WO2017051934A1 - Bio nano gold polysaccharide colloidal solution and its method of production - Google Patents

Bio nano gold polysaccharide colloidal solution and its method of production Download PDF

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Publication number
WO2017051934A1
WO2017051934A1 PCT/KP2015/000040 KP2015000040W WO2017051934A1 WO 2017051934 A1 WO2017051934 A1 WO 2017051934A1 KP 2015000040 W KP2015000040 W KP 2015000040W WO 2017051934 A1 WO2017051934 A1 WO 2017051934A1
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polysaccharide
nano gold
colloidal solution
bio
ginseng
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PCT/KP2015/000040
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French (fr)
Inventor
Son Sil KIM
Myong Se O
Chol Jin SON
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Kim Son Sil
Myong Se O
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Priority to CN201580036050.8A priority Critical patent/CN108024958A/en
Publication of WO2017051934A1 publication Critical patent/WO2017051934A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/722—Chitin, chitosan
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/242—Gold; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin

Definitions

  • the present invention relates to a bio nano gold polysaccharide colloidal solution including nano gold, water-soluble extract of ginseng cultivated in Kaesong area of the DPR of Korea, preferably ginseng polysaccharide, chitosan isolated from the husk of crab, preferably chitooligosaccharide, chondroitin sulfate as a kind of bio mucopolysaccharide and polysaccharide isolated from the sea fish.
  • the present invention also relates to the method of producing bio nano gold polysaccharide colloidal solution by bio reduction method, using the water-soluble extract of ginseng, preferably ginseng polysaccharide as a reducer, and chondroitin sulfate, chitosan, preferably chitooligosaccharide and polysaccharide isolated from the sea fish as dispersion stabilizers.
  • the present invention also relates to the use of the bio nano gold polysaccharide colloidal solution as medicines and health foods in the form of injection or internal medicine.
  • the nano gold eliminates active oxygen in the pancreas and acts as a signal transmission mechanism like insulin to accelerate intake of sugar.
  • the nano gold inhibits lipid oxidation, decreases blood viscosity and eliminates active oxygen, thereby increasing activity of lipoprotein lipase to prevent fat from accumulating into liver tissue, and to accelerate metabolism.
  • the nano gold acts as a natural stimulant to human body cells and improves the electrical signal transmission between the brain cells, to increase the general bioactivity including cerebral activity.
  • the general method of producing the nano gold is one that reduces chloroauric acid (HAuCl 4 ) in an aqueous solution by addition of a reducer and a dispersion stabilizer.
  • the commonly used reducers are sodium citrate, sodium thiocynate, white phosphorus, sodium borohydride (NaBH ), ascorbic acid and so on, and particularly, sodium citrate is widely used.
  • the method of producing the nano gold by the use of sodium citrate as a reducer has already been disclosed as Ferens method.
  • various methods such as Tacwich method, Cumar method and the like have been proposed.
  • the patent document CN1273154A described a nano gold powder and its production method using ascorbic acid, hydrazine, acetic acid or sodium borohydride as a reducer and polyvinyl pyrrolidone as a protective agent.
  • the size of the obtained nano gold particles was 10 ⁇ 20nm.
  • the patent document CN03128328 described a method of producing aqueous solution of nano gold particles by adding chloroauric acid or gold chloride to basic aqueous solution of nitromethane.
  • the size of nano gold particles obtained by this method was below lOnm by controlling a ratio of gold chloride to nitromethane or pH of nitromethane
  • the patent document CN1736637A described a method of producing monodispersed nano gold particles for immunochromato analysis.
  • sodium citrate was used as a reducer
  • the molar ratio of sodium citrate to chloroauric acid was 7-20.1
  • the reaction temperature was 80-99 °C
  • pH of aqueous solution of chloroauric acid was 2-5, thereby obtaining 20-40nm of nano gold.
  • the nano gold is effective in the treatment and prevention of various diseases, but the previous method of producing nano gold has some defects that biocompatibility of materials such as sodium borohydride, sodium citrate, nitromethane and so on is not high, the size of nano gold particles is large, a range of dispersion of particles is wide and dispersion stability is low.
  • sodium citrate is used as a reducer, there are defects that residue of oxidized aldehyde citrate may expose cytotoxicity and sodium citrate is not stabilized in gastric juice during infusion into human body.
  • polyvinyl pyrrolidone (K-30) is used as a dispersion stabilizer, the size of nano gold particles is small and nano gold is stabilized, but the possibility of giving rise to side effects on the human body due to injection of a large of amount is high.
  • the purpose of the present invention is to provide the bio nano gold polysaccharide colloidal solution which has a small size of nano gold particles, high dispersion stability and good biocompatibility, and its production method using water-soluble extract of ginseng which is natural substance, preferably ginseng polysaccharide as a reducer, and chondroitin sulfate which is natural substance and functional mucopolysaccharide, chitosan, preferably chitooligosaccharide and polysaccharide isolated from the sea fish as dispersion stabilizers.
  • the purpose of the present invention is to use the bio nano gold polysaccharide colloidal solution as medicines or health foods in the form of injection and internal medicine.
  • the present invention relates to a bio nano gold polysaccharide colloidal solution including nano gold, water-soluble extract of ginseng cultivated in Kaesong area of the
  • DPR of Korea preferably ginseng polysaccharide, chitosan isolated from the husk of crab, preferably chitooligosaccharide, chondroitin sulfate as a kind of bio mucopolysaccharide and polysaccharide isolated from the sea fish.
  • the present invention also relates to the method of producing the bio nano gold polysaccharide colloidal solution by bio reduction method, using the water-soluble extract of ginseng, preferably ginseng polysaccharide as a reducer, and chondroitin sulfate, chitosan, preferably chitooligosaccharide and polysaccharide isolated from the sea fish as dispersion stabilizers, wherein the said solution has a small size of nano gold particles, high dispersion stability and good biocompatibility.
  • the present invention also relates to the use of the bio nano gold polysaccharide colloidal solution as medicines and health foods in the form of injection or internal medicine.
  • the present invention provides the method of producing the bio nano gold polysaccharide colloidal solution by bio reduction method without using a chemical reducer such as sodium citrate or sodium borohydride.
  • a chemical reducer such as sodium citrate or sodium borohydride.
  • 2.5wt% of ginseng polysaccharide aqueous solution is added to secondary distilled water, stirring while heating up to 80 - 100°C, adding 6 ⁇ 10wt% of chitosan aqueous solution, 2 ⁇ 6wt% of chondroitin sulfate solution and 5000mg/L of chloroauric acid aqueous solution thereto, reacting for 20-40 minutes, thereby obtaining the nano gold polysaccharide colloidal solution.
  • This solution is cooled down to the room temperature, dialyzing by passing deionized water through a purified cellophane membrane for 6 hours to remove nonreactive ions, and making ultrafiltration (passing size of 0.1 m), to obtain the bio nano gold polysaccharide colloidal solution.
  • the nano gold particles in the obtained solution are monodispersion, their size is below 20nm and their concentration is 50mg/L, and this solution has high dispersion stability and good biocompatibility because of obtaining nano gold by bio reduction method.
  • bio nano gold polysaccharide colloidal solution does not any harm to the human body. It has been proved in experimentation and clinical trial that the bio nano gold polysaccharide colloidal solution has good effect on the treatment of various diseases including rheumatic arthritis, osteoporosis, chronic hepatitis, fatty liver, arterial hypertension, arteriosclerosis, hypertension and diabetes mellitus without side effect or virulence on human body.
  • Figure 1 shows a distribution curve of nano gold particles in the bio nano gold polysaccharide colloidal solution obtained by using sodium citrate as a reducer and polyvinyl pyi olidone as a dispersion stabilizer, measured by nano laser particle size analyzer (BT-90).
  • Figure 2 shows a distribution curve of nano gold particles in the bio nano gold polysaccharide colloidal solution according to the preferred embodiment of the invention, measured by nano laser particle size analyzer (BT-90).
  • the present invention relates to the bio nano gold polysaccharide colloidal solution which is obtained by the bio reduction method using the water-soluble extract of ginseng cultivated in Kaesong area of the DPR of Korea, preferably ginseng polysaccharide, as a reducer, and chondroitin sulfate which is mucopolysaccharide isolated from cartilage of animals or fishes and chitosan isolated from the husk of crab, preferably chitooligosaccharide, as dispersion stabilizers; and its producing method.
