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Supercritical CO2 liquorice extract anti-microbial and anti-inflammatory isolates and products made there from
The present invention provides, in one aspect, to products made from a novel and non-obvious supercritical CO2 extract of the roots of Glycyrrhiza sp., effective as an anti-inflammatory, anti-bacterial, anti-fungal and anti-adherent agent, including, but not limited to, products for oral care and body care. The present invention also provides, in another aspect, components isolated from the supercritical CO2 extract of the roots of Glycyrrhiza sp., effective as an anti-inflammatory, anti-bacterial, anti-fungal and anti-adherent agent, including, but not limited to, products for oral care and body care.
Bergeron, Chantal (Kennebunk, ME, US)
Gafner, Stefan (Kennebunkport, ME, US)
A61K8/35; A61P31/00
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DAVIS, DEBORAH A
Kevin, Farrell Pierce Atwood M. (Suite 350, One New Hampshire Avenue, Portsmouth, NH, 03801, US)
1. An oral care or body care composition comprising an extract of the root of the plant Glycyrrhiza sp., comprising an essentially glycyrrhizic acid free extract wherein the major components of the extract are prenylated flavonoids and wherein the root was extracted by a supercritical CO2 extraction process.
2. The oral care or body care composition of claim 1, wherein said extract is from Glycyrrhiza uralensis and wherein the major components of the extract are licoricidin and licorisoflavan A.
3. The oral care or body care composition of claim 1, wherein said extract is from Glycyrrhiza glabra and wherein the major component of the extract is glabridin.
4. The oral care composition of claim 1, wherein said oral care composition is selected from a group consisting of, dentifrice, toothpaste, denture cleaner, dental floss, toothpicks, mouthwash, mouth-rinse, pastilles, chewing gum, dissolvable tablets, chewable tablets or lozenges.
5. The dentifrice of claim 4, wherein said extract is at a concentration of about 0.002 wt. % to about 2.0 wt. %.
6. The denture cleaner of claim 4, wherein said extract is at a concentration of 0.002 wt. % to about 2.0 wt. %.
7. The mouthwash or mouth-rinse of claim 4, wherein said extract is at a concentration of 0.002 wt. % to about 1.0 wt. %.
8. The pastille, chewing gum or lozenge of claim 4, wherein said extract is at a concentration 0.005 wt. % to about 10.0 wt. %.
9. The dissolvable tablets of claim 4, wherein said extract is at a concentration of 0.01 wt. % to about 5.0 wt. %.
10. The dental floss of claim 4, wherein said extract is at a concentration of 0.1 wt.
11. The oral care or body care composition of claim 1, wherein said supercritical CO2 extraction process also comprises an ethanol modifier.
12. The oral care or body care composition of claim 11, wherein said ethanol modifier is at a concentration of about 2.0 wt. % to about 10 wt. %.
13. The oral care or body care composition of claim 1, wherein said prenylated flavonoids comprise about 1.0 wt. % to 20 wt. % of said extract.
15. The oral care or body care composition of claim 2, wherein said licoricidin and licorisoflavan A comprise about 1.0 wt. % to 20 wt. % of said extract.
17. The oral care or body care composition of claim 3, wherein said extract comprises glabridin, methylglabridin and glabrol and said glabridin, methylglabridin and glabrol comprise about 1.0 wt. % to 20 wt. % of said extract.
19. The oral care or body care composition of claim 11, wherein said extract comprises glabridin, methylglabridin and glabrol and said glabridin, methylglabridin and glabrol comprise between about 1.0 wt. % to 20 wt. % of said extract.
21. An oral care or body care composition comprising one or more of licoricidin and licorisoflavan A isolated from an extract of the root of the plant Glycyrrhiza sp.
22. The oral care or body care composition of claim 21, wherein the licoricidin and licorisoflavan A are isolated from an extract of the root of the plant Glycyrrhiza sp. and wherein the root was extracted by a supercritical CO2 extraction process.
23. The oral care or body care composition of claim 22, wherein said extract of the root of the plant Glycyrrhiza sp. and comprises an essentially glycyrrhizic acid free extract wherein the major components of the extract are prenylated flavonoids.
24. The oral care or body care composition of claim 21, wherein the licoricidin and locorisoflavan A have a purity of at least 90%.
25. The oral care composition of claim 21, wherein said oral care composition is selected from a group consisting of, dentifrice, toothpaste, denture cleaner, dental floss, toothpicks, mouthwash, mouth-rinse, pastilles, chewing gum, dissolvable tablets, chewable tablets or lozenges.
26. The dentifrice of claim 25, wherein one or more of said licoricidin and licorisoflavan A is at a concentration of about 0.01 wt. % to 2.0 wt %.
27. The denture cleaner of claim 25, wherein one or more of said licoricidin and licorisoflavan A is at a concentration of about 0.01 wt. % to 2.0 wt %.
28. The mouthwash or mouth-rinse of claim 25, wherein said licoricidin and licorisoflavan A is at a concentration of about 0.01 wt. % to 2.0 wt %.
29. The pastille, chewing gum or lozenge of claim 25, wherein said licoricidin and licorisoflavan A is at a concentration of 0.005-10.0%.
30. The dissolvable tablets of claim 25, wherein said licoricidin and licorisoflavan A is at a concentration of about 0.01 wt. to 5.0 wt. %.
31. The dental floss of claim 25, wherein said licoricidin and licorisoflavan A is at a concentration of about 0.1 wt. % to about 5.0 wt. % of a wax mixture used to coat or impregnate said dental floss.
32. The body care composition of claim 21, wherein said oral care composition is selected from a group consisting of, body lotions, skin creams, soaps, shampoos and conditioners, sun screens, anti-inflammatory topical agents, depilatory compositions, shaving cream, aftershave lotions or deodorants.
33. The body care composition of claim 32, wherein one or more of said licoricidin and licorisoflavan A is at a concentration of about 0.05 wt. % to 2.0 wt %.
Extracts from the root of plants of the genus Glycyrrhiza (Glycyrrhiza sp.), are used for flavorings, the extract imparting the flavor of licorice (liquorice), among other purposes. Current extraction methods use a hot water extraction method. This method preferentially isolates hydrophilic components of the plant root. The major single component isolated with the prior art extraction methods is glycyrrhizic acid. Glycyrrhizic acid is used predominately as a sweetener and a flavoring. Prior art extraction methods remove little or none of the hydrophobic or lipophilic components of the plant root.
Other prior art methods use organic solvents in the extraction process. These processes remove more of the lipophilic components of the plant root but have major environmental concerns connected with the use of the organic solvents. Furthermore, both of the prior art extraction processes (hot water and organic solvent) have significant problems in terms of, for example, waste generation and elimination. Organic solvent extracts have, by their very nature, the problem of spent organics to dispose of or recycle. Hot water extraction processes are preferred at extracting hydrophilic compounds are not effective in extracting lipophilic compounds. Additionally, the spent water must be treated before being put back into the water supply of the environment.
Various components of extracts of Glycyrrhiza sp. have been shown to have anti-inflammatory, antibacterial and anti-adherent effects. However, the effects seen by prior art extracts have been inconsistent. For example, in one study it was reported that incorporation of 0.25-0.5% of glycyrrhizic acid (a major component of licorice extracts made by prior art extraction methods) was ineffective in the removal or prevention of plaque build up (Goultschin, et al., J. Clin. Periodontol. 18:210-212, 1991).
Therefore, what is needed is a method for the extraction of the root of Glycyrrhiza sp. that produces less waste and causes a lesser impact on the environment than prior art extracts while at the same time producing an extract that is more effective in providing anti-inflammatory, antibacterial and anti-adherent properties by isolating a greater percentage of the total available lipophilic components of the plant root and, in particular, a greater total percentage of the available prenylated flavonoids of the plant root.
The present invention provides, in one aspect, novel and non-obvious methods of producing extracts from the roots of Glycyrrhiza sp. In one embodiment, the method of extraction of the present invention comprises utilizing a supercritical CO2 extraction process. Details of the process of the present invention are given below in the Description of the Preferred Embodiments. The methods of the present invention solve the problems of the prior art extraction methods by greatly reducing or eliminating the need for organic solvents during the extraction process and providing an extract that is rich in prenylated flavonoids (e.g., isoflavans, isoflavonol, flavanone, isoflavone) while also being virtually void or void of glycyrrhizic acid (e.g., with no detectable glycyrrhizic acid). The methods of the present invention also extract lipophilic components while extracting very little of the hydrophilic components. The method of the present invention also greatly reduces or eliminates the production of a waste water stream as a result of the extraction process.
The present invention further relates to the extracts made from the extraction processes of the present invention. In one embodiment, the extract of the present invention comprises an extract from G. uralensis comprising predominately licoricidin and licorisoflavan A (5-O-methylicoricidin) as the lipophilic components. No detectable glycyrrhizic acid, a hydrophilic component of the plant root, is recovered with the extraction process of the present invention. Both, licoricidin and licorisoflavan A are prenylated isoflavans, a particular type of flavonoids. For licoricidin, the molecular weight is m/z=424. For licorisoflavan A: molecular weight m/z=438; UV (MeOH): λ max=283 nm. In one embodiment, the extract of the present invention is isolated without using ethanol as a modifier during the extraction process. In this embodiment, the concentration ranges of licoricidin and licorisoflavan A are approximately 0.5-6.0% for both. In another embodiment, the extract of the present invention is produced using ethanol as a modifier during the extraction process. In this embodiment, the concentration ranges of licoricidin and licorisoflavan A are approximately 2.0-20.0% for licoricidin and 1.0-8.0% for licorisoflavan A. In yet another embodiment, the concentration of glycyrrhizic acid in the extracts is less than 0.10%. In yet another embodiment, the concentration of glycyrrhizic acid in the extracts is less than 0.01% or 0.001%. Furthermore, the supercritical CO2 extracts of the present invention also comprises significant amounts of fatty acids (plamitic and linoleic acids, in particular, for example).
In further studies it was discovered that certain components of the supercritical CO2 licorice extract of the present invention are exceptionally well suited in providing anti-inflammatory and anti-microbial effects. In this regard, licoricidin and licorisoflavan A provide the greatest level of anti-microbial effect. Additionally, in this regard, the present invention contemplates oral and body care compositions that comprise amounts of licoricidin and licorisoflavan A effective in providing anti-microbial and anti-inflammatory effects.
Other species of Glycyrrhiza provide extracts wherein the predominant lipophilic components are prenylated flavonoids although the exact prenylated flavonoids may differ. For example, an extract of G. glabra made by the extraction process of the present invention would have as the major prenylated flavonoids, glabridin, methylglabridin and glabrol.
When ethanol is used as a modifier in the extraction process of the present invention, the ethanol is at a concentration of between approximately 2.0 and 10%. In a preferred embodiment, the ethanol modifier is between approximately 4.0 and 6.0%. The use of ethanol is not necessary to produce the extracts of the present invention. Ethanol helps to extract highest amount of compounds which have less lipophilic properties than using CO2 alone.
The present invention also relates to products that are made from said extracts. Although the present invention is not limited to any particular use for the extract of the present invention, in a preferred embodiment, the extract is used in an oral care product. Examples of suitable oral care products in which the extract of the present invention can be used include, but are not limited to, dentifrices (e.g., toothpaste, toothpaste gels, toothpowders, denture cleaning agents and compounds, mouthwashes and mouth rinses, toothpicks, dental floss, chewing gums, pastilles, lozenges, dissolvable tablets, chewable tablets, etc.). Additionally, the extracts of the present invention may be used in body care products such as, but not limited to, skin creams, skin lotions, sun screen compositions, soaps, baby care products, shaving products, deodorants, shampoos, etc.
FIG. 1 shows a HPLC chromatogram of extracts of Glycyrrhiza uralensis generated with A) hot water extraction, B) ethanol extraction, C) ethyl acetate extraction, D) Supercritical CO2 extraction and E) Supercritical CO2 extraction with ethanol as a modifier.
FIG. 2 shows the chemical structures of licoricidin and licorisoflavan A, wherein R═H for licoricidin and R═Me for licorisoflavan A.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention relates to extracts from Glycyrrhiza sp. that have less environmental impact than prior art extraction methods and that extract a greater percentage of the lipophilic components while extracting fewer hydrophilic components than the prior art methods. The present invention also relates to uses for the extracts of the present invention. In another aspect, the present invention relates to an extraction process of Glycyrrhiza sp. that utilizes a supercritical CO2 extraction process.
Extracts may be made from the root of many different species of legume-like plants from the genus Glycyrrhiza and more particularly from the species Glycyrrhiza uralensis. The plants are native to southern Europe and parts of Asia. G. uralensis is used extensively in traditional Chinese medicine. Still, the present invention is not limited to any specific plant source. Other known species of Glycyrrhiza from which extracts my be made thorough the processes of the present invention include, but are not limited to, Glycyrrhiza acanthocarpa, Glycyrrhiza aspera, Glycyrrhiza astragalina, Glycyrrhiza bucharica, Glycyrrhiza echinata, Glycyrrhiza eglandulosa, Glycyrrhiza foetida, Glycyrrhiza foetidissima, Glycyrrhiza glabra, Glycyrrhiza gontscharovii, Glycyrrhiza iconica, Glycyrrhiza korshinskyi, Glycyrrhiza lepidota, Glycyrrhiza pallidiflora, Glycyrrhiza squamulosa, Glycyrrhiza triphylla, Glycyrrhiza uralensis and Glycyrrhiza yunnanensis.
Supercritical carbon dioxide refers to carbon dioxide with some unique properties. Carbon dioxide usually behaves as a gas in air or as a solid as dry ice. If the temperature and pressure are both increased, it can adopt properties midway between a gas and a liquid. It behaves like a supercritical fluid above its critical temperature (31.1 degrees Celsius) and pressure (73 atm=73.96 bar), expanding to fill its container like a gas, but with a density like that of a liquid. The actual temperature necessary to create a supercritical CO2 depends on the pressure and vice versa. For example, the higher the pressure, the lower the temperature necessary to reach the supercritical state. Likewise, the higher the temperature, the lower the pressure necessary to reach the supercritical state.
Although supercritical CO2 has been used in some instances as an extractant for other substances, it has not, to the best of our knowledge, been used as an extractant for the extraction of Glycyrrhiza sp root especially wherein the resulting extract comprised predominately prenylated flavonoids (prenylated isoflavans) and specifically licoricidin and licorisoflavan A from G. uralensis (and, similarly, the prenylated flavonoids glabridin, methylglabridin and glabrol from G. glabra) and was essentially free or void of glycyrrhizic acid. It was only through the empirical experimentation that the methods and compositions of the present invention were conceived and reduced to practice. There were no market pressures or other market considerations that would have led one practiced in the art to identify or develop the components of the present invention, modify the components as necessary to conceive and practice the present invention and to conceive and produce the products of present invention. It was only after the conceptual reduction to practice of the present invention that any market value was recognized.
Some of the environmental benefits of using supercritical CO2 are as follows. First, the CO2 that is used in the process is essentially unchanged and can be reused repeatably. Second, there is virtually no waste stream, i.e., no spent solvent, volatile organic compounds, contaminated waste water, etc., to deal with. Thus, the extract of the present invention is environmentally more sound than the extracts of the prior art methods.
The extracts of the present invention are unlike prior art extracts of Glycyrrhiza sp. The extracts of the present invention are high in the compounds known as prenylated flavonoids (e.g., licoricidin and licorisoflavan A). Both of these compounds have anti-inflammatory, antibacterial, anti-adherent and anti-fungal effects. For example, the extract of the present invention has been shown to have significant antibacterial activity against gram-positive bacteria such as Staphylococcus aureus and Streptocuccus mutans, gram-negative anaerobic bacteria like Porphyromonas gingivalis and Prevotella intermedia as well as antifungal activity against Aspergillus niger. Additionally, the extracts of the present invention are void or virtually void of glycyrrhizic acid when examined by high pressure liquid chromatography (HPLC) (see, Experimental Section, below). Glycyrrhizic acid has been used a sweetener and flavor in the prior art and is not needed in the compositions of the present invention.
Licoricidin and licorisoflavan A are two of the components of the supercritical CO2 extract of the present invention. They both showed antimicrobial activity (MIC) on Streptococcus mutans at 3.125 μg/ml, the principal causal agent of carries, and against Prevotella interrmedia at about 0.78 μg/ml and about 1.56 μg/ml for licoricidin and licorisoflavan A, respectively and against Porphyromonas gingivalis at 0.39 μg/ml and 0.78 μg/ml for licoricidin and licorisoflavan A, respectively. Prevotella sp and Porphyromonas gingivalis are involved in periodontitis. Both components showed also excellent activity as anti-inflammatory agents. Thus, it can be seen that the extract in general and these compounds in particular can excel in their ability to act as anti-inflammatory, antibacterial and as antifungal agents (See, Experimental section, below).
As mentioned above, the extract produced by the process of the present invention can be used in many products including oral care products and body care products for their anti-inflammatory, antibacterial, anti-adherent and antifungal properties. Below, we describe some of the products suitable for use with the extract of the present invention.
Oral Compositions
The Glycyrrhiza sp root (i.e., licorice extract) of the present invention may be formulated in a dental floss. For example, the extracts of the present invention may be impregnated within dental floss so that it comes into contact with the user's teeth during flossing. Concentrations of the extract of the present invention when used in a dental floss composition are about 0.1 to 5.0% by weight of the wax mixture used in coating the floss material. Preferred concentrations are about 0.5 to 3.0% by weight of the wax mixture used in coating the floss material. Dental floss may be used to ensure that the extracts of the present invention come into contact with the surfaces of the teeth that face each other and are hard to reach by some of the other means described. When licoricidin and licorisoflavan A are used as the antimicrobial agents in the floss of the present invention they can be used alone or in a mixture at total concentrations of about 0.01 wt % to 1.0 wt %, at total concentrations of about 0.05 wt % to 0.5 wt % or at total concentrations of about 0.1 wt % to 0.2 wt %.
In certain embodiments of the present invention, said dental floss is made as discussed below. One skilled in the art will realize that there are other methods and compositions for the manufacture of dental floss that are compatible with the licorice-based composition of the present invention.
The meaning of the words, "dental floss(es)," shall be herein understood to include both dental flosses and dental tapes as well as any other similar article. Moreover, the dental flosses and tapes used in the present invention may include any suitable or commercially available dental floss or tape. These flosses and tapes can be fabricated from either natural or synthetic sources examples of which include, but are not limited to, filaments or yarns of high and normal tenacity polymers, GoreTex™, nylons, polyolefins, polyethylenes, polypropylenes, fluorocarbon compounds, polytetrafluoroethylenes, rayons, dacrons, acrylics, acetate polymers, and other plastics alone or in combination. Natural substances may include, but are not limited to, cotton, wool, silk, linen, hemp, soy and other staple fibers alone or in combination. Blends of synthetic-natural fibers can also be used. However, synthetic filaments tend to fray less than natural fibers.
The tensile strength of floss must be evenly distributed along their length. This is the key with fibers—they will break at their weakest point, so even keeled tensile strength is the key. Thus, the dental floss of the present invention is related to fibers with high tensile strength while still being usable for cleaning between teeth. The denier of a floss or floss fiber measures it's weight and also to tensile strength. Denier is defined as the weight of 9,000 meters of uncoated floss in grams. There is a direct correlation between the numerical value of the denier and the thickness of the strand of floss: if this value increases, the thickness of the strand also increases. Thus, generally, the higher the denier, the higher the tensile strength, all else being equal. In one embodiment of the present invention, the denier of round floss is about 750 to 950 and for flat floss it is about 950 to 1150.
The length, diameter, structure or design of the floss itself is also not limited to any specific size, shape, arrangement or configuration and, thus, can be fabricated to suite any specific intention. It can, for example, be composed of a plurality of individual filaments that have been formed together to give a larger thread having a sufficiently small diameter to permit insertion between the teeth. It can also comprise a composite multifilament yarn bonded to an extruded monofilament or to another multifilament yarn. A single circular, square or rectangular shaped monofilament thread is also useful. Other suitable variations are also well known in the art and as such are also useable in the invention disclosed herein.
Binders, for example, are used in the invention disclosed herein to bind or otherwise attach to a dental floss the ingredients herein specified by this disclosure. They also provide the ability to alter the frictional characteristics of dental floss as well as help bind together the individual filaments comprising the floss itself. Moreover, the varieties used herein are not restricted to any specific types or compositions and are thus, given great freedom in their formulations, structures or make-ups. Examples of some suitable binders may therefore include, but are not limited to, natural waxes from plants (e.g., carnauba wax, soy wax and jojoba wax) as well as other water soluble or non-water soluble wax or wax-like compounds or water soluble or non-water soluble polymers, soaps, gums, resins (e.g., myrrh and propolis) and other substances known in the art.
Flosses may also make use of, for example, one or more solubilizing agents. Their function, as such, will be to aid in dissociation. Suitable solubilizing agents may therefore include, but are not limited to, filtered water, reverse osmosis water, distilled water and deionized water, alone or in combination. However, deionized water has been found preferable to the others.
Flosses may also utilize, for example, one or more flavoring agents. These preferably comprise oils or extracts derived from plants and fruits such as citrus oils, fruit essences, mint, peppermint oil, spearmint oil, clove oil, oil of wintergreen, anise, sassafras, sage, eucalyptus, marjoram, cinnamon, lemon, orange, banana, cherry, fennel, apple; pineapple, grape, strawberry and blueberry. Those skilled in the art will recognize that such natural flavoring agents may be used independently or combined in any sensorially acceptable blend. All such flavors and flavor blends are contemplated by the present invention.
To foster greater consumer appeal, flosses may also contain, for example, one or more natural sweetening agents. These may include, but are not limited to, xylitol, glycerol, sorbitol, maltitol, erythritol, sucrose, lactose, dextrose, maltose, dextrin, fructose, galactose and the like.
Fluorides have in the past been found to help prevent the incidence of carious lesions or caries. Caries are caused when teeth demineralize at a rate faster than they remineralize and most demineralization is caused by acid producing dental plaques. Remineralization, however, is promoted by calcium and phosphate, the chief remineralizing agents found also in saliva. Fluoride based compounds, therefore, provide protection from carious lesions or caries by acting as a catalyst to speed the precipitation of calcium phosphate, in the form of a hydroxy apatite, onto or into teeth. However, this is not fluoride's only role. It is also able to inhibit the activity of some bacterial enzymes and their acid producing processes, and at extremely high concentrations it can also kill certain plaque bacteria. Even more important, it tends to become incorporated into the apatite, as a fluoridated hydroxy apatite or "fluorapatite," creating a mineral that is appreciably less dissolvable by acid.
Hence, flosses may contain, for example, one or more fluoride based compounds. These compounds may also be slightly soluble in water or may be fully water soluble. They are, however, foremost characterized by their ability to release fluoride ions in water and their freedom from undesired reactions with the floss's other compounds. Among these materials are numerous fluoride-based compounds which can comprise inorganic fluoride salts such as soluble alkali metal, alkaline earth metal salts, and others. When a fluoride compound is employed, the amount used is dependent to a large extent upon the type of fluorine compound, its solubility, and the final formulation and structure selected. As such, substantial leeway is given to the quantities or amounts used as long as normal formulation and pharmaceutical safeguards are observed. Consequently, whenever fluoride based compounds are used within the formulations listed below they should amount to no more than 0.30 percent (w/w). However, it has been found that setting the maximum range at 0.24 percent (w/w) is preferable with 0.22 to 0.24 percent (w/w) being the best overall range to use.
The licorice supercritical CO2 extracts (Glycyrrhiza sp root extract) of the present invention may also be used with toothpastes, tooth gels and tooth powders. In one embodiment of the present invention, the concentration of the extract of the present invention used in dentifrices ranges from about 0.002 to 2.0% by weight. In a preferred concentration the range is between 0.02 to 1.0% by weight. When licoricidin and licorisoflavan.A are used as the antimicrobial agents in the dentifrice of the present invention they can be used alone or in a mixture at total concentrations of about 0.01 wt % to 1.0 wt %, at total concentrations of about 0.05 wt % to 0.5 wt % or at total concentrations of about 0.1 wt % to 0.2 wt %.
Compositions in the form of toothpastes, gels, liquid gels, denture cleansing liquids and pastes, and the like, will generally comprise a binder or thickening agent. Binders suitable for use herein include carrageenan (preferred) and/or natural gums such as gum karaya, xanthan gum (preferred), gum arabic (preferred) and gum tragacanth can also be used, as well as other agents known in the art. Colloidal magnesium aluminium silicate or finely divided hydrated silica can be used as part of the thickening agent to further improve texture. Binders/thickening agents can be used in an amount from about 0.1% to about 15.0%, preferably from about 1.0 to about 12% by weight of the total composition. The actives are fluoride and potassium nitrate, their level are described in their respective FDA monographs for anti-cavity and sensitivity. Active for gingivitis are still pending the finalization of the monograph. The abrasives are calcium carbonate, baking soda or hydrated silica.
Such compositions will typically comprise one or more sweeteners and flavorings. Examples of suitable sweeteners and flavorings for use in dentifrices are discussed above. pH balancing agents (e.g., citric acid, NaOH) as well as, surfactants (e.g., sodium lauryl sulfate), preservatives (e.g., benzoic acid, sorbic acid) stabilizers, etc., are also often used in dentifrice compositions, examples of which are also provided above. The compositions of the present invention may include botanicals as well.
In addition to the incorporation of licorice extract of the present invention, there may also be included in the dentifrice minor amounts, e.g., 0.01 to 2% by weight of other natural ingredients such as antioxidants, preservatives, pH adjusting agents, desensitizing agents, stabilizing agents, gelling agents, flavors, etc. A preferred gelling or binding agent is one or more of carrageenan or xanthan gum. Preferred flavorings are natural flavorings such as peppermint, spearmint, apricot and cinnamon, etc. For sensitive teeth, the formulation may contain an agent for relieving pain in people with sensitive teeth. A preferred ingredient for this purpose is potassium nitrate. Dispersing agents may be used in the present invention. Preferred dispersants are sodium lauryl sulfate or saponin containing plant extracts.
It is also desirable to include one or more humectants (moisture retaining agent) material in the toothpaste to keep the composition from hardening upon exposure to air. Preferred humectants are glycerin and sorbitol. Certain humectants can also impart a desirable sweetness to toothpaste compositions. Liquid dentifrice and mouthwashes can also contain a quantity of humectants. Suitable humectants are well known in the art. When present, humectants generally represent from about 10% to about 70%, by weight of the compositions of the invention.
Toothpowders may make use of many of the same ingredients as toothpastes except that they must be mixed in a dried state (i.e., dry milled) or mixed as a liquid composition and then dried via, for example, various known spray drying techniques. Spray drying is described as when a liquid form of a composition is sprayed as a mist into a hot, dry chamber wherein the aqueous portion of the mist is evaporated by the dry heat of the chamber leaving only the dry constituents of the composition in a powdered form. The powdered form of the composition has a moisture content of between about 0.1% to 5%. Toothpowders then rehydrate upon use either by the addition of water (e.g., with water applied by the user) at the time of use or by the user's saliva.
Dissolvable Tablets
Another aspect of the present invention is dissolvable denture cleaning tablet comprising the Glycyrrhiza sp. supercritical CO2 extract of the present invention. Still another aspect of the present invention is a dissolvable denture cleaning tablet comprising one or both of licoricidin and licorisoflavan A isolated, for example, from the supercritical CO2 extract of the present invention.
Such tablets may be solid, layered, have a liquid filled center, etc. The tablet should dissolve completely or nearly completely in an aqueous solution in less than about one hour and, preferably, in less than about 15 minutes. The tablet may be effervescent but need not be.
Water-soluble, denture cleanser tablets are made by first preparing and drying a granulation of ingredients using a suitable binder in an, for example, anhydrous alcohol solution. The resulting granular mixture is then dried to a moisture content of 0.4% or less, screened, and then thoroughly blended with the desired active ingredients along with binders, fillers, extenders, dyes, flavors, lubricants and the like in a suitable blending apparatus. The final blends are fed into a punch and die tableting press where it is compacted into tablets. Thereafter the tablets so formed are released and packaged.
Mouthwash and Mouthrinse
Typically, the mouthwashes and rinses of the present invention comprise the Glycyrrhiza sp. supercritical CO2 extract of the present invention in, for example, a water/glycerin solution and may additionally comprise one or more of flavor, humectant, sweetener, emulsifier (e.g., poloxamer) and colorant. Still another aspect of the present invention is a mouthwash comprising one or both of licoricidin and licorisoflavan A isolated, for example, from the supercritical CO2 extract of the present invention.
Mouthwashes can include glycerin at a level of from 0 to 60%, preferably from 0 to 30% by weight. The pH value of such mouthwash preparations is generally from about 3.5 to about 8.0 and preferably from about 4.0 to about 7.5. A pH greater than 8.7 would result in an unpleasant mouth feel. The oral liquid preparations may also contain surface active agents, i.e., surfactants, in amounts up to about 5.0% and more preferably between about 0.5 to 2.0%; and fluoride-providing compounds in amounts up to about 2.0% by weight of the preparation and more preferably about 0.0442% for sodium fluoride or 0.025% of the fluoride ion.
The mouthwashes and mouth rinses of the present invention may also comprise one or more alcohols. For example, ethanol.
Pastilles, Lozenges and Chewing Gum
The chewing gum compositions that comprises the Glycyrrhiza sp. supercritical CO2 extract of the present invention may be in the form of a conventional chewing gum or any other product form which is suitable for chewing. Still another aspect of the present invention is a chewing gum comprising one or both of licoricidin and licorisoflavan A isolated from the supercritical CO2 extract of the present invention. Suitable physical forms include sticks, squares and dragees (i.e., sugar coated gum; e.g., Chiclets™). The chewing gum may also have a liquid-filled center wherein the liquid center contains the licorice-based compositions (See, e.g., U.S. Pat. No. 6,280,780). The chewing gum may also be a digestible or dissolvable gum suitable for chewing. A chewing gum is typically retained in the oral cavity for a time sufficient to allow ingredients released to contact substantially all of the dental surfaces and/or oral tissues for purposes of oral activity.
The term "carrier materials" as used herein means any safe and effective additional chewing gum components used in the chewing gum compositions of the present invention. Such materials include elastomers, resins, plasticisers, fats, solvents, waxes, emulsifiers, softeners, bulking agents, sweeteners, absorbents, orally active metallic ions, cationic material, fluoride ion sources, additional anticalculus agents, antimicrobial agents, buffers, whitening agents, alkali metal bicarbonate salts, thickening materials, humectants, water, surfactants, titanium dioxide, flavoring agents, xylitol, coloring agents and mixtures thereof.
The chewing gum of the present invention is manufactured by methods known in the art. For example, the gum base is heated to 45° C. to soften. The mixer vessel is maintained at 45° C. during entire mixing process and additives as described herein as well as the extract of the present invention are added and mixed to homogeneity. Then the gum mixture is formed into sticks, squares, etc., wrapped and cooled. If desired, the gum is coated in a sugar or sugar-free candy coating.
The licorice composition may also be used in lozenge and pastille compositions. The carrier for the lozenges and pastilles is conveniently a sugar, such as glucose, lactose or sucrose, or a substantially non-cariogenic material, for example mannitol, xylitol, maltitol, erythritol or sorbitol.
In addition to the active ingredient and the carrier, the lozenges preferably contain one or more binders, such as gelatin (a vegetal gum, e.g., Arabic gum, is preferred) or liquid glucose BPC 1963, which in total may conveniently be present in an amount of from about 0.5 to 10% weight of the lozenge. A preferred range is from about 1 to 5% by weight.
The lozenges may additionally contain a lubricant, such as stearic acid or a stearate such as magnesium stearate to facilitate manufacture of the lozenge. When one or more lubricants are present, the total content thereof in the lozenge is preferably from 0.1 to 5% by weight.
The lozenges may be prepared by conventional lozenge making procedures, for example by admixing the 1,3-bis(2-carboxychromon-5-yloxy)-2-hydroxypropane or salt thereof with the adjuvant, diluent or carrier and compressing the mixture. In a preferred procedure, the bis-chromone and the adjuvant, diluent or carrier are desirably first granulated together before being compressed into the lozenge. The granulation step is preferably a wet granulation step, and a lubricant is desirably added immediately before the compression step.
Pastilles (sometimes known as jujubes or soft lozenge) are a hard, jelly-like preparation made from a mixture of glycerin, gelatin (or other natural gelifiant) and water, to which the extract of the present invention is incorporated. Flavor may be added too. The glyco-gelatin base may be melted by gentle heating and any ingredients added. The warmed base is then poured into moulds and allowed to set. For example, See, www.rpsgb.org.uk/pdfs/mussheet04.pdf.
Typical body care products include, for example, body lotions, skin creams, soaps, hair care products (for example, shampoos and conditioners), sun screens, anti-inflammatory topical agents, depilatory compositions, shaving products (for example, shaving cream and aftershave lotions), deodorant, baby care, etc. Body care products are products used on the external body (e.g., skin, hair, etc.) as, usually, topical treatments.
One practiced in the art knows how to formulate such body care products. For example, U.S. Pat. No. 6,861,062 to Silva, et al., (and incorporated herein by reference) discloses exemplary formulations and methods for making skin creams. Herbal compositions for skin care products are also known in the art (see, e.g., U.S. Pat. No. 6,586,018 to Fasano, which is incorporated herein by reference) discloses exemplary formulations and methods of manufacture.
Compositions and methods of producing shaving products are also known in the art. For example, U.S. Pat. No. 7,179,454 to Lucas, which is herein incorporated by reference, discloses several exemplary formulations and methods of manufacture. U.S. Pat. No. 6,479,043 to Tietjen, et al., (incorporated herein by reference) discloses exemplary formulations and methods of manufacture for depilatory agents.
Likewise, formulations and methods for the production of soaps, sun screen lotions and anti-inflammatory topical treatments are also known in the art.
Body care products of the present invention, in one embodiment, comprise an extract of the root of the plant Glycyrrhiza sp., comprising an essentially glycyrrhizic acid free extract wherein the major components of the extract are prenylated flavonoids and wherein the root was extracted by a supercritical CO2 extraction process.
In another embodiment, the extract is from Glycyrrhiza uralensis and the major components of the extract are licoricidin and licorisoflavan A.
In another embodiment, the extract is from extract is from Glycyrrhiza glabra and the major component of the extract is glabridin.
For example, a deodorant of the present invention, in one embodiment, comprises an extract of the present invention in combination with an antioxidant compound, preferably with an ingredient from the group of tocopherol and its derivatives, butyl hydroxyanisole (BHA), butyl hydroxytoluene (BHT), erythorbic acid, propyl gallate, sodium erythorbate, tertiary butyl hydroquinone (TBHQ), and rosemary extract, more preferably with ascorbic acid and salts thereof. Further, the deodorant may comprises certain metal salts of an unsaturated hydroxy carboxylic acid, preferably zinc ricinoleate. In a preferred embodiment, the extract of the present invention is at a concentration of about 0.01 to 5.0% by weight and in a more preferred embodiment, from about 0.05 to 2.0% by weight. When licoricidin and licorisoflavan A are used as the antimicrobial agents in the deodorant of the present invention they can be used alone or in a mixture at total concentrations of about 0.01 wt % to 1.0 wt %, at total concentrations of about 0.05 wt % to 0.5 wt % or at total concentrations of about 0.1 wt % to 0.2 wt %.
For body lotions, skin creams, soaps, hair care products, sun screens, anti-inflammatory topical agents, depilatory compositions, shaving products, baby care products the concentration of the extracts of the present invention are at a concentration of about 0.01-2% and more preferably 0.1-1%. When licoricidin and licorisoflavan A are used as the antimicrobial agents in the body care products of the present invention they can be used alone or in a mixture at total concentrations of about 0.01 wt % to 1.0 wt %, at total concentrations of about 0.05 wt % to 0.5 wt % or at total concentrations of about 0.1 wt % to 0.2 wt %.
Extraction Process: The licorice extract used in the following examples and in the manufacture of dentifrices of the present invention was made with a novel and non-obvious supercritical CO2 extraction process. The extraction process of the present invention, in one embodiment, was as follows. The root of Glycyrrhiza uralensis was cut, ground and powdered to create a raw material. The raw material was put into an extraction chamber (the extractor). The extraction chamber was fed with liquid CO2. The liquid CO2, brought from the working/storage tank, was cooled and pumped into the extraction chamber at 300 bar, 50° C. with the 5% addition of 96% ethanol. The CO2 extract was then metered through an evaporator and flowed into a separation tank.
Under supercritical conditions established in the extractor, CO2 has solvent properties for lipophilic ingredients whereas CO2 in the gas phase is without solvent power under the conditions in the separator (60 bar, 30° C.). Thus the extract was precipitated and the gas was regenerated in the separation tank. The CO2 was then liquefied by passing through a condenser and recycled to the working tank.
Comparison of the Supercritical CO2 Licorice Extract of the Present Invention with the Extracts Made by Prior Art Methods.
Broth microdilution minimum inhibitory concentration: For anaerobes, 190 μL of sterile, pre-reduced Wilkins Chalgren (WC) anaerobe broth with 0.075% cysteine were added to the first well of the test series in a 96 well plate, followed by 100 μL in each of four additional test wells. Ten μL of filter-sterilized stock solution of licorice CO2 extract, prepared at 40 mg/mL in ethanol, was added to the first well of the series. Contents of the first well were mixed thoroughly and serially diluted (1:1) with the remaining four wells in the series; 100 μL were discarded from the final well in the series. Suspensions of Porphyromanas gingivalis ATCC 33277 or Prevotella. intermedia ATCC 25611, diluted to approximately 1×106 cfu (colony forming units) per mL, were added to the test wells in 100 μL quantities. Appropriate growth promotion and sterility controls were included. Plates were incubated at 37° C. anaerobically, until turbidity in the growth control well was observed. The MIC (minimum inhibitory concentration) was recorded as the lowest concentration inhibiting growth of the test organism as viewed with the unaided eye. Streptococcus mutans ATCC 25175 was tested in similar fashion, with Tryptic Soy Broth (TSB) as the test medium and incubation of plates at 37° C. with 5% CO2. Staphylococcus aureus ATCC 6538 was tested using Tryptic Soy Broth (TSB) as the test medium and incubation of plates at 37° C. Aspergillus niger ATCC 16404 was tested, with Tryptic Soy Broth (TSB) as the test medium and incubated at room temperature (25° C.).
Results were recorded as the mode value from triplicate experiments vs. each bacterium. P. intermedia and P. gingivalis are gram negative bacteria involved in periodontitis. Streptococcus mutans is involved in caries formation. Both supercritical extracts were able to inhibit the growth of those 3 pathogenic bacteria at the lowest concentrations of extract tested. Supercritical licorice extracts of the present invention, with or without using or not ethanol as a modifier, were able to inhibit P. intermedia at a concentration of 12.5 μg/ml. The extract using ethanol as a modifier was able to inhibit the growth of P. gingivalis at the same level as chlorhexidine. The supercritical licorice extract of the present invention (with ethanol) was able to inhibit the growth of S. mutans, a cariogenic bacteria, at a concentration of 12.5 μg/ml. The supercritical licorice extract of the present invention without ethanol was only tested to 31.25 μg/ml. See, Table 1A.
TABLE 1A
Antibacterial activity against oral bacteria
CO2 - to licorice CO2 - EtOH
extract extract
(μg/ml) (μg/ml) Chlorhexidine
Prevotella intermedia 12.5 12.5 3.125
Porphyromonas 12.5 6.25 6.25
gingivalis
Streptococcus mutans <31.25* 12.5 1.56
*The lowest concentration tested was 31.25 μg/ml
Antibacterial Activity of Licoricidin and Licorisoflavan A
Licoricidin and licorisoflavan A are two of the components of the supercritical CO2 extract of the present invention. They both showed antimicrobial activity on Streptococcus mutans at 3.125 μg/ml, the principal causal agent of caries and against Prevotella intermedia at about 0.78 μg/ml and about 1.56 μg/ml and Porphyromanas gingivalis at 0.39 μg/ml and 1.56 μg/ml for licoricidin and licorisoflavan A, respectively, as shown in Table 1B. Porphyromonas gingivalis and Prevotella sp are involved in periodontitis. These concentrations were the minimum inhibitory concentrations (MIC). Both components showed also excellent activity as anti-inflammatory agents. MIC is defined by those skilled in the art as the lowest concentration of an antimicrobial agent that will inhibit the visible growth of a microorganism after overnight incubation. Minimum inhibitory concentrations are used by those skilled in the art to monitor the activity of new antimicrobial agents. Chlorhexidine is used here as a positive control and is frequently found as an antibacterial agent in, for example, mouthwash.
Broth microdilution minimum inhibitory concentration was performed as follows. Ten μL of filter-sterilized stock solution of pure compound, licoricidin or licorisoflavan A, prepared at 1 mg/mL in ethanol, was added to the first well of the series. Contents of the first well were mixed thoroughly and serially diluted (1:1) with the remaining seven wells in the series; 100 μL were discarded from the final well in the series. Suspensions of Porphyromanas gingivalis ATCC 33277 or Prevotella.intermedia ATCC 25611, diluted to approximately 1×106 cfu (colony forming units) per mL, were added to the test wells in 100 μL quantities. Appropriate growth promotion and sterility controls were included. Plates were incubated at 37° C. anaerobically, until turbidity in the growth control well was observed. The MIC (minimum inhibitory concentration) was recorded as the lowest concentration inhibiting growth of the test organism as viewed with the unaided eye. Streptococcus mutans ATCC 25175 was tested in similar fashion, with Tryptic Soy Broth (TSB) as the test medium and incubation of plates at 37° C. with 5% CO2.
Results were recorded as the mode value from triplicate experiments vs. each bacterium. P. intermedia and P. gingivalis are gram negative bacteria involved in periodontitis. Streptococcus mutans is involved in caries formation. Both compounds were able to inhibit the growth of those 3 pathogenic bacteria.
TABLE 1B
Licorisoflavan
Extract Licoricidin A Chlorhexidine
(μg/ml) (μg/ml) (μg/ml) (μg/ml)
S. mutans 12.50 3.125 3.125 1.56
P. gingivalis 6.25 0.39 0.78 6.25
P. intermedia 6.25 0.78 1.56 3.125
Biofilm formation and viability: A 24 h culture of P. gingivalis (ATCC 33277) in Todd-Hewitt broth supplemented with hemin and vitamin K (THB-HK) was diluted in fresh broth medium to obtain an optical density at 655 nm (OD655) of 0.07. Samples (100 μL) were added to the wells of a 96-well tissue culture plate containing 100 μL of serial dilutions (0 to 500 μg/mL) of sterile plant extracts in THB-HK. Control wells with no extract were also inoculated. After incubation for 48 h at 37° C. under anaerobic conditions, spent media and free-floating bacteria were removed by aspiration using a 26G needle and the wells were washed three times with distilled water. The P. gingivalis biofilms were stained with 0.4% crystal violet (100 μL) for 15 min. The wells were washed four times with distilled water to remove unbound crystal violet dye and dried for 2 h at 37° C. After adding 100 μL of 95% (v/v) ethanol to each well, the plate was shaken for 10 min to release the stain from the biofilms and the absorbance at 550 nm (A550) was recorded. Assays were run in triplicate and the means ±standard deviations of two independent experiments were calculated. See, Table 2.
The effect of plant fractions on P. gingivalis cell viability was investigated using the tetrazolium sodium 3′-{1-[(phenylamino)-carbonyl]-3,4-tetrazolium}-bis(4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT) reduction assay. Briefly, XTT was dissolved in PBS at 1 mg/mL and menadione was prepared in acetone at 1 mM. The XTT/menadione reagent contained 12.5 parts XTT/1 part menadione. A 48 h biofilm of P. gingivalis was prepared as above and treated with the plant fractions (0 to 250 μg/mL) for 2 h (anaerobiosis, 37° C.) prior to adding 25 μL XTT/menadione. After 1 h at 37° C., the absorbance at 490 nm (A490) was read using a microplate reader. The licorice extract of the present invention was able to inhibit the growth of P. gingivalis and also inhibit the formation of P. gingivalis. P. gingivalis was then unable to attach (anti-adherence). When licorice extract was applied after the biofilm was formed, there was no desorption of the biofilm but the viability of the biofilm was reduced which means that the biofilm was not removed but that the bacteria forming the biofilm died. See, Table 2.
Effect of licorice CO2 extract biofilm formation, adherence
properties and viability of P. gingivalis.
Bactericide
Inhibit effect on
P. gingivalis P. gingivalis
biofilm. Desorption of in a
(anti- P. gingivalis Growth of biofilm (cell
adherent) biofilm P. gingivalis viability)
Licorice CO2 4.2 — 4.2 8
LPS preparations: Aggregatibacter actinomycetemcomitans ATCC 29522 (syns; Actinobacillus actinomycetemcomitans) and P. gingivalis ATCC 33277 were grown in their appropriate culture media. LPS were isolated from these bacterial strains by a method routinely used in our laboratory.
Treatments of macrophages: U937 cells (ATCC CRL-1593.2), a human monoblastic leukemia cell line, was cultivated at 37° C. in a 5% CO2 atmosphere in RPMI-1640 supplemented with 10% FBS and 100 μg/mL of penicillin-streptomycin (RPMI-FBS). Monocytes (2×105 cells/ml) were incubated in RPMI-10% FBS containing 10 ng/ml of phorbol myristic acid (PMA) for 48 h to induce differentiation into adherent macrophage-like cells. Following the PMA treatment, the medium was replaced with fresh medium and the differentiated cells were incubated for an additional 24 h prior to use. Adherent macrophages were suspended in RPMI-10% FBS and centrifuged at 200×g for 8 min. They were washed and suspended in RPMI-10% FBS at a density of 1×106 cells/ml and seeded in a 6 well-plate (2×106 cells/well in 2 ml) at 37° C. in a 5% CO2 atmosphere.
The macrophages were treated with the licorice extract at concentrations up to 250 μg/ml and incubated at 37° C. in 5% CO2 for 2 h before stimulation with LPS at a final concentration of 1 μg/ml. After a 24 h incubation (37° C. in 5% CO2), the culture medium supernatants were collected and stored at −20° C. until used. Cells incubated in culture medium with or without licorice extract, but not stimulated with LPS, were used as controls.
Determination of cytokine levels: Commercial enzyme-linked immunosorbent assay (ELISA) kits (R&D Systems, Minneapolis, Minn., U.S.A.) were used to quantify IL-1β, IL-6, IL-8, and TNF-α concentrations in the cell-free culture supernatants according to the manufacturer's protocols. The absorbance at 450 nm was read in a microplate reader with the wavelength correction set at 550 nm.
Statistical analysis: Two-way analyses of variance were performed to compare the means of the different conditions. Differences were considered significant at the 0.05 level (P value).
Anti-inflammatory effect. The extracts of the present invention caused a significant inhibition in vitro of interleukin 1, interleukin 8 and tumor necrosis α production by macrophages produced from a U937 cells, a human monoblastic leukemia cell line stimulated with LPS of Aggregatibacter actinomycetemcomitans at a concentration of 10 μg/ml and at 5 μg/ml for interleukin 6. These results were confirmed in two independent experiments.
Licorice extract caused a significant inhibition in vitro of interleukin 6, interleukin 8 and tumor necrosis factor-α (TNF-α) production by macrophages stimulated with LPS of P. gingivalis at a concentration varying from 5-10 μg/ml. These results were confirmed in two independent experiments.
HPLC Analysis of the Supercritical CO2 Extract
Samples of the extracts of the present invention and extracts produced by prior art methods were analyzed by high pressure liquid chromatography (HPLC). The specifications for the procedure used were as follows: HPLC was performed on a Zorbax Eclipse XDB C-18 (Agilent Technologies, Santa Clara, Calif.) 250×4.6 mm i.d., 5 μm, with Zorbax C-18 Guard Column: (Cat. # HP 990967-902 and HP 820950-925).
Mobile Phase: MeCN (0.05% TFA)-H2O (0.05% TFA)
0 min. 45 55
25 min. 100 0
25.1 min. 45 55
Conditioning: at least 20 min.
Flow Rate: 1.0 ml/min
Col. Temp: 30° C.
Detector: 280 nm (bw 16, reference 450 nm,
bw 100)
Run time: 25 min.
Post time: 5 min.
The results are presented in FIG. 1. The first chromatogram (A) shows an extract with hot water and it contains only hydrophilic compounds. The peak eluting after 4.5 min is glycyrrhizic acid. According to the UV spectrum and the retention time, glycyrrhizic acid is only present in the hot water extract. The second chromatogram (B) is a 100% ethanol extract and the chromatogram (C) is an ethyl acetate extract, both are very similar in composition, with the exception that B contains more hydrophilic compounds (eluting between 0-4 min.). The major components of the CO2 extract are licoricidin (1, eluting after 16.5 min) and licorisoflavan A (2, eluting after 21 min.), together with an unidentified flavonoid peak 3 around 18 min. The supercritical extract using ethanol (EtOH) as a modifier contains more hydrophilic compounds that the supercritical extract without modifier, and contains the highest amounts of licoricidin and licorisoflavan A. Moreover, from an environmental point of view, the CO2 extract uses only a small percentage of ethanol (5-10%) to achieve a good balance of hydrophilic and lipophilic compounds. In both supercritical extracts, the licoricidin and licorisoflavan A are highly dominant.
Licoricidin and licorisoflavan A were isolated from the supercritical CO2 extract of the present invention as follows. A quantity of about 433 mg of licorice CO2/EtOH extract was submitted to medium pressure liquid chromatography (MPLC) with a Büchi C-600 MPLC system (Büchi Analytical, Flawil, Switzerland) using an ODS-based (Phenomenex Luna C-18(2), 100 Å) stationary phase using acetonitrile-water (45:55) as solvent and a flow rate of 5 mL/min. Fraction 3 contained licoricidin (32.8 mg), and licorisoflavan A (21.5 mg) was obtained from fraction 7. The purity of licoricidin was about 89% and the purity of licorisoflavan A was about 91%. In the context of the present invention, the term "isolated" in regards to the licoricidin and licorisoflavan A of the present invention includes purities of about 50% or greater, about 60% or greater, about 70 wt. % or greater, about 80 wt. % or greater, about 90 wt. % or greater, about 95 wt. % or greater or about 99 wt. % or greater.
Previous Patent: Glycyrrhizic acid compounds as a foamer in chemically-derived surfactant-free dentifrice
Next Patent: UTILIZATION OF RHINOLOGICALLY ACTIVE SUBSTANCES


text:
La Nebulosa E è una nebulosa oscura osservabile nella costellazione dell'Aquila; deve il suo nome alla sua particolare forma, che ricorda una lettera "E" maiuscola.

Si tratta in realtà di sue sistemi nebulosi separati fra loro, noti come B 142 e B 143; si individua circa 1 grado ad ovest della stella , facente parte dello stesso asterismo di Altair. B 143, la parte settentrionale, è la più scura ed anche la più estesa, e maschera completamente la luce delle stelle che le stanno dietro, al punto che appare intensamente nera; B 142 è invece meno densa, lasciando passare in parte la luce delle stelle di fondo. Entrambe si evidenziano bene in un telescopio amatoriale di medie dimensioni; la distanza dei due complessi nebulosi è stimata sui circa 2000 anni luce da noi.

Bibliografia

Voci correlate
Oggetti non stellari nella costellazione dell'Aquila

Collegamenti esterni

Nebulose oscure
Braccio di Orione

redpajama_set_name: RedPajamaWikipedia


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Home / security / Security: Oyo State VGN Seeks For Makinde Support
Security: Oyo State VGN Seeks For Makinde Support
The state commander Vigilante Group of Nigeria ( VGN) Oyo State command, Comrade Sunday Olajide (JP) has advised the Government of Oyo State to engage and support the service of his group in the fight against crime and criminality across the state..
Olajide gave the advice while addressing newsmen at a security summit, awards and fund raising programme organised by his group on Wednesday 28th December, 2022 at the State Secretariat in Agodi,Ibadan ,Oyo State.
He stated that insecurity will be reduced drastically if government engage and support the VGN in the fight against insecurity.
Commander Olajide noted that the group would be of help in the state quest in fighting against crime and criminality as its personnel understood the terrain of the state much more better than other security agencies.
" One thing that sets VGN apart from the other security apparatus in Nigeria is our grassroots base and the understanding of the locals.
" We are also respectable professionals and our community knowledge makes it easier for us when it comes to crime fighting job".
"The Vigilante Group of Nigeria ( VGN) is never transferred from one place to another like it occurs in the Nigerian police; we stay for as long as we wanted in our community and this gives us an edge when we talk of community policing than the men of the Nigerian police.' he concluded.
During the event, the South West commandant, Olusoji Sodiya described comrade Sunday Olajide as a worthy father in Yorubaland and a patriotic Nigerian whose dedication to humanity is worthy of emulation.
In his remarks, His Royal Highness, Oba Nureni Yusuf ,Alajia of Ajia commended the activities of Oyo state command of Vigilante Group of Nigeria ( VGN) in community policing.

redpajama_set_name: RedPajamaCommonCrawl


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Independent media's truth-telling campaign is exposing Congress, forcing many politicians to RETIRE – Brighteon.TV
Ann Vandersteel talked about the mass resignations in Congress on the Nov. 19 episode of her show "Steel Truth" on Brighteon.TV. She said that this is possibly a result of independent media relentlessly reporting on Congress' crimes.
A record number of incumbent members of Congress have announced their intention to retire from politics entirely. According to Vandersteel, this wave of mass resignations in Congress can be attributed at least partially to the hard work of independent media outlets and programs like her own.
"Let's talk about who's dropping out, shall we? Because things are starting to change," said Vandersteel. "I think the demons, the cabal, the RICO crime institute known as our federal government, also known as the domestic terrorists in this country, recognize that there is a real problem, that they are being exposed because of shows like this and others, that you're looking at record numbers of incumbents retiring from public office."
The notable members of Congress who are giving up on politics include several senators, such as Sens. Richard Burr of North Carolina, Pat Toomey of Pennsylvania, Rob Portman of Ohio, Roy Blunt of Missouri and Patrick Leahy of Vermont.
In the House of Representatives, Vandersteel took notice of the retirement announcements of Reps. Jackie Speier of California, Adam Kinzinger of Illinois, Michael Doyle of Pennsylvania, David Price of North Carolina and John Yarmuth of Kentucky.
"These are all folks who are saying, 'You know what? Calling it quits from public office. Going to walk away,'" said Vandersteel. "Probably because … there's a big dumpster fire on the Hill, it's burning down and they know it and they don't want to get caught in the fire."
Democratic retirements make Republican takeover of Congress more likely
As of Nov. 18, 26 members of the House have declared their intention to not seek re-election to their seats. Of those, 16 are Democrats and 10 are Republicans.
Of the Democrats, 10 have declared their intention to retire from politics entirely. Three are seeking seats in the Senate, one is running for governor and two others are running for other offices. (Related: Prediction: 2021 election results mean GOP could 'comfortably take back' House and Senate in 2022.)
In comparison, just 10 Republicans have announced their intention to not seek re-election – four will retire from politics, another four will seek a seat in the Senate and one each to run for governor or another office.
The latest Democrat to announce that he would not be seeking re-election is Rep. G.K. Butterfield, who has served as the representative for North Carolina's first congressional district since 2004.
The massive number of Democratic incumbents announcing their retirement, uncertainty about redistricting and President Joe Biden's sagging approval ratings add to the many other concerns the party has about maintaining its very slim majority in the House and the Senate. This is the most fragile majority the Democrats have had in the House in eight decades.
The leaders of the Republican Party are very confident that they will win back their majorities in both houses of Congress.
"We're going to take back the Senate, absolutely," said National Republican Senatorial Committee Chair Sen. Rick Scott of Florida. "We're going to do unbelievably in 2022 because we have the right message."
The former governor of Florida pointed out that the party's achievements in this year's elections – particularly in Virginia, as well as the massive ground it gained in solidly blue New Jersey – were historic. The gubernatorial election in Virginia is being read by the GOP as a key barometer ahead of next year's midterms.
Longtime Senate Republican leader Sen. Mitch McConnell of Kentucky said: "The fall of '22 is likely to be a very good election for Republicans… I think the wind is going to be at our back in both the House and Senate."
"In a cycle like this, no Democrat is safe," said National Republican Congressional Committee Chairman Rep. Tom Emmer of Minnesota.
"If you're a Democrat and President Biden won your seat by 16 points, you're in a competitive race next year," said House GOP leader Kevin McCarthy of California, emphasizing that the party can take even supposedly safe seats. "You are no longer safe."
Watch the entirety of the Nov. 17 episode of "Steel Truth" with Ann Vandersteel below. She brings on multiple guests on this episode, including John Mills, Tracy Ellis, Chris Burgard, Nick Searcy and Drs. Mark and Michele Sheerwood.
"Steel Truth" with Ann Vandersteel airs every Wednesday from 8-10 p.m. on Brighteon.TV.
Learn more about the collapse of the Democratic Party by reading the latest articles at JusticeDemocrats.news.
Ballotpedia.org
Axios.com
Tagged Under: 2022 election, Ann Vandersteel, Brighteon.tv, Congress, corruption, deception, democrats, elections, expose, politics, Republicans, retirement, Senate, Steel Truth


text:
Q: jquery-function doesn't show anything I'm trying to create a random generator and on another page if found a hint, that this would be easy using jQuery, so I tried the following.

  <title>hello</title>

it should work like this:
it loads a document with several lines of text ans splits it up at line break. this should be stored in an array and a random line should be displayed on the website.
My first idea was to write the text directly into an array but I thought loading it would be more efficient for the website.
Thanks for answering
PS: there isn't a error-message like "Error on this page" when the browser runs it.
Final Edit:
Thanks for helping!!!
Now it works.
Here's the solution:

        <title>hello</title>

A: You need to put document.write() inside your function(msg) as AJAX is asynchronous and load is using AJAX, so document.write() doesn't wait until load is finished calling your anonymous function
   $(document).ready(function() {
    $.get("hello.txt", function(msg) {
        var textArray = msg.split("\n");
        var zufall = Math.round ( ( textArray.length - 1 ) * ( Math.random() ) );
        $('body').append('
' + textArray[zufall] + '
');
    });
   });

EDIT:
I've just noticed you haven't included your jquery library o_O
Add the following above your

A: NiftyDude is right that you've put your document.write call outside the scope of your document.ready function. Also:

*

*It's also almost always a bad idea to use document.write. In this case you're waiting for an AJAX call to complete before using it, which means you're guaranteeing the document.write will overwrite the entire page body.

*You're using $('body').load, which is inappropriate in this case--you'll be adding text to the body manually.

Here's a fix:

  <title>hello</title>

 >

A: Try this alternate solution
$(document).ready(function() {
    $.ajax({
        url: "hello.txt",
        type: "GET",
        dataType: "text",
        success: function(data) {
            textArray = data.split("\n");
            zufall = Math.round ( ( textArray.length - 1 ) * ( Math.random() ) );
             document.write('
' + textArray[zufall] + '
');
        }
    });
});

Also make sure you have included the jquery file.

redpajama_set_name: RedPajamaStackExchange


text:
Category Archives: Opinion
Attacks on consumers mounting, over arbitration
In an amazingly lopsided editorial, the Albuquerque Journal published this hit piece, slamming the Consumer Financial Protection Bureau for its gutsy work to restore your ability to fight back in court, as a consumer, by joining forces with other consumers who have also been victimized by crooks who engage in illegal practices:
Albuquerque Journal editorial
Here's the letter to the editor I sent them, in response. However, it won't be too surprising if it doesn't appear in print — for reasons you can readily guess:
Funny — this newspaper didn't object when the car dealers got a special exemption from the Federal Arbitration Act, that allows them to sue anyone they please. Since then, they have sued auto manufacturers, the federal government, their customers, and each other, and somehow you are fine with that, but apparently think their customers do not deserve to have the same access to the courts.
When Congress restored the right to go to court, for car dealers, the National Automobile Dealers Association wrote to members of Congress and promised not to oppose restoring the same rights to car buyers. Then they turned around and killed a bill that would have done exactly that.
If consumers don't win back our rights through the CFPB's rulemaking, then it looks like we will have to resort to free market solutions, like not buying another car from a dealer until we have the same legal protections they do.
Here's the letter the car dealers sent to Members of Congress
And — in case you haven't already seen enough hypocrisy in this battle, here's what Republican Senator Chuck Grassley of Iowa had to say, in favor of the legislation he authored, giving car dealers a special exemption from being forced to arbitrate their claims, in order to purchase a franchise to sell cars:
"While arbitration serves an important function as an efficient alternative to court, some trade-offs must be considered by both parties, such as limited judicial review and less formal procedures regarding discovery and rules of evidence. When mandatory binding arbitration is forced upon a party, for example when it is placed in a boiler-plate agreement, it deprives the weaker party the opportunity to elect another forum. As a proponent of arbitration I believe it is critical to ensure that the selection of arbitration is voluntary and fair…Unequal bargaining power exists in contracts between automobile and truck dealers and their manufacturers. The manufacturer drafts the contract and presents it to dealers with no opportunity to negotiate…The purpose of arbitration is to reduce costly, time-consuming litigation, not to force a party to an adhesion contract to waive access to judicial or administrative forums for the pursuit of rights under State law."
Senator Grassley also said:
"This legislation will go a long way toward ensuring that parties will not be forced into binding arbitration and thereby lose important statutory rights. I am confident that given its many advantages arbitration will often be elected. But it is essential for public policy reasons and basic fairness that both parties to this type of contract have the freedom to make their own decisions based on the circumstances of the case."
Couldn't have said it better myself. So how come he and his colleagues in the House have changed their tune, when it comes to consumers?
Could it be that Sen. Grassley and the Republican Congress rely on campaign contributions from Wall Street crooks who pass on a tidy portion of the $$ they extract from consumers, via the Rip-off TAX? Hmmmmm….
Posted in Auto Industry Politics, Auto lending scams, Auto realiity check, Car Buyers: Beware, Car Dealers' Politics, Opinion	| Tagged Albequerque Journal, arbitration, campaign contributions, car dealers, CFPB, Chuck Grassley, Congress, consumer protection, court case, lawsuit, National Automobile Dealers Association, Ripoff, Ripoff clause, Senator Grassley, Wall Street
New York's Julie Menin: Tackling Predatory Car Lenders
New York's Commissioner of Consumer Affairs, Julie Menin, is determined to protect New Yorkers from predatory auto lending practices. Desperate used car buyers have been complaining to the agency, after they were cheated by unscrupulous car dealers who charged exorbitant interest rates for cars that often broke down soon after purchase, leaving them with ruined credit, deeper in debt, and without wheels.
According to the New York Times, auto loan debts sink many New Yorkers financially, averaging more than $12,000 — a burden that can prove impossible on an average annual income of just $36,000. Plus dealers commonly tack on high-priced add-ons that inflate the loans, without adding any value.
In response, the Department of Consumer Affairs is developing a "municipal auto loan initiative," to allow troubled borrowers to get auto loans directly from a number of lenders on more consumer-friendly terms. This innovative approach promises to provide New Yorkers with lower-cost, less risky access to the cars they need to get to work.
The Department is insisting that interest rates on the loans be fixed, at 16% or less, and that any application fees may not exceed $25.
CARS wishes New York and its courageous pro-consumer Commissioner Julie Menin great success. We hope that this innovative new program thrives and helps lift up thousands of New Yorkers who would otherwise fall prey to dealers itching to exploit them.
New York Times: New York City Starts Car Loan Program to Curb Abusive Practices
Posted in Consumer Champions, Opinion, Predatory auto lending, Used Car Scams, Used Lemons	| Tagged auto lending, auto loans, car dealer, car dealers, Commissioner of Consumer Affairs, Julie Menin, New York, predatory auto lending, used car lemons, used cars
CarMax – Too Risky for Wise Investors?
Thinking of investing in CarMax? You may want to take a close look at their breathtakingly risky practice of selling unsafe, recalled cars to consumers.
CarMax is already under fire from consumer groups, faces potential action by the Federal Trade Commission, and has been repeatedly exposed in undercover investigations by TV news organizations, including ABC's 20/20, over its sales of unsafe, recalled cars to consumers.
Here's the rub: CarMax advertises that all their cars must pass a "rigorous 125+ point inspection" before they can be sold as "CarMax Quality Certified" cars. But how can a car with a killer defect possibly pass a rigorous inspection and meet their standards?
Despite the mounting scrutiny, CarMax recklessly persists in selling "CarMax Quality Certified" unsafe, recalled cars at retail to consumers. Case in point: Even when competitors like AutoNation have wisely announced their decision to cease selling used cars with unrepaired Takata air bags, CarMax continues to sell them anyway.
Defying common sense and responsible business practices, CarMax somehow seems unable to bring itself to stop selling consumers cars with the notoriously defective air bags, which can explode on impact, hurling shrapnel at the driver and front-seat passenger's face and neck.. In cases that are making global headlines, the defective air bags have caused serious injuries, including blindness, while other hapless victims have bled to death.
This particular defect remains the focus of Congressional investigations in the U.S. Senate and House of Representatives. Takata also faces possible legal action by the National Highway Traffic Safety Administration, and by the US Department of Justice.
So — what does AutoNation know and take into account that CarMax doesn't seem to grasp?
Is CarMax waiting for a total PR catastrophe, before they stop making that added bit of profit by selling lots of unsafe, defective, recalled cars to consumers, instead of having them repaired or selling them for a somewhat lower price, at wholesale?
Whatever CarMax's motivation, wise investors may wish to rethink the company's self-inflicted level of exposure.
Posted in Auto safety tips, Car Buyers: Beware, Car Facts, Opinion, safety recall alert, Safety recalls, Safety Recalls, Used Car Scams, Used Lemons	| Tagged 20/20, ABC, air bags, auto safety recalls, CarMax, CarMax investor call, CarMax Quality Certified, Chrysler, deceptive advertising, defective air bags, exploding air bags, Federal Trade Commission, Fiat, Ford, Ford Motor Company, Ford recall, FTC, GM, GM recall, Honda, investment, investments, investor, investors, lemon car, lemons, National Highway Traffic Safety Administration, NHTSA, Nissan, recalled cars, safe cars, safety defects, safety recall, Takata air bags, Toyota, unsafe cars, used cars
"Regional" auto safety recalls place military families at risk
The refusal by Takata and some manufacturers to expand the safety recall of defective, exploding air bags to cover the entire nation is jeopardizing the safety of many of America's military families.
If you are a member of the Armed Forces, under Federal law, you are allowed to register your car in your official state of residence. Regardless where you are stationed, or the state where you and your family members are actually driving your car.
Auto manufacturers use data from RL Polk to identify owners of recalled vehicles and send them notices. But that data is based on where their vehicles are registered.
So if you are serving in the military, and register your car in New York, but are stationed in a high-humidity state like Florida, you may not receive the safety recall notice for your car. Even though Honda, Toyota, and other manufacturers, as well as the air bag supplier Takata, now acknowledge the air bags should be recalled in high-humidity states like Florida.
That's because, as far as RL Polk and the manufacturer are concerned, cars that are registered in New York are being driven in New York. They fail to account for the fact that if you're serving in the military, you may have registered your car in New York, but be stationed for years in a high-humidity state like Florida.
Florida is home to at least 29 Navy, Marine, Air Force, and Coast Guard bases, with over 50,000 active duty personnel. No doubt many of them have chosen to register their cars in their official state of residence, where the taxes may be lower, or it is simply more convenient.
What are Takata and auto manufacturers who installed the potentially deadly air bags in their cars doing to protect military families? It appears that the answer is nothing.
We hope that Members of Congress and the National Highway Traffic Safety Administration will pressure the manufacturers to ensure that members of the Armed Forces and their families are alerted to the hazards, and their cars are repaired, regardless where they are stationed, or where their cars are registered.
Better yet, all auto manufacturers and Takata should make the safety recall national, so all owners and their families can have the safety recall repairs performed, without having to pay out of pocket for the mistakes made by Takata and the manufacturers — and without being injured or killed by flying shrapnel from the defective air bags.
Posted in Auto safety tips, Car Buyers: Beware, Car Facts, Opinion, safety recall alert, Safety Recalls, scams against military	| Tagged air bags, Air Force, Coast Guard, defective air bags, exploding air bags, Honda, Marines, Military, Navy, safety recall, safety recalls, Takata, Toyota
Car dealers: "no love for liberals"
Keith Crain, publisher of Automotive News, the auto industry's leading trade publication, knows the auto industry inside out. His response to auto dealers' vitriolic reaction to Hillary Clinton's being invited to address the National Automobile Dealers Association:
"If anyone doubted that Hillary Clinton is a polarizing figure, all he had to do was look at the brouhaha caused by the National Automobile Dealers Association's selection of her as a keynote speaker at its convention next year in New Orleans…
The episode did demonstrate that the American new-vehicle dealer, who I've always felt is the last of the entrepreneurs in North America, basically has no love for liberals…"
Posted in Car Dealers' Politics, Opinion	| Tagged auto dealers, car dealers, Clinton, Hillary, Hillary Clinton, liberals, NADA
Good news for car buyers — Richard Cordray Confirmed!!
At last, in a huge, sweet victory for struggling consumers, Richard Cordray has been confirmed as Director of the Consumer Financial Protection Bureau. The CFPB, first envisioned by now-Senator Elizabeth Warren, was created to be a watchdog for consumers in the financial marketplace.
Democratic legislators in Congress created the agency when they voted for the Dodd-Frank Wall Street Reform Act, in the wake of the largest financial meltdown since the great Depression.
Since then, Republicans in Congress have tried repeatedly to weaken the agency and put it under their thumbs. That way, they could tie it in knots and keep it from doing its job. Republican senators had blocked Cordray's nomination for years, and relented only when Democratic Senators forced their hand, by threatening to change the filibuster rules that had allowed the Republican minority, at the behest of powerful, unscrupulous special interests, to block a vote on Cordray's nomination and other nominations to vitally important posts that directly affect the lives of ordinary Americans.
Cordray's confirmation is a huge victory for President Obama, US Senator Elizabeth Warren, the consumer and labor movements and allied groups, and other pro-consumer forces who joined together to form Americans for Financial Reform. And for all the individual consumers who petitioned Congress and spoke up for letting the agency do its job.
Republican members of Congress, and some Democratic members, led by US Rep. Gary Peters of Michigan, granted auto dealers a special exemption from the Consumer Financial Protection Bureau's authority, under the false claims that they don't engage in lending themselves (they do), and that they're not traded on Wall Street (many of them are).
However, the CFPB does have authority to police auto lending. It may also act to curb lenders from taking away consumers' Constitutional rights when they purchase a car, trapping them with "arbitration" clauses that keep them captive to a secret, private "arbitration" system that the lenders control.
This is welcome news indeed for the car-buying public. The agency has already issued a warning to auto lenders not to keep engaging in discriminatory lending practices that result in minority car buyers paying more for financing — not based on their creditworthiness, but on race.
The agency may also issue rules to curb auto dealer markups on interest rates, that cost car buyers over $25.8 billion annually in excessive interest charges pocketed by dealers and lenders — money that could be spent on technology that saves lives and helps clean the air and slow climate change.
If you have a complaint about auto lending, here's where to complain at the CFPB:
Consumer Financial Protection Bureau–file a complaint here
Posted in Auto Industry Politics, Car Dealers' Politics, Opinion	| Tagged arbitration, auto lenders, auto lending, CFPB, Consumer Financial Protection Bureau, consumer protection, Consumer Watchdog, Cordray confirmed, Richard Cordray, Senator Elizabeth Warren


text:
Q: Use Aspectj load-time weaving on provided dependencies? I was following the instructions in https://access.redhat.com/solutions/328513 to test out load-time weaving and I've got the example working without much of an issue.
My issue comes in when I want to weave a dependency that's already provided on the classpath as a JBoss module. I'm trying to gather some performance metrics from one of my project's dependencies but that dependency <scope>provided</scope> since it's already bundled with JBoss.
I can see weaving happen when I do something like @Pointcut("execution(* com.mypackage..*(..))") (so I know it's working on some level) but if I try @Pointcut("execution(* org.slf4j..*(..))") nothing gets woven.
I imagine there's something different happening for modules vs. war/ear deployments but I'm not familiar enough with the classloading process to make much headway. I would assume that since my aspects are provided as a global-module it would be loaded before any other module and then be able to affect their weaving but that doesn't appear to be the case.
Can anyone provide insight as to what's going on here?


text:
/ WWE
WOW: Women of Wrestling
WWE Backstage
Dark Side of the Ring
WWE SmackDown Here Comes the Pain
Fire Pro Wrestling World
Edge Talks Injury Recovery, What Made WrestleMania So Challenging, and Who He Wants To Wrestle Next
By Ryan Droste - July 11, 2020 03:57 pm EDT
There's no denying that 2020 has been a year of ups and downs for Adam Copeland, better known to WWE fans as Edge. Copeland started the year by making a surprise return to the WWE at the Royal Rumble in Houston and followed that up with two big matches with Randy Orton, one at WrestleMania and a sequel at Backlash. However, during that Backlash match, Copeland suffered a torn tricep that will keep the recently returned WWE star out of the ring for the next several months.
On Friday, ComicBook.com had a chance to speak with Copeland on a number of topics, including his new film Money Plane, as well as his outlook for future film projects (and even which comic book universe he would want to join if given the chance).
Today, in the final installment of our talk with Copeland, we discussed his return to wrestling and what the future holds for him in WWE. But first, we had to start off by asking how his recovery from the torn tricep is going and whether or not he knows what kind of timeline he is on for a return to the ring.
"I don't know, it was a month yesterday," Copeland said. "It's so hard to tell in that initial kind of two months where it's at and where everything is. I've always been happy with the fact that I rebound from injuries pretty quickly. I got back from a torn Achilles in six months which is kind of stupid. But you know I'm also older now so I don't know what that means. I've never had a surgery in my 40s so I don't know how quick I recover anymore, I guess is what I'm saying. So I don't know. I honestly don't know. One thing I have learned is rather than rushing back I need to listen to my body and I need to listen to my body more I think.
"Even with the Backlash match, my arm was sore going into it but I didn't realize, I didn't think anything was going on, it was just a little sore. Okay, well that makes sense. When I got the surgery the doctor said there was a pretty good chance it was partially torn going into the match. I didn't know that, I just thought my elbow is a little sore. But when you're a wrestler, stuff gets sore, that's what happens. So I just need to listen more I guess. Back to the point of how long? I don't know I'm just going to listen to my body and truly listen to my body, make sure I have self care, which I never really paid attention to before. Whether that entails yoga, cold plunges, saunas, whatever that is, I just need to do more of it, especially being 46 now."
(Photo: WWE)
When Copeland is fully recovered, he plans on returning to the ring and continuing the odds-defying comeback that he embarked on earlier this year. Copeland was forced to retire in April 2011 at the age of 37 due to neck injuries. However, Copeland's neck recovered over the years and he was medically cleared to return to the ring last year. That journey back to the ring was documented in a fantastic edition of the WWE 24 documentary series on the WWE Network earlier this year.
One thing is certain from talking to Copeland: he can't wait to get back into the ring and has a long list of competitors that he would like work with.
"It's super exciting. One of the main reasons I wanted to come back is really to try and help a new generation of guys who I can get in there with and have some fun with and hopefully teach too," he explained. "I was really really fortunate that I was able to get in with the Ric Flairs and the Shawn Michaels and the Undertakers and the Jerry Lawler and the Terry Funks and the Dory Funks and the Tom Prichards. All of these names that helped me, Bad News Brown, Rick Martel, they all helped me. It was their experience that helped me. So when I look at it and I look at this whole new crop of talent, I just think hey maybe I can help some of these guys. That's super exciting.
"That being said, it had to start with Randy (Orton) because I had to find my comfort level and see where I was at, see if I could still truly pull this off at the level that I wanted. With him as the opponent, I knew, A, he'd be able to test me. But that he's such a pro. I needed for my own confidence to get in with somebody that I know so well first. So I think we need to see that trilogy through, that needs to happen.
"Then, man, it's wide open. I'd love to wrestle everybody. If I look at NXT. I look at Finn Balor, I'd love to get in there with him, Damien Priest, Keith Lee, Johnny Gargano, Ciampa, there's so much talent down there. I'd love to show up at a TakeOver. Then I look at Raw and again there's just so many talented people so it's Aleistar Black, it's Andrade, and Garza, the Viking Raiders, Ricochet, and Cedric (Alexander)...And then I look at Smackdown and I say, okay well Reigns has got to happen and back to Raw, Rollins has got to happen, and then there's AJ (Styles), then there's Cesaro and there's Nakamura, get back in there with Sheamus again, Drew (McIntyre). I mean, it's really wide open and that's super exciting. It is a really really exciting thing. I also love the idea of not just the matches but the promos and trying to help some talent discover new layers and new places to go with their character in the context of promos too. That's all really fun stuff."
When Copeland returned to the ring at the Royal Rumble in Houston, there were over 40,000 fans present. Fast forward to his next match at WrestleMania 36 in April, and he's wrestling in front of an empty WWE Performance Center. The same goes for Backlash in June, no fans.
"It is super challenging (wrestling with no crowd). I'd like to say oh yeah, it's no problem. But it is challenging on so many levels. I think it's challenging for the announcers. When do we lay out? When do we talk? It's a different thing that we haven't had to deal with before. I think now everyone's kind of finding the pocket of what it is. But initially it was just so unheard of, how do you do this? How do you do it right? How do you do it wrong? I don't think there is a right or wrong, you just got to start throwing spaghetti at the wall and see what sticks," Copeland explained.
He continued, "That's where you get a Boneyard Match. It's like, that was great. Okay, we can do that. Okay well we'll have a little bit more forgiveness from the fan base with things that clearly are shot cinematically. It's a difficult prospect, it really is. I can't wait until audiences are back. It's just, honestly it's so much more fun. As a performer, as a live performer, as a wrestler, you feed off of those reactions. When those reactions aren't there, it's still fun, it's still the dream gig, but that's what you work for is those reactions. When you don't hear it it can kind of take you out of it a little bit. It hurts a lot more too (not having adrenaline). You get your natural adrenaline and survival mode but it's still just not the same as that roar or when you know you've got them in the palm of your hand. That's just such an amazing feeling.
"So I can't wait for that because the Rumble was just so great and it felt so good. Just hearing and feeling that audience again and in that realm, then you go to silence off of that. The Rumble felt like, all right I made it to the top of Everest, nine and a half years back, that baseball stadium reaction, and then the next match is in front of no one. So it's strange. But, you have to just make the best and try to pull the positives wherever you can. That's I think what the industry as a whole has tried to do."
Copeland's match with Randy Orton at WrestleMania 36, a "Last Man Standing Match," was initially supposed to be held at Raymond James Stadium in Tampa in front of over 65,000 fans. Just under three weeks before the show was to take place, WrestleMania had to be moved to the WWE Performance Center in Orlando due to the COVID-19 pandemic. Without fans present, the Edge vs. Orton match had to change in structure considerably. What we ended up getting was a match fought backstage all over the WWE Performance Center, rather than a bout that would have primarily been fought out in front of a screaming crowd at ringside in Tampa.
We asked if it was challenging for he and Orton to have to rework everything they had planned for the match in such a short amount of time.
"It was," Copeland acknowledged. "You know, I mean you hope your first Mania back in nine years would be in front of an audience but, again, you have to adapt and make do. It's all you can do. It was also like almost until the hour (of the show) we had to keep changing and adapting because the schedule, there was no fixed schedule. By the time we were actually filming our match it was like, I don't know, four in the afternoon so it was still sunlight. We had come up with a lot of ideas to go outside and onto the roof and these drone shots and all these things that just weren't possible because when it was airing during WrestleMania it wouldn't have coincided (with the time of the show's airing). So those plans had to get scrapped.
"But we didn't know, basically, until we were about to film. We're looking at the matches being filmed and we're like, okay, is it going to be dark? Is it going to be dark yet? Uh oh, it's not going to be dark (when they filmed the match). So up until last minute you just have to go okay, well this is what we have on our plate and this is how we have to figure this match out, which can be difficult. You got to be on your toes and be ready. That was WrestleMania this year."
If you missed it, don't forget to check out part one of our interview with Adam Copeland where he discusses his role in Money Plane, as well as how filming that role coincided with his training for a return to WWE. You can watch Money Plane on most digital platforms, including Amazon Prime and Apple.
Part two of our interview covered Copeland's ideal super hero roles and how he almost landed the role of Marvel's Cable, which you can read at this link.
Media: Please credit ComicBook.com and Ryan Droste when using quotes from this article.
NXT and AEW Dynamite's Jan. 20 Full Cards: Jon Moxley's Return, Fight Pit Match
Hangman Page Turns Down Joining The Dark Order on AEW Dynamite
WWE's Adam Pearce Clarifies Bizarre New Rule About the Royal Rumble
The Undertaker Explains Why He Struggles to Enjoy the Current WWE Product
NXT's Mercedes Martinez Reveals Why She Departed Retribution
Chad Gable Confirms Jason Jordan is Attempting a WWE Comeback
NXT's Mercedes Martinez Talks Dusty Rhodes Classic and Setting Her Sights on Io Shirai


text:
New Pedestrian Crossing
by News Staff | Sep 25, 2019 | News
There is a new crossing light for pedestrians. This handicap accessible crossing is located on North Pebble Beach Boulevard in front of the Community Association's Administration Building. Yield for pedestrians. Be prepared to stop when someone is in the crosswalk area.
DECEMBER 2021 NEWS is HOT off the PRESS!
Dec 1, 2021 | Hot Off The Press, News
In this issue… Ring in the December holidays with the annual Golf Cart Parade, celebrate 60 Years of SCC, set sail on America's Tall Ship, get to know some local clubs, remember a tireless volunteer who made a big difference, meet a local war...
SCC Celebrates 60 Years
Nov 30, 2021 | Features
SCC Celebrates 60 Years By Kai Rambow Sun City Center recently celebrated its 60th anniversary. The event, spread out over a Sunday afternoon, had the added bonus of reuniting people. "It's been almost two years since we saw you," was a...
Celebrate The Opening Of SCC
Celebrate The Opening Of SCCA Special Invitation From The History Society, December 30By Ilona Merritt "Time flies when you're having fun" … It seems like just yesterday that SCC celebrated our 50th anniversary. And what fun we had! Now, ten...
It's a pretty big deal
It's a pretty big deal By E. Adam Porter Editor, News of SCC & South County I heard a whispered conversation in the dining room and pretended not to notice, busying myself preparing the evening meal. It was beef stew night, so the slow...
"Together Again!" At the Holiday Golf Cart Parade
Nov 20, 2021 | News
"Together Again!" At the Holiday Golf Cart Parade By Diane M. Loeffler Kick off the holiday season by attending the December 4 SCC Holiday Golf Cart Parade. The parade starts at 10 a.m. in the parking lot just south of the Security Patrol...
NOVEMBER 2021 NEWS is HOT off the PRESS!
Oct 29, 2021 | Hot Off The Press, News
In this issue… Enjoy our FallFest coverage, including nearly three pages of photos, learn the history of the popular Bandstand concerts, read our interviews with the candidates for SCC Community Association Board of Directors, get the latest...
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