CN105380927B - A kind of preparation method of gossypol and its derivative palm wax solid fat pharmaceutical carrier - Google Patents
A kind of preparation method of gossypol and its derivative palm wax solid fat pharmaceutical carrier Download PDFInfo
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- CN105380927B CN105380927B CN201510874306.4A CN201510874306A CN105380927B CN 105380927 B CN105380927 B CN 105380927B CN 201510874306 A CN201510874306 A CN 201510874306A CN 105380927 B CN105380927 B CN 105380927B
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- gossypol
- palm wax
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- ketone
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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
- A61K9/48—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
- A61K9/5176—Compounds of unknown constitution, e.g. material from plants or animals
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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
- A61K31/11—Aldehydes
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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
- A61K9/0012—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
Abstract
Load the preparation method of gossypol and its derivative palm wax solid fat pharmaceutical carrier, organic solvent solution containing gossypol and its derivative is mixed with palm wax under the state that melts, vacuum distillation removes organic solvent, mixture is under the action of ultrasonic wave, nano particle is formed in aqueous surfactant solution, it dialyses and removes surfactant, after filtration sterilization, the palm wax solid fat pharmaceutical carrier of prepared gossypol can be directly used for intravenous injection administration；It is a kind of gossypol and its Derivatives as Drug Carriers preparation preparation means safely, conveniently, stable.
Description
Technical field
The present invention relates to a kind of preparation method of pharmaceutical carrier, the palm wax solid of specially a kind of gossypol and its derivative
The preparation method of fat pharmaceutical carrier.
Background technology
Gossypol is the double naphthalene aldehyde compounds of a kind of polyphenol hydroxyl, is the one kind extracted from the seed of malvaceae plant cotton
Natural products.
Gossypol has the function of effectively to inhibit spermiogenesis tail, was once widely used as a kind of male contraceptive agent.In recent years
The antitumor properties for coming gossypol and its derivative are found that they, which have kinds of tumor cells, inhibits cell Proliferation by people
Effect, especially have the effect of fine to prostate cancer.Gossypol and its derivative can also reduce the activity of archaeal dna polymerase, suppression
Tumour cell increment processed.Gossypol and its derivative can also be combined with tumour cell mitochondria BcL-2 receptors, promote tumour cell
Generate Apoptosis.
But gossypol and its derivative still have some shortcomings when in use, their poorly water-soluble, and in the environment
Easily oxidation.So it is a kind of selection well that gossypol and its derivative, which are carried in carrier,.Related gossypol and its spread out at present
The patent of biological agent is concentrated mainly on oral liquid, injection etc..Guarantor of Ke one et al. is prepared for water-soluble gossypol preparation, including
The preparations such as oral liquid, injection, powder, tablet and capsule (water-soluble gossypol preparation and preparation method thereof, application number：
95111745.9)；Li Baoqiu is prepared and has been applied for patent " gossypol intravenous injection fatty emulsion for the treatment of tumour " and " be used to treat
The cyclodextrin inclusion compound of the levorotation gossypol of tumour or its acetate " (application number：201010164008.3 with
201110051335.2)；But the dosage form of these oral medications is limited for antineoplaston effect, the emulsion agent of intravenous injection
Type is also unfavorable for drug effect in tumor tissues since carrier scale itself is larger.The carrier of nanoscale can utilize tumour
The enhancing permeability and retention effect of tissue itself make pharmaceutical carrier for more time, reach more preferable in tumor tissues internal stops
Therapeutic effect.At present about the report of the nano-carrier of gossypol and few, Zhan Yonghua et al. mesopore silicon oxide load gossypols
(a kind of one kettle way prepares the method for multi-functional gossypol nanometer formulation, application number：201310162469.0) and mesopore silicon oxide
Load another gossypol derivative (a kind of preparation method for the multi-functional mesoporous silicon nanometer formulation for carrying gossypol derivative, application
Number：201310016135.2).Above research mostly uses the carrier loaded gossypols such as mesopore silicon oxide silica, Silica hydrogel, still
Mesopore silicon oxide and Silica hydrogel cannot degrade quickly in vivo, affect its application in vivo.Li Ke et al. has been invented " from group
The method that dress method prepares gossypol and its derivative plunker nano-particle " (application number：201410668713.5).This method profit
Hydrophobic gossypol and its derivative are wrapped up with surfactant, a large amount of surfactant is unfavorable for it in organism
Interior use.
