Note: Descriptions are shown in the official language in which they were submitted.
CA 2,459,869 CA 02459869 2009-05-21
A SYSTEM FOR USE BY COMPOUNDING PHARMACISTS
TO PRODUCE HORMONE REPLACEMENT MEDICINE
CUSTOMIZED FOR EACH CONSUMER
BACKGROUND OF THE INVENTION
Field of the Invention
[0001] This invention relates to a concentrated hormone pharmaceutical
composition to be
use d in the production of hormone replacement therapy.
Description of the Related Art
[0002] Natural hormone replacement satrapy has been around for more than
twenty years.
The term "natural" comes from the fact that the hormones (estrogens such as
estradiol,
estrone, and estriol, testosterone, DHEA, pregnenolone and progesterone) come
from
natural sources. However, more importantly, the term means that the hormones
have the
exact same molecular structure as those produced by the body itself, thus the
body
recognizes the hormones as being "natural", because they are "bio-identical".
Therefore,
the shift to a more appropriate name, Bio-identical Hormone Replacement
Therapy (BHRT).
[0003] Some of the benefits of BHRT include: fewer side effects compared with
traditional
HRT; protection against heart disease, reduced risk of breast cancer, and
improved lipid
profile.
[0004] Bio-identical Hormone Replacement Therapy products are compounded by a
compounding pharmacist, which offers you and your physician a choice for
individualized
hormone replacement. General, the BHRT pharmaceutical compositions are sold in
the
form of ointments, creams, gels, pastes, capsules, troches, lozenges,
lollipops, tablet
triturates, sublingual tablets and tablets.
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{0006]A BHRT ointment, cream, gel, or paste may include, but
is not limited to, the active hormone or hormones, a
suitable solvent or solvents, including, but not limited to,
ethoxy diglycol, propylene glycol, alcohol, or glycerin and
any suitable ointment, cream, or gel base which allows for
transdermal absorption of bio-identical hormones.
[0007]Producing BHRT pharmaceutical compositions is a very
lucrative business for compounding pharmacies. However, the
process of producing the BHRT pharmaceutical compositions is
an extremely time-consuming process and has many risks and
subsequent costs associated with the compounding of BHRT
pharmaceutical compositions.
[0008]One of the main problems with compounding BHRT
pharmaceutical compositions is the substantial risk of
employee contamination (inhalation or transdermal absorption
of the hormones) with the hormones. The hormones used for
producing the BHRT pharmaceutical compositions are naturally
found in the body in physiological levels. Thus, when a
human is chronically exposed to higher than normal levels of
these hormones, they are at risk of developing serious
adverse medical effects, including, but not limited to, an
unnatural increased response by each system of the body
which is affected by each individual hormone, as well as an
increased risk of developing numerous varieties of cancer.
[0009] In addition, producing these BHRT pharmaceutical
compositions requires great skill and knowledge. It also
requires expensive equipment such as accurate electronic
scales, electronic mortars and pestles (EMP), and ointment
mills.
[00010] In order to diminish these risks, the compounding
pharmacies have developed an expensive and time-consuming
method to reduce employee exposure to these hormones. These
measures include, but are not limited to, the use of a
custom built clean room, high velocity air flow units fitted
with high emission particulate air (HEPA) filters, custom
built ventilation systems, protective suits, protective
eyewear, protective gloves, and protective HEPA filter
masks.
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[00011] The production of BHRT pharmaceutical compositions
is by itself a time-consuming process. Each ointment, cream,
gel, or paste must be specifically engineered for each
patient based on his or her distinct hormone profile, thus
the use of bulk compounding is precluded, because each
medication is produced custom fit for each patient.
[00012] Furthermore, bulk compounding or manufacturing of
hormone products is illegal in most states without a proper
license.
[00013] In order to produce these BHRT pharmaceutical
compositions safely and accurately, compounding pharmacies
need to invest a great deal of time and money into these
safety measures. The pharmacies would also need to employ a
specially trained staff; all these measures decrease
productivity substantially.
[00014] These measures are not only expensive, but also
create an unpleasant work environment. This is due to the
fact that the employee is covered from head to toe in
restrictive, uncomfortable protective gear. They are also
working in a room, which is noisy because of the high
velocity ventilation systems, which are in constant use.
[00015] In order to work with BHRT pharmaceutical
compositions, an employee must:
Be trained in the art of compounding BHRT ointments,
creams, gels, and pastes.
Ensure they are wearing all the necessary protective
gear.
Locate all of the ingredients.
Weigh all of the ingredients in the appropriate
environment, a clean room with proper ventilation and
filtration systems, to prevent exposure to harmful
chemicals.
Combine the ingredients using the EMP to ensure
thorough mixing. If the mixture is not thoroughly mixed,
then it will not contain a uniform concentration of the drug
throughout.
Run the mixture through an ointment mill to decrease
the particle size of the drug. This will increase
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absorbability, as smaller drug particles will more readily
penetrate the dermis. This process also ensures a non-
gritty, pharmaceutically elegant, and cosmetically pleasing
final product.
[00016] The combination of the potential risks associated
with producing BHRT pharmaceutical compositions, specially
trained employees to compound these compositions safely and
accurately, purchasing all the necessary equipment and
safety measures, and the actual time required to compound
each individual pharmaceutical composition result in an
.extremely time-consuming, hazardous, and expensive process.
[00017] The present inventor thought of the necessity of
providing pharmacies with a system that is easy to use and
saves time and money for those pharmacies dealing with BHRT
pharmaceutical products while decreasing risk and increasing
product quality.
SUNMARY OF THE INVENTION
[00018] The invention offers at least one of the following
advantages:
provides a concentrated pharmaceutical composition that
is easy to use and saves time and money to the pharmacies
dealing with BHRT pharmaceutical products.
provides a pharmaceutical composition having a higher
concentration of hormone than the concentration found in the
BHRT pharmaceutical products of the prior art.
provides a pharmaceutical composition that can be used
by the compounding pharmacist safely, accurately, quickly.
provides an inexpensive pharmaceutical composition with
individualized BHRT products such as ointments, creams,
gels, or pastes.
provides a color-coded hormone pharmaceutical
composition.
[00019] The concentrated composition of the present
invention can be manufactured to contain a higher
concentration of hormone (or combination of hormones) than
the standard concentration of hormones prescribed by
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physicians, thus the pharmacist can easily measure the
amount required to be incorporated into the EHRT product.
[00020] The concentrated composition of the present
invention could include any concentration of any hormone or
any combination of hormones in any proportion as long as the
concentration is greater than the accepted physician
prescribed concentrations to treat hormone deficiencies.
[00021] The present invention also relates to a metered
dispensing device including the composition of the invention
to provide a means to measure and combine, quickly and
accurately, quantities of hormones with appropriate
ointment, cream, or gel bases by the compounding pharmacist
while minimizing exposure to hazardous airborne hormone
particles. Thus, airborne particles are drastically reduced
because the hormones are incorporated into a liquid or semi-
solid form.
[00022] The present invention relates to a concentrated
hormone Pharmaceutical composition comprising:
from about 0.6 to about 80% of at least one hormone;
from about 20 to about 90.4 % of at least one solvent,
and
optionally a pharmaceutically acceptable carrier.
