WO2005020979A1 - Procede de preparation de compositions pharmaceutiques a base de nateglinide - Google Patents
Procede de preparation de compositions pharmaceutiques a base de nateglinide Download PDFInfo
- Publication number
- WO2005020979A1 WO2005020979A1 PCT/IB2004/051678 IB2004051678W WO2005020979A1 WO 2005020979 A1 WO2005020979 A1 WO 2005020979A1 IB 2004051678 W IB2004051678 W IB 2004051678W WO 2005020979 A1 WO2005020979 A1 WO 2005020979A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- process according
- nateglinide
- pharmaceutically acceptable
- particle size
- pharmaceutically
- Prior art date
Links
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
Definitions
- the present invention relates to a pharmaceutical composition comprising nateglinide, and a process for its preparation.
- U.S. Patent No. 6,559,188 describes compositions of nateglinide or a pharmaceutically acceptable salt thereof wherein lactose and microcrystalline cellulose are used as fillers alone or in combination. The final formulation is formed without a pulverization step.
- nateglinide when co-sifted and/or co- milled with pharmaceutical inert carriers, these inert carriers give a 'cushioning effect' to nateglinide, which leads to stable dosage forms with an enhanced dissolution profile.
- Finely milled particles possess a high surface energy and charge on them.
- a pharmaceutical inert carrier helps in neutralizing the surface charge by providing a layer between two particles and thereby separating them. This separation of particles leads to an increase in surface area and improved dissolution. Disclosure
- nateglinide includes co-milling nateglinide and one or more pharmaceutically inert carriers to form a blend; granulating the blend to form granules; drying and sizing the granules; and compressing the granules into tablets or filling into capsules.
- the nateglinide may be the Form B or the Form H type crystal modification.
- the silicate derivatives may be one or more of colloidal silicon dioxide, magnesium silicate, magnesium trisilicate, magnesium and aluminum silicate.
- the silicate derivative may be colloidal silicon dioxide.
- the cellulose derivatives may be one or more of microcrystalline cellulose and car- boxymethylcellulose .
- the clays may be one or more of veegum, bentonite and mixtures thereof.
- the ratio of nateglinide to the pharmaceutically inert carrier may be in a range from about 10:1 to about 1:2.
- the nateglinide may have a particle size of d90 ⁇ 45 ⁇ m or may have a particle size of d90 ⁇ 30 ⁇ m.
- Embodiments of the process may also include one or more pharmaceutically acceptable excipients with the co-milled blend prior to granulation.
- the one or more pharmaceutically acceptable excipients may include fillers, binders, disintegrants, surfactants, lubricants, colorings and flavoring agents
- Embodiments of the process may include one or more of the following features.
- the pharmaceutically inert carrier may be one or more of silicate derivatives, cellulose derivatives and clays.
- the silicate derivatives may be one or more of colloidal silicon dioxide, magnesium silicate, magnesium trisilicate, magnesium and aluminum silicate.
- the silicate derivative may be colloidal silicon dioxide.
- the cellulose derivatives may be one or more of macrocrystalline cellulose and car- boxymethylcellulose.
- the clays may be one or more of veegum, bentonite and mixtures thereof.
- the ratio of nateglinide to the pharmaceutically inert carrier may be in a range from about 10:1 to about 1:2.
- the nateglinide may have a particle size of d90 ⁇ 45 ⁇ m or may have a particle size of d90 ⁇ 30 ⁇ m.
- Embodiments of the process may also include one or more pharmaceutically acceptable excipients with the co-sifted blend prior to granulation.
- the one or more pharmaceutically acceptable excipients may include fillers, binders, disintegrants, surfactants, lubricants, colorings and flavoring agents
- the process may also include at least one other anti-diabetic compound with the co- milled blend prior to granulation.
- the antidiabetic compound may be glitazones, sulfonyl urea derivatives and metformin, either in free form or in form of a pharmaceutically acceptable salt.
- an oral pharmaceutical composition that includes nateglinide or pharmaceutically acceptable salts thereof and one or more pharmaceutically inert carriers.
- the nateglinide or a pharmaceutically acceptable salt thereof may have a particle size of d90 ⁇ 30 ⁇ m.
- a method for the treatment of metabolic disorders, type 2 diabetes mellitus, or a disease or condition associated with diabetes mellitus includes administering to a patient in need thereof a pharmaceutical composition that includes nateglinide or pharmaceutically acceptable salts thereof; and one or more pharmaceutically inert carriers.
- the nateglinide or a pharmaceutically acceptable salt thereof may have a particle size of d90 ⁇ 30 ⁇ m.
- the term 'nateglinide' as used herein includes nateglinide base as well as pharmaceutically acceptable salts thereof, in crystalline or amorphous form.
- the nateglinide may be the B- or H-type crystal modification.
- the particle size of the nateglinide may be d90 ⁇ 45 ⁇ m, or may be d90 ⁇ 30 ⁇ m.
- the term 'pharmaceutically inert carrier' refers to a substance, which is physiologically acceptable and compatible with the drug and other excipients in the dosage form and has a large surface area for drug particle adso ⁇ tion. By virtue of such adso ⁇ tion, the effective surface area exposed to the dissolution media is increased many fold, which thereby increases the rate of dissolution. Such adso ⁇ tion of the drug on the inert carrier's surface also prevents the re-agglomeration of drug particles due to the neutralization of surface charges on the drug particles generated during milling. Carriers also help in the wetting of a drug. These inert carriers improve the uptake of water by capillary action, thereby enhancing the drug's dissolution rate.
- the inert carriers also form a layer around the drug which provides a 'cushioning effect'. Due to this layer around the drug, the drug remains stable even upon the application of external stress.
- the ratio of nateglinide to the pharmaceutically inert carriers may be in the range of about 10:1 to about 1:2.
- Suitable pharmaceutically inert carriers include one or more of silicate derivatives such as, magnesium silicate, colloidal silicon dioxide, magnesium trisilicate, magnesium aluminum silicate; cellulose derivatives such as, microcrystalline cellulose, carboxymethylcellulose; and clays such as, veegum, bentonite and mixtures thereof.
- silicate derivatives such as, magnesium silicate, colloidal silicon dioxide, magnesium trisilicate, magnesium aluminum silicate
- cellulose derivatives such as, microcrystalline cellulose, carboxymethylcellulose
- clays such as, veegum, bentonite and mixtures thereof.
- colloidal silicon dioxide may be used alone or in combination with other cellulose derivatives.
- the process of co-milling nateglinide and pharmaceutically inert carriers may be carried out in one or more conventional milling instruments including air jet mill, multi mill, ball mill or any other method of particle attrition.
- the process of co- milling nateglinide with colloidal silicon dioxide may be carried out in an accelerated air-jet mill.
- the process of co-sifting nateglinide with colloidal silicon dioxide may be carried out by mixing and co-sifting repeatedly till a uniform mixture is formed.
- the co-sifted and/or co-milled mixture of nateglinide and pharmaceutically inert carriers may be further processed with pharmaceutically acceptable excipients into various dosage forms including one or more of tablets, capsules, and pills. These dosage forms, may be made by one or more of comminuting, mixing, granulation, melting, sizing, filling, drying, molding, immersing, coating, and compressing.
- compositions of nateglinide may be prepared by the process of blending co-sifted and/or co-milled mixtures with one or more pharmaceutically acceptable excipients; wet granulating the blend with a granulating fluid or solution/ dispersion of pharmaceutically acceptable excipients in the granulating fluid; drying and sizing the granules; and compressing the granules into tablets or filling into capsules.
- compositions of nateglinide may also be prepared by the process of blending the co-sifted and/or co-milled mixture with one or more pharmaceutically acceptable excipients; dry granulating the blend with a roller compactor or slugging; drying and sizing the granules; and compressing the granules into tablets or filling into capsules.
- compositions of nateglinide Form B which have a particle size of d90 ⁇ 45 ⁇ m, may be prepared by the process of blending the co-sifted and/or co-milled mixture with one or more pharmaceutically acceptable excipients; and compressing the blend into tablets or filling into capsules.
- the co-sifted/co-milled mixture of nateglinide and inert carriers may be further mixed with one or more anti-diabetic compound prior to granulation.
- Suitable compounds include one or more of glitazones, sulfonyl urea derivatives and metformin. These compounds may be in free form or in the form of a pharmaceutically acceptable salt.
- composition excluding the active drug substance.
- Suitable fillers include one or more of corn starch, lactose, white sugar, sucrose, sugar compressible, sugar confectioners, glucose, sorbitol, calcium carbonate, calcium phosphate-dibasic, calcium phosphate-tribasic, calcium sulfate, microcrystalline cellulose, silicif ⁇ ed microcrystalline cellulose, cellulose powdered, dextrates, dextrins, dextrose, fructose, kaolin, lactitol, mannitol, sorbitol, starch, starch pregelatinized, and sucrose.
- Suitable disintegrants include one or more of starch, croscarmellose sodium, crospovidone, and sodium starch glycolate.
- Suitable lubricants and glidants include one or more of colloidal anhydrous silica, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated castor oil, sucrose esters of fatty acids, microcrystalline wax, yellow beeswax, and white beeswax.
- Suitable coloring agents include one or more FDA approved colors for oral use.
- the tablets prepared by the present invention may be coated with one or more additional layers of film forming agents and/or pharmaceutically acceptable excipients.
- Suitable film forming agents include one or more of ethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose, carboxymethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropyl methyl phthalate, cellulose acetate, cellulose acetate trimelliatate, cellulose acetate phthalate; Waxes, such as, polyethylene glycol; methacrylic acid polymers, such as, Eudragit® RL and RS; and mixture thereof.
- Commercially available coating compositions marketed under various trade names, such as Opadry® may also be used for coating.
- PROCEDURE 1. Colloidal silicon dioxide and nateglinide are co-sifted by mixing repeatedly till a uniform mixture is formed.
- the co-sifted mixture of step 1 along with microcrystalline cellulose, lactose monohydrate and a part of croscarmellose sodium are mixed in a high shear mixer and granulated using aqueous solutions that include sodium lauryl sulphate and polyvinyl pyrrolidone.
- the wet granules are dried in a fluid bed drier, passed through a screen and then milled.
- the colloidal silicon dioxide and the rest of the croscarmellose sodium are mixed, passed through a screen and blended with the mixture of step 3.
- the magnesium stearate is passed through a screen, blended with the blend of step 4 and the resulting mixture is compressed to tablets.
- colloidal silicon dioxide and nateglinide are co-sifted repeatedly and mixed together in a low shear blender.
- the co-sifted mixture of step 1 along with microcrystalline cellulose, lactose monohydrate and a part of sodium starch glycolate are mixed in a high shear mixer and granulated using aqueous solutions containing sodium lauryl sulphate and polyvinyl pyrrolidone.
- the wet granules are dried in a fluid bed drier, passed through a screen and milled.
- the colloidal silicon dioxide and the rest of the sodium starch glycolate are mixed, passed through a screen and blended with the mixture of step 3. 5.
- the magnesium stearate is passed through a screen, blended with the blend of step 4 and the total mixture is compressed into tablets.
- Table 3 indicates that compositions having nateglinide particle size d90 ⁇ 45 ⁇ m show a better dissolution profile as compared to the compositions having particle size d90, > 45 ⁇ m.
