Indigenous and Improved Bacterially Fermented CBD, CBG and Related Cannabinoid Oral Dosage Forms

Abstract

The present invention is a cannabidiol (CBD), cannabigerol (CBG) or related cannabinoid oral dosage form including bacterially fermented hemp, typically compounded as a tablet or formulated within a capsule or as an additive to other dietary supplements or functional foods. The dosage forms contain dietary fiber, important to activity as the desired delivery system, having a ratio of one part soluble dietary fiber to 30 parts insoluble dietary fiber, which is an optimal fiber ratio for oral delivery and bioavailability of cannabidiol, cannabigerol and other desirable cannabinoids from either activated or native hemp.

Claims

1. A cannabinoid oral dosage form in unit dosage form, consisting essentially of bacterially fermented hemp, compounded as a tablet or within a capsule, powder or other unit dosage form, having a soluble dietary fiber to insoluble dietary fiber ratio of 1:30, having a maximum cannabinoid dose per unit dosage form of 25 mg, and having viable bacteria therein as a probiotic dietary supplement.

2. The cannabinoid oral dosage form according to claim 1, wherein said bacterially fermented hemp contains cannabinoid acids in chemically stabilized form.

3. A cannabinoid oral dosage form in unit dosage form, consisting essentially of bacterially fermented hemp, compounded as a tablet or within a capsule, powder or other unit dosage form as the predominant or exclusive ingredient and having increased cannabinoid in the amount of 12-300 percent compared to the starting hemp material prior to bacterial fermentation.

4. The oral dosage form of claim 1, wherein each oral dosage form contains less than 10% water as moisture and wherein said cannabinoid is one or more of cannabidiol, cannabigerol, cannabidivarin, cannabichromene, or cannabinol.

5. The oral dosage form of claim 1, wherein said hemp is fermented with one or more bacteria selected from the group consisting of Bacillus subtilis, Bacillus subtilis ssp Natto, Bacillus coagulans, Lactobacillus plantarum, Acetobacter pasteurianus, Acetobacter ghanensis, Komagataeibacter oboediens, and Komagataeibacter saccharivorans prior to compounding.

6. The oral dosage form of claim 1, wherein said dosage form contains no more than 10 mg cannabinoid per unit dosage form.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0009] 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 1-5 mg, once or twice a day, for an averaged sized human patient, with possible ethical dosing of up to 20 mg or more taken as often as three times per day. Veterinary dosing is generally pro rata by body mass/weight at similar levels. As the CBD industry matures, inevitably further dosing guidelines will become availablebut 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 of the whole native hemp or activated hemp, 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 bacterial fermentation to increase the profile of desirable cannabinoids only enhances the value of the present hemp product as a dietary supplement and wellness aid. In addition, the ratio of soluble dietary fiber (SDF) to insoluble dietary fiber (IDF) remains the same as in the starting hemp. This SDF/IDF ratio is 1:30, that is, for every 1 part of soluble dietary fiber in the hemp (native or activated), there is also 30 parts insoluble dietary fiber. This SDF/IDF ratio is discussed further, below.

[0010] 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 bacteria, no matter how the bacterial culture proceeds the bacteriaeven when still viableadd negligible weight to the finished fermented product. In other words, in the fermented hemp end product after careful drying, the presence of the dried probiotic bacteria constitute only 1% or less of the mass of the fermented hemp. Accordingly, 1 g dry weight of hemp, after bacterial fermentation, continues to contain 10% CBD if its starting content was 100% CBD and, after factoring in a 12% to 300% increase in CBD/CBDA or both due to the bacterial action, the cannabinoid dose per gram transitions to 112 mg to 300 mg per gram of the final fermented hemp product. It is therefore easily possible for those skilled in the art to measure, titrate and check products according to the invention to include the desired amount of bacterially fermented hemp into a unit dosage form, to provide unit dosage forms that contain, for example, 1 mg, 3 gm, 5 mg, 10 mg and even 20 mg CBD dosage forms by selecting the appropriate amount of the dried fermented material. Larger serving sizes of tablets or capsules can thus contain up to 20 mg CBD while still having a size that can be easily consumed without difficulty. The ability of hemp with bacterial fermentation to be formulated into oral dosage form capsulesor to be tabletted directly without additivesmeans that creation of dosing per unit is straightforward and well within the skill of the art. The combination itself, of taking hempnative or activatedand fermenting it with bacteria prior to creating one or more dosage forms from the fermentation product, is the gravamen of the present invention.

[0011] As set forth above, the present hemp starting material is fermented with any suitable bacterium, including but not limited to Bacillus subtilis, Bacillus subtilis ssp Natto, Bacillus coagulans, Lactobacillus plantarum. Acetobacter pasteurianus, Acetobacter ghanensis, Komagataeibacter oboediens, or Komagataeibacter saccharivorans, The presence of one or more of these probiotics and their fermentation products (and viable cultures) is the main exception, besides moisture, to the premise that, overall, the dosage form material is predominantly or completely whole hemp. In other words, except for further formulations in functional foods and other products in which the present fermented product can be an ingredient, it is important to recognize the versatilityand even the conformability for tabletting and the likeof just the bacterially fermented hemp that is subsequently gently dried and comminutedwithout need for a lot more processing or formulation as so many other active agents typically do need.

[0012] It almost goes without saying that organically sourced hemp, extracted without hydrocarbon-based or petroleum or coal tar derived solvents, is the best choice for the hemp starting material according to the present invention. By using organic hemp and avoiding noxious extraction solvents, 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.

[0013] Bacterially fermented hemp according to the present invention is typically dried, possibly further activated through decarboxylation and co-minuted prior to tabletting or encapsulating. 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. The co-minution may be but need not be to a (small) particle size generally within the range of powders. Generally speaking, bacterially 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/probiotic 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), terpenes or additional cofactors in the hemp. Having said that, however, the administration of hemp/bacterial probiotic 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 aboveis still within the scope of the present invention.

[0014] The primary disclosure of this patent application is directed to dosage forms in whichwith few exceptions such as added inert excipients, probiotics, botanicals, vitamins and minerals or adjusted or retained moisturebacterially fermented hemp is the main ingredient in an oral dosage form. Having said that, the subject bacterially fermented hemp has all sorts of secondary benefits as additives to other dietary supplements, nutritional dosage forms and functional foodsvirtually without limitation as to any application where probiotics can be added.

[0015] As disclosed above, hemp (prior to bacterial fermentation) contains total dietary fiber (TDF) having a ratio of 1 part SDF to 30 parts IDF. As compared to higher SDF-containing botanicals, such as for example oat bran or bananas, a ratio of 1:30 SDF/IDF is a notably low SDF/IDF ratio and, 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. 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, SDF is a highly desirable nutrient, that can even be partially digested by bacteria in the gut, but in the context of a cannabinoid delivery system SDF actually creates a binding system and subsequent removal from the body for an active agent, rather than a true delivery (release) system into the blood stream. By contrast, the high IDF inclusion assures the desirable release of the active agent promptly if not instantly in the stomach or upper gastrointestinal tract. Given this understanding of how the present oral dosage form works, moreover, it may be seen that the present oral composition, although botanical in initial source, is a highly engineered composition and not merely a product of nature at all. With the present oral dosage forms, the cannabinoid content is reduced (compared to native hemp) and yet the SDF/IDF ratio of 1:30, typical of native hemp, enhances delivery due to its high soluble fiber fraction.

[0016] 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. The ability of whole, unextracted (native or activated) hemp that is bacterially fermented is thus able to serve as a uniquely effective delivery system for any and all cannabinoids and any additional beneficial hemp components present, as to any hemp strain now known or developed in the future.

[0017] A number of interesting and beneficial things happen to hemp when it is subjected to bacterial fermentation. Unlike with fungal fermentation of spent extracted hemp, in which the hemp inevitably has to be sterilized prior to fungiculture, bacterial fermentation provides its own de facto sterilization (by competitive overgrowth dynamics) so that constituents of the hemp that are particularly desirable are not denatured due to excessive heating, when native hemp is the starting material. An example is terpeneswhich are plentiful in non-heat-treated hemp and do not disappear before or during bacterial fermentation. Therefore, bacterial fermentation can be applied to either activated hemp that has gone through a decarboxylated process, typically heat and pressure, or a native hemp that is raw and unheated. When desired, activated and raw/native hemp may be admixed for bacterial fermentation. The action of bacteria also creates metabolites with the substrate such as organic acids (acetic, malic, formic . . . ) which contribute to nutritive and active agent profiles and constituent diversity. Perhaps most important of all, fermentation of hemp with bacterial culture both increases and stabilizes (see Example 2 below) the cannabinoid acids (CBDA, CBGA etc) in the hemp, which is important in preserving the anti-nausea, anti-withdrawal symptom and pain management aspect of cannabinoid acids (un-de-carboxylated) themselves. Of course having all these benefits together with a novel probiotic makes for a much needed, new and useful composition, for administration in unit dosage form.

Example 1

[0018] 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 and certain exemplary specifications listed in the below table. 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 bacterial fermentation of the present invention). The fiber ratios of insoluble dietary fiber (IDF) to soluble dietary fiber (SDF), not shown in the below table, were 1:30 SDF/IDF.

TABLE-US-00001 TABLE I QD252 - Protein - Combustion Reference Accreditation Analysis Completed AOAC 990.03; AOAC A2LA ISO/IEC Jan. 15, 2020 992.15 17025: 2005 Parameter Result Protein 26.50% Nitrogen - Combustion 4.24% Protein Factor 6.25 QD250 - Ash Reference Accreditation Analysis Completed AOAC 942.05 A2LA ISO/IEC Jan. 15, 2020 17025: 2005 Parameter Result Ash 17.74% QD226 - Calories, Calculated Reference Accreditation Analysis Completed CFR - Atwater A2LA ISO/IEC Jan. 17, 2020 calculation 17025: 2005 Parameter Result Calories Calculated 323 kcal/100 g QD038 - Carbohydrates, Reference Accreditation Analysis Completed CFR 21-calc. A2LA ISO/IEC Jan. 17, 2020 17025: 2005 Parameter Result Carbohydrates, Calculated 46.25% QD148 - Moisture by Vacuum Reference Accreditation Analysis Completed AOAC 925.09 A2LA ISO/IEC Jan. 17, 2020 17025: 2005 Parameter Result Moisture and Volatiles - Vacuum 6.0% Oven QD251 - Calcium by ICP Reference Accreditation Analysis Completed AOAC 984.27 A2LA ISO/IEC Jan. 15, 2020 mod, 927.02 17025: 2005 mod

Example 2

[0019] Six samples of an activated hemp composition, all of the same mass, were individually autoclaved at 170 degrees F. for four hours, 170 degrees F. for two hours, 200 degrees F. for four hours, 200 degrees F. for two hours, 250 degrees F. for four hours and 250 degrees F. for two hours. The hemp starting material contained 75% native hemp and 25% of a noncannabinoid spice mix that was uniform throughout the tests conducted and reported in this example. After the autoclaving step, expected to accomplish at least partial decarboxylation of organic acids in the hemp material including cannabinoid acids, the cannabidiol, cannabidiol acid and total constituency of the autoclaved hemp material was measured and is shown in the following table as to the six described samples.

TABLE-US-00002 TABLE II Sample No. CBD % CBDA % Total CBD + CBDA % 1 1.95 0.73 2.60% 2 3.1 1.01 4 3 5.4 0.19 5.6 4 5.4 0.47 4.8 5 5 non-detectable 5 6 6.1 non-detectable 6.1
Samples identical to 1-6 after autoclaving were relabelled Samples 7-12 and were inoculated and incubated with Acetobacter, under identical inoculation and incubation parameters for all samples. After incubation, the CBD, CBDA and total combined CBD+CBDA constituencies were measured and reported as shown in the following table.

TABLE-US-00003 TABLE III Sample No. CBD % CBDA % Total CBD + CBDA % 7 6.3 3.2 9.10% 8 2.2 2.4 4.4 9 6.1 0.32 6.3 10 6.2 0.5 6.6 11 7.1 non-detectable 7.1 12 9.3 non-detectable 9.3
The above data (eliminating the outliers) illustrate that it is possible to increase individual CBD or CBDA constituents, or the combination of the two, by about a twelve percent increase up to about a 300% increase simply by the bacterial fermentation of the cannabinoid starting material.

[0020] Although the technology has been described with particularity above, with reference to specific materials and methods, the invention is only to be limited as is set forth in the following claims.