Nicotinic ummunonanotherapeutic drugs

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is presented is a composition for nicotinic immunonanotherapy containing synthetic nanocarriers having a polymeric surface conjugated with a variety of nicotine residues with the variety of the nicotinic residues on the nanocarrier form an immunogenic surface providing a low affinity, a high-avidity binding of the nicotinic residues to the surfaces of an antigen presenting cell (APC) compared with an antibody binding, and a pharmaceutically acceptable excipient. The invention provides the nanocarriers capable to stimulate an immune response in T-cells and/or B cells and to produce the antinicotin antibodies with the humoral and cellular response to be achieved in the absence of an exogenous adjuvant.

EFFECT: invention provides the absence of the non-specific response on an inflammation caused by an adjuvant.

17 cl, 37 dwg

 

The text descriptions are given in facsimile form.

1. Composition for nicotine immunochemotherapy containing:
(1) synthetic nanoneedle, having a polymer surface conjugate with many nicotine residue having the following structure, or its metabolite,

moreover, nicotine is covalently bonded to the polymer or lipid through one of R1-R7representing H, where R8represents an alkyl group; and
moreover, many nicotine residue on nanoneedle form immunodeficiency is agenoy surface, providing a low affinity, vysokoavidnyh binding of nicotine residue to the surfaces of antigen presenting cells (APCS) in comparison with the binding of an antibody;
nanoneedle optionally contain one or more targeting agents that recognize a target associated with a particular organ, tissue, cell or subcellular locale, and optionally contain one or more immunomodulatory agents that induce an immune response in b cells or T-cells or stimulate the immune system so that the immune response is enhanced, suppressed directed or redirected; and
(2) pharmaceutically acceptable excipient.

2. The composition according to claim 1, in which nanoneedle contain one or more target agents, the learning target associated with a particular organ, tissue, cell or subcellular locale, or one or more immunomodulatory agents that induce an immune response in b cells or T-cells or stimulate the immune system so that the immune response is enhanced, suppressed, is directed or redirected, and targeting agents or immunostimulatory agents associated with the surface of nanoneedles or encapsulated in nanoneedle.

3. The composition according to claim 1, where the synthetic nanoneedle able in order to aktivirovat antigen presenting cells, B-cells, CD4+T cells, NKT cells, or any combination of these types of cells when administered to a human.

4. The composition according to claim 1, where the synthetic nanoneedle capable of stimulating the production of anti-nicotine IgG antibodies when administered to a human.

5. The composition according to claim 1, where the synthetic nanoneedle able to induce humoral immune response in a patient man.

6. The composition according to claim 1, where the synthetic nanoneedle administered to the patient is a person, and these synthetic nanoneedle can be transported through the wall of the subcapsular sinus (SCS) SCS macrophages in the body of the patient.

7. The composition according to claim 2, where immunostimulating agent selected from the group consisting of TLR agonists, interleukin, interferon, cytokines, CD40 agonist, agonist inflammasome and adjuvant.

8. The composition according to claim 1, where the synthetic nanoneedle contain polymer molecules and where many nicotine residue covalently attached to these polymer molecules.

9. The composition of claim 8, where the variety of nicotine residues are (S)-(-)-nicotine residues and where synthetic nanoneedle contain a polymer having the structure (X)n-L1(Y)m-L2-A, where: X denotes the hydrophobic segment of the polymer; Y represents a hydrophilic segment polymer; n and m are selected from 0 and 1, provided that n and m are not both 0; L and L2independently selected from communication and the linker group; and a represents (S)-(-)-nicotine.

10. The composition according to claim 1, where R8represents methyl.

11. The composition according to claim 1, where nicotine is present on the surface of nanoneedle density equal to or greater than the density required to obtain at least 10% of the maximum immobilization observed for monoclonal antibodies (b) analysis of binding antigen presenting cells (APC), provided that in the analysis of binding ARS density premaxillae linking for many residues is at least two times greater than the density of premaxillae binding for this b.

12. The composition according to claim 11, where nicotine is present on the surface of nanoneedle density equal to or greater than the density required to obtain at least 20% of the maximum immobilization observed for b in the analysis of binding ARS.

13. The composition according to claim 11, where b is a clone AD5-8E7 anti-CD1c (BDCA-1) or clone 3D6.112, isotype rat IgG2a anti-D169 mouse antibodies, and density premaxillae binding to nicotine is at least four times greater than the density of premaxillae binding for b.

14. The composition according to claim 11, where the analysis of binding ADR includes:
(a) obtaining a variety of substrates having a coating isfunctioning residue at multiple densities of surface coating, where specified functional balance ability to communicate with dendritic cell (DC) or receptors on the surface of macrophages subcapsular sinus;
(b) bringing into contact a variety of substrates with a suspension of individual cells DC or macrophages subcapsular sinus within a predetermined period of time;
(c) removing unbound ARS from a variety of substrates and fixing related ARS with many substrates;
(d) determining the number of related ARS per unit surface area for each substrate in the lot of substrates;
(e) plotting the dependence of the result from (d) from density functional coating residue;
(f) obtaining the value of the maximum immobilization by determining the maximum number of related ARS per unit surface area of a variety of substrates; and
(g) obtaining values of density premaxillae binding determination of the density of surface coating, which provides 50% of the maximum.

15. The composition according to claim 1, in which nanoneedle is a self-assembling synthetic nanoneedle formed from amphiphilic molecules containing a hydrophilic immunomodulatory or antigenic molecule covalently linked to a hydrophobic polymer.

16. The composition according to claim 9, where the hydrophilic polymer is polite Anglican, as the hydrophobic polymer is polyglycolic acid, polylactic acid or poly(lactic acid/glycolic acid).

17. The composition according to claim 1, where nanoneedle contain the polymer, and nicotine associated with the polymer.



 

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