Standardized complex protein chains found in food sources provide all the necessary essential and non-essential amino acid complexes, glycoproteins and glycosaminoglycans (GAG) necessary for sustained human development. Whole food proteins also provide essential and non-essential fatty acid complexes, carbohydrate chains, vitamins, and minerals. Dietary protein serves many physiological functions including cell maintenance, repair, and structure, regulation and transport of hormones, enzymes, muscle contraction, immunologic response and essential life functions.
The process by which these proteins are cleaved into specific isolates through the digestive system is well known. Throughout this process complex chains are broken down into amino acid fractions and isolates then utilized for multiple metabolic processes. Further these isolates provide the necessary building blocks for RNA and DNA development as well as forming synergistic bonds for a multitude of endogenous processes. Our further understanding of these specific protein substrates and their beneficial effects on specific tissue reparation and disease processes has led to the development and manufacture of these isolates for therapeutic use as well as dietary supplementation.
Exogenous and endogenous proteins are made from 20 essential and non-essential amino acid groups. Eight amino acids are generally regarded as essential for humans: phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, leucine, and lysine. Additionally, cysteine, tyrosine, histidine and arginine are considered conditionally essential as they are required for gestation and child development. Essential amino acids are not synthesized endogenously, making it essential to include them from dietary sources. In addition, the amino acids arginine, cysteine, glycine, glutamine, histidine, proline, serine and tyrosine may also be considered conditionally essential, as they must be supplied exogenously to specific populations that do not synthesize them in adequate amounts.
Glycoproteins and glycosaminoglycans such as glucosamine, chondroitin sulfates, hepraran sulfate and hyaluronic acid are synthesized endogenously through biochemical processes and perform many regenerative functions in tissue development and repair.
Glucosamine esters were first identified as an important tissue modifier within the body in the late 1950s. This naturally occurring glycoprotein was found to be present in body tissues, with the highest concentrations present in the synovial and cartilage matrices. Trace levels are extracted from food sources and converted via digestive protein synthesis and the hexosamine glucose pathway into the active ester form glucosamine 6 phosphate. Research demonstrates the presence of glucosamine esters to have a mildly anabolic and beneficial effect on articular cartilage regeneration, by stimulating the two groups of cells responsible for cartilage maintenance and hyaluronan production: chondrocytes and synovicytes. When exposed to higher than normal levels of serum glucosamine, Chondrocytes produce more collagen, proteoglycans (the key structural matrices of fibiral, hyaline and articular cartilage) and hyaluronan (the viscous lubricant which bathes and nourishes the synovium).
Synovicytes similarly up-regulate nutrient flow and increase hyaluronic acid production. In vitro studies determine these anabolic responses are dose dependant. These findings led to the development of stabilized exogenous glucosamine forms in 1972. Their popularity as nutritional supplements has grown exponentially with the completion of multiple efficacy studies for their use in the treatment of osteoarthritis. The primary challenge for their use as a dietary supplement has been survivability of the TPF through the digestive system. Until now it has been difficult to overcome metabolic hurdles that prevent TPF delivery to serum, in high enough quantities to trigger the desired responses. The current invention is designed to enhance the bioavailability of three exogenous forms, Glucosamine HCl, Glucosamine NaCl and Glucosamine 2KCl.
Exogenous chondroitin sulfates have also gained favor as nutritional supplements for treatment of osteoarthritis due to their ability to influence tissue repair and suppress degenerative processes. When the articular cartilage becomes compromised; the chondrocytes excrete degenerative enzymes in order to remove the affected tissue so it may be replaced by healthy new cartilage. Under normal conditions this process maintains tissue equilibrium however through compressive failure, trauma or aging; an imbalance occurs and the degenerative process accelerates the onset of osteoarthritis. Chondroitin sulfate; specifically chondroitin 4-sulfate type A, has the potential to reduce the excretion of metalloproteinase, the primary degenerative enzyme inside the synovium. Chondroitin sulfates belong to the family of mucopolysaccharides, more specifically glycosaminoglycans and proteoglycans. In its purified exogenous form, chondroitin sulfate A-4 is comprised of two compounds galactosamine and glucuronic acid. The primary role of chondroitin sulfate A-4 in promoting joint health lies in the ability to reduce the degenerative enzymes metalloproteinase, bind water into the cartilage matrix and provide the basic raw material that comprises articular cartilage. It is theorized that by increasing the available pool of glycosaminoglycans via oral ingestion of chondroitin sulfate, the chondrocytes will be facilitated in their synthesis of proteoglycans thus aiding in the reparation process. This theory has proven accurate in modifying tissues and reducing clinical symptoms in both human and animal models. As chondroitin sulfates are rather large and complex molecules their metabolic fate through the digestive system has been the subject of controversy.
The use of exogenous TPF as dietary supplements has gained popularity world wide. Research science, Sports Medicine and Post-Surgical Rehabilitation have played a pivotal role in the expansive use of these isolates for both general and targeted health. Mounting clinical data demonstrates a link between the increased intake of these compounds and improvement in tissue healing, muscle hypertrophy, strength and athletic performance. Much of the data advancing the development, manufacture and use of these isolates is extrapolated from clinical trials and observations of the endogenous production and utilization of these isolates in living tissue. Unfortunately, the biochemical processes of digestion hinder and often prevent the utilization of these isolates when ingested. The problem with the bioavailability of these TPF isolates in their exogenous forms is three fold. First, the standard digestive enzymatic processes that are designed to cleave complex proteins into smaller usable isolates, expose the exogenous TPF to proteases that break-down complex biochemical bonds and denature much of the isolate. Secondly, gastric acids such as hydrochloric acid expose the isolates to extreme fluctuations in PH, that can result in mutagenic dissociations including: destruction of the TPF; conversion of the TPF into non-metabolized derivatives; and decreasing the digestibility of the TPF as a result of changes to specific rotation, isoelectric precipitation, and intra and interchain cross-linking of the TPF binding forces. Thirdly, epithelial cells of the stomach fundus, duodenum and small intestine metabolize these isolates for energy, resulting in limited survivability and subsequent limited delivery through the intestinal wall. The metabolic fate of many of these isolates is well known and demonstrated in multiple species applications. In the glycoprotein category one recent study found that only 6% of the ingested glycoprotein, glucosamine HCl and 9% of the glycoprotein glucosamine NaCl was detectable in serum after dosing. Previous radiomarker testing showed nearly 90% of this same glycoprotein was metabolized in the body, further indicating the digestive net loss for the glycopreotein through metabolic processes of over 80%. In regard to protein isolates in the form of amino acids, both animal and human studies indicate a similar reduction in the delivery to serum of the ingested compounds from about <11% to >70%. Glycosaminoglycans suffer a similar fate in uptake and utilization as evident in multiple transspecies trials at about <5% to >45%.
The separate use of some supplements to aid different metabolic functions has been used in the past. For example, N-acetyl D-Glucosamine has been included for the treatment of degenerative afflictions of the joint; as a method and agent for treating inflammatory disorders of the gastrointestinal tract; as a method for treatment of lower gastrointestinal tract disorder; and as a treatment for the prevention of interstitial cystitis.
Also, Green Chlorella has been used as a protective and ameliorating agent to improve Liver function, and as a preventive or therapeutic composition for viral infectious disease.
Additionally, Licorice root extracts have been used in enhanced animal food products; as a herbal composition for use in chemotherapy; as a therapeutic composition for the prevention and treatment of mucositis and mucosal disorders; as a bowel soother; a digestive aid; as a treatment for ulcers; in a composition and method for treating and preventing helicobactor-pylori-associated stomach gastritis, ulcers and cancer; and as an anti-inflammatory agent for liver function and autoimmune diseases.
Also, Potassium Citrate has been used in the treatment of autoimmune and other health disorders; prevention and treatment of hypertension; as part of a buffering agent that inhibits proton pumps and assists NSAID delivery; as part of a general health drink; in an essential nutritional drink for those with compromised digestive systems; for the treatment of osteoporosis; and as a treatment for potassium deficiencies.
Regardless of the merits of the previous research and products involving some or all of these ingredients, Applicants urge that there remains a need to combine these, and other ingredients, in a synergistic manner to improve TPF delivery.
USPTO Backgrounds
USPTO Backgrounds