MXPA05001241A - Organic acid salt of amlodipine. - Google Patents
Organic acid salt of amlodipine.Info
- Publication number
- MXPA05001241A MXPA05001241A MXPA05001241A MXPA05001241A MXPA05001241A MX PA05001241 A MXPA05001241 A MX PA05001241A MX PA05001241 A MXPA05001241 A MX PA05001241A MX PA05001241 A MXPA05001241 A MX PA05001241A MX PA05001241 A MXPA05001241 A MX PA05001241A
- Authority
- MX
- Mexico
- Prior art keywords
- amlodipine
- camphorsulfonate
- salt
- camphorsulfonic acid
- acid
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/86—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Abstract
Disclosed are a novel organic acid salt of amlodipine, its preparation method, and a pharmaceutical composition containing the same as a therapeutically active ingredient.
Description
AMLODIPINE ORGANIC ACID SALT
TECHNICAL FIELD
The present invention relates to a novel organic acid salt of amlodipine (3-ethyl 5-methyl ester of 2 - [(2-aminoethoxy) methyl] -4- (2-chlorophenyl) -1,4-dihydro-6-methyl ester methyl-3,5-pyridinecarboxylic acid), which is represented by the chemical formula 1 below, its method of preparation and a pharmaceutical composition containing the same as an effective ingredient. [Chemical formula 1]
TECHNICAL BACKGROUND
Amlodipine, which has activity to block calcium channels in the body, is used for the treatment of hypertension. This calcium channel blocker is found in many background techniques.
European patent publication No. 89,167 describes acid salts of amlodipine which can be formed from acids which can form non-toxic acid addition salts with pharmaceutically acceptable anions, such as hydrochloride, hydrobromide, sulfate, phosphate, acetate, maleate, fumarate , lactate, tartrate, citrate, gluconate, etc. The United States patent NO. 6,291, 490 introduces a pharmaceutical composition containing as active ingredient S - (-) - amlodipine, which possesses a potent activity to treat hypertension and simultaneously avoids adverse effects related to the administration of the racemic mixture of amlodipine. Both U.S. Patent No. 4,879,303 and Korean Patent Publication No. 1989-3375 describe amlodipine besylate, stating that amlodipine besylate is superior to other amlodipine salts, such as hydrochloride, acetate and mesylate in physical-chemical properties including (1) solubility, (2) stability, (3) non-hygroscopicity, and (4) processable character for tablet formulation. However, since the amlodipine besylate currently used have a relatively low solubility with pH 1-7.4, the saturation pH is considered an important factor. Salts that provide solutions that have a pH closer to that of blood (7.4) in distilled water are preferred because they are readily biocompatible and can be easily regulated to the required pH scale without altering their solubility. Since the saturation pH of amlodipine besylate is as low as pH 6.6, there is a need for salts whose saturation pH in distilled water is close to 7.4 (blood pH). Additionally, it has been found that amlodipine besylate is sensitive to light, which is why decomposition products are observed when the salt is exposed to light. Additionally, amlodipine besylate is disadvantageous due to the benzenesulfonic acid used in its production process. That is, benzenesulfonic acid is difficult to treat industrially, since it is corrosive and toxic. Additionally, its high hygroscopicity requires special procedures for its transportation, supply and use. Another disadvantage is that the water content of benzenesulfonic acid is high, totaling about 10%. To avoid these problems, ammonium benzenesulfonate is used as an alternative, but with the concomitant generation of ammonia gas. This method requires additional procedures for absorbing and deactivating the ammonia gas (PCT Publication No. W01999 / 52873).
BRIEF DESCRIPTION OF THE INVENTION
The result being the present invention, the intensive and complete investigation into therapeutically effective acid salts of amlodipine carried out by the present inventors seeking to overcome the problems faced in previous techniques, helped the discovery that amlodipine camphor sulfonate has excellent physico-chemical properties, including solubility, non-hygroscopicity, chemical and light stability and processable character for dose formation, as well as the fact that camphorsulfonic acid is less toxic and corrosive than benzenesulfonic acid, so amlodipine camphorsulfonate is industrial and medically useful . ThusIt is an object of the present invention to provide a camphor sulfonic acid salt of amlodipine. It is another object of the present invention to provide a method for preparing a camphor sulfonic acid salt of amlodipine. It is a further object of the present invention to provide a pharmaceutical composition containing the camphor sulfonic acid salt of amlodipine as a therapeutically active ingredient. In accordance with one aspect of the present invention, a camphor sulfonic acid salt of amlodipine is provided, preferably a light stable amlodipine camphor sulfonic acid salt, more preferably (1 S) - (+) - 10-amlodipine camphorsulfonate or (1 R) - (-) - 10-amlodipine camphorsulfonate, more preferably a crystalline salt of camphorsulfonic acid of amlodipine. In accordance with another aspect of the present invention, there is provided a method for preparing a camphor sulfonic acid salt of amlodipine, in which amlodipine reacts with camphorsulfonic acid and preferably with (1S) - (+) - 10-camphorsulfonic acid or (1 R) - (-) - 10-camphorsulfonic acid in an inert solvent.
In accordance with a further aspect of the present invention, there is provided an effective pharmaceutical composition for the treatment of ischemic heart disorders or hypertension, comprising a therapeutically effective amount of amlodipine camphorsulfonate and a pharmaceutically acceptable diluent or carrier, preferably in the form of dosage of tablets, capsules, solutions or injectables.
PREFERRED MODALITY OF THE INVENTION
The present invention encompasses amlodipine camphorsulfonate, represented by the following chemical formula 2.
[Chemical formula 2]
Compared with amlodipine besylate in its commercially acceptable form, amlodipine camphorsulfonate exhibits the same or better non-hygroscopic character, a processable formulation character and chemical stability. Especially, by providing solutions having a pH close to that of blood (7.4) and being more stable to light in comparison with conventional organic acid salts, the amlodipine camphorsulfonate of the present invention can be stored stably for a prolonged period without losing its medicinal effects as an antihypertensive agent. The present invention also encompasses light-stable amlodipine camphorsulfonate. The term "light-stable" as used herein means that after the salt is stored for 4 weeks at 25 ° C with exposure to sunlight, its mass remains at 90% or more of its original mass , preferably 95% or more, and more preferably 98% or more. The camphorsulfonic acid suitable for the preparation of the amlodipine camphorsulfonate of the present invention may be a racemic mixture or preferably an optically pure material; that is, (1 S) - (+) - 10-camphorsulfonic acid or (1 R) - (-) - 10-camphorsulfonic acid. The salts of camphorsulfonic acid of amlodipine according to the present invention may have a crystal form or an amorphous form, preferably a crystal form. The present invention also encompasses a method for preparing salts of camphor sulfonic acid of amlodipine. The salts can be prepared by reacting amlodipine with camphorsulfonic acid in an inert solvent, as observed in the following reaction formula 1.
[Reaction formula 1]
The camphorsulfonic acid used as the reagent should preferably be an optically pure material; that is, (1 S) - (+) - 10-camphorsulfonic acid or (1 R) - (-) - 10-camphorsulfonic acid. Camphor sulfonic acid, a stable and white solid with permission from the United States Food and Drug Administration (FDA) for use in pharmaceuticals, is commercially available as a white solid (purity 98% or greater) and does not show character hygroscopicity, corrosive character and toxicity. With these properties, camphorsulfonic acid can be easily handled and produced safely on a mass scale. Examples of inert solvent suitable for the preparation of the salts of the present invention include ethyl acetate, methanol, ethanol, isopropanol, acetonitrile, hexane, isopropyl ether, etc., preferably methanol. In the inert solvent, camphorsulfonic acid is used in the amount of 1-2 equivalents, and preferably in the amount of 1.02-1.2 equivalents, per equivalent of amlodipine. The reaction is carried out at -5 to 30 ° C and preferably at 0 to 15 ° C for 0.5 to 5 hours and preferably 1 to 3 hours.
In accordance with the method of the present invention, amlodipine camphorsulfonate can be prepared in a yield of 90% or greater. In addition, the present invention encompasses an effective pharmaceutical composition for treating ischemic heart disorders or hypertension, which comprises a therapeutically effective amount of amlodipine camphorsulfonate and a pharmaceutically acceptable diluent or carrier. The composition of the present invention can be formulated in oral dosage forms including, but without restriction, granules, powders, solutions, tablets, capsules, dry syrup and the like, or parenteral dosage forms including injectables. The composition of the present invention is preferably formulated in the dosage form of tablets, capsules, solutions or injectables. To be therapeutically effective, amlodipine camphor sulfonate is administered in the amount of 2-10 mg per day based on the weight of amlodipine. In a unit dose form, the amlodipine camphorsulfonate is contained in the amount of 3-16 mg. Under practical use, amlodipine camphorsulfonate can be combined as the active ingredient in colloidal aggregate with a pharmaceutically acceptable diluent or carrier selected from excipients, disintegrants, binders and lubricants, and mixtures thereof. The carrier can include a wide variety of forms, depending on the form of preparation desired for administration. To prepare the composition in a solid dose form as a tablet or a hard capsule, microcrystalline cellulose, lactose, low substituted hydroxycellulose and the like can be used as an excipient; glycolate sodium starch, anhydrous acid monophosphate and the like as a disintegrant; polyvinylpyrrolidone, low substituted hydroxypropylcellulose, hydroxypropylcellulose and the like as a binder, and magnesium stearate, silica, talc and the like as a lubricant. A formulation may comprise an additive to provide brightness to the tablet, such as anhydrous dibasic calcium phosphate. To prevent atmospheric moisture from entering the tablet, you can have a water-insoluble coating. The coating base may have a dense molecular structure and preferably be sparingly soluble in water. As the suitable base, a polymeric material selected from a copolymer of methacrylic acid, hydroxypropylmethylcellulose phthalate, cellulose acetate phthalate, hydroxypropylmethylcellulose acetate succinate, polyvinyl alcohol and combinations thereof can be chosen. In addition, the coating may comprise conventional additives such as plasticizers, preservatives, coloring agents, shields against light, etc. The composition of the present invention may be formed by solutions such as a sterile aqueous solution or injectables. Said solution preferably contains from 10 to 40% of propylene glycol and sodium chloride, sufficient to prevent hemolysis (for example about 1%).
A better understanding of the present invention can be achieved in light of the following examples which are set forth to illustrate, but should not be construed as restrictive of the present invention.
EXAMPLES
The amlodipine camphorsulfonate prepared according to the present invention was tested for various physical properties. First, the salt was formulated to be introduced into tablets, capsules and aqueous solutions to test the processable character of the dose formation. In addition, amlodipine camphorsulfonate was compared with amlodipine besylate with respect to its hygroscopicity, solubility, saturation pH, stability and light stability. In the following reference examples, conventional amlodipine salts were prepared according to methods described in the art.
REFERENCE EXAMPLE 1 Preparation of amlodipine besylate
Amlodipine was prepared as described in Korean patent application No. 87-809. The method described in Korean Patent Publication No. 95-7228 was adopted to produce amlodipine besylate.
REFERENCE EXAMPLE 2 Preparation of amlodipine paratoluenesulfonate
In 100 ml of methanol, 20 g of paratoluenesulfonic acid were dissolved. To the solution was added dropwise 40 g of the amlodipine which was prepared in reference example 1 in 500 ml of methanol, followed by stirring at 23 ° C for 3 hours. After filtration and separation, the solid thus produced was washed with 100 ml of methanol and 100 ml of n-hexane and dried under vacuum.
REFERENCE EXAMPLE 3 Preparation of amlodipine hydrochloride
To 100 ml of methanol, 12 ml of concentrated hydrochloric acid was added. 54 g of amlodipine prepared in reference example 1 were added dropwise in 500 ml of methanol, followed by stirring at 23 ° C for 3 hours. After filtration and separation, the solid thus produced was washed with 100 ml of methanol and 100 ml of n-hexane and dried under vacuum.
EXAMPLE 1 Preparation of (1S) - (+) - 10-camphor sulfonate of amlodipine
In a 1 L three-necked flask, (1S) - (+) - 10-camphorsulfonic acid (24.36 g, 1.05 equivalents) was dissolved in methane! (200 mi). To the flask was added dropwise a solution of amlodipine (40.8 g, 0.1 mol) in methanol (300 ml). The resulting solution was stirred at 23 ° C for 2 hours, cooled to 7 ° C and stirred again for 1 hour to produce precipitates. The precipitates were washed at 5 ° C with methanol (100 ml) and n-hexane (100 ml), filtered, dried at 35 ° C under vacuum to generate 57.6 g of (1S) - (+) - amlodipine camphorsulfonate as a white crystalline solid (90% yield). The element and melting point analyzes of amlodipine (S) - (+) - camphorsulfonate prepared above were determined.
TABLE 1
Melting point: 210 ° C (measured by the capillary melting point method with a heating rate of around 10C / minute).
EXAMPLE 2 Preparation of (1R) - (+) - amlodipyrta camphorsulfonate
In a 1 L three-necked flask, (1 R) - (+) - camphorsulfonic acid (24.36 g, 1.05 equivalents) was dissolved in methanol (200 ml). To the flask was added dropwise a solution of amlodipine (40.8 g, 0.1 mol) in methanol (300 ml). The resulting solution was stirred at 22 ° C for 2 hours, cooled to 7 ° C and stirred again for 1 hour and subsequently filtered to produce precipitates. The precipitates were washed at 5 ° C with methanol (100 ml) and n-hexane (100 ml), and dried at 35 ° C under vacuum to generate 57.6 g of (1 R) - (-) - amlodipine camphorsulfonate as a white crystalline solid (90% yield). The element and melting point analyzes of the (1R) - (-) - camphorsulfonate of amlodipine prepared above were determined.
TABLE 2
Melting point 210 ° C (measured by the capillary melting point method with a heating rate of about 1 ° C / minute) EXAMPLE 3 Tablet formulation containing amlodipine camphor sulfonate
The ingredients provided in Table 3 were formulated to prepare a tablet containing amlodipine camphor sulfonate.
TABLE 3
The ingredients were mixed and the mixture was compressed using a roll press from Jowoon Machinery, and subsequently formulated into the tablets using an Erweka tablet-forming machine. EXAMPLE 4 Formulation of tablet containing amlodipine camphor sulfonate
The ingredients given in Table 4 were formulated to prepare a tablet containing amlodipine camphor sulfonate.
TABLE 4
Lactose, cross povidone and polyvinylpyrrolidone were premixed
K90. The premix was granulated according to a fluidized bed assembly method (SPIRA FLOW) and the granules were mixed with the
The remaining ingredients were formulated into tablets using an Erweka tablet-forming machine.
EXAMPLE 5 Capsule formulation containing amlodipine camphor sulfonate
The ingredients given in Table 5 were formulated for
prepare a capsule containing amlodipine camphor sulfonate.
TABLE 5
Ingredients Contents (mg per tablet) amlodipine 5.0 ampersulfate with amlodipine base Low-substituted hydroxypropyl cellulose 65 Microcrystalline cellulose 120 Sodium starch glycolate 4 Magnesium stearate 2 The ingredients were mixed and the mixture was compressed using a roller press from Jowoon Machinen /, and subsequently the resulting materials were filled into hard gelatin capsules using a Bosche capsule filling machine.
EXAMPLE 6 Capsule formulation containing amlodipine camphorsulfonate
The ingredients shown in Table 6 were formulated to prepare a capsule containing amlodipine camphor sulfonate.
TABLE 6
Lactose, cross povidone and polyvinylpyrrolidone K90 were premixed. The premix was granulated according to a fluidized bed assembly method (SPIRA FLOW) and the granules were mixed with the remaining ingredients and filled into hard gelatin capsules using a typical capsule filler device (Bosche).
EXAMPLE 7 Test for hygroscopicity of amlodipine camphorsulfonate
The hygroscopicity of the amlodipine camphorsulfonate prepared in Example 1 and of the amlodipine besylate in Reference Example 1 was tested by measuring its water content (percentage of water, liquid filtration coefficient [Kfj) at 25 ° C with humidity varied The results are shown in Table 7 below.
TABLE 7
As shown in Table 7, the non-hygroscopicity of amlodipine camphor sulfonate is equal to or better than that of amlodipine besylate. With a hygroscopicity of 0.5% or less at a relative humidity of 95%, the salt is suitable for the formulation of tablets, capsules, injectables and the like.
EXAMPLE 8 Test for solubility of amlodipine camphorsulfonate
The solubilities of the amlodipine camphorsulfonate that was prepared in Example 1 and of the amlodipine besylate that was prepared in Reference Example 1 in various solvents at 25 ° C were measured. The results are given in Table 8 below. The solubilities (mg / ml) of Table 6 are values based on the weight of amlodipine converted from the salts.
TABLE 8
As shown in Table 8, the amlodipine camphorsulfonate in buffer solutions with various pH values and distilled water shows a solubility behavior similar to that of amlodipine besylate. However, although the saturation pH of amlodipine besylate is as low as pH 6.6, amlodipine camphorsulfonate shows a saturation pH of 7.2 which is closer to the blood pH value, indicating that amlodipine camphorsulfonate It has good pharmaceutical properties.
EXAMPLE 9 Test for the stability of amlodipine camphorsulfonate
1. Chemical stability of amlodipine camphorsulfonate in the solid state The amlodipine camphorsulfonate prepared in Example 1 and the amlodipine besylate which was prepared in Reference Example 1 were subjected to an accelerated test at 60 ° C and the results are summarized in Table 9 below.
TABLE 9
(% HPLC unit content) HPLC analysis conditions: Detector: UV Absorbency (at 237 nm) Column: C18 octadesil silica gel (4.6mmx150mm, 5μ) Mobile phase: potassium monobasic acid diphosphate (0.03M): methanol = 4: 6 (v / v) Flow rate: 1.5 ml / min As shown in table 9, almost no changes occurred in the amlodipine camphor sulfonate content, as in amlodipine besylate, as measured by the Accelerated test at 60 ° C. The data in Table 9 show that, compared to amlodipine besylate, the chemical stability of amlodipine, the chemical stability of amlodipine camphor sulfonate is excellent with respect to temperature.
2. - Chemical stability of amlodipine camphorsulfonate in aqueous state To investigate the stability in an aqueous state, the amlodipine camphorsulfonate prepared in Example 1 and the amlodipine besylate which was prepared in reference example 1 in distilled water were separately dissolved. The resulting aqueous solutions were stored at 25 ° C for 4 weeks in complete darkness, after which a measurement of the content of the salts was performed using HPLC under the same conditions as in the solid state. The results of the stability test protected against light indicate that no decomposing products or change in content were found in amlodipine camphor sulfonate and in amlodipine besylate.
EXAMPLE 10 Test for light stability of amlodipine camphorsulfonate
The amlodipine camphorsulfonate prepared in example 1, the amlodipine besylate, and other amlodipine salts prepared in reference examples 1 to 3 were used. These samples were stored at 25 ° C for 4 weeks while they were exposed to the sunlight. A measurement of the content of the salts was carried out using HPLC under the same conditions as in the chemical stability test. The results are given in table 10, below.
TABLE 10
As shown in Table 10, a lower reduction in the amlodipine camphor sulfonate content was found than in the other amlodipine salts. It was also found that amlodipine besylate turned from a white to yellow color, while amlodipine camphorsulfonate showed no color change. These data, therefore, show that amlodipine camphorsulfonate has a higher light stability than that of amlodipine besylate and is very convenient in the application for antihypertensives that are generally used over a long period.
Industrial applicability Overall, the data presented in the above examples indicate that the amlodipine camphorsulfonate of the present invention has excellent physico-chemical properties including non-hygroscopicity, chemical and light stability, solubility and processable character for its dosage formulation. In particular, with the saturation value of pH (pH 7.2) close to that of blood, amlodipine camphor sulfonate is easy to deliver in the body of a patient. Additionally, this salt can be stored for a prolonged period due to its superior stability to light. Additionally, free of corrosion and toxicity, camphor sulfonic acid is industrially useful.
Claims (9)
1. - A salt of camphor sulfonic acid of amlodipine.
2. - The camphor sulfonic acid salt of amlodipine according to claim 1, further characterized in that the salt of camphorsulfonic acid is stable to light.
3. - The camphor sulfonic acid salt of amlodipine according to claim 1, further characterized in that the camphorsulfonic acid is (1S) - (+) - 10-camphorsulfonic acid or (1 R) - (-) - 10-camphorsulfonic acid .
4. - The camphor sulfonic acid salt of amlodipine according to claim 1, further characterized in that the salt is in crystalline form.
5. A method for preparing camphor sulfonic acid salt of amlodipine, wherein amlodipine reacts with camphorsulfonic acid in an inert solvent.
6. - The method according to claim 5, further characterized in that the camphorsulfonic acid is (1S) - (+) - 10-camphorsulfonic acid or (1 R) - (-) - 10-camphorsulfonic acid.
7. - A pharmaceutical composition for the treatment of ischemic heart disorders or hypertension, comprising a therapeutically effective amount of the camphor sulfonic acid salt of amlodipine according to any one of claims 1 to 4, and a pharmaceutically acceptable diluent or carrier.
8. - The pharmaceutical composition according to claim 7, further characterized in that the composition is in the form of a dose of a tablet or a capsule.
9. - The pharmaceutical composition according to claim 7, further characterized in that the composition is in the form of doses of solutions or injectables.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020020044856A KR20040011751A (en) | 2002-07-30 | 2002-07-30 | An organic acid salt of amlodipine |
PCT/KR2003/001522 WO2004011432A1 (en) | 2002-07-30 | 2003-07-30 | Organic acid salt of amlodipine |
Publications (1)
Publication Number | Publication Date |
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MXPA05001241A true MXPA05001241A (en) | 2005-06-08 |
Family
ID=31185754
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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MXPA05001241A MXPA05001241A (en) | 2002-07-30 | 2003-07-30 | Organic acid salt of amlodipine. |
Country Status (8)
Country | Link |
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EP (1) | EP1549616A4 (en) |
JP (1) | JP2005538103A (en) |
KR (1) | KR20040011751A (en) |
CN (1) | CN1678583A (en) |
AU (1) | AU2003247208A1 (en) |
BR (1) | BR0313076A (en) |
MX (1) | MXPA05001241A (en) |
WO (1) | WO2004011432A1 (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
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KR100913791B1 (en) * | 2006-07-21 | 2009-08-26 | 한미약품 주식회사 | S---amlodipine camsylate or hydrate thereof and pharmaceutical composition containing same |
KR100821688B1 (en) | 2006-08-10 | 2008-04-11 | (주)유케이케미팜 | Separation method of enantiomer of Amlodipine racemate and process for preparing its hydrophilic drug |
WO2011098971A1 (en) | 2010-02-12 | 2011-08-18 | Pfizer Inc. | Salts and polymorphs of 8-fluoro-2-{4-[(methylamino}methyl]phenyl}-1,3,4,5-tetrahydro-6h-azepino[5,4,3-cd]indol-6-one |
CN101972254B (en) * | 2010-09-28 | 2012-05-30 | 石药集团欧意药业有限公司 | Solid preparation of levamlodipine or pharmaceutically-acceptable salts thereof, and preparation method thereof |
Family Cites Families (5)
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DK161312C (en) * | 1982-03-11 | 1991-12-09 | Pfizer | CHANGES FOR THE PREPARATION FOR THE PREPARATION OF 2-Amino-CO-Methyl-4-Methyl-4-Methyl-4-Methyl-4-Methyl-4-Methyl-4-Methyl-2-D-Hydroxy |
GB8608335D0 (en) * | 1986-04-04 | 1986-05-08 | Pfizer Ltd | Pharmaceutically acceptable salts |
GB8710493D0 (en) * | 1987-05-02 | 1987-06-03 | Pfizer Ltd | Dihydropyridines |
US6057344A (en) * | 1991-11-26 | 2000-05-02 | Sepracor, Inc. | Methods for treating hypertension, and angina using optically pure (-) amlodipine |
KR100452491B1 (en) * | 2001-03-29 | 2004-10-12 | 한미약품 주식회사 | A novel crystalline amlodipine camsylate and a preparing method thereof |
-
2002
- 2002-07-30 KR KR1020020044856A patent/KR20040011751A/en not_active Application Discontinuation
-
2003
- 2003-07-30 EP EP03771480A patent/EP1549616A4/en not_active Withdrawn
- 2003-07-30 BR BR0313076-2A patent/BR0313076A/en not_active IP Right Cessation
- 2003-07-30 JP JP2004524369A patent/JP2005538103A/en active Pending
- 2003-07-30 AU AU2003247208A patent/AU2003247208A1/en not_active Abandoned
- 2003-07-30 MX MXPA05001241A patent/MXPA05001241A/en unknown
- 2003-07-30 CN CNA038208768A patent/CN1678583A/en active Pending
- 2003-07-30 WO PCT/KR2003/001522 patent/WO2004011432A1/en active Application Filing
Also Published As
Publication number | Publication date |
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CN1678583A (en) | 2005-10-05 |
JP2005538103A (en) | 2005-12-15 |
BR0313076A (en) | 2005-06-28 |
AU2003247208A1 (en) | 2004-02-16 |
EP1549616A4 (en) | 2006-10-18 |
WO2004011432A1 (en) | 2004-02-05 |
KR20040011751A (en) | 2004-02-11 |
EP1549616A1 (en) | 2005-07-06 |
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