U.S. patent application number 14/067219 was filed with the patent office on 2014-03-06 for topical delivery of l-arginine to cause beneficial effects.
This patent application is currently assigned to Strategic Science & Technologies, LLC. The applicant listed for this patent is Strategic Science & Technologies, LLC. Invention is credited to Eric T. Fossel.
Application Number | 20140066511 14/067219 |
Document ID | / |
Family ID | 25461979 |
Filed Date | 2014-03-06 |
United States Patent
Application |
20140066511 |
Kind Code |
A1 |
Fossel; Eric T. |
March 6, 2014 |
TOPICAL DELIVERY OF L-ARGININE TO CAUSE BENEFICIAL EFFECTS
Abstract
A preparation is disclosed for producing enhanced blood flow in
tissue thus causing beneficial effects such as promoting hair
growth on scalp tissue lacking sufficient hair, restoring normal
sexual function in males with erectile dysfunction. Specifically,
this is a preparation which provides local delivery of the amino
acid L-arginine, an important biological precursor to the main
substance which is responsible for relaxation of blood vessels
permitting enhancement of blood flow. In the preferred embodiments,
the L-arginine is provided so that it can be topically applied to
the scalp or penis. The preparation also contains an agent which
aids in the transfer of L-arginine into the tissue. In the
preferred embodiments this agent overcomes the resistance to
transfer caused by the high charge density of L-arginine. In the
preferred embodiments this means is high ionic strength created by
addition of choline chloride, magnesium chloride and sodium
chloride. This preparation when applied nightly to scalp tissue
lacking sufficient hair for a period of time causes substantial
growth of hair on the scalp. Further, when applied to the penis of
a subject with erectile dysfunction causes restoration of normal
sexual function.
Inventors: |
Fossel; Eric T.; (Cambridge,
MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Strategic Science & Technologies, LLC |
Cambridge |
MA |
US |
|
|
Assignee: |
Strategic Science &
Technologies, LLC
Cambridge
MA
|
Family ID: |
25461979 |
Appl. No.: |
14/067219 |
Filed: |
October 30, 2013 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
12833874 |
Jul 9, 2010 |
8603519 |
|
|
14067219 |
|
|
|
|
08932227 |
Sep 17, 1997 |
7914814 |
|
|
12833874 |
|
|
|
|
Current U.S.
Class: |
514/565 ;
514/769; 514/788 |
Current CPC
Class: |
A61P 15/10 20180101;
A61K 31/198 20130101; A61K 9/127 20130101; A61K 9/7023 20130101;
A61K 47/02 20130101; A61Q 7/00 20130101; A61K 8/14 20130101; A61Q
19/00 20130101; A61K 8/0208 20130101; A61K 8/44 20130101 |
Class at
Publication: |
514/565 ;
514/769; 514/788 |
International
Class: |
A61K 9/70 20060101
A61K009/70; A61K 47/18 20060101 A61K047/18; A61K 31/198 20060101
A61K031/198; A61K 47/02 20060101 A61K047/02 |
Claims
1-32. (canceled)
33. An article, comprising: a trans-dermal patch comprising an
environment comprising one or more ionic salts together at a
concentration higher than the concentration of ionic salts in human
skin.
34. The article of claim 33, wherein the one or more ionic salts
comprises sodium chloride.
35. The article of claim 33, wherein the one or more ionic salts
comprises magnesium chloride.
36. The article of claim 33, wherein the one or more ionic salts
comprises choline chloride.
37. The article of claim 33, wherein the trans-dermal patch further
comprises L-arginine.
38. The article of claim 37, wherein the environment causes the
L-arginine to migrate from the patch into the skin once the patch
is applied to the skin.
39. The article of claim 33, wherein the trans-dermal patch further
comprises an L-arginine salt.
40. The article of claim 39, wherein the L-arginine salt comprises
L-arginine hydrochloride.
41. The article of claim 39, wherein the environment causes the
L-arginine salt to migrate from the patch into the skin once the
patch is applied to the skin.
42. The article of claim 33, wherein the trans-dermal patch further
comprises a penetrating agent.
43. A method, comprising applying the trans-dermal patch of claim
33 to the skin of a subject.
44. The method of claim 43, wherein the subject is a human.
Description
BACKGROUND
[0001] 1. Field of the Invention
[0002] This invention relates to topical application of a cream,
gel, or other vehicle which contains substances such as L-arginine
which delivers these substances into tissue for the purpose of
producing beneficial effects such as growth of hair on the scalp,
healing of leg ulcers secondary to diabetes or confinement to bed
and overcoming erectile dysfunction, as well as beneficial effects
through restoration of natural mechanisms based on improvement of
local blood supply.
[0003] 2. Prior Art
[0004] Approaches to improving local blood flow have been many and
consist of both systemic and topical approaches. Many beneficial
effects could be obtained should improvement in local blood flow be
achieved since impairment of local blood flow causes a variety of
negative consequences.
[0005] It has been recognized that deficiencies in blood flow in
the scalp occur in male pattern baldness. See G. Duplechain et al.,
J. Louisiana State Med Soc. 146, 7 (1994); P Klemp et al., J
Invests Dermatol 95, 725 (1989); S Toshitani et al., J Dermatol 17,
240 (1990). Topical minoxidil has been used as an agent for hair
growth in male pattern baldness with varying results. Though the
suggestion has been made that minoxidil operates through increase
in the blood supply to the scalp, many investigators have failed to
show such an effect. See E de Boer et al., Acta
Dermato-Venereoligica 68, 271 (1988); C Bunker et al., British J
Derm 117, 668 (1987).
[0006] It has long been recognized that impaired blood flow to the
penis is a major cause of erectile failure (impotence) in men. See
A Moradian et al. Am J. Med 85, 748, (1988); T Hwang et al. J
Formosan Med Assoc 89, 992 (1990). Further it has been recognized
by using isolated tissue in vitro and in animal experiments that
nitric oxide is an important mediator of relaxation of the vessels
in penile cavernous tissue. See H Kirkeby et al. Acta Physiol Scand
149, 385 (1993). Topical nitroglycerine has been used in the
treatment of impotence because of its ability to dilate vessels.
The results were inconclusive and the treatment not well tolerated
because of the cardiac response to nitroglycerine. See S Negelev J
Urology 143, 586 (1990).
[0007] Accordingly, several objects and advantages of the instant
invention are to induce the growth of hair on portions of human
scalp which has insufficient hair by means of enhancement of the
body's natural mechanisms. It is yet another object of the instant
invention to induce healing of superficial ulcers of the limbs by
means of enhancement of the body's natural mechanisms. It is still
another object of the instant invention to overcome erectile
failure restoring natural male sexual function by means of
enhancement of the body's own natural mechanisms.
SUMMARY OF THE INVENTION
[0008] It was discovered that topical application of a nitric oxide
precursor, L-arginine, in its various forms contained in a variety
of topical preparations, either by themselves or with other agents
to aid in penetration, such as a high ionic strength environment,
neutralization of its charge in a complex or by other means, or
included in a liposome or other biological carrier, when
administered to the scalp causes hair growth, when administered to
superficial ulcers causes healing and when administered to the
penis enhances erectile function.
[0009] In one embodiment of the invention, a penetrating cream
containing L-arginine at an effective concentration and a salt,
such as sodium chloride, at a concentration sufficient to create a
hostile biophysical environment for the L-arginine in the cream is
applied to nightly to the scalp containing a deficit of hair
induces hair growth within 3-4 months.
[0010] Further, in accordance with this invention, a penetrating
cream containing L-arginine in a concentration sufficient to
produce the desired effect along with sodium chloride or other
salts at a concentration sufficient to produce a hostile
biophysical environment when applied to the penis induces firm and
natural erections within 20 minutes.
[0011] Consequently, with the discovery of the present invention, a
means to restore hair growth on a portion of scalp scarce in hair
has been found. Further, with the discovery of the present
invention, a means to heal superficial ulcers has been found.
