Antimicrobial and antifungal properties of a two-layered nanofibre diabetic finger / heel / foot protective galosh and method of production

Abstract

The invention relates to a double-layered nanofibre diabetic toe / heel / foot protective galosh and production method, which is bio-based thermoplastic polyurethane and chitosan-based, aloe vera-enriched, simultaneously exhibiting antimicrobial / antifungal properties, wound healing-inducing, soft, ergonomic, porous, breathable, low moisture retention capacity, high air and water vapour permeability, double-layered nanofibre diabetic toe / heel / foot protective galosh and their production method.

Description

[0001] DESCRIPTION

[0002] ANTIMICROBIAL AND ANTIFUNGAL PROPERTIES OF A TWO-LAYERED NANOFIBRE DIABETIC FINGER / HEEL / FOOT PROTECTIVE GALOSH AND METHOD OF PRODUCTION

[0003] TECHNICAL FIELD

[0004] The invention relates to a bio-based thermoplastic polyurethane and chitosan- based, aloe vera-enriched, dual-layer nanofibre diabetic toe / heel / foot protective galosh and production method that simultaneously exhibits antimicrobial / antifungal properties, promotes wound healing, is soft, ergonomic, porous, breathable, has low moisture retention capacity, high air and water vapour permeability, double-layered nanofibre diabetic toe / heel / foot protective galosh and their production method.

[0005] PRIOR ART

[0006] Diabetes is a disease that develops as a result of elevated blood sugar levels due to the pancreas not producing sufficient insulin, a hormone that regulates blood sugar, or a malfunction in the use of the insulin produced. Diabetes is a chronic disease that is increasing not only in our country but throughout the world. The average age of onset of diabetes is decreasing every year. Diabetes, which is most commonly seen in the 10-14 age group during childhood, has unfortunately begun to appear in pre-school age children in recent years.

[0007] Diabetes is not only a national but also a global problem and has begun to be assessed internationally. According to the latest data from the International Diabetes Federation (IDF) Diabetes Atlas 10 (2021 ),

[0008] - 1 in 10 adults, or 537 million people, have diabetes,

[0009] - 541 million adults have impaired glucose tolerance (IGT), putting them at risk of type 2 diabetes,

[0010] - One person dies from diabetes every 5 seconds, with this number reaching 6.7 million in 2021 ,

[0011] - Healthcare costs related to diabetes have increased by 316% over the past 15 years,

[0012] - 10% of global healthcare expenditure is allocated to diabetes, amounting to 966 billion US dollars in 2021 , - By 2045, the number of people over the age of 20 with diabetes in Turkey is expected to reach 13.4 million, with annual diabetes-related healthcare costs per person reaching US$1 ,045.

[0013] - One in six newborns is affected by gestational diabetes (20 million), and 84% of them are reported to have a genetic predisposition to diabetes.

[0014] As can be seen, diabetes is one of the fastest growing global health emergencies of the 21 st century. In 2021 , 537 million people have diabetes. This number is expected to reach 643 million in 2030 and 783 million in 2045.

[0015] Diabetes is a condition that brings with it many complications. One of the most significant complications that complicates the patient's life is slow wound healing, recurrent infections, and diabetic foot syndrome. Due to reduced blood flow in diabetic patients, at least one in five will develop non-healing wounds, ulcers or infections at some point in their lives, which can lead to the loss of fingers, feet or legs. A simple shoe rub or ingrown toenail, which would heal quickly with appropriate treatment in healthy individuals, can develop into a diabetic foot ulcer in diabetic patients. For this reason, diabetic foot syndrome is considered a slow-developing but serious disease. Due to these two fundamental reasons, preventive measures and innovative medical products are of great importance in diabetes.

[0016] There are many medically focused studies on the diagnosis, treatment, and preventive factors of diabetic wound infections. The Turkish Society of Clinical Microbiology and Infectious Diseases (KLIMIK) Association's Diabetic Foot Infections Working Group (DAIQG) will organise the Vllth National (with international participation) Diabetic Foot Infections Symposium (UDAIS 2022). The report from this symposium will address diabetic foot syndrome in detail and outline the general requirements for medical treatment and prevention. In this context, it is reported that the feet of diabetic patients are more prone to dryness than those of healthy individuals, heel cracks frequently develop, and microbes entering through these cracks cause easier and more serious infections in feet with impaired or weakened blood flow. In addition, it has been stated that sweating in the feet of diabetic patients causes fungal growth on the toes and between the toes, which also predisposes them to wound development. It has been reported that traditional and complementary medicine practices exist for diabetic foot syndrome and that herbal products with various antimicrobial effects are used in these methods. The studies presented summarise that individuals with diabetic foot syndrome or at risk of developing it should pay attention to the following issues: products that come into direct and indirect contact with the feet must have antimicrobial and antifungal properties, offer a soft and ergonomic pressure surface, and be breathable and moisture-wicking ( ). In light of these requirements, it is important to develop alternative natural polymeric products that meet current needs through an engineering approach.

