JP2009073851A - Loxoprofen-containing medicinal preparation 2 - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To find a new medicinal composition that exhibits synergism relating to anti-inflammatory. <P>SOLUTION: The new medicinal composition comprises a combination of (1) one or more than two kinds of medicines selected from caffeine, allylisopropylacetylurea, bromovalerylurea, acetoaminophen, and ethenzamide and (2) loxoprofen. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to novel compositions having superior analgesic, anti-inflammatory and / or antipyretic effects, and the use of novel combinations of drugs to produce them.

Caffeine is a cardiotonic and central nervous stimulant,
Allylisopropylacetylurea and bromvalerylurea are hypnotics and sedatives,
Acetaminophens are used as analgesics and antipyretic agents,
Etenzamide is an analgesic and antipyretic
It is an extremely widely used drug.

  Loxoprofen, on the other hand, is a widely used drug as an analgesic and anti-inflammatory agent because it has less damage to the stomach.

However,
(1) one or more drugs selected from caffeine, allylisopropylacetylurea, bromvalerylurea, acetaminophens and etenzamid;
(2) A pharmaceutical composition combining loxoprofen is not known.

  As a result of intensive studies on synergistic effects when loxoprofen and other drugs are used, the present inventors have conducted (1) caffeine, allylisopropylacetylurea, bromvalerylurea, acetaminophen. And a novel pharmaceutical composition comprising one or more drugs selected from ethenzamid and (2) loxoprofen have excellent analgesic, anti-inflammatory and / or antipyretic effects. The present invention has been completed.

  Furthermore, another object of the present invention is to provide a preventive or therapeutic agent for the purpose of analgesia, anti-inflammation and / or antipyretic, as a combination which is administered simultaneously, separately or sequentially (1) One or more drugs selected from caffeine, allylisopropylacetylurea, bromvalerylurea, acetaminophens, and etenzamid and (2) loxoprofens are used as active ingredients.

The novel pharmaceutical composition of the present invention comprises:
(1) Caffeine, allyl isopropyl acetylurea, bromvalerylurea as a combination to be administered simultaneously, separately or sequentially for use as a preventive or therapeutic agent for the purpose of analgesia, anti-inflammatory and / or antipyretic , One or more drugs selected from acetaminophens and etenzaamide, and (2) loxoprofen as an active ingredient,
The novel analgesic, anti-inflammatory and / or antipyretic of the present invention is
(1) one or more drugs selected from caffeine, allyl isopropyl acetylurea, bromvalerylurea, acetaminophens and etenzamid, and (2) loxoprofens as an active ingredient,
The use of the present invention for producing a novel preventive or therapeutic agent for the purpose of analgesia, anti-inflammatory and / or antipyretic,
(1) One or more drugs selected from caffeine, allyl isopropyl acetylurea, bromvalerylurea, acetaminophens and etenzaamide as a combination to be administered separately or sequentially, and ( 2) Loxoprofen is used as an active ingredient.

As a preferred combination, when used as an analgesic, it is a combination of one or more drugs selected from caffeine, allyl isopropyl acetylurea, acetaminophens and etenzaamide, and loxoprofen. More preferably, it is a combination of one or two or more drugs selected from acetaminophens and ethenamide, and loxoprofen, and more preferably a combination of ethenamide and loxoprofen.
When used as an anti-inflammatory agent, it is a combination of one or more drugs selected from bromvalerylurea, caffeine and etenzaamide, and loxoprofen, and more preferably caffeine and loxoprofen. In combination with
When used as an antipyretic, it is preferably a combination of one or more drugs selected from allyl isopropyl acetylurea, bromvalerylurea and etezamide, and loxoprofen.

In the present invention,
The caffeine is not particularly limited as long as it is a caffeine derivative that can be generally used as a cardiotonic diuretic and a central nervous stimulant, but preferably caffeine or anhydrous caffeine listed in the pharmacopoeia. It is. In addition, since pharmacopoeia caffeine has one molecule of crystal water, caffeine hydrates and solvates are also included.

  Allyl isopropyl acetylurea is also called apronalide, and is generally not particularly limited as long as it is allyl isopropyl acetylurea that can be used as a hypnotic and sedative, and includes hydrates and solvates.

  Bromovaleryl urea is also called bromisoval, and is generally not particularly limited as long as it is bromvalerylurea that can be used as a hypnotic and sedative, and includes hydrates and solvates.

