CN115624528A - Gambogic acid freeze-dried emulsion and preparation method and application thereof - Google Patents
Gambogic acid freeze-dried emulsion and preparation method and application thereof Download PDFInfo
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- 239000000839 emulsion Substances 0.000 title claims abstract description 124
- GEZHEQNLKAOMCA-RRZNCOCZSA-N (-)-gambogic acid Chemical compound C([C@@H]1[C@]2([C@@](C3=O)(C\C=C(\C)C(O)=O)OC1(C)C)O1)[C@H]3C=C2C(=O)C2=C1C(CC=C(C)C)=C1O[C@@](CCC=C(C)C)(C)C=CC1=C2O GEZHEQNLKAOMCA-RRZNCOCZSA-N 0.000 title claims abstract description 67
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
The invention discloses a gambogic acid freeze-dried emulsion and a preparation method and application thereof. The garcinolic acid freeze-dried emulsion prepared by the invention solves the problem of poor water solubility of garcinolic acid, improves the solubility of the medicament, and can reduce the toxic and side effect on normal tissues, improve the oral bioavailability and improve the drug effect through the medicament release characteristic of the Pickering emulsion.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to garcinolic acid freeze-dried emulsion and a preparation method and application thereof.
Background
Gambogic acid is a kind of cagelike xanthone compounds extracted from the dried resin of natural plant Garcinia cambogia, and is one of the main active ingredients of Garcinia cambogia. Gambogic acid has strong anticancer activity, and has therapeutic effect on gastric cancer, lung cancer, breast cancer, lymphoma, skin cancer, etc., without influence on normal hematopoietic system and leukocyte. However, garcinolic acid has very poor water solubility, and although water solubility is increased under alkaline conditions, too high a pH value leads to hydrolysis of garcinolic acid. Meanwhile, gambogic acid is unstable and is easily decomposed under the influence of conditions such as temperature, humidity, solvent and the like, so that a lot of obstacles are brought to production and clinical application.
Two liquids which are not mutually soluble are mixed, wherein one liquid is dispersed in the other liquid in a form of liquid drops to form a heterogeneous liquid dispersion system called emulsion, and the absorption of the medicine can be obviously improved and the bioavailability can be improved after the medicine with strong fat solubility is prepared into the emulsion. The gambogic acid has extremely strong lipophilicity, the LogP can reach 7.24, and the solubility in various oil phases is good, so that the gambogic acid can be dissolved in the oil phases to prepare an emulsion, the oral bioavailability of the gambogic acid is improved, and the drug effect is improved.
The Pickering emulsion is a novel emulsion which uses nano or micron solid particles to replace the traditional organic surfactant to stabilize an emulsion system. Different from the traditional surfactant, the solid particles mainly rely on the adsorption of the solid particles on an oil-water interface and a space barrier formed by the interaction among the particles to stabilize the emulsion, and the Pickering emulsion has the unique advantages of greatly reducing the dosage of the traditional emulsifier and saving the cost; the toxic action of the solid particles to human bodies is far less than that of the surfactant; is environment-friendly; has strong interface stability.
Despite the high stability of Pickering emulsions, problems of delamination, oil separation, ostwald ripening, etc. are still unavoidable during long-term storage. Meanwhile, gambogic acid is also not good in stability under various environmental conditions.
Therefore, the application designs that gambogic acid is prepared into O/W type Pickering emulsion and solidified into dry emulsion so as to overcome the defects.
Disclosure of Invention
The invention aims to provide a gambogic acid freeze-dried emulsion and a preparation method and application thereof.
In order to achieve the purpose, the invention adopts the following technical scheme:
a garcinolic acid lyophilized emulsion is prepared from garcinolic acid, oil phase, chitosan, water, glacial acetic acid, sodium hydroxide and lyophilized protectant;
the oil phase is selected from medium chain triglycerides, castor oil, soybean oil or glycerol monolinoleate;
the freeze-drying protective agent is selected from mannitol, lactose, maltodextrin, trehalose, sucrose and glucose.
Further, the oil phase is medium chain triglyceride, and the lyoprotectant is maltodextrin.
The preparation method of the gambogic acid freeze-dried emulsion comprises the following steps:
and 5, adding a freeze-drying protective agent into the gambogic acid Pickering emulsion, and carrying out freeze drying to obtain the gambogic acid freeze-dried emulsion.
Further, the mass percentage concentration of the chitosan solution in the step 1 is 0.1-2%.
