USOO6596266 B2

(12) United States Patent (10) Patent No.: US 6,596,266 B2

Catalfo et all e 45) Date of Patent: e Jul. 22, 2003

(54) COMPOSITIONS CONTAINING MINOXIDIL 2001/0031286 A1 10/2001 Porras et al. ............... 424/750
SSALMETTO FOR TREATING FOREIGN PATENT DOCUMENTS
EP O728462 A2 8/1996
(75) Inventors: Chris Catalfo, Orlando, FL (US); Fred JP OS286835 2/1993
Mussari, Melbourne, FL (US); Stephen WO WO 92/16236 10/1992
H. Perry, Longwood, FL (US) WO
WO
WO O
WO95/0049
8/1.
1/199
(73) Assignee: Natural Science, Inc., Melbourne, FL WO WO95/25500 9/1995
(US) WO WO 97/03638 2/1997
WO WO 97/12602 4/1997
(*) Notice: Subject to any disclaimer, the term of this W W CS E.
patent is extended or adjusted under 35 WO WO 97/47276 12/1997
U.S.C. 154(b) by 0 days.
OTHER PUBLICATIONS
(21) Appl. No.: 09/789,294 Barry, B.W. and Bennett, S.L., “Effect of penetration
(22) Filed: Feb. 20, 2001 enhancers on the permeation of mannitol, hydrocortisone
and progesterone through human skin', J. Pharm. Pharma
(65) Prior Publication Data col., 1987, 535-546:39.
US 2002/0O28257 A1 Mar. 7, 2002 Brodland,s D.G. and Muller,s S.A.,s “Androgenetic Alopecia
f ar. , (Common Baldness)", Cutis, 1991, 173–176:47.
Related U.S. Application Data Katz, H.I., “Topical Minoxidil: Review of Efficacy”, Clinics
(60) Provisional application No. 60/183,553, filed on Feb. 18, in Dermatology, 1998, 195-199. 6.
2000. Prager, N. et al., “A Randomized, Double-Blind, Placebo
(51) Int. Cl. ........................... Alk 06 AIKiss SEAE",
(52) U.S. Cl. ........................ 424/74; 424/70.1; 424/725;
"E.R.R.
ment of Androgenetic Alopecia', The Journal Of alternative
424/727 and Complementary Medidicine, 2002, 143-152:8.
(58) Field of Search ................................ 424/750, 70.1, Puolakka, Jukka, "Serum Ferritin in the Evaluation of Iron
424/195.17, 74,725, 727; 435/975 Status in Young Healthy Women', Acta Obstet Gynecl
Scand Suppl., 1980, 35–41:95.
(56) References Cited Rushton, D. H. and Ramsay, I. D., “The imprtance of
U.S. PATENT DOCUMENTS adequate Serum ferritin levels during oral cyproterone acet
ete ethinyl Oestradiol treatment of diffuse androgen-depen
3,551,554. A 12/1970 Herschler dent alopecia in women’, Clinical Endocrinology, 1992
3,989.816 A 11/1976 Rajadhyaksha 421-427:36 s s s
4.017,641 A 4/1977 DiGiulio -1 V 66
4,082,881 A 4f1978 Chen et al. Sattar, A.B. et al., “Chemical composition and biological
4,132,781 A
4,139,619 A
1/1979 Stoughton
2/1979 Chidsey, III
E. of ls,
armazie,
from Some Lamiaceae plants',
, OZ-O): U.
4,485,054 A 11/1984 Mezei et al. * cited b
4,596,812 A 6/1986 Chidsey, III et al. cited by examiner
4,761.288 A 8/1988 Mezei
4,828.837 A 5/1989 Uster et al. Primary Examiner-David M. Naff
4,861,764 A 8/1989 Samour et al. ASSistant Examiner-Deborah K. Ware
5,026,691 A 6/1991 Kligman (74) Attorney, Agent, or Firm- Van Dyke & Associates,
5,030.442 A 7/1991 Uster et al. P.A.
