CN1893920A - Effervescent preparation of a basic medicinally active substance - Google Patents
Effervescent preparation of a basic medicinally active substance Download PDFInfo
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- CN1893920A CN1893920A CNA2004800373887A CN200480037388A CN1893920A CN 1893920 A CN1893920 A CN 1893920A CN A2004800373887 A CNA2004800373887 A CN A2004800373887A CN 200480037388 A CN200480037388 A CN 200480037388A CN 1893920 A CN1893920 A CN 1893920A
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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Abstract
The invention relates to an effervescent preparation containing an effervescent batch, at least one basic medicinal substance, and one or several optional agents. Said effervescent preparation is characterized in that alkalinization of the urine, and hence increased accumulation of the basic medicinal substance, is prevented. Also disclosed are medicaments containing said effervescent preparation, methods for the production thereof, and the use thereof.
Description
Technical field
The present invention relates to comprise the effervescent formulation of at least a basic medicinally active substance, it is characterized in that the rising accumulation of the alkalinization of urinating and consequent basic medicinally active substance is avoided.
Background technology
Effervescent formulation is known already as medicine, and it is used for the form of effervescent powder, tablet or granule.They are generally the solid preparation that comprises acid-base pair, thereby described acid-base pair is emitted CO once contacting with water promptly to react
2(EP 0 474 040, and EP 0 369 228, P.C.Schmidt, and I.Christin, Die Pharmazie, 1990,45,89-110).Compare with the tablet of routine, effervescent formulation can cause the dosage form disintegrate faster faster with the active component dissolving, and can cause the bioavailability of medicine better and faster thus.For having between for example apneusis time receiving or being easy to stimulate the active component of gastric mucosa, effervescent formulation is the dosage form that can alleviate the unfavorable character of described active component.Therefore, the medicine that contains effervescent formulation becomes universal day by day.
When the advantage with effervescent formulation changes alkalescent medicine over to, (vide infra: the research of pseudoephedrine accumulation behavior) find under study for action, many times of administrations contain pseudoephedrine for example as basic medicinally active substance, use conventional contain sodium bicarbonate as basic component and citric acid as the effervescent formulation of the effervescence combination of acidic components, in the patient, will produce the basic medicinally active substance accumulation that surpasses the intrinsic accumulation behavior of non-effervescent formulation.Thereby can not guarantee optimal treatment again, and the danger that can have side effects and raise.
Under physiological condition, alkalescent medicine is essentially the ionization form and therefore its renal excretion is very rapid.Since contain single electric charge cation (such as, for example for sodium) bicarbonate or carbonate cause the alkalinization of urine as alkali and citric acid as the application of the conventional effervescent formulation of acid, therefore, more alkalescent medicine is the unionized form.Thus, the discharge half-life is extended with alkaline active component and is accumulated in the systemic circulation, and this may cause benefit/risk assessment that alkalescent medicine changes.Document (people such as I.Kanfer, Pharmacotheraphy 1993,13, verified alkaline active component (for example pseudoephedrine) is discharged the strong dependence of half-life to the urine pH value in P.116-128).
Target is to seek to avoid urinating alkalinization and avoid the cumulative alkaline active component effervescent formulation of alkaline active component thus, thereby guarantees optimal treatment and can reduce the danger that has side effects.
Summary of the invention
Find shockingly that now the alkalinization of urine and the consequent rising accumulation that is higher than the basic medicinally active substance of the intrinsic accumulation behavior of non-effervescent formulation far away can be avoided by effervescent formulation according to the present invention.
The present invention relates to a kind of effervescent formulation, comprising effervescence combination, at least a basic medicinally active substance and one or more optional other active component, it is characterized in that, the rising accumulation of basic medicinally active substance is avoided.
The basic medicinally active substance that is used for the object of the invention have one can be protonated alkalescence primary, the second month in a season or uncle's nitrogen, such as, for example pseudoephedrine, chlorphenamine, phenylephrine, benadryl, clemastine, brompheniramine, hydroxyzine, tripelennamine, pyrilamine, mequitazine, phenergan, plug pyridine in heptan, doxylamine, dexchlorphenamine, epinephrine, phenamine, alimemazine, marezine, meclizine, hydroxyzine and azatadine and the acceptable salt of physiology thereof.Preferred pseudoephedrine, chlorphenamine, phenylephrine and clemastine and the acceptable salt of physiology thereof.Preferred especially pseudoephedrine and the acceptable salt of physiology thereof, such as, for example pseudoephedrine hydrochlorate and pseudoephedrine sulfate.The present invention equally also comprises the mixture of above-mentioned substance.
