EP0794762A1 - Compositions orales - Google Patents
Compositions oralesInfo
- Publication number
- EP0794762A1 EP0794762A1 EP96903496A EP96903496A EP0794762A1 EP 0794762 A1 EP0794762 A1 EP 0794762A1 EP 96903496 A EP96903496 A EP 96903496A EP 96903496 A EP96903496 A EP 96903496A EP 0794762 A1 EP0794762 A1 EP 0794762A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- agents
- pyrophosphate
- dentifrice
- binder
- tetrasodium pyrophosphate
- 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.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/20—Halogens; Compounds thereof
- A61K8/21—Fluorides; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/24—Phosphorous; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
Definitions
- the present invention relates to oral compositions.
- it relates to so-called baking soda dentifrice compostions containing pyrophosphate anticalculus agents and which have improved stability and aesthetics.
- Mature calculus consists of an inorganic portion which is largely calcium phosphate arranged in a hydroxyapatite crystal lattice structure similar to bone, enamel and dentin.
- An organic portion is also present and consists of desquamated epithelial cells, leukocytes, salivary sediment, food debris and various types of microorganisms.
- Dentifrice compositions containing pyrophosphate salts and sodium bicarbonate are also known, having been described for example, in U.S. Patent 5,180,576, to Winston et al., issued January 19, 1993, the disclosure of which is incorporated herein by reference in its entirety.
- Obtaining stable dentifrice compositions containing sodium bicarbonate and pyrophosphate effective for inhibiting dental calculus formation presents a processing challenge.
- Pyrophosphate dissolved in these dentifrice compositions is subsequently likely to recrystallize in the form of tetrasodium pyrophosphate decahydrate crystals. These crystals can grow into large, glass-like particles which have negative aesthetics and also have tartar control efficacy concerns.
- pyrophosphate/sodium bicarbonate-containing dentifrice compositions which are aesthetically acceptable and efficacious may be prepared by controlling the process conditions to insure that less than about 20% of the pyrophosphate is solubilized at any point in the process mixture.
- the process described in the above application still leads to solubilization of about 5% of the total pyrophosphate level.
- An object is also to provide stable dentifrice compositions containing sodium bicarbonate and tetrasodium pyrophosphate salt particles of predetermined and/or consistent size.
- Another object of this invention is to prepare such stable compositions by a process controlling the processing conditions such that the level of pyrophosphate ion dissolved in the composition is less than 100 ppm, preferably less than 10 ppm.
- a dentifrice composition comprising: a) from about 5% to about 50% by weight of sodium bicarbonate; b) a soluble fluoride ion source in an amount sufficient to provide from about lOppm to about 3500ppm of fluoride ion; c) at least about 1.5% by weight of tetrasodium pyrophosphate, of which some or all of the tetrasodium pyrophosphate is in the form of undissolved anhydrous tetrasodium pyrophosphate particles; and d) from about 50% to about 94% dentifrice carrier materials; and wherein further said composition has a soluble pyrophosphate ion content in the range from about 1 to about lOOppm, preferably from about 1.5 to about lOppm, more preferably from about 2 to about 5 ppm.
- the present invention also relates to a method of making the above dentifrice composition
- a) forming a premix of dentifrice carrier materials comprising one or more materials selected from binder/thickening agents, humectants, buffering agents, abrasive polishing materials, surfactants, sweetening agents, flavoring agents, titanium dioxide, and mixtures thereof, said premix including at least one or more binder/thickening agents and one or more buffering agents sufficient to provide a pH in step b) hereof greater than about pH 8; b) forming a paste by adding water to the premix in an amount sufficient to hydrate the binder/thickening agent; c) adding sodium bicarbonate to the resulting paste; d) thereafter adding tetrasodium pyrophosphate, all at once or in portions, to the paste at a temperature less than about 30°C, preferably less than about 25°C and preferably at a pH of greater than about pH8.
- the tetrasodium pyrophosphate is added to the mixture after all other sodium-containing salts present in the composition have been added thereto.
- the binder/thickening agent and buffering agent are added batchwise to the premix so as to provide multiple alternate layers of binder/thickening agent and buffering agent in the final premix, this being valuable from the viewpoint of achieving optimum paste rheology during the binder hydration step.
- the present invention relates to a method of manufacturing a baking soda dentifrice composition containing pyrophosphate tartar control agent.
- the dentifrice compositions produced by the present process may be in the form of toothpastes or gels.
- teethpaste as used herein, means paste and gel formulations unless otherwise specified.
- the present invention also relates to baking/pyrophosphate tartar control dentifrice compositions comprising anhydrous tetrasodium pyrophosphate particles.
- the present process and compositions comprise several essential components, as well as optional components. A detailed description of these components and the present process conditions are described hereinafter.
- the pyrophosphate salts used in the present process and compositions must include tetrasodium pyrophosphate.
- This material may be the anhydrous salt form or the decahydrate form, or any other species stable in sohd form in the dentifrice compositions.
- the salt is its solid particle form, which may be its crystalline and/or amorphous state, with the particle size of the salt preferably being small enough to be aesthetically acceptable and readily soluble during use.
- tetrasodium pyrophosphate salt particles are a necessary component of the present process and compositions, it is to be recognised that low levels of other pyrophosphate salts may be included in the process and compositions.
- Specific salts include tetra alkali metal pyrophosphate other than tetrasodium pyrophosphate, dialkali metal diacid pyrophosphates, trialkali metal monoacid pyrophosphate and mixtures thereof, wherein the alkali metals are sodium or potassium. (Pyrophosphate salts are described in more detail in Kirk & Othmer, Encyclopedia of Chemical Technology. Second Edition, Volume 15, Interscience Publishers (1958), incorporated herein by reference in its entirety).
- salts are useful in both their hydrated and ⁇ nhydrated forms. Because such salts are typically more soluble than the tetrasodium pyrophosphate salt, their inclusion in the process and compositions of the invention should be limited to avoid preparing compositions containing soluble pyrophosphate ion, and exclusion of such more soluble salts is preferred.
- the amount of pyrophosphate salt useful in these compositions is any tartar control effective amount, and is generally enough to provide at least about 1.0%, preferably from about 1.5% to. about 10%, more preferably from about 3.0% to about 6% P2O7 , by weight f the compositions. It is to be appreciated that the level of P2O7 is that amount capable of being provided to the composition (i.e., the theoretical amount at an appropriate pH) and that other pyrophosphate forms (e.g., HP2O7 ) may be present when a final product pH is established.
- the level of tetrasodium pyrophosphate salt preferably used in the present methods and compositions is therefore from about 1.5% to about 15%, and more preferably from about 2% to about 10%, by weight of the dentifrice composition.
- compositions contain from about 5% to about 50%, preferably from about 10% to about 30% sodium bicarbonate by weight of composition.
- a soluble fluoride ion source is also incorporated in the present compositions.
- the soluble fluoride ion source is used in amounts sufficient to provide from about 10 to about 3500 ppm of the fluoride ion.
- Preferred fluorides are sodium fluoride, stannous fluoride, indium fluoride, and sodium monofluorophosphate.
- Norris et al., U.S. Patent 2,946,1735, issued July 26, 1960 and Widder et al., U.S. Patent 3,678,154, issued July 18, 1972 disclose such salts as well as others. Both patents are incorporated herein by reference in their entirety.
- dentifrice carrier materials means any material safe and effective for use in the toothpaste compositions prepared according the present invention. Such materials are well known in the art and are readily chosen by one skilled in the art based on the physical and aesthetic properties desired for the dentifrice composition being prepared. Dentifrice carrier materials typically comprise from about 50% to about 94%, preferably from about 60% to about 80% by weight of the present compositions.
- the present compositions typically contain a binder/thickening material to provide a desirable consistency.
- Preferred binder/thickening agents are carboxyvinyl polymers, carrrageenan, hydroxyethyl cellulose and water soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose.
- Natural gums such as gum karaya, zanthan gum, gum arabic, and gum tragacanth can also be used.
- Colloidal magnesium aluminium silicate or finely divided silica can be used as part of the thickening agent to further improve texture.
- Thickening agents can be used in an amount from about 0.2% to about 5.0% by weight of the total composition.
- humectant material in a toothpaste to keep the composition from hardening upon exposure to air.
- Certain humectants can also impart a desirable sweetness or flavour to toothpaste compositions.
- Suitable humectants include glycerin, sorbitol, other edible polyhydric alcohols, and mixtures thereof, at a level of from about 15% to about 70% by weight of composition.
- Titanium dioxide can also be added to the present compositions. Titanium dioxide is a white powder which adds pigment to the compositions. Titanium dioxide generally comprises from about 0.25% to about 1% by weight of composition.
- Water is also present in the compositions of this process.
- Water employed in the preparation of commercially suitable toothpastes should preferably be deionized and free of organic impurities.
- Water generally comprises from about 12% to about 45%, preferably from about 15% to about 35%, more preferably from about 20% to about 30% by weight of composition. These amounts of water include the free water which is added plus that which is introduced with other materials such as with sorbitol.
- Buffering agents refer to agents that can be used to increase the pH of the compositions to a range of above about pH 8 as preferred for addition of the sodium bicarbonate and tetrasodium pyrophosphate. These agents include trisodium phosphate, sodium hydroxide and sodium carbonate. Sodium carbonate is preferred at a level of from about 0.5% to about 2% by weight of composition.
- abrasive pohshing material can also be included.
- the abrasive pohshing material contemplated for use in the compositions of the present invention can be any material which does not excessively abrade den tin. These include, for example, silicas including gels and precipitates, calcium carbonate, dicalcium orthophosphate dihydrate, calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate, insoluble sodium polymetaphosphate, hydrated alumina, and resinous abrasive materials such as paniculate condensation products of urea and formaldehyde, and others such as disclosed by Cooley et al. in U.S. Patent 3,070,510, December 25, 1962, incorporated herein by reference. Mixtures of abrasives can also be used.
- Sihca dental abrasives of various types are preferred because of their unique benefits of exceptional dental cleaning and pohshing performance without unduly abrading tooth enamel or dentin.
- the sihca abrasive can be precipitated silica or silica gels such as the sihca xerogels described in Pader et al., U.S. Patent 3,538,230, issued March 2, 1970 and DiGiulio, U.S. Patent 3,862,307, June 21, 1975, both incorporated herein by reference.
- sihca xerogels marketed under the tradename "Syloid” by W. R. Grace & Company, Davison Chemical Division.
- Preferred precipitated sihca materials include those marketed by the J. M. Huber Corporation under the tradename, "Zeodent", particularly the silica carrying the designation "Zeodent 119". These silica abrasives are described in U.S. Patent 4,340,583, July 29, 1982, incorporated herein by reference.
- the abrasive is preferably present at a level of from about 6% to 70%, more preferably from about 15% to about 25% by weight.
- the toothpaste compositions can also contain surfactants.
- Suitable surfactants are those which are reasonably stable and foam throughout a wide pH range, including non-soap anionic, nonionic, canonic, zwitterionic and amphoteric organic synthetic detergents. Many of these suitable agents are disclosed by Gieske et al. in U.S. Patent 4,051,234, September 27, 1977, incorporated herein by reference. Sodium alkyl sulphate and polyethylene glycol are preferred for use herein at a level of about 4% to about 3% by weight of compositions respectively. Flavouring agents can also be added to the present compositions.
- Suitable flavouring agents include oil of winter/green, oil of peppermint, oil of spearmint, oil of sassafras, and oil of clove.
- Sweetening agents which can be used include aspartame, acesulfame, saccharin, dextrose, levulose and sodium cyclamate.
- Flavouring and sweetening agents are generally used in toothpastes at levels of from about 0.005% to about 2% by weight of composition.
- compositions can also contain optional pharmaceutical agents (e.g., triclosan) and other tartar control agents.
- Optional tartar control agents include such known materials as synthetic anionic polymers (including polyacrylates and copolymers of maleic anhydride or acid and methyl vinyl ether (e.g., Gantrez), as described for example in U.S. Patent 4,627,977 to Gaffar et al., the disclosures of which are incorporated herein by reference in their entirety; as well as, e.g., polyamino propane sulfonic acid (AMPS)), polyphosphates (e.g. tripolyphosphate; hexametaphosphate), diphosphonates (e.g. EHDP; AHP), polypeptides (such as polyaspartic and polyglutamic acids), and mixtures thereof.
- synthetic anionic polymers including polyacrylates and copolymers of maleic anhydride or acid and methyl vinyl ether (e.g., Gantrez)
- the toothpaste compositions are prepared by mixing together the components described above according to the method of manufacturing.
- This method comprises the steps of: a) forming a premix of dentifrice carrier materials comprising one or more materials selected from binder/thickening agents, humectants, buffering agents, abrasive pohshing materials, surfactants, sweetening agents, flavoring agents, titanium dioxide, and mixtures thereof, said premix including at least one or more binder/thickening agents and one or more buffering agents sufficient to provide a pH in step b) hereof greater than about pH 8; b) forming a paste by adding water to the premix in an amount sufficient to hydrate the binder/thickening agent; c) adding sodium bicarbonate to the resulting paste; d) thereafter adding tetrasodium pyrophosphate, all at once or in portions, to the paste at a temperature less than about 30°C, preferably less than about 25°C and at a pH of greater than about pH8.