5,183,817 A 2/1993 Bazzano
5,407,944. A 4/1995 Goldman (57) ABSTRACT
5,466,695 A 11/1995 Poulos et al. C d/or f lati idil
5,578,599 A 11/1996 Diani et al. ompositions an ?or ormulations containing minoxidil as
5,609,858 A 3/1997 Buck an active ingredient in combination with other active agents
5,618,798 A 4/1997 Bar-Shalom and/or enhancer agents (e.g., saw palmetto extract and nettle
5,620.980 A 4/1997 Samour root extract) are provided. The compositions and/or formu
5,656,300 A 8/1997 Levin lations increase the hair growth capability of the composi
5,720.946 A 2/1998 Takeda et al. tion. Also disclosed are methods of using the compositions
5,750,107 A 5/1998 Nomura to treat male patterned baldness and to Stimulate hair growth
5,750,108 A 5/1998 Edwards on the Scalp, including both the apex and frontal regions of
5,763,361 A 6/1998 Harris et al. the Scal
5,834,014 A 11/1998 Weiner et al. p.
5,925,679 A 7/1999 Mather et al.
6,284.234 B1 * 9/2001 Niemiec et al. ......... 424/78.07 16 Claims, No Drawings
 US 6,596,266 B2
1 2
COMPOSITIONS CONTAINING MINOXDL minoxidil, and which will also provide hair regrowth Sooner,
AND SAW PALMETTO FOR TREATING in more abundance, and thicker, than is presently observed
BALDNESS using minoxidil and known penetration enhancers. Further,
CROSS-REFERENCE TO RELATED there is a need for a hair loSS treatment which can improve
APPLICATIONS hair growth at the frontal as well as apex regions of the Scalp.
The subject application claims the benefit under 35 USC BRIEF SUMMARY OF THE INVENTION
S119(e) of Provisional Application No. 60/183553 filed Feb. The Subject invention pertains to novel compositions
18, 2000. and/or formulations containing minoxidil as an active ingre
BACKGROUND OF THE INVENTION dient in combination with other active agents and/or
Androgenic alopecia is the Single largest type of recog enhancer agents which increases the hair growth capability
nizable alopecia to affect both men (50%) and women of the composition. Another aspect of the Subject invention
(30%), primarily of Caucasian origin. Androgenic alopecia pertains to methods of using the novel compositions to treat
or common baldness represents 99 percent of all cases of 15
male patterned baldness and to Stimulate hair growth on the
hair loss (Brodland and Muller, 1991). The condition is Scalp, including both the apex and frontal regions of the
characterized by the gradual conversion of terminal hair to Scalp. In addition to, or in place of minoxidil, glycerol oxido
Short, wispy, colorleSS Vellus hair. esters and/or ketoconazole can be added to the Subject hair
It is generally accepted that genetic hair loSS arises from growth compositions.
an inherited predisposition activated by circulating andro According to one aspect, the Subject invention pertains to
genic hormones. While many investigators have tried to a topical composition designed for application to the Scalp
isolate the causative androgen metabolite, no Single mol wherein Said composition comprises, in admixture with a
ecule has emerged. For example, in comparative Studies pharmaceutically acceptable carrier and minoxidil, one or
between non-balding controls, no significant difference more of the following components: Saw palmetto extract;
between mean hormonal values or amounts has been 25
nettle root extract; Capsaicin; Niacin, Gingko Biloba; horse
detected. See Puolakka, 1980. This suggests that a sensitiv tail eXtract; phospolipid; glycero oxido esters, urSolic acid;
ity or receptivity to hormones at the cell binding sites within ketoconazole; 1,4:3,6 dianhydro-2.5-di-O-methyl-D-
the dermal papilla is a possible factor. Several treatments are glucitol, cycoldextrin; peppermint oil; or milk thistle. A
based on this theory using anti-androgens Such as CPA particular aspect of the Subject invention pertains to a
(cyproterone acetate) in combination with ethinyl-estradiol composition for treating androgenic alopecia comprising
and the aldosterone antagonist Spironolactone, which, given minoxidil in combination with Saw palmetto extract. A
in dosages from 75 to 100 mg per day has shown Some further aspect of the Subject invention preferably comprises,
benefit. See e.g., Rushton and Ramsay, 1992; Rushton et al. in addition to the minoxidil and Saw palmetto extract, a
1991. nettle root extract.
Most treatment modalities currently employed (Such as 35 The Subject compositions and methods provide a Safe and
hair transplantation) have been performed based on the effective way to increase hair growth of the Scalp. These and
theory that Some hair follicles are genetically predisposed other advantageous aspects of the Subject invention are
for Sensitivity to androgens in the body. However, trans described in further detail below.
plantation methods can be painful and expensive, often DETAILED DISCLOSURE OF THE PREFERRED
resulting in an undesirable “fake” appearance. No Single 40
EMBODIMENTS
treatment modality has proven completely or repeatably
Successful in inducing, maintaining and/or increasing hair The Subject invention is directed to novel compositions
growth. and methods of using the same for treating androgenic
In 1980, the reversal of androgenic alopecia in a male alopecia, or male pattern baldness. The Subject compositions
patient receiving minoxidil for hypertension was revealed 45 comprise minoxidil as one active component in combination
and minoxidil has since been used to promote hair growth, with other compounds which act in combination with
most commonly by topical application (Zapacosta, 1980). minoxidil to Synergistically increase the effectiveness of the
Minoxidil's vasodilating effect on the scalp is one of the composition. AS used herein “minoxidil” refers to 24,
proposed mechanisms by which minoxidil promotes hair pyrimidihediamine6-(1-piperdinyl)-3-oxide, and analogs
growth. However, despite its popularity, minoxidil has not 50 and Salts thereof, as described in U.S. Pat. Nos. 4,139,619;
performed in a completely Satisfactory fashion in promoting 4,596,812; and 5,030,442 which are incorporated herein by
hair growth in all target populations. While minoxidil has this reference. Alternatively, glycerol oxido esters,
been shown to Stimulate Some hair growth at the apex region ketoconazole, or a combination thereof can be Substituted
of the Scalp, hair growth at the frontal region of the Scalp, for for minoxidil, or otherwise added to the Subject composi
the most part, has not been shown to be improved by 55 tions in addition to minoxidil.
minoxidil treatment alone. One embodiment of the subject invention is directed to a
Cosmetic treatment of age-related hair loSS in androgenic composition comprising minoxidil and Saw palmetto extract
alopecia patients with topical Solutions of minoxidil in combination with at least one other inert compound
(ROGAINE(R) alone, or in combination with skin penetra whereby said composition is in a pharmaceutically
tion enhancers, such as DMSO, has resulted in only mod 60 acceptable form Suitable for topical administration. Conven
erate regrowth of hair in less than 40% of Such patients tional pharmaceutical forms for this purpose include
(Katz, 1988). Moreover, treatments with topical solutions of ointments, Waxes, gels, lotions, pastes, jellies, SprayS,
minoxidil require multiple applications of the active ingre aeroSols, and the like in aqueous or nonaqueous formula
dient each day, which can be very inconvenient as well as tions. The term “ointment' embraces formulations
expensive. 65 (including creams) having oleaginous, absorption, water
There is a need for methods of treating hair loss that Soluble and emulsion-type bases, e.g., petrolatum, lanolin,
require fewer applications of active ingredient, e.g., polyethylene glycols, N-methyl-2-pyrrolidinone, oleyl alco
 US 6,596,266 B2
3 4
hol as well as mixtures of these. In an alternative added to the Subject compositions. Such anti-inflammatories
embodiment, the Subject invention is directed to a compo include Steroidal as well as non-Steroidal anti
Sition comprising minoxidil in combination with a nettle inflammatories. Examples of anti-inflammatory agents use
rOOt eXtract. ful in accord with the teachings he rein include
Some evidence Suggests that Saw palmetto extract can act corticosteroids, ibuprofen and derivatives thereof, aspirin
as a DHT inhibitor. The term “DHT inhibitor’ is used herein and derivatives thereof, aloe Vera, and combinations thereof.
in its broad Sense and relates to Substances that inhibit The concentrations of Steroidal compounds are preferably
enzymes responsible for producing dihydrotestosterone, 0.5% to 2.5% of the subject composition. The concentration
Such as 5-O-reductase, or otherwise block or mask activity of non-steroidal compounds is preferably from about 1% to
of DHT by binding to DHT thereby inactivating it and/or about 5%.
binding to DHT receptors. In addition to, or in place of saw Antimicrobials may also be added to the Subject compo
palmetto extract, other DHT inhibitors can be provided in Sitions for treating alopecia. Examples of antimicrobials
the Subject compositions, including, but not limited to, nettle include, but are not limited to, organic Solvents (e.g.,
root extract, azelaic acid (see e.g., U.S. Pat. No. 5,925,679), 15
alcohols) and oils or extracts (e.g., oil of wintergreen and
and ginko biloba. peppermint oil), urSolic acid, or combinations thereof.
In a more preferred embodiment, the Subject composition Compounds to aid in repair of hair, nails, and skin may
comprises minoxidil, Saw palmetto extract, and nettle root also be added to the Subject compositions. Examples of Such
extract, wherein the composition comprises about 1% to compounds include Selenium and Silica, which may be
about 5% minoxidil, about 3% to about 8% saw palmetto added in relatively isolated form or in the form of various
extract, and about 1% to about 3% nettle root extract. partially processed plant material or extracts (e.g., Horsetail
Diffusional resistance of the Stratum corneum to topically plantain or nettle root extract).
applied agents has been demonstrated with various drugs. In In a topical application, the compound or formulated
order to overcome this barrier effect a number of compounds composition can be applied to the area to be treated, in
can be added to the Subject compositions to enhance the 25 mammals. Such as the Scalp in humans, by Spraying, dabbing
transdermal delivery of drugs, Such as dimethyl Sulfoxide or Swabbing. Other leSS Specific methods can be employed
(DMSO); polyethylene glycol monolaurate; alkyl lactams; provided the active ingredient(s) are delivered to the region
long chain amides, Substituted 1,3-dioxacyclopentanes and of a hair follicle. Preferably, the compound or formulated
substituted 1,3-dioxacyclohexanes; 14:3,6 dianhydro-2.5- composition is periodically applied to the treatment area on
di-O-methyl-D-glucitol; or mixtures thereof. For example, a routine basis prior to, during and Subsequent to hair
U.S. Pat. No. 3,551,554 discloses DMSO, U.S. Pat. No. growth. Generally, the routine treatment would be to apply
3,989,816 discloses 1-substituted azacycloheptane-2-one, the compound or formulated composition at least daily,
U.S. Pat. No. 4,132,781 discloses a topical antibiotic com preferably twice daily although more frequent applications
position containing 2-pyrrolidone or an n-lower alkyl-2- can be used. The percentage by weight of the active ingre
pyrrollidone, U.S. Pat. No. 4,017,641 discloses propylene 35 dients minoxidil or other vasodilator herein utilized range at
glycol and 2-pyrrolidone-containing compositions and U.S. an effective amount which is an amount Sufficient to increase
Pat. No. 4,861,764 discloses 1,3-dioxolane and 1,3-dioxane normal hair growth or treat various forms of allopecia
derivatives as percutaneous absorption enhancers, U.S. Pat. whereby the hair growth is significantly more than if either
No. 4,082,881 discloses 1,4,3,6dianhydro-2,5,-di-O-methyl of the compounds were Solely administered. In topical
D-glucitol (see also Barry, Pharm. Pharmocol, 39:535-546 40 preparations the pharmaceutical carrier for topical applica
(1987)). WO92/16236 discloses methods and compositions tions constitutes a major amount of the preparation.
for enhancing the rate of absorption of topically adminis Typically, the active ingredient is in a range of from about
tered physiologically active compounds. Minoxidil is dis 0.01 to about 10 percent total weight of the topical
closed as one of these compounds. Also, the penetration composition, preferably 0.1 to 5 percent total weight.
enhancers can be amino alcohol derivatives which may form 45 Pharmaceutically acceptable salts of minoxidil or other
a 1,3-dioxane ring. vasodilators taught herein are for example acid addition Salts
Another example of an enhancing agent is 1,3- which may be chosen from the following: acetate, adipate,
dioxacycloalkane taught, for example, in U.S. Pat. No. alginate, aspartate, benzoate, benzeneSulfonate, bisulfitte,
5,620,980 whose teachings are incorporated herein by ref butyrate, citrate, camphorate, camphorSulfonate,
erence. Other agents include retin A or derivatives thereof 50 cyclopentane propionate, digluconate, dodeclSulfate,
Such as tretinoin. e thane Sultonate, fumarate, glucoheptanoate,
Other compounds which work to increase circulation to glycerophosphate, he misulfate, heptanoate, hexanoate,
the cells of the Scalp may be added to the Subject compo hydrochloride, hydrobromide, hydroiodide,
Sitions. These compounds are believed to not only increase 2-hydroxy ethane Sulfonate, lactate, male ate,
health of the cutaneous and Subcutaneous tissue of the Scalp, 55 methaneSulfonate, 2-naphthalenesulfonate, nicotinate,
but to aid in the delivery and penetration of active compo oxalate, pamoate, pectinate, perSulfate, 3-phenylpropionate,
nents as well. Compounds aiding in circulation which may picrate, pivalate, propionate, Succinate, tartrate, thiocyanate,
be used in accord with the teachings herein include, but are tosylate, and undecanoate.
