INDIGENOUS AND IMPROVED FUNGALLY FERMENTED CBD, CBG AND RELATED CANNABINOID ORAL DOSAGE FORMS

Abstract

The present invention is a novel and enhanced co-fermentation product of hemp and Cannabis, in which 1 part shredded or divided hemp stems, leaves and flowers are admixed into a slurry with 2 parts water and the slurry is sterilized prior to inoculation with solid or liquid mycelium culture. After inoculation, fermentation takes place at 66-70 degrees F. for 14-28 days, followed by drying of the fermented admixture at 110-165 degrees F. for 24-48 hours, prior to co-minuting or powdering the dried end product for incorporation in oral dosage forms such as pressed tablets, manufactured capsules or powder or as an ingredient in functional foods. By following these method steps including the initial creation of the 2:1 aqueous:hemp slurry, both hemp and mushroom component conversions occur to an unexpected degree.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application claims priority to U.S. Provisional Patent Application 62/912,930 filed 9 Oct. 2019, which is incorporated herein by reference.

FIELD OF THE INVENTION

The invention pertains to improved CBD and CBG (and related cannabinoids) delivery methods and dosage forms, namely, containing fermented hemp using a medicinal fungi culture.

BACKGROUND OF THE INVENTION

Cannabis indica, Cannabis sativa and Cannabis ruderalis are well established both as herbs and pharmaceuticals throughout history. More elusively but still historically, fungiculture is also a well established technology in the culinary and pharmaceutical arts. Both Cannabis and mushrooms enjoy a deep mystique in addition to their long histories, and both are also understood to embody—in the wrong hands—an element of danger as well. A recognized leader (if not “Father”) of modern Cannabis chemistry is Raphael Mechoulam, who spoke in April of 2019 to the ICBC International Cannabis Business Conference. In recounting his particular interest and history in studying Cannabis, he began his keynote address remembering that “In ancient Syria they used Cannabis for essentially all the things that people use Cannabis for today” and that “Cannabis was then used over the next couple of thousand years.” With Cannabis indica, Cannabis sativa and Cannabis ruderalis having thus had a long tenure as known active agents, The History Channel recently devoted an entire special issue magazine to the story of Cannabis throughout the world, indicating (without limitation) that Queen Victoria's physician probably prescribed versions of Cannabis medicaments for pain management, and so forth. Mechoulam corroborated this connection of Cannabis to royalty in his keynote, explaining that “Dr Russell Reynolds, who was the physician of Queen Victoria in England, used to import [Cannabis] from India (European Cannabis was not good enough for him) because she suffered from migraines.” Whereas there are no specific historic references to administration of Cannabis to the Queen at that time, Mechoulam points out that “it was obvious who it was for because she was the only patient that he had.” With a fast forward to the 2018 “Farm Bill” (Agricultural Improvements Act of 2018, 115th Congress, 2017-2018) the United States law now acknowledges that industrial hemp, a Cannabis plant with less than 0.3% tetrahydrocannabinol (THC), is not “marijuana” for the purpose of the Controlled Substances Act. This means that hemp-derived cannabidiol (CBD) and related cannabinoids such as cannabigerol (CBG) and cannabichromene (CBC) can now ostensibly be produced and sold as consumable agricultural products in the United States, whereas prior to the 2018 Farm Bill hemp could be grown and used in the U.S. only for research purposes under individual states' pilot programs and in certain categories such as clothing, industrial materials and products made from the plant's stalks or seeds. In other words, 2018 was a watershed year for health care providers, consumer packaged goods companies and the pharmaceutical industry, creating for the first time a legal (or nascently legal) domestic source of cannabinoids (initially focused on CBD)—from U.S.-grown hemp.

Thus, in the right hands, both Cannabis and mushrooms represent virtual pharmaceutical factories of important wellness and nutraceutical nutrients and compounds. Now that more-retail-cash-registers-than-not offer various CBD or other cannabinoid products for sale—sometimes many edible offerings such as individually wrapped chocolates containing cannabinoids along with topicals, oils and capsules—an interesting question remains—what magic might Cannabis and mushrooms make together?

