JP2019073449A - Oral therapeutic agent for myofascial pain - Google Patents

Abstract

To provide an oral therapeutic agent for myofascial pain having significant alleviation effect and therapeutic effect on myofascial pain.SOLUTION: An oral therapeutic agent for myofascial pain contains, as active ingredients, (A) acetaminophen and a salt thereof, and (B) at least one selected from a nonsteroidal anti-inflammatory agent and a salt thereof (excluding celecoxib, zaltoprofen, ketorolac, nimesulide, and aceclofenac).SELECTED DRAWING: Figure 1

Description

  The present invention relates to a therapeutic agent for internal use having a high alleviation effect and a healing effect on myopathic pain.

  Non-steroidal anti-inflammatory drugs (NSAIDs) analgesia by inhibiting the activity of cyclooxygenase-2 (COX-2) responsible for the production of the pain-promoting substance prostaglandin (PG) which is increased by inflammation, tissue damage, etc. , Exert an anti-inflammatory effect. Therefore, although NSAIDs are effective for pain involving COX due to inflammation and tissue damage, they are known to be less effective for pain in which the contribution of COX and PG is low such as cancer pain and neuropathic pain. For such pain, an analgesic having a mechanism of action different from that of COX, such as opioid receptors and various Na and Ca channels involved in pain, is used.

  In recent years, it has been shown that there are various pain generation pathways also for back pain. Back pain is roughly classified into specific back pain and nonspecific back pain from its pathological condition. Specific back pain, which accounts for 15% of total back pain, is considered to be back pain accompanied by underlying diseases such as fractures, inflammation, nerve compression, and tumors. Among these back pains, NSAIDs may be effective for back pain accompanied by inflammation. On the other hand, nonspecific low back pain which is considered to account for 85% of total back pain is mainly caused by muscles, intervertebral joints, intervertebral discs and the like as the main cause tissue.

  Myalgia, which is one of the causes of nonspecific back pain, is caused by physical pain not due to physical load such as bacterial or viral infection, and physical load such as bruise or sprain. It can be divided roughly into pain. Furthermore, these muscle pains can be classified according to the presence or absence of inflammation or damage to muscle tissue. Myalgia caused by bruises or sprains during infection or exercise is mainly pain accompanied by inflammation or tissue damage, and pain mainly based on such inflammation or tissue damage is mainly due to the involvement of COX and PG, and NSAIDs are effective. In general, NSAIDs are used for the purpose of pain relief.

Japanese Patent Publication 2009-501700

Pain clinic, 38: 645-654, 2017

  On the other hand, although myopathic pain, which is one of myalgias, is muscle pain that is caused by physical load on the muscle, unlike the above-mentioned muscle pain, cord-like induration, myoconstriction, tender point, trigger point It is diagnosed from the presence or absence of concomitant symptoms such as range of motion limitation, and these become important clinical findings. Although there are various hypotheses as the generation mechanism hypothesis of muscle and myofascial pain, there is a vicious cycle in which muscle contraction triggered by overload on muscle, muscle blood flow decrease, and acetylcholine activity increased by ischemia cause further muscle contraction. Has been advocated. In this respect, myofacial pain is different from the above-mentioned mere muscle damage such as infection and bruise and muscle pain due to inflammation. Recently, animal models have been developed for elucidating the pathogenesis of myofacial pain, and for the first time histologic and biochemical studies have become possible. Histological examination using an animal model has revealed that the muscle at the time of myofacial pain is not accompanied by inflammation or significant damage to muscle tissue. Furthermore, in the myofacial pain model, it has been reported that the NSAIDs celecoxib (CXB), zaltoprofen and ketoprofen have no analgesic effect even after administration of pain, and so far NSAIDs Membrane pain was thought to have no analgesic effect. In fact, recent biochemical studies have reported that the main cause of muscular and myofascial pain is not functional changes of nerve growth factor or ion channel but not COX-2 or PG, which are targets of NSAIDs. It has been shown that the condition is completely different from conventional inflammation and injury.

  As described above, NSAIDs are conventionally considered to be ineffective for myofascial pain because NSAIDs such as CXB and the like are ineffective, and acetylsalicylic acid (ASP: aspirin (registered trademark)) The effects of NSAIDs such as ibuprofen (IBP) and loxoprofen sodium hydrate (LOX) and acetaminophen (APAP) on myofacial pain were also unclear. At present, based on the above clinical findings, nerve block therapy by trigger point injection in which a local anesthetic is administered using a needle at a trigger point site is widely used in medical practice. However, this method is invasive, and there are problems such as injury 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 a remedy for internal use which has a higher alleviation effect and curative effect on myopathic pain.

  The present inventor created an animal model reflecting the pathophysiology of myofacial pain, and examined an active ingredient having a high curative effect on myofacial pain. As a result, it was found that acetaminophen (APAP) and certain nonsteroidal anti-inflammatory drugs (NSAIDs) show a high curative effect on myopathic pain. In particular, with celecoxib (CXB), which is one of non-steroidal anti-inflammatory drugs (NSAIDs), no analgesic effect is observed with CXB administration after pain onset, while APAP, ASP, IBP and LOX occur after pain onset It has been found that the analgesic effect is observed even with the administration of the present invention, and the present invention has been completed.

Accordingly, the present invention provides the following internal medicine therapeutic agent.
[1]. Myopathic pain, which contains as an active ingredient one or more selected from (A) acetaminophen and (B) non-steroidal anti-inflammatory drugs (except celecoxib, zaltoprofen, ketorolac, nimesulide, aceclofenac) Treatment for internal use.
[2]. The agent for treating myofacial pain according to [1], wherein the component (B) is (b-1) loxoprofen, (b-2) acetylsalicylic acid, (b-3) ibuprofen.
[3]. (A) The internal medicine therapeutic agent for muscular and fascial pain as described in [1] or [2] which has an acetaminophen as an essential component.
[4]. Further, (b-1) a therapeutic agent for oral and muscle myopathic pain according to [3], which comprises loxoprofen.
[5]. The muscle and fascia according to [4], wherein the blending mass ratio of the component (A) to the component (b-1) represented by (b-1): (A) is 1: 4.5 to 8.5. Internal medicine for sexual pain.
[6]. Further, (b-2) an agent for treating oral and muscular myalgia according to [3], which comprises acetylsalicylic acid.
[7]. The muscle and fascia according to [6], wherein the blending mass ratio of the component (A) to the component (b-2) represented by (b-2): (A) is 1: 0.3 to 1.0. Internal medicine for sexual pain.
[8]. The therapeutic agent for internal use for muscular and myofascial pain according to any one of [1] to [7], which is taken once after the onset of myopathic pain.

  According to the present invention, it is possible to provide an internal medicine for myofacial pain, which has a high alleviating effect and curative effect on myofacial pain.

It is a graph which shows the result of evaluation method 1 of the healing effect with respect to myofacial pain. It is a graph which shows the result of evaluation method 2 of the healing effect with respect to myofacial pain.

Hereinafter, the present invention will be described in detail.
The active ingredients of the therapeutic agent for oral and muscle myofascial pain according to the present invention are (A) acetaminophen and (B) non-steroidal anti-inflammatory drugs (except celecoxib, zaltoprofen, ketorolac, nimesulide, aceclofenac) Or more, and can be used alone or in appropriate combination of two or more.

[(A) component]
Acetaminophen (N- (4-hydroxyphenyl) acetamide) Acetaminophen can also be used as a pharmaceutically acceptable salt. These can be used singly or in appropriate 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 the pharmacological effect on myopathic pain of the present invention and the production are not problematic. The dose for humans is usually 65 to 1,000 mg / dose, preferably 95 to 500 mg / dose, more preferably 100 to 400 mg / dose, and still more preferably 130 to 300 mg / dose for adults. The effectiveness of the use of the present invention can be sufficiently obtained by setting the lower limit value or more, and the occurrence of side effects is suppressed by setting the upper limit value or less, and it is an internal medicine for muscle and fascia pain safe for the human body. Can. The number of administrations per day is appropriately selected from 1 to 4 times. The compounding amount of the agent (A) for the internal use treatment agent for muscular and myofascial pain (hereinafter sometimes referred to as a therapeutic agent) may be the above intake amount or an optional component (physiologically active substance or additive) described later Although it selects suitably by these, 3.0-70 mass% is preferable.

