Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
I
1 FIELD OF INVENTION
This invention relates to vehicles suitable for use in medic
canal preparations, for example, preparations incorporating a steroid.
BACKGROUND OF INVENTION
One of the oldest bases is an ointment prepared mainly from
petrolatum and mineral oil to which a medicine is added. This type of
ointment is greasy, not water washable and more importantly, has a
limited ability to release medicine carried by the ointment to the skin
to which the ointment and medicine are applied. A non-aqueous ointment
of more recent origin incorporates polyethylene glycol. However this
vehicle, although water washable has a greasy texture and does not
provide an occlusive coating on a treated surface of skin.
United States Letters Patent 3,592,930 and 3,888,995 disclose
vehicles for topical applications of medicines which vehicles consist of
an essentially an hydrous water washable base comprising from 15 - 45
parts by weight saturated fatty alcohol having from 16 - 24 carbon
atoms, from 45 - 80 parts by weight of a glycol solvent, O - 15 parts
by weight of compatible plasticizer, and from O to 15 parts by weight of
compatible coupling agent among other constituents.
The patents provide at column 3, lines 9-15 that:
"The plasticizer concentration can be within the range of from O to 15
percent. Concentrations above 15 percent may provide a composition
which has a consistency unsuitable for normal applications or cause
instability of the vehicle mixture and some separation of the components.
In general, the particular plasticizer concentration necessary to provide
a desired consistency, degree of smoothness and plasticity will vary
with the choice of the fatty alcohol component, the choice of glycol
solvent, and the ratio of these components in the vehicle."
The proposed vehicles however have not proved satisfactory.
Over prolonged storage periods in some formulations the components
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1 slowly separated. Furthermore when applied by the patient administering
his/her medication, such application causes the area of application to
sting.
In an attempt to reduce stinging, bases incorporating substantial
quantities of water have been tried. Depending on the medicine carried
in the base, because of the water content and resultant pi of the base,
the medicine carried in the base may be destroyed and the rate release
pattern of the medicine will be substantially changed
American Cyanamid Company has taken such an approach in Canadian
Letters Patent 1,052,269. In this patent, a new composition of matter
comprising a topical cream base is disclosed purporting to provide
enhanced penetration of steroids comprising:
OW
Ethoxylated stroll alcohol 5 to 25
Bouncily alcohol 0.9 to 4
Isopropyl palpitate 1 to 10
Glycerin 2 to 10
Soribitol solution US 2 to 10
Lactic or other acid as to
pi 3.0-7.0
Water quantity sufficient at 100
This base is described as being suitable for use with 0.005 to
5% (W/W) of a steroid wherein the steroid is selected from the group
consisting of triamcinolone astound; triamcinolone astound-
vale rate; 16~ , 17~ -cyclopentylidenediory-9~ -flyer ,12 dihydroxy-
1,4-pregnadiene-3, Dunn; and 16~ , 17~ -cyclopentyl-idenediory-9~ -
flour- , 21-dihydroxy-1, 4-pregnadiene-3, downstate. I am
also aware of US. Letters Patent 3,342,676; 3,352,753; 3,472,931 and
3,551,554 and Canadian Letters Patent 1,103,159.
SUMMARY OF INVENTION
.
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1 Unexpectedly, I have been able to provide a base which over-
comes the aforementioned difficulties with the prior art formulations.
To this end my base formulation is an hydrous and comprises:
(a) a compatible fatty alcohol between 5 and 35% by weight of the base
formulation, preferably between 10 and 25% by weight,
(b) a compatible glycol component between 20 and 75% by weight and
preferably between 30 and 55% by weight of the base formulation,
and
(c) a compatible plasticizer between about 20 and 35% (preferably between
25 and 35%) by weight of the base formulation.
Preferably the base formulation also comprises a compatible
acidic coupling agent of from 0 to I by weight of the base formulation
which agent modifies the pi of the base making it more compatible with
the skin and, with respect to some steroids, for example fluocininide,
triamcinalone astound, fluocinolone astound and, betamethasone-17-
vale rate, provides a suitable acidic medium for stability.
A suitable fatty alcohol may for example be any saturated
fatty alcohol having from about 12 to about 32 carbon atoms or mixtures
thereof including laurel alcohol, Seattle alcohol, stroll alcohol, isocetyl
alcohol, palmityl alcohol, and mixtures thereof.
A suitable glycol component may for example be propylene
glycol such as 1,2 propylenediol; 1,3 propylenediol, ethylene glycol,
dipropylene glycol and mixtures thereof.
A suitable plasticizer may comprise for example polyethylene
glycol having a molecular weight between about 400 and about 25,000;
1,2,6-hexanetriol, sorbitol and glycerol (glycerin), and, preferably
glycerin (glycerol).
A suitable coupling agent may include fatty acids having from
about 12 to about 32 carbon atoms, for example, Laurie acid, Starkey
acid, palmitic acid and bunk acid, and citric acid, and preferably
~'~3~5~
1 citric acid.
As a result of this invention, a base is provided which permits
the medicine to be taken wholly into solution to provide more uniform
mixtures of medicine and base, and which has improved plasticity and
smoothness.
It also provides a base which reduces stinging of the patient
(without the addition of water) when applying his/her medication thus
making i-t easier for the patient to comply with the doctor's prescribed
applications of the medicine.
DESCRIPTION OF EMBODIMENTS
The following embodiments of the invention were prepared as
illustrative of the invention.
EXAMPLE 1
1) 5% Stroll alcohol
15 2) 60% Propylene glycol 3
3) 4.5% Polyethylene glycol-6000 3 Viscosity at 20 = 26,250 cups
4) 30% Glycerin 3 Runny lotion like.
5) 0.5% 1,2, 6-Hexanetriol
EXAMPLE 2
20 1) 10% Stroll alcohol
2) 44% Propylene Glycol-6000 3
3) 4.5% Polyethylene glycol-6000 3 Viscosity at 20C = 42,500 cups
4) 30% Glycerin 3 soft cream
5) 0.5% 1,2,6 Hexanetriol
25 EXAMPLE
1) 15% Stroll alcohol 3
2) 50% Propylene glycol
3) 4.5% Polyethylene glycol-6000 3 Viscosity at 20C = 85,000 cups
4) 30% Glycerin 3 Elegant cream
5) 0.5% 1,2,6 Hexanetriol 3
sly
EXAMPLE 4
1) 20% Stroll alcohol
2) 45% Propylene glycol
3) 4.5% Polyethylene glycol-6000 ) Viscosity at 25C = 127,500 cups
4) 30% Glycerin ) Cream
5) 0.5% 1,2,6 - Hexanetriol
EXAMPLE 5
l) 34% Stroll alcohol
2) 31.0% Propylene glycol
3) 4.5% Polyethylene glycol-6000 ) Viscosity at 20C = 230,000 cups
4) 30% Glycerin ) Thick cream
5) 0.5% 1,2,6 - Hexanetriol
The stability of each of examples 2, 3, 4 and 5 was investigated.
Examples 2, 3, 4 and 5 were found very stable after more than two years
of controlled room temperature (15 - 30C). The antimicrobial effective-
news test as per US XX was performed on each of the examples and found
satisfactory against Candid albicans Escherichia golf, Aspergillus
Niger Pseudomonas aeruginosa and Staphylococcus Ayers. They met US
XX requirements for preservative bacteria challenge test. The primary
dermal irritation study in albino rabbits was better with marketed
product. A comparative study of the vasoconstrictor effect of Fluocinonide
hydrophilic creams 0.05% employing a base formulation according to an
embodiment of this invention and other bases was performed and it was
found that the formulations employing base formulations according to
embodiments of the invention compare favorably with other bases yet
still provide the aforementioned advantages.
As many changes can be made to the embodiments of the invention
without departing from the scope of the invention, it is intended that
all material disclosed therein shall be interpreted as illustrative of
the invention and not in a limiting sense.
