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| United States Patent | 4139619 |
| Link to this page | http://www.wikipatents.com/4139619.html |
| Inventor(s) | Chidsey, III; Charles A. (Denver, CO) |
| Abstract | This invention relates to a process for stimulating the growth of mammalian
hair comprising the application to mammalian skin of a compound of the
formula:
##STR1##
wherein R.sub.1 is a moiety selected from the group consisting of moieties
of the formula
##STR2##
wherein R.sub.3 and R.sub.4 are selected from the group consisting of
hydrogen, lower alkyl, lower alkenyl, lower aralkyl, and lower cycloalkyl,
and taken together R.sub.3 and R.sub.4 may be a heterocyclic moiety
selected from the group consisting of aziridinyl, azetidinyl,
pyrrolidinyl, piperidino, hexahydroazepinyl, heptamethylenimino,
octamethylenimino, morpholino, and 4-lower-alkylpiperazinyl, each of said
heterocyclic moieties having attached as substituents on the carbon atoms
0-3 lower alkyl groups, hydroxy or alkoxy wherein R.sub.2 is selected from
the group consisting of hydrogen, lower alkyl, lower alkenyl, lower
alkoxyalkyl, lower cycloalkyl, lower aryl, lower aralkyl, lower alkaryl,
lower alkaralkyl, lower alkoxyaralkyl, and lower haloaralkyl and the
pharmacologically acceptable acid addition salts thereof in association
with a topical pharmaceutical carrier. |
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Title Information  |
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Drawing from US Patent 4139619 |
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6-Amino-4-(substituted amino)-1,2-dihydro-1-hydroxy-2-iminopyrimidine,
topical compositions and process for hair growth |
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| Publication Date |
February 13, 1979 |
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| Filing Date |
August 19, 1977 |
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| Parent Case |
CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation of application Ser. No. 689,473, filed
May 24, 1976, now abandoned, which is a continuation of application Ser.
579,559, filed May 21, 1975, now abandoned, which in turn is a
continuation of application Ser. No. 396,820, filed Sept. 13, 1973, now
abandoned, which in turn is a continuation of application Ser. No.
213,743, filed Dec. 29, 1971, now abandoned. |
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Title Information |
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References |
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Other References |
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References |
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| Market Size |
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Estimate the gross annual revenues of the relevant market
sector:
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| Market Share |
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Estimate the percentage of the relevant market sector this invention will capture:
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| Reasonable Royalty |
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What percentage of gross sales should the inventor or assignee be paid?
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Public's "Guesstimation" of Royalty Value
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| Market Size | N/A | [No votes] | | x | Market Share | N/A | [No votes] | | x | Reasonable Royalty | N/A | [No votes] |
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Market Review |
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Technical Review |
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Claims |
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I claim:
1. A topical composition for application to mammalian skin comprising an
effective amount of a compound of the formula:
##STR3##
wherein R.sub.1 is a moiety selected from the group consisting of moieties
of the formula
##STR4##
wherein R.sub.3 and R.sub.4 are selected from the group consisting of
hydrogen, lower alkyl, lower alkenyl, lower aralky, and lower cycloalkyl,
and taken together R.sub.3 and R.sub.4 may be a heterocyclic moiety
selected from the group consisting of aziridinyl, azetidinyl,
pyrrolidinyl, piperidino, hexahydroazepinyl, heptamethylenimino,
octamethylenimino, morpholino, and 4-lower-alkylpiperazinyl, each of said
heterocyclic moieties having attached as substituents on the carbon atoms
0-3 lower alkyl groups, hydroxy or alkoxy, and wherein R.sub.2 is selected
from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower
alkoxyalkyl, lower cycloalkyl, lower aryl, lower aralkyl, lower alkaryl,
lower alkaralkyl, lower alkoxyaralkyl, and lower haloaralkyl and the
pharmacologically acceptable acid addition salts thereof, in association
with a topical pharmaceutical carrier selected from the group consisting
of ointments, lotions, pastes, jellies, sprays, and aerosols.
2. The composition of claim 1 wherein the concentration of the compound is
from about 0.1% to about 20% of the composition.
3. The composition of claim 1 wherein the compound is
6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine in the form
of the free base or acid addition salts thereof.
