WO2002007736A1 - The process for manufacturing of clear liquid pharmaceutical composition of azithromycin - Google Patents
The process for manufacturing of clear liquid pharmaceutical composition of azithromycin Download PDFInfo
- Publication number
- WO2002007736A1 WO2002007736A1 PCT/IB2001/001313 IB0101313W WO0207736A1 WO 2002007736 A1 WO2002007736 A1 WO 2002007736A1 IB 0101313 W IB0101313 W IB 0101313W WO 0207736 A1 WO0207736 A1 WO 0207736A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- azithromycin
- solution
- clear liquid
- pharmaceutical composition
- water
- Prior art date
Links
Classifications
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Definitions
- the objective of present invention is to manufacture clear liquid pharmaceutical composition of Azithromycin.
- Azithromycin is the U.S.A.N. (generic name) for 9a ⁇ aza-9a-methyl-9-deoxo-9a- homoerythromycin A, a broad spectrum antimicrobial compound derived from erythromycin A.
- Azithromycin was independently discovered by Bright, U.S. Pat. No. 4,474,768 and Kobrehel et al., U.S. Pat. No. 4,517,359. These patents disclose that azithromycin and certain derivatives thereof possess antibacterial properties and are accordingly useful as antibiotics.
- Azithromycin is a macrolide antibiotic used for treating infections. This is available in a solid oral dosage form and for intravenous use as, lyophilized powder. It is desirable to have a clear liquid formulation also for treating severe infections by intravenous administration of the drug.
- liquid preparation which is ready to use.
- it is not soluble in water or other known solvents, for this purpose, it is being marketed as lyophilized preparation which is reconstituted prior to use.
- the present invention describes a method for preparing clear liquid pharmaceutical composition of Azithromycin. This is made possible by solubilizing azithromycin in water at pH 4.0 to 6.0 and then adding sodium hydroxide, thereby changing the pH between 6.0 to 7.0.
- Azithromycin liquid so prepared as per the invention remains clear and was found to be stable for longer period.
- the objective of the present invention is to provide azithromycin as a liquid preparation which is stable and can be ready to use.
- azithromycin is soluble in water at pH between 4.0 to 6.0.
- azithromycin is soluble in other solvents like polyalcohols which comprises of propylene glycol, glycerine, polyethylene glycol and sorbitol.
- polyalcohols which comprises of propylene glycol, glycerine, polyethylene glycol and sorbitol.
- Citric acid anhydrous is dissolved in 200 ml Water for injection.
- the solution is filtered through 0.22 micron membrane and filled in vials.
- the vials are then sterlized by autoclaving at 120°C with 15 LB pressure for 20 minutes.
- Solvents which can be used for the preparation of liquid formulation of Azithromycin are:
- the preparation so prepared as per the present invention can be used for administration through oral or parenteral route.
Abstract
Azithromycin is a macrolide antibiotic used for treating infections. This is available in a solid oral dosage form. It is desirable to have a clear liquid formulaiton also for treating severe infections by intravenous administration of the drug. Currently, it is not possible to manufacture liquid preparation which is ready to use. As it is not soluble in water or other known solvents, for this purpose, it is being marketed as lyophilized preparation which is reconstituted prior to use. According to present invention, it is found that it is soluble in water at pH 5.0. The change in pH can be obtained by adding citric acid in a desired concentration. However, this solution is not stable, and precipitates are seen over the time. According to the present invention, this solution is stabilized by addition of sodium salts like sodium hydroxide, thereby changing its pH from 5.0 to 7.0. The solution so prepared remains clear and is stable for a longer period.
Description
FORM 2
THE PATENTS ACT, 1970
THE COMPLETE SPECIFICATION
(See section 10)
1. THE PROCESS FOR MANUFACTURING OF CLEAR LIQUID PHARMACEUTICAL COMPOSITION OF AZITHROMYCIN
2. Cadila Pharmaceuticals Limited, IRM House, Off CG. Road, Navrangpura, Ahmedabad- 380009, Gujarat, India, an Indian company.
3. The following specification particularly describes and ascertains the nature of this invention and the manner in which it has to be performed.
