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WO1997003655A1 - Solution claire et stable d'anti-inflammatoires non steroidiens a integrer dans des gelules de gelatine - Google Patents

Solution claire et stable d'anti-inflammatoires non steroidiens a integrer dans des gelules de gelatine Download PDF

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Publication number
WO1997003655A1
WO1997003655A1 PCT/US1996/010687 US9610687W WO9703655A1 WO 1997003655 A1 WO1997003655 A1 WO 1997003655A1 US 9610687 W US9610687 W US 9610687W WO 9703655 A1 WO9703655 A1 WO 9703655A1
Authority
WO
WIPO (PCT)
Prior art keywords
soft gelatin
derivatives
gelatin capsules
propionic acid
derivative
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.)
Ceased
Application number
PCT/US1996/010687
Other languages
English (en)
Other versions
WO1997003655A8 (fr
Inventor
James W. Munden
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pharmacia and Upjohn Co
Original Assignee
Pharmacia and Upjohn Co
Upjohn Co
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to AU63900/96A priority Critical patent/AU6390096A/en
Priority to EP96923374A priority patent/EP0839029A1/fr
Application filed by Pharmacia and Upjohn Co, Upjohn Co filed Critical Pharmacia and Upjohn Co
Priority to JP50667797A priority patent/JP2001503372A/ja
Publication of WO1997003655A1 publication Critical patent/WO1997003655A1/fr
Anticipated expiration legal-status Critical
Publication of WO1997003655A8 publication Critical patent/WO1997003655A8/fr
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/603—Salicylic acid; Derivatives thereof having further aromatic rings, e.g. diflunisal
    • 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
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • 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
    • 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
    • A61K31/54—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
    • A61K31/5415—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 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds

Definitions

  • This invention relates to the field of pharmaceutical drug compositions comprising combinations of dimethylisosorbide and non-steroidal anti-inflammatory drugs.
  • DMI has been used as a solvent to produce liquid solutions of aspirin, see U.S. Patent 4, 228,162, tetracyclines, see U.S. Patent 3,219,529, muscle relaxants, see U.S. Patent 3,699,230, and steroids, see U.S. Patent 4,082,881; however it is only rarely chosen as a carrier for filling soft gelatin capsules.
  • DMI has been suggested as a material to fill gelatin capsules where it is combined with etoposide, a drug used for the treatment of refractory testicular cancer and small cell lung cancer.
  • Etoposide is currently being marketed under the tradename VePesid ®, however, the suggested dimethylisosorbide containing formula is not known to be marketed. See U.S. Patent 4,927,638.
  • Etoposide is extremely soluble in a DMI.
  • DMI is also a suggestion of using DMI as part of a microemulsion solution used to fill soft gelatin capsules. See E.P. 0 650 721 Al.
  • Non-steroidal anti-inflammatory drugs such as ibuprofen, flurbiprofen, and naproxen as free acids are relatively insoluble in water and in many of the typical oil carriers used in soft gelatin capsules. Suspensions of these drugs in oil are possible for filling into soft gelatin capsules; however, as mentioned earlier these are not preferred by the consumer.
  • the soft gelatin capsules may contain compositions comprising about 30, 25, 20, 15, 10, 5 or 0 percent propylene glycol, more preferred is up to 50 percent polysorbate, or up to 50 percent polyethylene glycol.
  • the nsaid may be selected from: propionic acid derivatives, acetic acid derivatives, fenamic acid derivatives, biphenylcarboxylic acid derivatives, or oxicams and their derivatives.
  • the polysorbate may be polysorbate 80, the polyethylene glycol may be polyethylene glycol 400.
  • the nsaid is a compound or compounds selected from propionic acid derivatives, acetic acid derivatives, fenamic acid derivatives, biphenylcarboxylic acid derivatives, or oxicams and their derivatives.
  • the propionic acid derivative may be a compound or compounds selected from ibuprofen, naproxen, flurbiprofen, fenoprofen, ketoprofen, fenbufen, and fluprofen and their derivatives or their pharmaceutically acceptable salts, esters or derivatives.
  • the acetic acid derivative may be a compound or compounds selected from sulindac, indomethacin and their salts or derivatives, or a salt such as tolmetin sodium.
  • the fenamic acid derivative may be selected from mefenamic acid and its salts or derivatives, or a salt such as meclofenamate sodium.
  • the biphenylcarboxylic acid derivatives may be selected from difunisal and flufenisal and their salts and derivatives.
  • the oxicam may be selected from oxicam, piroxicam, sudoxicam, and isoxicam and their salts and derivatives. These compositions make pharmaceutically elegant solutions that are particularly suitable for filing soft gelatin capsules. Additional Description of the Invention and Description of the Preferred
  • DMI is dimethylisosorbide
  • Soft gelatin capsules are any type of gelatin capsule suitable for filling with liquid solutions. These capsules may be referred to with other names such as soft elastic capsules, soft gelatin, soft gel, soft liquid gel, sometimes makers of these products use trademark names such as, Liquid Gel ®, Liquid Caps ®, DOXIDAN ® etc.
  • non-steroidal anti-inflammatory to be combined in a pharmaceutically acceptable composition with DMI is selected from one of the following categories:
  • Propionic acid derivatives Acetic acid derivatives Fenamic acid derivatives Biphenylcarboxylic acid Oxicams.
  • NSAID or "nsaid” used herein is intended to mean any non ⁇ steroidal anti-inflammatory compound, including the salts and esters thereof, falling within one of the five structural categories above, but excluding acetaminophen and phenacetin.
  • the specific compounds falling within the foregoing definition of non- steroidal anti-inflammatory drugs for use in the present invention are known to those skilled in the art.
  • ibuprofen, naproxen, flurbiprofen, fenoprofen, ketoprofen, fenbufen, and fluprofen are particularly preferred compounds.
  • Preferred acetic acid derivatives include tolmetin sodium, sulindac, and indomethacin.
  • Preferred fenamic acid derivatives include mefenamic acid and meclofenamate sodium.
  • Preferred biphenylcarboxylic acid derivatives include difunisal and flufenisal.
  • Preferred oxicams include oxicam, piroxicam, sudoxicam, and isoxicam.
  • salts of these compounds are also be considered “pharmaceutically acceptable salts" and this refers to the relatively non-toxic, inorganic and organic acid addition salts and esters and, where the compounds of this invention also contain an acidic functional group, the alkali and alkaline earth metal salts.
  • These salts can be prepared by reacting the purified compound in its free acid form with a suitable organic or inorganic base and isolating the salt thus formed.
  • Representative alkali or alkaline earth salts include the sodium, potassium, calcium, and magnesium salts and the like.
  • Representative salts formed from reaction with organic bases include but are not limited to those such as formed with arginine, lysine and the like.
  • salts are readily prepared by methods known in the art.
  • the salts may produce compounds that are more water soluble than the free acids.
  • the compounds of this invention may be mixed with DMI in a suitable hydrated form.
  • DMI dimethyl methacrylate
  • polyethylene glycol polyethylene glycol
  • polypropylene glycol that are frequently given other names.
  • these terms should be defined in accordance with the CTFA Cosmetic Ingredient Dictionary, third edition, editors, Estrin, Crosley &
  • esters include but are not limited to those of methyl and ethyl alcohol as well as other alcohols which would be apparent to one skilled in the art. These esters are readily prepared by methods known in the art. The esters thus produced may form compounds that are more water soluble than the free acids. Additionally, the compounds of this invention may be mixed with DMI in a suitable hydrated form.
  • a clear solution of the drugs and types of drugs described by this disclosure and used to fill a soft gelatin capsule offer significant commercial advantages. These compositions make pharmaceutically elegant solutions that are particularly suitable for filing soft gelatin capsules. The capsules made with these solutions are also particularly pharmaceutically elegant.
  • compositions containing at least 40 percent DMI, as described herein produce a liquid that makes a pharmaceutically elegant fill for gelatin capsules.
  • These clear soft gelatin capsule compatible solutions are not easily obtained using other solvents, carriers, solutions or mixtures.
  • these drugs are relatively insoluble, they are ionizable and chemically reactive in aqueous media and therefore subject to transformation into esters or salts if not formulated properly.
  • the products which may form may be considered as new chemical entities (for regulatory purposes) or it is possible they may be classified as degradation products. In either case, this deviation from the original pure compound is most often undesirable.
  • the authors herein report solutions of the drugs which are not only compatible with soft gelatin capsules but which also prevent the degradation or reactions to form undesirable products.
  • compositions described herein will normally be administered orally, however; the gelatin capsules could also be administered rectally, in the form of pharmaceutical preparations comprising the active ingredient typically in the free acid form but possibly as a pharmaceutically acceptable non-toxic, addition salt, or ester such as the types listed above in association with a pharmaceutically acceptable carrier.
  • a pharmaceutically acceptable non-toxic, addition salt, or ester such as the types listed above in association with a pharmaceutically acceptable carrier.
  • the present invention describes how dimethylisosorbide (DMI) can be combined with non-steroidal anti-inflammatory drugs, such as aspirin, ibuprofen, flurbiprofen, and other common compatible carriers, or solvents, such as foodstock oils, oils and solvents such as soybean oil, cottonseed oil, peanut oil, corn oil, safflower oil, canola oil, olive oil, macadamia nut oil, polyethylene glycol, or polysorbate to produce a clear, aesthetically pleasing liquid filled gelatin capsule.
  • non-steroidal anti-inflammatory drugs such as aspirin, ibuprofen, flurbiprofen, and other common compatible carriers, or solvents, such as foodstock oils, oils and solvents such as soybean oil, cottonseed oil, peanut oil, corn oil, safflower oil, canola oil, olive oil, macadamia nut oil, polyethylene glycol, or polysorbate to produce a clear, aesthetically pleasing liquid filled gelatin capsule.
  • a foodstock type carrier oil is a nontoxic oil, it may be derived from a natural product such as soybean oil, cottonseed oil, peanut oil, corn oil, safflower oil, canola oil, olive oil, macadamia nut oil, or a similar synthetic substitutes, and the like.
  • Particularly appropriate compatible carriers or solvents are; the oils, propylene glycol, polysorbate and polyethylene glycol.
  • polysorbate 80, (one commercial version is named Tween ® 80) and polyethylene glycol 400 are especially suitable for forming clear stable solutions with the nsaids.
  • a compatible carrier or solvent such as food stock oils, or their pharmaceutically acceptable salts, esters and oils
  • polysorbate can be of any designation, such as polysorbates 20, 40, 60, 65, 80 or 85.
  • Polysorbate 80 works well. If the liquid composition contains polyethylene glycol, it should not be of a higher weight than what causes precipitation. Our investigations suggest one upper weight limit of polyethylene glycol is around 900, unless heating and cooling techniques are used. A weight of about 600 to 650 could be used. Polyethylene weights that cause appreciable precipitation in a short period of time would be unacceptable. If propylene glycol is used, its concentration should be less than about 35 percent, concentrations of 40 percent and higher appear to cause capsule deformities, thus diminishing the elegance of the soft gelatin capsule.
  • Liquid solution compositions containing 30 percent propylene glycol were suitable and solutions containing about 25, 20, 15, 10, 5 or 1 percent propylene glycol mixed with the DMI should all be suitable.
  • Food stuff oils are traditional gelatin capsule fill materials and they can also be used with DMI. Their use would only be limited to the extent that they caused precipitation of the drug or otherwise interfered with the elegant appearance of the soft gelatin capsule. Oil concentrations of about 60, 40, 30, 20, 10, or 5 percent should all be suitable. Various combinations of the above may also be suitable.
  • Various carriers, additives and other oils could be added to these solutions and compositions containing DMI.
  • the carriers, additives and oils can be mixed or combined in various combinations and other drugs, such as pseuodophrine, could also be added to the compositions, provided they do not cause significant precipitation or capsule deformation.
  • Ibuprofen has been found to be soluble at room temperature in dimethylisosorbide to the extent of 58 grams/100 ml. Flurbiprofen is soluble in dimethylisosorbide at room temperature to the extent of 45 grams/100 ml. Therapeutic doses of 200 mg ibuprofen or 50 mg of flurbiprofen are appropriate for delivery from a soft gelatin capsule.
  • a capsule as small as a #2 round or # 2 oval soft gel can be used for 50 mg of flurbiprofen while a # 6 round, # 7 x /2 oval, or # 6 oblong can be used to deliver 200 mg of ibuprofen. If one needed to incorporate this quantity of drug in 0.986ml to fill a #16 oval soft gelatin capsule, it would be necessary to utilize a carrier in addition to DMI.
  • the 200 mg of ibuprofen per capsule translates to 10.2 grams per 50 ml of fill while the 50 mg dose of flurbiprofen would require 2.55 grams of drug per 50 ml of fill. Based on the solubility of these drugs, there is sufficient capsule volume to dissolve them in DMI.
  • Examples 1 Approximately 50/50 or 40/60 blends of dimethylisosorbide and: corn oil, cottonseed oil, soybean oil, or propylene glycol were prepared and 10.2 grams of ibuprofen dissolved in 50 ml of each blend.
  • Examples 4 Approximately 50/50 blends of either dimethylisosorbide and polysorbate 80 (Tween 80) or dimethylisosorbide and polyethylene glycol (including peg 400) containing no drug, 10.2 grams/50 ml of ibuprofen or 2.55 grams/50ml of flurbiprofen were prepared.
  • Teween 80 dimethylisosorbide and polysorbate 80
  • dimethylisosorbide and polyethylene glycol including peg 400
  • Dimethylisosorbide compatibility with soft gelatin capsules was demonstrated by immersing intact DOXIDAN® capsules in dimethylisosorbide either alone or in combination as blends, as described above. All gelatin capsules remained intact except those where drug was combined with 60/40 or 50/50 blend of propylene glycol and dimethylisosorbide.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

