U.S. patent application number 12/925738 was filed with the patent office on 2011-03-24 for system for use by compounding pharmacists cists to produce hormone replacement medicine customized for each customer.
Invention is credited to Stephen A. Mamchur.
Application Number | 20110071122 12/925738 |
Document ID | / |
Family ID | 34375867 |
Filed Date | 2011-03-24 |
United States Patent
Application |
20110071122 |
Kind Code |
A1 |
Mamchur; Stephen A. |
March 24, 2011 |
System for use by compounding pharmacists cists to produce hormone
replacement medicine customized for each customer
Abstract
This invention provides a system for compounding a
pharmaceutical product for hormone replacement therapy. The system
has a set of concentrated reagent compositions, each containing one
or more steroid hormones dissolved in one or more solvents. The
needs of each consumer are ascertained, and a pharmaceutical
product is compounded for them using the concentrated reagent
compositions. Each product has a custom tailored combination of
steroid hormones at a concentration that is therapeutically
effective for the consumer in accordance with their needs.
Inventors: |
Mamchur; Stephen A.; (Prince
Albert, CA) |
Family ID: |
34375867 |
Appl. No.: |
12/925738 |
Filed: |
October 28, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10668075 |
Sep 22, 2003 |
7858607 |
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12925738 |
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60454915 |
Mar 14, 2003 |
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Current U.S.
Class: |
514/170 ;
356/402; 514/177; 514/178 |
Current CPC
Class: |
A61K 31/565 20130101;
A61K 31/568 20130101; G01N 33/74 20130101; Y10S 514/947 20130101;
Y10S 514/874 20130101; A61K 31/566 20130101; A61K 31/565 20130101;
A61K 47/26 20130101; Y10S 514/843 20130101; A61P 5/26 20180101;
Y10S 514/841 20130101; A61P 5/30 20180101; A61K 47/10 20130101;
A61K 2300/00 20130101; A61K 9/0014 20130101; A61K 31/56 20130101;
Y10S 514/899 20130101; A61K 31/57 20130101; A61K 47/38
20130101 |
Class at
Publication: |
514/170 ;
514/178; 514/177; 356/402 |
International
Class: |
A61K 31/57 20060101
A61K031/57; A61K 31/568 20060101 A61K031/568; A61K 31/566 20060101
A61K031/566; A61P 5/26 20060101 A61P005/26; A61P 5/30 20060101
A61P005/30; G01J 3/46 20060101 G01J003/46 |
Claims
1. A method of compounding a pharmaceutical product for hormone
replacement therapy, whereby each product is custom tailored
according to the needs of each individual consumer, the method
comprising: a) obtaining a plurality of concentrated reagent
compositions, each comprising one or more steroid hormones
dissolved in one or more solvents, wherein at least one of the
concentrated hormone reagent compositions in the plurality contains
a hormone that is not in other reagent compositions in the
plurality; b) ascertaining the needs of an individual consumer; c)
compounding concentrated reagent compositions selected from the
plurality into a pharmaceutical product such that: the
pharmaceutical product has a ratio of steroid hormones that is
custom tailored for said consumer; and the pharmaceutical product
contains a total concentration of steroid hormones that is
therapeutically effective for the consumer in accordance with their
needs.
2. The compounding method of claim 1, wherein step b) is
accomplished by way of a prescription from a doctor for replacement
of particular hormones in said individual each in a particular
amount.
3. The compounding method of claim 1, wherein the concentrated
reagent compositions compounded in step c) include a plurality of
concentrated reagent compositions, each containing a different
estrogen dissolved at a total concentration of at least 40 mg per
gram.
4. The compounding method of claim 1, wherein the concentrated
reagent compositions compounded in step c) include a reagent
composition that contains a plurality of estrogens dissolved at a
total concentration of between 10 and 60 mg of estrogens per
gram.
5. The compounding method of claim 1, wherein the concentrated
reagent compositions compounded in step c) include a reagent
composition that contains at least one androgen dissolved at a
concentration of at least 150 mg per gram, wherein said androgen is
selected from testosterone and dehydroepiandrosterone (DHEA).
6. The compounding method of claim 1, wherein the concentrated
reagent compositions compounded in step c) include a reagent
composition that contains at least one progestagen dissolved at a
concentration of at least 200 mg per gram, wherein said progestagen
is selected from progesterone and pregnenolone.
7. The compounding method of claim 1, whereby the pharmaceutical
product produced according to the method contains estriol,
estradiol, and estrone at a ratio of 8:1:1, 5:4:1, 6:3:1, or 7:2:1
by weight.
8. A reagent system for compounding pharmaceutical products
containing multiple steroid hormones for use in hormone replacement
therapy, wherein the system allows each of such products to be
custom tailored for each individual consumer; wherein the system
comprises a plurality of concentrated hormone reagent compositions,
each of which contains one or more steroid hormones dissolved in
one or more solvents; wherein at least one concentrated hormone
reagent composition in the system contains hormones that are
different from what is in other concentrated hormone reagent
compositions in the system; and wherein each of said reagent
compositions comprises a sufficient concentration of said one or
more hormones such that when combined with other compositions in
the system to form a custom tailored pharmaceutical product, the
concentration of said hormones in the product is sufficient to be
therapeutically effective for the consumer in accordance with their
needs.
9. The pharmaceutical compounding system of claim 8, wherein at
least one of said concentrated hormone reagent compositions is a
concentrated solution of one or more estrogens.
10. The pharmaceutical compounding system of claim 8, wherein each
of said concentrated reagent compositions is contained in a
graduated dispensing device.
11. The pharmaceutical compounding system of claim 8, comprising
concentrated reagent composition containing a plurality of
different estrogens dissolved at a total concentration of between
10 and 60 mg of estrogens-per gram.
12. The pharmaceutical compounding system of claim 8, comprising a
concentrated reagent composition containing at least one androgen
dissolved at a concentration of at least 150 mg per gram.
13. The pharmaceutical compounding system of claim 8, comprising a
concentrated reagent composition containing at least one
progestagen dissolved at a concentration of at least 200 mg per
gram.
14. The pharmaceutical compounding system of claim 8, comprising a
concentrated reagent composition containing estriol, a concentrated
reagent composition containing estradiol, and a concentrated
reagent composition containing estrone.
15. A kit comprising the concentrated reagent compositions of the
pharmaceutical compounding system of claim 8.
16. A method for preparing the pharmaceutical compounding system of
claim 8, comprising for each of said reagent compositions: a)
combining steroid hormones with said solvents; and b) processing
said combination in an ointment mill or homogenizer to achieve
complete dissolution of said hormones in the solvents.
17. A method of hormone replacement therapy, comprising: a)
ascertaining the individual needs of a consumer for replacement or
supplementation of one or more hormones; b) compounding a
pharmaceutical product according to the method of claim 1, whereby
the product is customized to the individual needs of the consumer
ascertained in step a); and c) providing said pharmaceutical
product to the consumer.
18. A method of hormone replacement therapy, comprising: a)
ascertaining the individual needs of a patient for replacement or
supplementation of one or more hormones; and b) prescribing for the
patient a pharmaceutical product to be compounded according to the
method of claim 1 such that the product will be customized to the
individual needs of the patient.
19. A method of quality control of a customized pharmaceutical
product intended for hormone replacement therapy, comprising: a)
obtaining a pharmaceutical product compounded according to the
method of claim 1 using one or more concentrated reagent
compositions containing a colorant; b) observing the color of the
pharmaceutical product after compounding; c) deducing the identity
of the hormones in the product from said color; and d) comparing
the hormones in the product with the hormones that need
supplementation in a particular consumer.
20. A method of quality control of a customized pharmaceutical
product intended for hormone replacement therapy, comprising: a)
obtaining a pharmaceutical product compounded according to the
method of claim 1 using one or more concentrated reagent
compositions containing a colorant; b) observing the color of the
pharmaceutical product after compounding; and c) determining
whether the ingredients of the product have been adequately mixed
according to whether the final product is a uniform color
throughout.
Description
REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of application Ser. No.
10/668,075 filed Sep. 22, 2003 which is a non-provisional
application of provisional application Ser. No. 60/454,915 filed
Mar. 14, 2003, the entire enclosures of all of the above are herein
incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates to a concentrated hormone
pharmaceutical composition to be used in the production of hormone
replacement therapies.
[0004] 2. Description of the Related Art
[0005] Natural Hormone Replacement Therapy 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).
[0006] 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.
[0007] Bio-identical Hormone Replacement Therapy products are
compounded by a compounding pharmacist, which offers you and your
physician a choice for individualized hormone replacement.
Generally the BHRT pharmaceutical compositions are sold in the form
of ointments, creams, gels, pastes, capsules, troches, lozenges,
lollipops, tablet triturates, sublingual tablets, and tablets.
[0008] 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.
[0009] 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.
[0010] 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.
[0011] 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.
[0012] 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.
[0013] 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.
[0014] Furthermore, bulk compounding or manufacturing of hormone
products is illegal in most states without a proper license.
[0015] 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.
[0016] 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.
[0017] In order to work with BHRT pharmaceutical compositions, an
employee must:
[0018] Be trained in the art of compounding BHRT ointments, creams,
gels, and pastes.
[0019] Ensure they are wearing all the necessary protective
gear.
[0020] Locate all of the ingredients.
[0021] Weigh all of the ingredients in the appropriate environment,
a clean room with proper ventilation and filtration systems, to
prevent exposure to harmful chemicals.
[0022] 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.
[0023] Run the mixture through an ointment mill to decrease 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 final product.
[0024] 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.
[0025] 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.
SUMMARY OF THE INVENTION
[0026] The invention offers at least one of the following
advantages:
[0027] provides a concentrated pharmaceutical composition that is
easy to use and saves time and money to the pharmacies dealing with
BHRT pharmaceutical products.
[0028] provides a pharmaceutical composition having a higher
concentration of hormone than the concentration found in the BHRT
pharmaceutical products of the prior art.
[0029] provides a pharmaceutical composition that can be used by
the compounding pharmacist safely, accurately, quickly.
[0030] provides an inexpensive pharmaceutical composition with
individualized BHRT products such as ointments, creams, gels, or
pastes.
[0031] provides a color-coded hormone pharmaceutical
composition.
[0032] 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 physicians, thus the pharmacist can easily
measure the amount required to be incorporated into the BHRT
product.
[0033] 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.
[0034] 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.
[0035] The present invention relates to a concentrated hormone
pharmaceutical composition comprising:
[0036] from about 0.6 to about 80% of at least one hormone;
[0037] from about 20 to about 90.4% of at least one solvent, and
optionally a pharmaceutically acceptable carrier.
[0038] In the preferred embodiment, the concentrated hormone
pharmaceutical composition is chosen from estradiol, estrone,
estriol, testosterone, DHEA, pregnenolone, progesterone, or
combination thereof.
[0039] The invention also relates to a concentrated hormone
pharmaceutical composition comprising:
[0040] from about 0.6 to about 50% of at least one hormone;
[0041] from about 50 to about 90.4% of at least one solvent,
and
[0042] optionally a pharmaceutically acceptable carrier
[0043] wherein the at least one hormone is chosen from estriol,
estradiol, or combination thereof.
[0044] 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.
[0045] Furthermore, the invention concerns a concentrated hormone
pharmaceutical composition comprising:
[0046] from about 0.6 to about 50% of at least one hormone;
[0047] from about 50 to about 90.4% of at least one solvent,
and
[0048] optionally a pharmaceutically acceptable carrier
[0049] wherein the at least one hormone is chosen from estriol,
estradiol, estrone, or combination thereof.
[0050] 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.
