Growth hormone is a hormone which stimulates growth of all tissues capable of growing. Growth hormone is released from the pituitary. The release is under tight control of a number of hormones and neurotransmitters either directly or indirectly. Growth hormone secretion is regulated by two hypothalamic peptides: growth hormone releasing hormone (GHRH), which exerts a stimulatory effect on GH release, and somatostatin, which exhibits an inhibitory influence. Growth hormone levels can be increased by administering compounds known to induce GH release, such as GHRH. Growth hormone releasing factor is a hormone produced in the brain which stimulates the release of growth hormone from the pituitary. It has been shown that the administration of growth hormone releasing factor stimulates growth hormone secretion from the pituitary. Administration of such growth hormone releasing agents and the resulting increase in the GH level provide important medical and physiological benefits, including the acceleration of growth, increase of muscular mass, and etc. Various ways are known to release growth hormone. For example, chemicals such as arginine, L-dopa, glucagon, vasopressin, and insulin induced hypoglycemia, as well as activities such as sleep and exercise, indirectly cause growth hormone to be released from the pituitary by acting in some fashion on the hypothalamus perhaps either to decrease somatostatin secretion or to increase the secretion of the known secretagogue growth hormone releasing factor (GRF) or an unknown endogenous growth hormone-releasing hormone or all of these.
Medications and other pharmaceutical products have traditionally been administered in doses via oral ingestion, nasal sprays or injections. These delivery methods have proven ineffective for patients needing a prolonged and constant supply of an active ingredient (such as growth hormone) delivered to the bloodstream. Particularly difficult are patients needing HGH dosing during sleep time hours. For these patients slow-dissolving HGH pills have been used. Sustained release HGH delivery systems are of interest because they can improve patient compliance, tolerability, product performance, and expand the market potential for a product. Clinically, recombinant human growth hormone (rhGH) is administered daily in growth hormone deficient (GHD) patients. Direct administration of human growth hormone may be effective in certain therapeutic applications. However, among other issues, since the half-life of growth hormone in the body is very short, direct administration leads to artificially increased levels in the concentration of circulating growth hormone, which then rapidly drop off. In recent years sustained release devices have been used for the delivery of protein pharmaceutical agents, primarily as a result of the availability of recombinant HGH products which have been developed for therapeutic applications in a wide variety of pathological conditions. Sustained release of HGH is critically important to achieve the best theraputic benefits. To decrease the dosing frequency and increase patient compliance several sustained growth hormone release formulations are developed and some have been FDA-approved. Controlled release compositions are suitable for use in continuously delivering growth hormone and have enhanced stability with little or no loss of activity. Such HGH releasers allow patients to decrease their dosing interval from daily to once or twice per month depending on rhGH requirements.
HGH releasers are compounds which stimulate the body's production or release of human growth hormone and include growth hormone releasing hormone (GHRH), clonidine, phenylalanine, L-dopa, arginine, ornithine, deprenyl, and somatostatin inhibitors. HGH will be effective whether it is supplied exogenously or released from the pituitary by such releasing agents. Consequently, the use of a growth hormone releaser is an acceptable variation on the use of growth hormone itself, in those patients who are able to release adequate growth hormone in response to such agents. Patients who are able to release appreciable but not sufficient HGH in response to such agents may be given both a releasing agent and exogenous HGH so as to attain the required HGH levels for thymic regeneration while minimizing the use of exogenous HGH, which is expected to be more expensive than HGH releasers. Furthermore, the entire HGH molecule may not be required for HGH action. Therefore, equivalent analogs such as genetically-engineered variants or fragments of HGH that retain the biological activity of HGH but that are less expensive or have fewer side effects are also acceptable variations. The dosage for any of these HGH alternatives are "HGH equivalent doses," that is they should yield the same desired level of or effect of HGH in the body. An example of an HGH "mimic" would be somatomedin C. The best mode process is also compatible with administration of drugs that block other side affects of HIGH, e.g., parlodel to block gynecomastia in men. |
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