Description:FORM 2

THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENT RULES, 2003

COMPLETE SPECIFICATION

(See Section 10 and Rule 13)

Title of invention:
AN AQUEOUS WOUND HEALING TOPICAL GEL FORMULATION AND METHOD

APPLICANT:
DOCUSES HEALTHCARE INDIA PRIVATE LIMITED
An Indian entity having address as,
408, The Lenora. Opp St Thomas School, New Citylight Road, Surat,Gujarat, 395007, India

The following specification particularly describes the invention and the manner in which it is to be performed.

CROSS-REFERENCE TO RELATED APPLICATIONS AND PRIORITY
The present application does not claim priority from any other patent application.

TECHNICAL FIELD
The present subject matter described herein, in general, relates to a field of a wound healing formulations, and more particularly relates to aqueous wound healing gel formulations and process for various applications, including pharmaceuticals and wound care.

BACKGROUND
A wound is any damage or break in the skin or underlying tissues, often resulting from an injury, trauma, surgery, or medical conditions. Wounds can vary widely in severity, depth, and cause, influencing how they are treated and how long they take to heal. They are generally classified into two main types such as acute wounds and chronic wounds.
Acute wounds include injuries such as cuts, burns, surgical incisions, and abrasions that typically follow a predictable healing process, moving through stages of inflammation, tissue formation, and remodelling until the wound is fully closed. These wounds generally heal within a few weeks without complications if properly managed.
In contrast, chronic wounds fail to progress through the normal stages of healing and remain open for prolonged periods, often over two to three months. These include pressure ulcers, diabetic foot ulcers, venous leg ulcers, and non-healing surgical wounds. Chronic wounds are often associated with underlying health conditions like diabetes, poor circulation, or compromised immune function, making them more challenging to treat. Proper wound care, tailored to the type and stage of the wound, is critical to promoting healing and preventing complications such as infection.
Chronic and non-healing wounds present a complex challenge for both healthcare practitioners and patients, as they deviate from the typical healing trajectory of acute wounds. While acute wounds proceed through a predictable series of stages beginning with inflammation, followed by tissue formation and eventual remodelling chronic wounds become stalled at one of these stages, often failing to progress or fully close. This stagnation can be attributed to various factors such as inadequate blood flow, persistent inflammation, infection, or underlying conditions like diabetes, venous insufficiency, or immobility.
As a result, chronic wounds like pressure ulcers, diabetic foot ulcers, venous leg ulcers, and non-healing surgical wounds remain open for extended periods, leading to sustained pain, increased risk of infection, and overall reduced quality of life for patients. Additionally, these wounds pose a significant economic burden, driving up healthcare costs due to prolonged treatment, frequent medical visits, and the need for specialized care.
The management of chronic wounds requires a multifaceted approach, addressing factors like infection control, moisture balance, and support for tissue regeneration. However, despite the availability of various wound care products, achieving consistent and effective outcomes remains a major challenge, making chronic wound management a critical area of focus in healthcare.
Current treatment options for chronic and non-healing wounds are often fragmented, requiring multiple products and approaches to address the various aspects of the wound healing process. Each stage of wound care presents unique challenges, and as such, different products are specialized for specific functions. For example, some products are aimed at haemostasis, helping to quickly stop bleeding in acute or freshly opened wounds, while others focus on debridement, the removal of necrotic or dead tissue to create a healthier wound bed that can better support healing.
In addition, maintaining the moisture balance of the wound is crucial; wounds that are too dry or too moist can delay healing, so specialized dressings are used to keep the environment optimal. Infection control is another critical aspect, with antimicrobial dressings or topical agents being used to prevent or treat infections that can severely hinder healing.
Also, the wound bed often requires nutritional support, including topical applications that provide growth factors or essential nutrients that promote cellular activity and repair. For wounds that are slow to close, products that manage inflammation and promote tissue proliferation help encourage new tissue growth. As the wound begins to heal, other products aid in re-epithelization, supporting the growth of new skin cells to close the wound surface.
Additionally, products are often used to minimize scarring, which can be particularly important for wounds in visible or sensitive areas. However, despite the availability of these products, the need for separate solutions means that wound care is a complex, time-consuming, and often costly process, with the potential for inconsistent outcomes due to variations in how products are applied and how different wounds respond to treatment.
Therefore, there has always been a long-standing need to develop a cost-effective and economically feasible gel formulation and the process for preparing the formulation that accelerates healing time and minimizes the reliance on multiple products.
SUMMARY
Before the present system and its components are described, it is to be understood that this disclosure is not limited to the particular system and its arrangement as described, as there can be multiple possible embodiments which are not expressly illustrated in the present disclosure. It is also to be understood that the terminology used in the description is for the purpose of describing the particular versions or embodiments only and is not intended to limit the scope of the present application. This summary is not intended to identify essential features of the claimed subject matter nor is it intended for use in detecting or limiting the scope of the claimed subject matter.
As disclosed herein, the present subject matter relates to an aqueous wound healing formulation (hereinafter may be alternatively referred to as ‘gel formulation’ or ‘formulation’) and a method of production of aqueous wound healing formulation.

