JP4298212B2 - Method for producing high melting point type epinastine hydrochloride - Google Patents

Method for producing high melting point type epinastine hydrochloride Download PDF

Info

Publication number
JP4298212B2
JP4298212B2 JP2002095200A JP2002095200A JP4298212B2 JP 4298212 B2 JP4298212 B2 JP 4298212B2 JP 2002095200 A JP2002095200 A JP 2002095200A JP 2002095200 A JP2002095200 A JP 2002095200A JP 4298212 B2 JP4298212 B2 JP 4298212B2
Authority
JP
Japan
Prior art keywords
epinastine hydrochloride
epinastine
alcohol
producing
method
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.)
Active
Application number
JP2002095200A
Other languages
Japanese (ja)
Other versions
JP2003286287A (en
Inventor
良輔 中村
涼介 佐々木
伸 池田
康弘 高橋
Original Assignee
大日本印刷株式会社
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 大日本印刷株式会社 filed Critical 大日本印刷株式会社
Priority to JP2002095200A priority Critical patent/JP4298212B2/en
Publication of JP2003286287A publication Critical patent/JP2003286287A/en
Application granted granted Critical
Publication of JP4298212B2 publication Critical patent/JP4298212B2/en
Application status is Active legal-status Critical
Anticipated expiration legal-status Critical

