MEDICINE LOADED NANO-CAPSULE ADDITIVE PMMA CEMENT

Abstract

Disclosed is a medicine loaded nano-capsule additive Polymethylmethacrylate (PMMA) cement and its production method.

Claims

1. A medicine loaded nanocapsule additive PMMA cement production method, a) preparation of polymers of active capsuling feature, b) synthesizing thermal sensitive nanocapsules, c) synthesizing bacteria sensitive nanocapsules, d) loading Vancomycin and/or tobramycin and/or gentamicin and/or linezolid and/or teicoplanin into nanocapsule in question, and e) loading loaded nanocapsules obtained in process step (d) into Polymethylmethacrylate (PMMA) polymer.

2. The production method of claim 1, comprising synthesizing thermal sensitive nanocapsules from Pluronic® F127 and poly(ε-lysine) (ε-PL).

3. The production method of claim 1, and comprising synthesizing bacteria sensitive nanocapsules from Pluronic® F127 and Hyaluronic acid.

4. The production method of claim 1, comprising adding 1 gr Vancomycin loaded nanocapsule and 40 mg Polymethylmethacrylate (PMMA) polymer.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0019] In this detailed description, the preferred applications of the invention have been described in a manner not forming any restrictive effect and only for purpose of better understanding of the matter.

[0020] The invention relates to medicine loaded nanocapsule additive PMMA cement and production method. The main agent for production of nanocapsules in the invention is a polymer with an encapsulation feature. The encapsulating polymers mentioned are triblock copolymers of conductive features and are fully biocompatible. Capsuling polymers used herein are activated by functional groups such as amine and carboxyl for use.

[0021] Nano capsule production under the invention is categorized in two as thermal sensitive and bacteria sensitive. In addition to encapsulating feature polymers, Hyaluronic acid (HA) is used to ensure effectivity in bacteria sensitive nanocapsule production. The HA in question is substrate of hyalurinidase enzyme released by Staphylococcus aureus bacteria. Increase of medicine release from antibiotic loaded nanocapsules is provided by help of HA. HA which is a substrate of Hyaluronidase enzyme secreted by Staphylococcus aureus bacteria is a type of polymer of bonding feature and is from glycosaminoglycans comprising anionic, long polysaccharides. They are known with general name of heteropolysaccharides which is a linear polymer comprising repetitive disaccharide units. For production of thermal sensitive nanocapsule, in addition to encapsulating feature polymers, cationic homopolymers capable to form loaded films easily by physical adsorption and electrostatic adsorption on various substrates including glass, metals, polymers and metallic oxides are used. Said cationic homopolymers which is basic material in thermal sensitive nanocapsule production provide opening and closing of polymer nanocapsule subject to temperature and adjustment of diffusion rate of medicine.

[0022] PMMA is the mixture with name of cement in orthopaedic surgery for several years as space filling or fixing agent in bone structure. In medicine loaded nanocapsule additive PMMA cement of the invention, PMMA is mixed with VCM. By use of method of the invention, tobramycin, gentamicin, linezolid and teicoplanin can also be used instead of Vancomycin for same purpose. Thus, local antibiotherapy effect is provided in the area of use.

[0023] In the medicine loaded nanocapsule additive PMMA cement production method of the invention, polymers of active encapsulating feature are prepared. In the next process step, thermal sensitive nanocapsules are synthesised by use of polymers/cationic homopolymers of encapsulating features. Then bacteria sensitive encapsulating feature polymers/hyaluronic acid base smart nanocapsules are synthesized. Synthesized thermal sensitive and bacteria sensitive nanocapsules have thermal sensitivity at range of 4° C. to 40° C. In addition, in order to provide dose control, in case of existence of Staphylococcus aureus in ambience, it comprises polymers/hyaluronic acid nanocapsules of smart capsuling feature comprising hyaluronidase enzyme substrate in about 90% of pathogen staphylococcus. Antibiotic release increases as a result of nano medicine release system interaction arising from hyaluronidase enzyme released in ambience having bacteria.

[0024] The bigger the size of thermal sensitive nanocapsule, the higher is wall permeability and the lower is the temperature. When temperature increases, nanocapsule size and permeability decreases. Since in stage of medicine loaded nanocapsule additive PMMA cement preparation, temperature reaches 60° C. to 80° C. for a short time period, nanocapsule permeability is decreased and VCM release is minimized. In this aspect, thermal sensitive nanocapsule use provides an advantage. After obtaining nanocapsules, VCM capsuling, incubation of nanocapsules in water solvent at low temperature and then removal of water and lyophilising and loading into the nanocapsules mentioned in a dialysis tube are performed. Average size of VCM loaded thermal sensitive nanocapsules is in range of 70-230 nm. This range is estimated taking into account the size in intra-cell applications.

[0025] Due to electrostatic interaction between HA and VCM in polymer/HA nanocapsules of encapsulating feature, it is targeted to achieve a higher encapsulating capability and release speed control in comparison to polymers/cationic homopolymer nanocapsules. The obtained medicine loaded nano capsules are contributed homogenously to standard PMMA polymer. In the mixing process mentioned here, preferably 1 g VCM loaded nanocapsule and 40 mg PMMA are used. Powder mixture obtained in the last process is mixed with monomer at 100 cycles/minute. As capsuling polymer Pluronic base polymers such as Pluronic®F127, Pluronic P123 or Pluronic F68 are used.

[0026] In order to solve above mentioned technical problems and achieve all advantages described in details below, the invention is a medicine loaded nanocapsule additive PMMA cement production method and comprises process steps of [0027] a) Preparation of polymers of active capsuling feature, [0028] b) Synthesizing thermal sensitive nanocapsules, [0029] c) Synthesizing bacteria sensitive nanocapsules, [0030] d) Loading VCM and/or tobramycin and/or gentamicin and/or linezolid and/or teicoplanin into said nanocapsule, [0031] e) Loading loaded nanocapsules obtained in process step (d) into PMMA polymer.