Abstract
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN1100/DEL/2003 | 2003-09-03 | ||
IN1100DE2003 | 2003-09-03 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2005020979A1 true WO2005020979A1 (fr) | 2005-03-10 |
Family
ID=34259940
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2004/051678 WO2005020979A1 (fr) | 2003-09-03 | 2004-09-02 | Procede de preparation de compositions pharmaceutiques a base de nateglinide |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2005020979A1 (fr) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005051360A1 (fr) * | 2003-11-28 | 2005-06-09 | Ranbaxy Laboratories Limited | Compositions pharmaceutiques comprenant de la nateglinide et un agent tensioactif |
WO2005117840A1 (fr) * | 2004-05-31 | 2005-12-15 | Ranbaxy Laboratories Limited | Compositions pharmaceutiques stables comprenant des granules pulverises de nateglinide de forme b |
WO2013066278A1 (fr) * | 2011-11-03 | 2013-05-10 | Mahmut Bilgic | Procédé de fabrication de formulations pharmaceutiques comprenant du natéglinide |
WO2013115739A1 (fr) * | 2012-01-31 | 2013-08-08 | Mahmut Bilgic | Procédé de préparation de formulations contenant du natéglinide et de l'acide lipoïque |
US10568839B2 (en) | 2011-01-11 | 2020-02-25 | Capsugel Belgium Nv | Hard capsules |
US11319566B2 (en) | 2017-04-14 | 2022-05-03 | Capsugel Belgium Nv | Process for making pullulan |
US11576870B2 (en) | 2017-04-14 | 2023-02-14 | Capsugel Belgium Nv | Pullulan capsules |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1258249A1 (fr) * | 1999-12-28 | 2002-11-20 | Ajinomoto Co., Inc. | Preparations orales pour diabetes |
US6559188B1 (en) * | 1999-09-17 | 2003-05-06 | Novartis Ag | Method of treating metabolic disorders especially diabetes, or a disease or condition associated with diabetes |
US20030095925A1 (en) * | 1997-10-01 | 2003-05-22 | Dugger Harry A. | Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders |
EP1334720A1 (fr) * | 2000-10-24 | 2003-08-13 | Ajinomoto Co., Inc. | Preparations contenant du nateglinide |
EP1334721A1 (fr) * | 2000-10-24 | 2003-08-13 | Ajinomoto Co., Inc. | Preparations de medicament contenant du nateglinide |
WO2003076393A1 (fr) * | 2002-03-11 | 2003-09-18 | Novartis Ag | Sels de nateglinide |
US20040002544A1 (en) * | 2002-06-28 | 2004-01-01 | Ajinomoto Co. Inc | Antidiabetic preparation for oral administration |
US20040152782A1 (en) * | 2002-07-03 | 2004-08-05 | Ronit Yahalomi | Process for preparing nateglinide and intermediates thereof |
-
2004
- 2004-09-02 WO PCT/IB2004/051678 patent/WO2005020979A1/fr active Application Filing
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030095925A1 (en) * | 1997-10-01 | 2003-05-22 | Dugger Harry A. | Buccal, polar and non-polar spray or capsule containing drugs for treating metabolic disorders |
US6559188B1 (en) * | 1999-09-17 | 2003-05-06 | Novartis Ag | Method of treating metabolic disorders especially diabetes, or a disease or condition associated with diabetes |
EP1258249A1 (fr) * | 1999-12-28 | 2002-11-20 | Ajinomoto Co., Inc. | Preparations orales pour diabetes |
EP1334720A1 (fr) * | 2000-10-24 | 2003-08-13 | Ajinomoto Co., Inc. | Preparations contenant du nateglinide |
EP1334721A1 (fr) * | 2000-10-24 | 2003-08-13 | Ajinomoto Co., Inc. | Preparations de medicament contenant du nateglinide |
WO2003076393A1 (fr) * | 2002-03-11 | 2003-09-18 | Novartis Ag | Sels de nateglinide |
US20040002544A1 (en) * | 2002-06-28 | 2004-01-01 | Ajinomoto Co. Inc | Antidiabetic preparation for oral administration |
