Note: Descriptions are shown in the official language in which they were submitted.
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APPLICATION UNDER THE PATENT
COOPERATION TREATY
TITLE: COMPOSITION AND METHOD FOR FACILITATING
THE HEALING OF NON-HEALING AND SLOW-
HEALING WOUNDS AND ULCERATIONS
CITATION TO PRIOR APPLICATION
This is a CONTINUATION-IN-PART with respect to U.S.
Application, Serial No. 10/992,636, filed 17 NOVEMBER
2004 (17.11. 2004) and of U.S. Application Serial No.
10/992,623, filed 17 November 2004 (17.11.2004) from both
of which priority is claimed under 35 U.S.C. 120 and
under provisions of the Paris Convention and of the
Patent Cooperation Treaty.
BACKGF2.OUND OF THE INVENTION
1. Field of the Invention
The present invention generally relates to an
improved composition for treatment of a skin condition.
More specifically, the present invention relates to an
improved composition for treatment for common types of
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skin ulcers, including diabetic, stasis, and decubitus
ulcers.
2. . Background Information
Wound healing is a highly complex process, involving
multiple, co-ordinated interactions of multiple factors
and agents. Poor wound healing in diabetics, patients on
dialysis, elderly in nursing homes, paralyzed/confined
patients in wheel chairs, and patients on hospice is
believed to relate to circulatory impairment and its
sequlae.
Extensive research leads the present inventors to
believe that the most vital elements for successful wound
healing are:
1. Nitric Oxide;
2. Endothelial nitric oxide synthase (eNOS/iNOS)
(enzyme to make NO from arginine which is in sufficient
amounts in properly functioning endothelium and not in
diabetic and other compromised patients);
3. L-arginine (arginine is needed in sufficient
amounts in local tissues to be acted on by eNOS to make
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NO and is.often deficient in diabetic and other
compromised populations);
4. Peptide growth factors (especially transforming
growth factor beta- TGF-beta);
5. A healthy blood supply (local and systemic);
6. Ability to form new blood supply (angiogenesis);
7. Elimination or absence of microbes causing
infection/excessive inflammation;
8. Sufficient macrophages;
9. Normal levels of homocysteine;
In highly compromised populations, such as
diabetics, dialysis patients, confined patients, and the
chronically ill and elderly, many of these essential
factors are missing, or are deleteriously defficient.
The present inventors believe that, when all the
above factors are in proper balance, de facto debridement
occurs, new cell island matrix flourish, pernicious
microbes are minimized, and the three stages of wound
healing (a healthy amount of inflammation, proliferation
and remodeling) occur efficiently and rapidly.
Various treatments for ulcer-type skin conditions
are known in the art, yet none addresses the totality of
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factors needed to adequately and successfully facilitate
healing of that which would be described clinically as
"non-healing" or "slow-healing" wounds and ulcerations.
Facts and statistics relating to non-healing and
slow-healing wounds and ulcerations, and their underlying
origins or propensities, are sobering.
Type II diabetes is one such factor, and is the most
common form of the disease, accounting for 90 to 95
percent of all diabetes cases.
Throughout the world, the incidence of Type II
diabetes is nearing epidemic proportions. Examination of
current and expected diabetic trends (and the detrimental
effects therefrom) is helpful for grasping the tremendous
need for the present invention.
By way of example, the Center for Disease Control
and Prevention ("CDC") reports an increase in the cases
of diagnosed adult diabetes of 49% between 1990 and 2000.
Further, the CDC estimates the diabetes, both diagnosed
and undiagnosed, affects approximately seventeen million
Americans (or some 6.2% of the U.S. population).
Diabetes is a prevalent disease and an ever-growing
domestic and international public health concern. The
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World Health organization estimates that approximately
150 million people are affected by diabetes; and, these
numbers are expected to only get worse (estimated 215
million people affected by 2010; estimated 300 million
5 people affected by 2025). Worldwide, diabetes has a
relatively high mortality rate. Diabetes is reportedly
among the top five causes of death by disease in most
countries, though this may be a conservative ranking.
More likely, diabetes is even more deadly as it is
frequently under-reported on death certificates.
