Combination Of A Novel Topical Gel And Oral Supplements For Healing Diabetic Foot And Other Wounds

Abstract

Disclosed are topical wound healing compositions useful in the holistic treatment of a patient's wound, particularly diabetic wounds of the foot. Methods of using these formulations topically and in coordinated use with certain oral supplements to improve treatment is also disclosed. In particular, formulations may include one or more of: water, Aloe Barbadensis leaf juice, micro silver, L-Arginine, locust bean gum, and Manuka honey. The topical formulations may be in the form of a gel.

Claims

1. A wound healing composition comprising of: Water in an amount of about 60-90%; micro silver in an amount of about 0.1% to about 5%, L-arginine HCl in an amount of about 1.0% to about 20%, glycerol in an amount of 1% to 10%, a gum in an amount of about 0.5% to about 5.0%, all by weight, in a hydrogel.

2. The composition of claim 1, further comprising Manuka honey in an amount of about 1% to about 50%.

3. A wound healing composition comprising of: Aloe barbadensis leaf juice 10% to-90%; micro silver in an amount of about 0.1% to about 5%, L-arginine HCl in an amount of about 1.0% to about 20%, glycerol in an amount of 1% to 10%, a gum in an amount of about 0.5% to about 5.0% all by weight, in a hydrogel.

4. The composition of claim 3, further comprising Manuka honey in an amount of about 1% to about 50%.

5. A wound healing gel composition consisting essentially of: aloe barbadensis leaf juice in an amount of about 10% to about 90%, allantoin in an amount of about 0.01% to about 1.0%, micro silver in an amount of about 0.1% to about 5%, L-arginine HCl in an amount of about 1.0% to about 20%, and at least one of Manuka honey of least 20 UFM+ in an amount of about 1% to about 50%, or locust bean gum in an amount of about 0.5% to about 5.0%, all by weight, in a hydrogel.

6. The composition of claim 5, including both said Manuka honey and said locust bean gum.

7. The composition of claim 6, further comprising: niacinamide (vitamin B3) present in an amount of about 1% to about 15% by weight.

8. The composition of claim 6, further comprising: provitamin B5 present in an amount of about 1% to about 15% by weight.

9. The composition of claim 6, further comprising: at least one zinc oxide or salt present in an amount of about 0.1 to about 20% by weight.

10. The composition of claim 6, further comprising: at least one magnesium oxide or salt present in an amount of about 0.1 to about 20% by weight.

11. The composition of claim 6, further comprising: hyaluronic acid present in an amount of about 0.01 to about 3% by weight.

12. The composition of claim 11, wherein the hyaluronic acid is super low molecular weight hyaluronic acid.

13. A topical wound healing composition comprising: aloe barbadensis leaf juice in an amount of about 50% to about 80%, allantoin in an amount of about 0.1% to about 0.5%, micro silver in an amount of about 0.2% to about 1%, L-arginine HCl in an amount of about 5.0% to about 10%, and either Manuka honey of least UMF20+ in an amount of about 5% to about 15%, or locust bean gum in an amount of about 2.0% to about 5.0%, or both, up to about 10% of a gel former, up to 5% of a thickener, up to about 10% of solvent, up to about 20.0% of an antioxidant, all by weight,

14. The composition of claim 13, wherein the gel former is carboxymethyl cellulose, the thickener is xanthan gum or bentonite clay, the solvent is glycerol and the antioxidant is ascorbic acid, citric acid or tocopherol.

15. The composition of claim 13, further comprising: hyaluronic acid present in an amount of about 0.1 to about 3% by weight.

16. The composition of claim 15, wherein the hyaluronic acid is super low molecular weight hyaluronic acid.

17. The composition of claim 13, further comprising: zinc oxide or a salt thereof present in an amount of about 0.1 to about 20% by weight.

18. The composition of claim 13, further comprising: magnesium oxide or a salt thereof present in an amount of about 0.1 to about 20% by weight.

19. The composition of claim 15, further comprising: niacinamide (vitamin B3) present in an amount of about 1% to about 15%, provitamin B5 present in an amount of about 1% to about 15%, zinc oxide or a salt thereof present in an amount of about 0.1% to about 20%, and magnesium oxide or a salt thereof present in an amount of about 0.1% to about 20%, all by weight.

20. A kit comprising: a topical wound healing composition comprising: aloe barbadensis leaf juice in an amount of about 50% to about 80%, allantoin in an amount of about 0.1% to about 0.5%, micro silver in an amount of about 0.2% to about 1%, L-arginine HCl in an amount of about 5.0% to about 10%, and either Manuka honey of least UMF20+ in an amount of about 5% to about 20%, or locust bean gum in an amount of about 2.0% to about 5.0%, or both, up to about 10% of a cellulose, up to 5% of a thickener, up to about 10% of solvent, up to about 20.0% of an antioxidant, all by weight, and an oral daily dose comprising at least one of L-arginine in an amount of about 1-30 g, Turmeric in an amount of about 1-10 g and piperine in an amount of about 1-50 mg.

21. The kit of claim 20, wherein the topical composition further comprises: hyaluronic acid present in an amount of about 0.1% to about 3%, niacinamide (vitamin B3) present in an amount of about 1% to about 15%, provitamin B5 present in an amount of about 1% to about 15%, at least one of zinc oxide or a salt thereof or magnesium oxide or a salt thereof present in an amount of about 0.1% to about 20%, all by weight.

22. The kit of claim 20, wherein the oral daily dose form is one or more tablets or capsules.

23. A method of treating a wound comprising the steps of applying to a wound of a patient a topical wound healing gel composition comprising: aloe barbadensis leaf juice in an amount of about 50% to about 80%, allantoin in an amount of about 0.1% to about 0.5%, micro silver in an amount of about 0.2% to about 1%, L-arginine HCl in an amount of about 5.0% to about 10%, and either Manuka honey of least UMF20+ in an amount of about 5% to about 15%, or locust bean gum in an amount of up to 10%, or both, up to about 10% of a gel former, up to 5% of a thickener, up to about 10% of solvent, up to about 20% of an antioxidant, all by weight, and orally administering to the patient a daily dose including at least one of L-arginine in an amount of about 1-30 g, Turmeric in an amount of about 1-10 g and piperine in an amount of about 1-50 g, and wherein said topical wound healing gel composition is administered topically once a day and the oral dose is divided into 2-4 daily doses.

Description

DETAILED DESCRIPTION

[0020] A list of wound healing ingredients is provided in the tables below. The present invention is not limited to the compositions described in these tables, but encompasses any and all the embodiments within the scope of this disclosure. Table 1 includes the primary active ingredients used in the wound healing formulations of the invention. Other active ingredients may be added in addition to one or more of the active ingredients of Table 1. Table 2 includes additional ingredients or excipients, which, in this instance, are exemplary gel forming materials.

TABLE-US-00001 TABLE 1 Wound Healing Active Ingredients General Specific More Preferable Formulation Formulations Formulation Ingredient % by weight % by weight % by weight Aloe Barbadensis 10.0-90.0 20.0-85.0 50.0-80.0 Leaf Juice Locust Bean Gum 0-5.0 0.5-5.0 1.0-4.0 Allantoin 0.01-1.0 0.05-0.8 0.1-0.5 Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 Manuka Honey 1.0-50.0 1.0-25 5.0-20.0 Zinc oxide 0.0-20.0 0.1-10.0 0.5-5.0 Magnesium 0.0-20.0 0.1-10.0 0.5-5.0 Oxide Super low 0.0-10.0 0.1-8.0 0.2-5.0 molecular weight hyaluronic acid (SLMW HA) L-Arginine-HCl 1.0-20.0 2.0-15.0 5.0-10.0 Hyaluronic Acid 0.0-3.0 0.01-2.0 0.2-2.0 Niacinamide 0.0-20.0 1.0-15.0 1.0-10.0 (Vitamin B3) Provitamin B5 0.0-20.0 1.0-15.0 1.0-10.0 Beta Glucan 0.0-10.0 0.1-8.0 0.5-5.0 Citric Acid 0.0-20.0 0.01-10.0 0.2-5.0

[0021] One formulation of the present invention includes at least some amount of aloe barbadensis leaf juice, allantoin, Manuka honey, L-arginine-HCl and Micro Silver, without synthetic preservatives. These active ingredients are not believed to have been used together and it was not appreciated that this particular combination provides benefits in terms of wound healing that could not have been expected. It has been discovered that by combining these specific ingredients the wound healing potential has been significantly enhanced.

[0022] Because of the physical and chemical limitations of these ingredients, it can be difficult to combine these ingredients particularly to produce a wound healing hydrogel or other formulation like an occlusive ointment, and the art did not recognize the potential synergy of these ingredients when used for a topical wound healing formulation. A formulation strategy has therefore been developed that combines these wound healing agents in a topical formulation, and in particular, a hydrogel formulation. The resultant topical formulations provide rapid wound hydration, anti-microbial activity, and anti-inflammatory effect to the wound. Furthermore, the ingredients present in the formulation take advantage of the wound milieu present at the wound site. A freshly debrided wound has high concentration of iNOS. The L-arginine present in the formulation and the iNOS present in the freshly debrided wound react and produce non specific signal transduction agent nitric oxide (NO). NO being a non specific signal transduction agent, sends signals to brain and elicits increased blood flow to the wound site. Increased blood flow at the wound site is likely to increase the platelets and neutrophils and in turn, platelet derived growth factor secretion is likely to be enhanced at the wound site and this has potential to enhance wound healing. It is important to mention at this point that after wound debridement, as time passes, iNOS level at the wound site decreases and arginase level increases. The same wound healing agent L-arginine, present in the formulation, gets metabolized differently with the enzyme arginase. Arginase metabolizes L-arginine into urea and ornithine. Ornithine further gets metabolized into proline which is essential for collagen synthesis which in turn facilitates wound closer.

