CA2092565A1 - Ibuprofen-diuretic combinations - Google Patents
Ibuprofen-diuretic combinationsInfo
- Publication number
- CA2092565A1 CA2092565A1 CA002092565A CA2092565A CA2092565A1 CA 2092565 A1 CA2092565 A1 CA 2092565A1 CA 002092565 A CA002092565 A CA 002092565A CA 2092565 A CA2092565 A CA 2092565A CA 2092565 A1 CA2092565 A1 CA 2092565A1
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- Prior art keywords
- ibuprofen
- diuretic
- effective amount
- female
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
-
- 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
- A61P7/10—Antioedematous agents; Diuretics
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- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
This invention relates to a pharmaceutical composition for use in the relief of pain, cramps, bloating and tension experienced during menstruation or premenstruation in a female in need of such relief comprising administering to such female: (i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen; and (ii) a diuretically effective amount of a diuretic; and (iii) optionally a tension relieving effective amount of pyrilamine maleate.
Description
~ W092/05786 PCT/US91/07~8 ' 2~925~
TITLE OF TH~ INVENTION
I~UPROF~N-DIURETIC COMBINATIONS
BACKGROUND OF THE INVENTIQN
The non-steroidal anti-inflammatory drugs (NSAID) have been utilized in the treatment of pain/
inflammation and have been disclosed as useful in the treatment, management and mitigation of cold symptoms and the pain associated therewith.
Ibuprofen (2-(4-isobutylphenyl)propionic acid) is a well known and commonly employed NSAID.
Recently. it has been found that a faster onset of pain relief and an enhanced analgesic response can be :
obtained by the utilization of the single enantiomer S(+)-ibuprofen in comparison to racemic ibuprofen, (see for e2ample U.S. Patent 4 t ~77,620).
`, ." .
~ W092/05786 PCT/US9~/07008 æ56 Diuretics, such as the thiazides, are useful in the relief of water retention. In optional combination with a tension reliever such as pyrilamine maleate. diuretics may offer relief of a variety of symptoms often appearing in the menstrual cycle such as cramps, bloating, tension, and irritability.
Combinations of ibuprofen with a diuretic ~uch as pamabrom have been discIosed in U.S. Patent 4,888.~43. ~owever~ despite the fact that the menstrual pain sufferer is in need of quick and enhaneed relief. there has been no consideration given to the employment of (S)-ibuprofen, or a salt thereo.f, in combination with a diuretic and optionallv with a tension reliever for the treatment of menstrual s~mptoms.
DETAIL~D DESCRIPTIQN OF THE INVENTION
This invention relates to a pharmaceutical -composition for use in the relief of pain, cramps, bloatin~ and tension experienced during menstruation or premenstruation in a female in need of such relief comprisin~ administering to such female:
(i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (P~)-ibuprofen; and (ii) a diuretically effective amount of a diuretic; and (iii) optionally a tension relieving effective amount of pyrilamine maleate.
This invention-is also directed ~o a method of relieving pain, cramps, bloating and tension, .
W~92/05786 PCT/US91/~7008 2 ~ 3i3 experienced durin~ menstruation or premenstruation in a female in need ~f such relief comprising administerin~ to such female:
~i) an anal~esically and anti-inflammatory effective amount ~f ~S)-ibuprofen, o} a salt thereof, substantially free of (R)-ibuprofen;
(ii) a diureticallv effective amount of a diuretic; and (iii~ optionallv a tension relieving effective amount of pyrilamine maleate.
This invention is also directed to a method o.f Pliciting an onset hastened and enhanced response for the relief of ~ain. cramps, bloating and tension e~perience`d durin~ menstruation or premenstruation in a female in need of such relief. comprising administering to such female:
(i) an anal~esically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen;
(ii) a diuretically effective amount of a diuretic; and (iii) optionally a tension relieving effective amount of pvrilamine maleate.
Substantiall~ free of (R)-ibuprofen should be taken to mean that the ration of (S)-ibuprofen to (R!-ibuprofen is at least 90:10.
Salts of (S)-ibuprofen includc salts with al~ali metals, such as sodium or potassium, salts :
with alkaline earth metals, such as calcium, or salts with other metals such as ma~nesium, aluminum, iron, zinc, copper. nickel or cobalt.
W092/0~786 PCT/US91/07008 ( . .
2 ~3 2~ ~ _ 4 _ Salts o~ ibuprofen further include the amino acid salts, particula:rlv the basic amino acids such as lysine and ~rginine. Specifically included within the above composition is (S)-ibuprofen-(s)-lysine.
(S)-ibupro~en may be prepared following the procedures disclosed in U.S. Patent 4,877,620. Metal .
salts of ibuprofen mav be obtained by contacting a hydro~ide~ or carbona~e with ibuprofen. Amino acid salts of ibuprofen m~v be obtained by contacting an amino acid in solution with ibuprofen.
The utili~ati~ of (S)-ibuprofen in an analgesic-antiinflammatory/diuretic combination ~ offers significant ~dvantages over the combination o~ i 15 racemic ibuprofen with a diuretic which has already :
been shown to have advantages over acetaminophen combinations (see for example U.S. Patent 4,888,343).
(5)-ibuprofen provides a faster onset of pain-antiinflanntatory relief and an enhanced degree of relief compared to racemic ibuprofen. These benefits are increased in an (S)-ibuprofen/diuretic combination as the inhibition of prostaglandin svnthetase and the water volume minimization may synergistically cooperate. This has not heretofore been observed because the art has not proposed the combination of the (S?-ibuprofen enantiomer, absent (R)-ibuprofen, with a diuretic. The presence of the (R)-ibuprofen m~y blur the synergistic effect.
The subJect using the (S)~ibuprofen/diuretic combination will no longer need to divert metabolic energy to the inversion of the (R)-enantiomer or the removal o~ this enantiomer. The absence of inversion , . , ... , .. . - , ,, . ,., . ,~ . . . . ... ..
W092/05786 PCT/US91/07~8 (~
~ ~ ~ 2 ~
reduces or eliminates the formation and incorporation into fatty tissue of hybrid-ibuprofen containing tri~lycerides~
Althou~h fluid retention is recognized or a possible side effect of ibuprofen usage the prior art has not heretofore considered the emplovment of an (S)-ibuprofen/diuretic combination. The absence of the (R)-ibuprofen in these combinations is particul~rly ad~anta~eous as a lesser metabolic burden is placed on the urogenital system for the excretion of the (R)-enantiomer or its metabolites.
The renal burden and renal to~icities sometimes associated with ibuprofen therapy are reduced or absent in a subst~ntiallv (~)-ibuprofen free composition.
The absence of (R)-ibuprofen provides for significant size and weight advantages in a combination dosage form, particularly a sustained release dosa~e form. Where a sustained release do~a~e of ibuprofen mav have required 800 to 1000 mg, the employment of (S)-ibuprofen reduces the weight to 4nO to 500 mg, and provides for a more practical size tablet for an ibuprofen/diuretic combination.
An effective amount of (S)-ibuprofen, or a pharmaceutically acceptable salt thereof, for use in a unit dose composition of this invention may range from 50 to 800 mg (S)-ibuproen. The preferred amount of (S)-ibuprofen is about 100 to 400 mg. The amount of a salt such as (S)-ibuprofen-(S)-lysine is determined based on the amount of (S)-ibuprofen contained therein.
The diuretic employed herein may be selected from the benzothiadiazides or acetazolamide and its . ~ ~
. - ..
, ... .. , . . . ,.. , . .. ~ ". . .. . , - .. .. .. , -, . ..... .. .. ... ...... . . . . . .. . ..
W092/05786 PCT/US91/07~B
_ analogs, or ethacrynic acid, or furosemide or bumetanide or a potassium-sparing diuretic such as amiloride or triamterene, or a xanthine or a combination diuretic such as pamabrom. Preferred diuretics include: Acetazolamide, dichlorophenamide, methazolamide, chlorothiazide, hydrochlorothiazide, benzthiazide, indapamide, trichlormethazide, methylclothiazide, polythiazide, ethacrynic acid, torasemide, furosemide, bumetamide, panabrom, amiloride, or triamterene. A particularly preferred diuretic is hydrochlorothiazide.
