[go: up one dir, main page]

WO2014050874A1 - Nouvelle forme cristalline de rosuvastatine de calcium et son procédé de fabrication - Google Patents

Nouvelle forme cristalline de rosuvastatine de calcium et son procédé de fabrication Download PDF

Info

Publication number
WO2014050874A1
WO2014050874A1 PCT/JP2013/075880 JP2013075880W WO2014050874A1 WO 2014050874 A1 WO2014050874 A1 WO 2014050874A1 JP 2013075880 W JP2013075880 W JP 2013075880W WO 2014050874 A1 WO2014050874 A1 WO 2014050874A1
Authority
WO
WIPO (PCT)
Prior art keywords
rosuvastatin calcium
group
crystals
hydrocarbon group
water
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/JP2013/075880
Other languages
English (en)
Japanese (ja)
Inventor
茂信 西口
直人 稲越
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.)
Towa Pharmaceutical Co Ltd
Original Assignee
Towa Pharmaceutical 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 Towa Pharmaceutical Co Ltd filed Critical Towa Pharmaceutical Co Ltd
Publication of WO2014050874A1 publication Critical patent/WO2014050874A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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 the formula 1 having HMG-CoA reductase inhibitory action.
  • Rosuvastatin calcium represented by the formula: bis ((3R, 5S, 4E) -7- ⁇ 4- (4-fluorophenyl) -6-isopropyl-2- [methanesulfonyl (methyl) amino] pyrimidin-5-yl) -3,5-dihydroxyhept-6-enoic acid ⁇ relates to a novel crystalline form of calcium.
  • Rosuvastatin calcium is an HMG-CoA reductase inhibitor sold as CRESTOR (registered trademark) in various countries around the world. In Japan, tablets that are effective or effective for hypercholesterolemia and familial cholesterolemia are on the market.
  • Patent Document 1 Japanese Patent No. 2664897 (Patent Document 1), Japanese Translation of PCT International Publication No. 2008-546730 (Patent Document 2), and Japanese Patent No. 4099333 (Patent Document 3) disclose methods for producing amorphous rosuvastatin calcium.
  • Patent No. 4996786 Patent Document 4 discloses rosuvastatin calcium A-type crystals
  • WO2010 / 081861 International Publication Patent Document 5 discloses rosuvastatin calcium anhydrous crystals and trihydrate crystals. ing.
  • crystals are superior to amorphous materials in terms of stability and are excellent for providing high-quality pharmaceuticals.
  • amorphous rosuvastatin calcium has the property of being easily decomposed at room temperature, a more stable crystal can be said to be an industrially preferable form.
  • crystals generally have lower solubility than amorphous, and crystal forms with low solubility can be disadvantageous from the viewpoint of pharmacology such as bioavailability.
  • Pharmaceutical compounds may have high hygroscopicity depending on the type and substance form.
  • the high hygroscopicity of a pharmaceutical compound is a disadvantageous factor in the manufacture of pharmaceutical products.
  • the hygroscopicity may be suppressed by performing crystallization as compared with the amorphous body.
  • the hygroscopicity of rosuvastatin calcium was measured, it was found that not only the amorphous body but also the crystal showed high hygroscopicity, which was a problem in production.
  • Patent Document 1 Japanese Patent No. 26488897 (Patent Document 1) and Japanese Translation of PCT International Publication No. 2008-546730 (Patent Document 2) disclose methods for producing amorphous rosuvastatin calcium, but these documents improve the chemical purity. Is not shown.
  • Patent Document 3 discloses a method for producing amorphous rosuvastatin calcium in which rosuvastatin is purified and isolated with another salt and then subjected to salt exchange.
  • the production method via another salt is inefficient in terms of workability and production cost, and the remaining salt is also a problem.
  • TW-1 type crystals are extremely stable and do not exhibit hygroscopicity, so they are also defined by the moisture value.
  • the rosuvastatin calcium TW-1 type crystal of the present invention comprises a liquid selected from an ester group, a ketone group, an ether group, an aliphatic hydrocarbon group, an aromatic hydrocarbon group, a halogenated hydrocarbon group, and a mixed liquid group thereof. Prepared from a mixture with water.
