CN1764441A - Formulations comprising tolterodine and cocoa powder and use thereof - Google Patents

Formulations comprising tolterodine and cocoa powder and use thereof Download PDF

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Publication number
CN1764441A
CN1764441A CNA2004800080871A CN200480008087A CN1764441A CN 1764441 A CN1764441 A CN 1764441A CN A2004800080871 A CNA2004800080871 A CN A2004800080871A CN 200480008087 A CN200480008087 A CN 200480008087A CN 1764441 A CN1764441 A CN 1764441A
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preparation
tolterodine
agent
oil
acid
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N－O·林德贝里
K·E·A·林德尔
A·C·马蒂诺
F·P·尼克拉松
K·M·蒂勒松
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Pfizer Health AB
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Abstract

The present invention provides a tolterodine-containing pharmaceutical formulation that comprises cocoa powder, process for manufacturing the formulation and use of the formulation for treating overactive bladder.

Description

Comprise preparation of tolterodine and cocoa powder and uses thereof
Invention field
The present invention relates to randomly to comprise the new Orally administered pharmaceutical preparation of the tolterodine of its salt, complex, prodrug and metabolite; The tolterodine that randomly comprises its salt, prodrug and metabolite produces the purposes of the medicine of anti-overactive bladder (overactive bladder) effect in Orally administered being used for of preparation; With by the Orally administered method that randomly comprises the tolterodine treatment of overactive blad-der of its salt, prodrug and metabolite.
Background
Tolterodine is a kind of effective and safe chemical compound that is used for the treatment of overactive bladder.US5,382,600 (Pharmacia ﹠amp; The effectiveness of synthesizing and be used for the treatment of overactive bladder of tolterodine is disclosed Upjohn AB).Under the oral dose of twice 1 of every days or 2mg, obtained best efficacy/side effect profile.
The molecular weight of tolterodine is 325.0, and the molecular weight of its tartrate is 475.6.Enantiomeric purity＞99%.The pKa value is 9.87, and at room temperature, the dissolubility in water is about 11mg/ml.Partition coefficient between the phosphate buffer of n-octyl alcohol and pH7.32 (Log P) is 1.83.
Figure A20048000808700071
Tolterodine, PNU-200583N, N-diisopropyl-3-(2-hydroxy-5-methyl base phenyl)-3-phenylpropylamine.
The metabolic main metabolic of tolterodine path causes forming the 5-HM metabolite by Cytochrome P450 2D6 mediation, (R)-N, N-diisopropyl-3-(2-hydroxyl-5-hydroxymethyl phenyl)-3-phenylpropylamine.This metabolite and tolterodine have similar pharmacological property-referring to Nilvebrant L, Gillberg P-G, Sparf B. " a kind of main metabolites of PNU-200577-tolterodine-Antimuscarinic effect and bladder selectivity " Pharmacol.Toxicol. (1997) 81:195-207.About with tolterodine at the similarity aspect the pharmacological property, referring to Brynne N, Dal é n P, Alv á nG, Bertilsson L and Gabrielsson J, Clin Pharmacol Ther 1998 (63): 529-39.
N-takes off the alkyl metabolite and is mediated by CYP3A, and can further be metabolized to the 5-hydroxy metabolite product that N-takes off alkyl.Referring to following flow chart.
As CH at the 5-HM metabolite 2When forming hydroxy-acid group on the OH group, form another metabolite.CH when the 5-HM metabolite that takes off alkyl at N- 2When forming hydroxy-acid group on the OH group, form another metabolite again.
Tolterodine of the present invention comprise its R-isomer, S-isomer and racemic mixture with and salt, complex, prodrug and metabolite.Main effect be available from its R-isomer and racemic mixture with and salt, complex, prodrug and metabolite.The example of salt has tolterodine 1-tartrate and tolterodine mesylate.The example of complex has the complex between tolterodine and the beta-schardinger dextrin-and the complex of tolterodine and ion exchange compositions such as ion exchange resin hydrochlorate.
Prior art
Above-mentioned US 5,382,600 does not disclose any and the similar preparation of the present invention.
WO 98/03067 discloses the transdermal administration of tolterodine S-isomer.
WO 00/12070 discloses the R-isomer of tolterodine and the transdermal administration of racemate.
Do not find the preparation that contain tolterodine similar in the prior art to the present invention.
Chocolate is different with cocoa powder, and it seldom as the composition in the drug products, only is used in the caccagogue up to now.An example is the ExLax that comprises sennoside that is sold by Novartis _, it is the caccagogue piece that has added chocolate.Purex is a kind of caccagogue of wherein preparing phenolphthalein with chocolate in list marketing the 1950's.Knownly there is not any compositions that comprises tolterodine and chocolate.
Now be surprisingly found out that: can obtain a kind of Orally administered tolterodine preparation as odor mask and formation agent (texturizer) by making the preparation that contains tolterodine comprise cocoa powder, it can need not to be aided with liquid and be applied, and has enough tastes to cover distasteful composition such as tolterodine with optional buffer agent.Unexposed up to now similar preparation, and the technical staff can not envision preparation of the present invention if do not spend creative work.
Therefore, as further described below, the present invention is new and creative.
Summary of the invention
The invention provides the Orally administered pharmaceutical preparation of the tolterodine that randomly comprises its salt, prodrug and metabolite, it is used to produce anti-overactive bladder effect, comprises forcing urine base instability, detrusor hyperreflexia, frequent micturition, urgent micturition and urgent urinary incontinence.Using can be to be applied to the human or animal.
Need not to add liquid can finish and use.Under all that situation that for example can't obtain clean water or other suitable liquid, as in travelling, need not using of extra liquid is a big advantage.Not noticeable when using in addition, this also is a big advantage when lecture and performance.In addition, preparation of the present invention should be melted in the mouth when using rather than be swallowed, and this is very big advantage for all that is swallowed the inconvenient people of conventional tablet.Therefore, a kind of useful especially dosage form of the present invention is disintegrate or thawing and need not the dosage form of drinking water or other liquid in mouth.
Said preparation is the dosage form that comprises the tolterodine for the treatment of effective dose.Herein " treatment effective dose " is the amount that is enough to produce anti-overactive bladder effect, comprises forcing urine base instability, detrusor hyperreflexia, frequent micturition, urgent micturition and urgent urinary incontinence." frequent micturition " mainly refers to urinate more than 2 times needing to urinate more than 8 times during 24 hours or need every night." urgent micturition " mainly refers to frequent, the strong and unexpected needs of urinating." urgent urinary incontinence " main phalangeal process is right urinate unconscious urinating after needing.
The amount of preferred tolterodine is lower than the amount that causes remarkable side effect.
The present invention is suitable for discreet self-administration." discreet self-administration " herein mean existence that treatment needs not the oneself of attracts attention use.
The present invention also provides the method for using preparation for treating overactive bladder of the present invention, and the method for using formulation preparation medicine of the present invention.Further feature of the present invention partly is significantly, and part is pointed out hereinafter.
The purpose of this invention is to provide the new Orally administered pharmaceutical preparation of the tolterodine that comprises cocoa powder.
Second purpose of the present invention provides the method for the described preparation of preparation.
The 3rd purpose of the present invention is to use the method for described formulations therapy for treating overactive bladder.
Other purpose of the present invention is that significantly the other purpose will become obvious from description and claim hereinafter to those skilled in the art.
The major advantage that preparation of the present invention provides is:
1) said preparation provides enough tastes to cover;
When 2) using, said preparation is without any need for extra liquid;
3) with comparing with the conventional tablet that liquid is used, owing to do not add liquid when using, thus use said preparation can not increase needs to treatment, because can not increase the burden of urinary system.
4) said preparation provides discreet self-administration;
5) said preparation can not resemble produce the conventional tablet direct patient perceptible with the getting in touch of medicine.
6) said preparation can provide rapid transmucosal absorption, especially when adding buffer agent.
Detailed Description Of The Invention
Main purpose of the present invention provides the pharmaceutical preparation that comprises tolterodine, and it can be used for treatment of overactive blad-der, comprises forcing urine base instability, detrusor hyperreflexia, frequent micturition, urgent micturition and urgent urinary incontinence.
More specifically, the purpose of this invention is to provide this preparation that comprises tolterodine that is used for transmucosal delivery, it mainly is being with or without the auxiliary disintegrate and/or the thawing in the oral cavity down of saliva or mechanical erosion or its combination, and said preparation can demonstrate the adhesiveness to organizing in the oral cavity afterwards.
Preferably, said preparation does not need to add liquid when using.With comparing with the conventional tablet that liquid is used, owing to do not add liquid when using, thus use said preparation can not increase needs to treatment, because can not increase the burden of urinary system.Do not produce extra urine.
The optional buffer agent that adds provides the of short duration variation of the local pH value of saliva.Therefore fractional more at high proportion tolterodine is converted to its lower ionized form.Thereby help to stride the mucosa infiltration, increase the absorption of activating agent.To those skilled in the art, one or more pKa of activating agent are depended in the selection that is apparent that buffer system.
It has surprisingly been found that: realized enough tastes of distasteful composition such as tolterodine itself and/or buffer agent are covered by using cocoa powder.Cocoa powder is as odor mask and constitute agent.
The definition of cocoa powder is the cocoa nib (cocoa nib) that some fat are removed and pulverize.The definition of cocoa nib is to remove the cacao bean that shells.The definition of cocoa butter is the oils and fats of extrusion the center (nuclear or grain) from cacao bean.
Cocoa powder is prepared by the cacao bean of baking.It is complicated chemical compound, comprises starch, cocoa butter, aminoacid, protein, xanthine, amine, monosaccharide and polysaccharide, phospholipid, flavone compound, pyrazine compounds etc.
Embodiment preferred is the preparation of heavily about 400mg, and it has following preferred prescription (w/w):
Composition Amount (%) Function
Tolterodine 1-tartrate 0.25 Activating agent
Hydrogenated soybean oil 43.55 Lipid components
Cocoa powder 18.00 Odor mask/formation agent
Mannitol 18.00 Diluent
Corn starch 13.35 Diluent
Aspartame 0.15 Sweeting agent
Acesulfame-K 0.10 Sweeting agent
Titanium dioxide 2.00 Coloring agent
Monosodium glutamate 0.60 The taste improver
Herba Menthae and vanilla flavor 3.00 Correctives
Soybean lecithin 1.00 Emulsifying agent
Embodiment
Be the non-limiting example of preparation embodiment of the present invention below.
Embodiment 1: the preparation of preferred embodiment
Preparation with a kind of heavy about 400mg of following preferred compositions (w/w) preparation:
Composition Amount (%) Function
Tolterodine 1-tartrate 0.25 Activating agent
Hydrogenated soybean oil 43.55 Lipid components
Cocoa powder 18.00 Odor mask/formation agent
Mannitol 18.00 Diluent
Corn starch 13.35 Diluent
Aspartame 0.15 Sweeting agent
Acesulfame-K 0.10 Sweeting agent
Titanium dioxide 2.00 Coloring agent
Monosodium glutamate 0.60 The taste improver
Herba Menthae and vanilla flavor 3.00 Correctives
Soybean lecithin 1.00 Emulsifying agent
Cocoa powder can use with the form of non-alkalization and the form of alkalization.The two all can be used for preparation of the present invention.When the slightly gentle taste of needs, the cocoa powder of preferred alkalization.
With a part of hydrogenated soybean oil fusing.Add solid constituent, i.e. tolterodine 1-tartrate, cocoa powder, mannitol, corn starch, aspartame, acesulfame-K, titanium dioxide, monosodium glutamate and correctives (if solid) and mix.By in roll-refiner, grinding the granularity that reduces solid constituent.If solid constituent has reached desired particle size, for example by with grind the granularity that has reached required before lipid component mixes, then save the rolling lappingout.After in roll-refiner, handling, mixture is mixed with the lipid component of remaining fusing, if perhaps solidified, then refuse, and mix with the hydrogenated soybean oil of remaining fusing.In suitable blender, carry out the mixing of melt.Add liquid component, i.e. soybean lecithin and correctives (if liquid).After carrying out appropriate pretreatment, if desired, prepare tablet or other solid dosage forms with suitable technique subsequently, as molding, extrude or congeal, comprise into ingot (pastillation).Also can adopt other appropriate preparation method.
Embodiment 2: the preparation of another embodiment
Basically according to embodiment 1 in identical mode prepare the preparation of a kind of heavy about 500mg, it has following preferred composition (w/w):
Composition Amount (%) Function
Tolterodine 1-tartrate 0.20 Activating agent
Cocoa powder 50.00 Odor mask/formation agent
Hydrogenated soybean oil 44.00 Lipid components
Titanium dioxide 2.50 Coloring agent
Sodium chloride 0.55 The taste improver
Aspartame 0.15 Sweeting agent
Acesulfame-K 0.10 Sweeting agent
Vanilla flavor 1.50 Correctives
Soybean lecithin 1.00 Emulsifying agent
Embodiment 3: the preparation of other embodiment
Basically according to embodiment 1 in identical mode prepare have following composition (w/w), heavily about 200mg is to the preparation of about 1000mg:
Composition Amount (%) Function
Tolterodine (alkali, prodrug, metabolite, salt or complex) 0.1-2 Activating agent
Cacaolike butter (cocoa butter equivalent, CBE) 35-55 Lipid components
Cocoa powder 8-55 Odor mask/formation agent
Diluent water soluble or dispersible is preferably the acinous powder 0-40 Diluent
Sweeting agent 0.2-3 Sweeting agent
Buffer agent 0-10 Buffer agent
Correctives 0-4 Correctives
The bitterness improver 0-3 The taste improver
Emulsifiers/solubilizers 0.3-6 Emulsifying agent
Coloring agent 0-3 Coloring agent
Embodiment 4: the preparation of alternative embodiment
By being replaced with the alternative compounds with equivalent functions, some excipient in the embodiment of the foregoing description obtained useful embodiment.
Can use cocoa powder with the form of its non-alkalization, the form or their mixture of its alkalization.
Diluent can be selected from one or more in the following chemical compound: sucrose, fructose, glucose, galactose, lactose, maltose, Nulomoline, pharmaceutically useful polyhydric alcohol such as xylitol, sorbitol, maltose alcohol, mannitol, hydroxyl isomaltulose (isomalt) and glycerol, or polydextrose, or starch, or their any mixture, but the degree of its adding only keeps enough taste masking effects for cocoa powder.
Lipid components is a lipid component, can be selected from the following chemical compound one or more:
-cocoa butter and cocoa butter substitute, comprise cacaolike butter (CBE), cocoa butter succedaneum (cocoabutter substitute, CBS), the cocoa butter alternative (cocoa butter replacer, CBR) and cocoa butter improver (CBI),
-Oleum Cocois, palm-kernel oil and feature be mainly based on lauric acid and myristic acid other similarly oil,
-Petiolus Trachycarpi oil, Adeps Bovis seu Bubali resin, candlenut oil, illipe fat, Fructus Mangifera Indicae kernel oil, sal tree fat (sal fat) and feature are mainly based on Palmic acid, oleic acid and stearic other similar oils and fats,
-Semen Maydis oil, Oleum helianthi, hybridization (hybrid) Oleum helianthi, Oleum Glycines, rapeseed oil, Canola oil, olive oil, Testa oryzae oil, Oleum Gossypii semen, Arachis (Semen arachidis hypogaeae, Semen arachidis hypogaeae) oil and feature are mainly based on oleic acid, linoleic acid plus linolenic acid and other oil of being hydrogenated to suitable fusing point
The oils and fats of-fish oil, Adeps Bovis seu Bubali, Adeps Sus domestica, butterfat and other animal derived and
-the synthetic fat, resterification fat, the tristearin that obtain by the chemical reaction that does not use acid, alkali or enzymatic fatty acid and glycerol,
Wherein said one or more chemical compounds are as the single component or the use that is mixed with each other, be crude product or utilize physics or the alkali refining method purified, or be carried out further processing, comprise catalytic hydrogenation, ester exchange, transesterify and fractionated.
One or more optional buffer agents can be selected from carbonate, bicarbonate, acetate, gluconate, glycerophosphate, phosphate or the glycinate of one or more sodium, potassium or ammonium, or their mixture.Most phosphates is not too suitable, because their taste makes us unhappy usually and is difficult to cover.Add one or more buffer agents and can increase the picked-up of through port transmucosal.
Sweeting agent can be selected from one or more artificial sweeteners, as sucrose, aspartame, acesulfame-K, glucide, saccharin sodium, cyclamate, glycyrrhizin, thaumatin (thaumatin (talin)), Sucralose (sucralose), dihydrochalcone (neohesperidin dihydrochalcone), alitame, miraculin (Synsepalum duleificum), monellin (dovyalis hebecarpa (serendipity berry)), stevside and/or its salt.
Emulsifying agent is soybean lecithin and/or egg lecithin preferably, but can replace with
-non-ionic surface active agent, polyglycerin ester as poloxamer, polyoxyethylene alkyl ether, castor oil derivatives, polyoxyethylene sorbitan fatty acid ester, monoglyceride, diglyceride and its ester, Myrj 45, fatty acid, comprise poly-castor oil acid polyglycerin ester (PGPR), sorbitan fatty acid ester
-anion surfactant, as fatty acid, fatty acid soaps, lactate, especially sodium stearoyl lactate and/or calcium, sodium lauryl sulphate and latanol,
-zwitterionic surfactant, as zwitterionic phospholipid, as phosphatidylcholine and PHOSPHATIDYL ETHANOLAMINE,
Or their mixture, fraction or derivant or together with lecithin.
Fusible and/or the oral tablet that can suck of preparation main composition of the present invention, but comprise that also other suitable is used for Orally administered dosage form, as buccal bioadhesive tablet, oral cavity paste and oral spray.
The present invention also comprises and comprises tolterodine, in addition also comprises the preparation that one or more have other activating agent of anti-overactive bladder effect, described other activating agent such as oxibutynin (oxobutynin), emepromium (emepromium), Spasmo 3, Propantheline and darifenacin.
In addition, present invention resides in treatment of overactive blad-der in the individuality, method is to use the above-mentioned Orally administered pharmaceutical preparation that comprises tolterodine to described individuality, randomly and one or more have other activating agent of anti-overactive bladder, and randomly merge the activating agent of administering therapeutic overactive bladder effects by one or more other route of administration, as use by transdermal administration, dosage forms for oral administration, suction, ointment, ointment and vaginal suppository (vagitories) use, and/or injection is used.

Claims (26)

1. comprise tolterodine, randomly comprise the Orally administered pharmaceutical preparation of its salt, complex, prodrug and metabolite, it is characterized in that it comprises cocoa powder.
2. the preparation of claim 1 is characterized in that tolterodine is its R-isomeric forms basically.
3. the preparation of claim 1 is characterized in that tolterodine is its S-isomeric forms basically.
4. the preparation of claim 1 is characterized in that tolterodine is racemic form basically.
5. the preparation of claim 1 is characterized in that it uses the metabolite of tolterodine (R)-N, N-diisopropyl-3-(2-hydroxyl-5-methylol-phenyl)-3-phenylpropylamine, randomly and tolterodine.
6. each preparation is characterized in that it also comprises one or more lipid components during aforesaid right required.
7. the preparation of claim 6 is characterized in that described one or more lipid components are selected from:
-cocoa butter and cocoa butter substitute comprise cacaolike butter (CBE), cocoa butter succedaneum (CBS), cocoa butter alternative (CBR) and cocoa butter improver (CBI),
-Oleum Cocois, palm-kernel oil and feature be mainly based on lauric acid and myristic acid other similarly oil,
-Petiolus Trachycarpi oil, Adeps Bovis seu Bubali resin, candlenut oil, illipe fat, Fructus Mangifera Indicae kernel oil, sal tree fat and feature are mainly based on Palmic acid, oleic acid and stearic other similar oils and fats,
-Semen Maydis oil, Oleum helianthi, hybridization Oleum helianthi, Oleum Glycines, rapeseed oil, Canola oil, olive oil, Testa oryzae oil, Oleum Gossypii semen, Arachis (Semen arachidis hypogaeae, Semen arachidis hypogaeae) oil and feature are mainly based on oleic acid, linoleic acid plus linolenic acid and other oil of being hydrogenated to suitable fusing point
The oils and fats of-fish oil, Adeps Bovis seu Bubali, Adeps Sus domestica, butterfat and other animal derived and
-the synthetic fat, resterification fat, the tristearin that obtain by the chemical reaction that does not use acid, alkali or enzymatic fatty acid and glycerol, wherein said one or more chemical compounds are as the single component or the use that is mixed with each other, be crude product or utilize physics or the alkali refining method purified, or be carried out further processing, comprise catalytic hydrogenation, ester exchange, transesterify and fractionated.
8. the preparation of claim 7 is characterized in that described one or more lipid components are selected from cacaolike butter (CBE), cocoa butter succedaneum (CBS) and cocoa butter alternative (CBR).
9. each preparation is characterized in that it also comprises one or more buffer agents during aforesaid right required.
10. the preparation of claim 9 is characterized in that described one or more buffer agents are selected from the carbonate of sodium, potassium or ammonium, bicarbonate, acetate, gluconate, glycerophosphate, phosphate or glycinate, or their mixture.
11. each preparation during aforesaid right requires is characterized in that it also comprises one or more sweeting agents and one or more correctivess randomly.
12. the preparation of claim 11 is characterized in that described one or more sweeting agents are sucrose, aspartame, acesulfame-K, glucide, saccharin sodium, cyclamate, glycyrrhizin, thaumatin (thaumatin), Sucralose, dihydrochalcone (neohesperidin dihydrochalcone), alitame, miraculin (Synsepalum duleificum), monellin (dovyalis hebecarpa), stevside and/or its salt.
13. each preparation is characterized in that it also comprises one or more emulsifiers/solubilizers during aforesaid right required.
14. the preparation of claim 13 is characterized in that described one or more emulsifiers/solubilizers are selected from:
-lecithin, preferably soya lecithin and/or egg lecithin,
-non-ionic surface active agent, polyglycerin ester as poloxamer, polyoxyethylene alkyl ether, castor oil derivatives, polyoxyethylene sorbitan fatty acid ester, monoglyceride, diglyceride and its ester, Myrj 45, fatty acid, comprise poly-castor oil acid polyglycerin ester (PGPR), sorbitan fatty acid ester
-anion surfactant, as fatty acid, fatty acid soaps, lactate, especially sodium stearoyl lactate and/or calcium, sodium lauryl sulphate and latanol,
-zwitterionic surfactant, as zwitterionic phospholipid, as phosphatidylcholine and PHOSPHATIDYL ETHANOLAMINE,
Or their mixture, fraction or derivant or together with lecithin.
15. the preparation of claim 14 is characterized in that described one or more emulsifiers/solubilizers are selected from lecithin, preferably soya lecithin and/or egg lecithin.
Each preparation during 16. aforesaid right requires, it is characterized in that it also comprises one or more and is selected from following material: one or more chemical compound sucrose, fructose, glucose, galactose, lactose, maltose, Nulomoline, pharmaceutically useful polyhydric alcohol such as xylitol, sorbitol, maltose alcohol, mannitol, the pure and mild glycerol of isomaltulose, or polydextrose, or starch, or their any mixture.
17. an Orally administered pharmaceutical preparation is characterized in that its unit dose has the weight of about 400mg and comprises Composition Amount (%w/w) Function Tolterodine 1-tartrate 0.25 Activating agent Hydrogenated soybean oil 43.55 Lipid components Cocoa powder 18.00 Odor mask/formation agent Mannitol 18.00 Diluent Corn starch 13.35 Diluent Aspartame 0.15 Sweeting agent Acesulfame-K 0.10 Sweeting agent Titanium dioxide 2.00 Coloring agent Monosodium glutamate 0.60 The taste improver Herba Menthae and vanilla flavor 3.00 Correctives Soybean lecithin 1.00 Emulsifying agent
18. an Orally administered pharmaceutical preparation is characterized in that its unit dose has the weight of about 500mg and comprises Composition Amount (%) Function Tolterodine 1-tartrate 0.20 Activating agent Cocoa powder 50.00 Odor mask/formation agent Hydrogenated soybean oil 44.00 Lipid components Titanium dioxide 2.50 Coloring agent Sodium chloride 0.55 The taste improver Aspartame 0.15 Sweeting agent Acesulfame-K 0.10 Sweeting agent Vanilla flavor 1.50 Correctives Soybean lecithin 1.00 Emulsifying agent
19. comprise tolterodine, randomly comprise the Orally administered pharmaceutical preparation of its salt, complex, prodrug and metabolite, it is characterized in that its unit dose has the weight of about 200-1000mg and comprises Composition Amount (%w/w) Function Tolterodine (alkali, prodrug, metabolite, salt or complex) 0.1-2 Activating agent Lipid components 35-55 Lipid components Cocoa powder 8-55 Odor mask/formation agent Diluent water soluble or dispersible is preferably the acinous powder 0-40 Diluent Sweeting agent 0.2-3 Sweeting agent Buffer agent 0-10 Buffer agent Correctives 0-4 Correctives The bitterness improver 0-3 The taste improver Emulsifiers/solubilizers 0.3-6 Emulsifying agent Coloring agent 0-3 Coloring agent
20. each preparation is characterized in that it also comprises other activating agent that one or more have anti-overactive bladder effect during aforesaid right required.
21. the preparation of claim 20 is characterized in that described one or more other activating agents are selected from oxibutynin, emepromium, Spasmo 3, Propantheline and darifenacin.
Each preparation during 22. aforesaid right requires, its be formulated into peroral dosage form and mainly other mucosa by buccal mucosa and/or oral cavity sending of tolterodine is provided.
23. each preparation can be used for purposes in the medicine of treatment of overactive blad-der in preparation during aforesaid right required.
24. the method for treatment of overactive blad-der in individuality, this method comprise the Orally administered pharmaceutical preparation that comprises tolterodine of described individuality being used among the claim 1-22 each.
25. the method for treatment of overactive blad-der in individuality, this method comprises the Orally administered pharmaceutical preparation that comprises tolterodine of described individuality being used among the claim 1-22 each, merges by one or more other route of administration and uses tolterodine and/or one or more have other activating agent of anti-overactive bladder effect.
26. the method for treatment of overactive blad-der in individuality of claim 25, wherein said one or more other approach are selected from transdermal and dosage forms for oral administration, and suck and use and injection is used.
CNA2004800080871A 2003-03-26 2004-03-16 Formulations comprising tolterodine and cocoa powder and use thereof Pending CN1764441A (en)

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SE0300830A SE0300830D0 (en) 2003-03-26 2003-03-26 New formulations and use thereof

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AU (1) AU2004224556A1 (en)
BR (1) BRPI0408743A (en)
CA (1) CA2519119A1 (en)
CL (1) CL2004000625A1 (en)
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CN1907136B (en) * 2006-07-28 2010-08-25 张新生 Vegetation health care milk-like liquid and preparation method thereof
CN102919738A (en) * 2007-06-13 2013-02-13 大塚制药株式会社 Equol-containing extract, method for production thereof, method for extraction of equol, and equol-containing food

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JP5702926B2 (en) 2009-10-16 2015-04-15 東レ・ダウコーニング株式会社 Treatment composition for wiping paper

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GB918955A (en) * 1960-05-19 1963-02-20 Thomae Gmbh Dr K Pharmaceutical laxative compositions comprising 4,4-dihydroxy-2-amino triphenylmethane
SE9803986D0 (en) * 1998-11-23 1998-11-23 Pharmacia & Upjohn Ab New compositions
JP2001114668A (en) * 1999-10-13 2001-04-24 Meiji Seika Kaisha Ltd Chocolate preparation
DE60021749T2 (en) * 1999-11-11 2006-04-20 Pfizer Health Ab PHARMACEUTICAL FORMULATION CONTAINING TOLTERODINE AND ITS USE

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1907136B (en) * 2006-07-28 2010-08-25 张新生 Vegetation health care milk-like liquid and preparation method thereof
CN102919738A (en) * 2007-06-13 2013-02-13 大塚制药株式会社 Equol-containing extract, method for production thereof, method for extraction of equol, and equol-containing food
US8900645B2 (en) 2007-06-13 2014-12-02 Otsuka Pharmaceuticals Co., Ltd. Equol-containing extract, method for production thereof, method for extraction of equol, and equol-containing food
US8993014B2 (en) 2007-06-13 2015-03-31 Otsuka Pharmaceutical Co., Ltd. Equol-containing extract, method for production thereof, method for extraction of equol, and equol-containing food
US9192185B2 (en) 2007-06-13 2015-11-24 Otsuka Pharmaceutical Co., Ltd. Equol-containing extract, method for production thereof, method for extraction of equol, and equol-containing food
CN102919738B (en) * 2007-06-13 2016-05-11 大塚制药株式会社 Containing the extracting method of the extract of equol, its preparation method, equol and containing the food of equol
US10681930B2 (en) 2007-06-13 2020-06-16 Otsuka Pharmaceutical Co., Ltd. Equol-containing extract, method for production thereof, method for extraction of equol, and equol-containing food

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JP2006521347A (en) 2006-09-21
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CA2519119A1 (en) 2004-10-07
AU2004224556A1 (en) 2004-10-07
WO2004084864A1 (en) 2004-10-07
CL2004000625A1 (en) 2005-01-07
BRPI0408743A (en) 2006-03-28
ZA200506710B (en) 2006-11-29
MXPA05010314A (en) 2006-05-19
EP1605920A1 (en) 2005-12-21

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