NANO-encapsulated complex containing extract of mitragyna speciosa

Abstract

The disclosure relates to the development of a nano-encapsulated extract of Mitragyna speciosa, commonly known as kratom, specifically designed for use in beverages, dietary supplements and natural health products. This extract is standardized to contain a precise concentration of mitragynine, the primary active alkaloid in kratom, ensuring consistent potency and efficacy in enhancing energy, alertness, and alleviating minor pain, such as delayed inset muscle soreness, associated with physical exertion. The disclosed technology outlines an extraction and encapsulation process that not only maximizes the yield of mitragynine but also ensures the removal of undesirable compounds and the encapsulation provides improved bioavailability, thereby enhancing the safety profile of the final product. The standardized extract may be easily incorporated into various beverage formulations, dietary supplements and natural health products, providing a reliable and effective herbal supplement option.

Description

74001-53 NANO-ENCAPSULATED COMPLEX CONTAINING EXTRACT OF MITRAGYNA SPECIOSA CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 705,552, filed on October 10, 2024. The entire disclosure of the above application is incorporated herein by reference. FIELD

[0002] The present technology relates to a botanical extract and, more particularly, to a nano-complexed extract of Mitragyna speciosa for use in a beverage, dietary supplement, and natural health product. INTRODUCTION

[0003] This section provides background information related to the present disclosure which is not necessarily prior art.

[0004] Mitragyna speciosa, commonly known as kratom, is a tropical tree native to Southeast Asia, which has been used for centuries as an herbal remedy and in cultural ceremonies. The leaves of the Mitragyna speciosa plant are known for containing various alkaloids, primarily mitragynine, which have been reported to produce stimulant and sedative effects depending on the dosage. Traditionally, the Mitragyna speciosa leaves are chewed fresh or dried, brewed as tea, or prepared as decoctions. More recently the leaves of Mitragyna speciosa have been converted into dry powdered extracts, leaf powders, and other forms for consumption.

[0005] Despite its well documented uses, the extraction and standardization of Mitragyna speciosa have posed significant challenges. Traditional methods of preparation often result in products with inconsistent potency and purity. This variability may lead to products that are either ineffective or, conversely, pose safety risks due to unexpectedly high concentrations of active compounds or oxidation products of the analytes. Furthermore, traditional extraction methods are often inefficient, failing to extract the full spectrum of beneficial compounds from the leaves.74001-53

[0006] Moreover, the regulatory landscape for kratom is complex and varies significantly by region, partly due to these inconsistencies in product quality and safety. In some areas, kratom is classified as a controlled substance, while in others, kratom remains a legal herbal supplement or is considered a food. The regulatory inconsistency can be attributed in part due to the lack of standardized, high-quality kratom products that may be reliably safe for consumer use.

[0007] Additionally, the existing extraction processes often use solvents that may not be environmentally friendly or could leave harmful residues in the final product, raising further safety concerns for consumers and challenges for manufacturers aiming to comply with health and safety regulations.

[0008] There is a continuing need for improved methods and compositions in the field of kratom extraction and standardization. Desirably, such advancements would address the inconsistency in the potency and purity of kratom extracts, provide safer and more environmentally friendly extraction methods, and result in a product that meets regulatory standards for safety and quality. SUMMARY

[0009] In concordance with the instant disclosure, an improved method and composition in the field of kratom extraction and encapsulation, and which addresses the inconsistency in the potency and purity of kratom extracts, provides safer and more environmentally friendly extraction methods, and result in a product that meets regulatory standards for safety and quality, have surprisingly been discovered.

[0010] The present technology includes articles of manufacture, systems, and processes that relate to the extraction, formulation, and encapsulation of Mitragyna speciosa for the creation of consistent, safe, and effective botanical ingredients for a beverage, dietary supplement, and natural health product designed to enhance energy, improve alertness, and alleviate minor pain.

[0011] In one embodiment, a method for extracting and encapsulating / complexing Mitragyna speciosa leaf product may include steps to optimize the yield and consistency of the active compounds, primarily mitragynine. The method may begin with the provision of high- quality Mitragyna speciosa leaf material, which may be subjected to a process of extraction involving acidified alcohol (or aqueous alcohol), precise temperature control, and constant74001-53 stirring to facilitate the extraction of desired alkaloids. Subsequent steps may include a filtration process to remove solid residue, followed by a concentration phase under reduced pressure. In certain embodiments, a slurry of 70-75% reduced volume may be achieved. The method may include a purification step after dissolution of the slurry into acidified solution, loading onto an ion exchange resin and elusion with varying ratios of alcohol and water to remove the undesired compounds. The diluent may be dried to produce a purified powdered Mitragyna speciosa extract of a standardized and high-quality. The final Mitragyna speciosa extract may be standardized to a target mitragynine concentration within the range of 10.0 ±0.5– 50.0±2.5% or 100-500 mg mitragynine per gram of dry weight, as required for the intended application. Advantageously, the method may be able to target the desired concentration to a precision of ±5% precision, utilizing only water and food grade ethanol (or other suitable alcohol) and ability to undertake a green process with minimal negative environment impact.

[0012] In an exemplary embodiment of the method, the standardized Mitragyna speciosa extract may be formulated with a co-ingredient to enhance the physicochemical properties including solubility, stability, and bioavailability. The formulation may take the form of a complex, emulsion, or encapsulation.

[0013] In another embodiment, a method for extracting and standardizing Mitragyna speciosa leaf product may include steps to optimize the yield and consistency of the active compounds, primarily mitragynine. The method may include the provision of high-quality Mitragyna speciosa leaf material, which may be subjected to a process involving acidified water, precise temperature control, and constant stirring to facilitate the extraction of a desired alkaloid, preserving the integrity of the alkaloid. Subsequent steps may include a filtration process to remove solid residue, followed by a concentration phase under reduced pressure to achieve a predetermined mitragynine concentration. The method may include an additional purification step to remove an undesired compound, facilitating the production of a standardized and high- quality kratom extract.

[0014] In another embodiment, a method for extracting Mitragyna speciosa leaf product may include steps to optimize the yield and consistency of the active compounds, primarily mitragynine. The method may include the provision of high-quality Mitragyna speciosa leaf material, which may be subjected to a process involving acetone, precise temperature control, and constant stirring to facilitate the extraction of desired alkaloids. Subsequent steps may74001-53 include a filtration process to remove solid residues, followed by a concentration phase under reduced pressure to achieve a predetermined mitragynine concentration. The method may include a purification step to remove undesired compounds, ensuring the production of a standardized and high-quality kratom extract.

[0015] Further areas of applicability will become apparent from the description provided herein. The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure. DRAWINGS

[0016] The drawings described herein are for illustrative purposes only of selected embodiments and not all possible implementations and are not intended to limit the scope of the present disclosure.

[0017] FIG.1 is a flowchart illustrating a method for extracting with water, according to some embodiments of the present disclosure;

[0018] FIG.2 is a flowchart illustrating a method for extracting with acetone, according to some embodiments of the present disclosure;

[0019] FIG.3 is a flowchart illustrating a method for extracting, purifying and complexing / encapsulating, according to some embodiments of the present disclosure; and

[0020] FIGS.4A-4B are flowcharts illustrating an alternative method for extracting, purifying and complexing / encapsulating, according to some embodiments of the present disclosure. DETAILED DESCRIPTION

[0021] The following description of technology is merely exemplary in nature of the subject matter, manufacture and use of one or more inventions, and is not intended to limit the scope, application, or uses of any specific invention claimed in this application or in such other applications as may be filed claiming priority to this application, or patents issuing therefrom. Regarding methods disclosed, the order of the steps presented is exemplary in nature, and thus, the order of the steps can be different in various embodiments, including where certain steps can be simultaneously performed, unless expressly stated otherwise. “A” and “an” as used herein74001-53 indicate “at least one” of the item is present; a plurality of such items may be present, when possible. Except where otherwise expressly indicated, all numerical quantities in this description are to be understood as modified by the word “about” and all geometric and spatial descriptors are to be understood as modified by the word “substantially” in describing the broadest scope of the technology. “About” when applied to numerical values indicates that the calculation or the measurement allows some slight imprecision in the value (with some approach to exactness in the value; approximately or reasonably close to the value; nearly). If, for some reason, the imprecision provided by “about” and / or “substantially” is not otherwise understood in the art with this ordinary meaning, then “about” and / or “substantially” as used herein indicates at least variations that may arise from ordinary methods of measuring or using such parameters.

[0022] Although the open-ended term “comprising,” as a synonym of non-restrictive terms such as including, containing, or having, is used herein to describe and claim embodiments of the present technology, embodiments may alternatively be described using more limiting terms such as “consisting of” or “consisting essentially of.” Thus, for any given embodiment reciting materials, components, or process steps, the present technology also specifically includes embodiments consisting of, or consisting essentially of, such materials, components, or process steps excluding additional materials, components or processes (for consisting of) and excluding additional materials, components or processes affecting the significant properties of the embodiment (for consisting essentially of), even though such additional materials, components or processes are not explicitly recited in this application. For example, recitation of a composition or process reciting elements A, B and C specifically envisions embodiments consisting of, and consisting essentially of, A, B and C, excluding an element D that may be recited in the art, even though element D is not explicitly described as being excluded herein.

[0023] As referred to herein, all compositional percentages are by weight of the total composition, unless otherwise specified. Disclosures of ranges are, unless specified otherwise, inclusive of endpoints and include all distinct values and further divided ranges within the entire range. Thus, for example, a range of “from A to B” or “from about A to about B” is inclusive of A and of B. Disclosure of values and ranges of values for specific parameters (such as amounts, weight percentages, etc.) are not exclusive of other values and ranges of values useful herein. It is envisioned that two or more specific exemplified values for a given parameter may define endpoints for a range of values that may be claimed for the parameter. For example, if Parameter74001-53 X is exemplified herein to have value A and also exemplified to have value Z, it is envisioned that Parameter X may have a range of values from about A to about Z. Similarly, it is envisioned that disclosure of two or more ranges of values for a parameter (whether such ranges are nested, overlapping or distinct) subsume all possible combination of ranges for the value that might be claimed using endpoints of the disclosed ranges. For example, if Parameter X is exemplified herein to have values in the range of 1–10, or 2–9, or 3–8, it is also envisioned that Parameter X may have other ranges of values including 1–9, 1–8, 1–3, 1–2, 2–10, 2–8, 2–3, 3–10, 3–9, and so on.

[0024] When an element or layer is referred to as being “on,” “engaged to,” “connected to,” or “coupled to” another element or layer, it may be directly on, engaged, connected or coupled to the other element or layer, or intervening elements or layers may be present. In contrast, when an element is referred to as being “directly on,” “directly engaged to,” “directly connected to” or “directly coupled to” another element or layer, there may be no intervening elements or layers present. Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g., “between” versus “directly between,” “adjacent” versus “directly adjacent,” etc.). As used herein, the term “and / or” includes any and all combinations of one or more of the associated listed items.

[0025] Although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers and / or sections, these elements, components, regions, layers and / or sections should not be limited by these terms. These terms may be only used to distinguish one element, component, region, layer or section from another region, layer or section. Terms such as “first,” “second,” and other numerical terms when used herein do not imply a sequence or order unless clearly indicated by the context. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the example embodiments.

[0026] Spatially relative terms, such as “inner,” “outer,” “beneath,” “below,” “lower,” “above,” “upper,” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. Spatially relative terms may be intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in74001-53 the figures is turned over, elements described as “below,” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the example term “below” can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.

[0027] The present technology improves the extraction and standardization processes of Mitragyna speciosa, ensuring that the resulting botanical extracts maintain consistent levels of active compounds, particularly mitragynine. Additionally, the present technology can minimize the amount of 7-hydroxymitragynine present in the final product, which is beneficial given the harmful nature of 7-hydroxymitragynine. This advancement not only enhances the efficacy and safety of the final product but also addresses environmental concerns by utilizing greener, more sustainable extraction methods. By providing a reliable and standardized product, the present technology significantly mitigates the risks associated with the variability of traditional kratom preparations and paves the way for broader acceptance and regulatory compliance of kratom- based products in various markets.

[0028] As shown in the FIGS.3 and 4A-4B, the present disclosure includes a method for extracting and standardizing Mitragyna speciosa leaf product, referred to herein as method 300. The method 300 may produce a standardized extract of Mitragyna speciosa, commonly known as kratom, which may be particularly useful for incorporation into beverages, dietary supplements, and natural health products. The method 300 may ensure consistent levels of the primary active alkaloid, mitragynine, while militating against oxidation (chemical alteration) of key alkaloids and removing / militating against the formation of an undesired compound, thereby enhancing both the safety and efficacy of the final product.

[0029] Method 300 may begin with a step 310 of providing Mitragyna speciosa leaf material. The Mitragyna speciosa leaf material used may be selected based on its quality and mitragynine content, ensuring that only high-quality Mitragyna speciosa leaves may be used in the extraction process. The initial selection may be crucial as the quality of the Mitragyna speciosa leaf material may impact the overall yield and quality of the final extract. In certain embodiments, the method 300 may include a step 312 of pre-treating the Mitragyna speciosa leaf material with an ultrasonic bath prior to extraction. The pre-treatment step 312 may increase the74001-53 yield of mitragynine by disrupting the cell structure of the Mitragyna speciosa leaves, making the alkaloid more accessible for extraction.

[0030] In step 320, the provided Mitragyna speciosa leaf material may be added to acidified alcohol or aqueous alcohol. The acidification of the alcohol may be achieved by adding citric acid, for example, which helps in the extraction of mitragynine and other desirable alkaloids from the leaf material. Other organic or mineral acids may be used without departing from the spirit of the invention. Some examples include, but are not limited to, tartaric acid, malic, ascorbic acid, acetic acid, phosphoric acid, lactic acid, or any of these acids in combination with citric acid. The acidification of the diluent may be achieved by adding citric acid, which helps in the extraction of mitragynine and other desirable alkaloids from the leaf material. The step 320 may also include heating the mixture with constant stirring, which facilitates the release of alkaloids into the solution.

[0031] The heating in step 320 may be conducted at a temperature of approximately 50°C. This specific temperature may be maintained to optimize the extraction of alkaloids while preventing the degradation of sensitive compounds within the leaf material. The constant stirring mentioned in this step 320 may be maintained for a predetermined duration, for example, about 2 hours, ensuring that the leaf material may be evenly exposed to the heated acidified solvent. In some embodiments, the heating step 320 may be performed under a nitrogen atmosphere to militate against oxidation of sensitive compounds, thereby preserving the integrity of the extract.

[0032] Following the heating and stirring process, the method 300 may include variations in the duration and temperature to accommodate different batch sizes or specific strains of Mitragyna speciosa that might have varying alkaloid profiles. For instance, the temperature may be adjusted slightly above or below 50°C, and the duration of heating and stirring may be extended or reduced based on preliminary tests that indicate optimal extraction efficiency for specific leaf material. These adjustments are considered non-limiting examples of how the process may be tailored to achieve the best results while maintaining the integrity of the active compounds. One of ordinary skill in the art may also select different temperatures and stirring durations as desired to suit specific extraction needs or to optimize the process for commercial scale-up.

[0033] Following the heating and stirring, the method 300 may include a step 330 of filtering the heated mixture to remove solid material. The step 330 may be crucial as it purifies74001-53 the mixture by separating the liquid extract from the residual leaf material. For example, the two- step filtration system may utilize a coarse filter to remove large particulate matter, followed by a finer filter to ensure the removal of finer particles. The purpose of the two-step filtration approach is to ensure the clarity and purity of the extract by systematically removing particles of different sizes with first the larger particulate matter, then the finer particles, which is crucial for producing a high-quality, standardized extract suitable for beverage and supplement applications.

[0034] For applications requiring extremely high purity, a microfiltration step may be included after the initial filtration to further purify the final extract. The microfiltration step ensures that the final product meets stringent quality standards.

[0035] Step 340 of method 300 involves concentrating the filtered mixture to achieve a slurry of reduced volume, typically 70-75%, for example. The concentration step 340 may be performed using an evaporator under reduced pressure, which efficiently concentrates the mixture without significant loss of volatile compounds.

[0036] In addition to using an evaporator under reduced pressure, alternative methods for concentrating the filtered mixture may include reverse osmosis, spray drying or other drying techniques, which could offer different advantages such as reduced energy consumption or enhanced preservation of sensitive compounds. Furthermore, the target concentration of mitragynine may be adjusted based on the intended use of the extract, whether for more potent medicinal formulations or for milder consumer health products. These variations are non-limiting examples that demonstrate the flexibility of the concentration step to accommodate different production requirements and goals. One of ordinary skill in the art may also select alternative concentrating methods and adjust the mitragynine concentration as desired to optimize the product's efficacy and stability.

[0037] In step 350, an undesired compound may be removed from the slurry to produce a standardized Mitragyna speciosa leaf extract. The step 350 of removing the undesired compound may further include a step 352 in which the slurry may be combined with acidified water and applied to a charged ionic resin. This process, in combination with step 354, of successive washes of the resin with alkaline water and water / alcohol mixtures, serves to remove the undesired compound, while concentrating the desired component. The resin may be eluted with ethanol or other alcohol, a diluent may be collected, and the diluent may be dried to a powder, in74001-53 a step 356. This purification step 350 may be critical for ensuring the integrity, stability and safety of the final extract.

[0038] In step 360 of the present method 300, the powder extract from step 350 may be nano-complexed within or with another compound. The nano-complexing may be engineered using advanced nanotechnology techniques, described herein, to achieve an optimal particle size that maximizes cellular uptake while minimizing potential cytotoxicity. The formulation process may involve the use of safe, environmentally friendly solvents and materials that may comply with regulatory standards for pharmaceutical products. The resulting nano-complex may be characterized by its uniform particle distribution, stable encapsulation efficiency, and the ability to target specific tissues or cells, enhancing the benefits of Mitragyna speciosa.

[0039] In another embodiment, the present disclosure provides a method 100 for preparing a fluidized extract of Mitragynina speciosa leaf, as shown in FIG.1, using acidified water to concentrate the active alkaloids and minimizing the undesired oxidation products, such as 7-hydroxymitragynine. The method 100 may include several steps: step 110 including starting with the selection and provision of high-quality Mitragyna speciosa leaf material. In step 120 the leaves may be added to acidified water to facilitate the extraction process. The mixture may be subjected to constant stirring for a predetermined amount of time, for example, about two hours, to optimize the alkaloid extraction. Following this, in step 130, a two-step filtration process may be employed to remove solid residues, ensuring the clarity and purity of the extract. The filtered mixture may be concentrated in step 140 to achieve a predetermined concentration of mitragynine to provide a concentrated mixture, typically to a targeted mitragynine concentration of 1.0 mg / ml mitragynine but the targeted concentration may fall within a specific range of 0.40- 1.25 mg / mL depending on the intended application with a ±4% precision. The method 100 may also include microfiltration for higher purity, step 150, as well as lyophilization, step 160, to produce a powder form, and encapsulation in biodegradable capsules for controlled release. The resulting standardized Mitragyna speciosa extract, characterized by consistent mitragynine content and absence of detectable levels of 7-hydroxymitragynine, offers significant potential for use in beverages and natural health products, providing benefits such as enhanced alertness, restored energy, and alleviation of minor pain, all while ensuring user safety and product reliability. The output of step 150 could be employed as a substrate in step 360, to complex the74001-53 ingredient with a co-ingredient to engineer using advanced nanotechnology techniques an optimal particle size that maximizes cellular uptake while minimizing potential cytotoxicity.

[0040] In another embodiment, the invention pertains to a method 200 for extracting and standardizing Mitragyna speciosa leaf product, designed to produce a high-quality extract with consistent levels of the active alkaloid mitragynine while militating against undesired compounds such as 7-hydroxymitragynine, as shown in FIG.2. The method 200, may include steps: step 210 including starting with the selection and provision of high-quality Mitragyna speciosa leaf material. In step 220 the Mitragyna speciosa leaves may be added to acidified acetone to facilitate the extraction process. The temperature of the acetone solution may be adjusted during the extraction. The temperature range of the extraction may be adjusted to between 10 °C to 50 °C to suit specific formulation requirements. A skilled artisan may select a suitable temperature within the scope of the present disclosure.

[0041] The mixture may be subjected to constant stirring for a predetermined amount of time, for example, about two hours, to optimize the alkaloid extraction. Following this, in step 230, a two-step filtration process may be employed to remove solid residues, ensuring the clarity and purity of the extract. The filtered mixture may be evaporated in step 240 using an evaporator under reduced pressure to produce a crude mitragynine extract. To further refine the crude extract, undesired compounds may be removed and the extract may be concentrated to a targeted mitragynine concentration of typically 5 % mitragynine, but the targeted concentration may fall within a specific range of 2% to 10%, depending on the intended application with a ±0.5% precision, using a selective chromatographic technique shown in step 250, producing a standardized extract and enhancing the safety profile of the final product. The output of The method could be employed in step 360, complexing the ingredient with a co-ingredient to engineer using advanced nanotechnology techniques an optimal particle size that maximizes cellular uptake while minimizing potential cytotoxicity.

[0042] Additional enhancements to methods 100, 200, 300 may include the addition of a defoaming agent during the concentrating step to militate against foaming, which may interfere with the evaporation process. The defoaming agent, typically a dimethylpolysiloxane solution, may be added in an amount ranging from 45 mL to 75 mL of a 10% solution per 150 L of extract. A skilled artisan may select a suitable defoaming agent within the present disclosure.74001-53

[0043] Another refinement in methods 100, 200, 300 may involve adjusting the pH of the extract after concentration. This pH adjustment may be crucial for stabilizing the extract and enhancing the solubility of mitragynine. The pH range may be adjusted to between 2.4 to 3.9 to suit specific formulation requirements.

[0044] Another refinement in method 100, 200, 300 may be adjusting the time of stirring during the extraction. The time of stirring may be adjusted to between 1 to 5 hours to suit specific formulation requirements. In particular embodiment, the time of stirring may be adjusted to about 2 hours. A skilled artisan may select a suitable stirring time within the scope of the present disclosure.

[0045] As described herein, further modifications to the methods 100, 200, 300 may include pre-treating the Mitragyna speciosa leaf material with an ultrasonic bath prior to extraction. The pre-treatment step may increase the yield of mitragynine by disrupting the cell structure of the leaves, making the alkaloids more accessible for extraction.

[0046] It should be appreciated that another refinement of method 100, 200 may be to perform the nano-encapsulation procedure on the liquid extract prior to evaporation. A skilled artisan can select a suitable timing for the nano-encapsulation procedure within the scope of the present disclosure.

[0047] The method 100, 200, 300 may also include the addition of a natural flavor enhancer to improve the taste of the extract without altering the efficacy of the active compounds. Additionally, a natural antioxidant may be supplemented in the acidified water to preserve the stability of mitragynine during the extraction process. A skilled artisan can select a suitable natural flavor enhancer and / or a natural antioxidant within the scope of the present disclosure.

[0048] It should be appreciated that to extend the shelf life of the Mitragyna speciosa extract, a natural preservative may be added during the concentration step or evaporation step of the method 100, 200, 300. This addition ensures that the final product remains stable and effective over a longer period. A skilled artisan can select a suitable natural preservative within the scope of the present disclosure.

[0049] The method 100, 200, 300 may also include a lyophilization step to produce a powder form of the standardized Mitragyna speciosa extract, which may be suitable for various74001-53 formulation applications. A skilled artisan may employ any drying process within the scope of the present disclosure.

[0050] In some embodiments, the method 100, 200, 300 may include a flocculation process. The flocculation process may include adjusting the pH of the contracted mixture with a basic reagent, applying an appropriate flocculant and mixing for a predetermined duration, collecting the precipitate, and drying to produce a free flowing powdered extract. In a particular embodiment, the pH of the aqueous extract may be adjusted with basic reagent to >8 and flocculant added during a flocculation process. The pH adjustment may be crucial for stabilizing the extract and enhancing the solubility of mitragynine. The pH range may be adjusted to between 2.475 to 3.825 to suit specific formulation requirements.

[0051] After thorough mixing for a predetermined duration, approximately 1-2 hours and settling for a predetermined amount of time, approximately 2-24 hours, the resulting precipitate may be collected and dried to produce a dry powdered extract of 15.0-60.0 mg mitragynine per gram dry weight (1.5-6.0±0.5% w / w). The flocculant process may include a further purification step to achieve a predetermined mitragynine concentration and remove undesired compounds, ensuring the production of a standardized and high-quality kratom extract.

[0052] Finally, the extract may be encapsulated in biodegradable capsules for controlled release, providing a convenient and precise dosage form for consumers, as described herein.

[0053] The nano-encapsulated Mitragyna speciosa extract produced by methods 100, 200 and 300 may be characterized by its consistent concentration within ±4% of the target level, ranging from within 0.40-1.25 mg / ml of mitragynine for liquid extracts and mitragynine concentrations of 2-10 ±0.5% (w / w) or 10 – 50% with a ±5% precision for solid extracts. For both extracts the absence of detectable levels of 7-hydroxymitragynine may also be confirmed. These standardized extracts may be used in the formulation of a beverage, a dietary supplement, and a natural health product, offering benefits such as improved alertness, restored energy, and alleviation of minor pain associated with physical exertion. The Mitragyna speciosa extract may be stored in containers at a temperature of 4°C to maintain stability and efficacy.

[0054] Following the formation of the nano-complex, the next step involves the removal of the solvent, typically through techniques like evaporation or lyophilization, which must be carefully controlled to preserve the integrity of the nano-complex and militate against degradation of the active compounds. The final product may be characterized using analytical techniques such as dynamic light74001-53 scattering (DLS) for particle size analysis, zeta potential measurements for surface charge determination, and high-performance liquid chromatography (HPLC) for quantification of the encapsulated mitragynine. A skilled artisan may select a suitable analytical technique within the scope of the present disclosure. These characterizations may confirm the quality and consistency of the nano-complexed Mitragyna speciosa extract, ensuring that each batch meets the specified criteria for therapeutic efficacy and safety. Through this advanced nano-complexing method, the bioactive compounds of Mitragyna speciosa are delivered more efficiently to the target site, enhancing their pharmacological effects and providing a basis for improved therapeutic applications.

[0055] The present invention relates to a novel nano-complex formulation including an extract of Mitragyna speciosa, commonly known as kratom. This nano-complex may be designed to enhance the bioavailability and efficacy of the primary active alkaloid, mitragynine, found in the kratom extract. The nano-complex encapsulates the Mitragyna speciosa extract in a biocompatible and biodegradable polymer matrix, which facilitates controlled release and improved absorption of mitragynine. The nano-encapsulation process may protect the alkaloid from degradation due to environmental factors such as pH, temperature, and enzymatic activity, thereby maintaining its therapeutic potency and extending shelf life.

[0056] Given the solubility and chemical properties of Mitragyna speciosa extract, particularly focusing on the primary alkaloid, mitragynine, which is moderately lipophilic, selecting the appropriate nano-encapsulation methods and materials may be helpful for enhancing its bioavailability, stability, and efficacy. Below are examples of tailored nano- encapsulation strategies and materials that may be best suited for this type of extract:

[0057] The nano-complex may be engineered using advanced nanotechnology techniques to achieve an optimal particle size that maximizes cellular uptake while minimizing potential cytotoxicity. The formulation process may involve the use of safe, environmentally friendly solvents and materials that may comply with regulatory standards for pharmaceutical products. The resulting nano-complex may be characterized by its uniform particle distribution, stable encapsulation efficiency, and the ability to target specific tissues or cells, enhancing the benefits of Mitragyna speciosa.

[0058] In addition to the enhanced delivery capabilities, the nano-complex of Mitragyna speciosa extract may offer significant advantages in terms of dosage accuracy and patient compliance. The standardized concentration of mitragynine within the nano-complex may enable74001-53 consistent dosing and therapeutic effects. This may be particularly beneficial where precise dosing and sustained release of active compounds may be crucial. The nano-complex formulation may therefore provide a significant advancement in the use of kratom, by providing a reliable, effective, and safe option for patients and healthcare providers.

[0059] The development of a method for nano-complexing an extract of Mitragyna speciosa represents a significant advancement in the field of botanical extracts, particularly for enhancing the delivery and efficacy of its primary alkaloids, such as mitragynine. The methods of the present disclosure include the encapsulation of Mitragyna speciosa extract within a nano-scale delivery system, utilizing biocompatible and biodegradable materials to form a stable nano-complex. As described herein, the process begins with the selection of appropriate encapsulating agents, which are typically polymers or lipids that may form nanoparticles or nano emulsions. These agents are chosen based on their ability to interact favorably with the alkaloid constituents of the extract, ensuring efficient encapsulation and stability.

[0060] The nano-complexing process involves dissolving the Mitragyna speciosa extract and the chosen encapsulant in a suitable solvent, followed by the application of techniques such as ultrasonication or high-pressure homogenization. These techniques facilitate the formation of nano- sized particles or emulsions, effectively encapsulating the extract within a protective matrix. The critical parameters, such as sonication time, pressure, and solvent composition, are meticulously optimized to achieve nanoparticles with the desired size, charge, and encapsulation efficiency. This optimization is crucial as it influences the release profile and bioavailability of the encapsulated alkaloids, ensuring that the therapeutic benefits of Mitragyna speciosa are maximized upon administration.

[0061] More specifically, nano-encapsulation may include specific methods and materials that could be employed for nano-encapsulation of this extract, including, but not limited to, nano-emulsion, nano-precipitation, liposome encapsulation, polymeric nanoparticles, and solid lipid nanoparticles (SLN). A skilled artisan may select a suitable method and material for nan- encapsulation within the scope of the present disclosure.

[0062] Nano emulsion may involve creating a nano-sized emulsion of the kratom extract in a continuous aqueous phase. This may be achieved using a high-energy process like ultrasonication or high-pressure homogenization. Nano emulsions may be used to provide an74001-53 improvement in the water solubility of lipophilic compounds and may enhance the oral bioavailability of mitragynine.

[0063] Nanoprecipitation, also known as solvent displacement, may include precipitating the kratom extract from a solution using a non-solvent that causes the extract to form nanoparticles. The method may be simple, does not require high energy, and may be used to form nanoparticles with a very narrow size distribution.

[0064] Liposome encapsulation involves the use of liposomes as vesicles made of lipid bilayers that may encapsulate both hydrophilic and lipophilic substances. Encapsulating Mitragyna speciosa extract in liposomes may protect the alkaloids from degradation and enhance their absorption through biological membranes.

[0065] Alternatively, biodegradable polymers like PLGA (poly(lactic-co-glycolic acid)), PCL (polycaprolactone), or natural polymers like alginate or chitosan may be used to form nanoparticles containing the kratom extract. These polymers may provide a controlled release of the encapsulated alkaloids. A skilled artisan may select a suitable biodegradable polymer within the scope of the present disclosure.

[0066] Solid Lipid Nanoparticles (SLN), which may be composed of solid lipids, these nanoparticles are stable at room temperature and may effectively encapsulate lipophilic compounds, protecting them from degradation and enhancing their bioavailability. A skilled artisan may select a suitable SLN within the scope of the present disclosure.

[0067] The above reference method may incorporate a variety of materials. For example, biodegradable synthetic polymers (e.g., PLGA, PCL) and natural polymers (e.g., alginate, chitosan, gelatin) may be selected for their biocompatibility and ability to provide controlled release. For liposome and SLN formulations, lipids such as phospholipids (e.g., phosphatidylcholine) and solid lipids (e.g., stearic acid, palmitic acid) are used. These materials may be considered biocompatible and effective at encapsulating lipophilic substances. Other lipids such as natural oils, such as coconut oil, olive oil may also serve as the lipid core in SLNs or NLCs, enhancing the solubility of mitragynine. Synthetic lipids, such as medium-chain triglycerides may also be used in lipid-based nanocarriers and nano emulsions, they help in stabilizing the formulation and improving the loading capacity. Surfactants, such as Tween 80, Poloxamer 188, Span 80, and lecithin, for example, may also be used to stabilize nanoparticles, preventing aggregation and ensuring uniformity in particle size. It should be appreciated that any74001-53 surfactant can be utilized for this purpose within the scope of the present disclosure. For certain natural polymers like gelatin and alginate, cross-linking agents such as glutaraldehyde (for gelatin) and calcium ions (for alginate) may be used to stabilize the nanoparticle structure.

[0068] When designing a nano-encapsulation system for Mitragyna speciosa extract, it is crucial to consider the stability of the active compounds, the intended release profile, and the route of administration. The choice of materials and methods should align with these factors to ensure optimal efficacy and safety of the final product. Additionally, regulatory compliance regarding the use of certain materials and solvents must be considered, especially for products intended for human consumption.

[0069] In one embodiment, a complex involving an extract of Mitragyna speciosa within a dextrin, and in certain embodiments, within a high branched cyclic dextrin (HBCD), is provided. The complex includes an approach to enhancing the solubility, stability, and bioavailability of the active alkaloids found in kratom, particularly mitragynine. High branched cyclic dextrin is known for exceptional ability to form inclusion complexes with various bioactive compounds, which may improve physicochemical properties. By encapsulating the Mitragyna speciosa extract within HBCD, the hydrophobic alkaloids are more effectively solubilized, facilitating easier absorption in the digestive tract. This encapsulation may also protect the sensitive alkaloids from degradation due to environmental factors such as light, heat, and pH changes, thereby extending the shelf life and efficacy of the kratom product.

[0070] The use of HBCD as a carrier molecule for Mitragyna speciosa extracts may not only enhance the physical properties of the extract but also modifies its release profile. This controlled release may be particularly beneficial for medicinal and therapeutic applications where a sustained release of active compounds is desired to maintain therapeutic levels without frequent dosing. The structure of HBCD may allow for a slow and steady release of the encapsulated alkaloids, which may provide more consistent therapeutic effects and reduce the incidence of side effects associated with peak dosing. Additionally, the improved solubility and stability may make the complex more suitable for various forms of administration, including oral capsules, powders, and liquid formulations, offering flexibility in how the product may be consumed.

[0071] Furthermore, the complexation of Mitragyna speciosa extract with HBCD may potentially mitigate some of the regulatory and safety concerns associated with kratom use. By74001-53 standardizing the composition of the Mitragyna speciosa extract and reducing the variability of active alkaloid content, the resultant product may be more reliable and predictable in its effects. This standardization may be crucial for gaining acceptance in markets where kratom faces regulatory scrutiny. Moreover, the improved safety profile resulting from the controlled release may help in establishing kratom as a viable option in the nutraceutical and pharmaceutical industries, where consistency and safety are paramount.

[0072] Overall, methods 100, 200, 300 provides a comprehensive and efficient approach to producing a high-quality, standardized extract of Mitragyna speciosa, addressing the needs and challenges associated with traditional kratom products.

[0073] Advantageously, the present disclosure addresses the significant challenges identified in the prior art by providing a method for extracting and encapsulating Mitragyna speciosa that ensures consistent levels of the active compound mitragynine and the removal of undesirable compounds such as 7-hydroxymitragynine. The method 100, 200, 300 not only enhances the safety and efficacy of the resulting extract but also ensures product reliability and consistency, which have been major issues with traditional kratom products. By incorporating steps such as precise acidification, controlled heating, meticulous filtration, and selective chromatographic techniques, the method significantly reduces variability in the active compound concentrations. Furthermore, the addition of natural preservatives and antioxidants during the extraction process may improve the stability and shelf life of the Mitragyna speciosa extract, addressing the problem of degradation and inconsistency found in naturally sourced products. This standardized approach to producing Mitragyna speciosa extract provides a safer, more reliable product for consumers, making the present disclosure a superior solution compared to the unpredictable and often unsafe products available in the prior art. EXAMPLES

[0074] Example embodiments of the present technology are provided below and are non- limiting.

[0075] Example 1: Preparation of Standardized Mitragyna speciosa Extract

[0076] In this example, the process of extracting and standardizing Mitragyna speciosa leaf product using the method 300 is demonstrated. High-quality Mitragyna speciosa leaves were sourced and verified for their mitragynine content using high-performance liquid74001-53 chromatography (HPLC). The Mitragyna speciosa leaves were then added to alcohol or aqueous alcohol with citric acid to achieve a pH of approximately 3.0. This mixture was heated to 60°C and stirred constantly for two hours to ensure optimal extraction of mitragynine and other alkaloids.

[0077] After the heating process, the mixture underwent a two-step filtration process. Initially, a coarse filter was used to remove large particulate matter, followed by a finer filter to ensure the removal of finer particles. The resulting clear liquid was then transferred to an evaporator where it was concentrated under reduced pressure until the mitragynine concentration reached 1 mg / mL, as verified by HPLC analysis. This concentration process also involved the addition of a dimethylpolysiloxane solution as a defoaming agent to prevent foaming during evaporation.

[0078] The concentrated extract was then subjected to a chromatographic technique specifically for removing oxidation products and bitter agents, thereby purifying the final product. The Mitragyna speciosa extract was then nano-complexed within another compound. The nano-complexed purified extract was tested again using HPLC to ensure that it met the predetermined specification of being substantially free from detectable levels of 7- hydroxymitragynine. The final standardized extract was stored in amber glass containers at 4°C to maintain its stability and integrity until further use.

[0079] Example 2: Application in Beverage Formulation

[0080] In this example, the standardized Mitragyna speciosa extract prepared as described in Example 1 was used to formulate an herbal beverage intended to improve alertness and restore energy. The beverage formulation involved diluting the extract to a final concentration of 40 mg of mitragynine per 500 mL serving. Natural flavor enhancers and a small amount of natural sweetener were added to improve the taste profile of the beverage without compromising the efficacy of the active compounds.

[0081] The beverage was subjected to stability testing to ensure that the active mitragynine content remained stable over time. Accelerated stability testing was conducted by storing the beverage at various temperatures for up to six months. The mitragynine content was periodically measured using HPLC, and the results confirmed that the active compound remained within 95% of its initial concentration throughout the testing period, demonstrating good stability.74001-53

[0082] Consumer testing was also conducted to assess the acceptability and perceived efficacy of the beverage. Participants reported increased alertness and energy after consuming the beverage, with no adverse effects reported. This example demonstrates the practical application of the standardized extract in a consumer product and highlights its potential benefits as a natural health product.

[0083] Example embodiments are provided so that this disclosure will be thorough and will fully convey the scope to those who are skilled in the art. Numerous specific details are set forth such as examples of specific components, devices, and methods, to provide a thorough understanding of embodiments of the present disclosure. It will be apparent to those skilled in the art that specific details need not be employed, that example embodiments may be embodied in many different forms, and that neither should be construed to limit the scope of the disclosure. In some example embodiments, well-known processes, well-known device structures, and well- known technologies are not described in detail. Equivalent changes, modifications and variations of some embodiments, materials, compositions and methods may be made within the scope of the present technology, with substantially similar results.

Claims

74001-53 CLAIMS What is claimed is:

1. A method for extracting and encapsulating Mitragyna speciosa leaf product, the method comprising steps of: providing Mitragyna speciosa leaf material; adding the Mitragyna speciosa leaf material to an acidified solvent with constant stirring to provide a heated mixture; filtering the heated mixture to remove solid material and provided a filtered mixture; concentrating the filtered mixture to achieve a predetermined concentration of mitragynine to provide a slurry; removing an undesired compound from the slurry to produce a standardized Mitragyna speciosa leaf extract; and nano-encapsulating the Mitragyna speciosa leaf extract.

2. The nano-encapsulated Mitragyna speciosa extract made by the method of claim 1, wherein the nano-encapsulated Mitragyna speciosa leaf extract is standardized to contain within ±4% of a target level, ranging from within 0.40-1.25 mg / ml of mitragynine for liquid extracts and mitragynine concentrations of 2 – 50% with a ±5% precision for solid extracts.

3. The method of Claim 1, further including evaporating the filtered mixture to achieve a crude Mitragyna speciosa extract.

4. The method of Claim 1, wherein the step of removing an undesired compound from the slurry to produce a standardized Mitragyna speciosa leaf extract includes combining the slurry with acidified water and applying the slurry to a charged ionic resin.74001-53 5. The method of Claim 4, wherein the step of removing an undesired compound from the slurry to produce a standardized Mitragyna speciosa leaf extract includes successively washing the charged ionic resin with alkaline water and a water / alcohol mixture.

6. The method of Claim 5, wherein the step of removing an undesired compound from the slurry to produce a standardized Mitragyna speciosa leaf extract includes eluting the charged ionic resin with ethanol, collecting a diluent and drying the diluent to a powder.

7. The method of Claim 1, wherein the nano-encapsulating step utilizes a nano-emulsion technique including creation of a nano-sized emulsion in a continuous aqueous phase.

8. The method of Claim 1, wherein the nano-encapsulating step utilizes a biodegradable polymer selected from a group consisting of PLGA (poly(lactic-co-glycolic acid)), PCL (polycaprolactone), alginate, and chitosan.

9. The method of Claim 1, wherein the nano-encapsulating step employs a solid lipid nanoparticle (SLN) composed of a solid lipid stable at room temperature.

10. The method of Claim 1, wherein the nano-encapsulating includes at least one of ultrasonication and high-pressure homogenization to facilitate formation of nano-sized particles.

11. The method of Claim 1, wherein the nano-encapsulation step utilizes a surfactant .74001-53 12. The method of Claim 1, wherein the nano-encapsulation step includes forming a nano- complex with cyclic dextrin as a carrier molecule.

13. The method of Claim 1, wherein the nano-encapsulation step includes solvent removal through at least one of evaporation and lyophilization.

14. The method of Claim 1, wherein the filtering step includes a two-step filtration process utilizing a coarse filter to remove large particulate matter and a finer filter to remove finer particles.

15. The method of Claim 1, further including pre-treating the Mitragyna speciosa leaf material with an ultrasonic bath prior to extraction to increase a yield of mitragynine.

16. The method of Claim 1, wherein the acidified solvent includes citric acid.

17. A consumable product containing a nano-encapsulated Mitragyna speciosa extract made by the method of Claim 1.

18. A beverage containing a nano-encapsulated Mitragyna speciosa extract as made by the method of Claim 1.

19. A method for extracting and encapsulating Mitragyna speciosa leaf product, the method comprising steps of: providing Mitragyna speciosa leaf material;74001-53 adding the Mitragyna speciosa leaf material to acidified water and heating with constant stirring to provide a heated mixture; filtering the heated mixture to remove solid material and provided a filtered mixture; concentrating the filtered mixture to achieve a predetermined concentration of mitragynine to provide a concentrated mixture; removing undesired compounds from the concentrated mixture to produce a standardized Mitragyna speciosa leaf extract; and nano-encapsulating the Mitragyna speciosa leaf extract.

20. A method for extracting and encapsulating Mitragyna speciosa leaf product, the method comprising steps of: providing Mitragyna speciosa leaf material; adding the Mitragyna speciosa leaf material to acidified acetone with constant stirring to provide a mixture; filtering the mixture to remove solid material and provide a filtered mixture; evaporating the filtered mixture to achieve a crude Mitragyna speciosa extract; concentrating and removing undesired compounds from the crude Mitragyna speciosa extract to produce a standardized Mitragyna speciosa leaf extract; and nano-encapsulating the Mitragyna speciosa leaf extract.

Images