WO1998027968A1 - Nouvelle formulation topique de medicaments anti-inflammatoires pour le traitement de la douleur localisee - Google Patents

Nouvelle formulation topique de medicaments anti-inflammatoires pour le traitement de la douleur localisee Download PDF

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Publication number
WO1998027968A1
WO1998027968A1 PCT/US1997/022826 US9722826W WO9827968A1 WO 1998027968 A1 WO1998027968 A1 WO 1998027968A1 US 9722826 W US9722826 W US 9722826W WO 9827968 A1 WO9827968 A1 WO 9827968A1
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WO
WIPO (PCT)
Prior art keywords
formulation
inflammatory drug
composition
inflammatory
drug
Prior art date
Application number
PCT/US1997/022826
Other languages
English (en)
Inventor
Marcel E. Nimni
Original Assignee
Nimni Marcel E
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
Application filed by Nimni Marcel E filed Critical Nimni Marcel E
Priority to AU55232/98A priority Critical patent/AU5523298A/en
Publication of WO1998027968A1 publication Critical patent/WO1998027968A1/fr

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Classifications

    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61K31/41—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
    • A61K31/415—1,2-Diazoles
    • A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
    • 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers

Definitions

  • the present invention is directed to a topical formulation containing an anti-inflammatory drug in an effective amount and which allows said anti -inflammatory to penetrate the skin.
  • Soft-tissue pain and swelling associated with arthritis have been successfully treated by the administration of oral nonsteroidal anti -inflammatory drugs, such a indomethacin and aspirin.
  • nonsteroidal anti -inflammatory drugs such as indomethacin and aspirin.
  • the basis of treatment with nonsteroidal anti -inflammatory drugs is the inhibition of other products of synthetic pathway or prostaglandin.
  • nonsteroidal drugs for arthritis is usually in doses higher than for analgesic use.
  • nonsteroidal drugs at therapeutic effective doses can cause severe side effects particularly of the GI system.
  • aspirin probably the most commonly used drug, at concentrations necessary to treat the inflammation associated with rheumatoid arthritis, can cause hearing loss, bleeding ulcers and increased coagulation time.
  • Fenoprofen can cause renal disorders in addition to GI problems.
  • Phenylbutazone can cause edema and hematological complications in addition to GI problems.
  • Indomethacin causes gastrointestinal bleeding, and exacerbation of renal insufficiency when administered in doses necessary to reach therapeutic concentrations at the site of action.
  • nonsteroidal anti -inflammatory agents for the topical administration.
  • the present invention is predicated on the discovery that formulations of indomethacin, a nonsteroidal, in one or a mixture of organic solvents and which include benzyl alcohol enhance penetration allowing the drug to concentrate in the skin and underlying tissues, i.e., muscle and cartilage, to a greater extent and remain for a longer period of time than when the drug is administered orally.
  • the specific formulations are comprised of a nonsteroidal drug in a therapeutic sufficient amount dissolved in a carrier system made up of a first solvent phase of a relatively high boiling solvent (e.g., benzyl alcohol) which acts to enhance dermal penetration, and a second solvent phase of a low boiling solvent (e.g. isopropyl alcohol). Both solvents are compatible and co-soluble in each other and of a type in which the nonsteroidal drug can be dissolved. When applied topically, the low boiling solvent will quickly dissipate due to the patient's temperature leaving a concentrated solution of the nonsteroidal drug in the remaining high boiling solvent which enhances penetration through the skin.
  • a carrier system made up of a first solvent phase of a relatively high boiling solvent (e.g., benzyl alcohol) which acts to enhance dermal penetration, and a second solvent phase of a low boiling solvent (e.g. isopropyl alcohol).
  • a relatively high boiling solvent e.g., benzyl alcohol
  • a low boiling solvent
  • the methods and compositions of the present invention are intended for treatment of soft tissue pains associated with arthritis and other localized inflammatory events of a patient, particularly human patients, but including other mammalian hosts.
  • Arthritis is a term that embraces a group of diseases characterized by pain and swelling particularly of the joints, which causes various levels of discomfort and disability; in many cases the underlying causes are poorly understood.
  • the curative effects of oral nonsteroidal anti- inflammatory drugs for arthritic and other soft tissue pains are well documented.
  • compositions of the present invention rely on administering a nonsteroidal anti-inflammatory drug, alone or a combination with one or more nonsteroidal anti-inflammatory drug in a concentration of 0.5 to 10%, in a vehicle containing benzyl alcohol in a concentration from 0.5 to 10%, and one or more solvent of low boiling point, such as acetone, isopropyl alcohol, ethyl alcohol.
  • the formulation can contain various inactive ingredients to make the formulation in the form of a cream or gel .
  • compositions of this invention are exemplary of the compositions of this invention. These formulations are illustrative only and are not intended to limit the scope of this invention and should not be so construed.
  • a solution for topically treating topically soft tissue pain is prepared as follows :
  • Formula 2 A solution as described in Formula 1 except that a different nonsteroidal anti -inflammatory drug is used, such as indomethacin, ibuprofen, tol etin, phenylbutazone, ketoprofen, etc.
  • Formula 3 A gel for the topical treatment of soft tissue pain is prepared as follows:
  • Formula 4 A gel as described in Formula 3 except that a different nonsteroidal anti -inflammatory drug is used, such as indomethacin, ibuprofen, tolmetin, phenylbutazone, ketoprofen, etc.
  • a different nonsteroidal anti -inflammatory drug such as indomethacin, ibuprofen, tolmetin, phenylbutazone, ketoprofen, etc.
  • a cream for the topical treatment of soft tissue pain is prepared as follows:
  • a different nonsteroidal anti -inflammatory drug such as indomethacin, ibuprofen, tolmetin, phenylbutazone, ketoprofen, or other nonsteroidal anti -inflammatory drug, or a combination of nonsteroidal anti -inflammatory drugs.

