A vulnerary multifunctional composition for on-time healing

Abstract

This invention relates to a vulnerary multifunctional composition, based on unripe coffee cherries (peel, mucilage, beans and silverskin), seed extract of Trigonella foenum-graecum, with one or more tissue-inducing molecules derived from the secondary metabolites of both plants. The unexpected and surprising ability of this new composition to solve the problems of chronic non-healing wounds addresses a long felt unmet need in the medical arts. Through a multifaceted approach, it combats microbial infections, reduces chronic inflammation, counters oxidative stress, enhances immune responses, promotes angiogenesis, regulates protease activity, stimulates collagen deposition, increases growth factor availability, facilitates cell migration, and prevents persistent infections. These novel integrated therapies represent a breakthrough in addressing macroscopic wound healing while targeting the underlying microscale mechanisms. This invention also relates to methods for preparing, using, and administering the multifunctional composition for timely healing in mammals with various skin lesions.

Description

[0001] A Vulnerary multifunctional composition for on-time healing

[0002] Description

[0003] BACKGROUND ART

[0004] Chronic wounds are a complex and widespread health issue affecting millions globally, caused by conditions such as pressure ulcers, diabetic foot ulcers, and venous and arterial leg ulcers.

[0005] These wounds are marked by a disrupted healing process, influenced by multiple factors within the wound bed's microenvironment.

[0006] Wound healing is a dynamic and intricate process, requiring a deep understanding of the underlying physiology for effective treatment.

[0007] By comprehending wound healing at the biochemical, physiological, cellular, and molecular levels, healthcare professionals can make informed clinical decisions to enhance the healing process.

[0008] Wound care faces challenges, especially with the increasing number of lower limb wounds in an ageing population, resulting in high healthcare costs.

[0009] Chronic wounds, such as venous ulcers and diabetic foot ulcers, require appropriate dressings to reduce healing time, costs, and infection risks.

[0010] Effective care involves standard protocols that address the wound's cause, prepare the wound bed, and use antibiofilm strategies to promote healing.

[0011] Debridement, crucial for wound bed preparation, is often limited by concerns over damaging vital tissue or causing pain.

[0012] There is a need for a product that enables fast, selective debridement of devitalized tissue and biofilm.The vulnerary composition addresses this need with its unique acidic and antioxidative action, softening tissue while providing antimicrobial and antibiofilm effects.

[0013] Understanding these processes is essential for resolving the complexities of chronic wounds and developing effective treatments.

[0014] In the field of wound care and treatment, most studies have traditionally focused on evaluating the effectiveness of specific dressings or treatments to address a limited set of issues related to wound healing.

[0015] These studies typically focus on two or three key factors, such as infection control, moisture balance, or reduction of inflammation.

[0016] While this approach provides valuable information about the effectiveness of individual dressings or treatments, it tends to oversimplify the complex nature of the processes that occur within wounds, and without analyzing the broader context of how these elements interact.

[0017] This limited focus leads to incomplete solutions, without effectively addressing the root causes of chronic wounds.

[0018] On the contrary, the author recognizes that chronic wounds exhibit an intricate interaction of eighteen (18) different problems, described below, that together impact the healing process, and addressing them individually prevents effective resolution of these wounds.

[0019] Infection: Typically, infection occurs early in the wound healing process and can exacerbate other issues if not addressed promptly.

[0020] Aggravated Bioburden: This follows infection and refers to an increase in the microbial load in the wound, which can further hinder healing.

[0021] Sustained Inflammation: Persistent inflammation often accompanies chronic wounds, contributing to tissue damage and impeding healing.

[0022] Immune Response Dysregulation: Dysregulation of the immune response can perpetuate inflammation and impair the body's ability to fight infection.Oxidative Damage: Oxidative stress can lead to tissue damage and hinder the healing process.

[0023] Hypoxia: Reduced oxygen supply to the wound site can impair cellular function and delay healing.

[0024] Disruption of the Extracellular Matrix: Damage to the extracellular matrix can impede cell migration and tissue repair.

[0025] Proteases Imbalances: Imbalance in protease activity can lead to excessive tissue degradation and delay healing.

[0026] Cytotoxic Exotoxins Injury: Toxins produced by bacteria or other pathogens can further damage tissue and impede healing.

[0027] Dysregulation of Growth Factors: Alterations in the regulation of growth factors can disrupt the normal healing process.

[0028] Microenvironment Disturbance: Changes in the wound microenvironment can affect cellular function and impede healing.

[0029] Angiogenic Dysregulation: Dysregulation of angiogenesis can impair the formation of new blood vessels essential for healing.

[0030] Elevated pH in Chronic Wounds: Altered pH levels in chronic wounds can hinder healing by affecting enzyme activity and cell function.

[0031] Necrotic Tissue and Slough: Accumulation of necrotic tissue and slough can impede healing and provide a favorable environment for infection.

[0032] Inadequate Inflow and / or Outflow: Poor blood flow to and from the wound site can limit nutrient and oxygen delivery and hinder healing.

[0033] Vascular Abnormalities (Microangiopathy and Macroangiopathy): These abnormalities can impair blood flow and nutrient delivery to the wound site, hindering healing.

[0034] Delayed or Inadequate Granulation Tissue Formation: Granulation tissue is essential for wound healing, and delays or inadequacies in its formation can prolong the healing process.Wound Heterogeneity: Variations in wound characteristics can affect healing outcomes.

[0035] Therefore, managing the eighteen (18) multifaceted challenges intrinsic to the treatment of chronic wounds involves the combination of multiple components within a single dressing, increasing the complexity of regulatory and validation protocols.

[0036] Over more than four decades, the author's extensive research on Trigonella foenum-graecum seeds for use in wound healing, which has led to obtaining related invention patents, and has been devoted to extensive exploration of the properties of the natural alkaloid trigonelline (N-methylnicotinic acid, structurally related to nicotinic acid).

[0037] During the development of this new patent, a key finding emerged: the natural alkaloid trigonelline (N-methylnicotinic acid), an important secondary metabolite, is more abundant in coffee than in fenugreek plants.

[0038] This discovery inspired the inventor to conduct groundbreaking research on the combined use of coffee and fenugreek.

[0039] The results of the study were surprising and unexpected. They arose from the interaction of trigonelline present in both coffee and fenugreek.

[0040] The synergistic interaction between these sources of trigonelline drastically and favorably modified the healing results when the combined composition was applied to wounds.

[0041] This constructive interaction produced healing effects that were significantly better than what would be expected from either plant used individually.

[0042] The most important research on the coffee plant, with documented uses in healing wounds, comes from the following studies:

[0043] Coffee for Wound Healing

[0044] Coffee belongs to the Rubiaceae family, Cinchonoideae subfamily, and the genus Coffea.The genus Coffea has over 80 species, with Coffea arabica and Coffea canephora being the most important.

[0045] Research on coffee’s therapeutic potential highlights the leaves, seeds, and by-products like silver skin, all of which contain bioactive compounds with promising benefits for wound healing.

[0046] Key components such as chlorogenic acid, caffeine, and trigonelline show pharmacological properties that promote tissue repair and regeneration.

[0047] Additionally, coffee extracts provide antioxidant, anti-inflammatory, and antimicrobial effects, essential for facilitating the healing process in diverse types of skin injuries.

[0048] Historically, coffee has been valued for its medicinal properties, with recent studies showing its ability to accelerate wound healing.

[0049] The compounds in coffee support this by promoting angiogenesis, stimulating collagen production, and offering antimicrobial and antioxidant benefits.

[0050] Research, including work by dos Santos et al. (2006)[1], has highlighted coffee's antibacterial, antiviral, and anti-inflammatory properties, as well as its ability to suppress metalloproteinase expression and reduce oxidative damage to macromolecules, in C. arabica extracts.

[0051] In the article titled " The Emerging Paradigm in Wound Treatment: A Compelling Change", Yuwono HS (2017)[2]highlights the effectiveness of medicinal plant remedies in wound treatment.

[0052] The author notes how empirical research has enhanced the understanding of these herbs, integrating their methods and dosages into modern medical practices.

[0053] Additionally, Yuwono highlights that the antimicrobial, pain relief, and anti-inflammatory properties of these substances contributed to their historical effectiveness in treating wounds.The article also points out the issue with some modern wound dressings, which can inadvertently remove new epithelial tissues due to their adhesive nature.

[0054] In conclusion, emphasizes the historical significance of herbal remedies in immune system support and wound healing, while addressing limitations of modern wound dressings.

[0055] Prior to his groundbreaking 2017 research, Dr. Hendro Sudjono Yuwono, Distinguished Professor of Surgery at Padjadjaran University, had already laid the foundation for his work on coffee's healing properties.

