Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1998-05-20
1999-11-02
Lee, Howard C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
4241841, 514 26, 536 41, 536 5, A61K 3170, A61K 31705, C07H 1524
Patent
active
059770813
ABSTRACT:
The present invention is directed to novel chemical compounds in which a lipophilic moiety such as a lipid, fatty acid, polyethylene glycol or terpene is covalently attached to a non-acylated or desacylated triterpene saponin via a carboxyl group present on the 3-O-glucuronic acid of the triterpene saponin. The attachment of a lipophile moiety to the 3-O-glucuronic acid of a saponin such as Quillaja desacylsaponin, lucyoside P, or saponin from Gypsophila, Saponaria and Acanthophyllum enhances their adjuvant effects on humoral and cell mediated immunity. Additionally, the attachment of a lipophile moiety to the 3-O-glucuronic acid residue of non- or des-acylsaponin yields a saponin analog that is easier to purify, less toxic, chemically more stable, and possesses equal or better adjuvant properties than the original saponin.
REFERENCES:
patent: 4235877 (1980-11-01), Fullerton
patent: 5057540 (1991-10-01), Kensil et al.
patent: 5273965 (1993-12-01), Kensil et al.
patent: 5443829 (1995-08-01), Kensil et al.
patent: 5508310 (1996-04-01), Rhodes
patent: 5583112 (1996-12-01), Kensil et al.
patent: 5650398 (1997-07-01), Kensil et al.
patent: 5750110 (1998-05-01), Prieels et al.
Kensil et al. Adv. Exp. Med. Biol., vol. 404: 165-172, 1996.
Pillion et al. J. Pharm. Sci., vol. 85(5): 518-524, 1996.
Cleland et al. J. Pharm. Sci., vol. 85(1): 22-28, 1996.
Recchia et al. Pharm. Res., vol. 12(12): 1917-1923, 1995.
Higuchi, Ryuichi et al. "An Acylated Triterpenoid Saponin From Quillaja Saponaria," Phytochemistry:27(4), 1165-1168 (1988).
International Search Report for International Application No. 09/081,647, mailed Oct. 13, 1998.
Akihisa, T., et al., "The 24.alpha.- and 24.beta.-Epimers of 24-Ethylcholesta-5,22-dien-3.beta.-ol in Two Clerodendrum Species," Phytochemistry 27:1169-1172 (1988).
ApSimon, J.W., et al., "Saponins from Marine Invertebrates," in Studies in Organic Chemistry 17: Chemistry and Biotechnology of Biologically Active Natural Products, Proceedings of the Second International Conference, Budapest, Aug. 15-19, 1983, Szantay, C., Ed., Elsevier: Amsterdam, pp. 273-286 (1984).
Bohn, J.A., and BeMiller, J.N., "(1.fwdarw.3)-.beta.-D-Glucans as biological response modifiers: a review of structure-functional activity relationships," Carbohydrate Polymers 28:3-14 (1995).
Bomford, R., et al., "Adjuvanticity and ISCOM formation by structurally diverse saponins," Vaccine 10:572-577 (1992).
Bowyer, P., et al., "Host Range of a Plant Pathogenic Fungus Determined by a Saponin Detoxifying Enzyme," Science 267:371-374 (1995).
Cox, J.C., and Coulter, A.R., "Adjuvants--a classification and review of their modes of action," Vaccine 15:248-256 (Feb. 1997).
Dalsgaard, K., "A Study of the Isolation and Characterization of the Saponin Quil A," Acta Vet. Scand. 19 (Suppl. 69):7-40 (1978).
Dalsgaard, K., "Saponin Adjuvants. III. Isolation of a Substance from Quillaja saponaria Molina with Adjuvant Activity in Foot-and-Mouth Disease Vaccines," Archiv fur die gesamte Virusforschung 44:243-254 (1974).
Higuchi, R., and Komori, T., "Structures of Compounds Derived from the Acyl Moieties of Quillajasaponin," Phytochemistry 26:2357-2360 (1987).
Higuchi, R., et al., "Structure of Desacylsaponins Obtained from the Bark of Quillaja Saponaria," Phytochemistry 26:229-235 (1987).
Hostettmann, K., et al., "Saponins," Methods in Plant Biochemistry 7:435-471 (1991).
Kensil, C.R., et al., "Structure/Function Studies on QS-21, a Unique Immunological Adjuvant from Quillaja saponaria," in Saponins Used in Traditional and Modern Medicine, Waller, G.R., and Yamasaki, K., eds., Plenum Press: New York, N.Y., pp. 165-172 (1996).
Kensil, C.R., et al., "Separation and Characterization of Saponins with Adjuvant Activity from Quillaja saponaria Molina Cortex," J. Immunol. 146:431-437 (1991).
Kensil, C.R., et al., "Structure/Function Relationship in Adjuvants from Quillaja saponaria Molina," Vaccines 92:35-40 (1992).
Lacaille-Dubois, M.A., and Wagner, H., "A review of the biological and pharmacological activities of saponins," Phytomedicine 2:363-386 (Mar. 1996).
Massiot, G., and Lavaud, C., "Structural Elucidation of Saponins," Studies in Natural Products Chemistry 15:187-224 (1995).
Newman, M.J., et al., "Saponin Adjuvant Induction of Ovalbumin-Specific CD8.sup.+ Cytotoxic T Lymphocyte Responses," J. Immunol. 148:2357-2362 (1992).
Osbourn, A.E., et al., "Saponin Detoxification by Plant Pathogenic Fungi," in Saponins Used in Traditional and Modern Medicine, Waller, G.R., and Yamasaki, K., Eds., Plenum Press: New York, N.Y., pp. 547-555 (1996).
Pillion, D.J., et al., "DS-1, a Modified Quillaja Saponin, Enhances Ocular and Nasal Absorption of Insulin," J. Pharm. Sci. 84:1276-1279 (1995).
Price, K.R., et al., "The Chemistry and Biological Significance of Saponins in Foods and Feedingstuffs," CRC Crit. Rev. Food Sci. Nutr. 26:27-135 (1987).
Schopke, Th., and Hiller, K., "Triterpenoid saponins. Part 6," Pharmazie 45:313-342 (1990).
Scott, M.T., et al., "Adjuvant Activity of Saponin: Antigen Localization Studies," Int. Archs. Allergy Appl. Immun. 77:409-412 (1985).
Sela, M., "Antigenicity: Some Molecular Aspects," Science 166:1365-1374 (1969).
Shibata, S., "Saponins with Biological and Pharmacological Activity," in New Natural Products and Plant Drugs with Pharmacological, Biological or Therapeutical Activity, Wagner, H., and Wolff, P., Eds., Springer-Verlag: Berlin, pp. 177-196 (1977).
Galenica Pharmaceuticals, Inc.
Lee Howard C.
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