not limited to, thistle, Ginkgo Biloba, and peppers (e.g., Pharmaceutically acceptable cationic addition Salts of
Cayenne pepper and Red pepper), urSolic acid (disclosed in 60 minoxidil or other vasodilators include: pharmacologically
Jap. Pat. No. 05286835, and Sattar et al., Pharmazie, acceptable metal cations, ammonium, amine cations, or
50:62-65 (1995)), or combinations thereof. quaternary ammonium cations. Especially preferred metal
Some have hypothesized that there is a chronic inflam cations are those derived from the alkali metals, e.g.,
matory process, Subtending to the hair bulbs, in patterned lithium, Sodium, and potassium, and from the alkaline earth
alopecia, leading to eventual Scarring of the lower follicle, 65 metals, magnesium and calcium, although cationic forms of
making regrowth impossible. To counter this inflammatory other metals, e.g., aluminum, Zinc, and iron are also within
degenerative process, anti-inflammatories may also be the Scope of this invention. Pharmacologically acceptable
 US 6,596,266 B2
S 6
amine cations are those derived from primary, Secondary, under conditions which cause splitting out of water from the
and tertiary amines. Sorbitol, leaving Sorbitan. In an even more preferred
The composition of the invention may be administered embodiment ethylene oxide is added along with the fatty
topically in a water-base cream, ointment, or gel form. acid esters in the condensation reaction to effect water
Several factors contribute to cosmetic advantages of the Solution.
water-base composition. High drug loading up to 5% or
more in non-crystalline form is possible, and the drug In an alternative embodiment, the components of the
remains in a non-crystalline form up to Several hours or Subject hair growth composition can be administered orally
more after administration, Since Solvent evaporation is rela as a safe dietary Supplement. Preferably, the dietary Supple
tively slow and evaporation can occur without leading to ment is taken concurrent to administration of the topical
drug crystallization. Since the composition contains little or compositions described herein.
no alcohol, it can be applied without Stinging.
The drug is efficiently taken up by the skin, by virtue of The Subject hair growth Stimulating compositions can be
the Selected amphipath, and different rates of uptake can be packaged in a kit with instructions for use and applicators
achieved by varying the drug or amphipath concentration, 15 commonly used in the art. The Subject compositions can be
and by Selection of different amphipathic compounds. contained in various bottles having engaged thereto Spray
The water-base composition may additionally contain nozzles for administrating the composition to the affected
lipoSome or lipid-emulsion particles in which the drug can aca.
be entrapped in non-crystalline form. See U.S. Pat. Nos.
4,485,054 and 4,761,288 for teachings on methods of encap The teachings of all patents and publications cited
Sulating minoxidil in multilamellar lipid vesicles to aid in throughout this specification are incorporated by reference
drug delivery. In one embodiment, a concentrated liposomal in their entirety to the extent not inconsistent with the
composition having desired cream or ointment consistency teachings herein.
can be formulated using a novel Solvent injection System.
The lipoSome formulation can have high loading, and a rate 25 Following are examples which illustrate procedures for
of drug uptake can be modulated by choice of lipid com practicing the invention. These examples should not be
ponents and relative molar amounts of lipid and drug. The construed as limiting. All percentages are by weight and all
lipid formulation is also expected to have the known mois Solvent mixture proportions are by Volume unless otherwise
turizing benefits of topical lipid formulations. In addition or noted. Where percentages do not amount to 100 percent, DI
alternatively, liposomes are loaded with Saw palmetto water is added to the formulation to meet the remaining
extract and/or nettle root extract. percentages.
In another embodiment, the composition is dispersed as
an aerosol form, Such as in a chlorofluorocarbon Solvent, for EXAMPLE 1.
delivery in Spray form. The Spray form has many advantages 35
of the water-base formulation, including high drug loading
and enhanced drug uptake. Additionally, the Spray compo Hair Growth Stimulating Formulation for Topical
Sition has the advantage that it can be applied in a more Administration
convenient manner and without matting the hair in the
treated Scalp region. 40
Other suitable additives/carriers that may be admixed pharmaceutically-acceptable 35% to 99%
with the minoxidil composition include, but are not limited carrier
to, water, glycols, esters, glycerine, alcohols, lipid materials, Minoxidil 1% to 5%
coloring agents, fragrances, anti-oxidants, thickening Extract of Nettle Root 1% to 3%
Saw Palmetto Extract 3% to 8%
agents, ultra-violet light Stabilizers, preservatives, and other 45
pharmaceutically accepted additives.
