Human growth hormone (hGH) is a single chain polypeptide hormone, the naturally occurring type of which consists of 191 amino acid residues. Growth hormone acts through binding to membrane receptors that belong to the cytokine receptor superfamily. Growth hormone may be used alone or in junction with other medicaments or growth factors such as epidermal growth factor (EGF) or fibroblast growth factor 2 (FGF2) designed to induce in cell genesis or proliferation in the CNS or PNS. HGH alone or in conjunction with other medicaments, peptides, growthfactors, steroids, lipids, glycosylated proteins or peptides, either simultaneous or in sequence, may be used in order to facilitate cell genesis or the generation of specific cell types in vivo or in vitro. It may also be used to induce immature, or multipotent cells to active specific developmental programs as well as specific genes in the aforementioned cells. Growth hormone is a key factor in promoting the normal development of children, and GH deficiency can lead to dwarfism. In adults the importance of GH is less well defined, although plasma levels of GH are similar in adults and children. It is possible that GH plays a role in tissue repair following injury.
Growth hormone may be administered by intramuscular or subcutaneous injection. Of these methods, subcutaneous injection may be preferred because it facilitates self-administration. The reason why HGH injection has been the sole way for administering physiologically active peptides is that, when they are, orally administered, physiologically active peptides are digested in the gastrointestinal tract. Oral administration of a physiologically active peptide or protein, however, causes hydrolysis of the peptide or protein by a digestive enzyme to decrease disadvantageously the absorbability from the digestive tract. Accordingly, such human growth hormone is usually administered by repetition of intramuscular or subcutaneous injections or by intravenous drip infusion. Proteins are similar to peptides in that they also consist of amino acids, but the molecules are larger and the majority of proteins are dependent on a well-defined three-dimensional structure as regards many of their properties, including biological activity and immunogenicity. Their three-dimensional structure can be destroyed relatively easily, for example by high temperatures, surface-induced denaturation and, in many cases, exposure to organic solvents. Proteins can degrade via a number of mechanisms, including deamidations of asparagine and glutamine; oxidation of methionine and, to a lesser degree, tryptophan, tyrosine and histidine; hydrolysis of peptide bonds; disulfide interchange; and racemization of chiral amino acid residues. Because proteins can easily degrade, the standard method for delivering such compounds has been daily injections.
The increased availability of growth hormone, due to advances in recombinant DNA technology, has allowed research into the use of this hormone at physiological dosage as replacement therapy for adults and children with GH deficiency (GHD) and at pharmacological dosages as a possible therapeutic agent for a number of disease states which include frailty associated with ageing, osteoporosis, morbid obesity, cardiac failure, major thermal injury, hypoglycemic unawareness in diabetes mellitus, various acute and chronic catabolic conditions and intoxication with poisonous substances that are degraded in the liver by microsomal enzymes. In combination with DHEA, its use has been proposed for regenerating an involuted thymus. A major disadvantage of HGH administration by injection is that trained personnel are often required to administer the drug. For self-administered drugs, many patients are reluctant or unable to give themselves injections on a regular basis. Injection is also associated with increased risks of infection. Other disadvantages of drug injection include variability of delivery results between individuals, as well as unpredictable intensity and duration of drug action. Despite these noted disadvantages, HGH injection remains the best delivery mode for best HGH theraputic effects. An injectable formulation for hGH has the advantages of eliminating reconstitution errors, thereby increasing dosing accuracy, as well as simplifying the use of the product clinically, thereby increasing patient compliance. |
|
