Delivery Systems for Recombinant Methionyl Human Growth

  • Jerome A. Moore
  • Helga Wilking
  • Ann L. Daugherty
Part of the NATO ASI Series book series (NSSA, volume 125)


The advent of recombinant DNA technology has lead to an increased interest in convenient, effective pharmaceutical dosage forms for polypeptide drugs. It is well known that there are many obstacles to delivery of these compounds by conventional dosage forms. Large molecular weight, solubility problems, suseptibility to enzymatic degradation, sensitivity to pH and temperature, and short in vivo half life are some of the problems that must be confronted. For drugs with such complex biological activities as most therapeutic polypeptides one of the biggest obstacles to development of delivery systems is lack of information on the mechanism of action of the drug.


Dosage Form Bile Salt Cocoa Butter Human Growth Hormone Sodium Salicylate 
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  1. Anik, ST., McRae, G., Nerenberg, C., Worden, A., Foreman, J., Hwang, J., Kushinsky, S., Jones, R.E. and Vickery, B., 1984, Nasal Absorption of Nafarelin Acetate, the Decapeptide [D-Nal (2)6] LHRH, in Rhesus Monkeys. J. Pharm. Sci. 73:684.PubMedCrossRefGoogle Scholar
  2. Bliss, C.I., 1956, Confidence limits for measuring the precision of bioassays. Biometrics, 12:491.CrossRefGoogle Scholar
  3. Finkelstein, J.W., Roffwarg, H.P., Boyar, R.M., Kream, J. and Hellman, L., 1972, Age related change in the twenty-four hour spontaneous secretion of growth hormone. J. Clin. Endocrinol. Metab. 35:665.PubMedCrossRefGoogle Scholar
  4. Goeddel, D.V., Heynecker, H.L., Hozumi, T., Arentzen, R., Itakura, K., Yansura, D.G., Ross, M.J., Miozzari, G., Crea, R., Seeburg, P.H., 1979, Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone. Nature, 281:544.PubMedCrossRefGoogle Scholar
  5. Gordon, G.S., Moses, A.C., Silver, R.D., Flier, J.S. and Carey, M.C., 1985, Nasal Absorption of Insulin: Enhancement by Hydrophobie Bile Salts. Proc. Nat’l. Acad. Sci. USA 82:7419.CrossRefGoogle Scholar
  6. Hirai, S., Yashiki, T. and Mima, H., 1981a, Absorption of Drugs from the Nasal Mucosa of Rat. Int. J. Pharm. 7:317.CrossRefGoogle Scholar
  7. Hirai, S., Yashiki, T. and Mima, H., 1981b, Mechanisms for the enhancement of the nasal absorption of insulin by surfactants. Int. J. Pharm. 9:173.CrossRefGoogle Scholar
  8. Kamada, A., Nishihata, T., Kim, S., Yamamoto, M., and Yata, N., 1981, Study of enamine derivatives of phenylglycine on the rectal absorption of insulin. Chem. Pharm. Bull., 29:2012.PubMedCrossRefGoogle Scholar
  9. Kim, S., Kamada, A., Higuchi, T., and Nishihata, T., 1982, Effect of enamine derivatives on the rectal absorption of insulin in dogs and rabbits. J. Pharm. Pharmacol., 35:100.CrossRefGoogle Scholar
  10. Muranishi, N., Kinugawa, M., Nakajima, Y., Muranishi, S., and Sezaki, H., 1980, Mechanism for the inducement of intestinal absorption of poorly absorbed drugs by mixed micelles I. Effects of various lipid-bile salt mixed micelles on the intestinal absorption of streptomycin in rat. Int. J. Pharm., 4:271.CrossRefGoogle Scholar
  11. Muranishi, S., Tokunaga, Y., Taniguchi, K., and Sezaki, H., 1977, Potential absorption of heparin from the small intestine and the large intestine in the presence of monoolein mixed micelles. Chem. Pharm. Bull., 25:1159.PubMedCrossRefGoogle Scholar
  12. Nishihata, T., Rytting, J., Kamada, A., Higuchi, T., Routh, M., and Caldwell, L., 1982, Enhancement of rectal absorption of insulin using salicylates in dogs. J. Pharm. Pharmacol, 35:148.CrossRefGoogle Scholar
  13. Notari, R. E., Biopharmaceutics and Clinical Pharmacokinetics, Marcel Dekker, Inc., New York, 1980, p.86.Google Scholar
  14. Sokal, R.R. and Rohlf, F.J., Biometry, W. H. Freeman and Co., San Francisco, 1981, p. 329.Google Scholar
  15. Theeuwes, F. and Yum, S.I., 1976, Principles of the design and operation of generic osmotic pumps for the delivery of semisolid or liquid formulations. Ann. Biomed. Eng. 4:343.PubMedCrossRefGoogle Scholar
  16. Wilhelmi, A.E., Growth hormone-measurement-bioassay. In: Berson, S.A., Yalow, R.S. (eds) Methods in Investigative and Diagnostic Endocrinology. North Holland, Amsterdam, vol 2A (1973) 296.Google Scholar
  17. Ziv, E., Kidron, M., Berry, E. M., and Bar-On, H., 1981, Bile salts promote the absorption of insulin from the rat colon. Life Sciences, 29:803.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • Jerome A. Moore
    • 1
  • Helga Wilking
    • 1
  • Ann L. Daugherty
    • 1
  1. 1.Pharmacological SciencesGenentech, Inc.USA

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