[0056] In a seminal 2014 study, Dr. Yuwono conducted research on using coffee powder for wound healing, demonstrating its effectiveness in reducing inflammation and supporting collagen proliferation and epithelialization.

[0057] This earlier work set the stage for his subsequent, more comprehensive investigations into coffee's multifaceted role in wound treatment.

[0058] This 2014 study provided the initial evidence that would later inform Dr. Yuwono's expanded other research, solidifying coffee's potential as a novel and effective agent in wound care management[3].

[0059] The study found that coffee powder aids in wound closure by managing exudates, thanks to its absorbent properties, which help control moisture and create a conducive environment for healing.

[0060] A key discovery was coffee powder's prolonged action due to its antioxidant and antibacterial properties.

[0061] Dr. Yuwono's research highlights coffee powder's potential to reduce inflammation, promote collagen production, absorb exudates, and provide lasting antioxidant and antibacterial benefits.

[0062] In three separate studies, Yuwono and collaborators explored the effectiveness of coffee in treating chronic wounds.

[0063] Their research, which included over 300 cases since 2003[2], demonstrated coffee’s ability to provide antioxidant, anti-inflammatory, andantibacterial benefits, while also activating skin microcirculation and emitting a pleasant aroma.

[0064] In a second study[4], Arimbi and Yuwono emphasized coffee’s role in diabetic ulcer healing by following the TIME concept (tissue management, infection control, moisture balance, wound edge).

[0065] The third study[5]concluded that using caffeinated coffee powder rather than caffeine alone is more effective for wound healing, as it contains a broader range of beneficial compounds.

[0066] Haesler (2023) conducted a study on the use of coffee powder for wound healing, particularly in low-resource settings.

[0067] The research found coffee powder to have antimicrobial, antiinflammatory, and antioxidant effects that promote tissue growth.

[0068] This author performed a systematic literature review, using databases such as CINAHL, Medline, and Cochrane Library, focusing on studies of topical coffee use in wound healing up to June 2023.

[0069] Sharma et al. (2021)[6]reviews the use of medicinal plants, including coffee, for wound healing, emphasizing its antioxidant, anti-inflammatory, and antimicrobial properties. The article suggests coffee powder's potential as a topical dressing for both acute and chronic wounds.

[0070] Additionally, the paper highlights the traditional use of green coffee extract and coffee bean powder in treating wounds, providing Evidence-Based insights into coffee’s wound healing capabilities[6].

[0071] Herliani, Yusyahadi, Yuwono, and their team propose that coffee and honey powder have been widely recognized as affordable and effective traditional wound treatments.

[0072] A study compared the healing effects of coffee powder, honey, and Negative Pressure Wound Therapy (NPWT), Robusta coffee powder was applied with gauze and changed every three days, while honey was applied every 2-3 days.

[0073] The research concluded that coffee powder offers a stronger antibacterial effect than honey. Both substances help fight inflammation byproducing hydrogen peroxide and a hyperosmolar liquid when interacting with wound fluids.

[0074] Coffee, however, stays in place better, improving skin microcirculation, stopping bleeding, and acting as a comprehensive wound dressing without disrupting new cells.

[0075] While NPWT effectively absorbs bacterial fluid, its negative pressure may hinder cell growth, as evidenced by higher cellular deformation in the NPWT group compared to the others[7].

[0076] Allred et al. (2009)[8]examined alkaloids, focusing on xanthines and trigonelline in coffee leaves.

[0077] Monteiro et al. (2019)[9]identified trigonelline, xanthines, and chlorogenic acids in four coffee species at various development stages: C. arabica, C. canephora, C. eugenioides, and C. racemosa.

[0078] Furthermore, various functional attributes of green coffee beans have been documented.

[0079] Esquivel and Jimenez (2012)

[0010] noted that green coffee beans (GCB) are abundant in bioactive compounds, with a notable presence of caffeine, trigonelline, and chlorogenic acids (CGAs).

[0080] Monteiro and Farah (2012)

[0011] emphasize that green coffee beans, from unripe coffee seeds, are abundant in CGA.

[0081] The content is approximately 6.5 times higher in immature beans compared to mature ones.

[0082] This difference is attributed to higher levels of polyphenol oxidase and peroxidase during the immature stages

[0011] .

[0083] Numerous studies additionally mention the functions of polyphenols, including those conducted by Kumbhare et al., 2012,

[0012] which highlight their antioxidant and antimicrobial properties, aiding in infection control and wound healing.Polyphenols also stimulate endothelial and fibroblast growth, supporting tissue regeneration, and regulate the extracellular matrix (ECM) for tissue remodeling and collagen synthesis.

[0084] In addition, Del Rio et al. (2013)

[0013] highlight that, beyond their antioxidant role, polyphenols regulate cellular signals and provide protection against chronic diseases

[0085] Phenolic compounds are classified into flavonoids and nonflavonoids.

[0086] As noted by Nurjanah et al. (2015), flavonoids function as antioxidants, protecting biological systems by transferring free radical electrons, chelating metals, activating antioxidant enzymes, and inhibiting oxidases

[0014] .

[0087] Bessada, S. M. F., Alves, R. C., & Oliveira, M. B. P. P. P. (2018) examined coffee silverskin extract (CSE) as a natural additive to support wound healing.

[0088] They identified bioactive compounds like polyphenols, caffeine, and melanoidins, attributing antioxidant and anti-inflammatory effects.

[0089] Coffee silverskin extract (CSE) encouraged fibroblast and keratinocyte activity, promoting faster healing through increased collagen synthesis and reduced inflammatory cytokines.

[0090] The review also discussed coffee grounds as a source of polyphenols, diterpenes, and chlorogenic acids for cosmetic and pharmaceutical uses, noting applications in anti-aging, sun protection, anti-cellulite products, and topical treatments for inflammatory skin conditions

[0015] .

[0091] According to the findings of Dong et al. (2015)

[0016] , Robusta coffee powders including caffeine, chlorogenic acids (CGA), trigonelline, carbohydrates, fats, amino acids, organic acids, volatile aroma compounds, and exhibit a pH range approximately between 5.67 and 5.73.

[0092] In a 2019 study by Humaryanto and O. R. Ave

[0017] , titled " Exploring the Potential of Green Coffee Extract for Wound Healing Treatment" and published in IOP Conference Series: Earth and Environmental Science, theresearchers explored the potential of green coffee extract in promoting wound healing.

[0093] The study highlighted chlorogenic acid, a key compound in coffee beans with known wound-healing properties.

[0094] According to Yuwono (2017)[2], when dealing with wounds in humans, it is essential to avoid causing additional trauma that can result from repetitive washing and rubbing.

[0095] These harmful actions are often exacerbated by frequent changes of wound dressings.

[0096] Corresponding to this author's findings, newly formed cells in the wound bed are vulnerable to damage when exposed to frequent washing and scrubbing, leading to the development of abnormal scars.

[0097] Concerns arise that this manipulation may be excessive or overly reactive, potentially affecting the wound bed adversely.

[0098] Newly grown cells on the wound bed become susceptible to damage due to washing and scrubbing, especially when done with high frequency susceptible to trauma that will slow the healing and cause the healing with an abnormal scar.

[0099] In US Patent US-10653614-B2, granted on May 19, 2020, Dusan Miljkovic (Coffee cherry cosmetic composition and methods), describes an extract and cosmetic preparation derived from quick-drying, underripe coffee cherries.

[0100] In claim 6, the extract is combined with coffee acids, essential monosaccharides, coffee mucilage polysaccharides, and trigonelline, with these compounds making up at least 1% of the extract's weight.

[0101] The formulation is intended for use in shampoos, lotions, creams, balms, or ointments, providing benefits such as antioxidant, antiinflammatory, UV protection, scar reduction, skin brightening, moisturization, wrinkle reduction, and antibacterial effects.

[0102] Differences between Miljkovic' s 614 patents focus on the maturation stage of the selected coffee (primarily red or almost ripe whole dried low-mycotoxin coffee cherries), and the method of extracting (alcohol dissolving, concentration, freeze-drying, and re-dissolution).

[0103] Additionally, the author uses unripe coffee cherries with the aim of addressing chronic wound issues, employing water as the extraction agent.

[0104] The trigonelline that is an intrinsic component of coffee, is complemented with trigonelline derived from the seed extract of Trigonella foenum-graecum.

[0105] An extensive analysis of both, is possible to synthesize in the next differences: Comparative Analysis of Patent US-10653614-B2 and New Patent application:

[0106] Both patents involve coffee cherry extracts but differ significantly in their composition and intended applications.

