Hair loss abstract
Compositions to prevent or reduce hair loss, allowing the body
to maintain normal, healthy hair growth, comprising a penetration
enhancer together with a testosterone blocker or a vascular enhancer,
Hair loss claims
What is claimed is:
1. A topical composition of matter comprising: a) a 5.alpha.-reductase
inhibitor, b) minoxidil, and c) trimethyl acetate.
2. The composition of claim 1, wherein said trimethyl acetate is
present in a concentration sufficient to aid in penetrating skin
to a depth of approximately the depth of hair bulbs.
3. The composition of claim 1, wherein said 5.alpha.-reductase
inhibitor comprises progesterone.
4. The composition of claim 3, wherein the ratio of 5.alpha.-reductase
inhibitor to minoxidil in the composition is approximately 0.5 grams:
5. An article of manufacture comprising: a) the composition of
claim 3, and b) a label indicating cosmetic use.
6. An article of manufacture comprising: a) the composition of
claim 3, and b) a label indicating pharmaceutical use.
7. The article of manufacture of claim 6, wherein said pharmaceutical
use comprises alopecia.
8. The composition of claim 3, further comprising a sunscreen.
9. A method comprising topically administering a composition of
matter comprising: a) a 5.alpha.-reductase inhibitor, b) minoxidil,
and c) trimethyl acetate.
10. The method of claim 9, wherein said trimethyl acetate is present
in a concentration sufficient to aid in penetrating skin to a depth
of approximately the depth of hair bulbs.
11. The method of claim 9, wherein said 5.alpha.-reductase inhibitor
12. The method of claim 11, wherein the ratio of 5.alpha.-reductase
inhibitor to minoxidil in the composition is approximately 0.5 grams:
13. The method of claim 9, used for a cosmetic use.
14. The method of claim 9, used for a pharmaceutical use.
15. The method of claim 14, wherein said pharmaceutical use is
preventing or treating alopecia.
16. The method of claim 11, further comprising administering a
17. A method for improving the skin penetration of a topically-applied
compound, the method comprising topically administering said compound
together with trimethyl acetate.
Hair loss description
My invention relates to preparations useful for maintaining normal,
healthy hair bulb function, for preventing hair loss, and for medically
treating androgenic alopecia and like dermatological diseases. I
will first review pertinent hair biology, then discuss prior art
teachings in the field, and then describe my invention.
Hair bulbs are responsible for normal, healthy hair growth and
retention. Hair bulbs are located in the skin, about 3/16 of an
inch below the skin surface. They are located just above the fatty
layer at the very lower most position of the skin.
The majority of facial and body hair growth is stimulated by androgens.
However, the growth of scalp hair has been shown, in genetically
programmed individuals, to be inhibited by 5.alpha.-dihydrotestosterone
("DHT") in individuals who exhibit a hereditary pre-disposition
to baldness. Ebling, Dermatol. Clin. S. 467 (1987); Lucky, 4 Biochem.
Soc. Transc. 597 (1988); Brodland et al., 47 Cutis 173 (1991). DHT
is produced by reducing testosterone with a 5.alpha.-reductase enzyme.
The phenotypic expression of baldness does not occur in the absence
of testosterone. Androgenic alopecia or common baldness represents
99 percent of all cases of hair loss. Broadland, id.
The mechanism through which androgens regulate the biology of hair
is by modulating the hair growth cycle. Ebling, 4 Biochem. Soc.
Trans. 597; Bergfield et al., 5 Dermatol. Clin. 491. The effect
of DHT on hair growth appears to be related to local rather than
systemic levels of the hormone. This is because the capacity of
scalp skin from balding individuals to convert testosterone ("T")
to DHT is greater than that observed in the scalp of non-balding
individuals. Lucky, supra; Schweikert et al., 38 J. Clin. Endocrinol.
