JPH10167958A - Loxoprofen sodium-containing oral cavity promptly soluble preparation and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject preparation that contains a non-steroidal analgesic and anti-inflammatory agent and is suitable for patients who cannot readily gulp down conventional pharmaceutical preparations together with water by admixing a specific compound. SOLUTION: This objective pharmaceutical preparation is obtained by freeze- drying an aqueous solution containing loxoprofen and/or its salt, a cyclodextrin derivative (β-cyclodextrin) and a binder (gelatin) (perfectly dissolved), or an aqueous solution containing loxoprofen sodium and/or its hydrate, β-cyclodextrin and a binder (perfectly dissolved). In preferred embodiment, the weight ratio of the active substance to β-cyclodextrin is 30-80% and/or the weight ratio of clathrate to the freeze-dried product is 60-95%. The dose of loxoprofen or loxoprofen sodium is preferably, for example, 5-200mg/kg body weight every administration and once to several times per day.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a nonsteroidal analgesic / anti-inflammatory drug loxoprofen ｛, ie, 2- [4- (2
-Oxocyclopentan-1-ylmethyl) phenyl]
Propionic acid. The present invention relates to a novel fast-dissolving freeze-dried preparation in the oral cavity containing Class I, which has excellent easy-to-take properties and a method for producing the same. INDUSTRIAL APPLICABILITY The present invention provides a dosage form suitable for patients (especially elderly and infants) who are difficult or difficult to take an existing oral administration preparation, and accordingly, it is expected to improve patient compliance. .

[0002]

2. Description of the Related Art Many drugs are orally administered as solid preparations such as tablets, capsules, powders, and granules. However, these formulations may be difficult or difficult to take, especially in the elderly and infants. Further, it has been pointed out that if the administration of the preparation becomes difficult, the compliance of the patient is reduced. On the other hand, there are known some formulations which dissolve or disintegrate in the oral cavity as dosage forms suitable for elderly people, infants or patients who dislike taking the medicine. For example, JP-A-53-446
No. 19 (JP-B-62-50445) and JP-A-61-118314 (JP-B-63-52).
No. 008) discloses a formulation for freezing a composition comprising a drug substance, a polymer carrier substance, and a solvent for a carrier substance, and sublimating the solvent from the frozen composition to form a network of a carrier substance containing the drug substance. The production method is described.

[0003] However, these inventions use gelatin, dextrin, hydrolyzed dextrin or alginic acid, do not use the cyclodextrin of the present invention, and therefore use the loxoprofen derivatives of the present invention. In fact, various attempts have not been made to produce a quick-dissolving lyophilized preparation in the oral cavity which is the subject of the present invention.

[0004] In addition, among the substances used above, "dextrins and hydrolyzed dextrins", which are literally similar to "cyclodextrins", are polysaccharides and are a feature of the prior art invention. , "Inactive substances not involved in the active substance are added to form a network of carrier substances, and the active substance is present on this network." And a cyclodextrin containing an active substance forms a network. "This is completely different from cyclodextrin which is a cyclic oligosaccharide used in the present invention.

On the other hand, JP-A-3-56412 describes a porous preparation produced by freeze-drying a paste obtained by adding a cyclodextrin to a drug substance, and mainly produces an unacceptable taste. Cyclodextrin has been added for concealment. However, the invention disclosed in this application is a suspension even in the preparation of an inclusion compound by a liquid route (coprecipitation) (the invention of the present application is in a solution state), and the state before freeze-drying is as follows: It is a solid (paste). In fact, in a statement dated April 16, 1992 regarding a notice of reason for refusal to the corresponding US application (USSN 07 / 526,726), Applicant states that "Finally, Applicants wo
uld like to point out that according to the invent
ion, a suspension is made and not a solution.As
olution would have lead to a too porous network no
t amenable to a solid form extrudable through a pa
(Finally, the applicant proposes that in the present invention, the solution
Instead, I would like to point out that a suspension is being produced . In a solution, a too porous network is formed, and what is formed by the cells is unlikely to be solid. ) ". In this respect, the present invention is completely different from the present invention in which a preferable rapidly dissolving lyophilized preparation in the oral cavity cannot be produced unless the aqueous solution is directly lyophilized. Furthermore, even if the invention according to the prior art is applied to loxoprofen, air is inevitable due to forced filling with a clay-like paste, resulting in non-uniform drug content, uneven shape, and uneven hardness. Uniformity and the like were generated, and the practicality was poor.

[0006]

DISCLOSURE OF THE INVENTION The present invention relates to a patient (especially elderly or infant) who has difficulty in swallowing an existing loxoprofen preparation which is taken with water or the like, or who has difficulty in swallowing it.
Provides a dosage form suitable for

The present inventors have conducted intensive studies over many years on a formulation of loxoprofen and / or a pharmacologically acceptable salt thereof, which has a rapid solubility in the oral cavity, and as a result, a known formulation has been obtained. Have found that a novel preparation having a different composition has excellent oral rapid solubility and an excellent method for producing the preparation, and have completed the present invention.

Yet another object of the present invention is to use loxoprofen and / or a pharmaceutically acceptable salt thereof for producing the preparation.

[0009]

The novel orally soluble preparation of the present invention contains loxoprofen and / or a pharmacologically acceptable salt thereof, cyclodextrin and a binder; loxoprofen and / or a pharmacologically acceptable salt thereof. Contains an acceptable salt, β-cyclodextrin and a binder;
Or, containing loxoprofen sodium and / or a hydrate thereof, β-cyclodextrin and a binder, and loxoprofen and / or a pharmaceutically acceptable salt thereof,
-An aqueous solution obtained by adding cyclodextrin and a binder is produced by freeze-drying, or loxoprofen sodium and / or a hydrate thereof contains β-
It is produced by freeze-drying an aqueous solution obtained by adding cyclodextrin and a binder. It should be noted that these oral fast-dissolving preparations can further contain one or more sweeteners, flavors, flavors, coloring agents, excipients and / or stabilizers. The weight ratio to cyclodextrin is 30 to 80% and / or the ratio between the weight of the clathrate and the dry weight of the lyophilized product is 60 to 95%.

[0010] On the other hand, the method for producing a novel oral fast-dissolving preparation of the present invention comprises the steps of: An aqueous solution obtained by adding β-cyclodextrin and a binder to loxoprofen and / or a pharmacologically acceptable salt thereof, and freeze-drying; or
Loxoprofen sodium and / or its hydrate,
The aqueous solution obtained by adding β-cyclodextrin and a binder is freeze-dried, and further contains one or more sweeteners, flavors, flavors, coloring agents, excipients and / or stabilizers. Preferably, the active substance β-
The weight ratio to cyclodextrin is 30 to 80% and / or the ratio between the weight of the clathrate and the dry weight of the lyophilized product is 60 to 95%.

Furthermore, the novel method of use of the present invention relates to a method for preparing a rapidly dissolving oral preparation, which comprises loxoprofen and / or loxoprofen.
Or use of a pharmacologically acceptable salt thereof, or use of loxoprofen sodium and / or a hydrate thereof for producing an oral rapidly dissolving preparation, preferably the oral rapid dissolving preparation. Is a rapidly dissolving oral preparation in which the weight ratio of the active substance to β-cyclodextrin is 30 to 80%, and / or the ratio of the weight of the clathrate to the dry weight of the lyophilized product is 60 to 80% It is a 95% oral fast-dissolving preparation.

In the above, "loxoprofen" refers to 2- [4- (2-oxocyclopentan-1-ylmethyl) phenyl] propionic acid.

The amount used depends on the symptoms, age, administration method and the like.
Body weight (preferably 10 mg / kg body weight), with an upper limit of 2
00 mg / kg body weight (preferably 150 mg / kg body weight)
It is desirable to administer once or several times a day depending on the symptoms.

Preferably, the weight ratio of “loxoprofen” to β-cyclodextrin is 30 to 8
0%.

"Pharmacologically acceptable salt" means "loxoprofen" because it can be converted into a salt, and such a salt is preferably a sodium salt, a potassium salt, a lithium salt. Alkali metal salts such as salts,
Metal salts such as alkaline earth metal salts such as calcium salts and magnesium salts, aluminum salts, iron salts, zinc salts, copper salts, nickel salts, and cobalt salts; inorganic salts such as ammonium salts, t-octylamine salts; Dibenzylamine salt, morpholine salt, glucosamine salt, phenylglycine alkyl ester salt, ethylenediamine salt, N-methylglucamine salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt, N, N′-dibenzylethylenediamine salt, Examples thereof include amine salts such as organic salts such as chloroprocaine salt, procaine salt, diethanolamine salt, N-benzyl-phenethylamine salt, piperazine salt, tetramethylammonium salt and tris (hydroxymethyl) aminomethane salt. still,
"Loxoprofen and pharmacologically acceptable salts thereof"
When left in the air, water may be absorbed, adsorbed water may be formed, or a hydrate may be formed. Such salts are also included in the definition.

"Cyclodextrin derivative" refers to α-
Cyclodextrin; β-cyclodextrin; γ-cyclodextrin; and hydroxypropyl-β-cyclodextrin, dimethyl-β-cyclodextrin, trimethyl-β-cyclodextrin, glycosyl-β-cyclodextrin, maltosyl-β-cyclodextrin And modified β-cyclodextrins, such as sulfated-β-cyclodextrin.

The amount of the "cyclodextrin derivative" to be added is preferably in a molar ratio to the active substance of 0.1 to 0.1.
2.0, and more preferably 0.5 to 1.5. Also, the ratio of the weight of the inclusion compound of the "cyclodextrin derivative" to the dry weight of the freeze-dried product is most preferably 60 to 95%.

The "binder" is essential for producing the structure of the preparation of the present invention, and is added for imparting favorable elasticity to the freeze-dried cake in handling the preparation. For example, oxides such as magnesium oxide; carbonates such as calcium carbonate; phosphates such as tricalcium phosphate; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate and magnesium metasilicate aluminate; Such as sulfates; crystalline cellulose, carboxymethylcellulose, low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium,
Cellulose derivatives such as internally crosslinked sodium carboxymethylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, carboxymethylcellulose; polypeptides such as gelatin; natural resins such as gum arabic and gum tragacanth; synthetics such as glycosyl gluten, xanthan gum Semi-synthetic resin; corn starch, potato starch, α
Polysaccharides such as starch, carboxymethyl starch, dextrin, dextran; alginates such as alginate; pectinates; water-dispersible starch derivatives; colloidal silica; bentonite; pullulan; polyvinyl alcohol; polyvinyl pyrrolidone; Polyethylene glycol; agar; hydrolysis products thereof and mixtures thereof, preferably polypeptides and agar, and the added amount is 1 to 5% (weight / volume), preferably 2 ４4% (weight / volume).

"Loxoprofen sodium" refers to 2
Refers to the sodium salt of-[4- (2-oxocyclopentan-1-ylmethyl) phenyl] propionic acid.

The amount used depends on the condition, age, administration method, etc., but for example, the lower limit is 5 mg / kg per dose.
Body weight (preferably 10 mg / kg body weight), with an upper limit of 2
00 mg / kg body weight (preferably 150 mg / kg body weight)
It is desirable to administer once or several times a day depending on the symptoms.

[0021] Preferably, the weight ratio of "loxoprofen sodium" to "cyclodextrin derivative" is 30 to 80%.

The term "hydrate thereof" means that "loxoprofen sodium" absorbs water when left in the air, and may adsorb water or form a hydrate. Salt.

The term “freeze-drying” is not particularly limited as long as it is a normal freeze-drying, and the freeze-drying involves adding a porous structure capable of rapidly disintegrating in water or directly in saliva to a preparation. Granted to

The "sweetener" is not particularly limited as long as it is a compound that usually produces sweetness. For example, mannitol, lactose, xylose, xylitol, glycol, sorbitol, glucose, maltodextrin, sucrose, maltose, mannitol And saccharides such as sorbitol, galactose and sucrose; aspartame and saccharin sodium.

The "flavoring agent" is not particularly limited as long as it is a compound usually used for improving the taste in the food or pharmaceutical industry. For example, citric acid, ascorbic acid,
Tartaric acid and the like can be mentioned.

The “flavor” is not particularly limited as long as it is a compound that is usually used for giving a smell in the food or pharmaceutical industry, and examples thereof include orange oil.

The "colorant" is not particularly limited as long as it is a compound which is usually used for coloring in the food or pharmaceutical industry, and for example, edible yellow No. 5 can be mentioned.

These sweeteners, flavors, coloring agents, etc.
Since it does not affect the rapid dissolution property in the oral cavity, which is a feature of the present preparation, but is intended to suppress discomfort to the preparation at the time of administration, an appropriate amount may be added.

The "excipient" is not particularly limited as long as it is a compound usually used in the pharmaceutical industry to adjust the form of a preparation. Examples thereof include the above-mentioned sugars; corn starch, potato starch, α-starch, dextrin Starch derivatives such as carboxymethyl starch; and silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate and magnesium metasilicate aluminate; phosphates such as calcium phosphate; carbonates such as calcium carbonate; calcium sulfate Inorganic excipients such as sulfates; and chemically modified starch and cellulose such as croscarmellose sodium, sodium carboxymethyl starch, and cross-linked polyvinyl pyrrolidone.

The "stabilizer" is not particularly limited as long as it is a compound usually used for stabilizing a preparation in the food or pharmaceutical industry. For example, paraoxybenzoic acid esters such as methylparaben and propylparaben Kind;
Alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol;
Thimerosal; dehydroacetic acid; and sorbic acid.

[0031]

BEST MODE FOR CARRYING OUT THE INVENTION The rapidly soluble oral preparation of the present invention can be produced by the method described below.

For example, an appropriate amount (for example, a preparation liquid comprising a unit formulation) is added to a column-shaped depression formed on a sheet.
(0.5 mL, 1.0 mL), freeze it, place it on a cooled lyophilization shelf and dry. Next, the freeze-dried sheet is taken out of the decompression chamber, and a metal foil (for example, aluminum foil or the like) is adhered to the sheet around the depression (for example, adhered with a sealed heat-sensitive adhesive or the like),
Then, the sheet can be manufactured by cutting the sheet appropriately (for example, when one sheet is divided into six pieces, each piece includes six depressions).

Here, the aqueous solution containing the clathrate to be lyophilized can be prepared at a temperature of 5 ° C. to 80 ° C., but is generally prepared at room temperature. The sheet to be used is not particularly limited as long as it is a metal or polymer compound that can form the sheet, but is preferably a sheet of a polymer compound such as a polypropylene sheet or an aluminum sheet. Metal sheet.

The column-shaped depression is not particularly limited as long as it has an appropriate number on one sheet. For example, there may be mentioned one in which 36 depressions are formed on one sheet. In addition, the size of each hollow is not particularly limited as long as it can produce a composition having a size that can be used as a drug, but, for example, the diameter is 1.5 cm,
One having a depth of 0.5 cm can be mentioned.

The drying temperature in the freeze-drying shelf is not particularly limited as long as the drug is stable.
-50 ° C to 80 ° C, more preferably -20 ° C to 50 ° C
C. and the drying time is preferably from 1 to 70 hours, more preferably from 10 to 40 hours. The change in the amount of the binder or water also means a change in the liquid amount of the unit formulation to be prepared, and thus a product having suitable physical properties (eg, solubility) can be produced.

[0036]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to Examples and Comparative Examples, but the scope of the present invention is not limited to these Examples.

[0037]

Embodiment 1 Sheet (for example, polypropylene sheet)
A column-shaped depression formed on the top (for example, the depression is 1
36 are formed on the sheet, and each depression has, for example, a diameter of 1.5 cm and a depth of 0.5 cm)
A preparation solution (1.0) comprising the following components (unit formulation)
mL). After freezing this sheet on dry ice, it is placed on a cooled freeze-drying shelf, and the shelf temperature is -20 ° C.
And dried for 30 hours. The sheet with the lyophilized preparation is removed from the vacuum chamber, a metal foil (eg, aluminum foil, etc.) is sealed to the sheet around the cavity with a heat-sensitive adhesive, and then the sheet is cut appropriately (eg, If one sheet is divided into six pieces, each piece contains six depressions.) Loxoprofen sodium 0.0681 g β-cyclodextrin 0.1500 g Gelatin 0.0400 g Distilled water Appropriate amount ───────────────────────── Total amount 1.0 mL Each hollow But loxoprofen sodium 68.1mg
, A good freeze-dried cake was obtained.

[0038]

Example 2 Example 2 was carried out in the same manner as in Example 1 except that a preparation solution comprising the following components (unit formulation) was used, and drying was performed at a shelf temperature of + 20 ° C. for 15 hours. Loxoprofen sodium 0.0681 g β-cyclodextrin 0.1500 g Gelatin 0.0200 g Distilled water qs ────────────────────────── total volume 1.0 mL each The hollow is loxoprofen sodium 68.1mg
, A good freeze-dried cake was obtained.

[0039]

Example 3 An operation was carried out in the same manner as in Example 2, except that a preparation solution comprising the following components (unit formulation) was used. Loxoprofen sodium 0.0681 g β-cyclodextrin 0.1000 g Polyvinylpyrrolidone K-90 0.0150 g Aspartame 0.0010 g Distilled water qs ─────────────────────── ─── Total volume 0.5mL Each hollow is loxoprofen sodium 68.1mg
, A good freeze-dried cake was obtained.

[0040]

Example 4 An operation was carried out in the same manner as in Example 2 using a preparation solution comprising the following components (unit formulation). Loxoprofen sodium 0.0681 g β-cyclodextrin 0.1000 g Agar 0.0300 g Aspartame 0.0010 g Distilled water Appropriate amount ────────────────────────── Total amount 1.0 mL each cavity is 68.1 mg of loxoprofen sodium
, A good freeze-dried cake was obtained.

[0041]

Example 5 An operation was carried out in the same manner as in Example 2 except that a preparation solution comprising the following components (unit formulation) was used. Loxoprofen sodium 0.0681 g β-cyclodextrin 0.1000 g Hydroxypropylcellulose-L 0.0300 g D-mannitol 0.0300 g Distilled water qs ───────────────────── ────────────── Total volume 1.0mL Each hollow is loxoprofen sodium 68.1mg
, A good freeze-dried cake was obtained.

[0042]

Example 6 The operation was carried out in the same manner as in Example 2 except that a preparation solution comprising the following components (unit formulation) was used. Loxoprofen sodium 0.0681 g β-cyclodextrin 0.1500 g Gelatin 0.0300 g Hydroxypropyl methylcellulose 2910 0.0100 g Distilled water qs ──────────────────────── ─────────── Total volume 1.0mL Each hollow is loxoprofen sodium 68.1mg
, A good freeze-dried cake was obtained.

[0043]

Example 7 The operation was carried out in the same manner as in Example 2 using a preparation solution comprising the following components (unit formulation). Loxoprofen sodium 0.0681 g β-cyclodextrin 0.1000 g Hydroxypropyl methylcellulose 2910 0.0150 g Sucrose 0.0200 g Saccharin sodium 0.0010 g Distilled water Appropriate amount ──────────────────── ─────────────── Total volume 0.5mL Each hollow is loxoprofen sodium 68.1mg
, A good freeze-dried cake was obtained.

[0044]

Example 8 The same procedure as in Example 2 was carried out using a preparation solution comprising the following components (unit formulation). Loxoprofen sodium 0.0681 g β-cyclodextrin 0.2000 g gelatin 0.0200 g sucrose 0.0200 g distilled water qs ─────────────────────────── ─── Total volume 0.5mL Each hollow is loxoprofen sodium 68.1mg
, A good freeze-dried cake was obtained.

[0045]

Example 9 The operation was carried out in the same manner as in Example 2 except that a preparation solution comprising the following components (unit formulation) was used. Loxoprofen sodium 0.0681 g Hydroxypropyl-β-cyclodextrin 0.2000 g Gelatin 0.0200 g Sucrose 0.0200 g Distilled water qs ──────────────────────── ──────────── Total volume 0.5mL Each hollow is loxoprofen sodium 68.1mg
, A good freeze-dried cake was obtained.

[0046]

Example 10 The operation was carried out in the same manner as in Example 2 except that a preparation solution comprising the following components (unit formulation) was used. Loxoprofen sodium 0.0681 g β-cyclodextrin 0.2000 g Gelatin 0.0200 g Maltose 0.0200 g Orange oil 0.0010 g Edible yellow No. 5 0.0010 g Distilled water qs ─────────────── ─────────── Total volume 1.0mL Each hollow is loxoprofen sodium 68.1mg
, A good freeze-dried cake was obtained.

[0047]

Example 11 The same procedure as in Example 2 was carried out using a preparation solution comprising the following components (unit formulation). Loxoprofen sodium 0.0681 g Dimethyl-β-cyclodextrin 0.2000 g Gelatin 0.0200 g Maltose 0.0200 g Orange oil 0.0010 g Edible yellow No. 5 0.0010 g Distilled water qs ───────────── ─────────────────────── Total volume 1.0mL Each hollow is loxoprofen sodium 68.1mg
, A good freeze-dried cake was obtained.

[0048]

[Comparative Example 1] A column-shaped hollow formed on a sheet
Preparation liquid (0.5m) consisting of the following components (unit formulation)
L). The sheet was placed on a cooled freeze-drying shelf and dried at a shelf temperature of -20 ° C for 30 hours. Loxoprofen sodium 0.0681 g D-mannitol 0.0150 g gelatin 0.0200 g distilled water qs ───────────────────────── total volume 0.5 mL During the drying process, it was candy-like, and a good freeze-dried cake could not be obtained.

[0049]

[Comparative Example 2] In a column-shaped recess formed on a sheet,
Preparation liquid (0.5m) consisting of the following components (unit formulation)
L). The sheet was placed on a cooled freeze-drying shelf and dried at a shelf temperature of -20 ° C for 30 hours. Loxoprofen sodium 0.0681 g Dextrin 0.0150 g Gelatin 0.0200 g Distilled water Appropriate amount ───────────────────────── Total amount 0.5 mL Good freeze-dried cake Could not get.

[0050]

[Comparative Example 3] In a column-shaped hollow formed on a sheet,
Preparation liquid (1.0 m) consisting of the following components (unit formulation)
L). The sheet was placed on a cooled freeze-drying shelf and dried at a shelf temperature of -20 ° C for 30 hours. Loxoprofen sodium 0.0681 g D-mannitol 0.0300 g Gelatin 0.0400 g Distilled water Appropriate amount ───────────────────────── Total amount 1.0 mL Good freezing No dried cake could be obtained.

[0051]

[Effect] As described above, 68.1 mg of loxoprofen sodium dihydrate (6% as an anhydride) was administered per dose.
0 mg) (Comparative Example 1, Comparative Example 2 and Comparative Example 3), the frozen product exhibited a candy during the drying step, and showed good results. No lyophilized cake could be obtained.

On the other hand, in the Examples, the oral fast-dissolving preparation of the present invention could be produced by adding the cyclodextrin derivative to loxoprofen sodium.

The present preparation is a solid preparation prepared by freeze-drying an aqueous solution or suspension, and is porous. It is immediately dissolved by saliva in the oral cavity and can be taken without water. It has features that make it easy to do.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Yuka Takahashi 1-58, Hiromachi, Shinagawa-ku, Tokyo Sankyo Co., Ltd.

Claims (20)

[Claims] (1) A fast-dissolving oral preparation comprising loxoprofen and / or a pharmaceutically acceptable salt thereof, a cyclodextrin derivative and a binder. 2. A rapidly dissolving oral preparation containing loxoprofen and / or a pharmacologically acceptable salt thereof, β-cyclodextrin and a binder. 3. A fast-dissolving oral preparation containing sodium loxoprofen and / or its hydrate, β-cyclodextrin and a binder. 4. A rapidly soluble oral preparation prepared by freeze-drying an aqueous solution obtained by adding β-cyclodextrin and a binder to loxoprofen and / or a pharmacologically acceptable salt thereof. 5. A rapidly dissolving oral preparation produced by freeze-drying an aqueous solution obtained by adding β-cyclodextrin and a binder to loxoprofen sodium and / or a hydrate thereof. 6. The method according to claim 1, wherein
Further, a rapidly dissolving oral preparation containing one or more sweeteners, flavors, flavors, coloring agents, excipients and / or stabilizers. 7. The method according to claim 1, wherein
The weight ratio of active substance to β-cyclodextrin is 3
0-80% oral fast dissolving preparation. 8. The method according to claim 1, wherein
An oral fast dissolving formulation wherein the ratio of the weight of the clathrate to the dry weight of the lyophilized product is 60-95%. 9. An oral cavity characterized by freeze-drying an aqueous solution (completely dissolved) obtained by adding a cyclodextrin derivative and a binder to loxoprofen and / or a pharmacologically acceptable salt thereof. A method for producing an internally fast dissolving preparation. 10. An aqueous solution (completely dissolved) obtained by adding β-cyclodextrin and a binder to loxoprofen and / or a pharmaceutically acceptable salt thereof is freeze-dried. A method for producing a rapidly soluble oral preparation. 11. An oral solution characterized by freeze-drying an aqueous solution (completely dissolved) obtained by adding β-cyclodextrin and a binder to loxoprofen sodium and / or a hydrate thereof. A method for producing a rapidly soluble preparation. 12. The method according to claim 9 or 11, further comprising one or more sweeteners, flavors, flavors, coloring agents, excipients and / or stabilizers. 13. A method for producing a rapidly soluble oral preparation according to any one of claims 9 to 12, wherein the weight ratio of the active substance to β-cyclodextrin is 30 to 80%. 14. The method for producing a rapidly soluble oral preparation according to any one of claims 9 to 13, wherein the ratio of the weight of the clathrate compound to the dry weight of the freeze-dried product is 60 to 95%. 15. Use of loxoprofen and / or a pharmaceutically acceptable salt thereof for producing a rapidly soluble oral preparation. 16. The loxoprofen and / or a pharmaceutically acceptable salt thereof according to claim 15, wherein the oral fast-dissolving preparation is an oral rapid-dissolving preparation having a weight ratio of the active substance to β-cyclodextrin of 30 to 80%. Use of salt. 17. The rapidly soluble oral preparation according to claim 15 or 16, wherein the ratio of the weight of the clathrate compound to the dry weight of the freeze-dried product is 60 to 95%. , Loxoprofen and / or a pharmacologically acceptable salt thereof. 18. Use of loxoprofen sodium and / or a hydrate thereof for producing a rapidly soluble oral preparation. 19. The loxoprofen sodium and / or hydrate thereof according to claim 18, wherein the oral rapid dissolving preparation is an oral rapid dissolving preparation having a weight ratio of the active substance to β-cyclodextrin of 30 to 80%. Use of. 20. The rapid oral dissolving preparation according to claim 18 or 19, wherein the ratio of the weight of the clathrate compound to the dry weight of the freeze-dried product is 60 to 95%. Use of loxoprofen sodium and / or hydrates thereof.