[0107] Components

[0108] Patent US-10653614-B2

[0109] Extract from primarily red or almost ripe whole dried low-mycotoxin coffee cherries. Coffee cherries are unbroken, unblemished, and have a surface less than 10% green and components include pulp, mucilage, and hull.

[0110] New Patent

[0111] Extract from 100% green unripe coffee cherries (including peel, mucilage, beans, and silverskin) and Seed extract of Trigonella foenum-graecum (fenugreek).

[0112] Key Differences in Components

[0113] Ripeness of Coffee Cherries:

[0114] US-10653614-B2 uses primarily red or almost ripe cherries.

[0115] New patent application uses 100% green unripe cherries.

[0116] Parts of Coffee Cherry Used:

[0117] US-10653614-B2 specifies pulp, mucilage, and hull.The new patent includes peel, mucilage, beans, and silverskin. Additional Ingredients:

[0118] US-10653614-B2 focuses solely on coffee cherry extract.

[0119] The new patent application incorporates fenugreek seed extract. Uses and Applications

[0120] Patent US-10653614-B2 primarily for cosmetic and dermatological applications.

[0121] Effects upon skin application: Scar reduction, Skin lightening, Moisturizing, Wrinkle reduction and antibacterial properties.

[0122] The new Patent application: Focused on wound healing and management.

[0123] Suitable for various wound types: Superficial and deep second-degree burns, Pressure ulcers, Leg ulcers, Surgical wounds, Trauma wounds (abrasions, lacerations, erosions), and Donor sites.

[0124] Key Differences in Uses

[0125] Primary Focus:

[0126] US-10653614-B2 targets cosmetic improvements and skin health. New patent application aims at wound healing and management. Application Range:

[0127] US-10653614-B2 is for general skin application

[0128] The new patent is specifically for wound coverage and wound healing effects.

[0129] Depth of Treatment:

[0130] US-10653614-B2 addresses surface-level skin concerns

[0131] New patent application tackles deeper skin injuries and wounds.Medical vs. Cosmetic:

[0132] US-10653614-B2 leans more towards cosmetic benefits.

[0133] New patent has a stronger medical and therapeutic focus.

[0134] Conclusion

[0135] While both patents utilize coffee cherry extracts, they differ significantly in their approach and intended uses.

[0136] Patent US-10653614-B2 focuses on cosmetic and dermatological benefits using ripe coffee cherries, targeting skin improvement and antiaging effects.

[0137] In contrast, the new patent application employs unripe coffee cherries combined with fenugreek extract to create a multifunctional vulnerary composition for wound management (include acute wounds, chronic wounds, burns, diabetic foot ulcers, leg ulcers, or any combination of these conditions) for promoting and accelerating wound healing in a subject in need.

[0138] This shift from cosmetics to medical applications represents a notable expansion in the potential uses of coffee cherry extracts in skincare and healthcare products.

[0139] Another example, Patent WO2014075157A1 (2014), describes a topical formulation based on coffee oil with a high capacity for healing skin wounds.

[0140] The composition maintains moisture in the wound area while keeping surrounding zones dry, accelerating the healing process and supporting systemic wound repair.

[0141] This formulation promotes tissue regeneration, improves blood circulation, relieves pain, kills bacteria, and reduces inflammation.

[0142] It is particularly effective for chronic diabetic foot ulcers, providing good healing results without toxic side effects or relapse.

[0143] In his invention granted as US patent US9387227B2 (2016) on 2016-07-12, by Gilbert Clinton Gee: Method for treatment of sores and lesions ofthe skin, describes a composition for the topical treatment of sores, lesions, ulcers, and other disorders of the skin, said composition includes a combination of a bee product (pollen, propolis, honey, or royal jelly) and caffeine.

[0144] Dusan Miljkovic, in his European patent EP1753387A2, titled Coffee Cherry Cosmetic Compositions and Methods, describes a cosmetic composition that includes a coffee cherry preparation, ideally an extract from sub-ripe, quick-dried coffee cherries.

[0145] The composition can be formulated as a shampoo, lotion, cream, balm, or ointment and offers multiple benefits, such as antioxidant, antiinflammatory, UV-protective, antimutagenic, chemoprotective, scarreducing, skin-lightening, moisturizing, wrinkle-reduction, and antibacterial effects.

[0146] Korean document KR 20010002411,

[0147] by □ □ □ □ □ □ □ □ □ □ □ □, describes a cosmetic composition having antioxidant effects, based on the combination of cacao extract, green tea leaf extract and coffee bean extract.

[0148] Japanese patent JPH0892057A (1996) states a cosmetic composition containing a coffee tree seed extract containing chlorogenic acid as an essential component, can be used as various cosmetic compositions in the fields of pharmaceuticals / quasi-drugs or cosmetics.

[0149] French patent: WO 1999063963 Al invention, by Karl Lintner (1999), refer a composition resulting from associating a plant extract obtained from Coffea arabica or Coffea canephora green coffee with shea butter used in cosmetic or dermo pharmaceutical compositions for preparing a medicine for healing, skin care and skin soothing effects.

[0150] French patent WO 2004054534 Al by Gilles Rubinstenn G., and Breton L., (2004), refer to the use of an extract of decaffeinated coffee grains in the preparation of a composition intended to correct or prevent the disorders associated with a greasy skin by an action diminishing the secretion of the sebum by topical administration.

[0151] Japanese Patent JP 2006528953 A (2010) by コティビー．ヴイ be relevant to Active preparation containing plant extract from green coffeebeans, Camellia sinensis leaves, Pangamic pinnata and the roots of Angelica archangelical, for cosmetic use.

[0152] Patent US 9427363 B2 (2016) by Sam Mun Park and Korean patent KR 20140077278 A (2014) by > > > refer to Pad coated with coffee intended to be in contact with the human skin and absorb physiological fluids such as blood, urine, and feces.

[0153] US 20230277718 Al (2021) by Nunes Agostinho F. J. and Garcia F. relates to a wound treatment dressing comprising: an absorbent layer comprising an odor-inhibiting mixture; wherein the odor-inhibiting mixture comprises spent coffee grounds, for the absorption of odors in wounds, including pressure ulcers, leg ulcers, cancerous wounds, diabetic foot ulcers, burns, traumatic or surgical wounds.

[0154] Brazilian Document BR PI0602842-A2 (2017) by Velazq Pereda, et al., claimed in the patent application the use of green coffee oil as an inducing agent for maintaining the physical characteristics of the skin in addition to reducing skin roughness and helping to reduce and prevent stretch marks, in cosmetic and pharmaceutical preparations

[0155] A Chinese Patent CN 112618617 A (2021) by

[0156]

[0157] provides a patch containing coffee powder as a main refreshing substance, convenient to attach to skin and free of clothes pollution.

[0158] Us patent Publication US 20120121721 Al (2012) by James M., claim a composition comprising from the curcuma genus, the coffea genus, noni juice (Citrifolla Morinda), aloe vera juice (Aloe barbadensis), gingko biloba and Camellia sinensis tea for improve skin cancer and pre-cancers, hemorrhoids, rashes, wounds, scars, age spots, polyps, bedsores, saddle sores, hot spots, insect bites, shingles, herpes, eczema, and psoriasis, among other maladies.

[0159] In claim 13 it establishes that the use of instant coffee is protected as part of the formulation, and key differences in components of the New Patent application: Extract from 100% green unripe coffee cherries (including peel, mucilage, beans, and silverskin) and Seed extract of Trigonella foenum-graecum (fenugreek).

[0160] Trigonelline (N-methylnicotinic acid):Lone, Malik, Naikoo, Raghu, & Tasduq (2020) state that trigonelline (N-methylpyridinium-3-carboxylate) is a heterocyclic alkaloidal phytochemical with numerous health benefits, primarily found in fenugreek seeds and coffee

[0017] .

[0161] Trigonelline, as refer by Visuvanathan et al., 2022, is native to the Mediterranean and Western Asia, contains bioactive compounds such as saponins, alkaloids, and flavonoids that contribute to its therapeutic potential

[0018] .

[0162] Fenugreek is a suitable plant candidate with a high prospect of being used as a credible medicinal plant to derive new drugs.

[0163] These properties exhibited are due to the content of the secondary metabolites, also known as phytochemicals, in the fenugreek plant.

[0164] Such metabolites are alkaloids, saponins, tannins, phenols, and many others.

[0165] Naika et al. (2022) indicates that the saponins present in trigonelline offer anti-inflammatory, antimicrobial, and antioxidant benefits.

