EP0451156A1 - Compositions a base de minoxidil et de substances vasoconstrictives pour le traitement de l'alopecie - Google Patents
Compositions a base de minoxidil et de substances vasoconstrictives pour le traitement de l'alopecieInfo
- Publication number
- EP0451156A1 EP0451156A1 EP89912176A EP89912176A EP0451156A1 EP 0451156 A1 EP0451156 A1 EP 0451156A1 EP 89912176 A EP89912176 A EP 89912176A EP 89912176 A EP89912176 A EP 89912176A EP 0451156 A1 EP0451156 A1 EP 0451156A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- minoxidil
- vasoconstrictor
- composition
- hair growth
- percent
- 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.)
- Withdrawn
Links
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 229960003632 minoxidil Drugs 0.000 title claims abstract description 47
- 239000000203 mixture Substances 0.000 title claims abstract description 42
- 239000005526 vasoconstrictor agent Substances 0.000 title claims abstract description 38
- 201000004384 Alopecia Diseases 0.000 title abstract description 13
- 231100000360 alopecia Toxicity 0.000 title abstract description 9
- 230000003779 hair growth Effects 0.000 claims abstract description 17
- 239000003937 drug carrier Substances 0.000 claims abstract description 5
- 238000011282 treatment Methods 0.000 claims description 17
- 230000000699 topical effect Effects 0.000 claims description 15
- 229960001102 betamethasone dipropionate Drugs 0.000 claims description 5
- CIWBQSYVNNPZIQ-XYWKZLDCSA-N betamethasone dipropionate Chemical group C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CIWBQSYVNNPZIQ-XYWKZLDCSA-N 0.000 claims description 5
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 claims description 4
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 claims description 4
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 claims description 4
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 claims description 4
- 229960002646 scopolamine Drugs 0.000 claims description 4
- 239000003246 corticosteroid Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 7
- 230000001737 promoting effect Effects 0.000 abstract 1
- 239000012049 topical pharmaceutical composition Substances 0.000 abstract 1
- 208000004631 alopecia areata Diseases 0.000 description 6
- 210000004761 scalp Anatomy 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 4
- 239000006071 cream Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 210000003780 hair follicle Anatomy 0.000 description 3
- 230000003676 hair loss Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 208000024963 hair loss Diseases 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- ZIMGGGWCDYVHOY-UHFFFAOYSA-N 3-hydroxy-2-imino-6-(1-piperidinyl)-4-pyrimidinamine Chemical compound N=C1N(O)C(N)=CC(N2CCCCC2)=N1 ZIMGGGWCDYVHOY-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- MLATXMYELRPHEP-UHFFFAOYSA-N [O-]S(O[N+]1=CC=CN=C1)(=O)=O Chemical compound [O-]S(O[N+]1=CC=CN=C1)(=O)=O MLATXMYELRPHEP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 206010068168 androgenetic alopecia Diseases 0.000 description 1
- 229940092732 belladonna alkaloid Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940068917 polyethylene glycols Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940107889 rogaine Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000003639 vasoconstrictive effect Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
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
-
- 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
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
-
- 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
- A61K8/63—Steroids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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 an improved composition for treating alopecia, including alopecia areata which can effect young children.
- the improved composition is effective in the treatment of alopecia which is generally defined as a baldness resulting from common male pattern baldness or hair loss disorders which can occur in females and young children. In the latter two situation, while the disorder poses little threat to the individuals health, it can be emotionally devastating. Therefore it is desirable to develop new and improved methods for restoring hair growth.
- the present invention comprises an application of minoxidil and vasoconstrictors which is herein demonstrated to have superior hair growth results over the application of minoxidil alone.
- Minoxidil and its analogs are well known in the treatment of hair loss.
- minoxidil is available by prescription as ROGAINE ® a trademark of The Upjohn Company, Kalamazoo, Michigan.
- the prepara ⁇ tion of minoxidil topical compounds for application to the scalp are also disclosed in U.S. Patents 4,139,619 and 4,596,812.
- Topical compositions of minoxidil for the treatment of hair growth, alopecia are known as disclosed in U.S. Patents 4,139,619 and 4,596,812. Also, background information on various minoxidil compounds and analogs is disclosed in U.S. Patents 3,382,247, 3,461,461, 3,644,364 and 4,287,338. Also, the use of a 2% solution of minoxidil with betamethasone cream was reported in Pediatric Dermatology, Vol. 4, No. 2, pages 136-158 (page 150) (1987) entitled "Special Symposium: Alopecia Areata Symposium". Summary of the Invention
- the subject invention is an improved composition for the 'promotion of hair growth or treatment of alopecia comprising minoxidil in an amount of at least 2.5 percent and a vasoconstrictor in an effective amount wherein hair growth is increased over the use of minoxidil alone.
- a vasoconstrictor is a corticosteroid or a scopolamine, preferably betamethasone dipropionate.
- the amount of a vasoconstrictor is from about 0.01 to about 1.0 percent, preferably about 0.01 to about 0.10 percent, more preferably 0.05 percent.
- composition can additionally include a pharmaceutical carrier adapted for topical application.
- the present invention is a method for treating or preventing alopecia comprising the topical administration to hair follicles of a composition comprising at least 2.5% minoxidil and a vasoconstrictor in an effective amount to treat or prevent alopecia.
- the topical administration can be preformed by applying the minoxidil and vasoconstrictor either separately or simultaneously as a single topical application.
- the composition is routinely applied to the hair follicles, preferably twice daily or daily.
- the improved topical composition for the treatment of hair growth comprises minoxidil and a vasoconstrictor.
- the minoxidil portion is 6-amino-l,2-dihydro-hydroxy-2-imino-4-piperidinopyrimidine and analogs thereof.
- the preparation of these compounds are describ- ed in U.S. Patents 3,382,247, 3,461,461 and 3,644,364 and J.M. McCall, et al., Journal of Organic Chemistry, 40, 3304 (1975) all of which are hereby incorporated by reference.
- Related compounds are sulfoxypyrimidinium, -pyridinium, and -triazinium which are described in U.S. Patent 4,287,338 herein incorporated by reference.
- the term "minoxidil” means any of the various forms of 6- amino-1,2-dihydro-hydroxy-2-imino-4-piperidinopyrimidine, derivatives and analogs thereof.
- Minoxidil is present in the composition in an amount of from about one to about five percent by weight (“percent"), preferably at least two and a half to about five percent. Best results can be achieved when the minoxidil is present in an amount of about five percent; however, when treating children lesser amounts of minoxidil is employed to avoid any adverse reactions.
- the vasoconstrictor portion of the composition provides enhanced action of the minoxidil and hair growth is significantly improved versus an application of only minoxidil.
- the vasoconstrictor is incorporated with minoxidil such that they can both be applied in a single application.
- the vasoconstrictor and minoxidil can be applied separately to the treatment area without departing from the improved benefit of this invention. Therefore, the term "composition" and amounts of either minoxidil and vasoconstrictor present therein are determined when both are present on the treatment area regardless of method of application.
- Vasoconstrictors appropriate for applying or compounding with minoxidil comprise potent topical corticosteriods which can include a class of natural and synthetic compounds. Typically these steroids are hormones secreted by the adrenal cortex and are noted for their vasoconstrictive actions.
- One preferred vasoconstrictor is betameth ⁇ asone dipropionate.
- Other agents such as scopolamine which is a belladonna alkaloid and has vasoconstrictor activity can be used.
- the vasoconstrictor is applied to the scalp or is present in the composition from about 0.01 to about 1.0 percent, preferably from about 0.01 to about 0.10 percent, more preferably 0.05 percent.
- the improved minoxidil composition is characterized by the presence of a vasoconstrictor as described above.
- the improved composition is a formulation of minoxidil and the vasocon- stricter suitable for topical administration.
- topical means a composition of minoxidil and a composition of vasoconstrictor or both incorporated in a suitable pharmaceutical carrier which can be applied to the treatment site for local action.
- Typical topical compositions include those pharmaceutical forms in which can be applied externally by direct contact with the surface to be treated.
- Conventional pharmaceutical forms for this purpose include ointments, waxes, lotions, pastes, jellies, sprays, aerosols, and the like in aqueous or nonaqueous formulations.
- the term "ointment” embraces formulations (including creams) having oleagin- ous, absorption, water-soluble and emulsion-type bases, e.g., petrolatum, lanolin, polyethylene glycols, as well as mixtures of these.
- minoxidil topical compositions are disclosed in U.S. Patents 4,139,619 and 4,596,812, both herein incorporated by reference.
- the preparation of topical compositions containing both minoxidil and a vasoconstrictor is the result of admixing the vaso ⁇ constrictor with the minoxidil topical composition.
- the improved composition can be applied to the area to be treated, such as the scalp in humans, by spraying, dabbing or swabbing. Other less specific methods can be employed provided the active ingredients, minoxidil and vasoconstrictor, are delivered to the region of the hair follicle.
- the composition is periodically applied to the treatment area on a routine basis prior to, during and subsequent to hair growth.
- the routine treatment would be to apply the minoxidil and vasoconstrictor at least daily, preferably twice daily.
- the alopecia areata is in remission treatment can be discontinued.
- Four patients with severe, treatment resistant alopecia areata were treated with one milliliter of a 2% topical minoxidil solution by applying it to their entire scalp.
- the patients also had their entire scalp treated with a 1 gram application of a vasoconstrictor, betamethasone dipropionate 0.05% cream.
- the vasoconstrictor in some treatments was applied 30 minutes before and in some cases 30 minutes after the minoxidil treatment. All four patients exhibited cosmeti- cally good hair growth and have maintained the regrowth with con ⁇ tinued treatment.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Abstract
Composition et procédé améliorés permettant de promouvoir la cro issance des cheveux ou de traiter l'alopécie, où la composition comprend au moins 2,5 pour cent de minoxidil et d'un vasoconstricteur en une quantité suffisante pour accroître davantage la croissance des cheveux que ne le ferait l'application du seul minoxidil. Ladite composition peut entrer dans une formulation topicale utilisant des porteurs pharmaceutiques appropriés. Le procédé consiste en l'administration locale du minoxidil et du vasoconstricteur en une quantité efficace pour stimuler la croissance des cheveux.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27936688A | 1988-12-02 | 1988-12-02 | |
| US279366 | 1994-07-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0451156A1 true EP0451156A1 (fr) | 1991-10-16 |
Family
ID=23068646
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP89912176A Withdrawn EP0451156A1 (fr) | 1988-12-02 | 1989-10-30 | Compositions a base de minoxidil et de substances vasoconstrictives pour le traitement de l'alopecie |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0451156A1 (fr) |
| JP (1) | JPH04501851A (fr) |
| KR (1) | KR910700039A (fr) |
| AU (1) | AU4500889A (fr) |
| WO (1) | WO1990006100A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2181584C1 (ru) * | 2001-04-25 | 2002-04-27 | Московская медицинская академия им. И.М. Сеченова | Стимулятор роста волос |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0542802T3 (da) * | 1990-08-10 | 1996-07-22 | Upjohn Co | Stimulering af hårvækst med kaliumkanalåbnere og 5alfa-reduktase-inhibitorer |
| US5130142A (en) * | 1990-10-31 | 1992-07-14 | The Practer & Gamble Company | Hair growth regulating composition comprising epithelium cell supernatant-derived growth factor |
| WO2006051287A1 (fr) * | 2004-11-10 | 2006-05-18 | Arrow International Limited | Préparation et méthode pour le traitement de l’alopécie aréata |
| EP3548035A4 (fr) * | 2016-11-30 | 2020-07-22 | Case Western Reserve University | Combinaisons d'inhibiteurs de 15-pgdh avec des corcostéroïdes et/ou des inhibiteurs du tnf et leurs utilisations |
| JP2020514323A (ja) | 2017-02-06 | 2020-05-21 | ケース ウエスタン リザーブ ユニバーシティ | 短鎖デヒドロゲナーゼ活性を調節する組成物と方法 |
| KR102921276B1 (ko) | 2018-11-21 | 2026-02-03 | 케이스 웨스턴 리저브 유니버시티 | 단쇄 데히드로게나아제 활성을 조절하는 조성물 및 방법 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2101044A2 (en) * | 1969-11-26 | 1972-03-31 | Orsymonde | Freeze-dried oil - in - water emulsions - for treatment of mouth , teeth, hair and scalp |
| ATE122873T1 (de) * | 1987-03-30 | 1995-06-15 | Upjohn Co | Kombination aus minoxidil und einer antiinflammatorischen substanz zur behandlung der alopezie. |
-
1989
- 1989-10-30 WO PCT/US1989/004775 patent/WO1990006100A1/fr not_active Ceased
- 1989-10-30 JP JP1511323A patent/JPH04501851A/ja active Pending
- 1989-10-30 KR KR1019900701675A patent/KR910700039A/ko not_active Withdrawn
- 1989-10-30 AU AU45008/89A patent/AU4500889A/en not_active Abandoned
- 1989-10-30 EP EP89912176A patent/EP0451156A1/fr not_active Withdrawn
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9006100A1 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2181584C1 (ru) * | 2001-04-25 | 2002-04-27 | Московская медицинская академия им. И.М. Сеченова | Стимулятор роста волос |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH04501851A (ja) | 1992-04-02 |
| KR910700039A (ko) | 1991-03-13 |
| AU4500889A (en) | 1990-06-26 |
| WO1990006100A1 (fr) | 1990-06-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 19901115 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
| 18W | Application withdrawn |
Withdrawal date: 19920413 |