[(B) component]
(B) Non-steroidal anti-inflammatory drugs (NSAIDs: Non-Steroidal Anti-Inflammatory Drugs) is a generic term for drugs having anti-inflammatory action, analgesic action, antipyretic action, and refers to anti-inflammatory drugs that are not steroids. The component (B) of the present invention is not particularly limited as long as celecoxib, zaltoprofen, ketorolac, nimesulide and aceclofenac are excluded. As non-steroidal anti-inflammatory drugs other than the above, salicylic acid, acetylsalicylic acid (aspirin (registered trademark)), aspirin aluminum, salsalate (sazapyrin), salicylamide, etendamide, sodium salicylate, ibuprofen, loxoprofen, diclofenac, ketoprofen, naproxen, Flurbiprofen, piroxicam, thiaprofenic acid, suprofen, tolmetin, aluminoprofen, benoxaprofen, benzidamine, sulindac, acemetacin, apometactine, anphenac, mofenolac, lorunoxicam, anpiroxicam, fenoprofen, tiaprofenic acid, oxaprofen Mefenamic acid, flufenamic acid, felbinac, azapropazone, fenbufen, etodolac, lov Coxibs, diflunisal, zomepirac and the like, and these can also be used salts that are pharmaceutically acceptable. Among them, (b-1) loxoprofen, (b-2) acetylsalicylic acid, and (b-3) ibuprofen are preferable from the viewpoint of the healing effect on myofacial pain.

  When the component (B) is blended, the amount of the component (B) blended is not particularly limited as long as it does not cause any problems in terms of the pharmacological effects on myopathic pain of the present invention and production. The dose for humans is usually 10 to 1,500 mg / dose for adults, preferably 15 to 1,000 mg / dose. By setting the lower limit value or more, the target efficacy is sufficiently obtained, and by setting the upper limit value or less, the occurrence of side effects is suppressed, and it is used as an internal medicine for muscle and fascia pain safe for the human body. be able to. The number of administrations per day is appropriately selected from 1 to 4 times. Although the compounding quantity in the therapeutic agent of (B) component is suitably selected by the said intake and the arbitrary components (physiologically active substance and additive) mentioned later, 0.1-70 mass% is preferable.

[(B-1) component]
Loxoprofen (2- [p- [2-oxocyclopentylethyl] Phenyl] Propionic Acid)
Loxoprofen can also be used in the form of its pharmaceutically acceptable salts, and may be present in the form of their hydrates, and examples thereof include loxoprofen sodium dihydrate (proportionate as water content) It corresponds to about 12% by mass in the drug powder). In the present invention, the amount and ratio of loxoprofen are all in terms of loxoprofen sodium dihydrate. The water content in the therapeutic agent includes the water content brought in from loxoprofen sodium dihydrate. Loxoprofen and salts thereof can be used alone or in combination of two or more.

  When the component (b-1) is blended, the amount of the component (b-1) blended is not particularly limited as long as it is within the range that does not cause any problems in the preparation of myopathic pain of the present invention. The dose for humans is usually 10 to 150 mg / dose for adults, preferably 15 to 100 mg / dose. By setting the lower limit value or more, the target efficacy is sufficiently obtained, and by setting the upper limit value or less, the occurrence of side effects is suppressed, and it is possible for the human body to be a therapeutic agent for muscular and myofascial pain. it can. The number of administrations per day is appropriately selected from 1 to 3 times. Although the compounding quantity in the therapeutic agent of (b-1) component is suitably selected by the said intake and the arbitrary components (physiologically active substance and additive) mentioned later, 0.5-70 mass% is preferable.

[(B-2) component]
Acetylsalicylic acid (Aspirin®, 2-Acetoxybenzoic Acid)
As acetylsalicylic acid, its pharmaceutically acceptable salts can also be used. These can be used singly or in appropriate combination of two or more. When mix | blending the (b-2) component, the compounding quantity of the (b-2) component will not be specifically limited if it is a range which does not have any problem in the pharmacological effect with respect to the myofacial pain of this invention, and manufacture. The dose for humans is usually 100 to 1,500 mg / dose for adults, preferably 300 to 1,000 mg / dose. By setting the lower limit value or more, the target efficacy is sufficiently obtained, and by setting the upper limit value or less, the occurrence of side effects is suppressed, and it is possible for the human body to be a therapeutic agent for muscular and myofascial pain. it can. The number of administrations per day is appropriately selected from 1 to 3 times. Although the compounding quantity in the therapeutic agent of (b-2) component is suitably selected by the said intake and the arbitrary components (physiologically active substance and additive) mentioned later, 10.0-70 mass% is preferable.