  • a liquid and water selected from an ester group, a ketone group, an ether group, an aliphatic hydrocarbon group, an aromatic hydrocarbon group, a halogenated hydrocarbon group, and a mixed liquid group thereof are added to rosuvastatin calcium.
  • the obtained solid is separated, dried, and then conditioned to obtain a TW-1 type crystal.
  • any material form may be used before the TW-1 type crystal is formed.
  • the raw material rosuvastatin calcium may be in any substance form, and the raw material may or may not be dissolved in the solution.
  • a liquid selected from an ester group, a ketone group, an ether group, an aliphatic hydrocarbon group, an aromatic hydrocarbon group, a halogenated hydrocarbon group, and a mixed liquid group thereof;
  • the total volume with water is preferably 0.3 to 35 mL, more preferably 10 to 30 mL, per 1 g of rosuvastatin calcium.
  • the mixing ratio of liquid and water selected from the ester group, ketone group, ether group, aliphatic hydrocarbon group, aromatic hydrocarbon group, halogenated hydrocarbon group, and mixed liquid group thereof is 24. Is preferably 1: 1 to 1: 1, more preferably 4: 1 to 2.5: 1.
  • aliphatic esters and aromatic esters preferably aliphatic esters, more preferably ethyl acetate, isopropyl acetate, and propyl acetate are used as the ester group.
  • aliphatic ketones aromatic ketones, preferably aliphatic ketones, more preferably lower aliphatic ketones, more preferably acetone, methyl ethyl ketone, and methyl isobutyl ketone are used.
  • ether group aliphatic ethers, aromatic ethers, preferably aliphatic ethers, more preferably acyclic aliphatic ethers, cyclic aliphatic ethers, more preferably dimethyl ether, tetrahydrofuran, and cyclopentylmethyl ether are used.
  • aliphatic hydrocarbon hexane, heptane or cyclohexane is preferably used.
  • aromatic hydrocarbon group benzene, toluene and xylene are preferably used.
  • halogen hydrocarbon group aliphatic halogen and aromatic halogen, preferably dichloromethane, 1,2-dichloroethane and chlorobenzene are used.
  • a liquid selected from an ester group, a ketone group, an ether group, an aliphatic hydrocarbon group, an aromatic hydrocarbon group, a halogenated hydrocarbon group, and a mixture thereof.
  • stirring can be performed for 3 hours, preferably 5 hours or more. At this time, a good yield can be obtained by adding seed crystals.
  • stirring can be performed in an arbitrary temperature range, preferably 10 ° C. to 50 ° C., more preferably 23 ° C. to 35 ° C.
  • the drying time of the solid drying stage of the present invention can be performed for any time, preferably 5 hours or more, more preferably 8 hours or more.
  • the drying pressure can be carried out under reduced pressure, preferably under reduced pressure of 200 mmHg or less. Moreover, it can also carry out by ventilating dry gas, such as nitrogen.
  • the drying temperature can be 20 ° C. to 60 ° C., preferably 30 ° C. to 50 ° C.
  • the humidity control used in the present specification is to adjust the moisture value of the solid.
  • the form of humidity control includes exposure of the solid to an atmosphere in a specific humidity condition, contact of the solid with water and water vapor, etc., and the solid is dynamic or static.
  • the atmosphere may be either dynamic or static.
  • the optimum humidity control form is preferably exposed to a humidity of 40%, more preferably 50% or more.
  • Any temperature can be used as the temperature at the time of humidity control according to the present invention, but it can be preferably 15 to 40 ° C.
  • the time required for conditioning the humidity of the present invention may vary depending on other conditions, but is any time, preferably 3 hours or more, more preferably 5 hours or more.
  • the water content of the TW-1 type crystal obtained by the present invention is about 2.1 to 2.4%.
  • the production of TW-1 type crystals by humidity control can be based on the presence or absence of a change in water content.