[0166] These compounds contribute to reducing inflammation, decreasing the risk of infection, and neutralizing free radicals that hinder the healing process

[0019] .

[0167] Zhao et al. (2024) emphasize that alkaloids such as trigonelline and Gentianine exhibit multiple beneficial properties.

[0168] These compounds demonstrate anti-inflammatory effects, stimulate collagen synthesis, provide vascular protection, and facilitate wound closure and tissue regeneration

[0020] .

[0169] Flavonoids, as refer by Visuvanathan et al., 2022

[0018] such as quercetin and rutin, function as antioxidants and protect blood vessels, modulating the immune response during healing.

[0170] Trigonelline’s immune modulation reduces excessive inflammation while promoting growth factors that support tissue regeneration.It enhances collagen synthesis for tissue repair and exhibits angiogenic properties, promoting new blood vessel formation to expedite healing

[0018] .

[0171] Overall Effects on Wound Healing

[0172] The synergistic action of bioactive compounds in fenugreek contributes to wound healing through multiple mechanisms, as reported by Salimabad et al. (2023)

[0021] :

[0173] • Enhanced collagen synthesis for tissue repair

[0174] • Promotion of angiogenesis (formation of new blood vessels) • Immune modulation to mitigate excessive inflammation

[0175] • Support of growth factors that facilitate tissue regeneration In conclusion, as referred to by the authors, fenugreek's secondary metabolites, notably trigonelline and other alkaloids, saponins, and flavonoids, work in concert to promote wound closure and tissue regeneration.

[0176] Their combined effects on collagen synthesis, angiogenesis, and immune modulation create a favorable environment for healing processes

[0021]

[0177] A study conducted at the Faculty of Chemical Sciences, University of San Carlos de Guatemala (1992) by Drs. Chang Espino, M. J., and Navas Escobedo L, evaluated the healing effects of fenugreek seeds (Trigonella foenum-graecum) and plantain leaves (Plantago major) on wounds in albino rats.

[0178] The conclusion stated that both promote epithelial tissue regeneration, aiding superficial wound healing without adverse reactions when applied topically.

[0179] Additionally, refer that Trigonella foenum-graecum contains the natural alkaloid trigonelline (N-methylnicotinic acid), structurally related to nicotinic acid

[0022] .

[0180] Wound Healing in Diabetic Patients:Research by Ghule et al. (2012) has shown that trigonelline exhibits significant anti-inflammatory and antioxidant effects, which are crucial in the wound healing process

[0023] .

[0181] These findings are supported by Zhou et al. (2017), who demonstrated that trigonelline reduced oxidative stress and inflammation in various diabetic animal models

[0024] .

[0182] The modulation of oxidative stress and inflammation by trigonelline, as observed in these studies, suggests potential benefits for wound healing, particularly in the context of diabetes-related complications.

[0183] These properties could be especially relevant for addressing the challenges of wound healing in diabetic patients, where oxidative stress and chronic inflammation often impede the healing process.

[0184] The patent US10195239B2, published on 2019-02-05, discloses an extract from Trigonella foenum-graecum (fenugreek).

[0185] The extract is obtained by mixing plant material from fenugreek with a liquid, incubating it for at least 3 hours, heating the mixture, and recovering the liquid extract.

[0186] This extract is useful in making pharmaceutical compositions, disinfectants, or preservation agents, and can be applied in treating or preventing inflammatory diseases or infections.

[0187] The patent US10195239B2 also includes claims regarding the use of the Trigonella foenum-graecum extract.

[0188] Claim 2 specifies that the extract can be used to treat inflammatory conditions such as diaper dermatitis, acne, asthma, or inflammation in the gastrointestinal tract.

[0189] Claim 3 further expands the application to infectious conditions, including infected or surgical wounds, impetigo, Staphylococcus infections (such as Staphylococcus aureus), infections in the mouth cavity, periodontal disease, eye infections, common cold, cold sores, Herpes simplex, warts, and pharyngitis.The WO2023059298A1 patent describes a cream with herbal components providing antiviral, antibacterial, antifungal, antiinflammatory, and analgesic properties.

[0190] It is used for treating skin infections, wounds, migraines, arthritis, and herpes zoster.

[0191] The formula contains 10-30% fenugreek, along with essential oils and mixtures from black seed and fenugreek, obtained through traditional or modern methods.

[0192] The cream may also include auxiliary substances like solvents and emollients and is applied as both a nutraceutical and pharmaceutical.

[0193] The JP2001511153A patent focuses on compositions derived from fenugreek seeds for the prevention and treatment of vascular degenerative diseases, particularly microvascular disorders and atherosclerotic lesions.

[0194] Claim 2 highlights the inclusion of Gymnema sylvestre, fenugreek seeds, and ginkgo for therapeutic benefits, and Claim 10 refers to its application in wound healing.

[0195] Patent WO2023059298A1 by Omer Elbasheer, with the title Cream containing fenugreek for the prevention and treatment of zoster, skin infections, wounds, migraines, and arthritis, publication 2023-04-13, describes a cream with antiviral, antibacterial, antifungal, antiinflammatory, and analgesic properties, intended for the prevention and treatment of skin infections, wounds, zoster, migraines, and arthritis.

[0196] The cream is composed of powders, essential oils, or mixtures derived from black seed and fenugreek, extracted using both modem and traditional methods.

[0197] The Claims specify that the cream is formulated to treat various conditions by incorporating fenugreek for its antiviral and antibacterial properties.

[0198] Fenugreek is included in concentrations ranging from 10% to 30%, with one formulation containing 20%.The composition combines black seed and fenugreek to enhance healing, making it suitable for treating a wide range of wounds, including acute, chronic, and traumatic injuries.

[0199] Patent US7645466B2, titled " Methods for deriving, isolating, and / or extracting amino acid compositions from Fenugreek seed", was presented by Steve S. Lee, Richard B. Hynson, Ke-Qin Zhang, Wu-Zhou Li, and Jing S. Zhou, and published on January 12, 2010.

[0200] It outlines methods for extracting bioactive compounds from Fenugreek seeds, with an emphasis on 4-hydroxyisoleucine and a range of amino acids.

[0201] These compounds include alkaloids, glycosides, volatile oils, saponins, flavonoids, fatty acids, vitamins, minerals, and carbohydrates.

[0202] The composition contains 10% to 70% 4-hydroxyisoleucine and 20% to 40% of other amino acids like arginine, aspartate, leucine, and lysine.

[0203] The extraction process involves soaking and crushing Fenugreek seeds to derive these bioactive components.

[0204] Patent C

[0205]

[0206] N102532248B, by W, ^3HE, H

[0207]

[0208] M1, in their patent Method for preparing Trigonella foenum-graecum saponin B, describes a method for preparing Trigonella foenum -graecum saponin B, used in traditional Chinese medicine for treating conditions like kidney deficiency, impotence, cold hernia, stomach issues, and leg pain caused by cold and dampness.

[0209] The method involves passing a water solution of total saponin extract from Trigonella foenum-graecum through various columns, such as polyamide, alkaline aluminum oxide, neutral aluminum oxide, or silica gel.

[0210] Juan Miguel Garcia Gilaberf s patent US-20150056175-A1, granted on 2015-02-26, titled " Composition to prevent and / or treat dermatosis and method to obtain it", mentions the use of honey from bees and fenugreek (Trigonella foenum-graecum), combined with 23 natural products, stevia, and lanolin.The composition is intended for the prevention and treatment of dermatitis, particularly psoriasis, which differs from the current application focused on treating chronic wounds with difficult healing.

[0211] Having presented all the previous information, it is evident that none of them focus on addressing the multiple problems associated with wounds, particularly chronic ones.

[0212] Therefore, the author's research has been directed for many years and through numerous investigations towards resolving these issues.

[0213] The multifunctional vulnerary composition represents an innovative solution, particularly effective in treating diabetic foot and leg ulcers.

[0214] It offers strong biocompatibility with the wound surface, aids healing, and helps prevent scarring.

[0215] This composition rapidly softens devitalized tissue, serving as an excellent alternative to sharp or mechanical debridement methods.

[0216] A novel research strategy involves developing vulnerary multifunctional compositions to support innate healing and combat the eighteen (18) different problems that affect incompletely healing lesions.

[0217] By integrating infection control, inflammation modulation, oxidation conversion, immune stimulation, ECM reactivation, microenvironment optimization, restoration of cellular and molecular mechanisms, promotion of angiogenesis, and enhancement of granulation tissue formation, the new composition offers a transformative and comprehensive solution for patients suffering from chronic wounds.

[0218] The combination of unripe coffee cherries, seed extract of Trigonella foenum-graecum, creates a dynamic constructive interaction that addresses multiple aspects of wound healing.

[0219] Each component brings its unique set of therapeutic properties, and when combined, their effects are amplified, leading to enhanced tissue restructuring and repair-regeneration.

[0220] Once applied, the softened tissue can be easily wiped away or gently scraped, leaving a cleaner wound bed.The combination of unripe coffee cherries, along with seed extract of Trigonella foenum-graecum, induces tissue repair and regeneration through multiple related mechanisms.

[0221] Their molecular mutually reinforcing effects increase the overall healing effectiveness observed during its use.

[0222] Connecting the Synergistic Potential:

[0223] The integration of these components has been successfully accomplished through the creation of this sophisticated vulnerary composition, which acts as an innovative combination therapy.

[0224] This state-of-the-art vulnerary composition offers prolonged contact with the wound and controlled release mechanisms, maximizing its therapeutic efficacy as observed in clinical applications.

[0225] The multifunctional vulnerary composition has been customized to address specific wound types, particularly diabetic foot and leg ulcers, and various stages of the healing process, ensuring precise and efficient delivery of active ingredients.

[0226] Its effectiveness in softening devitalized tissue, removing biofilm, and supporting wound bed preparation demonstrates its versatility across different wound healing stages.

[0227] Both coffee and fenugreek are rich in trigonelline, a bioactive alkaloid known for its potential health benefits, including antiinflammatory, antioxidant, and metabolic regulatory properties.

[0228] Coffee contains up to 7.2 g / kg of trigonelline, while fenugreek seeds also hold a significant concentration of this compound.

[0229] The author's personal research has focused on exploring the combined use of coffee extracts and fenugreek seeds or powder, with an emphasis on trigonelline.

[0230] This research specifically examines trigonelline's potential in regulating local oxidative stress and reducing inflammation in skin conditions, aiming to influence these effects for improving skin health and promoting healing.Trigonelline's role in improving collagen synthesis can complement the tissue rebuilding action of (N-methylnicotinic acid).

[0231] By aiding in the regulation of ROS production, it contributes to minimizing oxidative stress, promoting an environment conducive to healing.

[0232] The combination of these compounds forms a promising strategy for addressing chronic non-healing wounds.

[0233] Their collective actions create a synergistic effect that helps optimize the wound microenvironment, supporting tissue restoration and overall wound healing efficacy.

[0234] The invention relates to a unique combination of plant secondary metabolites from green coffee cherries and seed extract of Trigonella foenum-graecum, which synergistically addresses numerous issues within the tissue microenvironment.

[0235] The proposed composition promotes healing by delivering active metabolites that modulate cellular responses, signaling molecules, and extracellular matrix remodeling, facilitating the topical administration of therapeutic secondary metabolites for the recovery and reformation of the wound bed and surrounding tissue area.

[0236] This administration is directed to subjects in need thereof, encompassing humans and animals (mammals).

[0237] Application of the composition can be accomplished through various techniques with which trained physicians are familiar, including localized application of the formulation to a site of injury, in the form of films, pastes, sponges, or aerosols.

[0238] By combining macroscopic and micro-targeted care, this formulation provides an integrated approach to chronic and non-healing wounds.

[0239] The fusion of tissue repair and regeneration mechanisms offers an effective solution for enhanced wound healing outcomes, facilitating exceptional tissue restructuring and regeneration.Clinical studies have shown that using this specific composition expedites ulcer healing, leading to shorter hospital stays without significant adverse effects.

[0240] Topical application accelerates healing, resulting in complete epithelial regeneration and promoting the fast formation of granulation tissue.

[0241] Notably, patients treated with the vulnerary composition consistently experienced significantly shorter hospitalization periods compared to those who did not receive it, with no evidence of local or systemic complications.

[0242] Implementing this treatment could reduce wound care time and healthcare expenses, thereby improving the quality of life for individuals with chronic and acute wounds.

[0243] Such compositions may be used in therapeutic intervention to prevent, delay, mitigate, stabilize, and heal chronic and acute wounds and bums in a subject in need thereof.

[0244] From the description provided above, it can be concluded that no teaching of the prior art describes or suggests having such a synergistic combination of active ingredients from both plants, which provide the functional benefits of combating the damage caused to cells, and consequently to the skin.

[0245] BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

[0246] Not Applicable

[0247] SUMMARY OF THE INVENTION

[0248] The invention presents a vulnerary multifunctional composition for enhanced wound healing, combining secondary metabolites from green coffee cherries and Trigonella foenum-graecum seed extract.

[0249] This innovative formulation addresses both acute and chronic wounds, including bums, by synergistically targeting multiple pathophysiological factors at the microscale.The composition modulates cellular responses, signaling molecules, and extracellular matrix remodeling, offering an integrated approach to wound care.

[0250] The bioactive compounds demonstrate antibacterial, antiinflammatory, antioxidant, and immunomodulatory properties, particularly effective in treating diabetic foot and leg ulcers.

[0251] Applicable in various forms (films, pastes, sponges, aerosols), it provides prolonged wound contact and controlled release mechanisms, accelerating healing through enhanced granulation tissue formation and complete epithelial regeneration.

[0252] Clinical studies show reduced hospitalization periods and improved patient outcomes without significant adverse effects.

[0253] This versatile, biocompatible solution meets the need for advanced wound treatment in both humans and animals, offering a comprehensive therapeutic approach for optimal wound care management.

[0254] DETAILED DESCRIPTION

[0255] In the discussions herein, several terms are used.

[0256] To provide a clear and consistent understanding of the specification and claims, the following definitions are provided.

[0257] Acute - sharp, severe, having rapid onset, severe symptoms, and a short course, not chronic.

[0258] Angiogenesis - This occurs during the proliferative phase of healing when new blood vessels infiltrate the wound and endothelial budding forms capillaries.

[0259] Adhering dressing - the quality of clinging or being closely attached Antimicrobial agent - preventing the development or pathogenic action of microbes, helps decrease an infection and allows healing of a wound

[0260] Bacterial - unicellular microorganisms, lacking chlorophyll, many kinds of bacteria, creating an infectionChronic - long, drawn out, applied to a disease that is not acute. Chronic wound - covered with necrotic (dead) material and surrounded by cellulites, also is described as an infected wound.

[0261] Debridement - the process of removing dead / unhealthy and / or contaminated tissues, foreign bodies, and other debris on the wound, using mechanical, enzymatic, or sharp techniques.

[0262] Dressing - Any of various materials utilized for covering and protecting a wound.

[0263] Epidermis - the outer layer of skin.

[0264] Epithelialization-The process of the formation of new epithelial tissue -the upper layer of the skin- Eschar - a slough, especially one following a cauterization or bum -any agent used to destroy dead tissue and to cause sloughing which produces an eschar (a blackened area) in the treatment of skin disease.

[0265] Excision - Is a surgical procedure requiring incision through the deep dermis (including subcutaneous and deeper tissues) of open wounds, bum eschar, or bum scars.

[0266] Exudates - the material that often forms over an open wound. It consists of proteinaceous material from the wound itself.

[0267] Granulation tissue - Newly formed vascular tissue (fragile capillaries) normally produced in the healing of wounds of soft tissue and ultimately forming the scar; it consists of small, translucent, pink to red, nodular masses of granulations that fill in an open wound bed during the proliferative phase of healing.

[0268] Infection - The host response to bacterial, viral, or similar invasion. Inflammation - Anon-specific host response to invasion of foreign material.

[0269] Lesion - any visible, local abnormality of the tissues of the body, as a wound, sore, rash, or a boil.Necrosis - localized tissue death that occurs in groups of cells in response to disease or injury.

[0270] Purulent - producing or containing pus.

[0271] Sterilization - A process that kills and / or removes all classes of microorganisms and spores.

[0272] Stroma -The supportive framework of an organ usually composed of connective tissue. Superficial - confined to the surface.

[0273] Tissue regeneration - Healing in which lost tissue is replaced by proliferation of cells which reconstruct the normal architecture.

[0274] Tissue repair - Healing in which lost tissue is replaced by a fibrous scar, which is produced from granulation tissue.

[0275] Treatment or treating - refers to any means of control of a condition or disorder, including prevention or prophylaxis, cure and relief, or relief of development of the condition or disorder.

[0276] Ulcer - a circumscribed, craterlike lesion of the skin or mucous membrane resulting from necrosis that accompanies some inflammatory, infectious, or malignant processes.

[0277] Wound dressing - is a material applied to a wound or a diseased part of the body, with or without medication, to protect and assist healing.

[0278] The term “wound” used within the scope of the present invention describes acute wounds, chronic wounds, infectious wounds, abrasion wounds, tear wounds, bruise wounds, trauma wounds, knife wounds, skin cuts, surgical wounds, gun wounds, thermal wounds, chemical wounds, bites, stings and electrical-sourced wounds.

[0279] The term “biodegradable” implies that the material can be degraded by biological mechanisms like enzymatic degradation and / or microbial degradation.

[0280] As used herein, a “bio-active compound” may be defined as any substance that influences living tissue.From a wound care perspective, the growing prevalence and incidence of non-healing acute and chronic wounds is a concern, and numerous resources are available to clinicians across practice settings in wound-bum care, with limited success.

[0281] Accordingly, it is a general object of this invention to provide surgical dressing and methods of use and manufacture, which overcome the disadvantages of the prior art, and which fulfill the need set forth above.

[0282] In the first embodiment, a novel approach is presented that combines naturally origin secondary metabolites obtained from unripe coffee cherries and leaves, seed extract of Trigonella foenum-graecum extracts, to comprehensively address the complex events of chronic wound healing.

[0283] In this preferred embodiment, the term "natural origin" refers to compounds that have not been deliberately genetically modified or artificially altered, ensuring the preservation of their natural integrity and bioactivity.

[0284] These compounds remain in their naturally occurring state without intentional modification.

[0285] This perspective recognizes the interconnected nature of these events, with the goal of significantly improving outcomes for patients with chronic and challenging wounds and improving their quality of life.

[0286] In one embodiment, Coffee plant and Trigonella foenum-graecum seed metabolites offer an innovative solution for addressing diverse wounds.

[0287] Chlorogenic acid, found in coffee, acts as an antioxidant and antiinflammatory agent, fostering an optimal healing environment by reducing inflammation, oxidative stress, and promoting tissue regeneration.

[0288] Diosgenin, sourced from Trigonella foenum-graecum seeds, stimulates fibroblast activation and collagen synthesis, crucial for tissue repair and regeneration across various wound types.

[0289] In another embodiment, the bioactive dressing combines these secondary metabolites to release anti-inflammatory agents directly at thewound site, regulating inflammatory response while facilitating tissue repair.

[0290] In one embodiment, advanced wound dressings integrate antimicrobial agents and protease regulators derived from stimulant plants, including alkaloids, flavonoids, phenolics, and essential oils, to address aggravated bioburden in chronic wounds.

[0291] Chlorogenic acid from coffee contributes to managing planktonic bacteria through its antimicrobial properties while mitigating infection-related inflammation.

[0292] Diosgenin demonstrates the potential to disrupt biofilm formation, enhancing bacterial susceptibility to antimicrobial treatments.

[0293] In another embodiment, this combination creates an optimal environment for wound cleansing, efficiently removing foreign bodies and debris while promoting fibroblast activation and collagen synthesis.

[0294] In one embodiment, coffee plant secondary metabolites, especially polyphenols like chlorogenic acid and caffeic acid, combat oxidative damage during wound healing by scavenging ROS and decreasing oxidative stress.

[0295] In an embodiment focusing on immunity, quercetin and chlorogenic acid from coffee and fenugreek strengthen immune function while promoting efficient tissue healing.

[0296] In another embodiment, the solution addresses inadequate inflow and outflow issues through:

[0297] - Chlorogenic Acid's promotion of angiogenesis and vascular functionality

[0298] - Diosgenin's support of extracellular matrix synthesis and tissue perfusion

[0299] The combination specifically targets:

[0300] 1. Vascular abnormalities by improving blood vessel function and mitigating inflammation.2. Hypoxia through increased oxygen delivery and tissue oxygenation.

[0301] 3. Disrupted extracellular matrix (ECM) via repair and restoration.

[0302] 4. Protease regulation in chronic wounds through ECM stabilization. In situ tissue repair and regeneration harnesses the body's innate capacity by recruiting host endogenous cells or tissue-specific progenitor cells to the injury site.

[0303] The objective is to deliver active metabolites that modulate the spatial-temporal release of appropriate signals within the host microenvironment.

[0304] This multifunctional vulnerary composition comprises unripe coffee cherries (peel, mucilage, beans and silverskin) and seed extract of Trigonella foenum-graecum, promoting comprehensive tissue repair, regeneration, and restructuring.

[0305] In one embodiment of the present invention, a method for preparing the vulnerary multifunctional composition comprises:

[0306] preparing an excipient mixture in a suitable vessel by combining: - from about 10% to about 30% by weight of a lubricant.

[0307] - from about 1% to about 12% by weight of an emulsifier.

[0308] - from about 3% to about 25% by weight of a softener.

[0309] - from about 0.1% to about 2% by weight of a preservative.

[0310] - from about 0.1% to about 5% by weight of an absorbent; and - from about 3% to about 50% by weight of purified water as a vehicle.

[0311] Heating said excipient mixture to about 80°C while continuously blending until all components are fully incorporated and a homogeneous mixture is formed, and incorporating plant extracts into said homogeneousmixture while maintaining the temperature between about 30 °C and about 60°C under continuous agitation, wherein said plant extracts comprise:

[0312] - from about 5% to about 30% by weight of a Rubiaceae family extract; and

[0313] - from about 3% to about 15% by weight of a Trigonella extract. In a further embodiment, the method comprises maintaining continuous agitation during the incorporation of said plant extracts to ensure uniform distribution throughout the composition.

[0314] In yet another embodiment, the temperature is maintained within the specified range to preserve the stability and activity of the bioactive compounds present in said plant extracts.

[0315] According to a specific embodiment, the invention provides a method for formulating topical preparations, including pastes, creams, lotions, serums, gels, hydrogels, hydrocolloids, and films to facilitate effortless application and effective delivery of natural products to mammals damaged skin tissues, promoting enhanced tissue repair, regeneration, and restructuring.

[0316] While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the methods and in the steps or in the sequence of steps of the methods described herein without departing from the concept, spirit and scope of the invention.

[0317] The following examples are included to demonstrate preferred embodiments of the disclosure.

[0318] It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice.

[0319] However, those of skill in the art should, considering the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.While the fundamental novel features of the tissue disclosed herein have been described, it will be understood that various omissions, substitutions and changes in the form and details may be possible without departing from the spirit of the present disclosure.

[0320] Example No. 1

[0321] Mode for invention:

[0322] Extraction and Processing of Plant Materials:

[0323] The coffee is obtained in a coffee production unit located in the Municipality of Barberena, Department of Santa Rosa, Guatemala, where a range of fine Strictly Hard Bean coffees are produced.

[0324] Its main characteristics are the following:

[0325] • Altitude: 4,300 to 4,800 meters above sea level

[0326] • Soils: loam to clay loam

[0327] • Rainfall of 1,500 mm to 1,800 mm per year

[0328] • Water resources: natural springs that provide drinking water.

[0329] Selection of donor plants of raw material, aged between 3 and 5 years, from coffee plantations.

[0330] The green beans are hygienically harvested manually 120 days after flowering.

[0331] They are then strained in hygienic trays into the coffee yards for their natural dehydration process, under the rays of the sun.

[0332] The beans are dried in the sun for 60 days.

[0333] The mixture is stored in a glass container disinfected in a bain-marie to be sent to continue the subsequent steps in the following 24 hours.

[0334] Extracting and processing natural plant materials to produce fine powders to ensure the plant material is thoroughly dried and ground to a fine consistency to maximize surface area for subsequent extraction.Ultrasound- Assisted Extraction:

[0335] Perform ultrasound-assisted extraction of secondary metabolites from the fine powders derived from unripe coffee cherries (including peel, mucilage, beans, and silverskin) of coffee plants an extract derived from at least one species of the genus Trigonella belongs to the family Fabaceae Trigonella extract, followed by filtration.

[0336] Furthermore, it is possible to produce the mixture in a multifunctional vulnerary composition, based on cherries and unripe coffee (green coffee), fenugreek seed extract by other methods such as, for example, simple decoction, leaching, reflux extraction, extraction by ultrasound or microwave or finally by countercurrent techniques, without this list being exhaustive.

[0337] Formulation and Preparation of a Metabolite-Enhanced Hydrogel Concentration and Purification of Extracted Metabolites:

[0338] Concentrate and purify the extracted secondary metabolites to eliminate impurities and enhance the concentration of bioactive compounds.

[0339] This step ensures the final hydrogel contains the desired active ingredients.

[0340] Preparation of Excipients Mixture:

[0341] In a suitable vessel, combine the following excipients in specified concentrations to achieve their functional roles:

[0342] Lubricant: 10% to 30%

[0343] Emulsifier: 1% to 12%

[0344] Softener: 3% to 25%

[0345] Preservative: 0.1% to 2%

[0346] Absorbent: 0.1% to 5%

[0347] Purified water: 3% to 50% (acts as a vehicle)Heating and Blending:

[0348] Heat the excipient mixture to 80°C while continuously blending until all components are fully incorporated and a homogeneous mixture form.

[0349] Incorporation of plant extracts:

[0350] Gradually add the following plant extracts to the mixture from step 3 while maintaining the temperature between 30 °C to 60 °C and continuing agitation:

[0351] Rubiaceae Family Extract: 5% to 30%

[0352] Trigonella Extract: 3% to 15%

[0353] Ensure the mixture is well-blended to achieve uniform distribution of the extracts throughout the formulation.

[0354] Addition of antioxidants and regenerative Excipients:

[0355] Incorporate additional excipients with the following functions into the mixture from step 4, continuing to stir constantly:

[0356] Antioxidant: 0.1% to 3%

[0357] Regenerative Agent: 0.1% to 3%

[0358] pH Adjustment:

[0359] If necessary, adjust the pH of the mixture to the desired level by adding a pH buffer solution of 2 -Hydroxy-3,5-bis [(4-hydroxy-2-methyl-5-sulfophenyl) methyl] -4-methylbenzenesulfonic acid in a concentration range of 0.001% to 1%.

[0360] Preparation of the Gelifying Solution:

[0361] Dissolve the Gelifying agent, preferably agar-agar, in deionized water.

[0362] Gently heat the solution to a temperature at or below 40°C while stirring to fully dissolve and incorporate the Gelifying agent.

[0363] Incorporation of Plant Extracted Metabolites:Gradually add the concentrated plant metabolite extract to the Gelifying solution.

[0364] Keep stirring to ensure a uniform mixture and prevent lumps.

[0365] Adjust the pH to 3.8 for optimal gelation, with 2-Hydroxy-3,5-bis[(4-hydroxy-2-methyl-5 -sulfophenyl) methyl] -4-methylbenzenesulfonic acid.

[0366] Homogenization:

[0367] Homogenize the metabolite extract with the hydrogel materials at controlled temperatures to preserve the metabolites' composition and activity.

[0368] This step ensures even distribution of active compounds throughout the hydrogel.

[0369] Straining and Filtration:

[0370] Strain the solution through a fine mesh to remove lumps or undissolved particles, ensuring a smooth hydrogel.

[0371] Molding and Tray Filling:

[0372] Pour the hydrogel into trays or molds, filling each with a specific weight, such as 38.8 grams, to maintain consistency in product size and shape.

[0373] Gelation and Drying:

[0374] Leave the trays or molds at room temperature for 12 hours to allow the gel to set in a controlled environment.

[0375] Product Adjustment (if necessary):

[0376] Check the hydrogel's consistency and firmness. Adjust the formulation by modifying the Gelifying agent concentration or plant extract proportions as needed.

[0377] Packaging:

[0378] Package the molds in sterilization-compatible materials to ensure the product’s sterility and quality.Sterilization:

[0379] Sterilize the packaged hydrogels using ethylene oxide, plasma sterilization, or γ-radiation (2.5-3.5 MRad).

[0380] Storage:

[0381] Store the sterilized hydrogels in a cool, dry environment to maintain their properties and extend shelflife.

[0382] Example #2

[0383] Indications for use: The multifunctional vulnerary composition is suitable for both human and veterinary applications.

[0384] It can be used for temporary coverage of various wound types, including superficial and deep second-degree bums (partial thickness bums), pressure ulcers, leg ulcers, surgical wounds, trauma wounds (such as abrasions, lacerations, and erosions), and donor sites.

[0385] The composition can be formulated into various topical preparations, including pastes, creams, lotions, serums, gels, hydrogels, hydrocolloids, and films, to suit different wound care needs.

[0386] Prior to the placement of the multifunctional vulnerary composition, it is necessary to perform several actions, due to the impact they have on the healing of wounds:

[0387] Complete evaluation of the patient (including comprehensive vascular evaluation).

[0388] Determining the etiology of wound (i.e., acute, chronic, ischemic). Ascertain the underlying disease, e.g., venous / arterial.

[0389] Use a validated pressure ulcer classification system to document the level of tissue loss (i.e., Braden Scale, Norton Scale, Waterlow Score Card, Braden Q (for pediatric patients), or other appropriate tool in conjunction with clinical judgment.

[0390] Utilize appropriate and regular measurement of wound size (take a tracing of the wounds).Determining the bacterial bioburden of the injury by tissue biopsy or quantitative swab technique (i.e., Levine quantitative swab technique).

[0391] Sharp debridement and antibiotic therapy must be initiated as early as possible, and the blood glucose should be monitored closely and controlled.

[0392] Assess for osteomyelitis or skin neoplasms in chronic ulcers with appropriate Laboratory tests (biopsy of every non-healing wound) and x-rays as needed.

[0393] Nutritional assessment and lab evaluation of plasma proteins and Hematocrit-Hemoglobin.

[0394] Such information is essential to identify these factors and control them to facilitate faster wound healing whenever possible.

[0395] Placement Procedure of the multifunctional vulnerary composition Prepare wounds very meticulously, to guarantee lesion is entirely excised or surgically debrided, to ensure the wound bed and edges contain viable structures, free of debris and necrotic tissue.

[0396] With normal saline solution gently irrigated the injury.

[0397] Debride blister and loose skin.

[0398] Cleanse with warmed normal saline.

[0399] Avoid broad area of capillary bleeding which can lead to devitalized tissue.

[0400] To apply the paste (the preferred method of composition presentation):

[0401] Cleanse the wound with a saline or mild antiseptic solution.

[0402] Gently apply a thin layer of the honey, fenugreek, and oxide paste directly onto the wound bed.

[0403] Repeat the application, depending on the severity of the wound, although in most cases it is done every 5 to 7 days, except in DiaperDermatitis lesions, a situation in which it must be applied with each change of this infant garment.

[0404] Cover the wound with a sterile dressing to protect it from external contaminants.

[0405] Dressings to protect practical active dressing as follows:

[0406] High quality white nylon mesh and a tubular elastic bandage applied over the composition to facilitate its permanence and protect the site.

[0407] Both can be left in place for extended periods without detrimental effects to the underlying wound.

[0408] In this sense, preparing Bowl with sterile saline solution and immersing the nylon mesh (second dressing) for 10 seconds.

[0409] Next the wound bed with the composition is overlaid with this material in direct contact with wound surface and then bandaged with elastic tubular dressing (third dressing) to preserve adherence and permit easy inspections.

[0410] Careful inspection of the wound site and the clinical monitoring of patients' conditions allow the clinician to prolong the interval between dressing changes.

[0411] It is the opinion of the author that a maximum of one continuous week without a dressing change is acceptable if no signs of infection develop.

[0412] At seven or more days, the bandage can be removed with gentle saline irrigation or showering.

[0413] Do not forcibly remove sections of the bandage that have adhered to the wound.

[0414] Subsequently, with new watering, they are completely removed. Complications: The following complications are possible with the use of any wound dressings.If any of the conditions occur, the composition should be removed: infection, inflammation, allergic reaction, excessive redness, pain or swelling.

[0415] Complications that the surgeon may encounter further than infection include seroma and / or hematoma formation.

[0416] Although wound infection is rare, when this is suspected, appropriate bacterial identification is obligatory and according to the cultivated microorganisms’ antibiotics should be prescribed.

[0417] Example 3

[0418] Below are several clinical cases related to the new treatment using the composition described in this patent application, which have demonstrated its efficacy and safety, which support the inventive activity and the usefulness of the invention.

[0419] All patients were asked for their consent to use the product, usually in the form of a film.

[0420] Case study 1: Deep partial thickness bums, produced by hot ashes, 21 -year-old male patient, with lesions on both lower extremities, below the knees, lasting 24 hours.

[0421] He explained that 2 days before his presentation, he had placed his limbs in hot ashes.

[0422] The bums were circumferential, on both legs, and feet, with 15% total area with deep second-degree bums.

[0423] The first application for the film was undertaken on day 0.

[0424] His comorbidities were nutritional deficit.

[0425] The wound management objectives were to:

[0426] 1. Remove the devitalized tissue from the wound bed

[0427] 2. Reduce bioburden and infection

[0428] 3. Promote granulation and epithelial tissue formation.The patient was able to tolerate the procedure, finding it atraumatic. The film with the composition was only applied once, and Full healing was achieved on day 7.

[0429] The Surgeon found film extremely easy to use and was impressed by how quickly and effectively it debrided the wound bed. Clinical Case 2: Full thickness bums on the left mammary gland of 13 days' evolution, in a 63 -year-old patient.

[0430] History: Treatments with silver sulfadiazine-based creams, 10 days previously.

[0431] Comorbidities: Patient with controlled diabetes mellitus.

[0432] Initial evaluation: 45% slough, 55% hyper granulation tissues.

[0433] Treatment: cleaning with normal saline solution, and partial surgical removal of the slough.

[0434] Placement of the composition in the form of a film (one time only) as a primary dressing and a polyethylene cover as a secondary dressing.

[0435] Result: Complete repair and regeneration of the injured tissues in eight days.

[0436] Clinical Case 3: 4-year-old boy with bums caused by fireworks exploding in his pockets.

[0437] Initial clinical impression: Mixed depth burns, deep superficial and full thickness, with 10% extension on both thighs and suprapubic region.

[0438] Bum Appearance:

[0439] Color: the skin may appear pearly white at the center and cherry red at the periphery.

[0440] Sensitivity: hypo esthetic at the center.

[0441] Texture: dry the affected area and firm.Treatment: cleaning with normal saline solution, and partial surgical removal of the slough.

[0442] Application of the film composition as a primary dressing and a polyethylene cover as a secondary dressing.

[0443] After the first application of the film, all the eschar, slough and necrotic tissue were removed on the eighth day.

[0444] After the second application of the film, the wound bed was clean (80% granulation tissue and 20% epithelial tissue), ready for grafting, which was performed on day 18.

[0445] Clinical Case 4:

[0446] Female patient, 55 years old, with full thickness bums on the back of the entire left forearm and the entire hand, including fingers, caused by flame, 48 hours previously, with delayed attention during that time, secondary to epileptic seizure.

[0447] Comorbidities: Epileptic seizures from an early age.

[0448] The extent of the lesions was seen in 5%, where in all affected areas they may appear white and charred black, with leathery appearance.

[0449] Procedures: gentle washing and irrigation with normal saline solution, and placement of the composition in the form of a film, with two secondary dressings: polyethylene mesh, and Vaseline gauze, kept for seven days.

[0450] Evolution: after seven days, upon discovery, the appearance of a regular surface is noted, with deep red granulation tissue in the entire area, with the scars and necrotic tissues completely disappearing.

[0451] A second application of the product allowed the observation of perfect and healthy granulation tissue on the fourteenth day.

[0452] On the 22nd day, healthy granulation tissue was observed, free of infections, so a partial thickness graft was placed in a fine mesh.

[0453] Observations after one month of the lesions denote complete acceptance of the grafts.Clinical Case 5:

[0454] Child under 5 years of age, with deep bums caused by flame, affecting the entire dorsal surface of the left hand with extension to the fingers, 2 days of evolution without prior treatment.

[0455] The bum was classified as Full-Thickness Bums, with 3% extension, with the presence of the following signs:

[0456] Color: The skin may appear white in 80% and cherry red in the remaining 20%, with dry and firm texture.

[0457] Following the initial application of the film, on the seven days, most of the eschar around the wound edges had softened and could be gently removed with saline, and showed that the white coloration, characteristic of greater thickness, was only present in 30% of the extension.

[0458] The child did not experience any discomfort during the application, nor during his follow-up.

[0459] A new application of the film showed on day fourteen that the bum was completely covered with epithelial tissue and progressing towards healing.

[0460] Our results clearly indicate the synergistic effect of the materials used for the preparation of the films, they possess many healing-promoting activities and that the use of the vulnerary composition is effective in promoting and accelerating wound healing.

[0461] PATENT CITATION

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[0465] Bruno Grosselli L. and uses thereof

[0466] US9387227B2 2016-07- Gilbert Clinton Gee Method for 12 treatment of sores and lesions of the skin EP1753387A2 2012-05- Dusan Miljkovic Coffee 23 Cherry Cosmetic Compositio ns and Methods KR 2001-01- □ □ □ □ □ □ □ □ □ □ A stabilized 20010002411

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[0468] composition containing L-ascorbic acid JPH0892057A 1996-04- Yukinaga Nishibe, Cosmetic 09 Norihiro Tomono, blended Hisanori Hirasawa, with extract And Tadashi Okada of seed of coffee tree

[0469] WO 1999-12- Inventor Compositio 1999063963 Al 16 Karl Lintner ns for cosmetic or dermo pharmaceuti cal use containing a mixture of green coffee and shea butter extracts

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[0472] KR 2014-06- > > > The pad of 20140077278 24 spread coffee on it

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[0487] 2 US- 2015-02- Juan Miguel Garcia Compositio 2 20150056175- 26 Gilabert's n to prevent

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[0489] and / or treat dermatosis and method to obtain it Non-Patent Citation

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[0535] Industrial Applications

[0536] Coffee, one of the world's most traded commodities, generates significant by-products during production and processing.

[0537] These include skin, pulp, mucilage, parchment, silverskin, and immature / defective beans, accounting for approximately 50% of coffee fruit typically discarded.

[0538] This invention proposes novel applications for coffee by-products in topical formulations, highlighting their bioactive compounds and biological activity.The growing consumer preference for natural products and environmental concerns have sparked increased research interest in this area.

[0539] Key Benefits:

[0540] 1. Waste Reduction: Repurposes 50% of coffee fruit waste, reducing environmental contamination.

[0541] 2. Resource Valorization: Adds value to previously discarded materials.

[0542] 3. Cost-Effective Production: Offers low-cost alternatives for pharmaceutical and cosmetic formulations.

[0543] 4. Sustainable Practices: Promotes a circular economy model in the coffee industry.

[0544] 5. New Revenue Streams: Creates marketable products from waste materials.

[0545] 6. Eco-Friendly Formulations: Aligns with demand for natural, environmentally friendly products.

[0546] 7. Multi-Industry Application: Potential use in food, cosmetic, and pharmaceutical industries.

[0547] Extended Employment Opportunities: The need for additional interventions outside of coffee harvest seasons expands job offerings for field workers. This creates year-round employment in coffee-producing regions, stabilizing local economies and reducing seasonal unemployment.

[0548] The composition, based on bee honey, trigonelline, and zinc oxide, offers advantages in cost-effectiveness, ease of production, and simple application. These characteristics make it suitable for poor regions with limited medical resources.

[0549] Advanced manufacturing technology is expected to drive new product development in various industrial processes. The ingredients' sustainable and accessible sources enable consistent, profitable mass production, ensuring reliable supply for wound care in underserved areas.This invention addresses technological access concerns in developing countries, providing an economic product that improves patients' lives and solves a major problem for less developed regions. Additionally, it contributes to rural development by creating new job opportunities in coffee-producing areas throughout the year.

Claims

AMENDED CLAIMSreceived by the International Bureau on 09 September 2025Claim 1. A vulnerary multifunctional composition for on-time healing, comprising: (a) an extract derived from unripe coffee cherries (Coffea spp., family Rubiaceae); and (b) an extract derived from Trigonella foenum -graecum seeds; wherein the composition is for topical application to promote and expedite wound healing.Claim 2. The composition of claim 1, wherein the composition comprises 15-30% w / w Coffea extract, 5-35% w / w Trigonella foenum -graecum seed extract, and 45-55% w / w pharmaceutically acceptable excipients.Claim 3. The composition of any of claims 1-2, wherein both extracts inherently contain trigonelline (N-methylnicotinic acid) and comprise one or more secondary metabolite classes selected from alkaloids, flavonoids, and saponins.Claim 4. A method of preparing the composition of any of claims 1-3, the method comprising: drying green (unripe) coffee cherries and fenugreek seeds at 40 °C for 16 h; milling to a particle size of less than 100 pm; extracting each milled material in 70:30 ethanol: water at 40 °C with ultrasound at 40 kHz for 60 min; removing solvent by rotary evaporation; purifying by ultrafiltration at a 5 kDa molecular-weight cut-off; combining the Coffea and Trigonella extracts with pharmaceutically acceptable excipients; adjusting pH to 3.8 using a pharmaceutically acceptable acid; forming a hydrogel matrix with agar-agar; and terminally sterilizing the product by ethylene oxide, low-temperature plasma, or gamma irradiation at 2.5-3.5 MRad.Claim 5. The composition of any of claims 1-3 formulated as a cream, ointment, gel, spray, lotion, topical solution, dressing, bandage, or a combination thereof.Claim 6. A method of treating a wound selected from acute wounds, chronic wounds, burns, diabetic foot ulcers, and leg ulcers, the method comprising topically applying the composition of any of claims 1-3 to the wound.

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