[00023] In the preferred embodiment, the concentrated
hormone pharmaceutical composition is chosen from estradiol,
estrone, estriol, testosterone, DHEA, pregnenolone,
progesterone, or combination thereof.
[00024] The invention also relates to a concentrated
hormone pharmaceutical composition comprising:
from about 0.6 to about 50% of at least one hormone;
from about 50 to about 90.4 % of at least one solvent,
and
optionally a pharmaceutically acceptable carrier
wherein the at least one hormone is chosen from
estriol, estradiol, or combination thereof.
[00025] The at least one hormone is a combination of
estriol and estradiol in a ratio of 5:5, 6:4, 7:3, 8:2, or
9:1.
CA 02459869 2004-05-18
[00026] Furthermore, the invention concerns a concentrated
hormone pharmaceutical composition comprising:
from about 0.6 to about 50% of at least one hormone;
from about 50 to about 90.4 % of at least one solvent,
and
optionally a pharmaceutically acceptable carrier
wherein the at least one hormone is chosen from
estriol, estradiol, estrone, or combination thereof.
[00027] The at least one hormone is a combination of
estriol, estradiol, and estrone in a ratio of 5:4:1, 6:3:1,
7:2:1, or 8:1:1.
[00028] Furthermore, the invention concerns a concentrated
hormone pharmaceutical composition comprising:
from about 0.8 to about 80% of at least one hormone;
from about 20 to about 90.2 % of at least one solvent,
and
optionally a pharmaceutically acceptable carrier
wherein the at least one hormone is testosterone.
[00029] In addition, the invention concerns a concentrated
hormone pharmaceutical composition comprising:
from about 8 to about 90% of at least one hormone;
from about 10 to about 92 % of at least one solvent,
and
optionally a pharmaceutically acceptable carrier
wherein the at least one hormone is progesterone.
[00030] Furthermore, the invention concerns to a color-
coded concentrated hormone pharmaceutical.
[00031] Furthermore, the invention concerns a method for
producing a concentrated hormone pharmaceutical composition,
the method comprising the steps of:
measuring at least one hormone, a solvent and/or
optionally a carrier by using an electronic balance in a
clean room;
combining the ingredients of step a by using an
industrial scale mixer to ensure thorough mixing; and
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running the mixture of step b through a large-scale
ointment mill or homogenizer to decrease the particle
size of the drug, and
optionally, heating the concentrate to facilitate the
formation of a solution,
wherein the hormone concentration is from about 0.6 to
about 80%.
WOOM Furthermore, the present invention concerns a
concentrated hormone pharmaceutical composition comprising:
at least one hormone;
optionally a powdered base;
wherein the at least one hormone is chosen from
estriol, estradiol, estrone, or combination thereof; and
wherein the composition is in a powdered form.
[00033] Finally, the invention concerns a kit for
producing a liquid or semi-solid concentrated hormone
pharmaceutical composition, the kit comprising:
at least one hormone;
at least one solvent, and
optionally a pharmaceutically acceptable carrier,
wherein each element is packet in separated graduated
dispensing devices.
[00034] The foregoing has outlined rather broadly the more
pertinent and important features of the present invention in
order that the detailed description of the invention that
follows may be better understood, and so that the present
contribution to the art can be more fully appreciated.
Additional features of the invention that will be described
hereinafter form the subject matter of the claims of the
invention. It should be appreciated by those skilled in the
art that the conception and the specific embodiments
disclosed might be readily utilized as a basis for modifying
or formulating other liquid formulations for carrying the
same purposes of the present invention. It should also be
realized by those skilled in the art that such equivalent
formulations do not depart from the spirit and scope of the
invention as set forth in the appended claims.
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DETAILED DESCRIPTION OF THE INVENTION
[00035] The present invention concerns a pharmaceutical
composition, including high concentrations of hormone that
can be used by the compounding pharmacist safely,
accurately, quickly, and inexpensively to produce
individualized BHRT products such as ointments, creams,
gels, or pastes.
[00036] The present invention concerns a concentrated
hormone pharmaceutical composition comprising:
at least one hormone;
at least one solvent, and
optionally a pharmaceutically acceptable carrier
wherein the weight concentration of the at least one
hormone in said composition is equal or greater than 0.6%.
[00037] In one of the embodiments, the concentrated is in
a powdered form.
[00038] The term "pharmaceutically acceptable" means
approved by a regulatory agency of the Federal or a state
government or listed in the U.S. Pharmacopeia or other
generally recognized pharmacopeia for use in animals, and
more particularly in humans.
Hormones
[00039] The present invention contemplates the use of any
one of the steroid hormones derived from cholesterol
including, but not limited to, estrogen (estriol, estradiol,
or estrone), progesterone, testosterone,
dehydroepiandrosterone, norethisterone acetate, norgestrel,
levonorgestrel gestodene CPA chlormadinone acetate,
drospirorenone, and 3-ketodesogestrel.
[00040] The concentrates also could include, but not be
limited to, an estriol concentrate, an estradiol
concentrate, an estrone concentrate, a combination estriol,
estradiol, and estrone (triest) concentrate in any
proportion, preferably in a 8:1:1, 5:4:1, 6:3:1, or 7:2:1
ratio; a combination of estriol and estradiol concentrate
(blest) in any proportion, preferably in a 5:5, 6:4, 7:3,
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8:2, or 9:1 ratio; a combination estriol and estrone
concentrate, a combination estradiol and estrone
concentrate, a progesterone concentrate, a combination
progesterone and estriol concentrate, a combination
progesterone and estradiol concentrate, a combination
progesterone and estrone concentrate, a combination
progesterone and triest concentrate, a combination
progesterone, estriol, and estradiol concentrate, a
combination progesterone, estriol, and estrone concentrate,
a combination progesterone estradiol, and estrone
concentrate, any of the previously mentioned concentrates in
combination with testosterone i.e. a combination triest,
progesterone, and testosterone concentrate, a testosterone
concentrate, any of the previously mentioned concentrates in
combination with dehydroepiandrosterone (DHEA), and a DHEA
concentrate.
[00041] In addition, any of the sex hormones may be used.
Any androgen including, but not limited to, testosterone may
be used. Any progestogen including, but not limited to,
progesterone may be used. Any estrogen including, but not
limited to, estriol, estradiol, or estrone may be used.
[00042] The concentrated composition of the present
invention could include any concentration of any hormone or
any combination of hormones in any proportion as long as the
concentration is greater than the accepted physician
prescribed concentrations to treat hormone deficiencies.
[00043] The present invention provides a concentrated
pharmaceutical composition that contains any ratio of
estriol to estradiol (biest) having between 6 mg/g and 900
mg/g of biest, preferably between 8 mg/g and 200 mg/g, even
more preferably 10mg/g to 60 mg/g.
[00644] In addition, the present invention provides a
concentrated pharmaceutical composition that contains any
ratio of estriol, estradiol, and estrone (triest) having
between 6 mg/g and 900 mg/g of the triest, preferably
between 8 mg/g and 200 mg/g, even more preferably 10 mg/g
and 60 mg/g.