  • DSC of rosuvastatin calcium TW-1 has a characteristic peak.
  • the powder X-ray diffraction pattern was measured with X'Pert PRO PW3040 / 60 (X'CELERATOR detector) manufactured by PANalytical using CuK ⁇ radiation.
  • the moisture value of the rosuvastatin calcium TW-1 type crystal obtained by the production method of the present invention was measured with a Karl Fischer moisture meter (AQUACOUNTER AQV-2200, Hiranuma Sangyo Co., Ltd.) or a device equivalent thereto.
  • HPLC High Performance Liquid Chromatography
  • detector UV
  • software Empower2 column: (L-Column ODS, 3 ⁇ m, 4.6 ⁇ 150 mm), mobile phase: 0.1% acetic acid aqueous solution. / Acetonitrile, column temperature: room temperature, flow rate: 1.0 mL / min, wavelength: 242 nm, injection volume: 10 ⁇ L.
  • Example 1 Preparation of rosuvastatin calcium TW-1 type crystal 1
  • rosuvastatin calcium To 5 g of rosuvastatin calcium, 100 mL of ethyl acetate and 25 mL of water were added and stirred at 25 ° C. overnight. The resulting solid was collected by filtration, washed with 5 mL of ethyl acetate, and dried under reduced pressure at 40 ° C. This solid was allowed to stand at room temperature for 5.5 hours in the presence of a saturated sodium chloride aqueous solution in a desiccator to obtain 3.7 g of the title compound.
  • Example 4 Preparation of rosuvastatin calcium TW-1 type crystal 4 12.0 kg of rosuvastatin calcium was added to 204 L of ethyl acetate and dissolved by heating to 30 ° C., followed by foreign matter filtration. The dissolution tank and filtration path were washed with 36 L of ethyl acetate. The filtrates were combined and heated to 30 ° C., 60 L of purified water was added, 0.24 kg of seed crystals were further added, and the mixture was stirred at 30 ° C. for 20 hours. The resulting crystals were collected by filtration, washed with 30 L of purified water, and dried by blowing nitrogen at 50 ° C. to obtain 21.7 kg of dry crystals. Nitrogen adjusted to 25 ° C. and a relative humidity of 60 to 65% was passed through the crystal layer for 24 hours while analyzing the water content to obtain 10.3 kg of the title compound. The water content was 2.4%.
  • TW-1 type crystal of the present invention The effects of the TW-1 type crystal of the present invention are shown below. Trihydrate and anhydride crystals were prepared based on Patent Document 5, and A-type crystals were prepared based on Patent Document 4.
  • the rosuvastatin calcium TW-1 type crystal of the present invention did not show any deterioration at 70 ° C. for 9 days, and was found to be an extremely stable crystal form.
  • the rosuvastatin calcium TW-1 type crystal of the present invention is stable compared to the amorphous body, and surprisingly, contrary to the general tendency that the crystal is less soluble than the amorphous body, In contrast, it was more soluble than amorphous. That is, the solubility of the TW-1 type crystal in water was 8.03 mg / mL which is higher than 7.50 mg / mL of the amorphous substance. Furthermore, the solubility of the trihydrate crystal and the A type crystal was 1.89 mg / mL and 3.13 mg / mL, and the TW-1 type crystal showed solubility of 4 times and 2.5 times or more thereof, respectively. .
  • the rosuvastatin calcium TW-1 type crystal of the present invention did not show any hygroscopicity that is a manufacturing defect found in the amorphous, A-type and anhydrous crystals of rosuvastatin calcium disclosed heretofore. Even when the TW-1 type crystal was left to stand at 75% humidity for 2 days, the water content was 2.2%, and no increase in the water content was observed. On the other hand, the anhydrous crystal showing the same solubility as the TW-1 type crystal showed a significant improvement in moisture value, and it became clear that it had hygroscopicity.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/JP2013/075880 2012-09-27 2013-09-25 Nouvelle forme cristalline de rosuvastatine de calcium et son procédé de fabrication Ceased WO2014050874A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2012-213663 2012-09-27
JP2012213663 2012-09-27

