Development of modified pleural talk structures with antibacterial and Anti-inflammatory effects to prevent pleural effusion or pneumothorax

Abstract

Invention; It relates to a semi-synthetic composition with a modified talc structure suitable for use in the medical, chemical and medical sectors, pharmaceutical industry, and for the treatment of pleural inflammation.

Description

[0001] DEVELOPMENT OF MODIFIED PLEURAL TALK STRUCTURES WITH ANTIBACTERIAL AND ANTI-INFLAMMATORY EFFECTS TO PREVENT PLEURAL EFFUSION OR PNEUMOTHORAX

[0002] Field of the Invention

[0003] Invention; relates to a semi-synthetic composition with a modified talc structure suitable for use in the medical, chemical and biomedical sectors, pharmaceutical industry, and for the treatment of pleural inflammation.

[0004] State of the Art

[0005] Inflammation of the pleura, which develops due to water accumulation in the lungs due to various reasons, is a disease that causes many diseases and needs to be treated in a timely manner. Inflammation of the lung membrane, also called pleurisy, is known as pleural effusion in the medical world.

[0006] Many different factors can be mentioned in the formation of pleurisy. Tuberculosis is among the main causes of inflammation in the lung membranes. In tuberculosis patients, the pleural space accumulates more fluid than normal, which can cause inflammation.

[0007] Additionally, lung cancer is also a major risk factor for inflammation. Lung cancer may cause the pleura to weaken by being affected by cancerous cells, resulting in increased fluid in the pleural space. For this reason, lung cancer is considered one of the main causes of most lung inflammations.

[0008] Some medical problems such as infections caused by bacteria, respiratory diseases such as pneumonia, and inhalation of asbestos and similar harmful substances can also cause inflammation in the membrane as they weaken the lungs. there are studies on the treatment of inflammation of the lung membrane. One of these is the European Patent document numbered EP3374029B1. The invention described in this document relates to the use of a zeolite, which also has a cytotoxic effect, as a chemical agent in the pleurodesis process applied in cases of fluid accumulation (pleural effusion) or air accumulation (pneumothorax) in the lung-pleural space.

[0009] In addition, in state-of-the-art medical applications, pleurodesis is a procedure performed to close the pleural space to prevent recurrent pleural effusion or pneumothorax or to treat persistent pneumothorax. When pleurodesis occurs in a patient, first the pleural fluid is drained and then talc is applied to the pleural space. The talc application process consists of depositing the talc structure with the appropriate particle size directly into the relevant space. However, some important indications may be observed both during and after this procedure. The most important of these indications is infection.

[0010] There is a need for more effective and versatile treatment methods by modifying the technique in a multifunctional way.

[0011] Aim of the Invention

[0012] The present invention relates to semi-synthetic polymer-talc composite systems with anti-inflammatory properties that meet the above-mentioned requirements, eliminate all disadvantages and bring some additional advantages.

[0013] The primary purpose of the invention is to improve the directly applied talc structure in a multifunctional way and to create a functional biomedical application.

[0014] Another aim of the invention is to obtain a permanent antibacterial property without causing side effects, thanks to the kill-repel based polymeric modification used in polymeric structures. In order to fulfill the objectives described above, the invention is semi-synthetic polymer-talc composite systems that are biocompatible, biodegradable, have antibacterial effect and have anti-inflammatory properties, suitable for use in the treatment of pleural inflammation, and 2-(tert-butylamino)ethyl methacrylate is polymerized on the surface with 3-vinylpropyl-triethoxysilane. It contains talc modified to carry chlorine groups on its surface.

[0015] The structural and characteristic features and all the advantages of the invention will be more clearly understood thanks to the figures given below and the detailed description written with references to these figures, and therefore the evaluation should be made by taking these figures and the detailed explanation into consideration.

[0016] Figures Clarifying the Invention

[0017] Figure 1 : Schematic view of the synthesis of modified pleural talc structures with antibacterial and anti-inflammatory effects,

[0018] Figure 2: FTIR spectra of pure talc, vinyl modified talc and antibacterial talc structures

[0019] Figure 3: TGA thermograms of pure talc and antibacterial talc structures

[0020] Figure 4: DSC thermograms of pure talc and antibacterial talc structures

[0021] Figure 5: DTA thermograms of pure talc and antibacterial talc structures

[0022] Figure 6: SEM images of pure talc (6a, 6b), vinyl modified talc (6c, 6d) and antibacterial talc (6e, 6f) structures at different magnifications

[0023] Elements Helping to Understand Figures

[0024] 1 . Talc

[0025] 2. Silica surface

[0026] 3. Antibacterial polymeric surface a: 3-vinylpropyl-triethoxysilane b: 2-(tert-butylamino)ethyl methacrylate

[0027] Ell: Antibacterial talc

[0028] V: Vinyl modified talc

[0029] T: Talc

[0030] Detailed Description of the Invention

[0031] In this detailed description, the invention is explained only for a better understanding of the subject and in a way that does not create any limiting effect.

[0032] Subject of invention; Semi-synthetic polymer-talc composite systems, which are biocompatible, biodegradable, have antibacterial effects and have antiinflammatory properties, suitable for use in the treatment of pleura inflammation, are in their most basic form; 2-(tert-butylamino)ethyl methacrylate contains 3- vinylpropyl-triethoxysilane polymerized on the surface and talc whose surface is modified to carry chlorine groups. The particle size of the resulting semisynthetic polymer-talc composite system is preferably 100 pm.

[0033] In a preferred embodiment of the invention, the developed semi-synthetic polymer-talc composite system is formulated with lidocaine. Lidocaine aims to reduce pain.

[0034] Figure 1 shows the synthesis of modified pleural talc structures with antibacterial and anti-inflammatory effects. In the invention, firstly, the talc structure was modified to include antibacterial groups and It was then combined with lidocaine to reduce pain during application. In this way, discomfort that may occur during the application is prevented and the risk of infection after the application is reduced. For these processes, first the talc structures were separated into appropriate sizes. Then, chlorine groups were attached to the talc structure on appropriately sized talc structures using sol-gel reaction with 3-chloropropyltriethoxy silane. Then, 2-(tert-butylamino)ethyl methacrylate was polymerized by ATRP, which is a surface polymerization reaction using chlorine groups. In this way, charged organic groups were created on the talc surface and a permanent antibacterial feature was provided. During this process, the number of charged groups on the surface was changed by changing the ratio of 2-(tert-butylamino)ethyl methacrylate.

[0035] Thus, the optimum structure was tried to be determined. Four different ratios were studied. In the final stage of the study, a surface modification was carried out by binding a 3-vinylpropyl-triethoxysilane binding agent onto appropriately sized talc structures.

[0036] The talc structure functionalized with 3-vinylpropyl-triethoxysilane will then work with the kill and release principle and kill bacteria on the surface and 2-(tert butylamino)ethyl methacrylate was bound by free radical polymerization to provide a surface that would remove dead bacterial particles from the surface. For this process, 2-(tert-butylamino)ethyl methacrylate structure was polymerized as a network structure on the modified talc surface. Each obtained structure was first structurally characterized by FTIR spectrum.

[0037] Then, the amount of organic groups bound to the talc structure was determined by TGA thermogram. Thermal properties of the obtained structures were examined with DSC and DTA thermograms. The antimicrobial activities of the obtained gram (+) and gram (-) bacteria and fugus were examined. In this context, antimicrobial properties were determined using the disk diffusion method. In this context, the modified talc structure was pressed into discs with a diameter of approximately 1 cm and placed in previously prepared media. After the cultivation of the microorganism, it was incubated at 37 °C for 24 hours and the resulting zone diameters were determined. FTIR spectra performed for the chemical characterization of the obtained Pure Talc, vinyl modified talc and antibacterial talc structures are given in Figure 2. As can be seen, in the FTIR spectrum of the pure talc structure in Figure 2, the stretching vibration bands of the siloxane group (Si-O-Si) are found with intense peaks at 476 cm’1and 1040 cm’1, respectively, while the band at 677 cm’1reflects the Si-O-Mg bond.

[0038] The peak at 3676 cm’1belongs to the OH groups on the talc surface. When this structure is modified with 3-vinylpropyl-triethoxysilane groups, peaks belonging to aliphatic C-H groups appear around 2850-2950 cm’1, C=C peak at 1635 cm’1, C-C peak around 1360 cm’1, C-O-C peak around 1112 cm’1, and C-H peaks around 800 cm’1were seen in the spectrum.

[0039] The presence of these peaks confirms the modification on the surface. In addition, in this structure, due to the talc structure, there is Si-O-Si at approximately 1080 cm’1, a peak belonging to Mg-OH bending at 669 cm’1, and a peak belonging to Mg-0 bond at 533 cm’1. In addition to these peaks, there are peaks originating from polymeric groups attached to the surface in the antibacterial talc structure.

[0040] The peaks at 3000-2950 cm’1indicate aliphatic C-H stretching. The peak at 1750 to 1700 cm’1represents the carbonyl C=O stretch, i.e. uC=O. The peak at 1440 cm’1is due to C-N stretching. The peak at approximately 1320 cm’1is due to C-C bonding, and the peak at 800 cm’1is due to C-H groups. 35 All these peaks confirm that the desired structure has been obtained. TGA thermograms of the obtained pure talc and antibacterial talc structures are given in Figure 3.

[0041] While there is no mass loss in the pure talc structure up to 700°C, the organic groups bonded during modification in the antibacterial talc structure decompose around 200°C and show significant mass losses. The amount of mass loss increases as the amount of organic groups added. DSC of the obtained pure talc and antibacterial talc structures thermograms are given in Figure 4. In this way, while no thermal change is observed in the talc structure, two distinct exotherms are observed in the antibacterial modified talc structure at 180 - 280 °C and 300 - 420 °C. These exotherms result from the degradation of organic groups on the surface.

[0042] DTA thermograms of the obtained pure talc and antibacterial talc structures are given in Figure 5. In the DTA analysis of pure talc and antibacterial talc structures, there is a distinct and clear additional isotherm between 180 and 300 °C. This proves the existence of organic groups bonded to the structure.

[0043] SEM images of the obtained pure talc (6a, 6b), vinyl modified talc (6c, 6d) and antibacterial talc (6e, 6f) structures at different magnifications are given in Figure 6. Another important finding for talc structure is SEM analysis. In these analyses, talc structure and dimensions were determined. According to these findings, after the doping process on the structure and after surface modifications, the particle sizes of talc were observed to be suitable for use in pleural inflammation.

[0044] With the invention, semi-synthetic polymer-talc composite systems that are biocompatible, biodegradable, have antibacterial effects and show antiinflammatory properties have been developed for the treatment of pleural inflammation. In this way, more effective and versatile treatment methods have been developed by being modified multifunctionally.

[0045] This invention enabled the development of semi-synthetic and biocompatible systems that eliminate disease symptoms with a one-time injection. With the developed semi-synthetic formulation, the risk of infection is minimized and treatment is provided. The surface modifications and mixed drug formulations performed are unique and innovative. It is designed with biocompatible structures to increase cell compatibility and support cell growth.

[0046] The kill and release based polymeric modification used in polymeric structures is a first in the literature in terms of its application to the talc surface. It provides a permanent antibacterial feature without causing side effects

Claims

CLAIMS1. They are semi-synthetic polymer-talc composite systems that are biocompatible, biodegradable, have antibacterial effects and have antiinflammatory properties, suitable for use in the treatment of pleural inflammation. The feature of this system; It contains 2-(tert-butylamino)ethyl methacrylate, 3-vinylpropyl-triethoxysilane polymerized on the surface, and talc modified to carry chlorine groups on the surface.

2. The feature of the product described in claim 1 ; the particle size of the system is 100 pm.

3. Feature of the product according to claim 1 ; It is formulated with lidocaine.

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