Herbal formulation for the management of metabolic disorders, and method of preparation thereof

Abstract

The present invention relates to a synergistic herbal formulation comprising standardised extracts of Berbens aristata and Phyllanthus emblica for the management of elevated blood glucose levels, insulin resistance, prediabetes, and type 2 diabetes mellitus. The formulation includes Berberis aristata extract containing 1% to 30% berberine and a whole extract of Phyllanthus emblica comprising tannins, gallic acid, and ellagic acid. In preferred embodiments, lecithin is incorporated to enhance the bioavailability of berberine through phospholipid complexation. The invention also provides a scalable method for preparing the formulation using hydroalcoholic extraction and lyophilisation. The formulation demonstrates dual activity: reducing glucose levels and enhancing insulin sensitivity via PPAR-y modulation. Preclinical and clinical studies confirm its efficacy and safety. The formulation is suitable for oral administration in various dosage forms and offers a natural, steroid-free alternative to conventional antidiabetic agents. The invention further includes therapeutic kits and methods for treating metabolic disorders.

Description

HERBAL FORMULATION FOR THE MANAGEMENT OF METABOLICDISORDERS, AND METHOD OF PREPARATION THEREOFFIELD OF THE INVENTION

[0001] The present disclosure relates to the field of herbal formulations for metabolic health. More specifically, it pertains to a synergistic composition comprising extracts of Berberis aristata and Phyllanthus emblica. and a method for preparing the same, for use in the prevention and management of elevated blood glucose levels, insulin resistance, prediabetes, and related metabolic disorders.BACKGROUND OF THE INVENTION

[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.

[0003] Diabetes mellitus, particularly Type 2 Diabetes Mellitus (T2DM), is a chronic and progressive metabolic disorder characterised by sustained hyperglycemia resulting from insulin resistance, impaired insulin secretion, or both. It represents one of the most significant public health challenges worldwide, with its incidence rising sharply due to sedentary lifestyles, dietary imbalances, and genetic predispositions. The disease exerts a deleterious effect on multiple organ systems, including the cardiovascular system, kidneys, eyes, liver, and nervous system, ultimately leading to increased morbidity and premature mortality. In addition to the core metabolic disturbances, T2DM is frequently associated with dyslipidemia, chronic inflammation, oxidative stress, and endothelial dysfunction, making it a multifactorial condition requiring a comprehensive treatment approach.

[0004] Conventional pharmacological interventions for T2DM include oral hypoglycemic agents such as biguanides (e.g., metformin), sulfonylureas, thiazolidinediones, alphaglucosidase inhibitors, DPP-4 inhibitors, and insulin. While these agents have been proven effective in reducing blood glucose levels, they are often associated with a range of adverse effects, including gastrointestinal irritation, risk of hypoglycemia, hepatic and renal toxicity, weight gain, and cardiovascular complications. Specifically, thiazolidinediones such as rosiglitazone and pioglitazone act as Peroxisome Proliferator-Activated Receptor-gamma (PPAR-y) agonists and are known to improve insulin sensitivity. However, their use is constrained by safety concerns, including fluid retention, edema, risk of congestive heartfailure, and bone fractures. Furthermore, the long-term use of synthetic drugs may lead to decreased efficacy due to drug tolerance or receptor desensitisation, necessitating dose escalation or combination therapy, which further increases the risk of side effects.

[0005] The limitations of conventional antidiabetic therapies have generated a growing interest in plant-based alternatives that offer a holistic and multi-targeted approach to glycemic control. Herbal medicines have been used for centuries in traditional systems such as Ayurveda, Traditional Chinese Medicine, and Unani, with reported benefits in metabolic regulation. Several plant-derived compounds possess hypoglycemic, insulin-sensitising, antiinflammatory, and antioxidant properties. However, most herbal formulations on the market today suffer from key drawbacks, including a lack of standardisation of bioactive constituents, insufficient clinical validation, low bioavailability, absence of mechanistic understanding, and poor formulation stability. Many such preparations are empirical in nature and lack scientific rigour in design and development, limiting their global acceptance in modem evidence -based medicine.

[0006] Berberis aristata. a medicinal plant traditionally used for its antimicrobial, hepatoprotective, and antidiabetic properties, contains berberine, a well-documented alkaloid known for its ability to activate AMPK and modulate insulin signalling pathways. Phyllanthus emblica (Indian gooseberry or Amla) is another well-known adaptogenic herb, rich in tannins, gallic acid, and ellagic acid, which exert potent antioxidant, antiinflammatory, and metabolic regulatory effects. Although both of these plants individually possess anti-diabetic potential, there exists limited data on their synergistic action when combined in a scientifically optimised formulation. More importantly, berberine’s low aqueous solubility and poor intestinal absorption remain significant challenges, limiting its systemic bioavailability and therapeutic impact.

[0007] Thus, there exists a compelling unmet need for a safe, effective, and scientifically validated herbal alternative to current anti-diabetic drugs. The present invention fulfills this need by offering a dual-mechanism herbal formulation that acts as both an insulin sensitiser and an anti-hyperglycemic agent, suitable for long-term use in managing prediabetes, T2DM, metabolic syndrome, and associated disorders. This innovation not only aligns with modem pharmacognostic principles but also addresses regulatory, clinical, and consumer demands for clean-label, plant-based therapeutic solutions in metabolic healthcare.OBJECTIVE OF THE INVENTION

[0008] The primary objective of the present invention is to develop a scientifically validated, synergistic herbal formulation comprising standardised extracts of Berberis aristata and Phyllanthus emblica for the effective management of elevated blood glucose levels, insulin resistance, and related metabolic disorders, including prediabetes and type 2 diabetes mellitus.

[0009] A further objective is to enhance the bioavailability and stability of the formulation through phospholipid complexation, thereby improving therapeutic efficacy without the adverse effects associated with conventional synthetic antidiabetic agents.

[0010] Another objective of the invention is to provide a reproducible and scalable method of preparation that ensures consistency in phytoconstituent composition, pharmacological action, and patient safety.SUMMARY OF THE INVENTION

[0011] The present invention provides a novel and synergistic herbal formulation comprising an extract of Berberis aristata and a whole extract of Phyllanthus emblica, designed for the prevention and management of elevated blood glucose levels, insulin resistance, prediabetes, and related metabolic disorders. The Berberis aristata extract contains berberine in the range of 10% to 20% by weight, while the Phyllanthus emblica whole extract is a defined mixture of Phyllanthus emblica extract and juice powder in a 2: 1 weight ratio, comprising 40% to 60% tannins and 5 % to 20% gallic acid and ellagic acid.

[0012] The invention further discloses a method for preparing the formulation that includes aqueous, alcoholic, or hydroalcoholic extraction of the plant parts, followed by blending and lyophilisation. To overcome the known limitations of phytochemical instability and poor absorption — particularly in the case of berberine — the invention incorporates lecithin as a phospholipid carrier in an amount ranging from 3% to 30% by weight, enabling enhanced bioavailability, formulation stability, and shelf-life.

[0013] In an aspect, the present disclosure provides a herbal formulation comprising: an extract of Berberis aristata, and an extract of Phyllanthus emblica, wherein the formulation is for the management of elevated blood glucose levels and insulin resistance in a subject.

[0014] In another embodiment, the present disclosure provides a method of preparing the formulation as disclosed herein above, comprising:extracting the stem of Berberis aristata using an aqueous, alcoholic, or hydroalcoholic solvent at a temperature ranging from 50°C to 70°C for a duration of 2- 4hours to obtain a Berberis extract; extracting the fruit of Phyllanthus emblica using an aqueous, alcoholic, or hydroalcoholic solvent, wherein:(i) when a dry Phyllanthus emblica extract is used, the extraction is carried out at a temperature in the range of 55°C to 60°C for a duration of 2 hours; and(ii) when Phyllanthus emblica juice powder is used, the extraction temperature and duration are not applicable; mixing the Phyllanthus emblica extract and juice powder to prepare a whole extract in a weight ratio of 2: 1 ; and optionally combining the whole extract with lecithin and lyophilising the mixture to obtain the final formulation.

[0015] In another embodiment, the present disclosure provides a method of managing blood glucose levels or insulin resistance in a subject, comprising administering to the subject a therapeutically effective amount of the formulation as claimed in any one of the preceding claims.

[0016] In another embodiment, the present disclosure provides a herbal formulation comprising: an extract of Berberis aristata comprising 10% to 20% berberine by weight; and a whole extract of Phyllanthus emblica comprising 40% to 60% tannins and 5% to 20% gallic acid and ellagic acid by weight; wherein the formulation is adapted to reduce insulin resistance and elevated blood glucose levels in a subject.

[0017] In another embodiment, the present disclosure provides the use of a synergistic herbal formulation comprising Berberis aristata extract and Phyllanthus emblica extract in the manufacture of a medicament for reducing insulin resistance or modulating PPAR-y activity in a subject.

[0018] In another embodiment, the present disclosure provides a kit for the management of elevated blood glucose levels and insulin resistance in a subject, the kit comprising: a synergistic herbal formulation comprising an extract of Berberis aristata and a whole extract of Phyllanthus emblica,' and instructions for administration of the formulation to a subject in need thereof.

[0019] Various objects, features, aspects, and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments.BRIEF DESCRIPTION OF FIGURES

[0020] The accompanying drawings are included to provide a clear understanding of the present invention and a detailed description, and they constitute a part of this complete specification.

[0021] Figure 1 shows chemical structures of Gallic acid, Berberine and Ellagic acid

[0022] Figure 2 shows chromatograms of the standards of Gallic acid and Berberine

[0023] Figure 3 shows chromatograms of Nextberi Extract

[0024] Figure 4 shows the Insulin level of animals post-treatment of the respective group

[0025] Figure 5 shows the results of the OGTT (Oral Glucose Tolerance Test) on day 44

[0026] Figure 6 shows the Insulin levels of animals on day 44

[0027] Figure 7 shows the Matsuda index on day 44.DETAILED DESCRIPTION OF THE INVENTION

[0028] The following is a full description of the disclosure's embodiments. The embodiments are described in such a way that the disclosure is clearly communicated. The level of detail provided, on the other hand, is not meant to limit the expected variations of embodiments; rather, it is designed to include all modifications, equivalents, and alternatives that come within the spirit and scope of the current disclosure as defined by the attached claims. Unless the context indicates otherwise, the term "comprise" and variants such as "comprises" and "comprising" throughout the specification are to be read in an open, inclusive meaning, that is, as "including, but not limited to."

[0029] When "one embodiment" or "an embodiment" is used in this specification, it signifies that a particular feature, structure, or characteristic described in conjunction with the embodiment is present in at least one embodiment. As a result, the expressions "in one embodiment" and "in an embodiment" that appear throughout this specification do not necessarily refer to the same embodiment. Furthermore, in one or more embodiments, the specific features, structures, or qualities may be combined in any appropriate way.

[0030] Unless the context clearly demands otherwise, the singular terms "a," "an," and "the" include plural referents in this specification and the appended claims. Unless the content explicitly mandates differently, the term "or" is normally used in its broad definition, which includes "and / or."

[0031] All processes described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0032] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.

[0033] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.

[0034] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified, thus fulfilling the written description that follows, and the embodiments described herein, are provided by way of illustration of an example, or examples, of particular embodiments of the principles and aspects of the present disclosure. These examples are provided for explanation, and not as a limitation, of those principles and of the disclosure.

[0035] It should also be appreciated that the present invention can be implemented in numerous ways, including as a system, a method, or a device. In this specification, these implementations, or any other form that the invention may take, may be referred to as processes. In general, the order of the steps of the disclosed processes may be altered within the scope of the invention.

[0036] Various terms used herein are shown below. To the extent a term used in a claim is not defined below, it should be given the broadest definition that persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.Definition

[0037] For the purpose of the present disclosure, "Formulation" refers to a composition comprising two or more herbal extracts and optionally pharmaceutically acceptable excipients intended for oral administration.

[0038] For the purpose of the present disclosure, "Herbal formulation" refers to a composition derived entirely or predominantly from botanical sources, including extracts, powders, and concentrates of medicinal plants.

[0039] For the purpose of the present disclosure, "Synergistic" refers to the combined effect of two or more components being greater than the sum of their individual effects.

[0040] For the purpose of the present disclosure, "Berberis aristata extract" refers to a plant extract derived from the stem or root of Berberis aristata, standardised to contain a defined percentage of berberine.

[0041] For the purpose of the present disclosure, "Phyllanthus emblica extract" refers to an extract obtained from the fruit of Phyllanthus emblica, also known as Indian gooseberry or Amla, containing bioactive compounds such as gallic acid, ellagic acid, and tannins.

[0042] For the purpose of the present disclosure, "Whole extract of Phyllanthus emblica" refers to a blend of Phyllanthus emblica extract and Phyllanthus emblica juice powder in a predetermined weight ratio.

[0043] For the purpose of the present disclosure, "Berberine" refers to an isoquinoline alkaloid known for its antihyperglycemic, antimicrobial, and metabolic regulatory activity, present in Berberis aristata.

[0044] For the purpose of the present disclosure, "Gallic acid" refers to a polyphenolic compound present in Phyllanthus emblica known for its antioxidant and anti-inflammatory properties.

[0045] For the purpose of the present disclosure, "Ellagic acid" refers to a natural phenol antioxidant found in Phyllanthus emblica with antidiabetic, hepatoprotective, and anti-inflammatory activity.

[0046] For the purpose of the present disclosure, "PPAR-y" refers to Peroxisome Proliferator-Activated Receptor Gamma, a nuclear receptor involved in glucose metabolism, insulin sensitivity, and adipocyte differentiation.

[0047] For the purpose of the present disclosure, "Insulin resistance" refers to a condition in which body tissues exhibit reduced responsiveness to insulin, leading to impaired glucose uptake.

[0048] For the purpose of the present disclosure, "Pre-diabetes" refers to a metabolic state characterised by blood glucose levels higher than normal but not high enough to be classified as diabetes.

[0049] For the purpose of the present disclosure, "Diabetes mellitus" refers to a group of metabolic disorders characterised by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both.

[0050] For the purpose of the present disclosure, "Lecithin" refers to a phospholipid used in the present invention to form complexes with bioactive herbal constituents to enhance solubility and bioavailability.

[0051] For the purpose of the present disclosure, "Phospholipid complexation" refers to a method of formulation wherein lipophilic or poorly soluble compounds are combined with phospholipids to form stable complexes or vesicles.

[0052] For the purpose of the present disclosure, "Bioavailability" refers to the proportion of an administered substance that reaches the systemic circulation and is available for biological activity.

[0053] For the purpose of the present disclosure, "lyophilisation" refers to a freeze- drying technique used to remove moisture from botanical extracts to improve stability and shelf life.

[0054] For the purpose of the present disclosure, "Standardised extract" refers to an herbal extract adjusted to contain a specified amount of one or more marker compounds or active principles.

[0055] For the purpose of the present disclosure, "Dosage form" refers to the physical form in which the herbal formulation is administered, including tablets, capsules, powders, granules, suspensions, or gels.

[0056] For the purpose of the present disclosure, "Pharmaceutically acceptable excipient" refers to a non-toxic substance used in formulation for aiding stability, delivery, or administration without interfering with the therapeutic efficacy.

[0057] For the purpose of the present disclosure, "Subject" refers to a human or animal individual in need of prevention or treatment of elevated blood glucose or insulin resistance.

[0058] For the purpose of the present disclosure, "Therapeutically effective amount" refers to the amount of formulation sufficient to achieve a desired therapeutic effect without causing significant adverse effects.

[0059] For the purpose of the present disclosure, "PPAR-y modulator" refers to a substance that activates or enhances the activity of PPAR-y receptors involved in glucose and lipid metabolism.

[0060] For the purpose of the present disclosure, "Chronic hyperglycemia" refers to persistently high blood glucose levels associated with long-term complications in diabetic patients.

[0061] In an embodiment, the present invention discloses a synergistic herbal formulation comprising extracts of Berberis aristata and Phyllanthus emblica for the prevention and management of elevated blood glucose levels, insulin resistance, and related metabolic disorders, including prediabetes and type 2 diabetes mellitus. The invention also discloses a method for the preparation of this formulation in a reproducible, scalable, and pharmaceutically acceptable manner, ensuring improved stability, bioavailability, and therapeutic efficacy.

[0062] In one embodiment of the invention, the herbal formulation comprises an extract of Berberis aristata and an extract or whole extract of Phyllanthus emblica, wherein the weight ratio of Berberis aristata to Phyllanthus emblica ranges from 1:9 to 9: 1.

[0063] In a preferred embodiment, the formulation comprises Berberis aristata extract in an amount ranging from 10% to 90% by weight and Phyllanthus emblica extract or whole extract in an amount ranging from 10% to 90% by weight of the total composition.

[0064] In a more specific embodiment, Berberis aristata extract is present at 30% to 40% by weight, while Phyllanthus emblica whole extract is present at 50% to 60% by weight. In a highly preferred embodiment, the formulation comprises 35% Berberis aristata extract, 55% Phyllanthus emblica whole extract, and 10% lecithin by weight.

[0065] The Berberis aristata extract used in the present invention is standardised to contain berberine in the range of 10% to 20% by weight, preferably 10% to 20%, based on the total weight of the extract. The Phyllanthus emblica whole extract comprises a defined mixture of Phyllanthus emblica fruit extract and juice powder in a weight ratio of approximately 2: 1. This whole extract is standardized to contain 40% to 60% tannins and 5%to 20% of a combined amount of gallic acid and ellagic acid, which are known to contribute to antioxidant and metabolic regulatory properties.

[0066] In another embodiment, the formulation further comprises lecithin in an amount ranging from 3% to 30% by weight of the total formulation, preferably from 5% to 15%, to enhance the bioavailability and stability of the active phytoconstituents. Lecithin acts as a phospholipid complexing agent, forming a molecular complex with the berberine-rich Berberis aristata extract, thereby improving its solubility and gastrointestinal absorption. This lipid-based enhancement significantly increases systemic exposure of the active compounds and their therapeutic index.

[0067] In an embodiment, the present disclosure provides a herbal formulation comprising: an extract of Berberis aristata, and an extract of Phyllanthus emblica, wherein the formulation is for the management of elevated blood glucose levels and insulin resistance in a subject.

[0068] In another embodiment, the Berberis aristata extract comprises berberine in a concentration ranging from 10% to 20% by weight.

[0069] In another embodiment, the Phyllanthus emblica extract comprises tannins in a concentration of 40% to 60% and gallic acid and / or ellagic acid in a concentration of 5% to 20% by weight.

[0070] In another embodiment, the Phyllanthus emblica extract is a whole extract comprising a mixture of Phyllanthus emblica extract and juice powder in a weight ratio of 2: 1.

[0071] In another embodiment, said formulation further comprises lecithin in an amount ranging from 3% to 30% by weight of the formulation.

[0072] In another embodiment, the extract of Berberis aristata is complexed with lecithin to enhance its stability and bioavailability.

[0073] In another embodiment, said formulation further comprises one or more pharmaceutically acceptable excipients selected from the group consisting of diluents, binders, disintegrants, lubricants, stabilisers, and preservatives.

[0074] In another embodiment, the formulation is in a solid, liquid, suspension, or semi-solid dosage form.

[0075] In another embodiment, the formulation is adapted to modulate Peroxisome Proliferator- Activated Receptor gamma (PPAR-y) activity in adipocytes.

[0076] In another embodiment, the formulation further comprises chromium as an insulin sensitiser in an amount ranging from 0.5 ppm to 5 ppm.

[0077] In another embodiment, the Berberis aristata extract is complexed with lecithin to enhance bioavailability.

[0078] In another embodiment, said formulation further comprises lecithin in an amount ranging from 3% to 30% by weight.

[0079] In another embodiment, the extracts are lyophilised or spray-dried.

[0080] In another embodiment, said formulation further comprises an insulin sensitiser selected from chromium, magnesium, or zinc in the range of 0.5 ppm to 5 ppm.

[0081] In another embodiment, wherein the formulation is in a solid dosage form selected from tablets, granules, capsules, or lozenges.

[0082] In another embodiment, the present disclosure provides a method of preparing the formulation as disclosed herein above, comprising: extracting the stem of Berberis aristata using an aqueous, alcoholic, or hydroalcoholic solvent at a temperature ranging from 50°C to 70°C for a duration of 2- 4hours to obtain a Berberis extract; extracting the fruit of Phyllanthus emblica using an aqueous, alcoholic, or hydroalcoholic solvent, wherein:(i) when a dry Phyllanthus emblica extract is used, the extraction is carried out at a temperature in the range of 55°C to 60°C for a duration of 2 hours; and(ii) when Phyllanthus emblica juice powder is used, the extraction temperature and duration are not applicable; mixing the Phyllanthus emblica extract and juice powder to prepare a whole extract in a weight ratio of 2: 1 ; and optionally combining the whole extract with lecithin and lyophilising the mixture to obtain the final formulation.

[0083] In another embodiment, the present disclosure provides a method of managing blood glucose levels or insulin resistance in a subject, comprising administering to the subject a therapeutically effective amount of the formulation as claimed in any one of the preceding claims.

[0084] In another embodiment, the present disclosure provides a herbal formulation comprising: an extract of Berberis aristata comprising 10% to 20% berberine by weight; anda whole extract of Phyllanthus emblica comprising 40% to 60% tannins and 5% to 20% gallic acid and ellagic acid by weight; wherein the formulation is adapted to reduce insulin resistance and elevated blood glucose levels in a subject.

[0085] In another embodiment, the present disclosure provides the use of a synergistic herbal formulation comprising Berberis aristata extract and Phyllanthus emblica extract in the manufacture of a medicament for reducing insulin resistance or modulating PPAR-y activity in a subject.

[0086] In another embodiment, the present disclosure provides a kit for the management of elevated blood glucose levels and insulin resistance in a subject, the kit comprising: a synergistic herbal formulation comprising an extract of Berberis aristata and a whole extract of Phyllanthus emblica,' and instructions for administration of the formulation to a subject in need thereof.

[0087] In an additional embodiment, the formulation may optionally include one or more insulin sensitisers selected from chromium, magnesium, and zinc or their pharmaceutically acceptable salts. In one embodiment, the formulation includes chromium in an amount ranging from 0.5 ppm to 5 ppm by weight. The composition may also include pharmaceutically acceptable excipients such as diluents (e.g., lactose, microcrystalline cellulose), binders (e.g., polyvinylpyrrolidone), disintegrants (e.g., sodium starch glycolate), and lubricants (e.g., magnesium stearate) to support various dosage forms.

[0088] In a preferred embodiment, the formulation is provided as an oral solid dosage form selected from tablets, hard or soft gelatin capsules, granules, powders, or lozenges. In another embodiment, it is administered in a semi-solid or liquid dosage form, such as suspensions or gels. Each unit dose may contain 250 mg to 1000 mg of the formulation and may be administered once or twice daily, depending on the severity of the condition and the patient's profile.

[0089] In another embodiment, the method of preparing the formulation comprises extracting Berberis aristata stem or root using aqueous, alcoholic, or hydroalcoholic solvents selected from ethanol, methanol, or their mixtures with water in concentrations ranging from 30% to 80% (v / v). The extraction may be performed at room temperature or under controlled heating conditions not exceeding 80°C for a period of 12 to 48 hours. The extract is then filtered and concentrated under reduced pressure. Separately, the Phyllanthus emblica wholeextract is prepared by mixing Phyllanthus emblica extract and juice powder in a 2: 1 ratio, followed by lyophilisation or spray drying to obtain a stable dry powder.

[0090] The dried extracts are then mixed with lecithin in a suitable solvent such as ethanol to allow complexation. The mixture is homogenised and subsequently dried under vacuum, spray dried or freeze-dried to yield the final powdered formulation. This powder may then be blended with excipients and filled into capsules or compressed into tablets using conventional pharmaceutical techniques.

[0091] In an exemplary embodiment, the herbal formulation comprises Berberis aristata extract and Phyllanthus emblica whole extract in a weight ratio ranging from 1:9 to 9: 1. The formulation may optionally include lecithin and one or more pharmaceutically acceptable excipients.

[0092] In an additional embodiment, the Berberis aristata extract is present in the formulation in an amount ranging from 10% to 90% by weight, and the Phyllanthus emblica extract is present in an amount ranging from 10% to 90% by weight. The extracts are derived through aqueous, alcoholic, or hydroalcoholic extraction of the respective plant parts and are standardised for their key bioactives.

[0093] In a certain embodiment, the Berberis aristata extract is standardised to contain berberine in the range of 10% to 20% by weight of the extract. The Phyllanthus emblica whole extract is prepared by mixing Phyllanthus emblica fruit extract and Phyllanthus emblica juice powder in a 2: 1 ratio and contains 40% to 60% tannins and 5% to 20% of a combined amount of gallic acid and ellagic acid.

[0094] In another embodiment, the herbal formulation comprises Berberis aristata extract at 30% to 40%, Phyllanthus emblica whole extract at 50% to 60%, and lecithin at 3% to 30% by weight. The inclusion of lecithin enhances the bioavailability of berberine through molecular complexation and improves formulation stability.

[0095] In an alternative embodiment, the formulation further includes an insulin sensitiser selected from the group consisting of chromium, magnesium, and zinc. In a preferred example, chromium is present in a concentration ranging from 0.5 ppm to 5 ppm by weight.

[0096] In a further embodiment, the formulation is administered orally in the form of capsules, tablets, powders, suspensions, or lozenges. Each unit dose contains 250 mg to 1000 mg of the herbal composition and may be administered once or twice daily.

[0097] In one embodiment, the method of preparing the formulation comprises extracting Berberis aristata and Phyllanthus emblica plant materials separately using ethanolor hydroalcoholic solvents (30-80% v / v), concentrating the extracts, and lyophilising them to yield dry powders. The two extracts are blended in the defined ratio and then combined with lecithin using ethanol as the solvent, followed by homogenization and vacuum drying or freeze-drying.

[0098] In a preferred embodiment, the formulation is evaluated in 3T3-L1 adipocyte cell line assays for PPAR-y gene expression and in vivo models of high-fat diet and streptozotocin-induced diabetes. The formulation demonstrates significant upregulation of PPAR-y, reduced HOMA-IR index, and improvement in fasting plasma glucose (FPG), HbAlc, and lipid profiles.

[0099] In yet another embodiment, the formulation is provided as part of a therapeutic kit comprising unit-dose packs of the composition along with printed instructions for use in managing insulin resistance and metabolic syndrome.

[0100] In an exemplary embodiment, the formulation is branded and marketed under the name “NextBeri™” and packaged in protective, moisture-resistant containers with 30 or 60 doses per pack.

[0101] In an expanded embodiment, the formulation may also include excipients such as diluents (e.g., lactose, microcrystalline cellulose), binders (e.g., povidone), disintegrants (e.g., crospovidone), and lubricants (e.g., magnesium stearate) for improved manufacturability and patient compliance.

[0102] In another optional embodiment, the extracts may be encapsulated using liposomal or nanoemulsion techniques to further enhance targeted delivery and absorption in the gastrointestinal tract.

[0103] In an embodiment intended for personalised therapy, the formulation may be coadministered with standard antidiabetic agents such as metformin, or used as a standalone intervention in patients with early-stage insulin resistance or impaired fasting glucose.

[0104] Pharmacological studies, including in vitro PPAR-y expression assays using 3T3- L1 adipocyte cell lines and in vivo rodent models of high-fat diet and streptozotocin-induced diabetes, demonstrated that the formulation significantly improved glucose uptake, insulin sensitivity, and lipid metabolism when compared to individual plant extracts and standard drugs such as pioglitazone. The formulation was also found to modulate adiponectin levels and reduce pro-inflammatory cytokines such as TNF-a. Clinical investigations in human subjects further validated improvements in fasting plasma glucose (FPG), HbAlc, lipid profile, and HOMA-IR index with no serious adverse effects.

[0105] To address the existing challenges, the present invention discloses a novel, synergistic herbal formulation comprising standardised extracts of Berberis aristata and Phyllanthus emblica, specifically designed to improve glucose uptake, modulate insulin resistance, and regulate PPAR-y expression. The formulation leverages phospholipid complexation, particularly using lecithin, to enhance the bioavailability, stability, and therapeutic efficacy of the active phytoconstituents. The extracts are precisely mixed in defined ratios to maximise their complementary and synergistic effects while minimising variability and degradation. Extensive preclinical studies have confirmed the enhanced efficacy of the combined extracts in modulating key insulin signalling pathways and improving glycemic biomarkers, compared to their individual use. Furthermore, clinical evaluations have demonstrated meaningful improvements in HbAlc, fasting plasma glucose, lipid profile, and inflammatory markers, without adverse effects typically seen with synthetic drugs.

[0106] Conclusively, the present invention provides a novel, safe, and effective herbal formulation that addresses the limitations of current antidiabetic therapies. By integrating traditional knowledge with modem scientific validation, the invention offers a promising alternative for long-term metabolic health management. The formulation is stable, reproducible, and suitable for commercial scale-up and may be used alone or in combination with other antidiabetic agents as part of an integrated therapeutic strategy.

[0107] While the foregoing describes various embodiments of the disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof. The scope of the invention is determined by the claims that follow. The invention is not limited to the described embodiments, versions, or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art.EXAMPLES

[0108] The present invention is further explained in the form of the following examples. However, it is to be understood that the following examples are merely illustrative and are not to be taken as limitations upon the scope of the invention.

[0109] The present invention relates to a novel synergistic herbal formulation that is useful in reducing insulin resistance and blood glucose levels in people requiring management of blood glucose levels. The formulation of the present invention is effective in pre-diabetic conditions, and insulin-resistant patients. The herbal formulation comprisesBerberis aristata extract and Phyllanthus emblica extract in predefined quantity which is effective and safe for human use. Further, a PPAR-Gamma assay was performed to evaluate the efficacy of this herbal formulation for insulin-sensitizing activity. The invention involves the synergic formulation of herbs to reduce insulin resistance which is a key pathology for the development of pre-diabetes, and other similar disorders. The formulation also reduces the increased level of blood glucose in living bodies. The formulation has a dual mechanism of action, it acts as an insulin sensitizer and an anti-hyperglycemic agent. Therefore, it could be useful for the management of diabetes mellitus. The chemical structure of the extract is shown in Figure 1.Example 1 : Berberis aristata extract

[0110] Berberis aristata extract was prepared by extracting roots of Berberis aristata in ethanol.Example 2: Phyllanthus emblica whole extract

[0111] Phyllanthus emblica whole extract was prepared by mixing Phyllanthus emblica extract and Phyllanthus emblica juice powder in the proportion mentioned in the following table:Table 1: Details of Phyllanthus emblica whole extractExample 3: Novel herbal formulation (NextBeri™) The novel herbal formulation was prepared by -

[0112] A phospholipid, - lecithin was chosen for the formula. The phospholipid was solubilized in suitable alcohol by heating the mixture in a water bath. Berberis aristata extract was solubilized by dissolving in suitable alcohol. The solution was stored in a container that protected the solution from exposure to light. Then the phospholipid and extract solutions were mixed properly and concentrated. The Phyllanthus emblica whole extract was added in a proportion shown in Table 2. The solution was again homogenized well and lyophilized using a Freeze-Dryer, then stored in a cool, dry place and away from direct sunlight. HPLC Chromatogram of Berberis aristata and Phyllanthus emblica raw material and extract shown in Figures 2 and 3.Table 2: Novel herbal formulation (NextBeri™)Example 4: Evaluation of novel herbal formulation through PPAR gamma expression study

[0113] Results and conclusion: As depicted in Table 3. all the formulations showed increased PPAR gamma expression at lower concentrations (2.5 pg / mL). PPAR gamma expression of Phyllanthus Emblica (PE), Berberis aristata (BA), and PE+BA was compared to the PPAR y expression seen in DMSO-treated cells. All the formulations showed a concentration-dependent increase in PPAR gamma expression as compared to Vehicle Control (DMSO-treated cells). However maximum expression was seen in cells treated with PE + BA at higher concentration (10 pg / mL) i.e., a 16-fold increase. Pioglitazone-treated cells which served as the Standard control (SC) showed a 2-fold increase in the PPAR gamma expression. The result suggests that the formulation of the present invention has superior activity as compared to the standard drug Pioglitazone. Table 3: Effect of Herbal formulation on PPAR gamma gene expression by Real-Time PCR

[0114] All the samples showed an increase in PPAR gamma gene expression however optimum response was seen with the combination of Phyllanthus emblica and Berberis aristata at the highest concentration studied (10 pg / mL). The effect of Herbal formulation (HF) on PPAR gamma gene expression by Real-Time PCR is depicted in Figure 1.

[0115] Example 5 Evaluation of the management of blood sugar levels by NextBeri™ formulation against high-fat diet and streptozotocin (stz) induced for insulin resistance in rats. ResultsTable 4. Effect of Extract and Metformin on Glucose.

[0116] Insulin levels were increased throughout the study period for the disease control group as compared to other groups. Whereas normal animals showed constant insulin levels. Elevated Insulin levels get back to normal during the study period in treatment groups. Insulin at various day intervals is shown in Figure 4.Table 5. Effect of Plant Extract and Metformin on Glucose during OGTT.

[0117] The effect of NextBeri™ formulation and Metformin in the OGTT is shown in the graph and Tables 4 and 5 respectively. All disease-induced animals showed elevated levels of Insulin and glucose during OGTT as compared with normal control animals. At all the time intervals, treated animals showed significantly lower glucose and insulin levels than the disease-control animals. At the end of the study, group 5 showed significantly lower values of glucose and insulin (Figures 5, 6).Table 6. Effect of Extract and Metformin on Insulin.Table 7. Effect of Plant extract and Metformin on Insulin during OGTT.Table 8. Homeostasis model assessment-insulin resistance (HOMA)Table 9. Quantitative insulin sensitivity check index (QUICKI).Table 10. HOMA, QUICKI, and MATSUDA

[0118] On the day 18thHOMA values for diseased animals were elevated, whereas QUICKI values were lowered due to diabetes induction. Along with the treatment HOMA values decreased significantly as compared with normal.

[0119] Lowered QUICKI values were elevated when they were compared with diseased 5 animals after treatment.

[0120] Matsuda index decreased due to induction of the disease but it was significantly increased in standard and NextBeri™ (500 mg / Kg) as compared with disease control animals (Figure 7). High-fat diet and streptozotocin (stz) induced insulin resistance were developed in the rats. NextBeri™ was evaluated for its anti-diabetic effect. It showed significant activity 10 by lowering glucose throughout the study. A higher dose of 500 mg / kg was found to be more effective than other treated groups.Clinical Study

[0121] Study Title: A Randomized, placebo-controlled study to assess the efficacy & safety 15 of the combination of Berberis aristata and Phyllanthus emblica extract supplementation in prediabetic subjects.Treatment

[0122] Assessment of Inflammatory markersAssessment of oxidative stress markersAssessment of appetite regulatory hormonesBest Mode of Working the Invention

[0123] The best mode of working the present invention involves the preparation of a synergistic herbal formulation using standardized extracts of Berberis aristata and Phyllanthus emblica in specific proportions, enhanced with lecithin to improve 10 bioavailability and formulation stability.

[0124] In the preferred process, dried stem or root of Berberis aristata is coarsely powdered and extracted using a 70% v / v hydroalcoholic solvent (ethanol: water) under reflux conditions for 24 to 48 hours. The extract is filtered and concentrated under reduced pressure, followed by spray drying or lyophilization to obtain a fine powder standardized to contain 15 approximately 10% berberine.

[0125] Separately, Phyllanthus emblica fruit extract is prepared using an aqueous or hydroalcoholic extraction process. The extract is combined with Phyllanthus emblica juice powder in a 2: 1 ratio to form a whole extract containing 35-45% tannins and 5-10% of gallic acid and ellagic acid combined. This whole extract is also lyophilized to obtain a stable dry powder.

[0126] The two extracts are blended in a weight ratio of 35:55 (Berberis aristata'.Phyllanthus emblica) and combined with 10% lecithin dissolved in ethanol. The mixture is homogenized to facilitate complexation between the phospholipid and bioactives, followed by vacuum drying or freeze drying to remove residual solvent and yield the final powdered formulation.

[0127] The dried formulation is then mixed with suitable excipients such as microcrystalline cellulose, sodium starch glycolate, and magnesium stearate to produce a compressible blend. This blend is filled into hard gelatin capsules or compressed into tablets, each unit dose containing 500 mg of the active formulation. The preferred mode of administration is oral, twice daily after meals.

[0128] The formulation has shown significant efficacy in preclinical models of high-fat diet and STZ-induced diabetes, and in clinical studies involving prediabetic and diabetic individuals. It resulted in meaningful reductions in fasting plasma glucose, HbAlc, HOMA- IR index, and inflammatory markers, along with improved insulin sensitivity and lipid profile. No serious adverse effects or organ toxicity were observed during administration. This optimized combination of plant-derived bioactives and phospholipid enhancement represents the best current implementation of the invention for commercial and therapeutic applications.

[0129] The foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments is apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.ADVANTAGES OF THE INVENTION

[0130] The present invention provides a number of distinct and synergistic advantages over conventional antidiabetic therapies and existing herbal formulations. One of the primary advantages is the use of two scientifically validated herbal ingredients, Berberis aristata and Phyllanthus emblica, in standardized and optimized proportions to ensure reproducible therapeutic outcomes. The combination of these two extracts in a defined weight ratio offerssynergistic activity, enhancing glucose metabolism while simultaneously improving insulin sensitivity. The dual mechanism of action — targeting both blood glucose regulation and PPAR-y modulation — addresses the multifactorial nature of insulin resistance and metabolic syndrome more comprehensively than monotherapies or single-action agents.

[0131] The formulation overcomes the known limitations of berberine's poor solubility and bioavailability through the incorporation of lecithin, which forms a molecular complex with the bioactive constituents. This lipid-assisted delivery system significantly enhances intestinal absorption and systemic bioavailability, translating into better clinical efficacy at lower doses. Moreover, the formulation avoids the use of synthetic chemicals, hormones, or steroids, making it suitable for long-term use without the risk of adverse effects commonly associated with conventional oral hypoglycemic agents, such as weight gain, hepatotoxicity, fluid retention, or cardiovascular complications.

[0132] Another significant advantage is the incorporation of a whole extract of Phyllanthus emhlica. which contains not only purified extract but also juice powder, ensuring retention of a broader spectrum of phytochemicals that contribute to its antioxidant and antiinflammatory properties. The formulation also shows excellent safety and tolerability in both preclinical models and human studies, with no reported adverse effects over prolonged administration.

[0133] From a manufacturing standpoint, the formulation is stable, scalable, and compatible with various dosage forms including tablets, capsules, powders, and suspensions. It is easily adaptable to existing pharmaceutical infrastructure and can be integrated into wellness and preventive health regimens. Furthermore, the formulation demonstrates efficacy not just in lowering blood glucose levels but also in improving lipid profiles and reducing pro-inflammatory markers, offering a holistic benefit in managing cardiometabolic risks. Its performance in validated cell lines and animal models, as well as in early clinical trials, further confirms its potential as a next-generation plant-based therapeutic for metabolic health.

[0134] Thus, the invention provides a well-characterized, efficacious, safe, and commercially viable herbal formulation with superior advantages over current alternatives in the management of insulin resistance, prediabetes, type 2 diabetes, and associated metabolic conditions.

Claims

aim:

1. A herbal formulation comprising: an extract of Berberis aristata, and an extract of Phyllanthus emblica, wherein the formulation is for the management of elevated blood glucose levels and insulin resistance in a subject.

2. The formulation as claimed in claim 1, wherein the Berberis aristata extract comprises berberine in a concentration ranging from 10 % to 20% by weight.

3. The formulation as claimed in claim 1, wherein the Phyllanthus emblica extract comprises tannins in a concentration of 40% to 60%4. The formulation as claimed in claim 1, wherein the Phyllanthus emblica extract comprises gallic acid and / or ellagic acid in a concentration of 5 % to 20% by weight.

5. The formulation as claimed in claim 1, wherein the Phyllanthus emblica extract is a whole extract comprising a mixture of Phyllanthus emblica extract and juice powder in a weight ratio of 2: 1.

6. The formulation as claimed in claim 1, said formulation further comprising lecithin in an amount ranging from 3% to 30% by weight of the formulation.

7. The formulation as claimed in claim 1, wherein the extract of Berberis aristata is complexed with lecithin to enhance its stability and bioavailability.

8. The formulation as claimed in claim 1, said formulation further comprising one or more pharmaceutically acceptable excipients selected from the group consisting of diluents, binders, disintegrants, lubricants, stabilizers, and preservatives.

9. The formulation as claimed in claim 1, wherein the formulation is in a solid, liquid, suspension, or semi-solid dosage form.

10. The formulation as claimed in claim 1, wherein the formulation is adapted to modulate Peroxisome Proliferator-Activated Receptor gamma (PPAR-y) activity in adipocytes.

11. The formulation as claimed in claim 1, wherein the formulation further comprises chromium as an insulin sensitizer in an amount ranging from 0.5 ppm to 5 ppm.

12. The formulation as claimed in claim 1, wherein Berberis aristata extract is complexed with lecithin to enhance bioavailability.

13. The formulation as claimed in claim 1 and 11, said formulation further comprising lecithin in an amount ranging from 5% to 15% by weight.

14. The formulation as claimed in claim 1, wherein the extracts are lyophilized or spray- dried.

15. The formulation as claimed in claim 1, said formulation further comprising an insulin sensitizer selected from chromium, magnesium, or zinc in the range of 0.5 ppm to 5 ppm.

16. The formulation as claimed in claim 1, wherein the formulation is in a solid dosage form selected from tablets, granules, capsules, or lozenges.

17. A method of preparing the formulation as disclosed herein above, comprising: extracting the stem of Berberis aristata using an aqueous, alcoholic, or hydroalcoholic solvent at a temperature ranging from 50°C to 70°C for a duration of 2- 4hours to obtain a Berberis extract; extracting the fruit of Phyllanthus emblica using an aqueous, alcoholic, or hydroalcoholic solvent, wherein:(i) when a dry Phyllanthus emblica extract is used, the extraction is carried out at a temperature in the range of 55°C to 60°C for a duration of 2 hours; and(ii) when Phyllanthus emblica juice powder is used, the extraction temperature and duration are not applicable; mixing the Phyllanthus emblica extract and juice powder to prepare a whole extract in a weight ratio of 2: 1 ; and optionally combining the whole extract with lecithin and lyophilising the mixture to obtain the final formulation.

18. A method of managing blood glucose levels or insulin resistance in a subject, comprising administering to the subject a therapeutically effective amount of the formulation as claimed in any one of the preceding claims.

19. A herbal formulation comprising: an extract of Berberis aristata comprising 10% to 20% berberine by weight; and a whole extract of Phyllanthus emblica comprising 40% to 60% tannins and 5% to 20% gallic acid and ellagic acid by weight;wherein the formulation is adapted to reduce insulin resistance and elevated blood glucose levels in a subject.

20. Use of a synergistic herbal formulation comprising Berberis aristata extract and Phyllanthus emblica extract in the manufacture of a medicament for reducing insulin resistance or modulating PPAR-y activity in a subject.

21. Use of claimed synergistic formulation for use in reducing body weight or managing body fat percentage in a subject in need thereof.

22. A kit for the management of elevated blood glucose levels or insulin resistance or elevated HbAlc or elevated inflammatory markers, in a subject, the kit comprising: a synergistic herbal formulation comprising an extract of Berberis aristata and a whole extract of Phyllanthus emblica,' and instructions for the administration of the formulation to a subject in need thereof.

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