CS260162B1 - Mixture of ceruloplasmin,transferrin,secretory iga and serous immunoglubulins igg,iga for application on mucosa of gastrointestinal tract - Google Patents

Abstract

The solution is a mixture of ceruloplasmin, transferrin and serum immunoglobulins IgG, IgA and IgM or secretory SIgAs located in enteric capsules, po administration is achieved locally immunity in the intestine. The mixture consists of 10.0 to 25.0 mg of ceruloplasmin, 10.0 to 25.0 milligrams of transferrin and serum immunoglobulins at 6.5 to 50.0 mg of IgG, 2.5 to 20.0 mg IgA, 1.0 to 10.0 mg IgM or, secretory SIgA at 10.0 to 80.0 mg per 100 mg of the mixture. The product is used in therapy and prevention! and bacterial) etiolo- gi, in the intestinal tract, in paediatrics, gastroenterology, surgery, and clinical immunology.

Description

The solution is a mixture of ceruloplasmin, transferrin and serum immunoglobulins IgG, IgA and IgM or secretory SIgA housed in enteric-coated capsules which, after administration, produce induction of local immunity in the intestine. The mixture consists of 10.0 to 25.0 mg ceruloplasmin, 10.0 to 25.0 milligrams of transferrin and serum immunoglobulins in an amount of 6.5 to 50.0 mg IgG,

2.5 to 20.0 mg of IgA, 1.0 to 10.0 mg of IgM or secretory SIgA in an amount of 10.0 to 80.0 mg per 100 mg of the total composition.

It is used in therapy and prevention! in the field of intestinal tract, in paediatrics, gastroenterology, surgery and clinical immunology.

The invention relates to a composition composed of a mixture of ceruloplasmin, transferrin, serum immunoglobulins IgG, IgA, IgM or secretory SIgA for application to the mucosa of the gastrointestinal tract, wherein said proteins are encapsulated in enteric capsules which guarantee safe passage through the acidic contents of the stomach. t. j. to the small intestine mucosa.

Ceruloplasmin has a prominent catalytic function in the oxidation of plasma iron and thus allows its binding to transferrin, thus promoting the baikteriostatic and indeed immunostimulatory functions of transferrin. From a clinical point of view, viral infections become important! of the gastrointestinal tract, mainly rotaviruses, which are discussed, among other articles, by the authors:

Wiald, I., Morawski, K., Szabtol, W .: Chemical and Enzymatic Properties of Ceruloplasmin, Poet. Hig, Med. Dows, 13, Θ97,1968., Samuel, I .: Ralationships between Ceruloplasmin and Viral Immunity Virology, 33/1: 83-72, Letendre, E. D. Ceruloplasmin and Regulation of Transferrin Iron during Nelsseris Meningitis Infection on Silence. Infect. Immun. 45/1: 133-138, 1984. Blum. P. et al .: Survival of Oral Human Immune Serum Globulin ln the giastrointestinal fracture of low birth infants, Pedistr. Rs. 15: 1256-1260, 1980, Barhes, G. L. et al., A randomized trial of oral gammaglobulin low-blight-wavelength infants infected with rotavirus. Lancet 1: 1371-1373, 1982. Cs. AO 248 956 protects a mixture of IgG, transferrin and albumin immunoglobulins for i. in. and intraperitoneally suitable for use in septic processes in the abdominal cavity.

MS. AO 248 954 protects a mixture of immunoglobulins of the IgG, IgA and IgM type and transferrin for intravenous and intraperitoneal administration suitable for the treatment of septic diseases caused by viruses and gram-negative bacteria. MS. AO 249 225 which protects a mixture of ceruplasmin, transferrin for application to the mucosa. MS. AO 249 222 protects the mixture of ceruloplasmin, transferrin, IgG, IgA, IgM immunoglobulins for intravenous, intraperitoneal and intrathecal application, which we use in septic diseases in. abdominal cavity, in inflammatory diseases of the central nervous system, where you induce! Aerobic microorganisms are at the forefront. U Čs. AO 242 310 relates to the protection of an IgG-7S or IgG, IgA, IgM mixture for external use, which is useful in the treatment of purulent burns, leg ulcers, chronic non-healing wounds.

None of these immunoglobulin preparations directly induce local immunity to the intestinal mucosa, which appears to be important in gastrointestinal viral infections, particularly in neonates with a low birth weight of ^1, also verified by Barnes, GL et al.

The essence of the invention consists in:. Lastly, the composition comprises a mixture of ceruloplasmin, transferrin, immunoglobulins IgG, IgA, IgM or a mixture of ceruloplasmin, transferrin SIgA in an amount of 0.05 to 1.0 g per 1 gastro-capsule.

The proportion of individual proteins is as follows:

ceruloplasmin

10.0 to 25.0 mg / 100 mg, transferrin

10.0 to 25.0 mg / 100 mg, IgG immunoglobulins

6.5 to 50.0 mg IgA

2.5 to 20.0 mg,

IgM

1.0 to 10.0 mg per 100 mg or ceruloplasmin

10.0 to 25.0 mg / 100 mg, transferrin

10.0 to 50.0 mg / 100 mg, immunoglobulins SIgA

10.0 to 80.0 mg / 100 mg per enteric solvent capsule.

In this way, immunoglobulins become the place in the body where they are needed to control the infectious agent and induce appropriate local immunity, since the administration form of the immunoglobulins in the enteric capsules allows preservation of the native nature of the immunoglobulin molecule as it passes through the acidic environment of the stomach. The presence of ceruloplasmin and transferrin in addition to bacteriostatic shedding has a remarkable immunostimulatory function in relation to cellular immunity.

The preparation in preclinical tests was tested for the electrophoretic purity of the individual components and obtained the following values: 16% ceruloplasmin, 19% transferrin, 42% IgG, 14% IgA, 9% IgM

Harmlessness was checked! two species of animals, two mice and two guinea pigs. The application rate in one mouse was 0.5 ml product and in one guinea pig 5 ml product. There was no weight loss in all experimental animals over 7 days of observation. The stability of the formulation was controlled by heating at +37 degrees Celsius for 5 days during which no changes occurred. The hepatitis free assay was performed by ELISA with a negative result.

Example 1

100 mg of a formulation containing 25 IU; ceruloplasmin, 25 mg of transferrin, 15 mg of IgG, 7.5 mg of IgA, 2.5 mg of IgM are homogenized on a homogenizer and dispensed into 0.05 g enteric-coated capsules with a special sizing device.

1 'says I and d 2

100 ni; mixtures of a preparation containing 25 mg ceruloplasmin, 25 mg transferrin and 25 mg SlgA are homogenized on a homogenizer and dispensed into enteric-coated capsules of 0.1 g by special dispenser.

The individual components were obtained from native human plasma by ethanol fractionation using further purification methods using caprylic acid and rivanol. Ceruloplasmin was isolated at an isoelectric point at pH 4.4, transferrin at pH 5.8, and a mixture of immunoglobulins at pH 5.0.

Claims (1)

SUBJECT A mixture of ceruloplasmin, transferrin, secretory IgA and serum immunoglobulins IgG, IgA and IgM for administration to the gastrointestinal mucosa comprising 10.0-25.0 mg ceruloplasmin, 10.0-25.0 mg transferrin with serum iVYNALEZ munoglobulins in an amount of 6.5 to 50.0 mg IgG, 2.5 to 20.0 mg IgA, 1.0 to 10.0 mg IgM or secretory immunoglobulins SlgA in an amount of 10.0 to 80.0 mg per 100 mg of the total mixture in enteric-coated capsules ·