Publications (1)

Publication Number Publication Date
WO2014050874A1 true WO2014050874A1 (fr) 2014-04-03

Family

ID=50388269

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2013/075880 Ceased WO2014050874A1 (fr) 2012-09-27 2013-09-25 Nouvelle forme cristalline de rosuvastatine de calcium et son procédé de fabrication

Country Status (2)

Country Link
TW (1) TW201418227A (fr)
WO (1) WO2014050874A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2017061627A1 (ja) * 2015-10-09 2018-07-26 三栄源エフ・エフ・アイ株式会社 ポリフェノール含有固体組成物

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105153040B (zh) * 2015-10-15 2018-04-13 江苏师范大学 瑞舒伐他汀钙新晶型及其制备方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002539078A (ja) * 1999-01-09 2002-11-19 アストラゼネカ アクチボラグ 結晶質の化合物ビス［（ｅ）−７−［４−（４−フルオロフェニル）−６−イソプロピル−２−［メチル（メチルスルホニル）アミノ］ピリミジン−５−イル］（３ｒ，５ｓ）−３，５−ジヒドロキシ−６−ヘプテン酸］カルシウム塩
JP2007505090A (ja) * 2003-09-10 2007-03-08 アストラゼネカ・ユーケイ・リミテッド ビス［（ｅ）−７−［４−（４−フルオロフェニル）−６−イソプロピル−２−［メチル（メチルスルホニル）アミノ］ピリミジン−５−イル］（３ｒ，５ｓ）−３，５−ジヒドロキシ−６−ヘプテン酸］カルシウム塩の結晶形
JP2008528542A (ja) * 2005-01-31 2008-07-31 チバ ホールディング インコーポレーテッド ロスバスタチンカルシウム塩の結晶形
JP2008539278A (ja) * 2006-09-18 2008-11-13 テバ ファーマシューティカル インダストリーズ リミティド 結晶性ロスバスタチンカルシウム
WO2010081861A1 (fr) * 2009-01-14 2010-07-22 Krka, Tovarna Zdravil, D.D., Novo Mesto Procédé de préparation de rosuvastatine
CN102010375A (zh) * 2010-11-27 2011-04-13 天津市汉康医药生物技术有限公司 一种稳定晶型的瑞舒伐他汀钙化合物
KR20110106207A (ko) * 2010-03-22 2011-09-28 주식회사 대웅제약 신규 결정형의 로수바스타틴 칼슘염 및 그의 제조방법
WO2012011129A2 (fr) * 2010-07-22 2012-01-26 Msn Laboratories Limited Nouveau polymorphe de sel de calcium d'acide bis[(e)-7-[4-(4-fluorophényl)-6-iso-propyl-2-[méthyl (méthylsulfonyl)amino]pyrimidin-5-yl](3r,5s)-3,5-dihydroxyhept-6-énoïque]

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002539078A (ja) * 1999-01-09 2002-11-19 アストラゼネカ アクチボラグ 結晶質の化合物ビス［（ｅ）−７−［４−（４−フルオロフェニル）−６−イソプロピル−２−［メチル（メチルスルホニル）アミノ］ピリミジン−５−イル］（３ｒ，５ｓ）−３，５−ジヒドロキシ−６−ヘプテン酸］カルシウム塩
JP2007505090A (ja) * 2003-09-10 2007-03-08 アストラゼネカ・ユーケイ・リミテッド ビス［（ｅ）−７−［４−（４−フルオロフェニル）−６−イソプロピル−２−［メチル（メチルスルホニル）アミノ］ピリミジン−５−イル］（３ｒ，５ｓ）−３，５−ジヒドロキシ−６−ヘプテン酸］カルシウム塩の結晶形
JP2008528542A (ja) * 2005-01-31 2008-07-31 チバ ホールディング インコーポレーテッド ロスバスタチンカルシウム塩の結晶形
JP2008539278A (ja) * 2006-09-18 2008-11-13 テバ ファーマシューティカル インダストリーズ リミティド 結晶性ロスバスタチンカルシウム
WO2010081861A1 (fr) * 2009-01-14 2010-07-22 Krka, Tovarna Zdravil, D.D., Novo Mesto Procédé de préparation de rosuvastatine
KR20110106207A (ko) * 2010-03-22 2011-09-28 주식회사 대웅제약 신규 결정형의 로수바스타틴 칼슘염 및 그의 제조방법
WO2012011129A2 (fr) * 2010-07-22 2012-01-26 Msn Laboratories Limited Nouveau polymorphe de sel de calcium d'acide bis[(e)-7-[4-(4-fluorophényl)-6-iso-propyl-2-[méthyl (méthylsulfonyl)amino]pyrimidin-5-yl](3r,5s)-3,5-dihydroxyhept-6-énoïque]
CN102010375A (zh) * 2010-11-27 2011-04-13 天津市汉康医药生物技术有限公司 一种稳定晶型的瑞舒伐他汀钙化合物