To prevent hair loss, maintain the health of hair bulbs, or to
treat baldness, several compositions are known in the art. We discuss
Hair Loss Prevention
Hair loss prevention preparations are known in the art. These include
natural product preparations, biological products, vascular toners
and testosterone blockers. Several prior art compositions are discussed
in the accompanying Petition To Make Special and its accompanying
references, the contents of which are incorporated herein by reference.
Natural Products. Several inventors disclose natural compositions.
Casero, U.S. Pat. No. 5,340,579, discloses a composition comprising
(a) mucopolysaccharides, (b) human umbilical cord extract, (c) tetrahydrofurfuryl
nicotinate, and (d) pharmaceutically and cosmetically acceptable
excipients. Buck, U.S. Pat. No. 5,512,275 and 5,609,858, discloses
a formulation for the treatment of androgenic alopecia, comprising
liquor carbonis detergens in combination with spirits of camphor,
castor oil, isopropyl alcohol. Chizick et al., U.S. Pat. No. 5,972,345,
discloses a combination of saw palmetto extract, African pygeum
extract, and stinging nettle extract.
Biological Products. Hoke, U.S. Pat. No. 5,994,319, discloses using
genetic material as a anti alopecia therapeutic. Hoke proposes using
anti-sense oligonucleotides targeting 5-.alpha. reductases in conjunction
with other hair growth enhancers. Tien, U.S. Pat. No. 5,574,011,
discloses the use of a class of LHRH analogs for treating male pattern
baldness. Messenger, U.S. Pat. No. 6,020,327, discloses administering
aromatase inhibitors to treat hair loss. Liao et al., U.S. Pat.
Nos. 5,422,371 and 5,605,929, discloses a class of anti-androgenic
Vascular Toners. Several organic chemicals are known to affect
the hair growth and hair retention cycle. These include minoxidil.
I refer to minoxidil and similar kinds of compounds as "vascular
toners," because they are believed to be effective due to their
impact on local blood circulation.
Minoxidil has been shown to stimulate hair growth or inhibit the
loss of hair in a number of patients beginning to develop androgenic
alopecia. Minoxidil is the generic name for 6-(1-piperidinyl)-2,
4-pyrimidinediamaine 3-oxide. Its preparation is disclosed in Anthony,
W. C. et al., U.S. Pat. No. 3,382,247 (1968); McCall, J. M., et
al., 40 J. Organic Chem. 3304 (1975); Gorecki, D. K. J., 17 Analytical
Profiles of Drug Substances 185 (Academic Press, New York 1988).
It is more soluble (by weight minoxidil/volume of solvent) in non-polar
solvents than polar ones (75 mg/ml in propylene glycol; 44 mg/ml
in methanol; 6.5 in dimethyl sulfoxide; 2.2 mg/ml water).
Minoxidil is medically classified as an anti-hypertensive. It affects
heart rate and rhythm. It has thus been used in an oral formulation
as a cardiac drug. Andersson, O., 205 Acta Med. Scand. 213 (1979);
Moser, M., 26 Advan. Cardiol. 38 (1979). over dosage may create
cardiac arrhythmias or other adverse side effects. See e.g., Carlson,
E. S., 39 Toxicol. Applied Pharmacol. 1 (1977).
Minoxidil is also medically classified as an anti-alopecia agent.
Its efficacy in treating early male pattern baldness has been described
in numerous published articles. E.g., Olsen, E. A. et al., 13 J.
Am. Acad. Dermatol. 185 (1985); Novak, E., 24 Int. J. Dermatol.
82 (1982). Its limited percutaneous absorption and secretion is
described in Franz, J. T., 121 Arch. Dermatol. 203 (1985).
The mechanism by which minoxidil alters the hair growth cycle is
uncertain. It is thought to act by increasing vascular circulation
to the hair follicle. It is known that minoxidil effectiveness is
more pronounced in scalp areas which are more vascular.
Topical minoxidil is know to have certain shortcomings. It is effective
in only about eight percent of adult male users. It produces "lanugo,"
or baby-type, hair which is relatively thin. Further, and perhaps
most significantly, after approximately 30 months of continuous
use, minoxidil shows a sharp drop in effectiveness. After about
thirty months of use, about half of the new hair growth falls out.
Thus, while the user has somewhat more hair than originally, the
user has less hair than originally seen.
Testosterone Inhibitors. Inhibitors of steroid metabolism, particularly
those that inhibit the conversion of testosterone to dihydro testosterone,
have shown effects on hair cycles, including inhibition of hair
loss. One class of enzymes targeted by these inhibitors are the
steroid 5-.alpha. reductases.
Certain 5.alpha.-reductase inhibitors have been shown to inhibit
hair loss. For example, stump-tail macaque monkeys treated with
the 5.alpha.-reductase inhibitor 17b-N,N,- dimethylcarbamoyl- 4-methyl-
4-aza-5.alpha.-androstan- 3-one undergo significantly less age related
hair loss than untreated monkeys. Rittmaster et al., 65 J. Clin.
Endocrinol. Metab. 188 (1987). Similarly, finasteride, a 5.alpha.-reductase
inhibitor, miniaturizes scalp hair follicles, reversing the balding
process. "Merck's Propecia Shows Promise In Hair Loss,"
Marketletter (Mar. 31, 1997). These inhibitors are thought to work
by inhibiting the reduction of testosterone to DHT, as DHT is considered
to be the more active form. The use of a combination of finasteride
and minoxidil demonstrated that, in combination, these two drugs
increased the rate of hair growth when compared to either compound
administered alone. Diani, 74 J. Clin. Endocrinol. Metabol. 345.
Minoxidil used in conjunction with effectors of steroid metabolism,
leads to enhanced hair growth and decreased rates of hair loss.
Testosterone blockers are known in the art (I use the term "testosterone
blocker" to denote a competitive antiandrogen which inhibits
the binding of testosterone or DHT onto its cell surface binding
site, rather than a compound which is used to inhibit the reduction
of testosterone into DHT.). Also known is their use systemically
(orally or intravenously). As systemic therapeutics, they are known
in the art as having a key shortfall: their long term efficacy is
compromised by their blocking of the androgenic feedback inhibition
of gonadotropin secretion. This interference results in elevated
gonadotropin secretion, which in turn increases testicular secretion
of testosterone. The higher level of testosterone eventually overcomes
the action of the antiandrogen. Liao, supra, at col. 3, lines 16-31.
Thus, what is needed in the art is a safe and effective way to
maintain both the healthy function of hair bulbs, and the health
of existing hair, that avoids the shortfalls seen in the prior art.
I have invented a kind of hair loss prevention composition. My
invention is a new combination of already known types of compounds.
My invention can be used either cosmetically (to maintain healthy
hair growth) or pharmaceutically (to treat a medical condition).
It can be made using components already known in the art, allowing
one to enjoy the predictability of use available with these old
compounds. My invention is flexible enough, however, to also allow
one to substitute newly-discovered compounds substantially equivalent
to the already known compounds. Thus, my invention can be adapted
to allow the user to use the safest, most effective components then
I have found that certain compounds have greatly improved effectiveness
- achieving ten times the benefit, or an entire order of magnitude
- if combined with a skin penetration enhancer. The penetration
enhancer delivers these compounds to the hair bulb, where the compounds
are most needed.
I have thus found that testosterone blockers, if applied topically
(rather than systemically administered), are effective in preventing
hair loss, and if used in conjunction with a dermal penetration
enhancer. Such topical use avoids precipitating the systemic increase
in testosterone production seen with oral administration, by minimizing
systemic interference with normal gonadotropin secretion. I have
also found that vascular toners, if applied topically in conjunction
with a dermal penetration enhancer, work much better.
My invention includes a skin penetration enhancer used together
with a testosterone blocker or a vascular enhancer, or both. I first
discuss each component individually, and then discuss the combinations
of these components that I have found most acceptable.
