CN109674749A - A kind of high-content coenzyme Q 10 oral nano suspension and its preparation process - Google Patents
A kind of high-content coenzyme Q 10 oral nano suspension and its preparation process Download PDFInfo
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- CN109674749A CN109674749A CN201910028504.7A CN201910028504A CN109674749A CN 109674749 A CN109674749 A CN 109674749A CN 201910028504 A CN201910028504 A CN 201910028504A CN 109674749 A CN109674749 A CN 109674749A
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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
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- 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
- A61K9/10—Dispersions; Emulsions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The present invention relates to a kind of high-content coenzyme Q 10 oral nano suspension and its preparation processes.It is characterized by: loading cozymase Q 10 nano suspension using anti-solvent legal system detailed information fungin, Co-Q10 is dissolved with organic solvent, Co-Q10 solution is added dropwise in nanometer bacteria cellulose suspension according to certain volume ratio, stirring a period of time at room temperature, it is transferred in revolving bottle, negative-pressure vacuum removes organic solvent, obtains bacteria cellulose load cozymase Q 10 nano suspension.Present invention process process is simple, easy to operate, favorable reproducibility is low in cost, it is easy to be amplified to industrialization production, gained cozymase Q 10 nano suspension active constituent content is high, stability is good, applied bacteria cellulose, and yield is high, it is cheap, it is green safe, without being emulsified to Co-Q10, the complicated processings such as homogeneous obtain nano suspension, the structure and property of Co-Q10 itself will not be destroyed.
Description
Technical field
The present invention relates to a kind of high-content coenzyme Q 10 oral nano suspension and its preparation process, in particular to a kind of tool
There is the high-content Co-Q10 for the advantages that operating procedure is simple, is easily enlarged, easy industrialization, and Co-Q10 content is high, stability is good
Oral administration nanometer suspension and its preparation process.
Technical background
Co-Q10 is the fat-soluble quinones being widely present in a kind of organism, is called CoenzymeQ10 or vitamin coenzymes
Q10.Its quinoid and side chain isopentene group structure make it become important hydrogen carrier, cellular energy forming element, tool in respiratory chain
There is natural anti-oxidation function, facilitates human body cell and resist bacterium and eliminate interior free yl, cell is promoted to grow and realize
Self-regeneration.There are a variety of physiological activity such as anti-aging, anti-oxidant, strengthen immunity, antitumor, protection skin, in medicine, food
There is very big application potential with multiple industries such as cosmetics, be a kind of rare to integrate medicinal, nutrition and health care
Compound.The wide market that this product is widely applied recently as coenzyme in fields such as medicine, food additives.
Coenzyme is water-insoluble macromolecular substances, is insoluble in water, human body is difficult to absorb, and bioavilability is low, how to improve Co-Q10
Absorption be the research of current scientific circles hot spot.Bacteria cellulose is one kind by bacteriogenic nano-high molecule polysaccharide, is had
The advantages that high-purity, high-crystallinity, high mechanical strength, high water binding ability, high-biocompatibility and biodegradability, quilt
It is widely used in the fields such as food, medicine, cosmetics, has become the research hotspot of new bio medical material in the world at present.
The existing research much about nano-cellulose as pharmaceutical carrier is reported, outstanding slow release and long-term effect are all shown,
Specify huge potential quality of the bacteria cellulose as pharmaceutical carrier.Co-Q10 is loaded with bacterial fibers, Co-Q10 is prepared into
Nano suspension, so that improving Co-Q10 water solubility is the superior solution for solving the problems, such as that its bioavilability is low.
Summary of the invention
The present invention relates to a kind of high-content coenzyme Q 10 oral nano suspension and its preparation process, in particular to a kind of tool
There is the high-content Co-Q10 for the advantages that operating procedure is simple, is easily enlarged, easy industrialization, and Co-Q10 content is high, stability is good
Oral administration nanometer suspension and its preparation process.
Bacterial cellulose wet-coating is obtained first with bacteria cellulose Pseudomonas static culture is produced, wet film deionized water is clear
It washes, sodium hydroxide solution heating removes remaining medium and cell, is washed repeatedly to BC film, until pH is neutrality, then
Wet film dry, pulverize, obtain bacteria cellulose powder.By bacterial fibers powder and dilution heat of sulfuric acid according to certain mass ratio
Mixing, being placed in stirring to bacteria cellulose in thermostat water bath is in uniform starchiness, then uses deionized water diluted mixture,
The hydrogen peroxide for continuously adding volume of mixture 2%~10%, is stirred at room temperature.Finally, mixture is centrifuged, precipitating spend from
It after sub- water ultrasonic disperse, is transferred in bag filter, changes within 1~2 day a water, until solution is neutrality, bag filter inside and outside bag filter
Interior suspension is nanometer bacteria cellulose suspension, is placed in 4 DEG C of preservations, spare.Using anti-solvent legal system detailed information fungin
Cozymase Q 10 nano suspension is loaded, Co-Q10 is dissolved with organic solvent, certain density Co-Q10 solution is obtained, will receive
Rice bacteria cellulose suspension is diluted to a certain concentration, and Co-Q10 solution is added dropwise to nanometer bacteria according to certain volume ratio
It in cellulose suspension, at room temperature stirring a period of time, is transferred in revolving bottle, negative-pressure vacuum, removes organic solvent, gained is mixed
It closes object, that is, bacteria cellulose and loads cozymase Q 10 nano suspension.
Advantages of the present invention:
1 present invention process process is simple, and easy to operate, favorable reproducibility is low in cost, is easy to be amplified to industrialization production.
2 present invention gained cozymase Q 10 nano suspension active constituent content amounts are high, stability is good.
Bacteria cellulose applied by 3 present invention, yield is high, cheap, green safe.
4 present invention are without emulsifying Co-Q10, the complicated processings such as homogeneous obtain nano suspension, will not destroy
The structure and property of Co-Q10 itself.
Detailed description of the invention
Fig. 1 is the Co-Q10 original powder scanning electron microscope (SEM) photograph (A) of embodiment 1, bacteria cellulose film scanning electron microscope (SEM) photograph (B), nanometer
Bacteria cellulose scanning electron microscope (SEM) photograph (C), bacteria cellulose load cozymase Q 10 nano suspension scanning electron microscope (SEM) photograph (D)；Nanometer bacteria
Cellulose transmission electron microscope picture (E), bacteria cellulose load cozymase Q 10 nano suspension transmission electron microscope picture (F).
Fig. 2 is the Co-Q10 original powder (A) of embodiment 2, bacteria cellulose (B), nanometer bacteria cellulose (C), bacterial fibers
Infrared spectrogram, x-ray diffraction pattern, differential calorimetric scan result and the thermogravimetric point of element load cozymase Q 10 nano suspension (D)
Analyse result.
Fig. 3 is the molten water effect (left side) of Co-Q10 original powder and the bacteria cellulose load cozymase Q 10 nano suspension for implementing 2
(right side) figure.
Fig. 4 is that the bacteria cellulose of embodiment 1 loads comparison diagram before and after cozymase Q 10 nano suspension is placed at room temperature for 6 months.
Fig. 5 is saturating for Co-Q10 original powder and bacteria cellulose load the cozymase Q 10 nano suspension rats in vitro of embodiment 2
Skin experimental result.
Fig. 6 is that 2 Co-Q10 original powder of embodiment and bacteria cellulose load cozymase Q 10 nano suspension rat vivo biodistribution benefit
Expenditure experimental result.
Specific embodiment
With reference to the accompanying drawing and specific embodiment, the present invention is described further.
Embodiment 1
Bacterial cellulose wet-coating is obtained first with acetobacter xylinum static culture, wet film is cleaned with deionized water, hydroxide
Sodium solution heating removes remaining medium and cell, is washed repeatedly to BC film, until pH is neutrality, then by bacterial fibers
Plain wet film dry, pulverize, and obtain bacteria cellulose powder.By bacterial fibers powder and 50% dilution heat of sulfuric acid according to not on year-on-year basis
Example mixing is placed in thermostat water bath stirring to bacteria cellulose in uniformly thick, then uses deionized water diluted mixture,
The hydrogen peroxide for continuously adding volume of mixture 3%, stirs 0.5h at room temperature.Finally, mixture is centrifuged, precipitating uses deionization
It after water ultrasonic disperse, is transferred in bag filter, changes within 1~2 day a water, until solution is neutral inside and outside bag filter, in bag filter
Suspension is nanometer bacteria cellulose suspension, is placed in 4 DEG C of preservations, spare.It is negative using anti-solvent legal system detailed information fungin
Cozymase Q 10 nano suspension is carried, by Co-Q10 acetone solution, the Co-Q10 solution that concentration is 3mg/mL is obtained, by nanometer
Bacteria cellulose suspension is diluted with water into the suspension that bacterial fibers cellulose content is 0.5%, according to 0 solution of DPN diphosphopyridine nucleotide and nanometer
Co-Q10 solution is added dropwise in nanometer bacteria cellulose suspension by the volume ratio of bacteria cellulose suspension 1:2, at room temperature under
2min is stirred, negative-pressure vacuum removes organic solvent, and gained mixture, that is, bacteria cellulose loads cozymase Q 10 nano suspension.With
Laser nano particle size analyzer detects nanosuspension, detects that its Zeta potential is -28.6 ± 1.04mV, polydispersity index (PDI)
Value is 0.005 ± 0.002, and it is 13.0% that bacteria cellulose, which loads Co-Q10 content in cozymase Q 10 nano suspension,.Fig. 1, Fig. 4
Scanning electron microscope (SEM) photograph, transmission electron microscope picture and bacteria cellulose the load cozymase Q 10 nano suspension of respectively this example are placed at room temperature for 6
A month front and back comparison diagram.Electron-microscope scanning can be seen that fiber filament becomes thinner shorter in nanometer bacteria cellulose, and hole is finer and close,
Co-Q10 is uniformly distributed in nanometer bacteria cellulose.By placement in 6 months at room temperature, cozymase Q 10 nano suspension was still
It is more stable, it is not layered.Its Zeta potential and PDI value are measured, discovery is after placing 6 months, Zeta potential
Value is -38.4 ± 1.19mV, and PDI value is 0.03 ± 0.002.
Embodiment 2
Bacterial cellulose wet-coating is obtained first with acetobacter xylinum static culture, wet film is cleaned with deionized water, hydroxide
Sodium solution heating removes remaining medium and cell, is washed repeatedly to BC film, until pH is neutrality, then by bacterial fibers
Plain wet film dry, pulverize, and obtain bacteria cellulose powder.By bacterial fibers powder and 55% dilution heat of sulfuric acid according to not on year-on-year basis
Example mixing is placed in thermostat water bath stirring to bacteria cellulose in uniformly thick, then uses deionized water diluted mixture,
The hydrogen peroxide for continuously adding volume of mixture 4%, stirs 0.5h at room temperature.Finally, mixture is centrifuged, precipitating uses deionization
It after water ultrasonic disperse, is transferred in bag filter, changes within 1~2 day a water, until solution is neutral inside and outside bag filter, in bag filter
Suspension is nanometer bacteria cellulose suspension, is placed in 4 DEG C of preservations, spare.It is negative using anti-solvent legal system detailed information fungin
Cozymase Q 10 nano suspension is carried, by Co-Q10 acetone solution, the Co-Q10 solution that concentration is 2mg/mL is obtained, by nanometer
Bacteria cellulose suspension is diluted with water into the suspension that bacterial fibers cellulose content is 0.5%, according to 0 solution of DPN diphosphopyridine nucleotide and nanometer
Co-Q10 solution is added dropwise in nanometer bacteria cellulose suspension by the volume ratio of bacteria cellulose suspension 1:2, at room temperature under
3min is stirred, negative-pressure vacuum removes organic solvent, and gained mixture, that is, bacteria cellulose loads cozymase Q 10 nano suspension.With
Laser nano particle size analyzer detects nanosuspension, detects that its Zeta potential is 25.7 ± 1.25mV, polydispersity index (PDI) value
It is 0.005 ± 0.002, it is 9.1% that bacteria cellulose, which loads Co-Q10 content in cozymase Q 10 nano suspension,.Fig. 2,3,5,6
Respectively the molten water effect picture of the physical characterization result figure of this example, Co-Q10 original powder and Co-Q10 original powder and bacteria cellulose are negative
Carry cozymase Q 10 nano suspension transdermal test in vitro and bioavilability Comparative result.Infrared spectroscopy, X- diffraction, thermodynamic property table
Levying result proves that the crystallinity of nanometer bacteria cellulose reduces, good thermal stability, in anti-solvent precipitating preparation process, nanometer
The thermal stability of Co-Q10 is significantly improved compared with original powder in suspension, and Co-Q10 is by crystalline transformation at unformed shape.Bacterium
The dermal penetration rate of cellulose load cozymase Q 10 nano suspension is significantly larger than Co-Q10 original powder, and it is remote to accumulate infiltration capacity
Greater than Co-Q10 original powder, in 12h, the accumulation infiltration capacity of cozymase Q 10 nano suspension is 2.14 μ g/cm2, and CoQ10 original powder
Accumulating infiltration capacity is only 0.78 μ g/cm2, the accumulation infiltration capacity of cozymase Q 10 nano suspension is 2.74 times of Co-Q10 original powder.
Peak time of the cozymase Q 10 nano suspension in rat plasma is higher than Co-Q10 original powder, and maximum concentration improves 2.07
Times.The bioavilability of nano suspension is 3.62 times of original powder.
Claims (9)
1. a kind of high-content coenzyme Q 10 oral nano suspension and its preparation process, comprising the following steps: first with production bacterium
Cellulose Pseudomonas static culture obtains bacterial cellulose wet-coating, and wet film is cleaned with deionized water, sodium hydroxide solution heating removal
Remaining medium and cell wash BC film repeatedly, until pH is neutrality, then that bacterial cellulose wet-coating is dry, powder
It is broken, obtain bacteria cellulose powder.By bacterial fibers powder and 35%~65% dilution heat of sulfuric acid according to certain mass ratio
Mixing, being placed in stirring to bacteria cellulose in 35~65 DEG C of thermostat water baths is in uniform starchiness, then dilute with deionized water
Mixture is released, the hydrogen peroxide of volume of mixture 2%~10% is continuously added, stirs 0.5h at room temperature.Finally, by mixture from
The heart is transferred in bag filter after precipitating uses deionized water ultrasonic disperse, changes within 1~2 day a water, until solution inside and outside bag filter
For neutrality, suspension is nanometer bacteria cellulose suspension in bag filter, is placed in 4 DEG C of preservations, spare.Using anti-solvent legal system
Detailed fungin loads cozymase Q 10 nano suspension, and Co-Q10 is dissolved with organic solvent, obtains certain density coenzyme
Nanometer bacteria cellulose suspension is diluted to a certain concentration by Q10 solution, drips Co-Q10 solution according to certain volume ratio
It adds in nanometer bacteria cellulose suspension, at room temperature stirring a period of time, negative-pressure vacuum, removes organic solvent, gained mixing
Object, that is, bacteria cellulose loads cozymase Q 10 nano suspension.
2. being acetic acid Pseudomonas, rhizobium, Agrobacterium pseudomonas, colourless bar according to Pseudomonas described in claim 1
Pseudomonas, alcaligenes, Aerobacter azotobacter and Sarcina, preferably acetic acid Pseudomonas.
3. being drying or freeze-drying according to bacterial cellulose wet-coating drying means described in claim 1, preferably it is lyophilized.
4. the aqueous sulfuric acid for being 35%~65% according to dilution heat of sulfuric acid described in claim 1, preferably 45~60%；Bacterium is fine
The mass ratio for tieing up powder and dilution heat of sulfuric acid is 1:5~1:30, preferably: 1:10~1:20；Bacterial fibers powder and dilute sulfuric acid are molten
Liquid water bath with thermostatic control whipping temp is 35~65 DEG C, preferably 45~60 DEG C.
5. according to described in claim 1 be added hydrogen peroxide volume be volume of mixture 2%~10%, preferably 3%~6%.
6. being methanol, ethyl alcohol, acetone, preferred alcohol, acetone according to organic solvent described in claim 1.
7. being 0.5~5mg/mL, preferably 1~3mg/mL according to Co-Q10 concentration described in claim 1；Nanometer bacteria cellulose
Suspension concentration is 0.05%~3%, preferably 1%~2%；Co-Q10 solution and nanometer bacteria cellulose suspension volume ratio
For 1:5~5:1, preferably 1:3~3:1.
8. according to Co-Q10 solution described in claim 1 and nanometer bacteria cellulose suspension at room temperature mixing time be 0.5~
5min, preferably 1~3min.
9. according to bacteria cellulose described in claim 1 load cozymase Q 10 nano suspension in Co-Q10 content be 4%~
15%.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115501183A (en) * | 2022-10-03 | 2022-12-23 | 东北林业大学 | Oral paclitaxel-polymer micelle and preparation method thereof |
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| CN115501183A (en) * | 2022-10-03 | 2022-12-23 | 东北林业大学 | Oral paclitaxel-polymer micelle and preparation method thereof |
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