Importantly for present purposes - the occurrence of
diabetes and skin ulcers and non-healing wounds and
ulcerations is directly related. Accordingly, the sharp
increase in the number of diabetes cases has led to an
increase in the number of people affected by non-healing
and slow-healing wounds and ulcerations.
By way of example, diabetics have a fifteen percent
chance of developing a foot ulcer during their lifetime.
Of those diabetics that develop foot ulcers,
approximately twenty percent will require amputation.
(International J of Pharm Compounding 8(4) July/August
2004, 269). Such amputations are also increasing at an
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alarming rate. Between 1990 and 2000, the number of
amputations resulting from foot ulcers increased by
twenty six percent. This trend is expected not only to
continue, but to worsen in the coming years. Foot ulcers
cause approximately eighty five percent of all diabetic
amputation of the lower extremities (Emergency Medicine
36(8) Au 2004, 14-23). The number of such lower
extremity amputations (LEA's) now exceeds 100,000 per
year!
Recurring foot ulcers, and the amputations that may
result, present a continuing problem on a national and
global scale. In the event that an ulcer is successfully
treated, it is more likely than not that the ulcer will
reoccur. Recurrence rates associated with diabetic foot
ulcers and resulting LEA's are commonly as high as fifty
percent to seventy percent over a period of three to five
years.
Those skilled in the art of wound treatment realize
that the accepted standard of care is simply not working.
Current medications and modes of treatment all too
commonly fail to heal wounds and ulcers in compromised
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patients, and thereby fail to prevent such complications
as infection and gangrene.
Overall, fifty to eighty percent of patients having
diabetic foot ulcers will heal within six months-
assuming optimal management from a multi-disciplinary
team. (Emergency Medicine 36(8) August, 2004, 14-23).
However, all too common complications require
hospitalization, painful and expensive surgery, and a
prolonged rehabilitation regimen (if rehabilitation is
possible at all). With the incidence of ulcer recurrence
as high as seventy percent, the healing of one ulcer is
often rapidly followed by the development of a new one.
In view of the serious, and often unconquerable
consequences of diabetic ulcers alone, and in further
view of the need to address non-healing and slow-healing
wounds and ulcerations in other compromised patient
populations, a great need exists for an improved
treatment for non-healing and slow-healing wounds and
ulcertations. There is more, however.
Another collateral, or even related condition which
afflicts many in the same patient populations as those
discussed above with respect to non-healing and slow-
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healing wounds and ulcerations is that of peripheral
neuropathy. Many of the same conditions and
circumstances that contribute to non-healing and slow-
healing wounds and ulcerations also contribute to, cause,
or exacerbate peripheral neuropathy.
Known treatment regimens rely heavily on the use of
debridement and washing (clearly involved in the present
standard of care). In fact, with only conventional wound
treatment regimens available, such steps are necessary,
though debridement and washing typically results in
scarring, non-closure of the wound, and/or recurrence.
In summary, the present state of would care is
woefully deficient, and leaves many patients with'
unending pain, loss of extremities, general disability,
and even death.
SUMMARY OF THE INVENTION
In view of the above, the general purpose of the
present invention, which will be described subsequently
in greater detail, is to provide a uniquely efficacious
composition and associated method for the treatment of
non-healing and slow-healing wounds and ulcerations, as
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well as peripheral neuropathy, which composition and
method are neither anticipated, rendered obvious,
suggested, nor even implied by any of the known
compositions or methods of treatment, either alone or in
any combination thereof.
Therefore, it is an object of the present invention
to provide a composition for treatment of non-healing and
slow-healing wounds and ulcerations.
It is another object of the present invention to
provide a composition and method for treating (or
preventing) peripheral neuropathy.
it is another object of the present invention to
provide a compound and associated method of use thereof
in the treatment of wounds and ulcerations, which
composition and use thereof.obviates the need for
debridement in wound and ulcer treatment.
It is another object of the present invention to
provide a method for treatment of wounds and ulcerations,
with particular efficacy for previously non-healing and
slow-healing wounds and ulcerations.
