Pharmacological activity of tablets containing recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rats
| Autor: | Tomohiro Takaya, Kanji Takada, Yoshinori Nakahigashi, Yoshiteru Ushirogawa, Toshinori Tanaka, Shu-ichi Kishimoto |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
chemistry.chemical_classification
Protease Chromatography Kunitz STI protease inhibitor business.industry medicine.medical_treatment fungi Pharmaceutical Science Biological activity Enteric coating Dosage form Pulmonary surfactant Pharmacokinetics Biochemistry chemistry Medicine business medicine.drug Organic acid |
| Zdroj: | International Journal of Pharmaceutics. 101:89-96 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/0378-5173(94)90079-5 |
| Popis: | Several kinds of small tablets containing recombinant human granulocyte colony-stimulating factor (rhG-CSF) were prepared and the pharmacological activities of the tablets were evaluated in in vivo rat experiments. Except for rhG-CSF, organic acids, surfactant, protease inhibitors and/or enteric coating material were formulated as tablets. After a mixture of rhG-CSF was made with organic acid, surfactant and/or protease inhibitor, small tablets were made and then coated with an enteric-coating material. After the intraduodenal administration of several kinds of small test tablets, 3 mm × 0.7 cm, containing 100 and/or 50 μg rhG-CSF/rat, to rats through a gut incision, blood samples were obtained over a 96 h period from the rat tail artery and the blood total leucocyte (BTL) counts were measured as a pharmacological index of rhG-CSF. The results are expressed as a relative increase in BTL count as compared to the pre-dose level, baseline level. The area under the curves (AUC; % BTL increase × h) obtained was used as an index for the pharmacological activity of rhG-CSF when comparing the test with the placebo tablets. (1) The 2.5-fold increase in the formulated amount of surfactant (HCO-60 ® , polyoxyethylated castor oil derivative), increased the pharmacological activity of rhG-CSF about 2-fold; (2) protease inhibitors, such as soybean trypsin inhibitor and ovalbumin, did not exert any synergistic effect with organic acids with respect to the pharmacological activity of rhG-CSF; and (3) addition of citric acid to tablets mainly composed of tartaric and succinic acids significantly increased the pharmacological activity of rhG-CSF. This study shows the usefulness of both surfactant and organic acid as pharmaceutical additives for the development of an oral delivery system for rhG-CSF. |
| Databáze: | OpenAIRE |
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