FIELD OF INVENTION
The objective of present invention is to manufacture clear liquid pharmaceutical composition of Azithromycin.
BACKGROUND OF THE INVENTION
Azithromycin is the U.S.A.N. (generic name) for 9a~aza-9a-methyl-9-deoxo-9a- homoerythromycin A, a broad spectrum antimicrobial compound derived from erythromycin A. Azithromycin was independently discovered by Bright, U.S. Pat. No. 4,474,768 and Kobrehel et al., U.S. Pat. No. 4,517,359. These patents disclose that azithromycin and certain derivatives thereof possess antibacterial properties and are accordingly useful as antibiotics.
Azithromycin is a macrolide antibiotic used for treating infections. This is available in a solid oral dosage form and for intravenous use as, lyophilized powder. It is desirable to have a clear liquid formulation also for treating severe infections by intravenous administration of the drug.
Currently, it is not possible to manufacture liquid preparation which is ready to use. As it is not soluble in water or other known solvents, for this purpose, it is being marketed as lyophilized preparation which is reconstituted prior to use.
REFERENCES:
U.S. patent no. 4474768
N- ethyl 11-aza-10- eoxo-10-dihydro-erytromycin A, intermediates therefore.
Bright; Gene M
Pfizer Inc.
U.S. patent no. 4517359
11 -Methyl-11 -aza-4-0-cladinosyl-6-0-desosaminyl-15-ethyl-7, 13, 14- trihydroxy-3,5,7,9,12,14-hexamethyl-oxacyclopentadecane-2-one and derivatives thereof.
Kobrehel; Gabrijela; Djokic; Slobodan
Sour Pliva farmaceutska, kemijska prehrambena i kozmeticka industrija
SUMMARY OF THE INVENTION
The present invention describes a method for preparing clear liquid pharmaceutical composition of Azithromycin. This is made possible by solubilizing azithromycin in water at pH 4.0 to 6.0 and then adding sodium hydroxide, thereby changing the pH between 6.0 to 7.0.
Azithromycin liquid so prepared as per the invention remains clear and was found to be stable for longer period.
DESCRIPTION OF THE INVENTION
According to the present invention is described a method of preparing clear liquid pharmaceutical composition of Azithromycin.
The objective of the present invention is to provide azithromycin as a liquid preparation which is stable and can be ready to use.
According to present invention it is found that azithromycin is soluble in water at pH between 4.0 to 6.0.
It is also found that azithromycin is soluble in other solvents like polyalcohols which comprises of propylene glycol, glycerine, polyethylene glycol and sorbitol.
However when a solution is prepared using azithromycin at pH between 4.0 to 6.0, it does not remain stable for a long term and develops precipitation. Thus, the pharmaceutical composition prepared is not stable.
It is further observed as per the present invention that when pH is raised further, then azithromycin remains in solution and product is also stable for a longer time.
EXAMPLE 1 :
1. Citric acid anhydrous is dissolved in 200 ml Water for injection.
2. The pH of the above solution is adjusted to 4.0 to 6.0 with Sodium hydroxide.
3. Azithromycin is added to this solution and mixed.
4. Now Sodium hydroxide solution is added till clear solution is added, and the pH is between 6.0 to 7.0.
5. The solution is filtered through 0.22 micron membrane and filled in vials.
6. The vials are then sterlized by autoclaving at 120°C with 15 LB pressure for 20 minutes.
EXAMPLE 2:
Solvents which can be used for the preparation of liquid formulation of Azithromycin are:
1. Water
2. Polyalcohol: a) Propylene glycol b) Polyethylene glycol c) glycerine d) Sorbitol
The preparation so prepared as per the present invention can be used for administration through oral or parenteral route.
Claims
1. The process of manufacturing clear liquid pharmaceutical composition of Azithromycin, comprises the steps of: a) Adding azithromycin to solvent with appropriate pH. b) Mixing of above preparation to obtain clear liquid preparation.
2. The clear liquid preparation of azithromycin as claimed in claim 1 is further stabilized by bringing pH from 5.5 to 7.0.
3. The solvent as claimed in claim 1 is water.
4. The solvent as claimed in claim 1 is a polyalcohol like propylene glycol, glycerine, polyethylene glycol and the like.
5. The solvent as claimed in claim 1 and 4 is selected from propylene glycol, glycerine, polyethylene glycol, sorbitol and the like.
6. The solvent as claimed in claim 1 is made up of single ingredient or a combination of them.
7. The pH as claimed in claim 1 is between 4.0 to 6.0.
8. The process as described in claim 1 and as described in examples 1 and 2.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN687MU2000 | 2000-07-24 | ||
IN687/MUM/2000 | 2000-07-24 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2002007736A1 true WO2002007736A1 (en) | 2002-01-31 |
Family
ID=11097267
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2001/001313 WO2002007736A1 (en) | 2000-07-24 | 2001-07-23 | The process for manufacturing of clear liquid pharmaceutical composition of azithromycin |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2002007736A1 (en) |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1381601A1 (en) * | 2001-04-25 | 2004-01-21 | Hanmi Pharm. Co., Ltd. | Clathrate of azithromycin hydrate with 1,2-propyleneglycol, method for the manufacture thereof and pharmaceutical composition comprising same |
ES2220229A1 (en) * | 2003-05-29 | 2004-12-01 | Quimica Sintetica, S.A. | Addition salts of azithromycin and citric acid and process for preparing them |
US6861413B2 (en) | 2001-05-22 | 2005-03-01 | Pfizer Inc. | Stable non-dihydrate azithromycin oral suspensions |
US6977243B2 (en) | 2001-05-22 | 2005-12-20 | Pfizer Inc. | Crystal forms of azithromycin |
ES2289911A1 (en) * | 2003-05-29 | 2008-02-01 | Quimica Sintetica, S.A. | Addition salts of azithromycin and citric acid and process for preparing them |
US8106111B2 (en) | 2009-05-15 | 2012-01-31 | Eastman Chemical Company | Antimicrobial effect of cycloaliphatic diol antimicrobial agents in coating compositions |
CN102552918A (en) * | 2012-02-02 | 2012-07-11 | 山东齐都药业有限公司 | Stabilizer of lyophilized powder injection for azithromycin injection |
CN102755287A (en) * | 2012-07-20 | 2012-10-31 | 天津药业集团新郑股份有限公司 | Azithromycin oral liquid and preparation method thereof |
EP3307275A4 (en) * | 2015-06-10 | 2019-01-09 | Piedmont Animal Health, LLC | Injectable antibiotic formulations and use thereof |
CN112618496A (en) * | 2020-12-31 | 2021-04-09 | 海南葫芦娃药业集团股份有限公司 | Preparation method of azithromycin freeze-dried powder injection for injection |
CN112870171A (en) * | 2020-12-31 | 2021-06-01 | 海南葫芦娃药业集团股份有限公司 | Freeze-drying method of azithromycin for injection |
WO2022025831A1 (en) * | 2020-07-26 | 2022-02-03 | Verano Ilac Sanayi Ve Ticaret Anonim Sirketi | Pharmaceutical compositions for injection comprising tulathromycin |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0307128A2 (en) * | 1987-09-10 | 1989-03-15 | Pfizer Inc. | Azithromycin and derivatives as antiprotozoal agents |
WO2000057866A2 (en) * | 1999-03-31 | 2000-10-05 | Insite Vision Incorporated | Use of azalide antibiotics for the topical treatment or prevention of ocular infections |
EP1075837A2 (en) * | 1999-08-09 | 2001-02-14 | S.I.F.I. Società Industria Farmaceutica Italiana S.p.A. | Process for the preparation of aqueous formulations for ophthalmic use |
-
2001
