isotipendyl hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, dipheterol hydrochloride, triprolysine hydrochloride, triperenamine hydrochloride, tonsilamine hydrochloride, hydrochloric acid. Fenetazine, methodilazine hydrochloride, diphenhydramine salicylate, carbinoxamine diphenyldisulfonic acid, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline theocrate, mebuhydrolin napadisylate, promethazine methylene disalicylate, carbinoxamine maleate, dl-maleinate. Chlorpheniramine acid, diferrol phosphate, etc.), central excitatory components (sodium benzoate caffeine, caffeine, anhydrous caffeine, etc.), antitussive sputum components (codein phosphate, dextrometholphan hydrobromide, dimemorphan) Phosphate, Tipepidine hibenzate, methoxyphenamine hydrochloride, Trimethoquinol hydrochloride, Carbocysteine, Acetylcysteine, Ethylcysteine, dl-methylephedrine, Bromhexin hydrochloride, Therapeptase, Resoteam chloride, Ambroxol, Theophylline, Aminophyllin etc.), vitamin components (vitamin B1 and its derivatives and their salts, vitamin B ₂ and its derivatives and their salts, vitamin C and its derivatives and their salts, hesperidin and its derivatives and their salts, etc.) Can be mentioned.

As a binder, starch, pregelatinized starch, sucrose, gelatin, gum arabic powder, polyvinylpyrrolidone, pullulan, dextrin, hydroxypropylcellulose, cyclodextrin, hypromellose, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose , Polyvinyl alcohol, polyethylene glycol and the like.

Excipients include crystalline cellulose, lactose, lactose granules, methylethyl cellulose, xylitol, erythritol, trehalose, maltitol, lactitol, sorbitol, maltitol, carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl starch, carboxymethyl starch sodium. , Sodium hydrogen phosphate, calcium hydrogen phosphate, corn starch, powdered sugar, mannitol, L-cysteine and the like.

Examples of the disintegrant include carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, carboxymethyl cellulose calcium, low degree of substitution hydroxypropyl cellulose, hydroxypropyl starch, carboxymethyl starch sodium, crospovidone and the like.

As the lubricant, magnesium stearate, stearyl sodium fumarate, sucrose fatty acid ester, light anhydrous silicic acid and the like can be used.

Examples of the fragrance include menthol, limonene, vegetable essential oil (mentha oil, mint oil, lychee oil, orange oil, lemon oil, etc.) and the like.

Examples of the sweetener include sodium saccharin, aspartame, stevia, dipotassium glycyrrhizinate, acesulfame potassium, thaumatin, sucralose and the like.

As the acidulant, citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, lactic acid, salts thereof and the like can be used.

As the dosage form of the therapeutic agent of the present invention, capsules, powders, granules, pills, jellies and the like can be used, but tablets are preferable. By using tablets, it is possible to produce a pharmaceutical product having excellent manufacturability, ingestibility, and storage stability.

The obtained tablets may be coated with a coating agent, if necessary. As the coating agent, it is preferable to select one that does not significantly impair the disintegration property, and among them, a water-soluble polymer compound or a plasticizer is preferable. One type of coating agent may be used alone, or two or more types may be used in combination.

Examples of the water-soluble polymer compound include celluloses such as carmellose, hydroxypropylcellulose, hydroxypropylmethylcellulose (hypromerose), hydroxymethylcellulose, and methylcellulose; Polysaccharides of disaccharide or more (sugar (granule sugar, etc.), lactose, malt sugar, xylose, isomerized lactose, etc.), sugar alcohols (palatinit, sorbitol, lactitol, erythritol, xylitol, reduced starch saccharified product, martitol, mannitol, etc.) , Water candy, isomerized saccharides, oligosaccharides, sucrose, trehalose, reduced starch saccharified products (reduced starch decomposition products, etc.) and the like. In particular, hydroxypropylmethylcellulose (hypromellose) and polyvinyl alcohol are preferable from the viewpoint of excellent manufacturability and moisture resistance.

Examples of the plasticizer include those described in the Japanese Pharmacopoeia (Hirokawa Shoten) such as triethyl citrate, triacetin, and carnauba wax, and official documents such as the Pharmaceutical Additives Standard (Yakuji Nippo Co., Ltd.).