It is another object of the present invention to
provide a composition and associated method for treatment
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of non-healing and slow-healing wounds and ulcerations,
at least in part, by effecting to an unprecedented level,
improvement of circulation at the wound site and
associated healing in otherwise non-responsive patients.
5 It is another object of the present invention to
provide an improved composition for treatment of non-
healing and slow-healing wounds and ulcerations that
effects a high degree of pernicious microbe eradication,
without requiring debridement or other pre-medication
10 would or ulcer manipulation or alteration.
It is another object of the present invention to
provide an improved composition for treatment for non-
healing and slow-healing wounds and ulcerations that
facilitates peripheral nerve growth and regeneration.
It is yet another object of the present invention to
provide an improved composition for treatment for non-
healing and slow-healing wounds and ulcerations that
effects and utilizes synergistic action of Arginine,
Nitroglycerin and Curcumin.
In satisfaction of these and other related objects,
the present invention provides a composition and
associated treatment method for the treatment of non-
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healing and slow-healing wounds and ulcerations, as well
as the remediation or prevention of peripheral neuropathy
associated with impaired circulation. The present
invention, by way of a novel composition and associated
methods of applying that composition, yields results that
simply are not possible with any other known treatments.
The composition of the present invention comprises,
principally as active ingredients, nitroglycerin,
arginine, and curcumin which have been found by the
present inventors to work synergistically to increase the
absorption and distribution of each other, as well as to
effect an unprecedented therapeutic result. In addition,
however, other ingredients (such as the recited zinc and
aloe vera constituents) are instrumental in maintaining
the medicament on-site for treatment of wounds and
ulcerations, such that the optimal therapeutic result is
achieved.
A few practical examples, experienced first hand by
the present inventors, will reveal the unique benefits of
the present invention:
Patient B has had diabetes. for several years, the
last two of which he has been confined to a wheel chair.
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During this past year Patient B has been hospitalized for
non-healing pressure ulcers on his buttock region. Every
developed ulcer has caused a tremendous amount of pain an
suffering. Also, these ulcers have necessitated surgery
and costly medical bills. Complication of these ulcers
extended to the pelvic bone, which required removal of a
portion of the bone. The present composition was applied
to the wound one time per day for a period of three days.
By the third day of treatment the wound had decreased in
size by approximately twenty five percent. Also, the
wound was radically improved, where approximately thirty
percent of the wound had been covered with new white
granular tissue with obvious healing occurring throughout
the entire ulcer. During the next three days, the
composition was applied twice daily. After a total of
six days of treatment, the original wound was virtually
covered with new tissue growth.
Before application of the present composition,
Patient F had lost one finger tip to an ulcer and poor
circulation. Her entire hand was rigid and swollen.
Before treatment, several of Patient F's fingers were at
risk of amputation. After a week of application of the
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present composition, her hand was soft and mobile, had
better circulation, less pain, and a reduction of dark
areas marked by poor blood flow. A single lesion had
been open to the bone; however, after three days of
treatment the lesion went from oozing blood and pus to
being completely closed. According to standard treatment
protocols, Patient F's lesion would have been reopened
for further drainage. However, the present regimens
avoids such a necessity.
Patient F has an open scalp lesion of approximately
two centimeters in length. After three days of treatment
(where the patient continued to wash the wound against
Applicant's advise), the lesion had decreased by seventy
percent. From the fourth to sixth day, the patient did
not wash the wound. By the night of the forth day the
lesion has completely closed, By day six, the patient
reported a fifty percent reduction in pain such that she
could rest her head upon a pillow to sleep.
Patient G had a developing lesion between her
buttocks, which appeared to have a monilial infection.
Applicant fear the overlying yeast infection would block
entry of the present composition. After two days of
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treatment, the lesion had improved by some fifty percent.
After a week of treatment, the lesion had completely
healed and the patient reported a tremendous decrease in
pain and overall discomfort.