Solutions claires et stables sur les plans chimique et physique de médicaments anti-inflammatoires non stéroïdiens dissous dans du diméthylisosorbide ou dans des mélanges de diméthylisosorbide et d'huiles alimentaires, de propylène glycol, de polysorbate, de polyéthylène glycol ou d'autres véhicules ou solvants couramment employés, pouvant être encapsulées dans des gélules souples de gélatine.
PCT/US1996/010687 1995-07-20 1996-06-26 Solution claire et stable d'anti-inflammatoires non steroidiens a integrer dans des gelules de gelatine Ceased WO1997003655A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU63900/96A AU6390096A (en) 1995-07-20 1996-06-07 Stable clear solutions of non-steroidal anti-inflammatory drugs for incorporation into gelatin capsules
EP96923374A EP0839029A1 (fr) 1995-07-20 1996-06-07 Solution claire et stable d'anti-inflammatoires non steroidiens a integrer dans des gelules de gelatine
JP50667797A JP2001503372A (ja) 1995-07-20 1996-06-26 非ステロイド系抗炎症剤のゼラチンカプセルへの配合を目的とした安定な透明溶液

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US130495P 1995-07-20 1995-07-20
US1002196P 1996-01-16 1996-01-16
US60/010,021 1996-01-16
US60/001,304 1996-01-16

Publications (2)

Publication Number Publication Date
WO1997003655A1 true WO1997003655A1 (fr) 1997-02-06
WO1997003655A8 WO1997003655A8 (fr) 1999-08-19