Further, the pH value of the chitosan solution is adjusted to 6.0-7.0 in the step 2.
Furthermore, in the step 4, the high-speed shearing rotating speed is 2000-20000 rpm, the shearing time is 2-10 minutes, the homogenizing pressure is 5000-25000 psi, and the homogenizing times is 1-10 times.
Further, in the gambogic acid Pickering emulsion, the mass percentage concentration of the gambogic acid is 0.1-5%, the volume percentage concentration of the oil phase is 5-50%, and the mass percentage concentration of the chitosan is 0.05-2%.
Further, in the step 5, the dosage ratio of the gambogic acid Pickering emulsion to the freeze-drying protective agent is 100mL:5 to 30g.
The application of the gambogic acid freeze-dried emulsion in preparing a gambogic acid oral preparation.
The gambogic acid freeze-dried emulsion is applied to preparing medicaments for treating tumors.
According to the invention, the amino group of chitosan is deprotonated by adjusting pH, the surface charge is reduced, the molecular chain is contracted, and the chitosan self-aggregates into nano particles which can be rapidly adsorbed on an oil-water interface, so that the oil phase loaded with gambogic acid is emulsified into Pickering emulsion.
Compared with the existing oral carrier system for delivering gambogic acid, the invention has the advantages that:
(1) The Pickering gambogicacid freeze-dried emulsion prepared by the invention solves the problem of poor water solubility of gambogicacid, improves the solubility of the medicine, and can reduce the toxic and side effects on normal tissues, improve the oral bioavailability and improve the efficacy by the medicine release characteristic of the Pickering emulsion.
(2) The chitosan is linear polysaccharide which has wide sources, low price, safety and no toxicity, and the biocompatibility and the degradability of the chitosan are far superior to those of the traditional surfactant. And the chitosan self-aggregation nano-particles for preparing the stable Pickering emulsion only need to be adjusted in pH, so that the process is green and the operation is simple.
(3) The freeze-dried emulsion is a good preparation form, not only retains the advantages of the emulsion, but also removes the water in the emulsion, improves the stability and is convenient to transport and store. The freeze-dried Pickering emulsion can be further prepared into solid dosage forms such as granules, hard capsules or tablets.
Drawings
FIG. 1 is a graph showing the distribution of particle size after reconstitution of the lyophilized Pickering emulsion of gambogic acid in example 1;
FIG. 2 is a microscopic structure of the reconstituted garcinolic acid lyophilized Pickering emulsion of example 1;
fig. 3 is the release profile of the lyophilized Pickering emulsion of gambogic acid in example 1 in a release medium.
Detailed Description
The gambogic acid has poor oral absorption and low bioavailability due to extremely low water solubility; however, gambogic acid is highly lipophilic, so the present invention is designed to dissolve it into the oil phase and develop into Pickering emulsion. Despite the high stability of Pickering emulsions, problems of delamination, oil separation, ostwald ripening, etc. are still unavoidable during long-term storage. Meanwhile, gambogic acid is also not good in stability under various environmental conditions. The present invention is therefore further designed to employ a freeze-drying process to enhance the stability of the Pickering emulsion.
Through an early-stage groping experiment, the solubility of gambogic acid in medium chain triglyceride is higher, and a Pickering emulsion prepared by taking the medium chain triglyceride as an oil phase has good appearance property, smaller particle size, good stability and low viscosity, so the medium chain triglyceride is selected as the oil phase.
Meanwhile, the chitosan is linear polysaccharide which is wide in source, low in price, safe and non-toxic, and good in biocompatibility and degradability, and the self-aggregation nanoparticles for preparing the stable Pickering emulsion only need to adjust the pH value of a chitosan solution, so that the process is green and the operation is simple. Therefore, chitosan was chosen as the solid particle for stabilizing Pickering emulsions.
The prescription process of the gambogic acid Pickering emulsion is as follows:
1. screening of oil phase species
1.1 drug Loading
Weighing 1mL of oil phase medium chain triglyceride, soybean oil, castor oil and mono linoleic acid glyceride in a centrifuge tube, adding a certain amount of gambogic acid raw material medicine at room temperature (25 ℃), and placing on a test tube rotary mixer for continuous mixing. Observing the dissolution condition of the gambogic acid in each oil phase, if the solution is clear and transparent, continuously adding a certain amount of gambogic acid raw material medicine, and repeating the operation.
