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WO1991002497A1 - Nifedipine topique pour le traitement de l'hypersensibilite cutanee, oculaire et de la muqueuse, ainsi que d'etats inflammatoires et hyperproliferatifs - Google Patents

Nifedipine topique pour le traitement de l'hypersensibilite cutanee, oculaire et de la muqueuse, ainsi que d'etats inflammatoires et hyperproliferatifs Download PDF

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Publication number
WO1991002497A1
WO1991002497A1 PCT/US1990/004632 US9004632W WO9102497A1 WO 1991002497 A1 WO1991002497 A1 WO 1991002497A1 US 9004632 W US9004632 W US 9004632W WO 9102497 A1 WO9102497 A1 WO 9102497A1
Authority
WO
WIPO (PCT)
Prior art keywords
nifedipine
calcium channel
set forth
channel blocker
cutaneous
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/US1990/004632
Other languages
English (en)
Inventor
Richard J. Sharpe
Kenneth A. Arndt
Stephen J. Galli
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.)
Beth Israel Deaconess Medical Center Inc
Original Assignee
Beth Israel Deaconess Medical Center Inc
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 Beth Israel Deaconess Medical Center Inc filed Critical Beth Israel Deaconess Medical Center Inc
Publication of WO1991002497A1 publication Critical patent/WO1991002497A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
    • 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
    • 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
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin

Definitions

  • Severe or repeated inflammatory reactions can be followed by significant chronic changes, such as scarring of affected tissues.
  • these chronic changes can have serious long term consequences, including diminished vision or actual blindness.
  • leukocyte particularly mononuclear cells, lymphocytes, neutrophils, and eosinophils
  • psoriasis a common cutaneous disease associated with a hyperproliferating epidermis, also has an inflammatory component. It is now believed that cells found in the normal and abnormal skin, eye, or mucosal membranes secrete cytokines which are important in recruiting inflammatory leukocytes into these sites and in inducing chronic changes such as scarring.
  • atopic dermatitis and eczema other conditions involving pathogenic cutaneous, ocular, and mucosal inflammation include, but are not limited to psoriasis, acne vulgaris, arthropod bite reactions pyoderma gangrenosa, lichen planus, cutaneous lupus erythematosus, scleroderma, mycosis fungoides, burns, and drug eruptions. These conditions may result in the following one or more symptoms or signs: itching, swelling, reddening, blisters, crusting, pain, scaling, cracking, scarring or oozing of fluid involving the skin, eye or mucosal membranes.
  • agents which can be applied topically to prevent or suppress i.e. "treat" cutaneous, ocular, or mucosal hypersensitivity reactions, inflammation, hyperproliferation, or scarring, and which have favorable benefit to risk rations.
  • Optimally such agents should primarily act locally, and systemic absorption should not result in blood levels high enough to cause significant systemic toxicity. It is an object of the present invention to present a method for the topical treatment of reactions of cutaneous, mucosal, or ocular hypersensitivity.
  • compositions for the topical treatment of cutaneous or mucosal hypersensensitivity reactions, inflammation, hyperproliferation, or scarring containing a therapeutic amount of a calcium channel blocker such as nifedipine or related compounds such as verapamil, diltiaze , isradipine, McN-6186, bepridil, niludipine perhexiline, nicardipine, flunarizine, nilvadipine. nisoldipine, nitrendipine, felodipine, cinnarazine, and nimodipine.
  • a calcium channel blocker such as nifedipine or related compounds such as verapamil, diltiaze , isradipine, McN-6186, bepridil, niludipine perhexiline, nicardipine, flunarizine, nilvadipine.
  • compositions for the topical treatment of cutaneous, ocular or mucosal hypersensitivity reactions, inflammation, hyperproliferation or scarring which consists of dissolving or suspending a calcium channel blocker selected from a member of the group consisting of nifedipine, verapamil, diltiazem, isradipine, McN-6186, bepridil, niludipine, perhexiline, nicardipine, flunarizine, nilvadipine, nisoldipine, nitrendipine, felodipine, cinnarazine, and nimodipine, in an appropriate preparation for topical administration. It is further an object of this invention to present a method and composition for the topical treatment of cutaneous, ocular of mucosal hypersensitivity reactions, inflammation, hyperproliferation, or scarring in a fashion that limits significant systemic effects.
  • the subject invention concerns novel topical compositions and method for inhibition of cutaneous, occular or mucosal hypersensitivity reactions, inflammation, hyperproliferation, or scarring.
  • the preferred composition described herein comprises a calcium channel blocker, such as nifedipine, in vehicles suitable for topical application and cutaneous, ocular or mucosal absorption.
  • these compositions have been shown to be effective when applied topically in inhibiting cutaneous contact hypersensitivity reactions at the site of application, but at doses that do not inhibit this response at a distant site. This latter point is important since it shows that systemic absorption is not important for this effect.
  • nifedipine and other related calcium channel blocker drugs make them useful as topical agents in treating contact dermatitis, atopic dermatitis, eczematous dermatitis, lichen planus, psoriasis and cutaneous lupus erythematosus , scleroderma, inflammatory acne, arthropod bit reactions f> conjunctivitis, ulceris keratoconjunctivitis, vaginitis, photosensitivity conditions including sunburn, chemical burns and thermal burns.
  • the novel method may also be useful in reducing the infiltration of skin by malignant leukocytes in diseases such as mycosis fungoides.
  • the composition simply consists of a calcium channel blocker drug of the type described above, dissolved in a suitable carrier for topical administration. The method of treatment is to apply the composition onto the affected area of the skin, eye, or mucosal membrane.
  • the sole figure is a graph which shows the effects of topical nifedipine on cutaneous hypersensitivity reactions (inflammation) .
  • the x axis represents time points 0, 24 and 48 hours after challenging both ears of mice with oxazolone and the y axis is measurement of ear thickness in mm x 10 —2
  • the subject invention is based on the discovery that cutaneous, ocular or mucosal hypersensitivity reactions, inflammation, epithelial hyperproliferation, or scarring, can be treated by topical formulations of the calcium channel blocker nifedipine and its related compound. Moreover, this effect can be directed to the site of application and immediate surrounding area without a significant similar systemic effect.
  • the conditions that the subject invention is therapeutically beneficial in treating include cutaneous hypersentivity/inflammatory conditions such as contact dermatitis, atopic dermatitis, eczematous dermatitis, lichen planus, lupus erythematosus, scleroderma, inflammatory acne, arthropod bite reactions, burns, and photosensitivity conditions, including sunburn; cutaneous epidermal hyperproliferative conditions such as psoriasis and ichthyosis; and mucosal hypersensitivity/inflammatory conditions such as lichen planus, aphthous ulcers, vaginitis, proctitis, conjunctivitis, ulceris and keratoconjunctivitis.
  • cutaneous hypersentivity/inflammatory conditions such as contact dermatitis, atopic dermatitis, eczematous dermatitis, lichen planus, lupus erythematosus, scleroderma, inflammatory acne, arthropod bite reactions, burns
  • the subject invention pertains not only to nifedipine, a calcium channel blocker drug, but also to derivatives and other related compounds which have similar biologic activity with respect to the control of inflammation, function, migration, and proliferation of cutaneous and mucosal cells.
  • Other such related compounds may include, but are not limited to other calcium channel blockers such as verapamil, diltiazem, isradipine, McN-6186, bepridil, niludipine, perhexiline, nicardipine, flunarizine, nilvadipine, nisoldipine, nitrendipine, felodipine, cinnarazine, nimodipine, and analogues and derivatives thereof. Nifedipine and the above related compounds are presently used for controlling anginal attacks and hypertension.
  • other calcium channel blockers such as verapamil, diltiazem, isradipine, McN-6186, bepridil, niludipine, perhexiline, nicardipine, flunarizine, nilvadipine, nisoldipine, nitrendipine, felodipine, cinnarazine, nimodipine,
  • Calcium blocker drugs such as those listed above inhibit the transmembrane influx of calcium ions into many cell types including cardiac muscle, smooth muscle, leukocytes, and epithelial cells. Recent rn vitro studies have also shown nifedipine to be effective in suppressing tumor necrosis factor induced adherence of neutrophils, a type of leukocyte, to human umbilical vein endothelial cells. Since nifedipine has been used in the treatment of angina and hypertension, toxicity information is readily available. The information indicates that nifedipine has not been shown to be either carcinogenic or mutagenic or to have serious adverse reactions. By applying these agents topically, therapeutic local concentrations are attainable without the associated systemic side effects.
  • Nifedipine that is used in the present invention can be generally presented by the form ⁇ in:
  • R a hydrogen of alkyl of 1 to 3 carbon atoms
  • R ⁇ an alkyl of l to 4 carbon atoms
  • R 2 a hydrogen, halogen, or 1 or 2 lower alkyl, lower alkoxy, nitro, lower acylamino, lower alkyla ino or amino moieties
  • the nifedipine of the subject invention and the other related compounds showing similar biologic activity can be modified in order to enhance their usefulness as pharmaceutical compositions.
  • various modifications such as alteration of charge, can alter water and lipid solubility and thus alter the potential for percutaneous absorption.
  • the vehicle can be similarly modified to enhance cutaneous absorption, enhance the reservoir effect and minimize irritancy of of the composition.
  • topical formulation can be occluded to further enhance absorption.
  • Preservatives, stabilizers, emulsifiers, emulsion stabilizers, antioxidants, chelating agents, solvents, thickening agents, emollients, and humectants may be necessary or useful as part of the topical formulation.
  • natural or artificial flavorings or sweeteners may be added to enhance the taste of topical preparations applied for local effect to mucosal surfaces.
  • Inert dyes or colors may be added, particularly in the case of preparations designed for application to oral mucosal surfaces.
  • Suitable vehicles or carriers for topical application may contain a daily dose of between 0.1 milligrams and 120 grams of between 0.001% to 100% (all percentages are by weight) of the calcium channel blocker nifedipine or a related compound, and may be prepared by conventional techniques to be in conventional forms such as lotions, suspension, ointments, creams, gels, tinctures, suppositories, elixirs, solution, aerosols, sprays, powders, pastes or slow release polymers for topical application; or mouth rinses or rectal or vaginal suppositories for local/topical application to these respective mucosal surfaces.
  • Suitable pharmaceutical diluents, solvents or carriers include, water, alcohols, sterols, propylene glycol, glycerin, polyethylene glycol, diisopropyl adipate, 1,2,6-hexanetriol, isopropyl myristate, propylene carbonate, natural and/or synthetic or hardened oils and waxes, kaolin, talc, titanium dioxide, as well as suitable solubulizers or emulsifying laureth sulfate, sodium lauryl sulfate, sorbitan esters, stearic acid, cetyl alcohol, cetearyl alcohol, or stearyl alcohol.
  • Stabilizers such as benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, chlorocresol, citric acid, edetate disodium, parabens, sodium bisulfite may be added.
  • Thickening agents such as petrolatum beeswax, xanthan gum, or polyethylene, plus humectants such as sorbitol solution may also be added.
  • emollients such as mineral oil, lanolin and its derivatives, or squalene can be included as part of the topical formulation.
  • Natural or artificial sweeteners including glucose, fructose, sucrose, aspartase, and saccharin may be added to enhance the palatability of preparations applied to mucosal surfaces.
  • flavorings such as peppermint oil may be added
  • Inert dyes such as yellow dye number 6, may be added, particularly in the case of preparations designed for topical application to oral mucosal surfaces.
  • composition of the vehicle for the subject invention is comprised of about 0.51% by weight of nifedipine dissolved in a vehicle consisting of about; 38% ethanol, 9.8% water, 0.8: sodium laureth sulfate, 3.2% isopropyl alcohol, 30% propylene glycol, 1.03% glycerin, 0.026% peppermint oil, 0.026% saccharin, and 16.6% polyethylene glycol 400 (PEG 400).
  • the nifedipine used is obtained from Pfizer in capsule form under the trade name Procardia and the liquid capsule contents were used for the experiments.
  • mice were sensitized to 3% oxazolone (4-ethoxymethylene-2-phenyl- oxazol-5-one) in 4:1 acetone/olive oil, by applying 50 microliters to the shaved abdomen an 5 microliters to microliters to the shaved abdomen an 5 microliters to each hind footpad of each mouse, seven days earlier. On the day of treatment each side of both ears of the mice were challenged with 10 microliters of 0.5% oxazolone in 4:1 acetone/olive oil (i.e. 20 microliters per ear).
  • mice One hour after challenge 10 microliters of the nifedipine or control preparation was applied to each side of a given ear (i.e. 20 microliters per ear). Each thicknesses of the mice were measured just before challenging with oxazolone, bars 10, 20, 30 and 40. Of those mice given the nifedipine preparation only the right ears were treated, bars 80 and 120. The nifedipine preparation reduced the oxazolone induced inflammation (i.e.
  • the contact sensitivity reaction to oxazolone significantly in the right ears of treated mice at 24 hours, bar 80 and at 48 hours, bar 120, after challenge with oxazolone as compared to the right ears of mice treated with 20 microliters of the vehicle preparation without nifedipine, bars 60 and 100.
  • the left ears of the mice treated on the right ear with nifedipine showed no decrease in swelling, bars 70 and 110; ear thickness measurements of these ears were the same as those of ears treated with the vehicle preparation without nifedipine, bars 60 and 100, or of those of the left ears of the mice treated on the right ears with vehicle lacking nifedipine, bars 50 an 90.
  • nifedipine another vehicle preparation (not containing the active ingredient, nifedipine) has been shown to be ineffective in suppressing the ear swelling response.
  • This vehicle was composed of about 1.86% water, 1.06% glycerin, 0.026% peppermint oil, 0.026: saccharin, 17% propylene glycol.
  • the lack of suppression of ears swelling by tow complex vehicles (lacking the active ingredient nifedipine) is evidence that the calcium channel blocker nifedipine is necessary for the effect.
  • Topical preparations of nifedipine and other related compounds may be used in combination with other active compounds in order to enhance the topical preparation's anti-proliferative, anti-inflammatory, anti-hypersensitivity, or anti-scarring properties, or to achieve additional therapeutic effects such as relief of pain or itching.
  • topical nifedipine preparations may be combined with topical corticosteroids, anti-fungal agents or anti-bacterial agents.
  • a traditional acne drug such as erythromycin, clinda ycin, benzoyl peroxide or a retinoid could be included as part of the preparation.
  • an antifungal drug such as clotrimazole, for the treatment of dermatophyte or Candida infection.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Birds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Procédé et composition de traitement topique de réactions d'hypersensibilité cutanée, oculaire ou des muqueuses, ainsi que d'états inflammatoires ou hyperprolifératifs épithéliaux, y compris ceux associés aux cicatrices. La composition à appliquer sur une zone affectée de la peau, de l'÷il ou d'une membrane de la muqueuse, consiste en une quantité thérapeutique de nifédipine ou d'un composé apparenté à la nifédipine, qui a été incorporé dans un excipient approprié à une application topique.
PCT/US1990/004632 1989-08-21 1990-08-16 Nifedipine topique pour le traitement de l'hypersensibilite cutanee, oculaire et de la muqueuse, ainsi que d'etats inflammatoires et hyperproliferatifs Ceased WO1991002497A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US39684689A 1989-08-21 1989-08-21
US396,846 1989-08-21

Publications (1)

Publication Number Publication Date
WO1991002497A1 true WO1991002497A1 (fr) 1991-03-07

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ID=23568865

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PCT/US1990/004632 Ceased WO1991002497A1 (fr) 1989-08-21 1990-08-16 Nifedipine topique pour le traitement de l'hypersensibilite cutanee, oculaire et de la muqueuse, ainsi que d'etats inflammatoires et hyperproliferatifs

Country Status (5)

Country Link
AU (1) AU6291990A (fr)
IE (1) IE903013A1 (fr)
PT (1) PT95061A (fr)
WO (1) WO1991002497A1 (fr)
ZA (1) ZA906583B (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994017839A1 (fr) * 1993-02-09 1994-08-18 Arch Development Corporation Procede d'amelioration de la taille et de l'aspect d'une cicatrice
US5484788A (en) * 1993-03-26 1996-01-16 Beth Israel Hospital Association Buspirone as a systemic immunosuppressant
US5631017A (en) * 1993-03-26 1997-05-20 Beth Israel Deaconess Medical Center, Inc. Topical application of buspirone for treatment of pathological conditions associated with immune responses
US5637314A (en) * 1995-06-07 1997-06-10 Beth Israel Deaconess Medical Center, Inc. Topical and systemic application of buspirone or derivatives thereof for treating atopic dermatitis
EP0757558A4 (fr) * 1994-04-12 1999-06-16 Alza Corp Procedes de criblage des agents modulateurs des inflammations tegumentaires
EP1053745A1 (fr) * 1999-05-18 2000-11-22 L'oreal Utilisation d'au moins un inhibiteur d'au moins un canal calcique dans le traitement des rides
US6225327B1 (en) 1996-04-18 2001-05-01 Alcon Laboratories, Inc. Compounds which inhibit human conjunctival mast cell degranulation for treating ocular allergic-type complications
EP0994709A4 (fr) * 1997-06-30 2006-02-01 Allergan Inc Antagonistes du calcium servant a traiter la vitreoretinopathie proliferative
WO2006018024A3 (fr) * 2004-08-18 2006-04-06 Ace Aps Compositions cosmetiques et pharmaceutiques contenant des inhibiteurs de l'eca et/ou des antagonistes des recepteurs de l'angiotensine ii
WO2008018110A3 (fr) * 2006-08-10 2008-04-03 Carmine Antropoli Utilisation de nifépidine dans des compositions anti-rides
US20180344714A1 (en) * 2017-05-30 2018-12-06 University Of Saskatchewan Topical nifedipine formulations and uses thereof

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2758263B1 (fr) * 1997-01-16 1999-12-17 Oreal Utilisation d'un antagoniste ou d'un agoniste de serotonine specifiques respectivement du recepteur 5ht2 et 5ht1d dans une composition cosmetique ou dermatologique pour peaux sensibles et composition obtenue
US6031005A (en) * 1998-08-03 2000-02-29 Easterling; W. Jerry Composition and method for treating Peyronie's disease and related connective tissue disorders

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4637930A (en) * 1984-02-08 1987-01-20 Yamanouchi Pharmaceutical Co, Ltd. Transdermal formulation of nicardipine hydrochloride
US4766213A (en) * 1986-01-17 1988-08-23 Merck Patent Gesellschaft Mit Beschrankter Haftung 1,4-dihydropyridines

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4637930A (en) * 1984-02-08 1987-01-20 Yamanouchi Pharmaceutical Co, Ltd. Transdermal formulation of nicardipine hydrochloride
US4766213A (en) * 1986-01-17 1988-08-23 Merck Patent Gesellschaft Mit Beschrankter Haftung 1,4-dihydropyridines

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994017839A1 (fr) * 1993-02-09 1994-08-18 Arch Development Corporation Procede d'amelioration de la taille et de l'aspect d'une cicatrice
US5552162A (en) * 1993-02-09 1996-09-03 Arch Development Corporation Method for improvement of scar size and appearance
US5484788A (en) * 1993-03-26 1996-01-16 Beth Israel Hospital Association Buspirone as a systemic immunosuppressant
US5631017A (en) * 1993-03-26 1997-05-20 Beth Israel Deaconess Medical Center, Inc. Topical application of buspirone for treatment of pathological conditions associated with immune responses
EP0757558A4 (fr) * 1994-04-12 1999-06-16 Alza Corp Procedes de criblage des agents modulateurs des inflammations tegumentaires
US5637314A (en) * 1995-06-07 1997-06-10 Beth Israel Deaconess Medical Center, Inc. Topical and systemic application of buspirone or derivatives thereof for treating atopic dermatitis
US6225327B1 (en) 1996-04-18 2001-05-01 Alcon Laboratories, Inc. Compounds which inhibit human conjunctival mast cell degranulation for treating ocular allergic-type complications
EP0994709A4 (fr) * 1997-06-30 2006-02-01 Allergan Inc Antagonistes du calcium servant a traiter la vitreoretinopathie proliferative
US7230032B2 (en) 1997-06-30 2007-06-12 Allergan, Inc. Calcium blockers to treat proliferative vitreoretinopathy
US8101635B2 (en) 1997-06-30 2012-01-24 Allergan, Inc. Calcium blockers to treat proliferative vitreoretinopathy
FR2793681A1 (fr) * 1999-05-18 2000-11-24 Oreal Utilisation d'au moins un inhibiteur d'au moins un canal calcique dans le traitement des rides
EP1053745A1 (fr) * 1999-05-18 2000-11-22 L'oreal Utilisation d'au moins un inhibiteur d'au moins un canal calcique dans le traitement des rides
US6344461B1 (en) 1999-05-18 2002-02-05 Societe L'oreal S.A. Treating skin wrinkles/fine lines with calcium channel inhibitors
US6908925B2 (en) 1999-05-18 2005-06-21 L'oreal Treating skin wrinkles/fine lines with calcium channel inhibitors
WO2006018024A3 (fr) * 2004-08-18 2006-04-06 Ace Aps Compositions cosmetiques et pharmaceutiques contenant des inhibiteurs de l'eca et/ou des antagonistes des recepteurs de l'angiotensine ii
AU2005274574B2 (en) * 2004-08-18 2011-03-17 Ace Aps Cosmetic and pharmaceutical compositions comprising ACE inhibitors and/or angiotensin II receptor antagonists
WO2008018110A3 (fr) * 2006-08-10 2008-04-03 Carmine Antropoli Utilisation de nifépidine dans des compositions anti-rides
US20180344714A1 (en) * 2017-05-30 2018-12-06 University Of Saskatchewan Topical nifedipine formulations and uses thereof
US10543202B2 (en) 2017-05-30 2020-01-28 University Of Sasktachewan Topical nifedipine formulations and uses thereof

Also Published As

Publication number Publication date
ZA906583B (en) 1991-09-25
AU6291990A (en) 1991-04-03
PT95061A (pt) 1991-05-22
IE903013A1 (en) 1991-02-27

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