In one implementation, an aqueous wound healing formulation is disclosed. The formulation may comprise of a biodegradable polymer a biodegradable polymer in an amount of about 0.5 wt % to about 0.10 wt % based on the total weight of the formulation, wherein the biodegradable polymer is collagen. The formulation may comprise nano silver particulates having particle size of 1 to100 nm in an amount of about 0.0010 to 0.0030 % w/w based on the total weight of the formulation. Further, the formulation may comprise a vitamin as an antioxidant in an amount of about 0.10 to 0.30 %w/w based on the total weight of the formulation. The formulation may comprise a chelating agent in an amount of about 0.10 to 0.30 %w/w based on the total weight of the formulation. Additionally, the formulation may comprise a polymer in an amount of 0.5 to 1.5 % w/w based on the total weight of the formulation.
In one implementation, a method of production of an aqueous wound healing formulation is disclosed. The process may comprise dissolving a polymer in a solvent to form a gel matrix. The process may comprise adding an antioxidant such as a vitamin, a chelating agent, a nano silver particle, and at least biodegradable polymer such as collagen to the gel matrix. The process may comprise adding one or more additives selected from the group consisting of emulsifiers, polymers, and excipients to the gel matrix to obtain a mixture. Further, process may comprise mixing the mixture to achieve homogeneity. Furthermore, process may comprise adding sodium hydroxide (NaOH) to the mixture to maintain the pH and obtain the aqueous wound healing formulation.

BRIEF DESCRIPTION OF FIGURES
The detailed description is described with reference to the accompanying Figures. In the Figures, the left-most digit(s) of a reference number identifies the Figure in which the reference number first appears. The same numbers are used throughout the drawings to refer like features and components.

Figure 1 depicts the test results of pre and post application of an aqueous wound healing gel formulation (Referring to example 1).

Figure 2 depicts the test results of diabetic foot ulcer (DLU), post using an aqueous wound healing gel formulation after 14 days and post-treatment after 28 days (Referring to example 3).

Figure 3 depicts (300) a method for production of an aqueous wound healing formulation.