[(B-3) component]
Ibuprofen (2- (4-isobutylphenyl) Propionic Acid)
As ibuprofen, its pharmaceutically acceptable salts can also be used. These can be used singly or in appropriate combination of two or more. When the component (b-3) is blended, the amount of the component (b-3) blended is not particularly limited as long as the pharmacological effect on myopathic pain of the present invention and the production are not problematic. The dose for humans is usually 100 to 200 mg / dose for adults, preferably 130 to 200 mg / dose. By setting the lower limit value or more, the target efficacy is sufficiently obtained, and by setting the upper limit value or less, the occurrence of side effects is suppressed, and it is possible for the human body to be a therapeutic agent for muscular and myofascial pain. it can. The number of administrations per day is appropriately selected from 1 to 3 times. Although the compounding quantity in the therapeutic agent of (b-3) component is suitably selected by the said intake and the arbitrary components (physiologically active substance and additive) mentioned later, 3.0-70 mass% is preferable.

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

1: 4.5-8.5 are preferable and the compounding mass ratio of (A) component and (b-1) component represented by (b-1) :( A) is 1: 4.5-6. More preferable.
(B-2): The blending mass ratio of the component (A) to the component (b-2) represented by (A) is preferably 1: 0.3 to 1.0, and 1: 0.5 to 0. 7 is more preferable.
By setting the ratio to the lower limit value or more, a synergistic analgesic effect on muscular and myofascial pain can be easily obtained. On the other hand, by setting the ratio to the upper limit value or less, side effects can be suppressed and a high analgesic effect can be obtained. Furthermore, it can be set as the formulation excellent in manufacturability and the taking property (the size of a tablet, the number of taking, the taste (bitter taste suppression)).

  In the therapeutic agent of the present invention, optional components (physiologically active substance and additives) to be blended in the pharmaceutical preparation for internal use can be blended as long as the effects of the present invention are not impaired. As optional components, examples of additives include binders, excipients, disintegrants, lubricants, flavors, sweeteners, acidulants and the like. These can be used alone or in appropriate combination of two or more.

Examples of physiologically active substances include sedative hypnotic components (allyl isopropyl acetyl urea, brom valeryl urea, etc.), antihistaminic components (isotipendyl hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, dipheteraline hydrochloride, dipheterol hydrochloride, triprolidine hydrochloride, triperenamine hydrochloride, tondilamine hydrochloride, hydrochloric acid Phenetadine, methodzirazine hydrochloride, diphenhydramine salicylate, carbinoxamine diphenyldisulfonate, arimemazine tartrate, diphenhydramine tannate, diphenylpyraline theocric acid, mebuhydrolin napadisylate, promethazine methylene disalicylic acid salt, carbinoxamine maleate, chlorpheniramine maleate, d-maleic acid Chlorpheniramine acid, dipheterol phosphate etc.), central excitatory component (sodium benzoate) Um caffeine, caffeine, anhydrous caffeine, etc., antitussive and expectorant component (codeine phosphate, dextromethorphan hydrobromide, dimemorphan phosphate, tipepidine hibenzate, methoxyphenamine hydrochloride, trimethoqui Nole hydrochloride, carbocysteine, acetylcysteine, ethylcysteine, dl-methylephedrine, bromhexine hydrochloride, serrapeptase, lysozyme chloride, ambroxol, theophylline, aminophylline etc., vitamin components (vitamin B1 and its derivatives and salts thereof, Vitamin B ₂ and derivatives thereof and salts thereof, vitamin C and derivatives thereof and salts thereof, hesperidin and derivatives thereof and salts thereof, and the like can be mentioned.

  As a binder, starch, pregelatinized starch, sucrose, gelatin, gum arabic powder, polyvinyl pyrrolidone, pullulan, dextrin, hydroxypropyl cellulose, cyclodextrin, hypromellose, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxy methyl cellulose, hydroxypropyl methyl cellulose , Polyvinyl alcohol, polyethylene glycol and the like.

  As an excipient, crystalline cellulose, lactose, lactose granulated product, methyl ethyl cellulose, xylitol, erythritol, trehalose, multilol, 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.

  Disintegrants include carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, carboxymethylcellulose calcium, low substituted hydroxypropyl cellulose, hydroxypropyl starch, carboxymethyl starch sodium, crospovidone and the like.

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

  Examples of the flavor include menthol, limonene, plant essential oils (mint oil, mint oil, lychee oil, orange oil, lemon oil, etc.) and the like.

  As the sweetener, saccharin sodium, aspartame, stevia, dipotassium glycyrrhizinate, acesulfame potassium, thaumatin, sucralose and the like can be mentioned.

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

  As a dosage form of the therapeutic agent of the present invention, a capsule, a powder, a granule, a pill, a jelly, etc. can be used, and a tablet is preferable. By using a tablet, a preparation having excellent manufacturability, ease of administration, and storage stability can be produced.

