Patent Application: US-201313734973-A

Abstract:
a method of treatment of cancer with a formulation of liposomally encapsulated glutathione , that is preferably used orally , increases the level of glutathione in tissues in order to prevent and reverse the metabolic changes in cells that results in the formation of the metabolic “ fuel supply ” that supports cancer cells , and without which the cells can die out . the method prevents the oxidative stress that damages normal support cells such as stromal fibroblast cells . by blocking the “ fuel supply ,” the invention can protect , prevent and reverse these cells from the steps of autophagy and mitophagy , that results in the cells decreasing the normal production of atp for energy and using aerobic glycolysis for energy production . the use of oral liposomally encapsulated glutathione will maintain the presence and normal function of caveolin in fibroblast and other cells , thus preventing their conversion to autophagic tumor stromal cells .

Description:
the methods of manufacture described in keller et al u . s . pat . no . 5 , 891 , 465 , u . s . pat . no . 6 , 610 , 322 , and u . s . pat . no . 6 , 726 , 924 and u . s . provisional application no . 60 / 597 , 041 by this inventor are adopted herein and into the modes of this invention and can be applied to the examples without undue experimentation . liposomal formulations preferred in this invention can be purchased from biozone , inc . of pittsburgh , calif . reduced glutathione can be b purchased from sigma - aldrich of st . louis , mo . or from kyowa hakko usa , inc ., 767 3 rd ave . no . 9 , of new york city , n . y . 10017 with a western regional office at 85 enterprise , suite 430 , aliso viejo , calif . 92656 . liposomally encapsulated reduced glutathione can be purchased from your energy systems , llc , 555 bryant st ., suite 305 , palo alto , calif . 94301 . liposomal glutathione drink or spray 2500 mg per ounce or form suitable for encapsulation or gel a lipid mixture having components lecithin , and glycerin were commingled in a large volume flask and set aside for compounding . hydroxylated lecithin is the preferred ingredient . in a separate beaker , a water mixture having water , glycerin , glutathione were mixed and heated to , but not more than , 50 . degree . c . the water mixture was added to the lipid mixture while vigorously mixing with a high speed , high shear homogenizing mixer at 750 - 1500 rpm for 30 minutes . the homogenizer was stopped and the solution was placed on a magnetic stirring plate , covered with parafilm and mixed with a magnetic stir bar until cooled to room temperature . normally , a spoilage retardant such as potassium sorbate or bht would be added . the solution would be placed in appropriate dispenser for ingestion as a liquid or administration as a spray . analysis of the preparation under an optical light microscope with polarized light at 400 × magnification confirmed presence of both multilamellar lipid vesicles ( mlv ) and unilamellar lipid vesicles . the preferred embodiment includes the variations of the amount of glutathione to create less concentrated amounts of liposomally encapsulated glutathione . the amount of glutathione added to the formulation may range from 3 . 3 % to 8 . 5 % or higher . the methods of manufacture described in keller et al u . s . pat . no . 5 , 891 , 465 , u . s . pat . no . 6 , 958 , 160 and u . s . pat . no . 7 , 150 , 883 and u . s . provisional application no . 60 / 597 , 041 are incorporated in this description . concentrations of liposomally encapsulated glutathione from 3 . 3 %, 4 %, 5 %, 6 %, 7 %, 7 . 5 %, 8 %, 8 . 5 % or 9 % liposomally encapsulated glutathione may be formed and utilized for dosing by decreasing the amounts of glutathione and preplacing the material with an increase in the sterile water concentration . liposomally encapsulated reduced glutathione drink or spray 2500 mg per ounce or form suitable for encapsulation or gel : in %, according to w / w : deionized water 75 , glycerin 15 . 00 , lecithin 1 . 50 , extract potassium 0 . 10 sorbate glutathione 8 . 5 ( reduced ) a lipid mixture having components lecithin , ethyl alcohol and glycerin were commingled in a large volume flask and set aside for compounding . hydroxylated lecithin is the preferred ingredient . in a separate beaker , a water mixture having water , glycerin , glutathione were mixed and heated , but not more than , 50 . degree . c . the water mixture was added to the lipid mixture while vigorously mixing with a high speed , high shear homogenizing mixer at 750 - 1500 rpm for 30 minutes . the homogenizer was stopped and the solution was placed on a magnetic stirring plate , covered with parafilm and mixed with a magnetic stir bar until cooled to room temperature . a spoilage retardant such as potassium sorbate or bht would be added . the solution would be placed in appropriate dispenser for ingestion as a liquid or administration as a spray . analysis of the preparation under an optical light microscope with polarized light at 400 × magnification confirmed presence of both multilamellar lipid vesicles ( mlv ) and unilamellar lipid vesicles . the preferred embodiment includes the variations of the amount of glutathione to create less concentrated amounts of liposomally encapsulated glutathione . the amount of glutathione added to the formulation may range from 3 . 3 % to 8 . 5 % or higher . the methods of manufacture described in keller et al u . s . pat . no . 5 , 891 , 465 , u . s . pat . no . 6 , 958 , 160 and u . s . pat . no . 7 , 150 , 883 and u . s . provisional application no . 60 / 597 , 041 are incorporated in this description . concentrations of liposomally encapsulated glutathione from 3 . 3 %, 4 %, 5 %, 6 %, 7 %, 7 . 5 %, 8 %, 8 . 5 % or 9 % liposomally encapsulated glutathione may be formed and utilized for dosing by decreasing the amounts of glutathione and preplacing the material with an increase in the sterile water concentration . embodiment two of the invention includes the incorporation of the fluid liposome ( such as that prepared in example 1a ) into a gelatin based capsule to improve the stability , provide a convenient dosage form , and assist in sustained release characteristics of the liposome . the present embodiment relates to the use of glutathione in the reduced state encapsulated into liposomes or formulated as a preliposome formulation and then put into a capsule . the capsule can be a soft gel capsule capable of tolerating a certain amount of water , a two - piece capsule capable of tolerating a certain amount of water or a two - piece capsule where the liposomes are preformed then dehydrated . the liposome - capsule unit containing biologically encapsulated material can be taken in addition to orally , used for topical unit - of - use application , or other routes of application such as intra - ocular , intranasal , rectal , or vaginal . the composition of examples 1 and 2 may be utilized in the encapsulated embodiment of this invention . gelatin capsules have a lower tolerance to water on their interior and exterior . the usual water tolerance for a soft gel capsule is 10 % on the interior . the concentration of water in a liposome formulation can range from 60 - 90 % water . an essential component of the present invention is the formulation of a liposome with a relatively small amount of water , in the range of 5 - 10 %. by making the liposome in a low aqueous system , the liposome is able to encapsulate the biologically active material and the exposure of water to the inside lining of the capsule is limited . the concentration of water should not exceed that of the tolerance of the capsule for which it is intended . the preferred capsule for this invention is one that can tolerate water in the 15 - 20 % range . the methods described by keller et al , u . s . pat . no . 6 , 726 , 924 are incorporated in this description . components are commingled and liposomes are made using the injection method ( lasic , d ., liposomes , elsevier , 88 - 90 , 1993 ). when liposome mixture cooled down 0 . 7 ml was drawn into a 1 ml insulin syringe and injected into the open - end of a soft gelatin capsule then sealed with tweezers . filling of gel caps on a large scale is best with the rotary die method or others such as the norton capsule machine . liposomally encapsulated s - nitroso - l - glutathione ( gsno ) drink or spray 2500 mg per ounce or form suitable for encapsulation or gel a lipid mixture having components lecithin , and glycerin were commingled in a large volume flask and set aside for compounding . in a separate beaker , a water mixture having water , glycerin , glutathione were mixed and heated to , but not more than , 50 . degree . c . the water mixture was added to the lipid mixture while vigorously mixing with a high speed , high shear homogenizing mixer at 750 - 1500 rpm for 30 minutes . the homogenizer was stopped and the solution was placed on a magnetic stifling plate , covered with parafilm and mixed with a magnetic stir bar until cooled to room temperature . normally , a spoilage retardant such as potassium sorbate or bht would be added . the solution would be placed in appropriate dispenser for ingestion as a liquid or administration as a spray . analysis of the preparation under an optical light microscope with polarized light at 400 × magnification confirmed presence of both multilamellar lipid vesicles ( mlv ) and unilamellar lipid vesicles . the preferred embodiment includes the variations of the amount of glutathione to create less concentrated amounts of liposomally encapsulated glutathione . the amount of glutathione added to the formulation may range from 3 . 3 % to 8 . 5 % or higher the methods of manufacture described in keller et al u . s . pat . no . 5 , 891 , 465 are incorporated into this description or as described before may be used . embodiment number four of the present invention includes the creation of liposome suspension using a self - forming , thermodynamically stable liposomes formed upon the adding of a diacylglycerol - peg lipid to an aqueous solution when the lipid has appropriate packing parameters and the adding occurs above the melting temperature of the lipid . the method described by keller et al , u . s . pat . no . 6 , 610 , 322 is incorporated into this description . most , if not all , known liposome suspensions are not thermodynamically stable . instead , the liposomes in known suspensions are kinetically trapped into higher energy states by the energy used in their formation . energy may be provided as heat , sonication , extrusion , or homogenization . since every high - energy state tries to lower its free energy , known liposome formulations experience problems with aggregation , fusion , sedimentation and leakage of liposome associated material . a thermodynamically stable liposome formulation which could avoid some of these problems is therefore desirable . the present embodiment prefers liposome suspensions which are thermodynamically stable at the temperature of formation . the formulation of such suspensions is achieved by employing a composition of lipids having several fundamental properties . first , the lipid composition must have packing parameters which allow the formation of liposomes . second , as part of the head group , the lipid should include polyethyleneglycol ( peg ) or any polymer of similar properties which sterically stabilizes the liposomes in suspension . third , the lipid must have a melting temperature which allows it to be in liquid form when mixed with an aqueous solution . by employing lipid compositions having the desired fundamental properties , little or no energy need be added when mixing the lipid and an aqueous solution to form liposomes . when mixed with water , the lipid molecules disperse and self assemble as the system settles into its natural low free energy state . depending on the lipids used , the lowest free energy state may include small unilamellar vesicle ( suv ) liposomes , multilamellar vesicle ( mlv ) liposomes , or a combination of suvs and mlvs . in one aspect , the invention includes a method of preparing liposomes . the method comprises providing an aqueous solution ; providing a lipid solution , where the solution has a packing parameter measurement of p a ( p a , references the surface packing parameter ) between about 0 . 84 and 0 . 88 , a p v ( p v references the volume packing parameter ) between about 0 . 88 and 0 . 93 , ( see , d . d . lasic , liposomes , from physics to applications , elsevier , p . 51 1993 ), and where at least one lipid in the solution includes a polyethyleneglycol ( peg ) chain ; and combining the lipid solution and the aqueous solution . the peg chain preferably has a molecular weight between about 300 daltons and 5000 daltons . kinetic energy , such as shaking or vortexing , may be provided to the lipid solution and the aqueous solution . the lipid solution may comprise a single lipid . the lipid may comprise dioleolylglycerol - peg - 12 , either alone or as one of the lipids in a mixture . the method may further comprise providing an active compound , in this case glutathione ( reduced ); and combining the active compound with the lipid solution and the aqueous solution . the low molecular weight in the preferred embodiments more effectively deliver the liposomally encapsulated reduced glutathione in active reduced form as needed and thus result in the surprising effect of the invention . the absorption into cells is a particular advantage of the preferred embodiment of the invention . a topical cream or lotion containing reduced glutathione in a self - forming liposome sold under the brand name “ qusome ” ® by biozone laboratories , inc . of pittsburgh , calif . is another preferred embodiment . the qusome self - forming liposome can be formed containing reduced liposomally encapsulated glutathione in a concentration of 5 % reduced glutathione encapsulated in the liposome . most liposomes use energy provided as heat , sonication , extrusion , or homogenization for their formation , which gives them a high energy state . some liposome formulations can experience problems with aggregation , fusion , sedimentation and leakage of liposome associated material which this invention seeks to minimize and does minimize . the qusome is a more thermodynamically stable liposome formulation . the qusome self - forming liposome is self - forming at room temperature which that the mixing of the lipid and an aqueous lipid containing solution avoids alteration of the contents by heating . the resulting liposome is in a low free energy state so it remains stable and reproducible . the formulation of this embodiment is reviewed in example 3 . the methods of manufacture described in keller et al u . s . pat . no . 6 , 958 , 160 and u . s . pat . no . 7 , 150 , 883 are incorporated in this description . the most important details of that manufacturing are as follows : the lipids used to form the lipid vesicles and liposomes in the present formulations can be naturally occurring lipids , synthetically made lipids or lipids that are semisynthetic . any of the art known lipid or lipid like substances can be used to generate the compositions of the present invention . these include , but are not limited to , lecithin , ceramides , phosphatidylethanolamine , phosphotidylcholine , phosphatidylserine , cardiolipin and the like . such lipid components for the preparation of lipid vesicles are well known in the art , for example see u . s . pat . no . 4 , 485 , 954 , and “ liposome technology ”, 2nd ed , vol . i ( 1993 ) g . gregoriadis ed ., crc press , boca raton , fla . lipids with these properties that are particularly preferred in the present formulations include phospholipids , particularly highly purified , unhydrogenated lecithin containing high concentrations of phosphotidylcholine , such as that available under the trade name phospholipon 90 from american lecithin , or nattermann phospholipid , 33 turner road , danbury , conn . 06813 - 1908 . in formulating the liposomes , in one aspect , the invention includes a method of preparing liposomes . the method comprises providing an aqueous solution ; providing a lipid solution , where the solution has a p a between about 0 . 84 and 0 . 88 , a p v between about 0 . 88 and 0 . 93 , and where at least one lipid in the solution includes a polyethyleneglycol ( peg ) chain ; and combining the lipid solution and the aqueous solution . the peg chain preferably has a molecular weight between about 300 daltons and 5000 daltons . kinetic energy , such as shaking or vortexing , may be provided to the lipid solution and the aqueous solution . the lipid solution may comprise a single lipid . the lipid may comprise dioleolyglycerol - peg - 12 , either alone or as one of the lipids in a mixture . the method may further comprise providing an active compound ; and combining the active compound with the lipid solution and the aqueous solution . in another aspect , the invention includes a liposome suspension . the suspension comprises one or more lipids , where the lipids as an aggregate have a p a between about 0 . 84 and 0 . 88 , a p v between about 0 . 88 and 0 . 93 and a melting temperature of between about 0 to 100 degrees centigrade ; and where at least one lipid includes a polyethyleneglycol ( peg ) chain . the peg chain preferably has a molecular weight between about 300 daltons and 5000 daltons . the suspension may comprise a single lipid . the lipid may comprise dioleolylglycerol - peg - 12 . the suspension may further comprise an active compound , which may be selected from the group described above . in another aspect , the invention includes a composition for combining with an aqueous solution to form a liposome suspension . the composition comprises one or more lipids , where the lipids as an aggregate have a p a between about 0 . 84 and 0 . 88 , a p v , between about 0 . 88 and 0 . 93 and a melting temperature of between about 0 to 100 degrees centigrade ; and where at least one lipid includes a polyethyleneglycol ( peg ) chain . the peg chain preferably has a molecular weight between about 300 daltons and 5000 daltons . the composition may comprise a single lipid . the composition may comprise dioleolylglycerol - peg 12 . the composition may further comprise an active compound selected from the group above . the composition may be provided in a sealed container , where the container also contains an inert gas to prevent oxidative degradation . in another aspect , the invention includes a method of intravenously administering a therapeutic compound . the method comprises providing a composition including one or more lipids , where the lipids as an aggregate have a p a between about 0 . 84 and 0 . 88 , a p v between about 0 . 88 and 0 . 93 and a melting temperature of between about 0 to 100 degrees centigrade ; and where at least one lipid includes a polyethyleneglycol ( peg ) chain ; providing an active compound ; providing an aqueous solution ; combining the composition , compound and solution to form a liposome suspension ; and administering the liposome suspension intravenously . the method may further comprise providing kinetic energy to the liposome suspension . the method may also include providing the composition in a sealed container containing an inert gas . the peg chain preferably has a molecular weight between about 300 daltons and 5000 daltons . the composition may comprise a single lipid . the lipid may comprise dioleolylglycerol - peg - 12 . the active compound may be selected from the group above . in another aspect , the invention includes a method of solubilizing an active compound . the method comprises providing a composition including one or more lipids , where the lipids as an aggregate have a p a between about 0 . 84 and 0 . 88 , a p v between about 0 . 88 and 0 . 93 and a melting temperature of between about 0 to 100 degrees centigrade ; and where at least one lipid includes a polyethyleneglycol ( peg ) chain ; providing the active compound ; providing an aqueous solution ; and combining the active compound , the lipid and the aqueous solution to form a liposome suspension . the method may further comprise providing kinetic energy to the liposome suspension . the method may include providing the composition in a sealed container containing an inert gas . the peg chain preferably has a molecular weight between about 300 daltons and 5000 daltons . the composition may comprise , a single lipid . the lipid may comprise dioleolylglycerol - peg - 12 . the active compound may be selected from the group above . in another aspect , the invention includes a method of orally administering a therapeutic compound . the method comprises providing a composition including one or more lipids , where the lipids as an aggregate have a p a between about 0 . 84 and 0 . 88 , a p v between about 0 . 88 and 0 . 93 and a melting temperature of between about 0 to 100 degrees centigrade ; and where at least one lipid includes a polyethyleneglycol ( peg ) chain ; providing an active compound ; providing an aqueous solution ; combining the composition , compound and solution to form a liposome suspension ; and administering the liposome suspension orally in the form selected from the group comprising a two piece hard gelatin capsule , a soft gelatin capsule , or drops . peg - 12 glyceryl dioleate was obtained from global 7 ( new jersey ) for the following formulations . this can be substituted for the lecithin w / w % as needed to accomplish the formulation , or applied as set forth below . in the following formulations , the “ set percentage ” w / w % of reduced glutathione is selected from 3 . 3 %, 4 %, 5 %, 6 %, 7 %, 7 . 5 %, 8 %, 8 . 5 % or 9 % or amounts approximately to those percentages . spontaneous liposomes for intravenously administering therapeutic compounds or for a spray or drink a set percentage of reduced glutathione is dissolved in a sufficient amount of the solvent peg - 12 glyceryl dioleate , also called dioleolylglycerol - peg 12 , ( either referred to as “ pegdo ”) and gently mixed for about 5 minutes . a sufficient amount of pegdo should be about 10 % w / w . deionized water is slowly added to the solution . ingredients other than deionized water , the reduced glutathione and the pegdo may be added such as preferably 0 . 1 % w / w potassium sorbate and then the final amount of deionized water added is that amount which is necessary to have the percentages add up to 100 % w / w . taste or other flavor - masking ingredients could also be added before the deionized water is brought up to 100 % w / w . although taste ingredients can be added before or after the liposomal encapsulation formulation , the preferable mode is to add flavor or other taste masking ingredients after liposomal encapsulation formulation , and they may be ingredients such as corn syrup , honey , sorbitol , sugar , saccharin , stevia , aspartame , citrus seed extract , natural peppermint oil , menthol , synthetic strawberry flavor , orange flavor , chocolate , or vanilla flavoring in concentrations from about 0 . 01 to 10 %. the inventor has preferably used citrus seed extract . spontaneous liposomes for intravenously administered therapeutic compound and as a drug solubilization vehicle for use in spray or drink a set percentage of reduced glutathione is mixed with a sufficient amount of peg - 12 glyceryl dioleate , also called dioleolylglycerol - peg 12 , ( either referred to as “ pegdo ”) to bring the reduced glutathione into solution by vortexing and sonication for 10 minutes . a sufficient amount of pegdo should be about 5 % w / w . deionized water is added and gently mixed . ingredients other than deionized water , the reduced glutathione and the pegdo may be added such as preferably 0 . 1 % w / w potassium sorbate and then the final amount of deionized water added is that amount which is necessary to have the percentages add up to 100 % w / w . ingredients other than deionized water , the reduced glutathione and the pegdo may be added such as preferably 0 . 1 % w / w potassium sorbate and then the final amount of deionized water added is that amount which is necessary to have the percentages add up to 100 % w / w . taste ingredients or other flavor masking ingredients could also be added before the deionized water is brought up to 100 % w / w . although taste ingredients can be added before or after the liposomal formulation , the preferable mode is to add flavor or other taste masking ingredients after liposomal formulation , and they may be ingredients such as corn syrup , honey , sorbitol , sugar , saccharin , stevia , aspartame , citrus seed extract , natural peppermint oil , menthol , synthetic strawberry flavor , orange flavor , chocolate , or vanilla flavoring in concentrations from about 0 . 01 to 10 %. the inventor has preferably used citrus seed extract . the qusome self - forming liposome uses polyethyleneglycol ( peg ) is a steric stabilizer and the resulting liposome is of a moderate size , 150 nm - 250 nm . the combination of 150 nm - 250 nm size and the peg component is known to create long circulating liposomes . the size of the qusome self - forming liposome allows them to be sterile filtered . these attributes allow a secondary advantage of the invention by the qusome liposome encapsulating a radionuclide useful for targeting tumors with either diagnostic radionuclides or therapeutic radionuclides . the qusome self - forming liposome is of such as size and the presence of the steric stability with peg results in long circulation time and an increased accumulation in the fine trabecular mesh of blood vessels supplying growing tumors . this characteristic allows for improved diagnostics as more radionuclide accumulates around the tumor improving the image of scans . this characteristic of accumulating in the trabecular mesh of blood vessels leading to tumors also leads to an improved therapeutic . the accumulation of qusome self - forming liposomes in the blood vessel supply to tumors increases the radiation dosing to this area , creating damage to the tumor blood vessels creating an anti - angiogenic effect , resulting in a decreased supply of blood to the tumor and leading to death of tumor cells . the concentration of liposomally encapsulated glutathione in the liposomes resulting from the qusome formulation is 5 % for topical application . it is possible to use the qusome technology in creating an oral formulation also and the 8 . 25 % glutathione in w / w concentration encapsulated in the liposome may be used in the oral formulation . thus the invention in one aspect is a method for preventing or reversing the formation of autophagic stromal cells in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment by orally administering , to a patient having tissue that has become cancer - prone , a dose of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm , and where such administering raises the level of reduced glutathione within cancer stromal cells . another aspect of the invention is a method for preventing or reversing the formation of autophagic stromal cells in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment , by orally administering , to a patient having tissue that has become cancer - prone , liposome - encapsulated reduced glutathione at least daily , where such administration raises the level of reduced glutathione within cancer stromal cells by at least 30 % percent . another aspect of the invention is a method for enhancing the macrophage cell function in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment by orally administering , to a patient having tissue that has become cancer - prone , a dose of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm , where such administering raises the level of reduced glutathione within said macrophage cells . another aspect of the invention is a method for enhancing the macrophage function in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment by orally administering , to a patient having tissue that has become cancer - prone , liposome - encapsulated reduced glutathione at least daily , where such administration raises the level of gsh within said macrophage cells by at least 30 %. in radiation , or in chemotherapy which functions as a radiation mimic in terms of causing oxidative stress and generating free radicals , there is evidence of systemic oxidation in the blood of cancer - afflicted patients reflecting there is damage to peritumor cells and tissue . the invention functions to bring the peritumor cells to normal redox balance by supplying the liposomally encapsulated reduced glutathione intracellularly . thus , one aspect of the invention is a method of reducing undesirable cellular damage from radiation or chemotherapy treatment to a cancer patient by , beginning prior to the treatment , orally administering liposome - encapsulated reduced glutathione either at least twice daily to the patient for a period of at least 3 days or at least once daily for seven days , where such administration raises the level of gsh within peritumor stromal cells of the patient by at least 30 percent . a further refinement of this method is where each dose of such daily administration is between 6 mg / kg and 36 mg / kg weight of a patient of liposome - encapsulated reduced glutathione . yet another refinement is where the liposome - encapsulated glutathione is administered in the form of a gel cap . another aspect of the invention is the use of a composition to prevent or reverse the formation of autophagic stromal cells in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment treat , said composition having liposomally encapsulated reduced glutathione in the percentage of 8 . 25 % w / w . another aspect of the invention is the use of a composition to prevent or reverse the formation of autophagic stromal cells in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment treat , said composition having liposomally encapsulated reduced glutathione in the percentage of 8 . 5 % w / w . another aspect of the invention is a method for the prevention of the recurrence of cancer using oral liposomally encapsulated reduced glutathione to maintain the presence and normal function of caveolin in fibroblast and other cells , by orally administering , to a patient having tissue that has become cancer - prone , liposome - encapsulated reduced glutathione at least daily , where such administration raises the level of reduced glutathione to maintain the presence and normal function of caveolin in fibroblast cells to diminish their glycolytic support for epithelial cancer cells , thus preventing the conversion of a fibroblast to an autophagic tumor stromal cells . another aspect of the invention is a method for the restoration of altered tumor stromal cells and peri - tumor fibroblasts to more normal mitochondrial function for these cells , by administering , to a patient having tissue that has become cancer - prone , a dose of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally at least daily , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm , where such administration raises the level of gsh . another aspect of the invention is a method for enhancing the macrophage cell function in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment , by administering , to a patient having tissue that has become cancer - prone , a gel capsule and encapsulating with said gel capsule glutathione ( reduced ) said glutathione ( reduced ) being stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione ( reduced ) into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least about 123 mm , and where such administering raises the level of reduced glutathione within said macrophage cells . a further aspect is to use lecithin encapsulated within the gel capsule . a further aspect is to use up to 15 - 20 % water encapsulated within the gel capsule . a further aspect is to use glycerin encapsulated within the gel capsule . a further aspect is to use sorbitan oleate encapsulated within the gel capsule . a further aspect is to use polysorbate 20 encapsulated within the gel capsule . a further aspect is to use potassium sorbate encapsulated within the gel capsule . another aspect is to use a gel capsule to prevent or reverse the formation of autophagic stromal cells in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment treat , by delivering , to a patient having tissue that has become cancer - prone , glutathione orally via a gel capsule including reduced glutathione encapsulated in a liposomal pharmaceutical carrier within said gel capsule where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least about 123 mm . the further aspects of the prior paragraph can then be utilized in conjunction with this use . another aspect is the use of a composition to prevent or reverse the formation of autophagic stromal cells in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment treat , said composition having liposomally encapsulated reduced glutathione in the percentage of 8 . 25 % w / w . another aspect is the use of a composition to prevent or reverse the formation of autophagic stromal cells in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment treat , said composition having liposomally encapsulated reduced glutathione in the percentage of 8 . 5 % w / w . another aspect is a method for the prevention of the recurrence of cancer using oral liposomally encapsulated reduced glutathione to maintain the presence and normal function of caveolin in fibroblast and other cells , by orally administering , to a patient having tissue that has become cancer - prone , liposome - encapsulated reduced glutathione at least daily , where such administration raises the level of reduced glutathione to maintain the presence and normal function of caveolin in fibroblast cells to diminish their glycolytic support for epithelial cancer cells , thus preventing the conversion of a fibroblast to an autophagic tumor stromal cells . another aspect is a method for the restoration of altered tumor stromal cells and peri - tumor fibroblasts to more normal mitochondrial function for these cells , by administering , to a patient having tissue that has become cancer - prone , a dose of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally at least daily , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm , where such administration raises the level of gsh . another aspect of the invention is a pharmaceutical composition for preventing or reversing the effects of cancer - prone tissue comprising a therapeutic dose of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm , and the composition has sodium bicarbonate in a range of 1 . 5 % w / w to 8 . 5 % w / w , and the percentage of water / weight of the sum of the percentage of liposomally encapsulated reduced glutathione plus the percentage of water / weight of sodium bicarbonate in a dose is 1 . 5 % w / w to 8 . 5 % w / w . another aspect of the invention is a pharmaceutical composition for preventing or reversing the effects of cancer - prone tissue comprising a therapeutic dose of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm , and the percentage of water / weight sodium bicarbonate in a dose is from 1 . 5 % w / w to 8 . 5 % w / w . another aspect of the invention is a method of the prevention of weight loss and wasting associated with cancer progression and metastasis , by orally administering , to a patient having tissue that has become cancer - prone , a dose of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm . another aspect of the invention is a pharmaceutical composition for preventing or reversing the effects of cancer - prone tissue comprising a therapeutic dose of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm , and a daily dose of dichloroacetic acid ( dca ) in a range from 10 mg / kg to 100 mg / kg . a further aspect of this composition is to include triiodothyronine ( cytomel ) in a range of 5 micrograms to 15 micrograms . a further aspect of this composition is to include caffeine . another aspect of the invention is an anti - cancer pharmaceutical composition of edta and a liposomally encapsulated formulation of reduced glutathione , comprising a therapeutic dose of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm , and edta in a range of 100 mg to 3 grams in a single dose administered every other day . another aspect of the invention is a method for preventing or reversing the formation of autophagic stromal cells in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment , by administering , to a patient having tissue that has become cancer - prone , two therapeutic doses per day of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm , and administering arginine in two doses per day . another aspect of the invention is a method for preventing or reversing the formation of autophagic stromal cells in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment , by administering , to a patient having tissue that has become cancer - prone , two therapeutic doses per day of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm and by administering arginine in two doses per day . another aspect of the invention is a method for preventing or reversing the formation of autophagic stromal cells in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment , by administering , to a patient having tissue that has become cancer - prone , two therapeutic doses in a range of ½ teaspoon to 4 teaspoons per dose of gsno stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering gsno in a physiologically active state into cells . another aspect of the invention is a method for preventing or reversing the formation of autophagic stromal cells in a tissue that has become cancer - prone due to increased oxidation stress in the tissue or the tissue micro - environment , by administering , to a patient having tissue that has become cancer - prone , two therapeutic doses per day of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm , and administering , to a patient having tissue that has become cancer - prone , two therapeutic doses per day in a range of ½ teaspoon to 4 teaspoons per dose of gsno stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering gsno in a physiologically active state into cells . another aspect of the invention is an anti - cancer composition comprising d - alpha - tocopherol succinate encapsulated in liposomes ranging in size from 20 nm to 10 microns at a concentration of 400 mg of d - alpha - tocopherol succinate per 5 cc of liposomal liquid and a therapeutic dose of a reduced glutathione stabilized and encapsulated in a liposomal pharmaceutical carrier capable of being ingested orally , and capable of delivering glutathione ( reduced ) in a physiologically active state to improve symptoms in disease states by transfer of the glutathione into animal cells , where the concentration of reduced glutathione in the entrapped aqueous space of the liposomes is at least 123 mm . another aspect of the invention is a method of reducing the cancer promoting effects of mycotoxins , by administering an antifungal agent , and by administering , to a patient having tissue that has become cancer - 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