The results are shown in Table 1.
1.2 milk Forming ability
(1) Preparing 18mL of 0.75% (w/v) glacial acetic acid solution, weighing 90mg of chitosan powder and adding the chitosan powder into the glacial acetic acid solution under stirring at room temperature to prepare a chitosan solution with the concentration of 0.5% (w/v), wherein the mass ratio of chitosan to glacial acetic acid is 2:3; continuously stirring at room temperature to completely hydrate and dissolve the chitosan; the chitosan solution was then vacuum filtered to remove insoluble impurities.
(2) The chitosan solution was adjusted to pH 6.6 with sodium hydroxide solution to prepare an aqueous phase containing self-aggregated chitosan nanoparticles.
(3) And (3) taking 18mL of the aqueous phase obtained in the step (2), and adding 2mL of medium chain triglyceride, soybean oil, castor oil and glycerol monolinoleate respectively. Uniformly mixing the oil phase and the water phase by high-speed shearing to prepare a coarse emulsion, wherein the high-speed shearing rotating speed is 10,000rpm, and the shearing time is 5min; and (3) homogenizing the crude emulsion in a micro-jet homogenizer at the homogenizing pressure of 15,000rpm for 5 times to obtain the Pickering emulsion with stable self-aggregated chitosan nanoparticles.
Observing the appearance of the Pickering emulsion prepared from different oil phases, including color, smell, fluidity and the like; 0.1mL of the emulsion was diluted 1000-fold with purified water and the particle size was measured by dynamic light scattering using a nanometer particle sizer.
The results are shown in Table 1.
TABLE 1 drug loading and emulsion formation Capacity for different oil phases
As can be seen from table 1, medium chain triglycerides were selected as the oil phase of the Pickering emulsion because of their high drug loading, good appearance of the emulsion and relatively small average particle size.
2. pH of Chitosan solution
A plurality of portions of 18mL0.5% chitosan solution were prepared according to the method described under item 1.2, and the pH of the solution was adjusted to 6.0, 6.6, 6.7, 6.8, 6.9, and 7.0 with sodium hydroxide solution, respectively. 2mL of medium chain triglyceride was added and a Pickering emulsion was prepared according to the procedure under item 1.2. 0.1mL of the emulsion was diluted 1000-fold with purified water and the particle size was measured by dynamic light scattering using a nanometer particle sizer.
TABLE 2 particle size of emulsions prepared with different chitosan solution pH
| pH of Chitosan solution | Average particle diameter (nm) |
| 6.0 | 988.78 |
| 6.6 | 842.08 |
| 6.7 | 838.25 |
| 6.8 | 748.67 |
| 6.9 | 786.14 |
| 7.0 | / |
As can be seen from Table 2, when the pH of the chitosan solution reached 6.8, the particle size of the emulsion had the minimum value, so that the pH of the chitosan solution was optimally 6.8.
3. Concentration of chitosan solution
18mL of chitosan solutions with chitosan concentrations of 0.3%, 0.4%, 0.5%, 0.6%, 0.7% were prepared according to the method of item 1.2, and the pH of the solution was adjusted to 6.8 with sodium hydroxide solution. 2mL of medium chain triglyceride was added and a Pickering emulsion was prepared according to the procedure under item 1.2. 0.1mL of the emulsion was taken and diluted 1000-fold with purified water, and the particle size was determined by dynamic light scattering using a nano-particle sizer.
TABLE 3 particle size of emulsions prepared with chitosan solutions of different concentrations
| Concentration of Chitosan solution (%) | Average particle diameter (nm) |
| 0.3 | 1193.61 |
| 0.4 | 882.81 |
| 0.5 | 748.67 |
| 0.6 | 748.63 |
| 0.7 | 749.50 |
As can be seen from Table 3, the particle size of the emulsion is minimized when the chitosan concentration is 0.5%, so the chitosan concentration is optimally 0.5%.
4. Process screening
4.1 high shear rate
18mL of a 0.5% chitosan solution was prepared according to the method described under 1.2, and the pH of the solution was adjusted to 6.8 with a sodium hydroxide solution. 2mL of medium chain triglyceride was added, and Pickering emulsion was prepared according to the procedure under item 1.2, setting the high shear time to 5min, the microfluidization pressure to 15,000psi, the homogenization times to 5 times, and the high shear speeds to 5,000rpm, 10,000rpm, and 15,000rpm, respectively. 0.1mL of the emulsion was diluted 1000-fold with purified water and the particle size was measured by dynamic light scattering using a nanometer particle sizer.