Links

Images

Description

[0001]
[Technical field to which the invention belongs]
The present invention relates to an industrial production method of a high melting point crystal of epinastine hydrochloride, which is a therapeutic agent for allergic diseases.
[0002]
[Prior art]
Epinastine hydrochloride is known in two crystal polymorphs: a low-melting-type crystal that melts at about 250 to 263 ° C. and a high-melting-type crystal that melts at about 275 to 281 ° C. Several methods are known for producing epinastine hydrochloride.
[0003]
In JP-A-3-66311, epinastine hydrochloride suspended in methanol is treated with ether containing hydrogen chloride and precipitated with ether to obtain epinastine hydrochloride. It has been reported in WO 01/40229 that this drawback lies in the inclusion of low melting point type crystals.
[0004]
In WO 01/40229, it is obtained by suspending epinastine in water, adjusting the pH within a very narrow range using hydrochloric acid, and precipitating high-melting-type crystals of epinastine hydrochloride. This type of operation is extremely complex and not suitable for industrial production.
[0005]
[Problems to be solved by the invention]
Usually, a compound having a crystalline polymorph has various properties depending on the crystalline form. Therefore, when a compound having a crystalline polymorph is used as a pharmaceutical, it is often known that absorption and formulation problems occur due to differences in properties such as stability, solubility, and dissolution rate. In order for epinastine hydrochloride to ensure the uniform quality and certain functions and effects required as a pharmaceutical product, it is necessary to always provide a single crystalline compound in a constant manner.
[0006]
The conventional production methods have such disadvantages that a certain quality cannot be obtained and the operation is complicated, so that it cannot be said to be suitable for industrial production. The present invention provides a process for producing highly soluble crystals of epinastine hydrochloride that can be used on an industrial scale without the disadvantages of the prior art.
[0007]
[Means for Solving the Problems]
The inventors of the present invention have been diligently researching to improve the drawbacks of the conventional techniques. As a result, it has been found that the production method of the present invention can always obtain a high melting point type crystal of epinastine hydrochloride, and has led to the present invention.
[0008]
More specifically, the present invention is a method for producing a high melting point type crystal of epinastine hydrochloride characterized by having a melting peak: about 275 ° C. to 281 ° C. in differential thermal analysis (DSC) as shown in FIG. .
[0009]
DETAILED DESCRIPTION OF THE INVENTION
The production method of the high melting point type epinastine hydrochloride will be specifically described. In addition, the epinastine in this invention means the free form of epinastine hydrochloride, ie, 3-amino-9,13b-dihydro-1H-dibenz [c, f] imidazo [1,5-a] azepine.
[0010]
1) It is manufactured by heating and dissolving epinastine hydrochloride in alcohol, adding an ether solvent or an ester solvent, and crystallization. Examples of the alcohol include ethanol, 1-propanol, and 2-propanol. Examples of the ether solvent include isopropyl ether, t-butyl methyl ether, tetrahydrofuran, and the like, and t-butyl methyl ether and tetrahydrofuran are preferable from the viewpoint of safety of pharmaceuticals. Examples of the ester solvent include ethyl acetate and butyl acetate, and inexpensive ethyl acetate is preferable.
[0011]
2) Manufactured by dissolving epinastine hydrochloride in alcohol and crystallizing. Examples of the alcohol include alcohols having 3 to 4 carbon atoms. Specifically, 1-propanol, 2-propanol, 1-butanol and 2-butanol are used, and 1-propanol is particularly preferable from the viewpoint of yield.
[0012]
3) Manufactured by dissolving epinastine hydrochloride in dimethylformamide and crystallizing.
[0013]
4) It is manufactured by heating and dissolving epinastine hydrochloride in alcohol, adding acetonitrile and crystallizing. Examples of the alcohol include methanol, ethanol, 1-propanol, and 2-propanol.
[0014]
5) It is manufactured by heating and dissolving epinastine hydrochloride in dimethyl sulfoxide, adding acetone and crystallizing.
[0015]
6) Epinastine is suspended in alcohol, hydrogen chloride / alcohol is added and dissolved by heating, and then epinastine hydrochloride obtained by concentrating under reduced pressure is used for the production according to the methods 1) to 5). Examples of the alcohol include methanol, ethanol, 1-propanol, and 2-propanol.
[0016]
【Example】
EXAMPLES The present invention will be specifically described with reference to examples, but the present invention is not limited only to these examples.
[0017]
[Example 1]
1 g of epinastine hydrochloride was dissolved by heating in 2 ml of ethanol. Tetrahydrofuran (20 ml) was added thereto, and the crystals precipitated were collected by filtration and dried with ice-cooling to obtain 0.6 g of epinastine hydrochloride high melting point type crystals.
[0018]
[Example 2]
Epinastine hydrochloride (15 g) was dissolved in 60 ml of ethanol by heating. 150 ml of t-butyl methyl ether was added thereto, and the precipitated crystals were filtered and dried with stirring under ice cooling to obtain 13 g of epinastine hydrochloride high melting point type crystals.
[0019]
[Example 3]
Epinastine hydrochloride (15 g) was dissolved by heating in ethanol (45 ml). 225 ml of ethyl acetate was added thereto, and the precipitated crystals were filtered and dried with stirring under ice-cooling to obtain 11 g of epinastine hydrochloride high melting point crystals.
[0020]
[Example 4]
