TECHNICAL FIELD

The present invention relates to a nanotechnological magnetic biomaterial that incorporates a wide range of functions, from industry to pharmaceutical manufacturing, from quantitative health kits to medical products, from cancer drug targeting to in vivo agent transport, from the potential to hold constant spatial sequences of all kinds of enzymes and organic structures in the living body to oxygen transport.

PRIOR ART

Many technical and methods are currently being developed in both healthcare and industrial areas. From these studies to medical studies, it is the alternative, cost- effective and safe techniques that have been sought to be developed for both in vivo treatment/imaging/diagnosis and medical diagnosis, high optimization and stable quantitative analysis. In this regard, there are several studies ranging from alternative drug targeting methods to new fluorescent imaging systems, to the development of basic working methods of advanced techniques such as eliza.

It can also be mentioned that when chemistry, engineering, medical chemistry, biochemistry fields are monitored, it is shaped at the maximum desired result, with the lowest cost of product and the minimum energy that human power is the cause of choice. In this context, it can also be discussed that new medicines and their substitutes are constantly being tried to synthesize (such as pyrimidine, isoxazole substitutions) or work to reduce the loss of organic molecules used in the heavy industry, which are at high costs.

Lastly, alternative blood creation works, also covered by the inventor patent application, are also encountered in the literature. Examining these studies, it is observed that the analysis of the different methods (such as chemical binding, perfluorocarbons), or products (haemoglobin-based oxygen carriers) that have been moved to more advanced phases (such as safety whether it is harmful to health; effect on in vivo system and functions), are in progress, and that the development has been attempted.

PURPOSE OF THE INVENTION

The present invention is the development of a magnetic artificial blood biomaterial, an alternative to natural blood, to be used as a preoperative and operative; the development of medical and diagnostic equipment in the surface of synthesized iron oxide solid support; the implementation of modifications in order to target drugs, enzymes and derivatives containing amino and carbon functional groups (functional groups with the potential to be connected) for various purposes; minimizing high-cost enzymatic losses in heavy industry (industrial industry, manufacturing industry, multi production, organized industries) according to its potential for use in industry, allowing enzymes to remain stable in industrial processes without losing functionality at high temperatures and extreme pH.

LIST OF THE FIGURES

Figure 1: General process flow diagram of the solution, capable of removing oxygen-carrying carbon dioxide produced by iron-oxide magnetite (magnetic nanoparticles) and pure haemoglobin molecules, enzyme and amino/carboxyl functional group, enabling drug targeting and providing enzyme stabilization in the industry.

Figure 2: Drug, enzyme, and haemoglobin bonding flow diagram with amine group to magnetite coated with silanes containing an amine group and functioned with the bond of aldehydes (X: FesC , Fe203, CoFe204, C03O4; Y: 0, S; Z: drug, enzyme, haemoglobin; n 1 : number of carbon 3,4, 5...; n2: number of carbon 1 ,2, 3...).

Figure 3: Drug, enzyme, and haemoglobin bonding flow diagram with aldehyde group to magnetite coated with silanes containing an aldehydes group and functioned with the bond of amines (X: Fe304, Fe203, CoFe204, C03O4; Y: O, S; Z: drug, enzyme, haemoglobin; n 1 : number of carbon 3,4, 5...; n2: number of carbon 1 ,2, 3...).

Figure 4: Drug, enzyme, and haemoglobin bonding flow diagram with amine group to magnetite coated with silanes containing an amine group and functioned with the bond of aldehydes (X: Fe304, Fe203, CoFe204, C03O4; Y: 0, S; Z: drug, enzyme, haemoglobin; n 1 : number of carbon 1 ,2, 3...). Figure 5: Drug, enzyme, and haemoglobin bonding flow diagram with amine group to magnetite coated with silanes containing an amine group and functioned with the bond of aldehydes (X: FesC , Fe203, CoFe204, C03O4; Y: 0, S; Z: drug, enzyme, haemoglobin; n 1 : number of carbon 1,2, 3...) Figure 6: Drug, enzyme, and haemoglobin bonding flow diagram with amine group to magnetite coated with silanes containing polyaldehyde group (X: Fe304, Fe203, CoFe204, C03O4; Y: 0, S; Z: drug, enzyme, haemoglobin; n1: number of carbon 3,4, 2.3...; n2: number of carbon 1 ,2, 3...)