Described basic medicinally active substance uses with the treatment effective dose.The dosage of preferred pseudoephedrine hydrochlorate or pseudoephedrine sulfate is 10～100mg, and preferred especially its dosage is 20～70mg.
Optional one or more other active component that comprises of described effervescent formulation, such as, for example analgesic, antibiotic, hydryllin, antidepressants, antidiabetic drug, antihypertensive, anticoagulant, fatty depressant, antineoplastic agent, antiviral substance, anti-inflammatory substance, cough medicine, expectorant, muscle speed to delay medicine, anticonvulsant, diarrhea, antiasthmatics and antidiuretic.Analgesic can be used as preferably and mentions.
Described analgesic comprises, for example aspirin, acetaminophen, ibuprofen, naproxen, diclofenac, isopropylantipyrine, dipyrone and cox 2 inhibitor (such as, for example be celecoxib and rofecoxib).Representational antibiotic is, for example beta-Lactam antibiotic, chloromycetin, neomycin, tetracycline, cephalosporin, erythromycin, ciprofloxacin, Moxifloxacin, norfloxacin and enrofloxacin.Representational hydryllin is, for example fexofenadine, dimethindene, cromoglicic acid, cetirizine, loratadine, pyrilamine, chlorphenamine, tetrahydrozoline and antazoline.Representational antidepressants are, for example amitriptyline, fluoxetine, doxepin, maprotiline and imipramine.Representational antidiabetic drug is, for example acarbose, chlorpropamide, glibenclamide and tolbutamide.Representational antihypertensive is, for example amlodipine, nifedipine, felodipine, enalapril, ramipril, captopril, cilazapril, trandolapril, fosinopril, quinapril, moexipril, lisinopril and perindopril, Losartan, Candesartan, Irb and telmisartan.Representational anticoagulant is, for example dicoumarol and warfarin.Representational fatty depressant is, for example pravastatin, lovastatin, simvastatin, atorvastatin, fluvastatin, itavastatin, Pitavastatin, rosuvastatin and cerivastatin.Representational antineoplastic agent is, for example amycin, fluorouracil and methotrexate.Representational antiviral substance is, for example acycloguanosine.Representational antiinflammatory material is, for example cortisone, hydrocortisone, betamethasone, dexamethasone and prednisolone.Representational cough medicine is that for example codeine, paracodin, dextromethorphan and clobutinol, representational expectorant are, for example ambroxol, acetylcysteine, bromhexine and carbocisteine.Representational muscle speeds to delay medicine, for example diazepam, dantrolene, cyclobenzaprine and methocarbamol.Representational anticonvulsant is, for example phenytoin and barbiturate.Representational diarrhea is, for example loperamide and diphenoxylate.Representational antiasthmatics is, for example theophylline, beclometasone and epinephrine.Representational diuretic is, for example, and chlortalidone, indapamide, bendroflumethiazide, metolazone, cyclopenthiazide, polythiazide, mefruside, xipamide, chlorothiazide and Hydrochlorothiazide.The example of enumerating is appreciated that equally and comprises the acceptable salt of its corresponding physiology.The present invention equally also comprises the mixture of above-mentioned active component.
Other active component that can preferably mention is, for example aspirin, acetaminophen, ibuprofen, diclofenac, dipyrone and cox 2 inhibitor (such as, for example examine the acceptable salt of former times, rofecoxib and physiology thereof for Seeley).Be preferably the acceptable salt of aspirin, ibuprofen, acetaminophen, naproxen and physiology thereof especially.The present invention equally also comprises the mixture of above-mentioned active component.
Wherein optional other active component that contains uses with the treatment effective dose.Preferred dose is 0.5～5mmol.Special preferred dose is 0.8～3mmol.
Preferred acetysalicylic dosage is 100～1000mg, the dosage of acetaminophen is 100～1000mg, the dosage of ibuprofen is 100～1000mg, and the dosage of naproxen is that the accumulated dose of the mixture of 100～1000mg or these active component is 100～1000mg.