4.2 high shear time
A18mL0.5% chitosan solution was prepared according to the method described under item 1.2, and the pH of the solution was adjusted to 6.8 with a sodium hydroxide solution. Adding 2mL of medium chain triglyceride, preparing Pickering emulsion according to the process under item 1.2, setting the high-speed shearing rotation speed to be 10,000rpm, the microjet homogenization pressure to be 15,000psi, the homogenization times to be 5 times, and respectively setting the high-speed shearing time to be 2min, 5min, 8min and 10min. 0.1mL of the emulsion was taken and diluted 1000-fold with purified water, and the particle size was determined by dynamic light scattering using a nano-particle sizer.
4.3 microjet homogenization pressure
18mL0.5% chitosan solution was prepared according to the method given under 1.2, and the pH of the solution was adjusted to 6.8 with sodium hydroxide solution. 2mL of medium chain triglyceride was added, and Pickering emulsion was prepared according to the procedure under item 1.2, setting the high shear speed at 10,000rpm, the high shear time at 8min, the number of microfluidization homogenizers at 5 times, and the homogenize pressures at 10,000psi, 15,000psi, and 20,000psi, respectively. 0.1mL of the emulsion was diluted 1000-fold with purified water and the particle size was measured by dynamic light scattering using a nanometer particle sizer.
4.4 microfluidization number of homogenizers
A18mL0.5% chitosan solution was prepared according to the method described under item 1.2, and the pH of the solution was adjusted to 6.8 with a sodium hydroxide solution. Adding 2mL of medium chain triglyceride, preparing Pickering emulsion according to the process under item 1.2, setting the high-speed shearing rotation speed to be 10,000rpm, setting the high-speed shearing time to be 8min, setting the micro-jet homogenization pressure to be 15,000psi, and setting the homogenization times to be 2 times, 5 times and 8 times respectively. 0.1mL of the emulsion was diluted 1000-fold with purified water and the particle size was measured by dynamic light scattering using a nanometer particle sizer.
TABLE 4 particle size of emulsions prepared under different process conditions
According to the data in Table 4, it was determined that the Pickering emulsion was prepared at a high shear rate of 10,000rpm for 8min, and at a microjet homogenization pressure of 15,000psi for 5 times.
The invention is described in further detail below with reference to the figures and the specific examples, which should not be construed as limiting the invention. Modifications or substitutions to methods, procedures, or conditions of the invention may be made without departing from the spirit and scope of the invention. The experimental methods and reagents of the formulations not specified in the examples are in accordance with the conventional conditions in the art.
Example 1
Gambogic acid freeze-dried Pickering emulsion 1
The components and contents are as follows:
the preparation method of this example is as follows
(1) Preparing 18mL of 0.75% (w/v) glacial acetic acid solution, and adding 90mg of chitosan powder into the glacial acetic acid solution under stirring at room temperature to prepare 0.5% (w/v) chitosan solution; continuously stirring at room temperature to completely hydrate and dissolve the chitosan; the chitosan solution was then vacuum filtered to remove insoluble impurities.
(2) The chitosan solution was adjusted to pH6.8 with sodium hydroxide solution to prepare an aqueous phase containing self-aggregated chitosan nanoparticles.
(3) Accurately weighing 400mg gambogic acid into 2mL oil phase medium chain triglyceride, stirring at room temperature until gambogic acid is completely dissolved to form a clear single-phase solution, and obtaining 200mg/mL gambogic acid oil solution.
(4) Taking 18mL of the aqueous phase obtained in step (2), 2mL of gambogic acid-loaded oil phase was added. Uniformly mixing the oil phase and the water phase by high-speed shearing to prepare a coarse emulsion, wherein the high-speed shearing rotating speed is 10000rpm, and the shearing time is 8min; and (3) homogenizing the crude emulsion in a microfluidizer at the homogenizing pressure of 15000rpm for 5 times to obtain the Pickering emulsion with stable self-aggregated chitosan nanoparticles.
(5) Weighing 20% (w/v) maltodextrin into the Pickering gambogic acid emulsion obtained in the step (4), placing the Pickering gambogic acid emulsion in a cold trap of a freeze dryer for pre-freezing, and then carrying out freeze drying for 24h to completely remove water, thus obtaining the Pickering gambogic acid freeze-dried emulsion.