  The obtained tablet 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 and a plasticizer are preferable. The coating agents may be used alone or in combination of two or more.

  Examples of water-soluble polymer compounds include celluloses such as carmellose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose (hypromellose), hydroxymethyl cellulose and methyl cellulose; gum arabic, carboxyvinyl polymer, povidone, polyvinyl alcohol, polyacrylic acid, monosaccharides, Polysaccharides more than disaccharides (sugar (granulated sugar etc.), lactose, maltose, xylose, isomerized lactose etc.), sugar alcohol (palatinite, sorbitol, lactitol, erythritol, xylitol, reduced starch saccharate, maltitol, mannitol etc.) And starch syrups, isomerized saccharides, oligosaccharides, sucrose, trehalose, reduced starch saccharification products (reduced starch degradation products etc.) and the like. In particular, hydroxypropyl methylcellulose (hypromellose) and polyvinyl alcohol are preferable in terms of excellent manufacturability and moisture resistance.

  Examples of the plasticizer include those described in official documents such as the Japanese Pharmacopoeia (Hirokawa Shoten) such as triethyl citrate, triacetin, carnauba wax and the like and the pharmaceutical additive standard (Yakuhin Nipponsha Co., Ltd.).

[Treatment medicine for myofascial pain]
The component (A) and the component (B) of the present invention have a high alleviating effect and a curing effect on muscular and myofascial pain. It is used as an internal medicine therapeutic agent and an internal medicine alleviation agent for muscular and myofascial pain. Myopathic pain has the characteristics as described above, and the method of intake is not limited by "before pain" or "after pain", but the alleviating and curing effect of the present invention is "muscle and muscle Even after "membranous pain", it is sufficiently exerted. Furthermore, the number of intakes is not particularly limited, but even a single intake can sufficiently exert the alleviation and healing effect on myopathic pain.

[Method for evaluating the healing effect on myopathic pain]
This measurement method, which will be described in the examples described later, causes muscular and myofascial pain by applying an extensible contraction load 50 times to a predetermined muscle at a constant elongation angle and speed, and causes pain It is a method to evaluate pain by measuring the escape threshold when the development site muscle is mechanically stimulated. By using a mechanical stimulation probe having a tip diameter of 2.6 mm or more at the time of threshold measurement, it is possible to specifically detect only the nociception of muscles excluding skin sensation even in the case of percutaneous mechanical stimulation. In addition, since the tip diameter of the probe for mechanical stimulation is narrow and skin pain sensation is mixed in the Landercerite test and the Von Frey test which are widely used generally for pain evaluation, a method capable of specifically evaluating muscle pain It is not (Pain clinic, 38: 645-654, 2017).

  EXAMPLES The present invention will be specifically described below by showing Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following examples, unless otherwise specified, “%” of the composition indicates mass%, and the ratio indicates mass ratio.

[Method for evaluating the healing effect on myofacial pain-1]
(1) Preparation of muscle and myofascial pain model The left hind leg and lower leg muscle group of a rat (SD strain, ankle, 8 weeks old) was subjected to 50 times of extension contraction load according to the description of the literature (Pain Clinic, 38: 645-654, 2017).

(2) Sample i. Administration sample 1. Control: 5% gum arabic suspension solution Acetylsalicylic acid: 75 mg / kg
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 addition, when it is set as the single dose which a human takes, the said administration group can be made into the following ratios, for example. The following is indicated by the sample name.

ii. Preparation of sample The sample (3 times the amount of the component described in the administration group) and 1.5 g of gum arabic were weighed and mixed in a mortar, and then water was added to prepare a 30 mL suspension. As a control, 5% gum arabic suspension was used.
iii. Administration of sample The dose of the sample to the rat was 10 mL / kg, and an amount (example: 200 g of rat: 2 mL) according to the weight of the rat previously measured was taken into a disposable syringe equipped with an oral administration sonde for rat. It was orally administered orally.