The Selection of additives may impact on the effectiveness
of the composition. A particularly preferred Safe and effec EXAMPLE 2
tive composition is based on a cosmetic carrier wherein a
Solvent System is an aqueous alcoholic Solution containing 50
ethanol, propanol or isopropanol, together with a lower Hair Growth Stimulating Formulation for Topical
alkyl(Cl)glycol, Such as ethylene glycol or propylene Administration
glycol and, usually, a thickener or gelling agent. Another,
often useful additive is dimethicone or other volatile silicone
Solvent and carrier. 55
pharmaceutically-acceptable 35% to 99%
In a Specific embodiment, the Subject hair growth com carrier
positions can be provided in Shampoo and/or conditioner Minoxidil 1% to 5%
form, which can preferably be used on a daily basis. The Dimethyl Isosorbide 1% to 6%
Subject compositions can be added to Shampoo formulations Capsaicin O.5% to 2.5%
Niacin O.5% to 1.5%
commonly used in the art and readily produce by one skilled 60
Ginkgo Biloba 1% to 3%
in the art. In a preferred embodiment, mixtures of fatty acid Extract of Nettle Root 1% to 3%
esters of sorbitol and Sorbitol anhydrides (commonly called Horsetail Extract
Saw Palmetto Extract
2% to 4%
3% to 8%
polySorbates) are added to the Shampoo formulations. These Peppermint Oil 1% to 9%
compounds have nonionic properties that inhibit Shedding of Milk Thistle 2% to 8%
hair. PolySorbates are one of a group of nonionic Surfactants 65 Methyl Nicotinate O.5% to 4%
obtained by esterification of Sorbitol with one or three
molecules of a fatty acid (e.g. Stearic, lauric, oleic, palmitic)
 US 6,596,266 B2
7 8
EXAMPLE 3 EXAMPLE 6

Hair Growth Stimulating Formulation for Topical

Administration 5 Hair Growth Stimulating Formulation for Topical
Administration

Aloe Vera Gel 35% to 99%

Minoxidil 1% to 5% pharmaceutically-acceptable 35% to 99%
Dimethyl Isosorbide 1% to 6% 1O carrier
Rosemary Extract 2% to 8% Minoxidil 1% to 5%
Glycolic Acid 2% to 6% Extract of Nettle Root 1% to 3%
Pantothenic Acid 1% to 3% Saw Palmetto Extract 3% to 8%
Glycerine 10% to 12% phospholipid 2% to 8%
Safflower Oil 8% to 16%
Capsaicin O.5% to 2.5% 15
Niacin O.5% to 1.5%
Ginkgo Biloba 1% to 3%
Extract of Nettle Root 1% to 3%
Horsetail Extract 2% to 4% EXAMPLE 7
Saw Palmetto Extract 3% to 8%
Peppermint Oil 1% to 9%
Milk Thistle 2% to 8% 2O
Methyl Nicotinate O.5% to 4% Hair Growth Stimulating Formulation for Topical
Administration

EXAMPLE 4 25
pharmaceutically-acceptable 35% to 99%
carrier
Hair Growth Stimulating Formulation for Topical Mini Nettle Root 1. 5.
Administration Saw Palmetto Extract 3% to 8%
3O Phospholipid 2% to 8%
Niacin O.5% to 1.5%
Capsaicin O.5% to 2.5%
Aloe Vera Gel 35% to 99%
Minoxidi 19% to 5%
Dimethyl Isosorbide 1% to 6%
Rosemary Extract 2% to 8% 35
Glycolic Acid 2% to 6%
Pantothenic Acid 1% to 3% EXAMPLE 8
Glycerine 10% to 12%
Safflower Oil 8% to 16%
Spain s Formulation for Dietary Supplement for
Ginkgo Biloba 1% to 3% 40 Consumption in Conjunction with Topical
Extract of Nettle Root 1% to 3% Formulation
Horsetail Extract 2% to 4%
Saw Palmetto Extract 3% to 8%
Peppermint Oil 1% to 9%
Milk Thistle 2% to 8%
Methyl Nicotinate O.5% to 4% 45 Niacin 30 mg
Phospholipid 2% to 8% Vitamin Be 25 mg
Folate 200 mcg
Biotin 130 mcg
Panthothenic acid 30 mg
Iodine 150 mcg
EXAMPLE 5 50 Zinc 15 mg
pumpkin seed concentrate 60 mg
Ginkgo Biloba 30 mg
Hair Growth Stimulating Formulation for Topical E. root
-Histidine 100
50 mg
mg
Administration Aloe Vera gel 20 mg
Gotu Kola leaf 30 mg
55 Saw Palmetto berry 200 mg
Nettle leaf 180 mg
Aloe Vera Gel 35% to 99% Sage leaf 20 mg
Minoxidil 1% to 5% Hawthornberry 60 mg
Capsaicin O.5% to 2.5% Bovine extract 30 mg
Niacin O.5% to 1.5% 60 Sulfur 20 mg
Ginkgo Biloba 1% to 3% Silica 25 mg
Extract of Nettle Root 1% to 3%
Saw Palmetto Extract 3% to 8%
Peppermint Oil 1% to 9%
Milk Thistle 2% to 8%
Methyl Nicotinate O.5% to 4% The above formulation is preferably put in tablet form.
Phospholipid 2% to 8% 65 Preferably two tablets are taken twice a day concurrent with
administration of topical formulations described in
Examples 1-7 and elsewhere herein.
 US 6,596,266 B2
9 10
EXAMPLE 9 Ruston D. H., W. Futterwiet, D. H. Kingsley, P. Kingsley and
Topical Formulation M. J. Norris (1991) “Quantative assessment of spirono
lactone treatment in Women with diffuse androgen
dependent alopecia,” J. Soc. Cosmet. Shem. 42:317-325.
Zapacosta, A. R. (1980) N. Eng. J. Med. 303: 1480–1481.
Aloe Vera Gel 35% to 99% U.S. Pat. No. 3,551,554.
Minoxidil 3% to 5% U.S. Pat. No. 3,989,816.
Rosemary Extract O.5% to 1% U.S. Pat. No. 4,017,641.
Glycolic Acid O.2% to 1%
Tween 1% to 3% U.S. Pat. No. 4,132,781.
Glycerine-USP 5% to 7% U.S. Pat. No. 4,139,619.
Isopropyl alcohol 9% to 11% U.S. Pat. No. 4,485,054.
Capsaicin 1% to 2.5% U.S. Pat. No. 4,596,812.
Arlasolve DMI O.6% to 1%
Niacin O.5% to 1.5% U.S. Pat. No. 4,761,288.
glycerol Oxide esters 1% to 2% U.S. Pat. No. 4,861,764.
Ginkgo Biloba 1% to 3% 15 U.S. Pat. No. 5,030,442.
Extract of Nettle Root 1% to 3%
Horsetail Extract 1% to 2%
U.S. Pat. No. 5,620,980.
Peppermint Oil O.2% to 1% PCT Application No. WO92/16236.
Milk Thistle 1% to 2% What is claimed is:
Glydant Plus O.2% 1. A dietary Supplement comprising minoxidil, Saw pal
Methyl Nicotinate O.05% to 1% metto extract, and nettle root extract.
2. The dietary Supplement of claim 1 further comprising
one or more of the following components:
EXAMPLE 10
(a) niacin;
Clinical Study (b) vitamin B6;
25
Participants consisted of five males between the ages of (c) folate;
18 and 40, who were all experiencing hair loSS of various (d) biotin;
degrees. The participants applied the formulation described (e) panthothenic acid;
in Example 9 to their Scalps once daily, and ingested two (f) iodine;
tablets described in Example 8 twice daily. The scalps of the (g) Zinc;
participants were evaluated every four weeks. Clinic follow
up Visits consisted of photographs, progreSS questionnaires (h) pumpkin Seed concentrate;
completed by the participant, and Study drug compliance. (i) Ginkgo biloba;
The results with respect to the amount of hair loss or (i) fo ti root;
initiation of new hair growth is noted below: 35 (k) L-histidine;
Two months-participants report slowing of hair loSS and (l) aloe Vera gel,
the beginning Signs of new hair growth. (m) gotu kola leaf;
Three months-participants report no noticeable hair loSS (n) Sage leaf,
and new hair growth. Reports of new, “downy' type (o) Hawthorne berry;
hair where topical Solution has been applied were 40
(p) bovine extract;
given. (q) Sulfur, or
Four months-participants report that hair is slowly get
ting thicker, and Stronger. (r) Silica.
