Aqueous extract of mitragyna speciosa leaves and methods for making same

Abstract

The disclosure relates to the development of a standardized aqueous extract of Mitragyna speciosa, commonly known as kratom, specifically designed for use in beverages. The Mitragyna speciosa extract may be 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 associated with physical exertion. The method outlines an extraction process that not only maximizes the yield of mitragynine but also facilitates the removal of an undesirable compound, thereby enhancing the safety profile of the final product. The method involves the use of environmentally friendly extraction methods that are both efficient and scalable, suitable for commercial production. The standardized Mitragyna speciosa extract may be easily incorporated into various beverage formulations, providing a reliable and effective herbal supplement option.

Description

73999-53AQUEOUS EXTRACT OF MITRAGYNA SPECIOSA LEAVES AND METHODS FOR MAKING SAMECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 705,537, 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 standardized aqueous 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 the 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 Mitragyna speciosa leaves.73999-53

[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 may 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 an improved method and composition 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 products that meet 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 standardization, and which addresses the inconsistency in the potency and purity of kratom extracts, provides safer and more environmentally friendly extraction methods, and result in products that meet 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 standardized extraction and formulation of Mitragyna speciosa extract for the creation of consistent, safe, and effective botanical beverages for promoting enhanced energy, alertness, and alleviating minor pain.

[0011] In one embodiment, a method for extracting and standardizing Mitragyna speciosa leaf product includes 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 desired alkaloids, preserving their integrity. Subsequent steps may include a filtration process to remove solid73999-53 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, ensuring the production of a standardized and high-quality kratom extract.

[0012] In another embodiment, the Mitragyna speciosa extract produced by the method is standardized to contain from 0.40-1.25 mg / mL of mitragynine with a ±4% precision, depending on the intended application, and is substantially free from detectable levels of 7- hydroxymitragynine, a short-lived human metabolite and oxidation product of mitragynine that poses a safety risk when consumed. The Mitragyna speciosa extract may be particularly advantageous for use in various formulations, including beverages, dietary supplements and natural health products, due to its consistent potency and enhanced safety profile. The standardized Mitragyna speciosa extract offers potential benefits such as improved alertness, energy restoration, and alleviation of minor pain, making the Mitragyna speciosa extract a valuable component in health and wellness products. Additionally, the stability and purity of the Mitragyna speciosa extract are maintained through careful storage conditions, ensuring efficacy and quality over time.

[0013] In an exemplary embodiment, the present disclosure provides a method for extracting and standardizing Mitragyna speciosa leaf product, intended to produce a high-quality extract with consistent levels of the active alkaloid mitragynine while substantially eliminating an undesired compound, such as 7-hydroxymitragynine. The method, identified as method 100, involves several steps: starting with the selection and provision of high-quality Mitragyna speciosa leaf material, the Mitragyna speciosa leaves may be added to acidified water — precisely acidified by adding citric acid (or other organic or mineral acid) — to facilitate the extraction process. The mixture may be heated to approximately 90°C with constant stirring for about two hours to optimize the alkaloid extraction. Following heating and stirring, a two-step filtration process may be employed to remove solid residues, promoting the clarity and purity of the extract. The filtered mixture may be concentrated using an evaporator under reduced pressure to achieve a targeted mitragynine concentration, typically 1 mg / mL. The resultant liquid extract may be standardized to any target concentration within the range of 0.40 mg / mL to 1.25 mg / mL, depending on the intended application with a ±4% precision. To further refine the extract, an undesired compound may be removed using a selective technique, enhancing the safety profile of the final product. Additional enhancements may include the optional use of an ultrasonic bath for73999-53 pre-treating the leaf material to increase yield, the incorporation of natural flavor enhancers and antioxidants to improve taste and stability, and the addition of natural preservatives during concentration to extend shelf life. The method may also include incorporating microfiltration, ion exchange, osmotic separation, or microfluidics for formulating higher purity. The resulting standardized Mitragyna speciosa extract, is characterized by a 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.