Preferred especially acetysalicylic dosage is 250～500mg, and the dosage of acetaminophen is 250～500mg, and the dosage of ibuprofen is 100～300mg, and the dosage of naproxen is that the accumulated dose of the mixture of 250～500mg or these active component is 200～500mg.
A kind of preferred effervescent formulation is characterized in that, wherein exist effervescence combination, pseudoephedrine and one or more analgesic (such as, for example be aspirin, acetaminophen, naproxen and ibuprofen) and/or one or more cough medicines (such as, for example be dextromethorphan) and/or one or more expectorants (such as, for example be ambroxol and acetylcysteine), wherein the rising of Niao alkalinization and consequent basic medicinally active substance accumulation is avoided.Optional can with hydryllin (such as, for example be chlorphenamine) adding wherein.Described component can also be the acceptable salt form of they physiologys.
A kind of particularly preferred effervescent formulation is characterized in that, wherein exist effervescence combination, pseudoephedrine and one or more to be selected from other active component of aspirin, acetaminophen and ibuprofen, wherein the rising of Niao alkalinization and consequent basic medicinally active substance accumulation is avoided, and described component also may be the acceptable salt form of they physiologys.
Described effervescence combination is emitted CO by reacting with water or saliva contact
2, and described effervescence combination is made up of at least a basic component and at least a acidic components.
Carbonate can be used as the basic component of described effervescence combination and mentions.The carbonate that is used for the object of the invention is carbonate, sesquicarbonate and bicarbonate.Be preferably ammonium carbonate, ammonium bicarbonate, alkali carbonate, alkali metal hydrogencarbonate, alkaline earth metal carbonate and alkali metal bicarbonates, such as, for example be sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, calcium carbonate, calcium bicarbonate, miemite, magnesium carbonate, magnesium bicarbonate and basic magnesium carbonate.Preferred especially sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, calcium carbonate, calcium bicarbonate, magnesium carbonate, magnesium bicarbonate and basic magnesium carbonate.The same mixture that allows to use above-mentioned basic component.
The basic component of effervescence combination uses with the accumulated dose of 1～20mmol, preferably uses with the accumulated dose of 2～15mmol, especially preferably uses with the accumulated dose of 2～10mmol.
Described acidic components can have more than a dissociation constant, mean that it can have more than an acidic functionality.Described acidic components can be the organic or mineral acids for its anhydride, free acid or acid salt form, if there are a plurality of acidic functionalities, the some of them proton can be replaced by a cation or all cationes so.Be mentioned the example that can be used as acidic components and be tartaric acid, succinic acid, malic acid, malonic acid, maleic acid, fumaric acid, adipic acid, succinic acid, lactic acid, hydroxyacetic acid, α-alkyd, ascorbic acid, arabo-ascorbic acid, 1,3-propanedicarboxylic acid, aminoacid, phosphoric acid, diphosphonic acid, triphosphoric acid, Metaphosphoric acid, pyrophosphoric acid, polyphosphoric acid, sulphuric acid, two sulphuric acid and acid salt thereof (such as, for example potassium hydrogen tartrate or dibastic sodium phosphate) and the acceptable salt of other physiology.Preferred especially ascorbic acid, arabo-ascorbic acid, tartaric acid, phosphoric acid and acid salt thereof.The same mixture that allows to use above-mentioned acidic components.
The acidic components of effervescence combination use with the accumulated dose of 1～20mmol, preferably use with the accumulated dose of 2～15mmol.
If the basic component of effervescence combination only by alkaline earth metal carbonate and/or bicarbonate (such as, for example calcium carbonate, calcium bicarbonate, magnesium carbonate, magnesium bicarbonate and basic magnesium carbonate or its mixture) form, can use citric acid as acidic components so.A kind of preferred effervescence combination contains as the citric acid of acidic components with as the calcium carbonate of basic component.Equivalent proportion between the equivalent of citric acid and alkaline earth metal carbonate and/or the bicarbonate total yield is no more than 2: 1, preferably is no more than 1: 1.
If the equivalent proportion between the total yield of the equivalent of citric acid and alkali carbonate and/or bicarbonate is no more than 1: 3, preferably be no more than 1: 4, especially preferably be no more than 1: 5, allow to use citric acid and alkali carbonate and/or bicarbonate so.