[0051] Furthermore, the invention concerns a concentrated hormone
pharmaceutical composition comprising:
[0052] from about 0.8 to about 80% of at least one hormone;
[0053] from about 20 to about 90.2% of at least one solvent,
and
[0054] optionally a pharmaceutically acceptable carrier
[0055] wherein the at least one hormone is testosterone.
[0056] In addition, the invention concerns a concentrated hormone
pharmaceutical composition comprising:
[0057] from about 8 to about 90% of at least one hormone;
[0058] from about 10 to about 92% of at least one solvent, and
[0059] optionally a pharmaceutically acceptable carrier
[0060] wherein the at least one hormone is progesterone.
[0061] Furthermore, the invention concerns to a color-coded
concentrated hormone pharmaceutical.
[0062] Furthermore, the invention concerns a method for producing a
concentrated hormone pharmaceutical composition, the method
comprising the steps of:
[0063] measuring at least one hormone, a solvent and/or optionally
a carrier by using an electronic balance in a clean room;
[0064] combining the ingredients of step a by using an industrial
scale mixer to ensure thorough mixing; and
[0065] running the mixture of step b through a large-scale ointment
mill or homogenizer to decrease the particle size of the drug,
and
[0066] optionally, heating the concentrate to facilitate the
formation of a solution,
[0067] wherein the hormone concentration is from about 0.6 to about
80%.
[0068] Furthermore, the present invention concerns a concentrated
hormone pharmaceutical composition comprising:
[0069] at least one hormone;
[0070] optionally a powdered base;
[0071] wherein the at least one hormone is chosen from estriol,
estradiol, estrone, or combination thereof; and
[0072] wherein the composition is in a powdered form.
[0073] Finally, the invention concerns a kit for producing a liquid
or semi-solid concentrated hormone pharmaceutical composition, the
kit comprising:
[0074] at least one hormone;
[0075] at least one solvent, and
[0076] optionally a pharmaceutically acceptable carrier,
[0077] wherein each element is packet in separated graduated
dispensing devices.
[0078] 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.
DETAILED DESCRIPTION OF THE INVENTION
[0079] 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.
[0080] The present invention concerns a concentrated hormone
pharmaceutical composition comprising:
[0081] at least one hormone;
[0082] at least one solvent, and
[0083] optionally a pharmaceutically acceptable carrier
[0084] wherein the weight concentration of the at least one hormone
in said composition is equal or greater than 0.6%.
[0085] In one of the embodiments, the concentrated is in a powdered
form.
[0086] 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
[0087] 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.
[0088] 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
(biest) in any proportion, preferably in a 5:5, 6:4, 7:3, 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.
[0089] 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.
[0090] 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.
[0091] 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 10 mg/g to 60 mg/g.
[0092] 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.
[0093] 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.
[0094] 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.
[0095] 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.
[0096] 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.
[0097] 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.
[0098] 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 600 mg/g.
[0099] Furthermore, the present invention provides a concentrated
pharmaceutical compound that contains between 10 mg/g and 900 mg/g
of dehydroepiandrosterone or between 30 mg/g to 800 mg/g of
pregnenolone.
[0100] The invention also concerns a concentrated hormone
pharmaceutical composition comprising:
[0101] from about 0.6 to about 50% of at least one hormone;
[0102] from about 50 to about 90.4% of at least one solvent,
and
[0103] optionally a pharmaceutically acceptable carrier
[0104] wherein the at least one hormone is chosen from estriol,
estradiol, or combination thereof.
[0105] In addition, the invention concerns a concentrated hormone
pharmaceutical composition comprising:
[0106] from about 0.6 to about 50% of at least one hormone;
[0107] from about 50 to about 90.4% of at least one solvent,
and
[0108] optionally a pharmaceutically acceptable carrier
[0109] wherein the at least one hormone is chosen from estriol,
estradiol, estrone, or combination thereof.
[0110] Furthermore, the invention concerns a concentrated hormone
pharmaceutical composition comprising:
[0111] from about 0.8 to about 80% of at least one hormone;
[0112] from about 20 to about 90.2% of at least one solvent,
and
[0113] optionally a pharmaceutically acceptable carrier
[0114] wherein the at least one hormone is testosterone.
[0115] The invention also concerns a concentrated hormone
pharmaceutical composition comprising:
[0116] from about 8 to about 90% of at least one hormone;
[0117] from about 10 to about 92% of at least one solvent, and
[0118] optionally a pharmaceutically acceptable carrier
[0119] wherein the at least one hormone is progesterone.
Solvent (or Wetting Agent)
[0120] 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.
[0121] 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.
[0122] 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 interface with a solid to
liquid interface. The solvent or wetting agent should be miscible
with the carrier.
[0123] 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-ethyletherand) 50% propylene glycol mixture, water or mixtures
thereof. Any combination of solvents may be employed.
[0124] The solvent or wetting agent should satisfy the following
characteristics:
[0125] the solvent or solvents should wet the hormone;
[0126] the solvent should allow the hormone to be incorporated
therein;
[0127] the solvent or solvents should be compatible with the skin
with the least possible number of adverse effects;
[0128] the solvent or solvents should be smooth and pliable with no
adverse odor;
[0129] 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.
[0130] 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
[0131] The carrier can be any suitable carrier that can be
incorporated into a system, which can deliver bio-identical
hormones transdermaly.
[0132] The formulations for the delivery of the pharmaceutical
composition according to the present invention may be liquid,
ointments, and creams.
[0133] The carrier can be chosen from ointment base, powder base,
cream base, or a gel base.
[0134] 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.
[0135] 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.
[0136] 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.
[0137] Powders may be formulated with the aid of any suitable
powder base, such as talc, lactose, starch, and the like.
[0138] 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, 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 isoparaffin, 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 officinalis 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
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 1, 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.
[0139] The carrier should satisfy the following
characteristics:
[0140] the base should allow the wetted hormone to be incorporated
therein;
[0141] the base should be compatible with the skin with the least
possible number of adverse effects;
[0142] the base should be smooth and pliable with no adverse
odor;
[0143] the base should have a color appealing to the consumer;
[0144] the base must be stable and must provide a stable vehicle
for the medication; and
[0145] the base should be able to readily release the medication
incorporated therein into the skin.
Additional Ingredients
[0146] 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-hydroxymethyl-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.
[0147] 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, 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.
[0148] 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.
[0149] 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.
[0150] 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, 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.
[0151] 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.
[0152] 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.
[0153] 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.
[0154] 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 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 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.
[0155] 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.
[0156] 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 diglycol/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.
[0157] 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.
[0158] 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 diglycol/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.
[0159] In another embodiment, the concentrated hormone
pharmaceutical composition contains 64 mg/g testosterone
concentrate in a mixture of 50% ethoxy diglycol/50% propylene
glycol for women and 150 mg/g of a mixture of 50% ethoxy
diglycol/50% propylene glycol for men.
[0160] In another embodiment, the concentrated hormone
pharmaceutical composition contains 600 mg/g of progesterone
concentrate in vanishing cream type oil in water emulsion base.
[0161] 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.
[0162] 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.
[0163] In another preferred embodiment, the concentrated hormone
pharmaceutical composition comprises:
[0164] at least one hormone;
[0165] optionally a powdered base;
[0166] wherein the at least one hormone is chosen from estriol,
estradiol, or combination thereof; and
[0167] wherein the composition is in a powdered form.
[0168] 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.
[0169] In another preferred embodiment, the concentrated hormone
pharmaceutical composition comprising:
[0170] at least one hormone; and
[0171] optionally a powdered base;
[0172] wherein the at least one hormone is chosen from estriol,
estradiol, estrone, or combination thereof; and
[0173] wherein the composition is in a powdered form.
[0174] 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.
[0175] 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.
[0176] 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.
[0177] 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.
[0178] Color Coded-concentrated Pharmaceutical Composition
[0179] The present invention also provides a color-coded
concentrated hormone composition to help the pharmacist quickly
choose the composition to be used.
[0180] The advantage of having color-coded concentrates are as
follows:
[0181] helps to rapidly identify the concentrate.
[0182] 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
[0183] ensures complete mixing of the final product. When the final
product is a uniform color throughout, adequate mixing will have
taken place.
[0184] 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.
[0185] 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.
[0186] A pharmacist or technician trained in the art of compounding
BHRT ointments, creams, gels, and pastes will manufacture these
concentrates.
[0187] 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.
[0188] The present invention also contemplates a method for
producing the concentrated composition of the present invention.
The method comprises the steps of:
[0189] measuring at least one hormone, a solvent and/or optionally
a carrier by using an electronic balance in a clean room;
[0190] combining the ingredients of step a by using an industrial
scale mixer to ensure thorough mixing; and
[0191] running the mixture of step b through a large-scale ointment
mill or homogenizer to decrease the particle size of the drug,
and
[0192] optionally, heating the concentrate to facilitate the
formation of a solution, wherein the hormone concentration is from
about 0.6 to about 80%.
[0193] 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.
[0194] 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.
[0195] 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.
[0196] 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.
EXAMPLE 1
[0197] The formulation was made in the following manner (total
quantity: 120 ml and a concentration of 300 mg/g of testosterone)
[0198] 36 g of testosterone were weighed out. [0199] b) the volume
was brought up to 120 ml with approximately 84 ml of an anhydrous
gel base. [0200] 1 drop of blue food coloring was added. [0201] the
mixture was combined in an electronic mortar and pestle. [0202] the
mixture was run through an ointment mill to decrease the particle
size of the testosterone. [0203] the mixture was transferred into 4
30 ml luer lock syringes. [0204] This is what the mixture is sold
in.
EXAMPLE 2
[0205] The formulation, according to the invention, was made in the
following manner (total quantity: 1000 ml and a concentration of
62.5 mg/g of triest (estriol, estradiol, and estrone in an 8:1:1
ratio) [0206] 50 g of estriol were weighed out and wetted with 50
ml of ethoxy diglycol. [0207] 6.25 g of estradiol were weighed out
and wetted with 6.25 ml of ethoxy diglycol. [0208] 6.25 g of
estrone were weighed out and wetted with 6.25 ml of ethoxy
diglycol. [0209] 10 drops of red food coloring was added. [0210]
the volume was brought up to 1000 ml with approximately 875 ml of
oil in water emulsion type vanishing cream base. [0211] the mixture
was combined in an industrial mixer. [0212] the mixture was run
through an ointment mill to decrease the particle size of the
estrogens. [0213] the mixture was transferred into 33 30 ml luer
lock syringes. [0214] This is what the mixture is sold in.
EXAMPLE 3
[0215] The formulation, according to the invention, was made in the
following manner (total quantity: 5000 ml and a concentration of
400 mg/g of progesterone)
[0216] 2000 g of progesterone were weighed out.
[0217] the progesterone was combined with an oil phase, an
[0218] aqueous phase and an emulsifier to formulate a water in oil
emulsion type cream base with a final volume (including the
progesterone) of 5000 ml. [0219] 50 drops of yellow food coloring
was added. [0220] the mixture was combined in an industrial mixer.
[0221] the mixture was run through an ointment mill to decrease the
particle size of the progesterone.
[0222] the mixture was transferred into 83 60 ml luer lock
syringes.
[0223] This is what the mixture is sold in.
EXAMPLE 4
[0224] The formulation, according to the invention, was made in the
following manner (total quantity: 10000 ml and a concentration of
600 mg/g of progesterone (this is a paste)
[0225] 6000 g of progesterone were weighed out.
[0226] the progesterone was combined with 2000 ml of ethoxy
diglycol.
[0227] 100 drops of yellow food coloring was added.
[0228] an oil in water emulsion type vanishing cream base was used
to bring the final volume to 10000 ml, approximately 2900 g of the
cream. [0229] the mixture was combined in an industrial mixer.
[0230] the mixture was run through an ointment mill to decrease the
particle size of the progesterone.
[0231] the mixture was transferred into 50 ml ointment jar. This is
what the mixture is sold in.
EXAMPLE 5
[0232] The formulation, according to the invention, was made in the
following manner (total quantity: 2000 ml and a concentration of
300 mg/g of testosterone)
[0233] 600 g of testosterone were weighed out.
[0234] The testosterone was combined with approximately 400 ml of
ethoxy diglycol.
[0235] 15 drops of blue food coloring was added.
Approximately 1000 ml of a 1% hydroxypropylcellulose in ethoxy
diglycol anhydrous gel was added to bring the final volume to 2000
ml.
[0236] The mixture was combined in an industrial mixer.
[0237] The mixture was further mixed with a homogenizer to decrease
the particle size of the testosterone.
[0238] The mixture was transferred to 40 50 ml bottles fitted with
adapter caps. A 5 ml oral syringe and a 1 ml oral syringe, fitting
the adapter cap, were packaged with each bottle to be used as
measuring devices.
EXAMPLE 6
[0239] The formulation, according to the invention, was made in the
following manner (total quantity: 10000 ml and a concentration of
40 mg/g of triest (estriol, estradiol, and estrone in an 8:1:1
ratio))
[0240] 320 g of estriol were weighed out.
[0241] 40 g of estradiol were weighed out.
[0242] 40 g of estrone were weighed out.
[0243] 100 drops of red food coloring was added.
[0244] The volume was brought up to 10000 ml with a 50% ethoxy
diglycol and 50% propylene glycol combination.
[0245] The mixture was combined in an industrial mixer.
[0246] The mixture was heated to 60 degrees Celsius for 2 hours in
order to facilitate solution of the triest powder.
[0247] The solution was transferred into 100 100 ml bottles fitted
with adapter caps, accompanied with 1 ml, 5 ml, and 10 ml oral
syringes. This is what the mixture is sold in.
EXAMPLE 7
[0248] The formulation, according to the invention, was made in the
following manner (total quantity: 2000 ml and a concentration of 70
mg/g of testosterone)
[0249] 140 g of testosterone were weighed out.
[0250] 15 drops of blue food coloring was added.
[0251] The testosterone was combined with approximately 1860 ml of
ethoxy diglycol, enough to bring the final volume to 2000 ml.
[0252] The mixture was combined in an industrial mixer.
[0253] The mixture will now be a solution.
[0254] The solution was transferred to 40 50 ml bottles fitted with
adapter caps. A 5 ml oral syringe and a 1 ml oral syringe, fitting
the adapter cap, were packaged with each bottle to be used as
measuring devices.
EXAMPLE 8
[0255] The formulation, according to the invention, was made in the
following manner (total quantity: 2000 ml and a concentration of
150 mg/g of testosterone)
[0256] 300 g of testosterone were weighed out.
[0257] 15 drops of blue food coloring was added.
[0258] The testosterone was combined with approximately 1700 ml of
a 50% ethoxy diglycol and 50% propylene glycol mixture, enough to
bring the final volume to 2000 ml.
[0259] The mixture was heated to 60 degrees Celsius and mixed in an
industrial mixer.
[0260] The mixture will now be a solution.
[0261] The solution was transferred to 40 50 ml bottles fitted with
adapter caps. A 5 ml oral syringe and a 1 ml oral syringe, fitting
the adapter cap, were packaged with each bottle to be used as
measuring devices.
EXAMPLE 9
[0262] The formulation, according to the invention, was made in the
following manner (total quantity: 1000 gm and a concentration of
62.5 mg/gm of triest (estriol, estradiol, and estrone in an 8:1:1
ratio))
[0263] 50 g of estriol were weighed.
[0264] 6.25 g of estradiol were weighed out.
[0265] 6.25 g of estrone were weighed out.
[0266] The weight was brought up to 1000 gm with approximately
937.5 gm of lactose.
[0267] The mixture was combined in an industrial mixer.
[0268] The mixture was transferred to 10 100 gm jars.
EXAMPLE 10
[0269] The formulation, according to the invention, was made in the
following manner (total quantity: 1000 ml and a concentration of 40
mg/g of triest (estriol, estradiol, and estrone in an 8:1:1
ratio))
[0270] 32 g of estriol were weighed out.
[0271] 4 g of estradiol were weighed out.
[0272] 4 g of estrone were weighed out.
[0273] The three powders were combined.
[0274] 4 g of this combination were transferred into each of 10 100
ml bottles fitted with adapter caps.
[0275] Approximately 96 ml, enough to bring the final volume to 100
ml, of a 50% ethoxy diglycol and 50% propylene glycol mixture was
transferred to each of 10 other 100 ml bottles fitted with adapter
caps.
[0276] 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
[0277] The formulation, according to the invention, was made in the
following manner (total quantity: 100 ml and a concentration of 40
mg/g of triest (estriol, estradiol, and estrone in an 8:1:1
ratio))
[0278] 3.2 g of estriol were weighed out and transferred into a 100
ml bottle.
[0279] 0.4 g of estradiol were weighed out and transferred into a
100 ml bottle.
[0280] 0.4 g of estrone were weighed out and transferred into a 100
ml bottle.
[0281] Enough colored 50% propylene glycol/50% ethoxy diglycol
mixture to combine with the estriol, estradiol, and estrone to
bring the final volume to 100 ml, approximately 96 ml, was measured
and transferred into a 100 ml bottle.
EXAMPLE 12
[0282] The formulation, according to the invention, was made in the
following manner (total quantity: 120 ml and a concentration of 300
mg/g of testosterone)
[0283] 36 g of testosterone were weighed out.
[0284] The volume was brought up to 120 ml with approximately 84 ml
of a glycerin.
[0285] 1 drop of blue food coloring was added.
[0286] The mixture was combined in an electronic mortar and
pestle.
[0287] The mixture was run through an ointment mill to decrease the
particle size of the testosterone.
[0288] The mixture was transferred into 4 30 ml luer lock
syringes.
[0289] This is what the mixture is sold in.
[0290] 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.
[0291] These concentrates could be packaged in, or with, any
graduated dispensing device that lends itself to 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.
[0292] 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.
[0293] The pharmacist using the concentrate, according to the
invention, can easily incorporate the hormone into the compounding
BHRT ointments, creams, gels, or pastes by:
[0294] Putting on protective gloves.
[0295] Calculating the total amount of hormones needed to compound
a medication of a specific volume and concentration depending on
the patient necessities;
[0296] Determining how many milliliters of the appropriate
concentrate will contain the total amount of hormone needed for the
compound.
[0297] Measuring the volume of concentrate containing the total
amount of hormone needed. This is done using an appropriate liquid
or semi-solid measurement system.
[0298] Repeating steps 2 through 4 for each hormone to be present
in the final preparation.
[0299] 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.
[0300] Combining the ointment, cream, or gel base and the
concentrates on a glass ointment slab, using an EMP, mixing 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.
[0301] 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.
[0302] In addition, the invention concerns a kit for producing a
concentrated hormone pharmaceutical composition, the kit
comprising:
[0303] at least one hormone;
[0304] at least one solvent, and
[0305] optionally a pharmaceutically acceptable carrier,
[0306] wherein each element is packet in separated graduated
dispensing devices.
[0307] 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.
Advantages
[0308] 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.
[0309] Using these concentrates, combined with an appropriate
liquid or semi-solid measurement system, in the place of powdered
hormones and a scale, will dramatically 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.
[0310] 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.
[0311] 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.
[0312] 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 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.
[0313] 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.
[0314] 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 BHRT
ointments, creams, gels, and pastes. This will inevitably result in
an increase in the availability of these medications to the
public.
[0315] 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 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.
* * * * *