The amount of diuretic useful in the practice o~ the present invention may-vary from about 2 mg to 50 mg depending on the specific diurectic.
l~ The present compositions may be administered in the form of tablets, capsules, elixirs, syrups or a suspension. For oral administration the active components may be admixed with a pharmaceutically acceptable carrier such as lactose, starch, sucrose, cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol and in a liquid composition, ethyl alcohol. Acceptable binders such .
as PVP starch, gelatin, natural sugars, corn sweeteners, natural and synthetic gums such as 2~ acacia, sodium alginate, carboxymethylcellulose, polyethylene glycol and waxes, may also be admixed with the acti~e components. Where necessary lubricants such as boric acid, sodium benzoate, sodium acetate, sodium chloride and disintegrators such as ~tarch, methylcellulose, agar, bentonite and guar gum and super disintegrators such as docusate sodium, sodium starch glycollate or cross-linked PVP
may also be included.
WO 92/OS786 PCr/US91~07VI)8 (' The active components mav also be formulated in sustained release formulations. These ~ormulations may be employed in oral, dermal, rectal o~ vaginal administration. Such sustained release forms als~ include layered formulations which provide for distinct release ratio and thus may be more -beneficial in allowing ~or short and long term relief.
The following e~amples illustrate the compositions of the present invention and as such are 0 n~t to be considere~ as limiting the invention set forth in the claim.~ appended herete.
~XAMPLE 1 (S)-ibu~rofen~ Diuretic Tablet (S)-ibuprofen-~S)-lysine 342 mg Hvdrochlor~thiazide lS mg PVP 15 mg 20 Avicel P~lQl 40 mg :
Magnesium stearate 4 mg .:
~AMPL~ 2 (S~-ibuprofen-(S)-Lysine, Pvrilamine Maleate. Diuretic Tablet ,:
~S)-ibuprofen-(S)-lvsine 342 mg ~ydrochlorothiazide 15 mg Pyrilamine Maleate 8 mg 30 PVF 15 mg Avicel PE101 40 mg Ma~nesium stearate 4 mg ~ a '~ 6 ~ EXAMPI~E 3 (S~-ibuRrofen-(S)-lvsine~ Diuretic Sustained Release 5 (S)-ibuprofen 400 mg H~drochlorothiazide ~0 mg PVP 30 mg Avicel PH101 80 mg Magnesium stearate 8 mg 10 ~ethocel ~lOMCR 66 mg Me~hocel KlOOMLV 200 mg :.
TITLE OF TH~ INVENTION
I~UPROF~N-DIURETIC COMBINATIONS
BACKGROUND OF THE INVENTIQN
The non-steroidal anti-inflammatory drugs (NSAID) have been utilized in the treatment of pain/
inflammation and have been disclosed as useful in the treatment, management and mitigation of cold symptoms and the pain associated therewith.
Ibuprofen (2-(4-isobutylphenyl)propionic acid) is a well known and commonly employed NSAID.
Recently. it has been found that a faster onset of pain relief and an enhanced analgesic response can be :
obtained by the utilization of the single enantiomer S(+)-ibuprofen in comparison to racemic ibuprofen, (see for e2ample U.S. Patent 4 t ~77,620).
`, ." .
~ W092/05786 PCT/US9~/07008 æ56 Diuretics, such as the thiazides, are useful in the relief of water retention. In optional combination with a tension reliever such as pyrilamine maleate. diuretics may offer relief of a variety of symptoms often appearing in the menstrual cycle such as cramps, bloating, tension, and irritability.
Combinations of ibuprofen with a diuretic ~uch as pamabrom have been discIosed in U.S. Patent 4,888.~43. ~owever~ despite the fact that the menstrual pain sufferer is in need of quick and enhaneed relief. there has been no consideration given to the employment of (S)-ibuprofen, or a salt thereo.f, in combination with a diuretic and optionallv with a tension reliever for the treatment of menstrual s~mptoms.
DETAIL~D DESCRIPTIQN OF THE INVENTION
This invention relates to a pharmaceutical -composition for use in the relief of pain, cramps, bloatin~ and tension experienced during menstruation or premenstruation in a female in need of such relief comprisin~ administering to such female:
(i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (P~)-ibuprofen; and (ii) a diuretically effective amount of a diuretic; and (iii) optionally a tension relieving effective amount of pyrilamine maleate.
This invention-is also directed ~o a method of relieving pain, cramps, bloating and tension, .
W~92/05786 PCT/US91/~7008 2 ~ 3i3 experienced durin~ menstruation or premenstruation in a female in need ~f such relief comprising administerin~ to such female:
~i) an anal~esically and anti-inflammatory effective amount ~f ~S)-ibuprofen, o} a salt thereof, substantially free of (R)-ibuprofen;
(ii) a diureticallv effective amount of a diuretic; and (iii~ optionallv a tension relieving effective amount of pyrilamine maleate.
This invention is also directed to a method o.f Pliciting an onset hastened and enhanced response for the relief of ~ain. cramps, bloating and tension e~perience`d durin~ menstruation or premenstruation in a female in need of such relief. comprising administering to such female:
(i) an anal~esically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen;
(ii) a diuretically effective amount of a diuretic; and (iii) optionally a tension relieving effective amount of pvrilamine maleate.
Substantiall~ free of (R)-ibuprofen should be taken to mean that the ration of (S)-ibuprofen to (R!-ibuprofen is at least 90:10.
Salts of (S)-ibuprofen includc salts with al~ali metals, such as sodium or potassium, salts :
with alkaline earth metals, such as calcium, or salts with other metals such as ma~nesium, aluminum, iron, zinc, copper. nickel or cobalt.
W092/0~786 PCT/US91/07008 ( . .
2 ~3 2~ ~ _ 4 _ Salts o~ ibuprofen further include the amino acid salts, particula:rlv the basic amino acids such as lysine and ~rginine. Specifically included within the above composition is (S)-ibuprofen-(s)-lysine.
(S)-ibupro~en may be prepared following the procedures disclosed in U.S. Patent 4,877,620. Metal .
salts of ibuprofen mav be obtained by contacting a hydro~ide~ or carbona~e with ibuprofen. Amino acid salts of ibuprofen m~v be obtained by contacting an amino acid in solution with ibuprofen.
The utili~ati~ of (S)-ibuprofen in an analgesic-antiinflammatory/diuretic combination ~ offers significant ~dvantages over the combination o~ i 15 racemic ibuprofen with a diuretic which has already :
been shown to have advantages over acetaminophen combinations (see for example U.S. Patent 4,888,343).
(5)-ibuprofen provides a faster onset of pain-antiinflanntatory relief and an enhanced degree of relief compared to racemic ibuprofen. These benefits are increased in an (S)-ibuprofen/diuretic combination as the inhibition of prostaglandin svnthetase and the water volume minimization may synergistically cooperate. This has not heretofore been observed because the art has not proposed the combination of the (S?-ibuprofen enantiomer, absent (R)-ibuprofen, with a diuretic. The presence of the (R)-ibuprofen m~y blur the synergistic effect.
The subJect using the (S)~ibuprofen/diuretic combination will no longer need to divert metabolic energy to the inversion of the (R)-enantiomer or the removal o~ this enantiomer. The absence of inversion , . , ... , .. . - , ,, . ,., . ,~ . . . . ... ..
W092/05786 PCT/US91/07~8 (~
~ ~ ~ 2 ~
reduces or eliminates the formation and incorporation into fatty tissue of hybrid-ibuprofen containing tri~lycerides~
Althou~h fluid retention is recognized or a possible side effect of ibuprofen usage the prior art has not heretofore considered the emplovment of an (S)-ibuprofen/diuretic combination. The absence of the (R)-ibuprofen in these combinations is particul~rly ad~anta~eous as a lesser metabolic burden is placed on the urogenital system for the excretion of the (R)-enantiomer or its metabolites.
The renal burden and renal to~icities sometimes associated with ibuprofen therapy are reduced or absent in a subst~ntiallv (~)-ibuprofen free composition.
The absence of (R)-ibuprofen provides for significant size and weight advantages in a combination dosage form, particularly a sustained release dosa~e form. Where a sustained release do~a~e of ibuprofen mav have required 800 to 1000 mg, the employment of (S)-ibuprofen reduces the weight to 4nO to 500 mg, and provides for a more practical size tablet for an ibuprofen/diuretic combination.
An effective amount of (S)-ibuprofen, or a pharmaceutically acceptable salt thereof, for use in a unit dose composition of this invention may range from 50 to 800 mg (S)-ibuproen. The preferred amount of (S)-ibuprofen is about 100 to 400 mg. The amount of a salt such as (S)-ibuprofen-(S)-lysine is determined based on the amount of (S)-ibuprofen contained therein.
The diuretic employed herein may be selected from the benzothiadiazides or acetazolamide and its . ~ ~
. - ..
, ... .. , . . . ,.. , . .. ~ ". . .. . , - .. .. .. , -, . ..... .. .. ... ...... . . . . . .. . ..
W092/05786 PCT/US91/07~B
_ analogs, or ethacrynic acid, or furosemide or bumetanide or a potassium-sparing diuretic such as amiloride or triamterene, or a xanthine or a combination diuretic such as pamabrom. Preferred diuretics include: Acetazolamide, dichlorophenamide, methazolamide, chlorothiazide, hydrochlorothiazide, benzthiazide, indapamide, trichlormethazide, methylclothiazide, polythiazide, ethacrynic acid, torasemide, furosemide, bumetamide, panabrom, amiloride, or triamterene. A particularly preferred diuretic is hydrochlorothiazide.
The amount of diuretic useful in the practice o~ the present invention may-vary from about 2 mg to 50 mg depending on the specific diurectic.
l~ The present compositions may be administered in the form of tablets, capsules, elixirs, syrups or a suspension. For oral administration the active components may be admixed with a pharmaceutically acceptable carrier such as lactose, starch, sucrose, cellulose, magnesium stearate, dicalcium phosphate, calcium sulfate, mannitol and in a liquid composition, ethyl alcohol. Acceptable binders such .
as PVP starch, gelatin, natural sugars, corn sweeteners, natural and synthetic gums such as 2~ acacia, sodium alginate, carboxymethylcellulose, polyethylene glycol and waxes, may also be admixed with the acti~e components. Where necessary lubricants such as boric acid, sodium benzoate, sodium acetate, sodium chloride and disintegrators such as ~tarch, methylcellulose, agar, bentonite and guar gum and super disintegrators such as docusate sodium, sodium starch glycollate or cross-linked PVP
may also be included.
WO 92/OS786 PCr/US91~07VI)8 (' The active components mav also be formulated in sustained release formulations. These ~ormulations may be employed in oral, dermal, rectal o~ vaginal administration. Such sustained release forms als~ include layered formulations which provide for distinct release ratio and thus may be more -beneficial in allowing ~or short and long term relief.
The following e~amples illustrate the compositions of the present invention and as such are 0 n~t to be considere~ as limiting the invention set forth in the claim.~ appended herete.
~XAMPLE 1 (S)-ibu~rofen~ Diuretic Tablet (S)-ibuprofen-~S)-lysine 342 mg Hvdrochlor~thiazide lS mg PVP 15 mg 20 Avicel P~lQl 40 mg :
Magnesium stearate 4 mg .:
~AMPL~ 2 (S~-ibuprofen-(S)-Lysine, Pvrilamine Maleate. Diuretic Tablet ,:
~S)-ibuprofen-(S)-lvsine 342 mg ~ydrochlorothiazide 15 mg Pyrilamine Maleate 8 mg 30 PVF 15 mg Avicel PE101 40 mg Ma~nesium stearate 4 mg ~ a '~ 6 ~ EXAMPI~E 3 (S~-ibuRrofen-(S)-lvsine~ Diuretic Sustained Release 5 (S)-ibuprofen 400 mg H~drochlorothiazide ~0 mg PVP 30 mg Avicel PH101 80 mg Magnesium stearate 8 mg 10 ~ethocel ~lOMCR 66 mg Me~hocel KlOOMLV 200 mg :.
Claims (9)
1. A pharmaceutical composition for use in the relief of pain, cramps, bloating and tension in a female and adapted for unit dosage oval administration said composition comprising:
(i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen or a pharmaceutically acceptable salt thereof, substantially free of (R)-ibuprofen; and (ii) a therapeutically effective amount of a diuretic: and (iii) optionally a therapeutically effective amount of pyrilamine maleate.
(i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen or a pharmaceutically acceptable salt thereof, substantially free of (R)-ibuprofen; and (ii) a therapeutically effective amount of a diuretic: and (iii) optionally a therapeutically effective amount of pyrilamine maleate.
2. A composition of Claim 1 wherein the (S)-ibuprofen is present as the salt (S)-ibuprofen-(S)-lysine.
3. A composition of Claim 1 comprising at least 50 mg of (S)-ibuprofen.
4. A composition of Claim 1 wherein the diuretic is selected from the group consisting of:
Acetazolamide, dichlorophenamide, methazolamide, chlorothiazide, hydrochlorothiazide, benzthiazide, indapamide, trichlormethazide, methylclothiazide, polythiazide, ethacrynic acid, torasemide, furosemide. bumetamide, panabrom, amiloride, or triamterene.
Acetazolamide, dichlorophenamide, methazolamide, chlorothiazide, hydrochlorothiazide, benzthiazide, indapamide, trichlormethazide, methylclothiazide, polythiazide, ethacrynic acid, torasemide, furosemide. bumetamide, panabrom, amiloride, or triamterene.
5. A composition of Claim 4 wherein the diuretic is hydrochlorothiazide.
6. A method of relieving pain, cramps, bloating and tension, experienced during menstruation or premenstruation in a female in need of such relief comprising administering to such female:
(i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen; and (ii) a diuretically effective amount of a diuretic; and iii) optionally a tension relieving effective amount of pyrilamine maleate.
(i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen; and (ii) a diuretically effective amount of a diuretic; and iii) optionally a tension relieving effective amount of pyrilamine maleate.
7. A method of eliciting an onset hastened and enhanced response for the relief of pain, cramps, bloating and tension experienced during menstruation or premenstruation in a female in need of such relief. comprising administering to such female:
(i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen; and (ii) a diuretically effective amount of a diuretic: and (iii)optionally a tension relieving effective amount of pyrilamine maleate.
(i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen; and (ii) a diuretically effective amount of a diuretic: and (iii)optionally a tension relieving effective amount of pyrilamine maleate.
8. A method of reducing the side effects associated with the administration of an ibuprofen/
diuretic combination which comprises the administration of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen, and a diuretic.
diuretic combination which comprises the administration of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen, and a diuretic.
9. A method of reducing the size and weight of an ibuprofen/diuretic combination dosage form. which comprises combining (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen, and a diuretic.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58924290A | 1990-09-28 | 1990-09-28 | |
| US589,242 | 1990-09-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2092565A1 true CA2092565A1 (en) | 1992-03-29 |
Family
ID=24357215
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002092565A Abandoned CA2092565A1 (en) | 1990-09-28 | 1991-09-25 | Ibuprofen-diuretic combinations |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0550689A1 (en) |
| JP (1) | JPH06501475A (en) |
| AU (1) | AU8710691A (en) |
| CA (1) | CA2092565A1 (en) |
| WO (1) | WO1992005786A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5462950A (en) * | 1993-12-21 | 1995-10-31 | Eli Lilly And Company | Methods of treating menstrual symptoms and compositions therefore |
| GB9613470D0 (en) * | 1996-06-27 | 1996-08-28 | Ciba Geigy Ag | Small solid oral dosage form |
| EP2847175A4 (en) * | 2012-05-08 | 2016-04-20 | Cellix Bio Private Ltd | Compositions and methods for suppression of carbonic anhydrase activity |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4888343A (en) * | 1986-09-15 | 1989-12-19 | Bristol-Myers Company | Pharmaceutical compositions for relief of dysmenorrhea and/or premenstrual syndrome and process |
| DE3639038C2 (en) * | 1986-11-14 | 1997-02-06 | Helmut Dr Lukas | Use of S - (+) - ibuprofen for rapid treatment of human pain |
| US4851444A (en) * | 1987-07-10 | 1989-07-25 | Analgesic Associates | Onset-hastened/enhanced analgesia |
-
1991
- 1991-09-25 AU AU87106/91A patent/AU8710691A/en not_active Abandoned
- 1991-09-25 JP JP3516780A patent/JPH06501475A/en active Pending
- 1991-09-25 CA CA002092565A patent/CA2092565A1/en not_active Abandoned
- 1991-09-25 WO PCT/US1991/007008 patent/WO1992005786A1/en not_active Application Discontinuation
- 1991-09-25 EP EP91919392A patent/EP0550689A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP0550689A1 (en) | 1993-07-14 |
| EP0550689A4 (en) | 1994-02-16 |
| AU8710691A (en) | 1992-04-28 |
| WO1992005786A1 (en) | 1992-04-16 |
| JPH06501475A (en) | 1994-02-17 |
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