CA2588119A1 - Composition and method for facilitating the healing of non-healing and slow-healing wounds and ulcerations - Google Patents

Abstract

A composition for treatment of non-healing and slow-healing wounds and ulcerations, and for treating and preventing peripheral neuropathy. The composition is primarily characterized by a combination of nitroglycerin, arginine and curcumin. Preferred embodiments comprise emollient cream, mineral oil, and zinc oxide.

Description

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 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 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 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 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 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 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-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 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 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-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.

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 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 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 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 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 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);

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;

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, 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 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 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 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 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 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 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).

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 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

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 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.

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.

Claims (8)

1. A topical, medicinal composition comprising:
nitroglycerin; and arginine.

2. A topical, medicinal composition comprising:
nitroglycerin;

arginine; and curcumin.

3. A topical viscous medicament for topical application to wounds and ulcerations comprising:

nitroglycerin;
arginine; and curcumin;

said nitroglycerin, arginine; and said curcumin being suspended in a viscous carrier medium.

4. The medicament of Claim 3 wherein said nitroglycerin, arginine; and curcumin are present in approximately ten parts nitroglycerin, approximately ten parts arginine, and approximately 1 part curcumin.

5. The composition of claim 3 wherein said viscous carrier medium comprises an emollient cream and a zinc-containing ingredient.

6. The composition of claim 3 wherein said viscous carrier medium comprises an emollient cream and a quantum of mineral oil.

7. A topical medicament for treatment of wounds and ulcerations comprising:

Nitroglycerin (Nitrobid) 2% ointment;
Arginine (L) HCL Powder;

an emollient cream base;

a first measure of an oil;
curcumin powder;

a first measure of aloe vera approximately; and a zinc-based compound.

8. A topical medicament for treatment of wounds and ulcerations comprising:

Nitroglycerin (Nitrobid) 2% ointment, approximately 20 parts by weight;

Arginine (L) HCL Powder, approximately 20 parts by weight;

an emollient cream base;

a first measure of an oil;

curcumin powder, approximately 2 part by weight;

a first measure of aloe vera approximately 1 part by weight; and a zinc-based compound, approximately 2 part by weight.