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[00045] Furthermore, the present invention provides a
concentrated pharmaceutical composition that contains
between 10 mg/g and 900 mg/g of estriol, preferably between
15 mg/g and 300 mg/g, even more preferably 15 and 60 mg/g.
[00046] The present invention provides a concentrated
pharmaceutical composition that contains between 1 mg/g and
900 mg/g of estradiol, preferably between 1.5 mg/g and 100
mg/g.
[00047] The present invention also provides a concentrated
pharmaceutical composition that contains between 1 mg/g and
900 mg/g of estrone, preferably between 1.5 mg/g and 100
mg/g.
[00048] In addition, the present invention provides a
concentrated pharmaceutical composition that contains
between 10 mg/g and 800 mg/g of testosterone, preferably
between 15 mg/g and 900 mg/g, even more preferably between
15 mg/g and 300 mg/g, for use in a female BHRT product.
[00049] Furthermore, the present invention provides a
concentrated pharmaceutical compound that contains between
100 mg/g and 900 mg/g of testosterone, for use in a male
BHRT product.
[00050] In addition, the present invention provides a
concentrated pharmaceutical compound that contains between
200 mg/g and 900 mg/g of progesterone, more preferably
between 400 mg/g and 800 mg/g, even more preferably 600mg/g.
[00051] Furthermore, the present invention provides a
concentrated pharmaceutical compound that contains between
mg/g and 900 mg/g of dehydroepiandrosterone or between 30
mg/g to 800 mg/g of pregnenolone.
[00052] The invention also concerns a concentrated hormone
pharmaceutical composition comprising:
from about 0.6 to about 50% of at least one hormone;
from about 50 to about 90.4 % of at least one solvent,
and
optionally a pharmaceutically acceptable carrier
wherein the at least one hormone is chosen from
estriol, estradiol, or combination thereof.
CA 02459869 2004-05-18
[00053] In addition, the invention concerns a concentrated
hormone pharmaceutical composition comprising:
from about 0.6 to about 50% of at least one hormone;
and from about 50 to about 90.4 % of at least one solvent,
optionally a pharmaceutically acceptable carrier
wherein the at least one hormone is chosen from
estriol, estradiol, estrone, or combination thereof.
[00054] Furthermore, the invention concerns a concentrated
hormone pharmaceutical composition comprising:
from about 0.8 to about 80% of at least one hormone;
from about 20 to about 90.2 % of at least one solvent,
and
optionally a pharmaceutically acceptable carrier
wherein the at least one hormone is testosterone.
R0059 The invention also concerns a concentrated hormone
pharmaceutical composition comprising:
from about 8 to about 90% of at least one hormone;
from about 10 to about 92 % of at least one solvent,
and
optionally a pharmaceutically acceptable carrier
wherein the at least one hormone is progesterone.
Solvent (or Wetting agent)
[00056] The solvent or wetting agent can be any liquid
that can dissolve, partially dissolve, wet, or suspend the
hormone, or reduce the surface tension of a liquid to a
value below the hormones critical surface tension.
[00057] In order for a solid to be incorporated into a
liquid, the solids surface tension must be above the surface
tension of the liquid. The best solvents produce a low air
liquid surface tension, and are not readily adsorbed by the
solid so as to produce nonwetting behavior.
ROOM The wetting agent or solvent acts by lowering the
contact angle between the surface of the particle and the
wetting liquid. Wetting agents replace a solid to air
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interface with a solid to liquid interface. The solvent or
wetting agent should be miscible with the carrier.
[00059] The solvent or wetting agent could possibly be,
but is not limited to, one or more of the following in any
concentration: propylene glycol, ethoxy diglycol, glycerin,
mineral oil, fixed oil, emu oil, peanut oil, vitamin E oil,
acetone, amylene hydrate, benzyl benzoate, corn oil,
cottonseed oil, diethylene glycol monoethyl ether, ethyl
acetate, isopropyl alcohol, methyl alcohol, methylene
chloride, methyl isobutyl ketone, polyethylene glycol 300,
polyethylene glycol 400, polyethylene glycol 600, sesame
oil, alcohol, a 50% ethoxy diglycol (diethylene glycol mono-
ehyletherand) 50% propylene glycol mixture, water or
mixtures threrof. Any combination of solvents may be
employed.
gmow The solvent or wetting agent should satisfy the
following characteristics:
the solvent or solvents should wet the hormone;
the solvent should allow the hormone to be
incorporated therein;
the solvent or solvents should be compatible with the
skin with the least possible number of adverse
effects;
the solvent or solvents should be smooth and pliable
with no adverse odor;
the solvent or solvents should have a color appealing
to the consumer; and the solvent must be stable and
must provide a stable vehicle for the medication.
[00061] The scope of the present invention is not limited
by the solvents mentioned in the present application; any of
those known in the pharmaceutical and cosmetic industries
may be employed.
Pharmaceutically acceptable Carrier
[00062] The carrier can be any suitable carrier that can
be incorporated into a system, which can deliver bio-
identical hormones transdermaly.
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[00063] The formulations for the delivery of the
pharmaceutical composition according to the present
invention may be liquid, ointments, and creams.
gmoGc The carrier can be chosen from ointment base,
powder base, cream base, or a gel base.
[00065] Ointments are semisolid preparations, which are
typically based on petrolatum or other petroleum
derivatives. Creams containing the selected active agent,
are, as known in the art, viscous liquid or semisolid
emulsions, either oil-in-water or water-in-oil.
[00066] Cream bases are water-washable, and contain an oil
phase, an emulsifier, and an aqueous phase. The oil phase,
also sometimes called the "internal" phase, is generally
comprised of petrolatum and a fatty alcohol such as cetyl or
stearyl alcohol; the aqueous phase usually, although not
necessarily, exceeds the oil phase in volume, and generally
contains a humectant.
[00067] The specific ointment or cream base to be used, as
will be appreciated by those skilled in the art, is one that
will provide for optimum drug delivery. As with other
carriers or vehicles, an ointment base should be inert,
stable, nonirritating and non-sensitizing.
[00068] Powders may be formulated with the aid of any
suitable powder base, such as talc, lactose, starch, and the
like.
gmow The pharmaceutical carrier could possibly be
comprised of, but is not limited to, any or all of the
following ingredients: an oil in water emulsion base, a
water in oil emulsion base, an oleaginous base, an
absorption base, a water soluble base an anhydrous gel, a
pluronic F127/lecithin isopropyl palmitate gel, hydrous gel,
purified water, white petrolatum, cetearyl alcohol,
ceteareth-20, sorbitol solution, propylene glycol,
simethicone, glyceryl monostearate, polyethylene glycol
monostearate, sorbic acid, camellia sinensis (green tea)
leaf extract, cholesterol, beeswax, cyclomethicone, C 12-15
alkyl benzoate, plankton extract, acetyl ponta peptide-2,
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ocnethera biennis (evening primrose) root extract,
dimethicone, hexyldecanol, dextran, stearyl alcohol, cetyl
alcohol, pyrus malus (apple) fruit extract, acetyl
hexapeptide-2, alnus firmirolia (yashabushi) extract,
tocopheryl acetate (vitamin E acetate), glyceryl stearate,
thioctic acid (a-lipoic acid), PEG-100 stearate, ascorbyl
palmitate ( vitamin C palmitate), tocopherol (vitamin E),
tetrahexyldecyl ascorbate, sesamum indicum (sesame) seed
oil, retinyl palmitate (vitamin A palmitate), Prunus
armeniaca (apricot) kernel oil, willow bark extract,
phenoxyethanol, benzyl alcohol, potassium sorbate, glycerin,
panthenol (pro-vitamin B5), retinal (vitamin A), lavandula
agustifolia (lavender) oil, allantoin, polysorbate 20,
xanthan gum, titanium dioxide, tetrasodium EDTA, topheryl
linoleate (vitamin E linoleate), dimethylamino
methylpropanol, ceramide 2, quaternium-15, polyacrylamide,
magnesium aluminum silicate, laureth-7, citric acid, C13-14
isoparaf fin, aloe barbadensis (aloe vera) leaf juice,
cetearyl glucoside, 10-hydroxydecanoic acid, hydroxycaprylic
acid, prunus amygdalus dulcis (sweet almond)oil, zinc PCA,
zinc oxide, acacia, tragacanth, agar, pectin, gelatin,
methyl cellulose, carboxymethylcellulose, carbomer, vitis
vinifera (grape) seed extract, hibiscus sabdariffa flower
extract, triticum vulgare (wheat)germ oil, citic acid,
sodium hydroxymethylglycinate, isopropyl palmitate,
squalane, cetearyl glucoside, lecithin, pluronic, cucumis
sativus (cucumber) fruit extract, cetyl ricinoleate,
caprylic/capric triglycerides, allantoin, ubiquinone
(coenzyme Q10), helianthus annuus (hybrid sunflower) oil,
cyclomethicone sodium PCA, stearic acid, glyceryl stearate,
rose canina (rose hips) fruit oil, glycol, glycyrrhiza
glabra (licorice) extract,aesculus hippacastanum (horse
chestnut)extract, hydrolyzed yeast protein, calendula
off icinalis flower extract, centella asiatica (gotu kola)
extract, ruscus aculeatus (butcher's broom)root extract,
cyclopentasiloxane, evening primrose oil, PEG-75, PEG-150,
sodium PCA, calendula officinalis flower extract,
cyclopentasiloxane, hydrolyzed milk protein, ethoxy
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diglycol, lupinus albus seed oil, hydrophilic petrolatum,
wool alcohol, sodium lauryl sulfate, PEG 4000, PEG 400,
propylene glycol-ethanol, lecithin soya granular, sorbic
acid, polyacrylamide, cytel alcohol, magnesium aluminum
silicate, aloe vera (aloe barbadensis) prunus amygadalus
amara (bitter almond) kenel oil, pro-lipo multi-emulsion
liposomic system, propylparaben, methylparaben,
imidazolidimyl urea, pluronic F127, alcohol, sodium
hydroxide, DMAE, glycolic acid, edetate disodium dihydrate,
urea, stearic acid, glyceryl monostearate, isopropyl
myristate, polyoxyl 40 stearate, potassium sorbate,
anhydrous ointment base, lanolin, anhydrous lanolin,
emollient cream base, lanolin alcohol, mineral oil, glyceryl
monostearate, stearic acid flakes, sualene, triethanolamine,
krisgel 100, borago (borage) officinalis seed oil,
simethicone, salicylic acid, dehydroacetic acid, benzyl
alcohol, benzoic acid, benzethonium chloride, polysorbate
80, span, PEG-8 distearate/emerest 2712, hydrogenated
vegetable oil, mineral oil (heavy), mineral oil (light),
microethane FN 501, hydroxypropylcellulose,
hydroxymethylcellulose, methylcellulose, avicel, polyglygol
300, polyglycol 8000, paraffin waxes, propylene glycol
isostearate, isostearyl alcohol, white ointment USP, yellow
ointment NF, oleic acid USP, olive oil USP, paraffin USP,
petrolatum NF, spermaceti wax USP, synthetic spermaceti NF,
starch glycerite NF, white wax USP, yellow wax USP,
dbutylated hydroxy toluene, or combination thereof.
tamm The carrier should satisfy the following
characteristics:
the base should allow the wetted hormone to be
incorporated therein;
the base should be compatible with the skin with the
least possible number of adverse effects;
the base should be smooth and pliable with no adverse
odor;
the base should have a color appealing to the consumer;
the base must be stable and must provide a stable
vehicle for the medication; and
CA 02459869 2004-05-18
the base should be able to readily release the
medication incorporated therein into the skin.
Additional Ingredients
[00071] The concentrated pharmaceutical composition
according to the invention optionally can include
antioxidants to prevent oxidation of any of the components
therein. The antioxidant may include, but are not limited
to, ascorbic acid, sodium ascorbate, sodium formaldehyde
sulfoxylate, sodium bisulfite, sodium nitrite, sodium
thiosulfate, sodium metabisulfite, sodium sulfite, sulfur
dioxide, tannic acid, thioglycerol, tert-butyl-hydroquinone,
thioglycolic acid, thiolactic acid, thiosorbitol, thiourea,
tocopherols, butylated hydroxy toluene, acetone sodium
sulfate, acetylcysteine, lipoic acid (sodium salt),
tocopherol, ascorbyl palmitate, butylated hydroxyanisole,
calcium ascorbate, calcium bisulfite, calcium sulfite,
. cysteine, dilauryl thiodipropionate, dithiothreitol,dodecyl
gallate, ethoxyquin, ethyl gallate, gallic acid,
glutathione, gossypol, hydroquinone,4-hydroxymethy1-2,6-di-
tert-butylphenol, hypophosphorus acid, isoascorbic acid,
lecithin, monothioglycerol, B-naphthol, nordihydroguaiaretic
acid, octyl gallate, potassium metabisulfite, propyl
gallate, sesamol, or Vitamin E. These antioxidants are not
particularly limited; any of those known in the
pharmaceutical or cosmetic industries may be used.
[00072] In addition, the concentrated pharmaceutical
composition according to the invention optionally may
include preservatives to prevent the growth of bacteria or
fungi in the final product. These may include, but are not
limited to, thimerosal, benzyl alcohol, imidazolidinyl urea,
quaternium-15, benzalkonium chloride, chlohexidine,
chlorbutanol, phenol, cresol, chlorothymol, chloroxylenol,
P-chlorometaxylenol, sodium benzoate, potassium sorbate,
boric acid, methyl paraben, propylparaben, sorbic acid,
alcohol, benzethonium chloride, benzoic acids and salts,
benzyl alcohol, sodium benzoate, boric acids and salts,
cetylpyridinium chloride, cetyltrimethyl ammonium bromide,
16
CA 02459869 2004-05-18
chlorbutanol, clorocresol, imidazolidinyl urea, metacresol,
myristylgamma picolinium chloride, nitromersol,
parabens(benzyl, butyl, methyl, propyl), phenol, phenyl
phenol, phenylethyl alcohol, phenylmercuric acetate/nitrate,
sorbic acids and salts, thimerosal, hydroxybezoate esters
and phenyl ethyl alcohol. These preservatives are not
particularly limited; any of those known in the
pharmaceutical or cosmetic industries may be used.
[00073] Further, the concentrated composition of the
invention optionally can include chelating agents and
synergists added, which may include, but are not limited to,
EDTA and salts, alkyl gallates, ascorbic acid, boric acid,
citraconic acid, gluconic acid, hydroxyquinolone sulfate,
maleic acid, phosphoric acid, polysorbates, saccharic acid,
tartaric acid, tryptophan and citric acid. These chelating
agents and synergists are not particularly limited; any of
those known in the pharmaceutical or cosmetic industries may
be used.
[00074] Further, the concentrated composition of the
invention optionally can include emulsifying agents to
facilitate the formation of an emulsion. The emulsifying
agents may include, but are not limited to acacia,
tragacanth, agar, pectin, gelatin, methyl cellulose,
carboxymethylcellulose, PEG-40 castor oil, PEG 300,
polysorbate 20, polysorbate 40, polysorbate 80, sorbitan
monopalmitate, simethicone, or any synthetic anionic,
cationic, or nonionic emulsifying agents. These
emulsifying agents are not particularly limited; any of
those known in the pharmaceutical or cosmetic industries may
be used.
[00075] Further, the concentrated composition of the
invention optionally can include suspending agents to
increase viscosity. The suspending agents may include, but
are not limited to, acasia, bentonite,
carboxymethylcellulose, methycellulose,
hydroxypropylcellulose, carbomer resins, colloidal silicon
dioxide, sodium alginate, tragacanth, agar, alginic acid,
attapulgite, bentonite, carrageenan, cellulose,
17
CA 02459869 2004-05-18
microcrystalline cellulose, microcrystalline
carboxymethylcellulose, dextrin, gelatin, guar gum,
hydroxyethylcellulose, hydroxypropylmethyl-cellulose,
magnesium aluminum silicate, pectin, polaxamer, polyethylene
oxide, polyvinyl alcohol, povidone, propylene glycol
alginate, xanthan gum, and veegum. These suspending agents
are not particularly limited; any of those known in the
pharmaceutical or cosmetic industries may be used.
[00076] Further, the concentrated composition of the
present invention optionally can include stiffening agents
to increase viscosity. The stiffening agents may include,
but are not limited to, hydrogenated castor oil, cetostearyl
alcohol, cetyl alcohol, cetyl esters wax, hard fat,
paraffin, synthetic paraffin, stearyl alcohol, emulsifying
wax, white wax, and yellow wax. These stiffening agents are
not particularly limited; any of those known in the
pharmaceutical or cosmetic industries may be used.
[00077] Further, the concentrated composition of the
present invention optionally can include any substance,
which can increase or decrease the pH of the system added.
The pH modifiers can be either acidifying agents or
alkalizing agents. The pH can be modified to any pH, which
is deemed suitable. These pH modifiers may include but are
not limited to, (acidifying agents) acetic acid, acetic acid
glacial USP, citric acid, hydrochloric acid, fumaric acid,
lactic acid, nitric acid, phosphoric acid, sodium phosphate
monobasic, sulfuric acid, malic acid, tartaric acid
propionic acid, (alkalizing agents) ammonia solution,
ammonium carbonate, diethanolamine, monoethanolamine, sodium
bicarbonate, sodium borate, sodium phosphate dibasic,
trolamine, potassium hydroxide, sodium hydroxide, and sodium
carbonate. These PH modifiers are not particularly limited;
any of those known in the pharmaceutical or cosmetic
industries may be used.
[00078] Further, the concentrated composition of the
present invention optionally can include any solubilizing
agent. These agents may include but are not limited to,
benzalkonium chloride, cetylpyridium chloride, benzethonium
18
CA 02459869 2004-05-18
vz
chloride, docusate sodium, nonoxynol 9, octoxynol 9,
polaxamer(s), polyoxyl 35 castor oil, polyoxyl 40
hydrogenated castor oil, polyoxyl 10 oleyl ether, polyoxyl
20 cetostearyl ether, polyoxyl 40 stearate, polysorbate 20,
polysorbate 40, polysorbate 60, polysorbate 80, sodium
lauryl sulfate, sorbitan monolaurate, sorbitan monooleate,
sorbitan monopalmitate, sorbitan monostearate, and
tyloxapol. These wetting and/or solubilizing agents are not
particularly limited; any of those known in =the
pharmaceutical or cosmetic industries may be used.
[00079] Further, the concentrated composition of the
present invention optionally can include any substance,
which can increase the shelf life of said product. These
agents may include but are not limited to, vitamin E and
ascorbic acid. These substances are not particularly
limited; any of those known in the pharmaceutical or
cosmetic industries may be used.
[00080] In one embodiment, the concentrated hormone
pharmaceutical composition contains 32 mg/g estriol, 4 mg/g
estradiol, and 4 mg/g estrone concentrates (triest) in 960
mg/g of a mixture of 50% ethoxy diglyco1/50% propylene
glycol. The estriol, estradiol, and estrone are present in
the composition at 8:1:1, 6:3:1, 5:4:1 or 7:2:1 ratios.
[00081] After extensive research, the present inventor
discovered that the combination of ethoxy diglycol and
propylene glycol in any ratio has the ability to dissolve
the combination of estriol, estradiol, and estrone (triest)
in any ratio or testosterone alone better than using any of
the solvents alone.
[00082] In another embodiment, the concentrated hormone
pharmaceutical composition contains 32 mg/g estriol and 8
mg/g estradiol concentrates (biest) in 960 mg/g of a mixture
of 50% ethoxy diglyco1/50% propylene glycol. The estriol and
estradiol are present in the composition at 8:2, 5:5, 6:4,
7:3, or 9:1 ratio.
[00083] In another embodiment, the concentrated hormone
pharmaceutical composition contains 64 mg/g testosterone
concentrate in a mixture of 50% ethoxy diglyco1/50%
19
CA 02459869 2004-05-18
propylene glycol for women and 150 mg/g of a mixture of 50%
ethoxy diglyco1/50% propylene glycol for men.
[00084] In another embodiment, the concentrated hormone
pharmaceutical composition contains 600 mg/g of progesterone
concentrate in vanishing cream type oil in water emulsion
base.
[00om] In another embodiment, the concentrated hormone
pharmaceutical composition contains 0.8 g/g estriol, 0.1 g/g
estradiol, and 0.1 g/g estrone (triest) in a powdered form
optionally mixed with any amount of a filler or in the
following ratios: 8:1:1, 7:2:1, 6:3:1, or 5:4:1.
[00086] In another preferred embodiment, the concentrated
hormone pharmaceutical composition contains 0.8 g/g estriol
and 0.2 g/g estradiol (biest) in a powdered form optionally
mixed with any amount of a filler or in the following
ratios: 5:5, 6:4, 7:3, 8:2, or 9:1.
[00087] In another preferred embodiment, the concentrated
hormone pharmaceutical composition comprises:
at least one hormone;
optionally a powdered base;
wherein the at least one hormone is chosen from
estriol, estradiol, or combination thereof; and
wherein the composition is in a powdered form.
gmom The at least one hormone a combination of estriol,
estradiol in a ratio of 5:5, 6:4, 7:3, 8:2, or 9:1.
[00089] In another preferred embodiment, the concentrated
hormone pharmaceutical composition comprising:
at least one hormone; and
optionally a powdered base;
wherein the at least one hormone is chosen from
estriol, estradiol, estrone, or combination thereof; and
wherein the composition is in a powdered form.
CA 02459869 2004-05-18
[0*090] The at least one hormone is a combination of
estriol, estradiol, and estrone in a ratio of 5:4:1, 6:3:1,
7:2:1, or 8:1:1.
[00091] Examples of powdered bases suitable for use in the
pharmaceutical compositions disclosed herein include, but
are not limited to, talc, calcium carbonate,
microcrystalline cellulose, powdered cellulose, dextrates,
kaolin, rice, flour, chalk, silica gel, sodium stearate,
glycerol monostearate, mannitol, silicic acid, sorbitol,
starch, pre-gelatinized starch, and mixtures thereof.
glom In another embodiment of the present invention,
the at least one hormone is combined directly with the
pharmaceutically acceptable carrier (ointment, cream, powder
or gel base) without the prior use of a solvent or solvents.
[00093] In a further embodiment of the present invention,
the hormone is weighed and packaged unadulterated in an
appropriate container. The solvent or solvents and/or
optionally the ointment, cream, gel base, or powdered base
are packaged in a separate container. The two products are
sold together as a kit. The two components are to be
combined by whoever purchases the kit to formulate the
hormone concentrate system.
[00094] Color coded-concentrated pharmaceutical
composition
[00095] The present invention also provides a color-coded
concentrated hormone composition to help the pharmacist
quickly choose the composition to be used.
[00096] The advantage of having color-coded concentrates
are as follows:
helps to rapidly identify the concentrate.
ensures that all concentrates required to be contained
in a final product are present in said final product. This
is made possible because each combination and permutation of
the concentrates will result in a distinct color profile. If
the final product does not match the color profile for that
medication, you know you have done something wrong; and
21
CA 02459869 2004-05-18
ensures complete mixing of the final product. When the
final product is a uniform color throughout, adequate mixing
will have taken place.
[00097] The coloring agent could possibly be, but is not
limited to one of the following: acid red 52, basic fuchsin
USP, brilliant green, caramel NF, carmine NO.40, congo red,
D&C green NO.5, D&C green NO.6, D&C green NO. 8, D&C orange
NO.4, D&C red NO.4, D&C red NO.6, D&C red NO.17, D&C red NO.
22, D&C red NO.28, D&C red NO.33, D&C violet NO.2, D&C
yellow NO.8, D&C yellow NO.10, D&C yellow NO.11, F.D. &C.
blue NO.1, F.D. &C. blue NO.2, F.D. &C. green NO.3, F.D. &C.
red NO.3, F.D. &C. red NO.19, F.D. &C. red NO.40, F.D. &C.
yellow NO.5, F.D. &C. yellow NO.6, malachite green oxalate,
rose Bengal, saffron, scarlet red, and any food color in
liquid or powder form. The coloring agent is not
particularly limited; any of those known in the
pharmaceutical or cosmetic industries may be employed.
Preferably, the coloring agent will not noticeably color the
skin. It should be compatible with the skin with the least
number of adverse effects.
[00098] The concentrates according to the present
invention would be manufactured using extensive safety
measures. These include, but are not limited to, the use of
custom built clean rooms (a room designed specifically for
compounding with hazardous materials), high velocity air
flow units fitted with high emission particulate air (HEPA)
filters, custom built ventilation systems, protective suits,
protective eyewear, protective gloves, and protective HEPA
filter masks.
[00099] A pharmacist or technician trained in the art of
compounding BHRT ointments, creams, gels, and pastes will
manufacture these concentrates.
gmolom An advantage of the present invention is the
composition contains a high concentration of hormones
(higher than the prescribed levels), thus the pharmacist can
easily use the concentrates to produce a custom tailored
BHRT product without risking his own health.
22
CA 02459869 2004-05-18
[000101] The present invention also contemplates a method
for producing the concentrated composition of the present
invention. The method comprises the steps of:
measuring at least one hormone, a solvent and/or
optionally a carrier by using an electronic balance in a
clean room;
combining the ingredients of step a by using an
industrial scale mixer to ensure thorough mixing; and
running the mixture of step b through a large-scale
ointment mill or homogenizer to decrease the particle size
of the drug, and
optionally, heating the concentrate to facilitate the
formation of a solution,
wherein the hormone concentration is from about 0.6 to about
80%.
[000102] The concentrated hormone pharmaceutical
composition of the present invention may be further divided
with similar or different carrier materials to
concentrations that are suitable for practical use by the
compounding pharmacist.
[000103] If the medication is not thoroughly mixed, then it
will not contain a uniform concentration of the drug
throughout. A solution will provide the best distribution of
drug throughout the system.
[000104] Running the mixture through a large-scale ointment
mill or using a homogenizer decreases the particle size and
increases the absorbability, because smaller drug particles
will more readily penetrate the dermis. This process also
ensures a non-gritty, pharmaceutically elegant, and
cosmetically pleasing final product.
[00010] The present invention is also in combination with
a dispensing device to provide a means to measure and
combine, quickly and accurately, quantities of hormones with
appropriate ointment, cream, or gel bases while minimizing
exposure to hazardous airborne hormone particles. Thus,
airborne particles are drastically reduced because the
hormones are incorporated into a liquid or semi-solid form.
23
CA 02459869 2004-05-18
Example 1
[000106] The formulation was made in the following manner
(total quantity: 120 ml and a concentration of 300mg/g of
testosterone)
36g of testosterone were weighed out.
b) the volume was brought up to 120m1 with approximately
84 ml of an anhydrous gel base.
1 drop of blue food coloring was added.
the mixture was combined in an electronic mortar and
pestle.
the mixture was run through an ointment mill to decrease
the particle size of the testosterone.
the mixture was transferred into 4 30m1 luer lock syringes.
This is what the mixture is sold in.
Example 2
[000107] The formulation, according to the invention, was
made in the following manner (total quantity: 1000m1 and a
concentration of 62.5mg/g of triest (estriol, estradiol, and
estrone in an 8:1:1 ratio)
50g of estriol were weighed out and wetted with 50m1 of
ethoxy diglycol.
6.25g of estradiol were weighed out and wetted with 6.25m1
of ethoxy diglycol.
6.25g of estrone were weighed out and wetted with 6.25m1 of
ethoxy diglycol.
drops of red food coloring was added.
the volume was brought up to 1000m1 with approximately 875m1
of oil in water emulsion type vanishing cream base.
the mixture was combined in an industrial mixer.
the mixture was run through an ointment mill to decrease the
particle size of the estrogens.
the mixture was transferred into 33 30m1 luer lock syringes.
This is what the mixture is sold in.
24
CA 02459869 2004-05-18
=
Example 3
MOM] The formulation, according to the invention, was
made in the following manner (total quantity: 5000 ml and a
concentration of 400mg/g of progesterone)
2000g of progesterone were weighed out.
the progesterone was combined with an oil phase, an
aqueous phase and an emulsifier to formulate a water
in oil emulsion type cream base with a final volume
(including the progesterone) of 5000m1.
50 drops of yellow food coloring was added.
the mixture was combined in an industrial mixer.
the mixture was run through an ointment mill to decrease the
particle size of the progesterone.
the mixture was transferred into 83 60m1 luer lock syringes.
This is what the mixture is sold in.
Example 4
[000109] The formulation, according to the invention, was
made in the following manner (total quantity: 10000 ml and a
concentration of 600mg/g of progesterone (this is a paste)
6000g of progesterone were weighed out.
the progesterone was combined with 2000m1 of ethoxy
diglycol.
100 drops of yellow food coloring was added.
an oil in water emulsion type vanishing cream base was
used to bring the final volume to 10000m1, approximately
2900g of the cream.
the mixture was combined in an industrial mixer.
the mixture was run through an ointment mill to decrease the
particle size of the progesterone.
the mixture was transferred into 50m1 ointment jar. This
is what the mixture is sold in.
Example 5
[000110] The formulation, according to the invention, was
made in the following manner (total quantity: 2000 ml and a
concentration of 300mg/g of testosterone)
CA 02459869 2004-05-18
600g of testosterone were weighed out.
The testosterone was combined with approximately 400m1
of ethoxy diglycol.
15 drops of blue food coloring was added.
Approximately 1000m1 of a 1% hydroxypropylcellulose in
ethoxy diglycol anhydrous gel was added to bring the final
volume to 2000m1.
The mixture was combined in an industrial mixer.
The mixture was further mixed with a homogenizer to
decrease the particle size of the testosterone.
The mixture was transferred to 40 50m1 bottles fitted
with adapter caps. A 5m1 oral syringe and a lml oral
syringe, fitting the adapter cap, were packaged with each
bottle to be used as measuring devices.
Example 6
[000111] The formulation, according to the invention, was
made in the following manner (total quantity: 10000m1 and a
concentration of 40 mg/g of triest (estriol, estradiol, and
estrone in an 8:1:1 ratio))
320g of estriol were weighed out.
40g of estradiol were weighed out.
40g of estrone were weighed out.
100 drops of red food coloring was added.
The volume was brought up to 10000m1 with a 50% ethoxy
diglycol and 50% propylene glycol combination.
The mixture was combined in an industrial mixer.
The mixture was heated to 60 degrees Celsius for 2
hours in order to facilitate solution of the triest powder.
The solution was transferred into 100 100m1 bottles
fitted with adapter caps, accompanied with lml, 5m1, and
10m1 oral syringes. This is what the mixture is sold in.
26
CA 02459869 2004-05-18
Example 7
MOM The formulation, according to the invention, was
made in the following manner (total quantity: 2000 ml and a
concentration of 70mg/g of testosterone)
140g of testosterone were weighed out.
15 drops of blue food coloring was added.
The testosterone was combined with approximately 1860m1
of ethoxy diglycol, enough to bring the final volume to
2000m1.
The mixture was combined in an industrial mixer.
The mixture will now be a solution.
The solution was transferred to 40 50m1 bottles fitted
with adapter caps. A 5m1 oral syringe and a lml oral
syringe, fitting the adapter cap, were packaged with
each bottle to be used as measuring devices.
Example 8
[00OW] The formulation, according to the invention, was
made in the following manner (total quantity: 2000 ml and a
concentration of 150mg/g of testosterone)
300g of testosterone were weighed out.
15 drops of blue food coloring was added.
The testosterone was combined with approximately 1700m1
of a 50% ethoxy diglycol and 50% propylene glycol mixture,
enough to bring the final volume to 2000m1.
The mixture was heated to 60 degrees Celsius and mixed
in an industrial mixer.
The mixture will now be a solution.
The solution was transferred to 40 50m1 bottles fitted
with adapter caps. A 5m1 oral syringe and a lml oral
syringe, fitting the adapter cap, were packaged with each
bottle to be used as measuring devices.
[000114] Example 9
mom] The formulation, according to the invention, was
made in the following manner (total quantity: 1000gm and a
27
CA 02459869 2004-05-18
- _
concentration of 62.5mg/gm of triest (estriol, estradiol,
and estrone in an 8:1:1 ratio))
50g of estriol were weighed.
6.25g of estradiol were weighed out.
6.25g of estrone were weighed out.
The weight was brought up to 1000gm with approximately
937.5gm of lactose.
The mixture was combined in an industrial mixer.
The mixture was transferred to 10 100gm jars.
[000116] Example 10
[000117] The formulation, according to the invention, was
made in the following manner (total quantity: 1000m1 and a
concentration of 40mg/g of triest (estriol, estradiol, and
estrone in an 8:1:1 ratio))
32g of estriol were weighed out.
4g of estradiol were weighed out.
4g of estrone were weighed out.
The three powders were combined.
4g of this combination were transferred into each of 10
100m1 bottles fitted with adapter caps.
Approximately 96m1, enough to bring the final volume to
100m1, of a 50% ethoxy diglycol and 50% propylene glycol
mixture was transferred to each of 10 other 100m1
bottles fitted with adapter caps.
The bottles could be sold as a kit or as 2 separate
entities. 1 bottle of powder and 1 bottle of solvent would
constitute 1 kit. The purchaser would add the solvent to the
bottle containing the powder using an oral syringe so as not
to be exposed to the powdered hormones. With stirring, at 50
degrees Celsius, the combination would form a solution. This
solution is the hormone concentrate.
Example 11
[000118] The formulation, according to the invention, was
made in the following manner (total quantity: 100m1 and a
28
CA 02459869 2004-05-18
-
concentration of 40mg/g of triest (estriol, estradiol, and
estrone in an 8:1:1 ratio))
3.2g of estriol were weighed out and transferred into a
100m1 bottle.
0.4g of estradiol were weighed out and transferred into
a 100m1 bottle.
0.4g of estrone were weighed out and transferred into a
100m1 bottle.
Enough colored 50% propylene glycol/50% ethoxy diglycol
mixture to combine with the estriol, estradiol, and estrone
to bring the final volume to 100m1, approximately 96m1, was
measured and transferred into a 100m1 bottle.
Example 12
[000119] The formulation, according to the invention, was
made in the following manner (total quantity: 120 ml and a
concentration of 300mg/g of testosterone)
36g of testosterone were weighed out.
The volume was brought up to 120m1 with approximately
84 ml of a glycerin.
1 drop of blue food coloring was added.
The mixture was combined in an electronic mortar and
pestle.
The mixture was run through an ointment mill to
decrease the particle size of the testosterone.
The mixture was transferred into 4 30m1 luer lock
syringes. This is what the mixture is sold in.
[000120] The mixture of example 11 will be sold as a kit in
which the pharmacist will combine the elements to produce
the hormone concentrate system. The pharmacist will
transfer the liquid into the bottle containing the estriol,
then transfer this mixture into the bottle containing the
estradiol, then transfer this mixture into the bottle
containing the estrone. This final solution will be the
triest concentrate.
[000121] These concentrates could be packaged in, or with,
any graduated dispensing device that lends itself to
29
CA 02459869 2004-05-18
accurately measure specific volumes of liquids or semi-
solids including, but not limited to, a metered dose tube, a
metered dose pump, a metered dose syringe, a bottle, an
ointment jar, a metered dose spray bottle, a bottle fitted
with an adapter cap, and a luer lock syringe, a pipette, a
bottle top dispenser, a burette, and a metered dose scoop.
The packaging, dispensing, or measuring devices are not
particularly limited. Any of those known in the
pharmaceutical, chemical, or cosmetic industries may be
used.
[000122] A specific amount, different for each compound, of
these concentrates would be combined with an appropriate
amount of any ointment, cream, or gel base, suitable for
transdermal administration of bio-identical hormones, to
form a final product which contains the doctor prescribed
concentration of each bio-identical hormone.
[000123] The pharmacist using the concentrate, according to
the invention, can easily incorporate the hormone into the
compounding BERT ointments, creams, gels, or pastes by:
Putting on protective gloves.
Calculating the total amount of hormones needed to
compound a medication of a specific volume and
concentration depending on the patient necessities;
Determining how many milliliters of the appropriate
concentrate will contain the total amount of hormone needed
for the compound.
Measuring the volume of concentrate containing the
total amount of hormone needed. This is done using an
appropriate liquid or semi-solid measurement system.
Repeating steps 2 through 4 for each hormone to be
present in the final preparation.
Calculating the amount of the appropriate ointment,
cream, or gel base, which is needed for the final product.
This is accomplished by subtracting the total volume of
concentrates used from the total volume needed.
Combining the ointment, cream, or gel base and the
concentrates on a glass ointment slab, using an EMP, mixing
CA 02459869 2004-05-18
them an appropriate number of times between two luer lock
syringes attached together using a luer lock to luer lock
adapter or any other form of mixing. When the color is
uniform throughout, adequate mixing has taken place.
1000124] In another embodiment, the pharmaceutically
acceptable carrier is sold inside a metered dose device.
These will make unnecessary to use a scale in measuring and
making BHRT creams. This is a distinct advantage for
pharmacies not presently engaged in the art of compounding.
The only additional equipment needed is a spatula for
mixing. If the carrier is not packaged in a metered device,
then the cream would have to be weighed and measured using a
scale, which takes more time as well as additional cost to
purchase the scale.
gam In addition, the invention concerns a kit for
producing a concentrated hormone pharmaceutical composition,
the kit comprising:
at least one hormone;
at least one solvent, and
optionally a pharmaceutically acceptable carrier,
wherein each element is packet in separated graduated
dispensing devices.
[000126] In a further embodiment, the kit of the present
invention comprises separately packing the at least one
hormone and the at least one solvent in a container having
internal divisions, wherein the at least one hormone and the
at least one solvent are combined by the purchaser to form
the hormone concentrate system.
[000127] Advantages
[000128] The concentrated composition of the invention
offers numerous advantages over compounding BHRT ointments,
creams, gels, or pastes using a traditional method with
commercially available hormones in powder form.
[WM Using these concentrates, combined with an
appropriate liquid or semi-solid measurement system, in the
place of powdered hormones and a scale, will dramatically
31
CA 02459869 2004-05-18
reduce the risk of exposure to hazardous airborne hormone
particles. This is due to the fact that the powdered
hormones are incorporated into a liquid or semi-solid. This
means that the need for inconvenient, expensive, and time-
consuming safety measures is greatly reduced. Since there
are relatively few airborne particles, there is little or no
need for the use of custom built clean rooms (a room
designed specifically for compounding with hazardous
materials), high velocity air flow units fitted with HEPA
filters, custom built ventilation systems, protective suits,
protective eyewear, or protective HEPA filter masks. The
only safety measure definitely required is protective
gloves.
[000130] When the concentrates are manufactured, they are
mixed using an industrial mixer, which ensures thorough
mixing. This alleviates the need for purchasing and using an
EMP for compounding BHRT ointments, creams, gels, or pastes.
They are also run through a large ointment mill or
homogenizer to reduce the particle size of the drug. This
will increase absorbability, as smaller drug particles will
more readily penetrate the dermis. This process also ensures
a non-gritty, pharmaceutically elegant, and cosmetically
pleasing product. This alleviates the need for purchasing
and using an ointment mill for compounding BHRT ointments,
creams, gels, or pastes.
[000131] The concentrates of the present invention offer
the advantage that they are easier and most accurate to
measure. The fact that the hormones are in solution results
in a superior final product, the product produced from the
concentrates and dispensed to the patient. This is due to
the fact that there are no particles. All particles have
been solubilized. This results in a pharmaceutically elegant
and easily penetrateable final product.
[000132] The fact that the concentrates are color-coded
will greatly reduce the chance of compounding errors. The
color system should reduce the inadvertent use of one
hormone concentrate instead of another. It will also ensure
that all of the intended concentrates are present in the
32
CA 02459869 2004-05-18
final product. This is accomplished because each combination
and permutation of the concentrates will have a distinct
color profile. If the final product does not match its
profile, then you know something has been done incorrectly.
The color system will also help ensure that the final
product is uniformly mixed. When the final product is a
consistent color throughout, you will have adequate mixing.
At the present time, most compounding pharmacists do not
have an adequate system in place to ensure proper mixing.
Without proper mixing, the final product will not have a
uniform concentration of the hormones throughout the system.
Since the concentrate system alleviates the need
for most of the safety measures required for compounding
these medications, as well as the need for a scale, EMP, and
ointment mill, it significantly reduces the cost of
compounding these medications. The concentrate system also
significantly decreases the time needed to compound them.
This is because the number of steps needed to compound them
is drastically reduced. This increase in efficiency will
result in a proportional decrease in labor costs.
[0001341 The hormone concentrates and an appropriate liquid
or semi-solid measurement system will make it possible for
any pharmacist in any setting to safely and accurately
compound BHRT ointments, creams, gels, and pastes. At the
present time, only compounding pharmacists with elaborate
compounding facilities and the proper equipment can compound
them safely and accurately. Using this invention, any
pharmacist in any setting will now be able to safely,
quickly, inexpensively, and accurately compound BERT
ointments, creams, gels, and pastes. This will inevitably
result in an increase in the availability of these
medications to the public.
[0001351 The fact that each final product, the product
dispensed to the patient, has a distinct colour profile has
an additional benefit. It will help decrease the chance of
dispensing the wrong product to a patient. If a patient was
to receive a Tri-est cream (which should be pink) but a blue
cream was labeled Tri-Est, the pharmacist would be easily
33
CA 02459869 2004-05-18
able to identify the error. Also, the patient would be able
to tell that their previous cream was pink and this one is
blue, bringing this to the pharmacist's attention. At
present time all hormone creams are white, making it all but
impossible to detect, a labeling error. The colour coding
also decreases the likely hood of choosing the wrong cream
from the stock as each cream is readily identifiable. The
coloring system allows each final product to be
differentiated from one another.
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