[Oral treatment for myofascial pain]
Since the component (A) and the component (B) of the present invention have a high reducing effect and healing effect on myofascial pain, the above component is used as an active ingredient for myofascial pain. It is used as an internal therapeutic agent and an internal relieving agent for myofascial pain. Myofascial pain has the above-mentioned characteristics, and the ingestion method is not limited to "before pain" and "after pain", but the alleviating and healing effect of the present invention is "muscle / muscle". It is fully exerted even after the onset of fascial pain. Further, the number of times of ingestion is not particularly limited, but even a single ingestion can sufficiently exert a reducing and healing effect on myofascial pain.

[Evaluation method of healing effect for myofascial pain]
This measurement method, which will be described in Examples described later, causes muscle / myofascial pain by applying an eccentric contractile load to a predetermined muscle 50 times at a constant extension angle / velocity, resulting in pain. This is a method for evaluating pain by measuring the escape threshold when the muscle at the site of occurrence is mechanically stimulated. By using a mechanical stimulation probe with a tip diameter of 2.6 mm or more at the time of threshold measurement, it is possible to specifically detect only muscle pain sensation excluding skin sensation even in percutaneous mechanical stimulation. The Landar Celit test and Von Frey test, which are generally widely used for pain evaluation, are methods that can specifically evaluate muscle pain because the tip diameter of the probe for mechanical stimulation is small and skin pain sensation is mixed. Not (Pain Clinic, 38: 645-654, 2017).

Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. Unless otherwise specified in the following examples, "%" in the composition indicates mass%, and the ratio indicates mass ratio.

[Evaluation method of healing effect for myofascial pain-1]
(1) Preparation of myofascial pain model The left hind leg lower leg muscle group of a rat (SD system, ♂, 8 weeks old) was subjected to an eccentric contractile load 50 times according to the description in the literature (pain clinic, 38: 645-654, 2017).

(2) Sample i. Administration sample 1. Control: 5% gum arabic suspension solution 2. Acetylsalicylic acid: 75 mg / kg
3. 3. Loxoprofen sodium dihydrate: 6.81 mg / kg
4. Ibuprofen: 20 mg / kg
5. Acetaminophen: 30 mg / kg
6. Acetylsalicylic acid: 50 mg / kg + acetaminophen: 30 mg / kg
7. Ibuprofen: 13 mg / kg + acetaminophen: 13 mg / kg
8. Loxoprofen sodium dihydrate: 3.63 mg / kg + acetaminophen: 30 mg / kg
9. Celecoxib: 10 mg / kg

In the above-mentioned administration group, when it is taken as a single dose by humans, it can be, for example, the following ratio. Hereinafter, the sample name is used.

ii. Preparation of sample Weighed a sample (three times the amount of the component described in the administration group) and 1.5 g of gum arabic, mixed in a mortar, and then added water to prepare a 30 mL suspension. The control used was a 5% gum arabic suspension.
iii. Administration of sample The dose of the sample to the rat was 10 mL / kg, and the pre-measured amount according to the body weight of the rat (eg, 200 g of rat: 2 mL) was taken in a disposable syringe equipped with an oral administration sonde for rats. It was administered by gavage.

(3) Evaluation method The mechanical escape threshold (PWT; Paw Withdrawal Threat) of the anterior cervical muscle of the left hind limb of a rat (SD system, ♂, 8 weeks old) was measured 5 times per animal with a Von Frey 2390 electronic pain sensation measuring device. The average value of 5 times was used as the initial value. The day after the initial value measurement, an eccentric contractile load was applied to the lower leg muscle group on the PWT measurement side. The escape threshold was measured 5 times 24 hours after loading, and the average value of the 5 times was taken as the PWT at 0 hour of sample administration. Immediately after the PWT measurement at 0 hour after the sample administration, the sample was orally administered, and the PWT was measured every 1 hour until 4 hours after the administration.
The PWT at each time point was divided by the PWT of the control group at each time point, and the PWT increase rate (%) (rPWT) was calculated. The area under the curve (AUC0-4hr; Area under the Curve 0-4hr) of the rPWT curve from 0 hour to 4 hours after sample administration was calculated from the following formula. The results are shown in Table 2 and FIG.

(4) Evaluation results While the AUC of the celecoxib group was 0.5% · hr, acetylsalicylic acid was 16.9% · hr, loxoprofen sodium hydrate was 40.1% · hr, and ibuprofen was 36. 7% hr, acetaminophen 11.2% hr, acetylsalicylic acid + acetaminophen 13.6% hr, ibuprofen + acetaminophen 23.9% hr, loxoprofen sodium dihydrate + Acetaminophen was 37.9% hr, and a healing effect on myo-muscular pain was observed.

