Process for generating cannabinoid picoemulsions with antibiotic properties and the resulting picoemulsions

Abstract

A novel process for generating cannabinoid picoemulsions that result in sterile, injectable cannabinoid emulsions with increased bioavailability and antibiotic properties for the purpose of treating diverse medical conditions in both humans and animals, and the novel cannabinoid picoemulsions obtained.

Description

[Technical Field]

[0001] Areas of this disclosure This disclosure relates, in general, to a process for generating medical-grade cannabinoid-based products, and more specifically, to sterile, injectable cannabinoid picoemulsions characterized by increased bioavailability and antibiotic properties, and to novel cannabinoid picoemulsions obtained.

[0002] Cross-reference of related applications This U.S. non-practical patent application claims priority date to U.S. provisional application No. 63 / 521,641, entitled “CANNABINOID PICO EMULSION,” filed with the U.S. Patent and Trademark Office on 16 June 2023, the entire disclosure of which is incorporated herein by reference. [Background technology]

[0003] Background technology As our understanding of the pharmacological properties of cannabis continues to deepen, the exploration and use of THC (tetrahydrocannabinol), CBD (cannabidiol), and other cannabis-derived compounds for various medical purposes has increased significantly. Along with a growing number of studies providing scientific evidence support, cannabis-derived compounds are increasingly being incorporated into mainstream medical protocols to treat a wide range of medical conditions.

[0004] Traditionally, the methods of consumption or administration of cannabis have been limited to either smoking or ingestion. While these traditional modes of administration offer certain benefits, they also come with well-known drawbacks and limitations. For example, smoking cannabis involves inhaling smoke that can irritate the respiratory system and includes other harmful by-products of combustion that can present risks to overall health over time. Furthermore, some may not want smoking as a route of administration because it inevitably exposes others in the surrounding area to secondhand smoke. Some of these concerns can be mitigated by the use of e-cigarettes or vapes; however, vaping is also associated with various health risks. Smoking and vaping may also be undesirable for some who seek to treat medical conditions with cannabis because such conventional delivery systems can be associated with hedonistic cannabis use, which has traditionally been associated with stigma and various other social emotions (both positive and negative).

[0005] While the introduction of cannabis-based compounds via dietary consumption may be far less conspicuous than smoking and vaping, this route of administration also comes with its own limitations. For example, diet is traditionally associated with delayed onset of effects and unpredictable potency, making it difficult to control dosage and extremely challenging to achieve immediate effects. One reason for the challenges associated with predicting potency when ingesting cannabis-based compounds is that the gastrointestinal tract metabolizes THC, CBD, and other cannabinoids before they can reach the bloodstream. This process, known as first-pass metabolism, reduces the amount of desired cannabinoids that ultimately enter the bloodstream, resulting in reduced bioavailability and potentially requiring higher initial doses to achieve the desired effect.

[0006] Furthermore, when THC is metabolized, it can produce metabolites, such as 11-hydroxy-THC (also known as delta-11) and delta-10-THC, which can remain in the body for longer periods than THC itself. The prolonged presence of these metabolites can increase the risk of failing drug tests, even if the psychoactive effects of THC or other desired effects of the target cannabinoid are diminished, raising unnecessary concerns for those using cannabis for medical purposes.

[0007] Recognizing the limitations of conventional delivery methods, there is growing interest in alternative routes of administration that offer improved dosing accuracy, immediate bioavailability, and therapeutic efficacy. One such approach is the development of injectable or intravenous formulations of cannabis-derived compounds. By directly administering cannabinoids into the bloodstream, injectable formulations bypass gastrointestinal and hepatic metabolism, resulting in faster onset of action and increased bioavailability compared to conventional modalities.

[0008] Furthermore, injectable cannabis formulations offer the potential for more precise dosing, allowing healthcare providers to tailor treatment regimens more accurately to the individual needs of each patient. This can be particularly beneficial for conditions requiring rapid symptom relief or for patients with pulmonary or gastrointestinal problems that may impair or limit absorption into the bloodstream via conventional routes of administration.

[0009] One important parameter when developing injectable or intravenous cannabis formulations is emulsion droplet or micelle size. Generally speaking, smaller droplet sizes result in higher bioavailability.

[0010] Some researchers have also attempted to achieve higher cannabinoid bioavailability by modifying the polarity of cannabinoid molecules through glycosylation to increase their solubility. Glycosylation is the process of attaching sugar molecules (glycans) to cannabinoid molecules. This modification improves the water solubility of cannabinoids, thus potentially providing cannabinoid solutions characterized by uniformly dispersed, highly bioavailable molecules, and eliminating the need for surfactants and emulsifiers; however, glycogen groups also typically modify the way cannabinoids interact with the body's endocannabinoid receptors, which in turn alters the effects of cannabinoids on the body and the resulting medical benefits. Thus, while glycosylation of cannabinoids may still prove useful for a given function, to date, its medical benefits have been far more limited than those of cannabinoid emulsification. There remains a need to produce cannabinoid emulsions with the smallest possible droplet or micelle sizes.

[0011] Several pharmaceutical developers have succeeded in developing methods for generating cannabinoid emulsions with nanometer-range droplets, such as the method described in U.S. Utility Patent No. 10,738,268, known as Cannabis Nano-Emulsion Methods; however, to date, such conventional methods have not succeeded in generating stable cannabinoid emulsions in the picometer range.

[0012] Furthermore, while advances in cannabinoid nanoemulsions have garnered significant attention and support in scientific literature, there is a general consensus among pharmaceutical developers that greater advantages still exist that can be realized by developing stable cannabinoid emulsions in the picometer range. The most predictable advantage is the likely continued increase in bioavailability, as droplets or micelles, as with almost all emulsions of active ingredients, tend to become smaller as surface area increases. However, there may also be additional, less predictable advantages, such as the antibacterial and / or antimicrobial properties of finer cannabinoid emulsions, particularly with respect to Gram-negative bacteria.

[0013] Despite the consensus that stable cannabinoid picoemulsions are beneficial and worth pursuing, no one has succeeded in developing a method for producing such emulsions prior to this disclosure, because the production of emulsions having droplets or micelles in the picometer range involves overcoming several difficult technical challenges.

[0014] One such technical challenge in developing finer emulsions concerns the properties of their constituent components. Many conventional emulsions require a combination of one or more cannabinoid oils and surfactants; however, most cannabinoid oils also contain a variety of compounds other than the cannabinoid oil itself. These additional compounds range from natural phytochemicals such as various terpenes and flavonoids to residual solvent residues from extraction and / or other generally foreign impurities. Many of these additional compounds interfere with the intended bonding of the cannabinoid oil and surfactant, which can directly or indirectly affect the stability and size of the droplets or micelles of the resulting emulsion.

[0015] Such interference unnecessarily complicates the production of stable picoemulsions of cannabinoid oils, and thus the challenge of producing finer cannabinoid oil emulsions can be partially mitigated by simply initiating the process with higher purity ingredients. Given the clear and significant therapeutic benefits of developing stable cannabinoid picoemulsions, there is a need to address this and other technical challenges in producing finer cannabinoid emulsions.

[0016] This disclosure distinguishes itself from the prior art by providing previously unknown advantages, as described in the summary below. [Overview of the Initiative] [Problems that the invention aims to solve]

[0017] Summary of this disclosure This disclosure describes a novel process for generating sterile, injectable cannabinoid picoemulsions characterized by increased bioavailability and antibiotic properties for use in treating a variety of medical conditions. [Means for solving the problem]

[0018] The sterile and injectable cannabinoid picoemulsions resulting from this novel process are characterized by emulsion droplets or micelles ranging in size from approximately 4900 picometers to approximately 850 picometers. In one embodiment, the emulsion droplets or micelles range in size from approximately 4000 picometers to approximately 850 picometers. These picoemulsions offer significantly improved bioavailability compared to conventional cannabinoid nanoemulsions and exhibit potent antimicrobial properties, particularly against Gram-negative bacteria known to be resistant to conventional antibiotics.

[0019] Previous efforts in the pharmaceutical industry to develop cannabinoid emulsions were able to achieve emulsion droplets with a dispersed phase as small as about 5 nanometers, but generating a stable cannabinoid emulsion with droplets in the picometer range has proven to be an insurmountable challenge due to several technical hurdles. The novel process of the present disclosure includes several innovations that together overcome these previous intractable problems. Such innovations include the use of a cannabinoid isolate having a purity of about 99% rather than a full-spectrum cannabinoid oil, and the intentional supersaturation of about 5% of a surfactant having a hydrophilic-lipophilic balance (HLB) value of about 15 (where polysorbate 80 is the preferred surfactant). In one embodiment, the HLB is 15, while in other embodiments, the HLB falls within the range of about 14.9 to 15.1.

[0020] Surfactants play a role in emulsion chemistry by reducing the interfacial tension between two immiscible fluids, such as water and oil. Due to the unique structure of surfactants, which feature both hydrophobic and hydrophilic ends, the molecules are able to surround and bind to the droplets of the dispersed phase (in this case, oil), while at the opposite end, bind simultaneously to the continuous phase (in this case, deionized water). This dual interaction incorporates droplets of the originally immiscible fluids into the continuous phase, forming something that appears to be a homogeneous fluid at the macro level.

[0021] A key property of surfactants is the strength with which their hydrophilic (water-attracting) and lipophilic (oil-attracting) ends attract molecules with which they have an affinity. Surfactants are classified by their relative hydrophilic-hydrophobic affinity by a dimensionless number on a scale of 0 to 20 called the hydrophilic-lipophilic balance value or HLB. The processes and products of the present disclosure require a surfactant having an HLB value of about 15, for example, polysorbate 80. In another embodiment, while the processes and products of the present disclosure require a surfactant having an HLB value of 15, in other embodiments, surfactants having an HLB of about 14.9 to about 15.1 may be used. HLB values ​​within this range exhibit strong hydrophilic properties that are highly suitable for oil-in-water emulsions (as opposed to water-in-oil emulsions). The strength of the hydrophilic properties of surfactants having an HLB of about 15 ensures stability by preventing the separation of the oil and water phases over time.

[0022] Stability is particularly important when attempting to achieve very fine dispersions, such as picoemulsions, because if an emulsion becomes unstable, micelles tend to recombine to form larger ones, which occurs due to their natural tendency to achieve lower thermodynamic energy states. This process is called the Oswalting effect. The Oswalting effect occurs more broadly when there is insufficient bonding strength to remain attached to either the dispersed phase or the continuous phase, or both. This can also occur when there is an excess amount of impurities that interfere with the bonding of the surfactant and / or an insufficient amount of surfactant to produce a complete monolayer coating over the entire outer surface of each droplet in order to form a complete micelle. This novel process mitigates the Oswalting effect by ensuring that the initial mixture of components is properly saturated with the surfactant and that all components are approximately 99% pure cannabinoid isolates.

[0023] The process starts with the use of a cannabinoid isolate that is at least about 99% pure, or otherwise described as having impurities of about 10,000 ppm or less, which is significantly higher than the purity of cannabinoid oils used in conventional methods. Typical cannabinoid oils, sometimes referred to as full-spectrum cannabinoid oils, often contain a variety of impurities including terpenes, flavonoids, solvent residues from extraction, and, among other things, both naturally occurring and adventitious substances that can interfere with the binding between the cannabinoid oil and the surfactant, complicating the formation of stable micelles as previously discussed. By starting with a very pure cannabinoid isolate rather than a cannabinoid oil, these potential problems can be substantially reduced.

[0024] Cannabinoid isolates may be isolates selected from a wide range of cannabinoid oils, or isolates derived from a combination of multiple cannabinoid oils. The following is a non-exclusive list of cannabinoid oils from which cannabinoid oil isolates may be derived: cannabichromene (CBC), cannabichromeneic acid (CBCA), cannabiclomevalin (CBCV), cannabiclomevalic acid (CBCVA), cannabicyclool (CBL), cannabicycloalic acid (CBLA), cannabicyclovalin (CBLV), cannabidiol (CBD), cannabidiol monomethyl ether (CBDM), cannabidiolic acid (CBDA), cannabidiolcol (CBD-C1), cannabidivarin (CBDV), cannabidivaric acid (CBDVA), cannabiersoic acid B (CBEA-B), cannabiersoin (CBE), cannabiersoic acid A ( CBEA-A), Cannabigerol (CBG), Cannabigerol Monomethyl Ether (CBGM), Cannabigerol Acid (CBGA), Cannabigerol Acid Monomethyl Ether (CBGAM), Cannabigerovaline (CBGV), Cannabigerovalic Acid (CBGVA), Cannabinodiol (CBND), Cannabinodivaline (CBVD), Cannabinol (CBN), Cannabinol Methyl Ether (CBNM), Cannabinol-C2 (CBN-C2), Cannabinol-C4 (CBN-C4), Cannabinol Acid (CBNA), Cannabiol Cool (CBN-C1), Cannabivarin (CBV), 10-Ethoxy-9-Hydroxy-Delta-6a-Tetrahydrocannabinol, 8,9-Dihydroxy-delta-6a-tetrahydrocannabinol, cannabitriol (CBT), cannabitriol valine (CBTV), delta-8-tetrahydrocannabinol (Δ8-THC), delta-8-tetrahydrocannabinolic acid (Δ8-THCA), delta-9-tetrahydrocannabinol (THC), delta-9-tetrahydrocannabinol-C4 (THC-C4), delta-9-tetrahydrocannabinolic acid A (THCA-A), delta-9-tetrahydrocannabinolic acid B (THCA-B), delta-9-tetrahydrocannabinolic acid-C4 (THCA-C4), delta-9-tetrahydrocannabiolchol (THC -C1), delta-9-tetrahydrocannabiolcholic acid (THCA-C1), delta-9-tetrahydrocannabivarin (THCV), delta-9-tetrahydrocannabivaric acid (THCVA), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), cannabichromanone (CBCF), cannabifuran (CBF), cannabiglendol, cannabilipsol (CBR), cannabicitran (CBT), dehydrocannabifuran (DCBF), delta-9-cis-tetrahydrocannabinol (cis-THC), trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC), and OH-iso-HHCV.

[0025] Another factor in ensuring micelle stability within the picometer range is the introduction of a sufficient amount of surfactant. The precise theoretical amount of surfactant required can first be calculated by determining the theoretical total surface area of ​​such an amount that is intended to be emulsified when the desired amount of cannabinoid isolate is divided into spherical droplets of target size. This calculation can be performed using the following equation:

number

[0026] Next, the amount of surfactant required to form a single monolayer of surfactant coating on all of the theoretical total surface area of the spherical oil droplets is calculated by dividing the previously calculated total surface area (A 油 ) by the surface coverage area (A s ) of a single molecule of the selected surfactant (the surface coverage area of a single molecule of the selected surfactant is typically found in the chemical literature). The calculation can be performed with this equation:

Equation

[0027] Next, the previously calculated total number (N 界面活性剤 ) of surfactant molecules required to form a single monolayer over all of the total surface area of the spherical oil droplets can then be converted to a more meaningful number by dividing it by Avogadro's number and multiplying it by the molar mass of the selected surfactant using the following equation:

Equation

[0028] The result of this calculation provides the theoretical minimum amount of surfactant required to provide a single monolayer of surfactant coating, assuming that the droplets of the dispersed phase are of theoretical size in terms of surfactant mass; however, if the actual droplets are smaller than the theoretical size, then the total surface area of ​​the droplets may be nominally larger. To ensure that sufficient surfactant is available, the calculated mass of surfactant should be increased by approximately 5% to intentionally supersaturate the dispersed phase. Intentional supersaturation ensures the stability required to achieve and maintain a stable cannabinoid picoemulsion.

[0029] Once the desired amount of cannabinoid isolate and the corresponding amount of surfactant are calculated, the two components are mixed with deionized water, heated to a temperature of about 140 to 200 degrees Fahrenheit, and stirred or otherwise mechanically agitated to achieve maximum pre-sonication homogenization. In another embodiment, the two components are mixed with deionized water and heated to a temperature within about 10 degrees of the boiling point of the newly formed mixture.

[0030] After preheating and thorough stirring, the pre-sonication mixture is subjected to ultrasonic energy at a frequency of approximately 60 Hz to approximately 80 Hz with sufficient energy to generate the shear force necessary to break down the dispersed phase droplets into smaller droplets. This sonication process should be continued until the micelles reach a size of approximately 4900–850 picometers. Since emulsions in the picometer range should appear transparent, the micelle size distribution should show a consistent distribution; this is confirmed via one of several techniques, such as using dynamic light scattering (DLS); however, there may be extremely small spikes indicating the presence of any residual impurities. Other techniques that can be used to confirm that a cannabinoid picoemulsion with micelles in the desired size range has been achieved are small-angle X-ray scattering (SAXS) or nuclear magnetic resonance (NMR) spectroscopy.

[0031] To ensure sterility, the resulting emulsion is passed through a 0.1-micron mechanical filter. This filtration process is designed to remove any potential bacterial contamination, but is also effective in ensuring that larger inorganic particulate impurities do not degrade the emulsion.

[0032] A key advantage of this picoemulsion over existing conventional cannabinoid nanoemulsions is its dramatically increased bioavailability, which is particularly important for medical applications where the efficiency of drug delivery can significantly impact therapeutic outcomes. Smaller micelles allow for faster and more efficient absorption into the bloodstream, resulting in quicker onset of action and more precise drug delivery.

[0033] However, as mentioned above, in addition to improved bioavailability, picoemulsions exhibit significant antimicrobial properties, particularly against Gram-negative bacterial infections in both animals and humans. Gram-negative bacteria pose a significant challenge in the medical field due to their robust resistance to conventional antibiotics. These bacteria possess an outer membrane that is particularly effective in preventing the entry of harmful substances, including many antibiotics, desaturates, and other antimicrobial agents. This resistance is primarily due to the structure of their cell walls, which include a thick peptidoglycan layer sandwiched between the inner and outer cytoplasmic membranes.

[0034] The effectiveness of novel picoemulsions against Gram-negative bacteria is due to the extremely small size of the micelles, which can pass through the outer membrane of the bacteria via the porinous sites of the Gram-negative bacteria, which are tiny gateways through which Gram-negative bacteria transport molecules such as nutrients and metabolites across their outer membranes. Bacterial porinous sites are typically in the range of 1000–2000 picometers in size, which is large enough for many of the micelles of the picoemulsions produced by the procedure of this disclosure to penetrate; thereby bypassing the protective outer membrane of the bacteria.

[0035] Furthermore, in many cases where micelles reach the picometer size range, their shape is not spherical as assumed in theoretical calculations. Due to the binding force of the surfactant and other parameters, such as the shape of the dispersed phase molecule, micelles in the picometer range often take on a very elongated, rod-like configuration. Such a configuration may further allow larger micelles to penetrate bacterial porin sites if their thin dimensions are properly aligned with the porin site.

[0036] When micelles enter bacteria, the binding of surfactants to the dispersed phase is disrupted. Whether this disruption is due to the bacteria attempting to metabolize the micelles or some other mechanical or chemical influence, the stability of the micelles tends to decrease internally, which allows the Oswalding effect to be initiated. Micelles combine and grow, and eventually the combined size of the micelles physically destroys the cell membrane of the Gram-negative bacteria, leading to their death.

[0037] The significance of this finding cannot be overstated. Gram-negative bacteria are often multidrug-resistant (MOR) or broadly drug-resistant (XOR), which are the main cause of serious and difficult-to-treat infections that can be fatal. The ability of cannabinoid picoemulsions to effectively combat these bacteria offers a promising new therapeutic approach that could potentially reduce reliance on conventional antibiotics.

[0038] This novel process and the resulting products not only offer significantly improved bioavailability, but as mentioned earlier, the benefits extend beyond the realm of bioavailability, encompassing the rapidly growing field of antimicrobial agents, with cannabis picoemulsions emerging as a powerful weapon against antibiotic-resistant pathogens. Their effectiveness against Gram-negative bacteria, a group notorious for their resistance to conventional antibiotics, is particularly noteworthy. Leveraging the inherent antibacterial properties of cannabis-derived compounds, whose applications have been limited as described above, picoemulsions now offer a multifaceted approach to combating Gram-negative bacterial infections, thereby improving both patient and public health outcomes overall.

[0039] Therefore, the need to go beyond the limitations of nanoemulsion technology is highlighted by the potential benefits offered by picoemulsions, ranging from improved bioavailability to enhanced antimicrobial efficacy. By overcoming the inherent technical hurdles of particle size reduction and impurity mitigation, researchers are poised to unlock the full therapeutic potential of cannabis-derived compounds, thereby ushering in a new era in medical science.

[0040] This disclosure teaches the advantages of configurations and uses that produce the purposes described below:

[0041] The primary purpose inherent in the above disclosure is to provide a process for producing sterile and injectable cannabinoid picoemulsions;

[0042] Another object of the above disclosure is to provide a process for generating cannabinoid picoemulsions with higher bioavailability;

[0043] A further object of the above disclosure is to provide a process for producing cannabinoid picoemulsions having antibiotic properties;

[0044] A further object of the above disclosure is to provide cannabinoid picoemulsion products resulting from the disclosed process;

[0045] A further objective is to provide cannabinoid picoemulsions for use as pharmaceuticals for the treatment of medical conditions and / or for use in the preparation of pharmaceuticals;

[0046] A further objective is to provide cannabinoid picoemulsions for use as pharmaceuticals for the treatment of Gram-negative bacterial infections and / or for use in the preparation of pharmaceuticals;

[0047] Other features and advantages of this disclosure will become apparent, for example, from the following more detailed description, which will be interpreted in conjunction with the accompanying drawings illustrating the principles and characteristics of the processes described herein.

[0048] A brief explanation of some of the figures in the drawing. The accompanying drawings illustrate various exemplary embodiments and are part of this specification: the embodiments shown are presented for illustrative purposes only and not for limiting purposes. The elements shown are designated by numbers. Where designated, the elements are identified by the same numbers throughout. The accompanying drawings show at least one embodiment of the best mode of this disclosure. [Brief explanation of the drawing]

[0049] [Figure 1] Figure 1 is a flowchart illustrating the process for generating sterile, injectable cannabinoid picoemulsions characterized by increased bioavailability and antibiotic properties. [Figure 2] Figure 2 is a conceptual diagram illustrating micelles in a cannabis picoemulsion, characterized by droplets of cannabinoid oil that are isolated by the hydrophobic tails of multiple amphiphilic surfactant molecules, while the hydrophilic heads of such molecules are in contact with the surrounding continuous phase. [Figure 3]Figure 3 is a conceptual diagram illustrating a thermodynamically occurring phenomenon called Oswald maturation, in which several smaller micelles in an emulsion combine to form a single, larger, and more energetically desirable micelle. [Figure 4] Figure 4 is a dissected section of a conceptual diagram of a Gram-negative bacterium, characterized by its distinctive cell wall consisting of a thin peptidoglycan layer between the inner and outer cytoplasmic membranes. [Figure 5] Figure 5 is a conceptual cross-section of the characteristic cell wall of Gram-negative bacteria, including the porin region, a feature of the outer cytoplasmic membrane that mediates the diffusion of small hydrophilic molecules. [Figure 6] Figure 6 shows comparative cultures of the Gram-negative bacterium Pseudomonas aeruginosa with and without exposure to the cannabinoid picoemulsion of this disclosure. [Figure 7] Figure 7 shows comparative arrays of Pseudomonas aeruginosa, a Gram-negative bacterium with varying growth densities, exposed to various concentrations of the cannabinoid picoemulsions of this disclosure. [Modes for carrying out the invention]

[0050] Detailed description of exemplary embodiments The above drawings illustrate several exemplary embodiments of the processes and many of the features of the Disclosure in at least one of the preferred best-behavior embodiments which are further defined in detail in the following description. Those skilled in the art can modify and improve upon what is described herein without departing from the spirit and scope of the Disclosure. Therefore, it should be understood that what is described is for illustrative purposes only and should not be construed as a limitation of the scope of the processes or many of the features thereof.

[0051] A novel process for generating sterile, injectable cannabinoid picoemulsions characterized by increased bioavailability and antibiotic properties for use in treating a variety of medical conditions is described in more detail here.

[0052] Figure 1 shows an exemplary embodiment of a flowchart illustrating the basic steps in process 100 of the present disclosure. It begins with combining one or more cannabinoid isolates with a carefully calculated amount of surfactant. The surfactant should have a hydrophilic-lipophilic balance (HLB) value of about 15, preferably polysorbate 80, and deionized water 110. In another embodiment, the HLB is about 14.9 to about 15.1. An HLB value of about 15 exhibits strong hydrophilic properties, which are highly suitable for oil-in-water emulsions (as opposed to water-in-oil emulsions). The pre-sonication mixture is then stirred or otherwise mechanically agitated and heated to 140 to 200 degrees Fahrenheit 120. Once the pre-sonication mixture is heated and thoroughly mixed, it is subjected to ultrasonic energy at frequencies of 60 and 80 Hz. The collision should continue until the dispersed phase forms micelles in the range of 4900 to 850 picometers in diameter,130 and finally the resulting picoemulsion is passed through a 0.1 micron mechanical filter to sterilize the emulsion and remove any large impurities.140

[0053] Figure 2 is a conceptual diagram 200 of droplets of a dispersed phase (cannabinoid isolate) 210, sequestered by multiple surfactant molecules 220, each characterized by a hydrophilic head 240 and a lipophilic tail 230. Each lipophilic tail 230 binds to the cannabinoid isolate 210, and each hydrophilic bead 240 binds to the continuous phase (deionized water); thereby reducing the interfacial tension between the dispersed phase and the continuous phase.

[0054] Figure 3 is a conceptual diagram of the Oswalting effect, in which the smallest droplet size of the dispersed phase (possibly picometer size) 200 tends to combine with slightly larger droplets 250, contributing to its growing size, which in turn tends to combine with even larger droplets 260 and even larger droplets 270. This phenomenon arises from the thermodynamic force of surface tension and the fact that larger droplets are in a lower energy state. To produce a stable picoemulsion, this tendency must be prevented, which emphasizes the proper selection of a suitable surfactant and the use of a sufficient amount of such a surfactant.

[0055] Figure 4 is a perspective concept illustrating an exemplary Gram-negative bacterium 300 having a dissected section 310 illustrating a complex multilayer cell wall including a peptidoglycan cell wall 330 between two inner and outer cytoplasmic membranes 320, 340. It is this complex structural barrier that makes Gram-negative bacteria 300 resistant to many conventional antibiotics and makes infections with Gram-negative bacteria 300 particularly problematic.

[0056] Figure 5 is a conceptual perspective view of a cross-section of the cell wall of a Gram-negative bacterium 400. This figure illustrates a peptidoglycan layer 330 flanked by both the outer and inner cytoplasmic membranes 320, containing phospholipids 410 and, most importantly for this disclosure, porinous moieties 420 that control molecular uptake by the Gram-negative bacterium. Through the porinous moieties 420, picometer-sized cannabinoid micelles 200 can acquire invasion by passing through the protective outer layer, potentially leading to bacterial death. In the figure, picometer-sized cannabinoid micelles 200 are shown as spherical. It is important to note that when cannabinoid micelles 200 reach such small sizes, there their shape is determined by the various binding forces of surfactants that cause the micelles to take on an elongated shape.

[0057] Figure 6 shows comparative cultures of the Gram-negative bacterium Pseudomonas aeruginosa. The top two images are photographs of the bottom of Petri dish 500, which identified the starting conditions, while the bottom two images show the obtained bacterial growth. The Petri dish 500 on the left was exposed to the cannabinoid picoemulsion of this disclosure, while the Petri dish 500 on the right was not. It is visually clear that bacterial growth 510 was significantly inhibited by the cannabinoid picoemulsion.

[0058] Figure 7 shows a comparative array of Pseudomonas aeruginosa, a Gram-negative bacterium, at various growth densities exposed to various concentrations of the cannabinoid picoemulsion of this disclosure. In the array, the concentration of the cannabinoid picoemulsion increases along the x-axis, and the bacterial density increases along the y-axis. The presence of bacteria is indicated by light pink, and the absence of bacteria is indicated by dark purple. It is visually clear that bacterial survival decreases as the density of the cannabinoid picoemulsion increases.

[0059] The embodiments described in detail above are considered novel to the prior art. The terms used herein to describe these embodiments should be understood not only in terms of their generally defined meanings, but also to include structures, substances, or actions beyond the scope of their generally defined meanings by the specific definitions herein. Therefore, where an element may be understood in relation to this specification as having multiple meanings, its use should be understood as encompassing all possible meanings supported by the specification and by the terms describing the element.

[0060] The definitions of terms or elements in the drawings as described herein include not only combinations of elements as literally shown, but also all similar structures, materials or actions that perform substantially the same function in substantially the same manner to obtain substantially the same result. In this sense, it is intended that any one of the elements described and its various embodiments may be substituted with two or more elements, or that a single element may be substituted with two or more elements in a claim.

[0061] Any changes from the claimed subject matter, whether currently known or later devised and seen by those skilled in the art, are expressly construed as equivalents within the intended scope and various embodiments thereof. Thus, any substitutions, whether currently known or later known to those skilled in the art, are defined as being within the scope of the defined elements. Therefore, this disclosure is understood to include those specifically described and stated above, those conceptually equivalent, those obviously substituted, and those also incorporating essential ideas.

[0062] The scope of this statement should be interpreted only in conjunction with the attached claims, where it becomes clear that each named inventor considers the claimed subject matter to be patentable.

Claims

1. A process for producing a cannabinoid picoemulsion, wherein the process is: (a) A step of mixing deionized water, cannabinoid isolate, and surfactant to form a pre-sonication mixture; (b) A step of mechanically agitating the pre-ultrasonic mixture and heating it to the optimal ultrasonic temperature to promote homogenization; (c) A step of subjecting the pre-sonication mixture to ultrasonic energy to produce a cannabis picoemulsion containing micelles in the size range of approximately 850 to approximately 4900 picometers; (d) The process of passing the cannabis picoemulsion through a mechanical filter of approximately 0.1 micrometers for sterilization. Methods that include...

2. The process according to claim 1, wherein the surfactant is a surfactant having a hydrophilic-lipophilic balance (HLB) value of about 15.

3. The process according to claim 1, wherein the amount of surfactant is calculated by calculating the total surface area of ​​the amount of cannabinoid isolate that is intended to be emulsified when the amount of cannabinoid isolate is divided into spherical objects of equivalent size up to a desired emulsion droplet size, then calculating the amount of surfactant required to cover the total surface area, and then increasing the amount of surfactant by about 5%.

4. The process according to claim 1, wherein the surfactant is polysorbate 80.

5. The process according to claim 1, wherein the optimal ultrasonic treatment temperature is approximately 140 to approximately 200 degrees Fahrenheit.

6. The process according to claim 1, wherein the optimal ultrasonic treatment temperature is about 10 degrees lower than the boiling point of the mixture before ultrasonic treatment.

7. The process according to claim 1, wherein the optimal frequency of the ultrasonic energy is an ultrasonic energy with a frequency of approximately 60 Hz or higher.

8. The process according to claim 1, wherein the optimal frequency of the ultrasonic energy is an ultrasonic energy with a frequency of approximately 60 Hz to approximately 80 Hz.

9. The aforementioned cannabinoid isolates are cannabichromene (CBC), cannabichromeneic acid (CBCA), cannabiclomevalin (CBCV), cannabiclomevalic acid (CBVA), cannabicyclol (CBL), cannabicycloalic acid (CBLA), cannabicyclovaline (CBLV), cannabidiol (CBD), cannabidiol monomethyl ether (CBDM), cannabidiolic acid (CBDA), cannabidiolcol (CBD-C1), cannabidivaline (CBDV), cannabidivaric acid (CBDVA), cannabiersoic acid B (CBEA-B), cannabiersoin (CBE), cannabiersoic acid A (CBEA-A), and cannabigerol. Cannabinol (CBG), Cannabigerol Monomethyl Ether (CBGM), Cannabigerol Acid (CBGA), Cannabigerol Acid Monomethyl Ether (CBGAAM), Cannabigerovaline (CBGV), Cannabigerovalic Acid (CBGVA), Cannabinodiol (CBND), Cannabinodivaline (CBVD), Cannabinol (CBN), Cannabinol Methyl Ether (CBNM), Cannabinol-C2 (CBN-C2), Cannabinol-C4 (CBN-C4), Cannabinol Acid (CBNA), Cannabiol Cool (CBN-C1), Cannabivarin (CBV), 10-Ethoxy-9-Hydroxy-Delta-6a-Tetrahydrocannabinol, 8,9-Dihydroxy-delta-6a-tetrahydrocannabinol, cannabitriol (CBT), cannabitriol valine (CBTV), delta-8-tetrahydrocannabinol (Δ8-THC), delta-8-tetrahydrocannabinolic acid (Δ8-THCA), delta-9-tetrahydrocannabinol (THC), delta-9-tetrahydrocannabinol-C4 (THC-C4), delta-9-tetrahydrocannabinolic acid A (THCA-A), delta-9-tetrahydrocannabinolic acid B (THCA-B), delta-9-tetrahydrocannabinolic acid C4 (THCA-C4), delta-9-tetrahydrocannabiolcholic acid (THC-C1), delta-9-tetrahydrocannabiolcholic acid (THCA- The cannabinoid picoemulsion according to claim 1, which is a cannabinoid picoemulsion comprising about 99 percent pure isolate of one or more cannabinoids selected from the group consisting of C1), delta-9-tetrahydrocannabivarin (THCV), delta-9-tetrahydrocannabivaric acid (THVA), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), cannabichromanone (CBCF), cannabifuran (CBF), cannabiglendol, cannabilipsol (CBR), cannabicitran (CBT), dehydrocannabifuran (DCBF), delta-9-cis-tetrahydrocannabinol (cis-THC), trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC), and OH-iso-HHCV.

10. A cannabinoid picoemulsion formed by the process described in claim 1.

11. A cannabinoid picoemulsion formed by the process described in claim 2.

12. A cannabinoid picoemulsion formed by the process described in claim 3.

13. A cannabinoid picoemulsion formed by the process described in claim 4.

14. A cannabinoid picoemulsion formed by the process described in claim 5.

15. A cannabinoid picoemulsion formed by the process described in claim 6.

16. A cannabinoid picoemulsion formed by the process described in claim 7.

17. A cannabinoid picoemulsion formed by the process described in claim 8.

18. A cannabinoid picoemulsion formed by the process described in claim 9.

19. A method for treating a Gram-negative infection in a human or animal by introducing the cannabinoid picoemulsion described in claim 10 into the bloodstream of the human or animal.

20. A method for treating a Gram-negative infection in a human or animal by introducing the cannabinoid picoemulsion described in claim 11 into the bloodstream of the human or animal.

21. A method for treating a Gram-negative infection in a human or animal by introducing the cannabinoid picoemulsion described in claim 12 into the bloodstream of the human or animal.

22. A method for treating a Gram-negative infection in a human or animal by introducing the cannabinoid picoemulsion described in claim 13 into the bloodstream of the human or animal.

23. A method for treating a Gram-negative infection in a human or animal by introducing the cannabinoid picoemulsion described in claim 14 into the bloodstream of the human or animal.

24. A method for treating a Gram-negative infection in a human or animal by introducing the cannabinoid picoemulsion described in claim 15 into the bloodstream of the human or animal.

25. A method for treating a Gram-negative infection in a human or animal by introducing the cannabinoid picoemulsion described in claim 16 into the bloodstream of the human or animal.

26. A method for treating a Gram-negative infection in a human or animal by introducing the cannabinoid picoemulsion described in claim 17 into the bloodstream of the human or animal.

27. A method for treating a Gram-negative infection in a human or animal by introducing the cannabinoid picoemulsion described in claim 18 into the bloodstream of the human or animal.

28. Cannabinoid isolate dispersion component; Surfactant components; Aqueous continuous phase; A cannabinoid picoemulsion comprising the surfactant having a hydrophilic-lipophilic balance (HLB) value of about 15; The surfactant and the cannabinoid form a cannabinoid picoemulsion in which micelles have a size of approximately 850 picometers to approximately 4900 picometers.

29. The cannabinoid picoemulsion according to claim 28, wherein the surfactant is polysorbate 80.

30. The cannabinoid isolate dispersion component is cannabichromene (CBC), cannabichromeneic acid (CBCA), cannabiclomevalin (CBCV), cannabiclomevalic acid (CBCVA), cannabicyclol (CBL), cannabicycloalic acid (CBLA), cannabicyclovaline (CBLV), cannabidiol (CBD), cannabidiol monomethyl ether (CBDM), cannabidiolic acid (CBDA), cannabidiolcol (CBD-C1), cannabidivaline (CBDV), cannabidivaric acid (CBDVA), cannabiersoic acid B (CBEA-B), cannabiersoin (CBE), cannabiersoic acid A (CBEA-A), cannabige Cannabivalol (CBG), Cannabigerol monomethyl ether (CBGM), Cannabigerol acid (CBGA), Cannabigerol acid monomethyl ether (CBGAM), Cannabigerovaline (CBGV), Cannabigerovalic acid (CBGVA), Cannabinodiol (CBND), Cannabinodivaline (CBVD), Cannabinol (CBN), Cannabinol methyl ether (CBNM), Cannabinol-C2 (CBN-C2), Cannabinol-C4 (CBN-C4), Cannabinol acid (CBNA), Cannabiol cool (CBN-C1), Cannabivarin (CBV), 10-Ethoxy-9-hydroxy-delta-6a-tetrahydrocannabinol, 8,9-Dihydroxy-delta-6a-tetrahydrocannabinol, cannabitriol (CBT), cannabitriol valine (CBTV), delta-8-tetrahydrocannabinol (Δ8-THC), delta-8-tetrahydrocannabinolic acid (Δ8-THCA), delta-9-tetrahydrocannabinol (THC), delta-9-tetrahydrocannabinol-C4 (THC-C4), delta-9-tetrahydrocannabinolic acid A (THCA-A), delta-9-tetrahydrocannabinolic acid B (THCA-B), delta-9-tetrahydrocannabinolic acid C4 (THCA-C4), delta-9-tetrahydrocannabiolcholic acid (THC-C1), delta-9-tetrahydrocannabiolcholic acid (THCA- The cannabinoid picoemulsion according to claim 28, which is a cannabinoid picoemulsion comprising about 99 percent pure isolate of one or more cannabinoids selected from the group consisting of C1), delta-9-tetrahydrocannabivarin (THCV), delta-9-tetrahydrocannabivaric acid (THVA), 10-oxo-delta-6a-tetrahydrocannabinol (OTHC), cannabichromanone (CBCF), cannabifuran (CBF), cannabiglendol, cannabilipsol (CBR), cannabicitran (CBT), dehydrocannabifuran (DCBF), delta-9-cis-tetrahydrocannabinol (cis-THC), trihydroxy-delta-9-tetrahydrocannabinol (triOH-THC), and OH-iso-HHCV.

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