CA2002492A1 - Pharmaceutical ion exchange resin composition - Google Patents
Pharmaceutical ion exchange resin compositionInfo
- Publication number
- CA2002492A1 CA2002492A1 CA002002492A CA2002492A CA2002492A1 CA 2002492 A1 CA2002492 A1 CA 2002492A1 CA 002002492 A CA002002492 A CA 002002492A CA 2002492 A CA2002492 A CA 2002492A CA 2002492 A1 CA2002492 A1 CA 2002492A1
- Authority
- CA
- Canada
- Prior art keywords
- sugar
- alcohol
- ion exchange
- weight
- 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.)
- Abandoned
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
- A61K9/14—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
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
- A61K47/585—Ion exchange resins, e.g. polystyrene sulfonic acid resin
-
- 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
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
Abstract
PHARMACEUTICAL ION EXCHANGE RESIN COMPOSITION
ABSTRACT OF THE DISCLOSURE
An ion exchange resin composition which is readily dispersible in water is provided. This resin composition comprises a granulated ion exchange resin, a pharmacologically active ingredient bound thereto with a sugar or sugar alcohol, and a sufficient amount of water, alcohol or aqueous alcohol to facilitate granulation. The invention further comprises a method for the preparation of such ion exchange resin composition.
ABSTRACT OF THE DISCLOSURE
An ion exchange resin composition which is readily dispersible in water is provided. This resin composition comprises a granulated ion exchange resin, a pharmacologically active ingredient bound thereto with a sugar or sugar alcohol, and a sufficient amount of water, alcohol or aqueous alcohol to facilitate granulation. The invention further comprises a method for the preparation of such ion exchange resin composition.
Description
xoo~
~Ac~ÇR~UND OF TH~ INVENTION
Ion exchange resi~ compositions ~on~aining pharmacologically active ingredients ar~ ~nown. However, one of the major drawbacks o~
the known compositions is that the same are not sufficiently dispersible in water. ~he lack of dispersibility in wa~er r~duc~s the time required for the pharmacological agent to act.
~g,~' ,~
It is accordinqly a primary object of the present invention to provide pharma~eutical ion ex~hange resins with a high degree of dispercibility in water.
It is yet a ~urther objec~ of the present invention to provide a method of producin~ the water dispersible pharmaceutical ion exchange resins.
Other other o~jects ~n~ advantage6 of the present invention will be apparent fro~ a ~urther reading of the specification and of ' the appended olaims.
With the above and other object~ in view, the pres~nt invention mainly ~omprises a pharmaceutical ion exchange resin compo~ition which is readily dispersible in water, said composition comprising a granulated ion exchange resin having a pharmac~logiçally acti~e ingredient bound thereto, by means of a sugar or sugar alcohol in the presence of a cuffi~ient amount of Water, al.cohol or aqu~ous alcohol to facilitate the grahu1ation.
~ he ~hrase "readily dispersible in water" in accordance with the present invention, means that the composition must disberse, with stirring in twent~ times its own weight of water within ten seconds.
200249:~
The presen~ invention is applicable to any acidic or basic drug, which may be bound to the ion exchange resi~. Preferably, howeve~, active ingredients having a biological half life of eight hours or less ~re used.
Among the suitable types of pharmacological active agents that can be used in acco~a~ce with ~he present invention are the following:
i) Narcotic analgesic~, such as codeine, dihydrocodein, hydromorphone, morphlne, pen~azocine and propoxyphene, ii] Sympathomimetics, such as norephedrine and pseudoephedrein, iii) ~ntitussiYes, such as dextromethorphan, iv) Analgesics, such as aspirin, v) Antiemetics, such as metoclopramide, vi) Anticholinergic.~, such as atropine, ipratropium bromide and scopolamine, vii) Muscle relaxants, such as cyolo~enzaprine and papaverine, viii) sronchodilators~ ~uch a~ salbutamol, terbutaline and theophylline, ix~ Anti~ioti~s, such as amoxycillin, ampicillin, azloclllin, bacampicillin, ce~amandole, cefonicid, ce~otaxime, cefotetan, cefoxitin, ceftriaxone, mezlocillin and piperacillin, x) Antidepre~nts, ~uch as bupropion, nomifensine, and nortripyline, xi) Antiasthmatics, s~ch as cromolyn, xii) Antineoplactic~, such as tamoxifen, xiii) Antiepileptics, s~ch as valproic acid and phenytoin, xi~) Cardiovascular agents, such as propranolol.
~2-20024g2 Ahy of the above may be used in the form o~ their acid addition salts, or, if appropriate, alkali or alkaline ~arth metal salts.
A wide vartety of resins may be u3ed for the purpose~ of the presen~ inven~ion. In the case of ba~ic drugs, any pharmacologically compatible ~ationic resin may be u3ed. In the cas~ of acidic drug~, any pharmacologi~ally ~ompati~le anioni~ resin may be used.
Suitable ion exchange resins generally have acr~lic, me~ha~rylic, phenol formaldehyde or dextra~ m~t~ices. ~o~ver, a preferred cationic ion exchange ~esin is a gel styrene-divinyl benzene sulphonic acid ~esin, such as Amherlite IR lZo (Trademark) Amberlite XE 69 (Trademark) and Dowex 50~ (Trademark), while a preferred anionic ion exchange resin is a gel styrene-divinyl benzene quaternary ammonium resin, ~uch a~ ~o~ex SBR (Trademark~ and ~owex SAR (Trademark).
The parti~le ~ize and, if appli~able, the degree of cross linking of the resin is determined by, among other fao~ors, the drug emplo~ed and the rate of drug release required. P~eferably, however, the resin has a particle size of from ~.045 to 1 mm, especially from 0.~45 to 0.5 mm. If ~pplicable, the pr~ferred degree of cross-linking is from ~ to 16% partio~larly from 8% to 12%.
The amount of drug bound to the resin is also determined by t~e choice of drug, as well as by the resin employed. Pr~ferably the weight ratio of bound drug to resih is from 1:3 to 2:~. particularly ~rom 2:3 to 3:2.
A~sorption of the drug onto the ion exchange resin partic1es is a well known teehnique as shown in British P~tent Nos. 82~,337 and 1,218,102 and U.S. Patent No. ~,990,332, and demonstrated in the examples below. ~n general, the druq is mixed with an aqueous 200249;~
suspen~ion of the resin and the complex ~s ~hen dried. Ad~orption of the drug onto the resil~ is detec~ed by an a~say of the guspending ~luid.
Preferably the sugar or the sugar alcohol has a molecular weight of from 90 to 550, ~specially from 150 to 370. Suitable suqars and ~ugar al~oh~lg are sucrose, ~extro~e, maltose, fructose, lacto~e, mannitol, sor~i~ol ~r most preferably xylitol. The sugar or s~gar alco~ol is preferably finely d~vided, a~l of the sugar or sugar alcohol prefer~bly having particle sizes of 600 microns or less (30 mesh sieve). In a particula~ly pr~ferred e~bodi~nent of ~he present invention, at le~st 90% ~by weig~) of the sugar~sugar alcohol will have particle sizes of 250 microns or less (~o mesh sie~re).
The oonoentration o~ the s~g~r~gar alcohol in the composition of the present invention must be high enough to allow the composition to disperse readily in water. This means that there must be enough 6ugar/~ugar alcohol pre~ent to allow the composition to disperse ~within 10 seconds~ when added with stirring to 20 times its Weight of water. Generally, the composition will oontain fro~ 25% to ~9%, preferably from 70~ to 95~ (b~ weight) of the sugar~ugar alcohol.
The drug-resin complex and the RugarJsugar alcohol are granulated in the presence of sufficient water, aqueous alcohol or alcohol to facilitate granulation. The most suitable alcohols are Cl-C4 aliphAtic alcohols, especially tho~;~ having a boili.nq point, at 7~0mm Hg of 100C or less. Preferred al~ohol~ are ~thanol and isopropanol.
P~efer~bly, the a~ount o~ granulating medium employed i~
from 10 to 20%, especially from 2 to 7% by weight of the weight o~
the oomplex~ugar, ~uyar a~cohols mlx. I~ a par~loularly preferred embodiment of the present proce~s the mixt~re is granulated until the particle size of the sugar~sugar alcohol mat~heg the resin particle size. In the present specification, ~matches~ mean6 that at least ~0% tby weight) of the sugar/su~r alcohol has a particle size bekween 0.5 and 1.5 time~ the mean par~icle size of the drug-~esin complex. Once the drug-resin complex and the sug~r/sugar ~lcohol h~ve been granulated, the gra~ules formed are then dried, preferably until their water conten~ i~ below 3% (~y weight), when measured ~y the Karl Fischer method of moisture analy~is.
Optionally, the drug-resin complex or the granules may be film coated with a material that permits release of the drug from the composition at the controlled rate.
The film coat will generally include a water insoluble material such as:
~a) a wax, either alone or in admixture with a fatty alcohol (b) shellac or zein, (o) a water insoluble cellulo~e derivative, especially ethyl cellulose (d) a polymethacrylate, especially ~udragit (trademark).
Preferably, the film ~oat comprises a mixture of the water insoluble material ahd a water soluble material. The ratio of water insolu~le to water soluble material is determined by among other ractOrs, tne ~elease ra~e requlre~ an~ the solub1litY ch~lracteristics of the material~ selected.
The water s~l~bl~ material may be, for exa~ple, triacetin, propylene glycol, polyethylene glycol, polyvinylpyrrolidone or, which is preferred, a water soluhle cellulose, such as hydroxypropyl cellulose, or especially, hydroxypropylmethyl cellulose.
~5-~o~ z Suitable combinationæ of water insoluble and WatQr soluble mate~ialc for the film ~oat include shellac and polyvinylpyrrolidone or~ prefera~le ethyl cellulose and hydroxypropylmethyl cellulo~e.
Once the ~bove processing is complete, t~e compofiition may then be presented in a suit~ble dosage form, ~uch as a capsule or sachet~ This i~ done ~imply by filling the cap~ule or saohet with the f inished compositi~n.
~ he following examples are ~iven to further illustrate the preseht invention. The scope of the invention is not, however, meant to be limited to the specific details of the examples.
Morphine sulphate (pentahydrate, 3 OOgm) was added to pu~ified water ~EP, llOgm) and mixed until ~11 of the powder was evenly wetted. Wi~h continuous mixing a cationic ex~hange r~in, Dowex W50x8-200, (Trade~ark) hydrous app~ox 50~ (by weight) water, 60 gm) ~s added to the morphlne suspension. The stirring was continued for 24 hours at a rate that kept the resin suspended. The resin was then washed with purified water and dried in a fluid bed dryer.
Xylitol, (500gIn 90% (by weight) having a particle size les~
than 200~m) was mixed with the morphin~-resin complex (50gm) and xanthan gum (200gm) in a ~ranulator. With ~ontinuoue ~ixing, p~rified ~ater was addéd to the ~ixture until evanly watt~d light granules were forme~.
~ enerall~ the amount of water added wa~ 2.0 - 5.0~ tby weight3 of the xylitol/comlex/xanthan gum weight. The moist granules were ~hen d~ied in a fluid bed dryer until the water cont~n~ was below about 3.0% (by weight), Karl Fl~cher method~.
Each ~nit dose of ~his compo~ition had the following formulation, mg~unit dose Morphine Sulphate (absorbed on the res.in as morphine base)20 ~owex W50xs-200 ~Trademark) 20 Xylitol 500 Xanthan Gum 20 ~XAMPLE 2 The procesc of Ex~mple 1 was repeated to form a composition having the following formulation:
mq/unit dose Metoclopramide Hydrochloride (absorhed on the re~in as metoclopramide base 15 Dowex W50x8-200 (Tra~emark) 15 Xylitol 500 Xanthan Gum 20 ~XAMPLE 3 ~he process of Example 1 was repeated to form a composition having the following formation:
mq/unit dose Hydromorphone Hydrochloride tabsorbed on the resin as hydromorphone base) 4 Dowex W5~x16-100 tTradem~rk) 12 Xyl itol S00 Xanthan Gum 20 ~LPLE 4 ~ he process of EXample 1 was rep~ated to form a composition having the following formulation:
m~/unit do~ç
Theophylline Sodium (absorbed on the resin as theophylline base) 100 Dowex 2x8~200 (Trademark~ 200 Xylitol 87~
Xanthan Gum 45 Polyoxy 40-stea~ate (trademark) S
~'~
The pro~ess of Example 1 was repeated except that the xylitol/morphine-resin complex/xanthan gum was dry mixed to form a pow~er, rather than wet granulated.
~ ISPERS~BI I~Y OF RESIN cOMPOSITIONs ~N wATER
Unit doses of the granular and powder products, produced accordlng to Example 1 and the ~omparative Example, respectively, were ~dded to 100ml of water with continuous mixing.
The granular product immediately (within 10 seconds) formed an aqueous ~pension of the resin. By contrast, the powder product formed a wettec~ ~ass that took a number of minutes to disperse in the aqueous medium (and thereby form a resin BUspensi.on).
Further~ore, while the granulated product gives a homogeneous produ~t in which ~he drug substance is dispersed uniformly throughout the composition, the dry mixed powder was non-homogenous, the drug subs~ance being non-uniformly di~tributcd throughout the compo~ition.
While the invention has been clescribed in particular with respect to the above examples, it is apparent that variations and modi~ications of the invention can be made without departing from the ~pirit and ~cope thereof.
~Ac~ÇR~UND OF TH~ INVENTION
Ion exchange resi~ compositions ~on~aining pharmacologically active ingredients ar~ ~nown. However, one of the major drawbacks o~
the known compositions is that the same are not sufficiently dispersible in water. ~he lack of dispersibility in wa~er r~duc~s the time required for the pharmacological agent to act.
~g,~' ,~
It is accordinqly a primary object of the present invention to provide pharma~eutical ion ex~hange resins with a high degree of dispercibility in water.
It is yet a ~urther objec~ of the present invention to provide a method of producin~ the water dispersible pharmaceutical ion exchange resins.
Other other o~jects ~n~ advantage6 of the present invention will be apparent fro~ a ~urther reading of the specification and of ' the appended olaims.
With the above and other object~ in view, the pres~nt invention mainly ~omprises a pharmaceutical ion exchange resin compo~ition which is readily dispersible in water, said composition comprising a granulated ion exchange resin having a pharmac~logiçally acti~e ingredient bound thereto, by means of a sugar or sugar alcohol in the presence of a cuffi~ient amount of Water, al.cohol or aqu~ous alcohol to facilitate the grahu1ation.
~ he ~hrase "readily dispersible in water" in accordance with the present invention, means that the composition must disberse, with stirring in twent~ times its own weight of water within ten seconds.
200249:~
The presen~ invention is applicable to any acidic or basic drug, which may be bound to the ion exchange resi~. Preferably, howeve~, active ingredients having a biological half life of eight hours or less ~re used.
Among the suitable types of pharmacological active agents that can be used in acco~a~ce with ~he present invention are the following:
i) Narcotic analgesic~, such as codeine, dihydrocodein, hydromorphone, morphlne, pen~azocine and propoxyphene, ii] Sympathomimetics, such as norephedrine and pseudoephedrein, iii) ~ntitussiYes, such as dextromethorphan, iv) Analgesics, such as aspirin, v) Antiemetics, such as metoclopramide, vi) Anticholinergic.~, such as atropine, ipratropium bromide and scopolamine, vii) Muscle relaxants, such as cyolo~enzaprine and papaverine, viii) sronchodilators~ ~uch a~ salbutamol, terbutaline and theophylline, ix~ Anti~ioti~s, such as amoxycillin, ampicillin, azloclllin, bacampicillin, ce~amandole, cefonicid, ce~otaxime, cefotetan, cefoxitin, ceftriaxone, mezlocillin and piperacillin, x) Antidepre~nts, ~uch as bupropion, nomifensine, and nortripyline, xi) Antiasthmatics, s~ch as cromolyn, xii) Antineoplactic~, such as tamoxifen, xiii) Antiepileptics, s~ch as valproic acid and phenytoin, xi~) Cardiovascular agents, such as propranolol.
~2-20024g2 Ahy of the above may be used in the form o~ their acid addition salts, or, if appropriate, alkali or alkaline ~arth metal salts.
A wide vartety of resins may be u3ed for the purpose~ of the presen~ inven~ion. In the case of ba~ic drugs, any pharmacologically compatible ~ationic resin may be u3ed. In the cas~ of acidic drug~, any pharmacologi~ally ~ompati~le anioni~ resin may be used.
Suitable ion exchange resins generally have acr~lic, me~ha~rylic, phenol formaldehyde or dextra~ m~t~ices. ~o~ver, a preferred cationic ion exchange ~esin is a gel styrene-divinyl benzene sulphonic acid ~esin, such as Amherlite IR lZo (Trademark) Amberlite XE 69 (Trademark) and Dowex 50~ (Trademark), while a preferred anionic ion exchange resin is a gel styrene-divinyl benzene quaternary ammonium resin, ~uch a~ ~o~ex SBR (Trademark~ and ~owex SAR (Trademark).
The parti~le ~ize and, if appli~able, the degree of cross linking of the resin is determined by, among other fao~ors, the drug emplo~ed and the rate of drug release required. P~eferably, however, the resin has a particle size of from ~.045 to 1 mm, especially from 0.~45 to 0.5 mm. If ~pplicable, the pr~ferred degree of cross-linking is from ~ to 16% partio~larly from 8% to 12%.
The amount of drug bound to the resin is also determined by t~e choice of drug, as well as by the resin employed. Pr~ferably the weight ratio of bound drug to resih is from 1:3 to 2:~. particularly ~rom 2:3 to 3:2.
