WO2006025516A1 - ペロスピロン経皮投与用医薬組成物 - Google Patents
ペロスピロン経皮投与用医薬組成物 Download PDFInfo
- Publication number
- WO2006025516A1 WO2006025516A1 PCT/JP2005/016084 JP2005016084W WO2006025516A1 WO 2006025516 A1 WO2006025516 A1 WO 2006025516A1 JP 2005016084 W JP2005016084 W JP 2005016084W WO 2006025516 A1 WO2006025516 A1 WO 2006025516A1
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- Prior art keywords
- perospirone
- pharmaceutical composition
- administration
- transdermal administration
- tape
- Prior art date
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Classifications
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to a pharmaceutical composition for transdermal administration containing perospirone or a pharmaceutically acceptable acid addition salt. More specifically, the present invention is for systemic transdermal administration in which perospirone or a pharmaceutically acceptable acid addition salt is absorbed percutaneously and continuously delivered to the central tissue via the circulatory system. It relates to a pharmaceutical composition.
- Perospirone represented by formula (1) (cis-N- [4- [4- (1,2-benzisothiazo ⁇ 3-yl)-1- piperazi nyl] butyl] cyclohexane-l, 2-dicarboximide ) Is described in Patent Document 1.
- Perospirone or a pharmaceutically acceptable acid addition salt thereof has strong binding activity on donomin 2 (D2) receptor and serotonin 2 (5-HT2) receptor, and acts serotonin that acts antagonistically.
- D2 donomin 2
- 5-HT2 serotonin 2
- SDA -dopamine antagonist
- Non-Patent Documents 1, 2, and 3 The anti-serotonin action (rat) of the main metabolite is about 1/8 of perospirone of ID-15036 represented by the formula (2), which is the strongest, and the anti-dopamine action (rat) However, it is confirmed that it is weak! (Non-patent Document 4).
- Non-Patent Document 5 Kp can be predicted from the molecular weight and distribution coefficient, which is the physical property value of the drug (Non-patent Document 6), and therefore the predicted value Kp, Cv (solubility, which is the physical property value of the drug).
- a (lcm 2 ) the amount of drug permeation per unit area of the skin to which the preparation is applied can be calculated.
- the permeation amount of perospirone per unit area was calculated to be 0.71 ⁇ g / day / cm 2 .
- the amount of perospirone that permeates the skin is 18 / zg / day, but the perospirone permeation required as a transdermal agent is 120 g / day or more. Therefore, it was considered extremely difficult to absorb perospirone from the skin as predicted by Equation 1 above based on physical properties. That is, it was considered impossible to administer perospirone transdermally based on the above prediction based on the physical properties of the drug.
- a tandospirone transdermal agent for example, Patent Document 2
- the target diseases are psychosomatic disorders, depression in neurosis, fear Therefore, the target disease is different from schizophrenia, which is the target disease of perospirone.
- Patent Document 1 Japanese Patent Laid-Open No. 62-123179
- Patent Document 2 Japanese Patent Laid-Open No. 11-228414
- Non-Patent Document 1 Basic and Clinical 31, 543-568, 1997
- Non-Patent Document 2 Basic and Clinical 31, 737-753, 1997
- Non-Patent Document 3 Basic and Clinical 31, 2113-2157, 1997
- Non-Patent Document 4 Basic and Clinical 31, 893-902, 1997
- Non-Patent Document 5 Development of pharmaceuticals 13, 87-133, 1989
- Non-Patent Document 6 American Journal of Industrial Medicine 23, 711-719, 1993 Disclosure of Invention
- the problem to be solved by the present invention is to provide a means for administering perospirone or a pharmaceutically acceptable acid addition salt thereof that can suppress the production of metabolites and can maintain the concentration in the blood continuously. There is.
- the present invention is as follows.
- a pharmaceutical composition for systemic transdermal administration comprising perospirone or a pharmaceutically acceptable acid addition salt thereof as an active ingredient.
- composition for systemic transdermal administration according to the above 3 or 4, which is in the form of a tape, patch, patch, ointment, cream, lotion, liquid or gel preparation.
- a medicinal composition for transdermal administration containing perospirone or a pharmaceutically acceptable acid addition salt thereof, in which the production of metabolites is remarkably reduced and the concentration in blood can be maintained continuously. Things can now be provided.
- compositions of perospirone include, for example, inorganic acid addition salts such as hydrochloride, hydrobromide, sulfate, phosphate, nitrate, acetate, propionate, co Organic acid addition salts such as succinate, lactate, malate, tartrate, succinate, maleate, fumarate, methanesulfonate, p-toluenesulfonate, ascorbate, etc. It is done.
- the present invention also includes solvates such as hydrates of perospirone or a pharmaceutically acceptable acid addition salt thereof, and ethanol solvates.
- a dosage form conventionally used as an external preparation for example, a tape agent , Patches, poultices, ointments, creams, lotions, liquids, gel preparations, etc. Preferred are tapes and notches.
- External preparations of these dosage forms can be produced by ordinary methods using ordinary adhesives, bases, and the like.
- it can be produced in accordance with the description of “Transdermal Formulation Development Manual” supervised by Mitsuo Matsumoto (1985), Japanese Patent Nos. 2651616, W096 / 12465, and Japanese Patent Laid-Open No. 9-278651.
- Examples of adhesives for tapes and patches include acrylic adhesives, rubber adhesives, silicone adhesives, and the like.
- Examples of the acrylic pressure-sensitive adhesive include (co) polymers mainly composed of (meth) acrylic acid alkyl esters.
- This (co) polymer may be a copolymer of two or more types of (meth) acrylic acid alkyl ester, and a functional monomer copolymerizable with (meth) acrylic acid alkyl ester and (meth) acrylic. It may be a copolymer with an acid alkyl ester.
- Examples of the alkyl acrylate ester include alkyl acrylate ester esterified with a linear or branched alkyl having 1 to 18 carbon atoms.
- Functional monomers include, for example, monomers having a hydroxyl group (such as (meth) acrylic acid hydroxyethyl ester), monomers having a carboxyl group (such as ptyl maleate and crotonic acid), and monomers having an amide group ((meth) Acrylamide, etc.), monomers having an amino group (dimethylaminoacrylate, etc.), monomers having a pyrrolidone ring (N vinyl 2-pyrrolidone, etc.), and the like.
- a hydroxyl group such as (meth) acrylic acid hydroxyethyl ester
- monomers having a carboxyl group such as ptyl maleate and crotonic acid
- monomers having an amide group ((meth) Acrylamide, etc.)
- monomers having an amino group dimethylaminoacrylate, etc.
- monomers having a pyrrolidone ring N vinyl 2-pyrrolidone, etc.
- Examples of rubber-based adhesives include natural rubber, polyisopropylene rubber, polyisobutylene rubber, styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene block.
- the main component is a rubber elastic body such as a lock copolymer.
- silicone pressure-sensitive adhesive examples include those mainly composed of silicone rubber such as polydimethylsiloxane and diphenylsiloxane.
- a micro-reservoir type preparation in which perospirone or a pharmaceutically acceptable acid addition salt thereof is dispersed in these adhesives, and a solution of perospirone or a pharmaceutically acceptable acid addition salt thereof are filled. It can be a reservoir type preparation.
- bases for ointments and creams include fatty oils, lanolin, petrolatum, paraffin, plastibase, glycols, higher fatty acids, higher alcohols and the like. To these bases, stabilizers, preservatives, emulsifiers, suspending agents and the like are added as necessary.
- examples of the base of the lotion agent include ethanol, glycerin, glycol and the like.
- the base of the liquid agent for example, ethanol, water, glycol and the like are used.
- the base of the gel preparation for example, in the case of an oily gel, a liquid oil or fat is gelled with a gelling agent, and in the case of an aqueous gel, a gel such as carboxymethyl polymer, hydroxypropylcellulose, polybulu alcohol, etc. An agent is used.
- a solvent for dissolving perospirone or a pharmaceutically acceptable acid addition salt thereof in a reservoir-type preparation or lotion for example, berospirone or a pharmaceutically acceptable acid addition salt thereof can be dissolved.
- examples thereof include organic solvents and buffer solutions that are less irritating to the skin, or mixed solvents of the organic solvents and water or buffer solutions.
- the pH of the buffer solution is preferably neutral from the viewpoint of skin irritation.
- the pharmaceutical composition for transdermal administration of the present invention includes various pharmacologically acceptable additives such as stabilizers, antioxidants, fragrances, and fillings as long as they do not impair the purpose of the present invention.
- An agent or other percutaneous absorption enhancer can be added.
- the pH is preferably weakly basic.
- a tape agent and a notching agent because the perospirone concentration in blood can be controlled to a certain level.
- Additives added to tapes and notches include terbinol, myristate pill, 1-menthol, lauric acid, lauryl alcohol, crotamiton, and sebacic acid jetty. , N-methyl-2-pyrrolidone, Azone (registered trademark) and the like.
- the dose varies depending on the patient's condition such as age and weight, symptoms, and the form of the preparation. Usually, 0.01 mg to 1.0 g / day of perospirone is administered to an adult.
- Maintained blood perospirone concentration is a force that is controlled by the patient's symptoms Currently in clinical use, do not exceed the maximum blood concentration of orally administered ruperospirone hydrochloride dihydrate! However, the viewpoint power of side effects is also preferable.
- the effective blood berospirone concentration, antidopaminergic action and antiserotonin action can be sustained for 5 hours to 4 weeks, preferably 1 day to 1 week.
- Long-term antipsychotic action can be achieved by removing the used preparation and newly using the preparation of the present invention.
- Styrene Isoprene Styrene block copolymer (Quintac 3421) 2.00g, fluid paraffin 3.00g, polybutene (Nisseki Polybutene HV-300) 1.50g, alicyclic saturated hydrocarbon resin (Arcon p-100) 2.50g
- An adhesive solution was prepared by dissolving in hexane. Add to this solution so that the perospirone content in the plaster is 10%, stir well, then spread and dry the support to a thickness of about 100 m, and paste the release liner together 4cm X 4cm
- the perospirone tape preparation (Preparation 1) was produced.
- Styrene Isoprene Styrene block copolymer (Quintac 3421) 2.00g, Fluid paraffin 3.00g, Polybutene (Nisseki Polybutene HV-300) 1.50g, Alicyclic saturated hydrocarbon resin (Arcon p-100) 2.50g
- An adhesive solution was prepared by dissolving in hexane. To this solution was added so that the content of berospirone hydrochloride in the plaster was 10%, and after sufficient stirring, it was spread and dried to a thickness of about 100 m on the support, and a release liner was bonded to it. Cut to a size of 4 cm to produce a velopirone hydrochloride tape (formulation 2).
- Macrogol 4000 Japanese fats and oils
- Macrogol 400H Japanese fats and oils
- 9.5 g of this mixture and 0.5 g of belospirone hydrochloride hydrate were mixed to produce an aqueous ointment (formulation 4) of belospirone hydrochloride.
- Perospirone 0.5g and Plastibase 50W (registered trademark: Bristol Pharmaceutical) 9.5g were mixed to produce perospirone oily ointment (Formulation 5).
- Perospirone 0.7 g was dissolved in a phosphate buffer solution 70 ml containing 50% ethanol to prepare a perospirone solution (formulation 7).
- Styrene Isoprene Styrene block copolymer (Quintac 3421) 2.00g, Fluid paraffin 3.00g, Polybutene (Nisseki Polybutene HV-300) 1.50g, Alicyclic saturated hydrocarbon resin (Arcon p-100) 2.50g,
- a pressure-sensitive adhesive solution was prepared by dissolving 0.4 g of L-menthol in hexane. To this solution was added so that the perospirone content in the plaster was 10%, and after sufficient stirring, it was spread on the support at a thickness of about 100 / zm, dried, and a release liner was pasted together. X was cut into a size of 4 cm to produce a perospirone tape preparation (formulation 9).
- Verospirone ointment is produced from 6 g of perospirone, 2 g of carboxyvinyl polymer, 2 g of triethanolamine, 50 g of ethanol and 40 g of water.
- Styrene Isoprene Styrene block copolymer (Quintac 3421) 8g, Fluid paraffin 12g, Polybutene (Nisshi Polybutene HV-300) 6g, Alicyclic saturated hydrocarbon resin (Arcon P-100) 10g, Ethyl acetate 20ml
- Ad solution Add 4g of perospirone to this solution, stir well at 45 ° C, spread on polyethylene terephthalate film to a thickness of about 270m, dry, and attach release liner, perospirone tape agent (Formulation 10) was produced.
- Polyisobutylene (Opanol B100) lg, Polybutene (Nisseki Polybutene HV3OO) 0.75g, Alicyclic saturated hydrocarbon resin (Arcon P-100) 1.25g, Liquid paraffin 1.5g, Perospirone 0.5g and Hexane 20ml Dissolved in 2 ml of ethyl acetate. After thorough stirring and defoaming, a polyethylene terephthalate film was spread to a thickness of about 400 m, dried at room temperature, and a release liner was attached to produce a perospirone tape preparation. (Formulation 11)
- Polyisobutylene (Opanol B100) 1.25g, Polybutene (Nisseki Polybutene HV3OO) 0.5g, Alicyclic Saturated Hydrocarbon Hydrocarbon (Arcon P 100) 0.5g, Liquid Paraffin 0.25g, Isopropyl myristate 1.75g, Perospirone 0.75g was dissolved in 20 ml of hexane and 2 ml of ethyl acetate. After thorough stirring and defoaming, the film was spread on a polyethylene terephthalate film with a thickness of about 400 m, dried at room temperature, and a release liner was bonded to produce a perospirone tape ( Control example 1
- Styrene Isoprene Styrene block copolymer (Quintac 3421) 8g, Fluid paraffin 12g, Polybutene (Nisshi Polybutene HV-300) 6g, Alicyclic saturated hydrocarbon resin (Arcon P-100) 10g, Ethyl acetate 20ml
- an adhesive solution After sufficiently stirring this solution at 45 ° C, it is spread on a polyethylene terephthalate film to a thickness of about 270 ⁇ m, dried, and a release liner is applied to produce a placebo tape (control preparation 1). It was.
- the perospirone tape preparation (formulation 10) produced in Example 14 and the perospirone tape preparation (formulation 11) produced in Example 15 were used as models for tryptamine-induced forelimb clonic spasm in rats. Oh !, the anti-serotonin action was evaluated. The test method was carried out with reference to Jpn. J. Pharmacol. 53, 321-329 (1990).
- a tape preparation was affixed to the back of a 7-week-old SD rat whose hair was removed on the previous day, and 5 ml / Kg of water was orally administered.
- tryptamine hydrochloride was administered at a dose of 40 mg / Kg at the time determined in advance as the evaluation time. The appearance of clonic convulsions was observed for 5 minutes after administration of tryptamine hydrochloride, and if no forelimb clonic convulsions were observed, it was determined that the inhibitory effect on tryptamine-induced behavior was positive.
- Table 1 shows the applied perospirone tape preparation, evaluation time, number of individuals used for each, and evaluation results.
- control preparation 1 The placebo tape (control preparation 1) containing no perospirone prepared in Control Example 1 was applied to the back of a 7-week-old SD rat whose hair was removed on the previous day, and 3 mg of velopirone hydrochloride hydrate was added. Orally administered at a dose of / Kg or 0.5 mg / Kg. After administration, tryptamine hydrochloride was administered at a dose of 40 mg / Kg at a predetermined time as the evaluation time, and the tail vein was administered. The determination was made in the same manner as in Example 1. The evaluation results are shown in Table 1.
- the perospirone tape preparation (formulation 10) produced in Example 14 and the perospirone tape preparation (formulation 11) produced in Example 15 were evaluated for anti-dopamine action by the apomorphine-induced stereotyped behavior model in rats. .
- the test method was performed with reference to Jpn. J. Pharmacol. 53, 32 1-329 (1990).
- a tape preparation was affixed to the back of a 7-week-old SD rat whose hair was removed on the previous day, and 5 ml / Kg of water was orally administered.
- apomorphine hydrochloride was administered at a dose of 1.25 mg / Kg at the tail vein at a time determined as the evaluation time. For 30 minutes after the administration of apomorphine hydrochloride, it was determined that the inhibitory effect on the apomorphine hydrochloride-induced behavior was positive if the behavior of licking and mastication was observed without being observed.
- Table 2 shows the perospirone tape preparation and evaluation time, the number of individuals used and the evaluation results. [0048] Comparative Example 2
- control preparation 1 The placebo tape preparation (control preparation 1) containing no perospirone prepared in Control Example 1 was affixed to the back of a 7-week-old SD rat whose hair had been removed on the previous day, and 10 mg of verospirone hydrochloride hydrate was added. Orally administered at a dose of / Kg or 2 mg / Kg. After administration, apomorphine hydrochloride was administered at a dose of 1.25 mg / Kg at the time determined as the evaluation time, and the determination was made in the same manner as in Test Example 2. The evaluation results are shown in Table 2.
- a 7-week-old SD male rat was orally administered with 10 mg / kg of a solution of berospirone hydrochloride hydrate dissolved in distilled water for injection to a concentration of 2 mg / ml, and blood was collected over time.
- Test Example 3 the serum concentration of perospirone and its main metabolite ID-15036 was examined. Serum concentrations of perospirone and its main metabolite ID-15036 4 hours after administration of formulation 1 to 8 of test example 4 and 1 hour after administration of comparative example 3 (oral administration of belospirone hydrochloride) This is shown in Fig. 1.
- ID-15036Z perospirone concentration ratio of ID-15036 to perospirone (ID-15036Z perospirone) is shown in Table 3 for the preparations whose ID-15036 was measured above the lower limit of quantification.
- ID-15036 which is a metabolite of perospirone, rapidly metabolizes belospirone by oral administration, whereas serum concentration is about 4 times higher than that of perospirone.
- the serum concentration of perospirone was 7 to 19 times higher than that of ID-15036, contrary to the oral administration.
- the pharmaceutical composition for percutaneous administration of perospirone or belospirone hydrochloride of the present invention has an effect of maintaining the blood berospirone concentration for a long period of time compared to oral administration, and a metabolite (ID- 15036) It has been shown to have a surprisingly significant effect on controlling the concentration.
- the serum concentration of perospirone is shown in FIG. As is clear from FIG. 6, it was shown that the pharmaceutical composition for transdermal administration of perospyrone of the present invention has an effect of maintaining the blood verospirone concentration in units of several days for a long time.
- the pharmaceutical composition for transdermal administration containing perospirone according to the present invention or a pharmaceutically acceptable acid addition salt thereof significantly reduces the production of metabolites and continuously maintains the concentration in blood. Because it can be maintained, it can be used as a therapeutic agent.
- FIG. 1 Perospirone 4 hours after transdermal administration of preparations 1-8 manufactured in Examples 1-8 (Test Example 1) and 1 hour after oral administration of aqueous solution of berospirone hydrochloride of Comparative Example 1 2 is a graph showing the serum concentration of ID-15036, which is a major metabolite thereof.
- FIG. 2 Perospirone in blood and its main component in the transdermal administration of Formulation 1 produced in Example 1 It is a graph which shows the time transition of ID-15036 which is a metabolite.
- FIG. 3 is a graph showing the time course of blood perospirone and its main metabolite ID-15036 in the transdermal administration of Formulation 4 produced in Example 4.
- FIG. 4 is a graph showing the time course of blood perospirone and its main metabolite ID-15036 in the transdermal administration of Formulation 5 produced in Example 5.
- FIG. 5 is a graph showing the temporal transition of blood perospirone and its main metabolite ID-15036 when oral administration of belospirone hydrochloride hydrate in Comparative Example 1.
- FIG. 6 is a graph showing the time course of blood perospirone in transdermal administration of Formulation 11 produced in Example 15.
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Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
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US11/661,612 US20070254887A1 (en) | 2004-09-03 | 2005-09-02 | Pharmaceutical Composition for Transdermal Administration of Perospirone |
CA002578552A CA2578552A1 (en) | 2004-09-03 | 2005-09-02 | Medicinal composition for percutaneous perospirone administration |
JP2006531996A JPWO2006025516A1 (ja) | 2004-09-03 | 2005-09-02 | ペロスピロン経皮投与用医薬組成物 |
EP05776962A EP1787648A4 (en) | 2004-09-03 | 2005-09-02 | MEDICAL COMPOSITION FOR PERCUTANEOUS PEROSPIRON MANAGEMENT |
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JP2004-257633 | 2004-09-03 | ||
JP2004257633 | 2004-09-03 |
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US (1) | US20070254887A1 (ja) |
EP (1) | EP1787648A4 (ja) |
JP (1) | JPWO2006025516A1 (ja) |
KR (1) | KR20070059079A (ja) |
CN (1) | CN101056637A (ja) |
CA (1) | CA2578552A1 (ja) |
WO (1) | WO2006025516A1 (ja) |
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WO2007142295A1 (ja) | 2006-06-09 | 2007-12-13 | Dainippon Sumitomo Pharma Co., Ltd. | 新規テープ製剤 |
JP2022500362A (ja) * | 2018-08-29 | 2022-01-04 | イントラ−セルラー・セラピーズ・インコーポレイテッドIntra−Cellular Therapies, Inc. | 新規組成物および方法 |
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JP6076740B2 (ja) | 2010-01-07 | 2017-02-08 | アルカーメス ファーマ アイルランド リミテッド | 第四級アンモニウム塩プロドラッグ |
CN102302468A (zh) * | 2011-10-19 | 2012-01-04 | 成都恒瑞制药有限公司 | 一种盐酸哌罗匹隆快速释放片剂及其制备方法 |
KR101681611B1 (ko) | 2014-09-18 | 2016-12-12 | 현대건설 주식회사 | 건축구조물의 커튼월 |
CN112225732B (zh) * | 2019-07-15 | 2024-01-09 | 四川科瑞德制药股份有限公司 | 一种盐酸哌罗匹隆水合物晶型及其制备方法 |
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JPH11228414A (ja) * | 1998-02-06 | 1999-08-24 | Sumitomo Pharmaceut Co Ltd | タンドスピロン経皮剤 |
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JPH0625181B2 (ja) * | 1985-03-27 | 1994-04-06 | 住友製薬株式会社 | 新規なイミド誘導体 |
US5633009A (en) * | 1990-11-28 | 1997-05-27 | Sano Corporation | Transdermal administration of azapirones |
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US5916914A (en) * | 1997-08-08 | 1999-06-29 | Warner-Lambert Company | Compounds and method of treating psychosis and schizophrenia |
AU4062900A (en) * | 1999-04-06 | 2000-10-23 | Sepracor, Inc. | Methods and compositions for the treatment of neuroleptic and related disorders using ziprasidone metabolites |
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- 2005-09-02 JP JP2006531996A patent/JPWO2006025516A1/ja active Pending
- 2005-09-02 US US11/661,612 patent/US20070254887A1/en not_active Abandoned
- 2005-09-02 CA CA002578552A patent/CA2578552A1/en not_active Abandoned
- 2005-09-02 WO PCT/JP2005/016084 patent/WO2006025516A1/ja active Application Filing
- 2005-09-02 EP EP05776962A patent/EP1787648A4/en not_active Withdrawn
- 2005-09-02 KR KR1020077005138A patent/KR20070059079A/ko not_active Application Discontinuation
- 2005-09-02 CN CNA2005800381106A patent/CN101056637A/zh active Pending
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---|---|---|---|---|
WO2007142295A1 (ja) | 2006-06-09 | 2007-12-13 | Dainippon Sumitomo Pharma Co., Ltd. | 新規テープ製剤 |
US8354121B2 (en) | 2006-06-09 | 2013-01-15 | Dainippon Sumitomo Pharma Co., Ltd. | Tape preparation |
KR101390012B1 (ko) | 2006-06-09 | 2014-04-29 | 다이닛본 스미토모 세이야꾸 가부시끼가이샤 | 신규한 테이프 제제 |
JP2022500362A (ja) * | 2018-08-29 | 2022-01-04 | イントラ−セルラー・セラピーズ・インコーポレイテッドIntra−Cellular Therapies, Inc. | 新規組成物および方法 |
Also Published As
Publication number | Publication date |
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EP1787648A1 (en) | 2007-05-23 |
JPWO2006025516A1 (ja) | 2008-05-08 |
CA2578552A1 (en) | 2006-03-09 |
US20070254887A1 (en) | 2007-11-01 |
KR20070059079A (ko) | 2007-06-11 |
CN101056637A (zh) | 2007-10-17 |
EP1787648A4 (en) | 2010-06-23 |
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