Patent Application: US-201213717691-A

Abstract:
disclosed are compositions of matter , uses , and therapeutic interventions directed towards modulation of stem cell activity in a mammal . in particular the invention provides compositions whose end result modulates health , wellbeing , longevity and function of organ systems . within the scope of the invention are biologically active extracts , components thereof , and compositions made comprising such .

Description:
embodiments of the present invention are described below . it is , however , expressly noted that the present invention is not limited to these embodiments , but rather the intention is that modifications that are apparent to the person skilled in the art and equivalents thereof are also included . the invention teaches various compositions of herbs , vitamins and natural products for stimulation of stem cell numbers in circulation . therapeutic effects of augmenting circulating stem cell numbers derived from data demonstrating that augmentation of said numbers results in a beneficial effect in degenerative conditions such as stroke , ischemic cardiomyopathy , critical limb ischemia , and myocardial infarction . in the area of tissue regeneration , one application that comes to mind is mobilization of bone marrow stem cells in order to increase the amount of cells that enter the area of tissue injury . for example , it is known in many situations that injured tissue releases chemotactic signals that induce “ homing ” of stem cells . on example of this is after myocardial infarction there is a documented rise in plasma vegf which is associated with stem cell mobilization and entry into the peripheral circulation , theoretically on the way to the damaged myocardium [ 39 - 42 ]. such injury induced stem cell mobilization has also been documented in stroke [ 32 , 33 ], liver failure [ 43 ], renal ischemia reperfusion injury [ 44 ], and transplantation [ 45 ]. now the question is , if tissue injury can promote accelerated mobilization of stem cells to the injured area , and if in some cases more mobilization equals more protection from pathology [ 32 , 33 ], then would it not make sense to simply use g - csf administration to mobilize bone marrow stem cells with the idea of augmenting existing natural processes ? unfortunately numerous toxicities and expense limit this approach in one particular embodiment , the therapeutic composition provided is a mixture of ashwagandha , milk thistle , vitamin d3 , fucoidan and garcinia indica . said ingredients can be mixed at a ratio determined by one skilled in the art to elicit the desired amount of stem cell mobilization . mobilization of stem cells may be assessed by techniques known in the art , said techniques include flow cytometry to assess number of cells with a size , density and / or phenotypic profile of the desired stem cell population . it is apparent to one of skill in the art that if augmented numbers of hematopoietic stem cells are desired , then the practitioner may assess levels of cd34 , cxcr4 , cd133 , stem cell antigen or aldehyde dehydrogenase bright cells . additionally , methods are known in the art to assess circulating stem cell numbers based on ability of said cells to generate differentiated progeny in vitro . for example , if the practitioner of the invention is seeking to identify endothelial progenitor cells ( epc ), numbers of these cells in circulation may be assessed by flow cytometry to identify markers such as vegfr2 , or alternatively , to identify ability of the cells to form endothelial colonies in vitro . said endothelial colonies may be quantified by morphology or ability to uptake acetylated ldl . for the purposes of the current invention , within the definition of the term “ stem cell ” we include not only hematopoietic , endothelial , and mesenchymal stem cells , but also progenitor cells that have been committed to a certain lineage , for example , myeloid progenitor cells or lymphoid progenitor cells . other tissue committed cells in circulation are also covered by our definition of the word “ stem cells ”. in one specific embodiment , the therapeutic composition contains approximately 5 - 3000 mg ashwagandha , 50 - 10000 iu vitamin d3 , 10 - 10000 mg fucoidan , and 5 - 5000 mg of garcinia indica . in one specific embodiment , the therapeutic composition contains approximately 50 - 300 mg ashwagandha , 500 - 2000 iu vitamin d3 , 100 - 1000 mg fucoidan , and 50 - 500 mg of garcinia indica . in another embodiment said therapeutic composition is comprised of approximately 100 mg ashwagandha , 1000 iu vitamin d3 , 500 mg fucoidan , and 250 mg of garcinia indica . in certain embodiments ingredients may be added or extracted . for example , in patients with known high levels of oxidative stress , such as dialysis patients , antioxidants may be added to the therapeutic composition . said antioxidants may be natural , synthetic , or recombinant . specific antioxidants are well known in the art and may be determined by experimentation . example antioxidants include flavanoids , genistein , 1 - carnosine ; carotenoid ; co - enzyme q10 , green tea or extract thereof , vitamin a , vitamin b , vitamin c , vitamin e , zinc , selenium , resveratrol , lipoic acid , chlorophyll , gogji berries and extracts thereof , fish oil , and a superoxide dismutase . the compositions of the present invention may be administered in combination with a nutraceutically acceptable carrier . the active ingredients in such formulations may comprise from 1 % by weight to 99 % by weight , or alternatively , 0 . 1 % by weight to 99 . 9 % by weight . “ nutraceutically acceptable carrier ” means any carrier , diluent or excipient that is compatible with the other ingredients of the formulation and not deleterious to the user . the embodiments of the compositions described in the invention can be formulated in any suitable product form . such product forms include , but are not limited to liquid , aerosol spray , cream , dispersion , emulsion , foam , gel , lotion , ointment , powder , solid and solution . the present compositions preferably include a vehicle . a useful vehicle is one that is medically acceptable for ingestion or topical application . useful vehicles may include , but are not limited to , one or more aqueous systems , glycerin , alcohols , fatty alcohols , fatty ethers , fatty esters , polyols , glycols , vegetable oils , mineral oils , water , fruit juices , cultured dairy products , ( e . g ., yogurt ), dairy products ( e . g ., milk ), carbonated or non - carbonated beverages , and mixtures of the aforesaid . the powder compositions of the invention may be conveniently incorporated into a variety of liquids or solid compositions including , but not limited to , powders and other solids , liquid beverages ( teas , mineral water , milk and other dairy products ), capsules , tablets , ointments , skin creams , personal care products , pastas , soups , nutrient bars , cookies , breads , and other bakery items for use in wound healing or treatment of other acute or chronic conditions of the epidermis , mixture of the ingredients ashwagandha , milk thistle , vitamin d3 , fucoidan and garcinia indica is formulated for topical administration . the vehicle for topical application may be in one of various forms , e . g . a lotion , cream , gel , ointment , stick , spray , or paste . these product forms can be formulated according to well known methods . they may comprise various types of carriers , including , but not limited to , solutions , aerosols , emulsions , gels , and liposomes . the carrier may be formulated , for example , as an emulsion , having an oil - in - water or water - in - oil base . suitable hydrophobic ( oily ) components employed in emulsions include , for example , vegetable oils , animal fats and oils , synthetic hydrocarbons , and esters and alcohols thereof , including polyesters , as well as organopolysiloxane oils . such emulsions also include an emulsifier and / or surfactant , e . g . a nonionic surfactant , such as are well known in the art , to disperse and suspend the discontinuous phase within the continuous phase . the topical formulation may contain one or more components selected from a structuring agent , a thickener or gelling agent , and an emollient or lubricant . frequently employed structuring agents include long chain alcohols , such as stearyl alcohol , and glyceryl ethers or esters and oligo ( ethylene oxide ) ethers or esters thereof . thickeners and gelling agents include , for example , polymers of acrylic or methacrylic acid and esters thereof , polyacrylamides , and naturally occurring thickeners such as agar , carrageenan , gelatin , and guar gum . examples of emollients include triglyceride esters , fatty acid esters and amides , waxes such as beeswax , spermaceti , or carnauba wax , phospholipids such as lecithin , and sterols and fatty acid esters thereof . the topical formulations may further include other components as known in the art , e . g . astringents , fragrances , pigments , skin penetration enhancing agents , sunscreens , etc . in other embodiments , the nutraceutical compositions comprising of ashwagandha , milk thistle , vitamin d3 , fucoidan and garcinia indica may also be formulated for administration parenterally , transdermally , or by inhalation . an injectable composition for parenteral administration typically contains the active compound in a suitable iv solution , such as sterile physiological saline . the composition may also formulated as a suspension in a lipid or phospholipid , in a liposomal suspension , or in an aqueous emulsion . the therapeutic properties of the various components of the composition have been previously described , however , utilization of these compositions for stimulation of stem cell function has not been reported . in the current invention , therapeutic compositions seem to be associated with additive / synergistic effects of the named ingredients to augment stem cell mobilization , as well as to stimulate function and inhibit stem cell inhibitory activities such as oxidative stress or inflammatory mediator production . ashwagandha administered at 500 mg three times per day has been reported by sriranjini et al to normalize , or partially normalize balance in patients with cerebellar ataxia . ( sriranjini et al . improvement of balance in progressive degenerative cerebellar ataxias after ayurvedic therapy : a preliminary report . neurol india . 2009 march - april ; 57 ( 2 ): 166 - 71 ). therapeutic effects at controlling viral hepatitis have been also reported for ashwagandha . when the herb was used in combination with two other natural ingredients in the proprietary composition livwin , a reduction of viral load was observed in patients with hepatitis b and c . interestingly , the study was performed in double blind , placebo controlled setting ( keche et al . efficacy and safety of livwin ( polyherbal formulation ) in patients with acute viral hepatitis : a randomized double - blind placebo - controlled clinical trial . int j ayurveda res . 2010 october ; 1 ( 4 ): 216 - 9 ). improvement in endurance in athletes was also reported by administration of ashwagandha . in a clinical study , sandhu et al ( effects of withania somnifera ( ashwagandha ) and terminalia arjuna ( arjuna ) on physical performance and cardiorespiratory endurance in healthy young adults . int j ayurveda res . 2010 july ; 1 ( 3 ): 144 - 9 ) demonstrated superior augmentation of exercise time as compared to placebo controls after administration of 500 mg of the herb twice a day . stimulation of immune modulatory activity was previously ascribed to the ashwagandha herb , however no clinical utilization in the context of therapeutics was performed . the immune modulatory activity was associated with type 1 immunity , which is currently believed to inhibit stem cell activity . thus the use of ashwagandha in the context of stem cell stimulation is counterintuitive in the context of the existing art . an indication that this herb may have potential to modulate the stem cell compartment was provided in a study by davis and kuttan ( immunopharmacol immunotoxicol . 1999 november ; 21 ( 4 ): 695 - 703 . effect of withania somnifera on cytokine production in normal and cyclophosphamide treated mice ). the investigators found that administration of an extract from the powdered root of the plant withania somnifera ( family : solanaceae ) enhanced the levels of interferon gamma ( ifn - gamma ) ( 75 . 87 pg / ml ), interleukin - 2 ( il - 2 ) ( 14 . 16 pg / ml ). in one embodiment of the invention , the nutraceutical composition is utilized as an adjunct to stem cell therapy . numerous types of stem cell therapies exist and are known in the art that may be utilized in combination with the current invention . for example , said nutraceuticals can be used in combination with autologous bone marrow stem cell therapy , as currently practiced using devices such as the harvest , arteriocyte , tissue genesis , or bio - met device . the following references have been referred to in the text . the entire content of each reference is incorporated herein . without limitation all of the cells , proteins , markers , assays , and methods can be used with the technology described herein and / or can be combined with the methods and materials described herein . 1 . patchen , m . l ., et al ., mobilization of peripheral blood progenitor cells by betafectin pgg - glucan alone and in combination with granulocyte colony - 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