Figure 7: Drug, enzyme, and haemoglobin bonding flow diagram with polyamine group to magnetite coated with silanes containing an aldehyde or ketone group (X: Fe304, Fe203, CoFe204, C03O4; Y: 0, S; Z: drug, enzyme, haemoglobin; n1: number of carbon 3,4, 2.3...; n2: number of carbon 1 ,2, 3...)

Figure 8: Drug, enzyme, and haemoglobin bonding flow diagram with amine group to magnetite coated with an aldehyde (X: Fe304, Fe203, CoFe204, C03O4; Y: 0, S; Z: drug, enzyme, haemoglobin; n1 : number of carbon 2,3...)

Figure 9: Drug, enzyme, and haemoglobin bonding flow diagram with aldehyde or ketone group to magnetite coated with amine (X: Fe304, Fe203, CoFe204, C03O4; Y: 0, S; Z: drug, enzyme, haemoglobin; n1: number of carbon 2,3...)

Figure 10: Drug, enzyme, and haemoglobin bonding flow diagram with amine group to magnetite coated with polyaldehyde (X: Fe304, Fe203, CoFe204, C03O4; Y: 0, S; Z: drug, enzyme, haemoglobin; T: N, C, S; n1: number of carbon 3,4, 2.3...; n2: The number of carboxylic acids, aldehyde, alcohol or amines in the structure is 2,3...)

Figure 11: Drug, enzyme, and haemoglobin bonding flow diagram with aldehyde group to magnetite coated with polyamine (X: Fe304, Fe203, CoFe204, C03O4; Y: 0, S; Z: drug, enzyme, haemoglobin; T: N, C, S; n1 : number of carbon 3,4,

2.3...; n2: The number of carboxylic acids, aldehyde, alcohol or amines in the structure is 2,3...)

Figure 12: Drug, enzyme and haemoglobin binding flow diagram with amine group to magnetite coated with carboxylic acid functional group and containing polyaldehyde functional groups (X: Fe304, Fe203, CoFe204, C03O4; Y: 0, S, C; Z: drug, enzyme, haemoglobin; T: N, C, S; n1 : number of carbon 3,4, 2.3...; n2: Number of carboxylic acid, aldehyde, alcohol or amines in the structure 1, 2, 3...)

Figure 13: Drug, enzyme and haemoglobin binding flow diagram with aldehyde group to magnetite coated with carboxylic acid functional group and containing polyamine functional groups (X: Fe304, Fe203, CoFe204, C03O4; Y: 0, S, C; Z: drug, enzyme, haemoglobin; T: N, C, S; n1 : number of carbon 3,4, 2.3...; n2: Number of carboxylic acid, aldehyde, alcohol or amines in the structure 1, 2, 3...) Description of the references in the figures

1. Dissolving FeCh and FeSC salts

2. Precipitation with sodium hydroxide in a nitrogen atmosphere

3. Magnetic decantation

4. Washing with distilled water 5. Vacuum desiccator drying

6. Magnetic nanoparticle

7. Suspension with ultrasonic bath in pure water

8. Carboxylic acid

9. Mixing with ultrasonic mixer 10. Magnetic nanoparticle coated with carboxylic acid

11.Adding a reducer

12. Alcohol-coated magnetic nanoparticle (surface)

13. Mixing with ultrasonic bath in acetone

14. Adding an oxidant 15. Aldehyde-coated magnetic nanoparticle (surface)

16. suspension with ultrasonic bath at pH 7.4

17. Addition of ultra-pure haemoglobin, appropriate drug and enzyme

18. Mixing with rotator stirrer

19. Washing with pH 7.4 buffer 20. Preparation of haemoglobin, enzyme complex and drug immobilized magnetic nanoparticles

21.Addition of alcohol derivative coating agent

22. Washing with acetone

23. Drying in the oven 24. Alcohol-derived agent coated magnetic nanoparticle

25. Adding aldehyde

26. Adding a silane derivative coating agent

27. Amine-derived agent coated magnetic nanoparticle A. Process of producing nanotechnological biomaterials alternative to blood with haemoglobin, enzyme and drug binding properties

DETAILED DESCRIPTION OF THE INVENTION

The process of processing subject to the present invention consists essentially of three steps:

- Preparation of magnetic nanoparticles (6)

- Preparation of aldehyde and amine-coated magnetic nanoparticle (on surface) (15; 27),

- Haemoglobin, enzyme complex and drug immobilized magnetic nanoparticle preparation with aldehyde and amine functional group (20, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7, Fig. 8, Fig. 9, Fig. 10, Fig. 11 , Fig. 12 and Fig. 13)

These basic steps are accompanied by many intermediate steps. All steps are shown in the flow diagram given in figure 1 . When the steps of the process (A) of producing nanotechnological biomaterials with haemoglobin, enzyme and drug binding properties were examined, magnetic nanoparticles have been synthesized by precipitating with NaOH (sodium hydroxide), KOH (potassium hydroxide), NH3 (ammonia) in the nitrogen atmosphere (2) with sequential steps (3), washing with pure water (4) and washing in vacuum desiccator (5) (6).

Four different methods have been used to form the synthesized material into nanoparticles coated with the second basic step, carboxyl or amine group (15). In the first method, carboxylic acid and silane derivative coating agent have been added to the magnetic nanoparticles (7) suspended by an ultrasonic bath in pure water (8; 26) and mixed with an ultrasonic stirrer (9). Tartaric acid has been used as carboxylic acid, azelaic acid, malic acid, succinic acid, butyric acid, adipic acid, oxaloacetic acid, sebacic acid, aspartic acid as well as glyoxal, glutaraldehyde, succinynaldehyde, malondialdehyde as dialdehyde), alcohol (Pentan-1 ,5-diol, triethanolamine, propane- 1 , 2, 3-triol, ethane-1 , 1 ,2-triol, 3-(hydroxymethyl)pentane-1 ,2,5-triol) and silane ((3- Aminopropyl) triethoxysilane, (3-Aminopropyl) trimethoxysilane, N- (2-Am i noethyl )-3- aminopropyryltriethoxysilane, N, N-Bis (2-Hydroxypropyltriethyl) -3- aminopropyltriethylamine; chemicals having amine group. Carboxylic acid and amine groups are preferred because they have the ability to bind biological molecules by direct intermolecular interactions and are suitable for modification. The reason for selecting the silanes is that it has the ability to form an imine bond with the groups with aldehyde group due to the presence of amine group at the ends and it is easy to modify with a simple molecule such as glutaraldehyde. Alcohols are also suitable for weak intermolecular interactions and easy to convert to a functional group such as aldehyde by a simple method. The reason for the use of dialdehydes and substances with amino groups is preferred because they fall down to a single step for binding of magnetic nanoparticles and biological molecules. The carboxylic acid and amine-coated magnetic nanoparticles obtained in this way have been obtained (10; 27) and the surface alcohol-coated nanoparticles have been obtained by reducing with the addition of reducer (11) (12). NaBFU (Sodium borohydride), LiAIFU (lithium aluminium hydride), thiourea (CH4N2O2S), hydrosulphite (Na2S204) solutions have been used as reducers. The reason for the preference of these reducers is that they are strong and can reduce carboxylic acids up to the alcohol step. In this way, since the functional group will be alcohol, it can be used directly as a support material and it will be easy to convert to the aldehyde group. In addition, the preferred reducers are available in terms of toxic effects. By mixing these obtained particles with ultrasonic bath (13) in acetone medium and providing oxidation with the addition of oxidant (14), alcohol surfaces provided the outlet of aldehyde surface nanoparticles (15), the second basic process step. Pyridinium chlorochromate, potassium dichromate, sodium dichromate, ammonium dichromate, sodium permanganate, potassium permanganate and ammonium permanganate solutions have been used as oxidants. The preferred reason for the oxidants used is to ensure that the oxidation of alcohols takes place in a single step and stays on the aldehyde step. In this way, the aldehyde functional group will be obtained. In another method, magnetic nanoparticles coated with chemical agents in the form of silane and derivatives have been obtained. With this method, amine functional groups have been released on the particle surfaces (27).

In the aldehyde coated magnetic nanoparticle (surface) formation (15), the second method has been the preparation of magnetic nanoparticles (6) followed by the addition of an alcohol derived coating agent (21), mixing with ultrasonic stirrer (9), magnetic decantation (3) and purified water washing (4) intermediate steps followed respectively by acetone washing (22) and oven drying (23) to obtain an alcohol derived magnetic nanoparticle (24). For the transformation of these synthesized particles into aldehyde-coated magnetic nanoparticles (15), mixing with ultrasonic bath (13), adding oxidant (14), mixing with ultrasonic stirrer (9), washing with pure water (4) and drying steps in vacuum desiccator (5) have been applied in acetone as in the previous method. Pyridinium chlorochromate, potassium dichromate, sodium dichromate, ammonium dichromate, sodium permanganate, potassium permanganate and ammonium permanganate solutions have been used as oxidants. The third method for making aldehyde coated magnetic nanoparticle (surface)

(15) has been the preparation of magnetic nanoparticles (6) and their suspension with ultrasonic bath (7) in pure water, followed by intermediate steps (9), magnetic decantation (3), washing with acetone (22) and drying in vacuum desiccator (5) with mixing with the ultrasonic stirrer applied respectively, the surface of these particles could be converted into aldehyde-coated magnetic nanoparticle (surface) (15).

The fourth and final method of making aldehyde coated magnetic nanoparticle (15) has been to prepare magnetic nanoparticle (6) and then mix it in acetone in an ultrasonic bath (13) and add silane derivative coating agent (26). With this method, the synthesis of magnetic nanoparticles with the amine functional group could be achieved (27). Subsequently, following the steps of suspension (16) with ultrasonic bath (16), addition (25) of aldehyde, mixing (9) with ultrasonic stirrer (9), magnetic decantation (3), washing (4) with pure water, and drying (23) in the oven, respectively, the aldehyde coated magnetic nanoparticle (15) and the silane derivative agent could be transformed into coated magnetic nanoparticle (26). The nanoparticles synthesized over 4 different methods to form aldehyde and amine groups coated magnetic nanoparticles (15; 27) have been cleaned by magnetic decantation (3) washing with pH 7.4 buffer (19) by ultrasonic bath suspension (16), addition of ultrapure haemoglobin, appropriate enzyme and drug (with surface aldehyde and amine functional groups), mixing with rotator stirrer (18) steps. In this way, solutions could be obtained with the preparation of haemoglobin, enzyme complex and drug immobilized magnetic nanoparticles (20) on the surface of our study, which has surface modifications with oxygen, enzyme and drug transport properties (A).

Detailed formulas of the patented products obtained in accordance with the above mentioned 4 methods are given in Figs. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7, Fig. 8, Fig. 9, Fig. 10, Fig. 11 , Fig. 12 and Fig. 13.

Surface modifications serving the above-mentioned purposes, haemoglobin, enzyme and drug complex solutions bound to magnetic nanoparticles can be produced, used and applied in industry. There is a versatile use of the present invention. Time and cost will be reduced by using in-process steps where high temperatures and low and/or high pH values should be worked in heavy industry;

High potential for drug binding and targeting to cancerous tissue due to its magnetic properties and its ability to move to the desired region in the development of next-generation cancer drugs and treatment techniques;

Having the ability to save lives by transfusing to the patient regardless of antigens in case of emergency bleeding. Production and shelf life can be used for a long time in room conditions, it can be produced in the industry and used in the traffic bag, in the bags of our law enforcement agencies;