Synergistic nutraceutical composition for management of urinary tract infection

Abstract

The invention relates to a synergistic composition comprising extracts of Pelargonium sidoides and cranberry (Vaccinium macrocarpon) with at least one pharmaceutically acceptable excipient for promoting urinary tract health. The composition is useful in the prophylaxis, management, and treatment of urinary tract infections. By reducing reliance on antibiotics, it contributes to mitigation of antimicrobial resistance and provides a safe and effective approach to urinary tract health.

Description

[0001] SYNERGISTIC NUTRACEUTICAL COMPOSITION FOR MANAGEMENT OF URINARY TRACT INFECTION

[0002] RELATED APPLICATION:

[0003] The present application claims benefit of the Indian Provisional Application No. IN202421066043 filed on, September 30th, 2024 the entire contents of which are hereby incorporated by reference.

[0004] FIELD OF THE INVENTION

[0005] The present invention relates to the technical field of nutraceuticals and pharmaceutical compositions. More particularly, the invention provides a synergistic composition comprising an extract of Pelargonium sidoides. and cranberry (Vaccinium macrocarpon). and at least one pharmaceutically acceptable excipient, for use in promoting urinary tract health. The invention encompasses compositions and kits formulated for use in the prophylaxis, management, or treatment of urinary tract infections (UTIs), including but not limited to those caused by Escherichia coli. The invention further encompasses specific ratios, concentrations, dosage ranges, as well as oral dosage forms designed to achieve synergistic biological activity, enhanced anti-adhesion effects, and consistent therapeutic efficacy and further includes methods for preparation thereof. By virtue of this synergistic activity of its constituents, the composition offers a safe and natural approach to promoting urinary tract health and is further suitable for use as an adjunct to conventional therapeutic regimens, thereby potentially reducing reliance on antibiotic treatments and contributing to the mitigation of antimicrobial resistance.

[0006] BACKGROUND OF THE INVENTION

[0007] Urinary tract infections (UTIs) represent one of the most prevalent forms of bacterial infections globally affecting millions of individuals annually. UTIs may involve any region of the urinary system, including but not limited to the urethra, bladder, ureters, and kidneys. The etiological agent responsible for the majority of urinary tract infection is the bacterium Escherichia coli (E. coll), which accounts for up to 95% of all UTI cases. The clinical manifestations of UTIs vary in severity and may include, but are not limited to, dysuria (painful or difficult urination), increased urinary frequency or urgency, nocturia (nighttime urination), abnormal urine coloration, malodorous or strong-smelling urine, hematuria (presence of blood in the urine), and pyuria (presence of pus in the urine).

[0008] A plurality of factors are known to contribute to the onset and recurrence of UTIs. Primary contributing factors include pathogenic overgrowth, particularly by E. coli, as well as compromised or reduced immune functions. Certain strains of E. coli possess specific virulence factors, including but not limited to P-fimbriae, which promote adhesion to the uroepithelial, lining, thereby, impeding the elimination of the bacteria through normal urinary flow. Additionally, a compromised or weakened immune system may exhibit reduced efficacy by mounting a defense against pathogenic invasion thereby facilitating the persistence and recurrence of UTIs.

[0009] Antibiotic therapy represents the standard care of treatment of UTIs. Commonly prescribed antibiotics include, but are not limited to trimethoprim / sulfamethoxazole, fosfomycin, nitrofurantoin, and fluoroquinolones. Although antibiotics are generally effective in the treatment of urinary tract infections, their widespread use and misuse have contributed to the emergence and proliferation of antibiotic-resistant bacterial strains, thereby presenting a significant public health concern. Moreover, administration of antibiotics is associated with adverse side effects and disruption of the normal microbial balance which may result in additional complications including but not limited to gastrointestinal disturbances.

[0010] In view of the increasing challenges associated with antibiotic resistance and the undesirable side effects linked to conventional therapeutic regimens, there exists a continuing and unmet need for the development of alternative therapeutic modalities that are both efficacious and safe. Nutraceuticals, which encompass food-derived products exhibiting health-promoting properties, represents a promising alternative therapeutic approach. Such natural products are capable of exerting antimicrobial, anti-adhesion, and immunomodulatory effects, while advantageously avoiding the adverse effects commonly associated with synthetic drugs.

[0011] US20090175843 discloses a composition for the treatment of urinary tract infections, the composition comprising cranberry concentrate, cranberry extract or a combination thereof, in conjunction with D-mannose and at least one additional component selected from the group consisting of ascorbic acid, bromelain and inulin.

[0012] IN201641028209 discloses a nutraceutical composition comprising Cratcievci nurvalci in combination with piperine for supporting urinary tract health.

[0013] CN104784332 discloses a method for preparing a medicament for the treatment chronic urinary tract infection, the medicament being formulated on the basis of traditional Chinese medicine. The disclosed herbal ingredients comprise Daheiyao, Shanqingpi, Shiliangye, Xiaohuishun, Xiaoya Cong (translated as ‘small scallops ’), Artemisia chinensis, Schisandra, members of the Syringaceae family, water fern, rice flower, Sargassum, Shijiao grass, Niaobuqi, the ‘Four Heavenly Kings ’ (a traditional formula component), and licorice.