[0023] Aloe barbadensis leaf juice.sup.9 acts as a moisturizer and also as an anti-inflammatory agent. The high molecular weight carbohydrates present in the aloe act as immunomodulator. For better therapeutic outcome, it is essential to use aloe with higher concentration of high molecular weight carbohydrates.

[0024] Allantoin.sup.10 is a natural ingredient found in cow urine and some plants. It acts as a potent wound healing agent.

[0025] L-arginine.sup.15-19 is a conditionally essential amino acid. In healthy individuals body synthesizes needed L-arginine. However, in case of certain illnesses (demands for arginine increases and arginine supplementation plays a beneficial role. L-arginine plays a major role in wound healing. A freshly debrided wound contains high concentrations of the enzyme inducible N-oxide synthase (iNOS).sup.32 which metabolizes L-arginine to nitric oxide and citruline. Nitric oxide, a non-specific signal transduction agent, signals the brain to send platelets, neutrophils, and macrophages to the wound site to augment the wound healing process. After a few days the N-oxide synthase level decreases in the wound and the level of arginase increases. Arginase also requires L-arginine as a substrate and metabolizes it to urea and ornithine. Ornithine, which is subsequently converted to proline, participates in collagen synthesis, a major process in wound healing.

[0026] For a healing wound there is a persistent demand for L-arginine at the wound site.sup.33-34. Animal studies have shown decreased arginine levels in the wound fluid.sup.35-36 suggestive of a high local demand for arginine. Oral arginine taken alone may not be very effective in fulfilling the increased need for arginine at the wound site. Therefore, a topical formulation containing L-arginine, which will meet the local demand for increased L-arginine at the wound site, is highly desirable. As a consequence of the increased consumption of L-arginine by N-oxide synthase and arginase, the local L-arginine level at the wound site may decrease over time. This decrease may be effectively managed by reapplying the topical formulation according to an appropriate time schedule. But it is believed that using a formulation of the invention supplemented with oral L-arginine, and in particular, the use of oral supplementation with L-arginine with the use of such formulation that also includes L-arginine, can maximize wound healing.

[0027] Manuka Honey.sup.29-31 is a special honey variety which is produced by the bees in the Eastern New Zealand region feeding on Manuka bushes. Apart from traditional hydrogen peroxide present in all honeys, this honey also contains methylglyoxal (MGO) which imparts special antibacterial properties to this honey. It is very important to use only the Manuka honey which is certified to be Unique Manuka Factor Honey Association (UMFHA) as having a Unique Manuka Factor (UMF) of 16+, preferably 20+ or higher. In the formulation, Manuka honey provides antibacterial and/or anti-inflammatory properties. It is believed that the compound responsible for the UMF score is methylglyoxal.

[0028] In any of the foregoing formulations and methods, micro silver acts both as a preservative and, upon application to the wound site, acts as a broad-spectrum anti-microbial.sup.28. The anti-microbial power of micro silver comes from its ability to generate Ag.sup.+ ions, under aqueous conditions, from pure silver (Ag.sup.0). Ag.sup.+ kills microbes via three different mechanisms. It inhibits cellular ion transport by blocking the ion channels, inactivates intracellular enzymes by binding to them or intercalates with DNA and stops DNA replication. All these three mechanisms eventually lead to cell death. The present invention relates to a wound healing composition with significant antibacterial and anti-inflammatory actions, and including the benefit of promoting enhanced collagen synthesis. In some embodiments, natural, multifunctional, highly porous, medical grade, micro silver.sup.37 that is applied as part of the formulations applied directly to a wound.sup.27-28. This helps in minimizing the bacterial load at the wound site, which further promotes wound healing.

[0029] Micro silver.sup.27, 28 is an innovative form of pure metallic silver and it is manufactured using a purely physical, gas phase process, which produces highly pure, elemental silver without any ionic silver contamination. The average particle size of this silver measured by volume can range from about 0.10 to about 100 m, but is preferably about 10 micrometer. When applied on to the skin, micro silver collects mainly at the pore level and in the skin folds. The silver ions are released on to the surface of the skin and may thus react with the surrounding bacteria and yeast/fungi. Preferably, because of the particle size (average size 10 micrometer) it does not penetrate the skin and is always available on the skin surface to produce silver ions in presence of moisture. Micro silver plays dual role in the formulation it acts as a preservative and onto the skin, in presence of moisture, acts as antimicrobial agent by generating Ag+ and keeps the skin healthy. Other forms of silver and other micro silver products may also be used.

[0030] In still other embodiments, the formulation includes the five ingredients noted above, and in addition one or more of the ingredients such as hyaluronic acid.sup.7, 8, super low molecular weight (SLMW) hyaluronic acid, oxides (zinc and magnesium).sup.20-24. Indeed, formulations useful in accordance with the invention comprise: aloe barbadensis leaf juice, allantoin, micro silver.sup.5, Manuka Honey, L-arginine-HCL, hyaluronic acid, SLMW hyaluronic acid, and one or more gelling agents such as, without limitation, carboxymethyl cellulose, guar gum, xanthan gum, bentonite clay without synthetic preservatives. Various attributes of above ingredients are provided below:

[0031] Hyaluronic Acid.sup.10 is a high molecular weight polysaccharide and it is a very potent moisturizer. Because of its high molecular weight it does not penetrate the skin

[0032] Hyaluronic Acid SLMW is a hydrolyzed form of Hyaluronic acid and its molecular weight range is 8-15 killo dalton. Hyaluronic acid (sodium hyaluronate) is a natural polysaccharide (sugar) that occurs in body tissues including the skin providing hydration, stability, and lubrication. The SLMW (super low-molecular-weight) form is made by enzymatically cleaving high-molecular weight hyaluronic acid into small fragments (8-15 kDa). It is a off-white, water-soluble, odorless, fluffy powder. Other forms of hyaluronic acid may also be used.

[0033] A number of other active ingredients that may be present are identified in Table 1. These include beta glucan.sup.25, 26 which is a high molecular weight carbohydrate and it promotes wound healing. It increases macrophage infiltration, which stimulates tissue granulation, collagen deposition and re-epithelialization. Its preferred source is from the yeast.

[0034] One or more of magnesium and zinc oxides.sup.20-24 or salts may be used in the formulations to provide enhanced enzymatic activity to support wound healing. The average particle size for these two elements should be in micro meter range.

[0035] These formulations can also include other ingredients such as vitamins, pro-vitamins, glucans such as beta-glucan, stabilizers and anti-oxidants such as citric and ascorbic acids or tocopherol.

[0036] Excipients including fillers, viscosity modifiers, emollients, humectants pH adjusting substances, buffers, carriers and solvents such as glycerol and water may also be present. Some exemplary excipients include those found in Table 2. Particularly preferred carriers are gel-formers and materials useful in producing a gel formulation. These can include, for example, celluloses like carboxymethyl cellulose, glycerol, water and gums. Gelling and thickening agents like include gums like xanthan gum, guar gum, locust bean gum and bentonite clay. The amount of clay used can be up to 5%. The amount of gum used can be up to about 3% depending on how many gums are used. Generally, the amount of gum used over and above any locust bean gum used, can be as high as 3% by weight. If the formulation also includes locust bean gum, the total amount of all gums may be up to about 5% by weight.

[0037] These are used in varying amounts depending upon a number of factors including the desired use of the formulation (location of its use), the desired viscosity, desired lubricity, desired porosity, and the like. They are conventional agents used in conventional amounts which may vary as is determinable in the industry based on the specific properties of the individual materials selected. Exemplary materials and amounts that can be used when producing gel formulations in accordance with the present inventions include those shown in Table 2.

TABLE-US-00002 TABLE 2 Exemplary excipients More Preferable Preferable Formulation Formulation Formulation % by % by Ingredient % by weight weight weight Carboxymethyl 0.0-5.0 0.1-5.0 0.5.0-4.0 Cellulose Xanthan gum 0-5.0 0.5-5.0 1.0-4.0 Guar gum 0-5.0 0.5-5.0 1.0-4.0 Bentonite clay 0.0-5.0 0.1-4.0 0.5-3.0 Glycerol 0.0-10.0 1.0-8.0 3.0-5.0 Water q.s. q.s. q.s.

[0038] The formulations of the present invention can be adjusted in terms of their properties depending on how and where they are to be applied. The formulations could be relatively viscous so that it can be smeared into a wound, or can be relatively more solid to form a conforming pad to be placed over a wound. But they are all to be placed in contact with the skin and/or an open wound so they must be of a suitable pH, they must be made using medical or pharmaceutical grade ingredients, and they must not needlessly increase the discomfort of the patient. A preferred pH for the described formulation is between 4.8 to 7.4. If not provided as a topical gel, known formulations for preparing ointments, creams, serums, salves, pastes, and the like, may be used in conventional amounts as long as they are capable of delivering the active ingredients discussed herein.

[0039] Examples 1-12 propose particular formulations that can be made pursuant to various aspects of the invention. However, it will be appreciated that the amounts of the ingredients, and particularly the active ingredients, recited in these examples can be varied considerably as shown in Tables 3-14 below.

TABLE-US-00003 TABLE 3 Preferable More Preferable Formulation Formulation Formulation of Example Formulation % by % by 1, % Ingredient % by weight weight weight by weight Water 10.0-95.0 20.0-90.0 60.0-90.0 85.3 Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Guar gum 0-5.0 0.5-5.0 1.0-4.0 2.5 L-Arginine- 1.0-20.0 2.0-15.0 5.0-10.0 6.0 HCl Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 5.0 Citric Acid/ As needed for As needed for As needed for As needed NaOH adjusting adjusting adjusting for adjusting pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4

TABLE-US-00004 TABLE 4 Preferable More Formulation Formulation Preferable of Example Formulation % by Formulation 2, % Ingredient % by weight weight % by weight by weight Water 10.0-95.0 20.0-90.0 60.0-90.0 75.3 Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Guar gum 0-5.0 0.5-5.0 1.0-4.0 2.5 L-Arginine- 1.0-20.0 2.0-15.0 5.0-10.0 6.0 HCl Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 5.0 Manuka 1.0-50.0 1.0-25 5.0-20.0 10 Honey Citric As needed As needed As needed As needed Acid/ for adjusting for adjusting for adjusting for adjusting NaOH pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4

TABLE-US-00005 TABLE 5 Preferable More Formulation Formulation Preferable of Example Formulation % by Formulation 3, % Ingredient % by weight weight % by weight by weight Aloe 10.0-95.0 20.0-90.0 60.0-90.0 85.3 Barbadensis Leaf Juice Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Guar gum 0-5.0 0.5-5.0 1.0-4.0 2.5 L-Arginine- 1.0-20.0 2.0-15.0 5.0-10.0 6.0 HCl Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 5.0 Citric Acid/ As needed As needed As needed As needed NaOH for adjusting for adjusting for adjusting for adjusting pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4

TABLE-US-00006 TABLE 6 Preferable More Formulation Formulation Formulation Preferable of Example % by % by Formulation 4, % Ingredient weight weight % by weight by weight Aloe 10.0-95.0 20.0-90.0 60.0-90.0 75.3 Barbadensis Leaf Juice Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Guar gum 0-5.0 0.5-5.0 1.0-4.0 2.5 L-Arginine- 1.0-20.0 2.0-15.0 5.0-10.0 6.0 HCl Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 5.0 Manuka Honey 1.0-50.0 1.0-25 5.0-20.0 10 Citric Acid/ As needed As needed As needed As needed NaOH for adjusting for adjusting for adjusting for adjusting pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4

TABLE-US-00007 TABLE 7 Preferable More Preferable Formulation Formulation Formulation of Example Formulation % by % by 5, % Ingredient % by weight weight weight by weight Aloe 10.0-90.0 20.0-85.0 60.0-80.0 82.9 Barbadensis Leaf Juice Allantoin 0.01-1.0 0.05-0.8 0.1-0.5 0.3 Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Locust 0-5.0 0.5-5.0 1.0-4.0 2.5 bean gum Zinc oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Magnesium 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Oxide Super low 0.0-10.0 0.1-8.0 0.1-1.0 0.2 molecular weight hyaluronic acid (SLMW HA) L-Arginine- 1.0-20.0 2.0-15.0 5.0-10.0 6.0 HCl Niacinamide 0.5-10.0 0.75-8.0 1.0-5.0 1.0 (Vitamin B3) Provitamin B5 0.5-10.0 0.75-8.0 1.0-5.0 1.0 Beta Glucan 0.5-10.0 0.5-8.0 0.5-5.0 0.5 Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 5.0 Citric Acid/ As needed As needed As needed As needed NaOH for for for for adjusting adjusting adjusting adjusting pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4

TABLE-US-00008 TABLE 8 Preferable More Formulation Formulation Preferable of Example Formulation % by Formulation 6, % Ingredient % by weight weight % by weight by weight Aloe Barbadensis 10.0-90.0 20.0-85.0 60.0-80.0 67.9 Leaf Juice Allantoin 0.01-1.0 0.05-0.8 0.1-0.5 0.3 Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Locust Bean gum 0-5.0 0.5-5.0 1.0-4.0 2.5 Manuka Honey 1.0-50.0 1.0-25 5.0-20.0 15 Zinc oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Magnesium 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Oxide Super low 0.0-10.0 0.1-8.0 0.1-1.0 0.2 molecular weight hyaluronic acid (SLMW HA) L-Arginine-HCl 1.0-20.0 2.0-15.0 5.0-10.0 6.0 Niacinamide 0.5-10.0 0.75-8.0 1.0-5.0 1.0 (Vitamin B3) Provitamin B5 0.5-10.0 0.75-8.0 1.0-5.0 1.0 Beta Glucan 0.5-10.0 0.5-8.0 0.5-5.0 0.5 Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 5.0 Citric Acid/ As needed As needed As needed As needed NaOH for for for for adjusting adjusting adjusting adjusting pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4

TABLE-US-00009 TABLE 9 Preferable More Formulation Formulation Preferable of Example Formulation % by Formulation 7, % Ingredient % by weight weight % by weight by weight Aloe Barbadensis 10.0-90.0 20.0-85.0 60.0-80.0 82.9 Leaf Juice Allantoin 0.01-1.0 0.05-0.8 0.1-0.5 0.3 Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Xanthan gum 0-5.0 0.5-5.0 1.0-4.0 2.5 Zinc oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Magnesium Oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Super low 0.0-10.0 0.1-8.0 0.1-1.0 0.2 molecular weight hyaluronic acid (SLMW HA) L-Arginine-HCl 1.0-20.0 2.0-15.0 5.0-10.0 6.0 Niacinamide 0.5-10.0 0.75-8.0 1.0-5.0 1.0 (Vitamin B3) Provitamin B5 0.5-10.0 0.75-8.0 1.0-5.0 1.0 Beta Glucan 0.5-10.0 0.5-8.0 0.5-5.0 0.5 Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 5.0 Citric acid/NaOH As needed As needed As needed As needed for for for for adjusting adjusting adjusting adjusting pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4

TABLE-US-00010 TABLE 10 Preferable More Formulation Formulation Formulation Preferable of Example % by % by Formulation 8, % Ingredient weight weight % by weight by weight Aloe Barbadensis 10.0-90.0 20.0-85.0 60.0-80.0 67.9 Leaf Juice Allantoin 0.01-1.0 0.05-0.8 0.1-0.5 0.3 Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Xanthan gum 0-5.0 0.5-5.0 1.0-4.0 2.5 Manuka Honey 0.0-50.0 1.0-25 5.0-20.0 15 Zinc oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Magnesium Oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Super low 0.0-10.0 0.1-8.0 0.1-1.0 0.2 molecular weight hyaluronic acid (SLMW HA) L-Arginine-HCl 1.0-20.0 2.0-15.0 5.0-10.0 6.0 Niacinamide 0.5-10.0 0.75-8.0 1.0-5.0 1.0 (Vitamin B3) Provitamin B5 0.5-10.0 0.75-8.0 1.0-5.0 1.0 Beta Glucan 0.5-10.0 0.5-8.0 0.5-5.0 0.5 Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 5.0 Citric acid/ As needed As needed As needed As needed NAOH for for for for adjusting adjusting adjusting adjusting pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4

TABLE-US-00011 TABLE 11 Preferable More Formulation Formulation Preferable of Example Formulation % by Formulation 9, % by Ingredient % by weight weight % by weight weight Aloe Barbadensis 10.0-90.0 20.0-85.0 60.0-80.0 82.9 Leaf Juice Allantoin 0.01-1.0 0.05-0.8 0.1-0.5 0.3 Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Guar gum 0-5.0 0.5-5.0 1.0-4.0 2.5 Zinc oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Magnesium Oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Super low 0.0-10.0 0.1-8.0 0.1-1.0 0.2 molecular weight hyaluronic acid (SLMW HA) L-Arginine-HCl 1.0-20.0 2.0-15.0 5.0-10.0 6.0 Niacinamide 0.5-10.0 0.75-8.0 1.0-5.0 1.0 (Vitamin B3) Provitamin B5 0.5-10.0 0.75-8.0 1.0-5.0 1.0 Beta Glucan 0.5-10.0 0.5-8.0 0.5-5.0 0.5 Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 5.0 Citric acid/NaOH As needed As needed As needed As needed for for for for adjusting adjusting adjusting adjusting pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4

TABLE-US-00012 TABLE 12 Preferable More Formulation Formulation Formulation Preferable of Example % by % by Formulation 10, % by Ingredient weight weight % by weight weight Aloe 10.0-90.0 20.0-85.0 60.0-80.0 67.9 Barbadensis Leaf Juice Allantoin 0.01-1.0 0.05-0.8 0.1-0.5 0.3 Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Guar gum 0-5.0 0.5-5.0 1.0-4.0 2.5 Manuka Honey 0.0-50.0 1.0-25 5.0-20.0 15 Zinc oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Magnesium 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Oxide Super low 0.0-10.0 0.1-8.0 0.1-1.0 0.2 molecular weight hyaluronic acid (SLMW HA) L-Arginine- 1.0-20.0 2.0-15.0 5.0-10.0 6.0 HCl Niacinamide 0.5-10.0 0.75-8.0 1.0-5.0 1.0 (Vitamin B3) Provitamin B5 0.5-10.0 0.75-8.0 1.0-5.0 1.0 Beta Glucan 0.5-10.0 0.5-8.0 0.5-5.0 0.5 Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 1.0 Citric acid/ As needed As needed As needed As needed NaOH for adjusting for adjusting for adjusting for adjusting pH 6.8-7.4 pH 6.8-7.4 pH 6.8-7.4 pH 6.8-7.4

TABLE-US-00013 TABLE 13 Preferable More Formulation Formulation Formulation Preferable of Example % by % by Formulation 11, % by Ingredient weight weight % by weight weight Aloe Barbadensis 10.0-90.0 20.0-85.0 60.0-80.0 82.9 Leaf Juice Allantoin 0.01-1.0 0.05-0.8 0.1-0.5 0.3 Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Carboxymethyl 0-5.0 0.5-5.0 1.0-4.0 2.5 cellulose Zinc oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Magnesium Oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Super low 0.0-10.0 0.1-8.0 0.1-1.0 0.2 molecular weight hyaluronic acid (SLMW HA) L-Arginine-HCl 1.0-20.0 2.0-15.0 5.0-10.0 6.0 Niacinamide 0.5-10.0 0.75-8.0 1.0-5.0 1.0 (Vitamin B3) Provitamin B5 0.5-10.0 0.75-8.0 1.0-5.0 1.0 Beta Glucan 0.5-10.0 0.5-8.0 0.5-5.0 0.5 Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 5.0 Citric acid/NaOH As needed As needed As needed As needed for for for for adjusting adjusting adjusting adjusting pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4

TABLE-US-00014 TABLE 14 Preferable More Formulation Formulation Formulation Preferable of Example % by % by Formulation 12, % by Ingredient weight weight % by weight weight Aloe 10.0-90.0 20.0-85.0 60.0-80.0 67.9 Barbadensis Leaf Juice Allantoin 0.01-1.0 0.05-0.8 0.1-0.5 0.3 Micro Silver 0.1-5.0 0.2-2.0 0.2-1.0 0.2 Carboxymethyl 0-5.0 0.5-5.0 1.0-4.0 2.5 cellulose Manuka Honey 0.0-50.0 1.0-25 5.0-20.0 15 Zinc oxide 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Magnesium 0.0-20.0 0.1-10.0 0.2-1.0 0.2 Oxide Super low 0.0-10.0 0.1-8.0 0.1-1.0 0.2 molecular weight hyaluronic acid (SLMW HA) L-Arginine- 1.0-20.0 2.0-15.0 5.0-10.0 6.0 HCl Niacinamide 0.5-10.0 0.75-8.0 1.0-5.0 1.0 (Vitamin B3) Provitamin B5 0.5-10.0 0.75-8.0 1.0-5.0 1.0 Beta Glucan 0.5-10.0 0.5-8.0 0.5-5.0 0.5 Glycerol 1.0-10.0 2.0-8.0 3.0-6.0 5.0 Citric acid/ As needed As needed As needed As needed for NaOH for adjusting for adjusting for adjusting adjusting pH pH 4.8-7.4 pH 4.8-7.4 pH 4.8-7.4 4.8-7.4

[0040] The amount of wound healing formulation used in accordance with the present invention can vary with many factors known to persons of ordinary skill in this art. The composition and concentration of the actives contained in the formulation, whether or not it is being administered along with oral supplementation, the size and nature of the wound all can play a role in how much of the formulation is applied and how frequently and for how long. As one example, however, approximately 0.5 g of the gel formulation is applied per sq cm of the wound area. In one embodiment, the formulation should be applied once a day for the first 7 days followed by alternate days application. The wound should be cleaned with normal saline or mild soap prior to each new application of the formulation.

[0041] In one embodiment, wound care and treatment is accomplished using both external formulation application and by providing various important factors to the body system internally as well. Gels, those including one or more of L-arginine, aloe barbadensis and those without any of them, can be applied externally while one or more of L-arginine, turmeric and/or piperine is administered to the subject orally as well. The gel and the oral doses do not have to be given on any particularly coordinated schedulei.e. eat a certain amount of 1-arginine within 1 hour of application of a gel formulation of the invention. Oral L-arginine should be given up to 30 g per day such as 1-3 g three times a day. Turmeric/piperine should be given up to 10 g/50 mg per day such as 1 capsule (1 gm turmeric+10 mg piperine) three times a day. These ingredients may be given in the form of any oral delivery device such as a tablet, capsule, caplet, powder, spray, film and liquid, such as a syrup. However, preferably they are given as a capsule or an oral solution.

[0042] In one embodiment, patients should take 1 capsule of oral L-arginine (1000 mg) and one capsule of turmeric (1000 mg) mixed with peprine (10 mg) three times a day. The patients may also take, instead of oral capsules, equivalent dose of the L-arginine and/or Turmeric with peprine in the form of a solution rather than a capsule.

Examples

[0043] The formulations 1 & 3 are prepared by using either water or aloe barabadensis leaf juice (85.3%) along with micro silver (0.2%), guar gum (2.5%), L-arginine-HCl (6%), Glycerol (6%). The formulations 2 & 4 are prepared by reducing the water or aloe barbadensis leaf juice from the formulations 1 & 3 by 10% and adding 10% of Manuka honey to each and rest of the ingredients remained the same. The formulations of 5, 7, 9 & 11 are prepared by using 4 different gums (5-Locust bean gum, 7-Xanthan gum, 9-Guar gum and 11-Carboxymethyl cellulose) and the formulations of examples 6, 8, 10, & 12 are prepared by reducing the amount of Aloe barbadensis leaf juice from 82.9% to 67.9% and adding Manuka honey at 15%. The nature of the ingredients used in these formulations, should not provoke any allergic reactions unless that particular subject belongs to groups who are predisposed to be allergic to these ingredients. Since these formulations use mainly natural ingredients, they may also be considered safe as ingredients.

[0044] Example 1: Water 85.3%; Micro silver0.2%; Guar gum2.5%; L-Arginine-HCl6%; Glycerol5%; Citric Acid to adjust pH to between 6.0 and 7.4. Procedure for making the formulations: Water or in other examples Aloe barbadensis leaf juice is added in the mixing vessel first. While vigorously stirring the liquid, remaining ingredients are added sequentially. Following the addition of all the ingredients, the resultant gel is mixed for another hour. Upon completion of the mixing, the gel pH was measured and, if needed, adjusted with citric acid/NaOH.

