WO2005089412A2 - Tissue detoxification and health supplements and methods of making and using them - Google Patents
Tissue detoxification and health supplements and methods of making and using them Download PDFInfo
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- WO2005089412A2 WO2005089412A2 PCT/US2005/008839 US2005008839W WO2005089412A2 WO 2005089412 A2 WO2005089412 A2 WO 2005089412A2 US 2005008839 W US2005008839 W US 2005008839W WO 2005089412 A2 WO2005089412 A2 WO 2005089412A2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/04—Chelating agents
Definitions
- This invention relates to preparations and formulations comprising beneficial phytochemical ingredients that are serviceable as health supplements for the body, including a human body, and particularly for tissues susceptible to cancer, including, e.g. prostate tissue and breast tissue, for example, female breast tissue.
- These preparations and formulations of the invention can be used to maintain the health of a tissue or organ, e.g., breast tissue, act as a prophylactic to disease or condition, or ameliorate a disease state or condition.
- This invention also relates to preparations comprising chelating agents that are effective (serviceable) for heavy metal detoxification of humans and animals.
- this invention provides novel preparations of chelating agents encapsulated in micelles or liposomes comprising the triple combination of 1) micelles or liposomes comprising alpha lipoic acid and 2) micelles or liposomes comprising EDTA (ethylene- diaminetetraacetic acid) or other chelators; and furthermore, in different embodiments, 3) magnesium chloride is optionally an additional ingredient in these novel preparations.
- compositions and formulations of the invention can be used to maintain the health of a tissue or organ, act as a prophylactic to a disease or condition, or ameliorate a disease state or condition.
- This invention also relates to combinations, such as kits, comprising both a preparation of chelating agents, and a preparation of phytochemical ingredients.
- Tissue Health The ability to maintain the health of and to achieve the detoxification of tissues can be aided by many dietary supplements. However, in disease states, e.g. cancer, the cause of the disease may become refractory or resistant to a single-pronged approach to health and detoxification. Thus, this invention provides multi-pronged approaches that make advantageous use of novel combinations of ingredients that provide beneficial effects. Toxicity and poisoning. Heavy metal poisoning is a serious medical problem that is receiving even more emphasis in recent years as the ability to detect toxic metals, as well as the ability to understand the detrimental affects associated therewith, have progressed compared to the past.
- toxic heavy metals such as lead, arsenic and mercury may very easily enter the body as a consequence of, to name a few examples, accumulated exposure, accidents, environmental pollution, and oral consumption (e.g. food or paint).
- exposures to lead and mercury are wide-spread and well documented.
- Poisoning from excessive concentrations of substances that would other wise be beneficial at lower concentrations is also known; e.g. iron poisoning has been reported.
- Arsenic can get into the body, e.g. as a result of industrial pollution. Also of concern are radioactive toxic heavy metals that pose an additional problem due to their radioactivity.
- Toxic heavy metals are also known to concentrate in various organs of the body. Plutonium, for example, usually deposits in the liver, and it is known that as much as 30 to 60% or more of an administered amount of plutonium will oftentimes deposit in the liver. The toxic heavy metal, plutonium in this example, remains in the organ and is only very slowly removed, thereby increasing the potential for tumors.
- Intravenous (IN.) chelation is expensive, time-consuming, and has poor patient compliance.
- Traditional oral chelation therapies are cheaper, but they are relatively ineffective at their intended purposes, and, at higher doses, are accompanied by side effects.
- the oral administration of chelating agents by traditional approaches is problematic not only because their poor absorption and bioavailability prevents them from reaching the bodily stores of toxins and heavy metals, but furthermore they can chelate beneficial substances in the digestive tract.
- 3) Using traditional therapies, neither parenterally (e.g. by IN.) nor orally administered chelating agents are able to enter the intracellular compartments where toxins and heavy metals are also present.
- chelation is very expensive and time-consuming, typically requiring a patient make a series of 20 to 50 visits to a physician's office or hospital (at least 30 visits are typically required), with each visit often taking from 3-4 hours, during which time the patient is typically seated, and costing up to $100 or more per visit.
- Oral chelation products are commercially available, and they are marketed as much less expensive alternatives to IN. chelation therapies.
- EDTA is very poorly absorbed when administered by mouth; and the general consensus is that typically only about five percent or less is absorbed. Although even that small amount does remove lead from the body, it also been reported to increases the absorption of lead. Other serious potential problems have been reported as well.
- EDTA When given intravenously, thus bypassing any absorption problems, a full therapeutic treatment of EDTA can be completed with 20 to 50 daily doses.
- the replenishment of the lost essential trace elements by dietary supplementation can then take place during the remaining 315+ days of the year after the treatment, when the exogenously administered chelating agent(s) such as EDTA have been excreted or eliminated, and are not present to interfere. Because such a small amount is absorbed by mouth, oral EDTA is often given every day, but for up to 20 times or more as long, to accumulate what is alleged to be an effective dose, and there is no interim opportunity to replenish the essential nutrients that are being continuously blocked and depleted during the chelation therapy.
- the daily administration of chelating agents such as EDTA by mouth may cause progressive deficiencies of zinc, manganese and other essential trace nutrients, which are an essential part of the body's antioxidant defenses.
- SOD superoxide dismutase
- the daily intake of chelation agents by mouth may actually worsen the condition of the patients being treated.
- Intravenous chelation therapy has been reported to stimulate the release of parathyroid hormone (parathormone) in a pulsatile manner, but orally administered chelation therapies, such as with EDTA, have not. Thus, if that mechanism of action is important to achieve the intended benefit, oral EDTA cannot achieve the goal.
- chelating agents typically remain extracellularly or outside of cells.
- orally administered EDTA reaches only very low concentrations outside cell surfaces in the body and for brief periods of time, while intravenous infusions result in much higher levels, and can be maintained for several hours.
- intravenously administered EDTA can only chelate unwanted metals and toxins, if, e.g. they travel out of cell walls by diffusion. In contrast, this is not believed to occur to a significant extent - if at all - with chelators such as EDTA when taken by mouth. In sum, neither traditional approach achieves significant intracellular levels of chelating agents, and is thus unable to readily exert its actions intracellularly.
- the preparations of the present invention comprise antioxidants that have effects that may be additive or synergistic to the effects of chelators such as EDTA; however, these antioxidants may be lipophilic. Because many parenterally suitable fluids such as saline, dextran, blood, stabilized hemoglobin solutions, etc., are all aqueous solutions, a problem with therapies based on lipid soluble antioxidants, such as alpha-lipoic acid, is the poor water solubility of these ingredients. The solubility may be enhanced by adding benzyl alcohol or DMSO, but such solvents introduce additional side effects.
- the invention provides preparations comprising encapsulated chelating agents comprising at least one member of a first group, at least one member of a second group and at least one member of a third group, wherein members of the first group are selected from the group consisting of R-(+)-alpha-lipoic acid, S-(-)-alpha-lipoic acid, R/S-alpha- lipoic acid, R/S-gamma-lipoic acid, isomers of alpha lipoic acid, dihydrolipoic acid or DHLA, animal and vegetable oils, hydrocarbon oils, ester oils, silicone oils, higher fatty acids, higher alcohols, sun-screening agents, vitamins, and ferulic acid; members of the second group comprises at least one chelating group; and members of the third group are selected from the group consisting of lecithin, phosphatidylcholme, phosphatidylserine, phosphatidylethanolamine, dilinoleyl
- one or more members of the first group, one or more members of the second group, and one or more members of the third group are admixed to generate a microsphere or a liposome.
- the invention provides preparations comprising encapsulated bioavailable chelating agents comprising at least one member of a first group, at least one member of a second group and at least one member of a third group, wherein members of the first group are selected from the group consisting of R-(+)-alpha-lipoic acid, S-(-)-alpha-lipoic acid, R/S-alpha-lipoic acid, R/S-gamma-lipoic acid, other isomers of alpha lipoic acid, dihydrolipoic acid or DHLA, animal and vegetable oils, hydrocarbon oils, ester oils, silicone oils, higher fatty acids, higher alcohols, sun-screening agents, vitamins, and ferulic acid, wherein at least about 1% of the members of the first group in the preparation are encapsulated
- kits or formulations comprising two preparations, a first preparation and a second preparation, wherein said first preparation comprises a phospholipid, a chelating agent, magnesium chloride, and alpha lipoic acid; and the second preparation comprises diindolemethane, grape extract or grape skin extract or wine extract, calcium D-glucarate, medium chain triglycerides or a phospholipid or a combination thereof.
- the grape extract or grape skin extract or wine extract can be a red grape extract, a red grape skin extract or a red wine extract.
- the chelating agent comprises EDTA (ethylene-diaminetetraacetic acid), diethylenetriamine-pentaacetic acid (DTP A), ethyleneglycol-bis[beta-aminoethyl ether] -N,N'-tetra-acetic acid (EGTA), triethylenetetraaminehexaacetic acid (TTHA), N-hydroxyethylenediaminehexaacetic-acid (HEDHA), 1 ,4,7-triazacyclononane-N,N',N"-triacetic acid (NOTA), 1 ,4,7, 10- tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA), N'-hydroxy- ethylenediamine-N,N,N'-triacetic acid (HEDTA), other polyaminopolycarboxylic acids, iminodiacetic acid (IDA), cyclam, penicillamine, dimercaptosuccinic acid, tart
- the invention provides preparations comprising diindolemethane, grape extract or grape skin extract or wine extract, calcium D-glucarate, a medium chain triglyceride, a phospholipid, and at least one vitamin B9 molecule.
- the grape extract or grape skin extract or wine extract can be a red grape extract, a red grape skin extract or a red wine extract.
- the at least one vitamin B9 molecule can be folate, folic acid and or folinic acid.
- the vitamin B9 molecule comprises folic acid and folinic acid.
- kits or formulations comprising two preparations, a first preparation and a second preparation
- said first preparation comprises a plant indole, indole-3-carbinol (13 C) or its dimer 3,3'-diindolylmethane (DIM), grape extract or grape skin extract or wine extract, calcium D-glucarate, medium chain triglycerides, a phospholipid, and at least one vitamin B9 molecule
- the second preparation comprises a phospholipid, a chelating agent, magnesium chloride and alpha lipoic acid.
- the chelating agent can comprise EDTA (ethylene-diaminetetraacetic acid), diethylenetriamine-pentaacetic acid (DTP A), ethyleneglycol-bis[beta-aminoethyl ether]- N,N'-tetra-acetic acid (EGTA), triethylenetetraaminehexaacetic acid (TTHA), N- hydroxyethylenediaminehexaacetic-acid (HEDHA), 1 ,4,7-triazacyclononane-N,N',N"- triacetic acid (NOTA), l,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid (DOTA), N'-hydroxy-ethylenediamine-N,N,N'-triacetic acid (HEDTA), other polyaminopolycarboxylic acids, iminodiacetic acid (IDA), cyclam, penicillamine, dimercaptosuccinic acid, tart
- the at least one vitamin B9 molecule can be a folate, a folic acid and/or a folinic acid.
- the vitamin B9 molecule comprises folic acid and folinic acid.
- the invention provides methods for detoxification of an animal comprising administering an effective amount of the preparation of the invention.
- the invention provides methods for detoxification of an animal comprising administering an effective amount of the formulation of the invention.
- the invention provides methods for detoxification of an animal comprising administering an effective amount of the preparation of the invention.
- the detoxification can comprise heavy metal detoxification, wherein the metal can be arsenic, lead, cadmium or mercury.
- the animal is a human.
- the invention provides methods wherein formulation or preparation is administered by inoculation, infusion or injection, topical application or by absorption through epithelial or mucocutaneous linings.
- the invention provides liquids comprising the preparation of the invention, or formulation of the invention.
- the invention provides capsules, sprays, powders, lotions, tablets or pills comprising a preparation of the invention or formulation of the invention.
- the invention provides foods or food supplements comprising a preparation of the invention or a formulation of the invention.
- the food or food supplement can comprise a flavored bar, a power bar, a diet bar, an energy bar or a nutritional bar.
- the invention provides methods for maintaining the health of a tissue comprising administering an effective amount of a preparation of the invention or a formulation of the invention.
- the tissue can be a breast tissue or a prostate tissue.
- the invention provides methods for ameliorating a disease or condition in an individual comprising administering an effective amount of a preparation of the invention or a formulation of the invention.
- the disease or condition can affect breast tissue or prostate tissue.
- the invention provides preparations or formulations wherein at least a fraction of the microsphere or liposome further comprises a gas comprising a nitrogen gas, oxygen gas, atmospheric air, gaseous mixtures containing nitrogen gas, gaseous mixtures containing oxygen gas, or a combination thereof.
- the invention provides preparations or formulations of the invention wherein the microsphere or liposome is homogeneous in size or in content, or, heterogeneous in size or in content.
- the invention provides preparations or formulations comprising encapsulated chelating agents comprising at least one member of a first group, at least one member of a second group and at least one member of a third group, wherein members of the first group comprise at least one hydrophobic antioxidant; members of the second group comprises at least one chelating group; and members of the third group comprise at least on member selected from the group consisting of lecithin, phosphatidylcholme, phosphatidylserine, phosphatidylethanolamine, dilinoleylphosphatidylcholine, lysolipids, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylcholme, phosphatidic acid, sphingomyelin, cholesterol, cholesterol sulfate, cholesterol hemisuccinate, tocopherol hemisuccinate, phosphatidylethanolamine, phosphatidylinositol, fatty acids
- the invention provides preparations or formulations comprising at least one member of a first group and at least one member of a second group, wherein the member of the first group comprises a plant indole, and the member of the second group in this or any preparation or formulation of the invention can comprise a plant flavonoid, a polyphenol, a stilbene, a 3,5,4'-trihydroxy stilbene, a resveratrol, a piceatannol, a grape extract, a grape skin extract or a wine extract, or an equivalent compound.
- the invention provides preparations or formulations comprising at least one member of a first group and at least one member of a second group, wherein the member of the first group comprises a plant indole, and the member of the second group comprises a D-glucaric acid, a salt of a D-glucaric acid, a potassium hydrogen D- glucarate (PHG), a derivatized D-glucaric acid, a D-glucaro-l,4-lactone, a 1,4-GL, 2-keto- 3-deoxy-D-glucarate, a 4-deoxy-5-keto-D-glucarate, or an equivalent compound.
- the member of the first group comprises a plant indole
- PEG potassium hydrogen D- glucarate
- PEG potassium hydrogen D- glucarate
- the invention provides preparations or formulations comprising at least one member of a first group and at least one member of a second group, wherein the member of the first group comprises a plant indole, and the member of the second group comprises a medium chain triglyceride (MCT).
- MCT medium chain triglyceride
- the at least half of the content of the preparation or formulation in this or any preparation or formulation of the invention can comprise at least 80% of MCTs having a length of between C 5 and C ⁇ .
- the MCT can be derived from coconut oil, palm kernel oil, camphor tree drupes, butter or a combmation thereof.
- the MCT can comprise a lauric oil, or glycerol esters of caprylic acid, octanoic acid, capric acid or decanoic acid.
- the invention provides preparations or formulations comprising at least one member of a first group and at least one member of a second group, wherein the member of the first group comprises a plant indole, and the member of the second group comprises lecithin, phophatidylcholine, phosphatidylserine, phosphatidylethanolamine, dilinoleylphosphatidylcholine, lysolipids, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylcholme, phosphatidic acid, spliingomyelin, cholesterol, cholesterol sulfate, cholesterol hemisuccinate, tocopherol hemisuccinate, phosphatidylethanolamme, phosphatidylinositol, fatty acids, palmitic acid, stearic acid, oleic acid, linolenic acid, linoleic acid, glycosphingolipid
- the plant indole can comprise an indole-3-carbinol (13 C) or its dimer 3,3 -diindolylmethane (DIM), grape extract or grape skin extract or wine extract.
- the invention provides preparations or formulations comprising at least one member of a first group and at least one member of a second group, wherein the member of the first group comprises a medium chain triglyceride (MCT), and the member of the second group comprises a D-glucaric acid, a salt of a D-glucaric acid, a potassium hydrogen D-glucarate (PHG), a derivatized D-glucaric acid, a D-glucaro-l,4-lactone, a 1,4-GL, 2-keto-3-deoxy-D-glucarate, a 4-deoxy-5-keto-D-glucarate, or an equivalent compound.
- MCT medium chain triglyceride
- PEG potassium hydrogen D-glucarate
- the invention provides preparations or formulations for oral administration comprising a chelating agent and a phospholipid, wherein the chelating agent and phospholipid are encapsulated in a microsphere or liposome comprising a compound selected from the group consisting of lecithin, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamme, dilinoleylphosphatidylcholine, lysolipids, dipahnitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylcholine, phosphatidic acid, sphingomyelin, cholesterol, cholesterol sulfate, cholesterol hemisuccinate, tocopherol hemisuccinate, phosphatidylethanolamine, phosphatidylinositol, fatty acids, palmitic acid, stearic acid, oleic acid, linolenic acid, linoleic
- the invention provides preparations or formulations wherein the chelating agent comprises disodium EDTA (ethylene-diaminetetraacetic acid), diethylenetriamine- pentaacetic acid (DTP A), ethyleneglycol-bis[beta-aminoethyl ether] -N,N'-tetra-acetic acid (EGTA), triethylenetetraaminehexaacetic acid (TTHA), N- hydroxyethylenediaminehexaacetic-acid (HEDHA), l,4,7-triazacyclononane-N,N',N"- triacetic acid (NOTA), l,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA), N'-hydroxy-ethylenediamine-N,N,N'-triacetic acid (HEDTA), other polyaminopolycarboxylic acids, iminodiacetic acid (IDA), cyclam, penicill
- the phospholipid can comprise alpha lipoic acid.
- the preparation can comprise disodium EDTA, phospholipid, magnesium chloride and alpha lipoic acid.
- the preparation can comprise about 1 gm of disodium EDTA, about 30 gm of phospholipid, about 150 mg of magnesium chloride and about 100 mg of alpha lipoic acid.
- the invention provides preparations formulated for oral administration, spraying, applying topically to a mucous membrane, inhaling, injecting or applying by using a patch or an implant, comprising indole-3-carbinol (I3C) or its dimer 3,3'- diindolylmethane (DIM), calcium D-glucarate and a red wine extract or grape extract or grape skin extract, wherein the indole-3-carbinol (13 C) or its dimer 3,3'-diindolylmethane (DIM), calcium D-glucarate and red wine extract are encapsulated in a microsphere or liposome comprising a compound selected from the group consisting of lecithin, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, dilinoleylphosphatidylcholine, lysolipids, dipalmitoylphosphatidylcholine, distearoylphosphatidyl
- kits comprising these formulations, and in one aspect, the kit comprising instructions on using the formulation.
- the preparation further comprises a medium chain triglyceride.
- the preparation can comprise calcium, diindolylmethane, red wine extract, calcium D- glucarate, medium chain triglyceride and lecithin.
- the preparation can comprises about 24 mg calcium, about 100 mg diindolylmethane, about 200 mg red wine extract, about 200 mg calcium D-glucarate, about 45 mg medium chain triglyceride and about 45 mg lecithin.
- the invention provides preparations or formulations comprising at least one member of a first group and at least one member of a second group, wherein the member of the first group comprises a plant indole, and the member of the second group comprises a fat soluble vitamin or equivalent compound.
- the fat soluble vitamin or equivalent compound can comprise vitamin A, D, E or K, retinol, retinol derivatives, retinoic acid, carotenoids, lycopene, lutein, 1,25-dihydroxyvitaminD, calciferol, calcipotriol, cholecalciferol, ergocalciferol (vitamin D2), irradiated ergocalciferol, alpha tocopherol, tocopherol, tocopheryl acetate, tocopheryl succinate, phylloquinones, menaquinones, menadione or menatetrenone (vitamin ?K2).
- the invention provides preparations or formulations comprising at least one member of a first group and at least one member of a second group, wherein the member of the first group comprises a plant indole, and the member of the second group comprises a lycopene, carotenoid, carotenes, xanthophyll, alpha-carotene, beta-carotene, lutein, cyptoxanthin, zeaxanthin and/or a plant-derived lycopene.
- the plant-derived lycopene in this or any preparation or formulation of the invention can comprise a blueberry-derived or a tomato-derived lycopene.
- the invention provides preparations or formulations comprising at least one member of a first group and at least one member of a second group, wherein the member of the first group comprises a medium chain triglyceride (MCT), and the member of the second group comprises a fat soluble vitamin or equivalent compound.
- MCT medium chain triglyceride
- the fat soluble vitamin or equivalent compound in this or any preparation or formulation of the invention can comprise vitamin A, D, E or K, retinol, retinol derivatives, retinoic acid, carotenoids, lycopene, lutein, 1,25-dihydroxyvitamin D, calciferol, calcipotriol, cholecalciferol, ergocalciferol (vitamin D2), irradiated ergocalciferol, alpha tocopherol, tocopherol, tocopheryl acetate, tocopheryl succinate, phylloquinones, menaquinones, menadione or menatetrenone (vitamin ?K2).
- the present invention provides a therapy method for toxic heavy metal poisoning whereby both intracellularly deposited toxic heavy metals as well as extracellularly deposited toxic heavy metals can be removed from the body.
- said body is a human body or an animal body (e.g. a pet or other raised animal, e.g., a farm or zoo animal).
- this invention provides different products that comprise (contain at least) all the combinations and permutations of ingredients selected from members of Group 1 (e.g. in Table 3), members of Group 2 (e.g. in Table 3), members of Group 3 (e.g. in Table 3), members of Group 4 (e.g. in Table 3), members of Group 5 (e.g.
- the invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3 : a) one or more members selected from Group 1 (e.g. DIM, or diindolylmethane); and b) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol).
- Group 1 e.g. DIM, or diindolylmethane
- Group 2 e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3 : a) one or more members selected from Group 1 (e.g. DIM); and b) one or more members selected from Group 3 (e.g. calcium D-glucarate).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); and b) one or more members selected from Group 4 (e.g. medium chain triglycerides).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3 : a) one or more members selected from Group 1 (e.g. DIM); and b) one or more members selected from Group 5 (e.g. lecithin and phosphatidyl choline).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); and b) one or more members selected from Group 6 (e.g. lycopenes and carotenoids).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3 : a) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); and b) one or more members selected from Group 3 (e.g. calcium D-glutarate).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g.
- red wine extract,, resveratrol, and piceatannol e.g. red wine extract,, resveratrol, and piceatannol
- Group 4 e.g. medium chain triglycerides
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); and b) one or more members selected from Group 5 (e.g. lecithin and phosphatidyl choline).
- Group 2 e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol
- Group 5 e.g. lecithin and phosphatidyl choline
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 3 (e.g. calcium D-glutarate); and b) one or more members selected from Group 4 (e.g. medium chain triglycerides).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 3 (e.g. calcium D-glutarate); and b) one or more members selected from Group 5 (e.g. lecithin and phosphatidyl choline).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); and b) one or more members selected from Group 6 (e.g. lycopenes and carotenoids).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 4 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 3 (e.g. calcium D-glutarate); and b) one or more members selected from Group 6 (e.g. lycopenes and carotenoids).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); and c) one or more members selected from Group 3 (e.g. calcium D-glucarate).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g.
- red wine extract,, resveratrol, and piceatannol and c) one or more members selected from Group 4 (e.g. medium chain triglycerides).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for wliich non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); and c) one or more members selected from Group 5 (e.g. lecithin and phosphatidyl choline).
- Group 1 e.g. DIM
- Group 2 e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol
- Group 5 e.g. lecithin and phosphatidyl
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 4 (e.g. medium chain triglycerides); and b) one or more members selected from Group 6 (e.g. lycopenes and carotenoids).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 3 (e.g. calcium D-glucarate); and c) one or more members selected from Group 4 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 3 (e.g. calcium D-glucarate); and c) one or more members selected from Group 5 (e.g. lecithin and phosphatidyl choline).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3 : a) one or more members selected from Group 1 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 4 (e.g. medium chain triglycerides); and c) one or more members selected from Group 5 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 3 (e.g. calcium D-glucarate); and c) one or more members selected from Group 6 (e.g. lycopenes and carotenoids).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); b) one or more members selected from Group 3 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 4 (e.g. medium chain triglycerides); and c) one or more members selected from Group 6 (e.g. lycopenes and carotenoids).
- Group 1 e.g. DIM
- Group 4 e.g. medium chain triglycerides
- Group 6 e.g. lycopenes and carotenoids
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); b) one or more members selected from Group 4 (e.g. medium chain triglycerides); and c) one or more members selected from Group 5 (e.g. lecithin and phosphatidyl choline).
- Group 2 e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol
- Group 4 e.g. medium chain triglycerides
- Group 5 e.g. lecithin and phosphatidyl choline
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); b) one or more members selected from Group 3 (e.g. calcium D-glucarate); and c) one or more members selected from Group 6 (e.g. lycopenes and carotenoids).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3 : a) one or more members selected from Group 3 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); b) one or more members selected from Group 4 (e.g. medium chain triglycerides); and c) one or more members selected from Group 6 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); c) one or more members selected from Group 3 (e.g. calcium D-glucarate); and d) one or more members selected from Group 4 (e.g. medium chain triglycerides).
- Group 1 e.g. DIM
- Group 2 e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol
- Group 3 e.g. calcium D-glucarate
- Group 4 e.g. medium chain triglycerides
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); c) one or more members selected from Group 3 (e.g. calcium D-glucarate); and d) one or more members selected from
- Group 5 e.g. lecithin and phosphatidyl choline.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 3 (e.g. calcium D-glucarate); b) one or more members selected from Group 4 (e.g. medium chain triglycerides); and c) one or more members selected from Group 6 (e.g. lycopenes and carotenoids).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 2 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected.from Group 3 (e.g. calcium D-glucarate); c) one or more members selected from Group 4 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); c) one or more members selected from Group 4 (e.g. medium chain triglycerides); and d) one or more members selected from Group 6 (e.g.
- Group 1 e.g. DIM
- Group 2 e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol
- Group 4 e.g. medium chain triglycerides
- one or more members selected from Group 6 e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3 : a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 2 (e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); c) one or more members selected from Group 3 (e.g. calcium D-glucarate); d) one or more members selected from Group 4 (e.g. medium chain triglycerides); and e) one or more members selected from Group 5 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 3 (e.g. calcium D-glucarate); c) one or more members selected from Group 4 (e.g. medium chain triglycerides); and d) one or more members selected from Group 6 (e.g. lycopenes and carotenoids).
- Group 1 e.g. DIM
- Group 3 e.g. calcium D-glucarate
- Group 4 e.g. medium chain triglycerides
- Group 6 e.g. lycopenes and carotenoids
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. DIM); b) one or more members selected from Group 3 (e.g. calcium D-glucarate); c) one or more members selected from Group 4 (e.g. medium chain triglycerides); and d) one or more members selected from Group 6 (e.g. lycopenes and carotenoids).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g.
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g. grape extract or grape skin exfract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol); c) one or more members selected from Group 3 (e.g. calcium D-glucarate); d) one or more members selected from Group 4 (e.g. medium chain triglycerides); and e) one or more members selected from Group 6 (e.g. lycopenes and carotenoids).
- this invention provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g.
- DIM DIM
- members selected from Group 2 e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol
- Group 3 e.g. calcium D-glucarate
- members selected from Group 4 e.g. medium chain triglycerides
- members selected from Group 5 e.g. lecithin and phosphatidyl choline
- members selected from Group 6 e.g. lycopenes and carotenoids
- the term "at least one member” in reference to exemplary alternative embodiments comprises minimally every integer value from one to at 20, inclusive; i.e. in one aspect it means at least one member, in another aspect it means at least two members, in another aspect it means at least three members, ..., etc, and in another aspect it means at least 20 members.
- Alternative embodiments can comprise more than 20 members.
- this invention provides every combination and permutation of ingredients exemplified in Table 1 (i.e. Groups A-G).
- this invention provides every combination and permutation of ingredients exemplified in from Table 3 (i.e. Groups 1-5).
- this invention provides every combination and permutation of ingredients selected from both Table 1 (i.e.
- kits may have two preparations: 1) a preparation comprising ingredients from Table 1; and 2) a preparation comprising ingredients from Table 3; the two preparations may be physically separate; and, by way of non-limiting exemplification, the first preparation may be a liquid preparation that is consumed using a spoon, while the second preparation may be a preparation that is in the form of vegetable capsules (v-caps) that can be consumed like any capsule, tablet or pill.
- v-caps vegetable capsules
- this invention provides a preparation of encapsulated bioavailable chelating agents comprising the following ingredients: a) one or more members selected from a first group consisting of: R-(+)-alpha- lipoic acid (substantially enantiomerically pure), S-(-)-alpha-lipoic acid (substantially enantiomerically pure), R/S-alpha-lipoic acid (racemic mixture), R/S-gamma-lipoic acid (racemic mixture), other isomers of alpha lipoic acid, derivatives of alpha lipoic acid, dihydrolipoic acid (DHLA); wherein at least 1% of said one or more members from said first group is in microspheres or liposomes; and b) one or more members selected from a second group consisting of: ethylene- diaminetetraacetic acid (EDTA), ethyleneglycol-bis[beta-aminoethyl ether] -N,N'-tetra- ace
- microspheres or liposomes and c) one or more members selected from a third group consisting of: lecithin, phophatidylcholine, phosphatidylserine, phosphatidylethanolamine, dilinoleylphosphatidylcholine, lysolipids, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylcholine, phosphatidic acid, sphingomyelin, cholesterol, cholesterol sulfate, cholesterol hemisuccinate, tocopherol hemisuccinate, phosphatidylethanolamine, phosphatidylinositol, palmitic acid, stearic acid, oleic acid, linolenic acid, linoleic acid; wherein at least 1 % of said one or more members from said third group is in a microsphere or a liposome.
- This invention provides, in non-limiting embodiments, novel preparations of chelating agents encapsulated in micelles or liposomes comprising the triple combination of: 1) micelles or liposomes comprising alpha lipoic acid or a derivative thereof and 2) micelles or liposomes comprising a chelating agent, such as EDTA; and furthermore, in different embodiments, optionally 3) magnesium chloride.
- the micelles or liposomes can comprise what has been termed "essential phospholipids".
- Biologically active and bioactive are used interchangeably, and can refer to in vitro, ex vivo and/or in vivo situations.
- Phvsiological solutions suitable for intravenous injection or infusion include: e.g. Saline.
- normal (physiologic) saline is used in the preparations and formulations of the invention.
- other pharmaceutically acceptable solutions can be utilized including, but not limited to, 0.9% saline solution, 5% dextrose solution, lactated Ringer's solution, 5% dextrose in lactated Ringer's solution, dextrose- saline combinations, albumin-containing solutions, dextran, dextran-saline combinations, etc. and equivalent solutions.
- POEBACA preparation(s) of encapsulated bioavailable chelating agents(s). Both plural and singular meanings are included.
- POEBACAI ingredient(s) for making up (a) preparation(s) of encapsulated bioavailable chelating agents(s).
- POEBACA encapsulated bioavailable chelating agents
- Alternative embodiments of POEBACA comprise the following ingredients (or "PEOBACAI"), for which non-limiting examples are listed in Table 1: a) one or more members selected from Group A (e.g. alpha lipoic acid); b) one or more members selected from Group B (e.g. EDTA); c) one or more members selected from Group C (e.g. lecithin); d) optionally, in separate embodiments, one or more members selected from Group D (e.g.
- magnesium chloride e) optionally, in separate embodiments, one or more members selected from Group E (glutathione); f) optionally, in separate embodiments, one or more members selected from Group F (e.g. vinpocetine); g) optionally, in separate embodiments, one or more members selected from Group G (e.g. nitrogen gas); wherein the ingredients are prepared in a manner that provides the encapsulation of a significant fraction of one or more ingredient(s) into liposomes or microspheres.
- This invention also provides novel preparations comprising the following (optionally encapsulated) edible ingredients, for which non-limiting examples are listed in Table 3: a) one or more members selected from Group 1 (e.g.
- DIM DIM
- members selected from Group 2 e.g. grape extract or grape skin extract or wine extract, e.g. red wine extract,, resveratrol, and piceatannol
- Group 3 e.g. calcium D-glucarate
- members selected from Group 4 e.g. medium chain triglycerides
- one or more members selected from Group 5 e.g. lecithin
- this invention provides that a serviceable ingredient that is a member of Group 4, can be a preparation in which at least half of the content by weight is MCTs, said at least half of the content by weight of MCTs comprising at least about 40% MCTs having lengths between C 5 and C ⁇ .
- said at least half of the content by weight of MCTs can range from at least about 40% to at least about 95% (also including eveiy integer value in this range) MCTs having lengths between C 5 and C ⁇ -
- a serviceable ingredient that is a member of Group 4 can be a preparation in which at least half of the content by weight is MCTs, said at least half of the content by weight of MCTs comprising at least about 90% MCTs having lengths between C5 and Cn.
- Exemplary numbers of Group A members e.g. alpha lipoic acid.
- "preparations of encapsulated bioavailable chelating agents" i.e.
- POEBACA polystyrene-maleic anhydride copolymer
- n 1, 2, 3, ..., 100
- the minimum number of members selected from Group A that is contained in each embodiment ranges from one to one hundred (including every integer value in between), i.e. at least one, at least two, at least three, at least four, ..., and up to at least 100.
- one alternative embodiment of this invention provides a POEBACA comprising at least one member selected from Group A; another alternative embodiment of this invention provides a POEBACA comprising at least two members selected from Group A; another alternative embodiment of this invention provides a POEBACA comprising at least three members selected from Group A; etc. ; another alternative embodiment of this invention provides a POEBACA comprising at least one hundred members selected from Group A; for convenience these are referred to as alternative embodiments Al to A100, and these separate embodiments are intended to be the subject matter of separate claims according to this invention. Exemplary numbers of Group B members (e.g. EDTA). In alternative embodiments "preparations of encapsulated bioavailable chelating agents" (i.e.
- POEBACA poly(ethylene glycol)
- n 1, 2, 3, ..., 100, including every integer value within the range of 1 to 100.
- the minimum number of members selected from Group B that is contained in each embodiment ranges from one to one hundred (including every integer value in between), i.e. at least one, at least two, at least three, at least four, ..., and up to at least 100.
- one alternative embodiment of this invention provides a POEBACA comprising at least one member selected from Group B; another alternative embodiment of this invention provides a POEBACA comprising at least two members selected from Group B; another alternative embodiment of this invention provides a POEBACA comprising at least three members selected from Group B; etc. ; another alternative embodiment of this invention provides a POEBACA comprising at least one hundred members selected from Group B; for convenience these are referred to as alternative embodiments Bl to B 100, and these separate embodiments are intended to be the subject matter of separate claims according to this invention. Exemplary numbers of Group C members (e.g. lecithin). In alternative embodiments of "preparations of encapsulated bioavailable chelating agents" (i.e.
- POEBACA polystyrene-maleic anhydride copolymer
- n 1, 2, 3, ..., 100
- the minimum number of members selected from Group C that is contained in each embodiment ranges from one to one hundred (with every integer value in between), i.e. at least one, at least two, at least three, at least four, ..., and up to at least 100.
- one alternative embodiment of this invention provides a POEBACA comprising at least one member selected from Group C; another alternative embodiment of this invention provides a POEBACA comprising at least two members selected from Group C; another alternative embodiment of this invention provides a POEBACA comprising at least three members selected from Group C; etc. ; another alternative embodiment of this invention provides a POEBACA comprising at least one hundred members selected from Group C; for convenience these are referred to as alternative embodiments Cl to 100, and these separate embodiments are intended to be the subject matter of separate claims according to this invention.
- Group D members e.g. magnesium chloride.
- "preparations of encapsulated bioavailable chelating agents" i.e.
- n 1, 2, 3, ..., 20, including every integer value within the range of 1 to 20.
- the minimum number of members selected from Group D that is contained in each embodiment ranges from one to twenty (including every integer value in between), i.e. at least one, at least two, at least three, at least four, ..., and up to at least 20.
- one alternative embodiment of this invention provides a POEBACA comprising at least one member selected from Group D; another alternative embodiment of this invention provides a POEBACA comprising at least two members selected from Group D; another alternative embodiment of this invention provides a POEBACA comprising at least three members selected from Group D; etc. ; another alternative embodiment of this invention provides a POEBACA comprising at least twenty members selected from Group D; for convenience these are referred to as alternative embodiments DI to D20, and these separate embodiments are intended to be the subject matter of separate claims according to tins invention. Exemplary numbers of Group E members (e.g. glutathione). In alternative embodiments "preparations of encapsulated bioavailable chelating agents" (i.e.
- POEBACA poly(s)
- n 1, 2, 3, ..., 20, including every integer value within the range of 1 to 20.
- the minimum number of members selected from Group E that is contained in each embodiment ranges from one to twenty (including every integer value in between), i.e. at least one, at least two, at least three, at least four, ..., and up to at least 20.
- one alternative embodiment of this invention provides a POEBACA comprising at least one member selected from Group E; another alternative embodiment of this invention provides a POEBACA comprising at least two members selected from Group E; another alternative embodiment of this invention provides a POEBACA comprising at least three members selected from Group E; etc. ; another alternative embodiment of this invention provides a POEBACA comprising at least twenty members selected from Group E; for convenience these are referred to as alternative embodiments El to E20, and are intended to be claimed subject matter according to this invention.
- Exemplary numbers of Group F members e.g. vinpocetine.
- "preparations of encapsulated bioavailable chelating agents” i.e. POEBACA
- POEBACA encapsulated bioavailable chelating agents
- one alternative embodiment of this invention provides a POEBACA comprising at least one member selected from Group F; another alternative embodiment of this invention provides a POEBACA comprising at least two members selected from Group F; another alternative embodiment of this invention provides a POEBACA comprising at least three members selected from Group F; etc. ; another alternative embodiment of this invention provides a POEBACA comprising at least twenty members selected from Group F; for convenience these are referred to as alternative embodiments FI to F20, and these separate embodiments are intended to be the subject matter of separate claims according to this invention.
- Alternative numbers of Group G members e.g. nitrogen gas).
- "preparations of encapsulated bioavailable chelating agents" i.e.
- POEBACA poly(ethylene glycol)
- n 1, 2, 3, ..., 20, including every integer value within the range of 1 to 20.
- the minimum number of members selected from Group G that is contained in each embodiment ranges from one to twenty (including every integer value in between), i.e. at least one, at least two, at least three, at least four, ..., and up to at least 20.
- one alternative embodiment of this invention provides a POEBACA comprising at least one member selected from Group G; another alternative embodiment of this invention provides a POEBACA comprising at least two members selected from Group G; another alternative embodiment of this invention provides a POEBACA comprising at least three members selected from Group G; etc. ; another alternative embodiment of this invention provides a POEBACA comprising at least twenty members selected from Group G; for convenience these are referred to as alternative embodiments Gl to G20, and these separate embodiments are intended to be the subject matter of separate claims according to this invention. Exemplary numbers of members from Groups A through G.
- This invention further provides the additional aspects that result from all the possible combinations and permutations of the alternative embodiments of Al to A100, Bl to B100, Cl to C100, DI to D20, El to E20, FI to F20, and Gl to G20.
- (100 alternative embodiments corresponding to Al to A 100) x (100 alternative embodiments corresponding to Bl to B100) x (100 alternative embodiments corresponding to Cl to CIOO) x (20 alternative embodiments corresponding to DI to D20) x (20 alternative embodiments corresponding to El to E20) x (20 alternative embodiments corresponding to FI to F100) x (100 alternative embodiments corresponding to Gl to G20) 160,000,000,000 or one hundred and sixty billion alternative aspects, and these separate aspects are intended to be the subject matter of separate claims according to this invention.
- Exemplary amounts of ingredients In alternative aspects, the relative amounts of each ingredient that can comprise a
- R-(+)-alpha-lipoic acid substantially enantiomerically pure
- S-(-)-alpha- lipoic acid substantially enantiomerically pure
- R/S-alpha-lipoic acid racemic mixture
- R/S-gamma-lipoic acid racemic mixture
- other isomers of alpha lipoic acid derivatives of alpha lipoic acid (such as the dihydro version of these alpha lipoic acid isomers, also known as dihydrolipoic acid or DHLA)
- animal and vegetable oils hydrocarbon oils, ester oils, silicone oils, higher fatty acids, higher alcohols, sunscreening agents, vitamins, ferulic acid
- lecithin that contains at least 20% phosphatidyl choline (this invention provides separate embodiments where the lecithin content of phosphatidyl choline is approximately each integer value between 20% and 90%).
- Sulfur-Containing Amino Acids Sulfur-Containing Peptides, Sulfur- Containing Proteins Glutathione, methionine, cysteine Plant aUcaloids (e.g. vinpocetine, vincamine), coenzyme Q10, and analogues coenzyme Q10 (e.g. idebenone)
- G Gaseous ingredient Nitrogen gas, oxygen gas, atmospheric air, gaseous mixtures containing nitrogen gas, gaseous mixtures containing oxygen gas. Table 2. Amounts of ingredients to be protected as claimed by this invention. Values are normalized to 2 oz or approximately 56 grams.
- Table 3 Exemplary ingredients used in the methods and compositions of the invention.
- Group Group Members Non-limiting examples are listed for each group
- Group Group Members Non-limiting examples are listed for each group
- Plant indoles including sources of plant indoles (e.g. DIM).
- Sources of plant indoles include including vegetables, as well as parts thereof (e.g. skin, flesh, seeds, etc.) and extracts thereof (e.g. skin extracts), belonging to or related to the mustard famUy (Cruciferae or Brassicaceae), which includes the alyssum, candytuft, cabbage, radish, broccoli, and many weeds.
- DIM is also found in grapes, teas (e.g. black teas), cranberry, cherries, blackberries and other berries.
- I3C Indole-3-carbinol
- DIM dimer 3,3'-diindolylmethane
- Diindolylmethane, or DIM, and Indole-3-carbinol (I3C) can be isolated from or found in cruciferous vegetables, or, be synthetic
- Plant flavonoids Plant flavonoids, polyphenols. stilbenes and related substances (PFPSARS), including sources of plant flavonoids, polyphenols, stilbenes. and related substances (e.g. 3,5,4 -trihydroxy stilbene or resveratrol. piceatannol, and grape extract or grape skin extract or wine extract, e.g. red wine extract).
- PFPSARS Plant flavonoids, polyphenols. stilbenes and related substances
- sources of plant flavonoids e.g. 3,5,4 -trihydroxy stilbene or resveratrol. piceatannol
- grape extract or grape skin extract or wine extract e.g. red wine extract
- Sources of plant polyphenols include at least 70 to 80 species (if not a lot more), e.g. mulberries, peanuts, and grapes, as well as parts thereof (e.g. skin, flesh, seeds, etc.) and extracts thereof (e.g. skin extracts such as curcumin skin extract and grape extract or grape skin extract or wine extract, e.g. red wine extract,), as well as in wines and vinegars.
- species e.g. mulberries, peanuts, and grapes
- parts thereof e.g. skin, flesh, seeds, etc.
- extracts thereof e.g. skin extracts such as curcumin skin extract and grape extract or grape skin extract or wine extract, e.g. red wine extract,
- PFPSARS are also found, by way of non-limiting examples, in a) Piper methvsticum, kava kava, Piperaceae, plant in flower; b) Pinus resinosa, red pine, Pinaceae, trees in forest; c) Saccharum officinarum, sugar cane, Poaceae, drawing; d) Vitis vinifera, grape, Vitaceae, fruits; Morus alba, mulberry, Moraceae, male and female flowers; e) Marchantia polymorpha, a liverwort, gametophytes and sporophytes; f) Orchis militaris. Helm Knabenkraut, Orchidaceae, flowers; and g) huzhang (Polygonum cuspidatum aka "tiger cane” or giant knotweed).
- Resveratrol and its metabolite piceatannol E.g. Resveratrol and its metabolite piceatannol. It is appreciated that substances such as resveratrol and piceatannol can be modified or derivatized (form a chemical point of view), and both the alternative use of and the additional use of these modified or derivatized substances are also protected by this invention.
- Glucaric acid and derivatives thereof e.g. calcium d-glucarate and 1,4-GL including sources thereof.
- Calcium D-glucarate is the calcium salt of D-glucaric acid, a natural substance found in many fruits and vegetables.
- D-glucaric acid e.g. potassium hydrogen D-glucarate or PHG
- D-glucaric acid can be modified or derivatized (form a chemical point of view)
- both the alternative use of and the additional use of these different salts or derivatized substances e.g. D- glucaro-l,4-lactone or 1,4-GL, 2-keto-3-deoxy-D-glucarate, and 4-deoxy-5- keto-D-glucarate
- Group Group Members (Non-limiting examples are listed for each group) Medium Chain Triglycerides and sources thereof (e.g. a preparation in which at least half of the content by weight is MCT, said at least half of the content comprising at least 80% between C ⁇ and On MCTs).
- Sources of medium chain triglycerides or MCTs include coconut oil, palm kernel oil, camphor tree drupes, and butter. MCT are also available as a supplement.
- Medium chain triglycerides are medium-chain fatty acid esters of glycerol.
- Medium-chain fatty acids are fatty acids containing from six to 12 carbon atoms.
- Coconut and palm kernel oils are also called lauric oils because of their high content of the 12 carbon fatty acid, lauric or dodecanoic acid.
- Medium-chain triglycerides used for nutritional and other commercial purposes are sometimes derived from lauric oils.
- lauric oils are hydrolyzed to medium-chain fatty acids and glycerol. The glycerol is drawn off from the resultant mixture, and the medium-chain fatty acids are fractionally distilled.
- the medium-chain fatty acid fraction used commercially is sometimes mainly comprising the eight carbon caprylic or octanoic acid and the 10 carbon capric or decanoic acid. There are much smaller amounts of the six carbon caproic or hexanoic acid and the 12 carbon lauric acid in the commercial products.
- the caprylic- and capric-rich mixture is finally re-esterified to glycerol to produce medium-chain triglycerides that are mainly glycerol esters of caproic ( ) capiylic (Cg), capric (Cio) and lauric acid ( 2 ) in a ratio of approximately 2:55:42: 1.
- MCTs have chemical structures well known in the art.
- Group Group Members Non-limiting examples are listed for each group) Phospholipids and sources thereof (e.g. lecithin)
- Examples include lecithin, phophatidylcholine, phosphatidylserine, phosphatidylethanolamine, dilinoleylphosphatidylcholine, lysolipids, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylcholine, phosphatidic acid, sphingomyelin, cholesterol, cholesterol sulfate, cholesterol hemisuccinate, tocopherol hemisuccinate, phosphatidylethanolamine, phosphatidylinositol, fatty acids (e.g.
- glycosphingolipids glucolipids, glycolipids, sulphatides, lipids bearing sulfonated mono-, di-, oligo- or polysaccharides, lipids with ether and ester-linked fatty acids, triglycerides, lipoproteins (high or low density), cholesterol, and other lipids and polymerized lipids.
- Lycopenes and carotenoids include alpha-carotene, beta-carotene, lutein, cyptoxanthin, zeaxanthin and plant-derived lycopenes (e.g. blueberry-derived and tomato- derived lycopenes).
- Table 4 Amounts of ingredients used in compositions and methods of the invention. Values are normalized to a "00" capsule, containing approximately 800 mg total (typically in the range of approximately 700 - 900 mg).
- the instant preparations comprise ingredients exemplified in Table 1, and, in one aspect, are orally ingestible.
- these preparations can be liquids (e.g. that can be orally ingested with the help of a spoon), or capsules, tablets, and pills.
- they can also be formed into flavored bars (e.g. similar to what bars that are marketed as “power bars”, “diet bars”, “energy bars”, and “nutritional bars”).
- This invention provides that the instant preparations comprising ingredients exemplified in Table 3 are orally ingestible.
- these preparations can be liquids (e.g.
- ingredients required herein are ingredients that are commercially available from numerous commercial sources.
- grape extract or grape skin extract or wine extract e.g. red wine extract
- edible grape extract or grape skin extract or wine extract e.g. red wine extract
- Grape extract or grape skin extract or wine extract e.g. red wine extract
- enocianina Grape extract or grape skin extract or wine extract, e.g. red wine extract
- Table 2 the relative amounts of each ingredient (POEBACAI) have been expressed in the context of a 2 ounce dose. This is for convenience and consistency, but in separate embodiments this invention provides that that dosages or other sizes can be prepared and administered, particularly ranging, by way of non-limiting exemplification, from about 0.1 ounce to about 128 ounces (or one gallon), including every 0.1 ounce increment in between.
- Alternative amount(s) of Group A members e.g. alpha lipoic acid.
- This invention provides separate embodiments wherein per 2 ounces the total amount of ingredient(s) from Group A (e.g.
- alpha lipoic acid collectively is from about 0.01 mg to about 20,000 mg inclusive, including specifically each increment of about 0.01 mg within this range.
- this invention provides separate embodiments wherein per 2 ounces the total amount of each specific Group A ingredient(s) individually is from about 0.01 mg to about 20,000 mg inclusive, including specifically each increment of about 0.01 mg within this range.
- this invention provides preparations of encapsulated bioavailable chelating agents (i.e. POEBACA) wherein the total amount of Group A members (e.g. alpha lipoic acid) is about 0.01 mg; 2) in another embodiment, this invention provides preparations of encapsulated bioavailable chelating agents (i.e.
- this invention provides preparations of encapsulated bioavailable chelating agents (i.e. POEBACA) wherein the total amount of Group A members (e.g. alpha lipoic acid) is about 0.03 mg; etc.; and 4) in another embodiment, this invention provides preparations of encapsulated bioavailable chelating agents (i.e. POEBACA) wherein the total amount of Group A members (e.g. alpha lipoic acid) is about 20,000 mg.
- Alternative amount(s) of Group B members e.g. EDTA).
- This invention provides separate embodiments wherein per 2 ounces the total amount of ingredient(s) from Group B (e.g. EDTA) collectively is from about 0.01 mg to about 30,000 mg inclusive, including specifically each increment of about 0.01 mg within this range. Furthermore, this invention provides separate embodiments wherein per 2 ounces the total amount of each specific Group B ingredient(s) individually is from about 0.01 mg to about 30,000 mg inclusive, including specifically each increment of about 0.01 mg within this range.
- Group B e.g. EDTA
- Group C members e.g. lecithin
- This invention provides separate embodiments wherein per 2 ounces the total amount of ingredient(s) from Group C (e.g. lecithin) collectively is from about 0.01 mg to about 40,000 mg inclusive, including specifically each increment of about 0.01 mg within this range.
- this invention provides separate embodiments wherein per 2 fluid ounces the total amount of each specific Group C ingredient(s) individually is from about 0.01 mg to about 40,000 mg inclusive, including specifically each increment of about 0.01 mg within this range.
- Alternative amount(s) of Group D members e.g. magnesium chloride. This invention provides separate embodiments wherein per 2 ounces the total amount of ingredient(s) from Group D (e.g.
- magnesium chloride collectively is from about 0.01 mg to about 10,000 mg inclusive, including specifically each increment of about 0.01 mg within this range.
- this invention provides separate embodiments wherein per 2 ounces the total amount of each specific Group D ingredient(s) individually is from about 0.01 mg to about 10,000 mg inclusive, including specifically each increment of about 0.01 mg within this range.
- Alternative amount(s) of Group E members e.g. glutathione.
- This invention provides separate embodiments wherein per 2 ounces the total amount of ingredient(s) from Group E (e.g. glutathione) collectively is from about 0.01 mg to about 10,000 mg inclusive, including specifically each increment of about 0.01 mg within this range.
- this invention provides separate embodiments wherein per 2 fluid ounces the total amount of each specific Group E ingredient(s) individually is from about 0.01 mg to about 10,000 mg inclusive, including specifically each increment of about 0.01 mg within this range.
- Alternative amount(s) of Group F members e.g. vinpocetine .
- This invention provides separate embodiments wherein per 2 ounces the total amount of ingredient(s) from Group F (e.g. vinpocetine) collectively is from about 0.01 mg to about 10,000 mg inclusive, including specifically each increment of about 0.01 mg within this range.
- this invention provides separate embodiments wherein per 2 ounces the total amount of each specific Group F ingredient(s) individually is from about 0.01 mg to about 10,000 mg inclusive, including specifically each increment of about 0.01 mg within this range.
- Alternative percentages of encapsulated Group G members e.g. nitrogen gas.
- This invention provides separate embodiments wherein one or more gases may be contained in a percentage of the liposomes or micropsheres in a POEBACA.
- the gas comprises nitrogen gas, oxygen gas, atmospheric air, gaseous mixtures containing nitrogen gas, gaseous mixtures containing oxygen gas, or a combination thereof.
- the percent of liposomes or micropsheres that contains a gas is from about 1% to about 100%, including every integer value in between.
- Alternative methods of administration This invention provides POEBACA that can be admimstered by several routes, including intravenous, topical, and oral.
- this invention provides forms of POEBACA that can be admimstered by inoculation, infusion or injection, (e.g., intraperitoneal, intramuscular, subcutaneous, infra-aural, intra-articular, intra-mammary, etc.), topical application (e.g., on areas, such as eyes, ears, skin or on afflictions such as wounds, burns, etc.), and by absorption through epithelial or mucocutaneous linings (e.g. vaginal and other epithelial linings, gastrointestinal mucosa, etc.).
- inoculation infusion or injection
- topical application e.g., on areas, such as eyes, ears, skin or on afflictions such as wounds, burns, etc.
- epithelial or mucocutaneous linings e.g. vaginal and other epithelial linings, gastrointestinal mucosa, etc.
- this invention provides POEBACA in liquid forms that can be administered orally.
- the POEBACA can be also prepared as capsules, tablets, powders, sprays, aerosols, pellets (e.g. for animal consumption), suppositories, or creams and ointments.
- the POEBACA can be also prepared as physiological solutions suitable for IN. administration or other parenteral administration.
- this invention also provides all the possible combinations of ingredient quantities that are possible (e.g. the total of all the ingredients or POEBACAI does not surpass 100% of the relevant total dosage of the POEBACA, and admixing or solubility limitations are not exceeded).
- this invention also provides that a POEBACA may include ingredients (or POEBACAI) that are not contained in micropsheres or liposomes in addition to ingredients that are contained in liposomes, and that these ingredients may be the same or different substances.
- this invention also provides that for each ingredient (or POEBACAI) the percent that is contained in micropsheres or liposomes (in contrast to the percentage that is not contained in micropsheres or liposomes, but rather is in solution) may be from about 0.1% to about 100.0%, including every 0.1% increment within mis range. This provides at least about 1000 separate aspects that are intended for protection according to this invention.
- this invention also provides that in a single POEBACA, the micropsheres or liposomes may be fairly homogeneous in size or in content; alternatively they may be fairly heterogeneous in size or in content.
- Alternative Group A members e.g. alpha lipoic acid.
- Group A members include: antioxidants, particularly hydrophobic antioxidants and other hydrophobic ingredients.
- Group A members include, but are not limited to: R-(+)-alpha-lipoic acid
- Group A members also include, but are not limited to: fatty acids, lysolipids, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylcholine, phosphatidic acid, sphingomyelin, cholesterol, cholesterol sulfate, cholesterol hemisuccinate, tocopherol hemisuccinate, phosphatidylethanolamine, phosphatidylinositol, glycosphingolipids, glucolipids, glycolipids, sulphatides, lipids bearing sulfonated mono-, di-, oligo- or polysaccharides, lipids with ether and ester- linked fatty acids, and polymerized lipids and equivalent compounds.
- Group B members include: chelators or chelating agents.
- Group B members include, but are not limited to: EDTA, EGTA, DPTA, TTHA, HEDHA, NOT A, DOT A, HEDTA, other polyaminopolycarboxylic acids, iminodiacetic acid (IDA), cyclam, penicillamine, dimercaptosuccinic acid, tarfrate, thiomalic acid, crown ethers, nitrilotriacetatic acid (NTA), 3,6-dioxaoctanedithioamide, 3,6-dioxaoctanediamide, salicyladoximine, dithio-oxamide, 8-hydroxyquinoline, cupferron, 2,2'-thiobis( ethyl acetoacetate), 2,2'-dipyridyl, and derivatives thereof and equivalent compounds.
- IDA iminodiacetic acid
- NDA nitrilotriacetatic acid
- Group C members include: phospholipids, lipids and fatty acids.
- Group C members include, but are not limited to: lecithin, phophatidylcholine, phosphatidylserine, phosphatidylethanolamine, dilinoleylphosphatidylcholine, lysolipids, dipahnitoylphosphatidylcholine, distearoylphosphatidylcholine, phosphatidylcholine, phosphatidic acid, sphingomyelin, cholesterol, cholesterol sulfate, cholesterol hemisuccinate, tocopherol hemisuccinate, phosphatidylethanolamine, phosphatidylinositol, fatty acids (e.g.
- Group D members include: magnesium salts.
- Group D members include, but are not limited to: magnesium chloride, magnesium gluconate, magnesium carbonate, calcium magnesium citrate, magnesium sulfate, other salts of magnesium, and other forms of magnesium and equivalent compounds.
- Alternative Group E embers e.g. glutathione.
- Group E embers include: sulfur-containing amino acids, sulfur- containing peptides, sulfur-containing proteins, and other sulfur-containing substances.
- Group E members include, but are not limited to: glutathione, methionine, cysteine, glutathione-containing peptides and proteins, me omne-containing peptides and proteins, cysteine-containing peptides and proteins, glutathione-containing substances, methionine- containing substances, cysteine-containing substances and equivalent compounds.
- Alternative Group F members e.g. vinpocetine.
- Group F members include: Vinpocetine, vincamine, idebenone and equivalent compounds.
- Group G members include: Nitrogen gas, atmospheric air, and other mixtures of gases that contain nitrogen, oxygen, mixtures of gases that contain oxygen, argon, and mixtures of gases that contain argon, etc. and equivalent compounds Lipophilic Anti-oxidants (e.g. alpha lipoic acid).
- the compositions and methods of the invention use alpha-lipoic acid; which in addition to its non-toxicity and lipophilicity has the advantage of being rapidly converted in tissues into its reduced form, dihydrolipoic acid (DHLA). DHLA also has potent antioxidant effects.
- the present invention provides a lipophilic antioxidant in an aqueous physiological fluid, such as a resuscitation fluid by lipid encapsulation, e.g. by providing liposomal formation methods to form stable micellular solutions of alpha-lipoic acid or other lipophilic antioxidant(s).
- the present invention seeks to overcome previous limitations by solubilizing alpha-lipoic acid in aqueous solution without the use of solvents such as harsh organic solvents.
- Alpha-lipoic acid and other antioxidants are rendered soluble in aqueous solutions by the use of liposomal formation processes, such as ulfrasonication. Because the .alpha.-lipoic molecule contains a polar (water soluble) carboxy-acid group and a non-polar, lipid soluble chain of carbon and sulfur atoms, the molecule is amphipathic, i.e., it has the ability to form micelles. Micelles may be formed in aqueous solution if a molecule possesses both polar and non-polar groups.
- a number of the water soluble ends of the alpha-lipoic acid molecule are on the outside of aggregations of alpha-lipoic acid.
- a number of the non-polar, lipid soluble tails are directed inward forming a tiny droplet, a micelle, which is water soluble.
- Ulfrasonication of amphipathic molecules into micelles such as can be done with alpha- lipoic acid also has the possibility of creating mixed micelles. In this manner a mixture of alpha-lipoic acid with other antioxidants, which may not have the ability to form micelles alone for lack of any polar group, can be contained within a micelle of alpha-lipoic acid.
- miceUes containing alpha-lipoic acid and purely non-polar but highly lipid soluble antioxidants can be used to convey antioxidants to the tissues.
- hemorrhagic shock which have as their final common pathway oxidant-inducing injury to tissues and can be ameliorated (e.g., treated) and/or prevented with the compositions and methods of the invention.
- various chelating agents are used in the compositions and methods of the invention.
- polyaminopolycarboxylic acid or EDTA ethylene-diaminetetraacetic acid
- EDTA ethylene-diaminetetraacetic acid
- DTP A diethylenetriaminepentaacetic acid
- EGTA ethyleneglycol-bis[.beta.-aminoethyl ether]-N,N'-tetra- acetic acid
- EGTA is also provided as chelating agent.
- EGTA is more specific for particular substances such as calcium when compared to other substances such as magnesium, and thus may be used as a alternative ingredient when it is desirable to chelate calcium (e.g. as is found in arterial plaques, and thus for diminishing arterial plaques) more than for chelating magnesium.
- DMSA dimercaptosuccinic acid
- it is one effective oral chelating agent that is absorbed orally, and is more effective at chelating particular substances such as mercury, cadmium, lead, and arsenic in comparison to other substances; and thus DMSA may be used as a alternative ingredient when it is desirable to chelate mercury, cadmium, lead and arsenic (such for the detoxification of poisoning from lead, mercury, cadmium or arsenic) more than for chelating other substances.
- DTP A diethylenetriamine-pentaacetic acid
- TTHA triethylenetetraaminehexaacetic acid
- HEDHA N-hydroxyethylenediaminehexaacetic-acid
- NOTA 1,4,7,10- tetraazacyclododecane-N,N',N",N'"-tetraacetic acid
- HEDTA N'-hydroxy- ethylenediamine-N,N,N'-triacetic acid
- chelating agents used in the compositions and methods of the invention include iminodiacetic acid (IDA), cyclam, penicillamine, dimercaptosuccinic acid, tartrate, thiomalic acid, crown ethers, nitrilotriacetatic acid (NTA), 3,6- dioxaoctanedithioamide, 3,6-dioxaoctanediamide, salicyladoximine, dithio-oxamide, 8- hydroxyquinoline, cupferron, 2,2'-thiobis(ethyl acetoacetate), 2,2'-dipyridyl.
- IDA is a alternative chelating headgroup which is selective for copper ions.
- Exemplary chelators for use in the present invention include, but are not limited to, ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA); the disodium, trisodium, tetrasodium, dipotassium, tri-potassium, dilithium and diammonium salts of EDTA; the barium, calcium, cobalt, copper, dysprosium, europium, iron, indium, lanthanum, magnesium, manganese, nickel, samarium, strontium, and zinc chelates of EDTA; trans- 1 ,2-diaminocyclohexane-N,N,N',N'-tetraaceticacid monohydrate; N,N-bis(2- hydroxyethyl)glycine; l,3-diamino-2-hydroxypropane-N,N,N',N'-tetraacetic acid; 1,3- diaminopropane-N,N,N'
- the chelators for use in conjunction with the present invention may include ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA); the disodium, trisodium, tetrasodium, dipotassium, tripotassium, dilithium and diammonium salts of EDTA; 1,3- diamino-2-hydroxypropane-N,N,N',N'-tefraacetic acid; 1 ,3-diaminopropane-N,N,N',N'- tetraacetic acid; 0,0'-bis(2-aminoethyl)ethyleneglycol-N,N,N',N'-tefraacetic acid; and 7,19,30-trioxa-l,4,10,13,16,22,27,33-octaazabicyclo[l 1,11,11] pentatriacontane hexahydrobromide.
- EDTA
- the chelators for use in the present invention may include ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA); the disodium salt of EDTA; 1,3- diaminopropane-N,N,N',N'-tetraacetic acid; and 0,0'-bis(2-aminoethyl)ethyleneglycol- N,N,N',N'-tetraacetic acid.
- EDTA ethylenediamine-N,N,N',N'-tetraacetic acid
- the disodium salt of EDTA 1,3- diaminopropane-N,N,N',N'-tetraacetic acid
- 0,0'-bis(2-aminoethyl)ethyleneglycol- N,N,N',N'-tetraacetic acid ethylenediamine-N,N,N',N'-tetraacetic acid
- the invention provides a preparation (or POEBACA), wherein said chelator in said POEBACA may be selected from the group of chelators consisting of EDTA free acid, EDTA 2Na, EDTA 3Na, EDTA 4Na, EDTA 2K, EDTA 2Li, EDTA 2NH.sub.4, EDTA 3K, Ba(II)-EDTA, Ca(II)-EDTA, Co(II)-EDTA, Cu(II)- EDTA, Dy(III)-EDTA, Eu(III)-EDTA, Fe(III)-EDTA, In(III)-EDTA, La(III)-EDTA, Mg(II)-EDTA, Mn(II)-EDTA, Ni(II)-EDTA, Sm(III)-EDTA, Sr(II)-EDTA, Zn(II)-EDTA, CyDTA, DHEG, DTPA-OH, DTPA, EDDA, EDDP
- Alternative chelating agents may also be selected from ethylenebis (oxyethylene nitrilio)tetraacetic acid (EGTA) and ethylene diamine tetracetic acid (EDTA), sodium citrate, or oxalate salts such as sodium, potassium, ammonium or lithium oxalate.
- Alternative chelating groups include those derived from polyaminopolycarboxylic groups, e.g. those derived from EDTA, DTPA, DOTA, TETA, TETRA, TITRA or 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime (HMPAO) or from such groups substituted, e.g.
- this invention provides a preparation (or POEBACA), wherein the chelating group is derived from ethylene diaminetetraacetic acid (EDTA), diethylene triamine pentaacetic acid (DTPA), ethylene glycol-0,0'-bis(2-aminoethyl)- N,N,N',N'-tetraacetic acid (EGTA), N,N'-bis(hydroxybenzyl)ethylenediamine-N,N'- diacetic acid (HBED), triethylenetetramine hexaacetic acid (TTHA), substituted EDTA or -DTPA l,4,7,10-tetra-azacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA) and
- EDTA ethylene diaminetetraacetic acid
- DTPA diethylene triamine pentaacetic acid
- EGTA ethylene glycol-0,0'-bis(2-aminoethyl)- N,N,
- this invention provides a preparation (or POEBACA), wherein the chelating group is derived from 1, 4,7,10-tetraazacyclotridecane- 1,4,7, 10- tefraacetic acid (TITRA), 1 ,4,8, 11 -tetraazacyclotefradecane (TETRA); EDTA, DTPA, DOTA, TETA, TITRA, TETRA or 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime (HMPAO) substituted by p-isothiocyanato-phenyl-C.sub.1-3 alkyl, in free form or in pharmaceutically accepted salt form.
- HMPAO 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime
- this invention provides a preparation (or POEBACA), comprising R/S-gamma-lipoic acid (6,8-dimercaptooctanoic acid) or R/S-alpha-lipoic acid (D,L-thioctic acid).
- a preparation or POEBACA
- R/S-gamma-lipoic acid (6,8-dimercaptooctanoic acid) or R/S-alpha-lipoic acid (D,L-thioctic acid).
- “substantially enantiomerically pure" l,2-dithiolane-3-pentanoic acid (thioctic acid, alpha-lipoic acid) is within the range from at least about 80% pure to at least about 99% pure inclusive as well as every 1% increment within this range (i.e. at least about 80% pure, at least about 81% pure, at least about 82% pure, etc.).
- D,L-thioctic acid can used in the form of the racemic mixture.
- a racemic mixture can be comprising two isomers that are found at a ratio within the range from about 20%:80 % to about 80%:20% inclusive as well as every 1% increment within this range (i.e. about 20%:80%, about 21%:79%, about 22%:78%, etc.).
- optically active R-(+)-alpha- lipoic acid is used.
- R-(+)-alpha-lipoic acid is a natural substance that is found in animals and humans, and it acts as coenzyme in the oxidative decarboxylation of .alpha. -keto acids.
- Microspheres and liposomes The invention provides compositions, and methods of using them, wherein ingredients of the composition are encapsulated in a microsphere or a liposome or a combination thereof.
- Specific, but non-limiting, examples of microspheres according to this invention are provided herein.
- Specific, but non-limiting, examples of ways of making, administering, and using microspheres or liposomes according to this invention are provided herein.
- this invention provides that the micropsheres can be made using lecithin (and/or alternative ingredients as per Table 1 and 2) in amounts in the range from about 0.1 gram to about 40 grams inclusive, including specifically each increment of about 0.1 gram within this range, in a total of 2 ounces of final POEBACA product.
- this invention provides POEBACA comprising gas-filled microspheres.
- the invention further relates to methods for employing such microspheres as delivery systems to deliver the POEBACAI.
- this invention provides POEBACA comprising at least one member selected from the group consisting of animal and vegetable oils, hydrocarbon oils, ester oils, silicone oils, higher fatty acids, higher alcohols, sunscreening agents, vitamins, alpha lipoic acid, ferulic acid, and flavors and said solid or semi-solid oU component is at least one member selected from the group consisting of animal and vegetable oils, hydrocarbon oils, ester oils, higher fatty acids, higher alcohols, waxes, sunscreening agents and flavors.
- Example 1 Amounts of ingredients Table 2, above, sets forth the amount of ingredients used in exemplary compositions of the invention. Values are normaUzed to 2 oz or approximately 56 grams
- Example 2 Exemplary method for making a microsphere or liposome
- Example 4 Amounts of ingredients Table 4, above, sets forth the amount of ingredients used in exemplary compositions of the invention. Values are normalized to a "00" capsule, containing approximately 800 mg total (typically in the range of approximately 700 - 900 mg)
- Example 5 Exemplary method for making an exemplary breast and prostate health supplement of the invention
- CAPSULE FILL 760 mg
- PREPARATION 1. Sift calcium-D-glucarate into a planetary mixer (e.g. Hobart) or v-blender tumbler through # 18 mesh screen. 2. Sift grape extract or grape skin extract or wine extract, e.g. red wine extract, into a planetary mixer (e.g. Hobart) or v-blender tumbler through # 18 mesh screen. Mix for 8+ minutes 3. Sift DIM into a planetary mixer (e.g.
- Example 6 Combination kits (as exemplified by a l it comprising Prep A and Prep B).
- a detoxification preparation, Prep A is made.
- Prep A is a fluid, and it contains per 2 fluid ounces:
- Prep B is in the form size "00" vegetable capsules (Vcap or v-cap), and it contains per capsule:
- kits or a combinations of preparations comprising: i) a first preparation that contains ingredients selected from the Groups A-G as exemplified in Table 1 and in the amounts as exemplified in Table 2; and ii) a second preparation containing ingredients selected from Groups 1-5 as exemplified in Table 3 and in the amounts as exemplified in Table 4.
- Examples 4 and 6 provide non limiting exemplifications of such a kit, e.g., where the two exemplary preparations in the kit are Prep A and Prep B.
- This invention also provides modifications and alterations of the provided Examples, specifically according the different embodiments of preparations provided herein.
- each ingredient in a particular preparation can be altered and modified in specific embodiments, and these amounts include those amounts listed in Table 2 (including in the last column of Table 2), and those amounts listed in Table 4 (including in the last column of Table 4).
- This invention also provides methods for using such a kit, as is exemplified in Examples 4 and 5, e.g., that comprise: i) a first preparation that contains ingredients selected from the Groups A-G as exemplified in Table 1 and in the amounts as exemplified in Table 2; and ii) a second preparation containing ingredients selected from Groups 1-5 as exemplified in Table 3 and in the amounts as exemplified in Table 4.
- Prep B (e.g. for breast or prostate tissue health) is taken orally as follows. a) On Day 1, the consumer, e.g. human or animal (e.g. a pet or livestock) starts taking Prep B; the suggested amount for a typical 75 kg adult is: two size "00" capsules per day, (e.g. one with breakfast and one with dinner). This regimen is maintained daily for weeks or months or years. In one aspect, Prep B is incorporated into the regular diet, and it is taken daily, e.g. for years.
- Prep A for detoxification
- the suggested amount is: 2-4 ounces per week (e.g. for a regimen lasting 5-20 weeks (e.g. depending on the systemic levels of toxins or heavy metals), e.g. at night, and at least one or two hours after the last meal of the day.
- Prep A can be taken one time a week (e.g. 1 or 2 oz. each time) or two times a week (1 or 2 oz. each time).
- Prep A can be discontinued after the 10-20 week regimen is completed.
- Prep A can be taken independently of Prep B, e.g. as illustrated in Example 7, but without Prep B.
- Prep B can be taken independently of Prep A, e.g. as illustrated in Example 7, but without Prep A.
- this invention intends to reserve protection for all the embodiments and aspects described herein, such as products that contain (or methods that use) any ingredients from any of Groups A, B, C, D, E, F, 1, 2, 3, 4, and/or 5, with further modifications (or claim limitations) through the addition of anywhere from one to 100 vitamins as exemplified in Table 5 (specifically Groups 6 and 7), and in the amounts as illustrated in Table 6; the result is additional embodiments and aspects intended for patent protection (as patent claims containing limitations regarding ingredient quantities and/or quantity ranges).
- Table 5 are non-limiting examples of molecular forms as provided herein. It is provided that it is the intent of this invention to specifically include not only the specific examples listed in Table 5, but also derivatives, precursors, and active metabolites of the vitamins listed in Table 5, as these are known in the art, and this invention seeks patent protection for embodiments and aspects provided herein (e.g.
- beta-carotene is a precursor to vitamin A, and it is thus provided according to this invention.
- Thiamine is sometimes spelled thiamin.
- Cobalamin is sometimes spelled cobalamine.
- Folates are classified as vitamin B9, but sometimes as vitamin B8.
- Group Group Members (Non-limiting examples are listed for each group)
- Group Group Members (Non-limiting examples are listed for each group)
- Water soluble vitamins such as vitamin C and the B vitamins (e.g. folic acid and folinic acid)
- Vitamin C including ascorbic acid and ascorbates, such as calcium ascorbate, chromium ascorbate, magnesium ascorbate, manganese ascorbate, molybdenum ascorbate, sodium ascorbate, zinc ascorbate, 1-ascorbic acid, 1- (+)-ascorbic acid, 1,3-ketothreohexuronic acid; also including metabolites such as dehydroascorbate (oxidized ascorbic acid), calcium threonate, xylonate and lyxonate; also including precursors and derivatives such as ascorbyl palmitate (a vitamin C ester, likely to hydrolyzed to ascorbic acid and palmitic acid).
- ascorbic acid and ascorbates such as calcium ascorbate, chromium ascorbate, magnesium ascorbate, manganese ascorbate, molybdenum ascorbate, sodium ascorbate, zinc ascorbate, 1-ascorbic acid, 1- (+)-as
- B-Vitamins including Bl (thiamine), B2 (riboflavin), B3 (niacin, niacinamide, inositol hexaniacinate, nicotinamide, nicotinic acid), B5 (pantothenates, such as pantothenic acid, calcium pantothenate, pantethine), B6 (pyridoxine, PLP, Pyridoxal-5'-Phosphate), B7 (biotin), B9 (folinic acid, folic acid, folates such as methylfolate, or 5-formyl tetrahydro folate), and B12 (cobalamin and derivatives such as, hydroxycobalamin, methylcobalamin, adenosylcobalamin, cyanocobalamin, hydroxycyanocobalamin). Products containing variations of these vitamins are also included herein (for patent protection) and include, e.g. folinic acid (e.g. as calcium folin
- Fat soluble vitamins such as vitamins A, D, E, and K
- Vitamin A including retinol and retinol derivatives such as retinoic acid
- carotenoids which includes over 600 members such as lycopene and lutein.
- Vitamin D including 1,25-dihydroxyvitaminD, calciferol, calcipotriol, cholecalciferol, ergocalciferol (vitamin D2), irradiated ergocalciferol
- Vitamin E including alpha tocopherol, tocopherol, tocopheryl acetate, tocopheryl succinate.
- Vitamin K including forms such as phylloquinones, menaquinones, menadione, and menatetrenone (vitamin ? 2).
- Amounts are in reference to a daily dose, the form of which may be, e.g., a powder, a liquid, a pill (including a capsule, a tablet), a "power bar”, & /or a candy (including candy bars, hard candies, “gummy” candies, and gum balls).
- a daily dose the form of which may be, e.g., a powder, a liquid, a pill (including a capsule, a tablet), a "power bar”, & /or a candy (including candy bars, hard candies, “gummy” candies, and gum balls).
- CAPSULE SIZE "00"
- Vcaps CAPSULE FILL 660 to 740 mg
- PREPARATION 1. Sift calcium-D-glucarate mto a planetary mixer (e.g. Hobart) or v-blender tumbler through # 18 mesh screen. 2. Sift Grape extract or grape skin extract or wine extract, e.g. red wine extract, into a planetary mixer (e.g. Hobart) or v-blender tumbler through # 18 mesh screen. Mix for 8+ minutes 3. Sift DIM into a planetary mixer (e.g. Hobart) or v-blender tumbler through # 18 mesh screen. Mix for 8+ minutes. Optionally, sift lycopenes and or carotenoids into a planetary mixer (e.g.
- the benefits of using the preparations provided herein are many and can be additive or synergistic in regards to individual ingredients in a preparation comprising a plurality of ingredients.
- I3C indole-3-carbinol
- DIM dimer 3, 3 '-diindolylmethane
- Both compounds have been reported to be clinically effective in treating precancerous lesions of the cervix and laryngeal papillomas, pathologies with a human papillomavirus (HPV).
- HPV human papillomavirus
- this invention provides a preparation (or POEBACA), comprising ocular drug delivery vehicle of an oil-in-water submicron emulsion consisting essentially of about 0.5 to 50% of a first component of an oil, about 0.1 to 10% of a second component of an emulsifier, comprising a phospholipid, about 0.05 to 5% of a non-ionic surfactant and an aqueous component, said submicron emulsion having a mean droplet size in the range of 0.05 to 0.5 ⁇ m, and a weight ratio of surfactant to oil of about 1:1 or less.
- this invention provides a method for transferring ingredients making up a preparation of encapsulated bioavailable chelating agents (i.e. POEBACAI) across a cellular membrane by encapsulating said ingredients within liposomes and carrying said POEBACAI to the cellular membrane where the liposomes will be taken up by the cells, thereby transferring the POEBACAI across the cellular membrane.
- POEBACAI can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the POEBACAI to the interior of the cell.
- the released POEBACAI will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.
- this invention provides a method of transferring POEBACAI across a cellular membrane comprising: encapsulating said POEBACAI within liposomes; and carrying said liposome encapsulated POEBACAI to said cellular membrane, whereby said liposome encapsulated POEBACAI will transfer across said cellular membrane.
- this invention provides a method of introducing a POEBACAI into the interior of a cell in accordance with the method of claim 1 wherein said ceUular membrane is the membrane wall of said cell and said encapsulated POEBACAI passes through the membrane wall of said cell into the interior of said cell, wherein said liposomes will be decomposed, thereby releasing said POEBACAI to the interior of said cell.
- this invention provides a method wherein said cell is a ceU of a living organism and said POEBACAI is carried to said cell by injecting a saline suspension of said liposome POEBACAI into the blood stream of said living organism whereby said POEBACAI is carried to the cell within the blood
- this invention provides a method for the removal of intracellularly deposited toxic heavy metals comprising: encapsulating a POEBACAI agent within liposomes; introducing said liposomal POEBACAI into the blood system by one or more of the following routes: oral administration, intravenous injection or infusion, by topical lotion, spray or cream, or transdermal patch; whereby said liposome POEBACAI is carried to said body cells within said blood system; said liposome POEBACAI is passed through the cell wall into the interior of said body cell; said POEBACAI is released to the interior of said cell by the biological degradation of said liposome by lysosomal enzymes, said released POEBACAI complexing said intracellular
- this invention provides a preparation or POEBACA wherein said liposomes are prepared from a mixture of lecithin and cholesterol.
- this invention provides a POEBACAI comprising a member chosen from the group consisting of EDTA, EGTA, and DTPA.
- this invention provides a detoxification method wherein said toxic heavy metals are selected from the group consisting of plutonium, gold, mercury, and lead, beryllium, and cadmium. Any gel can be used in the practice of the present invention.
- the materials which can be used to form such gels include but are not limited to: carbohydrates such as ceUulosics, methylcellulose, starch and modified starch, agarose, gum arabic, ghatti, karay, fragacanth, guar, locust bean gum, tamarind, carageenan, alginate, xanthan, chickle, collagen, polyacrylamide, polysiloxanes (polyanhydrides, e.g., malic anhydride copolymers, polyacrylates, e.g., hydroxyethylpolymethycrylate polymethylmethacrylate, polyethylethacrylate polymethacrylate, ethylenevinylacetate copolymers, ethylenevinylalcohol copolymers, polyorthoesters, .epsilon.-caprolactones, amino acid polymers such as gelled albumin, amino acid polymers and copolymers and gelatins, and other organic or inorganic poly
- the resulting liposome-gel matrix can be implanted in tissues.
- soft gel matrices such as agarose, collagen and the like containing sequestered liposomes may be injected in vivo.
- gels such as methylceUulose can be formed in the tissues after inoculation of liposomes in a suspension containing the gel material. After inoculation the suspension forms a gel and the liposomes remain sequestered in the gel matrix rather than dispersed and cleared.
- the release of a liposome entrapped bioactive chelating agent or other POEBACAI is prolonged and the relative concentration of the agent at the site of inoculation is increased.
- Virtually any POEBACAI (including chelating agents) as well as virtually any other bioactive agent can be entrapped within the liposomes for use according to the present invention.
- Such agents include but are not limited to antibacterial compounds, antiviral compounds, antifungal compounds, anti-parasitic compounds, tumoricidal compounds, proteins, toxins, vitamins, trace minerals, heavy metals, enzymes, hormones, neurotransmitters, lipoproteins, glycoproteins, immunoglobulins, immunomodulators, dyes, radiolabels, radio-opaque compounds, fluorescent compounds, polysaccharides, cell receptor binding molecules, anti-inflammatories, antiglaucomic agents, mydriatic compounds, anesthetics, nucleic acids, polynucleotides, etc.
- two or more POEBACAI (including chelating agents) or other bioactive agents may be entrapped in one liposome population which is sequestered in the gel matrix.
- two or more liposome populations (of the same or different types of liposomes, e.g. mixtures of SPLVs, ?MPVs, SUVs, LUVs, REVs, etc.) which each entrap the same or different POEBACAI (including chelating agents) or other bioactive chelating agents may be sequestered in the gel matrix.
- the gel can be used as a vehicle for the same or different bioactive chelating agents and other POEBACAI than those entrapped by liposomes.
- a drug compound i.e., compound A
- a sustained dose of the same or another compound i.e., compound B
- this is readily accomplished by entrapping compound B in liposomes, sequestering the liposomes in a gel matrix containing compound A, and administering the same in vivo in a single inoculation.
- rapid delivery of compound A by diffusion from the gel, and slow sustained delivery of compound B by release from the liposomes is effected.
- the release of the bioactive chelating agents may be controlled by the type of liposomes used and the membrane composition of the liposome bilayers as well as by the type and porosity of the gels used.
- the rate of release is also dependent upon the size and composition of the bioactive chelating agent itself.
- the liposome itself is the first rate limiting factor in the release of entrapped bioactive chelating agents.
- the rate of release may depend upon the number of bilayers, the size of the liposomes and most importantly the bilayer composition.
- stabilizers such as sterols, cholesterols and the like can be added to the phospholipid bilayers in order to alter the permeability of the liposome, e.g., as described by Papahadjopoulos, D., Kimilberg, H. K., 1974, in Progress in Surface Science, ed. S. G. Davison, pp. 141-232, Oxford: Pergamon; Demel, R. A., Bruckdorf, K. R., Van Deenan, L. L., 1972, Biochem. Biophys. Acta, 255:331-347.
- it is important that the stable liposomes will release their contents upon contact with body fluids or culture media. The rate of release may be controlled by modifying liposome membranes accordingly using known methods.
- the liposome-gel compositions of the present invention may be used for sustained delivery of a bioactive chelating agent to cells and/or fluids in vivo and in vitro.
- the liposome-gel compositions of the present invention may be administered before or after gel formation.
- Routes of administration include but are not limited to: inoculation, injection or infusion, (e.g., intraperitoneal, intramuscular, subcutaneous, intra-aural, infra-articular, mtra-mammary, etc.), topical application (e.g., on areas, such as eyes, ears, skin, mucous membranes, or on afflictions such as wounds, burns, etc.), and by absorption through epithelial or mucocutaneous linings (e.g., nasal, oral, vaginal and other epithelial linings, gastrointestinal mucosa, and the like).
- inoculation e.g., intraperitoneal, intramuscular, subcutaneous, intra-aural, infra-articular, mtra-mammary, etc.
- topical application e.g., on areas, such as eyes, ears, skin, mucous membranes, or on afflictions such as wounds, burns, etc.
- Uposome-gel preparations of the present invention may be inoculated or infused in vivo to provide for the sustained systemic release of the bioactive chelating agent.
- Such applications may be particularly useful for the systemic release of drags such as hormones (e.g., to control growth, fertility, sugar metabolism, etc.) or antimicrobials to control and treat infections, etc.
- the liposome-gel preparation may be applied topically.
- Topical application may be particularly useful for the treatment of wounds (either surgical or non-surgical wounds) where the sustained release of POEBACAI (including chelating agents), antimicrobials and/or blood clotting factors may be helpful in the healing process.
- the liposome-gel preparation may be topically applied to burns for the sustained release of POEBACAI (including chelating agents), antimicrobials and or cell growth factors.
- the liposome-gel preparation may also be applied in the ear to treat infections by providing sustained release of POEBACAI (including chelating agents), antimicrobials; this would reduce the necessity of repeated applications of the bioactive chelating agent in the form of ear drops.
- a liposome-gel preparation may be administered orally for sustained release.
- the liposome-gel preparations of the present invention may also be used in vifro to provide for sustained release of a POEBACAI (including chelating agents) into the cell or tissue culture medium.
- POEBACAI including chelating agents
- POEBACAI may also include but are not limited to nutrients, drugs, hormones, growth factors, etc.
- the liposome-gel preparation may be used as a support for cell adhesion and growth; for instance, a liposome-collagen gel may be especially useful for culturing muscle cells, nerve cell, or liver cells. When the liposome-gel preparation is applied as an overlay, a liposome- agarose gel may be particularly useful.
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Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
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JP2007504087A JP2007529543A (en) | 2004-03-17 | 2005-03-17 | Tissue detoxification and health supplements and methods of making and using them |
MXPA06010614A MXPA06010614A (en) | 2004-03-17 | 2005-03-17 | Tissue detoxification and health supplements and methods of making and using them. |
EP05725790A EP1734978A2 (en) | 2004-03-17 | 2005-03-17 | Tissue detoxification and health supplements and methods of making and using them |
CA002559938A CA2559938A1 (en) | 2004-03-17 | 2005-03-17 | Tissue detoxification and health supplements and methods of making and using them |
EA200601705A EA200601705A1 (en) | 2004-03-17 | 2005-03-17 | DETOXIFICATION OF TISSUES AND HEALTHY ADDITIVES, METHODS OF THEIR PRODUCTION AND APPLICATION |
AU2005223618A AU2005223618A1 (en) | 2004-03-17 | 2005-03-17 | Tissue detoxification and health supplements and methods of making and using them |
BRPI0508914-0A BRPI0508914A (en) | 2004-03-17 | 2005-03-17 | tissue detoxification and health supplements and processes for obtaining and using them |
Applications Claiming Priority (12)
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US56073604P | 2004-03-17 | 2004-03-17 | |
US60/560,736 | 2004-03-17 | ||
US10/804,264 | 2004-03-18 | ||
US10/804,268 US20050208119A1 (en) | 2004-03-18 | 2004-03-18 | Encapsulated oral chelating preparations |
US10/804,268 | 2004-03-18 | ||
US10/804,264 US20050208118A1 (en) | 2004-03-18 | 2004-03-18 | Preparations of encapsulated bioavailable chelating agents for detoxifying humans and animals |
US10/815,414 | 2004-03-31 | ||
US10/815,414 US20050209170A1 (en) | 2004-03-18 | 2004-03-31 | Breast health preparations |
US10/816,769 US20050209551A1 (en) | 2004-03-18 | 2004-04-01 | Detoxification and breast health preparations |
US10/816,769 | 2004-04-01 | ||
US11/019,491 | 2004-12-21 | ||
US11/019,491 US20060134244A1 (en) | 2004-12-21 | 2004-12-21 | Breast health supplement and detoxification preparations |
Publications (2)
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WO2005089412A2 true WO2005089412A2 (en) | 2005-09-29 |
WO2005089412A3 WO2005089412A3 (en) | 2006-08-24 |
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PCT/US2005/008839 WO2005089412A2 (en) | 2004-03-17 | 2005-03-17 | Tissue detoxification and health supplements and methods of making and using them |
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EP (1) | EP1734978A2 (en) |
JP (1) | JP2007529543A (en) |
AU (1) | AU2005223618A1 (en) |
BR (1) | BRPI0508914A (en) |
CA (1) | CA2559938A1 (en) |
WO (1) | WO2005089412A2 (en) |
Cited By (9)
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WO2007057688A1 (en) * | 2005-11-17 | 2007-05-24 | Institutt For Akvakulturforskning As | Method for adminstering carotenoids to salmonids |
JP2007262054A (en) * | 2006-03-02 | 2007-10-11 | Taisho Pharmaceut Co Ltd | Liquid preparation for oral administration |
JP2009029776A (en) * | 2007-04-03 | 2009-02-12 | Rohm & Haas Electronic Materials Llc | Metal-plating composition and method |
WO2009078366A1 (en) * | 2007-12-14 | 2009-06-25 | Ezaki Glico Co., Ltd. | α-LIPOIC ACID NANOPARTICLE AND METHOD FOR PRODUCING THE SAME |
WO2011144650A1 (en) * | 2010-05-21 | 2011-11-24 | Raw Materials International Llc - Swiss Branch | Pharmaceutical aqueous compositions comprising lipoic acid as an antioxidant |
WO2012130698A1 (en) | 2011-03-25 | 2012-10-04 | Iiaa Limited | Composition comprising a diindolylmethane and a retinoid to treat a skin condition |
MD493Z (en) * | 2011-06-29 | 2012-10-31 | Государственный Медицинский И Фармацевтический Университет "Nicolae Testemitanu" Республики Молдова | Method for prophylaxis of postradiation complications in oncological diseases |
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WO2015148317A1 (en) * | 2014-03-24 | 2015-10-01 | Specialty Nutrition Group, Inc. | Compositions for enhancing detoxification and uses thereof |
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JP2009159929A (en) * | 2007-12-13 | 2009-07-23 | Fujifilm Corp | Oily composition |
JP5407079B2 (en) * | 2008-02-19 | 2014-02-05 | ディーエスエム アイピー アセッツ ビー.ブイ. | New use of 3,3'-diindolylmethane |
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WO2020132723A1 (en) * | 2018-12-28 | 2020-07-02 | Universidade Estadual De Campinas - Unicamp | Miniemulsions of bioactive fractions of passiflora, compositions including such miniemulsions and formulations |
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- 2005-03-17 WO PCT/US2005/008839 patent/WO2005089412A2/en active Application Filing
- 2005-03-17 AU AU2005223618A patent/AU2005223618A1/en not_active Abandoned
- 2005-03-17 EP EP05725790A patent/EP1734978A2/en not_active Withdrawn
- 2005-03-17 BR BRPI0508914-0A patent/BRPI0508914A/en not_active Application Discontinuation
- 2005-03-17 JP JP2007504087A patent/JP2007529543A/en active Pending
- 2005-03-17 CA CA002559938A patent/CA2559938A1/en not_active Abandoned
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US9907785B2 (en) | 2011-03-25 | 2018-03-06 | Skintech Life Science Limited | Composition comprising a diindolylmethane and a retinoid to treat a skin condition |
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CN106163571B (en) * | 2014-02-18 | 2020-10-16 | 麦迪西斯医药公司 | Use of reverse micelle systems for delivery of chelators of radionuclides and metals |
EA037605B1 (en) * | 2014-02-18 | 2021-04-20 | Медзис Фарма | Use of reverse-micellar systems for delivering chelators of radionuclides and metals |
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Also Published As
Publication number | Publication date |
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BRPI0508914A (en) | 2007-08-14 |
AU2005223618A1 (en) | 2005-09-29 |
EP1734978A2 (en) | 2006-12-27 |
CA2559938A1 (en) | 2005-09-29 |
JP2007529543A (en) | 2007-10-25 |
WO2005089412A3 (en) | 2006-08-24 |
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