If optional other active component that exists be sour, so acidic active component (such as, for example aspirin, acetaminophen and ibuprofen) can partly or completely replace the acidic components in the effervescence combination.
Same preferred effervescence combination is the combination of at least a acidic components and at least a basic component, wherein the equivalent proportion between acidic components total yield and the basic component total yield is 1: 1～3: 1, be preferably 1: 1～2.5: 1, and be preferably 1: 1～1.5: 1 especially.
Same preferred effervescent formulation is characterized in that, wherein exist the effervescence combination comprise citric acid and calcium carbonate, pseudoephedrine and one or more to be selected from other active component of aspirin, acetaminophen and ibuprofen, wherein the rising of Niao alkalinization and consequent basic medicinally active substance accumulation is avoided, and described component content also may exist for the acceptable salt form of they physiologys.
In addition, the present invention relates to contain the medicine of with good grounds effervescent formulation of the present invention and at least a other auxiliary agent.
The pharmaceutical auxiliary agent that those of skill in the art know also is described in for example following handbook: " Handbook of Pharmaceutical Excipients ", Wade, A.﹠amp; Weller, P.J., American Pharmaceutical Association, Washington, 1994 the 2nd edition.
Other auxiliary agent that can mention for example is binding agent, lubricant, spice, wetting agent, sweeting agent, defoamer, diluent, pigment and stabilizing agent.
The binding agent that can mention for example is ethylene glycol, Polyethylene Glycol, glucose, sucrose, sugar, starch, Nulomoline, mannitol, cellulose, methylcellulose and derivant thereof.
The lubricant that can mention for example is magnesium stearate, stearic acid, Talcum, paraffin, castor oil hydrogenated, Polyethylene Glycol, fumaric acid, adipic acid, sodium benzoate, sodium stearyl fumarate and salt thereof.Preferred examples is sodium salt, potassium salt, ammonium salt, calcium salt and the magnesium salt of fumaric acid and adipic acid.
The spice that can mention is for example for being applicable to the synthetic perfume and the natural perfume material of food article.Preferred examples is orange spice, Citrus aurantium Linn. spice, Optarom orange, Oleum Eucalypti, Oleum menthae, Rhizoma et radix valerianae and lemon flavouring.Particularly preferred example is orange spice, Citrus aurantium Linn. spice and Optaromorange.
The wetting agent that can mention for example is dioctyl sodium sulphosuccinate and sodium lauryl sulfate.
The sweeting agent that can mention for example is saccharin sodium, sodium cyclamate (cyclamat), Nulomoline and aspartame (Aspartam).
The defoamer that can mention for example is silicone oil.
The diluent that can mention for example is starch and cellulose.
The pigment that can mention for example is applicable to the pigment of food article for titanium dioxide, beet root powder, beta-carotene and all.
The stabilizing agent that can mention for example is polyvinyl alcohol, polyvinylpyrrolidone, Polyethylene Glycol and derivant thereof.
The acceptable salt of physiology that is used for the object of the invention can be the acid-addition salts that chemical compound and mineral acid, carboxylic acid or sulfonic acid form.Particularly preferred salt is, for example the salt that forms of those and hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulfonic acid, ethyl sulfonic acid, toluenesulfonic acid, benzenesulfonic acid, naphthalenedisulfonic acid, acetic acid, propanoic acid, lactic acid, tartaric acid, citric acid, fumaric acid, maleic acid or benzoic acid.
Yet, the salt that can mention can also be the salt that forms with the alkali of routine, such as, for example for alkali metal salt (for example sodium salt or potassium salt), alkali salt (for example calcium salt or magnesium salt) or be derived from ammonia or organic amine (such as, for example be diethylamine, triethylamine, ethyl diisopropyl amine, procaine, dibenzyl amine, N-methylmorpholine, dihydro abietyl amine, 1-ephenamine or methyl piperidine) ammonium salt.
In addition, the present invention relates to the purposes that effervescent formulation is used for the treatment of disease.Depend on the active component that exists in the effervescent formulation, described effervescent formulation is preferred for treating influenza infection, bacterial infection, fever, coryza, cough, flu or allergy.
