• 한국생물공학회:학술대회논문집
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• 2000.04a
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• pp.541-545
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• 2000

For the sustained release formulation of recombinant human growth hormone (rhGH), dissociable rhGH aggregates were microencapsulated within poly(D,L-lactic-co-glycolic acid) [PLGA] microparticles. rhGH aggregates with 2 - 3 m Particle diameter were first produced by adding a small volume of aqueous rhGH solution into a partially water miscible organic solvent phase(ethyl acetate) containing PLGA. These rhGH aggregates were then microencapsulated within PLGA polymer phase by extracting ethyl acetate into an aqueous phase pre-saturated with ethyl acetate. The resultant microparticles were 2 - 3 m in diameter similar to the size of rhGH aggregates, suggesting that PLGA polymer was coated around the protein aggregates. Release profiles of rhGH from these microparticles were greatly affected by changing the volume of the incubation medium. The release rhGH species consisted of mostly monomeric form with having a correct conformation. This study reveals that sustained rhGH release could be achieved by microencapsulating reversibly dissociable protein aggregates within biodegradable polymers.

• Archives of Plastic Surgery
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• v.35 no.3
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• pp.235-242
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• 2008

Purpose: Due to increasing interest in the treatment of spinal cord injuries, many histopathological studies have been conducted to prove that many neurotrophic factors including growth hormone are important for regeneration of the injured spinal cord. Growth hormone has to be given everyday, however, and this negatively affects compliance in clinical trials. Recently, the invention of sustained release growth hormone (SRGH) that can be given just once a week may both help the regeneration of injured spinal cord and, at the same time, be more compliant and convenient for clinical patients. Methods: In this study, thirty 7-week-old female Spraque-Dawley rats were subjected to a weight-driven impact spinal cord injury. They were divided into 3 groups and Group I and II were injected with SRGH once a week for 4 weeks; Group I were injected into the injured spinal cord area, while Group II were injected into the peritoneal cavity. Meanwhile, Group III were injected with normal saline solution. The functional outcome was evaluated using the Basso-Beattie-Bresnahan motor rating score and the inclined plane test was done 4 weeks after the first injection. Histopathological examination was performed at the same time and the amount of residual white matter was measured in all groups. Results: After 4 weeks, Groups I and II showed greater improvement than Group III(the control group) in the functional test. In the control group, invasion of atypical phagocytes, axonal degeneration, edema and cavity formation in the posterior site of spinal cord gray matter was observed in histopatholgical examination. The rate of residual white matter in Group III was less than in the other groups. Conclusion: Data showed significant functional and histopathological improvement in the groups treated with SRGH into the spinal and peritoneal cavity compared with the control group. SRGH is therefore beneficial because it helps with regeneration of the injured spinal cord and improves the compliance and convenience of patients.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.417.2-418
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• 2002

The rhGH-loaded PLGA microsphere formulation was prepared using a double emulsion process from hydrophilic 0:50 poly(D.L-lactide-co-glycolide) (PLGA) polymers. To investigate the sustained efficacy of this formulation, ts pharmacodynamic characteristics were analyzed. It showed particle size of ca 53.1 $\mu\textrm{m}$ with high drug ncorporation efficiency and it was sucutaneously administrated to hypophysectomized rats and whole body rowth responses of this formulation were compared to those of the different dosing patterns of rhGH. (omitted)

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.301.2-302
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• 2001

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.424.2-424.2
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• 2002

The in vivo release characteristics of rhGH-loaded PLGA microsphere prepared using a double emulsion process from hydrophilic 50:50 poly(D.L-lactide-co-glycolide) (PLGA) polymers were analyzed. This formulation showed particle size of ca 53.1$\mu\textrm{m}$ with high drug incorporation efficiency. To investigate in vivo release kinetics without the interference of formation of antibodies to rhGH in the experimental animals, the animals were immunosuppressed by treatment with Cyclosporin. (omitted)

• Clinical and Experimental Pediatrics
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• v.52 no.11
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• pp.1249-1259
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• 2009

Purpose:From a societal perspective, we evaluated the cost-effectiveness of a novel sustained-release injection of recombinant human growth hormone (GH) administered on a weekly basis compared with that of the present daily GH injection for the treatment of children with GH deficiency. Methods:Health-related utility for GH therapy was measured based on the visual analogue scale. During July 2008, caregivers of 149 children receiving GH therapy form 2 study sites participated in a web-based questionnaire survey. The survey required the caregivers to rate their current subjective utility with daily GH injections or expected utility of weekly GH injections. Because there was no difference in the costs of the daily and weekly therapies, for the purposes of this study, only drug acquisition costs were considered. Results:Switching from daily to weekly injection of GH increased the utility from 0.584 to 0.784 and incurred an extra cost of 4,060,811 Korean won (KW) per year. The incremental cost-utility ratio (ICUR) for a base case was 20,305,055 KW per quality-adjusted life year (QALY) gained. Scenario analyses showed that the ICUR ranged from 15,751,198 to 25,489,929 KW per QALY. Conclusion:The ICUR for a base case and worst case scenario analyses ranged from 0.85 to 1.37-times per capita gross domestic product of Korea, which is considered to be within the generally accepted willingness-to-pay threshold. Thus, it is concluded that switching from daily to weekly injection of GH would be cost-effective.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.572-584
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• 2002

Rapid development in molecular biology and recent advancement in recombinant technology increase identification and commercialization of potential protein drugs. Traditional forms of administrations for the peptide and protein drugs often rely on their parenteral injection, since the bioavailability of these therapeutic agents is poor when administered nonparenterally. Tremendous efforts by numerous investigators in the world have been put to improve protein formulations and as a result, a few successful formulations have been developed including sustained-release human growth hormone. For a promising protein delivery technology, efficacy and safety are the first requirement to meet. However, these systems still require periodic injection and increase the incidence of patient compliance. The development of an oral dosage form that improves the absorption of peptide and especially protein drugs is the most desirable formulation but one of the greatest challenges in the pharmaceutical field. The major barriers to developing oral formulations for peptides and proteins are metabolic enzymes and impermeable mucosal tissues in the intestine. Furthermore, chemical and conformational instability of protein drugs is not a small issue in protein pharmaceuticals. Conventional pharmaceutical approaches to address these barriers, which have been successful with traditional organic drug molecules, have not been effective for peptide and protein formulations. It is likely that effective oral formulations for peptides and proteins will remain highly compound specific. A number of innovative oral drug delivery approaches have been recently developed, including the drug entrapment within small vesicles or their passage through the intestinal paracellular pathway. This review provides a summary of the novel approaches currently in progress in the protein oral delivery followed by factors affecting protein oral absorption.