Palm wax is a kind of natural plants wax extracted from the leaf of babassu palm, has and reduces plant moisture
The effect of evaporation.Palm wax has good emulsibility in itself, is one of the most widely used vegetable wax in industry.As one
Kind natural products, palm wax also have good biocompatibility.
Current related palm wax is mostly to use it for the industry such as coating, papermaking, vehicle maintenance liquid as the patent of preparation
Product scope.It is mainly cosmetics that palm wax is used as routine use report as natural products.Lu Fei et al. using palm wax as
A kind of main component (production method of edible lipstick, application number CN201310309559.8) of lipstick.Palm wax is used as
The report of pharmaceutical carrier is seldom, and Wen Deer G Mendozas et al. prepare (the production of potassium citrate wax-matrix tablet using palm wax
It is sustained the method for potassium citrate wax-matrix tablet, application number：CN201280075895.4).It is carried palm wax as medicament nano
Body preparation and having no has been reported that.
Invention content
The purpose of the present invention is to provide the preparation sides of a kind of gossypol and its palm wax solid fat pharmaceutical carrier of derivative
Method, among fat-soluble medicine gossypol and its derivative are carried on palm wax nano particle, drugloading rate is high, biocompatibility
It is good, available for being injected intravenously；Medical solid fat nano particle is prepared using supersound method, simple production process, product is steady
Qualitative good, nano particle diameter is uniform.
In order to achieve the above object, the technical proposal of the invention is realized in this way.
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of gossypol and its derivative, includes the following steps：
Step 1: 5-100mg gossypols and its derivative are dissolved in 1-20mL organic solvents, under 100K Hz ultrasounds
Disperseed, jitter time is 3-30 minutes, and gossypol ORGANIC SOLVENT MIXTURES is made；
The gossypol and its derivative include：Gossypol acetate, apo- gossypol, levorotation gossypol, apo- gossypol ketone (ApoG2),
One kind in gossypol ketone, methyl gossypol, gossypol schiff bases, monoaldehyde gossypol, acetyl gossypol or monoether gossypol；
The organic solvent is ethyl alcohol, chloroform, ether, hexamethylene, one or both of n-hexane organic solvent than
Example 1:1-1:Mixture between 10 (V/V)；
Step 2: take 0.5-1g palm waxs, heating and melting；Gossypol in step 1 and its derivative organic solvent are mixed
Object 10-20mL is sufficiently mixed with the palm wax melted, is removed the organic solvent in system using Rotary Evaporators vacuum distillation,
Obtain the gossypol palm wax mixture of 5-100mg/mL；
Step 3: configuration concentration is the aqueous surfactant solution of 0.5-1% (M/V):
The surfactant is pluronic F127, Pluronic F68, dodecyl trimethyl ammonium chloride, 16
One kind or ratio in alkyl trimethyl ammonium bromide, Tween-20, Tween-80, Arlacel-80 is 1:1-1:It is mixed between 10 (M/M)
Close object；
Step 4: by the gossypol palm wax mixture heating and melting in step 3,50 μ L-1ml are taken in test tube, add in 1-
30mL aqueous surfactant solutions under the conditions of ice-water bath, using ultrasonic probe, are divided using 100-400w power ultrasonics 2-10
Clock forms it into nano-solid fat particle；
Step 5：It is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, in removal system
Surfactant；
Step 6: using 220nm membrane filtrations, the palm wax solid fat drug for obtaining load gossypol and its derivative carries
Body.
A kind of preparation process of the palm wax solid fat pharmaceutical carrier of gossypol and its derivative of the present invention, will contain
The organic solvent solution of gossypol and its derivative is mixed with palm wax under the state that melts, and vacuum distillation removes organic solvent, obtains
The mixture arrived forms nano particle under the action of ultrasonic wave in aqueous surfactant solution.Dialysis removes surface-active
Agent, after filtration sterilization, prepared gossypol and its derivative palm wax solid fat pharmaceutical carrier can be directly used for intravenous injection to
Medicine.
The present invention selects palm wax to be prepared for the gossypol of high concentration ratio and its derivative palm first as drug packaging material
Wax mixture, then by it in aqueous surfactant solution ultrasonic disperse, formed solid fat nano particle；Said preparation is on the one hand
On the other hand it is special to assign the slow release that gossypol and its derivative are stablized for the shortcomings that overcoming gossypol and its derivative poorly water-soluble
Property, while also there is good biocompatibility, improve the therapeutic effect of gossypol and its derivative；Obtained it is a kind of safety,
The gossypol and its derivative intravenous injection medicine-carried system stablize, is reliable, treated.
Description of the drawings
Fig. 1 is the flow chart of the palm wax solid fat pharmaceutical carrier preparation of gossypol and its derivative.
Fig. 2 is the particle diameter distribution of the palm wax solid fat pharmaceutical carrier of gossypol and its derivative, respectively embodiment one, six
With ten gained.
Fig. 3 is the transmission electron microscope photo of gossypol and its derivative palm wax solid fat pharmaceutical carrier obtained by example IV.
Specific embodiment
The present invention is described in detail with reference to the accompanying drawings and detailed description.
Embodiment one
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of gossypol acetate, includes the following steps：
Step 1: by 25mg gossypol acetates in 10mL ethyl alcohol, disperseed under 100K Hz ultrasounds, jitter time 3
Minute, gossypol acetate alcohol mixture is made；
Step 2: 1g palm waxs are taken, heating and melting, by the gossypol acetate alcohol mixture 10mL in step 1 and thawing
Palm wax is sufficiently mixed, and is removed the ethyl alcohol in system using Rotary Evaporators vacuum distillation, is obtained the gossypol acetate of 25mg/mL
Palm wax mixture；
Step 3: configuration concentration is the pluronic F127 aqueous solutions of 0.5% (M/V)；
Step 4: by the gossypol acetate palm wax mixture heating and melting in step 3,50 μ L are taken in test tube, are added in
4mL 0.5% (M/V) pluronic F127 solution, under the conditions of ice-water bath, using ultrasonic probe, using 400w power ultrasonics 2
Minute forms it into nano-solid fat particle；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load gossypol acetate is obtained.
The palm wax solid fat pharmaceutical carrier grain size that method therefor prepares load gossypol acetate in the present embodiment is 58nm, carries medicine
Measure is 2.5%.
Embodiment two
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of apo- gossypol ketone, includes the following steps：
Step 1: 50mg apo- gossypol ketone is dissolved in 20mL ethyl alcohol, disperseed under 100K Hz ultrasounds, disperseed
Time is 30 minutes, and apo- gossypol ketone alcohol mixture is made；
Step 2: take 0.5g palm waxs, heating and melting；By the apo- gossypol ketone alcohol mixture 20mL in step 1 with melting
The palm wax of change is sufficiently mixed, using Rotary Evaporators vacuum distillation by system ethyl alcohol remove, obtain 100mg/mL Ah
Plain cotton phenolic ketone palm wax mixture；
Step 3: configuration concentration is the pluronic F127 aqueous solutions of 1% (M/V)；
Step 4: by the apo- gossypol ketone palm wax mixture heating and melting in step 3,100 μ L is taken to add in test tube
Enter 4mL 1% (M/V) pluronic F127 solution, under the conditions of ice-water bath, using ultrasonic probe, using 400w power ultrasonics 10
Minute forms it into nano-solid fat particle；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load apo- gossypol ketone is obtained.
The palm wax solid fat pharmaceutical carrier grain size of apo- gossypol ketone prepared by method therefor is 78nm in the present embodiment, is carried
Dose is 10%.
Embodiment three
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of apo- gossypol, includes the following steps：
Step 1: 50mg apo- gossypols are dissolved in the mixture of 14mL ether and 6mL ethyl alcohol, in 100K Hz ultrasounds
Under disperseed, jitter time be 15 minutes, apo- gossypol ether alcohol mixture is made；
Step 2: take 1g palm waxs, heating and melting；By the apo- gossypol ether alcohol mixture 20mL in step 1 with melting
The palm wax of change is sufficiently mixed, and is removed the ether in system and ethyl alcohol using Rotary Evaporators vacuum distillation, is obtained 50mg/mL
Apo- gossypol palm wax mixture；
Step 3: configuration concentration is the Pluronic F68 aqueous solution of 1% (M/V)；
Step 4: by the apo- gossypol palm wax mixture heating and melting in step 3,500 μ L are taken in test tube, are added in
10mL 1% (M/V) Pluronic F68 solution under the conditions of ice-water bath, using ultrasonic probe, is divided using 400w power ultrasonics 2
Clock forms it into nano-solid fat particle；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load apo- gossypol is obtained.
The palm wax solid fat pharmaceutical carrier grain size of apo- gossypol prepared by method therefor is 71nm in the present embodiment, carries medicine
Measure is 5%.
Example IV
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of levorotation gossypol, includes the following steps：
Step 1: 32mg levorotation gossypols are dissolved in 16mL hexamethylenes, disperseed under 100K Hz ultrasounds, disperseed
Time is 15 minutes, and levorotation gossypol cyclohexane mixtures are made；
Step 2: take 0.8g palm waxs, heating and melting；By the levorotation gossypol cyclohexane mixtures 16mL in step 1 with melting
The palm wax of change is sufficiently mixed, and is removed the hexamethylene in system using Rotary Evaporators vacuum distillation, is obtained a left side of 40mg/mL
Revolve gossypol palm wax mixture；
Step 3: configuration concentration is the dodecyl trimethyl ammonium chloride and cetyl trimethylammonium bromide of 1% (M/V)
1:10 (M/M) mixture aqueous solutions；
Step 4: by the levorotation gossypol palm wax mixture heating and melting in step 3,100 μ L are taken in test tube, are added in
The dodecyl trimethyl ammonium chloride of 6mL1% (M/V) and the 1 of cetyl trimethylammonium bromide:10 (M/M) mixtures are water-soluble
Under the conditions of ice-water bath, using ultrasonic probe, nano-solid fat particle is formed it into for 10 minutes using 100w power ultrasonics for liquid；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load levorotation gossypol is obtained.
The palm wax solid fat pharmaceutical carrier grain size of levorotation gossypol prepared by method therefor is 65nm in the present embodiment, carries medicine
Measure is 4%.
Embodiment five
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of methyl gossypol, includes the following steps：
Step 1: 32mg methyl gossypols are dissolved in 16mL n-hexanes, disperseed under 100K Hz ultrasounds, disperseed
Time is 15 minutes, and methyl gossypol hexane mixture is made；
Step 2: take 0.8g palm waxs, heating and melting；By the methyl gossypol hexane mixture 16mL in step 1 with melting
The palm wax of change is sufficiently mixed, and is removed the n-hexane in system using Rotary Evaporators vacuum distillation, is obtained the first of 40mg/mL
Base gossypol palm wax mixture；
Step 3: configuration concentration is the dodecyl trimethyl ammonium chloride and cetyl trimethylammonium bromide of 1% (M/V)
1:1 (M/M) mixture aqueous solution；
Step 4: by the methyl gossypol palm wax mixture heating and melting in step 3,100 μ L are taken in test tube, are added in
The dodecyl trimethyl ammonium chloride of 6mL 1% (M/V) and the 1 of cetyl trimethylammonium bromide:1 (M/M) mixture is water-soluble
Under the conditions of ice-water bath, using ultrasonic probe, nano-solid fat particle is formed it into for 10 minutes using 100w power ultrasonics for liquid；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load methyl gossypol is obtained.
The palm wax solid fat pharmaceutical carrier grain size of methyl gossypol prepared by method therefor is 68nm in the present embodiment, carries medicine
Measure is 4%.
Embodiment six
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of gossypol schiff bases, includes the following steps：
Step 1: 60mg gossypol schiff bases is dissolved in the mixture of 6mL ethyl alcohol and 6mL ether, in 100K Hz ultrasounds
Under disperseed, jitter time be 20 minutes, gossypol schiff bases natalite is made；
Step 2: take 1g palm waxs, heating and melting.By the gossypol schiff bases natalite 16mL in step 1 with
The palm wax of thawing is sufficiently mixed, and is removed the ethyl alcohol in system and ether using Rotary Evaporators vacuum distillation, is obtained 60mg/
The gossypol schiff bases palm wax mixture of mL；
Step 3: configuration concentration is the Tween-20 aqueous solution of 1% (M/V)；
Step 4: by the gossypol schiff bases palm wax mixture heating and melting in step 3,1mL is taken in test tube, is added in
20mL 1% (M/V) Tween-20 solution under the conditions of ice-water bath, using ultrasonic probe, is made for 5 minutes using 200w power ultrasonics
It forms nano-solid fat particle；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load gossypol schiff bases is obtained.
The palm wax solid fat pharmaceutical carrier grain size of gossypol schiff bases prepared by method therefor is 82nm in the present embodiment, is carried
Dose is 6%.
Embodiment seven
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of monoaldehyde gossypol, includes the following steps：
Step 1: 70mg monoaldehyde gossypols are dissolved in 14mL chloroforms, disperseed under 100K Hz ultrasounds, during dispersion
Between for 20 minutes, monoaldehyde gossypol chloroform mixture is made；
Step 2: take 1g palm waxs, heating and melting；By the monoaldehyde gossypol chloroform mixture 14mL in step 1 and thawing
Palm wax is sufficiently mixed, and is removed the chloroform in system using Rotary Evaporators vacuum distillation, is obtained the monoaldehyde gossypol of 70mg/mL
Palm wax mixture；
Step 3: configuration concentration is the Tween-80 aqueous solution of 0.8% (M/V)；
Step 4: by the monoaldehyde gossypol palm wax mixture heating and melting in step 3,1mL is taken in test tube, is added in
25mL 0.8% (M/V) Tween-80 solution, under the conditions of ice-water bath, using ultrasonic probe, using 300w power ultrasonics 8 minutes
Form it into nano-solid fat particle；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load monoaldehyde gossypol is obtained.
The palm wax solid fat pharmaceutical carrier grain size of monoaldehyde gossypol prepared by method therefor is 83nm in the present embodiment, carries medicine
Measure is 7%.
Embodiment eight
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of acetyl gossypol, includes the following steps：
Step 1: 80mg acetyl gossypols are dissolved in 16mL chloroforms, disperseed under 100K Hz ultrasounds, during dispersion
Between for 25 minutes, acetyl gossypol chloroform mixture is made；
Step 2: take 1g palm waxs, heating and melting；By the acetyl gossypol chloroform mixture 16mL in step 1 and thawing
Palm wax is sufficiently mixed, and is removed the chloroform in system using Rotary Evaporators vacuum distillation, is obtained the acetyl gossypol of 80mg/mL
Palm wax mixture；
Step 3: the Tween-20 and the 2 of Arlacel-80 that configuration concentration is 1% (M/V):3 (M/M) mixture aqueous solutions；
Step 4: by the acetyl gossypol palm wax mixture heating and melting in step 3,1mL is taken in test tube, is added in
The Tween-20 of 20mL 1% (M/V) and the 2 of Arlacel-80:3 (M/M) mixture aqueous solutions, under the conditions of ice-water bath, use ultrasound
Probe, nano-solid fat particle is formed it into for 5 minutes using 400w power ultrasonics；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load acetyl gossypol is obtained.
The palm wax solid fat pharmaceutical carrier grain size of acetyl gossypol prepared by method therefor is 79nm in the present embodiment, carries medicine
Measure is 8%.
Embodiment nine
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of monoether gossypol, includes the following steps：
Step 1: 45mg monoether gossypols are dissolved in 18mL chloroforms, disperseed under 100K Hz ultrasounds, during dispersion
Between for 27 minutes, monoether gossypol chloroform mixture is made；
Step 2: take 0.5g palm waxs, heating and melting；By the monoether gossypol chloroform mixture 18mL in step 1 with melting
Palm wax be sufficiently mixed, using Rotary Evaporators vacuum distillation by system chloroform remove, obtain the monoether cotton of 90mg/mL
Phenol palm wax mixture；
Step 3: configuration concentration is the pluronic F127 aqueous solutions of 1% (M/V)；
Step 4: by the monoether gossypol palm wax mixture heating and melting in step 3,100 μ L are taken in test tube, are added in
The pluronic F127 aqueous solutions of 5mL 1% (M/V), under the conditions of ice-water bath, using ultrasonic probe, using 100w power ultrasonics
Form it within 10 minutes nano-solid fat particle；
Step 5：It is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load monoether gossypol is obtained；
The palm wax solid fat pharmaceutical carrier grain size of monoether gossypol prepared by method therefor is 67nm in the present embodiment, carries medicine
Measure is 9%.
Embodiment ten
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of gossypol ketone, includes the following steps：
Step 1: 50mg gossypol ketone is dissolved in the mixture of 20mL chloroforms and 2mL ethyl alcohol, under 100K Hz ultrasounds
Disperseed, jitter time is 30 minutes, and gossypol ketone chloroform alcohol mixture is made；
Step 2: take 0.5g palm waxs, heating and melting；By the gossypol ketone chloroform alcohol mixture 22mL in step 1 with melting
The palm wax of change is sufficiently mixed, and is removed the chloroform in system and ethyl alcohol using Rotary Evaporators vacuum distillation, is obtained 100mg/
The gossypol ketone palm wax mixture of mL；
Step 3: configuration concentration is the dodecyl trimethyl ammonium chloride aqueous solution of 0.5% (M/V)；
Step 4: by the gossypol ketone palm wax mixture heating and melting in step 3,50 μ L are taken in test tube, add in 4mL
0.5% (M/V) dodecyl trimethyl ammonium chloride solution under the conditions of ice-water bath, using ultrasonic probe, is surpassed using 200w power
Sound forms it into nano-solid fat particle for 5 minutes；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load gossypol ketone is obtained.
The palm wax solid fat pharmaceutical carrier grain size of gossypol ketone prepared by method therefor is 85nm in the present embodiment, drugloading rate
It is 10%.
Embodiment 11
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of gossypol acetate, includes the following steps：
Step 1: by 5mg gossypol acetates in 1mL ethyl alcohol, disperseed under 100K Hz ultrasounds, jitter time is 3 points
Gossypol acetate alcohol mixture is made in clock；
Step 2: take 1g palm waxs, heating and melting；By the gossypol acetate alcohol mixture 10mL in step 1 and thawing
Palm wax is sufficiently mixed, and is removed the ethyl alcohol in system using Rotary Evaporators vacuum distillation, is obtained the gossypol acetate of 5mg/mL
Palm wax mixture；
Step 3: configuration concentration is the pluronic F127 aqueous solutions of 0.5% (M/V)；
Step 4: by the gossypol acetate palm wax mixture heating and melting in step 3,1mL is taken in test tube, is added in
30mL 0.5% (M/V) pluronic F127 solution, under the conditions of ice-water bath, using ultrasonic probe, using 400w power ultrasonics
Form it within 10 minutes nano-solid fat particle；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load gossypol acetate is obtained.
The palm wax solid fat pharmaceutical carrier grain size that method therefor prepares load gossypol acetate in the present embodiment is 80nm, carries medicine
Measure is 0.5%.
Embodiment 12
A kind of preparation method of the palm wax solid fat pharmaceutical carrier of apo- gossypol ketone, includes the following steps：
Step 1: 100mg apo- gossypol ketone is dissolved in 20mL ethyl alcohol, disperseed under 100K Hz ultrasounds, disperseed
Time is 30 minutes, and apo- gossypol ketone alcohol mixture is made；
Step 2: take 1g palm waxs, heating and melting；By the apo- gossypol ketone alcohol mixture 20mL in step 1 with melting
Palm wax be sufficiently mixed, using Rotary Evaporators vacuum distillation by system ethyl alcohol remove, obtain the apo- of 100mg/mL
Gossypol ketone palm wax mixture；
Step 3: configuration concentration is the dodecyl trimethyl ammonium chloride and cetyl trimethylammonium bromide of 1% (M/V)
10:1 (M/M) mixture aqueous solution；
Step 4: by the apo- gossypol ketone palm wax mixture heating and melting in step 3,50 μ L are taken in test tube, are added in
The dodecyl trimethyl ammonium chloride of 1mL1% (M/V) and the 10 of cetyl trimethylammonium bromide:1 (M/M) mixture is water-soluble
Under the conditions of ice-water bath, using ultrasonic probe, nano-solid fat particle is formed it into for 10 minutes using 400w power ultrasonics for liquid；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as to removing body
Surfactant in system；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load apo- gossypol ketone is obtained.
The palm wax solid fat pharmaceutical carrier grain size of apo- gossypol ketone prepared by method therefor is 88nm in the present embodiment, is carried
Dose is 10%.
Claims (3)
1. a kind of preparation method of the palm wax solid fat pharmaceutical carrier of gossypol and its derivative, includes the following steps：
Step 1: 5-100mg gossypols and its derivative are dissolved in 1-20mL organic solvents, carried out under 100K Hz ultrasounds
Dispersion, jitter time are 3-30 minutes, and gossypol ORGANIC SOLVENT MIXTURES is made；
The gossypol and its derivative include：Gossypol acetate, apo- gossypol, levorotation gossypol, apo- gossypol ketone ApoG2, gossypol ketone,
One kind in methyl gossypol, gossypol schiff bases, monoaldehyde gossypol, acetyl gossypol or monoether gossypol；
The organic solvent is that one or both of ethyl alcohol, chloroform, ether, hexamethylene, n-hexane organic solvent are pressed in ratio
V/V 1:1-1:Mixture between 10；
Step 2: take 0.5-1g palm waxs, heating and melting；By the gossypol in step 1 and its derivative ORGANIC SOLVENT MIXTURES
10-20mL is sufficiently mixed with the palm wax melted, is removed the organic solvent in system using Rotary Evaporators vacuum distillation, is obtained
To the gossypol palm wax mixture of 5-100mg/mL；
Step 3: configuration concentration M/V is the aqueous surfactant solution of 0.5-1%；
The surfactant is pluronic F127, Pluronic F68, dodecyl trimethyl ammonium chloride, cetyl
One kind in trimethylammonium bromide, Tween-20, Tween-80, Arlacel-80 or in M/M ratios 1:1-1:Mixing between 10
Object；
Step 4: by the gossypol in step 3 and its derivative palm wax mixture heating and melting, 50 μ L-1mL are taken in test tube,
1-30mL surfactant solutions are added in, under the conditions of ice-water bath, using ultrasonic probe, using 100-400w power ultrasonics 2-10
Minute forms it into nano-solid fat particle；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as in removal system
Surfactant；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load gossypol and its derivative is obtained.
2. according to a kind of gossypol shown in claim 1 and its preparation side of the palm wax solid fat pharmaceutical carrier of derivative
Method, it is characterised in that：
Step 1: 50mg apo- gossypol ketone is dissolved in 20mL ethyl alcohol, disperseed under 100K Hz ultrasounds, jitter time
It is 30 minutes, apo- gossypol ketone alcohol mixture is made；
Step 2: take 0.5g palm waxs, heating and melting；By the apo- gossypol ketone alcohol mixture 20mL in step 1 and thawing
Palm wax is sufficiently mixed, and is removed the ethyl alcohol in system using Rotary Evaporators vacuum distillation, is obtained the apo- cotton of 100mg/mL
Phenolic ketone palm wax mixture；
Step 3: configuration concentration is the pluronic F127 aqueous solutions of 1% (M/V)；
Step 4: by the apo- gossypol ketone palm wax mixture heating and melting in step 3,100 μ L are taken in test tube, add in 4mL
1% (M/V) pluronic F127 solution under the conditions of ice-water bath, using ultrasonic probe, is made for 10 minutes using 400w power ultrasonics
It forms nano-solid fat particle；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as in removal system
Surfactant；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load apo- gossypol ketone is obtained.
3. according to a kind of gossypol shown in claim 1 and its preparation side of the palm wax solid fat pharmaceutical carrier of derivative
Method, it is characterised in that：
Step 1: 50mg gossypol ketone is dissolved in the mixture of 20mL chloroforms and 2mL ethyl alcohol, carried out under 100K Hz ultrasounds
Dispersion, jitter time are 30 minutes, and gossypol ketone chloroform alcohol mixture is made；
Step 2: take 0.5g palm waxs, heating and melting；By the gossypol ketone chloroform alcohol mixture 22mL in step 1 and thawing
Palm wax is sufficiently mixed, and is removed the chloroform in system and ethyl alcohol using Rotary Evaporators vacuum distillation, is obtained 100mg/mL's
Gossypol ketone palm wax mixture；
Step 3: configuration concentration is the dodecyl trimethyl ammonium chloride aqueous solution of 0.5% (M/V)；
Step 4: by the gossypol ketone palm wax mixture heating and melting in step 3,50 μ L are taken in test tube, add in 4mL
0.5% (M/V) dodecyl trimethyl ammonium chloride solution under the conditions of ice-water bath, using ultrasonic probe, is surpassed using 200w power
Sound forms it into nano-solid fat particle for 5 minutes；
Step 5: it is dialysed using the spin dialysis pipe of 300,000 dalton of molecular cut off to sample, so as in removal system
Surfactant；
Step 6: using 220nm membrane filtrations, the palm wax solid fat pharmaceutical carrier of load gossypol ketone is obtained.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102652724A (en) * | 2011-03-04 | 2012-09-05 | 台湾美联生物科技有限公司 | Composition containing blueweed oil and lipid, preparation method and application of composition |
| CN104523606A (en) * | 2014-11-20 | 2015-04-22 | 西安交通大学 | Method used for preparing gossypol and gossypol derivative pluronic nanoparticle via self-assembling |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102652724A (en) * | 2011-03-04 | 2012-09-05 | 台湾美联生物科技有限公司 | Composition containing blueweed oil and lipid, preparation method and application of composition |
| CN104523606A (en) * | 2014-11-20 | 2015-04-22 | 西安交通大学 | Method used for preparing gossypol and gossypol derivative pluronic nanoparticle via self-assembling |
Non-Patent Citations (1)
| Title |
|---|
| Preparation and characterization of ketoprofen-loaded solid lipid nanoparticles made from beeswax and carnauba wax;Soheila Kheradmandnia等;《Nanomedicine: Nanotechnology, Biology, and Medicine》;20101231;第6卷(第6期);第753-759页 * |
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