- the amount of pyrophosphate dissolved in the mixture for the methods and composition of the present invention is in the range from about 1 to about lOOppm, preferably from about 1.5 to about lOppm, more preferably from about 2 to about 5ppm, measured as pyrophosphate ion.
- a method of measuring the amount of pyrophosphate dissolved in the mixture and compositions is described and exemplified hereinafter in the Examples.
- paste and gel dentifrices having a pyrophosphate ion content of about 3.3%.
- the paste compositions are prepared as follows. To the humectants (sorbitol, glycerine, PEG-6) at ambient temperature is added a particulate mix of sodium saccharin, sodium fluoride, sodium carbonate, sodium carboxymethylcellulose and titanium dioxide, the sodium carbonate and sodium carboxymethylcellulose (CMC) being each added to the particulate mix in two equal batches in the order carbonate, CMC, carbonate, CMC to provide a so-called "layered" particulate mixture. To this liquid premix is then added water in amount sufficient to hydrate the binder, followed by sihca . To this mixture is added sodium bicarbonate, followed by tetrasodium pyrophosphate, in sohd form. The final paste product is then obtained by addition of flavour and sodium alkyl sulphate solution.
- humectants sorbitol, glycerine, PEG-6
- CMC sodium carboxymethylcellulose
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Emergency Medicine (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Cosmetics (AREA)
Abstract
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9500746.4A GB9500746D0 (en) | 1995-01-14 | 1995-01-14 | Oral compositions |
GB9500746 | 1995-01-14 | ||
PCT/US1996/000526 WO1996021420A1 (fr) | 1995-01-14 | 1996-01-05 | Compositions orales |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0794762A1 true EP0794762A1 (fr) | 1997-09-17 |
EP0794762A4 EP0794762A4 (fr) | 1999-09-15 |
Family
ID=10768060
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP96903496A Withdrawn EP0794762A4 (fr) | 1995-01-14 | 1996-01-05 | Compositions orales |
Country Status (15)
Country | Link |
---|---|
EP (1) | EP0794762A4 (fr) |
JP (1) | JPH11500420A (fr) |
KR (1) | KR19980701414A (fr) |
CN (1) | CN1168093A (fr) |
AU (1) | AU4756996A (fr) |
BR (1) | BR9606974A (fr) |
CA (1) | CA2208692C (fr) |
CZ (1) | CZ221697A3 (fr) |
GB (1) | GB9500746D0 (fr) |
HU (1) | HUP9801282A3 (fr) |
MX (1) | MX9705295A (fr) |
PE (1) | PE64496A1 (fr) |
PL (1) | PL321282A1 (fr) |
TR (1) | TR199700619T1 (fr) |
WO (1) | WO1996021420A1 (fr) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5885556A (en) * | 1996-01-11 | 1999-03-23 | The Procter & Gamble Company | Tartar control oral compositions |
US5939052A (en) * | 1996-11-21 | 1999-08-17 | The Procter & Gamble Company | Dentifrice compositions containing polyphosphate and fluoride |
KR100478211B1 (ko) * | 1997-10-01 | 2005-08-11 | 애경산업(주) | 미백치약조성물 |
WO2008157197A1 (fr) * | 2007-06-12 | 2008-12-24 | Rhodia Inc. | Esters de mono-, di- et polyol alkoxylate phosphate utilisés dans des formulations d'hygiène buccodentaire et procédés d'utilisation |
RU2010116347A (ru) * | 2007-09-27 | 2011-11-10 | Геркулес Инкорпорейтед (Us) | Псевдоожиженная суспензия водорастворимого и/или способного набухать в воде полимера и ее (тпс) смесь для применения в средствах ухода за зубами и бытовой химии |
JP5394635B2 (ja) * | 2007-12-07 | 2014-01-22 | 正一 中村 | 洗浄添加剤及びその製造方法 |
AU2009212335B2 (en) * | 2008-02-08 | 2011-12-01 | Colgate-Palmolive Company | Compositions comprising basic amino acid and soluble carbonate salt |
JP6139551B2 (ja) * | 2011-12-01 | 2017-05-31 | スリーエム イノベイティブ プロパティズ カンパニー | 一成分自己接着性歯科用組成物、その製造方法、及び使用 |
