KR20220021915A - Composite Materials Manufacturing Method for Viruses Adsorption - Blocking and Apoptosis-Inactivation Function - Google Patents

Abstract

The present invention relates to a method for manufacturing a complex having virus adsorption and apoptosis functions, and more particularly, to a method for manufacturing a composite material of hydroxyapatite having virus adsorption characteristics and copper or platinum having virus killing characteristics. In order to solve the above problems in a virus blocking composite material according to the present invention, the method comprises the following steps: (1) mixing a calcium salt-containing material, a phosphate-containing material, and a metal salt; (2) adding an aqueous solution strongly alkaline in slightly acid to the mixture; (3) reacting the mixture in the step (2) by ball milling; and (4) drying and pulverizing the reactant in the step (3).

Description

Composite Materials Manufacturing Method for Viruses Adsorption - Blocking and Apoptosis-Inactivation Function }

Entering the 21st century, SARS in 2002, swine flu in 2009, MERS in 2015, Middle East Respiratory Syndrome in 2015, COVID-19 in 2019 (COVID-19, coronavirus infection-19). ), a new virus that is highly contagious to humans and has a high risk of death is becoming more frequent, and its appearance cycle is getting shorter. And with globalization, movement between countries/urbanization and movement between countries is easy, so the rate of spread is fast, social and economic damage is rapidly increasing, and mutations of new viruses are occurring rapidly. In addition, there is a problem in that the time required for the development of vaccines and therapeutics may increase according to the emergence of new viruses. Therefore, there is a need for materials that can be applied to personal and daily quarantine products that can effectively block the virus.

Hydroxapatite is an inorganic component constituting the teeth and bones of the human body. It is mainly used as a bioceramic material and as a biomaterial substitute for medical use. Because it has both cation and anion exchange properties, it is a high-performance adsorption material for purification of high-purity biopharmaceuticals. is being used Therefore, it is used for adsorption and separation of RNA, Viruses, Membrane Proteins, Vaccines, Polyclonal & Monoclonal Antibodies, DNA, Antibody Fragment, etc.

In addition, metallic ions generally exhibit sterilization properties, and have a trace action in which a trace amount of metal ions disrupt the metabolism of microorganisms and kill them through direct contact. Among them, copper ions penetrate and penetrate the external cells of the virus, destroying the cell membrane, and accelerating cell damage to damage and kill the DNA inside the virus. In addition, it is reported that the virus-destroying effect is very excellent, and theoretically, it can be effective against all kinds of viruses. In addition, platinum is also known to destroy proteins or DNA in contact with bacterial viruses.

Therefore, through the complexation of hydroxyapatite, which exhibits high adsorption properties for various viruses, and copper or platinum, which has virus apoptosis properties, it led to the invention of a composite material with virus adsorption-blocking and apoptosis-inactivation properties.

Copper or platinum, which has a virus-killing effect, can only expect a virus-killing action when it comes into contact with a virus. Therefore, it is necessary to allow the direct action of copper or platinum ions, which are effective for virus killing-inactivation.

Accordingly, the present invention relates to a method for preparing a complex having virus adsorption-blocking and apoptosis-inactivation functions, wherein hydroxyapatite having adsorption characteristics for DNA, RNA, protein, antibody, virus, etc., copper or platinum with virus killing characteristics It relates to a method for manufacturing a composite material capable of adsorption-blocking and killing-inactivation of ions bound to a virus.

The complex of hydroxide apatite and metal ion provides antibacterial properties using silver as in domestic patent registration 10-1764596 and domestic patent application 10-2017 -0049388, and inorganic substances such as sericite and silitazole as in domestic patent registration 10-2051622 There are methods for manufacturing inorganic antibacterial agents complexed with silver, copper, zinc, and the like. However, the above methods have disadvantages in that the process is complicated and high manufacturing cost may be required, such as undergoing various reactions or sintering at a high temperature of 600 to 1300 degrees.

Therefore, in the present invention, hydroxide apatite and copper or platinum composite materials for adsorption-blocking and death-inactivation of various viruses are manufactured in a simplified process and low-cost economical method so that they can be applied to various hygiene/prevention products. .

In order to solve the above problems, the present invention has been reached through many intensive studies.