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PCT/US1996/010687 Ceased WO1997003655A1 (fr) 1995-07-20 1996-06-26 Solution claire et stable d'anti-inflammatoires non steroidiens a integrer dans des gelules de gelatine

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Country Link
EP (1) EP0839029A1 (fr)
JP (1) JP2001503372A (fr)
AU (1) AU6390096A (fr)
WO (1) WO1997003655A1 (fr)

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003508434A (ja) * 1999-09-02 2003-03-04 バナー ファーマキャップス， インコーポレーテッド イブプロフェン含有ソフトゲル
EP1348436A1 (fr) * 2002-03-30 2003-10-01 Boehringer Ingelheim International GmbH Suppositoires de meloxicam
US7135191B2 (en) * 1997-09-04 2006-11-14 Zsolt Istvan Hertelendy Urogenital or anorectal transmucosal vaccine delivery system
WO2011060944A2 (fr) 2009-11-20 2011-05-26 Gp Pharm, S.A. Capsules de principes actifs pharmaceutiques et d'esters d'acides gras polyinsaturés
US20130178448A1 (en) * 2010-02-05 2013-07-11 Wilson Caparros-Wanderley Treatment of Respiratory Disorders
US8920820B2 (en) 2001-12-12 2014-12-30 Boehringer Ingelheim Vetmedica Gmbh Highly concentrated stable meloxicam solutions for needleless injection
US8992980B2 (en) 2002-10-25 2015-03-31 Boehringer Ingelheim Vetmedica Gmbh Water-soluble meloxicam granules
US9101529B2 (en) 2009-10-12 2015-08-11 Boehringer Ingelheim Vetmedica Gmbh Containers for compositions comprising meloxicam
US9149480B2 (en) 2010-03-03 2015-10-06 Boehringer Ingeleheim Vetmedica GmbH Use of meloxicam for the long-term treatment of musculoskeletal disorders in cats
US9173856B2 (en) 2010-04-19 2015-11-03 Qlt Inc. Therapeutic regimen and methods for treating or ameliorating visual disorders associated with an endogenous retinoid deficiency
US9265742B2 (en) 2010-10-29 2016-02-23 Infirst Healthcare Limited Compositions and methods for treating inflammatory pain
US9271950B2 (en) 2010-10-29 2016-03-01 Infirst Healthcare Limited Compositions for treating chronic inflammation and inflammatory diseases
US9308213B2 (en) 2010-10-29 2016-04-12 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US9504664B2 (en) 2010-10-29 2016-11-29 Infirst Healthcare Limited Compositions and methods for treating severe pain
US9737500B2 (en) 2010-10-29 2017-08-22 Infirst Healthcare Limited Compositions and methods for treating severe pain
US9744132B2 (en) 2010-10-29 2017-08-29 Infirst Healthcare Limited Solid solution compositions and use in chronic inflammation
US9795568B2 (en) 2010-05-05 2017-10-24 Boehringer Ingelheim Vetmedica Gmbh Low concentration meloxicam tablets
US9993557B2 (en) 2000-06-20 2018-06-12 Boehringer Ingelheim Vetmedica Gmbh Highly concentrated stable meloxicam solutions
US10130606B2 (en) 2009-09-15 2018-11-20 Novelion Therapeutics Inc. Pharmaceutical formulations comprising 9-cis-retinyl esters in a lipid vehicle
US10548901B2 (en) 2004-02-23 2020-02-04 Boehringer Ingelheim Vetmedica Gmbh Meloxicam for the treatment of respiratory diseases in pigs
US10695432B2 (en) 2010-10-29 2020-06-30 Infirst Healthcare Limited Solid solution compositions and use in severe pain
US10695431B2 (en) 2010-10-29 2020-06-30 Infirst Healthcare Limited Solid solution compositions and use in cardiovascular disease
US10828267B2 (en) 2012-03-01 2020-11-10 Retinagenix Therapeutics, Inc. Therapeutic regimens and methods for improving visual function in visual disorders associated with an endogenous retinoid deficiency
US11202831B2 (en) 2010-10-29 2021-12-21 Infirst Healthcare Limited Solid solution compositions and use in cardiovascular disease
US11224659B2 (en) 2010-10-29 2022-01-18 Infirst Healthcare Limited Solid solution compositions and use in severe pain
US11730709B2 (en) 2010-10-29 2023-08-22 Infirst Healthcare Limited Compositions and methods for treating severe pain

