CA2341522A1 - Novel pharmaceutical salt form - Google Patents
Novel pharmaceutical salt form Download PDFInfo
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- CA2341522A1 CA2341522A1 CA002341522A CA2341522A CA2341522A1 CA 2341522 A1 CA2341522 A1 CA 2341522A1 CA 002341522 A CA002341522 A CA 002341522A CA 2341522 A CA2341522 A CA 2341522A CA 2341522 A1 CA2341522 A1 CA 2341522A1
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- Prior art keywords
- salt
- agent
- base
- useful
- saccharinate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
The saccharinate salt of synthetic non-alkaloidal medicinal organic bases provides a novel salt form possessing improved organoleptic properties as we ll as reduced solubility.
Description
NOVEL PHARMACEUTICAL SALT FORM
Cross Reference to Related Application This application claims priority from provisional application USSN 60/098,154 filed August 27, 1998.
5 Background of the Invention The present invention relates to a novel salt form of certain pharmacologically active organic bases and their preparation. The class will be exemplified by the saccharinate salt of buspirone, a useful anti-anxiety agent.
10 It is known that while many organic bases function as useful pharmacologic agents, nonetheless salt forms are often pharmaceutically preferred for reasons of enhanced solubility, ease of compounding, and stability. It is also well accepted that oral dosing of drugs is a preferred route of administration. However, most organic bases possess a very bitter taste 15 which, for acceptable oral administration, requires masking by various methods familiar to pharmaceutical formulation practitioners such as the incorporation of sweeteners, flavorings, organoleptic enhancers, and the like.
The intense bitter taste of most bases can be relieved somewhat by substituting a salt form of the pharmacologically active agent for the base in 20 pharmaceutical formulations; e.g., the hydrochloride salt. Some salt forms of drugs are more effective than others in reducing the objectionable taste of the pharmaceutical formulation. It is known that patient compliance in adhering to a drug regimen is negatively affected by pharmaceutical products that are objectionable in taste, particularly in instances where the patient 25 disorder is accompanied by loss of appetite, nausea, and vomiting.
In U.S. 4,362,730, Rader, et al. disclosed and claimed the saccharinate salt of vincamine, a pharmaceutically active alkaloid.
Vincamine saccharinate was described as having improved solubility and taste characteristics. Greater solubility for the saccharinate salt of vincamine 30 differs from the reduced solubility seen for the saccharinates of the present convention.
Cross Reference to Related Application This application claims priority from provisional application USSN 60/098,154 filed August 27, 1998.
5 Background of the Invention The present invention relates to a novel salt form of certain pharmacologically active organic bases and their preparation. The class will be exemplified by the saccharinate salt of buspirone, a useful anti-anxiety agent.
10 It is known that while many organic bases function as useful pharmacologic agents, nonetheless salt forms are often pharmaceutically preferred for reasons of enhanced solubility, ease of compounding, and stability. It is also well accepted that oral dosing of drugs is a preferred route of administration. However, most organic bases possess a very bitter taste 15 which, for acceptable oral administration, requires masking by various methods familiar to pharmaceutical formulation practitioners such as the incorporation of sweeteners, flavorings, organoleptic enhancers, and the like.
The intense bitter taste of most bases can be relieved somewhat by substituting a salt form of the pharmacologically active agent for the base in 20 pharmaceutical formulations; e.g., the hydrochloride salt. Some salt forms of drugs are more effective than others in reducing the objectionable taste of the pharmaceutical formulation. It is known that patient compliance in adhering to a drug regimen is negatively affected by pharmaceutical products that are objectionable in taste, particularly in instances where the patient 25 disorder is accompanied by loss of appetite, nausea, and vomiting.
In U.S. 4,362,730, Rader, et al. disclosed and claimed the saccharinate salt of vincamine, a pharmaceutically active alkaloid.
Vincamine saccharinate was described as having improved solubility and taste characteristics. Greater solubility for the saccharinate salt of vincamine 30 differs from the reduced solubility seen for the saccharinates of the present convention.
The present invention concerns a novel salt form of non-alkaloidal medicinal organic bases that renders the normally bitter-tasting drug much more palatable, thereby facilitating its pharmaceutical formulation for oral routes of administration where taste comes into play; such as liquid 5 suspensions, lozenges, chewable tablets, chewing gums, and the like.
When applied to synthetic organic base medicinals, as opposed to alkaloids, solubility of the salt is generally less than for more standard pharmaceutical salts such as halides, sulfates, and the like.
Detailed Description of the Invention 10 The saccharinate salt of certain non-allkaloidal organic bases provides novel salt forms demonstrating improved organoleptic properties. For certain medicinals the saccharinate salt also provides a means of sustaining drug release by virtue of decreased aqueous solubility of the saccharinate compared to more standard pharmaceutical salts such as halides, sulfates, 15 phosphates, and the like. The saccharinate salts are conveniently synthesized by salt interchange on admixture of solutions of sodium saccharinate and acid addition salts; e.g., the hydrochloride salt, of medicinal organic bases. Other salt-forming reactions, well-known to one skilled in the pharmaceutical sciences, may also be employed.
20 Various classes of orally-active non-alkaloidal synthetic medicinal organic bases are intended applications of the present invention. Some of these medicinal bases fall into the following medical use categories:
~ antiinfectives such as erythromycin;
~ oncolytics;
25 ~ analgesics such as codeine, meperidine, pentazocine, butorphanol, buprenorphine;
~ psychopharmacologics;
~ neurologics;
~ anesthetics;
When applied to synthetic organic base medicinals, as opposed to alkaloids, solubility of the salt is generally less than for more standard pharmaceutical salts such as halides, sulfates, and the like.
Detailed Description of the Invention 10 The saccharinate salt of certain non-allkaloidal organic bases provides novel salt forms demonstrating improved organoleptic properties. For certain medicinals the saccharinate salt also provides a means of sustaining drug release by virtue of decreased aqueous solubility of the saccharinate compared to more standard pharmaceutical salts such as halides, sulfates, 15 phosphates, and the like. The saccharinate salts are conveniently synthesized by salt interchange on admixture of solutions of sodium saccharinate and acid addition salts; e.g., the hydrochloride salt, of medicinal organic bases. Other salt-forming reactions, well-known to one skilled in the pharmaceutical sciences, may also be employed.
20 Various classes of orally-active non-alkaloidal synthetic medicinal organic bases are intended applications of the present invention. Some of these medicinal bases fall into the following medical use categories:
~ antiinfectives such as erythromycin;
~ oncolytics;
25 ~ analgesics such as codeine, meperidine, pentazocine, butorphanol, buprenorphine;
~ psychopharmacologics;
~ neurologics;
~ anesthetics;
~ respiratory agents;
~ cardiovascularslcardio-renal agents ~ endocrine agents;
~ metabolic agents;
~ gastrointestinal agents;
~ antiallergenics; and ~ immunologics.
Psychopharmalogics can be subclassed as:
~ anxiolytics; e.g., benzodiazepines such as alprazolam, azapirones such as buspirone;
~ antipsychotics; e.g., phenothiazines such as chlorpramazine and thioridazine, piperazines such as fluphenazine, thioxanthenes such as thiothixene, butyrophenones such as haloperidol, dibenzoxapines such as loxapine, dihydroindolones such as molindone; and ~ affective disorder agents such as imipramine, trazodone, nefazodone, fluoxetine, sertraline, and the like, dextroamphetamine and methylphenidate.
Neurologics can be represented by procyclidine, biperiden, 20 amantadine and selegiline; ergotamines and methylsergide; scopolamine, cyclizine, hydroxyzine and the like.
Anesthetics are represented by benzocaine, dibucaine, lidocaine, procaine and the like.
~ cardiovascularslcardio-renal agents ~ endocrine agents;
~ metabolic agents;
~ gastrointestinal agents;
~ antiallergenics; and ~ immunologics.
Psychopharmalogics can be subclassed as:
~ anxiolytics; e.g., benzodiazepines such as alprazolam, azapirones such as buspirone;
~ antipsychotics; e.g., phenothiazines such as chlorpramazine and thioridazine, piperazines such as fluphenazine, thioxanthenes such as thiothixene, butyrophenones such as haloperidol, dibenzoxapines such as loxapine, dihydroindolones such as molindone; and ~ affective disorder agents such as imipramine, trazodone, nefazodone, fluoxetine, sertraline, and the like, dextroamphetamine and methylphenidate.
Neurologics can be represented by procyclidine, biperiden, 20 amantadine and selegiline; ergotamines and methylsergide; scopolamine, cyclizine, hydroxyzine and the like.
Anesthetics are represented by benzocaine, dibucaine, lidocaine, procaine and the like.
Respiratory agents are represented by epinephrine, phenylephrine, phenylpropanolamine and pseudoephedrine; isoproterenol and terbutaline.
Cardiovasculars can be subclassed as:
~ inotropics such as dobutamine;
Cardiovasculars can be subclassed as:
~ inotropics such as dobutamine;
5 ~ antiarrhythmics such as acecainide, disopipramide;
~ ~3-blockers such as propranolol, atenolol, nadolol;
~ calcium blockers such as diltiazem, nifedipine and nimodipine;
~ vasodilators such as papaverine and isoxsuprine;
~ antihypertensives such as hydralazine; and 10 ~ diuretics such as triamterene and amiloride.
Endocrine agents such as bromocryptine and clomiphene; and metabolic agents such as phenformin.
Gastrointestinal agents such as metaclopramide or cimetidine.
The present invention involves stable crystalline saccharinate salts of 15 orally administrable medicinal bases. Saccharin, chemically 1,2-benzisothiazol-3(2H)-one 1,1,dioxide, is used as a sweetener, most r commonly in the form of its sodium salt dihydrate. While it is used as a sweetener in pharmaceutical applications, its use is as a component of a mixture of ingredients. While saccharine provides a sweet taste in dilute 20 aqueous solutions where it is about 500 times sweeter than sugar with the sweet taste still detectable in 1:100,000 dilution; nonetheless saccharin has a bitter, metallic aftertaste. Because saccharin's taste is most pleasant in dilute solution, care must be exercised in formulating saccharin in its solid state because of a very objectionable taste.
25 By contrast the current invention relates to actual salt forms, as opposed to mixtures, comprising the organic base cation and the WO 00!12067 PCT/US99/19575 saccharinate anion. In this form the medicinal has pleasant organoieptic properties even in its solid form. As such, the saccharinate salts offer the potential for pharmaceutical formulations without requiring large amounts of other organoleptic enhancers such as sweeteners, flavors, and the like which 5 are usually required to render medicinal bases palatable. The advantages of saccharinate salts would especially be evident in formulating oral suspensions, chewable tablets, lozenges, and quick-melt dosage forms.
Another aspect of the present invention relates to the general reduction in solubility of the saccharinate salts of the non-alkaloidal medicinal 10 bases compared to more common acid addition salts of the medicinal bases such as hydrohalide, sulfate, phosphate salts and the like. With reduced solubility drug release is slowed and extended release of the drug usually occurs. Therefore, the saccharinate salts offer a method for providing extended release dosing for certain medicinals.
15 The present invention is illustrated by the following examples but is not limited to them.
Example 1 - Buspirone Saccharinate Buspirone hydrochloride (8-4[4-(2-pyrimidinyl)-1-piperazinyl])butyl]-8-azaspiro[4.5]decane-7,9-dione hydrochloride 4.22 g, 10 mmole) dissolved in 20 a minimal amount of water was added to a concentrated solution of sodium saccharinate (2.05 g, 10 mmole) with stirring. The mixture was chilled and the supernatant aqueous layer decanted from the heavier oil layer which was dissolved in methylene chloride. The methylene chloride solution was washed with water and then dried (MgSO,). The dried solution was filtered 25 and concentrated in vacuo to a clear oil. Trituration in ether provided a pale yellow saccharinate salt, m.p. 142-145 °C.
Analysis:
Calculated for CZ, H3,N502~C,HSN03S: C, 59.14; H, 6.38; N, 14.78; S, 5.64.
30 Found: C, 59.14; H, 6.46; N, 14.89; S, 5.51.
~ ~3-blockers such as propranolol, atenolol, nadolol;
~ calcium blockers such as diltiazem, nifedipine and nimodipine;
~ vasodilators such as papaverine and isoxsuprine;
~ antihypertensives such as hydralazine; and 10 ~ diuretics such as triamterene and amiloride.
Endocrine agents such as bromocryptine and clomiphene; and metabolic agents such as phenformin.
Gastrointestinal agents such as metaclopramide or cimetidine.
The present invention involves stable crystalline saccharinate salts of 15 orally administrable medicinal bases. Saccharin, chemically 1,2-benzisothiazol-3(2H)-one 1,1,dioxide, is used as a sweetener, most r commonly in the form of its sodium salt dihydrate. While it is used as a sweetener in pharmaceutical applications, its use is as a component of a mixture of ingredients. While saccharine provides a sweet taste in dilute 20 aqueous solutions where it is about 500 times sweeter than sugar with the sweet taste still detectable in 1:100,000 dilution; nonetheless saccharin has a bitter, metallic aftertaste. Because saccharin's taste is most pleasant in dilute solution, care must be exercised in formulating saccharin in its solid state because of a very objectionable taste.
25 By contrast the current invention relates to actual salt forms, as opposed to mixtures, comprising the organic base cation and the WO 00!12067 PCT/US99/19575 saccharinate anion. In this form the medicinal has pleasant organoieptic properties even in its solid form. As such, the saccharinate salts offer the potential for pharmaceutical formulations without requiring large amounts of other organoleptic enhancers such as sweeteners, flavors, and the like which 5 are usually required to render medicinal bases palatable. The advantages of saccharinate salts would especially be evident in formulating oral suspensions, chewable tablets, lozenges, and quick-melt dosage forms.
Another aspect of the present invention relates to the general reduction in solubility of the saccharinate salts of the non-alkaloidal medicinal 10 bases compared to more common acid addition salts of the medicinal bases such as hydrohalide, sulfate, phosphate salts and the like. With reduced solubility drug release is slowed and extended release of the drug usually occurs. Therefore, the saccharinate salts offer a method for providing extended release dosing for certain medicinals.
15 The present invention is illustrated by the following examples but is not limited to them.
Example 1 - Buspirone Saccharinate Buspirone hydrochloride (8-4[4-(2-pyrimidinyl)-1-piperazinyl])butyl]-8-azaspiro[4.5]decane-7,9-dione hydrochloride 4.22 g, 10 mmole) dissolved in 20 a minimal amount of water was added to a concentrated solution of sodium saccharinate (2.05 g, 10 mmole) with stirring. The mixture was chilled and the supernatant aqueous layer decanted from the heavier oil layer which was dissolved in methylene chloride. The methylene chloride solution was washed with water and then dried (MgSO,). The dried solution was filtered 25 and concentrated in vacuo to a clear oil. Trituration in ether provided a pale yellow saccharinate salt, m.p. 142-145 °C.
Analysis:
Calculated for CZ, H3,N502~C,HSN03S: C, 59.14; H, 6.38; N, 14.78; S, 5.64.
30 Found: C, 59.14; H, 6.46; N, 14.89; S, 5.51.
Example 2 - Taste Preference Testing Under single-blind conditions, three small glass plates were set out for taste-testing. Plate #1 contained buspirone hydrochloride. Plate #2 contained buspirone saccharinate, and Plate #3 contained 1:1 molar 5 equivalent amounts of buspirone hydrochloride and sodium saccharinate in the form of a physical mixture. Tasting volunteers were asked to taste each of the samples and give their preference. All volunteers selected Plate #2 (buspirone saccharinate) as the best tasting sample. By contrast, both Plates #1 and #3 were labeled as objectionable to highly objectionable in 10 taste by the volunteers.
Claims (14)
1. The saccharinate salt of non-alkaloidal organic medicinal bases capable of acid addition salt formation.
2. The salt of claim 1 wherein the base is a useful non-alkaloidal orally-active drug selected from the group consisting of psychopharmacologics, analgesics, neurologics, anesthetics, respiratory agents, cardiovascular-renal agents, hematologic agents, endocrine and metabolic agents, gastrointestinal agents, dermatologic agents, antiinflammatories, antiallergics, immunologics, oncolytics, and antiinfectives.
3. The salt of claim 2 wherein the base is a useful orally-active antiinfective agent.
4. The salt of claim 2 wherein the base is a useful orally-active analgesic agent.
5. The salt of claim 2 wherein the base is a useful orally-active cardiovascular-renal agent.
6. The salt of claim 2 wherein the base is a useful orally-active gastrointestinal agent.
7. The salt of claim 2 wherein the base is a useful orally-active neurologic agent.
8. The salt of claim 2 wherein the base is a useful orally-active psychopharmacologic agent.
9. The psychopharmacologic agent of claim 8 that is useful in depression.
10. The psychopharmacologic agent of claim 8 that is useful in anxiety.
11. The psychopharmacologic agent of claim 10 that is an azapirone.
12. The azapirone of claim 11 selected from buspirone and gepirone.
13. The azapirone of claim 11 is buspirone saccharinate.
14. The method of producing a saccharinate salt comprising the mixing of a solution of an acid addition salt of the medicinal base with a solution of sodium saccharinate.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9815498P | 1998-08-27 | 1998-08-27 | |
| US60/098,154 | 1998-08-27 | ||
| PCT/US1999/019575 WO2000012067A1 (en) | 1998-08-27 | 1999-08-26 | Novel pharmaceutical salt form |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2341522A1 true CA2341522A1 (en) | 2000-03-09 |
Family
ID=22267557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002341522A Abandoned CA2341522A1 (en) | 1998-08-27 | 1999-08-26 | Novel pharmaceutical salt form |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1107738A4 (en) |
| JP (1) | JP2003525855A (en) |
| CN (1) | CN1348363A (en) |
| AU (1) | AU6021199A (en) |
| CA (1) | CA2341522A1 (en) |
| WO (1) | WO2000012067A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023177294A1 (en) | 2022-03-18 | 2023-09-21 | Plethora Therapeutics B.V. | Transmucosal delivery of psychoactive compounds |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19940740A1 (en) * | 1999-08-31 | 2001-03-01 | Gruenenthal Gmbh | Pharmaceutical salts |
| DE10013712A1 (en) * | 2000-03-20 | 2001-09-27 | Nutrinova Gmbh | Nicotine salts with improved taste, process for their preparation and their use |
| DE10045521A1 (en) | 2000-03-31 | 2001-10-04 | Roche Diagnostics Gmbh | Determining amplification efficiency of a target nucleic acid comprises measuring real-time amplification of diluted series, setting signal threshold value, and determining cycle number at which threshold is exceeded |
| DE10109763A1 (en) * | 2001-02-28 | 2002-09-05 | Gruenenthal Gmbh | Pharmaceutical salts |
| US20050176790A1 (en) * | 2001-02-28 | 2005-08-11 | Johannes Bartholomaus | Pharmaceutical salts |
| DE10130504B4 (en) | 2001-06-25 | 2005-02-03 | Nutrinova Nutrition Specialties & Food Ingredients Gmbh | Xanthine and phenazone acesulfame H complexes with improved taste, process for their preparation and their use |
| EP1928437A2 (en) | 2005-08-26 | 2008-06-11 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| EP2258358A3 (en) | 2005-08-26 | 2011-09-07 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
| JP2009512711A (en) | 2005-10-21 | 2009-03-26 | ブレインセルス，インコーポレイティド | Regulation of neurogenesis by PDE inhibition |
| EP1942879A1 (en) | 2005-10-31 | 2008-07-16 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| CA2651813A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| CA2709219A1 (en) * | 2007-12-12 | 2009-06-18 | Ultimorphix Technologies B.V. | Solid forms of tenofovir disoproxil |
| US7935817B2 (en) | 2008-03-31 | 2011-05-03 | Apotex Pharmachem Inc. | Salt form and cocrystals of adefovir dipivoxil and processes for preparation thereof |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| DE202010001237U1 (en) | 2010-01-21 | 2010-04-01 | Grünenthal GmbH | Combination of tramadol and acetaminophen as effervescent tablet |
| EP2592078A1 (en) | 2011-11-11 | 2013-05-15 | Almirall, S.A. | New cyclohexylamine derivatives having beta2 adrenergic agonist and M3 muscarinic antagonist activities |
| TW201517906A (en) * | 2013-07-25 | 2015-05-16 | Almirall Sa | Combinations comprising MABA compounds and corticosteroids |
| TW201617343A (en) | 2014-09-26 | 2016-05-16 | 阿爾米雷爾有限公司 | New bicyclic derivatives having [beta]2 adrenergic agonist and M3 muscarinic antagonist activities |
| CN107868117B (en) * | 2016-09-28 | 2021-04-23 | 中国科学院苏州纳米技术与纳米仿生研究所 | Stenazole saccharinate and preparation method and application thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1288002A (en) * | 1954-06-14 | 1962-03-24 | Pfizer & Co C | Improvements in manufacturing processes for imidazoline compounds |
| ES271829A1 (en) * | 1960-12-19 | 1962-03-01 | Tanabe Seiyaku Co | Benzophenone-2-carboxylic acid addition salts of 1-methyl-3-(di-thienylmethylene)piperidine and process for the preparation thereof |
| US4711784A (en) * | 1986-01-07 | 1987-12-08 | Warner-Lambert Company | Encapsulation composition for use with chewing gum and edible products |
| US5837277A (en) * | 1992-06-04 | 1998-11-17 | Smithkline Beecham Corporation | Palatable pharmaceutical compositions |
-
1999
- 1999-08-26 AU AU60211/99A patent/AU6021199A/en not_active Abandoned
- 1999-08-26 WO PCT/US1999/019575 patent/WO2000012067A1/en not_active Application Discontinuation
- 1999-08-26 CN CN99810139A patent/CN1348363A/en active Pending
- 1999-08-26 CA CA002341522A patent/CA2341522A1/en not_active Abandoned
- 1999-08-26 JP JP2000567187A patent/JP2003525855A/en active Pending
- 1999-08-26 EP EP99968215A patent/EP1107738A4/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023177294A1 (en) | 2022-03-18 | 2023-09-21 | Plethora Therapeutics B.V. | Transmucosal delivery of psychoactive compounds |
| NL2031332B1 (en) * | 2022-03-18 | 2023-09-29 | Plethora Therapeutics B V | Transmucosal delivery of psychoactive compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000012067A1 (en) | 2000-03-09 |
| JP2003525855A (en) | 2003-09-02 |
| EP1107738A1 (en) | 2001-06-20 |
| AU6021199A (en) | 2000-03-21 |
| CN1348363A (en) | 2002-05-08 |
| EP1107738A4 (en) | 2003-01-22 |
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