- 2001-07-23 WO PCT/IB2001/001313 patent/WO2002007736A1/en active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0307128A2 (en) * | 1987-09-10 | 1989-03-15 | Pfizer Inc. | Azithromycin and derivatives as antiprotozoal agents |
WO2000057866A2 (en) * | 1999-03-31 | 2000-10-05 | Insite Vision Incorporated | Use of azalide antibiotics for the topical treatment or prevention of ocular infections |
EP1075837A2 (en) * | 1999-08-09 | 2001-02-14 | S.I.F.I. Società Industria Farmaceutica Italiana S.p.A. | Process for the preparation of aqueous formulations for ophthalmic use |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2002253698B2 (en) * | 2001-04-25 | 2005-12-08 | Hanmi Pharm. Co., Ltd. | Clathrate of azithromycin hydrate with 1,2-propyleneglycol, method for the manufacture thereof and pharmaceutical composition comprising same |
EP1381601A4 (en) * | 2001-04-25 | 2004-06-16 | Hanmi Pharm Ind Co Ltd | Clathrate of azithromycin hydrate with 1,2-propyleneglycol, method for the manufacture thereof and pharmaceutical composition comprising same |
EP1381601A1 (en) * | 2001-04-25 | 2004-01-21 | Hanmi Pharm. Co., Ltd. | Clathrate of azithromycin hydrate with 1,2-propyleneglycol, method for the manufacture thereof and pharmaceutical composition comprising same |
US7205394B2 (en) | 2001-04-25 | 2007-04-17 | Hanmi Pharm. Co., Ltd. | Clathrate of azithromycin hydrate with 1,2-propyleneglycol, method for the manufacture thereof and pharmaceutical composition comprising same |
US7307156B2 (en) | 2001-05-22 | 2007-12-11 | Pfizer Inc. | Crystal forms of azithromycin |
US7309782B2 (en) | 2001-05-22 | 2007-12-18 | Pfizer Inc. | Crystal forms of azithromycin |
US6977243B2 (en) | 2001-05-22 | 2005-12-20 | Pfizer Inc. | Crystal forms of azithromycin |
US7053192B2 (en) | 2001-05-22 | 2006-05-30 | Pfizer Inc. | Crystal forms of azithromycin |
US7081525B2 (en) | 2001-05-22 | 2006-07-25 | Pfizer Inc. | Crystal forms of azithromycin |
US7105179B2 (en) | 2001-05-22 | 2006-09-12 | Pfizer Inc. | Crystal forms of azithromycin |
US6861413B2 (en) | 2001-05-22 | 2005-03-01 | Pfizer Inc. | Stable non-dihydrate azithromycin oral suspensions |
US7282486B2 (en) | 2001-05-22 | 2007-10-16 | Pfizer Inc | Crystal forms of azithromycin |
CN100415764C (en) * | 2003-05-29 | 2008-09-03 | 新特提卡化学股份有限公司 | Addition salts of azithromycin and citric acid and process for preparing them |
ES2220229A1 (en) * | 2003-05-29 | 2004-12-01 | Quimica Sintetica, S.A. | Addition salts of azithromycin and citric acid and process for preparing them |
ES2289911A1 (en) * | 2003-05-29 | 2008-02-01 | Quimica Sintetica, S.A. | Addition salts of azithromycin and citric acid and process for preparing them |
WO2004106355A1 (en) * | 2003-05-29 | 2004-12-09 | Quimica Sintetica, S.A. | Addition salts of azithromycin and citric acid and process for preparing them |
US8106111B2 (en) | 2009-05-15 | 2012-01-31 | Eastman Chemical Company | Antimicrobial effect of cycloaliphatic diol antimicrobial agents in coating compositions |
CN102552918A (en) * | 2012-02-02 | 2012-07-11 | 山东齐都药业有限公司 | Stabilizer of lyophilized powder injection for azithromycin injection |
CN102755287A (en) * | 2012-07-20 | 2012-10-31 | 天津药业集团新郑股份有限公司 | Azithromycin oral liquid and preparation method thereof |
EP3307275A4 (en) * | 2015-06-10 | 2019-01-09 | Piedmont Animal Health, LLC | Injectable antibiotic formulations and use thereof |
US10286003B2 (en) | 2015-06-10 | 2019-05-14 | Piedmont Animal Health, Llc | Injectable antibiotic formulations and use thereof |
