Single dose immunization against tetanus toxin cation dextran microspheres and preparation method thereof

A technology of tetanus toxoid and dextran, which is applied in the direction of pharmaceutical formulas, medical preparations of non-active ingredients, bacterial antigen components, etc., can solve the problem of low encapsulation volume and encapsulation efficiency, low encapsulation rate, coagulation and problems such as precipitation, to achieve the effect of improving vaccination coverage, realizing full-course immunization, and reducing the number of injections

Inactive Publication Date: 2010-10-27
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, the microspheres prepared from polylactic acid and its copolymers reported in domestic and foreign literature mainly have the following deficiencies: (1) polylactic acid and its copolymers as drug carriers are hydrophobic materials, which are hydrophilic to hydrophilic vaccines or drugs. The compatibility is not strong, resulting in low encapsulation volume and encapsulation efficiency; (2) the organic solvent used in the double emulsion method is often used in the preparation to easily cause protein aggregation and precipitation, and the vaccine activity is lost; (3) the initial burst release amount is large, Up to 30% to 40%; (4) Polylactic acid and its copolymers produce an acidic environment during the degradation process, causing changes in the natural conception of proteins or vaccines, and reducing antigenicity
Due to the two-phase aqueous process of microsphere preparation and better water solubility of the protein, its encapsulation efficiency is not high and the drug loading capacity is low, such as Vlugt-Wensink et al. (European Journal of Pharmaceutics and Biopharmaceutic, 2007, 67: 589-596), The encapsulation rate is 50%-70%, the drug loading is 4.16%-5.67%; and the cross-linking agent used in the emulsification cross-linking method often destroys the structure of the protein or vaccine

Method used

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  • Single dose immunization against tetanus toxin cation dextran microspheres and preparation method thereof
  • Single dose immunization against tetanus toxin cation dextran microspheres and preparation method thereof
  • Single dose immunization against tetanus toxin cation dextran microspheres and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] (1) 71 mg of hydroxyethyl methacrylate dextran (molecular weight 20,000, DS=3) was dissolved in 1.577 g of water, and 35 μl of dimethylaminoethyl methacrylate was added under stirring to obtain hydroxyethyl methacrylate Dextran phase;

[0038] (2) 20,001 g of polyethylene glycol was dissolved in 3.34 ml of water to obtain the polyethylene glycol phase;

[0039] (3) under stirring (1000rpm), the hydroxyethyl methacrylate dextran phase is added to the polyethylene glycol phase;

[0040] (4) Under stirring (500rpm), add 0.1ml tetramethylethylenediamine (20%, V / V, 4M hydrochloric acid to neutralize) and 0.18ml potassium persulfate (50mg / ml) into the upper solution respectively , cross-link for 1h (37 degrees) after stopping stirring;

[0041] (5) Wash off the supernatant with water under centrifugation, and freeze-dry to obtain blank microsphere powder.

[0042] (6) Weigh 70 mg of blank microsphere powder, add 5 ml of 1 mg / ml tetanus toxoid solution, incubate for 24 hours ...

Embodiment 2

[0045] (1) 71 mg of hydroxyethyl methacrylate dextran (molecular weight 20,000, DS=3) was dissolved in 1.577 g of water, and 35 μl of dimethylaminoethyl methacrylate was added under stirring to form hydroxyethyl methacrylate Dextran phase;

[0046] (2) 20,001 g of polyethylene glycol is dissolved in 5 ml of water to form a polyethylene glycol phase;

[0047] (3) under stirring (2000rpm), the hydroxyethyl methacrylate dextran phase is added to the polyethylene glycol phase;

[0048] (4) Under stirring (500rpm), add 0.1ml tetramethylethylenediamine (20%, V / V, 4M hydrochloric acid to neutralize) and 0.18ml potassium persulfate (50mg / ml) into the upper solution respectively , cross-link for 1h (37 degrees) after stopping stirring;

[0049] (5) Wash off the supernatant with water under centrifugation, and freeze-dry to obtain blank microsphere powder.

[0050] (6) Weigh 70 mg of blank microsphere powder, add 5 ml of 0.5 mg / ml tetanus toxoid solution, incubate for 24 hours (4° C....

Embodiment 3

[0053] (1) 71 mg of hydroxyethyl methacrylate dextran (molecular weight 20,000, DS=3) was dissolved in 1.577 g of water, and 35 μl of dimethylaminoethyl methacrylate was added under stirring to form hydroxyethyl methacrylate Dextran phase;

[0054] (2) Polyethylene glycol 60001g is dissolved in 5ml water to form a polyethylene glycol phase;

[0055] (3) under stirring (500rpm), the hydroxyethyl methacrylate dextran phase is added to the polyethylene glycol phase;

[0056] (4) Under stirring (500rpm), add 0.1ml tetramethylethylenediamine (20%, V / V, 4M hydrochloric acid to neutralize) and 0.18ml potassium persulfate (50mg / ml) into the upper solution respectively , cross-link for 1h (37 degrees) after stopping stirring;

[0057] (5) Wash off the supernatant with water under centrifugation, and freeze-dry to obtain blank microsphere powder.

[0058] (6) Weigh 70 mg of blank microsphere powder, add 5 ml of 1.5 mg / ml tetanus toxoid solution, incubate for 24 hours (4° C.), and cen...

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Abstract

The invention relates to the filed of pharmaceutical preparation, in particular to single dose immunization against tetanus toxin cation dextran microspheres and a preparation method thereof. The single dose immunization against tetanus toxin cation dextran microspheres are prepared by carrying tetanus toxin after electrostatic interaction on cation hydroxyethyl acrylate dextran microspheres. The tetanus toxin controlled release microspheres can reduce the injection frequency of tetanus vaccine, improve the vaccination coverage and reduce the drop-out rate, thereby effectively preventing tetanus and providing a single dose tetanus toxin controlled release vaccine preparation with long-term effect and realizing the whole course immunity by one injection.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a preparation of hydroxyethyl methacrylate cationic dextran microspheres loaded with tetanus toxoid and a preparation method thereof. Background technique [0002] The main purpose of the Global Childhood Vaccine Initiative (CVI), initiated by five international organizations including the World Health Organization, is to promote the development, introduction, and improvement of existing and newly created vaccines to strengthen the protection of children around the world from infectious diseases. Research to improve the delivery system of tetanus toxoid is one of the main goals of CVI. Whether tetanus can be controlled and eliminated depends on high-level vaccination, but the current basic immunization against tetanus requires three consecutive injections of vaccine within three months. The high number of vaccinations and the long vaccination cycle make the drop-out rat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/08A61K47/36A61P31/04
Inventor 郑春丽朱家壁刘晓庆赵玉娜
Owner CHINA PHARM UNIV
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