You can use a variety of skin penetration enhancers to make compositions
that work as I intend. Penetration enhancers and skin penetrating
formulations are known in the art. These include the variety of
formulations used from time to time for both psoriasis treatment
pharmaceuticals, and psoriasis prevention nutritional supplements
The penetration enhancer (or penetration agent) should be accepted
for human use by relevant government agencies. Thus, dimethyl sulfoxide,
while within the scope of the claims, is not a preferred penetration
enhancer where that compound is not approved for human topical use.
The penetration enhancer should not chemically react with any other
ingredient to impair or alter the composition's stability and shelf
life. Thus, one should examine the possible reactivity of a given
penetration enhancer with a given testosterone blocker or vascular
The penetration agent should be cosmetically acceptable. Thus,
while I have tested dimethyl acetate, I do not favor it. While it
is within the scope of the claims, it is a weak penetration enhancer.
Thus, one needs to use a lot of it. In these high amounts, it smells
bad. In contrast, methyl acetate is odorless, and I have tested
and found it acceptable.
Several inventors disclose liposome technology to deliver cosmetic
and dermatology materials. See, for example, Lishko et al., U.S.
Pat. No. 5,753,263, discloses using liposomes to selectively deliver
a composition to hair follicles. Liposomes are made of fatty material,
and are suitable for delivering homogenous types of materials. As
such, it may be difficult for a liposome to in fact work with a
combination of a polar compound (like a minoxidil vascular toner)
and a non-polar compound (such as a progesterone testosterone blocker).
I thus do not consider liposome technology within the scope of the
term "penetration enhancer" in this patent.
My invention works with a variety of vascular toners. One can make
compositions within the scope of my invention with minoxidil analogs
or derivatives, or with other anti-alopecia agents, such as diphencyprone,
which work in a similar way, by improving local blood flow to the
affected hair bulbs. Because it has such a broad volume of use and
scientific study, I prefer to use minoxidil. I thus use it as an
example throughout this specification.
A vascular toner, if used to maintain healthy function of hair
bulbs, must be delivered to the small blood vessels feeding the
hair bulbs. I have thus found that the effectiveness of the vascular
toner is greatly improved if it is topically applied along with
a penetration enhancer. This allows the vascular toner to act locally.
The vascular toner must be carefully titrated against the penetration
enhancer. For example, for a given concentration of minoxidil, one
needs to use the penetration enhancer in the appropriate concentration.
If a given penetration enhancer is used in a too high concentration,
the minoxidil may penetrate through the skin and reach the systemic
blood circulation. It can there, if present in sufficient amount,
cause side effects as seen by taking oral minoxidil. Thus, it is
necessary to adjust the amounts of penetration enhancer and vascular
toner, depending on the concentration and specific identity of the
enhancer and the toner.
Adding a penetration enhancer to the vascular toner appears to
fundamentally change the biological mechanism by which the vascular
toner works. This is shown by the qualitatively different results
seen between minoxidil and my compounds. The two products produce
different types of hair, and for different time periods.
Minoxidil without a penetration enhancer (as available in ROGAINE.TM.
topical minoxidil U.S.P.) produces a different kind of hair than
does minoxidil used with a penetration enhancer. It is known in
the art that topical minoxidil without a penetration enhancer (as
is commercially available in ROGAINE (.TM.) topical minoxidil U.S.P.,
commercially available from Pharmacia & Upjohn Inc., Bridgewater,
N.J.) results in thin, baby-like, temporary hair, called "lanugo"
hair. I have found that my compounds, by contrast, result in good,
coarse, "terminal" hair, hair which is normal, permanent
This indicates that minoxidil without and with penetration enhancer
may act on different types of hair bulbs, or produce different responses
from the same hair bulbs. Minoxidil without enhancer is only weakly
soluble in polar solvents. See supra. It thus has difficulty diffusing
to the deeply located hair bulbs (roots) which are located just
above the deep fat layer. Minoxidil without enhancer may thus affect
only hair bulbs located close to the skin surface, or located in
a less fatty skin layer, or hair bulbs most sensitive to changes
in blood flow. Alternatively, it may affect the same hair bulbs,
but with such weak or attenuated effect that the hair bulbs produce
a different type of hair.
