WO1999059552A1 - Preparations a liberation controlee - Google Patents
Preparations a liberation controlee Download PDFInfo
- Publication number
- WO1999059552A1 WO1999059552A1 PCT/JP1999/002499 JP9902499W WO9959552A1 WO 1999059552 A1 WO1999059552 A1 WO 1999059552A1 JP 9902499 W JP9902499 W JP 9902499W WO 9959552 A1 WO9959552 A1 WO 9959552A1
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- WIPO (PCT)
- Prior art keywords
- release
- drug
- controlled
- layer
- preparation
- Prior art date
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Classifications
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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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
Definitions
- the present invention relates to a multiple release preparation and a method for producing the same. More specifically, the present invention relates to a preparation having a mechanism of rapidly releasing a drug in the inner core after a certain release delay time by coating the inner core portion with a release controlling layer. The present invention relates to a drug product which is capable of releasing a drug multiple times at intervals with a single dose by adding a drug releasing portion to the drug. In addition, the present invention relates to a preparation which releases different components with a time lag by separately containing a plurality of drugs in an inner core portion and a single or a plurality of drug release layers. Background art
- Oral controlled release formulations have the advantage of reducing the burden on patients by reducing the number of doses and improving low compliance.
- a technique for such an oral controlled release preparation there is widely known a method of sustaining drug release to maintain the blood concentration, that is, a so-called sustained release preparation (theophylline sustained release preparations such as theophylline and propranolol hydrochloride). Release formulation).
- the blood concentration of the drug is always maintained, so that some drugs are susceptible to resistance, and those that are susceptible to the first-pass effect in the liver are rapidly released.
- problems such as a decrease in bioavailability as compared with the case where the drug is taken with a drug that releases lipase.
- formulations that release more than once in a single dose are useful.
- different drugs can be administered in one dose.
- Controlled release formulations that can be released multiple times at time intervals are useful.
- a formulation technology for releasing a drug multiple times for the purpose of reducing the number of doses a water-soluble polymer material or a wax that forms a matrix is used as a release controlling base, and water is used. Covers inner core containing swelling disintegrant There are known techniques (for example, Japanese Patent Application Laid-Open No.
- An object of the present invention is to select a release control base that makes it easy to control the water content and that can release a plurality of times without using a base as a release control base in view of the above-mentioned problems of the prior art.
- Another object of the present invention is to provide a drug product that can accurately control the time interval between multiple releases (hereinafter referred to as lag time) and that is less susceptible to the environment in the gastrointestinal tract and a manufacturing technique therefor.
- the present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, are selected from fumaric acid, DL-tributophan, and L-tyrosine, which are low-molecular substances having a low dissolution rate under physiological conditions. If one or more species are included as the base of the release control layer, the control of the water content is easy, and the release control with the desired lag time without the use of waxes as the release control base Have been found to be possible, and have completed the present invention.
- the present invention relates to the manufacture of a pharmaceutical composition
- a pharmaceutical composition comprising one or more bases selected from an inner core containing one or more drugs to be controlled for release, fumaric acid, DL-tributophan and L-tyrosine.
- a controlled release layer which is a coating layer substantially free of a drug to be controlled for release manufactured by adding an acceptable additive, and one or more drugs to be controlled for release
- a controlled-release preparation having a drug-release layer containing the same as a component, which satisfies the following conditions.
- the inner core is located inside the controlled release formulation.
- the controlled release preparation has at least one controlled release layer covering at least the inner core portion, and may further have at least one controlled release layer and / or at least one drug release layer.
- the controlled release preparation contains a controlled release layer and a drug release layer, these are alternately coated.
- the outermost layer may be either a release controlling layer or a drug releasing layer.
- the outermost layer is a drug release layer, it may cover the entire surface of the release control layer immediately below, or may cover a part of the surface.
- the type of drug contained in the core portion of the controlled release formulation and the drug release layer is independently selected.
- the inner core portion and each drug release layer may be prepared so that the contained drug is immediately released or may be prepared so as to have sustained release.
- the core part and the single drug release layer are composed of multiple layers containing only one kind of drug. You may.
- the present invention it is produced by adding one or more bases selected from fumaric acid, DL-tributophan, and L-tyrosine to an additive acceptable for pharmaceutical production, Using a controlled release layer that is substantially free of the drug to be controlled for release, one or more drugs to be controlled for release are prepared to be released quickly or slowly.
- the present invention provides a controlled-release preparation having a portion constituted by coating an inner core portion.
- the present invention provides the following steps A to E,
- A. Form an inner core containing one or more drugs to be controlled for release, and form one or more groups selected from fumaric acid, DL-tryptophan and L-tyrosine.
- Forming a controlled release layer by coating the composition with an additive that is acceptable for drug manufacture in the agent and containing substantially no drug to be controlled for release, to obtain a double-structured molded body;
- step B By coating or laminating a component containing one or more drugs to be controlled for release on the double-structured molded product obtained in step A above Forming a drug release layer,
- step D a step of forming a drug release layer by coating or laminating a component containing one or more drugs to be controlled for release on the molded article obtained in the step C,
- step E a step of forming a controlled-release layer in step C and a step of forming a drug-release layer in step D described above at least once or more to obtain a target controlled-release preparation
- a controlled-release preparation comprising at least step A, and optionally further comprising steps B, B and C, steps B to D, or steps B to E, as required.
- a method for producing a controlled release preparation characterized in that the controlled preparation satisfies the above conditions (1) to (8).
- FIG. 1 is a schematic diagram showing an example of the controlled release preparation of the present invention, which comprises an inner core portion containing a controlled release drug and a controlled release layer.
- FIG. 2 is an example of the controlled release preparation of the present invention, and is a schematic diagram of a tablet in which a primary release component (drug release layer) is coated on the outer periphery of the controlled release layer.
- a primary release component drug release layer
- FIG. 3 shows an example of the controlled release preparation of the present invention, in which a primary release component (drug release layer) is laminated on the release control layer (only a part of the surface of the release control layer is covered). It is a schematic diagram of the tablet which is formed.
- a primary release component drug release layer
- FIG. 4 shows an example of the controlled release formulation of the present invention.
- the tablet of Fig. 2 is used as the inner core, and the primary release component (drug release layer) is coated on the outer periphery of the release control layer, enabling three releases.
- FIG. 4 is a schematic diagram of a tablet used as an example.
- FIG. 5 shows an example of the controlled release formulation of the present invention.
- the tablet of Fig. 2 is used as the inner core, and the primary release component is laminated on the release control layer (only a part of the surface of the release control layer is coated).
- FIG. 2 is a schematic diagram of a tablet that allows three releases.
- FIG. 6 is a graph showing the results of the release test of Example 2.
- FIG. 7 is a graph showing the results of the release test of Example 3.
- FIG. 8 is a graph showing the results of the release test of Example 4.
- FIG. 9 is a graph showing the results of an absorption lag time measurement experiment in Example 6.
- FIG. 10 is a diagram showing the correlation between the release lag time and the absorption lag time in Example 6.
- the controlled release preparation of the present invention may have any configuration as long as the preparation satisfies the above conditions (1) to (8).
- the controlled release formulation of the present invention comprises a unit consisting of at least two components.
- the inner core portion (the most controlled release preparation containing a controlled release drug) is prepared so that one or more drugs to be controlled for release are released promptly or sustainedly (sustained).
- a “release control layer” that covers the inner core and controls the lag time of drug release from the inner core, which does not substantially contain the drug to be controlled for release. ( Figure 1 ) .
- the multiple release formulation of the present invention comprises at least three components. In other words, it contains the drug to be controlled for release, and releases the drug after a predetermined lag time.
- the “inner core part (secondary release part located inside the controlled release formulation)” Controlled release layer that controls the lag time of drug release from the inner core by coating the inner core portion, containing substantially the same and / or different drug as the drug whose release is to be controlled. Covering all of the controlled release layer, or laminating on the outside of the controlled release layer (that is, coating on a part of the outside of the controlled release layer), and immediately or continuously (sustained release) after administration. It consists of a “drug release layer (primary release section)” (Figs. 2 and 3).
- the drug When taking the preparations shown in Figs. 2 and 3, the drug is first released from the drug release layer (primary release part), and then after a predetermined lag time, the drug is released from the inner core part (secondary release part). As it is released, two doses can be released in one dose.
- the outside of the components shown in FIG. Coated with a second release-controlling layer that does not substantially contain the same, and coated with a drug-releasing layer all over the outside of the second release-controlling layer, or laminated with a drug-releasing layer (ie, the second release-controlling layer).
- a drug release layer is coated on the outer part of the controlled release layer), and a formulation consisting of five components is also included ( Figures 4 and 5).
- the drug When taking the preparations of Figs. 4 and 5, the drug is first released from the outermost drug release layer (primary release section), and then, after a predetermined lag time, the second drug release layer (secondary release section) is released. After a predetermined lag time from the secondary release, the drug is released from the inner core part (tertiary release part), and three doses can be released with one dose.
- a controlled release formulation composed of two components a controlled release formulation composed of three components, and a controlled release formulation composed of five components are exemplified.
- the outermost layer may be either a drug release layer or a release control layer.
- the inner core portion and the drug release layer may be either immediate release or sustained release, and can be appropriately selected depending on the purpose of use of the preparation.
- the controlled release preparation of the present invention has a drug release layer
- the type of drug contained in the inner core part and the drug release layer may be the same or a plurality of types.
- a preparation comprising the five components shown in FIG. 4, the following combinations can be exemplified.
- Combination 1 Primary emission unit— ⁇ , Secondary emission unit— ⁇ , Tertiary emission unit—A
- Combination 2 Primary emission unit—A, Secondary emission unit—B, Tertiary emission unit — C
- Combination 3 Primary emission unit—A, Secondary emission unit—B, Tertiary emission unit—A
- Combination 4 Primary emission unit—A and B, Secondary emission unit—A and B , Tertiary discharge—A and B
- Combination 5 Primary release section and B, Secondary release section ⁇ A, Tertiary release section ⁇ A and B
- Combination 6 Primary release section—A and B, Secondary release section ⁇ A, Tertiary release section—A and C
- the primary release portion means the outermost drug release layer
- the secondary release portion means the second drug release layer
- the tertiary release portion means the inner core portion.
- A, B, and C represent different drugs.
- the drug released from each release portion is of the same type, and such a formulation is a formulation that releases the same component a plurality of times (a so-called pulse-type formulation).
- the pulsatile formulation has the following remarkable advantages.
- the advantage of combination 5 is that the combination treatment of A taken three times a day and B taken twice a day can be taken once a day.
- the advantage of combination 6 is 1
- the combined treatment of A taken three times a day and B and C taken once a day can be taken once a day.
- the lag time of drug release from the inner core is controlled by the disintegration time of the release control layer, but in order to disintegrate at a predetermined time (usually several hours to ten and several hours) after ingestion, release It is necessary to use a low-molecular substance having a low dissolution rate under physiological conditions as a base material for the control layer.
- a low-molecular substance having a low dissolution rate under physiological conditions include fumaric acid, DL-tributophan, L-tyrosine and the like, and one or more of these can be used as a base.
- the compounding amount in these release control layers is usually 60 to 99%, preferably 75 to 98%, more preferably 90 to 95%.
- the inner core portion is molded and, together with the components of the release control layer, compressed using, for example, a nucleated tableting machine, and the inner core portion is formed into a release control layer. (Fig. 1).
- the component of the immediate release portion is coated on the molded product having the double structure using, for example, a coating machine (Fig. 2), or is laminated by pressing using a tableting machine (Fig. 2). 3) A two-release preparation can be produced.
- the molded article of FIG. 2 is formed into a triple-structured molded article together with the composition of the second release control layer by, for example, tableting using a nucleated tableting machine.
- the components can be coated, for example using a coating machine ( Figure 4), or pressurized and laminated using a tableting machine ( Figure 5) to produce a triple release formulation. . Therefore, the most important point for producing the multiple-release preparation of the present invention lies in producing the molded article having the double structure shown in FIG.
- a method for producing a molded article having a double structure will be described in more detail.
- the base used for the release control layer will be described by taking fumaric acid as an example.
- an inner core containing the drug to be controlled for release is manufactured.
- the inner core can be manufactured so that the release of the drug it contains is at a therapeutically desired state or rate.
- the inner core portion There is no particular limitation on the size and shape of the inner core portion, but it is desirable to make the core as small as possible from the aspect of ingestibility since it is covered with the release controlling layer.
- Examples of the form of the core portion include tablets, capsules, and granules, which are suitable for the physicochemical properties of the drug contained in the core portion and that the release characteristics of the drug change during the molding process of the release control layer. There is no particular limitation as long as it is in a proper configuration.
- fumaric acid granules obtained by pulverizing fumaric acid are used as the main raw materials, and binders and excipients are added to produce fumaric acid granules.
- the method of pulverizing fumaric acid includes known methods, for example, dry pulverization such as jet pulverization, hammer mill pulverization, pin mill pulverization and ball mill pulverization, or wet pulverization, and is not particularly limited.
- dry pulverization such as jet pulverization, hammer mill pulverization, pin mill pulverization and ball mill pulverization, or wet pulverization, and is not particularly limited.
- the particle size of the fumaric acid pulverized powder affects the lag time of controlled release.
- the particle size needs to be set finely, and the average particle size is preferably 100 / xm or less, more preferably 50 m or less.
- the granulation of fumaric acid granules can be performed by a conventionally known method, for example, high-speed stirring granulation, fluidized bed granulation, tumbling fluidized bed granulation, spray drying, extrusion granulation, and the like. There is no particular limitation.
- a medically acceptable additive is added to the fumaric acid granules, and the mixture is uniformly mixed to obtain blended granules.
- a cored tableting machine is used to compress and mold the inner core to obtain a molded product having a double structure.
- the drug is released multiple times in a single dose, such as diflupine, hydrochloride, nicorandil, methoctyl pramide, proproterol hydrochloride, etc. Drugs that may benefit from
- the method for producing the multiple-release preparation of the present invention has been described by taking the case of tablets as an example.However, the target dosage form of the controlled-release preparation of the present invention is not limited to tablets, and may be a solid preparation. All can be applied.
- Example 1 the target dosage form of the controlled-release preparation of the present invention is not limited to tablets, and may be a solid preparation. All can be applied.
- Example 1 Preparation of fumaric acid granules
- fumaric acid granules composed of fumaric acid, calcium hydrogen phosphate, and corn starch were produced.
- Raw material composition ratio (%) (%)
- the corn starch 2.28 fumaric acid was pre-treated by a wet milling device Mycolloider, and the slurry containing water was spray-dried to produce fumaric acid granules having an average particle size of 150 to 250. .
- Blue No. 1 was selected as a model raw material, and an inner core tablet was produced according to the following formulation.
- the formulation is as follows, corntenophane is added as a starch paste of 10% concentration except calcium stearate, and it is mixed with other raw materials, mixed and kneaded with a Shinagawa universal mixing stirrer, sized with a speed mill and dried. After adding calcium stearate, ⁇
- Subtotal 40 Each tablet contains 376 mg of fumaric acid granules, 20 mg of stearic acid, 4 mg of stearic acid, and 4 mg of stearic acid.
- the outer layer formed of the compounding powder was adjusted so as to be located at the center of the tablet, and pressed into a tablet having a diameter of 8.5 mm to obtain a controlled-release tablet.
- Example 1 shows an example of a method for producing a controlled-release tablet when fumaric acid is used as a controlled-release base. By breaking the tablet obtained in this example in the diameter direction, it was confirmed that the core tablet had the shape shown in FIG. Example 2
- the core drug of the core tablet was made into a round tablet with a diameter of 5 mm according to the prescription below Nico. Ingredients Prescription (mg / tablet)
- Calcium stearate 0.3 Fumaric acid granules manufactured as shown in Example 1 were used in an amount of 47 Omg per tablet, to which 25 mg of stearic acid and 5 mg of calcium stearate were added as a lubricant to obtain a compounding powder.
- the tablets and the compounded powder were subjected to pressure molding using a tableting machine similar to the tableting method of Example 1 to obtain controlled-release tablets having a diameter of 9.5 mm.
- Example 2 The above tablet prepared in Example 2 was subjected to a dissolution test using a test solution of 37 under the condition of 50 OmL of water in 37 under the first method of dissolution test of the Japanese Pharmacopoeia, and nicorandil in the eluate sampled over time was analyzed by HP LC. Quantification and the results shown in Fig. 6 confirmed that the function of causing rapid release was achieved after a certain drug release suppression time (lag time). In addition, symbols of ⁇ , ⁇ , and mouth in FIG. 6 indicate the dissolution test results of three different tablets of the same lot.
- Example 2 stearic acid was used as a lubricant, and the content of stearic acid in the constituent components forming the controlled release layer was 5%, but the content ratio was 0%, 5%, 10%, and 15%.
- the blended powder was adjusted to vary, and tablets were molded in the same manner as in Example 2 to obtain four types of controlled-release tablets.
- Example 3 in which the content ratio of stearic acid added to the formulation of the outer layer as a lubricant in Example 2 was changed, the lag time of the tablets manufactured using the outer layer of each content ratio was as shown in FIG. Acid content has little effect on controlled release, and formulations without tearic acid can maintain a sufficiently long lag time It was confirmed. Therefore, it was confirmed that the basic mechanism of this controlled release is not provided by wax, but by the controlled release base. In Fig. 7, nicorandil eluted over time was quantified as in Example 2, and the time during which the elution was 5% or less was defined as the lag time.
- Example 4
- Hydrochloric acid roll was selected as the target drug for controlled release, and it was molded into a circular shape with a diameter of 5 mm according to the following formulation to produce a core tablet.
- a total of 50.0 fumaric acid granules produced as shown in Example 1 were used in an amount of 47 Omg per tablet, and 25 mg of stearic acid and 5 mg of calcium stearate were added as lubricants to obtain a powder mixture.
- the core-containing core tablet and the compounded powder were subjected to pressure molding using a tableting machine similar to that of the controlled-tablet tableting method of Example 1 to obtain controlled-release tablets of ⁇ 9.5 mm.
- Example 4 controlled-release tablets were produced using propranolol as the target drug for controlled-release.
- the dissolution of the tablet was also confirmed under the same conditions as in Example 2, and it was verified that release started with a certain lag time (Fig. 8).
- the symbols ⁇ , ⁇ , and mouth in FIG. 8 indicate the dissolution test results for three different tablets of the same lot.
- Example 5
- Example 5 showed that the present invention can be carried out by using such a method without using a tablet for the inner core. As a result, it was shown that a drug to be controlled for release, which is not limited to the dosage form, can be set in the inner core.
- Example 6
- Fumaric acid granules produced as shown in Example 1 were used in an amount of 47 Omg per tablet, to which 25 mg of stearic acid and 5 mg of calcium stearate were added as lubricants, or as shown in Example 1. 517 mg per tablet of fumaric acid granules prepared as described above, and 27.5 mg of stearic acid and 5.5 mg of calcium stearate as a lubricant were added to the blended powder. Using the indicated nicorandil tablets, tablets were produced at various tableting pressures with average lag times of 140, 250, and 365 minutes in dissolution tests (in vitro), respectively.
- the nicorandil-containing preparation shown in Example 6 was administered to a beagle dog, blood was collected every hour, and the time immediately before the drug first appeared in the blood was calculated as the absorption (in vitro) lag time.
- the correlation with the release lag time was examined, a positive and favorable relationship was obtained, and it was confirmed that the drug was released with the lag time even in the living body.
- Fig. 9 shows typical blood concentration curves when four dogs were used
- Fig. 10 shows the relationship between various release lag times and absorption lag times.
- the present invention it is possible to reduce the number of times a patient takes a drug and improve low compliance, and it has been difficult to apply a sustained-release preparation due to concerns about the occurrence of resistance. It is possible to reduce the number of doses of a given drug.
- the first release of the drug allows pre-treatment to enhance the effect of the second release of the drug in a single dose.
- the compounding ratio of the controlled-release low-molecular-weight base and the binder, the amount of the controlled-release layer, the shape of the tablet, and in the case of a tablet, the molding pressure can be adjusted to an arbitrary value. It is possible to set the release lag time.
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Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT99919574T ATE272395T1 (de) | 1998-05-15 | 1999-05-14 | Präparationen zur kontrollierten freisetzung |
AU37300/99A AU748359B2 (en) | 1998-05-15 | 1999-05-14 | Controlled-release formulations |
JP2000549217A JP5048177B2 (ja) | 1998-05-15 | 1999-05-14 | 放出制御製剤 |
EP99919574A EP1077065B1 (en) | 1998-05-15 | 1999-05-14 | Controlled release formulations |
US09/700,214 US6544554B1 (en) | 1998-05-15 | 1999-05-14 | Regulated release preparations |
DE69919155T DE69919155T2 (de) | 1998-05-15 | 1999-05-14 | Formulierungen zur mehrfachfreisetzung |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10/133219 | 1998-05-15 | ||
JP13321998 | 1998-05-15 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1999059552A1 true WO1999059552A1 (fr) | 1999-11-25 |
Family
ID=15099526
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1999/002499 WO1999059552A1 (fr) | 1998-05-15 | 1999-05-14 | Preparations a liberation controlee |
Country Status (10)
Country | Link |
---|---|
US (1) | US6544554B1 (ja) |
EP (1) | EP1077065B1 (ja) |
JP (1) | JP5048177B2 (ja) |
KR (1) | KR100630290B1 (ja) |
CN (1) | CN1211078C (ja) |
AT (1) | ATE272395T1 (ja) |
AU (1) | AU748359B2 (ja) |
DE (1) | DE69919155T2 (ja) |
TW (1) | TW592730B (ja) |
WO (1) | WO1999059552A1 (ja) |
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Publication number | Priority date | Publication date | Assignee | Title |
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JPWO2004024188A1 (ja) * | 2002-09-12 | 2006-01-05 | 日本メジフィジックス株式会社 | 薬物の血漿蛋白質結合を制御するための製剤 |
JP2008505873A (ja) * | 2004-07-08 | 2008-02-28 | アバンテイス・フアルマ・エス・アー | ニコランジルを含む組成物、調製方法及び使用 |
JP2008520378A (ja) * | 2004-11-19 | 2008-06-19 | スミスクライン・ビーチャム・コーポレイション | 個人別に療法を合わせるために可変用量の薬物併用製品を特注で調剤する方法 |
JP2014517843A (ja) * | 2011-05-24 | 2014-07-24 | テバ ファーマシューティカル インダストリーズ リミティド | 医薬組成物用の圧縮コア |
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ITMI20041689A1 (it) | 2004-09-01 | 2004-12-02 | Bojidar Mihaylov Stankov | Nuove formulazioni di rilascio controllato contenenti 5-idrossitriptofano e triptofano |
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KR101118866B1 (ko) * | 2008-11-28 | 2012-03-19 | 한올바이오파마주식회사 | 박동성 방출 제제 및 그 제조방법 |
US10596127B2 (en) | 2013-03-14 | 2020-03-24 | Wellesley Pharmaceuticals, Llc | Composition for reducing the frequency of urination, method of making and use thereof |
EP3355877A4 (en) * | 2015-09-30 | 2019-05-15 | Wellesley Pharmaceuticals, LLC | COMPOSITION FOR REDUCING URINATION FREQUENCY, METHOD FOR THE PREPARATION AND USE THEREOF |
JP2022529189A (ja) * | 2019-04-19 | 2022-06-17 | ホフマン・テクノロジーズ・エルエルシー | 持続放出製剤 |
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US5188836A (en) | 1990-07-27 | 1993-02-23 | Warner-Lambert Company | Sustained release formulations |
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- 1999-05-14 JP JP2000549217A patent/JP5048177B2/ja not_active Expired - Fee Related
- 1999-05-14 AT AT99919574T patent/ATE272395T1/de not_active IP Right Cessation
- 1999-05-14 EP EP99919574A patent/EP1077065B1/en not_active Expired - Lifetime
- 1999-05-14 TW TW088107880A patent/TW592730B/zh not_active IP Right Cessation
- 1999-05-14 AU AU37300/99A patent/AU748359B2/en not_active Ceased
- 1999-05-14 KR KR1020007012646A patent/KR100630290B1/ko not_active IP Right Cessation
- 1999-05-14 WO PCT/JP1999/002499 patent/WO1999059552A1/ja active IP Right Grant
- 1999-05-14 US US09/700,214 patent/US6544554B1/en not_active Expired - Fee Related
- 1999-05-14 DE DE69919155T patent/DE69919155T2/de not_active Expired - Lifetime
- 1999-05-14 CN CNB998061573A patent/CN1211078C/zh not_active Expired - Fee Related
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JPS6430A (en) * | 1987-03-24 | 1989-01-05 | Chugai Pharmaceut Co Ltd | Gradually releasing preparation |
JPH0899906A (ja) * | 1995-01-17 | 1996-04-16 | Chugai Pharmaceut Co Ltd | フマル酸含有徐放性製剤 |
JPH09221416A (ja) * | 1996-02-06 | 1997-08-26 | Jagotec Ag | 医薬錠剤およびその製造方法 |
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JPWO2004024188A1 (ja) * | 2002-09-12 | 2006-01-05 | 日本メジフィジックス株式会社 | 薬物の血漿蛋白質結合を制御するための製剤 |
JP2008505873A (ja) * | 2004-07-08 | 2008-02-28 | アバンテイス・フアルマ・エス・アー | ニコランジルを含む組成物、調製方法及び使用 |
JP2008520378A (ja) * | 2004-11-19 | 2008-06-19 | スミスクライン・ビーチャム・コーポレイション | 個人別に療法を合わせるために可変用量の薬物併用製品を特注で調剤する方法 |
US8383579B2 (en) | 2004-11-19 | 2013-02-26 | GlaxoSmithKline, LLC | Method for customized dispensing of variable dose drug combination products for individualizing of therapies |
JP2014517843A (ja) * | 2011-05-24 | 2014-07-24 | テバ ファーマシューティカル インダストリーズ リミティド | 医薬組成物用の圧縮コア |
Also Published As
Publication number | Publication date |
---|---|
ATE272395T1 (de) | 2004-08-15 |
CN1211078C (zh) | 2005-07-20 |
KR100630290B1 (ko) | 2006-09-29 |
JP5048177B2 (ja) | 2012-10-17 |
AU748359B2 (en) | 2002-06-06 |
EP1077065A4 (en) | 2002-03-13 |
DE69919155T2 (de) | 2005-08-04 |
EP1077065B1 (en) | 2004-08-04 |
EP1077065A1 (en) | 2001-02-21 |
AU3730099A (en) | 1999-12-06 |
US6544554B1 (en) | 2003-04-08 |
DE69919155D1 (de) | 2004-09-09 |
TW592730B (en) | 2004-06-21 |
KR20010043538A (ko) | 2001-05-25 |
CN1301151A (zh) | 2001-06-27 |
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