In addition, the present invention relates to the method for a kind of production, it is characterized in that the component of described effervescent formulation is formulated into medicament forms conventional in the field of pharmaceutical preparations according to effervescent formulation of the present invention.Preferably can be powder, granule, pearl agent (beads), pill or tablet.Be preferably powder, granule and tablet especially.Suitable known method can be used for producing according to medicine of the present invention.
The present invention comprises the combination of all preferable range equally.
Determine the test of accumulation behavior:
In order to study the accumulation behavior of effervescent formulation neutral and alkali active medicinal matter, in the various situations of following three kinds of preparations, with the treatment effective dose administration of basic medicinally active substance to equate: preparation A is as the effervescent formulation that will study, preparation B is as non-effervescent formulation, formulation C is as the standard effervescent formulation, wherein preparation B does not comprise effervescence component and formulation C contains the conventional effervescence combination of only being made up of 600mg sodium bicarbonate and 1000mg citric acid.Every day in 5 consecutive days, with the administration simultaneously of three preparations, the dosage number of every day depends on the basic medicinally active substance of use, and the dosage of this material is used quite with conventional.After 5 days, the corresponding plasma content A of basic medicinally active substance, B and C are measured.The intrinsic accumulation behavior of plasma content B reflection basic medicinally active substance.If the difference between plasma content A and the plasma content B surpasses 1: 2 with respect to the accumulation ratio of the difference between plasma content C and the plasma content B, preferably surpass 1: 3, especially preferably surpass 1: 4, so just there is the rising accumulation of basic medicinally active substance.Described accumulation is than equaling difference between plasma content A and the plasma content B divided by the difference between plasma content C and the plasma content B.
A kind of preferred effervescent formulation comprises effervescence combination, at least a basic medicinally active substance and one or more optional other active component, it is characterized in that, the accumulation ratio is less than 1: 2, preferably less than 1: 3, especially preferably less than 1: 4.
The research of pseudoephedrine accumulation behavior
In two kinds of different preparations, the accumulation behavior as the pseudoephedrine of basic medicinally active substance is studied.Preparation 1 contains 60mg pseudoephedrine hydrochlorate, 500mg acetyl aminophenol and 1 Alka-Seltzer
Cold﹠amp; Cough ANC 6 (containing 600mg citric acid and 1000mg sodium bicarbonate), preparation 2 contains 20ml Sudafed
The child separates nasal congestion liquid medicine (being equivalent to the 60mg pseudoephedrine hydrochlorate).17 continuous individually dosed in, every 6 hours two kinds of preparations are dissolved in respectively in the 120ml water, and in 2 minutes, be administered to 32 subjects in all cases, make all 4 dosage of administration and the dosage of administration in the 5th day of every day of winning day in the 4th day.In the end dosed administration was measured the pseudoephedrine plasma content after 12 hours, and meansigma methods is that meansigma methods is 120.23ng/ml in 236.9ng/ml and the subjects group of accepting preparation 2 in accepting the subjects group of preparation 1.Plasma content has shown the rising accumulation of pseudoephedrine.