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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)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte à une formulation topique contenant de l'alcool benzylique en tant qu'agent favorisant la pénétration, ainsi qu'un médicament anti-inflammatoire, en quantité suffisante, ladite formulation permettant au médicament anti-inflammatoire de pénétrer dans la peau.
PCT/US1997/022826 1996-12-20 1997-12-11 Nouvelle formulation topique de medicaments anti-inflammatoires pour le traitement de la douleur localisee WO1998027968A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU55232/98A AU5523298A (en) 1996-12-20 1997-12-11 Novel topical formulation of anti-inflammatory drugs for the treatment of localized pain

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US77127196A 1996-12-20 1996-12-20
US08/771,271 1996-12-20

Publications (1)

Publication Number Publication Date
WO1998027968A1 true WO1998027968A1 (fr) 1998-07-02

Family

ID=25091273

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/022826 WO1998027968A1 (fr) 1996-12-20 1997-12-11 Nouvelle formulation topique de medicaments anti-inflammatoires pour le traitement de la douleur localisee

Country Status (2)

Country Link
AU (1) AU5523298A (fr)
WO (1) WO1998027968A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006100485A1 (fr) * 2005-03-24 2006-09-28 Transphase Limited Préparation à usage local et ses applications
JP2008534483A (ja) * 2005-03-24 2008-08-28 トランスフェイズ・リミテッド 経皮局所用組成物およびその使用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3867528A (en) * 1973-10-11 1975-02-18 American Cyanamid Co Steroidal topical cream base
US4804541A (en) * 1987-08-11 1989-02-14 Moleculon, Inc. Transdermal administration using benzyl alcohol
US4954487A (en) * 1979-01-08 1990-09-04 The Procter & Gamble Company Penetrating topical pharmaceutical compositions
US5288498A (en) * 1985-05-01 1994-02-22 University Of Utah Research Foundation Compositions of oral nondissolvable matrixes for transmucosal administration of medicaments

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3867528A (en) * 1973-10-11 1975-02-18 American Cyanamid Co Steroidal topical cream base
US4954487A (en) * 1979-01-08 1990-09-04 The Procter & Gamble Company Penetrating topical pharmaceutical compositions
US5288498A (en) * 1985-05-01 1994-02-22 University Of Utah Research Foundation Compositions of oral nondissolvable matrixes for transmucosal administration of medicaments
US4804541A (en) * 1987-08-11 1989-02-14 Moleculon, Inc. Transdermal administration using benzyl alcohol

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006100485A1 (fr) * 2005-03-24 2006-09-28 Transphase Limited Préparation à usage local et ses applications
JP2008534482A (ja) * 2005-03-24 2008-08-28 トランスフェイズ・リミテッド 局所用組成物およびその使用
JP2008534483A (ja) * 2005-03-24 2008-08-28 トランスフェイズ・リミテッド 経皮局所用組成物およびその使用

Also Published As

Publication number Publication date
AU5523298A (en) 1998-07-17

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