As with any newly popular ingredient, there are opportunities for high quality products as well as those of lesser value and benefit. There are currently reliable, responsible hemp growers and manufacturers and, presumably, also formulators and peddlers reminiscent of the “snake oil salesmen” of the American 1800s. Chinese snake oil was a legitimate anti-inflammatory substance for decades if not centuries, prior to fake iterations that appeared later in the U.S. The original Chinese snake oil was made from the oil of the Chinese water snake, which was rich in the omega-3-fatty acids that are known to reduce inflammation. This “snake oil” in its original form was indeed effective as a topical medicament to treat arthritis and bursitis and, eventually, the putative product made its way to the United States—if not the omega-3-rich water snake itself, or its curative extract. The point here is that with hemp-derived cannabinoids, as with anything else, responsible sourcing, processing and quality control in manufacturing are the bedrock of any superior pharmaceutically active agent. The pressures of manufacturing in light of a population clamoring for cannabinoids are particularly intense, in world in which side-effect—or addiction—minimized pain management is still an elusive if (not scandal-laden) goal.

It is interesting that, as a general practice regarding naturally-occurring active agents—and particularly those of herbal sources—there seems to be a knee-jerk compulsion to extract and synthesize the active agent or chemical compound from its botanical (herb or spice) source. Extracting and synthesizing digitalis from foxglove, a natural herb, is of course a prime example in pharmaceutical history. In theory there is nothing wrong with extraction processes—although in practice there can indeed be negative implications to extraction, in particular as to the molecule(s) to be extracted. Extraction agents such as petroleum or coal-tar derived solvents can create residues or even alter the chemical composition of the sought-after molecule. Worse, beneficial co-factors present in the natural product, in this case an herb, can be separated from the active agent so as to lose the synergy of administration of the whole herb with its known and yet-to-be discovered compounds. Even today, when Cannabis indica, Cannabis sativa and Cannabis ruderalis are on the brink of becoming “health food” [so to speak] instead of “Just Say No!” fodder, the temptation seems to be ubiquitous to extract, isolate and even synthesize key constituents within them, in order to obtain their active compound(s) for further commercialization. The question which the present inventor asked, therefore, was—whether traditional extraction or isolation is the only processing method that can deliver the true benefits of hemp and its constituent cannabinoids, when the use of hemp and mushrooms (fungi) are contemplated together? And, if extraction or isolation is not the best approach, what additional beneficial conversions are possible to enhance the power and constituency of hemp and fungi for functional foods and dietary supplementation?

SUMMARY OF THE INVENTION

The present invention is a novel and enhanced co-fermentation product of hemp and Cannabis, in which one part shredded or divided hemp aerial parts, primarily leaves and flowers, are admixed into a slurry with two parts water, and the slurry thus created is sterilized prior to inoculation with solid mycelium culture. After inoculation, fermentation takes place at 66-70 degrees F. for 14-28 days, followed by drying of the fermented admixture at a constant temperature of 115-165 degrees F. for 24-48 hours, prior to comminuting or powdering the dried fermentation product for incorporation in oral dosage forms such as pressed tablets, manufacture capsules, nutritional powders or in functional foods and beverages. Hemp and mushroom cultures co-fermented in this way creates unique composite nutraceuticals containing properties unattainable in either hemp or mushrooms alone. The inventive method is different from traditional mushroom culture in many ways, including but not limited to the typical solid medium fungiculture of the prior art, which largely or completely separate the mushrooms from their growth media. The present method steps, moreover, contribute to new and unexpectedly improved results as to constituent diversity in the fermentation product. By following the inventive method steps including the initial creation of the 2:1 aqueous:hemp slurry, both hemp and mushroom component conversions occur to an unexpected degree.

DETAILED DESCRIPTION OF THE INVENTION

The present supplement, pharmaceutical and nutraceutical preparation and method for delivering active ingredients, center on a powdered form of a fermented, native or activated unextracted hemp biomass containing cannabinoids including but not limited to cannabidiol (CBD) and cannabigerol (CBG), dietary fiber of a particular ratio, vitamins, minerals, flavonoids, terpenes, fatty acids and amino acids. The powder can be optionally blended with other botanical ingredients and compressed into a tablet form, encapsulated or manufactured into a nutritional powder for administration to or consumption by an animal or human in need of a reliably sourced cannabinoid oral dosage form. Fermentation is conducted with any complex fungi (nutritional or culinary fungi or mushroom mycelial culture) suitable for consumption or oral administration, including but not limited to Ganoderma lucidum, Ganoderma japonicum, Ganoderma applanatum, Ganoderma Tsugae, Lentinula edodes, Grifola frondosus, Tremella fuciformia, Tremella mesenterica, Cordyceps sinensis, Cordyceps Hericium erinaceus, Polyporous umbellatus, Scizophylum commune, Fomes fomentaris, Inonotuus obliquus, Lepiota procera, Auricularia auricula, Tuber melanosporum, Tricholoma matsutake, Hericium coralloides, Trametes versicolor, Phellinus linteus, Poria cocos, Antrodia camphorata, Flammulina velutipes, Pleurotus ostreatus, Pleurotus energyii, or Agaricus blazeii. The co-fermented cultured material is carefully dried and comminuted into a powder prior to inclusion in a dosage form, such as a pressed tablet or manufactured capsule. Such a dosage form containing the inventive powders retains bioactive fungal compounds from the fermentation, alongside cannabinoid and botanical constituents. While the present fermented native or activated hemp biomass is well suited for use alone, it may be admixed with other ingredients, whether active agents or excipients, fillers or comestible ingredients comprising dietary supplements or functional food ingredients. Hemp for the purpose of this patent application is hemp which meets the standards of the 2018 Farm Bill, that is, is a native Cannabis (various species and varieties) which contains no more than 0.3% tetrahydro cannabinol (THC) on a dry weight basis. Activated hemp is hemp that has been heated or treated, with more discussion regarding activation and its consequences' appearing later in this specification. Native hemp is raw, that is, unheated and untreated, hemp. Native or activated hemp which remain unextracted, for the purposes of the present fungal fermentation and further steps, contain interesting naturally occurring co-factors, known and currently unknown, including without limitation other cannabinoids, dietary fiber, fatty acids, amino acids, and flavonoids. These known and unknown co-factors inevitably enhance any or all of delivery, bioavailability and efficacy of the CBD/cannabinoid(s) in vivo.

This invention takes the native or activated hemp starting material and subjects it to sterilization followed by fungal fermentation specifically with mushroom or fungi mycelia, to convert and enhance the constituent molecules and compounds in the hemp to an increasingly diverse and prized spectrum of nutrients and active agents—all while keeping the hemp (or Cannabis) in its unextracted state. A key part of the present invention therefore inheres in the synergy achieved by using unextracted hemp (or Cannabis) as the starting material for a mushroom culture fermentation, and deploying the fermentation product as a further constituent, usually powdered, in a tablet or capsule (or equivalent) ingredient as a CBD/CBG/cannabinoid oral dosage form or in other comestible dietary supplements or functional foods. Careful drying techniques are used after fermentation.

Another key component to the invention is in the engineering of the cannabinoid delivery system, with a beneficial soluble dietary fiber (SDF)/insoluble dietary fiber (IDF) ratio, in the unextracted native or activated hemp itself, of 1:30 SDF/IDF, allowing for effective formulation and delivery of key constituents.

Finally, the invention inheres in part in the unique method for making the fermented hemp, as follows. First a slurry is prepared with the unextracted native or activated hemp (and optionally another botanical) with the hemp-to-water ratio being 1:2. If another botanical is present, it is not counted toward the 1:2 hemp to water ratio. The slurry preferably contains hemp particles smaller in major dimension than 1 cm, which can be prepared by mechanical shearing techniques known in the art. The slurry thus formed is sterilized by heating it at 200-250 degrees F. and optionally increased pressure for 2-4 hours—mushroom culture always takes place in sterilized media and the sterilization step does not form a part of the present inventive method. However, the use of 2 parts water to one part hemp does form part of the inventive method, together with the important post-sterilization steps of fermenting at 66-70 degrees F. for 14-28 days, followed by drying of the fermented admixture at 110-165 degrees F. for 24-48 hours, followed by comminuting or powdering the dried end product for incorporation in oral dosage forms such as pressed tablets, or in functional foods. By following the above described method steps including the initial creation of the 2:1 aqueous: hemp slurry, both hemp and mushroom component conversions occur to an unexpected degree discussed further, below.

As with popular or over-the-counter dosage forms, particularly for active agents known to control pain, dosing is tantamount to safe and effective treatment. When it comes to CBD or CBG, general dosing guidelines suggest that a recommended initial dose is somewhere in the range of 2.5-5 mg, once or twice a day, for an averaged sized human patient, with possible safe and effective dosing of up to 20 mg taken as often as three times per day. Veterinary dosing is generally pro rata by body mass/weight at similar levels. As the cannabinoid industry matures, inevitably further dosing guidelines will become available—but as with all active agents a serious challenge is to prevent inadvertent (or intentional) overdose. One benefit of the present formulations inheres in the retained diluent function of the whole native hemp or activated hemp (or native Cannabis or activated Cannabis), compared to other dosage forms that contain extracts, which retained diluent in turn assures relatively lower dosing in the inventive material per se. In addition to the lower cannabinoid (i.e. CBD, CBG) concentration, along with synergistic co-factors which provides a more balanced, “whole food” effect with less chance of deleterious side effects, the ability of the present fungal fermentation to increase the profile of desirable constituents only enhances the value of the present method and product. In addition, the ratio of soluble dietary fiber (SDF) to insoluble dietary fiber (IDF) will remain similar but not exactly the same as in the starting hemp. This SDF/IDF ratio is slightly higher than 1:30, that is, for every slightly-more-than 1 part of soluble dietary fiber in the Cannabis (native or activated), there is also 30 parts insoluble dietary fiber, and the fungal fermentation process itself is responsible for increasing the digestibility of the dietary fiber fraction of the cannabis in a beneficial way.

If native or activated hemp has, for example, a starting content of 10% CBD, one gram of the hemp starting material will contain about 100 mg CBD. When one cultures one gram hemp with fungus according to the present method, approximately ⅓ of the fermentation product is mushroom mass and ⅔ is Cannabis or Cannabis plus bontanical(s), reducing the CBD (in this case) content to about 67 mg CBD. However, much more goes on during fungal fermentation than merely a dilution of the Cannabis with a co-created mushroom mycelial biomass. Importantly, fungal fermentation of Cannabis uniquely causes conversion of indigestible fiber in the Cannabis into bioactive pharmaceutical or nutritional compounds. This is a fiber conversion such as only a mushroom culture can do!—which conversion in turn has three ramifications. First, when Cannabis is co-fermented with fungi, the conversion of some of the indigestible dietary fiber inherently increases the bioavailability of the botanical, in this case hemp. Second, the mushroom fermentation does not simply convert insoluble dietary fiber in the Cannabis to soluble dietary fiber, but creates a wide panoply of fermentation products of to create a broad spectrum of nutrients and bioactive compounds that were not present in the Cannabis to start with. Also, mushroom culture—particularly according to the present specific method—activates or potentiates biologically active compounds in the Cannabis, and not just the cannabinoids. Again, a wide variety of nutrients and beneficial compounds in the Cannabis are made more bioavailable due to co-fermentation with a mushroom mycelial culture, by a number of mechanisms including but not limited to solubilization, digestion, encapsulation, and derivatization. The present invention does not claim to be the first to harness the power of mushroom culture for bioconversion—but the present technology does represent and new and surprisingly improved method of enhancing this biodiversity with the particular method steps which enhance all these biological processes in ways never before achieved. All this means that, by co-fermenting Cannabis with mushroom mycelial culture, a greater panel of constituent compounds and compositions will result compared to the compounds and compositions present in the original Cannabis, due to the complex and facilitated conversions that occur resulting from the present method steps. Finally, the fungal growth of the present invention inherently produces antibacterial, anti-yeast and anti-viral compounds, and by the use of the present method steps including the drying method, these desirable antimicrobial compounds are retained in the final end product and are then combined with an wide-spectrum of active agents disclosed herein.

It almost goes without saying that organically sourced hemp (Cannabis) is the best choice for the hemp starting material according to the present invention. By using organic hemp or Cannabis, the presence of pesticides or other solvent residues or undesirable adulterants in the hemp is reduced to a beneficial minimum. Not only is the reduction of these extraneous contaminants good in and of itself, but the absence of unwanted residues maximizes the original confluence of the indigenous cannabinoids such as CBD with its synergistic co-factors, known (see list above) or unknown. Of course even though the present invention is limited, as to commercialization, at this writing to hemp under the 2018 Farm Bill, during the life of this patent as the laws may change, the invention will be understood to embrace all Cannabis as can be legally fermented according to this invention.

Fermented hemp using fungal culture according to the present invention is typically dried as described above and co-minuted prior to tabletting, encapsulating or powdering or other end use. Dehydration to a moisture content of below 15%, preferably below 10% and more preferably to 5-6% is important in the creation of the present oral dosage forms, but only at the specified heat. The co-minution may be but need not be to a (small) particle size generally within the range of powders. Generally speaking, fermented hemp particles of at least 100 microns in diameter, up to irregularly shaped particles of up to about 5 mm in their longest dimension, are best for tabletting or encapsulating according to the present invention. Surprisingly, hemp/mushroom particles of this size are beneficially self tabletting without added ingredients and with a minimum of compression energy, that is, not enough pressure to generate significant heat. Avoidance of excessive processing also prevents the generation of unwanted heat that can denature cannabinoids (CBD, CBG) or additional cofactors in the hemp such as terpenes. Having said that, however, the administration of hemp/mushroom co-fermentation product as a powder (that is, in traditional powder particle size distributions smaller than 100 microns) and as predominantly the only oral dosage form constituent as described above—is still within the scope of the present invention.

The primary disclosure of this patent application is directed to dosage forms in which—with few exceptions such as added inert excipients, probiotics, botanicals, vitamins and minerals or adjusted or retained moisture—fermented hemp using a fungal culture is the main ingredient in an oral dosage form. Having said that, the subject fermented hemp (or Cannabis) has all sorts of secondary benefits as additives to other dietary supplements, nutritional dosage forms and functional foods—virtually without limitation.

As disclosed above, hemp (after fungal fermentation) contains total dietary fiber (TDF) having a ratio of slightly more than 1 part SDF to 30 parts IDF (meaning a resulting ratio of 1 part SDF to 25-29 parts IDF). As compared to much higher SDF-containing botanicals, such as for example oat or wheat bran, a ratio of 1:30 SDF/IDF—and even the reduced SDF/IDF ratio of 1:25-29—is a notably low SDF level than other “high fiber” comestibles. For the purposes of the present invention, this high inclusion of IDF is extremely beneficial to delivery of CBD and other cannabinoids from an oral dosage form—even though the fungal co-fermentation increases the native Cannabis SDF component slightly. The benefits are explained as follows. SDF, upon oral administration, tends to create a sol/gel in the gastrointestinal tract, which in turns tends to retain in solution, i.e. binding or suspension, other molecules in its vicinity such as, in this case, cannabinoids. In other contexts besides cannabinoid administration, SDF is a highly desirable compound, that can even be partially digested by bacteria in the gut, but in the context of a cannabinoid delivery system SDF actually creates an unwanted binding system and subsequent elimination of cannabinoids, rather than a true delivery (release) system from the gut into the blood stream. By contrast, the high IDF inclusion assures the desirable release of the cannabinoid active agent promptly if not instantly in the stomach or upper gastrointestinal tract. The present co-fermentation product of Cannabis and mushrooms, prepared by the present method steps, gives a “best of both worlds” phenomenon, in that a minor fraction of the IDF is metabolized by the mushroom culture creating new and beneficial compounds (fungal metabolites) to enhance, by rebalancing, the SDF fraction slightly, and yet the desirable high IDF ratio is predominantly maintained while at the same time the spectrum of constituents metabolized by the mushrooms from the IDF is broadened in the end fermentation product. As set forth above, the inventor believes that this slight alteration in SDF/IDF ratio amounts, in reality, to an adjusted SDF/IDF ratio of 1:25-29.

Important cannabinoids in hemp are not limited to cannabidiol (CBD). Known significant cannabinoids other than THC include, without limitation, cannabigerol (CBG), cannabidivarin (CBDV), cannabichromene (CBC), cannabinol (CBN) and combinations thereof. Various strains of hemp tend to present different ratios of these cannabinoids and, in due course, the desired ratios will also inevitably be genetically engineered, if not traditionally cross-bred. Whole, unextracted (native or activated) hemp that is fermented with fungal mycelium is thus able to serve as a uniquely effective delivery system for any and all cannabinoids, including any additional beneficial hemp or Cannabis components now known or developed in the future.

The following example is illustrative.

EXAMPLE 1

As a test to illustrate the fiber ratios in native or activated hemp, a quantity of native hemp was subjected to a traditional extraction of cannabinoids (not a part of the invention herein) by moderate crushing and extraction of cannabinoids to create a “hemp pomace” which continued to include cannabinoids therein. The extraction was performed by carbon dioxide solvent extraction. The resulting pomace was carefully air dried at 115 degrees Fahrenheit to prevent denaturing of all compounds and compositions in the pomace. A representative dried pomace prepared according to the above method steps contained 6% moisture. Because only liquid was extracted from the native hemp, the fiber ratios of the resulting dried pomace were representative of the fiber ratios in the starting native hemp (one form of hemp used in the fungal fermentation of the present invention). The fiber ratios of insoluble dietary fiber (IDF) to soluble dietary fiber (SDF) were 1:30 SDF/IDF.

Although the invention has been described with particularity above, the invention is only to be limited insofar as is set forth in the accompanying claims.

Claims

1. A method of co-fermenting one or more species of Cannabis with mycelial culture of one species of mushroom, comprising the steps of:

a) dividing any of aerial parts (leaves or flowers) of one or more Cannabis species into particles having a major dimension of 1 cm or smaller to create a quantity of shredded Cannabis;

b) admixing one part by weight of said shredded Cannabis from step a) with two parts by weight of water to form a slurry;

c) sterilizing said slurry at at least 200 degrees F. for 2-4 hours and allowing the slurry to cool to 66-70 degrees F.;

d) inoculating said slurry with solid mycelium culture;

e) incubating an inoculated slurry formed in step d) at 66-70 degrees F. for 14-28 days to form a mycelial biomass;

f) drying said mycelial biomass at 110-165 degrees F. for 24-48 hours to create a co-fermentation product; and

g) co-minuting said co-fermentation product to an aggregate of particulates.

2. The method of claim 1, wherein said Cannabis is selected from the group consisting of: Cannabis indica, Cannabis sativa and Cannabis ruderalis.

3. The method of claim 1, wherein said Cannabis is hemp as defined by the 2018 Farm Bill.

4. The method of claim 1, wherein said mushroom species is selected from the group consisting of: Ganoderma lucidum, Ganoderma japonicum, Ganoderma applanatum, Ganoderma Tsugae, Lentinula edodes, Grifola frondosus, Tremella fuciformia, Tremella mesenterica, Cordyceps sinensis, Cordyceps militaris, Hericium erinaceus, Polyporous umbellatus, Scizophylum commune, Fomes fomentaris, Inonotuus obliquus, Lepiota procera, Auricularia auricula, Tuber melanosporum, Tricholoma matsutake, Hericium coralloides, Trametes versicolor, Phellinus linteus, Poria cocos, Antrodia camphorata, Flammulina velutipes, Pleurotus ostreatus, Pleurotus energyii, and Agaricus blazeii.

5. The method of claim 1, wherein said particulates further comprise a powder.

6. The method of claim 1, wherein the incubating step e) is conducted at 68 degrees F.

7. A co-fermentation product resulting from the method of claim 1.

8. The product according to claim 7, wherein said co-fermentation product has a SDF/IDF ratio of 1:25-29.

9. The product according to claim 7, wherein said co-fermentation product contains compounds formed by mushroom culture metabolism of insoluble dietary fiber and other nutrients in said Cannabis.

10. The product according to claim 7, wherein at no time after inoculating said slurry are said Cannabis and said mushroom components separated from said co-fermentation product.