US20040152782A1 (en) * | 2002-07-03 | 2004-08-05 | Ronit Yahalomi | Process for preparing nateglinide and intermediates thereof |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005051360A1 (fr) * | 2003-11-28 | 2005-06-09 | Ranbaxy Laboratories Limited | Compositions pharmaceutiques comprenant de la nateglinide et un agent tensioactif |
WO2005117840A1 (fr) * | 2004-05-31 | 2005-12-15 | Ranbaxy Laboratories Limited | Compositions pharmaceutiques stables comprenant des granules pulverises de nateglinide de forme b |
US10568839B2 (en) | 2011-01-11 | 2020-02-25 | Capsugel Belgium Nv | Hard capsules |
WO2013066278A1 (fr) * | 2011-11-03 | 2013-05-10 | Mahmut Bilgic | Procédé de fabrication de formulations pharmaceutiques comprenant du natéglinide |
WO2013115739A1 (fr) * | 2012-01-31 | 2013-08-08 | Mahmut Bilgic | Procédé de préparation de formulations contenant du natéglinide et de l'acide lipoïque |
US11319566B2 (en) | 2017-04-14 | 2022-05-03 | Capsugel Belgium Nv | Process for making pullulan |
US11576870B2 (en) | 2017-04-14 | 2023-02-14 | Capsugel Belgium Nv | Pullulan capsules |
US11878079B2 (en) | 2017-04-14 | 2024-01-23 | Capsugel Belgium Nv | Pullulan capsules |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2485947C2 (ru) | Фармацевтические композиции энтакапона, леводопы и карбидопы с улучшенной биодоступностью | |
TWI389691B (zh) | 可口服且具有活性成分快速釋出之固態醫藥劑型 | |
JP6173521B2 (ja) | ナルブフィンを含有する製剤及びそれらの使用 | |
JP4773456B2 (ja) | 生体利用率を向上させた経口用製剤 | |
US6696496B2 (en) | Low water-soluble venlafaxine salts | |
WO2008072534A1 (fr) | Préparation médicale sous forme solide contenant un mannitol ou un lactose | |
KR20170139170A (ko) | 4-아미노-5-플루오로-3-[6-(4-메틸피페라진-1-일)-1h-벤즈이미다졸-2-일]-1h-퀴놀린-2-온 락테이트 일수화물을 포함한 제약 조성물 | |
US20070219250A1 (en) | Pharmaceutical Compositions of Nateglinide | |
US20030190352A1 (en) | Compositions of venlafaxine base | |
WO2005020979A1 (fr) | Procede de preparation de compositions pharmaceutiques a base de nateglinide | |
JP2023184662A (ja) | イストラデフィリン製剤 | |
US20200054560A1 (en) | Palbociclib compositions and methods thereof | |
US20090030057A1 (en) | Pharmaceutical composition of telmisartan | |
EP2293791B1 (fr) | Compositions pharmaceutiques d'entacapone co-micronisée avec des alcools de sucre | |
WO2006013444A1 (fr) | Preparations de compositions pharmaceutiques stables de nateglinide et procedes de preparation de celles-ci | |
US20080044468A1 (en) | Processes For The Preparation Of Oral Dosage Formulations Of Modafinil | |
WO2005092319A1 (fr) | Compositions pharmaceutiques a desintegration rapide, comprenant du nateglinide et un delitant | |
JP2001213890A (ja) | トレハロース粒子 | |
WO2005016315A1 (fr) | Compositions pharmaceutiques de nateglinide | |
WO1999020277A1 (fr) | Composition medicamenteuse a dissolution rapide | |
WO2005117840A1 (fr) | Compositions pharmaceutiques stables comprenant des granules pulverises de nateglinide de forme b | |
WO2014157603A1 (fr) | Composition pharmaceutique pour administration orale | |
EP4023215A1 (fr) | Comprimé pelliculé comprenant du tériflunomide | |
WO2022119541A1 (fr) | Formulation de comprimé pelliculé comprenant de la dapagliflozine et du chlorhydrate de metformine | |
EP2257278A1 (fr) | Compositions de comprimés oraux contenant du natéglinide et un système agent tensioactif-agent de réglage du ph |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
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 |