Specific embodiments
Embodiment embodiment
Embodiment 1
Effervescent tablet comprises:
1. aspirin 500mg
2. pseudoephedrine hydrochlorate 30mg
3. citric acid 1000mg
4. calcium carbonate 555mg
5. mannitol 803mg
6. sorbitol 100mg
7. polyvinylpyrrolidone (K30) 0.5mg
8. sodium lauryl sulfate 0.5mg
Embodiment 2:
Effervescent tablet comprises:
1. aspirin 500mg
2. pseudoephedrine hydrochlorate 30mg
3. ascorbic acid 200mg
4. citric acid 800mg
5. calcium carbonate 555mg
6. mannitol 803mg
7. sorbitol 100mg
8. polyvinylpyrrolidone (K30) 0.5mg
9. sodium lauryl sulfate 0.5mg
Embodiment 3:
Granulae effervescentes comprises:
1. aspirin 500mg
2. pseudoephedrine hydrochlorate 30mg
3. sucrose 5.120mg
4. ascorbic acid 30mg
5. tartaric acid 750mg
6. sodium bicarbonate 690mg
7. sodium carbonate 150mg
8. transparent premix material 2mg
9. orange spice 30mg
Embodiment 4:
Effervescent tablet comprises:
1. aspirin 500mg
2. pseudoephedrine hydrochlorate 30mg
3. ascorbic acid 240mg
4. sodium dihydrogen phosphate 900mg
5. sodium bicarbonate 450mg
6. sodium carbonate 100mg
Embodiment 5:
Granulae effervescentes comprises:
1. ibuprofen 200mg
2. pseudoephedrine hydrochlorate 30mg
3. citric acid 400mg
4. calcium carbonate 200mg
5. aspartame 13mg
6. orange spice 100mg
7. Citrus aurantium Linn. spice 20mg
8.Optarom?Orange
* 200mg
*Make the optimized concentrated lemon juice of taste
Embodiment 6:
Effervescent tablet comprises:
1. aspirin 250mg
2. acetaminophen 250mg
3. pseudoephedrine sulfate 30mg
4. citric acid 800mg
5. calcium carbonate 400mg
Embodiment 7:
Granulae effervescentes comprises:
1. aspirin 500mg
2. pseudoephedrine hydrochlorate 30mg
3. citric acid 180mg
4. sodium dihydrogen phosphate 900mg
5. sodium bicarbonate 450mg
6. sodium carbonate 100mg
Embodiment 8:
Effervescent tablet comprises:
1. aspirin 500mg
2. pseudoephedrine hydrochlorate 30mg
3. sodium carbonate 280mg
Embodiment 9:
Effervescent tablet comprises:
1. pseudoephedrine hydrochlorate 30mg
2. citric acid 2882mg
3. calcium carbonate 750mg
Embodiment 10:
Effervescent tablet comprises:
1. pseudoephedrine hydrochlorate 30mg
2. ascorbic acid 1321mg
3. sodium bicarbonate 630mg
Claims (23)
1. effervescent formulation, it contains at least a basic medicinally active substance, it is characterized in that, and the rising accumulation of basic medicinally active substance is avoided.
2. according to the effervescent formulation of claim 1, it is characterized in that the accumulation ratio was less than 1: 2.
3. according to each effervescent formulation of claim 1～2, it is characterized in that at least a material that is selected from pseudoephedrine, chlorphenamine, phenylephrine, clemastine and the acceptable salt of physiology thereof exists as basic medicinally active substance.
4. according to each effervescent formulation of claim 1～3, it is characterized in that pseudoephedrine, pseudoephedrine hydrochlorate or pseudoephedrine sulfate exist as basic medicinally active substance.
5. according to each effervescent formulation of claim 1～4, it is characterized in that, wherein contain one or more other active component.
6. according to the effervescent formulation of claim 5, it is characterized in that analgesic exists as one or more other active component.
7. according to the effervescent formulation of claim 5, it is characterized in that at least a aspirin, acetaminophen, ibuprofen, diclofenac, dipyrone, Seeley of being selected from examined the material of former times, rofecoxib and the acceptable salt of physiology thereof and existed as other active component.
8. according to claim 5 effervescent formulation, it is characterized in that the mixture of these materials that the ibuprofen that dosage is the aspirin of 250～500mg, acetaminophen that dosage is 250～500mg, dosage is 100～300mg, the naproxen that dosage is 250～500mg or accumulated dose are 200～500mg exists as other active component.
9. according to the effervescent formulation of claim 4, it is characterized in that, wherein have a kind of effervescence combination, pseudoephedrine and at least a other active component that is selected from aspirin, acetaminophen, naproxen, ibuprofen, dextromethorphan, ambroxol, acetylcysteine and the acceptable salt of physiology thereof.
10. according to the effervescent formulation of claim 4, it is characterized in that, wherein have a kind of effervescence combination, pseudoephedrine and at least a other active component that is selected from aspirin, acetaminophen, naproxen, ibuprofen, dextromethorphan, ambroxol, acetylcysteine, chlorphenamine and the acceptable salt of physiology thereof.
11. the effervescent formulation according to claim 10 is characterized in that, wherein has effervescence combination, pseudoephedrine hydrochlorate and aspirin and/or ibuprofen.
12. according to each effervescent formulation of claim 1～11, it is characterized in that the mixture of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, calcium carbonate, calcium bicarbonate, magnesium carbonate, magnesium bicarbonate, basic magnesium carbonate or these materials exists as the basic component of effervescence combination.