In contrast, my compounds produce normal, terminal hair. This indicates
that my compounds act directly on the mature, adult hair bulbs responsible
for terminal hair growth.
Further, it is known in the art that minoxidil users experience
a sudden drop in hair thickness after about thirty months of usage.
I thus have sought the time at which my compounds have a sudden
drop in effectiveness. Surprisingly, I have found that my compounds
apparently do not lose effectiveness at all, even after using them
for substantially greater than thirty months. This confirms that
while my compounds appear to simply restore or preserve normal hair
bulb function, the prior art compositions do not restore normal
hair bulb function, but actually provoke an abnormal function--the
growth by an adult of baby like, temporary hair. That this function
is abnormal is confirmed by its drop in effectiveness after thirty
months; such a drop in efficacy indicates a "tolerance"
acquired against the intervention, rather than the maintenance of
a permanent, healthy state.
This indicates that the physiological mechanisms and biomedical
pathways of the two preparations are different. Minoxidil alone,
in the concentrations typically used, may actually temporarily alter
a normal adult body function (causing the adult body to temporarily
produce infant hair). In contrast, my invention simply maintains
the normal function of the healthy adult body hair bulb, allowing
it to continue to produce normal adult hair as long as the compound
I have also found that the effect of the formulations depends on
location of administration. Using the specific formulations disclosed
here, I have observed decreases in hair loss, and a consequent statistically
significant increase in the amount of healthy mature hair, after
4.0-4.5 months on the frontal scalp. On the crown and back of the
head, by contrast, I have observed statistically significant results
after 4.5-5.0 months. The frontal scalp may react faster because
it enjoys greater vascularization and blood flow than the other
parts of the scalp.
My invention works with a variety of testosterone blockers. I prefer
to use a blocker already approved for human use by the United States
Food & Drug Administration, as these types of testosterone blockers,
if used in pharmaceutical (as opposed to cosmetic) versions of my
invention, do not need to undergo as lengthy and expensive a process
to verify their safety and efficacy as used in pharmaceutical products.
Examples include flutamide, cyproterone acetate, spironolactone,
progesterone, or analogs or derivatives of any of these (e.g., 17-hydroxy-16-methylene-.DELTA..sup.6
I have found several surprising things about testosterone blockers.
First, they are not actually necessary for my invention to work;
minoxidil alone is effective on 8% of patients, while the same amount
of minoxidil administered with the proper amount of a penetration
enhancer is effective on 35% of patients. Second, testosterone blockers
added to such a mix are synergistically beneficial, increasing the
efficacy from 35% to 85% of patients.
One testosterone blockler is the anti alopecia compound cioteronel.
Cioteronel is the common name for hexahydro-4-(5-methoxyheptyl)-2(1H)-pentalenone.
It is also known, or is commercially available, as X-ANDRON.TM.,
CPC-10997, CYOCTOLT.TM., and EXANDRON.TM.. It is a clear, colorless
oil, soluble in lipid and relatively non-polar solvents. Its preparation
is disclosed in Kasha, W. J., PCT Int'l Patent Application 83/04,019
(1983), 101 Chem. Abstr. 23037k (1984). Its use is disclosed in
U.S. Pat. No. 4,689,345. Its inhibition of DHT binding in vitro
is disclosed in Rec. Adv. Chemotherapy (Proc. 14.sup.th Int'l Congr.
Chemotherapy Antimicrob., Sect. 1) at 261-70 and 273-74 (Univ. Tokyo
Press, 1985). Its cutaneous metabolism and clinical pharmacokinetics
is disclosed in de Zeeuw et al., 7 Pharm. Res. 638 (1990), Weichers
et al., 65 Int. J. Pharm. 77 (1990).