Example 2
Gambogic acid freeze-dried Pickering emulsion 2
The components and contents are as follows:
the preparation method of this example is the same as example 1.
Example 3
Gambogic acid freeze-dried Pickering emulsion 3
The components and contents are as follows:
the preparation method of this example is the same as example 1.
Test example 1
Samples of the garcinolic acid lyophilized Pickering emulsions prepared in examples 1 to 3 were evaluated for appearance, redispersibility, and particle size change rate. The evaluation criteria are as follows:
(1) appearance: the product has the advantages of no collapse, no shrinkage, no wall adhesion, uniform color, no mottle, and fine texture.
(2) Redispersibility: taking a proper amount of the freeze-dried Pickering emulsion of each embodiment, adding water according to the required amount, shaking for dispersion, and quickly dispersing after shaking to obtain the emulsion with good redispersibility; if need shake many times, or need supersound, vortex is poor.
(3) Rate of change of particle size: taking a proper amount of the freeze-dried Pickering emulsion of each embodiment, adding water according to the required amount, shaking for dispersion, and measuring the particle size d of the freeze-dried Pickering emulsion by dynamic light scattering 1 And the particle size d of the emulsion before freeze-drying 0 By comparison, the particle size change (%) was calculated according to the formula:
the results are shown in the following table:
TABLE 5 Freeze-dried emulsions prepared with different lyoprotectants
| Name (R) | Appearance of the product | Redispersibility | Rate of change in particle diameter (%) |
| Mannitol | White loose powder | Is poor | 255.12 |
| Lactose | With mottled and partially sticky | Good effect | 106.9 |
| Maltodextrin | Looser yellow powder | Good effect | 99.70 |
From the above results, it is clear that, when maltodextrin was selected as the freeze-drying protective agent, the gambogic acid freeze-dried Pickering emulsion was excellent in appearance, redispersibility, and particle size change rate.
Test example 2
Taking 0.2g of the gambogic acid freeze-dried Pickering emulsion prepared in the example 1, adding 1mL of purified water, hydrating and oscillating the emulsion, recovering the emulsion, diluting the emulsion by 1000 times by using the purified water, and measuring the particle size and the polydispersity index of the emulsion by using a nanometer particle size analyzer through dynamic light scattering, wherein the particle size is 336.21 +/-3.15 nm, and the polydispersity index is 0.115 +/-0.022; the Zeta potential was determined using electrophoretic light scattering and was 35.37. + -. 0.95mV. As shown in fig. 1.
0.2g of the garcinolic acid lyophilized Pickering emulsion prepared in example 1 was added with 1mL of purified water, and the mixture was reconstituted into an emulsion after hydration and shaking, diluted 10-fold with purified water, and the form was observed with a microscope. As shown in fig. 2, the emulsion morphology after reconstitution was good.
Test example 3
In vitro Release assay
The in vitro release behavior of the garcinolic acid lyophilized Pickering emulsion prepared in example 1 in simulated intestinal fluid was examined by direct drug release method. 0.5g of the lyophilized Pickering emulsion of gambogic acid prepared in example 1 was precisely weighed, directly put into 100mL of PBS (pH 6.8) containing 0.5% (w/v) Tween 20, sealed and placed in a constant temperature gas bath shaker (37 ℃,100 rpm), and simultaneously a blank release medium was placed for fluid replacement. After 0.25h, 0.5h, 1h, 2h, 2.5h and 4h after the start of the in vitro release experiment, 1mL of the solution is taken out of the beaker and filtered by a 0.22 μm water-based filter membrane, and the subsequent filtrate is taken as the test solution. And immediately replenishing the same volume of release medium at the same temperature to maintain the total volume constant. And (3) detecting and analyzing the test solution by using HPLC, taking time as an abscissa and cumulative release as an ordinate, and drawing an in vitro release curve.
C 1 、C 2 、…、C n : the concentration of the sample to be tested is sampled for the 1 st, the 2 nd, the … and the n times;
V 0 v: release medium initial volume and sampling volume;
w: the total dosage is added.
The results are shown in fig. 3, the drug can diffuse from the oil phase into the release medium more rapidly, and the release rate is faster; after 4h, gambogic acid in Pickering emulsion was almost completely released.