(3) Evaluation method The mechanical withdrawal threshold (PWT; Paw Withdrawal Throshould) of the anterior tibia muscle of the left hind leg of a rat (SD strain, rabbit, 8 weeks old) was measured 5 times for 1 mouse with a Von Frey 2390 electronic pain measuring device. The average value of 5 times was taken as the initial value. The extensor contraction load was applied to the lower thigh muscle group on the PWT measurement side the day after the initial value measurement. After 24 hours of loading, the escape threshold was measured 5 times, and the mean value of 5 times was taken as PWT at 0 hour of sample administration. Immediately after PWT measurement at 0 hour of sample administration, the sample was orally administered, and PWT was measured every 1 hour until 4 hours after administration.
The PWT at each time point was divided by the PWT of the control group at each time point to calculate the PWT increase rate (%) (rPWT). The area under the curve (AUC 0-4 hr; Area under the Curve 0-4 hr) of the rPWT curve from 0 hours to 4 hours of sample administration was calculated by the following formula. The results are shown in Table 2 and FIG.

(4) Evaluation results The AUC of celecoxib group is 0.5% · hr, whereas 16.9% · hr for acetylsalicylic acid, 40.1% · hr for loxoprofen sodium hydrate, and 36. 1 for ibuprofen. 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 was observed for myopathic pain.

[Method for evaluating the healing effect on myofacial pain-2]
(1) Preparation of muscle and myofascial pain model The extensor contraction load was applied 50 times to the left hind leg and lower leg muscle group of the rat (SD strain, brow, 8 weeks old) according to the description of the literature (Pain Clinic , 38: 645-654, 2017).

(2) Sample i. Administration sample 1. Control: 5% gum arabic suspension solution Acetylsalicylic acid: 250 mg / kg
3. Acetaminophen: 150 mg / kg
4. Loxoprofen sodium hydrate: 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 served as a control. The dose of loxoprofen sodium was calculated as loxoprofen sodium dihydrate.

ii. Preparation of sample The sample (3 times the amount of the component described in the administration group) and 1.5 g of gum arabic were weighed and mixed in a mortar, and then water was added to prepare a 30 mL suspension. As a control, 5% gum arabic suspension was used.
iii. Administration of sample The dose of the sample to the rat was 10 mL / kg, and an amount (example: 200 g of rat: 2 mL) according to the weight of the rat previously measured was taken into a disposable syringe equipped with an oral administration sonde for rat. It was orally administered orally.

(3) Evaluation method It carried out like evaluation method 1 until PWT of 0 hours of sample administration was obtained. Immediately after PWT measurement at 0 hour after sample administration, the sample was orally administered, and PWT at 1 hour after administration was measured.
The difference (ΔPWT) between PWT (PWT 0 hr) after sample administration and 1 hour after sample administration PWT (PWT 1 hr) was calculated according to the following formula, and the amount of PWT change due to the sample was evaluated. The results are shown in Table 3 below and FIG.

(4) Evaluation results Acetylsalicylic acid: PWT increased by 250 mg / kg 20.7 g, acetaminophen: 150 mg / kg 22.2 g, loxoprofen sodium dihydrate: 18.6 mg / kg 16.4 g Acetylsalicylic acid: 250 mg / kg + acetaminophen: 60.0 g at 150 mg / kg, loxoprofen sodium dihydrate: 18.2 mg / kg + acetaminophen: 44.1 g at 150 mg / kg, A synergistic effect was obtained by combining salicylic acid and loxoprofen with acetaminophen.

Claims (8)

  Myopathic pain, which contains as an active ingredient one or more selected from (A) acetaminophen and (B) non-steroidal anti-inflammatory drugs (except celecoxib, zaltoprofen, ketorolac, nimesulide, aceclofenac) Treatment for internal use.   The therapeutic agent for internal use for muscular / facial pain according to claim 1, wherein the component (B) is (b-1) loxoprofen, (b-2) acetylsalicylic acid, (b-3) ibuprofen.   The therapeutic agent for internal use for muscular and fascial pain according to claim 1 or 2, wherein (A) acetaminophen is an essential component.   Furthermore, the internal medicine therapeutic agent for muscular and fascial pain of Claim 3 containing (b-1) loxoprofen.   The muscle and fascia according to claim 4, wherein the blending mass ratio of the component (A) to the component (b-1) represented by (b-1): (A) is 1: 4.5 to 8.5. Internal medicine for sexual pain.   Furthermore, the internal-treatment therapeutic agent for muscular and fascial pain of Claim 3 containing (b-2) acetylsalicylic acid.   The muscle and fascia according to claim 6, wherein a blending mass ratio of the component (A) to the component (b-2) represented by (b-2): (A) is 1: 0.3 to 1.0. Internal medicine for sexual pain.   The therapeutic agent for internal use for muscular and myofascial pain according to any one of claims 1 to 7, which is taken once after the onset of myopathic pain.

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