In its preferred form (as presently believed, though
variations in relative constituency will fall well within
the scope of the present invention), the present
composition comprises: nitroglycerin (Nitrobid) 2%
ointment, an emollient cream base (PCCA emollient cream
formulation), mineral oil (light 65-75 VIS liquid),
Curcumin Powder 95% (or a curcumin-containing ingredient,
such as a measure of tumeric sufficient to provide the
desired measure of curcumin, or even a synthetic
curcumin), Aloe Vera (freeze dried 200:1 powder), Zinc
Oxide USP, and Arginine (L) USP (HCL powder). This
composition is formed as the triturate powders and wet
powders are combined with the mineral oil and then
thoroughly mixed with emollient cream, QS'ed to the
desired volume.
Associated application of the present composition
are generally characterized by the topical application.
However, application by injection of the aforementioned
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composition may be appropriate under certain
circumstances. When injected, the medication is
typically delivered by syringe in amount depending on the
size and depth of the particular lesion. Generally,
5 syringes between 3~ CC and 2CC are sufficient.
The treatment protocol essentially involves leaving
the wound alone to heal on its own. That is, the wound
is not to be interfered with and use of anti-bacterial or
anti-microbial soaps is to be avoided. Debridement and
10 washing of the wound are to be avoided (such has been
discovered to promote scarring, non closure, and
recurrence of the ulcer). After application of the
composition (usually b.i.d.), the wound is typically
covered with a tefla pad (or some equivalent) and
15 breathable tape. This allows the wound to remain fairly
dry (substantially free of any undue moisture) and open
to the surrounding air.
While the characteristics unique to this treatment
protocol may at some point, at first appear to be subtle
distinctions vis a vis existing prior art, these
distinctions self-evidently yield a regimen that is
different from any such known in the art and produces
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unexpected (and previously unachievable) results. For
instance, the present method increases blood flow to
nerves thereby increasing nerve growth. This expedites
the growth of new island cells and allows skin to take
root and grow. This appears to be a primary reason for
the improved results not seen in any of the known
treatment regimen for wound, ulcer or neutopathy
consitions.
Further, Applicant has devised a compound that
creates effective vasodilation of the underlying-
capillary bed in patients with compromised vascular
function The present invention eliminates the need for
debridement while acting as an agent or substantially
eradicating pernicious microbes.
While the synergistic action of the three primary
constituents are likely not fully understood or explained
at this time, the individual actions of the
nitroglycerine, arginine and curcumin, and some aspects
of their complimentary actions have been revealed, at
least in part, through the present inventors' research
and experimentation,
Nitroglycerine
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Nitroglycerin is a nitrate that has been approved by
the FDA since 1938 to dilate blood vessels. It is
frequently used in the management of angina pectoris. It
was first synthesized in 1846 and first used in cardiac
therapeutics by physicians since 1879.
Nitroglycerin is a nitric oxide (NO) donor. NO is a
small radical that is pivotal for wound healing. Nitrates
preferentially dilate blood vessels that are compromised.
Nitroglycerin acts by donating nitric oxide, which
relaxes the walls of blood vessels, especially large
microvessels.
Non healing wounds especially in diabetic and
dialysis patients are notoriously deficient in nitric
oxide, as well as the specific enzymes that are involved
in nitric oxide local production and in the substrate
needed to make NO (the amino acid L-arginine).
Why is NO essential to enhance healing at the wound
site?
1. NO improves angiogenesis (Angiogenesis is the
process by which new blood vessels form by sprouting from
pre-existing vessels);
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2. NO improves inflammation (healthy inflammation is
stage one of wound healing, but then it must be
contained. NO does not allow it to intensify);
3. NO promotes cell proliferation;
4. NO enhances matrix deposition;
5. NO helps speeds up remodeling;
6. NO promotes re-eptithlialization (Journal of
Investigative Dermatology 1999 Dec;113(6):1090-8) which
enhances closure of the wound.
7. NO decrease viscosity by inhibiting platelet
aggregation (diabetics and dialysis patients, and often
ill and elderly, have excessive clotting of platelets
which reduces circulation and healing) (Biological
Pharmacology Bulletin 2003 Aug;26(8):1135-43); and
8. Nitrates enhance circulation by increasing red
blood cell (erythrocyte) deformability. (International
Journal of Clinical Pharmacologic Therapeutics 1998
Jul; 36 (7) :398-402 . )
Therefore, nitroglycerin:
1. Enhances arterial and venous vasodilation/
circulation in large microvessels by donating NO;
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2. Enhances erythrocyte deformability (enhances
local circulation);
3. Decreases blood viscosity (improving local
circulation); and
4. Improves tissue-oxygen tension (tcp02) (improving
circulation and distribution of vital factors to all
cells).
In the past, a problem with the use of nitroglycerin
is that of headaches occurring in a significant number of
patients. Among its many other positive attributes, the
present composition, though utilizing nitroglycerin,
produces no reported problems with headaches. The
present inventors believe that this somehow relates to
the presence of curcumin in the composition.
Another feature of nitroglycerine, as revealed
through prior investigations for use in wound care,
relates to the rapidity of its physiological reactions
and ultimate dissipation. This characteristic has greatly
limited nitroglycerine's efficacy, when used alone, in
wound care, because, to put it plainly, it did not stick
around long enough to effect significant would healing.
Further still, prior attempts to use nitroglycerin alone,
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or in other combinations, revealed some patients'
tendency to develop tolerance for the drug, with reduced
efficacious results (such as were, to a limited degree,
achieved in the first instance).
5 The combination of L-arginine and curcumin with
nitroglycerine, as later detailed, provides a therapeutic
compound which is more long acting, overcomes the
tolerance issue, and also eliminates the headache side
effects.
10 Curcumin
Curcumin (diferuloylmethane), is a natural product
and the most active isolated substance obtained from the
plant Curcuma longa (tumeric). Curcumin promotes wound
healing by a number of mechanisms.
15 Curcumin significantly accelerates wound healing as
it enhances 'expression of TGF-betal and TGF-beta tllrc,
both in normal and impaired healing wounds as
demonstrated by immunohistochemistry (Biofactors
2002;16(1-2) :29-43) .
20 Curcumin increases eNos/iNQS within a wound.
As discussed above, NO is a vital factor in wound healing
and its production is regulated by inducible nitric oxide
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synthetase (iNOS) or also called endothelial NO (eNOS)
During cutaneous wound repair, iNOS is induced in large
quantities, in a normal non compromised patient.
Decreased circulation, poor nutrition, deficient local
enzymes, excess sugar within cells, insufficient arginine
levels, all decrease the inducibility of iNOS. The
presence of a functionally active iNOS is a crucial
prerequisite for normal wound reeptithelialization (J
Investigative Dermatology 1999 Dec;113(6):1090-8)
Curcumin enhances macrophage production (white
blood cells that function to engulfs and kill foreign
pathogens and microbes)
Curcumin augments vasodilation (Biological
Pharmaceutical Bulletin 2003 Aug;26(8):1135-43).
Curcumin demonstrates anti-inflammatory action
against mediators of inflammation (Phytomedicine 2005
Jun;12(6-7):445-52. Purified curcumin (More than other
curcuminoids in tumeric: demethoxy- or
bisdemethoxycurcumin) was found to reduce inflammatory
mediators in vitro study.
In experimental animals curcumin has been shown to
be anti-diabetic, anti-inflammatory, cytotoxic and have
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anitoxidant properties (Medical Science Monitor 2005
Jul"11(7):BR228-234).
Curcumin helps fight off pathogens acting as a
natural antibiotic.
Curcumin has been found to be effective against
bacteria, viruses and fungi.
Curcumin reduced mediators of inflammation from
Neisseria gonorrhoeae-induced NF-kappaB signaling.
Curcumin abolished the adherence of bacteria to cells in
infection, emphasizing the high potential of curcumin as
an anti-microbial compound without cytotoxic side effects
(Biological Chemistry 2005 May;386(5):481-90).
Curcumin has antimicrobial action (Journal of
Ethnopharmacology 2005 May 13;99(1):147-51 (Letters of
Applied Microbiology 2004;39(5):401-6).
Curcumin has antifungal properties - 100% phytotoxic
against Lemma minor, Fitoterapia 2005 Mar;76(2):254-7.
Curcumin is anti-inflammatory, antioxidant,
anticarcinogenic, antiviral and antiinfectious activities
(Critical Reviews for Food Science and Nutrition
2004;44 (2) :97-111) .