Test example 4
Stability test
The garcinolic acid lyophilized Pickering emulsion prepared in example l was stored at room temperature (25 ℃) and 4 ℃ for three months, respectively. The appearance, the redispersibility and the particle size change rate of the freeze-dried Pickering emulsion of 0 th month, 1 th month, 2 th month and 3 rd month are observed, and no significant difference exists. Further, the content of the drug is measured by high performance liquid chromatography, and the change is hardly found, so that the stability of the gambogic acid freeze-dried Pickering emulsion is good.
TABLE 6 stability test results of Gambogic acid lyophilized Pickering emulsion
From the above results, it is clear that the stability of the garcinolic acid lyophilized Pickering emulsion preparation prepared by the present invention is good.
Claims (9)
1. A garcinolic acid freeze-dried emulsion is characterized in that: the freeze-dried emulsion is obtained by freeze-drying gambogic acid Pickering emulsion, and the gambogic acid Pickering emulsion comprises the following components in percentage by mass and volume: 0.1-5% of gambogic acid, 5-50% of an oil phase, 0.05-2% of chitosan, 0.075-3% of glacial acetic acid, 0.1-5% of sodium hydroxide, 5-30% of a freeze-drying protective agent and the balance of water;
the oil phase is selected from medium chain triglycerides, castor oil, soybean oil or glycerol monolinoleate;
the freeze-drying protective agent is selected from mannitol, lactose, maltodextrin, trehalose, sucrose and glucose.
2. The lyophilized emulsion of gambogic acid according to claim 1, wherein: the oil phase is medium chain triglyceride, and the freeze-drying protective agent is maltodextrin.
3. The method for preparing a garcinolic acid lyophilized emulsion according to claim 1, wherein: the method comprises the following steps:
step 1, dissolving chitosan in a glacial acetic acid solution to obtain a chitosan solution;
step 2, adjusting the pH value of the chitosan solution to be used as an emulsion water phase;
step 3, dissolving gamboge acid in the oil phase to obtain a gamboge acid oil solution;
step 4, adding the gambogic acid oil solution into the emulsion water phase, preparing a coarse emulsion through high-speed shearing, and homogenizing the coarse emulsion through microjet to obtain a gambogic acid Pickering emulsion;
and 5, adding a freeze-drying protective agent into the gambogic acid Pickering emulsion, and carrying out freeze drying to obtain the gambogic acid freeze-dried emulsion.
4. The production method according to claim 3, characterized in that: in the step 1, the mass percentage concentration of the chitosan solution is 0.1-2%.
5. The production method according to claim 3, characterized in that: and (2) adjusting the pH value of the chitosan solution to 6.0-7.0.
6. The production method according to claim 3, characterized in that: in the step 4, the high-speed shearing rotating speed is 2000-20000 rpm, the shearing time is 2-10 minutes, the homogenizing pressure is 5000-25000 psi, and the homogenizing times are 1-10 times.
7. The production method according to claim 3, characterized in that: in the step 5, the dosage ratio of the gambogic acid Pickering emulsion to the freeze-drying protective agent is 100mL:5 to 30g.
8. Use of the lyophilized emulsion of gambogic acid according to claim 1 for the preparation of an oral formulation of gambogic acid.
9. Use of a lyophilized emulsion of gambogic acid according to claim 1 for the preparation of a medicament for the treatment of tumors.
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| CN108783373A (en) * | 2018-04-03 | 2018-11-13 | 上海应用技术大学 | A kind of citral pickering emulsion and preparation method thereof |
| CN110151696A (en) * | 2019-06-27 | 2019-08-23 | 西南大学 | A kind of puerarin freeze-drying pik woods emulsion and preparation method thereof |
| CN114404362A (en) * | 2022-02-15 | 2022-04-29 | 南京芩康医药科技有限公司 | Gambogic acid oral composition and application thereof in preparation of tumor treatment medicines |
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| CN105663141A (en) * | 2016-03-24 | 2016-06-15 | 北京茗泽中和药物研究有限公司 | Ophthalmic emulsion with difluprednate |
| CN108783373A (en) * | 2018-04-03 | 2018-11-13 | 上海应用技术大学 | A kind of citral pickering emulsion and preparation method thereof |
| CN110151696A (en) * | 2019-06-27 | 2019-08-23 | 西南大学 | A kind of puerarin freeze-drying pik woods emulsion and preparation method thereof |
| CN114404362A (en) * | 2022-02-15 | 2022-04-29 | 南京芩康医药科技有限公司 | Gambogic acid oral composition and application thereof in preparation of tumor treatment medicines |
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