[0014] IN202041038568 discloses a nutraceutical food formulation intended for patients suffering from chronic kidney disorder (CKD), the formulation being designed to assist in the management of symptoms and metabolic functions associated therewith. The disclosed formulation comprises alfalfa extract, a blend ofprebiotics and probiotics, one or more anti-inflammatory agents, vitamins, and buffering agents.

[0015] Pelargonium sidoides. commonly referred to as African geranium, has been traditionally used in herbal medicine and is reported to useful in the management of respiratory related conditions, including bronchitis, the common cold, chronic obstructive pulmonary disease (COPD), sore throat and asthma.

[0016] Cranberries are a rich source of proanthocyanidins (PACs), particularly Type-A PACs, which have been shown to inhibit bacterial adhesion within the urinary tract. Unlike conventional cranberry-based compositions that rely solely on Type-A proanthocyanidins (PACs) to reduce bacterial adhesion in the urinary tract, the present invention provides a novel combination of natural bioactives that synergistically exert antimicrobial, anti-adhesion, and immunomodulatory effects, thereby offering enhanced efficacy and safety not suggested or disclosed in the prior art.

[0017] In view of the limitations observed in the prior art for managing urinary tract infections (UTIs) using nutraceuticals, there exists an unmet need for the development of a synergistic formulation capable of overcoming the deficiencies and shortcomings associated with such prior-art compositions.

[0018] OBJECTIVE OF THE INVENTION

[0019] A primary object of the present invention is to provide a synergistic nutraceutical composition comprising Pelargonium sidoides extract, cranberry extract, and at least one pharmaceutically acceptable excipient.

[0020] Another object of the present invention is to provide a composition adapted for use in the prevention, management, or treatment of urinary tract infections (UTIs), particularly those caused by Escherichia coli.

[0021] Another object of the present invention is to provide a composition in which the ratio of Pelargonium sidoides extract to cranberry extract is defined within specific ranges, thereby ensuring enhanced synergistic activity. Another object of the present invention is to provide a composition in which the extracts are present in defined concentration ranges (% w / w) relative to the total composition, thereby enabling reproducible formulation.

[0022] Another object of the present invention is to provide a composition in which the extracts are present in defined weight ranges per unit dosage form, such as tablets or capsules, thereby ensuring effective delivery.

[0023] Another object of the present invention is to provide a composition formulated in a variety of oral dosage forms, including but not limited to tablets, capsules, powders, suspensions, syrups, gummies, solutions, emulsions, sachets, or modified-release formulations, thereby enhancing patient compliance and providing versatility in administration.

[0024] Another object of the present invention is to provide a composition comprising pharmaceutically acceptable excipients selected from diluents, disintegrants, binders, lubricants, glidants, solubilizing agents, suspending agents, flavoring agents, preservatives, buffering agents, solvents, and mixtures thereof.

[0025] Another object of the present invention is to provide a composition demonstrating enhanced biological activity, wherein the anti-adhesion effect against Escherichia coli is at least about 34% greater than the combined individual effects of the extracts, or wherein the wti-Escherichia coli effect is at least about 39% greater than the combined individual effects of the extracts.

[0026] Another object of the present invention is to provide a kit comprising Pelargonium sidoides extract and cranberry extract, the kit being adapted for use in the prevention or management of urinary tract infections.

[0027] Another object of the present invention is to provide a composition that offers a comprehensive approach to UTI management, combining antimicrobial, anti- adhesion, and immunomodulatory effects through the synergistic action of Pelargonium sidoides and cranberry extracts.

[0028] Another object of the present invention is to provide a composition that can serve as a safe, natural, and effective alternative or adjunct to conventional antibiotic therapies, thereby potentially reducing reliance on antibiotics and contributing to the mitigation of antimicrobial resistance.

[0029] Another object of the present invention is to provide a composition that augments the effects of conventional antibiotics, thereby potentially reducing the dosage and duration of antibiotic treatment required for the management of urinary tract infections.

[0030] Another object of the present invention is to provide a natural, plant-based composition for the prevention or treatment of urinary tract infections, which minimizes side effects while promoting overall urinary tract health.

[0031] Another object of the present invention is to provide a standardized nutraceutical composition comprising Pelargonium sidoides and cranberry extracts in specified ratios and concentrations, thereby ensuring consistent efficacy and safety for consumers.

[0032] SUMMARY OF THE INVENTION

[0033] The present invention relates to a synergistic nutraceutical composition comprising Pelargonium sidoides extract, cranberry extract, and at least one pharmaceutically acceptable excipient. The composition demonstrates synergistic activity, providing enhanced effects that are significantly greater than the combined individual activities of the extracts.

[0034] In certain embodiments, the composition is adapted for use in the prevention or management of urinary tract infections (UTIs), particularly those associated with Escherichia coli. The synergistic combination of Pelargonium sidoides and cranberry extracts provides a multifaceted approach, wherein the antimicrobial and immunomodulatory properties of Pelargonium sidoides complement the antiadhesion and anti-inflammatory properties of cranberry extract. As a result, the composition is effective in reducing bacterial adhesion and promoting overall urinary tract health.

[0035] The composition may be formulated with pharmaceutically acceptable excipients such as diluents, binders, disintegrants, lubricants, solubilizing agents, suspending agents, preservatives, buffering agents, solvents, and flavoring agents, and may be administered in a variety of oral dosage forms including tablets, capsules, powders, suspensions, syrups, sachets, solutions, emulsions, gummies, and modified-release formulations. In certain embodiments, the extracts are present in defined ratios, concentration ranges (% w / w), or unit dosage amounts (mg), thereby ensuring reproducibility, stability, and consistent efficacy of the composition.

[0036] In another embodiment, the invention provides a kit comprising Pelargonium sidoides extract and cranberry extract, the kit being adapted for use in the prevention or management of urinary tract infections.

[0037] By virtue of its synergistic action, the present invention offers a safe, natural, and effective nutraceutical composition that may be used independently or as an adjunct to conventional therapies, thereby contributing to improved UTI management, potentially reducing the dosage and duration of antibiotic treatment, and mitigating the development of antibiotic resistance.

[0038] BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure- 1: Synergistic anti-adhesion effects against E. coli

[0040] Figure-2: Synergistic anti- / :'. coli effects

[0041] DETAILED DESCRIPTION OF THE INVENTION The following detailed description of the present subject matter and its various embodiments. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention. It will be understood that other embodiments may be utilized, and modifications may be made without departing from the scope of the present subject matter.

[0042] References to “an”, “one”, or “various” embodiments in this disclosure are not necessarily directed to the same embodiment, and such references are intended to encompass more than one embodiment. Accordingly, the following detailed description is not to be construed in a limiting sense, and the scope of the invention is defined solely by the appended claims, together with the full scope of legal equivalents to which such claims are entitled.

[0043] In one embodiment, the present invention provides a synergistic nutraceutical composition comprising Pelargonium sidoides extract, cranberry extract, and at least one pharmaceutically acceptable excipient.

[0044] The combination of these two extracts produces a synergistic effect greater than the sum of their individual effects, thereby offering an improved therapeutic outcome. The Pelargonium sidoides extract may be obtained by aqueous or hydroalcoholic extraction of the roots, while the cranberry extract may be prepared from whole fruit, fruit powder, or juice concentrate, and may optionally be standardized to contain proanthocyanidins. For the purposes of the present invention, both extracts are sourced from established commercial suppliers and are not derived directly from biological resources.

[0045] Another embodiment of the present invention provides an alternative to conventional antibiotics, particularly in light of increasing antibiotic resistance. By offering a natural, synergistic composition, this invention serves as an adjunctive therapy to synthetic drugs, thereby potentially reducing the reliance on antibiotics. In one embodiment, the present invention provides a nutraceutical composition exhibiting a synergistic anti -E.coli effect. In another embodiment, the nutraceutical composition demonstrates a synergistic anti-adhesion effect against E.coli. Yet another embodiment, the nutraceutical composition with a synergistic immune- stimulatory effect. In further embodiment, the nutraceutical composition augments antibiotics effect against E.coli.

[0046] Another embodiment of the present invention provides a comprehensive, natural, and effective solution for managing urinary tract infections, harnessing the synergistic effects of Pelargonium sidoides extract and Cranberry extract.

[0047] In one embodiment, the present invention specifies the ratios and concentrations of Pelargonium sidoides and Cranberry extracts to ensure consistent and effective outcomes. The defined ranges are designed to maximize the synergistic benefits and therapeutic efficacy of the composition.

[0048] In another embodiment, the present invention provides a synergistic pharmaceutical composition comprising Pelargonium sidoides extract, cranberry extract, and at least one pharmaceutically acceptable excipient, the composition being adapted for use in the prevention or management of urinary tract infections (UTIs). The synergistic activity of Pelargonium sidoides extract and cranberry extract contributes to enhanced anti-adhesion effects against Escherichia col , a primary causative pathogen in UTIs and further enhances an -Escherichia coli effects.

[0049] In another embodiment, the present invention provides a synergistic pharmaceutical composition comprising Pelargonium sidoides extract and cranberry extract in a defined weight ratio. The ratio of Pelargonium sidoides extract to cranberry extract is maintained between 1: 1.2 to 1:50, 1:0.02 to 1: 1500, 1:0.04 to 1:725, 1:0.07 to 1:475, 1:0.11 to 1:350, 1:0.15 to 1:260, 1:0.20 to 1 :200, 1:0.24 to 1: 157.14, 1 :0.27 to 1: 125, 1:0.34 to 1: 108.89 or 1:0.4 to 1:80. The ratio may be expressed on a weight-to-weight basis relative to the active components or standardized extracts. In yet another embodiment, the present invention provides a synergistic pharmaceutical composition comprising Pelargonium sidoides extract and cranberry extract in defined concentrations relative to the total composition. The Pelargonium sidoides extract is present in an amount ranging from about 0.47% to 22.22%, 0.85% to 21.43%, 0.87% to 20.62%, 0.89%% to 19.84%, 0.90% to 18.75%, 0.90% to 18.18 or 0.90% to 17.54% of the total composition, while the cranberry extract is present in an amount ranging from about 3.21% to 93.46%, 3.99% to 93.33%, 4.69% to 92.59%, 4.74% to 92.45%, 5.80% to 91.95%, 6.22% to 91.76%, 6.22% to 90.91% or 6.88% to 89.90% of the total composition. These concentration ranges are selected to provide optimal bioactivity while ensuring formulation stability and patient compliance.

[0050] In another embodiment, the present invention provides a synergistic pharmaceutical composition comprising Pelargonium sidoides extract and cranberry extract in defined amounts per unit dosage form. The Pelargonium sidoides extract is present in an amount ranging from 20 mg to 540 mg, 1 mg to 500 mg, 2 mg to 475 mg, 3 mg to 400 mg, 4 mg to 350 mg, 5 mg to 325 mg, 6 mg to 300 mg, 7 mg to 275 mg, 8 mg to 250 mg, 9 mg to 250 mg or 10 mg to 250 mg and the cranberry extract is present in an amount ranging from 100 mg to 1500 mg, 10 mg to 1500 mg, 20 mg to 1450 mg, 30 mg to 1425 mg, 40 mg to 1400 mg, 50 mg to 1300 mg, 60 mg to 1200 mg, 67 mg to 1100 mg, 67 mg to 1000 mg, 84 mg to 980 mg, or 100 mg to 800 mg per unit dosage form.

[0051] In a further embodiment, the present invention provides a synergistic pharmaceutical composition comprising Pelargonium sidoides extract, cranberry extract, and at least one pharmaceutically acceptable excipient, wherein the composition is formulated in a variety of oral dosage forms. The dosage form may be selected from tablets, capsules, pills, powders, hard capsules filled with liquids or solids, soft capsules containing liquid or semisolid fills, granules, pellets, caplets, mini-tablets, gummies, suspensions, syrups, solutions, emulsions, sachets, or modified-release formulations, or any other formulation intended for oral administration. The selection of dosage form may depend on factors such as the desired release profde, bioavailability, patient compliance, manufacturing convenience, or stability considerations.

[0052] In another embodiment, the present invention provides a synergistic nutraceutical composition comprising Pelargonium sidoides extract, cranberry extract, and at least one pharmaceutically acceptable excipient. The pharmaceutically acceptable excipient is selected from the group of diluents, disintegrants, binders, lubricants, glidants, solubilizing agents, suspending agents, flavoring agents, preservatives, buffering agent, solvents, and mixtures thereof. The composition of the present invention may optionally contain one or more additional pharmaceutically acceptable excipients to enhance stability, palatability, or manufacturability.

[0053] Pharmaceutically acceptable excipients are included in the composition to ensure stability, efficacy, and ease of administration.

[0054] In certain embodiments, the pharmaceutically acceptable excipient is a diluent. The diluent includes, but are not limited to calcium carbonate, dicalcium phosphate, tricalcium phosphate, magnesium carbonate, calcium sulfate, magnesium oxide, microcrystalline cellulose, cellulose powder, maltodextrin, lactose anhydrous, lactose monohydrate, sucrose, mannitol, sorbitol, xylitol, starch, pregelatinized starch, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene glycol, polyvinylpyrrolidone, xanthan gum, or a mixture thereof or like thereof. According to the present invention, the composition may comprise a diluent in an amount ranging from 1% to 98% by w / w of the total composition.

[0055] In certain embodiments, the pharmaceutically acceptable excipient is a binder. The binder includes, but are not limited to microcrystalline cellulose, carboxymethylcellulose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, Hypromellose, low-substituted hydroxypropyl cellulose, methylcellulose, pregelatinized starch, starch, povidone, Polyvinylpyrrolidone, copovidone, carbomer, sodium alginate, acacia, agar, guar gum, maltodextrin, pectin, tragacanth, or a mixture thereof or like thereof. According to the present invention, the composition may comprise a binder in an amount ranging from 0.1% to 12% by w / w of the total composition.

[0056] In certain embodiments, the pharmaceutically acceptable excipient is a lubricant. The lubricant includes, but are not limited to magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, polyethylene glycol, colloidal silicon dioxide, or glyceryl behenate, zinc stearate or a mixture thereof or like thereof. According to the present invention, the composition may comprise a lubricant in an amount ranging from 0.5% to 10% by w / w of the total composition.

[0057] In certain embodiments, the pharmaceutically acceptable excipient is a glidant. The glidant includes, but are not limited to colloidal silicon dioxide, hydrophobic colloidal silica, silicon dioxide, talc, tribasic calcium phosphate, or a mixture thereof or like thereof. According to the present invention, the composition may comprise a glidant in an amount ranging from 0.5% to 10% by w / w of the total composition.

[0058] In certain embodiments, the pharmaceutically acceptable excipient is a disintegrant. The disintegrant includes, but are not limited to alginic acid, calcium alginate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, chitosan, com starch, pregelatinized starch, croscarmellose sodium, crospovidone, docusate sodium, low-substituted hydroxypropyl cellulose, methylcellulose, povidone, sodium alginate, sodium starch glycolate, cross-linked hydroxypropyl cellulose, or a mixture thereof or like thereof. According to the present invention, the composition may comprise a disintegrant in an amount ranging from 0.4% to 15% by w / w of the total composition.

[0059] In certain embodiments, the pharmaceutically acceptable excipient is a surfactant or solubilizing agents. The surfactant or solubilizing agents includes, but are not limited to polysorbates, sorbitan esters, polyethylene glycol esters, polyoxyethylene stearates, polyoxyethylene castor oil derivatives, poloxamers, sodium lauryl sulfate, sodium dodecyl sulfate, sodium stearate, sodium dioctyl sulfosuccinate, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, lecithin, phosphatidylcholine, lauryl betaine, or a mixture thereof or like thereof.

[0060] In certain embodiments, the pharmaceutically acceptable excipient is a suspending agent. Suitable suspending agents include, but are not limited to, natural gums such as acacia, tragacanth, xanthan gum, guar gum, locust bean gum, carrageenan, and alginates; cellulose derivatives such as sodium carboxymethylcellulose, hydroxypropyl methylcellulose, methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, and microcrystalline cellulose; clays and silicates such as bentonite, kaolin, and magnesium aluminum silicate; synthetic or semi-synthetic polymers such as carbomers, polyvinylpyrrolidone, polyacrylic acid derivatives, and poloxamers; as well as gelatin, starch, pregelatinized starch, pectin, sodium starch glycolate, or a mixture thereof or like thereof.

[0061] In certain embodiments, the pharmaceutically acceptable excipient is a flavoring agent. Suitable flavoring agents include, but are not limited to, natural flavoring substances such as essential oils (e.g., peppermint, spearmint, clove, cinnamon, anise, fennel, cardamom, citrus oils, and ginger oil), fruit extracts and concentrates (e.g., apple, cherry, banana, strawberry, raspberry, pineapple, mango, peach, grape, blueberry, cranberry), cocoa, and vanilla; synthetic flavoring substances such as artificial fruit flavors, chocolate, caramel, butterscotch, coffee, and cola; sweetenerbased flavoring agents such as aspartame, saccharin, acesulfame potassium, sucralose, stevia extract, xylitol, sorbitol, mannitol, and maltitol; and additional additives used for flavor modulation including flavor enhancers (e.g., glycyrrhizin, monosodium glutamate) and masking agents such as cyclodextrins, vanillin, and ethyl maltol or a mixture thereof or like thereof. In certain embodiments, the pharmaceutically acceptable excipient is a preservative. Suitable preservatives include, but are not limited to, parabens such as methylparaben, propylparaben, ethylparaben, butylparaben, and their sodium salts; benzoates such as benzoic acid, sodium benzoate, and potassium benzoate; sorbates such as sorbic acid, potassium sorbate, and calcium sorbate; alcohols and phenolic compounds such as ethanol, benzyl alcohol, phenol, cresol, and chlorocresol; quaternary ammonium compounds such as benzalkonium chloride and cetylpyridinium chloride; formaldehyde donors such as imidurea; chelating agents such as EDTA and its salts; sodium dehydroacetate; or a mixture thereof or like thereof.

[0062] In certain embodiments, the pharmaceutically acceptable excipient is a buffering agent. Suitable buffers for suspensions include, but are not limited to, phosphate buffers such as sodium phosphate (monobasic, dibasic, and tribasic), potassium phosphate (monobasic and dibasic), sodium dihydrogen phosphate, and disodium hydrogen phosphate; citrate buffers such as citric acid, sodium citrate, and potassium citrate; acetate buffers such as acetic acid, sodium acetate, and potassium acetate; carbonate and bicarbonate buffers such as sodium bicarbonate, potassium bicarbonate, sodium carbonate, and potassium carbonate; and other buffering agents such as lactic acid, sodium lactate, tromethamine (Tris), boric acid, sodium borate, glycine, or a mixture thereof or like thereof.

[0063] In certain embodiments, the pharmaceutically acceptable excipient is a solvent. Suitable solvents for suspensions include, but are not limited to, aqueous solvents such as purified water, distilled water, and water for injection; alcohols such as ethanol and glycerol; polyols such as propylene glycol, polyethylene glycol, sorbitol solution, and mannitol solution; oils such as vegetable oils (e.g., soybean, sunflower, peanut, olive, sesame, com, cottonseed, and coconut oil), medium chain triglycerides, castor oil, and mineral oil; esters and other co-solvents such as triacetin and propylene carbonate; or a mixture thereof or like thereof. In yet another embodiment, the present invention provides a synergistic pharmaceutical composition comprising Pelargonium sidoides extract, cranberry extract, and at least one pharmaceutically acceptable excipient, wherein the composition exhibits enhanced biological activity compared to the individual extracts administered alone. The composition is adapted to provide enhanced antiadhesion activity against Escherichia coli. with the enhancement being at least about 34% greater than the combined individual activities of the extracts. In certain embodiments, the composition is adapted to provide enhanced an -Escherichia coli effects, with the enhancement being at least about 39% greater than the combined individual activities of the extracts. The composition of the present invention provides an unexpected advantage in the prevention and management of urinary tract infections.

[0064] In another embodiment, the present invention provides a kit comprising Pelargonium sidoides extract and cranberry extract, wherein the kit is adapted for use in the prevention or management of urinary tract infection. The extracts may be provided in separate dosage units or combined within a single packaging system. In certain embodiments, the Pelargonium sidoides extract is supplied in a first container and the cranberry extract in a second container, wherein both containers are packaged together in a single kit. In other embodiments, the kit may comprise blister packs, sachets, bottles, or pouches, each containing one or more dosage forms of the extracts. Optionally, the kit may comprise instructions for administration, indicating that the extracts are to be co-administered for achieving synergistic activity against Escherichia coli adhesion and thereby providing prophylactic or therapeutic benefit in urinary tract infection management.

[0065] In another embodiment, the present invention provides a synergistic pharmaceutical composition comprising Pelargonium sidoides extract and cranberry extract in defined amounts and proportions, formulated for oral administration. The Pelargonium sidoides extract is present in an amount ranging from about 1 mg to about 500 mg per unit dosage form, and the cranberry extract is present in an amount ranging from about 10 mg to about 1500 mg per unit dosage form. The weight ratio of Pelargonium sidoides extract to cranberry extract is maintained between 1:0.02 to 1: 1500. The composition is formulated for oral administration. The composition is adapted to provide enhanced anti-adhesion activity against Escherichia coli. with the enhancement being at least about 34% greater than the combined individual activities of the extracts. The composition provides a synergistic effect in the prevention and management of urinary tract infections.

[0066] The composition of the present invention can be prepared using conventional methods known in the art for formulating oral dosage forms. Depending on the desired final product, the formulation may be prepared through direct compression, wherein the active pharmaceutical ingredient is blended with suitable excipients such as fillers, binders, disintegrants, and lubricants, followed by compression into tablets. Alternatively, the composition may be processed through granulation techniques, including wet or dry granulation, to enhance flow properties and compressibility. The prepared formulation can be filled into sachets or capsules for ease of administration. Additionally, the composition can be supplied as a powder or granules for reconstitution into an oral suspension. Other suitable processes may also be employed to achieve the desired dosage form while ensuring stability, efficacy, and patient compliance. The processes for the preparation of nutraceutical compositions are well known in the art.

[0067] The ratio of Pelargonium sidoides to Cranberry extract is 1:0.02 to 1: 1500.

[0068] The percentage of Pelargonium sidoides extract is ranging from 1% to 50% or 9.09% to 25% of combined total weight of Pelargonium sidoides extract and Cranberry extract.

[0069] The percentage of Cranberry extract is ranging from 65% to 99% or 75.00% to 90.91% of combined total weight of Pelargonium sidoides extract and Cranberry extract. The present invention provides several advantages over prior art. It offers a synergistic composition with enhanced anti-adhesion and antibacterial activity against Escherichia coli. It provides a safe, natural alternative or adjunct to antibiotics, potentially reducing the dosage and duration of antibiotic therapy and thereby contributing to the mitigation of antimicrobial resistance. The composition is versatile, being suitable for multiple dosage forms, which improves patient compliance.

[0070] EXAMPLES

[0071] The following examples are provided to further illustrate the invention and its various embodiments. These examples are intended solely for the purpose of explanation and should not be construed as limiting the scope of the invention in any manner. It will be understood by those skilled in the art that modifications, variations, and equivalents of the described examples may be made without departing from the spirit and scope of the invention as defined by the appended claims.

[0072] Example 1: Composition

[0073] Following is a general composition formula as per the present invention:

[0074] Process for preparation of example 1 :

[0075] 1. Accurately weigh each ingredient in separate containers.

[0076] 2. Sift the previously weighed active ingredients and excipients through a sieve.

[0077] 3. Combine the contents from step 2 to prepare suitable oral dosage form.

[0078] Example 2A - Composition - Sachet

[0079] Example 2B - Composition - Sachet

[0080] Manufacturing process of Sachet:

[0081] 1. All the active ingredients and excipients were accurately weighed as per the batch formula, passed through a #30 mesh (-600 pm), and silica were passed through #60 (-250 pm).

[0082] 2. Sweetener premix was made by geometrically mixing sucralose with ~10x its weight of maltodextrin for uniformity.

[0083] 10 3. In a blender charge -50% maltodextrin, actives (Pelargonium + Cranberry), mannitol, citric acid, sodium citrate, silicon dioxide sweetener premix and flavour were blended. 4. The blend underwent in-process checks including blend uniformity and flow properties.

[0084] 5. The blended powder was filled into pre-formed sachets.

[0085] 6. Sachets were sealed and packed into suitable packs, labelled, and stored

[0086] 5 under recommended conditions.

[0087] Example 3A - Composition - Tablets

[0088] Example 3B - Composition - Tablets

[0089] 1. All the active ingredients and excipients were accurately weighed as per the batch formula, passed through a #30 mesh (-600 pm), silica and magnesium stearate were passed through #60 (-250 pm).

[0090] 5 2. Charge actives (Pelargonium + Cranberry), MCC (-70% of total MCC q.s.), pregelatinized starch and PVP K30 were blended for 8-10 min or until homogeneous.

[0091] 3. The pre-blend were compacted to ribbons / flakes and milled through 0.8-1.0 mm screen to a controlled PSD.

[0092] 10 4. Granules were transferred to a blender and blended with remaining MCC, croscarmellose sodium, colloidal silicon dioxide and magnesium stearate.

[0093] 5. The blend from Step 4 was compressed to form tablets and film coated.

[0094] 6. The finished products were packed into HDPE bottles with desiccant or alu- alu blisters to prevent moisture, labelled, and stored under recommended

[0095] 15 conditions.

[0096] Example 4 - Composition - Capsules 500

[0097] Manufacturing process of Capsules:

[0098] 1. All the active ingredients and excipients were accurately weighed as per the batch formula, passed through a #30 mesh (-600 pm), silica and magnesium

[0099] 5 stearate were passed through #60 (-250 pm).

[0100] 2. In a blender Pelargonium, Cranberry extracts, MCC, pregelatinized starch, crospovidone were added and blended to form pre blend.

[0101] 3. Colloidal silicon dioxide and Magnesium stearate were added to the blender along with the pre-blend and mixed thoroughly to achieve a homogeneous

[0102] 10 blend.

[0103] 4. The blend from Step 3 were filled into capsules.

[0104] 5. The finished products were packed blister or HDPE bottles with desiccant to prevent moisture, labelled, and stored under recommended conditions.

[0105] 15 Example 5 - Composition - Suspension

[0106] Manufacturing process of Suspension:

[0107] 1. All the active ingredients and excipients were accurately weighed as per the batch formula and passed through an appropriate mesh sieve to remove

[0108] 20 lumps and ensure uniform particle size. . The xanthan: sprinkle xanthan gum was prehydrated into -20% of batch water under high-shear agitation to avoid lumps. NaCMC solution was prepared in separate vessel and combined with xanthan slurry.

[0109] 3. Sorbitol was dissolved into main vessel and PVP K30 was added and mixed until dissolved / suspended.

[0110] 4. Sodium benzoate was dissolved in a small portion of water and added to main vessel. Citric acid gradually added to make pH upto -3.5-4.0.

[0111] 5. Pelargonium and Cranberry powders were blended together and prewetted with small portion of polysorbate 80 (diluted) to avoid floating.

[0112] 6. Wetted actives were slowly added to the hydrated viscosity system under low shear, then mixing was gently increased to disperse. Homogenized at medium speed until uniform suspension and desired particle distribution are achieved. Optionally the bulk was passed through a 600-800 pm screen to remove large agglomerates.

[0113] 7. After mixing the final product of step-6 is filled in suitable containers and sealed. The containers were packed, labelled, and stored under recommended conditions.

[0114] EXAMPLE 3: Animal Study

[0115] Objective of the study: To evaluate the anti-adhesion and axA -Escherichia coli (UPEC) activities of Pelargonium sidoides (PS) and Cranberry (CR) extracts, both individually and in combination, using a human uroepithelial cell model.

[0116] Safety Precautions: All personnel handling bacterial cultures will wear appropriate PPE (lab coat, gloves, safety goggles).

[0117] Test system:

[0118] • Cell line: Human bladder epithelial cells (5637).

[0119] • Bacterial strain: Uropathogenic E. coli (UPEC) CFT073.

[0120] Preparation of Test Items: • Cranberry extract (CR): Standardized to proanthocyanidin (PAC) equivalents; stock prepared in DPBS at 100x working concentration. Final test concentration: 345.8 pg / mL PAC equivalent.

[0121] • Pelargonium sidoides extract (PS): Standardized extract; stock prepared in DPBS at 100x working concentration. Final test concentration: 50 pg / mL.

[0122] • Combination group (PS + CR): Mixture of CR and PS at above test concentrations.

[0123] Anti-Adhesion Assay:

[0124] Host Cell Preparation:

[0125] • 5637 cells seeded at 5 x 104- 1 x 105cells / well in 96-well plates.

[0126] • Incubated at 37 °C, 5% CO2, >90% humidity until 80-90% confluent.

[0127] Bacterial Preparation:

[0128] • UPEC grown overnight in LB broth at 37 °C, 200 rpm.

[0129] • Diluted 1 : 100 in fresh broth and incubated to mid-log phase (ODeoo = 0.4- 0.6).

[0130] • Adjusted to ODeoo ~ 0.5 (~5 x 108CFU / mL).

[0131] • Diluted to obtain MOI 50: 1 (5 x 106CFU per 1 x 105host cells).

[0132] Assay:

[0133] • Confluent cells pre-treated with vehicle control, positive control, negative control, or test extracts (PS, CR, PS+CR) for 1 h at 37 °C.

[0134] • Cells washed with DPBS and infected with UPEC (MOI 50: 1) for 30-60 min.

[0135] • Non-adherent bacteria removed by PBS wash (3 x).

[0136] • Host cells lysed with Tween-20

[0137] • Lysates serially diluted and plated on LB agar.

[0138] • Colonies counted after 18-24 h and expressed as CFU / plate.

[0139] Anti- / :', colt (CFU Reduction) Assay:

[0140] Bacterial Preparation:

[0141] • Overnight UPEC culture diluted 1 : 100 in fresh broth and incubated to midlog phase (ODeoo = 0.4-0.6). • Adjusted to ~1 x 106CFU / mL in DPBS.

[0142] Treatment Groups:

[0143] • The cells were treated in following treatment groups in triplicates:

[0144] DPBS= Dulbecco’s Phosphate Buffer Saline

[0145] Procedure:

[0146] • 900 pL bacterial suspension + 100 pL treatment solution (final volume 1 mL).

[0147] • Incubated at 37 °C, 100-200 rpm, for 2 h.

[0148] • Ten-fold serial dilutions prepared in sterile PBS / saline.

[0149] • 100 pL plated on LB agar (duplicate plates).

[0150] • Incubated at 37 °C for 18-24 h.

[0151] • Colonies enumerated and expressed as CFU / plate.

[0152] 7. Data Analysis:

[0153] • Results expressed as mean ± standard deviation (SD).

[0154] Replicates:

[0155] • All experiments conducted in triplicates (n=3 per group).

[0156] • Each experiment repeated independently at least twice to confirm reproducibility.

[0157] Animal study results:

[0158] Significance of anti-adhesion effects against E. coli: Adhesion of uropathogenic Escherichia coli (UPEC) to uroepithelial cells is the critical first step in urinary tract infection (UTI) pathogenesis, enabling colonization, biofilm formation, and persistence within the urinary tract. Therefore, demonstrating anti-adhesion activity provides mechanistic evidence of a product’s potential to prevent UTI by blocking 5 bacterial colonization at its earliest stage. A higher degree of anti-adhesion effect is indicative of better prophylactic efficacy against UTI, whereas lower activity corresponds to reduced preventive potential. Unlike bactericidal strategies, antiadhesion approaches reduce infection risk without promoting antimicrobial resistance, making them particularly relevant for long-term prophylaxis in recurrent 10 UTI management. Study results of the anti-adhesion effects against E. coli are provided in table 2.

[0159] Table 2:

[0160] * in combination group (T3) compared to the sum of change in individual Test groups (T1+T2)

[0161] 15

[0162] An - Escherichia coli activity (Anti- E.coli) is a critical parameter in assessing the anti-UTI potential of a product, since uropathogenic E. coli (UPEC) is the predominant causative agent of urinary tract infections. Reduction in bacterial viability, as measured by colony-forming units (CFU), indicates the ability of a 20 product to lower pathogen load and thereby reduce colonization, infection severity, and recurrence. A higher anti- / :', coli effect corresponds to greater efficacy, while lower activity suggests reduced preventive or therapeutic potential. Study results of the Anti-Escherichia coli activity are provided in table 3.

[0163] 25 Table 3:

[0164] * in combination group (T3) compared to the sum of change in individual Test groups (T1+T2)

[0165] The results of the study as presented in the tables above clearly demonstrate that the present invention provides a synergistic nutraceutical composition comprising

[0166] 5 Pelargonium sidoides extract and cranberry extract, which represents a technical advance over existing nutraceutical or conventional therapies for urinary tract infections (UTIs). The combination produces an unexpected synergistic effect, delivering at least about 34% greater anti-adhesion activity against Escherichia coli and at least about 39% greater anti- / :'. coli effects compared to the extracts

[0167] 10 administered individually. This dual-extract formulation integrates multi mechanism action within a single standardized composition, ensuring reproducibility, stability, and consistent efficacy. The ability to formulate the composition in multiple oral dosage forms including tablets, capsules, powders, suspensions, further enhances versatility and patient compliance.

[0168] 15

[0169] The invention also offers clear economic and industrial significance. By reducing reliance on antibiotics, the composition helps mitigate antimicrobial resistance while lowering healthcare costs associated with recurrent infections and prolonged antibiotic use. Its plant derived, well-tolerated ingredients make it suitable for

[0170] 20 widespread consumer and clinical adoption. The composition can be readily manufactured using conventional processes. Thus, the invention combines technical innovation with economic benefit and is capable of industrial application in the nutraceutical and pharmaceutical sectors, offering a safe, effective, and commercially viable solution for UTI management.

[0171] 25

Claims

I / WE CLAIMS:

1. A synergistic nutraceutical composition comprising:(a) Pelargonium sidoides extract;(b) Cranberry extract; and(c) At least one pharmaceutically acceptable excipient.

2. The synergistic nutraceutical composition as claimed in claim 1, wherein the composition is adapted for use in the treatment of urinary tract infection.

3. The synergistic nutraceutical composition as claimed in claim 1, wherein the weight ratio of Pelargonium sidoides extract to cranberry extract is 1:0.02 to 1: 1500.

4. The synergistic nutraceutical composition as claimed in claim 1, wherein the composition comprises:(a) Pelargonium sidoides extract in an amount ranging from 0.47% to 22.22 % w / w of the total composition; and(b) cranberry extract in an amount ranging from 3.21 % to 93.46 % w / w of the total composition.

5. The synergistic nutraceutical composition as claimed in claim 1, wherein the composition comprises:(a) Pelargonium sidoides extract in an amount ranging from 1 mg to 500 mg; and(b) cranberry extract in an amount ranging from 10 mg to 1500 mg, by weight per unit dosage form.

6. The synergistic nutraceutical composition as claimed in claim 1, wherein the composition is in a dosage form selected from tablet, capsule, pill, powder, hard capsule fdled with liquid or solids, soft capsule, granule, pellet, caplet, mini-tablet, gummy, suspension, syrup, solution, emulsion, sachet, modified-release formulation, or any other formulation intended for oral administration.

7. The synergistic nutraceutical composition as claimed in claim 1, wherein at least one pharmaceutically acceptable excipient is selected from the group of diluents, disintegrants, binders, lubricants, glidants, solubilizing agents, suspending agents, flavoring agents, preservatives, buffering agent, solvents, and mixtures thereof.

8. The synergistic nutraceutical composition as claimed in claim 1, wherein the composition is adapted to provide enhanced anti-adhesion activity against Escherichia coli, the enhancement being at least 34% greater than the combined individual activities of the extracts, or adapted to provide enhanced anti- Escherichia coli effects, the enhancement being at least 39% greater than the combined individual activities of the extracts.

9. A kit comprising:(a) Pelargonium sidoides extract; and(b) cranberry extract; wherein the kit is adapted for use in the prevention or management of urinary tract infection.

10. The synergistic nutraceutical composition as claimed in claim 1, wherein the composition comprises:(a) Pelargonium sidoides extract in an amount ranging from 1 mg to 500 mg;(b) cranberry extract in an amount ranging from 10 mg to 1500 mg; wherein the weight ratio of Pelargonium sidoides extract to cranberry extract is 1:0.02 to 1: 1500; and wherein the composition is formulated for oral administration and is adapted to provide enhanced anti-adhesion activity against Escherichia coli, the enhancement being at least 34% greater than the combined individual activities of the extracts.

Images