A~sorption of the drug onto the ion exchange resin partic1es is a well known teehnique as shown in British P~tent Nos. 82~,337 and 1,218,102 and U.S. Patent No. ~,990,332, and demonstrated in the examples below. ~n general, the druq is mixed with an aqueous 200249;~
suspen~ion of the resin and the complex ~s ~hen dried. Ad~orption of the drug onto the resil~ is detec~ed by an a~say of the guspending ~luid.
Preferably the sugar or the sugar alcohol has a molecular weight of from 90 to 550, ~specially from 150 to 370. Suitable suqars and ~ugar al~oh~lg are sucrose, ~extro~e, maltose, fructose, lacto~e, mannitol, sor~i~ol ~r most preferably xylitol. The sugar or s~gar alco~ol is preferably finely d~vided, a~l of the sugar or sugar alcohol prefer~bly having particle sizes of 600 microns or less (30 mesh sieve). In a particula~ly pr~ferred e~bodi~nent of ~he present invention, at le~st 90% ~by weig~) of the sugar~sugar alcohol will have particle sizes of 250 microns or less (~o mesh sie~re).
The oonoentration o~ the s~g~r~gar alcohol in the composition of the present invention must be high enough to allow the composition to disperse readily in water. This means that there must be enough 6ugar/~ugar alcohol pre~ent to allow the composition to disperse ~within 10 seconds~ when added with stirring to 20 times its Weight of water. Generally, the composition will oontain fro~ 25% to ~9%, preferably from 70~ to 95~ (b~ weight) of the sugar~ugar alcohol.
The drug-resin complex and the RugarJsugar alcohol are granulated in the presence of sufficient water, aqueous alcohol or alcohol to facilitate granulation. The most suitable alcohols are Cl-C4 aliphAtic alcohols, especially tho~;~ having a boili.nq point, at 7~0mm Hg of 100C or less. Preferred al~ohol~ are ~thanol and isopropanol.
P~efer~bly, the a~ount o~ granulating medium employed i~
from 10 to 20%, especially from 2 to 7% by weight of the weight o~
the oomplex~ugar, ~uyar a~cohols mlx. I~ a par~loularly preferred embodiment of the present proce~s the mixt~re is granulated until the particle size of the sugar~sugar alcohol mat~heg the resin particle size. In the present specification, ~matches~ mean6 that at least ~0% tby weight) of the sugar/su~r alcohol has a particle size bekween 0.5 and 1.5 time~ the mean par~icle size of the drug-~esin complex. Once the drug-resin complex and the sug~r/sugar ~lcohol h~ve been granulated, the gra~ules formed are then dried, preferably until their water conten~ i~ below 3% (~y weight), when measured ~y the Karl Fischer method of moisture analy~is.
Optionally, the drug-resin complex or the granules may be film coated with a material that permits release of the drug from the composition at the controlled rate.
The film coat will generally include a water insoluble material such as:
~a) a wax, either alone or in admixture with a fatty alcohol (b) shellac or zein, (o) a water insoluble cellulo~e derivative, especially ethyl cellulose (d) a polymethacrylate, especially ~udragit (trademark).
Preferably, the film ~oat comprises a mixture of the water insoluble material ahd a water soluble material. The ratio of water insolu~le to water soluble material is determined by among other ractOrs, tne ~elease ra~e requlre~ an~ the solub1litY ch~lracteristics of the material~ selected.
The water s~l~bl~ material may be, for exa~ple, triacetin, propylene glycol, polyethylene glycol, polyvinylpyrrolidone or, which is preferred, a water soluhle cellulose, such as hydroxypropyl cellulose, or especially, hydroxypropylmethyl cellulose.
~5-~o~ z Suitable combinationæ of water insoluble and WatQr soluble mate~ialc for the film ~oat include shellac and polyvinylpyrrolidone or~ prefera~le ethyl cellulose and hydroxypropylmethyl cellulo~e.
Once the ~bove processing is complete, t~e compofiition may then be presented in a suit~ble dosage form, ~uch as a capsule or sachet~ This i~ done ~imply by filling the cap~ule or saohet with the f inished compositi~n.
~ he following examples are ~iven to further illustrate the preseht invention. The scope of the invention is not, however, meant to be limited to the specific details of the examples.
Morphine sulphate (pentahydrate, 3 OOgm) was added to pu~ified water ~EP, llOgm) and mixed until ~11 of the powder was evenly wetted. Wi~h continuous mixing a cationic ex~hange r~in, Dowex W50x8-200, (Trade~ark) hydrous app~ox 50~ (by weight) water, 60 gm) ~s added to the morphlne suspension. The stirring was continued for 24 hours at a rate that kept the resin suspended. The resin was then washed with purified water and dried in a fluid bed dryer.
Xylitol, (500gIn 90% (by weight) having a particle size les~
than 200~m) was mixed with the morphin~-resin complex (50gm) and xanthan gum (200gm) in a ~ranulator. With ~ontinuoue ~ixing, p~rified ~ater was addéd to the ~ixture until evanly watt~d light granules were forme~.
~ enerall~ the amount of water added wa~ 2.0 - 5.0~ tby weight3 of the xylitol/comlex/xanthan gum weight. The moist granules were ~hen d~ied in a fluid bed dryer until the water cont~n~ was below about 3.0% (by weight), Karl Fl~cher method~.