DETAILED DESCRIPTION
Reference throughout the specification to “various embodiments,” “some embodiments,” “one embodiment,” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, appearances of the phrases “in various embodiments,” “in some embodiments,” “in one embodiment,” or “in an embodiment” in places throughout the specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner in one or more embodiments.
The words “comprising”, “having”, “containing”, and “including”, and other forms thereof are intended to be equivalent in meaning and be open-ended in that an item or items following any one of these words is not meant to be exhaustive listing of such item or items or meant to be limited to only the listed item or items. It must also be noted that the singular forms “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise. Although any methods similar or equivalent to those described herein may be used in the practice or testing of embodiments of the present disclosure, the exemplary methods are described. The disclosed embodiments are merely exemplary of the disclosure, which may be embodied in various forms.
Various modifications to the embodiment may be readily apparent to those skilled in the art and the generic principles herein may be applied to other embodiments. However, a skilled person in the art may readily recognize that the present disclosure is not intended to be limited to the embodiments illustrated but is to be accorded the widest scope consistent with the principles and features described herein. A detailed description of the invention will be described hereinafter.
The embodiments, examples and alternatives of the preceding paragraphs or the description and drawings, including any of their various aspects or respective individual features, may be taken independently or in any combination. Features described in connection with one embodiment are applicable to all embodiments, unless such features are incompatible.
The embodiments, examples and alternatives of the preceding paragraphs or the description and drawings, including any of their various aspects or respective individual features, may be taken independently or in any combination. Features described in connection with one embodiment are applicable to all embodiments, unless such features are incompatible.
The present disclosure relates to an aqueous wound healing formulation and a method (300) of production of an aqueous wound healing formulation is disclosed. The formulation may be a gel formulation. The method overcomes the major drawback of inability to effectively manage both infection control and tissue regeneration simultaneously, often resulting in compromised healing or the need for frequent dressing changes.
Referring to Figure 3, the disclosed method (300) overcomes said drawbacks by integrating nano silver particles, collagen, the chelating agent such as disodium ethylenediamine tetra acetic acid (EDTA), and a vitamin as an antioxidant component into a stable gel matrix. This formulation ensures a sustained release of active components, providing continuous antimicrobial activity, protecting growth factors from enzymatic degradation, and maintaining a moist microenvironment conducive to healing. Additionally, the gel's ability to control pH levels and maintain optimal consistency enhances its absorption at the wound bed, promoting faster and more efficient tissue regeneration while minimizing the risk of cytotoxicity.
In one embodiment of the present disclosure, the aqueous wound healing formulation is disclosed. This formulation is water-based topical gel formulation, ensuring optimal hydration of the wound site while facilitating a moist environment conducive to tissue repair. The formulation can be administered for healing a deep cut by cicatrisation, granulation, deep wound healing, and tissue regeneration, reparative healing, and restoration. The formulation can be administered for but not limited to deep would healing, topical would healing, wound dressing, and diabetic ulcer wound dressing.
It combines one or more active ingredients with soothing and anti-inflammatory properties, aimed at reducing pain, swelling, and the risk of infection. The gel's consistency ensures easy application, creating a protective barrier over the wound that helps prevent contamination while allowing the skin to breathe. This formulation is particularly effective for various wound types, including minor cuts, abrasions, diabetic ulcers and surgical incisions, offering a promising solution for both clinical and home-based wound management.
In an embodiment, the aqueous wound healing formulation comprises of a biodegradable polymer, such that the biodegradable polymer is collagen. Collagen, a natural protein known for its biocompatibility and regenerative properties, plays a critical role in promoting wound healing. By incorporating collagen into the gel, the formulation aids in supporting cellular growth and migration, which are essential for tissue repair and regeneration. The biodegradable nature of collagen ensures that it gradually breaks down as the new tissue forms, minimizing the need for manual removal and reducing the risk of irritation.
In an embodiment, the collagen is selected from collagen I, collagen III or a combination thereof. Collagen I and III are essential structural proteins naturally found in the skin and connective tissues, playing a pivotal role in the wound healing process. Collagen I provides strength and structure, while collagen III offers flexibility and is particularly abundant during the early stages of wound repair.
In an embodiment, the collagen I is a bovine collagen type- I which is used in the range of 1.0 to 3.0 % w/w. Preferably, the bovine collagen type- I is used in the range of 1.5 to 2.5 % w/w. More preferably, the bovine collagen type- I is used in the range of 1.8 to 2.2 % w/w based on the total weight of the formulation.
In another embodiment, the collagen III is used in an amount of about 0.001 wt% to about 0.50 wt% based on the total weight of the formulation. Preferably, the collagen is used in an amount of about 0.01 wt% to about 0.20 wt%. More preferably, the collagen is used in an amount of 0.5 wt % to 0.10 wt % based on the total weight of the formulation.
Incorporating these types of collagen into the formulation provides a scaffold that supports cellular adhesion, proliferation, and migration, which are crucial for tissue regeneration. The combination of the collagen I and the collagen III can mimic the natural extracellular matrix more closely, offering a balanced environment that promotes the formation of new tissue and accelerates the repair of damaged skin. This delivery matrix is designed to be gradually absorbed by the body as the wound heals, providing continuous support throughout the healing process while reducing the need for frequent reapplication.
In an embodiment, the aqueous wound healing formulation comprises of nano silver particulates. Nano silver, known for its broad-spectrum antimicrobial activity, targets a wide range of bacteria, fungi, and viruses. The small size of the nano silver particles allows them to penetrate bacterial cell walls more effectively, disrupting their cellular function and inhibiting their growth. When incorporated into the gel, these nano silver particulates create a protective layer over the wound, reducing the risk of contamination while promoting a sterile environment for healing. Additionally, the controlled release of silver ions from the nanoparticles ensures prolonged antimicrobial activity without causing significant cytotoxicity to healthy cells.
In another embodiment, the silver nano particulates having particle size of 1 to 500 nm. Preferably, the silver nano particulates having particle size of 1 to 300 nm. More preferably, the silver nano particulates having particle size of 1 to 100 nm.
In yet another embodiment, the silver nano particulates are present in an amount of about 0.0010 to 0.0030 % w/w of the formulation. Preferably, the silver nano particulates are present in an amount of about 0.0015 to 0.0025 % w/w of the formulation. More preferably, the silver nano particulates are present in an amount of 0.0018 to0.0022 %w/w based on the total weight of the formulation.
In an embodiment, the aqueous wound healing formulation comprises of a vitamin as an antioxidant. Oxidative stress can occur during the inflammatory phase of wound healing, leading to an imbalance between free radicals and antioxidants, which can damage cells and delay recovery. Incorporating an antioxidant vitamin, such as vitamin C (3-O- ethyl ascorbic acid), into the gel helps neutralize these free radicals, reducing inflammation and protecting the surrounding healthy cells.
For instance, vitamin C, plays a vital role in collagen synthesis, enhancing the structural integrity of new tissue. The presence of one or more vitamin in the formulation supports a more balanced healing environment, minimizing cell damage and fostering a quicker, more efficient recovery process. Additionally, the gel's antioxidant properties help reduce scarring and promote smoother skin regeneration, making it an effective choice for a variety of wound types.
In another embodiment, the aqueous wound healing formulation comprises of a vitamin as an antioxidant in an amount of about 0.10 to 0.30 %w/w based on total weight of the formulation. Preferably, the antioxidant such as vitamin is used in an amount 0.15 to 0.25 % w/w based on total weight of the formulation. More preferably, the antioxidant such as vitamin is used in an amount 0.18 to 0.22 %w/w based on total weight of the formulation.
In an embodiment, the aqueous wound healing formulation comprises of a chelating agent selected from at least one of capryl hydroxamic acid, citric acid, gluconolactone, kojic acid, lactobionic acid, tetra-hydroxypropyl ethylenediamine, phytic acid, and disodium ethylenediamine tetra acetic acid (EDTA). Preferably, the chelating agent is disodium EDTA.
In a related embodiment, the disodium EDTA works by binding to metal ions such as calcium, magnesium, and iron, which are often present in wound environments and can promote bacterial growth or biofilm formation. By isolating these metal ions, disodium EDTA disrupts bacterial cell walls and weakens the structure of biofilms, making microorganisms more susceptible to antimicrobial agents within the gel formulation.
This helps to maintain a cleaner wound environment, reducing the risk of infection and promoting faster healing. Additionally, disodium EDTA can aid in reducing oxidative stress by chelating iron ions, which can catalyse the formation of harmful free radicals. Its inclusion in the formulation ensures a more controlled and sterile environment, supporting the natural healing process while also enhancing the effectiveness of other active ingredients.
In another embodiment, the aqueous wound healing formulation comprises of disodium EDTA as a chelating agent in an amount of about 0.10 to 0.30 %w/w based on total weight of the formulation. Preferably, the EDTA is used in an amount 0.15 to 0.25 % w/w based on total weight of the formulation. More preferably, the disodium EDTA is used in an amount 0.18 to 0.22 %w/w based on total weight of the formulation.
Disodium EDTA is used as a chelating agent due to its ability to sequester metal ions, which has important applications across pharmaceutical, food, and medical industries. Disodium EDTA’s safety profile is well-established, with proven efficacy across a range of doses, including for pediatric use. Clinicians employ disodium EDTA to treat various conditions, such as arsenic poisoning and cardiovascular diseases, by binding and removing toxic metals from the body.
In microbiology, disodium EDTA’s role as a cation chelator helps destabilize the outer membrane of Gram-negative bacteria, enhancing the effectiveness of antimicrobials, including nano-silver and systemic antibiotics. By sequestering essential cations, disodium EDTA weakens the biofilm matrix, promoting bacterial detachment and making bacteria more susceptible to antimicrobial agents. It has shown efficacy in reducing the resistance of multi-drug-resistant (MDR) bacterial strains, even at sub-minimal inhibitory concentrations (sub-MIC), by inhibiting efflux pump genes like acrA and acrB in E. coli and K. pneumoniae, and mexA, mexB, and oprM in P. aeruginosa, which are essential for biofilm development.
Furthermore, disodium EDTA acts as an efflux pump inhibitor, reducing biofilm formation, while its chelating properties, when combined with Vitamin C, enhance antioxidant effects, making it a valuable agent for both antimicrobial and biofilm-targeted therapies.
In another embodiment, the polymer may be selected from at least one of hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), polyethylene glycol (PEG), alginate, xanthan gum, gelatin, polyvinyl alcohol (PVA), carbomer and chitosan. The incorporation of these diverse polymers in the aqueous wound healing formulation enhances stability, texture, and the delivery of active ingredients, ultimately improving therapeutic effects and the overall user experience. Preferably, the polymer is a carbomer.
In a related embodiment, the carbomer is used in the range of 0.5 to 1.5 % w/w. Preferably, the carbomer is used in the range of 0.8 to 1.2 % w/w. More preferably, the carbomer is used in the range of 0.9 to 1.1 % w/w based on the total weight of the formulation.
In an embodiment, the aqueous wound healing formulation comprises of one or more additives such as excipients which play essential roles in enhancing the gel's stability, consistency, and overall effectiveness. Polymers contribute to the gel's viscosity and rheological properties, enabling it to maintain its form while providing a protective barrier over the wound. They also can enhance the controlled release of active ingredients, ensuring sustained therapeutic effects.
Additionally, excipients such as preservatives, stabilizers, and pH adjusters are included to maintain the formulation's integrity, prolong shelf life, and ensure compatibility with the skin. By carefully selecting and optimizing these additives, the formulation achieves a balanced combination of therapeutic efficacy, user-friendliness, and stability, making it a comprehensive solution for effective wound management.
In yet another embodiment, the excipients may be selected from at least one of fragrance, pH adjuster, solvent, humectant, preservative, stabilizer or a combination thereof.
In an embodiment, the fragrance is often included to enhance the sensory experience of the product, providing a pleasant scent that can improve user compliance.
In a related embodiment, the fragrance is used in the range of 0.10 to 0.30 % w/w. Preferably, the fragrance is used in the range of 0.15 to 0.25 % w/w. More preferably, the fragrance is used in the range of 0.18 to 0.22 % w/w based on the total weight of the formulation.
In an embodiment, the pH adjuster is selected from at least one of potassium hydroxide (KOH), triethanolamine (TEA), citric acid, lactic acid, sodium citrate, phosphoric acid, ammonium hydroxide and sodium hydroxide (NaOH). Preferably, the pH adjuster is sodium hydroxide which helps to maintain the gel's stability and compatibility with the skin.
In a related embodiment, the pH adjuster is used in the range of 0.10 to 0.30 %w/w. Preferably, the pH adjuster is used in the range of 0.15 to 0.25 %w/w. More preferably, pH adjuster is used in the range of 0.18 to 0.22 %w/w based on the total weight of the formulation.
In an embodiment, the solvent is selected from at least one of ethanol, isopropyl alcohol, pentylene glycol, dimethyl sulfoxide (DMSO), and polysorbate 20. Preferably, the solvent is polysorbate 20.
In a related embodiment, the solvent is added in the range of 0.3 to 0.7 % w/w. Preferably, the solvent is added in the range of 0.4 to 0.6 % w/w. More preferably, the solvent is added in the range of 0.45 to 0.55 % w/w based on the total weight of the formulation.
Demineralised water is added as an excipient which ensures that other ingredients are effectively dissolved and evenly distributed throughout the formulation.
In a related embodiment, the demineralised water is used in the range of 50 to 100 % w/w. Preferably, the demineralised water is used in the range of 75 to 100 % w/w. More preferably, the demineralised water is used in the range of 81 to 99 % w/w based on the total weight of the formulation.
In an embodiment, the humectant is selected from at least one of butylene glycol, sorbitol, hyaluronic acid, glycerine and propylene glycol. Preferably, propylene glycol is a powerful humectant, draws moisture into the skin, promoting hydration and maintaining a moist environment conducive to wound healing.
In a related embodiment, the propylene glycol is used in the range of 3.5 to 5.5 % w/w. Preferably, the propylene glycol is used in the range of 4.0 to 5.0 % w/w. More preferably, the propylene glycol is used in the range of 4.05 to 4.95 % w/w based on the total weight of the formulation.
In an embodiment, the preservative is selected from at least one of chlorhexidine gluconate, benzalkonium chloride, sodium benzoate, methylparaben and propylparaben, benzyl alcohol, sorbic acid (and potassium sorbate), silver citrat, ethylhexylglycerin, caprylyl glycol, iodopropynyl butylcarbamate (IPBC) and phenoxyethanol & triethylene glycol. Preferably, the preservative is phenoxyethanol & triethylene glycol.
In a related embodiment, the phenoxyethanol & triethylene glycol is used in the range of 0.5 to 1.5 % w/w. Preferably, the phenoxyethanol & triethylene glycol is used in the range of 0.8 to 1.2 % w/w. More preferably, the phenoxyethanol & triethylene glycol is used in the range of 0.9 to 1.1 % w/w based on the total weight of the formulation.
In an embodiment, the stabilizer may be selected from at least one of sodium bisulphate, propyl gallate, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) and sodium metabisulphite. Preferably, the stabilizer is sodium metabisulphite.
In a related embodiment, the sodium metabisulphite is used in the range of 0.10 to 0.30 %w/w. Preferably, sodium metabisulphite is used in the range of 0.15 to 0.25 %w/w. More preferably, sodium metabisulphite is used in the range of 0.18 to 0.22 %w/w based on the total weight of the formulation.
In an embodiment, the viscosity of the aqueous wound healing formulation ranges between 20,000 to 50,000 cps. Preferably, the viscosity of the aqueous wound healing formulation range between 10,000 to 80,000 cps. More preferably, the viscosity of the aqueous wound healing formulation range between 28000 to 36000 cps.

The viscosity provides the formulation with a desirable thickness, allowing it to adhere effectively to the wound site without running or dripping, thereby maintaining a protective barrier against external contaminants. A viscosity within this range also facilitates the controlled release of active ingredients, ensuring that they are delivered to the affected area gradually over time.

Additionally, the gel’s viscosity contributes to a soothing, moisturizing effect, enhancing user comfort during application of the aqueous wound healing formulation. The balance achieved in this viscosity range ensures that the gel is not only easy to spread but also provides sufficient coverage, supporting the healing process by maintaining a moist environment that is conducive to tissue regeneration. Ultimately, the viscosity of the formulation plays a pivotal role in its efficacy, usability, and overall therapeutic success in wound care management.

In an embodiment, the pH of the aqueous wound healing formulation ranges from 3.50 to 8.00. Preferably, the pH of the formulation ranges from 4.50 to 7.00. More preferably, the pH of the formulation ranges from 5.30 to 6.50.

This slightly acidic pH range closely mimics the natural pH of human skin, which typically falls between 4.5 and 6.5, thereby minimizing the risk of irritation and allergic reactions upon application. Maintaining a pH within this range also enhances the stability of active ingredients in the formulation, ensuring that they retain their efficacy over time.

Furthermore, the pH range of 5.30 to 6.50 supports the optimal function of enzymes and biological processes involved in wound healing, such as collagen synthesis and cell proliferation. By creating an environment that is conducive to the skin's natural healing mechanisms, this pH range contributes to a more effective and comfortable user experience, facilitating faster recovery and improved overall outcomes in wound care.

In an embodiment, the bulk density of the aqueous wound healing formulation ranges between 0.900 to 1.200. Preferably, the bulk density of the aqueous wound healing formulation ranges between 0.950 to 1.100. More preferably, the bulk density of the aqueous gel formulation ranges between 0.996 to 1.050.

The bulk density of the aqueous wound healing formulation is a critical parameter that influences its performance, stability, and application characteristics. It is defined as the mass of the gel divided by its volume, including both the solid and void spaces within the formulation. A well-formulated aqueous gel typically maintains a balance between the gel's components, including active ingredients, polymers, and excipients.

The bulk density affects the gel's viscosity and its ability to spread evenly over the skin, which is essential for effective wound coverage and healing. A higher bulk density may indicate a more concentrated formulation, potentially leading to enhanced efficacy, while a lower density could suggest a lighter gel that might be easier to apply but may require more frequent applications. Controlling the bulk density of the gel formulation ensures that it meets the desired therapeutic and aesthetic criteria, providing optimal benefits for wound management and user satisfaction.

In one embodiment, a method (300) for production of an aqueous wound healing formulation is disclosed comprising the following steps.

The method may comprise dissolving (301) a polymer in a solvent to form a gel matrix.
This method begins by selecting an appropriate polymer, such as carbomer, known for its exceptional thickening and stabilizing properties. Carbomer is a high molecular weight polymer that, when introduced to a solvent like deionized water, swells and disperses to create a viscous gel. The dissolution process typically requires gentle agitation to ensure even hydration and prevent clumping, which can compromise the consistency of the gel. As the carbomer absorbs water, it forms a gel matrix that provides the structure and stability necessary for the formulation.

The gel matrix not only serves as a vehicle for the active ingredients allowing for their uniform distribution but also enhances the overall performance of the gel by improving its application properties, such as spread ability and adhesion to the skin. Furthermore, the pH of the solution may need to be adjusted, to achieve the desired viscosity and ensure that the gel maintains its integrity over time.

The method further comprises a step of adding (302) an antioxidant, a chelating agent, a nano silver particle, and a biodegradable polymer to the gel matrix. This step is crucial for enhancing the therapeutic efficacy and stability of the aqueous gel formulation. The incorporation of antioxidants, such as vitamin C, helps to neutralize free radicals that can damage skin cells and impede the healing process, thereby promoting overall skin health and recovery. EDTA serves as a chelating agent, binding to metal ions that could catalyse oxidative reactions, thus further protecting the integrity of the formulation and its active ingredients.

The addition of nano silver particles provides antimicrobial properties, effectively reducing the risk of infection at the wound site while facilitating faster healing through their bactericidal action. Moreover, incorporating a biodegradable polymer such as collagen not only contributes to the structural integrity of the gel but also enhances its biocompatibility and promotes cell proliferation, essential for tissue regeneration. Together, these components work synergistically within the gel matrix to create a multifunctional wound healing formulation that addresses various aspects of skin repair, offering a protective, nourishing, and healing environment for optimal recovery.

In another embodiment, the method may comprise a step of adding (303) one or more additives selected from the group consisting of emulsifiers, polymers, and excipients to the gel matrix to obtain a mixture. This step is essential for optimizing the formulation's properties and enhancing its performance. Emulsifiers, such as polysorbates or lecithin, facilitate the integration of oil and water phases, ensuring a stable and homogenous gel that enhances the delivery of active ingredients. The incorporation of additional polymers can further modify the viscosity and texture of the gel, allowing for tailored consistency and enhancing user experience during application.

Moreover, the inclusion of excipients such as preservatives, pH adjusters, or humectants contributes to the overall stability and shelf-life of the formulation. Preservatives inhibit microbial growth, ensuring the gel remains safe for use over time, while pH adjusters help maintain the optimal acidity level for skin compatibility. Humectants, like polyethylene glycol, attract moisture to the skin, improving hydration and comfort. By carefully selecting and adding these additives to the gel matrix, the resulting mixture not only meets the desired therapeutic efficacy but also provides enhanced sensory attributes, ensuring a user-friendly and effective topical product suitable for various wound care applications.

Furthermore, the method may comprise a step of (304) mixing the above mixture to at a temperature between 10°C and 50°C. Preferably the temperature is in the range of 15°C and 45°C. More preferably the temperature is in the range of 20°C and 40°C. The temperature range is to maintain the stability of the nano silver particles and achieve homogeneity. Mixing within this controlled temperature range helps to prevent potential agglomeration or degradation of the nano silver particles, which could occur at higher temperatures, thereby preserving their effectiveness in promoting wound healing. Additionally, maintaining a consistent temperature during mixing aids in achieving a uniform viscosity and texture, allowing for better dispersion of the particles throughout the gel matrix.

The gentle heat also promotes the dissolution of any solid ingredients, ensuring a smooth and homogenous formulation. By adhering to this temperature control during the mixing process, the final aqueous wound healing gel not only exhibits enhanced stability and performance but also ensures that the therapeutic benefits of the nano silver particles are maximized, resulting in a product that is both effective and user-friendly.

Additionally, the method may comprise a step of adding (305) sodium hydroxide (NaOH) to the mixture to maintain the pH and obtain the aqueous wound healing formulation.

As the pH of the gel plays a significant role in its stability, effectiveness, and compatibility with the skin. Sodium hydroxide serves as a pH adjuster, allowing formulators to fine-tune the acidity or alkalinity of the gel to ensure it falls within the optimal range for skin health, typically between 4.5 and 7.0. By carefully controlling the pH, the formulation can enhance the stability of active ingredients, ensuring they remain effective throughout the product’s shelf life.

Furthermore, maintaining the correct pH is essential for preventing skin irritation and promoting an environment conducive to wound healing, as certain pH levels can influence cellular activities such as collagen synthesis and cell migration. The addition of NaOH must be done gradually and with continuous mixing to prevent overshooting the desired pH level, ensuring that the final formulation is both safe and effective for topical and would dressing application. Ultimately, this careful adjustment leads to a well-balanced aqueous wound healing formulation that meets both therapeutic objectives and user comfort.

Examples are set forth below to further illustrate the nature of the invention and the manner of carrying it out. However, the invention should not be considered as being limited to the details thereof.
Examples:
Example 1: Preparation of the aqueous wound healing gel formulation
The preparation of the aqueous wound healing gel formulations begins with the preparation of a gel matrix by dissolving 1% Carbomer in 100 mL of deionized water under constant stirring at room temperature (25°C) until it is fully hydrated. Once dissolved, the gel is allowed to swell for at least 30 minutes to ensure optimal consistency. The active ingredients are then added to the gel matrix to create different formulations:
Formulation A includes 0.1% Nano Silver and 0.5% Collagen, which are mixed until homogeneous using a double contra mixture;
Formulation B combines 0.1% Nano Silver, 0.5% Collagen, and 0.5% Vitamin C; Formulation C consists of 0.1% Nano Silver, 0.5% Collagen, and 0.1% EDTA; and
Formulation D integrates all previous components with the addition of both 0.5% Vitamin C and 0.1% EDTA.
Following the incorporation of active ingredients, the pH of each formulation is adjusted to the optimal range of 5.5 to 6.5 using diluted sodium hydroxide (NaOH) to ensure skin compatibility. The prepared formulations are then stored at 1 to 30°C until use. Also, the prepared formulation has a shelf life of 20 to 40 months. Additionally, a control gel is prepared without any active ingredients, following the same steps as the active formulations. The experimental design involves applying each formulation topically to full-thickness skin wounds such as a diabetic leg of a subject (with informed consent for clinical study) once daily for 10 days, with wound area measurements taken on Days 0, 5, and 10 using digital planimetry to evaluate the efficacy of the formulations in promoting wound healing.

Table 1: The following table illustrates the impact of the formulations having different percentage of components showing healing results: (Refer figure 1)
Formulation Day 0
(wound area cm2) Day 5
(wound area cm2) Day 10
(wound area cm2) % healing Observations
Formulation A 10.0 7.8 5.5 45% Reduced inflammation; noticeable healing.
Formulation B 10.0 6.0 3.0 70% Significant healing; reduced scarring
Formulation C 10.0 7.0 4.0 60% Good healing; less redness and swelling.
Formulation D 10.0 4.5 1.5 85% Rapid healing; minimal scarring; optimal recovery.

Table 2: The below table illustrates the impact of bulk density of the aqueous wound healing gel formulation and its performance

Formulations Bulk density Texture Ease of application Retention on wound site Performance
Formulation A 0.950 g/mL Light, slightly airy Good spread ability Dries out quickly Not ideal, dries too quickly
Formulation B 1.000 g/mL Smooth, balanced Good spread ability Retains moisture well Good Performance
Formulation C 1.020 g/mL Smooth, slightly dense Good spread ability Good moisture retention Good Performance
Formulation D 1.100 g/mL Thick, denser Harder to spread Long-lasting protection Less ideal, harder to apply

This table highlights how the formulations with a bulk density close to 1.000 to 1.050 g/mL offer the best performance for wound healing applications, balancing ease of use and prolonged effectiveness.

Table 3: The below table illustrates the impact of pH on the healing performance of the aqueous wound healing gel formulation
Formulations pH Skin compatibility healing Irritation potential
Formulation A 4.50 Slightly acidic Good antimicrobial environment Higher irritation
Formulation B 5.80 Closest to skin’s natural pH Optimal healing environment Low irritation
Formulation C 6.30 Slightly above skin’s pH Promotes cellular repair Low irritation
Formulation D 7.50 Alkaline Slow healing processes Low irritation

This table emphasizes that the formulations with pH values in the range of 5.30 to 6.50 (such as Formulations B and C) are the most effective for wound healing, providing a balance between comfort and optimal healing conditions.

Example 2: Particle Size Test
The particle size distribution of the nano silver particulates in the aqueous wound healing gel formulation was analysed using a dynamic light scattering (DLS) method. A sample of the gel was diluted with deionized water and subjected to DLS analysis. The results indicated that the majority of the nano silver particles were within the size range of 10 to 50 nm, with an average particle size of 30 nm. Additionally, the polydispersity index (PDI) (PDI is a measure used to assess the distribution of molecular mass or particle size in a given sample) was calculated to be 0.2, indicating a narrow size distribution and uniformity of the particle size. These findings confirm that the nano silver particulates are well within the desired size range of 1 to 100 nm, which is crucial for their effective antimicrobial action and integration into the gel matrix.

Example 3: Case study: Effective reduction of a chronic diabetic foot ulcer using nano silver, vitamin C, and collagen in the formulation (refer figure 2)
Chronic diabetic foot ulcers (DFUs) are a common complication in diabetic subject, often leading to severe infections, delayed healing, and increased risk of amputation.
Table 4: Illustrates the subject patient information (with consent)
Parameter Details
Age 67 years
Gender Male
Lifestyle Non-smoker; occasional alcohol use
Medical history Diabetes Mellitus, Hypertension, Chronic Kidney Disease (currently on dialysis)
Family history No family history
Weight 60 kg

Table 5: Illustrates the wound characteristics (with consent)
Parameter Description
Location Left heel
Tissue type Necrotic (black/brown), infected, sloughy
Wound edges Maceration, dehydration, undermining, rolled edges, oedema
Exudate levels Low

Table 6: Illustrates the pathological findings of the patient
Renal function tests:
Investigation Result Unit Reference Range
Blood urea 66.4 mg/dl 16.6 to 48.5
Blood urea nitrogen 31.0 mg/dl 8 to 23
Serum Creatinine 5.23 mg/dl 0.7 to 1.4
Uric acid 4.6 mg/dl 3.4 to 7.0
Sodium (Na) 131.7 mmol/L 135 to 150
Potassium (K) 5.3 mmol/L 3.5 to 5.0
Chlorides (Cl) 107.6 mmol/L 94 to 110

Table 7: Illustrates the complete blood count of the patient
Investigation Result Unit Reference
Haemoglobin (Hb) 9 g/dL 13.8 to 17.2
Total Leucocyte (WBC) Count 9490 cells/ µL 4,000 to 11,000

Wound Assessment
• Severe diabetic foot ulcers with tissue necrosis and infection,
• Low exudation and partially dry wound,
• Presence of yellowish slough and necrotic tissue requiring debridement.
• Delayed healing with discoloured peri-wound area, inflammation, and swelling,
• Presence of yellowish slough/pus indicates ongoing infection and poor wound healing, and
• Discoloured peri-wound area shows signs of inflammation, including swelling and potential tissue breakdown.
Diagnosis:
The patient presented with a chronic, severe diabetic foot ulcer characterized by necrotic and sloughy tissue, signs of infection, and delayed healing.

Treatment challenges:
The patient presented multiple treatment challenges that complicated the management of the chronic diabetic foot ulcer. The wound had persisted for 8 weeks, indicating a chronic nature and delayed healing. Significant necrosis and slough further complicated the healing process, while the culture report revealed that Klebsiella pneumoniae was resistant to several antibiotics, limiting treatment options. Additionally, underlying health conditions, including diabetes mellitus, Hypertension, and chronic kidney disease, hindered the patient’s healing potential. The wound exhibited low exudate and partial dryness, necessitating careful management to maintain an optimal moist environment. Moreover, ongoing inflammatory processes required attention to prevent further tissue breakdown and promote healing.
Therapeutic Intervention:
Initial Debridement and VAC Therapy:
Debridement was performed to remove necrotic and infected tissue. Vacuum-Assisted Closure (VAC) therapy was applied during the first visit to manage exudate and prepare the wound bed for further treatment.
Application of aqueous wound healing formulation:
The formulation was applied as a gel for thrice a week for the first week, followed by twice a week in an outpatient setting. Combined with standard wound dressings to promote healing, reduce infection, and improve vascularization of the wound bed.
Frequency of Dressings:
Initially thrice a week; after significant improvement, reduced to twice a week in the fourth week.
Home Care Instructions:
The patient was instructed to continue wound care at home using aqueous wound healing gel formulation for twice-weekly dressings to ensure consistent and effective management.
Table 8: Observation table
Parameter Observation
Wound bed Pink & moist, indicating good vascularization and strong foundation for healing.
Necrotic tissue Significant reduction in slough and necrotic tissue observed.
Wound edges Signs of contraction, indicating healing progress.
Granulation tissue Robust and bright red appearance, suggesting well-vascularized granulation tissue.
Epithelial tissue Visible signs of epithelial tissue formation along wound edges, indicating wound closure initiation.
Peri-wound area Less swollen and more integrated, indicating reduced inflammation and continued healing.

Conclusion:
In conclusion, the application of the formulation comprising nano-silver, vitamin C, and collagen demonstrated significant efficacy and safety in treating a chronic diabetic foot ulcer in a patient with multiple comorbidities. Complete wound closure was achieved within five weeks, with notable improvements in tissue health and no reported adverse effects. Said gel effectively promoted granulation tissue formation, reduced infection, and accelerated the healing process, even in the context of antibiotic-resistant bacteria. This case study underscores the potential of wound care products such as aqueous wound healing gel formulations to enhance patient outcomes and mitigate the risk of serious complications, such as amputations, in individuals with diabetes.
The presently disclosed aqueous wound healing formulation and production method may have the following advantageous functionalities over the conventional art:
• Moisture balance and faster healing
• Reduced risk of cytotoxicity
• Reduced inflammation
• Strong haemostatic effect and exudate absorption
• Provides cellular support for healing
• Promotion of angiogenesis (Formation of new blood vessels)
• Growth factor stability

The foregoing description shall be interpreted as illustrative and not in any limiting sense. A person of ordinary skill in the art would understand that certain modifications would be encompassed within the scope of this disclosure. The embodiments, examples and alternatives of the preceding paragraphs or the description and drawings, including any of their various aspects or respective individual features, may be taken independently or in any combination. Features described in connection with one embodiment are applicable to all embodiments unless such features are incompatible.
, Claims:WE CLAIM:
1. An aqueous wound healing formulation, comprising:
a biodegradable polymer in an amount of 0.001 wt % to 0.50 wt % based on the total weight of the formulation, wherein the biodegradable polymer is collagen;
nano silver particulates having particle size of 1 to 500 nm in an amount of 0.0010 to 0.0030 % w/w based on the total weight of the formulation;
a vitamin as an antioxidant in an amount of 0.10 to 0.30 %w/w based on the total weight of the formulation;
a chelating agent in an amount of 0.10 to 0.30 %w/w based on the total weight of the formulation; and
a polymer in an amount of 0.5 to 1.5 % w/w based on the total weight of the formulation.
2. The formulation as claimed in claim 1, wherein the collagen is selected from collagen I, collagen III or a combination thereof.
3. The formulation as claimed in claim 1, wherein the vitamin as an antioxidant is vitamin C (3-O- ethyl ascorbic acid).
4. The formulation as claimed in claim 1, wherein the chelating agent is selected from at least one of capryl hydroxamic acid, citric acid, gluconolactone, kojic acid, Lactobionic acid, tetra-hydroxypropyl ethylenediamine, phytic acid and disodium ethylenediamine tetra acetic acid (EDTA).
5. The formulation as claimed in claim 1, wherein the polymer is a carbomer.
6. The formulation as claimed in claim 1, wherein a viscosity of the formulation ranges between 20,000 to 50,000 cps.
7. The formulation as claimed in claim 1, wherein a pH of the formulation ranges from 3.50 to 8.00.
8. The formulation as claimed in claim 1, wherein a bulk density of the formulation ranges between 0.996 to 1.050 gm/ml.
9. A method (300) for production of an aqueous wound healing formulation, comprising:
dissolving (301) a polymer in a solvent to form a gel matrix;
adding (302) an antioxidant, a chelating agent, a nano silver particle, and a biodegradable polymer to the gel matrix;
adding (303) one or more additives selected from the group consisting of emulsifiers, polymers, preservatives, stabilizers, and excipients to the gel matrix to obtain a mixture;
mixing (304) the above mixture to achieve homogeneity; and
adding (305) sodium hydroxide (NaOH) to the mixture to maintain the pH and obtain the aqueous wound healing formulation.
10. The method as claimed in claim 9, wherein the mixing step is carried out at a temperature between 10°C and 50°C to maintain the stability of the nano silver particles.

Dated this 13th day of November 2024


PRIYANK GUPTA
AGENT FOR THE APPLICANT
IN/PA- 1454