[0014] In another exemplary embodiment, the liquid Mitragyna speciosa extract may be lyophilized, with or without excipients, to produce a standardized Mitragyna speciosa powder extract. The liquid Mitragyna speciosa extract may also be combined with co-ingredients, such as linear or cyclic polysaccharides, to enhance the physicochemical properties, such as solubility, stability and bioavailability.

[0015] In another exemplary embodiment, a method for extracting and concentrating Mitragyna speciosa leaf product includes steps to optimize the yield and consistency of the active compounds, primarily mitragynine. The method begins with the provision of high-quality Mitragyna speciosa leaf material, which may produce an aqueous extract with a targeted concentration within the range of 0.40 mg / mL to 1.25 mg / mL, depending on the intended application, with a ±4% precision. The pH of the aqueous Mitragyna speciosa extract may be adjusted with basic reagent to >8 and flocculant added during a flocculation process. After thorough mixing (1-2 hours) and settling (2-24 hours) the resulting precipitate may be collected and dried to produce a dry powdered Mitragyna speciosa extract of 15.0-60.0 mg mitragynine per gram dry weight (1.5-6.0±0.5% w / w). The method 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.

[0016] 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.73999-53DRAWINGS

[0017] 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.

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

[0019] FIGS. 2A-2D is a flowchart illustrating a method for extracting, according to another embodiment of the present disclosure.DETAILED DESCRIPTION

[0020] 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 may be different in various embodiments, including where certain steps may be simultaneously performed, unless expressly stated otherwise. “A” and “an” as used herein 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.

[0021] 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 embodiment73999-53 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 signifimayt 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.

[0022] 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 Parameter 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.

[0023] 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 elements73999-53 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.

[0024] 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.

[0025] 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 in 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” may 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.

[0026] 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 method of the present disclosure significantly mitigates the risks associated with the variability of73999-53 traditional kratom preparations and paves the way for broader acceptance and regulatory compliance of kratom-based products in various markets.

[0027] As shown in the Figures 1 and 2A-2D, the present disclosure provides a method for extracting and standardizing Mitragyna speciosa leaf product, referred to herein as method 100. The method 100 may produce a standardized extract of Mitragyna speciosa, commonly known as kratom, which may be particularly useful for incorporation into beverages, dietary supplement, natural health products, and other products. The method 100 promotes consistent levels of a primary active alkaloid, mitragynine, while militating against oxidation (chemical alteration) of key alkaloids and militating against formation of an undesired compound, thereby enhancing both the safety and efficacy of the final product.

[0028] Method 100 begins with a step 110 of providing Mitragyna speciosa leaf material. The Mitragyna speciosa leaf material used may be selected based on quality and mitragynine content, ensuring that only high-quality leaves are used in the extraction process. The initial selection is important to the success of the method 100 as the quality of the Mitragyna speciosa leaf material impacts the overall yield and quality of the final Mitragyna speciosa extract. In certain embodiments, the method 100 may include a step 112 of pre-treating the leaf material with an ultrasonic bath prior to extraction. The pre-treatment step 112 may increase the yield of mitragynine by disrupting the cell structure of the Mitragyna speciosa leaves, making the alkaloid more accessible for extraction.

[0029] In step 120, the provided Mitragyna speciosa leaf material may be added to acidified water. The acidification of the water may be achieved by adding citric acid, for example, which helps in the extraction of mitragynine and other desirable alkaloids from the leaf material in a step 122. 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 in a step 124. The step 120 may also include heating the mixture of Mitragyna speciosa leaf and acidified water with constant stirring, which may facilitate the release of the alkaloid into the mixture.

[0030] The heating in step 120 may be conducted at a predetermined temperature. In a particular embodiment, the predetermined temperature may be about 90°C. The predetermined temperature may be maintained to optimize the extraction of the alkaloid while militating against73999-53 the degradation of a sensitive compound within the leaf material. The constant stirring mentioned in the step 120 may be maintained for a predetermined duration of about 2 hours, for example, ensuring that the Mitragyna speciosa leaf material may be evenly exposed to the heated acidified water.

[0031] In certain embodiments, the heating step 120 may be performed under a nitrogen atmosphere to militate against oxidation of sensitive compounds, thereby preserving the integrity of the Mitragyna speciosa extract.

[0032] It should be appreciated that the method 100 may include variations in the duration of heating and stirring and temperature of heating to accommodate different batch sizes or specific strains of Mitragyna speciosa that might have varying alkaloid profiles as step 126. For instance, the temperature may be adjusted slightly above or below 90°C (for example within the range of approximately 80-105°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. For example, the heating may be for as short a period of time at 1 hour and for as long as 3 hours. 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 predetermined temperatures and predetermined stirring durations as desired to suit specific extraction needs or to optimize the process for commercial scale-up.

[0033] Following the heating and stirring step 120, the method 100 may include a step 130 of filtering the heated mixture to remove solid material. The step 130 may be important as filtration purifies the mixture by separating the liquid Mitragyna speciosa extract from the residual Mitragyna speciosa leaf material. The filtration employed may optionally include a two- step filtration system, step 132, enhancing the clarity and purity of the filtered mixture. 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 Mitragyna speciosa extract by systematically removing particles of different sizes with first the larger particulate matter, then the finer particles, which is important for producing a high-quality, standardized Mitragyna speciosa extract suitable for beverage and supplement applications.73999-53

[0034] For applications requiring extremely high purity, a microfiltration step 134 may be included after the initial filtration to further purify the final Mitragyna speciosa extract. The step 134 ensures that the final product may meet stringent quality standards.

[0035] Step 140 of the method 100 may include concentrating the filtered Mitragyna speciosa mixture to achieve a predetermined concentration of mitragynine. The concentration step 140 may be performed using an evaporator under reduced pressure, which may efficiently concentrate the mixture without significant loss of volatile compounds, in a step 142. The target concentration of mitragynine may be set at 1 mg / mL, at any target level within the specific range of 0.40 mg / mL to 1.25 mg / mL being particularly effective, with a ±4% precision.

[0036] In addition to using an evaporator under reduced pressure in step 142, alternative methods for concentrating the filtered mixture may include reverse osmosis, spray dying or freeze-drying / lyophilization techniques, which may 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 140 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 efficacy and stability of the product.

[0037] To extend the shelf life of the extract, a natural preservative may be added during the concentration step 140 in a further step 144. This addition ensures that the final product remains stable and effective over a longer period.

[0038] Additional enhancements to method 100 may include the addition of a defoaming agent during the concentrating step 140 to militate against foaming, which may interfere with the evaporation process, in a step 144. 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 and concentration within the present disclosure.

[0039] In step 150, an undesired compound, such as a bittering components, waxy substance or artefact of processing, may be removed from the concentrated mixture. The purification step 150 may be important for ensuring the safety of the final Mitragyna speciosa73999-53 extract. The removal of an undesired compound may be achieved using a chromatographic technique that selectively binds the undesired compound, allowing for separation from the desired mitragynine in a step 152. It should be appreciated that the step 150 may include removing detectable levels of 7-hydroxymitragynine from the Mitragyna speciosa leaf material.

[0040] In another embodiment, the liquid Mitragyna speciosa extract produced using the method 100 may proceed to a flocculation process step 160 that involves adjusting the pH of the contracted mixture with a basic reagent, step 162, applying an appropriate flocculant and mixing for a predetermined duration, step 164, collecting the precipitate, step 166, and drying the precipitate to produce a free flowing powdered Mitragyna speciosa extract, step 168. The pH of the aqueous extract may be adjusted with a basic reagent to >8 and flocculant may be added during a flocculation process. The pH adjustment step 162 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. A skilled artisan can select a suitable pH for adjustment within the scope of the present disclosure.

[0041] 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) in the steps 166 and 168. The flocculant process step 160 may include a further purification step to achieve a predetermined mitragynine concentration and remove an undesired compound, facilitating the production of a standardized and high-quality kratom extract.

[0042] The method 100 may also include the addition of a natural flavor enhancer to improve the taste of the Mitragyna speciosa extract without altering the efficacy of the active compounds in a step 170. Additionally, a natural antioxidant may be supplemented in the acidified water to preserve the stability of mitragynine during the extraction process. A skilled artisan may select a suitable natural flavor enhancer and natural antioxidant within the scope of the present disclosure.

[0043] Another embodiment of the method 100 may include a step 180 of lyophilization, spray drying, or other drying step to produce a powder form of the standardized Mitragyna speciosa extract, which may or may not be in combination with excipients to be suitable for73999-53 various formulation applications. A skilled artisan may select a suitable technique within the scope of the present disclosure.

[0044] In another embodiment, the Mitragyna speciosa extract may be mixed with a coingredient to encapsulate or create a complex with enhanced physicochemical properties, including but not limited to improved solubility, stability, and bioavailability. This may include encapsulation in biodegradable capsules for controlled release, providing a convenient and precise dosage form for consumers.

[0045] The standardized Mitragyna speciosa extract produced by method 100 may be characterized by its consistent concentration within ±4% of the target level, ranging from within 0.40-1.25 mg / ml of mitragynine or for dry embodiments of the aqueous extract 15-60 mg mitragynine per gram of dry weight (1.5-6.0±0.5% w / w). Aqueous-based extracts that have been combined with excipients, co-ingredients or flocculants, with or without additional purification may exhibit an expansive range of mitragynine content in the final product, ranging from 0.5- 40% w / w and with a precision of 4% on the intended concentration. All aqueous-based ingredients may exhibit the absence of detectable levels of 7-hydroxymitragynine. The standardized extract(s) may be used in the formulation of beverages, dietary supplements and natural health products, offering benefits such as improved alertness, restored energy, and alleviation of minor pain associated with physical exertion. The extract may be stored in a sealed container at room temperature, protected from light for 30 days to 10 months.

[0046] Overall, the method 100 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.

[0047] Advantageously, the present disclosure addresses the significant challenges identified by providing a method 100 for extracting and standardizing Mitragyna speciosa that facilitates consistent levels of the active compound mitragynine and the removal of undesirable compounds such as 7-hydroxymitragynine, while maintaining a broad spectrum of the compounds found in the underlying plant material. The method 100 not only enhances the safety and efficacy of the resulting extract but also promotes product reliability and consistency, which have been major issues with various kratom products. By incorporating steps such as precise acidification, controlled heating, meticulous filtration, and selective chromatographic techniques, the method 100 significantly reduces variability in the active compound concentrations.73999-53Furthermore, the addition of natural preservatives and antioxidants during the extraction process improves the stability and shelf life of the 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 it a superior solution compared to the unpredictable and often unsafe products available in the prior art.

[0048] In use, the Mitragyna speciosa extract produced by the method 100 described herein may provide a broad spectrum of physiological effects, which vary depending on the dosage. At lower concentrations, mitragynine acts as a stimulant, providing increased energy, enhanced alertness, and a more positive mood, which may be beneficial for individuals dealing with fatigue or mild depression. The stimulant effect aligns with traditional uses where laborers in Southeast Asia consumed kratom to endure long hours of work.

[0049] At moderate doses, the Mitragyna speciosa extract exhibits properties that may temporarily alleviate pain without the significant sedative effects that are common in conventional opioids, which makes Mitragyna speciosa extract a potential alternative for managing chronic pain, particularly for patients who are seeking pain relief but need to avoid the lethargy associated with traditional pain medications. The pain-relieving properties of kratom are primarily attributed to its action on opioid receptors, yet kratom does not have the same risk profile as opioids, which are known for high potential for addiction and overdose.

[0050] Furthermore, at higher doses, the Mitragyna speciosa extract has sedative effects, which may be used to aid sleep and reduce anxiety or anxiety-like symptoms. Thus, the Mitragyna speciosa extract may be useful for to help individuals suffering from insomnia or anxiety disorders, providing a natural alternative to synthetic sedatives and anxiolytics. Additionally, the anxiolytic and antidepressant properties of the extract may be harnessed in mental health treatment, offering a complementary approach to existing therapies.

[0051] As a dietary supplement, the extract of Mitragyna speciosa may be marketed for the potential to boost energy, helping to maintain a positive or enhanced mood, and improve focus. This makes the Mitragyna speciosa extract particularly appealing to individuals seeking a natural alternative to conventional stimulants. Unlike many synthetic stimulants that may cause jitteriness or a sudden crash in energy levels, kratom is believed to provide a more balanced and73999-53 sustained energy boost, making it suitable for consumption during the day to enhance productivity and mental clarity.

[0052] A full spectrum Mitragyna speciosa extract created by the method 100 of the present disclosure, which includes a wide range of alkaloids present in the raw plant material, offers several benefits over isolates that contain only specific alkaloids such as mitragynine or 7- hydroxymitragynine. One of the primary advantages of a full spectrum extract may be the entourage effect, a phenomenon where multiple components in the extract synergistically interact to enhance the overall therapeutic effects and reduce potential side effects. This holistic approach facilitates that users experience a more balanced effect, mirroring the natural properties of the plant as used traditionally in Southeast Asia for centuries.

[0053] Unlike isolated compounds, the full spectrum maintains a variety of alkaloids that may target different pathways in the body. This may lead to more effective and long-lasting benefits without the high risk of tolerance. This may provide a significant improvement in quality of life, offering benefits with fewer side effects. Additionally, the presence of various alkaloids may help mitigate the sedative effects that are often pronounced in high doses of isolated mitragynine, leading to a more manageable and functional state during treatment.

[0054] Moreover, a full spectrum Mitragyna speciosa extract may also provide enhanced mood and additional benefits. The various alkaloids may work together to improve mood, reduce anxiety, and enhance cognitive function. The stimulant effects at lower doses may increase alertness and energy, which may be particularly beneficial for individuals needing a natural boost during day-to-day activities. By preserving the natural complexity of the kratom plant, the full spectrum Mitragyna speciosa extract may ensure a more nuanced and balanced interaction with the systems of the body, potentially reducing the risk of adverse effects associated with higher concentrations of any single alkaloid.

[0055] Kratom, derived from the Mitragyna speciosa plant, exhibits its therapeutic effects primarily through its main alkaloids, mitragynine and 7-hydroxymitragynine. These compounds function as partial agonists at the mu-opioid receptors in the brain. Additionally, these alkaloids influence serotonergic and adrenergic systems, enhancing mood and providing stimulant effects at lower doses. The interaction with dopaminergic pathways further potential uses of the extract.73999-53EXAMPLES

[0056] Example embodiments of the present technology are provided below and are nonlimiting.

[0057] Example 1:

[0058] The following sections are an in-depth description of the specifications.

[0059] 1Unidentified Mitragynine speciosa alkaloids checked against the NIST database to determine putative identities.73999-5373999-53'Unidentified Mitragynine speciosa alkaloids checked against the NIST database to determine putative identities

[0060] Methods used to assess standardized aqueous extract of Mitragyna speciosa, and raw material used for manufacturing aqueous extract of Mitragyna speciosa are listed below and on the specification sheet above. Descriptions of the methods are described briefly below. All USP and AO AC contaminant testing methods are as per pharmacopeial standards using official methods of analysis compliant with USP.

[0061] AOAC2017.14

[0062] Used for the determination of the alkaloid HPLC profile and to quantify the alkaloids mitragynine, speciogynine, paynantheine and speciociliatine, and the determination of presence or absence of 7-hydroxymitragynine. Performed on raw material, standardized aqueous extract of Mitragyna speciosa, and finished products. HPLC method using DAD detection.

[0063] SQP-ATM-02-00

[0064] Used for the detection of alkaloids and to determine their relative percentages. Performed on raw material, standardized aqueous extract of Mitragyna speciosa, and dietary supplement finished products. GC-MS method peaks detected by the method are checked against the NIST database to determine their putative identities. The peak areas of all alkaloid signals are used to determine relative alkaloid content.

[0065] SOP- ATM-03 -00

[0066] Used for the detection and quantification of flavonoids in the sample. Performed on raw material, standardized aqueous extract of Mitragyna speciosa, and finished products. HPLC method using DAD detection.73999-53

[0067] APAC 984,27

[0068] Used for the detection and quantification of elemental impurities. Performed on raw material, standardized aqueous extract of Mitragyna speciosa, and dietary supplement finished products. ICP-MS emission spectrometry method.

[0069] APAC 986,32

[0070] Used in the detection and quantification of total microbial load in the material. Performed on standardized aqueous extract of Mitragyna speciosa, and dietary supplement finished products.

[0071] USP <61>

[0072] Used for the detection and quantification of coliforms present in material and to determine their relative percentages. Performed on standardized aqueous extract of Mitragyna speciosa, and dietary supplement finished products.

[0073] APAC 985,21

[0074] Used for the detection and quantification of yeasts and molds in the material. Performed on standardized aqueous extract of Mitragyna speciosa, and dietary supplement finished products.

[0075] USP-NF <2022>

[0076] Used for the detection and quantification of specific coliforms in the material. Performed on standardized aqueous extract of Mitragyna speciosa, and dietary supplement finished products.

[0077] Example 2: Preparation of Standardized Mitragyna Speciosa Extract

[0078] In this example, the process of extracting and standardizing Mitragyna speciosa leaf product using the method 100 is demonstrated. High-quality Mitragyna speciosa leaves were sourced and verified for mitragynine content using high-performance liquid chromatography (HPLC). The leaves were then added to water acidified with citric acid to achieve a pH of approximately 3.0. This mixture was heated to 90°C and stirred constantly for two hours to ensure optimal extraction of mitragynine and other alkaloids.

[0079] 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 concentration73999-53 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.

[0080] The concentrated extract was then subjected to a chromatographic technique specifically designed to bind and remove 7-hydroxymitragynine, thereby purifying the final product. The 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 stability and integrity until further use.

[0081] Example 3: Application in Beverage Formulation

[0082] 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 Mitragyna speciosa 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.

[0083] 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.

[0084] 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.

[0085] Example 4: Enhancement of Extraction Yield

[0086] In this example, an enhancement of the extraction yield of mitragynine from Mitragyna speciosa leaves was explored by pre-treating the leaves with an ultrasonic bath prior to the extraction process described in Example 1. Leaves were submerged in water and subjected73999-53 to ultrasonic waves for 30 minutes, which was intended to disrupt the cell walls and increase the release of alkaloids during the subsequent extraction process.

[0087] Following the ultrasonic pre-treatment, the leaves were processed according to the method 100 described in Example 1. The yield of mitragynine was measured and compared to a control batch of leaves that were not subjected to ultrasonic pre-treatment. The results indicated a signifimayt increase in the yield of mitragynine in the ultrasonically pre-treated batch, demonstrating the effectiveness of this pre-treatment step in enhancing the efficiency of the extraction process.

[0088] Further analysis was conducted to ensure that the ultrasonic pre-treatment did not adversely affect the quality or stability of the extracted mitragynine. The stability of the extract from the pre-treated leaves was monitored over a period of three months, and no signifimayt degradation of mitragynine was observed. This example illustrates an effective method to enhance the yield of active compounds from botanical materials, potentially reducing the cost and increasing the efficiency of the production of standardized extracts.

[0089] 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

73999-53CLAIMSWhat is claimed is:

1. A method for extracting and standardizing Mitragyna speciosa leaf product, the method comprising steps of: providing Mitragyna speciosa leaf material; 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 provide a filtered mixture; concentrating the filtered mixture to achieve a predetermined concentration of mitragynine and provide a concentrated mixture; and removing an undesired compound from the concentrated mixture to produce a standardized Mitragyna speciosa leaf extract.

2. The method of Claim 1, wherein the step of adding the Mitragyna speciosa leaf material to acidified water and heating with constant stirring to provide a heated mixture further includes heating the mixture to 90°C with constant stirring for 2 hours.

3. The method of Claim 1, wherein the step of adding the Mitragyna speciosa leaf material to acidified water and heating with constant stirring to provide a heated mixture further includes acidifying the water by adding citric acid.

4. The method of Claim 1, wherein the step of filtering the heated mixture to remove solid material and provided a filtered mixture includes employing a two-step filtration process to remove solid residue.73999-535. The method of Claim 1 , wherein the step of concentrating the filtered mixture to achieve a predetermined concentration of mitragynine to provide a concentrated mixture includes using an evaporator under reduced pressure.

6. The method of Claim 1, wherein the step of concentrating the filtered mixture to achieve a predetermined concentration of mitragynine to provide a concentrated mixture includes concentrating the filtered mixture until the predetermined concentration of mitragynine is within a range of 0.40 mg / mL to 1.25 mg / mL with ±4% precision.

7. The method of Claim 1, wherein the step of removing the undesired compound from the concentrated mixture to produce a standardized Mitragyna speciosa leaf extract includes using a chromatographic technique that selectively binds the undesired compound.

8. The method of Claim 1, wherein the step of removing the undesired compound from the concentrated mixture to produce a standardized Mitragyna speciosa leaf extract includes removing detectable levels of 7-hydroxymitragynine from the Mitragyna speciosa leaf material.

9. The method of claim 1, further including lyophilizing the standardized Mitragyna speciosa leaf extract to produce a standardized powder extract.

10. The method of claim 1, further including subjecting the concentrated mixture to a flocculation process including adjusting a pH of the concentrated mixture with a basic reagent; adding flocculant and mixing for a predetermined duration; allowing settling for a predetermined amount of time; and73999-53 collecting and drying a resulting precipitate to produce a dry powdered extract.

11. The method of Claim 10, wherein the flocculation process includes adjusting the pH of the concentrated mixture with basic reagent to >8.

12. The method of Claim 11, wherein the flocculation process includes adding flocculant and mixing for 1-2 hours.

13. The method of Claim 12, wherein the flocculation process includes allowing settling for 2-24 hours.

14. The method of Claim 1, wherein the step of adding the Mitragyna speciosa leaf material to acidified water includes acidifying the water with an organic acid selected from the group consisting of citric acid, tartaric acid, malic acid, ascorbic acid, acetic acid, and lactic acid.

15. The method of Claim 1, further including pre-treating the Mitragyna speciosa leaf material with an ultrasonic bath prior to adding to the Mitragyna speciosa leaf material to the acidified water.

16. The method of Claim 1, further including adding a natural preservative during the concentration step to extend shelf life of the extract.

17. A standardized Mitragyna speciosa extract made by the method of Claim 1.73999-5318. The standardized Mitragyna speciosa extract made by the method of claim 1, wherein the standardized Mitragyna speciosa leaf extract is standardized to contain 1 mg / mL of mitragynine and is substantially free from detectable levels of 7-hydroxymitragynine.

19. A consumable product containing Mitragyna speciosa extract made by the method of Claim 1.

20. A beverage containing Mitragyna speciosa extract as made by the method of Claim 1.

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