Effervescent Tablet Comprising L-Arginine Used for Healing Wounds

Technical Field

The invention relates to a composition comprising L-arginine and a production method of said composition for use as a food supplement in order to heal wounds.

The Prior Art

Due to illness or trauma, various wounds can be seen on the human body. Wound healing is known as a biological process in which some cellular structures play a role. Depending on the age and health status of the person, the wound healing rate may also change. Various improvements are being worked on in the technical field to ensure wound healing. However, most of these improvements relates to the pharmaceutical field, and there are no compositions that can be used as food supplements and allow the wound healing process quickly and effectively.

The documents determined in the patent and literature research carried out for the state of the art are summarized below.

A Japanese patent application application number JP33983996 A discloses the use of an agent to induce wound healing. This agent is stated to contain a gelatinous hydrocarbon containing one or more compounds selected from glutamine, chitin, chitosan or derivatives thereof.

A Japanese patent application application number JP2O13264338 A relates to a wound therapeutic agent that ameliorates a symptom of wound and bedsore. The document states that said therapeutic agent contains bifidobacteria and glutamine, dietary fiber and oligosaccharide as active ingredient. As a result, due to the above-mentioned negativities and the inadequacy of the existing solutions on the subject, it was necessary to make an improvement in the relevant technical field.

Brief Description of the Invention

The present invention relates to a composition and production method for use in wound healing, which meets the above-mentioned requirements, eliminates all disadvantages and brings some additional advantages.

The invention is inspired by the present situations and aims to solve the above- mentioned disadvantages.

The main objective of the invention is to obtain a composition in effervescent tablet dosage form comprising L-arginine to be used as a food supplement in order to heal wounds. L-arginine in the composition of the invention, is a precursor for nitric oxide, which is required in the inflammatory process of wound healing. It is also used in the production of collagen. L-arginine supplementation has been observed to increase collagen deposition in wounds.

The structural and characteristic features of the invention and all its advantages will be understood more clearly due to the detailed description given below, and therefore the evaluation should be made by taking into account the detailed description.

Detailed Description of the Invention

In this detailed description, preferred embodiments of the composition subject to the invention are explained only for a better understanding of the subject.

The invention relates to a composition in effervescent tablet dosage form comprising L- arginine to be used as a food supplement in order to heal wounds, and to a production method of the said composition. In addition to L-arginine, Sodium Selenite (45%), Ludipress, Sodium Hydrogen Carbonate, Citric Acid (E33O), Ascorbic Acid, Polyethylene Glycol (E 1521), pineapple flavor, PVP K30, Zinc Sulphate, Vitamin E, Stevia, Vitamin D3, B12, Folic Acid,

Vitamin C, Microcrystallinecellulose, HPMC Capsule, Bromelain, Vitamin E, Magnesium Stearate, L-Glutamine, Calendula powder, Grape Seed extract, Turmeric, Zinc, Hyaluronic Acid, Iron, Vitamin A, Copper , Vitamin B12, Vitamin K2, Biotin, Selenium, Vitamin D3 can also be found in the composition.

The components of the composition of the invention in effervescent tablet dosage form, the applicable and preferred weight percent ratios of the mentioned components, and the mg amounts per effervescent tablet are given in the table below.

The components of the composition of the invention in capsule dosage form and the weight percent ratios of the mentioned components are given in the table below.

The composition in the invention can be produced in different drug dosage forms (capsules, tablets, etc.). In an embodiment of the invention, the effervescent tablet form, which allows the use of more active substance, is preferred. For example, when the composition is produced in capsule form, the capsule contains 200-300 mg L-arginine instead of 600 mg L-arginine. Since active ingredients with low water solubility are used in the capsule product, the capsule form is preferred so that the solution obtained from the effervescent tablet does not form a blurry image. In this sense, the effervescent product cannot be produced as capsules due to the amount by weight, and the capsule product cannot be produced as effervescent tablet due to the solubility of the factors.

The effervescent tablet comprising the composition of the invention comprises Ludipress (lactose monohydrate), Sodium Hydrogen Carbonate, Citric Acid (E33O), Polyethylene Glycol (E 1521) as excipients.

Pineapple Flavor, PVP K30, Stevia excipients are also optional ingredients. Stevia is a kind of plant and acts as a sweetener. Due to stevia, no sugar is used in the final product, and it is ensured that the product is of a quality that can be used by diabetic patients.

In the production method of the composition of the invention, first of all, lactose monohydrate, vitamin B 12 and folic acid are preferably added into the cubic mixer and mixed preferably for 2 minutes. In the next step, L-ascorbic Acid and L-arginine are added to the said cubic mixer and the cubic mixer is mixed preferably for 10 minutes. Next, Kollidon 30 and anhydrous citric acid are added into the cubic mixer and mixed preferably for 10 minutes. In addition to the existing mixture, Sodium Hydrogen Carbonate acid is added into the cubic mixer and preferably mixed for 10 minutes. After the pineapple flavor is added into the cubic mixer, the mixing process is preferably continued for 15 minutes. Zinc, Vitamin E, Vitamin D and Sodium selenite are added into the cubic mixer and mixed preferably for 15 minutes. Steviase is added into the cubic mixer and mixed preferably for 15 minutes. In the next process, turmeric extract is added into the cubic mixer and mixed preferably for 15 minutes. Polyethylene Glycol is added into the cubic mixer and mixed preferably for 10 minutes.

After the component adding and mixing processes are completed, the tablet pressing is started. Tablet is adjusted so that each tablet is preferably 3.6 g, and filling is carried out in 10, 15 or 20 tubes according to the appropriate effervescent tube size. The mouth of the the tubes is closed with a silica gel and spiral cap. Finally, laboratory test samples are taken and the mixture is prepared for filtration and filling, if the measurement values are appropriate.

L-arginine in the composition of the invention increases the general DNA synthesis in the lesion. Thus, increased DNA synthetic rate indicates a higher stimulus of protein synthesis for wound healing and cellular proliferation. Arginine supplementation has been found to significantly reduce inflammatory reactions by suppressing the expression of responsive cytokines and chemokines. Patients experiencing trauma/hemorrhagic shock are less likely to achieve wound healing due to decreased collagen synthesis and a higher probability of wound dehiscence after surgery. It shows that dietary arginine greatly alleviates this condition and increases wound strength. However, in clinical studies, arginine supplementation has been applied to treat scar formation after surgery. For certain conditions, such as diabetic wound healing and frostbite injury healing, arginine has the potential to play a vital role in the healing of damaged tissue, as described in recent reports.

It has been observed that selenium (sodium selenite) in the composition of the invention mimics the effect of insulin and improves glucose homeostasis by stimulating tyrosine kinases in insulin signaling pathways. In this sense, selenium administration also provides an increased rate of angiogenesis and enhanced antioxidant enzyme status, leading to faster wound closure in diabetic conditions. SOD plays a fundamental role in oxygen defense metabolism in mammals by reducing superoxide free radicals to hydrogen peroxide, which is readily reduced to water by catalase and glutathione peroxidase. A decrease in SOD levels and an increase in LPO were observed in diabetic wounds that healed after selenium administration. Superoxide radical accumulation at the wound site appears to be responsible for long-term healing, as the level of SOD is reduced in diabetic patients compared to non-diabetic wounds. In diabetic wounds, selenium application significantly increases SOD levels, which eventually scavenge superoxide radical from wounds. Selenium is a nonmetal having some metal properties. The use of selenium in nanoform is promising for regenerative medicine. It is well known that nanoselenium is a highly effective long-acting antioxidant. There are currently studies that conclusively demonstrate the ability of selenium compounds to inhibit bacterial growth and bacterial biofilm formation. Selenium has reported significant antiproliferative activity against HeLa and HepG2 cell lines.

Zinc in the composition of the invention is stored 85% in muscle and bone, 11% in skin and liver, and the rest in other tissues, and is found everywhere in the body. Considering the 3000 proteins that require zinc, the importance of zinc for numerous physiological processes is not surprising. It is known to be essential in growth, immune function, tissue maintenance and wound healing. Zinc levels are markedly increased in the early inflammatory phase of wound healing. Experiments in the rat wound healing model have shown that within the first 24 hours after injury, there is a 15% to 20% increase in zinc levels at the wound margin, with an increase of up to 30% during subsequent granulation tissue development and epidermal. It has been demonstrated that zinc treatments reduce wound remnants and promote epithelialization. Treatment of zinc deficiency results in better wound healing compared to those with zinc deficiency. Especially in diabetic patients, higher glucose levels can inhibit the nutrient absorption process and cause depletion of various nutrients (eg magnesium, zinc, B12, Be, folic acid).