4. A process for increasing the rate of terminal hair growth in mammalian
species comprising the application to mammalian skin at the locale of
terminal hair of an effective amount of a compound of the formula:
##STR5##
wherein R.sub.1 is a moiety selected from the group consisting of moieties
of the formula
##STR6##
wherein R.sub.3 and R.sub.4 are selected from the group consisting of
hydrogen, lower alkyl, lower alkenyl, lower aralkyl, and lower cycloalkyl,
and taken together R.sub.3 and R.sub.4 may be a heterocyclic moiety
selected from the group consisting of aziridinyl, azetidinyl,
pyrrolidinyl, piperidino, hexahydroazepinyl, heptamethylenimino,
octamethylenimino, morpholino, and 4-lower-alkylpiperazinyl, each of said
heterocyclic moieties having attached as substituents on the carbon atoms
0-3 lower alkyl groups, hydroxy or alkoxy, and wherein R.sub.2 is selected
from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower
alkoxyalkyl, lower cycloalkyl, lower aryl, lower aralkyl, lower alkaryl,
lower alkaralkyl, lower alkoxyaralkyl, and lower haloaralkyl and the
pharmacologically acceptable acid addition salts thereof, in association
with a topical pharmaceutical carrier.
5. The process of claim 4 wherein the concentration of the compound applied
is from about 0.1% to about 20% of the composition.
6. The process of claim 4 wherein compound applied is
6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine.
7. A process for the conversion of vellus hair to growth as terminal hair
comprising the application to mammalian skin at the locale of vellous hair
of an effective amount of a compound of the formula:
##STR7##
wherein R.sub.1 is a moiety selected from the group consisting of moieties
of the formula
##STR8##
wherein R.sub.3 and R.sub.4 are selected from the group consisting of
hydrogen, lower alkyl, lower alkenyl, lower aralkyl, and lower cycloalkyl,
and taken together R.sub.3 and R.sub.4 may be a heterocyclic moiety
selected from the group consisting of aziridinyl, azetidinyl,
pyrrolidinyl, piperidino, hexahydroazepinyl, heptamethylenimino,
octamethylenimino, morpholino, and 4-lower-alkylpiperazinyl, each of said
heterocyclic moieties having attached as substituents on the carbon atoms
0-3 lower alkyl groups, hydroxy or alkoxy, and wherein R.sub.2 is selected
from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower
alkoxyalkyl, lower cycloalkyl, lower aryl, lower aralkyl, lower alkaryl,
lower alkaralkyl, lower alkoxyaralkyl, and lower haloaralkyl and the
pharmacologically acceptable acid addition salts thereof, in association
with a topical pharmaceutical carrier.
8. The process of claim 7 wherein the concentration of the compound applied
is from about 0.1% to about 20% of the composition.
9. The process of claim 7 wherein the compound applied is
6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine. |
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Claims |
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Description |
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The active compounds of the present invention and method for their
preparation are disclosed in U.S. Pat. No. 3,461,461, issued Aug. 12, 1969
and U.S. application Ser. No. 132,153, filed Apr. 7, 1971.
BRIEF DESCRIPTION OF THE INVENTION
This invention relates to pharmaceutical compositions for topical
application comprising a compound of the formula I, in the form of the
free base or acid addition salts thereof, in association with a
pharmaceutical carrier adapted for topical application to mammalian skin.
Another aspect of the invention is a process for increasing the rate of
terminal hair growth and a process for stimulating the conversion of
vellus hair to growth as terminal hair.
DETAILED DESCRIPTION
Alopecia (baldness) a deficiency of hair, either normal or abnormal, is
primarily a cosmetic problem in humans. It is a deficiency of terminal
hair, the broad diameter, colored hair that is readily seen. However, in
the so-called bald person although there is a noticeble absence of
terminal hair the skin does contain vellus hair which is a fine colorless
hair which may require microscopic examination to determine its presence.
This vellus hair is a precursor to terminal hair. A compound of the
formula I can be used to stimulate the conversion of vellus hair to growth
as terminal hair as well as increasing the rate of growth of terminal
hair.
The present invention finds application in all mammalian species, including
both humans and animals. In humans, the compounds of the subject invention
can be applied for example, to the head, pubic area, upper lip, eyebrows,
and eyelids. In animals raised for their pelts, e.g. mink, the compounds
can be applied over the entire surface of the body to improve the overall
pelt for commercial reasons. The process can also be used for cosmetic
reasons in animals, e.g. applied to the skin of dogs and cats having bald
patches due to mange or other diseases.