Another testosterone blocker is progesterone, pregn-4-ene-3, 20-dione
(commercially available as CORLUTINA.TM., CORLUVITE.TM., CYCLOGETS.TM.,
GESTIRON.TM., GESTONE.TM., LIPOLUTIN.TM., LUTOCYCLIN.TM., PROGESTIN.TM.,
CP progesterone powder, etc . . . ). Progesterone is insoluble in
water and soluble in alcohol, acetone, dioxane, and concentrated
sulfuric acid. It is sparingly soluble in vegetable oils. Its isolation,
structure and biological activity is described at length in Bardin
et al. (eds.), Progesterone and Progestins (Raven Press, New York
1982). I prefer to use progesterone as the sole testosterone blocker.
The penetration enhancer and the vascular toner or testosterone
blocker, or both, may be mixed with a carrier vehicle. You can use
a variety of vehicles to make my invention. The vehicle is simply
a cosmetically safe, medically safe solvent for the active ingredients.
The vehicle should not adversely and significantly chemically react
with the active ingredients.
For example, propylene glycol, water and isopropyl alcohol may
be used as vehicles. These may be used alone or in combination.
The vehicle can optionally provide functions in addition to simply
dissolving the active ingredients. For example, one can use a moisturizing
vehicle, or a vehicle containing sunscreen. For a moisturizing or
moisture retaining vehicle, one can use a vehicle made from a combination
of (ranked in order of quantity used) water, mineral oil, petrolatum,
lanolin, sorbitol solution, stearic acid, lanolin alcohol, cetyl
alcohol, glyceryl stearate/PEG-100 stearate, triethanolamine, dimethicone,
propylene glycol, tri(PPG-3 myristyl ether) citrate, disodium EDTA,
methylparaben, ethylparaben, propylparaben, fragrance, xanthan gum,
butylparaben, and methyldibromo glutaronitrile.
It may be desirable to use a vehicle containing one or more sunscreens.
This is because my preparations are used on the tops of balding
scalps. Balding scalps are often largely unprotected from sun damage,
as the user may not wear headgear and the balding scalp lacks the
sun shielding dense hair layer present on a healthy scalp. Adding
sunscreen thus can protect the scalp from possible sun damage. Sunscreens,
and vehicles containing sunscreen compounds, are widely known in
the art. See, e.g., U.S. Pat. No. 4,522,807.
Other cosmetic vehicles are widely known in the art. I prefer to
use VEHICLE/NT.TM. as the vehicle. I prefer to use VEHICLE/N(.TM.)
because it has a cosmetically attractive "feel" to the
user. Vehicle/N(.TM.) is commercially available from the Neutrogena
Dermatologics division of Johnson & Johnson, Inc., New Brunswick,
N.J. It is currently available in two formulations, regular and
mild. They are both versatile liquid vehicles for extemporaneous
compounding of topical drugs. Both formulations solublize selected
dermatological agents and provide astringent and drying actions.
The VEHICLE/N(.TM.) ingredients are SD alcohol 40 (45%), purified
water (<45%), laureth-4 (>4%), isopropyl alcohol (4%) and
propylene glycol (<4%). The VEHICLE/N(.TM.) mild ingredients
are purified water (>37.5%), SD alcohol-40 (37.5%), isopropyl
alcohol (5%) and laureth-4 (<5%). To compound with VEHICLE/N,
add the appropriate quantity of active ingredient to yield the intended
VEHICLE/N(.TM.) is available as 50 mL of vehicle in a plastic bottle
with applicator top. The bottle is filled only to 3/4 capacity,
to ensure proper mixing. For 50 mL of VEHICLE/N, use the following
Desired Concentration 0.1% 0.2% 0.5% 1.0% Bulk Active 50 mg 100
mg 250 mg 500 mg Tablets 1 .times. 250 mg 4 .times. 150 mg 1.2%
soln Desired Concentration 2.0% 3.0% 4.0% 5.0% Bulk Active 1.0 gm
1.5 gm 2.0 gm 2.5 gm
For fastest dissolution, when tablets are used, crush them to a
powder and then add the powder to the vehicle. When capsules are
used, add the capsule contents only to the vehicle, and discard
the capsule shell. Shake the mixture gently. Most capsule contents
and bulk active ingredients will dissolve within minutes, though
some may take longer.
VEHICLE/N.TM. is available in a bottle with an APPLIDERM(.TM.)
applicator top. The APPLIDERM(.TM.) applicator unit automatically
filters the compounded mixture and provides a convenient, spill-proof,
self-contained unit for topical application. To use the APPLIDERM(.TM.)
applicator unit, push the applicator firmly into the bottle using
the white cap as a holder. Screw the cap all the way down to seat
the applicator. Shake well. If tablets are dissolved in the vehicle,
then the user should be instructed to allow the solution to stand
overnight and to shake vigorously before the first use. VEHICLE/N(.TM.)
should not be used near fire or open flame due to alcohol content.
Both VEHICLE/N(.TM.) and VEHICLE/N(.TM.) mild contain substantial
alcohol and are not suitable for use in acute dermatoses. Stinging
may be noted if used on irritated or abraded skin. Avoid contact
with eyes or eyelids. If the product accidentally comes in contact
with eyes, rinse thoroughly with water and contact physician. Keep
out of reach of children. VEHICLE/N(.TM.) and VEHICLE/N(.TM.) mild
are contraindicated in persons who have shown hypersensitivity to
any of the listed ingredients.
Given a constant amount of testosterone blocker or vascular toner,
I have found that lower concentrations of penetration enhancer can
decrease the efficacy of the final formulation, while higher concentrations
of penetration enhancer increase the risk of adverse side effects
due to systemic penetration of the other active ingredient(s).
Similarly, you may use different testosterone blockers for the
same effect, and may use more or less of it. Using more testosterone
blocker allows one to use relatively less penetration enhancer,
or a weaker enhancer. Titration of the two components against one
another is a conventional technique well known in the art of pharmaceutical
and cosmetics formulation. Such techniques are already used to titrate
formulations for the wide variety of trans-dermal drugs and cosmetics
For example, in a four ounce quantity of liquid containing 5 drops
of trimethyl acetate, I prefer to use one percent (by volume) of
soluble progesterone (U.S.P.).
A preferred formulation is:
Minoxidil 1.0 gm bulk powder Soluble progesterone (U.S.P.) 0.5
gm Trimethyl acetate 5 drops Vehicle N (TM) 50 mL
The following preparation is acceptable, and within the scope of
the claims, but I do not prefer it:
Minoxidil 1.0 gm bulk powder Soluble progesterone (U.S.P.) 0.5
gm Methyl acetate 5 drops Vehicle N (TM) 50 mL
Alternatively, an ethyl alcohol--water--propylene glycol solution
may be used as the diluents and vehicle. For 100 mL of this formulation,
ethyl alcohol 95% 75.5 cc purified water 18.5 cc propylene glycol
6.0 cc progesterone 1.5 gm minoxidil 2.0-5.0 gm methyl acetate 5.0
These are my preferred formulations. These may be varied as desired,
but it is necessary to watch for unwanted side effects possibly
due to unwanted systemic penetration of the active ingredient(s).
For example, minoxidil is pharmaceutically and cosmetically effective
topically at anywhere from about 0.01 grams to about 50 grams per
four ounces, depending on the frequency of topical administration.
Testosterone blockers are also pharmaceutically and cosmetically
effective topically at anywhere from about 0.01 grams to about 50
grams per four ounces, depending on the frequency of topical administration.
With the higher concentrations, however, increasing the amount of
penetration enhancer creates a greater risk of adverse side effects.
I have discussed several different specific formulas. I have found
these most useful. One can, however, vary the constituents to achieve
the same effect without having a substantially different product.
For example, one can use a different testosterone blocker, or a
weaker penetration enhancer in a higher concentration.
Thus, the legal scope of my patent is not limited to the specific
examples I discuss herein; rather, the legal coverage of this patent
is defined by the appended claims and their equivalents.