Each ~nit dose of ~his compo~ition had the following formulation, mg~unit dose Morphine Sulphate (absorbed on the res.in as morphine base)20 ~owex W50xs-200 ~Trademark) 20 Xylitol 500 Xanthan Gum 20 ~XAMPLE 2 The procesc of Ex~mple 1 was repeated to form a composition having the following formulation:
mq/unit dose Metoclopramide Hydrochloride (absorhed on the re~in as metoclopramide base 15 Dowex W50x8-200 (Tra~emark) 15 Xylitol 500 Xanthan Gum 20 ~XAMPLE 3 ~he process of Example 1 was repeated to form a composition having the following formation:
mq/unit dose Hydromorphone Hydrochloride tabsorbed on the resin as hydromorphone base) 4 Dowex W5~x16-100 tTradem~rk) 12 Xyl itol S00 Xanthan Gum 20 ~LPLE 4 ~ he process of EXample 1 was rep~ated to form a composition having the following formulation:
m~/unit do~ç
Theophylline Sodium (absorbed on the resin as theophylline base) 100 Dowex 2x8~200 (Trademark~ 200 Xylitol 87~
Xanthan Gum 45 Polyoxy 40-stea~ate (trademark) S
~'~
The pro~ess of Example 1 was repeated except that the xylitol/morphine-resin complex/xanthan gum was dry mixed to form a pow~er, rather than wet granulated.
~ ISPERS~BI I~Y OF RESIN cOMPOSITIONs ~N wATER
Unit doses of the granular and powder products, produced accordlng to Example 1 and the ~omparative Example, respectively, were ~dded to 100ml of water with continuous mixing.
The granular product immediately (within 10 seconds) formed an aqueous ~pension of the resin. By contrast, the powder product formed a wettec~ ~ass that took a number of minutes to disperse in the aqueous medium (and thereby form a resin BUspensi.on).
Further~ore, while the granulated product gives a homogeneous produ~t in which ~he drug substance is dispersed uniformly throughout the composition, the dry mixed powder was non-homogenous, the drug subs~ance being non-uniformly di~tributcd throughout the compo~ition.
While the invention has been clescribed in particular with respect to the above examples, it is apparent that variations and modi~ications of the invention can be made without departing from the ~pirit and ~cope thereof.
Claims (20)
1. Readily water dispersible pharmaceutical ion exchange resin composition, said composition comprising a pharmacologically active ingredient bound to a granulated ion exchange resin with sugar or a sugar alcohol in the presence of water, alcohol or aqueous alcohol in an amount sufficient to facilitate granulation of said ion exchange resin.
2. Composition according to claim 1 wherein said sugar or sugar alcohol is sucrose, dextrose, maltose, fructose, lactose, mannitol, sorbitol or xylitol.
3. Composition according to claim 1 wherein said sugar alcohol is xylitol.
4. Composition according to claim 1 wherein said sugar alcohol has a particle size of 600 microns or less.
5. Composition according to claim 4 wherein at least 90% by weight of said sugar or sugar alcohol has a particle size of 250 microns or less.
6. Composition according to claim 1 wherein said composition contains 25-99% by weight of the sugar or sugar alcohol.
7. Composition according to claim 1 wherein said composition contains 70-95% by weight of said sugar or sugar alcohol.
8. Composition according to claim 1 wherein the amount of water, alcohol or aqueous alcohol is from 1-20% by weight of the weight of said pharmacologically active agent, ion exchange resin and sugar or sugar alcohol.
9. Composition according to claim 8 wherein the amount of water, alcohol or aqueous alcohol is from 2-7% by weight.
10. Composition according to claim 1 wherein the particle size of said granulated ion exchange resin is substantially the same as the particle size of said sugar or sugar alcohol.
11. Composition according to claim 1 in a capsule or sachet.
12. Method of producing a pharmaceutical ion exchange composition that is readily dispersible in water, said method comprising granulating a pharmaceutically compatible ion exchange resin, having a pharmacologically active ingredient bound thereto with a sugar or sugar alcohol in the presence of a sufficient amount of water, alcohol or aqueous alcohol to facilitate granulation.
13. Method according to claim 12 wherein said sugar of sugar alcohol is sucrose, dextrose, maltose, fructose, lactose; mannitol, sorbitol of xylitol.
14. Method according to claim 12 wherein said sugar of sugar alcohol is xylitol.
15. Method according to claim 12 wherein said sugar of sugar alcohol has a particle size of of 600 microns or less.
16. Method according to claim 12 wherein at least 90% by weight of said sugar of sugar alcohol has a particle size of 250 microns or less.
17. Method according to claim 12 wherein the amount as sugar or sugar alcohol is between 25-99% by weight.
18. Method according to claim 12 wherein the amount of water, alcohol or aqueous alcohol utilized is in an amount of 1-20% by weight of the combined weight of said pharmacologically active agent, said resin and said sugar as sugar alcohol.
19. Method according to claim 12 wherein the granulation is continued until the particle size of the ion exchange resin matches the size of the sugar or sugar alcohol.