[0045] Example 2: Water75.3; Micro silver0.2%; Guar gum2.5%; L-Arginine-HCl6%; Glycerol6%; Manuka honey 10%; Citric Acid to adjust pH to between 6.0 and 7.4.

[0046] Example 3: Aloe Barbadensis Leaf Juice85.3%; Micro silver0.2%; Guar gum2.5%; L-Arginine-HCl6%; Glycerol6%; Citric Acid to adjust pH to between 6.8 and 7.4.

[0047] Example 4: Aloe Barbadensis Leaf Juice75.3%; Micro silver0.2%; Guar gum2.5%; L-Arginine-HCl6%; Glycerol6%; Citric Acid to adjust pH to between 6.0 and 7.4.

[0048] Example 5: Aloe Barbadensis Leaf Juice82.9%; Allantoin0.3%; Micro silver0.2%; Locust bean gum2.5%; Zinc oxide0.2%; Magnesium Oxide0.2%; SLMW HA0.2%; L-Arginine-HCl6%; niacinamide (Vitamin B3)1%; Provitamin B51.0%; Beta Glucan0.5%; Glycerol5%; Citric Acid to adjust pH to between 6.8 and 7.4.

[0049] Example 6: Aloe Barbadensis Leaf Juice67.9%; Allantoin0.3%; Micro silver0.2%; Locust bean gum2.5%; Manuka honey15%; Zinc oxide0.2%; Magnesium Oxide0.2%; SLMW HA0.2%; L-Arginine-HCl6%; niacinamide (Vitamin B3)1%; Provitamin B51.0%; Beta Glucan0.5%; Glycerol5%; Citric Acid to adjust pH to between 6.8 and 7.4. This formulation can be made using the process described generally in Example 1.

[0050] Example 7: Aloe Barbadensis Leaf Juice82.9%; Allantoin0.3%; Micro silver0.2%; Xanthan gum2.5%; Zinc oxide0.2%; Magnesium Oxide0.2%; SLMW HA0.2%; L-Arginine-HCl6%; niacinamide (Vitamin B3)1%; Provitamin B51.0%; Beta Glucan0.5%; Glycerol5%; Citric Acid to adjust pH to between 6.8 and 7.4. This formulation can be made using the process described generally in Example 1.

[0051] Example 8: Aloe Barbadensis Leaf Juice67.9%; Allantoin0.3%; Micro silver0.2%; Xanthan gum2.5%; Manuka honey15%; Zinc oxide0.2%; Magnesium Oxide0.2%; SLMW HA0.2%; L-Arginine-HCl6%; niacinamide (Vitamin B3)1%; Provitamin B51.0%; Beta Glucan0.5%; Glycerol5%; Citric Acid to adjust pH to between 6.8 and 7.4. This formulation can be made using the process described generally in Example 1.

[0052] Example 9: Aloe Barbadensis Leaf Juice82.9%; Allantoin0.3%; Micro silver0.2%; Guar gum2.5%; Zinc oxide0.2%; Magnesium Oxide0.2%; SLMW HA0.2%; L-Arginine-HCl6%; niacinamide (Vitamin B3)1%; Provitamin B51.0%; Beta Glucan0.5%; Glycerol5%; Citric Acid to adjust pH to between 6.8 and 7.4. This formulation can be made using the process described generally in Example 1.

[0053] Example 10: Aloe Barbadensis Leaf Juice67.9%; Allantoin0.3%; Micro silver0.2%; Guar gum2.5%; Manuka honey15%; Zinc oxide0.2%; Magnesium Oxide0.2%; SLMW HA 0.2%; L-Arginine-HCl6%; niacinamide (Vitamin B3)1%; Provitamin B51.0%; Beta Glucan0.5%; Glycerol5%; Citric Acid to adjust pH to between 6.8 and 7.4. This formulation can be made using the process described generally in Example 1.

[0054] Example 11: Aloe Barbadensis Leaf Juice82.9%; Allantoin0.3%; Micro silver0.2%; Carboxymethyl cellulose2.5%; Zinc oxide0.2%; Magnesium Oxide0.2%; SLMW HA0.2%; L-Arginine-HCl6%; niacinamide (Vitamin B3)1%; Provitamin B51.0%; Beta Glucan0.5%; Glycerol5%; Citric Acid to adjust pH to between 6.8 and 7.4. This formulation can be made using the process described generally in Example 1.

[0055] Example 12: Aloe Barbadensis Leaf Juice67.9%; Allantoin0.3%; Micro silver0.2%; Carboxymethyl cellulose2.5%; Manuka honey15%; Zinc oxide0.2%; Magnesium Oxide0.2%; SLMW HA0.2%; L-Arginine-HCl6%; niacinamide (Vitamin B3)1%; Provitamin B51.0%; Beta Glucan0.5%; Glycerol5%; Citric Acid to adjust pH to between 6.8 and 7.4. This formulation can be made using the process described generally in Example 1.

[0056] In all of the above examples, anyone skilled in the art of mixing ingredients and forming gels knows the order in which the different constituents must be added to prepare the respective formulations.

REFERENCES

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