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US20110090954A1 (en) * 2009-10-21 2011-04-21 Cohen Robert A Video Codes with Directional Transforms

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EP0359184A1 (fr) * 1988-09-12 1990-03-21 Bristol-Myers Squibb Company Solutions d'etoposide
WO1992000725A1 (fr) * 1990-07-13 1992-01-23 Farcon Ag Compositions pharmaceutiques liquides de traitement oral presentant une activite anti-inflammatoire

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
US4228162A (en) * 1979-07-09 1980-10-14 Research Corporation Dimethyl isosorbide in liquid formulation of aspirin
EP0359184A1 (fr) * 1988-09-12 1990-03-21 Bristol-Myers Squibb Company Solutions d'etoposide
WO1992000725A1 (fr) * 1990-07-13 1992-01-23 Farcon Ag Compositions pharmaceutiques liquides de traitement oral presentant une activite anti-inflammatoire

Cited By (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7135191B2 (en) * 1997-09-04 2006-11-14 Zsolt Istvan Hertelendy Urogenital or anorectal transmucosal vaccine delivery system
JP2003508434A (ja) * 1999-09-02 2003-03-04 バナー ファーマキャップス， インコーポレーテッド イブプロフェン含有ソフトゲル
US9993557B2 (en) 2000-06-20 2018-06-12 Boehringer Ingelheim Vetmedica Gmbh Highly concentrated stable meloxicam solutions
US8920820B2 (en) 2001-12-12 2014-12-30 Boehringer Ingelheim Vetmedica Gmbh Highly concentrated stable meloxicam solutions for needleless injection
US10098891B2 (en) 2001-12-12 2018-10-16 Boehringer Ingelheim Vetmedica Gmbh Highly concentrated stable meloxicam solutions for needleless injection
WO2003082297A1 (fr) * 2002-03-30 2003-10-09 Boehringer Ingelheim International Gmbh Suppositoires de meloxicam contenant par exemple du polyethyleneglycol
EP1348436A1 (fr) * 2002-03-30 2003-10-01 Boehringer Ingelheim International GmbH Suppositoires de meloxicam
US8992980B2 (en) 2002-10-25 2015-03-31 Boehringer Ingelheim Vetmedica Gmbh Water-soluble meloxicam granules
US9066955B2 (en) 2002-10-25 2015-06-30 Boehringer Ingelheim Vetmedica Gmbh Water-soluble meloxicam granules
US10548901B2 (en) 2004-02-23 2020-02-04 Boehringer Ingelheim Vetmedica Gmbh Meloxicam for the treatment of respiratory diseases in pigs
US10130606B2 (en) 2009-09-15 2018-11-20 Novelion Therapeutics Inc. Pharmaceutical formulations comprising 9-cis-retinyl esters in a lipid vehicle
US10736865B2 (en) 2009-09-15 2020-08-11 Retinagenix Therapeutics, Inc. Pharmaceutical formulations comprising 9-cis-retinyl esters in a lipid vehicle
US9101529B2 (en) 2009-10-12 2015-08-11 Boehringer Ingelheim Vetmedica Gmbh Containers for compositions comprising meloxicam
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WO2011060944A2 (fr) 2009-11-20 2011-05-26 Gp Pharm, S.A. Capsules de principes actifs pharmaceutiques et d'esters d'acides gras polyinsaturés
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JP2001503372A (ja) 2001-03-13
AU6390096A (en) 1997-02-18
WO1997003655A8 (fr) 1999-08-19
EP0839029A1 (fr) 1998-05-06

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