20. Method according to claim 12 wherein after granulation the granules are dried until the water content thereof is below 3% by weight.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8826407.2 | 1988-11-11 | ||
| GB888826407A GB8826407D0 (en) | 1988-11-11 | 1988-11-11 | Pharmaceutical ion exchange resin composition |
| GB8828592.9 | 1988-12-07 | ||
| GB888828592A GB8828592D0 (en) | 1988-12-07 | 1988-12-07 | Pharmaceutical ion exchange resin composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2002492A1 true CA2002492A1 (en) | 1990-05-11 |
Family
ID=26294609
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002002492A Abandoned CA2002492A1 (en) | 1988-11-11 | 1989-11-08 | Pharmaceutical ion exchange resin composition |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US5071646A (en) |
| EP (1) | EP0368682B1 (en) |
| JP (1) | JP2825202B2 (en) |
| AT (1) | ATE123218T1 (en) |
| AU (1) | AU621949B2 (en) |
| CA (1) | CA2002492A1 (en) |
| DE (1) | DE68922894T2 (en) |
| DK (1) | DK175154B1 (en) |
| ES (1) | ES2075061T3 (en) |
| GB (1) | GB2225941B (en) |
| IE (1) | IE893625L (en) |
Families Citing this family (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9003904D0 (en) * | 1990-12-07 | 1990-12-07 | Astra Ab | METHOD FOR THE MANUFACTURE OF A PHARMACEUTICAL DOSAGE FORM |
| SE9003903D0 (en) * | 1990-12-07 | 1990-12-07 | Astra Ab | NEW PHARMACEUTICAL FORMULATIONS |
| US5275820A (en) * | 1990-12-27 | 1994-01-04 | Allergan, Inc. | Stable suspension formulations of bioerodible polymer matrix microparticles incorporating drug loaded ion exchange resin particles |
| US5840339A (en) * | 1991-07-30 | 1998-11-24 | Kunin; Robert | Blood cholesterol reducing pharmaceutical composition |
| SE9103110D0 (en) * | 1991-10-24 | 1991-10-24 | Kabi Pharmacia Ab | NEW DRUG FORMULATION |
| US5478577A (en) * | 1993-11-23 | 1995-12-26 | Euroceltique, S.A. | Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level |
| US5968551A (en) | 1991-12-24 | 1999-10-19 | Purdue Pharma L.P. | Orally administrable opioid formulations having extended duration of effect |
| US5958459A (en) * | 1991-12-24 | 1999-09-28 | Purdue Pharma L.P. | Opioid formulations having extended controlled released |
| US5296228A (en) * | 1992-03-13 | 1994-03-22 | Allergan, Inc. | Compositions for controlled delivery of pharmaceutical compounds |
| US5350584A (en) * | 1992-06-26 | 1994-09-27 | Merck & Co., Inc. | Spheronization process using charged resins |
| USRE39300E1 (en) | 1993-01-28 | 2006-09-19 | Virginia Commonwealth University Medical College Of Virginia | Inhibiting the development of tolerance to and/or dependence on an addictive substance |
| US5321012A (en) * | 1993-01-28 | 1994-06-14 | Virginia Commonwealth University Medical College | Inhibiting the development of tolerance to and/or dependence on a narcotic addictive substance |
| IL119660A (en) * | 1993-05-10 | 2002-09-12 | Euro Celtique Sa | Controlled release formulation comprising tramadol |
| IL110014A (en) * | 1993-07-01 | 1999-11-30 | Euro Celtique Sa | Solid controlled-release oral dosage forms of opioid analgesics |
| US7740881B1 (en) | 1993-07-01 | 2010-06-22 | Purdue Pharma Lp | Method of treating humans with opioid formulations having extended controlled release |
| US5879705A (en) * | 1993-07-27 | 1999-03-09 | Euro-Celtique S.A. | Sustained release compositions of morphine and a method of preparing pharmaceutical compositions |
| US5843480A (en) * | 1994-03-14 | 1998-12-01 | Euro-Celtique, S.A. | Controlled release diamorphine formulation |
| GB9422154D0 (en) * | 1994-11-03 | 1994-12-21 | Euro Celtique Sa | Pharmaceutical compositions and method of producing the same |
| US5931809A (en) | 1995-07-14 | 1999-08-03 | Depotech Corporation | Epidural administration of therapeutic compounds with sustained rate of release |
| GB9517883D0 (en) * | 1995-09-01 | 1995-11-01 | Euro Celtique Sa | Improved pharmaceutical ion exchange resin composition |
| GB9519363D0 (en) | 1995-09-22 | 1995-11-22 | Euro Celtique Sa | Pharmaceutical formulation |
| WO1998036737A1 (en) * | 1997-02-25 | 1998-08-27 | The Procter & Gamble Company | Wet granulating method |
| US5980882A (en) * | 1997-04-16 | 1999-11-09 | Medeva Pharmaceuticals Manufacturing | Drug-resin complexes stabilized by chelating agents |
| RU2241458C2 (en) | 1997-12-22 | 2004-12-10 | Эро-Селтик, С.А. | Combinations of agonist/antagonist for opioid |
| US6806294B2 (en) | 1998-10-15 | 2004-10-19 | Euro-Celtique S.A. | Opioid analgesic |
| US8545880B2 (en) * | 1999-02-26 | 2013-10-01 | Andrx Pharmaceuticals, Llc | Controlled release oral dosage form |
| US6210716B1 (en) | 1999-02-26 | 2001-04-03 | Andrx Pharmaceuticals, Inc. | Controlled release bupropion formulation |
| EP2295043A1 (en) | 1999-10-29 | 2011-03-16 | Euro-Celtique S.A. | Controlled release hydrocodone formulations |
| US10179130B2 (en) | 1999-10-29 | 2019-01-15 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
| JP2003522144A (en) | 2000-02-08 | 2003-07-22 | ユーロ−セルティーク，エス．エイ． | Controlled release compositions comprising opioid agonists and antagonists |
| MXPA02008183A (en) * | 2000-02-24 | 2002-11-29 | Upjohn Co | New drug combinations. |
| US6855721B1 (en) | 2000-07-28 | 2005-02-15 | Indevus Pharmaceuticals, Inc. | Methods and compositions for alleviating stuttering |
| CN101317825A (en) | 2000-10-30 | 2008-12-10 | 欧罗赛铁克股份有限公司 | Controlled release hydrocodone formulations |
| UA81224C2 (en) | 2001-05-02 | 2007-12-25 | Euro Celtic S A | Dosage form of oxycodone and use thereof |
| US20110104214A1 (en) | 2004-04-15 | 2011-05-05 | Purdue Pharma L.P. | Once-a-day oxycodone formulations |
| CN1525851A (en) | 2001-05-11 | 2004-09-01 | ������ҩ������˾ | Abuse-resistant controlled-release opioid dosage form |
| SI1416842T1 (en) | 2001-07-18 | 2009-06-30 | Euro Celtique Sa | Pharmaceutical combinations of oxycodone and naloxone |
| ES2326794T3 (en) | 2001-08-06 | 2009-10-20 | Euro-Celtique S.A. | FORMULATIONS OF OPIOID AGONISTS WITH LIBERABLE AND SEQUESTED ANTAGONISTS. |
| US20030044458A1 (en) | 2001-08-06 | 2003-03-06 | Curtis Wright | Oral dosage form comprising a therapeutic agent and an adverse-effect agent |
| US20030157168A1 (en) | 2001-08-06 | 2003-08-21 | Christopher Breder | Sequestered antagonist formulations |
| US20030099711A1 (en) * | 2001-08-29 | 2003-05-29 | David Meadows | Sustained release preparations |
| US20030180249A1 (en) * | 2002-03-18 | 2003-09-25 | Khanna Satish Chandra | Dosage forms for hygroscopic active ingredients |
| ES2546010T3 (en) | 2002-04-05 | 2015-09-17 | Euro-Celtique S.A. | Pharmaceutical preparation containing oxycodone and naloxone |
| PT1551372T (en) | 2002-09-20 | 2018-07-23 | Alpharma Pharmaceuticals Llc | Sequestering subunit and related compositions and metohds |
| US6893660B2 (en) * | 2002-11-21 | 2005-05-17 | Andrx Pharmaceuticals, Inc. | Stable pharmaceutical compositions without a stabilizer |
| US20040202717A1 (en) | 2003-04-08 | 2004-10-14 | Mehta Atul M. | Abuse-resistant oral dosage forms and method of use thereof |
| MY135852A (en) | 2003-04-21 | 2008-07-31 | Euro Celtique Sa | Pharmaceutical products |
| US20050036977A1 (en) * | 2003-08-11 | 2005-02-17 | Dilip Gole | Taste-masked resinate and preparation thereof |
| CN1845722A (en) * | 2003-09-03 | 2006-10-11 | 马林克罗特公司 | Granular sustained release preparation and production thereof |
| US20050181050A1 (en) * | 2004-01-28 | 2005-08-18 | Collegium Pharmaceutical, Inc. | Dosage forms using drug-loaded ion exchange resins |
| US7429617B2 (en) * | 2004-04-27 | 2008-09-30 | Medicinova, Inc. | Phenoxyalkycarboxylic acid derivatives in the treatment of interstitial cystitis |
| CN1968697B (en) * | 2004-05-14 | 2012-05-16 | 株式会社绿十字 | Neuroprotective properties of dextrorotatory morphinans |
| EP1604666A1 (en) | 2004-06-08 | 2005-12-14 | Euro-Celtique S.A. | Opioids for the treatment of the Chronic Obstructive Pulmonary Disease (COPD) |
| US20080095842A1 (en) * | 2004-12-06 | 2008-04-24 | Antarkar Amit K | Rapidly Disintegrating Taste Masked Compositions and a Process for Its Preparations |
| EP1846040A2 (en) * | 2005-01-28 | 2007-10-24 | Collegium Pharmaceutical, Inc. | Non-ionic non-aqueous vehicles for topical and oral administration of carrier-complexed active agents |
| EP1702558A1 (en) | 2005-02-28 | 2006-09-20 | Euro-Celtique S.A. | Method and device for the assessment of bowel function |
| US8343546B2 (en) * | 2005-09-13 | 2013-01-01 | Coating Place, Inc. | Ion exchange resin treated to control swelling |
| US7811604B1 (en) | 2005-11-14 | 2010-10-12 | Barr Laboratories, Inc. | Non-effervescent, orally disintegrating solid pharmaceutical dosage forms comprising clozapine and methods of making and using the same |
| BRPI0709606B8 (en) | 2006-03-16 | 2021-05-25 | Tris Pharma Inc | orally administrable liquid suspension with modified release characteristics |
| PL2526932T3 (en) | 2006-06-19 | 2017-12-29 | Alpharma Pharmaceuticals Llc | Pharmaceutical composition |
| US8623418B2 (en) | 2007-12-17 | 2014-01-07 | Alpharma Pharmaceuticals Llc | Pharmaceutical composition |
| WO2009088385A1 (en) * | 2008-01-04 | 2009-07-16 | Capricorn Pharma Inc. | Resin-complex granulation for water-soluble drugs and associated methods |
| SG174286A1 (en) | 2009-03-10 | 2011-10-28 | Euro Celtique Sa | Immediate release pharmaceutical compositions comprising oxycodone and naloxone |
| US20120107381A1 (en) * | 2009-05-13 | 2012-05-03 | Relypsa, Inc. | Powder formulations of potassium-binding active agents |
| JP2013119550A (en) | 2011-12-08 | 2013-06-17 | Medicinova Inc | Method for treating nonalcoholic fatty liver disease and nonalcoholic steatohepatitis |
| US8962687B2 (en) | 2012-12-05 | 2015-02-24 | Medicinova, Inc. | Method of treating liver disorders |
| WO2014167440A1 (en) * | 2013-03-26 | 2014-10-16 | Wockhardt Limited | Modified release pharmaceutical compositions of cyclobenzaprine or salts thereof |
| NZ716267A (en) | 2013-07-23 | 2017-05-26 | Euro Celtique Sa | A combination of oxycodone and naloxone for use in treating pain in patients suffering from pain and a disease resulting in intestinal dysbiosis and/or increasing the risk for intestinal bacterial translocation |
| ES2843511T3 (en) | 2013-07-25 | 2021-07-19 | Medicinova Inc | Methods to reduce blood levels of triglycerides, total cholesterol, and low-density lipoproteins |