US10729709B2 (en) | 2015-06-10 | 2020-08-04 | Piedmont Animal Health Inc. | Injectable antibiotic formulations and use thereof |
AU2016274949B2 (en) * | 2015-06-10 | 2021-07-15 | Dechra Veterinary Products, Llc | Injectable antibiotic formulations and use thereof |
US11628180B2 (en) | 2015-06-10 | 2023-04-18 | Dechra Veterinary Products, Llc | Injectable antibiotic formulations and use thereof |
WO2022025831A1 (en) * | 2020-07-26 | 2022-02-03 | Verano Ilac Sanayi Ve Ticaret Anonim Sirketi | Pharmaceutical compositions for injection comprising tulathromycin |
CN112618496A (en) * | 2020-12-31 | 2021-04-09 | 海南葫芦娃药业集团股份有限公司 | Preparation method of azithromycin freeze-dried powder injection for injection |
CN112870171A (en) * | 2020-12-31 | 2021-06-01 | 海南葫芦娃药业集团股份有限公司 | Freeze-drying method of azithromycin for injection |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2478643C2 (en) | Macrocyclic polymorphs, compositions containing such polymorphs, and methods for using and preparing them | |
WO2002007736A1 (en) | The process for manufacturing of clear liquid pharmaceutical composition of azithromycin | |
JPS60169415A (en) | Non-aqueous ivermectin prescription having improved antivermifugal activity | |
JP2003522108A (en) | Macrolide aqueous solution | |
CN102209542A (en) | Octenidine composition | |
KR20030068203A (en) | Cyclodextrin-containing pharmaceutical preparation | |
US6861413B2 (en) | Stable non-dihydrate azithromycin oral suspensions | |
WO2004096822A3 (en) | Pyridyl substituted ketolide antibiotics | |
WO2004112761A2 (en) | Stable 5, 10-methylene-tetrahydrofolate pharmaceutical compounds | |
AU717148B2 (en) | Water miscible erythromycin solutions | |
JP2003171274A (en) | Medicinal composition and disinfectant for treating infection with drug-resistant microorganism | |
CN1046632C (en) | Injectable preparations containing cephalosporin medicament | |
CN102617643B (en) | Riboflavin sodium phosphate compound | |
DE60200391T2 (en) | Antibacterial azide compositions | |
HU217553B (en) | Process for the preparation of azithromycin dihydrochloride | |
EP0302836B1 (en) | Pharmaceutical compositions for topical use containing miocamycin | |
EP1189913B1 (en) | Diphosphate salt of a 4"-substituted-9-deoxo-9a-aza-9a-homoerythromycin derivative and its pharmaceutical composition | |
EP1498141B1 (en) | Stable non-dihydrate azithromycin oral suspensions | |
ES2268446T3 (en) | DERIVATIVES 9A-N- (N '- (4- (SULFONIL) PHENYLCARBAMOIL)) REPLACED FROM 9-DESOXO-9-DIHIDRO-9A-AZA-9A-HOMOERITROMICINA AY 5-O-DESOSAMINIL-9-DESOXO-9-DIHYD -9A-AZA-9A-HOMOERITRONOLIDO A. | |
WO2000004906A1 (en) | Non-aqueous anthelmintic composition | |
PL124423B1 (en) | Process for preparing novel epimer d of sesquisodium salt of oxa-beta-lactamidicarboxylic acid | |
EP0369503B1 (en) | Method for the control of pneumocystis carinii | |
US20070270356A1 (en) | Substituted 9A-N-[N'-(Benzenesulfonyl)Carbamoyl-Y-Aminopropyl] and 9A-N-[N'(B-Cyanoethyl)-N'-(Benzenesulfonyl)Carbamoyl-Y-Aminopropyl]Derivatives of 9-Deoxo-9-Dihydro-9A-Aza-9A-Homoerithomycin A | |
CN102552302B (en) | Compound josamycin nano-emulsion antibacterial drug and preparation method thereof | |
KR910001310B1 (en) | 3-substituted-7-substituted amino cephalosporanic acid alkali metal salts and its process |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
122 | Ep: pct application non-entry in european phase |