CN105902530B - A kind of polydanshinolate lipid nano particle and preparation method - Google Patents
A kind of polydanshinolate lipid nano particle and preparation method Download PDFInfo
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Abstract
The present invention provides a kind of polydanshinolate lipid nano particle, it is made of polydanshinolate, lecithin, matrix material, polyethylene glycol (2000) stearate, mass percent is 10%-30% polydanshinolate, 20%-60% lecithin, 10%-70% matrix material, 0%-30% polyethylene glycol (2000) stearate.Polydanshinolate provided by the invention has slowly releasing effect from the release in lipid nano particle.Polydanshinolate from lipid nano particle by Oral Administration in Rats gastric infusion, drug polydanshinolate in rat body the residence time up to 24 hours or more, drug in rat body absolute bioavailability up to 80% or more.Polydanshinolate lipid nano particle Orally-administrable provided by the invention improves gastrointestinal tract absorption of drugs, improves and provides the oral absorption of polydanshinolate, significantly improve the bioavilability of polydanshinolate.
Description
Technical field
The invention belongs to pharmaceutical technology fields, are related to polydanshinolate lipid nano particle and based on salvia root polyphenol acid
The application of salt-phosphatide complexes lipid nano particle preparation method and the nanoparticle in oral preparation.
Background technique
Person in middle and old age's cardiovascular and cerebrovascular disease mainly includes hypertension, coronary heart disease, cerebral apoplexy, congenital heart disease, the idiopathic heart
Popular name for, rheumatic heart disease, cardiomyopathy and pulmonary heart disease etc..With the development of the society, people's lives get used to eating habit
There is earth-shaking variation than before, in recent years, cardiovascular number of patients is in rising trend, and the trend of rejuvenation occurs, it
Pathogenic factor be it is diversified, process slowly and non-evident sympton.Once morbidity, disability rate is higher, and patient loses life certainly
Reason ability, and long-term therapeutic process is needed, heavy burden is brought to patient itself and family.
In recent years, domestic and foreign scholars have done numerous studies to the pharmacological action and clinical application of polydanshinolate, discovery
Polydanshinolate all has valuable pharmacological effect to organs such as the heart, brain, liver, kidneys, and has good development in clinical application
Prospect.Polydanshinolate is that the existing neolignan skeleton of one kind extracted from Radix Salviae Miltiorrhizae has the object of coffee phthalein depside structure again
Matter includes salviandic acid A, B, C, D, E, F, G, H, I, Rosmarinic acid, alkannic acid etc..Polydanshinolate is by extracting in Radix Salviae Miltiorrhizae
Various danshinolic acids mixture, account for about 80% magnesium danshinoacetate as the main effective ingredient of Radix Salviae Miltiorrhizae, because its decoct, it is concentrated
The reason of journey, finally all exists in a salt form, wherein based in the form of magnesium salts, collectively referred to as polydanshinolate.By several
Research in 10 years, having proven to polydanshinolate has many-sided pharmacological action: protection of ecs, it is anti-oxidant, adjust TXA2/PGI2,
TFPI-1 is adjusted, TFPI-2, Endothelin inhibition, Ca2+ antagonism, inhibits β-AP, reduces vasopermeability, adjusts Na+-K+-
ATPase, stablize mitochondrial membrane, improve brain energy metabolism, VEGF, bFGF expression inhibit ICAM-1, inhibits VCAM-1, inhibits
MMP-2, it reduces LDH, inner membrance tune is induced to die.
Its action target spot and mechanism are broadly divided into following sections: calcium channel blocking improves microcirculation；Inhibit thromboxane
A2 (TXA2) synzyme, inhibits the aggregation of blood platelet；A large amount of phenolic hydroxyl groups remove free radical, strong anti-oxidation；Inhibit adhesion molecule
(ICAM-1) expression and Apoptosis mitigate vascular endothelial cell damage；The endothelial cell migration for promoting monocyte induction, lures
Emissarium is newborn, or even has inhibiting effect to cancer cell.Although the product of salvia root polyphenol acid salt is in terms of cardiovascular and cerebrovascular disease
Good effect is shown, but is ground in various aspects such as pharmaceutical dosage form, administration route, bioavilabilities there are still many problems
Study carefully and show that polydanshinolate takes orally astigmat, such as oral tanshin polyphenolic acid B is 2.3% in rat vivo biodistribution availability, and salviandic acid A is only
Have 20.5%, oral salvianolic acid drug bioavailability is low, to directly affect the therapeutic effect of drug.Therefore understanding
On the basis of physical and chemical properties of drugs and mechanism of action, selects suitable method to improve the absorption efficiency of drug in vivo, improve mouth
Bioavilability is taken, is current clinical urgent problem to be solved.
New agent technology development in recent years is getting faster, also more and more mature, as nano-emulsion and Submicron Emulsion, microballoon with it is micro-
Capsule, nanoparticle, liposome make drug within the necessary time by the means of preparation, press certain speed at suitable position
Release, and effective blood concentration is maintained in longer time, toxic side effect is reduced, reaches and improves curative effect purpose, but do not change
The pharmacological action of drug.These dosage forms have curative effect high, long action time and that adverse reaction is few etc. are excellent compared with regular dosage form
Point.Lipid nano particle is the submicron drug delivery system of new generation to grow up early 1990s, refer to partial size 10~
The particle of 1000nm is the micelle administered vehicle system after liposome, emulsion, particle and milimicron particle, for drug controlled release
System.Lipid nano particle is carrier by solid natural or the lipoid synthesized such as lecithin, triacylglycerol etc., by Drug absorbability or package
Manufactured a new generation's nanoparticle drug delivery system in lipid film；It is lipid nano particle set fat emulsion, polymer nanoparticle, poly-
The advantages of closing object nanocapsule, nanosphere, liposome: physical stability is high, drug leakage is few, targeting, toxicity is low, has sustained release
Property is easy to the advantages of being mass produced；Solid lipid nano granule is made in drug, be conducive to the absorption for improving drug and improves medicine
Object bioavilability makes drug accumulation in specific target tissue, increases curative effect, reduces toxic side effect.
Phosphatide have it is amphipathic, not only containing polar group (phosphoric acid, choline) but also having non-polar group (fatty acid) in structure,
Good biocompatibility, it is nontoxic and have certain pharmacological activity, on the one hand can be used as emulsifier, can be used for preparing solid lipid and receive
The grain of rice；On the other hand can be compound with water soluble drug, improve the lipophilicity of drug.The formation of phosphatide complexes and without chemistry
Variation, structurally, the oxygen atom of hydroxyl has stronger an electronics tendency on phosphorus atoms in phosphatide, and nitrogen-atoms have it is stronger
Betatopic tendency, under certain condition, phosphatide is easy to water soluble drug and is compounded to form phosphatide complexes.
The present invention is based on the features that polydanshinolate is easy to become solution in water, prepare polydanshinolate-phosphorus using phosphatide first
Fat complexes increase the fat-soluble of drug；On this basis using matrix material and polyethylene glycol stearate as main material system
Standby polydanshinolate lipid nano particle improves the oral bio of polydanshinolate by the oral absorption of lipid nano particle
Availability.This method can effectively encapsulate water soluble drug, to realize that polydanshinolate oral administration lays the foundation.
Summary of the invention
It is an object of the present invention to provide polydanshinolate lipid nano particle, the nanoparticle by polydanshinolate,
Lecithin, matrix material, polyethylene glycol (2000) stearate composition, mass percent are 10%-30% salvia root polyphenol acid
Salt, 20%-60% lecithin, 10%-70% matrix material, 0%-30% polyethylene glycol (2000) stearate；Wherein Radix Salviae Miltiorrhizae
Polyphenol hydrochlorate is Chinese medical extract, and specific composition see the table below；The matrix material can be glyceryl laurate ester, monostearate
One or two kinds of compositions such as glyceride, stearic acid, oleic acid, Medium chain fatty phenolic acid glyceride, caprylic/capric triglyceride.
A second object of the present invention is to provide polydanshinolate lipid nano particle preparation methods, especially by with lower section
Case is realized:
(1) preparation of salvia root polyphenol acid salt phospholipid compound
Solvent method preparation: precision weighs lecithin 20mg, and 1mL methanol is added in eggplant-shape bottle in polydanshinolate 10mg:
Tetrahydrofuran (1:9) mixed solution, 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C except dereaction
Solvent is stood overnight, and is prepared into salvia root polyphenol acid salt phospholipid compound yellow solid powder.
(2) prepared by polydanshinolate lipid nano particle
Solvent diffusion method prepares polydanshinolate lipid nano particle, specific method: precision is weighed is with mass percent
Salvia root polyphenol acid salt phospholipid compound, the matrix material of 10%-70% and the polyethylene glycol of 0%-30% of 30%-90%
(2000) stearate, total 10mg are added the dissolution of 1mL methanol and are used as organic phase, and 60 DEG C of water-bath heating melt material completely.
It is injected into rapidly in 9ml distilled water under 400rpm mixing speed using syringe, 60 DEG C of constant temperature water baths, is persistently stirred 5 minutes,
It is cooled to room temperature, is freeze-dried up to polydanshinolate lipid nano particle.
Polydanshinolate provided by the invention has slowly releasing effect from the release in lipid nano particle.Polydanshinolate
From lipid nano particle by Oral Administration in Rats gastric infusion, drug polydanshinolate in rat body the residence time up to 24 hours with
On, drug in rat body absolute bioavailability up to 80% or more.Polydanshinolate lipid nano particle provided by the invention
Orally-administrable improves gastrointestinal tract absorption of drugs, improves and provides the oral absorption of polydanshinolate, significantly improve pellet
Join the bioavilability of polyphenol hydrochlorate.
Detailed description of the invention
Fig. 1: polydanshinolate lipid nano particle transmission electron microscope photo.
Fig. 2: the drug release profiles of polydanshinolate lipid nano particle.
Fig. 3: mean blood plasma concentration-time graph of rat oral gavage polydanshinolate lipid nano particle.
Specific embodiment
The present invention is further described in conjunction with the accompanying drawings and embodiments.
Embodiment one
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
Polydanshinolate fat complexes 3mg, glycerin monostearate 7mg, addition 1mL methanol, which dissolves, is used as organic phase, and 60 DEG C of water-bath
Heating, melts material completely.It is injected into rapidly in 9ml distilled water under 400rpm mixing speed using syringe, 60 DEG C of water
Constant temperature is bathed, persistently stirs 5 minutes, is cooled to room temperature, is freeze-dried up to polydanshinolate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 84.20 ± 12.66nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 42.34% and 10.61%.
Embodiment two
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
Polydanshinolate fat complexes 6mg, glycerin monostearate 4mg, addition 1mL methanol, which dissolves, is used as organic phase, and 60 DEG C of water-bath
Heating, melts material completely.It is injected into rapidly in 9ml distilled water under 400rpm mixing speed using syringe, 60 DEG C of water
Constant temperature is bathed, persistently stirs 5 minutes, is cooled to room temperature, is freeze-dried up to polydanshinolate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 60.20 ± 12.16nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 46.34% and 12.61%.
Embodiment three
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
Polydanshinolate fat complexes 9mg, glycerin monostearate 1mg, addition 1mL methanol, which dissolves, is used as organic phase, and 60 DEG C of water-bath
Heating, melts material completely.It is injected into rapidly in 9ml distilled water under 400rpm mixing speed using syringe, 60 DEG C of water
Constant temperature is bathed, persistently stirs 5 minutes, is cooled to room temperature, is freeze-dried up to polydanshinolate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 50.08 ± 16.32nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 38.25% and 8.97%.
Example IV
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
Polydanshinolate fat complexes 3mg, stearic acid 7mg are added the dissolution of 1mL methanol and are used as organic phase, and 60 DEG C of water-bath heating make material
Material melts completely.It is injected into rapidly in 9ml distilled water under 400rpm mixing speed using syringe, 60 DEG C of constant temperature water baths are held
Continuous stirring 5 minutes, is cooled to room temperature, and is freeze-dried up to polydanshinolate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 80.22 ± 13.12nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 39.34% and 11.12%.
Embodiment five
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
Polydanshinolate fat complexes 6mg, stearic acid 4mg are added the dissolution of 1mL methanol and are used as organic phase, and 60 DEG C of water-bath heating make material
Material melts completely.It is injected into rapidly in 9ml distilled water under 400rpm mixing speed using syringe, 60 DEG C of constant temperature water baths are held
Continuous stirring 5 minutes, is cooled to room temperature, and is freeze-dried up to polydanshinolate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 72.19 ± 17.22nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 43.78% and 12.19%.
Embodiment six
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
Polydanshinolate fat complexes 9mg, stearic acid 1mg are added the dissolution of 1mL methanol and are used as organic phase, and 60 DEG C of water-bath heating make material
Material melts completely.It is injected into rapidly in 9ml distilled water under 400rpm mixing speed using syringe, 60 DEG C of constant temperature water baths are held
Continuous stirring 5 minutes, is cooled to room temperature, and is freeze-dried up to polydanshinolate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 61.19 ± 14.29nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 33.15% and 9.12%.
Embodiment seven
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
Polydanshinolate fat complexes 3mg, glyceryl laurate ester 7mg are added the dissolution of 1mL methanol and are used as organic phase, and 60 DEG C of water-bath add
Heat melts material completely.It is injected into rapidly in 9ml distilled water under 400rpm mixing speed using syringe, 60 DEG C of water-baths
Constant temperature is persistently stirred 5 minutes, is cooled to room temperature, and is freeze-dried up to polydanshinolate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 90.13 ± 14.29nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 35.17% and 12.15%.
Embodiment eight
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
Polydanshinolate fat complexes 6mg, glyceryl laurate ester 4mg are added the dissolution of 1mL methanol and are used as organic phase, and 60 DEG C of water-bath add
Heat melts material completely.It is injected into rapidly in 9ml distilled water under 400rpm mixing speed using syringe, 60 DEG C of water-baths
Constant temperature is persistently stirred 5 minutes, is cooled to room temperature, and is freeze-dried up to polydanshinolate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 80.12 ± 12.37nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 39.18% and 13.19%.
Embodiment nine
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
Polydanshinolate fat complexes 9mg, glyceryl laurate ester 1mg are added the dissolution of 1mL methanol and are used as organic phase, and 60 DEG C of water-bath add
Heat melts material completely.It is injected into rapidly in 9ml distilled water under 400rpm mixing speed using syringe, 60 DEG C of water-baths
Constant temperature is persistently stirred 5 minutes, is cooled to room temperature, and is freeze-dried up to polydanshinolate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 69.57 ± 17.29nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 29.12% and 8.19%.
Embodiment ten
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
Polydanshinolate fat complexes 6mg, glycerin monostearate 3mg, oleic acid 1mg are added the dissolution of 1mL methanol and are used as organic phase,
60 DEG C of water-bath heating, melt material completely.It is injected into 9ml distilled water rapidly using syringe under 400rpm mixing speed
In, 60 DEG C of constant temperature water baths are persistently stirred 5 minutes, are cooled to room temperature, and are freeze-dried up to polydanshinolate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 97.12 ± 15.89nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 33.19% and 8.34%.
Embodiment 11
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
Polydanshinolate fat complexes 6mg, glycerin monostearate 1mg, oleic acid 3mg are added the dissolution of 1mL methanol and are used as organic phase,
60 DEG C of water-bath heating, melt material completely.It is injected into 9ml distilled water rapidly using syringe under 400rpm mixing speed
In, 60 DEG C of constant temperature water baths are persistently stirred 5 minutes, are cooled to room temperature, and are freeze-dried up to polydanshinolate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 105.9 ± 12.77nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 25.45% and 7.29%.
Embodiment 12
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
The dissolution of 1mL methanol is added in polydanshinolate fat complexes 6mg, glycerin monostearate 3mg, medium-chain fatty glyceride 1mg
As organic phase, 60 DEG C of water-bath heating melt material completely.It is injected into rapidly under 400rpm mixing speed using syringe
In 9ml distilled water, 60 DEG C of constant temperature water baths are persistently stirred 5 minutes, are cooled to room temperature, and are freeze-dried up to polydanshinolate rouge
Matter nanoparticle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 111.9 ± 15.28nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 19.79% and 8.19%.
Embodiment 13
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
The dissolution of 1mL methanol is added in polydanshinolate fat complexes 6mg, glycerin monostearate 1mg, medium-chain fatty glyceride 3mg
As organic phase, 60 DEG C of water-bath heating melt material completely.It is injected into rapidly under 400rpm mixing speed using syringe
In 9ml distilled water, 60 DEG C of constant temperature water baths are persistently stirred 5 minutes, are cooled to room temperature, and are freeze-dried up to polydanshinolate rouge
Matter nanoparticle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 124.5 ± 11.51nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 11.59% and 5.12%.
Embodiment 14
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
It is molten that 1mL methanol is added in polydanshinolate fat complexes 6mg, glycerin monostearate 3mg, caprylic/capric triglyceride 1mg
Solution is used as organic phase, and 60 DEG C of water-bath heating melt material completely.It is injected rapidly under 400rpm mixing speed using syringe
Into 9ml distilled water, 60 DEG C of constant temperature water baths are persistently stirred 5 minutes, are cooled to room temperature, and are freeze-dried up to polydanshinolate
Lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 119.5 ± 18.27nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 11.92% and 6.83%.
Embodiment 15
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
It is molten that 1mL methanol is added in polydanshinolate fat complexes 6mg, glycerin monostearate 1mg, caprylic/capric triglyceride 3mg
Solution is used as organic phase, and 60 DEG C of water-bath heating melt material completely.It is injected rapidly under 400rpm mixing speed using syringe
Into 9ml distilled water, 60 DEG C of constant temperature water baths are persistently stirred 5 minutes, are cooled to room temperature, and are freeze-dried up to polydanshinolate
Lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 130.7 ± 17.17nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 7.16%h and 5.77%.
Embodiment 16
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
1mL first is added in polydanshinolate fat complexes 6mg, glycerin monostearate 3mg, polyethylene glycol (2000) stearate 1mg
Alcohol dissolution is used as organic phase, and 60 DEG C of water-bath heating melt material completely.It is rapid using syringe under 400rpm mixing speed
It is injected into 9ml distilled water, 60 DEG C of constant temperature water baths, persistently stirs 5 minutes, be cooled to room temperature, be freeze-dried up to salvia root polyphenol
Hydrochlorate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 50.50 ± 15.18nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 72.18% and 16.18%.
Embodiment 17
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
1mL first is added in polydanshinolate fat complexes 6mg, glycerin monostearate 2mg, polyethylene glycol (2000) stearate 2mg
Alcohol dissolution is used as organic phase, and 60 DEG C of water-bath heating melt material completely.It is rapid using syringe under 400rpm mixing speed
It is injected into 9ml distilled water, 60 DEG C of constant temperature water baths, persistently stirs 5 minutes, be cooled to room temperature, be freeze-dried up to salvia root polyphenol
Hydrochlorate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 45.72 ± 11.99nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 71.17% and 15.83%.
Embodiment 18
1. the preparation of polydanshinolate fat complexes
Solvent method preparation: precision weighs lecithin 20mg and polydanshinolate 10mg in eggplant-shape bottle, and 1mL first is added
Alcohol: tetrahydrofuran solution (1:9) makes it dissolve, and 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure immediately in 40 DEG C
Reaction dissolvent is removed, stands overnight, is prepared into polydanshinolate-lecithin yellow solid powder, i.e. salvia root polyphenol
Hydrochlorate phosphatide complexes.
2. prepared by polydanshinolate lipid nano particle
Polydanshinolate lipid nano particle is prepared in solvent diffusion method, specific method: precision, which weighs, to be prepared
1mL first is added in polydanshinolate fat complexes 6mg, glycerin monostearate 1mg, polyethylene glycol (2000) stearate 3mg
Alcohol dissolution is used as organic phase, and 60 DEG C of water-bath heating melt material completely.It is rapid using syringe under 400rpm mixing speed
It is injected into 9ml distilled water, 60 DEG C of constant temperature water baths, persistently stirs 5 minutes, be cooled to room temperature, be freeze-dried up to salvia root polyphenol
Hydrochlorate lipid nano particle.
Using its particle size of the measurement of dynamic light scattering determination polydanshinolate lipid nano particle, 1mL is taken to freeze
Polydanshinolate lipid nano particle solution before drying dilutes 10 times, is surveyed with particle size and surface potential detection instrument
Fixed, partial size is 33.12 ± 16.34nm.
Using the encapsulation rate and drugloading rate for adjusting acid centrifuging method cooperation Syrups by HPLC polydanshinolate, take freezing dry
Nanoparticle solution before dry is appropriate, instills the hydrochloric acid of appropriate 0.1mol/L, and 13000rpm is centrifuged 30min, supernatant is taken to cross 100nm
Filter membrane takes 20 μ L sample introduction of filtrate efficient liquid phase, calculates separately entrapment efficiency and drugloading rate as the following formula.
Encapsulation rate=(medication amount/total dosage in lipid nano particle) × 100%
Drugloading rate=(medication amount/drug-carrying nanometer particle total amount in lipid nano particle) × 100%
After measured, the encapsulation rate of polydanshinolate lipid nano particle and drugloading rate are respectively 60.18% and 11.61%.
3. the morphologic observation of polydanshinolate lipid nano particle
Lipid nano particle before taking example one, two, three, 18 to be freeze-dried respectively is diluted to concentration appropriate, will dilute
Nanoparticle solution drops to the copper mesh of covering carbon film afterwards, spontaneously dries, and phosphotungstic acid dyed, with transmission electron microscope observation its
Form, lipid nano particle form is as shown in Figure 1, nanoparticle is spherical, and A is embodiment one in figure, and B is embodiment two, and C is to implement
Example three, D are embodiment 18.
4. the vitro drug release of polydanshinolate lipid nano particle is investigated
Lipid nano particle solution 8mL before taking example one, two, three, 18 to be freeze-dried respectively separately takes and contains in bag filter
The salvia root polyphenol acid saline solution of equivalent is placed in bag filter as a control group, and bag filter is placed in and fills 40mL deionized water
50mL discharges in pipe.Be put into isothermal vibration, shake speed 100rmp, temperature is set as 37 DEG C, respectively at 0.5,1,2,4,6,8,10,
12,24,48,72,96h samples 2mL, while supplementing the medium of 2mL, after measured the release row of polydanshinolate lipid nano particle
For as shown in Fig. 2, drug-carrying nanometer particle compares with positive control, the rate of release of drug is slack-off.
5. polydanshinolate lipid nano particle is studied in Pharmacokinetics in Rat
In polydanshinolate nanoparticle before taking example one, two, three, 18 the to be freeze-dried respectively medicine generation in rat body, is dynamic
Mechanics study: taking weight is SD healthy rat 36 of 200 ± 5g, is randomly divided into 6 groups, every group six, preceding fasting 12h is administered,
Free water, gastric infusion, every rat distinguish stomach-filling about 1.0mL, dosage 100mg.kg-1(based on polydanshinolate
Calculate), the 1st group of intravenous injection stomach-filling polydanshinolate glucose injection, the 2nd group of stomach-filling salvia root polyphenol acid salting liquid, the 3rd,
4,5,6 groups of rats distinguish stomach-filling SLN-10%, SLN-20%, pSLN-20% and SLN-30% solution, gastric infusion, after administration
1,2,4,6,8,10,12,24,36,48,72,96,120,144h acquires 1mL whole blood in tail vein.Blood sample is placed in prior warp
In the centrifuge tube of 1% heparin rinse, 4000rpm obtains upper plasma after being centrifuged 15min.Salvia root polyphenol acid is measured using HPLC method
Salt blood concentration (sample volume is 20 μ L), mean blood plasma concentration-time graph such as Fig. 3 institute of polydanshinolate lipid nano particle
Show, polydanshinolate lipid nano particle increased retention in rat body, bioavilability improves.
Claims (2)
1. a kind of polydanshinolate lipid nano particle, which is characterized in that the nanoparticle is by polydanshinolate, lecithin, rouge
Material, polyethylene glycol 2000 stearate composition, the nanoparticle are realized by following steps:
(1) preparation of salvia root polyphenol acid salt phospholipid compound
Lecithin 20mg is weighed, polydanshinolate 10mg is in eggplant-shape bottle, and the 1mL methanol of 1:9 is added: tetrahydrofuran mixing is molten
Liquid, 40 DEG C of heating stirrings to reaction system, which become, to be clarified, and is dried under reduced pressure removing reaction dissolvent in 40 DEG C immediately, is stood overnight, prepares
Obtain salvia root polyphenol acid salt phospholipid compound yellow solid powder；
(2) prepared by polydanshinolate lipid nano particle
Weigh with mass percent be 60% salvia root polyphenol acid salt phospholipid compound, 10%-20% glycerin monostearate and
The polyethylene glycol 2000 stearate of 20%-30%, total 10mg are added the dissolution of 1mL methanol and are used as organic phase, and 60 DEG C of water-bath are heated,
Melt material completely, is injected into rapidly in 9ml distilled water under 400rpm mixing speed using syringe, 60 DEG C of water-bath perseverances
Temperature is persistently stirred 5 minutes, is cooled to room temperature, and is freeze-dried up to polydanshinolate lipid nano particle.
2. a kind of polydanshinolate lipid nano particle according to claim 1, which is characterized in that the salvia root polyphenol
Hydrochlorate is Chinese medical extract, is made of 80% magnesium danshinoacetate and 20% mixture, and the mixture is by Radix Salviae Miltiorrhizae acetic acid dipotassium, different
Radix Salviae Miltiorrhizae acetic acid dipotassium, alkannic acid magnesium, alkannic acid dipotassium, danshensu potassium, Rosmarinic acid sodium, salvianolic acid G magnesium composition.
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