Field of invention

This invention relates a medical nanogold injection mainly containing nanogold less than 30nm and its manufacturing method.

Background and object of invention

Today, various nanomatenals are used as drug or drug carrier in medical field with a rapid development of nanotechnology and expansion of applicable field of nanomatenals, especially the nanogold is widely applied to the medical field because of its special physical and chemical properties.

It is known that the nanogold removes active oxygen from a pancreas and it consider that the nanogold activates as signal transmitter to promotes insufflation of glucose.

Alos, it is known that the nanogold induces the activity of cyclooxygenase which is an enzyme producing prostaglandin E2 causing pain, changes the transmission of pain signal by prostaglandin E2 increasing excitability of a nerve cell and thereby achieves the effect of alleviating pain.

By study, it is proved that as result of injecting the nanogold to mouse which doesn't suppress an appetite due to lack of heptyne receptor and suffers from diabetes by hypertrophy, dysfunction of the mouse's brain is improved and the mouse's blood sugar value is lower.

The nanogold inhibits lipid membrane oxidation, improves blood viscosity and eliminates active oxygen, thereby increases activity of lipid lytic enzyme protein, inhibits accumulation of lipid on the liver tissue and activates metabolism.

As the effect on cell membrane permeability of nanogold has been known, it is experimentally proved that where the nanogold is combined with an antitumor agent of high molecular weight, removal ratio of tumor can be remarkably increased; thereby it makes a great advance in treatment of tumor.

Gold exists in vital blood in amount of 0.1-0.2 g/kg.

l As the gold isn't assimilated by food, it must be supplied from an outside. If the gold lacks than the necessary amount, it has various bad effects on body and causes a disease.

According to data, as a result of observation on effect of nanogold on body, where the solution of nanogold has been injected into patients with immune deficiency or leucopenia by radiation injury in amount of 0.02mg a day for 7 days, the patients have been restored to normal.

Also, the nanogold increases osmotic pressure in a kidney and removes inflammation in urethra system.

It considers that where the nanogoid is injected into patients with rheumatoid arthritis or neuralgia and the nanogold is accumulated about 0.8mg, the patients are completely cured.

As a result of injecting nanogold into a patient with arthritis a in amount of O.Olmg a day for 5 days, 14 of 16 patients are completely cured.

A very small amount of the nanogold kills a germ or inhibits its growth.

Like this, the development of injection by the nanogold which the effect of treatment of disease is clear and injecting into a body is possible has a great significant in treatment and prevention of disease.

The manufacturing method of the nanogold has been already known.

The general method for synthesizing of nanogold is to reduce chloroauric acid (HAuCl ₄ ) in an aqueous solution state.

The normal reducing agents are sodium citrate, sodium thiocynate, white phosphorus, sodium borohydride(NaBH ₄ ), ascorbic acid and etc, in particular sodium citrate is widely used as reducing agents.

Frens method is known as the manufacturing method of nanogold by sodium citrate. This method describes the detailed method to obtain the nanogold particulars with various particle sizes (13-150nm), which changes a concentration of sodium citrate in granulation stage by reduction reaction between sodium citrate and chloroauric acid, it as follow:

Taking 5ml of 1% chloroauric acid (HAuC ) solution, diluting to be 100ml, heating until boiling and adding 5ml of 1% sodium citrate during mixing so that molar ratio of sodium citrate to Au is 3.5:1, boiling for 5 minutes to yield red solution of nanogold particulars. The mean particle size of the obtained nanogold is 30nm.

In addition, other methods are known.

In CN 1273154 A, Subgold-potasium cyanide was dissolved in water and reducing agent solution consisting of reducing agent and protective agent was added, wherein the reducing agent could be ascorbic acid, hydrazine, acetic acid or sodium borohydride and the protective agent was polyvinylpyrrolidone.

Gold in Subgold-potasium cyanide was reduced and became nanogold power. The particle size of the obtained nanogold was between 10~30nm.

In CN03128328, chloroauric acid or gold chloride was added to basic aqueous solution of nitromethane to yield a gold particle of nano size. By changing a ratio of gold chloride to nitromethane or controlling pH of nitromethane, the gold particle less than lOnm was obtained. This method had the advantage that the process was very simple, reaction was quick, reaction condition was smooth and cost of production was lower.

In CN1736637A, a nanogold was made by reducing chloroauric acid using sodium citrate as reducing agent in aqueous medium, which characterized that the molar ratio of sodium citrate to chloroauric acid was 7.0-20:1, the temperature of reaction system remained between 80-90 ^° C, the nanogold of 20~40nm was made by controlling pH of aqueous solution of chloroauric acid between 2.0-2.5, adding sodium citrate during mixing and reacting until the color didn't change any more.

As mentioned above, the nanogold injection has an effect on treatment and prevention of various diseases, but the prior manufacturing methods of the nanogold have problems as follows: 1) safety on body was not high; 2) the particle of nanogold must be very fine at level of nanometer; 3) stability did not be achieved.

The object of the invention is to define a composition of the nanogold injection and to manufacture the nanogold injection which has very fine particles and good stability using the reducing method by sodium citrate, but by differing from the prior in addition way of materials. Simple explanation

This invention differs from the prior manufacturing method of nanogold colloidal solution, in which sodium citrate was added to boiling chloroauric acid, and describes the method that polyvinyl pyrrolidone is added to boiling aqueous solution of sodium citrate and mushroom-polysaccharide and then chloroauric acid is added.

That is, it describes the method to obtain the nano particles of very small size by change of an addition way of reaction materials.

The particle size of the obtained nanogold is smaller than one by Frens method. Consequently, it can increase the effectiveness of the nanogold and the number of particles per a unit volume.

Furthermore, it inhibits growth and agglutination of nanogold particles during reaction and after reaction and increases stability of the nanogold injection by using polyvinyl pyrrolidone (PVP, molecular weight less than 40,000) as stabilizer of nano particle.

The pH of the obtained nanogold colloidal solution is controlled between 6-8 (this range is compatible with body) by using caustic soda (NaOH), the solution is passed through filter membrane (passing size is less than 50nm) and is autoclaved to yield the nanogold injection.

Detailed explanation The rate of reaction between chloroauric acid and sodium citrate in boiling state is very fast.

Therefore, an important solution to fine the nano particles and inhibit its agglutination is to more quickly stabilize the nano seed crystal produced in reaction.

In chloroauric acid reduction by sodium citrate, sodium citrate plays two roles as follow: one is to reduce chloroauric acid and another is a stabilizing action to inhibit agglutination of the nano particles by adhering to the surface of nanogold particles produced. In stabilizing the nano particles produced, there is different between the case of adding sodium citrate to aqueous solution of chloroauric acid and the case of adding chloroauric acid to aqueous solution of sodium citrate.

In case of adding sodium citrate to aqueous solution of chloroauric acid, as the concentration of sodium citrate is relatively small during reaction, the produced nanogold particles aren't enough stabilized and are agglutinated each other.

Whereas, in case of adding chloroauric acid to aqueous solution of sodium citrate, because the concentration of sodium citrate is increased during reaction, the produced nanogold particles are easily stabilized and aren't agglutinated each other, consequently the nano particles are smaller than the former.

Where using a stabilizer, as sodium citrate which activates to stabilize exists together with the stabilizer during reaction in latter, the concentration of stabilizer is thicker than the former. Accordingly, stability of the nano particle is better and consequently, the size of the nano particle is smaller.

The detailed explanation of the invention is as follow;

Example 1: 5ml of 10% aqueous solution of sodium citrate is added to 250ml of aqueous solution of mushroom-poly saccharide, mixing at a rate of 500rpm, heating until boiling, increasing the mixing rate to 1500rpm and putting 10ml of aqueous solution of chloroauric acid (Au 2500mg/L). Then reacting more than 20 minutes and cooling to room temperature. pH of reactant controls as 7 by caustic soda solution, making 500ml of the total solution by adding a distilled water, filtering through bacteria filter membrane(pore size of 40~50nm) and autoclaving the filtrate. The mean particle size of the obtained nanogold is 25nm.

Example 2: 5ml of 10% aqueous solution of sodium citrate is added to 250ml of aqueous solution of mushroom-polysaccharide, mixing at a rate of 500rpm, heating until boiling, adding 3ml of 10wt% aqueous solution of polyvinyl pyrrolidine(PVP k- 30) thereto, increasing the mixing rate to 1500rpm and putting 10ml of aqueous solution of chloroauric acid(Au 2500mg/L). Then reacting more than 20 minutes and cooling to room temperature. pH of reactant controls as 7 by caustic soda solution, making 500ml of the total solution by adding a distilled water, filtering through bacteria filter membrane(pore size of 40~50nm) and autoclaving the filtrate. The mean particle size of the obtained nanogold is 15nm.

Example 3: 10ml of aqueous solution of chloroauric acid (Au 2500mg/L) is added to 250ml of aqueous solution of mushroom-polysaccharide, mixing at a rate of 500rpm, heating until boiling, increasing the mixing rate by 1500rpm and adding 5ml of 10% aqueous solution of sodium citrate. Then reacting more than 20 minutes and cooling to room temperature. pH of reactant controls as 7 by caustic soda solution, making 500ml of the total solution by adding a distilled water, filtering through bacteria filter membrane(pore size of 40~50nm) and autoclaving the filtrate. The mean particle size of the obtained nanogold is 32nm.