30 g of epinastine hydrochloride was dissolved by heating in 90 ml of 1-propanol. After cooling to room temperature over 30 minutes, the precipitated crystals were filtered and dried with ice-cooling and stirring to obtain 24 g of epinastine hydrochloride high melting point type crystals.
[0021]
[Example 5]
1 g of epinastine hydrochloride was dissolved in 5 ml of dimethylformamide by heating. Under ice-cooling and stirring, the precipitated crystals were filtered and dried to obtain 0.8 g of epinastine hydrochloride high melting point type crystals.
[0022]
[Example 6]
3 g of epinastine hydrochloride was dissolved by heating in 3 ml of methanol. 10 ml of acetonitrile was added thereto, and about 1/5 amount of the solvent was distilled off under reduced pressure. 2 ml of acetonitrile was added to the residual mixture, and the crystals that precipitated were filtered and dried with stirring under ice cooling to obtain 1.6 g of high-melting-point crystals of epinastine hydrochloride.
[0023]
[Example 7]
1 g of epinastine hydrochloride was dissolved by heating in 2 ml of dimethyl sulfoxide. Acetone (5 ml) was added thereto, and the precipitated crystals were filtered and dried with stirring under ice cooling to obtain 0.7 g of epinastine hydrochloride high melting point crystals.
[0024]
[Example 8]
Epinastine 52g was suspended in ethanol 240ml. Under stirring, 64% of 13% hydrogen chloride / ethanol was added and dissolved by heating at 40 ° C. To this was added 3 g of activated carbon, and the mixture was stirred at 40 ° C. for 30 minutes. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. 125 ml of ethanol was added to the residue and dissolved by heating, then cooled and returned to room temperature. Tetrahydrofuran (1200 ml) was added thereto, and the crystals precipitated were filtered and dried under ice-cooling and stirring to obtain 36 g of high-melting-point crystals of epinastine hydrochloride.
[0025]
[Example 9]
Epinastine (5 g) was suspended in ethanol (23 ml). Under stirring, 4.4 g of 18% hydrogen chloride / ethanol was added and dissolved by heating at 40 ° C. To this was added 0.3 g of activated carbon, and the mixture was stirred at 40 ° C. for 30 minutes. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. 23 ml of ethanol was added to the residue and dissolved by heating, and then cooled and returned to room temperature. To this was added 57 ml of t-butyl methyl ether, and the crystals precipitated were collected by filtration and dried with ice-cooling to obtain 4.9 g of high-melting-type crystals of epinastine hydrochloride.
[0026]
[Example 10]
Epinastine (5 g) was suspended in ethanol (23 ml). Under stirring, 4.4 g of 18% hydrogen chloride / ethanol was added and dissolved by heating at 40 ° C. To this was added 0.3 g of activated carbon, and the mixture was stirred at 40 ° C. for 30 minutes. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. 17 ml of ethanol was added to the residue and dissolved by heating, then cooled and returned to room temperature. 86 ml of ethyl acetate was added thereto, and the crystals precipitated were filtered and dried under ice-cooling and stirring to obtain 4.1 g of a high melting point crystal of epinastine hydrochloride.
[0027]
[Example 11]
Epinastine (5 g) was suspended in ethanol (23 ml). Under stirring, 4.4 g of 18% hydrogen chloride / ethanol was added and dissolved by heating at 40 ° C. To this was added 0.3 g of activated carbon, and the mixture was stirred at 40 ° C. for 30 minutes. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. 17 ml of 1-propanol was added to the residue, dissolved by heating, cooled and returned to room temperature, and the crystals precipitated were filtered and dried with stirring under ice cooling to obtain 4.6 g of high-melting-point crystals of epinastine hydrochloride.
[0028]
[Example 12]
Epinastine 82g was suspended in ethanol 380ml. Under stirring, 66.1 g of 19% hydrogen chloride / ethanol was added and dissolved by heating at 40 ° C. 4 g of activated carbon was added thereto, and the mixture was stirred at 40 ° C. for 30 minutes. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. 470 ml of dimethylformamide was added to the residue, dissolved by heating, cooled and cooled to room temperature, and the crystals precipitated were filtered and dried with stirring under ice cooling to obtain 67 g of high-melting-point crystals of epinastine hydrochloride.
[0029]
[Example 13]
Epinastine (2.5 g) was suspended in methanol (10 ml). Under stirring, 2.2 g of 18% hydrogen chloride / methanol was added, and the mixture was heated and dissolved at 40 ° C., and then concentrated under reduced pressure. 3 ml of methanol was added to the residue and dissolved by heating, 10 ml of acetonitrile was added, and about 1/5 amount of the solvent was distilled off under reduced pressure. 2 ml of acetonitrile was added to the residual mixture, and the crystals precipitated were filtered and dried with stirring under ice cooling to obtain 1.4 g of high-melting-point crystals of epinastine hydrochloride.
[0030]
[Example 14]
Epinastine (5 g) was suspended in ethanol (23 ml). Under stirring, 4.4 g of 18% hydrogen chloride / ethanol was added and dissolved by heating at 40 ° C. To this was added 0.3 g of activated carbon, and the mixture was stirred at 40 ° C. for 30 minutes. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. To the residue, 10 ml of dimethyl sulfoxide was added and dissolved by heating, and then cooled and returned to room temperature. Acetone (25 ml) was added thereto, and the crystals precipitated were filtered and dried with stirring under ice-cooling to obtain 4 g of high-melting-point crystals of epinastine hydrochloride.
[0031]
【The invention's effect】
According to the production method of the present invention, there is an effect that a high melting point type crystal of epinastine hydrochloride can be easily produced by a simple operation.
[0032]
[Brief description of the drawings]
FIG. 1 is a differential thermal analysis (DSC) of a high melting point crystal of epinastine hydrochloride.

Claims (17)

  1. Epinastine hydrochloride is treated with alcohol containing hydrogen chloride to prepare epinastine hydrochloride, the epinastine hydrochloride is dissolved in an alcohol having 2 or more carbon atoms, and an ether solvent is added. Law.
  2. The method for producing a high melting point type crystal of epinastine hydrochloride according to claim 1, wherein the alcohol having 2 or more carbon atoms in which epinastine hydrochloride is dissolved is an alcohol having 2 to 3 carbon atoms.
  3.   The method for producing a high melting point type crystal of epinastine hydrochloride according to claim 2, wherein the alcohol having 2 to 3 carbon atoms is ethanol.
  4.   The method for producing a high-melting-point crystal of epinastine hydrochloride according to claim 1, wherein the ether solvent is t-butyl methyl ether or tetrahydrofuran.
  5. A method for producing a high melting point crystal of epinastine hydrochloride, comprising treating epinastine with an alcohol containing hydrogen chloride to prepare epinastine hydrochloride, dissolving the epinastine hydrochloride in an alcohol and adding an ester solvent .
  6. The method for producing a high melting point type crystal of epinastine hydrochloride according to claim 5, wherein the alcohol for dissolving epinastine hydrochloride is an alcohol having 2 to 3 carbon atoms.
  7.   The method for producing a high melting point crystal of epinastine hydrochloride according to claim 6, wherein the alcohol having 2 to 3 carbon atoms is ethanol.
  8.   6. The process for producing a high melting point type epinastine hydrochloride crystal according to claim 5, wherein the ester solvent is ethyl acetate.
  9. A method for producing a high-melting-point crystal of epinastine hydrochloride, comprising treating epinastine with an alcohol containing hydrogen chloride to prepare epinastine hydrochloride, and dissolving the epinastine hydrochloride in alcohol to crystallize.
  10. The method for producing a high melting point type crystal of epinastine hydrochloride according to claim 9, wherein the alcohol in which epinastine hydrochloride is dissolved is an alcohol having 3 to 4 carbon atoms.
  11.   The method for producing a high melting point crystal of epinastine hydrochloride according to claim 10, wherein the alcohol having 3 to 4 carbon atoms is 1-propanol.
  12. A method for producing a high-melting-point crystal of epinastine hydrochloride, comprising treating epinastine with an alcohol containing hydrogen chloride to prepare epinastine hydrochloride , dissolving the epinastine hydrochloride in dimethylformamide , and crystallizing the epinastine.
  13. A method for producing a high-melting-point crystal of epinastine hydrochloride, comprising treating epinastine with an alcohol containing hydrogen chloride to prepare epinastine hydrochloride, dissolving the epinastine hydrochloride in alcohol and adding acetonitrile.
  14. The method for producing a high melting point type crystal of epinastine hydrochloride according to claim 13, wherein the alcohol in which epinastine hydrochloride is dissolved is an alcohol having 1 to 3 carbon atoms.
  15.   The method for producing a high melting point type crystal of epinastine hydrochloride according to claim 14, wherein the alcohol having 1 to 3 carbon atoms is methanol.
  16. A method for producing a high melting point crystal of epinastine hydrochloride, comprising treating epinastine with an alcohol containing hydrogen chloride to prepare epinastine hydrochloride, dissolving the epinastine hydrochloride in dimethyl sulfoxide and adding acetone.
  17. The method for producing a high melting point type crystal of epinastine hydrochloride according to any one of claims 1 to 16, wherein the alcohol containing hydrogen chloride is an alcohol having 1 to 3 carbon atoms.
JP2002095200A 2002-03-29 2002-03-29 Method for producing high melting point type epinastine hydrochloride Active JP4298212B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2002095200A JP4298212B2 (en) 2002-03-29 2002-03-29 Method for producing high melting point type epinastine hydrochloride