[0017] Statistical evaluations indicate that at least 20% of chronic diabetes patients will face diabetic foot syndrome problems, and this situation is expected to pose a serious problem for the healthcare sector and its costs in the near future. Therefore, there is a need for new protectors that prevent diabetic foot syndrome or trigger the healing of wounds.

[0018] BRIEF DESCRIPTION OF THE INVENTION

[0019] The invention relates to a bio-based thermoplastic polyurethane and chitosan- based, aloe vera-enriched, soft, ergonomic, porous, breathable, low moisture retention, high air and water vapour permeability, double-layered nanofibre diabetic toe / heel / foot protective galosh and their production method. The toe / heel / foot protective galosh obtained using the production method in our invention prevent diabetic foot syndrome and the progression of small-scale lesions. The galosh, which are worn directly in contact with the skin under the sock, have certain characteristics. First of all, they create a thin, soft, ergonomic pressure surface, maintaining the patient's comfort. They minimise the formation of new wounds. They do not cause sweating and inhibit microbial and fungal growth. If a wound has already formed, its antimicrobial and healing-promoting structure triggers rapid wound closure.

[0020] The advantages the product offers to diabetic patients are highlighted under the following main headings:

[0021] - Breathability: Its breathable structure helps keep feet dry, thereby reducing the risk of infection.

[0022] - Antimicrobial and Antifungal Properties: Chitosan and aloe vera content provide protection against infections, which is important for the foot health of diabetic patients.

[0023] - Soft and Comfortable: The biopolyurethane-based bottom layer provides soft support, reducing pressure on the feet, which can help prevent the formation of diabetic foot ulcers. - Easy Cleaning: Being washable is a major advantage in terms of hygiene. Diabetics should pay particular attention to foot care.

[0024] - Reusable: Its durable construction ensures the galosh have a long lifespan, making them an economical choice.

[0025] The product derived from our innovation offers the following advantages:

[0026] - The quality of life for existing diabetes patients can be maintained at a certain level of well-being, even if it does not match that of healthy individuals.

[0027] - Patients' reliance on the healthcare sector can be reduced.

[0028] - The burden on the healthcare sector can be reduced both in terms of workload and economically.

[0029] - Diabetes patients can be prevented from experiencing limb loss through the measures taken.

[0030] - The number of individuals who become unable to work due to limb loss associated with diabetes at an early age can be reduced.

[0031] - Disability pensions resulting from diabetic limb loss can be prevented.

[0032] - It will be possible to ensure that they can support the national economy and development throughout their lives.

[0033] DETAILED DESCRIPTION OF THE INVENTION

[0034] Our invention uses Bio-Thermoplastic Polyurethane (TPU), chitosan and aloe vera as raw materials, which are biological and renewable. The biopolyurethane bottom layer provides soft pressure and ergonomics for the foot, while the chitosan and aloe vera-based top layer prevents microbial growth with its antimicrobial and antifungal properties. Furthermore, antimicrobial activity is enhanced by adding antimicrobial plant essential oils (pine turpentine, thyme, eucalyptus, mint, lavender, cinnamon, lemon, rosemary, sage, etc.) to the structure. These raw materials are biodegradable, environmentally friendly, and biocompatible.

[0035] The nanofibre technology in our invention provides a breathable structure with a high moisture desorption rate, preventing the foot from sweating. The layer has a micro-hole / mesh structure. The galosh are ergonomically designed to fit the foot / toe / heel structure perfectly, completely covering the toes without restricting movement. In other words, our invention is specifically designed for the foot, toes and heel area. This product has a minimum usage period of 3 months. The production method of our invention is based on the electrospinning of a two- layer nanofibre structure consisting of bio-based thermoplastic polyurethane (TPU) and chitosan-aloe vera. The production process consists of a series of technical steps (six steps) ranging from material preparation to electrospinning processes and giving the product its final form. This method enables the production of an innovative, ergonomic and functional product with high precision control parameters.

[0036] - Material Preparation for the Bottom Layer: Bio-based thermoplastic polyurethane (TPU) is dissolved in a solvent (e.g., a mixture of dimethylformamide and tetrahydrofuran) at a concentration range of 10-15% to prepare a polymer solution suitable for electrospinning. The mixture is homogenised in a magnetic stirrer at 400-600 rpm for 4-6 hours. The viscosity range suitable for electrospinning is determined to be 800-1200 cP (centipoise).

[0037] - Material Preparation for the Top Layer: Chitosan (with a deacetylation degree above 85% and a molecular weight between 100-200 kDa) is dissolved in a 2-10% concentration of 1-2% (v / v) acetic acid solution to achieve a specific viscosity. Aloe vera extract (at a ratio of 1 -5%) is added to the chitosan mixture. Subsequently, to enhance the antimicrobial and antifungal effect, at least one of the plant essential oils pine turpentine, thyme, eucalyptus, mint, lavender, cinnamon, lemon, rosemary and sage is added to the chitosan-aloe vera mixture (thyme oil 0.5%, lavender oil 0.3%). The prepared solution is stirred in a magnetic stirrer until a homogeneous mixture is obtained (at 400-800 rpm for 4-6 hours). To increase the mechanical and chemical resistance of the chitosan-based top layer, cross-linking agents (e.g., glutaraldehyde; at least one of epichlorohydrin) can be added to the polymeric solution to achieve three-dimensional matrix formation. The surface tension of the chitosan solution to be used in electrospinning is 40-50 mN / m, and its conductivity is 8-10 mS / cm.