MX366957B (es) * | 2015-11-13 | 2019-07-29 | Procter & Gamble | Composiciones dentífricas con estabilidad mejorada del fluoruro. |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994023691A2 (fr) * | 1993-04-08 | 1994-10-27 | The Procter & Gamble Company | Compositions orales de traitement de la plaque dentaire et de la gingivite, contenant un agent antibacterien non cationique et un sel de bicarbonate |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1023666A (fr) * | 1973-01-29 | 1978-01-03 | Eric Baines | Dentrifices transparents |
US3927202A (en) * | 1973-01-29 | 1975-12-16 | Colgate Palmolive Co | Dentifrices |
US4784788A (en) * | 1985-12-14 | 1988-11-15 | Colgate-Palmolive Co. | Cleaning paste with soluble abrasive |
US5180576A (en) * | 1991-08-30 | 1993-01-19 | Church & Dwight Co., Inc. | Anticalculus dentifrices |
US5215740A (en) * | 1991-10-25 | 1993-06-01 | Church & Dwight Co., Inc. | Buffering system for anticalculus dentifrices |
US5290542A (en) * | 1993-04-08 | 1994-03-01 | The Procter & Gamble Company | Oral compositions for treating plaque and gingivitis |
WO1994024991A1 (fr) * | 1993-04-23 | 1994-11-10 | The Procter & Gamble Company | Procede de fabrication d'un dentifrice anti-tartre a base de levure chimique |
US5326554A (en) * | 1993-04-23 | 1994-07-05 | The Procter & Gamble Company | Oral compositions for treating plaque and gingivitis |
US5376360A (en) * | 1993-08-30 | 1994-12-27 | Church & Dwight Co., Inc. | Baking soda toothpaste containing soluble pyrophosphate salts |
-
1995
- 1995-01-14 GB GBGB9500746.4A patent/GB9500746D0/en active Pending
-
1996
- 1996-01-05 WO PCT/US1996/000526 patent/WO1996021420A1/fr not_active Application Discontinuation
- 1996-01-05 CZ CZ972216A patent/CZ221697A3/cs unknown
- 1996-01-05 JP JP8521854A patent/JPH11500420A/ja active Pending
- 1996-01-05 TR TR97/00619T patent/TR199700619T1/xx unknown
- 1996-01-05 PL PL96321282A patent/PL321282A1/xx unknown
- 1996-01-05 HU HU9801282A patent/HUP9801282A3/hu unknown
- 1996-01-05 CN CN96191427A patent/CN1168093A/zh active Pending
- 1996-01-05 KR KR1019970704803A patent/KR19980701414A/ko not_active Application Discontinuation
- 1996-01-05 EP EP96903496A patent/EP0794762A4/fr not_active Withdrawn
- 1996-01-05 AU AU47569/96A patent/AU4756996A/en not_active Abandoned
- 1996-01-05 CA CA002208692A patent/CA2208692C/fr not_active Expired - Fee Related
- 1996-01-05 BR BR9606974A patent/BR9606974A/pt not_active Application Discontinuation
- 1996-01-05 MX MX9705295A patent/MX9705295A/es unknown
- 1996-01-12 PE PE1996000023A patent/PE64496A1/es not_active Application Discontinuation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994023691A2 (fr) * | 1993-04-08 | 1994-10-27 | The Procter & Gamble Company | Compositions orales de traitement de la plaque dentaire et de la gingivite, contenant un agent antibacterien non cationique et un sel de bicarbonate |
Non-Patent Citations (1)
Title |
---|
See also references of WO9621420A1 * |
Also Published As
Publication number | Publication date |
---|---|
JPH11500420A (ja) | 1999-01-12 |
MX9705295A (es) | 1997-10-31 |
CA2208692C (fr) | 2001-06-05 |
EP0794762A4 (fr) | 1999-09-15 |
AU4756996A (en) | 1996-07-31 |
TR199700619T1 (en) | 1998-02-21 |
HUP9801282A2 (hu) | 1999-01-28 |
HUP9801282A3 (en) | 1999-03-01 |
WO1996021420A1 (fr) | 1996-07-18 |
CA2208692A1 (fr) | 1996-07-18 |
BR9606974A (pt) | 1997-11-04 |
PL321282A1 (en) | 1997-11-24 |
CZ221697A3 (en) | 1997-12-17 |
GB9500746D0 (en) | 1995-03-08 |
KR19980701414A (ko) | 1998-05-15 |
PE64496A1 (es) | 1997-03-19 |
CN1168093A (zh) | 1997-12-17 |
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