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WO1988004171A1 - Utilisation du nicorandil pour le traitement de l'alopecie - Google Patents

Utilisation du nicorandil pour le traitement de l'alopecie Download PDF

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Publication number
WO1988004171A1
WO1988004171A1 PCT/US1987/002915 US8702915W WO8804171A1 WO 1988004171 A1 WO1988004171 A1 WO 1988004171A1 US 8702915 W US8702915 W US 8702915W WO 8804171 A1 WO8804171 A1 WO 8804171A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
alopecia
hair
pharmaceutically acceptable
pharmaceutical composition
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/US1987/002915
Other languages
English (en)
Inventor
Jackson B. Hester, Jr.
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
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
Application filed by Upjohn Co filed Critical Upjohn Co
Publication of WO1988004171A1 publication Critical patent/WO1988004171A1/fr
Anticipated expiration legal-status Critical
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
    • A61K31/33—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
    • A61K31/435—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
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • the present invention relates to methods, compositions and solutions for treating human alopecia, including male pattern alopecia (androgenic alopecia) and alopecia areata, involving the use of N-[2-(nitrooxy)ethyl]-3-pyridine carboxamide(nicorandil) and pharmaceutically acceptable salts thereof in association with a pharmaceutical carrier adapted for topical application.
  • Terminal hairs are coarse, pigmented, long hairs in which the bulb of the hair follicle is seated deep in the dermis.
  • Vellus hairs are fine, thin, non-pigmented short hairs in which the hair bulb is located superficially in the dermis. As alopecia progresses, a transition takes place in the area of approaching baldness wherein the hairs themselves are changing from the terminal to the vellus type.
  • the anagen phase is the period of active hair growth and, insofar as scalp hair is concerned, this generally lasts from 3-5 years.
  • the catagen phase is a short transitional phase between the anagen and telogen phases which, in the case of scalp hair, lasts only 1-2 weeks.
  • the final phase is the telogen phase which, for all practical purposes, can be denominated by a "resting phase” where all growth ceases and the hair eventually is shed preparatory to the follicle commencing to grow a new one.
  • Scalp hair in the telogen phase is also relatively short-lived, some three to four months elapsing before the hair is shed and a new one begins to grow.
  • the remaining result associated with alopecia is the severe diminution of hair follicles.
  • a bald human subject will average only about 306 follicles per square centimeter, whereas, a non-bald one in the same age group (30-90 years) will still have an average of 460 follicles per square centimeter.
  • This amounts to a one-third reduction in hair follicles which, when added to the increased proportion of vellus hair follicles and the increase number of hair follicles in telogen, is both significant and noticeable. It is written that approximately 50% of the hairs must be shed to produce visible thinning of scalp hair.
  • the androgenic hormone testosterone was known, for example, to stimulate hair growth when applied topically to the deltoid area as well as when injected into the beard and pubic regions. Even oral administration was found to result in an increased hair growth in the beard and pubic areas as well as upon the trunk and extremities. While topical application to the arm causes increased hair growth, it is ineffective on the scalp and some thinning may even result. Heavy doses of testosterone have been even been known to cause male pattern alopecia.
  • Minoxidil is a well-known pharmaceutical compound. It is marketed by the Upjohn Company as the active ingredient in LONITEN ® Tablets for the treat- ment of hypertension. It is also useful in topical compositions for the treatment of baldness. The structure and use of this compound is described in U.S. Patents 4,139,619 and 4,596,812. This compound has varying degrees of efficacy for hair growth purposes, depending on the patient, the degree of baldness, the dose and the nature of the topical composition.
  • the present invention provides a novel, non-obvious and effective treatment for human baldness, such as pattern baldness.
  • U.S. Patent 4,200,640 discloses the use of nicorandil and its pharmaceutically acceptable salts for treating circulatory disease, such as coronary vasodilating action, antihypertensive action, antiarrhythmic action, anticoagulative action and peripheral vasodilating action and, thus, it is useful for treating ischemic heart disease, as an antihypertensive drug, anticoagulative drug, antiarrhythmic drug, and as a peripheral vasodilator Including cerebral vasodilator and renal vasodilator.
  • circulatory disease such as coronary vasodilating action, antihypertensive action, antiarrhythmic action, anticoagulative action and peripheral vasodilating action and, thus, it is useful for treating ischemic heart disease, as an antihypertensive drug, anticoagulative drug, antiarrhythmic drug, and as a peripheral vasodilator Including cerebral vasodilator and renal vasodilator.
  • WIer et al, Br. J. Pharme (1986), 88, pp. 121-128 describe the effects of nicorandil on electrical and mechanical activity on 86 Rb efflux in rat blood vessels.
  • U.S. Patent 4,596,812 discloses the use of minoxidil, 6-amino- 1,2-dihydro-1-hydroxy-2-Imino-4-piperidinopyrimidine, as a therapeutic agent to treat alopecia and arrest and reverse male pattern alopecia.
  • U.S. Patent 4,139,619 discloses the use of minoxidil and related 6-amino-4-(substituted amino)-1,2-dihydro-l-hydroxy-2-imino- pyrimidines as a means for (a) Increasing the rate of growth of terminal hair, and (b) converting vellus hair to growth as terminal hair.
  • the use of retinoids alone or in combination with minoxidil and related substituted pyrimidines to increase the rate of hair growth is disclosed in PCT publication numbers US85/04577, PCT US83/02558 and PCT US82/02833.
  • minoxidil sulfate (2,6,-diamino-4-(1-piperidinyl)-1- (sulfooxy)-pyrimidinium hydroxide, inner salt)
  • minoxidil sulfate 2,6,-diamino-4-(1-piperidinyl)-1- (sulfooxy)-pyrimidinium hydroxide, inner salt
  • a method of treating humans for alopecia which comprises topically applying to the human scalp an effective amount of a pharmaceutical composition containing a compound of Formula I or a pharmaceutically acceptable salt thereof;
  • a topical pharmaceutical composition for the treatment of alopecia consisting of a compound of Formula I or a pharmaceutically acceptable salt thereof and a pharmaceutical carrier adapted for topical application.
  • this invention relates to the method for treating humans for alopecia, Including androgenic alopecia (male pattern baldness; male pattern alopecia) and alopecia areata, which comprises regular topical application to the affected areas of the human skin a pharmaceutical composition containing as at least one of its active ingredients a compound of Formula I. It also encompasses the use of a compound of Formula I as a therapeutic agent to arrest and reverse androgenic alopecia.
  • compositions contemplated by this invention include pharmaceutical compositions adapted for topical application to the human scalp.
  • Conventional pharmaceutical forms for this purpose include ointments, lotions, pastes, jellies, gels, mousses, sprays, foams, aerosols, and the like.
  • ointment embraces formulations (including creams) having oleaginous, absorption, water- soluble and emulsion-type bases, e.g., petrolatum, lanolin, poly- ethylene glycols, as well as mixtures of these.
  • the compounds may also be formulated into lipsomal preparations or lipid emulsions or dissolved in conventional solvents such as acetonitrile, dimethylformamide (DMF), dimethylacetamide (DMA), alcohol, propanol, and the like.
  • the percentage by weight of the compound of the Formula I herein utilized typically ranges from about 0.1% to about 10.0% of the pharmaceutical preparation, preferably from about 1% to about 5% and in these preparations the aforesaid pharmaceutical carrier for topical application constitutes a major amount of the said preparation.
  • the pharmaceutical preparations of the subject invention are applied on a regular basis, with or without occlusion, for a period of time sufficient to effect hair growth.
  • Occlusion of the prepar ation may be obtained by any conventional means such as bandages, plastic coverings, shower caps swimming caps, etc.
  • the percentage of active ingredient (Formula I) as well as frequency of application may be varied as necessary or desirable to achieve the desired results.
  • Example 1 The present invention is seen more by fully the examples given below.
  • Example 1 The present invention is seen more by fully the examples given below.
  • Vibrissae follicles from neonatal mice were cultured in Delbeco' s-minimum essential medium (Modified Eagles Medium - manufactured by DIfco Company) with 20% fetal calf serum. Hair growth was measured by recording increases in hair shaft length during culture and by determining incorporation of 35 S cysteine in hair shafts. The administration of 0.1 mg/ml of nicorandil to this medium stimulated hair growth as measured by both of these endpoints.
  • Delbeco' s-minimum essential medium Modified Eagles Medium - manufactured by DIfco Company
  • the propylene glycol and 150 liters of alcohol are added to a mixing tank, the Nicorandil is added and dissolved in the propylene glycol/- alcohol mixture and additional alcohol added to make 250 liters.
  • the resulting Nicorandil topical solution is packaged in suitable dispensing bottles, accompanied by a metered dropper, and applied to the prewashed scalp as a total dose of 1 ml., beginning in the center of the affected area. Twice daily application for 2 to 7 months or longer may be required before evidence of hair growth stimulation can be expected in the treatment of early, progressive male pattern baldness. Onset and degree of hair growth stimulation can be expected to vary considerably among patients.
  • Nicorandil topical solutions are similarly prepared in accordance with the foregoing procedure by utilizing 0.25 kg. and 2.5 kg., respectively of Nicorandil for the 5.0 kg. utilized In the preparation of the 2% solution of Example 2. Following the procedure of the preceding Examples 1 and 2, inclusive, compositions are similarly prepared substituting an equimolar amount of another compound within the scope of Formula I for Nicorandil. Following the procedure of the preceding Examples 1 and 2, inclusive, compositions are similarly prepared substituting an equimolar amount of the various pharmaceutically acceptable salts of nicorandil.

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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)
  • Bioinformatics & Cheminformatics (AREA)
  • Birds (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cosmetics (AREA)
  • Pyridine Compounds (AREA)

Abstract

Procédé de traitement de la calvitie chez l'homme, y compris celui de l'alopécie connue sous le nom de "calvitie masculine", comprant l'application régulière sur la zone affectée du cuir chevelu d'une composition contenant comme l'un de ses ingrédients au moins le composé de formule (I). Ce procédé comprend également l'utilisation du composé dans une composition pharmaceutique à titre d'agent thérapeutique en vue de stopper et d'inverser le processus de la calvitie masculine.
PCT/US1987/002915 1986-12-12 1987-11-10 Utilisation du nicorandil pour le traitement de l'alopecie Ceased WO1988004171A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US94119186A 1986-12-12 1986-12-12
US941,191 1986-12-12

Publications (1)

Publication Number Publication Date
WO1988004171A1 true WO1988004171A1 (fr) 1988-06-16

Family

ID=25476079

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1987/002915 Ceased WO1988004171A1 (fr) 1986-12-12 1987-11-10 Utilisation du nicorandil pour le traitement de l'alopecie

Country Status (4)

Country Link
EP (1) EP0333743A1 (fr)
JP (1) JPH02501570A (fr)
AU (1) AU8276987A (fr)
WO (1) WO1988004171A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989006530A1 (fr) * 1988-01-21 1989-07-27 Leo Pharmaceutical Products Ltd. A/S (Løvens Kemis Nouvelle preparation topique servant au traitement de l'alopecie

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0232007A (ja) * 1988-07-21 1990-02-01 Shiseido Co Ltd 養毛剤

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4200640A (en) * 1976-04-02 1980-04-29 Chugai Seiyaku Kabushiki Kaisha Nitric ester of N-(2-hydroxyethyl)nicotinamide and pharmaceutical use
US4596812A (en) * 1976-05-24 1986-06-24 The Upjohn Company Methods and solutions for treating male pattern alopecia
WO1986004231A1 (fr) * 1985-01-25 1986-07-31 The Upjohn Company Sulfates de pyrimidine favorisant la croissance des cheveux
EP0243248A1 (fr) * 1986-04-18 1987-10-28 Laboratoires Pharmaceutiques Roche-Posay Compositions pour le traitement de la calvitie et des alopécies

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60261985A (ja) * 1984-06-08 1985-12-25 Shipbuild Res Assoc Japan スラリー圧送用フリーピストンポンプにおける空気抜き装置

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4200640A (en) * 1976-04-02 1980-04-29 Chugai Seiyaku Kabushiki Kaisha Nitric ester of N-(2-hydroxyethyl)nicotinamide and pharmaceutical use
US4596812A (en) * 1976-05-24 1986-06-24 The Upjohn Company Methods and solutions for treating male pattern alopecia
WO1986004231A1 (fr) * 1985-01-25 1986-07-31 The Upjohn Company Sulfates de pyrimidine favorisant la croissance des cheveux
EP0243248A1 (fr) * 1986-04-18 1987-10-28 Laboratoires Pharmaceutiques Roche-Posay Compositions pour le traitement de la calvitie et des alopécies

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989006530A1 (fr) * 1988-01-21 1989-07-27 Leo Pharmaceutical Products Ltd. A/S (Løvens Kemis Nouvelle preparation topique servant au traitement de l'alopecie

Also Published As

Publication number Publication date
AU8276987A (en) 1988-06-30
JPH02501570A (ja) 1990-05-31
EP0333743A1 (fr) 1989-09-27

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