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2002095200A JP4298212B2 (en) 2002-03-29 2002-03-29 Method for producing high melting point type epinastine hydrochloride

Publications (2)

Publication Number Publication Date
JP2003286287A JP2003286287A (en) 2003-10-10
JP4298212B2 true JP4298212B2 (en) 2009-07-15

Family

ID=29238797

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2002095200A Active JP4298212B2 (en) 2002-03-29 2002-03-29 Method for producing high melting point type epinastine hydrochloride

Country Status (1)

Country Link
JP (1) JP4298212B2 (en)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7407955B2 (en) 2002-08-21 2008-08-05 Boehringer Ingelheim Pharma Gmbh & Co., Kg 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
DE102004054054A1 (en) 2004-11-05 2006-05-11 Boehringer Ingelheim Pharma Gmbh & Co. Kg Process for preparing chiral 8- (3-amino-piperidin-1-yl) -xanthines
JP2007519757A (en) * 2004-12-01 2007-07-19 テバ ジョジセルジャール ザ−トケルエン ムケド レ−スベニュタ−ルシャシャ−グ Preparation method of pimecrolimus
JP4895510B2 (en) * 2005-02-23 2012-03-14 合同酒精株式会社 Method for producing variolamine
WO2007002314A2 (en) * 2005-06-22 2007-01-04 Teva Pharmaceutical Industries Ltd. Polymorphic forms of tegaserod maleate
CN103951667A (en) 2006-05-04 2014-07-30 勃林格殷格翰国际有限公司 Polymorphs
PE20110235A1 (en) 2006-05-04 2011-04-14 Boehringer Ingelheim Int pharmaceutical combinations comprising metformin and linagliptin
AR071175A1 (en) 2008-04-03 2010-06-02 Boehringer Ingelheim Int pharmaceutical composition comprising an inhibitor of dipeptidyl peptidase-4 (DPP4) and a companion drug
KR20190016601A (en) 2008-08-06 2019-02-18 베링거 인겔하임 인터내셔날 게엠베하 Treatment for diabetes in patients inappropriate for metformin therapy
UY32030A (en) 2008-08-06 2010-03-26 Boehringer Ingelheim Int "Treatment for diabetes in patients unsuitable for therapy with metformin"
CN107011345A (en) 2008-12-23 2017-08-04 勃林格殷格翰国际有限公司 The salt form of organic compound
TW201036975A (en) 2009-01-07 2010-10-16 Boehringer Ingelheim Int Treatment for diabetes in patients with inadequate glycemic control despite metformin therapy
WO2011064352A1 (en) 2009-11-27 2011-06-03 Boehringer Ingelheim International Gmbh Treatment of genotyped diabetic patients with dpp-iv inhibitors such as linagliptin
MX341025B (en) 2010-05-05 2016-08-04 Boehringer Ingelheim Int Gmbh * Combination therapy.
WO2011161161A1 (en) 2010-06-24 2011-12-29 Boehringer Ingelheim International Gmbh Diabetes therapy
US9034883B2 (en) 2010-11-15 2015-05-19 Boehringer Ingelheim International Gmbh Vasoprotective and cardioprotective antidiabetic therapy
PL2731947T3 (en) 2011-07-15 2019-07-31 Boehringer Ingelheim International Gmbh Substituted dimeric quinazoline derivative, its preparation and its use in pharmaceutical compositions for the treatment of type i and ii diabetes
US9555001B2 (en) 2012-03-07 2017-01-31 Boehringer Ingelheim International Gmbh Pharmaceutical composition and uses thereof
JP6224084B2 (en) 2012-05-14 2017-11-01 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Xanthine derivatives as DPP-4 inhibitors for the treatment of glomerular epithelial cell related disorders and / or nephrotic syndrome
WO2013174767A1 (en) 2012-05-24 2013-11-28 Boehringer Ingelheim International Gmbh A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference
CN104098575B (en) * 2013-04-15 2016-06-01 四川科瑞德凯华制药有限公司 Brilliant type of a kind of Epinastine Hydrochloride and its production and use
WO2015128453A1 (en) 2014-02-28 2015-09-03 Boehringer Ingelheim International Gmbh Medical use of a dpp-4 inhibitor
JP2019517542A (en) 2016-06-10 2019-06-24 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Combination of linagliptin and metformin

Also Published As

Publication number Publication date
JP2003286287A (en) 2003-10-10

Similar Documents

Publication Publication Date Title
ES2336287T5 (en) Polymorphic modifications of 2- (3-cyano-4-isobutyloxyphenyl) -4-methyl-5-thiazolecarboxylic acid and processes for its preparation
US6245911B1 (en) Donepezil polycrystals and process for producing the same
JP2011513497A (en) Preparation of lenalidomide
US9416097B2 (en) Crystalline minocycline base and processes for its preparation
US20040167157A1 (en) Process for preparation of amidine derivatives
US4246164A (en) Process for the resolution of (+)- and (-)-6-methoxy-α-methyl-2-naphthaleneacetic acid
US20060004203A1 (en) Modified pictet-spengler reaction and products prepared therefrom
US4224239A (en) Process for preparing optically active amino acid or mandelic acid
EP2305635B1 (en) Formoterol tartrate, process and polymorph
US20080194828A1 (en) Method of Preparing Esomeprazole and Salts Thereof
USRE34672E (en) Pharmaceutical composition containing a stable modification of torasemide
CZ267694A3 (en) Process for preparing clavulanic acid, use and salts thereof
CN1832946A (en) Process for producing imide compound
SK2802001A3 (en) Crystalline forms of eto2c-ch2-(r)cgl-aze-pab-oh
EP0595345B1 (en) Process for producing alanylglutamine
KR0179639B1 (en) Method for the preparation of formoterol and related compounds
JP4590038B2 (en) Process for the production of enantiomerically pure imidazolyl compounds
LT3813B (en) Process for preparing 3-formamido-4-hydroxy-alpha£n£1-methyl-2(p-methoxyphenyl)ethylaminomethyl|benzyl alkohol fumarate (formoterol) and related compounds and derivatives thereof
US7999106B2 (en) Processes for the preparation of clopidogrel hydrogen sulfate polymorphic form I
JP2004530638A (en) Crystalline venlafaxine base, and novel venlafaxine hydrochloride polymorphic form, as well as methods for their preparation
HU188201B (en) Process for the resulation of trans-5-aryl-2,3,4,4a,5,9b-hexahydro-1h-pyrido/4,3-b/-indol derivatives
JP4100908B2 (en) Production method of basic antibiotics and inorganic acid salts and oxalate intermediates
CN106478482A (en) A kind of synthetic method of Oxiracetam
AU2009205606A1 (en) Crystalline 2-(4-cyclopropanesulphonyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydropyran-4-yl)-propionamide
AU2006219727B2 (en) Crystallisation and purification of glycopyrronium bromide

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20050318

A711 Notification of change in applicant

Free format text: JAPANESE INTERMEDIATE CODE: A711

Effective date: 20070725

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20081028

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20081222

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20090414

A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20090415

R150 Certificate of patent or registration of utility model

Free format text: JAPANESE INTERMEDIATE CODE: R150

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20120424

Year of fee payment: 3

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20120424

Year of fee payment: 3

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20130424

Year of fee payment: 4

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20140424

Year of fee payment: 5