The pharmaceutical compositions contemplated by this invention include
pharmaceutical compositions suited for topical and local action.
The term "topical" as employed herein relates to the use of a compound of
the formula I, incorporated in a suitable pharmaceutical carrier, and
applied at the site of baldness for exertion of local action. Accordingly,
such topical compositions includ those pharmaceutical forms in which the
compound is applied externally by direct contact with the skin surface to
be treated. Conventional pharmaceutical forms for this purpose include
ointments, lotions, pastes, jellies, sprays, aerosols, and the like. The
term "ointment" embraces formulations (including creams) having
oleaginous, absorption, water-soluble and emulsion-type bases, e.g.,
petrolatum, lanolin, polyethylene glycols, as well as mixtures of these.
The percentage by weight of the compound of the formula I herein utilized
ranges from about 0.1% to about 20.0% of the pharmaceutical preparation,
preferably from about 0.5% to about 2% and in these preparations the
aforesaid pharmaceutical carrier for topical application constitutes a
major amount of the said preparation.
The following examples describe the manner and process of making and using
the invention and set forth the best mode contemplated by the inventor of
carrying out the invention but are not to be construed as limiting.
EXAMPLE 1 Topical Cream
One-thousand gm. of topical cream is prepared from the following types and
amounts of ingredients:
______________________________________
6-amino-1,2-dihydro-
1-hydroxy-2-imino-4-
piperidinopyrimidine
free base 1 gm.
Polysorbate 80 50 gm.
Tegacid regular* 150 gm.
Spermaceti 100 gm.
Propylene glycol 50 gm.
Methylparaben 1 gm.
Deionized water q.s. 1000 gm.
______________________________________
*Self-emulsifying glyceryl monostearate from Goldschmidt Chemical
Corporation, New York, N.Y.
The Tegacid and spermaceti are melted together at a temperature of
70-80.degree. C. The methylparaben is dissolved in about 500 gm. of water
and the propylene glycol, polysorbate 80, and
6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine free base are
added in turn, maintaining a temperature of 75-80.degree. C. The
methylparaben mixture is added slowly to the Tegacid and spermaceti melt,
with constant stirring. The addition is continued for at least 30 minutes
with additional stirring until the temperature has dropped to
40-45.degree. C. Finally, sufficient water is added to bring the final
weight to 1000 gm. and the preparation stirred to maintain homogeneity
until cooled and congealed.
The composition is applied to bald human scalp three times a day to
stimulate the growth of terminal hair.
EXAMPLE 2 Topical Cream
One-thousand gm. of topical cream is prepared from the following types and
amounts of ingredients:
______________________________________
6-amino-1,2-dihydro-
1-hydroxy-2-imino-4-
piperidinopyrimidine
free base 200 gm.
Tegacid regular* 150 gm.
Polysorbate 80 50 gm.
Spermaceti 100 gm.
Propylene glycol 50 gm.
Methylparaben 1 gm.
Deionized water q.s. 1000 gm.
______________________________________
*Self-emulsifying glyceryl monostearate from Goldschmidt Chemical
Corporation, New York, N.Y.
The Tegacid and spermaceti are melted together at a temperature of
70-80.degree. C. The methylparaben is dissolved in about 500 gm. of water
and the propylene glycol, polysorbate 80, and
6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine free base are
added in turn, maintaining a temperature of 75-80.degree. C. The
methylparaben mixture is added slowly to the Tegacid and spermaceti melt,
with constant stirring. The addition is continued for at least 30 minutes
with additional stirring until the temperature has dropped to
40-45.degree. C. Finally, sufficient water is added to bring the final
weight to 1000 gm. and the preparation stirred to maintain homogeneity
until cooled and congealed.
The composition is applied to bald human scalp once daily to stimulate the
growth of terminal hair.
EXAMPLE 3 Topical Ointment
One thousand gm. of a 2% 6-amino-1,2-dihydro-1-hydroxy-2
-imino-4-piperidinopyrimidine free base ointment is prepared from the
following types and amounts of ingredients:
______________________________________
6-amino-1,2-dihydro-
1-hydroxy-2-imino-4-
piperidinopyrimidine
free base 20 gm.
Zinc oxide 50 gm.
Calamine 50 gm.
Liquid petrolatum (heavy)
250 gm.
Wool fat 200 gm.
White petrolatum q.s. 1000 gm.
______________________________________
The white petrolatum and wool fat are melted and 100 gm. of liquid
petrolatum added thereto. The
6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine free base,
zinc oxide, and calamine are added to the remaining liquid petrolatum and
the mixture milled until the powders are finely divided and uniformly
dispersed. The mixture is stirred into the white petrolatum, melted and
cooled with stirring until the ointment congeals.
The foregoing ointment can be applied topically to mammalian skin for
increased rate of terminal hair growth.
The foregoing composition can be prepared by omitting the zinc oxide and
calamine.
EXAMPLE 4 Ointment
One-thousand gm. of an ophthalmic ointment containing 10%
6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine free base is
prepared from the following types and amounts of ingredients:
______________________________________
6-amino-1,2-dihydro-
1-hydroxy-2-imino-4-
piperidinopyrimidine
free base 100 gm.
Light liquid petrolatum
250 gm.
Wool fat 200 gm.
White petrolatum q.s. 1000 gm.
______________________________________
The 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine free base
is finely divided and added to the light liquid petrolatum. The wool fat
and white petrolatum are melted together, strained, and the temperature
adjusted to 45-50.degree. C. The liquid petrolatum slurry is added and the
ointment stirred until congealed. Suitably the ointment is packaged in 30
gm. tubes.
The foregoing ointment can be applied to the eyelid to enhance the growth
of eyelashes. Similarly the composition can be applied to the brow for
eyebrow growth.
EXAMPLE 5 Solution
One-thousand c.c. of an aqueous solution containing 5%
6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine hydrochloride
is prepared from the following types and amounts of ingredients:
______________________________________
6-amino-1,2-dihydro-
1-hydroxy-2-imino-4-
piperidinopyrimidine
hydrochloride 50 gm.
Polyethylene glycol 4000
120 gm.
Myristyl-.gamma.-picolinium chloride
0.2 gm.
Polyvinylpyrrolidone 1 gm.
Deionized water q.s. ad
1000 c.c.
______________________________________
The ingredients are dissolved in the water and the resulting solution is
sterilized by filtration. The solution is aseptically filled into sterile
cntainers.
The composition so prepared can be used in the topical treatment of
baldness by application to the scalp daily.
EXAMPLE 6 Lotion
______________________________________
6-amino-1,2-dihydro-
1-hydroxy-2-imino-4
piperidinopyrimidine
free base 1 gm.
N-methyl pyrolidone 40 gm.
Propylene glycol q.s. 1000 gm.
______________________________________
The 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine free base
is dissolved in the vehicle of N-methyl pyrolidone and propylene glycol.
The composition can be used for application to dogs or cats having hair
loss due to mange.
EXAMPLE 7 Aerosol
An aerosol containing approximately 0.01%
6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine free base is
prepared from the following types and amounts of materials:
______________________________________
6-amino-1,2-dihydro-1-
hydroxy-2-imino-4-
piperidinopyrimidine
free base 1.5 gm.
Absolute alcohol 4.37 gm.
Dichlorodifluoroethane 1.43 gm.
Dichlorotetrafluoroethane
5.70 gm.
______________________________________
The 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine free base
is dissolved in the absolute alcohol and the resulting solution filtered
to remove particles and lint. This solution is chilled to about minus
30.degree. C. To this is added the chilled mixture of
dichlorodifluoromethane and dichlorotetrafluoroethane. Thirteen ml.
plastic-coated amber bottles are cold filled with 11.5 gm. each of the
resulting solution and capped.
The composition can be sprayed on the scalp daily to convert vellus hair to
growth as terminal hair.
EXAMPLE 8 Dusting Powder
One thousand grams of a powder are prepared from the following types and
amounts of ingredients:
______________________________________
6-amino-1,2-dihydro-
1-hydroxy-2-imino-4-
piperidinopyrimidine
free base 10 gm.
Bentonite 100 gm.
Talc q.s. 1000 gm.
______________________________________
The powdered ingredients are mixed together and dusted on the fur of minks
for increased rate of hair growth.
EXAMPLE 9
Following the procedure of the preceding Examples 1 through 8, inclusive,
compositions are similarly prepared substituting an equimolar amount of a
compound within the scope of fomula 1 disclosed in Examples 1 through 29,
inclusive, of U.S. Pat. No. 3,461,461, issued Aug. 12, 1969, for the
compound of the example.
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Description |
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