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Patent 1139664 Summary

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(12) Patent: (11) CA 1139664
(21) Application Number: 343238
(54) English Title: OLEAGINOUS EMOLLIENT VEHICLE FOR STEROID FORMULATIONS
(54) French Title: EXCIPIENT EMOLLIENT OLEAGINEUX POUR LES PREPARATIONS DE STEROIDES
Status: Expired
Bibliographic Data
(52) Canadian Patent Classification (CPC):
  • 167/196
(51) International Patent Classification (IPC):
  • A61K 31/57 (2006.01)
  • A61K 8/63 (2006.01)
  • A61K 47/10 (2017.01)
  • A61K 47/44 (2006.01)
(72) Inventors :
  • WONG, THOMAS M. (United States of America)
(73) Owners :
  • SQUIBB (E.R.) & SONS, INC. (Afghanistan)
(71) Applicants :
(74) Agent: OSLER, HOSKIN & HARCOURT LLP
(74) Associate agent:
(45) Issued: 1983-01-18
(22) Filed Date: 1980-01-08
Availability of licence: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): No

(30) Application Priority Data:
Application No. Country/Territory Date
4,100 United States of America 1979-01-17

Abstracts

English Abstract


SN43

Abstract

OLEAGINOUS EMOLLIENT VEHICLE FOR STEROID FORMULATIONS

A novel ointment-like composition comprising not
less than 40% by weight of isosteraryl alcohol is provided
for the topical administration of corticosteroids.


Claims

Note: Claims are shown in the official language in which they were submitted.



The embodiments of the invention in which an exclusive
property or privilege is claimed are defined as follows:-

1. A composition for the topical administration of a
corticosteroid comprising an effective amount of the cortico-
steroid and not less than 40% by weight of the composition of
isostearyl alcohol.


2. A composition in accordance with claim 1 further com-
prising a wax having a melting point of 60° to 90°C and a poly-
hydric alcohol ester of a fatty acid.


3. A composition in accordance with claim 2 wherein the
wax is carnauba wax and the fatty acid ester is ethylene gly-
col distearate.


4. A composition in accordance with claim 1, 2 or 3
further comprising an additional solvent.


5. A composition in accordance with claim 1, 2 or 3
further comprising propylene carbonate as an additional sol-
vent.


6. A composition in accordance with claim 1, 2 or 3
further comprising about 1% by weight to 7% by weight propy-
lene carbonate as an additional solvent.



7. A composition in accordance with claim 1 which in-
cludes 5% by weight to 12% by weight of a wax having a melt-
ing point of 60° to 90°C, and 4% by weight to 10% by weight
of a polyhydric alcohol ester of a fatty acid.


11


8. A composition in accordance with claim 1, 2 or 3
wherein the corticosteroid is present in an amount of from
about 0.01% by weight to about 1.0% by weight.


9. A composition in accordance with claim 1, 2 or 3
wherein the corticosteroid is present in an amount of from
about 0.025% by weight to about 0.5% by weight.


10. A composition for the topical administration of a
corticosteroid comprising from about 0.01% by weight to about
1.0% by weight of the corticosteroid, not less than 40% by
weight of isostearyl alcohol, 5% by weight to 12% by weight
of a wax having a melting point of 60° to 90°C, 4% by weight
to 10% by weight of a polyhydric alcohol ester of a fatty acid,
and about 1% by weight to 7% by weight propylene carbonate.


12

Description

Note: Descriptions are shown in the official language in which they were submitted.


~ 4 SN43


OLEAGINOUS EMOLLIENT VEHICLE FOR STEROID FORMNLATIONS

The present invention relates to an oleaginous
emollient vehicle for steroid formulations.
It is an object of this invention to provide
an ointment-like vqhicle which eliminates the feeling
of greasiness when applied to the skin without
sacrificing the oc~lusive property of an ointment.
It is a further object of this invention to
provide an ointment-like vehicle which is not
affected by temper~ture extremes. More specifically,
it is an object of this invention to provide a
steroid vehicle which at temperatures up to 50C
does not show evidence of bleeding or syneresis,
and which can be extruded from tubes at refrigerator
temperatures without difficulty.
It is an object of this invention to provide
an ointment-like vehicle for steroid formulations
which has enhanced emolliency and improved occlusive
properties.
It is an object of this invention to provide
an ointment-like steroid vehicle which does not
stain clothing or bedding with which it comes in
contact.
It is an object of this invention to provide




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a vehicle for steroid formulations which will provide
for uniform distribution of the steroid and enhance
therapeutic efficacy.
These and other objects which will be apparent
to the practitionçr of this invention can be achieved
by utilizing isos$earyl alcohol in place of vegetable
oil or petroleum hydrocarbons in an ointment-like
vehicle. M~re sp~cifically, the isostearyl alcohol
should make up at least 40% by weight of the steroid
formulation .
Corticosterolds have been used for the treatment
of various dermatoses when applied topically. The
steroids have been formulated as creams, ointments,
lotions and aerosol sprays. Of the various form~
ulations, ointments have in the past received the
least patient acceptance. Ointments do, however, have
the beneficial therapeutic affect of occlusiveness,
a highly desirable characteristic for topical
steroid therapy.
Early ointment formulations used in topical
steroid therapy were based largely on fats, grease
and petrolatum. Early synthetic bases for use in
ointments are described in United States patent
2,627,938 and 2,628,187 which describe a petroleum
oil vehicle which has been thickened with poly-
ethylene. Although these vehicles have gained wide
acceptance in the steroid field they do have
serious disadvantages. Cosmetically they are not
as elegant as patients would like. More specifically,
they impart a lingering greasy feeling to the skin,
which is most noticeable on hairy skin. These
ointment bases are also water insoluble and, there-
fore, difficult to wash off the skin. Still further,

SN43
11~9~i4
3--


oil bases of the past are prone to stain garments
and bedding with which they come in contact.
Aside from the cosmetic problems enumerated
above, ointment bases possess serious physical
stability problems when petroleum vehicles are
employed. Excessive temperatures can cause
softening or melting of the vehicle and result ~
in the separation of suspended components. This I
separation of suspended components (breaking down
of the gel structure is a serious problem hecause
uniform distribution of the active steroid ingredient
is considered important for successful topical
corticosteroid treatment. The steroids are not
soiuble in petrolatum vehicles and, therefore, a
steroid suspension is the only choice for incor-
poration of the steroid into a petrolatum vehicle. -
More recently, Carbowax, a mixture of poly-
ethylene glycol polymers has been used as an
ointment-like base. These compositions have the
advantage of being water-washable, but they are
still greasy and cosmetically inelegant. Further-
more, Carbowax vehicles are not occlusive.
United States patent 3,592,930 issued July 13,
1971, discloses an ointment-like vehicle which is
said to be water-washable and occlusive and which
comprises as its essential ingredients a fatty
alcohol having 16 to 24 carbon atoms and a glycol.
The glycol solvent is said to function as a solvent
for a glycol-soluble drug or as a carrier for a
glycol-insoluble drug. The fatty alcohol component
is said to be "a solid component which naturally



* Trade Mark
.

il~9~4 SN43


thickens the composition".
United States patent 3~924,004 discloses a
formulation comprising a saturated fatty alcohol
having from 16 to 24 carbon atoms, propylene
carbonate, and a glycol solvent.
In its broad~st aspect, the present invention
comprises the use ~f at least 40% weight of isostearyl
alcohol in a steroid formulation. The isostearyl alcohol
will serve both as a principal solvent for the
formulation and as an emollient. The fatty alcohols
used in the prior ~rt have been the lower molecular
weight fatty alcohQls in minor amounts, or when larger
amounts of fatty alcohol have been used, the higher
molecular weight solid fatty alcohols. While the
lower molecular weight fatty alcohols are fluids they
are undesirable because of their odor and because of
their tendency to irritate the skin. Isostearyl
alcohol Oll the other hand is a non-irritating liquid
which does not have as strong an odor as its lower
molecular weight homologs.
In a preferred embodiment of this invention the
steroid formulation will also contain 5-12~ by weight
of a high melting point wax (melting point range
60-90C), e.g., carnauba wax, candellia wax, ozokerite

;4
_5-

wax, and beeswax, and 4-10~ by weight of a moderately
high melting polyhydric alcohol ester of a fatty acid
(melting point range 60-90C), e.g., propylene glycol
distearate and ethylene glycol distearate. The wax
and the polyhydric alcohol ester of a fatty acid
together form a ne$work (or matrix) within which is
contained the steroid partially dissolved in the
isostearyl~alcohol. The formulation can also contain
a simple fatty acid ester which functions as a non-
greasy emollient. The emollient wiil disappear when
rubbed into the skin and lends lubricity to the skin.
Exemplary of the simple fatty acid esters contemplated
are isopropyl myristate and isopropyl palmitate.
Cosolvents may also be used along with the
isostearyl alcohol. Particularly preferred as a
cosolvent is propylene carbonate, which may be used
in an amount from about 1% to 7% by weight of the
formulation. When using a cosolvent it may be advan-
tageous to include in the formulation a coupler.
The term "coupler" is used to describe a compound
which insures the miscibility of the solvents. When
propylene carbonate is used as a cosolvent with
isostearyl alcohol, polyoxypropylene stearyl ether
serves as an effective coupler.
To enhance the occlusive property of the ointment-
like vehicle a polysiloxane such as dimethylpoly-
siloxane liquid may be employed in an amount of about
5% to 10% by weight of the formulation.
The ointment-like steroid vehicle described
herein can also contain various additional ingredients
which are conventional in the pharmaceutical art.

9~
SN43
-6-

These additional ingredients can be used to improve
the stability, homogeneity, consistency, emolliency,
penetrability and the cosmetic elegance of the
vehicle. The choice of particular ingredients is
5 within the level of ordinary skill in the art and
the practitioner of this invention will choose
the various adjuvants depending on the particular
qualities he wishes the vehicle to have. For example,
the art recognizes the equivalence of 1,3-butylene
glycol and a simple fatty acid ester in an ointment
formulation. The 1,3-butylene glycol can be used
in place of all, or part, of the simple fatty acid
ester as a non-greasy emollient.
A method for preparing the preferred steroid
15 formulations of this invention comprises first
dissolving the steroid drug in the cosolvent. To
a separate container, preferably a steam jacketed
stainless steel vessel equipped with a stirrer, is
added the rest of the ingredients with the exception
20 of the polysiloxane. These are melted together and
stirred until a clear melt is effected. To this
solution is added the steroid dissolved in the
cosolvent and the resulting solution is stirred and
heated. The mixture is next shock-cooled and the
25 resultant formulation is then placed in a planetary
type mixer to which is added the polysiloxane
ingredient. To improve the quality of the finished
product, the resultant formulated mixture may he
passed through a roller mill.

1~9~4 SN43
-7-

Alternately, the above-described procedure can be
modified b~ including high shearing equipment in
the steam ~acketed stainless steel vessel. Immediately
prior to shock-cooling, the mixture of ingredients
can be sub~ected to high shear. In this method, the
polysiloxane ingredient can be added prior to the
- high shear mixing.
The vehicle described herein is suitable for use
with topical antiinflammatory steroi'ds. Exemplary
Of the steroids contemplated are the acetonide
derivatives of steroids of the pregnane series
described in United States patent 3,048,581. Included
within the steroids described by this patent are
triamcinolone acetonide and halcinonide. It is
emphasized that these steroids are meant to be
exe~plary only and it is not meant to limit this
invention to use with any particular steroid or
group of topically active antiinflammatory steroids.
The steroid~ incorporated in the formulation of this
invention may be present in an amount of from about
0.01% by weight t4 about 1.0% by weight, preferably
from ahout 0.025% by weight to about 0.5~ by weight.
The following examples are specific embodiments
of this invention.

1139~j64
SN43
-8-

Example
The various ingredients set forth below are
formulated into oleaginous emollient vehicles for
steroid formulations. Alternative methods of
formulation are s~t forth below.

Method I
The carnaub~ wax and ethylene glycol distearate
are mixed with is~propyl myristate ~formulations 1-7)
or 1,3-butylene g~ycol (formulations 8-14), polyoxy-
propylene stearyl ether and isostearyl alcohol.
While stirring, t~e mixture is heated until the
wax melts and the temperature is maintained at
80-85C for a few minutes. In a separate container,
the halcinonide is-dissolved in propylene carbonate
with the aid of heat. The halcinonide solution is
combined with the wax mixture and the temperature
of the mixture is brought to 80-85C. The molten
mixture is transfqrred to a shock cooling machine
and quickly cooled using water maintained in the
20-30C range. The emollient base obtained is
gently heated to 35C and combined with Corning DC
200 fluid (also heated to 35C) in a planetary
mixer. The emollient is then passed through a roller
mill.
Method II
The carnauba wax and ethylene glycol distearate
are mixed with isopropyl myristate (formulation 1-7)
or 1,3-butylene glycol (formulations 8-141, polyoxy-
propylene stearyl ether and isostearyl alcohol.

~ SN43
_g_

While stirring the mixture is heated until the wax
melts and the temperature is maintained at 80-85C
for a few minutes. In a separate container, the ,~
halcinonide is dissolved in propylene carbonate with ~l
5 the aid of heat. The halcinonide solution is i,
combined with the molten wax mixture and the Corning
DC 200 Fluid is then added. The temperature of the j
mixture is raised to 80-85C and the mixture is
subjected to high shear stirring which is maintained
until just prior to transfer to a shock cooling
machine for immediate quick cooling using water
maintained in the 20-30 range.




* Trade Mark

;4 SN43

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Representative Drawing

Sorry, the representative drawing for patent document number 1139664 was not found.

Administrative Status

For a clearer understanding of the status of the application/patent presented on this page, the site Disclaimer , as well as the definitions for Patent , Administrative Status , Maintenance Fee  and Payment History  should be consulted.

Administrative Status

Title Date
Forecasted Issue Date 1983-01-18
(22) Filed 1980-01-08
(45) Issued 1983-01-18
Expired 2000-01-18

Abandonment History

There is no abandonment history.

Payment History

Fee Type Anniversary Year Due Date Amount Paid Paid Date
Application Fee $0.00 1980-01-08
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
SQUIBB (E.R.) & SONS, INC.
Past Owners on Record
None
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
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Document
Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Drawings 1994-01-05 1 15
Claims 1994-01-05 2 48
Abstract 1994-01-05 1 9
Cover Page 1994-01-05 1 11
Description 1994-01-05 10 308