13., it is characterized in that the mixture of ascorbic acid, arabo-ascorbic acid, tartaric acid, phosphoric acid and acid salt thereof or these materials exists as the acidic components of effervescence combination according to each effervescent formulation of claim 1～12.
14., it is characterized in that citric acid exists as acidic components, and have only alkaline earth metal carbonate or bicarbonate or its mixture to exist as the effervescence combination basic component according to each effervescent formulation of claim 1～13.
15. effervescent formulation according to claim 15, it is characterized in that, citric acid exists as acidic components, and have only alkaline earth metal carbonate or bicarbonate or its mixture to exist as the effervescence combination basic component, wherein the equivalent proportion between the equivalent of citric acid and alkaline earth metal carbonate and/or the bicarbonate total yield is no more than 2: 1.
16. according to each effervescent formulation of claim 1～15, it is characterized in that, citric acid exists as acidic components, and alkali carbonate and/or bicarbonate exist as the effervescence combination basic component, and wherein the equivalent proportion between the equivalent of citric acid and alkali carbonate and/or the bicarbonate total yield is no more than 1: 3.
17. according to each effervescent formulation of claim 14～15, it is characterized in that, wherein have pseudoephedrine hydrochlorate, aspirin, citric acid and calcium carbonate.
18., it is characterized in that at least a other active component is the acid of partly or completely replacing the effervescence combination acidic components according to each effervescent formulation of claim 1～12.
19., it is characterized in that the equivalent proportion between acidic components total yield and the basic component total yield is 1: 1～3: 1 according to each effervescent formulation of claim 1～18.
20. a medicine, it contains each described effervescent formulation of claim 1～19 and at least a other auxiliary agent.
21. according to the medicine of claim 20, it is the form of powder, granule, pearl agent, pill or tablet.
22. each described effervescent formulation of claim 1～19 is used for the purposes of the medicine of production for treating disease.
23. the method for production claim 20 or 21 described medicines is characterized in that, powder, granule, pearl agent, pill or tablet are prepared and be processed into to each component.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10359790.5 | 2003-12-19 | ||
| DE10359790A DE10359790A1 (en) | 2003-12-19 | 2003-12-19 | Effervescent preparation of a basic pharmaceutically active substance |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1893920A true CN1893920A (en) | 2007-01-10 |
Family
ID=34683574
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2004800373887A Pending CN1893920A (en) | 2003-12-19 | 2004-12-07 | Effervescent preparation of a basic medicinally active substance |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP1696874A1 (en) |
| JP (1) | JP2007515418A (en) |
| KR (1) | KR20060109492A (en) |
| CN (1) | CN1893920A (en) |
| AR (1) | AR046955A1 (en) |
| AU (1) | AU2004308590A1 (en) |
| BR (1) | BRPI0417796A (en) |
| CA (1) | CA2550342A1 (en) |
| DE (1) | DE10359790A1 (en) |
| EC (1) | ECSP066649A (en) |
| IL (1) | IL176356A0 (en) |
| MA (1) | MA28276A1 (en) |
| MX (1) | MXPA06006658A (en) |
| NO (1) | NO20063327L (en) |
| WO (1) | WO2005063199A1 (en) |
| ZA (1) | ZA200604946B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102438598A (en) * | 2009-05-27 | 2012-05-02 | 株式会社茶山医化 | Multi-layer tablet comprising effervescent layer |
| CN104622831A (en) * | 2013-11-06 | 2015-05-20 | 江苏豪森药业股份有限公司 | Oral tablet and preparation method thereof |
| CN107951034A (en) * | 2017-12-01 | 2018-04-24 | 郑州拓洋生物工程有限公司 | Vitamin effervescent formulation and preparation method thereof |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9078824B2 (en) | 2007-09-24 | 2015-07-14 | The Procter & Gamble Company | Composition and method of stabilized sensitive ingredient |
| RU2011123762A (en) * | 2008-11-11 | 2012-12-20 | Берко Иладж Ве Кимия Сан. А.С. | PHARMACEUTICAL COMPOSITION CONTAINING IBUPROFEN, PSEUDOEPHEDRINE AND CHLORPHENIRAMINE |
| WO2013109224A1 (en) * | 2012-01-18 | 2013-07-25 | Mahmut Bilgic | Pharmaceutical compositions comprising diclofenac |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4613497A (en) * | 1984-02-29 | 1986-09-23 | Health Products Development, Inc. | Dry, water-foamable pharmaceutical compositions |
| CA2021548A1 (en) * | 1989-09-01 | 1991-03-02 | Ronald Nash Duvall | Effervescent cold or sinus allergy medicine composition having reduced sodium content |
| CA2084028A1 (en) * | 1991-11-27 | 1993-05-28 | Harish B. Pandya | Hot flu composition |
| AU7407194A (en) * | 1993-08-03 | 1995-02-28 | Warner-Lambert Company | Pleasant tasting effervescent cold/allergy medications |
| JP2000063269A (en) * | 1998-08-20 | 2000-02-29 | Taiho Yakuhin Kogyo Kk | Solid preparation |
-
2003
- 2003-12-19 DE DE10359790A patent/DE10359790A1/en not_active Withdrawn
-
2004
- 2004-12-07 JP JP2006544276A patent/JP2007515418A/en not_active Withdrawn
- 2004-12-07 CA CA002550342A patent/CA2550342A1/en not_active Abandoned
- 2004-12-07 CN CNA2004800373887A patent/CN1893920A/en active Pending
- 2004-12-07 AU AU2004308590A patent/AU2004308590A1/en not_active Abandoned
- 2004-12-07 WO PCT/EP2004/013886 patent/WO2005063199A1/en active Application Filing
- 2004-12-07 EP EP04803578A patent/EP1696874A1/en not_active Withdrawn
- 2004-12-07 MX MXPA06006658A patent/MXPA06006658A/en active IP Right Grant
- 2004-12-07 KR KR1020067011963A patent/KR20060109492A/en not_active Application Discontinuation
- 2004-12-07 BR BRPI0417796-7A patent/BRPI0417796A/en not_active IP Right Cessation
- 2004-12-17 AR ARP040104747A patent/AR046955A1/en not_active Application Discontinuation
-
2006
- 2006-06-15 IL IL176356A patent/IL176356A0/en unknown
- 2006-06-15 ZA ZA200604946A patent/ZA200604946B/en unknown
- 2006-06-16 EC EC2006006649A patent/ECSP066649A/en unknown
- 2006-06-26 MA MA29140A patent/MA28276A1/en unknown
- 2006-07-18 NO NO20063327A patent/NO20063327L/en not_active Application Discontinuation
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102438598A (en) * | 2009-05-27 | 2012-05-02 | 株式会社茶山医化 | Multi-layer tablet comprising effervescent layer |
| CN102438598B (en) * | 2009-05-27 | 2015-06-10 | 株式会社茶山医化 | Multi-layer tablet comprising effervescent layer |
| CN104958273A (en) * | 2009-05-27 | 2015-10-07 | 株式会社茶山医化 | Multi-layer tablet comprising effervescent layer |
| CN104958273B (en) * | 2009-05-27 | 2017-10-13 | 株式会社茶山医化 | Multilayer tablet containing effervescent layer |
| CN104622831A (en) * | 2013-11-06 | 2015-05-20 | 江苏豪森药业股份有限公司 | Oral tablet and preparation method thereof |
| CN107951034A (en) * | 2017-12-01 | 2018-04-24 | 郑州拓洋生物工程有限公司 | Vitamin effervescent formulation and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| DE10359790A1 (en) | 2005-07-21 |
| MA28276A1 (en) | 2006-11-01 |
| ZA200604946B (en) | 2007-09-26 |
| JP2007515418A (en) | 2007-06-14 |
| IL176356A0 (en) | 2006-10-05 |
| AU2004308590A1 (en) | 2005-07-14 |
| BRPI0417796A (en) | 2007-03-20 |
| ECSP066649A (en) | 2006-10-25 |
| NO20063327L (en) | 2006-07-18 |
| KR20060109492A (en) | 2006-10-20 |
| AR046955A1 (en) | 2006-01-04 |
| MXPA06006658A (en) | 2006-08-31 |
| CA2550342A1 (en) | 2005-07-14 |
| WO2005063199A1 (en) | 2005-07-14 |
| EP1696874A1 (en) | 2006-09-06 |
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