Drug – bio-affecting and body treating compositions – Lymphokine – Interleukin
Patent
1994-02-14
1996-07-09
Sayala, Chhaya D.
Drug, bio-affecting and body treating compositions
Lymphokine
Interleukin
530351, 530363, 514 12, A61K 4505
Patent
active
055342515
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a novel stabilized medicinal composition of an interleukin-1.alpha. (IL-1.alpha.) active substance.
PRIOR ART AND ITS PROBLEMS
The resolution was passed at the Second International Lymphokine Workshop that the physiologically active substance reported earlier under the varied names of lymphocyte activating factor (LAF), mitogenic protein, helper peak-1, T-cell replacing factor III (TRF-III) or T-cell replacing factor Me (TRFM), B-cell activating factor, B-cell differentiation factor, etc. should thenceforth be referred to by the unified designation of interleukin-1 (IL-1) [Cellular Immunol., 48, 433-436 (1979)]. This decision was based on the reasoning that these bioactive substances cannot be discriminated as different chemical entities but were merely so designated with attention paid to various aspects of physiological activity.
IL-1, mentioned above, has been reported to activate T- and B-lymphocytes, enhances the production of interleukin-2 (IL-2) and antibodies, acts on the hepatocytes to encourage protein synthesis and increases the production of prostaglandins [cf. Reviews of Infectious Disease, Vol. 6, No. 1, 51-59 (1984), New England J. of Med., 311, 1413 (1984), etc] More recently, the existence of genes coding for polypeptides having LAF activity or their precursors have been reported [Proc. Natl. Acad. Sci., 81, 7907-7911 (1984); Nature, 315, 641 (1985); Nucleic Acids Research, 13 (16) 5869 (1985)] and a polypeptide having the amino acid sequence designated as SEQ ID NO:1 in the sequence listing presented hereinafter came to be known as IL-1.alpha..
The inventors of the present invention, who also made an intensive exploration into IL-1.alpha. as a homogeneous or discrete substance, already established a production technology for the substance and elucidated its characteristics as a chemical entity as well as its physiological activities. Based on the research findings so generated, the inventors found, too, that a polypeptide which can be designated by the amino acid sequence given in the sequence listing presented hereinafter has LAF activity but that despite its correspondence to physiologic genes as reported, this peptide was a labile substance. Meanwhile, it was known that the administration of IL-1.alpha. as a drug to human subjects entails the onset of fewer as a side effect and this was found to be a serious drawback in the medicinal application of IL-1.alpha..
As the result of further investigations, the inventors of the present invention succeeded in providing a new IL-1.alpha. derivative differing from said IL-1.alpha. in amino acid sequence, which is definitely free from pyrogenicity and particularly suited for medicinal uses [cf. Japanese Patent Application Kokai S63-164899 and Kokai H2-167298].
The above IL-1.alpha. derivative has a variety of activities such as LAF activity, tumor growth inhibitory activity (activity to specifically inhibit the growth of tumor cells), activity to enhance the production of various cytokines such as CSF (colony stimulating factor), interferons (IFN), interleukin-2 (IL-2), interleukin-3 (IL-3), etc. (an action, for example, on human cells to significantly enhance the production of said cytokines), antiinflammatory activity (particularly the activity to effectively arrest the progression of arthritis in animal models of arthritis), radiation hazard preventing effect (the property to prevent or inhibit tissue damages and serious side effects associated with systemic radiotherapy in bone marrow transplantation, radiotherapy for cancer or accidental exposure to radiation), antithrombotic effect, platelet increasing effect (blood increasing effect), etc. and is of value as a drug, namely an immunopotentiator for the promotion of antibody production, potentiation of vaccines, etc., an antitumor agent, a stimulant for enhanced production of cytokines such as CSF, IL-2, IL-3, etc., an antiinflammatory agent, a radiation injury protectant, an antithrombotic agent, a therapeutic agent for thrombocytopenia
REFERENCES:
patent: 4816436 (1989-03-01), Jacobs
patent: 5120534 (1992-06-01), Hirai et al.
Wang et al., J. Parenteral Sci & Tech., vol. 42 (2S), pp. 53-526, 1988.
Hamblin, "Lymphokines", IRL Press, pp. 19-20, 1988.
Dinarello, The FASEB Journal, vol. 2, pp. 108-115, 1988.
Nakayama Yasuo
Sugahara Yuji
Otsuka Pharmaceutical Co. Ltd.
Sayala Chhaya D.
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