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WO2013080271A1 - Analgésique - Google Patents

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Publication number
WO2013080271A1
WO2013080271A1 PCT/JP2011/077348 JP2011077348W WO2013080271A1 WO 2013080271 A1 WO2013080271 A1 WO 2013080271A1 JP 2011077348 W JP2011077348 W JP 2011077348W WO 2013080271 A1 WO2013080271 A1 WO 2013080271A1
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WO
WIPO (PCT)
Prior art keywords
release layer
buprenorphine
pharmaceutically acceptable
acceptable salt
pain associated
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP2011/077348
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English (en)
Japanese (ja)
Inventor
拓司 福野
重松　紀仁
忠与 宮坂
隆雄 戸田
信吾 土居
祥一 川添
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fuso Pharmaceutical Industries Ltd
Toyobo Co Ltd
Original Assignee
Fuso Pharmaceutical Industries Ltd
Toyobo 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 Fuso Pharmaceutical Industries Ltd, Toyobo Co Ltd filed Critical Fuso Pharmaceutical Industries Ltd
Priority to PCT/JP2011/077348 priority Critical patent/WO2013080271A1/fr
Publication of WO2013080271A1 publication Critical patent/WO2013080271A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids

Definitions

  • the present invention relates to a medicament for alleviating pain associated with disc herniation, pain associated with degenerative spondylosis, or pain associated with spinal stenosis, and a pain relieving method using the same. More specifically, the present invention reduces pain associated with herniated disc, pain associated with degenerative spondylosis, or pain associated with spinal canal stenosis, comprising buprenorphine or a pharmaceutically acceptable hydrochloride thereof as an active ingredient.
  • the present invention relates to an intraoral mucosa patch preparation and a pain relieving method using the same.
  • Buprenorphine N-cyclopropylmethyl-7 ⁇ - (S-1-hydroxy-1,2,2-trimethylpropyl) -6,14-endo-ethano-6,7,8,14-tetrahydronorolipabin
  • It is a derivative of thebaine and is a non-anesthetic analgesic with high fat solubility. It is known that buprenorphine has a powerful analgesic effect 20 to 30 times that of morphine and has few side effects such as mental disorders and respiratory depression. Therefore, it is used for pre-anesthetic medication, maintenance of anesthesia, postoperative pain and cancer pain.
  • Buprenorphine is mainly used as an injection and a suppository because its bioavailability by oral administration is as low as about 10%.
  • Development of sublingual tablets containing buprenorphine, percutaneous absorption preparations, oral mucosal patch preparations, and the like has been promoted from the viewpoint of improving bioavailability, handling, and sustainability.
  • Patent Document 1 (which is incorporated herein by reference) discloses a buprenorphine-containing oral mucosa patch preparation in which the blood concentration of buprenorphine is maintained within a certain therapeutically effective range for a certain period of time by a single administration. Has been.
  • Buprenorphine is mainly used as an analgesic for cancer pain, pain associated with myocardial infarction and postoperative pain.
  • Patent Document 2 (which is incorporated herein by reference) reports that buprenorphine is also effective for analgesia of neuralgia after herpes zoster.
  • an object of the present invention is to provide a pharmaceutical use or method for more effectively using buprenorphine or a pharmaceutically acceptable salt thereof.
  • the inventors of the present invention have conducted research day and night to solve the above problems, and surprisingly, buprenorphine, which has been conventionally used as an analgesic for cancer pain and pain after myocardial infarction, is a pain associated with disc herniation.
  • the present inventors have found that the present invention has a particularly excellent palliative effect on specific pains such as pain associated with degenerative spondylosis and pain associated with spinal stenosis. Based on such findings, the present inventors have conducted further studies, and as a result, by administering buprenorphine for a certain period of time, the specific pain is significantly higher than pain associated with other diseases. It was found to be relaxed. The present invention has been completed based on this finding.
  • Item 1 An immediate release layer containing buprenorphine or a pharmaceutically acceptable salt thereof as an active ingredient, and a sustained release layer containing buprenorphine or a pharmaceutically acceptable salt thereof as an active ingredient, A medicament for alleviating pain associated with disc herniation, pain associated with degenerative spondylosis, or pain associated with spinal stenosis, which is an oral mucosa patch form.
  • the sustained-release layer further contains (a) polyvinyl pyrrolidone or a pharmaceutically acceptable salt thereof, (b) polyacrylic acid or a pharmaceutically acceptable salt thereof, and (c) sodium bicarbonate.
  • Item 1 The medicine according to Item 1.
  • Item 4. The medicament according to Item 2 or 3, wherein the sustained-release layer contains 7 to 7.5 parts by weight of (c) with respect to 100 parts by weight of (b).
  • Item 5 The medicament according to any one of Items 1 to 4, wherein the immediate release layer contains polyvinylpyrrolidone or a pharmaceutically acceptable salt thereof.
  • Item 6 The medicament according to any one of Items 1 to 5, wherein the active ingredient contained in the immediate release layer and the sustained release layer is buprenorphine hydrochloride.
  • Item 7 An immediate release layer containing buprenorphine or a pharmaceutically acceptable salt thereof as an active ingredient, And a sustained-release layer containing buprenorphine or a pharmaceutically acceptable salt thereof as an active ingredient, And a medicament in the form of an oral mucosal patch is administered to a patient suffering from pain associated with disc herniation, pain associated with degenerative spondylosis, or pain associated with spinal stenosis.
  • Item 8 An immediate release layer containing buprenorphine or a pharmaceutically acceptable salt thereof as an active ingredient, And a sustained-release layer containing buprenorphine or a pharmaceutically acceptable salt thereof as an active ingredient, And a medicament in the form of an oral mucosal patch is administered to a patient suffering from pain associated with disc herniation, pain associated with degenerative spondylosis, or pain associated with spinal stenosis.
  • pain associated with disc herniation, degenerative spondylosis, or spinal stenosis can be more effectively alleviated.
  • FIG. 1 shows the alleviation of pain associated with degenerative spondylosis by the medicament of the present invention.
  • FIG. 2 shows the alleviation of pain associated with spinal stenosis by the medicament of the present invention.
  • FIG. 3 shows the effect of alleviating pain associated with disc herniation by the medicament of the present invention.
  • the medicament of the present invention contains buprenorphine or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the pharmaceutically acceptable salt of buprenorphine can be appropriately selected from the viewpoint of stability and the like, for example, inorganic salts such as hydrochloride, sulfate, phosphate and the like, and maleate and succinate. Organic acid salt etc. can be mentioned.
  • the active ingredient contained in the medicament of the present invention is a pharmaceutically acceptable salt of buprenorphine, more preferably buprenorphine hydrochloride.
  • the medicament of the present invention is an oral mucosa patch form having a sustained release layer and an immediate release layer.
  • Buprenorphine or a pharmaceutically acceptable salt thereof as an active ingredient is contained in both the sustained-release layer and the rapid-release layer.
  • Oral mucosa patch form means that the medicine has a shape suitable for sticking to the oral mucosa such as gums and maxilla, and buprenorphine which is an active ingredient or its pharmaceutically acceptable by sticking the medicine to the oral mucosa Means that it has a shape suitable to be released and absorbed through the oral mucosa into the blood vessels.
  • the sustained-release layer and the rapid-release layer are preferably applied more quickly than the active ingredient contained in the sustained-release layer by applying the medicament of the present invention to the oral mucosa.
  • the immediate release layer has a structure that disintegrates relatively quickly than the sustained release layer.
  • JP-A-8-291070 discloses a bilayer oral mucosal patch preparation for continuous release of buprenorphine or a pharmaceutically acceptable salt thereof.
  • WO2008 / 111647 also discloses a method for producing an oral mucosa patch preparation in which buprenorphine hydrochloride is uniformly dispersed in the preparation and the stability of buprenorphine hydrochloride is improved Is disclosed. Therefore, the medicament of the present invention can be produced according to these descriptions.
  • the sustained-release layer of the medicament of the present invention comprises (a) polyvinylpyrrolidone or a pharmaceutically acceptable salt thereof (hereinafter referred to as “(a) component” as appropriate), (b) polyacrylic acid or The pharmaceutically acceptable salt thereof (hereinafter referred to as “component (b)” as appropriate) and / or (c) sodium hydrogen carbonate (hereinafter referred to as “component (c)” where appropriate).
  • a sustained release action can be obtained by the binding property of polyvinylpyrrolidone or a pharmaceutically acceptable salt thereof and the adhesiveness of polyacrylic acid or a pharmaceutically acceptable salt thereof. Conceivable.
  • sodium bicarbonate is used to enable the continuous release of buprenorphine even in an acidic environment.
  • Formulated as a pH adjuster since the release of buprenorphine can be hindered by a decrease in the swelling ability of polyacrylic acid under acidic conditions, sodium bicarbonate is used to enable the continuous release of buprenorphine even in an acidic environment. Formulated as a pH adjuster.
  • Polyvinylpyrrolidone or a pharmaceutically acceptable salt thereof may be a polymer composed only of N-vinyl-2-pyrrolidone as a monomer, and does not interfere with the properties as a sustained-release layer or a rapid-release layer. As long as it is a copolymer containing other monomer components. Examples of other monomer components include polyvinyl alcohol, alginic acid, and pharmaceutically acceptable salts thereof. When such other monomer components are contained in polyvinyl pyrrolidone, the proportion is usually preferably 30 mol% or less.
  • the polyacrylic acid or a pharmaceutically acceptable salt thereof may be a homopolymer obtained by polymerizing only acrylic acid, but contains other monomer components as long as the properties required for the sustained-release layer are not disturbed. May be.
  • the proportion of the other components is preferably 30 mol% or less.
  • the pharmaceutically acceptable salt of polyvinylpyrrolidone or acrylic acid is not particularly limited as long as sustained release of buprenorphine or a pharmaceutically acceptable salt thereof from the sustained release layer is possible.
  • sodium salt And alkali metal salts such as potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, and ammonium salts.
  • the content of the component (a) and the component (b) in the sustained release layer is 80% or more when the total content of the component (a) and the component (b) is 100% of the mass of the entire sustained release layer. It is preferable.
  • the sustained-release layer can contain additives described later in addition to the component (a), the component (b), and the component (c).
  • the amount of component (c) in the sustained-release layer is not particularly limited as long as the pH in the sustained-release layer can be neutralized (for example, maintained at pH 6 to 8) in a neutral oral environment. However, it is preferably 7.0 to 7.5 parts by weight with respect to 100 parts by weight of the component (b) in the sustained release layer. If it is 7.0 parts by weight or more, the swelling ability of polyacrylic acid can be sufficiently ensured even in a neutral environment, and buprenorphine or a pharmaceutically acceptable salt thereof can be more reliably released. Can do. On the other hand, if it exceeds 7.5 parts by weight, the swelling of the carboxyvinyl polymer becomes too great, and the release of buprenorphine or a pharmaceutically acceptable salt thereof can be excessively fast.
  • the immediate release layer preferably contains polyvinylpyrrolidone or a pharmaceutically acceptable salt thereof in addition to the active ingredient.
  • the content of polyvinylpyrrolidone or a pharmaceutically acceptable salt thereof incorporated in the immediate release layer is not particularly limited, but the active ingredient is relatively fast with respect to the release rate of the active ingredient from the sustained release layer. From the viewpoint of releasing the amount, it is preferably 50% or less of the entire rapid release layer in terms of mass.
  • additives as described later can be appropriately blended in the immediate release layer.
  • the pharmaceutical of the present invention contains buprenorphine or a pharmaceutically acceptable salt thereof in an amount effective for alleviating pain associated with disc herniation, degenerative spondylosis or spinal stenosis.
  • the amount of the active ingredient in the medicine is usually 0.05 to 1.5 mg per product.
  • the content of the active ingredient per pharmaceutical agent of the present invention is preferably 0.1-1 mg, more preferably 0.3-0. .8 mg.
  • the blending ratio of the active ingredient in the sustained-release layer and the active ingredient in the immediate-release layer can be appropriately adjusted according to the required pain relieving action. For example, when the immediate effect of pain relief is required, a larger amount of the active ingredient can be blended in the immediate release layer than in the sustained release layer. On the other hand, when it is desired to maintain the blood concentration of the active ingredient at a certain effective value or more for a long period of time, many active ingredients can be added to the sustained-release layer.
  • the content of buprenorphine or a pharmaceutically acceptable salt thereof blended in the sustained release layer is 0.05 to 1.0 mg, preferably 0.07 to 0.7 mg.
  • the content of the active ingredient blended in the immediate release layer is usually 0.01 to 0.7 mg, preferably 0.03 to 0.5 mg.
  • the sustained-release layer and the rapid-release layer include excipients, binders, lubricants, coloring agents, flavoring agents, fragrances, surfactants, and sweeteners that are commonly used in the field of pharmaceutical preparations. , And additives such as preservatives can be blended.
  • excipients include starch, crystalline cellulose, lactose, anhydrous silicic acid, mannitol, talc, sorbitol, and anhydrous calcium phosphate.
  • binder include starch, dextrin, tragacanth, gelatin, hydroxypropylcellulose, sodium alginate and the like.
  • lubricant include magnesium stearate, talc, and stearic acid.
  • the colorant include blue No. 1, yellow No. 4, caramel, copper chlorophyllin sodium and titanium dioxide.
  • flavoring agent include menthol, peppermint oil, limonene, cineol, citric acid, malic acid, fumaric acid, tartaric acid, and various fragrances.
  • surfactant examples include various anionic surfactants, nonionic surfactants, amphoteric surfactants, and cationic surfactants.
  • sweetening agent examples include xylitol, erythritol, sodium saccharin, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, and perilartin.
  • preservative examples include p-hydroxybenzoate ester and sodium benzoate.
  • the medicament of the present invention is suitable for application to the oral mucosa, its shape and size are not particularly limited.
  • it can be a track field tablet or a round tablet.
  • the medicament of the present invention is in the form of a tablet having a two-layer structure, and the thickness thereof is usually 0.5 to 3 mm, preferably 1 to 2.5 mm.
  • the medicament of the present invention can be produced by a technique known in the art.
  • the medicament of the present invention is prepared by mixing each component of the sustained-release layer and each component of the rapid-release layer separately to prepare a granule, which is formed into a two-layer structure using a punch, a die, or a press. Can be manufactured by tableting. The following describes one preferred method for producing the medicament of the present invention.
  • Buprenorphine for example, buprenorphine hydrochloride
  • the 90% cumulative diameter of buprenorphine hydrochloride is preferably 160 ⁇ m or less, more preferably 100 ⁇ m or less, and still more preferably 90 ⁇ m or less.
  • the 50% cumulative diameter of buprenorphine hydrochloride is preferably 100 ⁇ m or less, more preferably 60 ⁇ m or less.
  • the 50% cumulative size of buprenorphine hydrochloride is preferably 10 ⁇ m or more.
  • the 90% cumulative diameter and 50% cumulative diameter of buprenorphine hydrochloride can be measured by conventional methods.
  • buprenorphine hydrochloride is dispersed in McIlvine buffer (pH 9.0) containing about 0.1% of a surfactant such as Triton X-100, and the volume-based particle size distribution of buprenorphine hydrochloride is measured with a particle size distribution meter. . From the measurement results obtained, assuming that the total volume is 100%, the volume is accumulated in order from the smallest particles, and the particle size of the particles when the cumulative volume reaches 50% of the total is taken as the 50% cumulative diameter. Similarly, the particle diameter when the cumulative volume is 90% is defined as 90% cumulative diameter.
  • the particle diameter can be adjusted according to a conventional method, for example, using a general pulverizer such as a hammer mill, and repeatedly performing pulverization and particle size distribution measurement until an appropriate particle diameter is obtained.
  • a general pulverizer such as a hammer mill
  • ⁇ Buprenorphine hydrochloride with adjusted particle size is mixed with other ingredients.
  • the blending components may be appropriately selected. However, since the rapid release layer disintegrates relatively quickly and releases buprenorphine hydrochloride, it is preferable to blend relatively many components used as an excipient or a disintegrant. For example, D-mannitol and / or talc are preferably blended. In addition, additives as described above can also be blended.
  • Mixing of buprenorphine hydrochloride and other components is preferably carried out dry without using water. This is because buprenorphine hydrochloride may become unstable when water is used. Mixing can be performed using a general mixer. The mixture is preferably adjusted in particle size by sieving, etc. in order to suppress adhesion between particles.
  • Granules are prepared using the mixture and an aqueous solution of polyvinylpyrrolidone as a binder.
  • Granules can be prepared under general conditions using a fluid bed granulator common in the pharmaceutical field.
  • the granules are thoroughly dried.
  • the drying conditions such as temperature and time are not particularly limited as long as each component does not deteriorate.
  • the obtained granules are preferably adjusted in particle size by sieving or the like.
  • Buprenorphine for example, buprenorphine hydrochloride
  • Buprenorphine for example, buprenorphine hydrochloride
  • the 90% cumulative diameter of buprenorphine hydrochloride compounded in the sustained release layer is preferably 160 ⁇ m or less, and more preferably 100 ⁇ m or less.
  • the 50% cumulative diameter of buprenorphine hydrochloride is the same as that of buprenorphine hydrochloride blended in the immediate release layer.
  • ⁇ Buprenorphine hydrochloride with adjusted particle size is mixed with other ingredients. Since the sustained release layer gradually disintegrates and releases buprenorphine hydrochloride continuously, as described above, (a) polyvinylpyrrolidone or a pharmaceutically acceptable salt thereof, (b) polyacrylic acid or a pharmaceutical thereof And (c) sodium hydrogen carbonate. In addition, the above-mentioned additives can be blended in the sustained release layer.
  • the mixing of each component can be performed with a general mixer.
  • the mixture is preferably adjusted in particle size.
  • the particle size adjustment is preferably performed by pulverization and sizing from the viewpoint of suppressing reduction of active ingredients and non-uniformity. Crushing and sizing is not mere sieving or the like but pulverizing the mixture with a power mill or the like and sizing while suppressing adhesion between particles.
  • Granules for sustained release layer are granulated from the above mixture.
  • Granules may be prepared by a conventional method, for example, by compressing the mixture.
  • the obtained granules are preferably sized, and pulverized sized.
  • the granule for immediate release layer and the granule for sustained release layer produced as described above are tableted using a tableting device to obtain a tablet having a two-layer structure.
  • the tableting device is not particularly limited as long as it can produce a bilayer tablet.
  • the tableting conditions can be adjusted from the tablet sample in consideration of the mass of the sustained-release layer and the quick-release layer, the hardness of the tablet, the thickness of the tablet, and the like.
  • the medicament of the present invention produced as described above is not only suppressed in the amount of buprenorphine hydrochloride in the production process but also excellent in storage stability. For example, even when stored for 6 months in a harsh environment of a temperature of 40 ° C. and a relative humidity of 75%, the amount of buprenorphine related substances is suppressed.
  • the method for alleviating each pain using the medicament of the present invention can be carried out by administering the medicament of the present invention to a patient suffering from pain associated with disc herniation, degenerative spondylosis, or spinal stenosis. it can. Since the medicament of the present invention is an oral mucosa patch form, it is administered by applying it to the oral mucosa (for example, the gums, the inside of the cheek).
  • the medicament of the present invention can be used preferably by sticking so that the sustained-release layer side is in contact with the oral mucosa.
  • the immediate release layer disintegrates to release buprenorphine
  • the sustained release layer gradually disintegrates to gradually release buprenorphine hydrochloride. Therefore, the medicament of the present invention can suppress a rapid increase in the blood concentration of buprenorphine compared to an injection or the like.
  • the use of the medicament of the present invention can relieve pain associated with disc herniation, degenerative spondylosis, or spinal stenosis continuously while suppressing the occurrence of side effects. Furthermore, the medicament of the present invention also contributes to providing more comfortable sleep for patients suffering from the various types of pain described above.
  • intervertebral disc herniation is a disease that often causes neuralgia due to compression of the spinal cord and nerve roots due to degeneration of the annulus fibrosus of the disc.
  • Degenerative spondylosis is a lesion caused by a degenerative change of the spinal column, often accompanied by nodal pain, back pain, or back pain.
  • spinal canal stenosis the spinal canal is congenitally narrowed or acquired narrowly, compressing nerves and causing pain from the waist to the thigh and calf.
  • the dosage and administration schedule of the medicament of the present invention can be appropriately adjusted in consideration of the severity of pain in the patient and the age, weight, sex, etc. of the patient.
  • a drug containing 0.1 to 1.0 mg of buprenorphine or a pharmaceutically acceptable salt thereof may be used once or twice a day to cause pain. Administration can be continued until some injury or symptom is improved.
  • the medicament of the present invention is preferably administered for 8 weeks or longer, more preferably 12 weeks or longer, and further preferably 16 weeks or longer.
  • the mixture was compressed by a roller compactor (Freund Sangyo, model: TF-MINI). Further, it was crushed with an oscillator (manufactured by Kikusui Seisakusho, model: 35C-2M). Further, the particles were sized with a power mill (Dalton, model: P-02S), and then sieved with a sieve having an opening of 500 ⁇ m. *
  • the ratio of polyvinylpyrrolidone to the total of polyvinylpyrrolidone and polyacrylic acid in the sustained-release layer is about 83.8% by mass, and the ratio of sodium hydrogen carbonate to polyacrylic acid in the sustained-release layer is about 7. It was 4% by mass.
  • the double-layered tablet for oral mucosal patch in which the blending amount of buprenorphine hydrochloride alone is doubled and the blending amount of buprenorphine hydrochloride in the immediate release layer and the sustained release layer is 0.2 mg and 0.4 mg, respectively.
  • these buprenorphine hydrochloride tablets are referred to as 0.3 mg tablets and 0.6 mg tablets, respectively.
  • Test Example Continuous Administration Test Asian patients from the age of 20 to 74 years who suffered from the following pain with which consent was obtained for this study were targeted for administration.
  • Patient group 66 patients suffering from pain associated with degenerative spondylosis 66 patients suffering from pain associated with spinal canal stenosis 67 patients suffering from pain associated with disc herniation 32 patients suffering from neuralgia after herpes zoster 146 patients with complex local pain 55 affected patients 29 patients with postoperative neuropathic pain 29 patients with post-lumbar pain syndrome 15
  • 0.3 mg tablets were administered to each subject once a day, and appropriately changed to 0.6 mg tablets while confirming the analgesic effect and safety so that the analgesic effect lasted for 24 hours.
  • the analgesic effect sustained for 24 hours was not obtained by administration of the 0.6 mg tablet or due to the occurrence of an adverse event, the 0.6 mg tablet was changed to the 0.3 mg tablet as necessary.
  • FIG. 1 shows a patient suffering from pain associated with osteoarthritis, a patient suffering from neuralgia after herpes zoster, a patient suffering from pain associated with complex local pain, a patient suffering from pain associated with postoperative neuropathy, and the lumbar spine Evaluation results from patients with postoperative pain syndrome are shown.
  • the pain associated with osteoarthritis was dramatically alleviated by administering the medicament of the present invention. This alleviating effect became more prominent by continuously administering the medicament of the present invention, and after 8 weeks from the start of administration, an even better alleviating effect than the effect on neuralgia after herpes zoster was obtained.
  • FIG. 2 shows a patient suffering from pain associated with spinal stenosis, a patient suffering from neuralgia after herpes zoster, a patient suffering from pain associated with complex local pain, a patient suffering from pain associated with postoperative neuropathy, and the lumbar spine Evaluation results from patients with postoperative pain syndrome are shown.
  • the pain associated with spinal stenosis was dramatically alleviated by administering the medicament of the present invention. This alleviating effect became more prominent by continuously administering the medicament of the present invention, and after 8 weeks from the start of administration, an even better alleviating effect than the effect on neuralgia after herpes zoster was obtained.
  • FIG. 3 shows a patient suffering from pain associated with herniated disc, a patient suffering from neuralgia after herpes zoster, a patient suffering from pain associated with complex local pain, a patient suffering from pain associated with postoperative neuropathy, and a post-lumbar surgery Evaluation results from patients with pain syndrome are shown.
  • the medicament of the present invention exhibits an excellent palliative action on pain associated with disc herniation. This alleviating effect is significantly better than the alleviating effect on neuralgia after herpes zoster.
  • the medicament of the present invention exhibits a particularly excellent palliative effect on pain associated with disc herniation, pain associated with degenerative spondylosis, or pain associated with spinal stenosis.
  • many patients suffering from pain due to disc herniation, pain associated with spondylosis, or pain associated with spinal stenosis can be improved by administering the medicament of the present invention.

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Abstract

La présente invention vise à proposer un nouveau médicament ou procédé qui utilise de la buprénorphine ou un sel pharmaceutiquement acceptable de celle-ci. La présente invention concerne en particulier un médicament pour soulager la douleur associée à l'hernie discale, la douleur associée à l'arthrose de la colonne vertébrale ou la douleur associée à la sténose du canal rachidien, le médicament se liant à la muqueuse buccale et contenant de la buprénorphine ou un sel pharmaceutiquement acceptable de celle-ci.
PCT/JP2011/077348 2011-11-28 2011-11-28 Analgésique Ceased WO2013080271A1 (fr)

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PCT/JP2011/077348 WO2013080271A1 (fr) 2011-11-28 2011-11-28 Analgésique

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WO2013080271A1 true WO2013080271A1 (fr) 2013-06-06

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