  Acetaminophens are also referred to as paracetamol, and are generally not particularly limited as long as they are acetaminophen derivatives that can be used as analgesics and antipyretics, and acetaminophen, a pharmacologically acceptable salt thereof (preferably, Alkali metal salts such as sodium salt, potassium salt and lithium salt, alkaline earth metal salts such as calcium salt and magnesium salt, metal salts such as aluminum salt, iron salt, zinc salt, copper salt, nickel salt and cobalt salt Inorganic salts such as ammonium salts, t-octylamine salts, dibenzylamine salts, morpholine salts, glucosamine salts, phenylglycine alkyl ester salts, ethylenediamine salts, N-methylglucamine salts, guanidine salts, diethylamine salts, triethylamine salts , Dicyclohexylamine salt, N, N′-dibenzylethyl Diamine salts, chloroprocaine salts, procaine salts, diethanolamine salts, N-benzyl-phenethylamine salts, piperazine salts, tetramethylammonium salts, amine salts such as organic salts such as tris (hydroxymethyl) aminomethane salts) or other derivatives Pharmacologically acceptable salts include hydrates and solvates.

  Other derivatives are mainly prodrugs (derivatives that are cleaved in the human body by a biological method such as hydrolysis to produce a free form or a salt thereof. Whether such a derivative is a rat or mouse. It can be determined by injecting intravenously into laboratory animals such as the following, and then examining the body fluid of the animal and detecting the original compound or pharmacologically acceptable salt thereof)), but acetanilide or phenacetin And the like wherein the main active metabolite is acetaminophen. Preferably, acetaminophen itself is used.

  Ethenzamide is also known as ethoxybenzamide, and is generally not particularly limited as long as it is ethenzamide that can be used as an analgesic and antipyretic, and includes hydrates and solvates.

“At the same time” means taking at about the same time,
“Separately” means taking separately at different times, for example, taking one drug on the first day and another drug on the second day.

  “Sequentially” refers to taking in order, for example, taking one drug first and then taking another drug after a predetermined time.

  A novel combination of (1) one or more drugs selected from (1) caffeine, allylisopropylacetylurea, bromvalerylurea, acetaminophens and etenzaamide, and (2) loxoprofen The pharmaceutical composition showed significant synergistic effects on analgesic, anti-inflammatory and / or antipyretic effects.

(1) One or more drugs selected from caffeine, allyl isopropyl acetylurea, bromvalerylurea, acetaminophens and etenzaamide as a combination to be administered separately or sequentially, and ( 2) The novel pharmaceutical composition and the like of the present invention containing loxoprofen as an active ingredient has excellent analgesic, anti-inflammatory and / or antipyretic effects, and is not toxic. It is useful as a prophylactic and therapeutic agent.

  The novel pharmaceutical composition of the present invention comprises (1) an appropriate amount of one or more drugs selected from caffeine, allylisopropylacetylurea, bromvalerylurea, acetaminophens, and etenzamid; 2) It is formulated according to a conventional method so as to contain an appropriate amount of loxoprofen as an active ingredient.

  In addition, when administering "separately" or "sequentially", according to a conventional method, each chemical | medical agent will be formulated separately.

  The amount of each drug used varies depending on symptoms, age, administration method, and the like, but it is desirable to administer one to several times per day within the following allowable range.

  The allowable amount of caffeine that can be used is 5 mg (preferably 10 mg) as the lower limit and 500 mg (preferably 250 mg) as the upper limit per day.

  The allowable amount of allylisopropylacetylurea that can be used is 5 mg (preferably 10 mg) as the lower limit and 400 mg (preferably 180 mg) as the upper limit per day.

  The allowable amount of bromovalerylurea that can be used is 10 mg (preferably 20 mg) as a lower limit and 1500 mg (preferably 600 mg) as an upper limit per day.

  The allowable amount of acetaminophen that can be used is 5 mg (preferably 10 mg) as the lower limit and 2000 mg (preferably 1000 mg) as the upper limit per day.

  The allowable amount of etezamide that can be used is 5 mg (preferably 10 mg) as the lower limit and 2000 mg (preferably 1500 mg) as the upper limit per day.

  The allowable amount of loxoprofen that can be used is 5 mg (preferably 10 mg) as the lower limit and 500 mg (preferably 180 mg) as the upper limit per day.

Examples of the pharmaceutical composition of the present invention include compositions for oral administration such as tablets, capsules, granules, powders, liquids or syrups, and these compositions further include
Excipients (eg sugar derivatives such as lactose, sucrose, sucrose, mannitol, sorbitol; starch derivatives such as corn starch, potato starch, alpha starch, dextrin; cellulose derivatives such as crystalline cellulose; gum arabic; dextran; Organic excipients such as pullulan: and silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, calcium silicate, magnesium metasilicate magnesium phosphate; phosphates such as calcium hydrogen phosphate; carbonates such as calcium carbonate Salts; inorganic excipients such as sulfates such as calcium sulfate can be mentioned).
Lubricants (for example, stearic acid metal salts such as stearic acid, calcium stearate, magnesium stearate; talc; colloidal silica; waxes such as bee gum and gay wax; boric acid; adipic acid; sulfates such as sodium sulfate Glycol, fumaric acid, sodium benzoate, DL leucine, fatty acid sodium salt, lauryl sulfate such as sodium lauryl sulfate and magnesium lauryl sulfate, silicic acids such as anhydrous silicic acid and silicic acid hydrate, and the starch derivative Can be mentioned)
Binders (for example, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, macrogol, and the same compounds as the above-mentioned excipients),
Disintegrants (eg low substituted hydroxypropylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium, cellulose derivatives such as internally crosslinked sodium carboxymethylcellulose; chemically modified starches such as carboxymethyl starch, sodium carboxymethyl starch, crosslinked polyvinylpyrrolidone -Cellulose can be mentioned.),
Stabilizers (paraoxybenzoates such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol; thimerosal; dehydroacetic acid; And sorbic acid.),
Flavoring agents (for example, commonly used sweeteners, acidulants, fragrances, etc.),
Additives such as diluents can be used.

  Hereinafter, the present invention will be described more specifically with reference to test examples and formulation examples.

(1) Test drug Loxoprofen sodium dihydrate was used by our company.

All doses were calculated in terms of loxoprofen sodium anhydride.
(2) Drugs used Anhydrous caffeine is manufactured by Wako Pure Chemicals, allylisopropylacetylurea is manufactured by Kongo Chemical, bromvalerylurea is manufactured by Yoshida Pharmaceutical, acetaminophen is manufactured by Sigma, and ethenzamide is manufactured by Yoshida Pharmaceutical. Used.
(3) Animals used and breeding environment Wistar Imado male rats 5 weeks old (Daikenken) and ddy male mice 4 weeks old (Japan SLC) were used.

Rats and mice can freely ingest solid samples (mouse, rat breeding F-2, Funabashi Farm) and tap water in an animal pack under constant temperature and humidity (temperature 22 ± 1 ° C, humidity 55 ± 5%). After preliminary breeding for 7 days, animals with good health were selected and tested.
(4) Administration method The drug was used by dissolving or suspending in a 0.5% tragacanth solution, regardless of whether it is easily soluble or not.

In the case of single administration, the amount of the solution was 0.1 ml / 10 g for mice and 0.5 ml / 100 g for rats, and in the case of combination use, a single ½ amount was orally administered.
(5) Statistical processing The results were expressed as mean ± standard error.

The 50% inhibitory dose (ID ₅₀ value) was calculated by determining a regression line between the inhibition rate and dose of each animal by the least square method.

The 95% confidence limit was calculated from Fieller's formula.
[Test Example 1]
Analgesic action (acetic acid rising (Writhing method))
This was performed according to the method of Koster et al. (Koster R., Anderson M. and De Beer E .: J. Fed. Proc. 18, 412 (1958)).

  A group of 5 to 10 ddy male mice of 5 weeks old was fasted for 16 hours from the day before the experiment.

  Loxoprofen sodium dihydrate (measured using 20, 40, 80 and 160 mg / kg each) itself, and anhydrous caffeine (80 mg / kg), allylisopropylacetylurea (12.5 mg / kg), Composition of acetaminophen (9.4 mg / kg) or etenzamide (18.8 mg / kg) and loxoprofen sodium dihydrate (measured using 20, 40, 80 and 160 mg / kg each) Were simultaneously administered orally at a rate of 0.05 ml / 10 g, and 30 minutes later, a 0.6% acetic acid aqueous solution was intraperitoneally administered at a rate of 0.1 ml / 10 g.

  The rising number for 10 minutes was measured 10 minutes after administration of the acetic acid aqueous solution.

  In the control group, 0.5% tragacanth solution (0.1 ml / 10 g) was orally administered and measured in the same manner.

The inhibition rate of each composition with respect to the average rising number of the control group was calculated, and using this data, the ID ₅₀ value was calculated as shown in Table 1.

In addition,
Anhydrous caffeine (A),
Allyl isopropyl acetyl urea (B),
Acetaminophen (C),
Etenzamid (D),
Loxoprofen sodium dihydrate is represented by (E), but for each combination drug other than loxoprofen sodium dihydrate, the dose at which no effect was exhibited was determined in advance and set.

  It can be seen from Table 2 that the drug itself does not exhibit an analgesic action at the use dose of each of the above drugs except for loxoprofen sodium dihydrate.

ロキソプロフェンナトリウム・２水和物との配合剤において、上記のように、エテンザミドが最も相乗的に効果（約６倍）を発揮した。無水カフェイン、アリルイソプロピルアセチル尿素及びアセトアミノフェンも約２倍作用の増強が認められた。

In the combination with loxoprofen sodium dihydrate, as described above, etenzamide exhibited the most synergistic effect (about 6 times). Anhydrous caffeine, allyl isopropyl acetylurea and acetaminophen were also found to be about 2-fold potentiated.

Therefore, the composition of the present invention showed a remarkable synergistic effect on analgesic action.
[Test Example 2]
Anti-inflammatory effect (carrageenan foot edema method)
The method of Winter et al. (Winter CA, Risley EA and Nuss GW: Proc. Soc. Exp. Biol. Med. 111, 544 (1965)) was carried out with some modifications as follows.

  A group of 5 to 10 Wistar Imado rats of 6 weeks old was fasted for 16 hours from the day before the experiment.

  Loxoprofen sodium dihydrate (measured using 1.0, 2.0 and 4.0 mg / kg each) itself, as well as anhydrous caffeine (20 mg / kg), allylisopropylacetylurea (100 mg / kg) ), Bromvalerylurea (50 mg / kg), acetaminophen (37.5 mg / kg) or etenzamide (37.5 mg / kg) and loxoprofen sodium dihydrate (0.2, 0.25, 0.5) , 1.0 and 2.0 measured using mg / kg each) at the same time, orally at a rate of 0.25 ml / 100 g, and 30 minutes after drug administration, 1% carrageenan solution (Viscarin 402) 0.05 ml was injected subcutaneously into the rat's right hind paw footpad to induce inflammatory edema.

The volume of the right hind paw before carrageenin injection and 3 hours after the injection was measured with a paw volume measuring device (TK-105, Muromachi Kikai). -1)
(1—Individual edema intensity in composition administration group / average edema intensity in control group) × 100
The inhibition rate was calculated, and the ID ₅₀ value was calculated using this data as shown in Table 3.

  In the control group, 0.5% tragacanth solution (0.5 ml / 100 g) was orally administered and measured in the same manner.

Also, the formula,
(1-individual edema intensity in drug administration group / average edema intensity in control group) × 100
More inhibition rate was calculated.

In addition,
Anhydrous caffeine (A),
Allyl isopropyl acetyl urea (B),
Bromvalerylurea (B2),
Acetaminophen (C),
Etenzamid (D),
Loxoprofen sodium dihydrate is represented by (E), but for each combination drug other than loxoprofen sodium dihydrate, the dose at which no effect was exhibited was determined in advance and set.

  It can be seen from Table 4 that at the doses used for each of the above drugs, excluding loxoprofen sodium dihydrate, the drug itself does not exhibit an anti-inflammatory effect.

ロキソプロフェンナトリウム・２水和物との配合剤において、上記のように、無水カフェイン及びエテンザミドとの併用で約４．５倍の作用の増強が認められた。また、アリルイソプロピルアセチル尿素及びアセトアミノフェンとの併用でも作用の増強が認められた。

In the combination preparation with loxoprofen sodium dihydrate, as described above, the combined use with anhydrous caffeine and ethenamide was confirmed to have an action enhancement of about 4.5 times. In addition, the combined use with allyl isopropyl acetylurea and acetaminophen was also enhanced.

  Furthermore, in combination with bromvalerylurea, an increase in the inhibition rate was seen compared to single administration, and a mild synergistic effect was observed.

Therefore, the composition of the present invention showed a remarkable synergistic effect on the anti-inflammatory action.
[Test Example 3]
Antipyretic action
The method of Roszkowski et al. (Roszkowski A.P., Rooks WH, Tomolonis AJ and Miller LM: J. Pharmacol. Exp. Ther. 179, 114 (1971)) was carried out with some modifications as follows.

  A group of 5 to 10 6-week-old Wistar Imado rats was used.

  Yeast (Brewers yeast, manufactured by Sigma) was pulverized in a mortar, suspended in physiological saline, and adjusted to a concentration of 25%.

  The yeast suspension was fasted after being injected subcutaneously in the back of the rat at a rate of 2 ml / rat.

  The next day (19 hours after yeast injection), about 5 cm was inserted into the rectum using a catheter type thermistor thermometer (MGA III, manufactured by Nihon Kohden), and the temperature was measured.

  Animals that fever 1.5 ° C. or more from the average rectal temperature of healthy animals were selected and grouped so that the average fever temperature of each group was approximately equal, and loxoprofen sodium dihydrate (0.4, 0.8 and 1.6 Measured using each mg / kg) as well as anhydrous caffeine (80 mg / kg), allylisopropylacetylurea (50 mg / kg), bromvalerylurea (25 mg / kg), acetaminophen (9. 4 mg / kg) or etezamide (18.8 mg / kg) and loxoprofen sodium dihydrate (measured using 0.2, 0.4, 0.8 and 1.6 mg / kg each) The composition was simultaneously administered orally at a rate of 0.25 ml / 100 g.

  The control group received 0.5% tragacanth solution (0.5 ml / 100 g).

  The rectal temperature 1 hour after administration was measured, and the average rectal temperature of healthy animals measured at the same time was subtracted to obtain the fever temperature.

The inhibition rate of each composition with respect to the average exothermic temperature of the control group was calculated, and using this data, the ID ₅₀ value was calculated as shown in Table 5.

  Moreover, the inhibition rate of each drug with respect to the average fever temperature of the control group was calculated.

In addition,
Anhydrous caffeine (A),
Allyl isopropyl acetyl urea (B),
Bromvalerylurea (B2),
Acetaminophen (C),
Etenzamid (D),
Loxoprofen sodium dihydrate is represented by (E), but for each combination drug other than loxoprofen sodium dihydrate, the dose at which no effect was exhibited was determined in advance and set.

  It can be seen from Table 7 that at the doses used for each of the above drugs, excluding loxoprofen sodium dihydrate, the drug itself does not exhibit an anti-inflammatory effect.

ロキソプロフェンナトリウム・２水和物との配合剤において、上記のように、アセトアミノフェン及びエテンザミドとの併用で約２倍の作用の増強が認められた。また、アリルイソプロピルアセチル尿素及び無水カフェインとの併用でも作用の増強が認められた。

In the combination with loxoprofen sodium dihydrate, as described above, the combined use with acetaminophen and etenzaamide was found to have an approximately 2-fold increase in action. In addition, the combined use with allyl isopropyl acetylurea and anhydrous caffeine was observed to enhance the action.

  Furthermore, in the combined use with allyl isopropyl acetylurea and bromvalerylurea, a marked increase in the inhibition rate was seen compared to single administration, and a synergistic effect was observed. A slight synergistic effect was also observed with etenzamide.

Therefore, the composition of the present invention showed a remarkable synergistic effect on the antipyretic action.
[Formulation Example 1] (Hard capsule)
Unit capsules were prepared by filling each of the standard halved hard gelatin capsules with the following formulation:

Loxoprofen sodium dihydrate 60mg (converted as anhydride)
Anhydrous caffeine 80mg
Allyl isopropyl acetyl urea 60mg
Magnesium stearate 7mg
Microcrystalline cellulose 60mg
70mg starch
Lactose 13mg
350mg total
[Formulation Example 2] (Tablet)
Tablets were produced according to a conventional method according to the following formulation per tablet.

Loxoprofen sodium dihydrate 60mg (converted as anhydride)
Anhydrous caffeine 80mg
Allyl isopropyl acetyl urea 60mg
Magnesium stearate 7mg
Microcrystalline cellulose 60mg
70mg starch
Lactose 13mg
350mg total
A coating was applied as desired.
[Formulation Example 3] (Tablet)
Tablets were produced according to a conventional method according to the following formulation per tablet.

Loxoprofen sodium dihydrate 40mg (converted as anhydrous)
Acetaminophen 165mg
Magnesium stearate 7mg
Microcrystalline cellulose 60mg
70mg starch
Lactose 8mg
350mg total
A coating was applied as desired.
[Formulation Example 4] (Tablets)
Tablets were produced according to a conventional method according to the following formulation per tablet.

Loxoprofen sodium dihydrate 45mg (converted as anhydrous)
Acetaminophen 125mg
Magnesium stearate 6mg
Microcrystalline cellulose 40mg
Starch 60mg
Lactose 24mg
300mg total
A coating was applied as desired.
[Formulation Example 5] (Tablet)
Tablets were produced according to a conventional method according to the following formulation per tablet.

Loxoprofen sodium dihydrate 40mg (converted as anhydrous)
Ethenzamid 165mg
Anhydrous caffeine 80mg
Magnesium stearate 8mg
Microcrystalline cellulose 20mg
Starch 80mg
Lactose 7mg
400mg total
A coating was applied as desired.
[Formulation Example 6] (Tablet)
Tablets were produced according to a conventional method according to the following formulation per tablet.

Loxoprofen sodium dihydrate 45mg (converted as anhydrous)
Ethenzamid 125mg
Anhydrous caffeine 80mg
Magnesium stearate 8mg
Microcrystalline cellulose 30mg
Starch 80mg
Lactose 32mg
400mg total
A coating was applied as desired.
[Formulation Example 7] (Tablet)
Tablets were produced according to a conventional method according to the following formulation per tablet.

Loxoprofen sodium dihydrate 45mg (converted as anhydrous)
Allyl isopropyl acetyl urea 60mg
Acetaminophen 125mg
Anhydrous caffeine 80mg
Magnesium stearate 8mg
Microcrystalline cellulose 32mg
Starch 80mg
430mg total
A coating was applied as desired.
[Formulation Example 8] (Tablet)
Tablets were produced according to a conventional method according to the following formulation per tablet.

Loxoprofen sodium dihydrate 45mg (converted as anhydrous)
Ethenzamid 125mg
Allyl isopropyl acetyl urea 60mg
Anhydrous caffeine 80mg
Magnesium stearate 8mg
Microcrystalline cellulose 32mg
Starch 80mg
430mg total
A coating was applied as desired.
[Formulation Example 9] (Effervescent Tablet)
Effervescent tablets were produced according to a conventional method according to the following formulation per tablet.

Loxoprofen sodium dihydrate 45mg (converted as anhydrous)
Ethenzamid 125mg
Anhydrous caffeine 80mg
β-cyclodextrin 254mg
Aspartame 30mg
Citric acid 965mg
Sodium bicarbonate 813mg
Lactose 38mg
Magnesium stearate 50mg
Total 2400mg
[Formulation Example 10] (Quick dissolving tablet or chewable tablet)
A fast dissolving tablet or chewable tablet was produced according to a conventional method according to the following formulation per tablet.

Loxoprofen sodium dihydrate 45mg (converted as anhydrous)
Ethenzamid 125mg
Anhydrous caffeine 80mg
β-cyclodextrin 300mg
Aspartame 30mg
D-mannitol 106mg
Magnesium stearate 14mg
700mg total

Claims (6)

(1) one drug selected from acetaminophens or etenzaamide and (2) loxoprofen as a combination to be administered simultaneously, separately or sequentially for use as a prophylactic or therapeutic agent for the purpose of analgesia A pharmaceutical composition containing sucrose as an active ingredient. (1) An analgesic containing one kind of drug selected from acetaminophens or etenzaamide and (2) loxoprofens as an active ingredient. (1) one drug selected from acetaminophens or etenzaamide as a combination to be administered simultaneously, separately or sequentially for use as a prophylactic or therapeutic agent for anti-inflammatory purposes, and (2) A pharmaceutical composition comprising loxoprofen as an active ingredient. (1) One type of drug selected from acetaminophens or etezamide and (2) an anti-inflammatory agent containing loxoprofens as an active ingredient. (1) one drug selected from acetaminophens or etenzaamide and (2) loxoprofen as a combination to be administered simultaneously, separately or sequentially for use as a prophylactic or therapeutic agent for the purpose of antipyretic A pharmaceutical composition containing sucrose as an active ingredient. (1) An antipyretic containing one drug selected from acetaminophens or etenzaamide and (2) loxoprofen as an active ingredient.