In order to solve the above problems in the virus blocking composite material according to the present invention, (1) mixing a calcium salt-containing material, a phosphate-containing material, and a metal salt; (2) adding a weakly acidic to strongly alkaline aqueous solution to the (1) mixture; (3) reacting the (2) mixture by ball milling; (4) It consists of the steps of drying and pulverizing the reactant (3) above, and the virus adsorption-blocking and death-inactivation composite material is prepared through the above processes.

Step (1) of the present invention is to prepare a mixture composed of a calcium salt-containing material and a phosphate-containing material and a metal salt material. In the method for preparing the mixture, the molar ratio of calcium salt and phosphate, that is, the Ca/P molar ratio is 1.0 to 2.0, and the most preferable Ca/P molar ratio is 1.6 to 1.8, and the metal salt is 0.1 to 0.1 of the total of the calcium salt and the phosphate-containing material. It is added in a weight ratio of 20%, and the most preferable content is 0.5 to 5% by weight.

Calcium salt sources in step (1) include calcium hydroxide, calcium carbonate, calcium chloride, calcium nitrate, calcium oxide, calcium sulfate, calcium silicate, calcium gluconate, calcium arsenate, calcium acetate, calcium bromide, glycerin calcium phosphate, calcium lactate. , calcium citrate, calcium pyropionate, calcium ascorbate and their anhydrides and hydrates, tetracalcium phosphate, tricalcium phosphate, octacalcium phosphate, dicalcium dihydrate, dicalcium phosphate, calcium pyrophosphate, calcium dihydrate pyrophosphate, It is used by selecting from the group consisting of calcium dihydrogen phosphate and calcium metaphosphate. Sources of phosphate include orthophosphoric acid, phosphorus pentoxide, monobasic ammonium phosphate, diammonium phosphate, metaphosphoric acid, pyrophosphate, dibasic sodium phosphate, triphosphate, phosphoric acid, dipotassium phosphate, dibasic magnesium phosphate, tripotassium phosphate, trisodium phosphate, Sodium phosphate monobasic, potassium phosphate monobasic, phosphoryl chloride, polymetaphosphate, magnesium triphosphate, tetracalcium phosphate, tricalcium phosphate, octacalcium phosphate, dicalcium phosphate dihydrate, dicalcium phosphate, calcium pyrophosphate, calcium dihydrate pyrophosphate, You can use it by selecting it from the group consisting of calcium dihydrogen phosphate and calcium metaphosphate. Sources of metal salts include copper compounds such as cuprous chloride, cupric chloride, cuprous iodide, copper nitrate, copper pyrophosphate, and copper sulfate, or chloroplatinic acid, platinum oxide, platinum dioxide, platinum chloride, cuprous chloride, and platinum hydrochloride. , platinum hydroxide, platinum nitrate, etc., can be used by selecting from the group constituting platinum compounds.

Step (2) is a step of adding an aqueous solution to the mixture of calcium salt, phosphate, and metal salt materials prepared in step (1) and adjusting the aqueous solution from weak acidity to strong alkalinity. A method for adjusting the pH of the aqueous solution in this step To adjust the pH, either directly add inorganic salts or use an aqueous alkali solution mixed with inorganic salts. At this time, the pH of the aqueous solution becoming weakly acidic and strongly alkaline is pH 6.0 to pH 14.0, and according to the present invention, pH 7.0 to pH 10.0 is most suitable. If the pH is too low, the reactivity may be lowered, and the formation of hydroxyapatite due to the reaction of calcium salt and phosphate may be delayed. If the pH is too high, the pH of the composite material may become too high after the reaction. If the pH is high, there is no problem when applied to non-contact products with the human body, but it may cause allergic reactions when applied to products that come into contact with the human body.

The basic source may be selected from the group consisting of alkaline compounds such as sodium hydroxide, potassium hydroxide, ammonia, lithium hydroxide, calcium hydroxide, and magnesium hydroxide.

Step (3) is a step of reacting the mixture of steps (1) and (2) by ball milling. , the added metal salt material, copper or platinum, is more easily substituted into the hydroxide apatite crystal structure. The ball mill operates at a speed of 100Rpm ~ 400Rpm, and the most desirable speed is 200Rpm ~ 300RpM. The aqueous solution adjusted to the appropriate pH in step (2) and the aqueous solution to which the mixture is added are reacted for 1 hour to 240 hours at a ball mill temperature of 10°C to 110°C. The most preferable is to perform the ball mill reaction at 25°C to 80°C and 24 hours to 72 hours. When the reaction is performed by ball milling, the higher the speed and temperature, the faster the reaction and substitution occurs. The reaction temperature may be set to room temperature, but if it is set to room temperature, the reaction time may increase.

Step (4) is a step of drying and pulverizing the complex that has undergone the process of step (3). In this step, the synthesized complex may be filtered through a centrifuge or filter. During filtration, the pore size of the filter paper can be selected and used according to the particle size, and the centrifuge is used for filtering at a speed of 1,000 RPM to 10,000 RPM, most preferably 3,000 RPM to 5,000 RPM. The filtered composite is dried at a temperature of 100 ° C. to 500 ° C., and most preferably dried at 150 ° C. to 200 ° C. The dried composite is pulverized using a pulverizer. Pulverization is performed by crushing to 1 mm or less through a coarse grinder and pulverizing to 50 μm or less through a fine grinder to prepare a fine composite powder.

In addition, when surface treatment of polymers such as fibers, metals, ceramics, etc. or used as a raw material for manufacturing a composite matrix, it is also possible to omit the process of step (4) and apply the composite prepared only by the process up to step (3).

Therefore, using the copper/platinum-containing hydroxide apatite prepared by the present invention, that is, a virus adsorption-blocking and killing-inactivation complex, filters such as masks, air purifiers, daily quarantine products, or medical and military products for virus blocking can be applied to

The present invention has the following effects.

Influenza viruses such as swine flu (swine flu) that have recently been contagious worldwide, severe acute respiratory syndrome (SARS, SARS-CoV), Middle East respiratory syndrome (MERS, MERS-CoV), and coronavirus infection-19 (coronavirus) 19, it is important to effectively block coronaviruses such as COVID-19. In particular, in the case of SARS and MERS in the past, there was no transmission without symptoms, but there is a risk that COVID-19 is highly contagious even when asymptomatic, and various mutations of the virus are occurring. Therefore, it is necessary to develop and manufacture materials that can be applied to products that can fundamentally block various viruses and mutated viruses such as the emergence of new viruses.

Hydroxapatite has very strong adsorption properties for viruses or DNA or RNA, which is the basis of viruses, and copper or platinum kills viruses. Therefore, it is possible to fundamentally block various viruses by adsorbing-blocking and killing-inactivating viruses by supporting copper or platinum ions on hydroxyapatite.

Through the present invention, it is possible to manufacture a composite material that blocks various viruses at the source and kills them, so it can be applied to hygiene/prevention-related products such as masks and filters, so that effective life prevention is possible during the development period of vaccines and therapeutics.

FIG. 1 shows the results of X-ray diffraction analysis of hydroxyapatite prepared in Example 1. FIG.
FIG. 2 shows a scanning electron microscope photograph of the hydroxide apatite-platinum ion composite particles prepared in Example 1. FIG.
3 shows a scanning electron microscope photograph of the hydroxide apatite-copper ion composite particles prepared in Example 2.

74.09 g of calcium hydroxide and 115.3 ml of 85% phosphoric acid (Ca/P molar ratio 1.67) and 0.2 g of ferric chloride are weighed and mixed. While mixing the mixed solution, the pH is adjusted to 10 while adding 3M aqueous sodium hydroxide solution. The adjusted mixed aqueous solution was added to the 1L Ball Mill Port, 1kg of 1mm and 3mm zirconia balls were put in each, and the temperature of the ball mill was set to 60℃, and then ball milled at a speed of 250RPM for 48 hours. After the ball mill reaction, it was filtered and washed, and dried at 150° C. for 15 hours. The dry complex was coarsely pulverized and pulverized to obtain a fine complex powder.

378.17 g of dibasic calcium phosphate and 111.15 g of calcium hydroxide (Ca/P molar ratio 1.67) and 30 g of copper chloride are weighed and mixed. 500ml of distilled water was added to the mixture, added to a 2L Ball Mill Port, and 0.9 kg of alumina balls of 1mm, 3mm and 5mm sizes were added, respectively, and the ball mill was performed at room temperature at a speed of 280RPM for 48 hours. After the ball mill reaction, it was filtered and washed, and dried at 120° C. for 24 hours. The dry composite was pulverized to obtain a fine composite powder.

236.15 g of calcium nitrate, 73.37 g of ammonium phosphate (Ca/P molar ratio 1.8) and 10 g of copper chloride are weighed, mixed, and put into a 2L Ball Mill Port. After putting 1,000 ml of an aqueous alkali solution containing 40 g of sodium hydroxide in 1,000 ml of distilled water into a 2L ball mill port, 1.3 kg of 3mm and 5mm size alumina balls were put into each, and the ball milled at a speed of 200RPM for 12 hours. After the ball mill reaction, it was filtered, dried at 150° C. for 10 hours, and then fine powder of 50 μm or less was obtained using a grinder.

344.18 g of dibasic calcium phosphate and 100.09 g of calcium carbonate (Ca/P molar ratio 1.67) and 20 g of copper chloride are weighed and mixed. 1,000 ml of distilled water is added to the mixture, and the pH is adjusted to 10 while adding 1M aqueous sodium hydroxide solution while stirring. The mixed aqueous solution was added to a 2L Ball Mill Port, and 1.3 kg of 1 mm alumina balls and 1 kg of 3 mm alumina balls were put, and the ball mill was performed at room temperature at a speed of 250 RPM for 72 hours. After the ball mill reaction, it was filtered and washed, and dried at 120° C. for 24 hours. The dry composite was pulverized to obtain a fine composite powder.

Claims (10)

(1) mixing the calcium salt-containing material and the phosphate-containing material and the metal salt
(2) adding an aqueous solution to the mixture and adjusting it to be an aqueous solution of weak acidity to strong alkalinity
(3) reacting the mixture by ball milling
(4) A method for producing a complex of virus adsorption and apoptosis functions comprising the steps of filtration, washing, drying and pulverization The method of claim 1,
In the step (1), the concentration ratio of calcium salt and phosphate, that is, the molar ratio of Ca/P, is 1.0 to 2.0. The method of claim 1,
Calcium hydroxide, calcium carbonate, calcium chloride, calcium nitrate, calcium oxide, calcium sulfate, calcium silicate, calcium gluconate, calcium arsenate, calcium acetate, calcium bromide, glycerin calcium phosphate, calcium lactate as the calcium salt raw material in step (1) , calcium citrate, calcium pyropionate, calcium ascorbate and their anhydrides and hydrates, tetracalcium phosphate, tricalcium phosphate, octacalcium phosphate, dicalcium dihydrate, dicalcium phosphate, calcium pyrophosphate, calcium dihydrate pyrophosphate, Method for manufacturing a complex with virus adsorption and apoptosis function, characterized in that calcium dihydrogen phosphate and calcium metaphosphate The method of claim 1,
Orthophosphoric acid, phosphorus pentoxide, monobasic ammonium phosphate, diammonium phosphate, metaphosphoric acid, pyrophosphate, dibasic sodium phosphate, triphosphate, phosphoric acid, potassium diphosphate, dimagnesium phosphate, tripotassium triphosphate, Sodium triphosphate, sodium phosphate monobasic, potassium monophosphate, phosphoryl chloride, polymetaphosphate, magnesium triphosphate, tetracalcium phosphate, tricalcium phosphate, octacalcium phosphate, dicalcium phosphate dihydrate, dicalcium phosphate, calcium pyrophosphate, dihydrate Method for manufacturing a complex with virus adsorption and apoptosis function, characterized in that it is calcium pyrophosphate, calcium dihydrogen phosphate, and calcium metaphosphate The method of claim 1,
A method for producing a complex having a virus adsorption and apoptosis function, characterized by a copper compound and a platinum compound as a metal salt raw material in the step (1) The method of claim 1,
In the step (1), the content of the metal salt is 0.1 to 30% of the total weight of the calcium salt and the phosphate. The method of claim 1,
In the step (2), the pH of the weakly acidic or strongly alkaline aqueous solution is in the range of pH 6.0 to pH 14.0 The method of claim 1,
In the step (2), as an alkaline source, sodium hydroxide, potassium hydroxide, ammonia, lithium hydroxide, calcium hydroxide, and magnesium hydroxide are used. The method of claim 1,
A method for producing a complex with virus adsorption and apoptosis function, characterized in that the reaction is carried out at a ball mill temperature of 10°C to 110°C in step (3) The method of claim 1,
A method for producing a complex having a virus adsorption and apoptosis function, characterized in that the ball mill is reacted for 1 hour to 240 hours in step (3)

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