Curcumin shows antibacterial, anti-inflammatory, and
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antineoplastic activity (J Pharmacologic Pharmacology
2000 May:55(5):593-601. Study assessed curcumin in vitro,
and with skin absorption of Wistar rats.
Curcumin enhances angiogenesis (Journal of
Physiologic Pharmacology 2005 Mar;56 Suppl 1:51-69.
Angiogenesis is a prerequisiste for wound healing.
Curcumin is frequently studied for it's role in enhancing
angiogenesis).
Curcumin has been shown in many animal studies to
accelerate the repair of excision wounds in mice whole
body exposed to various doses of gamma radiation (Journal
of Surgical Research 2004 Jul;120(1):127-38.
Radiation disrupts normal response to injury and
inhibits normal wound healing and increasing the time of
healing. Rats pretreated with curcumin and then exposed
to radiation, enhanced wound contraction, decreased
healing time, increased synthesis of collagen,
hexosamine, DNA, and NO, and improved fibroblast and
vascular densities. (Surgical Research 2004
Jul;120(1):127-38)/
Topical curcumin enhances cutaneous wound healing in
rats and guinea pigs. Curcumin was effective both orally
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and topically in diabetic rats and mice. (Wound Repair
Regeneration 1998 Mar-Apr'6(2):167-77.
Wounds of animals-treated with curcumin showed
earlier re-epithelialization, improved
hneovascularization, increased mmigratioh of various
cells including dermal myodfibroblasts, fibroblasts, and
macrophages into the wound bed, higher collagen content,
and increase in transforming growth factor-betal
confirmed by in situ hybridization and laser scan
cytometry.
Transforming growth factor-betal enhances wound
healing and curcumin increases the mRNA transcripts for
this growth factor, demonstrating that it enhances the
bodies own production of this growth factor, in a natural
manner, which may be one mechanism of enhanced wound
healing by curcumin (Wound Repair and Regeneration 1998
Mar-Apr; 6 (2) :167-77) .
With respect to safety, curcumin has been used in
Phase 1 clinical trials. There was no treatment-related
toxicity up to 8,000 mg/day and beyond that the only real
problem being the bulky volume was unacceptable to the
patients. This was taken orally, and our new drug is via
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the skin, which reduces systemic exposure significantly.
(Anticancer Research 2001 Jul-Aug;21(4B):2895-900)
With respect to the contribution of Arginine to the
efficacy of the present composition, NO is generated in
5 the local endothelium through the oxidation of the amino
acid L-arginine. This occurs due to the-action of the
enzyme eNOS/iNOS.
NO casues vascular smooth muscle to relax causing
vasodilation. In addition to being the substrate for
10 eNOS, L-arginie facilitates the dimerization of two
identical subunits (Diabetes Care. 2004
Jan;27(1):284-5), forming a homodimer. The enzyme is only
active in the dimeric form. Under proper conditions,
dimerization occurs rapidly, on a timescale of minutes.
15 Once formed, the dimmer is stable (Journal of Biological
Chemistry 2002 277:310200-31010)
Arginine
Arginine is a substrate to make NO, a particular
benefit in use for diabetic and dialysis patients, both
20 who have impaired wound healing, in part, because of a
reduction in nitric oxide at wound sites, as is a
characteristic of their conditions. The amino acid
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L-arginine is the only substrate for nitric oxide
synthesis.
Treatment in diabetically rendered mice with
L-arginine injections significantly increased wound fluid
nitrite/nitrate levels. The data demonstrated that the
impaired wound healing of diabetic rats can be partially
corrected by L-arginine supplementation, and that this
effect is accompanied by enhance wound nitric oxide
synthesis. Wound Repair Regeneration 2003
May-Jun;11(3):198-203).
NO is a small radical, formed-directly from the
amin I o acid L-arginine by three distinct isoforms of the
enzyme nitric oxide synthase. The inducible isoform
(iNOS) is synthesized in the early phase of wound healing
by inflammatory cells, mainly macrophages. Curcumin
enhances this production.
During the next proliferative phase, many cells
participate in NO synthesis.
NO released through iNOS regulates collagen
formation, cell proliferation (new growth of cells to
fill in the wound), and wound contraction (for the wound
to start growing smaller in the healing process).
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Arginine together with NO and curcumin administration
promotes these aspects of wound healing.
Arginine regulates dimerization locally, and
enhances wound strength and collagen deposition in
rodents and humans (Wound Repair Regeneration 2003
May-Jun; 11 (3) :198-203)
Synergy between Arginine and Nitroglycerin
Arginine dilates small microvessels. The present
inventors believe that L-arginine and nitroglycerin
compliment each other, in part, because nitroglycerine
rapidly dilates relatively larger vessels than optimally
does arginine, whereas arginine tends to reside longer at
the wound site (or any other tissue site of
administration). Thus, nitroglycerine "opens the door"
for arginine to get where it needs to be to effect wound
healing, after which, though the nitroglycerine (and its
effects) have passed, the arginine remains to effect
wound healing.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
In the preferred embodiment of the present
medicament, and in the medicament upon which an
associated method of treatment is based, the primary
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active ingredients are Nitroglycerin, Arginine, and
Curcumin. In this preferred embodiment, the
Nitroglycerin is in the form of two percent ointment
(NITROBID); the arginine is in the form of Arginine (L)
USP, and the Curcumin is in 95% powder form.
The preferred nitroglycerin-arginine-curcumin-based
compositions of the present invention may be prepared
according to the following disclosure and protocol, with
variations appropriate to a desired scale or production
as will be apparent to person skilled in the production
of pharmaceutical preparations:
A. Constituents of Preferred Embodiment of
Composition for remediation of dermal anomalies
Ingredients Quantity
Nitroglycerin (Nitrobid) 2% ointment 10 GM
Arginine (L) HCL Powder 10 GM
PCCA Emollient cream base 100 GM
Mineral Oil, Light 65-75 VIS liquid 8.33 ML
Curcumin 95% Powder .07 GM
Aloe Vera freeze dried 200:1 powder .2 GM
Zinc Oxide USP 1 GM
Total: 124.5 GM
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29
B. General Mixing Procedure of Preferred
Embodiment of the Composition of the present invention:
1. Triturate powders and wet powders with mineral
oil and mix thoroughly with emollient cream.
2. Q.S. to desired volume.
The formed composition may then be applied topically
to any wound or ulceration (without debridement or
washing), usually b.i.d. A treatment period between
three and ten days is thought to be sufficient to heal
the large majority of treated wounds. Extremely specific
dosage is not now believed to be critical, and a "general
coverage" of the wound site, generally such as one would
apply a sun screen or other lotion, will produce the
therapeutic result.
As with any multi-constituent composition, the
recited, relative measures of constituent ingredients may
be varied to some degree, without noticeably affecting
the therapeutic effect of the present composition.
For example, the present .2% Nitroglycerin
formulation described above (2mg per gram of medicament)
is believed optimal, but.lmg per gram to 50mg per gram is
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believed still safe (non-toxic) and efficacious, and,
even if not optimal, still within the scope of the
present invention, when used in combination witharginine
and curcumin.
5 Likewise, the present formulation of arginine (0.1%
or 100mg per gram at 10%) is believed variable between
lmg per gram up to 1000mg per gram, with retained safety
and efficacy. Curcumin is presently shown at an.08o
strength (.8mg per gram), and a range of .1 mg per gram
10 up to 50 mg per gram of medicament is believe efficacious
and safe (and clearly within the scope of the present
invention if efficaciously used as described, with the
other active ingredients)..
Furthermore, no evidence presently available would
15 indicate that variations of relative constituency would
defeat efficacy or safety. For example, even a 1:2 ratio
(in either direction) of nitroglycerine and arginine
would not, it is presently believed, defeat the essential
therapeutic effects of the present composition, though
20 the recited formulation appears to be roughly a center
point of the efficacious mixture.
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31
Therefore, although the invention has been described
with reference to specific embodiments, this description
is not meant to be construed in a limited sense. Various
modifications of the disclosed embodiments, as well as
alternative embodiments of the inventions will become
apparent to persons skilled in the art upon the reference
to the description of the invention. It is, therefore,
contemplated that the appended claims will cover such
modifications that fall within the scope of the
invention.