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2017061627A1 (ja) * 2015-10-09 2018-07-26 三栄源エフ・エフ・アイ株式会社 ポリフェノール含有固体組成物

Also Published As

Publication number Publication date
TW201418227A (zh) 2014-05-16

Similar Documents

Publication Publication Date Title
US10035802B2 (en) Solid state forms of ibrutinib
EP3174855B1 (fr) Sels conformères de 7-fluoro-2-(4-fluorophényl)-3-(1-méthyl-1h-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tétrahydroquinoléine-5-carboxylate de (2s,3s)-méthyle et leurs procédés de préparation
WO2017009784A1 (fr) Formes à l'état solide de sel de trisodium du complexe valsartan/sacubitril et de sacubitril
ES2834110T3 (es) Proceso para preparar ácidos (1R,3R)- y (1S,3S)-2,2-dihalo-3-(fenilo sustituido)ciclopropanocarboxílicos
KR20170078710A (ko) Jak 키나아제 억제제 바이설페이트의 결정형 및 이의 제조방법
WO2011140328A1 (fr) Intermédiaires de saxagliptine, formes polymorphiques de saxagliptine et leurs procédés de synthèse
JP2020172529A (ja) （４ｓ）−４−［４−シアノ−２−（メチルスルホニル）フェニル］−３，６−ジメチル−２−オキソ−１−［３−（トリフルオロメチル）フェニル］−１，２，３，４−テトラヒドロピリミジン−５−カルボニトリルの製造方法
EP2334685A2 (fr) Disodium de pemetrexed amorphe
WO2014050874A1 (fr) Nouvelle forme cristalline de rosuvastatine de calcium et son procédé de fabrication
CN105566384A (zh) 一种(E)-2-芳基-α,β-不饱和羰基膦酸酯衍生物的制备方法
US10717729B2 (en) Thiamine-organic acid salt
KR20140017207A (ko) 로수바스타틴 이소프로필 아민염, 이의 제조 방법 및 이를 이용한 로수바스타틴 헤미칼슘염의 제조방법
JP6768065B2 (ja) ベンゾピラン誘導体の精製方法、ベンゾピラン誘導体の結晶形およびベンゾピラン誘導体の結晶形の製造方法
CN116621817A (zh) 一种富马酸恩赛特韦的晶型及其制备方法、药物组合物和用途
CN107438595A (zh) 晶型及其制备方法
CA2523233C (fr) Sel d'acide (2s,3s)-3-[[(1s)-1-isobutoxymethyl-3-methylbutyl]carbamoyl]oxyrane-2-carboxylique
KR20180105450A (ko) 피마살탄 콜린염 및 이의 수화물의 제조방법
KR20180048939A (ko) 안드로겐 수용체 억제제의 결정체 형태 및 그의 제조 방법
EP3712136A1 (fr) Polymorphe de tébuconazole et son procédé de préparation
JP5613780B2 (ja) ラミブジンシュウ酸塩及びその製造方法
KR101019201B1 (ko) 덱시부프로펜 알지닌염의 제조방법
KR101158517B1 (ko) 고 순도 피타바스타틴 칼슘염 결정형 ａ의 제조방법
JP2019529410A (ja) 純粋で安定な結晶のラルテグラビルカリウム３型の製造方法
CN116283926A (zh) 枸橼酸坦度螺酮的制备方法及其在制剂中的应用
JP2021161097A (ja) テネリグリプチンの新規結晶形及びその製造方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13841225

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 13841225

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP