Claims for Patent: 7,722,857

Summary for Patent: 7,722,857

Title:	Immunoadjuvant
Abstract:	An immunoadjuvant comprising one kind or two or more kinds of immunostimulating substances carried separately by two or more kinds of different microparticle immunostimulating substance carriers, and comprising at least a combination of (a) an inorganic substance such as microparticle calcium phosphate having a size phagocytizable by cells, and (b) precipitates of a soluble protein and a mucopolysaccharide formed by coacervation as the microparticle immunostimulating substance carriers, which is highly safe and can exhibit potent immunoadjuvant activity.
Inventor(s):	Ohno; Tadao (Ibaraki, JP), Uchimura; Eiji (Chiba, JP)
Assignee:	Cell-Medicine, Inc. (Ibaraki, JP)
Application Number:	12/159,907
Patent Claims:	1. An immunoadjuvant comprising one kind or two or more kinds of immunostimulating substances carried by each of two or more kinds of different microparticle immunostimulating substance carriers, which at least comprises a combination of (a) microparticle calcium phosphate having a size phagocytizable by cells, and (b) a precipitate of a soluble protein and a mucopolysaccharide formed by coacervation as said microparticle immunostimulating substance carriers, wherein the microparticle calcium phosphate of (a) is microparticle calcium phosphate having a Ca/P molar ratio of 1.3 or higher, containing 1 to 15% by weight of carbonate groups CO.sub.3.sup.2-, and having a degree of crystallinity, in an XRD spectrum obtained with a CuK.alpha. ray, not lower than a degree of crystallinity defined by appearance of broad peaks having centers at 2.theta. values of 26.degree., 32.degree. and 34.degree. and appearance of a shoulder with a Miller index of 300 at 33.degree., and not higher than a degree of crystallinity defined by appearance of peaks or shoulders having centers at 26.degree., 28.1.degree., 29.degree., 32.degree., 33.degree. and 34.degree. and by separation of peaks with Miller indexes of 211 and 112. 2. The immunoadjuvant according to claim 1, wherein the microparticle calcium phosphate of (a) is calcium phosphate having a maximum diameter of 1 .mu.m or smaller. 3. The immunoadjuvant according to claim 1, wherein the soluble protein in (b) is albumin. 4. The immunoadjuvant according to claim 1, wherein the mucopolysaccharide in (b) is heparin. 5. The immunoadjuvant according to claim 1, wherein the precipitates of a soluble protein and a mucopolysaccharide formed by coacervation of (b) are precipitates crosslinked by using an inter-protein molecule crosslinking agent. 6. The immunoadjuvant according to claim 1, wherein the immunostimulating substance consists of one kind or two or more kinds of inducers of a substance selected from the group consisting of cytokines, chemokines, cell growth factors, and hormones. 7. The immunoadjuvant according to claim 1, wherein the immunostimulating substance consists of one kind or two or more kinds of substances selected from the group consisting of tuberculin, tuberculin purified protein derivative (PPD), soluble ingredients originating in microorganisms, trehalose 6,6'-dimycolate, lipopolysaceharides, lipid A, oligonucleotides, .beta.-glucans, keyhole limpet hemocyanin, muramyl dipeptide, bestatin, levamisole, cytokines, chemokines, cell growth factors, and hormones. 8. The immunoadjuvant according to claim 7, wherein the soluble ingredients originating in microorganisms consist of one kind or two or more kinds of extracts selected from the group consisting of alcohol extracts, acetone extracts, pyridine extracts and hot water extracts of microorganisms. 9. The immunoadjuvant according to claim 7, wherein the microorganisms are bacteria. 10. The adjuvant according to claim 1, which is for internal administration to a mammal including human together with an antigen to induce a systemic immune response to the antigen. 11. The immunoadjuvant according to claim 10, wherein the antigen consists of one kind or two or more kinds of substances selected from the group consisting of fungi, Actinomycetes, bacteria, viruses, phages, rickettsias, protozoans, ingredients of fungi, ingredients of Actinomycetes, ingredients of bacteria, ingredients of viruses, ingredients of phages, ingredients of rickettsias, ingredients of protozoans, tumor tissues, tumor cells, tumor cell ingredients, tumor antigen proteins, and tumor antigen peptides. 12. The immunoadjuvant according to claim 1, which is for administration into a tumor tissue of a mammal including human denatured by a physical means to induce an antitumor immune response. 13. The immunoadjuvant according to claim 12, wherein the physical means consists of one kind or two or more kinds of means selected from the group consisting of microwave irradiation, radiofrequency ablation, cryoablation, electrotome heating, hot water injection, alcohol injection, embolization, radiation exposure, laser beam irradiation and sonic disruption. 14. The immunoadjuvant according to claim 1, which is for administration to a mammal including human after externally mixed with immunocompetent cells to induce a systemic immune response in the living body of the mammal. 15. The immunoadjuvant according to claim 14, wherein the immunocompetent cells consists of one kind or two or more kinds of cells selected from the group consisting of dendritic cells, macrophages, B lymphocytes, T lymphocytes, natural killer cells, natural killer T cells, and hematopoietic stem cells. 16. A vaccine containing the immunoadjuvant according to claim 1 and an antigen.

Details for Patent 7,722,857

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Par Pharmaceutical Companies, Inc.	APLISOL	tuberculin, purified protein derivative	Injection	103782	04/20/1998		2040-01-28
Sanofi Pasteur Limited	TUBERSOL	tuberculin, purified protein derivative	Injection	103941	02/24/2000		2040-01-28