CN108653210A - A kind of preparation method of Yupingfeng polysaccharide-liposome - Google Patents
A kind of preparation method of Yupingfeng polysaccharide-liposome Download PDFInfo
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- CN108653210A CN108653210A CN201810604721.1A CN201810604721A CN108653210A CN 108653210 A CN108653210 A CN 108653210A CN 201810604721 A CN201810604721 A CN 201810604721A CN 108653210 A CN108653210 A CN 108653210A
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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
- A61K9/127—Liposomes
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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
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
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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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Abstract
The invention discloses a kind of preparation methods of Yupingfeng polysaccharide-liposome comprising following processing step：1) Yupingfeng polysaccharide purification；2) liposome formulation；3) Yupingfeng polysaccharide buffer；4) liposome preparation.The present invention prepares Yupingfeng polysaccharide-liposome using reverse evaporation, and by carrying out purification process early period and each raw material proportioning of adjustment and technological parameter to Yupingfeng polysaccharide, the encapsulation rate of gained Yupingfeng polysaccharide-liposome suspension is set to be up to 86% or more, and the prepared Yupingfeng polysaccharide-liposome obtained has excellent stability and Cell permeable, to have important clinical meaning to improving bioavailability and reducing Yupingfeng polysaccharide dosage, and then effectively push the research and development of Yupingfeng polysaccharide novel formulation.
Description
Technical field
The present invention relates to chemical and medicine industry field, more particularly to a kind of preparation method of liposome.
Background technology
Yupingfeng polysaccharide is made of astragalus polyose, sposknikovan and soluble polysaccharide isoreactivity polysaccharide.Show according to correlative study
Yupingfeng polysaccharide can promote the growth and development of the immune organs such as people and animal thymus, spleen, enhance the activity of immunocyte, improve
The effect of inoculation of various vaccines and the duration for postponing antibody, therefore, Yupingfeng polysaccharide has solely in terms of immunological regulation
Special advantage.However that there are stability is poor, bioavilability is low, is easily degraded and is worn to cell for traditional Yupingfeng polysaccharide formulation
The shortcomings of saturating power is weak, encapsulation rate is generally less than 50%, and the effect of be administered by traditional administering mode and bad.It is existing
Have mostly by polysaccharide-modified to improve its bioactivity to preferably play its drug effect to Yupingfeng in technology, however these change
The effect is unsatisfactory for property, complex process, poor controllability.Therefore bioavilability, the stabilization of Yupingfeng polysaccharide how to be improved
Property and therapeutic effect, reduce dosage, be of great significance to the research and development of its Yupingfeng polysaccharide novel formulation.
Invention content
It is an object of the invention in view of the above shortcomings of the prior art, provide a kind of preparation of Yupingfeng polysaccharide-liposome
Method.
The technical solution used in the present invention is：A kind of preparation method of Yupingfeng polysaccharide-liposome comprising following work
Skill step：
1) Yupingfeng polysaccharide purification：Take Yupingfeng Thick many candies to be dissolved in distilled water, after be poured slowly into resin column, repeat it is more
It is secondary, then eluant, eluent is poured slowly into resin column, then so that eluent is flowed into bottle,suction using vacuum filtration pump, collects bottle,suction
In eluent, it is concentrated, vacuum drying, Yupingfeng polysaccharide powder must be purified；
2) liposome formulation：It is 7 that soybean lecithin and cholesterol, which are pressed material quality ratio,:1~9:1 to be dissolved in chloroform jointly molten
In liquid, be subsequently placed in rotating speed be 60~75r/min, temperature carried out under conditions of being 37 DEG C decompression rotary evaporation processing, it is to be formed
Ether Film Fractionation is added after thin film, obtains liposome film liquid；
3) Yupingfeng polysaccharide buffer：Will purifying Yupingfeng polysaccharide powder obtained by step 1) be dissolved in a concentration of 4~
In the phosphate buffer solution of 5mg/mL, the phosphate buffer solution containing Yupingfeng polysaccharide is obtained；
4) liposome preparation：By material quality than obtained by the step 3) for the half of cholesterol containing Yupingfeng polysaccharide
Phosphate buffer solution is added in liposome film liquid obtained by step 2), and ultrasonic mixing handles 75~95s, then it is 60 to be placed in rotating speed
~75r/min, temperature carry out decompression rotary evaporation and all volatilize to ether under conditions of being 37 DEG C, be placed in 4 DEG C of preservations, obtain jade screen
Wind polysaccharide-liposome.
Specifically, the material quality of soybean lecithin and cholesterol compares its final Yupingfeng polysaccharide-liposome in the present invention
The material quality ratio of the encapsulation rate important of suspension, soybean lecithin and cholesterol is much or how small can make its packet
Envelope rate declines.And the cholesterol in the present invention and the material quality of the phosphate buffer solution containing Yupingfeng polysaccharide compare its jade
The formation efficiency important of screen polysaccharide-liposome, when the additive amount of the phosphate buffer solution is the one of cholesterol
When half, liposome can be made quickly to be formed.
As being further improved for said program, purity >=80% of step 1) the purifying Yupingfeng polysaccharide powder,
It is advantageously implemented higher bioavailability.
As being further improved for said program, the pH of phosphate buffer solution described in step 3) is 7.4, is conducive to
The stability of raising system.
As being further improved for said program, the resin volume in resin column described in step 1) is resin column volume
2/3。
As being further improved for said program, eluent described in step 1) is the ethyl alcohol that mass percent is 50%.
As being further improved for said program, the vacuum drying time described in step 1) is 12h.
The present invention is with the following method measured the encapsulation rate of every sample：
A, the preparation of calibration curve：The calibration of Yupingfeng polysaccharide is established with dextran standard and anthrone-concentrated sulfuric acid development process
Curve, and using the absorbance of indices in anthrone-concentrated sulfuric acid determination of color sample.According to the Regressive calibration curve of foundation
Equation converses the quality of required indices, to calculate the encapsulation rate of each test specimens.
B, it respectively takes 10mL to be respectively put into freezing ultra-lowing centrifuge the Yupingfeng polysaccharide-liposome suspension prepared to carry out
(4 DEG C, 10000r/min) 30min is centrifuged, supernatant is sucked out, 50mL is settled to PBS.By the sediment (packet after centrifugation
Seal Yupingfeng polysaccharide-liposome) PBS solution washes clean is used, and it is diluted to 20mL.With Anthrone-sulfuricacid method measure supernatant and
The absorptance of sediment simultaneously substitutes into the content that regression equation acquires Yupingfeng polysaccharide, and formula is：
Drug total amount × 100% of encapsulation rate (%)=be encapsulated in liposome drug content/addition；
Or in drug total amount-supernatant of encapsulation rate (%)=addition drug total amount/addition drug total amount × 100%.
The beneficial effects of the invention are as follows：The present invention prepares Yupingfeng polysaccharide-liposome using reverse evaporation, and by right
Yupingfeng polysaccharide carries out purification process early period and each raw material proportioning of adjustment and technological parameter, keeps gained Yupingfeng polysaccharide-liposome outstanding
The encapsulation rate of liquid is up to 86% or more, and the prepared Yupingfeng polysaccharide-liposome obtained has excellent stability and cell-penetrating
Property, to have important clinical meaning to improving bioavailability and reducing Yupingfeng polysaccharide dosage, and then effectively push away
The research and development of dynamic Yupingfeng polysaccharide novel formulation.
Specific implementation mode
The present invention is specifically described with reference to embodiment, in order to technical field personnel to the present invention
Understand.It is necessary to it is emphasized that embodiment is only intended to, the present invention will be further described herein, should not be understood as to this
The limitation of invention protection domain, fields person skilled in the art, the non-intrinsically safe that the present invention is made according to foregoing invention content
The modifications and adaptations of property, should still fall within protection scope of the present invention.Mentioned raw materials following simultaneously are unspecified, are
Commercial product；The processing step or preparation method not referred in detail be processing step known to a person skilled in the art or
Preparation method.
Embodiment 1
A kind of preparation method of Yupingfeng polysaccharide-liposome comprising following processing step：
1) Yupingfeng polysaccharide purification：Take Yupingfeng Thick many candies to be dissolved in distilled water, after be poured slowly into resin column, resin column
In resin volume be the 2/3 of resin column volume, repeatedly, then 50% ethyl alcohol is poured slowly into resin column, then used
Vacuum filtration pump makes eluent flow into bottle,suction, collects the eluent in bottle,suction, and concentrated, vacuum drying 12h obtains purity
>=80% purifying Yupingfeng polysaccharide powder；
2) liposome formulation：It is 7 that soybean lecithin and cholesterol, which are pressed material quality ratio,:1 is dissolved in chloroformic solution jointly,
It is subsequently placed in that rotating speed is 75r/min, temperature carries out decompression rotary evaporation processing under conditions of being 37 DEG C, after thin film to be formed
Ether Film Fractionation is added, obtains liposome film liquid；
3) Yupingfeng polysaccharide buffer：Purifying Yupingfeng polysaccharide powder obtained by step 1) is dissolved in a concentration of 5mg/mL
Phosphate buffer solution (pH 7.4) in, obtain the phosphate buffer solution containing Yupingfeng polysaccharide；
4) liposome preparation：By material quality than obtained by the step 3) for the half of cholesterol containing Yupingfeng polysaccharide
Phosphate buffer solution is added in liposome film liquid obtained by step 2), and ultrasonic mixing handles 75s, then it is 75r/ to be placed in rotating speed
Min, temperature carry out decompression rotary evaporation and all volatilize to ether under conditions of being 37 DEG C, be placed in 4 DEG C of preservations, it is beautiful to obtain embodiment 1
Screen polysaccharide-liposome.
After measured, the encapsulation rate of 1 Yupingfeng polysaccharide-liposome of embodiment is 87.95%.
Embodiment 2
A kind of preparation method of Yupingfeng polysaccharide-liposome comprising following processing step：
1) Yupingfeng polysaccharide purification：Take Yupingfeng Thick many candies to be dissolved in distilled water, after be poured slowly into resin column, resin column
In resin volume be the 2/3 of resin column volume, repeatedly, then 50% ethyl alcohol is poured slowly into resin column, then used
Vacuum filtration pump makes eluent flow into bottle,suction, collects the eluent in bottle,suction, and concentrated, vacuum drying 12h obtains purity
>=80% purifying Yupingfeng polysaccharide powder；
2) liposome formulation：It is 9 that soybean lecithin and cholesterol, which are pressed material quality ratio,:1 is dissolved in chloroformic solution jointly,
It is subsequently placed in that rotating speed is 60r/min, temperature carries out decompression rotary evaporation processing under conditions of being 37 DEG C, after thin film to be formed
Ether Film Fractionation is added, obtains liposome film liquid；
3) Yupingfeng polysaccharide buffer：Purifying Yupingfeng polysaccharide powder obtained by step 1) is dissolved in a concentration of 4mg/mL
Phosphate buffer solution (pH 7.4) in, obtain the phosphate buffer solution containing Yupingfeng polysaccharide；
4) liposome preparation：By material quality than obtained by the step 3) for the half of cholesterol containing Yupingfeng polysaccharide
Phosphate buffer solution is added in liposome film liquid obtained by step 2), and ultrasonic mixing handles 95s, then it is 60r/ to be placed in rotating speed
Min, temperature carry out decompression rotary evaporation and all volatilize to ether under conditions of being 37 DEG C, be placed in 4 DEG C of preservations, it is beautiful to obtain embodiment 2
Screen polysaccharide-liposome.
After measured, the encapsulation rate of 2 Yupingfeng polysaccharide-liposome of embodiment is 86.82%.
Embodiment 3
A kind of preparation method of Yupingfeng polysaccharide-liposome comprising following processing step：
1) Yupingfeng polysaccharide purification：Take Yupingfeng Thick many candies to be dissolved in distilled water, after be poured slowly into resin column, resin column
In resin volume be the 2/3 of resin column volume, repeatedly, then 50% ethyl alcohol is poured slowly into resin column, then used
Vacuum filtration pump makes eluent flow into bottle,suction, collects the eluent in bottle,suction, and concentrated, vacuum drying 12h obtains purity
>=80% purifying Yupingfeng polysaccharide powder；
2) liposome formulation：It is 8 that soybean lecithin and cholesterol, which are pressed material quality ratio,:1 is dissolved in chloroformic solution jointly,
It is subsequently placed in that rotating speed is 70r/min, temperature carries out decompression rotary evaporation processing under conditions of being 37 DEG C, after thin film to be formed
Ether Film Fractionation is added, obtains liposome film liquid；
3) Yupingfeng polysaccharide buffer：Purifying Yupingfeng polysaccharide powder obtained by step 1) is dissolved in a concentration of 4.5mg/
In the phosphate buffer solution (pH 7.4) of mL, the phosphate buffer solution containing Yupingfeng polysaccharide is obtained；
4) liposome preparation：By material quality than obtained by the step 3) for the half of cholesterol containing Yupingfeng polysaccharide
Phosphate buffer solution is added in liposome film liquid obtained by step 2), and ultrasonic mixing handles 85s, then it is 70r/ to be placed in rotating speed
Min, temperature carry out decompression rotary evaporation and all volatilize to ether under conditions of being 37 DEG C, be placed in 4 DEG C of preservations, it is beautiful to obtain embodiment 3
Screen polysaccharide-liposome.
After measured, the encapsulation rate of 3 Yupingfeng polysaccharide-liposome of embodiment is 88.38%.
Above-described embodiment is the preferred embodiment of the present invention, it is all with similar technique of the invention and made by equivalence changes,
The protection category of the present invention should all be belonged to.
Claims (6)
1. a kind of preparation method of Yupingfeng polysaccharide-liposome, it is characterised in that comprise the technical steps that：
1) Yupingfeng polysaccharide purification：Take Yupingfeng Thick many candies to be dissolved in distilled water, after be poured slowly into resin column, repeatedly, then
Eluant, eluent is poured slowly into resin column, then so that eluent is flowed into bottle,suction using vacuum filtration pump, collects in bottle,suction
Eluent, concentrated, vacuum drying, must purify Yupingfeng polysaccharide powder；
2) liposome formulation：It is 7 that soybean lecithin and cholesterol, which are pressed material quality ratio,:1~9:1 is dissolved in chloroformic solution jointly
In, be subsequently placed in rotating speed be 60~75r/min, temperature carried out under conditions of being 37 DEG C decompression rotary evaporation processing, to be formed one
Ether Film Fractionation is added after layer film, obtains liposome film liquid；
3) Yupingfeng polysaccharide buffer：Purifying Yupingfeng polysaccharide powder obtained by step 1) is dissolved in a concentration of 4~5mg/mL
Phosphate buffer solution in, obtain the phosphate buffer solution containing Yupingfeng polysaccharide；
4) liposome preparation：By material quality than the phosphoric acid containing Yupingfeng polysaccharide obtained by the step 3) for the half of cholesterol
Salt buffer solution is added in liposome film liquid obtained by step 2), and ultrasonic mixing handles 75~95s, then be placed in rotating speed be 60~
75r/min, temperature carry out decompression rotary evaporation and all volatilize to ether under conditions of being 37 DEG C, be placed in 4 DEG C of preservations, obtain Yupingfeng
Polysaccharide-liposome.
2. a kind of preparation method of Yupingfeng polysaccharide-liposome according to claim 1, it is characterised in that：Step 1) is described
Purify purity >=80% of Yupingfeng polysaccharide powder.
3. a kind of preparation method of Yupingfeng polysaccharide-liposome according to claim 1, it is characterised in that：Institute in step 3)
The pH for stating phosphate buffer solution is 7.4.
4. a kind of preparation method of Yupingfeng polysaccharide-liposome according to claim 1, it is characterised in that：Institute in step 1)
It is the 2/3 of resin column volume to state the resin volume in resin column.
5. a kind of preparation method of Yupingfeng polysaccharide-liposome according to claim 1, it is characterised in that：Institute in step 1)
It is the ethyl alcohol that mass percent is 50% to state eluent.
6. a kind of preparation method of Yupingfeng polysaccharide-liposome according to claim 1, it is characterised in that：Institute in step 1)
It is 12h to state the vacuum drying time.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810604721.1A CN108653210A (en) | 2018-06-12 | 2018-06-12 | A kind of preparation method of Yupingfeng polysaccharide-liposome |
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| CN201810604721.1A CN108653210A (en) | 2018-06-12 | 2018-06-12 | A kind of preparation method of Yupingfeng polysaccharide-liposome |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111012920A (en) * | 2019-12-17 | 2020-04-17 | 佛山科学技术学院 | Jade screen polysaccharide liposome and preparation method thereof |
| CN111195231A (en) * | 2020-02-07 | 2020-05-26 | 佛山科学技术学院 | Preparation method of radix sileris polysaccharide liposome immunopotentiator |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102100728A (en) * | 2009-12-17 | 2011-06-22 | 苏州知微堂生物科技有限公司 | Technology and method for preparing novel combined formulation of jade-screen powder |
| CN103536534A (en) * | 2013-09-29 | 2014-01-29 | 南京农业大学 | Preparation method of radix rehmanniae polysaccharide liposome |
| CN105294880A (en) * | 2015-12-04 | 2016-02-03 | 佛山科学技术学院 | Purification method of polysaccharides from Yu-Ping-Feng powder |
-
2018
- 2018-06-12 CN CN201810604721.1A patent/CN108653210A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102100728A (en) * | 2009-12-17 | 2011-06-22 | 苏州知微堂生物科技有限公司 | Technology and method for preparing novel combined formulation of jade-screen powder |
| CN103536534A (en) * | 2013-09-29 | 2014-01-29 | 南京农业大学 | Preparation method of radix rehmanniae polysaccharide liposome |
| CN105294880A (en) * | 2015-12-04 | 2016-02-03 | 佛山科学技术学院 | Purification method of polysaccharides from Yu-Ping-Feng powder |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111012920A (en) * | 2019-12-17 | 2020-04-17 | 佛山科学技术学院 | Jade screen polysaccharide liposome and preparation method thereof |
| CN111195231A (en) * | 2020-02-07 | 2020-05-26 | 佛山科学技术学院 | Preparation method of radix sileris polysaccharide liposome immunopotentiator |
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