CN110123751A - A kind of milk thistle class medicament nano cream dust composition and preparation method thereof - Google Patents
A kind of milk thistle class medicament nano cream dust composition and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to field of pharmaceutical preparations, a kind of milk thistle class medicament nano cream dust composition and preparation method thereof is disclosed.The composition formula contains the substance of following weight percent: 1%~10% milk thistle class drug, 5%~50% oily phase, 5-30% emulsifier, 0-30% assistant for emulsifying agent, 10%~85% filler, 0%~20% glidant.This nanometer of pulvis can keep nano-emulsion to promote absorption characteristic, improve bioavilability, increase curative effect, and be readily transported, store；Preparation process simple process, is easy to industrialization.
Description
Technical field
The invention belongs to pharmaceutical preparation preparation field, it is related to a kind of milk thistle class medicament nano cream dust composition and its system
Preparation Method.
Technical background
With the acceleration of the modern life, the people of new era are faced with from various pressure.It stays up late, drink and height is negative
The reasons such as lotus physical work can all lead to the overload of liver.In addition, epidemic disease, virus etc. all can invade liver just
Chang Gongneng, the major disease for then causing liver also gradually cause the concern of people, the theory day of masses' liver protection, nourishing the liver and protect liver
It is increasingly deep.
For liver cell protection there is a variety of theories, scavenging activated oxygen, improves liver cell oxidation resistance at present
As being widely recognized as and one of the theory received.Natural drug has huge compound library, and flavonoids, phenols, terpene etc. are changed
Closing object has extensive antioxidation.
Milk thistle (silybum marianum L.Gaertn) is composite family Silybum herbaceous plant, originates in southern Europe, north
It is non-.Milk thistle is a kind of European folk herbal medicine, its extract is just used for controlling for disease in the liver and gallbladder early in B.C. four th-Century Western
It treats.
Silymarin (silymarin) is a kind of novel flavone compound extracted from milk thistle seed, mainly at
Point have silibinin (silybin/silibinin), Isosilybin (isosilybin), silydianin (silydianin) and
Silychristin (silychristin) etc..Wherein, with silibinin content highest, biological activity is also most strong.Basis and clinic
Research confirms that milk thistle drug has the effects that liver protection, anti-inflammatory, immunological regulation, reducing blood lipid and anti-oxidant, therefore by countries in the world
It is widely used in the treatment of various liver diseases.
With the accumulation of milk thistle preparation evidence-based medical, milk thistle preparation is by Chinese " non-alcoholic fatty liver
Sick practice guidelines (2010) ", " alcoholic liver disease practice guidelines (2010) ", " drug induced hepatic injury diagnosis and treatment guide (2015) " and
Multi-sections hepatopathy practice guidelines such as " liver inflammation and its prevention and treatment Consensus of experts " are classified as anti-inflammatory liver protection therapeutic agent.
Currently, milk thistle preparation used in clinically is mainly Silymarin Capsule and silymarin tablet, such as Seeley guest
The silybin meglumine tablets of peace, the Silybin Capsules of Tianjin day Shi Lishengte pharmaceutical Co. Ltd, Australia Swisse company
Milk Thistle piece, Nature's bounty company, the U.S. Milk Thistle grass liver detoxification capsule and Puritan ' s Pride company, the U.S.
Milk thistle Milk Thistle grass extract soft capsule, Madaus AG's production Silymarin Capsule etc..But due to its indissoluble
Yu Shui and common solvent, ordinary solid preparation oral absorption difference, bioavilability is low, to influence its clinical efficacy.Milk thistle
Class drug belongs to typical II class drug in biological agent categorizing system (BCS) (i.e. solubility low but good penetrability), therefore, leads to
It crosses the solubility for improving milk thistle class drug and dissolution rate is the effective way for improving its bioavilability.
Nano-emulsion can significantly improve insoluble drug solubility, promote insoluble drug oral absorption, and have to liver
Significant targeting.Milk thistle class drug development is prepared into nano-emulsion preparation, and the ordinary tablet of milk thistle class drug in the market
Agent or capsule formulation, which are compared, has better liver protection, liver protection effect.But liquid emulsion there are small product sizes big, transport fiber crops
Tired, the problems such as emulsion droplet is unstable.
Summary of the invention
The purpose of the present invention is the disadvantages lower for milk thistle class drug ordinary preparation bioavilability, provide a kind of water
Fly the milk powder agent of Ji class medicament nano.Said preparation preparation process is simple, property is more stable, and has the work of more preferably clinical liver protecting
With.
It is a further object to provide the preparation methods of above-mentioned nano-emulsion pulvis.
The purpose of the present invention is what is realized by following technical proposal:
A kind of milk thistle class medicament nano cream dust composition, the composition formula contain the object of following weight percent
Matter:
1%~10% milk thistle class drug,
5%~50% oily phase,
5-30% emulsifier,
0-30% assistant for emulsifying agent,
10%~85% filler,
0%~20% glidant.
The amount summation of each substance is 100% in specific formula.
The milk thistle class medicament nano cream dust composition, wherein milk thistle class drug includes silibinin, different water
Fly Ji guest, Silychristin, silydianin, silymarin and their chemical derivative or phosphatide complexes.
The milk thistle class medicament nano cream dust composition, wherein oil be mutually soybean oil, it is castor oil, olive oil, sweet
Oily three esters, ethyl oleate, isopropyl myristic acid ester, median chain triglyceride oil (MCT), Unigly GO 102S, sad certain herbaceous plants with big flowers acid are poly-
One of glycol glycerin ester, ethyl linoleate, oleic acid, mono-/bis-or three palmitinic acid sucrose esters are a variety of.
The milk thistle class medicament nano cream dust composition, wherein emulsifier be phosphatide, cholesterol, Arabic gum,
Tragacanth, albumin, casein, Tween 80, poloxamer, mono-fatty acid glyceride, triglycerin aliphatic ester, gathers gelatin
Stearine, sucrose monolaurate, fatty acid sorbitan (sapn), poly- sorb is smooth, sells pool (myrj), Brij
(brij), one of Emulsifier EL-60, Crodaret or a variety of；
Assistant for emulsifying agent is ethyl alcohol, normal propyl alcohol, n-butanol, isopropanol, ethylene glycol, propylene glycol, glycerol, polyglycerol ester, dehydration
One of sorbitol ester, polyethylene glycol, diethylene glycol monoethyl ether (Transcutol) are a variety of.
The milk thistle class medicament nano cream dust composition, wherein filler is soluble sucrose, glucose, cream
One of sugar, beta-cyclodextrin, mannitol, maltodextrin, soluble starch are a variety of.
The milk thistle class medicament nano cream dust composition, wherein glidant be colloidal silicon dioxide, it is talcum powder, hard
One of fatty acid magnesium, L-cysteine, L-Leu, glutamic acid are a variety of.
The preparation method of the milk thistle class medicament nano cream dust composition, wherein this method includes following operation step
It is rapid:
A: respective substance is weighed by formula ratio, drug is dissolved in the oily solution being made of oily phase, emulsifier, assistant for emulsifying agent
In, and milk thistle class medicament nano emulsion is prepared by emulsifying process with aqueous medium；
B: filler and glidant are added in above-mentioned nanoemulsions, by stirring to dissolve or dispersing, pass through drying
Nano-emulsion pulvis is made in technique；
Or
A: respective substance is weighed by formula ratio, drug is dissolved in the oily solution being made of oily phase, emulsifier, assistant for emulsifying agent
In, filler and glidant are dissolved or dispersed in aqueous medium, and the two is prepared into milk thistle class drug and is received by emulsifying process
Rice milk agent；
B: nano-emulsion pulvis is made by drying process in liquid nanoemulsion；
Or
A: weighing respective substance by formula ratio, drug be dissolved in organic solvent, is redispersed in by emulsifier, helps emulsification
In the oily solution that agent, oil are mutually constituted, and milk thistle class medicament nano emulsion is prepared by emulsifying process with aqueous medium；
B: filler and glidant are added in above-mentioned nanoemulsions, by stirring to dissolve or dispersing, pass through drying
Nano-emulsion pulvis is made in technique；
Or
A: weighing respective substance by formula ratio, drug be dissolved in organic solvent, is redispersed in by emulsifier, helps emulsification
In the oily solution that agent, oil are mutually constituted, filler and glidant are dissolved or dispersed in aqueous medium, and the two passes through emulsification work
Skill is prepared into milk thistle class medicament nano emulsion；
B: nano-emulsion pulvis is made by drying process in liquid nanoemulsion；
The aqueous medium includes water for injection, pure water, mannitol solution, phosphate solution, dextran solution, grape
Sugar aqueous solution, sodium-chloride water solution, amino acid solution, vitamin solution, carbohydrate solutions or their any two kinds
Or two or more mixture；Organic solvent includes ethyl acetate, chloroform, methylene chloride, ethyl alcohol, acetone.
The emulsifying process refers to using high-speed mixing equipment or the equipment for being provided simultaneously with high pressure and high shear force, makes to mix
Object achievees the purpose that efficiently to mix, disperse and emulsify；The drying process includes spray drying, fluidized bed drying and freeze-drying
Technique, wherein preferably spray drying method；
Average grain diameter is 10- after the milk thistle medicament nano milk powder agent for using the preparation method to be prepared is redissolved with water
1000nm, preferably 10-300nm.
The milk thistle class medicament nano cream dust composition can also be further developed as including powder, tablet, glue
Wafer, granule, pill, micropill preparation other solid pharmaceutical preparations.
The beneficial effects of the present invention are:
1, the preparation process simple process of milk thistle class medicament nano cream, be easy to industrialization, and significant increase powder-refining with water
The solubility of Ji class drug, improves its bioavilability.
2, milk thistle class medicament nano cream is made as pulvis by drying process, good fluidity, stability is high, facilitates product
Packing, storage and transport, be also convenient for patient carry and take.
3, nano-emulsion pulvis of the invention can also be further developed as other solid pharmaceutical preparations, such as tablet, capsule.
Milk thistle class drug is made into a nanometer pulvis by this patent, directly powder or can be further developed as tablet, capsule
Agent is swallowed, and can also before use be dissolved it with cold water or warm water, be reverted to nanoemulsions and be used further to take orally.Nanometer pulvis can
It keeps nano-emulsion to promote absorption characteristic, improves bioavilability, increase curative effect, and be readily transported, store.
Detailed description of the invention
Fig. 1 Mouse oral blood plasma (A) and liver organization (B) drug-time through when curve (n=5).
Specific embodiment
Further instruction is subject to the present invention below by embodiment, but following embodiments are not intended to limit the power of this patent
Sharp range.
Embodiment 1: the preparation of silybin nanostructured cream
Weigh Unigly GO 102S (oily phase), sad certain herbaceous plants with big flowers acid polyethylene glycol glyceride (emulsifier), diethylene glycol mono-ethyl
Ether (assistant for emulsifying agent), lecithin (emulsifier) prepare uniform miscella phase according to 1:1:1:0.2 weight ratio, and vortex stirs evenly,
2400mg miscella phase is weighed, 100mg silymarin is added, is allowed to dissolve.It will be mutually added drop-wise to containing medicine oil in 20 times of pure water, it is high
Make its emulsification under speed stirring, nano-emulsion is made.
Embodiment 2: the preparation of silybin nanostructured cream
According to median chain triglyceride oil (oily phase): Emulsifier EL-60 or Crodaret (emulsifier):
Diethylene glycol monoethyl ether (assistant for emulsifying agent): lecithin (emulsifier)=1:4.5:4.5:0.68 proportional arrangement miscella phase,
Vortex stirs evenly, and weighs miscella phase 2400mg, and 90mg silibinin is added, and stirring is allowed to dissolve, and is added to 20 times pure
In water, high-pressure homogeneous technique is allowed to emulsify, and nano-emulsion is made.
Embodiment 3: the preparation of silybin nanostructured cream
According to median chain triglyceride oil (oily phase): Emulsifier EL-60 or Crodaret (emulsifier):
Diethylene glycol monoethyl ether (assistant for emulsifying agent): lecithin (emulsifier)=1:3:6:0.68 proportional arrangement miscella phase is vortexed
It stirs evenly, weighs miscella phase 2400mg, 100mg silibinin is added, stirring is allowed to dissolve, and is added to 20 times of pure water
In, its emulsification is made under high-speed stirred, nano-emulsion is made.
Embodiment 4: the preparation of silymarin nano-emulsion
According to ethyl linoleate (oily phase): Emulsifier EL-60 or Crodaret (emulsifier): dehydration
Sorbitol ester (assistant for emulsifying agent)=1:2:8 proportional arrangement miscella phase, vortex stir evenly, and weigh miscella phase 2400mg,
80mg silymarin is added, stirring is allowed to dissolve, is added in 20 times of pure water, uses Emulsiflex-05 high pressure homogenizer
(Canadian Avestin company) 500bar is recycled twice, and nano-emulsion is made.
Embodiment 5: the preparation of silymarin nano-emulsion
According to median chain triglyceride oil (oily phase): sucrose monolaurate (emulsifier): glycerol (assistant for emulsifying agent): phosphatide
The proportional arrangement miscella phase of (emulsifier)=1:1:9:0.68, vortex stir evenly, and weigh miscella phase 2400mg, are added
75mg silibinin, stirring are allowed to dissolve, are added in 20 times of pure water, make its emulsification using high-speed stirred, and nano-emulsion is made.
Embodiment 6: the preparation of silybin nanostructured cream
According to soybean oil (oily phase): poloxamer (emulsifier): glycerol (assistant for emulsifying agent)=1:6:4 proportional arrangement mixing
Oily phase weighs miscella phase 2400mg, and 75mg silibinin is added, and stirring is allowed to dissolve, be added in 20 times of pure water, uses
400KHz ultrasound 20 minutes, is made nano-emulsion.
Embodiment 7: the preparation of silybin nanostructured cream
100mg silibinin is dissolved using 200mL ethyl alcohol, separately according to soybean oil (oily phase): poloxamer (emulsifier): sweet
Oily (assistant for emulsifying agent): the two is uniformly mixed by lecithin (emulsifier)=1:7:3:0.68 ratio miscella phase.It is added to 20
In pure water again, makes its emulsification stirring be allowed to emulsify using high-pressure homogeneous technique, nano-emulsion is made.
Embodiment 8: spray drying process prepares silybin nanostructured milk powder agent
The silybin nanostructured newborn lotion of 50mL is prepared according to embodiment 1,5g solubility is added in nano-emulsion obtained and forms sediment
Powder (filler).The nanoemulsions are spray-dried, spray drying condition are as follows: inlet temperature is 120 DEG C, and outlet temperature is
80 DEG C, charging rate 4mL/min, intake 40L/min.Product recovery rate is 60.2%, and redissolving solution partial size is
517nm。
Embodiment 9: spray drying process prepares silybin nanostructured milk powder agent
The silybin nanostructured newborn lotion of 50mL is prepared according to embodiment 2, wherein emulsifying pure water used is previously added 5g lactose
(filler) and 1g colloidal silicon dioxide (glidant).The nanoemulsions are spray-dried, spray drying condition are as follows: import
Temperature is 120 DEG C, and outlet temperature is 80 DEG C, charging rate 4mL/min, intake 40L/min.Product recovery rate is
57.2%, redissolving solution partial size is 203nm.
Embodiment 10: spray drying process prepares silybin nanostructured milk powder agent
Silibinin lotion is prepared according to embodiment 3, lactose 5g (filler) is added in lotion obtained, leucine
1.5g (glidant), makes it dissolve, is spray-dried, spray drying condition are as follows: inlet temperature is 120 DEG C, and outlet temperature is
80 DEG C, charging rate 4mL/min, intake 40L/min, pulvis 75.8% is recycled, redissolves partial size 88nm.
Embodiment 11: spray drying process prepares silybin nanostructured milk powder agent
The silybin nanostructured newborn lotion of 50mL is prepared according to embodiment 5, wherein emulsifying pure water used is previously added 5g sucrose
(filler) and 1.5g talcum powder (glidant).The nanoemulsions are spray-dried, spray drying condition are as follows: inlet temperature
It is 120 DEG C, outlet temperature is 80 DEG C, charging rate 4mL/min, intake 40L/min.Product recovery rate is 73.3%,
Redissolving solution partial size is 180nm.
Embodiment 12: spray drying process prepares silybin nanostructured milk powder agent
The silybin nanostructured newborn lotion of 50mL is prepared according to embodiment 6, wherein emulsifying pure water used is previously added 5g grape
Sugared (filler) and 0.5g magnesium stearate (glidant).The nanoemulsions are spray-dried, spray drying condition are as follows: import
Temperature is 120 DEG C, and outlet temperature is 80 DEG C, charging rate 4mL/min, intake 40L/min.Product recovery rate is
73.3%, redissolving solution partial size is 321nm.
Embodiment 13: fluidized bed drying prepares silymarin nano-emulsion pulvis
50mL silymarin nano-emulsion lotion is prepared according to embodiment 1, is previously added sweet dew wherein emulsifying in pure water used
Alcohol 5g (filler) and 0.5g L-cysteine (glidant).The nanoemulsions are subjected to fluidized bed drying, fluidized bed drying
Condition are as follows: air mass flow 50Nm3/ h, unit area loading capacity are 2000g/m2, fluidized bed bed temperature is 70 DEG C.Product returns
Yield is 34.8%, redissolves solution partial size 172nm.
Embodiment 14: fluidized bed drying prepares silybin nanostructured milk powder agent
The silybin nanostructured newborn lotion of 50mL is prepared according to embodiment 3,5g maltodextrin is added in nano-emulsion obtained
(filler) and 0.5g L-cysteine (glidant).The nanoemulsions are subjected to fluidized bed drying, fluidized bed drying condition
Are as follows: air mass flow 50Nm3/h, unit area loading capacity are 2000g/m2, fluidized bed bed temperature is 70 DEG C.Product recovery rate
It is 62.9%, redissolves solution partial size 159nm.
Embodiment 15: fluidized bed drying prepares silymarin nano-emulsion pulvis
50mL silymarin nano-emulsion lotion is prepared according to embodiment 4, wherein emulsifying pure water used is previously added 5g β-ring
Dextrin (filler) and 0.5g magnesium stearate (glidant).The nanoemulsions are subjected to fluidized bed drying, fluidized bed drying condition
Are as follows: air mass flow 50Nm3/ h, unit area loading capacity are 2000g/m2, fluidized bed bed temperature is 70 DEG C.Product recovery rate
It is 61.2%, redissolves solution partial size 247nm.
Embodiment 16: fluidized bed drying prepares silybin nanostructured milk powder agent
The silybin nanostructured newborn lotion of 50mL is prepared according to embodiment 6, is previously added 5g cream in pure water used wherein emulsifying
Sugared (filler) and 0.5g colloidal silicon dioxide (glidant).The nanoemulsions are subjected to fluidized bed drying, fluidized bed drying item
Part are as follows: air mass flow 50Nm3/h, unit area loading capacity are 2000g/m2, fluidized bed bed temperature is 70 DEG C.Product recycling
Rate is 56.1%, redissolves solution partial size 271nm.
Embodiment 17: freeze-drying prepares silybin nanostructured milk powder agent
The silybin nanostructured newborn lotion of 50mL is prepared according to embodiment 1, is previously added 5g cream in pure water used wherein emulsifying
Sugared (filler).The nanoemulsions are freeze-dried, product recovery rate is 89.5%, redissolves solution partial size 187nm.
Embodiment 18: freeze-drying prepares silymarin nano-emulsion pulvis
50mL silymarin nano-emulsion lotion is prepared according to embodiment 4,5g solubility is added in nano-emulsion obtained and forms sediment
Powder (filler).The nanoemulsions are freeze-dried, product recovery rate is 90.3%, redissolves solution partial size 503nm.
Embodiment 19: freeze-drying prepares silymarin nano-emulsion pulvis
50mL silymarin nano-emulsion lotion is prepared according to embodiment 5, pure water used is emulsified and is previously added 5g glucose
(filler).The nanoemulsions are freeze-dried, product recovery rate is 91.5%, redissolves solution partial size 227nm.
Embodiment 20: freeze-drying prepares silybin nanostructured milk powder agent
The silybin nanostructured newborn lotion of 50mL is prepared according to embodiment 7,5g mannitol is added in nano-emulsion obtained and (fills out
Fill agent).The nanoemulsions are freeze-dried, product recovery rate is 92.2%, redissolves solution partial size 192nm.
Embodiment 21: Evaluation on distribution in Mouse oral pharmacokinetics and liver
The Kunming kind health white mouse 90 of weight 20g ± 2g is chosen, half male and half female, fasting 12h is randomly divided into 2 groups.It will be real
Apply example 14 preparation silybin nanostructured milk powder agent and silibinin suspension (with 10%PVP suspending), according to 32mg/Kg (with
SLB meter) dosage to Oral Administration in Rats, takes blood in 10min, 15min, 30min, 1h, 2h, 4h, 8h, 12h and for 24 hours eyeground, blood sample is used
Anticoagulant heparin, centrifugal separation plasma.Mouse cervical dislocation is put to death, and is taken the same one leaf liver of position of right side of mice, is used physiological saline
It rinses, filter paper blots its moisture, weighed total amount (blood is based on the 8% of mouse weight).
Blood sample treatments: precision is drawn 150 μ L of blood plasma and is placed in 10mL tool plug centrifuge tube, and people's phosphate buffer is added
(pH5.0) 0.5mL, 50 μ L glucosiduronic acid enzyme solutions (enzymatic activity is equivalent to 90U) mix, cultivate 18h in 37 DEG C of water-baths.Add
2 μ gmL of people-150 μ L, 1M Na of alpha-Naphthol inner mark solution2CO3100 μ L of solution, 500 μ L of borate buffer solution (pH 8.0),
It mixes.T-butyl methyl ether 4mL, vortex 5min is added, centrifugation takes organic layer 3mL, and vacuum is drained under 45 DEG C of water-baths, and residue is used
100 μ L of mobile phase dissolution, centrifugation take 20 μ L sample introduction of supernatant, and HPLC method analyzes blood sample concentration.
Hepatic tissue processing: precise weighing hepatic tissue is set in heparin tube, and 1.2mL physiological saline, homogenate is added.Precision pipettes
0.6mL homogenate is set in 10mL tool plug centrifuge tube, by blood sample processing method same treatment, is divided by above-mentioned HPLC method
Analysis.
HPLC condition: chromatographic column is Shimadzu C18Chromatographic column (150mm × 4.6mm i.d, 5 μm)；Mobile phase is methanol:
0.025moL·L-1KH2PO4(PH3.0)=45:55；Flow velocity is 1mLmin- 1；Column temperature: 40 DEG C；Detection wavelength 288nm.
Blood plasma and hepatic tissue pharmaceutical concentration-time curve are as shown in Figure 1, and using the non-compartment model analysis of PKSolver2
Pharmacokinetic data available, the results are shown in Table 1.Compared with silibinin suspension, silybin nanostructured cream medicine powder is in blood
AUC improve nearly 7 times, illustrate for silibinin to be prepared into nanoemulsion, increase insoluble drug release in vitro, promote intestines inhale
It receives, to improve oral administration biaavailability.It is distributed in liver after silybin nanostructured milk powder agent is oral and also significantly improves, AUC is improved
Nearly 3 times, show that said preparation has better liver protection effect.
Table 1: Mouse oral blood plasma and hepatic tissue pharmacokinetic parameters (n=5)
Claims (10)
1. a kind of milk thistle class medicament nano cream dust composition, it is characterised in that the composition formula contains following weight percent
The substance of ratio:
1%~10% milk thistle class drug,
5%~50% oily phase,
5-30% emulsifier,
0-30% assistant for emulsifying agent,
10%~85% filler,
0%~20% glidant.
2. milk thistle class medicament nano cream dust composition according to claim 1, it is characterised in that the powder-refining with water
Ji class drug includes silibinin, Isosilybin, Silychristin, silydianin, silymarin and their chemical derivative
Or phosphatide complexes.
3. milk thistle class medicament nano cream dust composition according to claim 1, it is characterised in that the oil is mutually
Soybean oil, castor oil, olive oil, triglycerides, ethyl oleate, isopropyl myristic acid ester, median chain triglyceride oil, polyglycereol
One of oleate, sad certain herbaceous plants with big flowers acid polyethylene glycol glyceride, ethyl linoleate, oleic acid, mono-/bis-or three palmitinic acid sucrose esters or
It is a variety of.
4. milk thistle class medicament nano cream dust composition according to claim 1, it is characterised in that the emulsifier
For phosphatide, cholesterol, Arabic gum, tragacanth, gelatin, albumin, casein, Tween 80, poloxamer, single glycerin fatty
Acid esters, triglycerin aliphatic ester, polyglycerol stearate, sucrose monolaurate, fatty acid sorbitan, poly- sorb is smooth, sell pool,
One of Brij, Emulsifier EL-60, Crodaret are a variety of；
The assistant for emulsifying agent is ethyl alcohol, normal propyl alcohol, n-butanol, isopropanol, ethylene glycol, propylene glycol, glycerol, polyglycerol ester, takes off
One of water sorbitol ester, polyethylene glycol, diethylene glycol monoethyl ether are a variety of.
5. milk thistle class medicament nano cream dust composition according to claim 1, it is characterised in that the filler
For one of soluble sucrose, glucose, lactose, beta-cyclodextrin, mannitol, maltodextrin, soluble starch or a variety of.
6. milk thistle class medicament nano cream dust composition according to claim 1, it is characterised in that the glidant
For one of colloidal silicon dioxide, talcum powder, magnesium stearate, L-cysteine, L-Leu, glutamic acid or a variety of.
7. the preparation method of milk thistle class medicament nano cream dust composition as described in claim 1, it is characterised in that the party
Method includes following operating procedure:
A: weighing respective substance by formula ratio, and drug is dissolved in the oily solution being made of oily phase, emulsifier, assistant for emulsifying agent,
And milk thistle class medicament nano emulsion is prepared by emulsifying process with aqueous medium；
B: filler and glidant are added in above-mentioned nanoemulsions, by stirring to dissolve or dispersing, pass through drying process
Nano-emulsion pulvis is made；
Or
A: weighing respective substance by formula ratio, and drug is dissolved in the oily solution being made of oily phase, emulsifier, assistant for emulsifying agent,
Filler and glidant are dissolved or dispersed in aqueous medium, and the two is prepared into milk thistle class medicament nano by emulsifying process
Emulsion；
B: nano-emulsion pulvis is made by drying process in liquid nanoemulsion；
Or
A: weighing respective substance by formula ratio, drug be dissolved in organic solvent, be redispersed in by emulsifier, assistant for emulsifying agent,
In the oily oily solution mutually constituted, and milk thistle class medicament nano emulsion is prepared by emulsifying process with aqueous medium；
B: filler and glidant are added in above-mentioned nanoemulsions, by stirring to dissolve or dispersing, pass through drying process
Nano-emulsion pulvis is made；
Or
A: weighing respective substance by formula ratio, drug be dissolved in organic solvent, be redispersed in by emulsifier, assistant for emulsifying agent,
In the oily oily solution mutually constituted, filler and glidant are dissolved or dispersed in aqueous medium, and the two passes through emulsifying process, system
It is standby to obtain milk thistle class medicament nano emulsion；
B: nano-emulsion pulvis is made by drying process in liquid nanoemulsion.
8. preparation method according to claim 7, it is characterised in that the aqueous medium includes water for injection, pure water, sweet
Reveal alcoholic solution, phosphate solution, dextran solution, glucose solution, sodium-chloride water solution, amino acid solution, vitamin
Solution, carbohydrate solutions or their two or more any mixture；Organic solvent include ethyl acetate,
Chloroform, methylene chloride, ethyl alcohol, acetone.
9. preparation method according to claim 7, it is characterised in that the emulsifying process refers to using high-speed mixing equipment
Or the equipment for being provided simultaneously with high pressure and high shear force, bring the mixture to the purpose of efficiently mixing, dispersion and emulsification；The drying
Technique includes spray drying, fluidized bed drying and freeze drying process, wherein preferably spray drying method；It prepares to obtain milk thistle
Average grain diameter is 10-1000nm after medicament nano milk powder agent is redissolved with water, preferably 10-300nm.
10. milk thistle class medicament nano cream dust composition described in claim 1, it is characterised in that the composition can also be into
The exploitation of one step is other solid pharmaceutical preparations for including powder, tablet, capsule, granule, pill, micropill preparation.
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