WO2004012724A1 - Preparation anti-inflammatoire et analgesique destinee a une utilisation externe et possedant d'excellentes proprietes de penetration et de diffusion - Google Patents

Preparation anti-inflammatoire et analgesique destinee a une utilisation externe et possedant d'excellentes proprietes de penetration et de diffusion Download PDF

Info

Publication number
WO2004012724A1
WO2004012724A1 PCT/JP2003/009229 JP0309229W WO2004012724A1 WO 2004012724 A1 WO2004012724 A1 WO 2004012724A1 JP 0309229 W JP0309229 W JP 0309229W WO 2004012724 A1 WO2004012724 A1 WO 2004012724A1
Authority
WO
WIPO (PCT)
Prior art keywords
inflammatory
indomethacin
steroidal anti
external preparation
lidocaine
Prior art date
Application number
PCT/JP2003/009229
Other languages
English (en)
Japanese (ja)
Inventor
Hidetoshi Hamamoto
Masaki Ishibashi
Sueko Matsumura
Keiko Yamasaki
Hideakira Yokoyama
Akihiko Hirata
Takeru Fujii
Original Assignee
Medrx Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Medrx Co., Ltd. filed Critical Medrx Co., Ltd.
Priority to AU2003248088A priority Critical patent/AU2003248088A1/en
Publication of WO2004012724A1 publication Critical patent/WO2004012724A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to an external preparation having an anti-inflammatory and analgesic effect.
  • non-steroidal anti-inflammatory analgesics have been known as anti-inflammatory analgesics with relatively few side effects.
  • This non-steroidal anti-inflammatory analgesic is a prostaglandin involved in inflammation and pain by inhibiting cyclooxygenase, which catalyzes the first reaction of arachidonic acid cascade, a metabolic pathway that enhances pain. It has the effect of suppressing the production of gin.
  • prostaglandin since prostaglandin has unfavorable effects such as inflammation and pain, it exerts a variety of effects in vivo, so it is necessary to administer non-steroidal anti-inflammatory drugs to produce prostaglandins. Suppression as described above may cause serious side effects.
  • cyclooxygenase type I an isozyme of cyclooxygenase, is involved in gastric mucosal protection and renal function.If this is inhibited by non-steroidal anti-inflammatory analgesics, digestive disorder and renal function disorder Can occur.
  • non-steroidal anti-inflammatory analgesics have extremely poor percutaneous absorption, and the effect when administered as an external preparation may be extremely lower than when administered orally. Therefore, various techniques for improving the transdermal absorbability of non-steroidal anti-inflammatory drugs have been studied.
  • Japanese Patent Application Laid-Open No. 2001-265540 discloses an indameshin patch, which shows that the patch is excellent in percutaneous absorption and has no problem of skin irritation. Is described.
  • technologies that have been designed to improve the transdermal absorbability, and that the formulation has been designed from the viewpoint of the delivery of non-steroidal anti-inflammatory drugs to the blood through the skin.
  • transdermal absorbability studies using blood levels as the index are by no means satisfactory for evaluating the value of drug delivery systems for nonsteroidal anti-inflammatory drugs.
  • topical preparations containing non-steroidal anti-inflammatory analgesics are intended for local anti-inflammatory analgesia
  • the target of the analgesic is not the blood, but the tissue itself that is causing inflammation and pain Because.
  • conventional formulation design did not take into account the permeability and diffusivity of the deeper part of the dermis.
  • the diclofenac sodium-containing emulsified external preparation described in Japanese Patent Application Laid-Open No. 9-112452 tested not only the concentration of diclofenac sodium in plasma but also the concentration of diclofenac sodium in muscle tissue immediately below the drug-coated part. Have been. However, this concentration of drug in muscle is not at a satisfactory level, and no experiment has been performed from the viewpoint of drug diffusion in muscle tissue.
  • the patch of Japanese Patent Application Laid-Open No. 2001-265540 contains indomethacin, polyethylene glycol, a water-soluble polymer compound and a cross-linking agent.
  • the external preparation disclosed in Japanese Unexamined Patent Application Publication No. 9-124452 includes diclofenacnatrium, dialkyl ester of sulfonic acid, oleyl alcohol and polyhydric alcohol as constituents.
  • the percutaneous absorption of the drug is improved by using the skin absorption of a solvent, etc., but since this solvent etc. diffuses quickly in the tissue, the drug can be transported deeply. It is thought that it is difficult to reach non-steroidal anti-inflammatory analgesics to deep tissues because the solvent concentration cannot be maintained as high as possible.
  • the external anti-inflammatory analgesic composition described in Japanese Patent Application Laid-Open No. 2002-128689 contains a local anesthetic instead of a solvent together with a non-steroidal anti-inflammatory analgesic.
  • the gist is that.
  • only skin permeability is tested, and no consideration is given to permeability or diffusivity in tissues deeper than the skin.
  • only loxoprofen sodium was evaluated as a non-steroidal anti-inflammatory analgesic.
  • This sodium loxoprofen is an arylpropionic non-steroidal anti-inflammatory drug
  • the arylpropionate non-steroidal anti-inflammatory drug does not improve the permeability and diffusivity in tissues even in the presence of a local anesthetic. Hardly observed.
  • a non-steroidal anti-inflammatory drug cannot penetrate and diffuse deep into the skin, even if the preparation has high skin permeability, the drug must remain in the skin tissue and cause secondary damage .
  • Such secondary disorders may include skin irritation and slowed absorption efficiency. That is, it is considered that when the concentration of the nonsteroidal anti-inflammatory drug in the skin tissue increases, the concentration gradient with the drug existing on the skin surface decreases, and the absorption efficiency decreases. Therefore, even if the content of the non-steroidal anti-inflammatory drug in the external preparation is increased, the absorption amount does not increase and its effect does not increase, so that the concentration of the non-steroidal anti-inflammatory drug in the external preparation to date is at most 1 %.
  • various external preparations containing a nonsteroidal anti-inflammatory agent which have been known to improve skin permeability have been known.
  • the problem to be solved by the present invention is an external preparation containing a non-steroidal anti-inflammatory agent, which is not only stable and less irritating to the skin, but also has a high permeability to tissues deeper than the skin.
  • Another object of the present invention is to provide an anti-inflammatory and analgesic external preparation which has an excellent inflammability and diffusibility and can directly act on muscles and joint tissues having inflammation and pain. Disclosure of the invention
  • the present inventors have prepared various external preparations of a nonsteroidal anti-inflammatory drug, and have conducted intensive studies on their tissue permeability and diffusivity. As a result, they found that all the above-mentioned problems could be solved by selecting an aryl acetic acid-based non-steroidal anti-inflammatory agent and adding a local anesthetic to it for use as an external preparation, and completed the present invention. And Was.
  • the antiinflammatory and analgesic external preparation of the present invention is characterized by containing an aryl acetic acid nonsteroidal anti-inflammatory agent and a local anesthetic.
  • the content ratio of the aryl acetic acid non-steroidal anti-inflammatory agent and the local anesthetic is such that the ratio of the local anesthetic agent to 1 part by mass of the aryl acetic acid non-steroidal anti-inflammatory agent is 0.2 to 5 parts by mass. It is preferred to be parts by mass. This is because the effects of the present invention can be more reliably exerted by appropriately defining the content ratio of the arylacetic acid non-steroidal anti-inflammatory agent and the local anesthetic.
  • Lidocaine is preferred as the local anesthetic. This is because the effect is demonstrated by the examples described later.
  • indomethacin or diclofenac sodium is preferable. This is because it is not only a typical aryl acetic acid nonsteroidal anti-inflammatory drug, but its effect is demonstrated by the examples described later.
  • Indomethacin and diclofenac sodium have extremely poor solubility in the base for external preparations, but the addition of a local anesthetic such as lidocaine can improve the solubility and stability in external preparations. become.
  • the greatest feature of the external preparation according to the present invention is that, by incorporating a local anesthetic, the allylic acetic acid non-steroidal anti-inflammatory agent has extremely low permeability and diffusibility below the skin tissue after penetrating the skin. It is in an excellent point.
  • an allylacetic acid-based non-steroidal anti-inflammatory agent is selected and used in combination with a local anesthetic, the permeability and diffusion into deep tissues can be significantly improved. Completed the invention.
  • the external preparation of the present invention has excellent transdermal absorbability, improved absorption efficiency due to an increase in drug concentration, and improved skin irritant properties of aryl acetic acid nonsteroidal anti-inflammatory drugs. And its stability is good.
  • the external preparation according to the present invention is used as an antiphlogistic analgesic, but the use for treating chronic pain may be excluded.
  • the present inventors have separately filed an application for an external preparation for treating chronic pain.
  • the “aryl acetic acid non-steroidal anti-inflammatory agent” used in the present invention is a non-steroid anti-inflammatory agent which is substituted by an aryl group containing a heteroaryl group such as an aromatic hydrocarbon group and a quindole group.
  • Acetic acid in its structure, and the ⁇ -position of the acetic acid is a methylene group (that is, the acetic acid group in the structure is substituted only by the aryl group, and is substituted by another group such as a lower alkyl group).
  • aryl acetic acid non-steroidal anti-inflammatory agent examples include indole acetic acid compounds such as indomethacin; phenyl acetic acid compounds such as diclofenac, ibufenac, alclofenac, methiadic acid, and anfenac; Examples include non-steroidal anti-inflammatory agents such as pyrrole acetic acid such as tolmetin; and naphthyl acetic acid such as nabumetone and salts thereof, and it is preferable to use one or more of them.
  • indomeicine or diclofenac sodium is particularly preferred.
  • indomethacin has poor transdermal absorbability when not dissolved in a base, but has poor stability in a dissolved state.However, if the constitution of the present invention is adopted, these problems are also solved. Can be solved.
  • the “local anesthetic” used in the present invention is not particularly limited as long as it has been conventionally used as a local anesthetic for medical use.
  • lidocaine, tetracaine, proforce, jib force, benzocaine, Bupiva force in, Mepiva force in and These salts can be mentioned, and it is preferable to use one or more of these salts.
  • lidocaine is particularly preferred. This is because the examples described later demonstrate that excellent effects can be exhibited.
  • the “local anesthetic” used preferably has a cationic group such as an amino group.
  • the cation group and the carboxyl group in the acetic acid structure of the aryl acetic acid nonsteroidal anti-inflammatory drug are ion-associated, so that each ion group is coated with a hydrophobic part to improve the pharmacokinetics, solubilization, transdermal This is because absorption and skin irritation are considered to be improved.
  • a local anesthetic when these local anesthetics are dissolved in a dissolving agent together with diclofenac sodium, they become soluble in solvents, such as esters, which were difficult to dissolve when diclofenac sodium alone is used. Thus, a better preparation can be prepared.
  • heating and mixing diclofenac sodium with these topical anesthetics also forms an oily component, and can be formulated without a dissolving agent. That is, in the present invention, a local anesthetic can be used not only for reducing skin irritation but also as a solubilizing agent or a solubilizing agent for aryl acetic acid nonsteroidal anti-inflammatory agents.
  • the percutaneous absorbability of the arylacetic acid-based non-steroidal anti-inflammatory drug can be improved by including these local anesthetics.
  • the content of the local anesthetic is 0.2 to 5 parts by mass (preferably 0.5 to 3 parts by mass) with respect to 1 part by mass of the aryl acetic acid non-steroidal anti-inflammatory agent, the above effect is particularly obtained. Is high.
  • the amount of the aryl acetic acid non-steroidal anti-inflammatory agent to be added to the external preparation of the present invention is preferably from 0.3 to 50% by mass, more preferably from 1 to 50% by mass, based on the whole external preparation. If the amount is less than 0.3% by mass, the analgesic effect may be insufficient, and if it exceeds 50% by mass, side effects tend to become strong.
  • the amount of the local anesthetic compounded in the external preparation of the present invention is preferably 0.1 to 50% by mass, more preferably 1 to 50% by mass, based on the whole external preparation. If the amount is less than 1% by mass, the analgesic effect may be insufficient, and if the amount is more than 50% by mass, side effects may increase.
  • Salts of local anesthetics that can be used as the active ingredient of the present invention include, for example, hydrofluoride, hydrochloride, hydrobromide, hydroiodide, etc .; Inorganic acid salts such as salts, perchlorates, sulfates and phosphates; salts of lower alkanesulfonic acids such as methanesulfonate, trifluoromethanesulfonate and ethanesulfonate; benzenesulfonate; -Aryl sulfonates such as toluenesulfonate; amino acid salts such as ordinate and glutamate; and carboxylate salts such as fumaric acid, succinic acid, cunic acid, tartaric acid, oxalic acid and maleic acid Can be mentioned.
  • the hydrochloride can be most preferably used.
  • Examples of the dosage form of the external preparation according to the present invention include ointments, lotions, aerosols, plasters, aqueous cataplasms and the like. There is no particular limitation.
  • the external preparation of the present invention may contain, if necessary, excipients (eg, sugars such as sucrose; starch derivatives such as dextrin; cellulose derivatives such as carmellose sodium; water-soluble polymers such as xanthan gum). , Coloring agents, lubricants (eg, metal stearate such as calcium stearate and magnesium stearate; lauryl sulfate such as sodium lauryl sulfate and magnesium lauryl sulfate; starch derivatives in the above-mentioned excipients, etc.
  • excipients eg, sugars such as sucrose; starch derivatives such as dextrin; cellulose derivatives such as carmellose sodium; water-soluble polymers such as xanthan gum.
  • excipients eg, sugars such as sucrose; starch derivatives such as dextrin; cellulose derivatives such as carmellose sodium; water-soluble polymers such as xanthan gum.
  • Binders eg, excipients and macrogol mentioned above
  • emulsifiers emulsifiers
  • thickeners wetting agents (eg, glycerin), stabilizers (eg, parahydroxybenzoic acid such as methylparaben, propylparaben)
  • Esters such as chlorobutanol, benzyl alcohol and phenylethyl alcohol Alcohols; benzalkonium chloride; phenols such as phenol and cresol; thimerosal; acetic anhydride; sorbic acid, etc.), preservatives, solvents (eg, water, ethanol, glycerin, etc.), solubilizers, suspensions
  • An agent eg, sodium carmellose
  • a buffer eg, a pH adjuster, a base (eg, polyethylene glycol, crotamiton, getyl sebacate, petrolatum, etc.) and the like can be blended in usual amounts.
  • a base
  • the amount of the external preparation according to the present invention varies depending on the type of the active ingredient contained, the condition and age of the patient, etc., but it is generally preferable to apply the composition to an adult once to several times a day. . More preferably, it is applied once or twice a day, but the number of administrations may be increased depending on the symptoms.
  • Figure 1 Graph showing the permeation and diffusion properties of a test solution containing indomethacin.
  • Fig. 2 Graph showing the permeation and diffusivity of a test solution containing indomethacin.
  • FIG. 3 Graph showing permeation and diffusivity of a test solution containing ketoprofen.
  • Fig. 7 Graph showing the penetration and diffusion of fenacnadium at the mouth of the jig.
  • FIG. 8 Graph showing permeation and diffusion of fenacnadium.
  • Figure 1 shows the permeation and diffusion properties of test solutions No. 1, 4 (concentration 1%), 2, 5 (5%), 3, 6 (10%) containing indomethacin using polyethylene glycol as a base. This is a graph, and is a superimposed bar graph in which the concentrations of indomethacin in fractions 2, 3, and 4 are overlaid. Since fraction 1 is the part that directly touches the test solution, no measurement was performed.
  • Figure 2 is a graph showing the permeation and diffusion properties of test solutions No. 7, 10 (1%), 8, 11 (5%), 9, 12 (10%) containing indomethacin using crotamiton as the base material. Yes, a multi-layered bar graph similar to Figure 1.
  • test solutions Nos. 13 to 18 containing ketoprofen or loxoprofen sodium, which is an arylpropionic non-steroidal anti-inflammatory drug were prepared.
  • FIG. 3 is a graph for comparing the permeation and diffusion properties of a test solution containing lidocaine with and without lidocaine in a test solution using arylpropionic acid-based ketoprofen as a nonsteroidal anti-inflammatory agent.
  • Fig. 4 is a graph showing the osmotic diffusivity of test solutions Nos. 15 and 16 containing loxoprofen sodium.
  • Fig. 5 is also a graph showing the permeation and diffusion properties of Test Solutions Nos. 17 and 18 containing loxoprofen sodium, showing the effect of adding lidocaine hydrochloride. These results also did not show any effect of improving loxoprofen sodium permeability. Therefore, the effect of adding lidocaine, a local anesthetic, on the permeation and diffusion of nonsteroidal anti-inflammatory drugs is unique to aryl acetic acid-based drugs, and even if they are structurally similar, It was clarified that propionic acid was not found at all. (Example 2)
  • test solutions Nos. 19 to 22 containing diclofenac sodium, which is an arylacetic acid non-steroidal anti-inflammatory drug, were prepared.
  • a gauze was applied to a 9 cm-diameter dish, and 10 g of the test solution No. 3, 6, 19 to 22 was added to moisten the gauze.
  • FIG. 6 is a graph showing the concentration of indomethacin in the fractions 1 to 2 cm and 2 to 3 cm of the test solutions 3 and 6 from the left.
  • the fraction of 0 to 1 cm was excluded because it was the part that was in direct contact with the test solution.
  • Figure 7 is a graph showing the concentration of diclofenac sodium in fractions 1-2 cm and 2-3 cm in test solutions 19 and 20 from the left.
  • FIG. 8 is a graph showing the concentration of diclofenac sodium in fractions 1 to 2 cm and 2 to 3 cm of the test solutions 21 and 22 from the left.
  • test agent containing loxoprofen sodium No. 15 to 18 was tested for the osmotic diffusivity in muscle tissue in the same manner as in Example 2 above. The results are shown in FIGS. 9 and 10.
  • FIG. 9 is a graph showing loxoprofen sodium concentrations of the fractions 1 to 2 cm and 2 to 3 cm of the test solutions 15 and 16 from the left.
  • FIG. 10 is a graph showing the concentrations of sodium oxofen and phen sodium in the fractions 1-2 cm and 2-3 cm of the test solutions 17 and 18 from the left.
  • indomethacin and lidocaine were heated and mixed to form an oily substance. Jetyl sebacate, a preservative and perserin were mixed.
  • a film-forming ointment was prepared by the usual production method at the following compounding ratio (total amount: 100).
  • a film-forming ointment was prepared by the usual production method at the following compounding ratio (total amount: 100).
  • lg was applied to an area of about 2.5 cm 2 inside the upper arm of six subjects, covered with gauze, and after 24 hours, the ointment was wiped off. The wiped ointment was collected, and the drug absorption rate was calculated by measuring the drug concentration. The drug concentration is measured by extracting the collected ointment or film-forming ointment with methanol and analyzing it by high performance liquid chromatography. Done. Table 8 shows the results.
  • Comparative Formulation Example No. 28 which is an ointment containing no local anesthetic
  • Comparative Formulation Example No. 29 had an absorption rate of 2.1%. Only yields are shown. This is because the indomethacin content of No. 28 is 1%, while the indomethacin content of No. 29 is 10%. It is considered that absorption slowed down.
  • the ointments of Formulation Examples Nos. 23 to 25 according to the present invention have indomethacin concentrations of 1, 5, and 10%, respectively, but exhibit an absorption rate of 10% or more regardless of such concentrations. This is probably because lidocaine, which is a local anesthetic, enhances the infiltration and diffusion of indomethacin into tissues, and does not stay immediately below the application part, but is constantly absorbed.
  • the permeation and diffusion of the aryl acetic acid non-steroidal anti-inflammatory drug in the tissue is significantly improved by the addition of the local anesthetic, and the excessive increase in drug concentration immediately below the administration site is suppressed. Has been proved to be improved.
  • Formulation Example No. 23 to 25 ointment and Formulation Example No. 26, 27 film-forming ointment were applied to 6 subjects in the same manner as in Test Example 1 and covered with gauze. After an hour, the ointment was wiped off. After that, skin irritation was observed at the applied part at 1, 24, and 48 hours. No skin irritation was judged as “one”, weak skin irritation was judged as “soil”, and skin irritation was judged as “+”. Table 9 shows the results. Table 9
  • the numbers in the table indicate the number of subjects included in each category.
  • Ointments containing diclofenac sodium (No. 32) and plasters (No. 33) were prepared according to the formulation in Table 10.
  • diclofenac sodium and lidocaine were heated and mixed to form an oil, and then the preservative and plastibase were mixed.
  • a mixer as a mixer, and heat and mix butylhydroxytoluene, styrene-isoprene-styrene block copolymer, alicyclic saturated hydrocarbon resin, polybutene and liquid paraffin at 120-160 ° C.
  • diclofenac sodium, lidocaine hydrochloride and a solution prepared by dissolving lidocaine in glycol salicylate and isopropyl myristate were added and mixed, spread directly on a polyester cloth and cut into a desired size to prepare a plaster.
  • the external preparation containing diclofenac sodium and a local anesthetic has improved low solubility in the external preparation composition of diclofenac sodium and has no precipitation during storage, and is stable. It was confirmed that.
  • a film-forming ointment was prepared according to the following formulation. Table 1 2
  • a plaster was prepared according to the following formulation by a solvent method using a toluene derivative as a solvent. Table 13
  • the anti-inflammatory and pain external preparation containing the aryl acetic acid non-steroidal anti-inflammatory agent according to the present invention not only has excellent skin absorbability, but also has significantly improved permeability and diffusivity in tissues thereafter. .
  • the slow absorption of the drug is suppressed, so that even if a relatively large amount of an aryl acetic acid-based non-steroidal anti-inflammatory agent is added to the preparation, the effect can be exhibited as it is.
  • the skin irritation of the arylacetic acid non-steroidal anti-inflammatory drug is also reduced.
  • the anti-inflammatory analgesic external preparation of the present invention is extremely excellent as an anti-inflammatory analgesic.

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une préparation externe renfermant un agent anti-inflammatoire non stéroïdal à stabilité élevée, irritant peu la peau, possédant d'excellentes propriétés de pénétration et de diffusion dans un tissu situé au-dessous de la peau et pouvant, par conséquent, agir directement sur le tissu d'un muscle ou d'une articulation enflammé ou endolori. Dans cette préparation anti-inflammatoire et analgésique, un composé d'acide arylacétique est utilisé comme agent non stéroïdal et un anesthésique local est également ajouté, de manière à obtenir ainsi les propriétés susmentionnées.
PCT/JP2003/009229 2002-08-02 2003-07-22 Preparation anti-inflammatoire et analgesique destinee a une utilisation externe et possedant d'excellentes proprietes de penetration et de diffusion WO2004012724A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003248088A AU2003248088A1 (en) 2002-08-02 2003-07-22 Antiinflammatory and analgesic preparation for external use having excellent penetration and diffusion properties

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2002-226464 2002-08-02
JP2002226464 2002-08-02
JP2003060126 2003-03-06
JP2003-60126 2003-03-06

Publications (1)

Publication Number Publication Date
WO2004012724A1 true WO2004012724A1 (fr) 2004-02-12

Family

ID=31497625

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2003/009229 WO2004012724A1 (fr) 2002-08-02 2003-07-22 Preparation anti-inflammatoire et analgesique destinee a une utilisation externe et possedant d'excellentes proprietes de penetration et de diffusion

Country Status (2)

Country Link
AU (1) AU2003248088A1 (fr)
WO (1) WO2004012724A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001047559A1 (fr) * 1999-12-27 2001-07-05 Teikoku Seiyaku Co., Ltd Pastilles a usage externe
JP2002128699A (ja) * 2000-10-26 2002-05-09 Sankyo Co Ltd 消炎鎮痛外用剤組成物

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001047559A1 (fr) * 1999-12-27 2001-07-05 Teikoku Seiyaku Co., Ltd Pastilles a usage externe
JP2002128699A (ja) * 2000-10-26 2002-05-09 Sankyo Co Ltd 消炎鎮痛外用剤組成物

Also Published As

Publication number Publication date
AU2003248088A1 (en) 2004-02-23

Similar Documents

Publication Publication Date Title
US5093133A (en) Method for percutaneous delivery of ibuprofen using hydroalcoholic gel
US5807568A (en) Enhanced delivery of topical compositions containing flurbiprofen
KR101517494B1 (ko) 디클로페낙의 신규한 비수용성 국소 용액 및 이를 제조하는 과정
US5854281A (en) Preparation for percutaneous absorption
JPH03193728A (ja) 消炎鎮痛貼付剤
JP4627945B2 (ja) 経皮吸収製剤
US7655687B2 (en) Anti-inflammatory analgesic for external use
JP4807721B2 (ja) 消炎鎮痛外用剤
JP4541686B2 (ja) 非ステロイド系消炎鎮痛剤を含有するテープ剤
US20070254887A1 (en) Pharmaceutical Composition for Transdermal Administration of Perospirone
JP2002516879A (ja) 非ステロイド性消炎鎮痛剤の経皮投与用組成物
KR100332210B1 (ko) 소염진통성분을 포함하는 경피투여 조성물 및 매트릭스형경피투여 패취제
JP2004323502A (ja) 浸透拡散性に優れた消炎鎮痛外用剤
JP2003335663A (ja) 消炎鎮痛外用剤
JP2005145932A (ja) 消炎鎮痛外用剤
WO2004012724A1 (fr) Preparation anti-inflammatoire et analgesique destinee a une utilisation externe et possedant d'excellentes proprietes de penetration et de diffusion
KR100552649B1 (ko) 펠비낙 함유 소염진통용 플라스터
KR20070059758A (ko) 비스테로이드성 항염증제와 국소마취제를 포함하는 경피투여 조성물
JP6512905B2 (ja) フェンタニル含有貼付剤
JP3472359B2 (ja) チミペロン含有貼付剤
JP2004123632A (ja) 消炎鎮痛外用剤
JP4694131B2 (ja) 消炎鎮痛外用剤
JP2005213192A (ja) 消炎鎮痛外用剤
KR20210133821A (ko) 피록시캄을 함유하는 경피 흡수 제제
JPH0930972A (ja) オキサトミド含有経皮適用製剤

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase