CN100475211C - Oral itraconazole composition being not affected by ingested food and process for preparing same - Google Patents
Oral itraconazole composition being not affected by ingested food and process for preparing same Download PDFInfo
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- CN100475211C CN100475211C CNB2004800258516A CN200480025851A CN100475211C CN 100475211 C CN100475211 C CN 100475211C CN B2004800258516 A CNB2004800258516 A CN B2004800258516A CN 200480025851 A CN200480025851 A CN 200480025851A CN 100475211 C CN100475211 C CN 100475211C
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- itraconazole
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- surfactant
- acidulant
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- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/485—Inorganic compounds
Abstract
A viscous and glassy composition for oral administration comprising itraconazole, an acidifying agent, an amphiphilic additive, a surfactant and an oil provides a high in vivo bioavailability of itraconazole which is little influenced by ingested food.
Description
Technical field
The present invention relates to oral itraconazole composition, the bioavailability of Itraconazole improves and the influence of the food that is not subjected to be taken in the said composition; The invention still further relates to its preparation method.
Background technology
Known triazole compounds Itraconazole has excellent antifungal activity.But, because the Itraconazole dissolubility is very low, in water, be lower than 1 μ g/ml, and, in gastric juice, be the non-form of dissociating, so the bioavailability of Itraconazole oral administration be very low because its pKa value is 3.7.In addition, the oral administration bioavailability individual variation of known Itraconazole is big, and depends on the food of some other factor as being taken in.
The open WO 85/02767 of pct international patent and a kind of method that adopts the Itraconazole cyclodextrin clathrate to improve the Itraconazole dissolubility of U.S. Patent No. 4,764,604 instructions.But the problem that this method exists is that the part (incremental increase) that increases of Itraconazole dissolubility is very little and need the preparation process of multiple complexity.
The open WO 94/05263 of pct international patent discloses a kind of micropill (bead) preparation of coating, wherein core is that materia medica inertia or neutral sucrose, dextrin, starch etc. are made, and by the mixture coating of Itraconazole and hydrophilic polymer, then, with the micropill reuse polymer that obtains for example Polyethylene Glycol carry out coating.The pellet preparations of this coating can be available from Janssen Pharmaceutica (Beerse, Belgium), commodity be called itraconazole (
) capsule.But the preparation process of above-mentioned preparation is very complicated, because the mean size of micropill only is 600～700 μ m, easily reunites in preparation process.In addition, the Itraconazole bioavailability of said preparation according to its ingest preceding or ingest after take and produce very big difference.
The solid dispersion of the open WO 97/44014 a kind of Itraconazole of instruction of pct international patent in water-soluble polymer, it adopts the mixture with Itraconazole and water-soluble polymer to be prepared by fusion-expressing technique under 245 ℃～265 ℃ condition.According to its record, the bioavailability of this solid dispersion Itraconazole improves, and is not subjected to the influence of the food taken in, and said preparation can be available from Janssen Pharmaceutica (Beerse, Belgium), commodity be called itraconazole (
) sheet.But the preparation process of solid dispersion is controlled the obstruction of a lot of difficulties of various state-variables aspect, and the interior bioavailability of the body of Itraconazole is still low in the above-mentioned dispersion.
The itraconazole of the pH 2 that is mixed with by hydroxypropyl-beta-cyclodextrin inclusion, hydrochloric acid, propylene glycol, purified water, sodium hydroxide, saccharin sodium and sorbitol with Itraconazole (
) solution can be available from (the Beerse of Janssen Pharmaceutica, Belgium), when before ingesting, taking, it shows very high Itraconazole bioavailability, the concentration of Itraconazole is low to moderate 10mg/ml but its problem is, therefore must take in a large number, and when its contact intestinal juice, active component is separated out precipitation rapidly, and it is only effective to the fungal infection of esophagus.
Recently, the international publication WO 98/55148 of PCT discloses a kind of high viscosity composition, and it is included in dissolubility is very low in the water medicine, cyclodextrin, water soluble acid and water solublity organic polymer.But the viscosity height of this compositions, therefore a large amount of dispersants must be used for reducing the viscosity of capsule preparation process.In addition, said composition shows very low dissolution rate under pH 6.8 or higher neutrality or alkali condition, be lower than 1%.
In this respect, in korean application No.2000-83717, inventor of the present invention proposes a kind of microemulsion preconcentrate (preconcentrate), it is included in dissolubility is very low in the water antiviral drugs, phosphoric acid, cosurfactant, surfactant and oil, and further proposes another kind improved micro emulsion composition on above-mentioned preconcentrate basis in korean application No.2001-36930.But these compositionss show Itraconazole dissolution rate unsatisfactory under pH 6.8 or higher neutrality or alkali condition, so their Itraconazole bioavailability depends on the food of being taken in more or less.
Summary of the invention
Therefore, main purpose of the present invention is to provide a kind of oral itraconazole composition, and its Itraconazole bioavailability improves and be not subjected to the influence of institute's dietary intake.
Another purpose of the present invention is to provide a kind of method for preparing above-mentioned Orally administered composition.
According to an aspect of the present invention, the invention provides a kind of composition for oral administration of thickness glassy state, it comprises Itraconazole, acidulant, amphipathic additive, surfactant and oil.
According to a further aspect in the invention, the invention provides a kind of method that is used to prepare above-mentioned composition, it may further comprise the steps: (a) Itraconazole is dissolved in the mixture of acidulant, amphipathic additive and volatile solvent equably, (b) surfactant and oil are dissolved in the resulting solution, and (c) from wherein removing volatile solvent.
Description of drawings
Above-mentioned and other purpose of the present invention and characteristics all will by following to the explanation of invention and with reference to the accompanying drawings Fig. 1 illustrated, Fig. 1 has shown the Itraconazole bioavailability of preparation before and after ingesting for preparing in embodiment 1 and the comparative example respectively.
The specific embodiment
The Itraconazole that comprises of the present invention can be prepared by following composition as composition of active components:
(1) acidulant
Acidulant is used to dissolve Itraconazole in the present invention, and its representational example comprises: phosphoric acid, acetic acid, hydrochloric acid, nitric acid, sulphuric acid, citric acid, fumaric acid, maleic acid, with and aqueous solution, wherein preferred 85% phosphoric acid or its dilute solution.
(2) amphipathic additive
The viscosity that amphipathic additive is used to dissolve Itraconazole in the present invention and regulates compositions is to being suitable for being filled into capsular degree.The suitable amphipathic additive that can be used among the present invention comprises transcutol (diethylene glycol one ether, Gattefosse), Isosorbide dimethyl ether (1,4:3,6-two dehydrations-2,5-dimethyl-D-sorbitol), glycofurol (tetrahydrofurfuryl alcohol polyglycol ether), propylene glycol (1, the 2-dihydroxypropane), Allyl carbonate (4-methyl-2-oxygen-1, the 3-dioxolane), solutol (15 hydroxy stearic acid macrogol esters, BASF), with and composition thereof, wherein preferred transcutol.
(3) volatile solvent
Through adopting but be not present in the end product, it helps Itraconazole to dissolve under the effect of acidulant to volatile solvent in preparation process.In the present invention, be preferably used as volatile solvent for nonpoisonous organic solvent such as alcohols, for example ethanol, propanol and isopropyl alcohol, it is easily flung to being lower than under 100 ℃ the temperature.
(4) surfactant
The surfactant that uses among the present invention helps oil and hydrophilic composition to form the Emulsion of homogeneous and makes Emulsion keep stable in storage process.The representational example of described surfactant comprises:
1. (polyoxyethylene glycolated) natural or hydrogenated vegetable oil of polyoxygenated ethylene alcoholization, as the natural or castor oil hydrogenated of polyoxygenated ethylene alcoholization (
BASF;
Nikkol),
2. polyoxygenated ethylidene-sorbitan-fatty acid ester, wherein fatty acid for single-or three-lauric acid, Palmic acid, stearic acid or oleic acid (tell
ICI), and
3. polyoxygenated ethylidene fatty acid ester, as polyoxygenated ethylidene stearate (Myrj, ICI).
(5) oil
The oil component that is used for the present invention should be compatible with surfactant, and can form stable microemulsion in aqueous medium.It can be the acceptable oil of a kind of materia medica such as tocopherol and its derivant, comprises tocopheryl acetate, succinic acid tocopherol and Polyethylene Glycol-1000-succinic acid tocopherol (TPGS).
The preparation process of the present composition comprises: (a) Itraconazole is dissolved in the mixture of acidulant, amphipathic additive and volatile solvent, (b) surfactant and oil are dissolved in the resulting solution, and (c) in the mixed solution of gained, remove volatile solvent.
In step (c), removing of volatile solvent can be adopted conventional method, for example heats under ambient pressure or vacuum, and preferred range is 40 ℃～100 ℃, and more preferably temperature range is 40 ℃～80 ℃.
In above preparation method, the amount ranges of Itraconazole, acidulant, amphipathic additive, volatile solvent, surfactant and oil is 1: 0.5～15: 0.5～20: 0.5～20: 0.5～15: 0.5～15 according to weight ratio, be preferably 1: 1～10: 1～15: 1～15: 1～10: 1～and 10.
The present invention does not contain in the final composition of volatile solvent and comprises Itraconazole, acidulant, amphipathic additive, surfactant and oil, their weight ratio scope is 1: 0.5～15: 0.5～20: 0.5～15: 0.5～15, preferred 1: 1～10: 1～15: 1～10: 1～10.
In addition, the present composition can comprise materia medica acceptable additive such as the antioxidant that is used for oral administration.
Pharmaceutical composition of the present invention can be mixed with different pharmaceutical preparation according to common process arbitrarily, for example powder, granule, tablet, coated preparation and liquid preparation.For example, can be prepared as follows hard capsule: in described pharmaceutical composition, add lubricant and other medical additive, mixture is processed into powder or granule, described powder or granule are filled in the hard gelatin capsule; Can be prepared as follows tablet: in described pharmaceutical composition, add suitable additive, mixture is made tablet; Can pass through described pharmaceutical composition preparation liquid preparation soluble in water; Can be prepared as follows coated preparation: with the solution coating of described pharmaceutical composition sugar pill as
(Edward MendellCo., UK).
Prepared itraconazole composition of the present invention is the clear glass attitude, that is, it does not possess flowability, and has high viscosity under 25 ℃, and viscosity is at least 10,000cps.This can be by the amphipathic additive that uses among the present invention and volatile solvent combined effect and realizes.The compositions of high-viscosity glass attitude is compared consolidation more with the micro emulsion composition of routine.
The present composition has self-emulsifying microemulsion to generate high stability and the particulate ability of available (available) microemulsion in body fluid when oral administration.Therefore, even because the present composition also can keep high and stable Itraconazole dissolution rate under pH6.8 or higher neutrality or alkali condition, so its Itraconazole bioavailability is not subjected to the influence of the food taken in; The Itraconazole bioavailability of the present composition is identical before and after ingesting, AUC
Before ingestingAnd AUC
After ingestingRatio approaches 1 (AUC: the haemoconcentration area under curve), be preferably 0.8 or higher.
Following embodiment is used for further setting forth the present invention, and is not to be used to limit the scope of the invention.
In addition, except that indicating especially, hereinafter solid accounts for solid mixture, liquid accounts for liquid and solid accounts for the percentage ratio of liquid respectively based on mass/mass (wt/wt), volume/volume (vol/vol) and mass/volume (wt/vol).
Embodiment
Embodiment 1: the preparation of hard capsule-1)
Adopt following feedstock production hard capsule:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 208
Transcutol 83
Polyoxygenated ethylidene-50-castor oil hydrogenated (
50) 70
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
Itraconazole is dissolved in equably in 85% phosphoric acid, transcutol and the alcoholic acid mixture, then to wherein adding other composition and dissolving.Then, the mixture heating under 55 ℃ that obtains was concentrated in 4 hours, obtain not having mobile thickness transparent composition from wherein flinging to ethanol.By the conventional method described in the Pharmacopoeia Coreana rules of preparations compositions is filled in the hard capsule.
Embodiment 2: preparation of soft capsule
Adopt following composition to prepare soft capsule:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 200
Transcutol 150
Polyoxygenated ethylidene-50-castor oil hydrogenated (
50) 80
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
The preparation process that adopts above composition to repeat among the embodiment 1 obtains not having mobile thickness transparent composition.By the conventional method described in the Pharmacopoeia Coreana rules of preparations compositions is filled in the soft capsule.
Embodiment 3: the preparation of hard capsule-2)
Adopt following composition to prepare hard capsule by the preparation process among the embodiment 1:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 200
Transcutol 83
Polyoxygenated ethylidene-50-castor oil hydrogenated (
50) 200
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
Embodiment 4: the preparation of hard capsule-3)
Adopt following composition to prepare hard capsule by the preparation process among the embodiment 1:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 200
Transcutol 83
Polyoxygenated ethylidene-50-castor oil hydrogenated (
50) 200
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
Embodiment 5: the preparation of hard capsule-4)
Adopt following composition to prepare hard capsule by the preparation process among the embodiment 1:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 200
Transcutol 83
Polyoxygenated ethylidene-50-castor oil hydrogenated (
50) 150
EL 150
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
Embodiment 6: the preparation of hard capsule-5)
Adopt following composition to prepare hard capsule by the preparation process among the embodiment 1:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 200
Transcutol 83
EL 80
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
Embodiment 7: the preparation of hard capsule-6)
Adopt following composition to prepare hard capsule by the preparation process among the embodiment 1:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 200
Transcutol 83
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
Embodiment 8: the preparation of hard capsule-7)
Adopt following composition to prepare hard capsule by the preparation process among the embodiment 1:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 200
Transcutol 83
Polyoxygenated ethylidene-50-castor oil hydrogenated (
50) 200
Dl-alpha-tocopherol 120
(
*Be not present in the final composition)
Embodiment 9: the preparation of hard capsule-8)
Adopt following composition to prepare hard capsule by the preparation process among the embodiment 1:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 150
Transcutol 83
Polyoxygenated ethylidene-50-castor oil hydrogenated (
50) 70
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
Embodiment 10: the preparation of hard capsule-9)
Adopt following composition to prepare hard capsule by the preparation process among the embodiment 1:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 208
Isosorbide dimethyl ether 83
Polyoxygenated ethylidene-50-castor oil hydrogenated (
50) 70
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
Embodiment 11: the preparation of hard capsule-10)
Adopt following composition to prepare hard capsule by the preparation process among the embodiment 1:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 208
Glycofurol 83
Polyoxygenated ethylidene-50-castor oil hydrogenated (
50) 70
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
Embodiment 12: the preparation of hard capsule-11)
Adopt following composition to prepare hard capsule by the preparation process among the embodiment 1:
Amount (mg/ capsule)
Itraconazole 50
Hydrochloric acid 150
Isosorbide dimethyl ether 83
Polyoxygenated ethylidene-50-castor oil hydrogenated (
50) 70
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
Comparative example: the preparation of hard capsule
Adopt the preparation process among the embodiment 1, use following composition and do not use amphipathic additive transcutol to prepare hard capsule:
Amount (mg/ capsule)
Itraconazole 50
Phosphoric acid 85% 208
Polyoxygenated ethylidene-50-castor oil hydrogenated (
50) 70
Dl-alpha-tocopherol 60
(
*Be not present in the final composition)
Test example 1: dissolution test
Preparation of the present invention, the preparation in the comparative example, this skin core among the embodiment 1 have been measured according to the dissolution test method II (oar method) in the Pharmacopoeia Coreana rules of preparations
Capsule, this skin core
Sheet and this skin core
The Itraconazole dissolution rate of solution (Korea S Yang Sen), experiment condition is as follows:
Experimental provision: Erweka DT80 (Erweka, Germany)
Testing liquid: 900ml simulated gastric fluid (pH 1.2)
900ml phosphate buffer (pH 6.8)
Testing liquid's temperature: 37 ± 0.5
Rotating speed: 100 ± 4rpm
Analytical method: liquid chromatography
-chromatographic column: Cosmosil C18 (150mm * 4.6mm; Nacalai tesque, Japan)
-mobile phase: acetonitrile/phosphate buffer (pH 7.0)=60: 40
-flow velocity: 1.2ml/min
-detector: UV 255nm
-sampling volume: 10 μ l
The stripping quantity of Itraconazole represents that by the accumulative total burst size of Itraconazole in 45 minutes the result as shown in Table 1 and Table 2.
Table 1
Dissolution rate in the simulated gastric fluid (pH 1.2)
Table 2
Dissolution rate in the phosphate buffer (pH 6.8)
As shown in Table 1 and Table 2, when pH 1.2 or pH 6.8, the preparation of embodiment 1 is compared with the preparation of comparative example and commercial preparation and is shown higher Itraconazole stripping quantity.Especially, the result shows that under pH 6.8 conditions, the Itraconazole dissolution rate of preparation is compared with the commercial preparation and increased significantly among the embodiment 1.
Test example 2: absorption test in the body
In order to investigate the bioavailability of the Itraconazole that is contained in the preparation of the present invention, the interior absorption test of body of carrying out as described below.
Make 20 14～15 week age, heavily about 300g male Sprague-Dawly rat fasting 48 hours, but permission is freely drunk water.Be divided into two groups then, 10 every group.Subsequently, test after two groups of rats provide common solid feed and water to be used to ingest.
To the preparation of two groups of rats difference orally give embodiment 1 preparations of the present invention and comparative example, dosage is 20mg Itraconazole/kg rat body weight.Before administration and after the administration 1,2,3,4,5,7 and 24 hour, directly from the heart blood sample collection of rat, and from separation of serum wherein.
The carbonate buffer solution (pH 10.0) that in 500 each blood serum sample of μ l, adds 50 μ l internal standard substance solution (methanol solution that contains 500 μ g/ml econazole nitrates) and 200 μ l 1M.To wherein adding 7ml extractant (normal heptane: isoamyl alcohol (isoamylalchol)=9: 1), and the jolting under 80rpm of gained mixture obtained extract in 5 minutes.With extract 3, under the 000rpm centrifugal 10 minutes, and under blanket of nitrogen, fling to solvent in 50 ℃.In the gained residue, add 200 μ l and contain 65% acetonitrile solution of 0.05% triethylamine, and measure described mixture with HPLC under the following conditions.The result such as the table 3 and shown in Figure 1 of observation:
-chromatographic column: Inertsil ODS2 (250 * 4.6mm, 5 μ m; GL science, Japan)
-mobile phase: 65% acetonitrile solution that contains 0.05% triethylamine
-detector: UV 258nm
-flow velocity: 1.2ml/min
-sample size: 100 μ l
Table 3
* 1Haemoconcentration area under curve to 48 hours
* 2The haemoconcentration maximum
* 3Time when haemoconcentration reaches maximum
Result among table 3 and Fig. 1 shows that the Itraconazole bioavailability that is observed by preparation of the present invention is subjected to the influence of the food taken in little more than the preparation of comparative example.
Though described the present invention by above specific embodiments, it should be appreciated by those skilled in the art, can carry out various improvement and change to the present invention in the defined scope of appended invention claim.
Claims (4)
1. the preparation method that comprises the Orally administered composition of Itraconazole, acidulant, amphipathic additive, surfactant and oil, it may further comprise the steps: (a) Itraconazole is dissolved in the mixture of acidulant, amphipathic additive and volatile solvent equably, (b) again surfactant and oil are dissolved in the resulting solution, and (c) from wherein removing volatile solvent
Wherein said Itraconazole: acidulant: amphipathic additive: volatile solvent: surfactant: the weight ratio scope of oil is 1: 0.5～15: 0.5～20: 0.5～20: 0.5～15: 0.5～15,
Wherein said amphipathic additive is selected from following group: diethylene glycol one ether, Isosorbide dimethyl ether, tetrahydrofurfuryl alcohol polyglycol ether, propylene glycol, Allyl carbonate, 15 hydroxy stearic acid macrogol esters and their mixture, and
Wherein said grease separation is in following group: tocopherol, tocopheryl acetate, succinic acid tocopherol, Polyethylene Glycol-1000-succinic acid tocopherol (TPGS) with and composition thereof.
2. the method in the claim 1, wherein said volatile solvent is ethanol, propanol or isopropyl alcohol.
3. the method in the claim 1, wherein said acidulant is selected from following group: phosphoric acid, hydrochloric acid and aqueous solution thereof.
4. the method in the claim 1, wherein said surfactant is selected from following group: the natural or hydrogenated vegetable oil of polyoxygenated ethylene alcoholization, polyoxygenated ethylidene-sorbitan-fatty acid ester, polyoxygenated ethylidene fatty acid ester with and composition thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2003-0063147A KR100529766B1 (en) | 2003-09-09 | 2003-09-09 | Oral itraconazole composition which is not affected by ingested food and preparation thereof |
| KR1020030063147 | 2003-09-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1849123A CN1849123A (en) | 2006-10-18 |
| CN100475211C true CN100475211C (en) | 2009-04-08 |
Family
ID=36096818
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004800258516A Expired - Fee Related CN100475211C (en) | 2003-09-09 | 2004-09-07 | Oral itraconazole composition being not affected by ingested food and process for preparing same |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1663231A4 (en) |
| JP (1) | JP2007505103A (en) |
| KR (1) | KR100529766B1 (en) |
| CN (1) | CN100475211C (en) |
| AU (1) | AU2004270069B2 (en) |
| BR (1) | BRPI0414192A (en) |
| CA (1) | CA2538019C (en) |
| IL (1) | IL173743A (en) |
| MX (1) | MXPA06002239A (en) |
| RU (1) | RU2006111477A (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2876909C (en) | 2012-06-21 | 2022-08-16 | Mayne Pharma International Pty. Ltd. | Itraconazole compositions and dosage forms, and methods of using the same |
| CN104688536B (en) * | 2015-02-03 | 2016-06-08 | 常州制药厂有限公司 | A kind of preparation method of itraconazole preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100336090B1 (en) * | 1998-06-27 | 2002-05-27 | 윤승원 | Solid dispersed preparation of poorly water-soluble drug containing oil, fatty acid or mixture thereof |
| US6383471B1 (en) * | 1999-04-06 | 2002-05-07 | Lipocine, Inc. | Compositions and methods for improved delivery of ionizable hydrophobic therapeutic agents |
| KR100435141B1 (en) * | 2000-12-28 | 2004-06-09 | 한미약품 주식회사 | Composition for oral administration of poorly soluble antifungal agent and process for the preparation thereof |
| KR100455216B1 (en) * | 2001-06-27 | 2004-11-09 | 한미약품 주식회사 | Composition for oral administration of poorly soluble antifungal agent and process for the preparation thereof |
-
2003
- 2003-09-09 KR KR10-2003-0063147A patent/KR100529766B1/en not_active IP Right Cessation
-
2004
- 2004-09-07 RU RU2006111477/15A patent/RU2006111477A/en not_active Application Discontinuation
- 2004-09-07 CA CA002538019A patent/CA2538019C/en not_active Expired - Fee Related
- 2004-09-07 BR BRPI0414192-0A patent/BRPI0414192A/en not_active IP Right Cessation
- 2004-09-07 MX MXPA06002239A patent/MXPA06002239A/en not_active Application Discontinuation
- 2004-09-07 CN CNB2004800258516A patent/CN100475211C/en not_active Expired - Fee Related
- 2004-09-07 EP EP04774524A patent/EP1663231A4/en not_active Withdrawn
- 2004-09-07 AU AU2004270069A patent/AU2004270069B2/en not_active Ceased
- 2004-09-07 JP JP2006526025A patent/JP2007505103A/en active Pending
-
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Also Published As
| Publication number | Publication date |
|---|---|
| CA2538019C (en) | 2009-09-01 |
| RU2006111477A (en) | 2006-08-27 |
| CN1849123A (en) | 2006-10-18 |
| IL173743A (en) | 2012-08-30 |
| BRPI0414192A (en) | 2006-10-31 |
| CA2538019A1 (en) | 2005-03-17 |
| AU2004270069A1 (en) | 2005-03-17 |
| EP1663231A4 (en) | 2009-04-29 |
| EP1663231A1 (en) | 2006-06-07 |
| IL173743A0 (en) | 2006-07-05 |
| JP2007505103A (en) | 2007-03-08 |
| MXPA06002239A (en) | 2006-06-20 |
| KR100529766B1 (en) | 2005-11-17 |
| AU2004270069B2 (en) | 2008-03-13 |
| KR20050026169A (en) | 2005-03-15 |
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Assignee: Beijing Hanmei Pharmaceutical Co., Ltd. Assignor: Hanmi Pharm. Co., Ltd. Contract record no.: 2012990000235 Denomination of invention: Oral itraconazole composition which is not affected by ingested food and process for preparing same Granted publication date: 20090408 License type: Exclusive License Open date: 20061018 Record date: 20120416 |
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