  • the obtained bio nano gold polysaccharide colloidal solution has a small size of nano gold particles, good dispersion stability and no side effects on the human body.
  • the present invention also relates to the use of the bio nano gold polysaccharide colloidal solution as medicines and health foods in the form of injection or interhal medicine.
  • the water-soluble extract of ginseng particularly ginseng polysaccharide consists of starch and pectic substances, so that it has sufficient functional group to reduce tetrachloroauric acid to gold.
  • Chitosan also plays a secondary role in reduction. Stabilizing the nano seed crystal obtained in the process of reaction quickly is an important way to decrease the size of nano particles and prevent their flocculation.
  • the present invention solved this problem by using, as dispersion stabilizers, chitosan, preferably chitooligosaccharide, chondroitin sulfate and polysaccharide isolated from the sea fish.
  • water-soluble extract of ginseng has a long molecular chain and basic functional group in molecule, it is very advantageous to dispersion stabilization of nano particles.
  • the water-soluble extract of ginseng plays two roles, the one is an action reducing chloroauric acid and the other is a cooperative action with therapeutic effect of nano gold to increase the therapeutic effect.
  • chitosan, chondroitin sulfate and polysaccharide isolated from the sea fish play two roles, i.e. as a dispersion stabilizer and as a factor increasing the therapeutic effect.
  • bio nano gold polysaccharide colloidal solution according to the present invention and its production method will be described in detail through the following embodiment.
  • 500fli2 Of secondary distilled water, stirring at 500rpm while heating up to 8O ⁇ 100°C, adding 20m£ of 6wt% chitosan aqueous solution and 30m£ of 2 wt% chondroitin sulfate solution thereto.
  • the solution is dialyzed by passing deionized water through the purification cellophane membrane for 6 hours to remove nonreactive ions, making ultra filtration (O. lpi of passing size) and adding secondary distilled water until the amount of solution is 1000mJ2.
  • the nano gold particles in the obtained nano gold polysaccharide colloidal solution have monodispersion and their size is below 20nm.
  • the average size of nano gold particles is lOnm and minimum size is 5nm.
  • the concentration of nano gold is 50mg L
  • the concentration of chitosan aqueous solution is 0.12 wt%
  • the concentration of chondroitin sulfate is 0.06 wt%
  • the concentration of ginseng polysaccharide is 100 mg/L.
  • bio nano gold polysaccharide colloidal solution according the present invention is used as medicines and health foods and this solution is injected into the human body in the form of injection or internal medicine.
  • bio nano gold polysaccharide colloidal solution is used as medicines and health foods
  • natural functional substances such as extract of various medicinal herbs or their refined components, preferably one or more of chlorella glycoprotein, soybean saponin, glucoside, ginseng extract, genital gland and digestive gland of asteroidea, active component of fish's eyeball, salvianolic acid isolated from salvia miltiorrhiza, mucopolysaccharide isolated from the husk of fugu porphyreus, plant flavonoid, preferably flavonoid of cuscuta japonica's seed and flavonoid of epimedium koreanum are further added.
  • isotonic substance of the injection is sodium chloride (product registered in the Korean Pharmacopoeia).
  • Table 1 shows maximum absorption wavelength, absorbance and average size of nano gold particles in the nano gold colloidal solutions which are obtained by using sodium citrate as a reducer and polyvinyl pyrrolidone as stabilizer and by using ginseng polysaccharide as a reducer and chitosan and chondroitin sulfate as dispersion stabilizers, respectively.
  • Table 2 shows size of nano gold particles in the bio nano gold polysaccharide colloidal solution according to shelf life.

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Abstract

A bio nano gold polysaccharide colloidal solution, its producing method and use as medicines and health foods, wherein the solution includes nano gold, water-soluble extract of ginseng cultivated in Kaesong area of the DPR of Korea, preferably ginseng polysaccharide, chitosan, preferably chitooligosaccharide, chondroitin sulfate and polysaccharide isolated from the sea fish.

Description

Bio nano gold polysaccharide colloidal solution and its method of production
Field of Invention
The present invention relates to a bio nano gold polysaccharide colloidal solution including nano gold, water-soluble extract of ginseng cultivated in Kaesong area of the DPR of Korea, preferably ginseng polysaccharide, chitosan isolated from the husk of crab, preferably chitooligosaccharide, chondroitin sulfate as a kind of bio mucopolysaccharide and polysaccharide isolated from the sea fish.
The present invention also relates to the method of producing bio nano gold polysaccharide colloidal solution by bio reduction method, using the water-soluble extract of ginseng, preferably ginseng polysaccharide as a reducer, and chondroitin sulfate, chitosan, preferably chitooligosaccharide and polysaccharide isolated from the sea fish as dispersion stabilizers.
The present invention also relates to the use of the bio nano gold polysaccharide colloidal solution as medicines and health foods in the form of injection or internal medicine.
Background and purpose of invention
Today, with the rapid development of nano science and technology and the extension of application field of nano materials, various nano materials are widely used as medicines or carrier of medicines in the medical field. Particularly, the prospect of application of nano gold is good in the medical field due to its peculiar physicochemical property.
It has been found that the nano gold eliminates active oxygen in the pancreas and acts as a signal transmission mechanism like insulin to accelerate intake of sugar.
It has been also found that the nano gold changes the process of transmission of pain signal of prostaglandin E2 (PGE2) which is the main cause of pain, to achieve an analgesic effect.
The nano gold inhibits lipid oxidation, decreases blood viscosity and eliminates active oxygen, thereby increasing activity of lipoprotein lipase to prevent fat from accumulating into liver tissue, and to accelerate metabolism.
The nano gold acts as a natural stimulant to human body cells and improves the electrical signal transmission between the brain cells, to increase the general bioactivity including cerebral activity. With the discovery of the effect of the cell membrane permeability of nano gold, it has been experimentally proved that where the nano gold is used together with the anticancer medicine with large molecular weight, a reduction rate of tumour could be remarkably raised, thereby bringing out an epochal advance in the treatment of cancer.
The methods of producing the nano gold have already been known in various documents.
The general method of producing the nano gold is one that reduces chloroauric acid (HAuCl4) in an aqueous solution by addition of a reducer and a dispersion stabilizer.
The commonly used reducers are sodium citrate, sodium thiocynate, white phosphorus, sodium borohydride (NaBH ), ascorbic acid and so on, and particularly, sodium citrate is widely used.
The method of producing the nano gold by the use of sodium citrate as a reducer has already been disclosed as Ferens method. In addition to this method, various methods such as Tacwich method, Cumar method and the like have been proposed.
The patent document CN1273154A described a nano gold powder and its production method using ascorbic acid, hydrazine, acetic acid or sodium borohydride as a reducer and polyvinyl pyrrolidone as a protective agent. The size of the obtained nano gold particles was 10 ~ 20nm.
The patent document CN03128328 described a method of producing aqueous solution of nano gold particles by adding chloroauric acid or gold chloride to basic aqueous solution of nitromethane. The size of nano gold particles obtained by this method was below lOnm by controlling a ratio of gold chloride to nitromethane or pH of nitromethane
The patent document CN1736637A described a method of producing monodispersed nano gold particles for immunochromato analysis. In this method, sodium citrate was used as a reducer, the molar ratio of sodium citrate to chloroauric acid was 7-20.1, the reaction temperature was 80-99 °C and pH of aqueous solution of chloroauric acid was 2-5, thereby obtaining 20-40nm of nano gold. As mentioned above, the nano gold is effective in the treatment and prevention of various diseases, but the previous method of producing nano gold has some defects that biocompatibility of materials such as sodium borohydride, sodium citrate, nitromethane and so on is not high, the size of nano gold particles is large, a range of dispersion of particles is wide and dispersion stability is low.
Where sodium citrate is used as a reducer, there are defects that residue of oxidized aldehyde citrate may expose cytotoxicity and sodium citrate is not stabilized in gastric juice during infusion into human body.
And, where polyvinyl pyrrolidone (K-30) is used as a dispersion stabilizer, the size of nano gold particles is small and nano gold is stabilized, but the possibility of giving rise to side effects on the human body due to injection of a large of amount is high.
The purpose of the present invention is to provide the bio nano gold polysaccharide colloidal solution which has a small size of nano gold particles, high dispersion stability and good biocompatibility, and its production method using water-soluble extract of ginseng which is natural substance, preferably ginseng polysaccharide as a reducer, and chondroitin sulfate which is natural substance and functional mucopolysaccharide, chitosan, preferably chitooligosaccharide and polysaccharide isolated from the sea fish as dispersion stabilizers.
And, the purpose of the present invention is to use the bio nano gold polysaccharide colloidal solution as medicines or health foods in the form of injection and internal medicine.
Brief description of Invention
The present invention relates to a bio nano gold polysaccharide colloidal solution including nano gold, water-soluble extract of ginseng cultivated in Kaesong area of the
DPR of Korea, preferably ginseng polysaccharide, chitosan isolated from the husk of crab, preferably chitooligosaccharide, chondroitin sulfate as a kind of bio mucopolysaccharide and polysaccharide isolated from the sea fish.
The present invention also relates to the method of producing the bio nano gold polysaccharide colloidal solution by bio reduction method, using the water-soluble extract of ginseng, preferably ginseng polysaccharide as a reducer, and chondroitin sulfate, chitosan, preferably chitooligosaccharide and polysaccharide isolated from the sea fish as dispersion stabilizers, wherein the said solution has a small size of nano gold particles, high dispersion stability and good biocompatibility.
The present invention also relates to the use of the bio nano gold polysaccharide colloidal solution as medicines and health foods in the form of injection or internal medicine.
The present invention provides the method of producing the bio nano gold polysaccharide colloidal solution by bio reduction method without using a chemical reducer such as sodium citrate or sodium borohydride. 2.5wt% of ginseng polysaccharide aqueous solution is added to secondary distilled water, stirring while heating up to 80 - 100°C, adding 6~10wt% of chitosan aqueous solution, 2~6wt% of chondroitin sulfate solution and 5000mg/L of chloroauric acid aqueous solution thereto, reacting for 20-40 minutes, thereby obtaining the nano gold polysaccharide colloidal solution. This solution is cooled down to the room temperature, dialyzing by passing deionized water through a purified cellophane membrane for 6 hours to remove nonreactive ions, and making ultrafiltration (passing size of 0.1 m), to obtain the bio nano gold polysaccharide colloidal solution.
The nano gold particles in the obtained solution are monodispersion, their size is below 20nm and their concentration is 50mg/L, and this solution has high dispersion stability and good biocompatibility because of obtaining nano gold by bio reduction method.
Even after the process of heating the obtained bio nano gold polysaccharide colloidal solution at 110°C for 40 minutes was repeated 5 - 6 times, not any dregs settled in the solution.
And, even after adding lOOmfi of 0.9% or 1.2% of salt water or sea water to 30mfi of the bio nano gold polysaccharide colloidal solution and putting it more than 1 month, not any dregs settled in the solution.
This demonstrates that the dispersion stability of the bio nano gold polysaccharide colloidal solution according to the present invention is very high.
Subculture of stem cell has been made by adding the bio nano gold polysaccharide colloidal solution and there was no virulence by 10 generations. This demonstrates that the bio nano gold polysaccharide colloidal solution does not any harm to the human body. It has been proved in experimentation and clinical trial that the bio nano gold polysaccharide colloidal solution has good effect on the treatment of various diseases including rheumatic arthritis, osteoporosis, chronic hepatitis, fatty liver, arterial hypertension, arteriosclerosis, hypertension and diabetes mellitus without side effect or virulence on human body.
Brief description of figures
Figure 1 shows a distribution curve of nano gold particles in the bio nano gold polysaccharide colloidal solution obtained by using sodium citrate as a reducer and polyvinyl pyi olidone as a dispersion stabilizer, measured by nano laser particle size analyzer (BT-90).
Figure 2 shows a distribution curve of nano gold particles in the bio nano gold polysaccharide colloidal solution according to the preferred embodiment of the invention, measured by nano laser particle size analyzer (BT-90).
Detailed description of Invention
The present invention relates to the bio nano gold polysaccharide colloidal solution which is obtained by the bio reduction method using the water-soluble extract of ginseng cultivated in Kaesong area of the DPR of Korea, preferably ginseng polysaccharide, as a reducer, and chondroitin sulfate which is mucopolysaccharide isolated from cartilage of animals or fishes and chitosan isolated from the husk of crab, preferably chitooligosaccharide, as dispersion stabilizers; and its producing method.
The obtained bio nano gold polysaccharide colloidal solution has a small size of nano gold particles, good dispersion stability and no side effects on the human body.
The present invention also relates to the use of the bio nano gold polysaccharide colloidal solution as medicines and health foods in the form of injection or interhal medicine.
The water-soluble extract of ginseng, particularly ginseng polysaccharide consists of starch and pectic substances, so that it has sufficient functional group to reduce tetrachloroauric acid to gold. Chitosan also plays a secondary role in reduction. Stabilizing the nano seed crystal obtained in the process of reaction quickly is an important way to decrease the size of nano particles and prevent their flocculation.
The present invention solved this problem by using, as dispersion stabilizers, chitosan, preferably chitooligosaccharide, chondroitin sulfate and polysaccharide isolated from the sea fish.
As the water-soluble extract of ginseng has a long molecular chain and basic functional group in molecule, it is very advantageous to dispersion stabilization of nano particles.
In the present invention, the water-soluble extract of ginseng plays two roles, the one is an action reducing chloroauric acid and the other is a cooperative action with therapeutic effect of nano gold to increase the therapeutic effect.
Also, chitosan, chondroitin sulfate and polysaccharide isolated from the sea fish play two roles, i.e. as a dispersion stabilizer and as a factor increasing the therapeutic effect.
The bio nano gold polysaccharide colloidal solution according to the present invention and its production method will be described in detail through the following embodiment. Embodiment: 4m£ of 2.5wt% ginseng polysaccharide aqueous solution is added to
500fli2 Of secondary distilled water, stirring at 500rpm while heating up to 8O~100°C, adding 20m£ of 6wt% chitosan aqueous solution and 30m£ of 2 wt% chondroitin sulfate solution thereto.
Then, the stirring speed is increased up to 2000rpm and 10ml. of chloroauric acid aqueous solution (Au 5000mg L) is added.
After reacting for 20 ~ 40 minutes, the solution is dialyzed by passing deionized water through the purification cellophane membrane for 6 hours to remove nonreactive ions, making ultra filtration (O. lpi of passing size) and adding secondary distilled water until the amount of solution is 1000mJ2. The nano gold particles in the obtained nano gold polysaccharide colloidal solution have monodispersion and their size is below 20nm. The average size of nano gold particles is lOnm and minimum size is 5nm.
In the nano gold polysaccharide colloidal solution, the concentration of nano gold is 50mg L, the concentration of chitosan aqueous solution is 0.12 wt%, the concentration of chondroitin sulfate is 0.06 wt% and the concentration of ginseng polysaccharide is 100 mg/L.
It will be understood that the above mentioned embodiment should not be interpreted to limit the scope of invention.
The bio nano gold polysaccharide colloidal solution according the present invention is used as medicines and health foods and this solution is injected into the human body in the form of injection or internal medicine.
Where the bio nano gold polysaccharide colloidal solution is used as medicines and health foods, natural functional substances such as extract of various medicinal herbs or their refined components, preferably one or more of chlorella glycoprotein, soybean saponin, glucoside, ginseng extract, genital gland and digestive gland of asteroidea, active component of fish's eyeball, salvianolic acid isolated from salvia miltiorrhiza, mucopolysaccharide isolated from the husk of fugu porphyreus, plant flavonoid, preferably flavonoid of cuscuta japonica's seed and flavonoid of epimedium koreanum are further added.
Where the bio nano gold polysaccharide colloidal solution is injected into the human body in the form of injection, isotonic substance of the injection is sodium chloride (product registered in the Korean Pharmacopoeia).
Table 1 shows maximum absorption wavelength, absorbance and average size of nano gold particles in the nano gold colloidal solutions which are obtained by using sodium citrate as a reducer and polyvinyl pyrrolidone as stabilizer and by using ginseng polysaccharide as a reducer and chitosan and chondroitin sulfate as dispersion stabilizers, respectively.
Table 2 shows size of nano gold particles in the bio nano gold polysaccharide colloidal solution according to shelf life.
Table 1 Maximum absorption wavelength, absorbance and average size of nano gold particles of the nano gold colloidal solution according to various reducers and dispersion stabilizers
Figure imgf000009_0001
Table 2 Size of nano gold particles in the bio nano gold polysaccharide colloidal solution according to shelf life
Figure imgf000009_0002

Claims

Claims
1. The bio nano gold polysaccharide colloidal solution including nano gold, water- soluble extract of ginseng cultivated in Kaesong area of the DPR of Korea, preferably ginseng polysaccharide, chitosan, preferably chitooligosaccharide, chondroitin sulfate and polysaccharide isolated from the sea fish.
2. The bio nano gold polysaccharide colloidal solution according to claim 1, wherein nano gold particles are monodispersion, average size of which is below 20nm, and their concentration is 50~5000mg/L, preferably, 250 ~ 500 mg/L.
3. The bio nano gold polysaccharide colloidal solution according to claim 1, wherein molecular weight of water-soluble extract of ginseng, preferably ginseng polysaccharide is
150 ~ 300 thousands and its concentration is 100~1000mg/L, preferably 300 ~ 600 mg L.
4. The bio nano gold polysaccharide colloidal solution according to claim 1, wherein concentration of chitosan, preferably chitooligosaccharide is 0.1~lwt% and concentration of chondroitin sulfate is 0.06-0.3 wt%.
5. The method of producing the bio nano gold polysaccharide colloidal solution comprising the following steps: adding 4 ~ 40mfi of 2.5wt% water-soluble extract of ginseng, preferably ginseng polysaccharide to 500mfi of secondary distilled water and stirring at 500rpm while heating up to 80 - 100 °C; - adding 20mJ2 of 6 - 10wt% chitosan solution, preferably chitooligosaccharide solution and then adding 30m# of 2 - 6wt% chondroitin sulfate solution and polysaccharide isolated from the sea fish; increasing stirring speed up to 2000rpm and adding 10 - 100m2 of 5000mg/L aqueous solution of chloroauric acid at 80 - 100°C; - reacting for 20 - 40 minutes while keeping temperature at 80 - 100 "C; after reaction, cooling the reactant down to room temperature, dialyzing by passing deionized water through the purified cellophane membrane for 6 hours to remove nonreactive ions, thereby obtaining the bio nano gold polysaccharide colloidal solution; and - ultrafiltering (0.1 #m of passing size) this solution and adding secondary distilled water until the total amount of solution is lOOOmfi.
6. The method of producing the bio nano gold polysaccharide colloidal solution according to claim 5, wherein a mixing ratio of water-soluble extract of ginseng, preferably ginseng polysaccharide, and chloroauric acid is 1 : 4 ~ 40.
7. The method of producing the bio nano gold polysaccharide colloidal solution according to claim 5, wherein a mixing ratio of chitosan, preferably chitooligosaccharide, and chondroitin sulfate which are dispersion stabilizers is 2 : l(mass ratio).
8. Use of the bio nano gold polysaccharide colloidal solution as medicines or health foods, wherein this solution is injected in the form of injection or internal medicine.
9. Use of the bio nano gold polysaccharide colloidal solution according to claim 8, wherein natural functional substances such as extract of various medicinal herbs or their refined components, preferably one or more of chlorella glycoprotein, soybean saponin, glucoside, indum extract, genital gland and digestive gland of asteroidea, active component of fish's eyeball, salvianolic acid isolated from salvia miltiorrhiza, mucopolysaccharide isolated from the husk of fugu porphyreus, plant flavonoid, preferably flavonoid of cuscuta japonica's seed and flavonoid of epimedium koreanum are further added.
10. Use of the bio nano gold polysaccharide colloidal solution according to claim 9, wherein where the solution is used in the form of injection, isotonic substance of the injection is sodium chloride (product registered in the Korean Pharmacopoeia).
PCT/KP2015/000040 2015-09-24 2015-12-28 Bio nano gold polysaccharide colloidal solution and its method of production WO2017051934A1 (en)

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