[0038] - Electrospinning Process Substrate Production: The TPU solution for the electrospinning process is placed in the electrospinning device. Specific parameters are set during the spinning process: Voltage: 15-20 kV; Needle- Collector Distance: 10-15 cm; Flow Rate: 0.5-1 mL / hour. The resulting nanofibre film is deposited homogeneously onto the collector surface. The electrospinning process is carried out at 30-40% relative humidity and 25°C. The TPU solution is deposited homogeneously onto the rotating cylindrical collector. The bottom layer thickness (e.g. 250-500 pm) is adjusted according to the application.

[0039] - Electrospinning Process Top Layer Production: The chitosan-aloe vera- plant essential oil solution prepared for the top layer is applied onto the TPU layer in the electrospinning device. A second electrospinning process is performed with the same parameters , thus creating a double-layered structure. The top layer thickness is adjusted between 150-250 pm depending on the application. The electrospinning process ensures homogeneous bonding of the layers at the nano level.

[0040] The double-layered nanofibre structure obtained after production is dried in a vacuum oven at 40-60°C. A cross-linking agent can be added to the chitosan top layer solution, or in the final stage, the chitosan layer can be exposed to glutaraldehyde vapourfor a certain period (e.g. 2 hours) to provide chemical stabilisation. This process increases the solubility and mechanical strength of the biopolymer.

[0041] - Cutting and Shaping: The dried nanofibre material is cut and shaped to fit the anatomy and dimensions of the foot, toes, and heel. Ergonomic form is achieved using special moulds. At this stage, a low-temperature (30-35°C) thermoforming process is carried out in 3D moulding machines to obtain an ergonomic form.

[0042] - Sterilisation and Packaging: Products are sterilised using an appropriate sterilisation method (e.g., 15 minutes of exposure to UV light) to reduce the risk of infection. Sterilised products are packaged in airtight, user-friendly packaging.

[0043] The final product is optimised according to the area of use so that the moisture desorption rate is < 10 minutes from 95% humidity to 10% humidity, it has a tensile strength of 3-7 MPa, an air permeability value of at least 10-15 mL / cm2 / s, and a service life of at least 3 months.

Claims

CLAIMS1. A dual-layer nanofibre diabetic toe / heel / foot protective galosh with antimicrobial / antifungal properties, wound-healing properties, soft, ergonomic, porous, breathable, low moisture retention capacity, high air and water vapour permeability, characterised by; bio-thermoplastic polyurethane (TPU), chitosan, aloe vera and pine turpentine, thyme, eucalyptus, mint, lavender, cinnamon, lemon, rosemary, sage containing at least one of the following plant essential oils.

2. It is an antimicrobial / antifungal, wound-healing, soft, ergonomic, porous, breathable, low moisture retention, high air and water vapour permeability, double-layered nanofibre diabetic toe / heel / foot protective galosh production method, characterised by;- Dissolving bio-based thermoplastic polyurethane (TPU) in a solvent at a concentration range of 10-15%,- Homogenising the mixture in a magnetic stirrer at 400-600 rpm for 4-6 hours,- Dissolving chitosan in a 2-10% concentration in a 1 -2% (v / v) acetic acid solution,- Adding 1 -5% aloe vera extract to the chitosan mixture,- Afterwards, adding at least one of the following plant essential oils to the chitosan-aloe vera mixture: pine turpentine, thyme, eucalyptus, mint, lavender, cinnamon, lemon, rosemary, and sage,- Stirring the prepared solution in a magnetic stirrer at 400-800 rpm for 4- 6 hours,- To increase the mechanical and chemical resistance of the chitosan- based top layer, adding at least one of the cross-linking agents glutaraldehyde and epichlorohydrin to the polymeric solution to ensure the formation of a three-dimensional matrix,- Placing the TPU solution in the electrospinning device for the electrospinning process,- Conducting the electrospinning process at 30-40% relative humidity and 25°C temperature,- Adjusting the thickness of the bottom layer to 250-500 pm depending on the application,- Applying the chitosan-aloe vera-plant essential oil solution onto the TPU layer in the electrospinning device,- Performing a second electrospinning process to create a doublelayered structure,- Adjusting the top layer thickness to 150-250 pm depending on the application,- Drying the resulting double-layered nanofibre structure in a vacuum oven at 40-60°C,- Cutting and shaping the dried nanofibre material to fit the anatomy and dimensions of the foot, toes, and heel,- Performing thermoforming at 30-35°C in 3D moulding machines to achieve an ergonomic form,- Sterilising the products under UV light for 15 minutes,- packaging the sterilised products in airtight, user-friendly packaging.