3. A topical composition for application to the Scalp, Said
Five months-participants fuller hair and definite reduc composition comprising a admixture of minoxidil, Saw
tion of hair loss. 45
palmetto extract, and nettle root extract.
Comments of hair growth with respect to location was 4. A topical composition for application to the Scalp, Said
dependent on the individual, location of each participants composition comprising, in admixture of pharmaceutically
hair loSS, and where the topical Solution was applied. Some acceptable carrier, minoxidil, and Saw palmetto extract and
participants reported hair growth in the apex area, as well as one or more of the following:
growth in the frontal region of the Scalp. 50
a.) Nettle root extract;
It should be understood that the examples and embodi b.) Capsaicin;
ments described herein are for illustrative purposes only and
that various modifications or changes in light thereof will be c.) Niacin;
Suggested to perSons Skilled in the art and are to be included d.) Gingko Biloba;
within the Spirit and purview of this application and the 55 e.) horsetail extract;
Scope of the appended claims. f) phospholipid;
Reference g) glycerol oxide esters;
h.) cyclodextrin;
Brodland and Muller (1991) Cutis 47:173–176. i.) ketoconazole;
KatzX, H. I. (198) Clin. Dermatol., 6:196-199. 60
j.) uroSolic acid
Puolakka, J. (1980) Acta. Obset. Gynecol. Scand, Suppl. k.) polySorbate;
95:35-41.
Rushton, D. H., D. D. Ramsay (1992) “The importance of 1.) 1.4.3,6dianhydro-2,5-di-O-methyl-D-glucitol;
adequate Serum ferritin levels in cyproterone acetate and m.) peppermint oil
ethinyl-oestradiol therapy in women with diffuse 65 n.) Silica
androgen-dependent alopecia,” Clin. Edocrinal. o.) milk thistle; or
36:421-427. p.) methyl nicotinate.
 US 6,596,266 B2
11 12
5. The topical composition of claim 4, wherein minoxidil carrier, minoxidil, Saw palmetto extract, nettle root extract,
comprises about 1 percent to about 5 percent, by weight, of capsaicin, niacin, and horsetail eXtract.
Said composition. 12. The topical composition of claim 11, wherein minoxi
6. The topical composition of claim 4, wherein Said dil comprises about 1 percent to about 5 percent, nettle root
pharmaceutically acceptable carrier is water, glycols, esters, extract comprises about 1 percent to about 3 percent, cap
alcohols, lipids, or combinations thereof. Saicin comprises about 0.5 percent to about 2.5 percent,
7. The topical composition of claim 6, wherein said niacin comprises about 0.5 percent to about 2.0 percent and
pharmaceutically acceptable carrier is a mixture ofisopropyl horsetail eXtract comprises about 2 percent to about 4
alcohol and glycerine. percent, by weight, of Said composition.
8. Akit for Stimulating hair growth comprising a container 13. The topical composition of claim 11 further compris
having the composition of claim 4 disposed therein and ing methyl nicotinate.
instructions for use. 14. The topical composition of claim 13, further compris
ing phospholipid.
9. A topical composition for application to the Scalp, said 15. A method of Stimulating hair growth in a patient
composition comprises a pharmaceutically acceptable comprising obtaining a composition according to claim 11,
carrier, minoxidil, Saw palmetto extract, nettle root extract 15 and administering Said composition to Said patient's Scalp.
and phospholipid. 16. The method of claim 15, further comprising
10. The topical composition of claim 9, wherein minoxidil co-administering, orally, a dietary Supplement comprising
comprises about 1 percent to about 5 percent, nettle root minoxidil, Saw palmetto extract, and nettle root extract,
extract comprises about 1 percent to about 3 percent and wherein co-administering occurs prior to, concurrently, or
phospholipid comprises about 2 percent to about 8 percent, Subsequent to Said administering of Said topical composi
by weight, of Said composition. tion.
11. A topical composition for application to the Scalp, said
composition comprises a pharmaceutically acceptable