Additionally, with the discovery of the present invention, a means
to overcome erectile dysfunction has been found.
[0012] In preferred embodiments, the delivery vehicle is a
penetrating cream, the L-arginine is present as L-arginine
hydrochloride in a concentration sufficient to produce the desired
effect and the agent which creates the hostile biophysical
environment is sodium chloride at a concentration sufficient to aid
in tissue absorption.
[0013] These and other objects and features of the present
invention will become apparent to those skilled in the art from
reading the description of the invention, which follows.
DETAILED DESCRIPTION OF THE INVENTION
[0014] The preferred embodiment consists of a base cream with the
properties of excellent absorption into the skin which also
contains L-arginine hydrochloride (12.5% w/v), choline chloride
(10%), sodium chloride (5% w/v) and magnesium chloride (5% w/v).
The components of the base cream may be those commonly found in
hand creams, such as water, mineral oil, glyceryl stereate,
squalene, propylene glycol stearate, wheat germ oil, glyceryl
stearate, isopropyl myristate, steryl stearate, polysorbate 60,
propylene glycol, oleic acid, tocopherol acetate, collagen,
sorbitan stearate, vitamin A & D, triethanolamine,
methylparaben, aloe vera extract, imidazolidinyl urea,
propylparaben, and BHA. L-arginine hydrochloride provides a
precursor to the molecule, nitric oxide, NO. Nitric oxide is the
substance that relaxes the blood vessels, allowing for increased
blood flow. Choline chloride, sodium chloride and magnesium
chloride provides a high ionic strength environment for the highly
charged molecule, L-arginine. This high ionic strength environment
is an example of a hostile biophysical environment for L-arginine.
That is, the highly charged ionic strength is an unfavorable
environment for the highly charged L-arginine making the L-arginine
anxious to move to a more hospitable, less charged environment such
as human tissue. The base cream containing L-arginine, choline
chloride, sodium chloride and magnesium chloride is the agent which
produces beneficial effects such as hair growth, healing of ulcers
such as leg ulcers or restoration of normal erectile function in
males suffering from erectile dysfunction.
[0015] The cream acts effectively to induce hair growth on human
scalp lacking sufficient hair when applied nightly to the bald area
each night for several months. Hair growth is naturally a slow
process. However, substantial hair growth is achieved over large
areas of scalp with results becoming evident in a few weeks and
substantial within several months. Yet further, the cream acts to
promote healing of superficial ulcers such as those sometimes found
on the legs of persons with severe diabetes. Application twice
daily for a period of two weeks causes substantial healing and in
many cases complete healing is achieved within this time period or
slightly longer (3-4 weeks). Still further, the cream acts to
overcome erectile dysfunction in males causing restoration of
natural sexual function. These applications and others share as a
common mechanism of action, improvement in local blood flow.
OTHER EMBODIMENTS
[0016] Other Active Agents
[0017] While L-arginine hydrochloride is the preferred active agent
because it is the agent in nature itself, it is non-toxic, is
highly soluble and it is inexpensive, other agents could be used
which are also precursors or donors of nitric oxide. These include
D,L-arginine, L-arginine, alkyl (ethyl, methyl, propyl, isopropyl,
butyl, isobutyl, t-butyl) esters of L-arginine and salts thereof.
Pharmaceutically acceptable salts include hydrochloride, glutamate,
butyrate, and glycolate.
[0018] In the case of an alternative active agent were used it
would be simply substituted for L-arginine in a delivery
preparation and the preparation used as in the case of the
L-arginine preparation.
[0019] Other Means of Effecting or Improving Absorption
[0020] A variety of means for effecting or improving absorption of
the active agent can be envisioned. One principle behind the
absorption of a highly charged molecule such as L-arginine into
tissue is to either create a biophysically hostile environment in
the delivery vehicle such that L-arginine would prefer to be in
tissue, or to package L-arginine in such a way that it is carried
into tissue or neutralize its charge by derivitization or forming a
neutral salt. Examples of biophysically hostile environments,
include but are not limited to; high ionic strength by the addition
of ionic salts such as sodium chloride, magnesium chloride or
choline chloride; high or low pH by adding pharmaceutically
acceptable acids or bases; and highly hydrophobic environments by
decreasing water content and increasing lipid, oil and/or wax
content. Examples of packaging which would be carried into tissue
includes liposomes or emulsions of collagen, collagen peptides or
other components of skin or basement membrane. Examples of
neutralization of charge include delivery of the active agent in
the form or an ester or salt such as arginine glutamate which is
electronically neutral.
[0021] In each case of creating a hostile biophysical environment
for the active agent, the agent was added to an appropriate
preparation. In the case of creating a high ionic strength ions
such as but not limited to sodium chloride, potassium chloride,
choline chloride, magnesium chloride, lithium chloride, alone or in
combination were added in high concentration. Other highly charged
molecules such as polylysine, polyglutamine, polyaspartate or
copolymers of such charged amino acids may be used to create the
hostile biophysical environment. Alternatively a hostile
biophysical environment may be created by placing the highly
charged L-arginine in an hydrophobic, oily environment such as in
an oil-based cream containing little or no water. Absorption may
further be aided by combining the use of hostile biophysical
environments with the use of penetrating agents such as oleoresin
capsicum or its constituents or molecules containing heterocyclic
rings to which are attached hydrocarbon chains.
EXAMPLE 1
[0022] In this example a 53 year old man with a scalp lacking
sufficient hair consisting of a severely receding hairline as well
as large "bald spot" on the top rear of his head was provided with
a penetrating cream containing L-arginine hydrochloride (12.5%
w/v), choline chloride (10% w/v), sodium chloride (5% w/v) and
magnesium chloride (5% w/v). The cream was applied to the bald
areas each night before going to bed and was rubbed in extensively
for maximal absorption. New hair growth was noted within 2-3 weeks.
Within 4 months the receding hairline (previously 4 cm of bald
skin) had returned to normal and the "bald spot" previously more
than 7 cm in diameter had been reduced to an area of less than 2 cm
with even this area showing some new hair growth.
EXAMPLE 2
[0023] In a 54 year old man with a history of impotence twice daily
administration of a penetrating cream containing L-arginine
hydrochloride (12.5% w/v), choline chloride (10% w/v), sodium
chloride (10% w/v) and magnesium chloride (5% w/v) directly to the
penis twice daily for 7 days brought initial relief from the
symptoms of impotence and allowed the subject to resume normal
sexual activity. This relief of symptoms was maintained by
continuation of the treatment daily.
EXAMPLE 3
[0024] In a 62 year old man with a history of impotence placed a
condom containing a water based penetrating cream containing
L-arginine hydrochloride (12.5% w/v), choline chloride (10% w/v),
sodium chloride (5% w/v) and magnesium chloride (5% w/v) was worn
on the flaccid penis for 30-60 minutes before erection was desired.
At that time, when sexual performance was needed, an erection was
easily obtained and normal sexual activity was conducted.
[0025] Accordingly, it can be seen that in the present invention I
have provided agents, which when applied to scalp lacking
sufficient hair causes hair growth through utilization of one of
the body's own mechanisms. This effect is achieved by providing the
biochemical substrate at the local site from which nitric oxide is
produced. Nitric oxide causes increased local blood flow, which
enables the growth of hair. Further I have provided agents which
when applied to leg ulcers cause healing through use of the body's
own mechanisms. Still further I have provided agents that when
applied to a penis subject to erectile dysfunction causes
restoration of normal sexual function. This effect is achieved by
providing the biochemical substrate at the local site from which
the controlling substance, nitric oxide is produced. Nitric oxide
causes increases in local blood flow allowing the body's own
healing cells and substances to reach the ulcer site.
[0026] Although the description above contains many specificities,
these should not be construed as limiting the scope of the
invention but as merely providing illustrations of some of the
presently preferred embodiments of this invention. Various other
embodiments and ramifications are possible within this scope.
[0027] Thus the scope of the invention should be determined by the
appended claims and their legal equivalents, rather than by the
examples given.
* * * * *