Vitamin E in the composition of the present invention protects cell membranes and polyunsaturated lipids from ROS attack by inducing the activation of various signal transduction pathways, thanks to its scavenging activity, and is therefore mostly known for its antioxidant role. Increasing wound closure rate is considered as one of the benefits of vitamin E supplementation. Thus, these findings may stimulate research into the effects of vitamin E supplementation in people with poorly controlled hyperglycemia to improve healing after tissue damage. Vitamin E also modulates the expression of connective tissue growth factor and regulates gene expression and transcription, thus facilitating the protection of wounds against infections such as methicillin-resistant Staphylococcus aureus. Overall, these findings suggest that vitamin E supplementation is beneficial for wound repair and immune function.

One of the components in the composition of the invention is vitamin C. Ascorbic acid is a necessary cofactor for the synthesis of collagen, proteoglycans and other organic components of the intracellular matrix of tissues such as bones, skin, capillary walls and other connective tissues. Clinical manifestations of ascorbic acid deficiency include bleeding gums, weak immunity, easy bruising, bleeding, slow healing of wounds and fractures. Ascorbic acid has only shown the benefit of vitamin C in people with vitamin C deficiency who use low doses of ascorbic acid to repair damaged tissue. Infection from impaired immunity is one of the most common and clinically important barriers to wound healing. In addition, dysregulation of cellular immunity and cytokines may impair wound healing. Ascorbic acid has been shown to improve immune function in humans. Studies suggest that higher doses of ascorbic acid should be used in nondeficient individuals for optimal wound repair. In addition, the transient increase in metabolic requirements for vitamin C deficiency resulting from wounds or surgical cuts and the metabolic requirement of vitamin C for collagen synthesis are indicators of higher vitamin C doses in non-deficient individuals.

Another component in the composition of the invention is vitamin B12. Strategies to prevent diabetes mellitus have emerged recently, including nutritional and therapeutic support regarding B vitamin supplementation. Various studies have demonstrated the protective effects of B vitamins in diabetic patients. In one study, circulating and tissue concentrations of water-soluble vitamins were shown to be significantly reduced in diabetic subjects. In animal models, diabetes significantly lowers folate, vitamin Be and vitamin B12 levels in kidney, heart, liver and muscle.

Folic acid, in the composition of the invention, reduces oxidative stress, increases fibroblast production, biological production of collagen and collagen production rate. Thus, it aids in wound healing. In addition, folic acid significantly reduces lipid degradation, protein nitrotyrosination and glutathione depletion in diabetic wounds. In conclusion, folic acid supplementation obtained by the invention can improve impaired wound healing by suppressing oxidative stress in diabetic mice. Daily supplementation with folic acid improves the healing delay caused by diabetes. Studies show that folic acid supplementation accelerates wound healing and shortens wound healing time. In particular, it has been observed that the healing of diabetic wounds accelerates.

Vitamin D3 or cholecalciferol production takes place by meeting the receptors on the skin with ultraviolet radiation from sunlight. Active vitamin D has been shown to have potent anti-inflammatory and anti-cancer properties that increase in the skin. It has been previously shown that vitamin D can promote wound repair without causing complete incision closure. It is known that wound repair occurs by activating vitamin D. Studies have shown that it accelerates wound healing as well as correcting the problems in skin cells in diabetic patients.

In the process of using the composition in the invention, it is recommended to use the composition once a day, by adding 1 effervescent tablet to 1 glass (200 ml) of water for adults aged 11 and over. It should be waited for 2 minutes to dissolve and a whole glass is drunk. It is not recommended to exceed the recommended daily portion. In addition, it is important to keep the composition out of the reach of children, to consult a doctor in case of pregnancy and lactation, and in case of illness or drug use. However, if the security seal is broken or there is open packaging, it should not be used, and it should be kept in a dry place below 25 °C. In addition, it should be known that supplements will not replace normal nutrition.