[Evaluation method for healing effect on myofascial pain-2]
(1) Preparation of myofascial pain model The left hind leg lower leg muscle group of a rat (SD system, ♂, 8 weeks old) was subjected to an eccentric contractile load 50 times according to the description in the literature (pain clinic). , 38: 645-654, 2017).

(2) Sample i. Administration sample 1. Control: 5% gum arabic suspension solution 2. Acetylsalicylic acid: 250 mg / kg
3. 3. Acetaminophen: 150 mg / kg
4. Loxoprofen sodium dihydrate : 18.2 mg / kg
5. Aspirin: 250 mg / kg + acetaminophen: 150 mg / kg
6. Loxoprofen sodium dihydrate: 18.2 mg / kg + acetaminophen: 150 mg / kg
A drug-free sample (containing only gum arabic) was prepared and used as a control. The dose of loxoprofen sodium was calculated as loxoprofen sodium dihydrate.

ii. Preparation of sample Weighed a sample (three times the amount of the component described in the administration group) and 1.5 g of gum arabic, mixed in a mortar, and then added water to prepare a 30 mL suspension. The control used was a 5% gum arabic suspension.
iii. Administration of sample The dose of the sample to the rat was 10 mL / kg, and the pre-measured amount according to the body weight of the rat (eg, 200 g of rat: 2 mL) was taken in a disposable syringe equipped with an oral administration sonde for rats. It was administered by gavage.

(3) Evaluation method The same procedure as evaluation method-1 was performed until a PWT of 0 hours after sample administration was obtained. Immediately after PWT measurement 0 hours after sample administration, the sample was orally administered, and PWT was measured 1 hour after administration.
The difference (ΔPWT) between PWT (PWT0hr) 0 hours after sample administration and PWT (PWT1hr) 1 hour after sample administration was calculated from the following formula, and the amount of change in PWT depending on the sample was evaluated. The results are shown in Tables 3 and 2 below.

(4) Evaluation results PWT increased by 250 mg / kg of acetylsalicylic acid is 20.7 g, acetaminophen: 150 mg / kg is 22.2 g, and loxoprofen sodium dihydrate: 18.6 mg / kg is 16.4 g. On the other hand, acetylsalicylic acid: 250 mg / kg + acetaminophen: 150 mg / kg is 60.0 g, loxoprofen sodium dihydrate: 18.2 mg / kg + acetaminophen: 150 mg / kg is 44.1 g, and acetyl. A synergistic effect was obtained by combining salicylic acid and loxoprofen with acetaminophen.

Claims (8)

(A) Acetaminophen and
(B) With one selected from loxoprofen (b-1) and acetylsalicylic acid (b-2)
As an active ingredient ,
(B-1): The compounding mass ratio of the component (A) represented by (A) and the component (b-1) is 1: 4.5 to 8.5, or
(B-2): The compounding mass ratio of the component (A) represented by (A) and the component (b-2) is 1: 0.3 to 1.0.
Oral treatment for myofascial pain. (A) Acetaminophen and (B) Loxoprofen (b-1) are contained as active ingredients, and (b-1): (A) and (b-1) components represented by (A). The oral therapeutic agent for myofascial pain according to claim 1, wherein the compounding mass ratio is 1: 4.5 to 8.5. (A) Acetaminophen and (B) Acetylsalicylic acid (b-2) are contained as active ingredients, and (b-2): (A) component and (b-2) component represented by (A). The oral therapeutic agent for myo-muscular pain according to claim 1, wherein the compounding mass ratio of is 1: 0.3 to 1.0. (B-2): The muscle according to claim 1 or 3, wherein the compounding mass ratio of the component (A) and the component (b-2) represented by (A) is 1: 0.5 to 0.7.・ Oral treatment for myofascial pain. (A) The oral therapeutic agent for myofascial pain according to any one of claims 1 to 4, wherein the dose of acetaminophen per adult is 65 to 1,000 mg. (B) The oral therapeutic agent for myofascial pain according to claim 1 or 2, wherein the dose of loxoprofen (b-1) per adult is 10 to 150 mg. (B) The myofascial pain according to any one of claims 1, 3 and 4, wherein the dose of acetylsalicylic acid (b-2) per adult is 100 to 1,500 mg. Oral remedy. The oral therapeutic agent for myofascial pain according to any one of claims 1 to 7, which is taken once after the onset of myofascial pain.

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