| US20150321989A1 (en) | 2014-05-08 | 2015-11-12 | Medicinova, Inc. | Method of treating idiopathic pulmonary fibrosis |
| US9346754B2 (en) | 2014-05-08 | 2016-05-24 | Medicinova, Inc. | Method of treating advanced non-alcoholic steatohepatitis |
| CN106470678A (en) | 2014-06-02 | 2017-03-01 | 美迪诺亚公司 | Suppression or the Fibrotic method for the treatment of |
| JP6827924B2 (en) | 2014-11-26 | 2021-02-10 | メディシノバ・インコーポレイテッドＭｅｄｉｃｉＮｏｖａ， Ｉｎｃ． | Pharmaceuticals and compositions comprising a combination of ibudilast and riluzole |
| US11590228B1 (en) | 2015-09-08 | 2023-02-28 | Tris Pharma, Inc | Extended release amphetamine compositions |
| CN109890371A (en) | 2016-08-26 | 2019-06-14 | 斯瑞尼瓦萨饶·韦帕切杜 | Composition and its method |
| US11590081B1 (en) | 2017-09-24 | 2023-02-28 | Tris Pharma, Inc | Extended release amphetamine tablets |
| WO2022251464A1 (en) | 2021-05-28 | 2022-12-01 | Medicinova, Inc. | Phenoxyalkylcarboxylic acid derivatives and their use in lowering triglyceride levels |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB791281A (en) * | 1955-01-13 | 1958-02-26 | Genatosan Ltd | Pharmaceutical products |
| GB822728A (en) * | 1955-07-14 | 1959-10-28 | Pfizer & Co C | Vitamin products and process of preparing same |
| GB835932A (en) * | 1956-03-27 | 1960-05-25 | Ciba Ltd | Process for the manufacture of therapeutic tablet granulations |
| FR792M (en) * | 1959-11-13 | 1961-09-11 | ||
| US3138525A (en) * | 1961-06-16 | 1964-06-23 | Hoffmann La Roche | Castor wax-amprotropine-resin compositions |
| GB982150A (en) * | 1961-09-29 | 1965-02-03 | Glaxo Group Ltd | Therapeutic resin complexes |
| BE635819A (en) * | 1962-08-06 | |||
| DE2706660A1 (en) * | 1977-02-17 | 1978-08-24 | Merck Patent Gmbh | GRANULATES CONTAINING ASCORBIC ACID AND THE PROCESS FOR THEIR MANUFACTURING |
| GB1566609A (en) * | 1977-03-10 | 1980-05-08 | Reckitt & Colmann Prod Ltd | Pharmaceutical compositions containing cholestyramine and alginic acid |
| US4221778A (en) * | 1979-01-08 | 1980-09-09 | Pennwalt Corporation | Prolonged release pharmaceutical preparations |
| DE2929456A1 (en) * | 1979-07-20 | 1981-02-05 | Lentia Gmbh | COMPOSITION WITH EXTENDED BRONCHOLYTIC AND TOCOLYTIC EFFECTIVENESS, A METHOD FOR THE PRODUCTION THEREOF AND BRONCHOLYTIC AND TOKOLYTICALLY ACTIVE AGENT |
| US4404346A (en) * | 1980-08-05 | 1983-09-13 | Rohm And Haas Company | Production of powdered resin and the powdered resin so produced |
| US4369175A (en) * | 1981-07-27 | 1983-01-18 | Ciba-Geigy Corporation | Process for the manufacture of prolonged action vincamine preparations, the vincamine preparations so obtained, and medicaments containing them |
| CH655507B (en) * | 1983-01-12 | 1986-04-30 | ||
| US4847362A (en) * | 1985-02-01 | 1989-07-11 | New York University | Method for purifying antihemophilic factor |
| EP0200252B1 (en) * | 1985-05-02 | 1999-03-10 | Yamanouchi Europe B.V. | Tablets comprising trimethoprim and a sulfonamide |
| EP0199855A1 (en) * | 1985-05-02 | 1986-11-05 | Gist-Brocades N.V. | Tablets comprising tromethoprim and a sulfonamide |
| US4748361A (en) * | 1985-12-05 | 1988-05-31 | Mitsubishi Kinzoku Kabushiki Kaisha | Permanent magnet electric motor |
| US4788055A (en) * | 1985-12-09 | 1988-11-29 | Ciba-Geigy Corporation | Resinate sustained release dextromethorphan composition |
| DD249634B1 (en) * | 1986-06-04 | 1988-09-21 | Bitterfeld Chemie | CHOLESTEROL SENDING AGENT AND METHOD FOR THE PRODUCTION THEREOF |
| IL90245A (en) * | 1988-05-11 | 1994-04-12 | Glaxo Group Ltd | Resin adsorbate comprising ranitidine together with a synthetic cation exchange resin, its preparation and pharmaceutical compositions containing it |
-
1989
- 1989-11-08 CA CA002002492A patent/CA2002492A1/en not_active Abandoned
- 1989-11-09 US US07/434,416 patent/US5071646A/en not_active Expired - Lifetime
- 1989-11-09 JP JP1290147A patent/JP2825202B2/en not_active Expired - Lifetime
- 1989-11-09 AU AU44530/89A patent/AU621949B2/en not_active Expired
- 1989-11-10 GB GB8925492A patent/GB2225941B/en not_active Revoked
- 1989-11-10 AT AT89311701T patent/ATE123218T1/en not_active IP Right Cessation
- 1989-11-10 ES ES89311701T patent/ES2075061T3/en not_active Expired - Lifetime
- 1989-11-10 DE DE68922894T patent/DE68922894T2/en not_active Expired - Lifetime
- 1989-11-10 IE IE893625A patent/IE893625L/en not_active IP Right Cessation
- 1989-11-10 DK DK198905645A patent/DK175154B1/en not_active IP Right Cessation
- 1989-11-10 EP EP89311701A patent/EP0368682B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP0368682A1 (en) | 1990-05-16 |
| GB2225941A (en) | 1990-06-20 |
| US5071646A (en) | 1991-12-10 |
| AU4453089A (en) | 1990-05-17 |
| ATE123218T1 (en) | 1995-06-15 |
| DE68922894D1 (en) | 1995-07-06 |
| ES2075061T3 (en) | 1995-10-01 |
| EP0368682B1 (en) | 1995-05-31 |
| IE893625L (en) | 1990-05-11 |
| DK564589A (en) | 1990-05-12 |
| GB2225941B (en) | 1992-12-09 |
| GB8925492D0 (en) | 1989-12-28 |
| DK564589D0 (en) | 1989-11-10 |
| AU621949B2 (en) | 1992-03-26 |
| JP2825202B2 (en) | 1998-11-18 |
| DK175154B1 (en) | 2004-06-21 |
| JPH02243618A (en) | 1990-09-27 |
| DE68922894T2 (en) | 1996-01-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |