CN108653206B - Baicalein nano suspension and preparation method thereof - Google Patents
Baicalein nano suspension and preparation method thereof Download PDFInfo
- Publication number
- CN108653206B CN108653206B CN201810616241.7A CN201810616241A CN108653206B CN 108653206 B CN108653206 B CN 108653206B CN 201810616241 A CN201810616241 A CN 201810616241A CN 108653206 B CN108653206 B CN 108653206B
- Authority
- CN
- China
- Prior art keywords
- baicalein
- phospholipid
- nanosuspension
- injection
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
Abstract
The invention belongs to the field of pharmaceutical preparations, and discloses a baicalein nanosuspension and a preparation method thereof. The prescription of the baicalein nanosuspension contains the following substances in percentage by mass: 0.1-2% of baicalein phospholipid complex, 0.05-10% of phospholipid, 0-680.1-3% of F-8910%, 1-10% of glycerol and the balance of water. The invention has simple and convenient process, low cost and energy consumption, improved drug-loading rate of the preparation, improved stability and high safety.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and relates to a baicalein nanosuspension and a preparation method thereof.
Background
Baicalein is an important active ingredient of traditional Chinese medicine scutellaria baicalensis, and has various pharmacological effects of resisting bacteria, resisting viruses, resisting inflammation, protecting liver, benefiting gallbladder, promoting urination, resisting cancer and the like. The baicalein has poor water solubility, the hydrolysis degree in water is 17.5 mu g/mL, and the solubility in soybean oil is less than 0.3 mg/mL; the solubility in water tends to increase with increasing pH, but degradation occurs readily above pH 7.0. Baicalein is metabolized rapidly in vivo, and oral bioavailability is low, and can not be directly made into injection.
In the prior art, researches on baicalein preparations are conducted by exploring different types of emulsions, submicron emulsions, micelle injections, liposomes and the like, but all have the defects, such as limited drug loading capacity of an oil phase, adoption of surfactants which are not commonly used for intravenous injection, such as Solutol and SDS, adoption of toxic organic solvents, such as dimethyl sulfoxide and the like, low safety, poor stability and the like.
Nanosuspensions (nanosuspensions) are stable nanocolloidal dispersions formed by dispersing a drug in a medium with an appropriate amount of a stabilizing agent and by crushing or controlled crystallization techniques. The technology can make the medicine into nanometer, increase the specific surface area, and thus improve the dissolution rate and solubility of the insoluble medicine. At present, no baicalein nanosuspension is reported.
Disclosure of Invention
The invention aims to solve the technical problems and provides a baicalein nanosuspension.
The invention also aims to provide a preparation method of the baicalein nanosuspension.
The purpose of the invention is realized by the following technical scheme:
a baicalein nanosuspension is prepared from the following substances in percentage by mass:
0.1-2% of baicalein phospholipid complex
0.05 to 10 percent of phospholipid
F-68 0.1～3％
1-10% of glycerol
The balance being water.
The baicalein nanosuspension comprises the following substances in percentage by mass in the formula:
0.5-1% of baicalein phospholipid complex
0.05 to 10 percent of phospholipid
F-68 0.2～1.5％
1-8% of glycerol
The balance being water.
The baicalein nanosuspension comprises the following substances in percentage by mass in the formula:
0.1-1% of baicalein phospholipid complex
0.05 to 10 percent of phospholipid
F-68 0.5～1％
1-5% of glycerol
The balance being water.
The baicalein nanosuspension comprises the following substances in percentage by mass in the formula:
baicalein phospholipid complex 0.38%
0.1 percent of phospholipid
F-68 0.58％
2.4 percent of glycerin
The balance being water.
The baicalein nanosuspension comprises the baicalein and phospholipid in a weight ratio of 1: 1 to 5.
The baicalein nanosuspension comprises the baicalein and phospholipid in a weight ratio of 1: 3.
the preparation method of the baicalein nanosuspension comprises the following steps:
1) dissolving baicalein, phospholipid and tetrahydrofuran according to the proportion of 1g: 1-5 g:70ml, heating at 30-45 ℃, refluxing for 1-2h, vacuumizing to remove tetrahydrofuran, and drying in a vacuum drying oven at 20-40 ℃ to obtain a baicalein-phospholipid complex;
2) stirring baicalein phospholipid complex, phospholipid and glycerol according to the prescription amount, and uniformly mixing to obtain a semisolid dispersion; the prescription amount of F-68 is dissolved in water for injection;
3) adding the semi-solid dispersion into an F-68 aqueous solution, and shearing and dispersing at high speed under an ice bath condition to form a coarse suspension;
4) placing the crude mixed suspension into a high-pressure homogenizer, and homogenizing for 4-10 times at the room temperature of 400-800 bar;
5) filtering, bottling, and sterilizing under hot pressure.
Further, the preferred prescription is:
baicalein phospholipid complex 1g +3g
Phospholipid 10g
F-68 0.6g
Glycerol 5g
Water for injection to 100ml
The preparation process comprises the following steps:
1) dissolving baicalein, phospholipid and tetrahydrofuran (1g:3g:70ml) in a three-necked flask, heating at 40 deg.C, refluxing for 1-2 hr, vacuumizing to remove tetrahydrofuran, and drying in a vacuum drying oven (30 deg.C) for 12 hr to obtain baicalein-phospholipid complex
2) Stirring baicalein phospholipid complex, phospholipid and glycerol, and mixing to obtain semisolid dispersion; the prescription dose of F-68 is dissolved in the water for injection
3) Adding the semi-solid dispersion into an F-68 aqueous solution, and shearing and dispersing at high speed under an ice bath condition to form a coarse suspension;
4) placing the crude mixed suspension into a high-pressure homogenizer, and homogenizing at room temperature (400-800bar for 4-10 times);
5) filtration (0.45um microfiltration);
6) filling nitrogen for encapsulation;
7) sterilizing at 121 deg.C under hot pressure for 15-40 min.
Description of the drawings:
phospholipid and F-68(Pluronic F-68) are surfactants in the formula, serve as stabilizing agents of the nano suspension, and glycerol is used for adjusting the osmotic pressure of the injection.
By preparing the baicalein intermediate carrier-baicalein phospholipid compound, the dispersion state of the medicament is changed, so that the medicament is easier to crush and disperse, and the prepared nano suspension has high physical stability and can resist hot-pressing sterilization, low temperature, freeze thawing and the like.
The preparation can also be added with a proper amount of mannitol and freeze-dried to obtain freeze-dried powder. Adding sterilized water for injection for re-dissolving before use.
The invention has the beneficial effects that:
compared with the baicalein preparation in the prior art, the baicalein nanosuspension provided by the invention has the following advantages:
1. advantages of prescription
1.1 compared with emulsion or submicron emulsion, it needs no oil phase, has simple process, improved drug-loading rate, and improved stability (autoclave stability and long-term stability).
1.2 compared with micelle injection, except for phospholipid and F-68 which can be used by intravenous injection, other surfactants (such as Solutol, Tween-80 and the like) are not used, so that the safety is high.
1.3 compared to liposomes, cholesterol was not used.
The invention does not use cholesterol, saves cost and simplifies the process. Liposome preparation methods such as (thin film ultrasound) generally require the addition of cholesterol during membrane formation, which introduces a large amount of organic solvents. The method only needs to add a small amount of tetrahydrofuran when the phospholipid complex is formed and is easy to remove. The cost is saved and the energy consumption is lower.
1.4 the physical stability is good: under the condition of hot-pressing sterilization, the good physical stability is still kept (the original state is kept, and no precipitate is separated out); centrifuging at 4000rpm for 10min, and no layering is observed; standing at 4 deg.C for 12h, standing at 40 deg.C for 12h, circulating for 3 times, centrifuging at 4000rpm for 10min, and no layering.
1.5 the drug loading is high: can reach 1.0mg/ml, which is obviously higher than the sub-micro emulsion of baicalein phospholipid complex.
1.6 the particle size is about 200nm, the polydispersity index is 0.125 and the Zeta potential is-22 mV.
2. The process has the advantages that:
no long-time medium grinding and no emulsification are needed.
Detailed Description
The invention is further illustrated by the following examples
Example 1
Prescription:
baicalein phospholipid complex 1g +3g
Phospholipid 10g
F-68 0.6g
Glycerol 5g
Water for injection to 100ml
The preparation process comprises the following steps:
1) dissolving baicalein, phospholipid and tetrahydrofuran (1g:3g:70ml) in a three-necked flask, heating at 40 deg.C, refluxing for 1-2 hr, vacuumizing to remove tetrahydrofuran, and drying in a vacuum drying oven (30 deg.C) for 12 hr to obtain baicalein-phospholipid complex
2) Stirring baicalein phospholipid complex, phospholipid and glycerol according to the prescription amount, and uniformly mixing to obtain a semisolid dispersion; the prescription amount of F-68 is dissolved in water for injection;
3) adding the semi-solid dispersion into an F-68 aqueous solution, and shearing and dispersing at high speed under an ice bath condition to form a coarse suspension;
4) placing the crude mixed suspension into a high-pressure homogenizer, and homogenizing at room temperature (400-800bar for 4-10 times);
5) filtration (0.45um microfiltration);
6) filling nitrogen for encapsulation;
7) sterilizing at 121 deg.C under hot pressure for 15-40 min.
Long-term stability: according to the market package of the injection, the injection is placed for 12 months at the room temperature of 25 ℃ plus or minus 2 ℃ and the relative humidity of RH60 percent plus or minus 10 percent, and the sampling is carried out once every 3 months and respectively carried out at 0, 3, 6, 9 and 12 months. And (3) respectively inspecting parameters such as appearance, particle size, encapsulation efficiency, pH, osmotic pressure and the like.
Long term stability
Hot-pressing sterilization: packaging 5ml of baicalein nanometer suspension in ampoule bottle, and sterilizing at 121 deg.C under hot pressure for 15 min. Particle size, encapsulation efficiency, pH and osmotic pressure changes before and after sterilization were compared.
Stability before and after sterilization
Example 2
Prescription:
baicalein phospholipid complex 2g +6g
Phospholipid 10g
F-68 1g
Glycerol 2.25g
Water for injection to 200ml
The preparation process comprises the following steps:
1) dissolving baicalein, phospholipid and tetrahydrofuran (1g:3g:70ml) in a three-necked flask, heating at 40 deg.C, refluxing for 1-2 hr, vacuumizing to remove tetrahydrofuran, and drying in a vacuum drying oven (30 deg.C) for 12 hr to obtain baicalein-phospholipid complex
2) Stirring baicalein phospholipid complex, phospholipid and glycerol, and mixing to obtain semisolid dispersion; the prescription dose of F-68 is dissolved in the water for injection
3) Adding the semi-solid dispersion into an F-68 aqueous solution, and shearing and dispersing at high speed under an ice bath condition to form a coarse suspension;
4) placing the crude mixed suspension into a high-pressure homogenizer, and homogenizing at room temperature (400-800bar for 4-10 times);
5) filtration (0.45um microfiltration);
6) filling nitrogen for encapsulation;
7) sterilizing at 121 deg.C under hot pressure for 15-40 min.
Long-term stability: according to the market package of the injection, the injection is placed for 12 months at the room temperature of 25 ℃ plus or minus 2 ℃ and the relative humidity of RH60 percent plus or minus 10 percent, and the sampling is carried out once every 3 months and respectively carried out at 0, 3, 6, 9 and 12 months. And (3) respectively inspecting parameters such as appearance, particle size, encapsulation efficiency, pH, osmotic pressure and the like.
Long term stability
Hot-pressing sterilization: packaging 5ml of baicalein nanometer suspension in ampoule bottle, and sterilizing at 121 deg.C under hot pressure for 15 min. Particle size, encapsulation efficiency, pH and osmotic pressure changes before and after sterilization were compared.
Stability before and after sterilization
Example 3
Prescription:
baicalein phospholipid complex 0.5g +1.5g
Phospholipid 10g
F-68 1.2g
Glycerol 5g
Water for injection to 100ml
The preparation process comprises the following steps:
1) dissolving baicalein, phospholipid and tetrahydrofuran (1g:3g:70ml) in a three-necked flask, heating at 40 deg.C, refluxing for 1-2 hr, vacuumizing to remove tetrahydrofuran, and drying in a vacuum drying oven (30 deg.C) for 12 hr to obtain baicalein-phospholipid complex
2) Stirring baicalein phospholipid complex, phospholipid and glycerol, and mixing to obtain semisolid dispersion; the prescription dose of F-68 is dissolved in the water for injection
3) Adding the semi-solid dispersion into an F-68 aqueous solution, and shearing and dispersing at high speed under an ice bath condition to form a coarse suspension;
4) placing the crude mixed suspension into a high-pressure homogenizer, and homogenizing at room temperature (400-800bar for 4-10 times);
5) filtration (0.45um microfiltration);
6) filling nitrogen for encapsulation;
7) sterilizing at 121 deg.C under hot pressure for 15-40 min.
Long-term stability: according to the market package of the injection, the injection is placed for 12 months at the room temperature of 25 ℃ plus or minus 2 ℃ and the relative humidity of RH60 percent plus or minus 10 percent, and the sampling is carried out once every 3 months and respectively carried out at 0, 3, 6, 9 and 12 months. And (3) respectively inspecting parameters such as appearance, particle size, encapsulation efficiency, pH, osmotic pressure and the like.
Long term stability
Hot-pressing sterilization: packaging 5ml of baicalein nanometer suspension in ampoule bottle, and sterilizing at 121 deg.C under hot pressure for 15 min. Particle size, encapsulation efficiency, pH and osmotic pressure changes before and after sterilization were compared.
Stability before and after sterilization
Example 4
Prescription:
the preparation process comprises the following steps:
1) dissolving baicalein, phospholipid and tetrahydrofuran (1g:3g:70ml) in a three-necked flask, heating at 40 deg.C, refluxing for 1-2 hr, vacuumizing to remove tetrahydrofuran, and drying in a vacuum drying oven (30 deg.C) for 12 hr to obtain baicalein-phospholipid complex;
2) adding baicalein-phospholipid complex into soybean oil, dispersing by high-speed shearing, dissolving, and adding phospholipid to obtain oil phase; adding glycerol poloxamer, etc. into water phase;
3) heating the oil phase and the water phase to 55 ℃, and adding the oil phase into the water phase;
4) shearing and emulsifying at high speed under ice bath condition to prepare primary emulsion, and homogenizing the primary emulsion at room temperature (400 and 800bar for 4-10 times);
5) filtration (0.45um microfiltration);
6) filling nitrogen for encapsulation;
7) sterilizing at 121 deg.C under hot pressure for 15-40 min.
Long-term stability: according to the market package of the injection, the injection is placed for 12 months at the room temperature of 25 ℃ plus or minus 2 ℃ and the relative humidity of RH60 percent plus or minus 10 percent, and the sampling is carried out once every 3 months and respectively carried out at 0, 3, 6, 9 and 12 months. And (3) respectively inspecting parameters such as appearance, particle size, encapsulation efficiency, pH, osmotic pressure and the like.
Long term stability
Hot-pressing sterilization: packaging 5ml of baicalein submicron emulsion in an ampoule bottle, and sterilizing at 121 deg.C under hot pressure for 15 min. Particle size, encapsulation efficiency, pH and osmotic pressure changes before and after sterilization were compared.
Example 5
Baicalein 1g
Phospholipid 10g
Solutol 0.1g
15g of glycerol
Water for injection to 500ml
The preparation process comprises the following steps:
1) adding phospholipid, Solutol and glycerol into water, and preparing a coarse suspension by using high-speed shearing dispersion under the ice bath condition;
2) homogenizing the crude suspension (600-800bar, 6-10 times) to prepare micelles;
3) filtration (0.45um microfiltration);
4) filling nitrogen for encapsulation;
5) sterilizing at 121 deg.C under hot pressure for 15-40 min.
Long-term stability: according to the market package of the injection, the injection is placed for 12 months at the room temperature of 25 ℃ plus or minus 2 ℃ and the relative humidity RH of 60 percent plus or minus 10 percent, and samples are taken once every 3 months and respectively taken at 0, 3, 6, 9 and 12. And (3) respectively inspecting parameters such as appearance, particle size, encapsulation efficiency, pH, osmotic pressure and the like.
Long term stability
Hot-pressing sterilization: packaging 5ml of baicalein micelle in ampoule bottle, and sterilizing at 121 deg.C under hot pressure for 15 min. Particle size, encapsulation efficiency, pH and osmotic pressure changes before and after sterilization were compared.
Stability of autoclave sterilization
Example 6
Prescription:
baicalein 1g
Phospholipid 10g
0.1g of cholesterol
15g of glycerol
Water for injection to 500ml
The preparation process comprises the following steps:
1) weighing phospholipid, baicalein and cholesterol, and adding a proper amount of dichloromethane for dissolving;
2) under the condition of water bath at 30 ℃, organic solvent is removed by rotary evaporation to form a uniform film;
3) adding water of the formula amount, hydrating at 35 ℃ for 30min, and homogenizing (600-800bar, 6-10 times);
4) adding glycerol and filtering (0.45um microporous membrane);
5) filling nitrogen for encapsulation;
6) sterilizing at 121 deg.C under hot pressure for 15-40 min.
Long-term stability: according to the market package of the injection, the injection is placed for 12 months at the room temperature of 25 ℃ plus or minus 2 ℃ and the relative humidity RH of 60 percent plus or minus 10 percent, and samples are taken once every 3 months and respectively taken at 0, 3, 6, 9 and 12. And (3) respectively inspecting parameters such as appearance, particle size, encapsulation efficiency, pH, osmotic pressure and the like.
Long term stability
Hot-pressing sterilization: packaging baicalein liposome 5ml in ampoule bottle, and sterilizing at 121 deg.C under hot pressure for 15 min. Particle size, encapsulation efficiency, pH and osmotic pressure changes before and after sterilization were compared.
Stability of autoclave sterilization
Physical stability determination method:
and (3) hot-pressing sterilization stability: packaging 5ml of each baicalein preparation in an ampoule bottle, autoclaving at 121 deg.C for 15min, and observing the appearance of each preparation before and after sterilization.
Centrifugal stability: centrifuging each baicalein preparation at 4000rpm for 10min, and observing the appearance of each preparation before and after centrifugation to determine whether layering precipitation phenomenon occurs
Low-temperature experiment: placing each baicalein preparation at 4 deg.C for 12h, placing at 40 deg.C for 12h, circulating for 3 times, centrifuging at 4000rpm for 10min, and observing whether there is layering or precipitation phenomenon in appearance of each preparation before and after centrifugation.
Physical stability of each preparation
Claims (6)
1. The baicalein nanosuspension is characterized in that the prescription of the baicalein nanosuspension contains the following substances in percentage by mass and is prepared by the following preparation method:
the rest is water for injection;
the method comprises the following steps:
1) dissolving baicalein, phospholipid and tetrahydrofuran according to the proportion of 1g: 1-5 g:70ml, heating at 30-45 ℃, refluxing for 1-2h, vacuumizing to remove tetrahydrofuran, and drying in a vacuum drying oven at 20-40 ℃ to obtain a baicalein-phospholipid complex;
2) stirring baicalein phospholipid complex, phospholipid and glycerol according to the prescription amount, and uniformly mixing to obtain a semisolid dispersion; the prescription amount of F-68 is dissolved in water for injection;
3) adding the semi-solid dispersion into an F-68 aqueous solution, and shearing and dispersing at high speed under an ice bath condition to form a coarse suspension;
4) placing the crude mixed suspension into a high-pressure homogenizer, and homogenizing for 4-10 times at the room temperature of 400-800 bar;
5) filtering, bottling, and sterilizing under hot pressure.
2. The baicalein nanosuspension according to claim 1, wherein the prescription of the baicalein nanosuspension comprises the following substances in percentage by mass:
the balance of water for injection.
3. The baicalein nanosuspension according to claim 2, wherein the prescription of the baicalein nanosuspension comprises the following substances in percentage by mass:
the balance of water for injection.
4. The baicalein nanosuspension according to claim 1, wherein the mass ratio of baicalein to phospholipids in the baicalein phospholipid complex is 1: 1 to 5.
5. The baicalein nanosuspension according to claim 4, wherein the mass ratio of baicalein to phospholipid in the baicalein phospholipid complex is 1: 3.
6. a process for the preparation of a baicalein nanosuspension as claimed in claim 1, characterized in that the process comprises the steps of:
1) dissolving baicalein, phospholipid and tetrahydrofuran according to the proportion of 1g: 1-5 g:70ml, heating at 30-45 ℃, refluxing for 1-2h, vacuumizing to remove tetrahydrofuran, and drying in a vacuum drying oven at 20-40 ℃ to obtain a baicalein-phospholipid complex;
2) stirring baicalein phospholipid complex, phospholipid and glycerol according to the prescription amount, and uniformly mixing to obtain a semisolid dispersion; the prescription amount of F-68 is dissolved in water for injection;
3) adding the semi-solid dispersion into an F-68 aqueous solution, and shearing and dispersing at high speed under an ice bath condition to form a coarse suspension;
4) placing the crude mixed suspension into a high-pressure homogenizer, and homogenizing for 4-10 times at the room temperature of 400-800 bar;
5) filtering, bottling, and sterilizing under hot pressure.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810616241.7A CN108653206B (en) | 2018-06-14 | 2018-06-14 | Baicalein nano suspension and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810616241.7A CN108653206B (en) | 2018-06-14 | 2018-06-14 | Baicalein nano suspension and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108653206A CN108653206A (en) | 2018-10-16 |
| CN108653206B true CN108653206B (en) | 2020-04-07 |
Family
ID=63775932
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810616241.7A Active CN108653206B (en) | 2018-06-14 | 2018-06-14 | Baicalein nano suspension and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108653206B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110051654A (en) * | 2019-04-19 | 2019-07-26 | 天津中医药大学 | The ophthalmically acceptable lipid nano particle preparation of baicalein and preparation method thereof of N- trimethyl chitin modification |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102824356A (en) * | 2012-09-25 | 2012-12-19 | 江西中医学院 | Baicalin nano crystal suspension, nano crystal dry powder and methods for preparing baicalin nano crystal suspension and nano crystal dry powder |
| CN107281100A (en) * | 2016-03-30 | 2017-10-24 | 上海现代药物制剂工程研究中心有限公司 | A kind of preparation method of insoluble drug nanosuspension |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101704838A (en) * | 2009-11-30 | 2010-05-12 | 浙江大学 | Baicalein phospholipid complex and preparation method thereof |
-
2018
- 2018-06-14 CN CN201810616241.7A patent/CN108653206B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102824356A (en) * | 2012-09-25 | 2012-12-19 | 江西中医学院 | Baicalin nano crystal suspension, nano crystal dry powder and methods for preparing baicalin nano crystal suspension and nano crystal dry powder |
| CN107281100A (en) * | 2016-03-30 | 2017-10-24 | 上海现代药物制剂工程研究中心有限公司 | A kind of preparation method of insoluble drug nanosuspension |
Non-Patent Citations (1)
| Title |
|---|
| Panax Notoginseng Saponins as a Novel Nature Stabilizer for Poorly Soluble Drug Nanocrystals:A Case Study with Baicalein;Yuanbiao Xie,et al;《Molecules》;20160830;第21卷(第1149期);1-11 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108653206A (en) | 2018-10-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | Cancer nanomedicines stabilized by π-π stacking between heterodimeric prodrugs enable exceptionally high drug loading capacity and safer delivery of drug combinations | |
| WO2010139278A1 (en) | Preparation method of drug loaded emulsion | |
| CN106420610B (en) | A kind of ionic liquid micro emulsion and its application | |
| CN100415221C (en) | Method for preparing curcumin lyophilized liposome | |
| CN101569607B (en) | Di-demethoxycurcumin precursor liposome and preparation method thereof | |
| WO2012028101A1 (en) | Liquid compositions of insoluble drugs and preparation methods thereof | |
| WO2011069414A1 (en) | Injection solution and injection formulation of traditional chinese medicine volatile oil and preparation mehtod therof | |
| CN102824356A (en) | Baicalin nano crystal suspension, nano crystal dry powder and methods for preparing baicalin nano crystal suspension and nano crystal dry powder | |
| CN100506208C (en) | Chansu-loaded nanoliposome and preparation method thereof | |
| CN104224710B (en) | A kind of docetaxel nanometer micella, its preparation method and application | |
| WO2012146057A1 (en) | Curcuminoid injection solution and intravenous injection | |
| CN107496186A (en) | A kind of Kaempferol nano-composition and its preparation method and application | |
| CN101612121A (en) | The preparation of microemulsion containing paclitaxel method | |
| WO2016177346A1 (en) | Cabazitaxel fat emulsion injection, and preparation method and use thereof | |
| CN101088523B (en) | Nanometer solid lipid particle of active skullcap components and its prepn process and prepn | |
| CN113197852A (en) | Cannabidiol nano micelle preparation and preparation method thereof | |
| CN106946975A (en) | A kind of triptolide derivative and preparation method thereof and preparation | |
| CN105726494B (en) | Andrographolide nano suspension composition and its preparation method and application | |
| CN108653206B (en) | Baicalein nano suspension and preparation method thereof | |
| US20070042009A1 (en) | Topical composition for delivery of salicylates | |
| CN105287377A (en) | Taxol polymer micelle drug-loading system and preparation method and application thereof | |
| WO2007009355A1 (en) | Paclitaxel injection and preparation method thereof | |
| CN101658495B (en) | Hydrobromic acid lappaconitine solid lipid nano particle and preparation method thereof | |
| CN110251487B (en) | Preparation method and application of alcohol soluble protein nanoparticles for improving drug-loading rate and oral bioavailability of docetaxel | |
| CN111568882A (en) | Compound curcumin nanoparticle and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |