CN109091458B - Crocetin microemulsion and preparation method of freeze-dried powder thereof - Google Patents
Crocetin microemulsion and preparation method of freeze-dried powder thereof Download PDFInfo
- Publication number
- CN109091458B CN109091458B CN201811028777.3A CN201811028777A CN109091458B CN 109091458 B CN109091458 B CN 109091458B CN 201811028777 A CN201811028777 A CN 201811028777A CN 109091458 B CN109091458 B CN 109091458B
- Authority
- CN
- China
- Prior art keywords
- crocetin
- microemulsion
- solution
- freeze
- dissolving
- 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
Images
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- 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
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a crocetin microemulsion and a preparation method of a freeze-dried powder thereof, wherein the crocetin has strong antioxidant activity, can protect the cardiovascular system, can inhibit skin cancer and the like, and has potential application value in medicines, health-care foods and cosmetics; but the crocetin is difficult to dissolve in water and common organic solvents, and the use of the crocetin is severely limited. The invention provides a method for effectively increasing the water solubility of crocetin based on the micro-emulsification principle, so that the solubility of crocetin in water is increased by 800 times, the problem that crocetin is difficult to dissolve in water is solved, and a foundation is laid for the application of crocetin.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a crocetin microemulsion and a preparation method of a lyophilized powder thereof.
Background
Saffron is a rare herbal medicine, is originally produced in mediterranean regions, and has the effects of promoting blood circulation to remove blood stasis, cooling blood and removing toxic substances, resolving stagnation and tranquilizing mind and the like. It has now been shown that the major active substance of saffron is crocin (crocin), which is hydrolyzed to remove gentiobiose and form crocetin (crocetin). Crocetin has strong antioxidant activity, and can protect cardiovascular system and inhibit skin cancer[1]Has the functions of treating skin diseases, and has potential in medicine and skin care productsThe application value of the method is high. However, the crocetin molecule (with a relative molecular weight of 328g/mol) is smaller than the crocin molecule (with a relative molecular weight of 976g/mol), has stronger adhesion to the skin, and can easily penetrate the epidermis to exert physiological activity when added to cosmetics as an active substance. In addition, animal experiments also demonstrated this. Zhang Ying[2]The pharmacological kinetics of the crocin is studied by rats as experimental subjects, and only the crocin is detected in the plasma of the rats, but the crocin is not detected. This indicates that the oral crocin is absorbed in the form of crocetin and exerts its efficacy. The aglucone of the crocin-gentiobiose is linked by a beta-1, 6-glycosidic bond, cannot be hydrolyzed by amylase of a human body, and can only be hydrolyzed by cellulase secreted by intestinal microorganisms. Therefore, it is more directly effective as a medicinal material or a cosmetic material in the form of crocetin.
Crocetin belongs to carotenoid compounds, has high crystallinity and low solubility in common solvents. Experiments show that the crocetin is hardly dissolved in water and n-hexane and hardly dissolved in common organic solvents such as methanol, ethanol, ethyl acetate and the like, which brings difficulty to preparation of a preparation form of the crocetin and limits application research and clinical tests of the crocetin. Patent CN2007101765373 proposes dissolving crocetin with ethanol or methanol, and dispersing and embedding with high molecular dispersant such as cyclodextrin to increase water solubility of crocetin. It has been found that crocetin has limited solubility in ethanol or methanol or aqueous alcohol, requires a large amount of organic solvents, and is toxic to methanol. In addition, cyclodextrin has low solubility in ethanol, forms a sticky dough, and is difficult to stir and mix. Glow of a week[3]The crocetin microcapsule is prepared by a high-pressure homogenization method, and micron-sized encapsulated crocetin particles can be obtained. However, this method requires a high-pressure homogenizer. The equipment has high cost, high energy consumption and low production efficiency (the treatment capacity of a common model is 10L/hr).
Disclosure of Invention
The invention aims to overcome the defects or problems in the background art and provides a crocetin microemulsion and a preparation method of a freeze-dried powder thereof.
In order to achieve the purpose, the invention adopts the following technical scheme:
a crocetin microemulsion is prepared by dissolving crocetin with alkali solution, adding surfactant and macromolecular compound, and acidifying to form microemulsion; the method comprises the following specific steps:
(1) putting alkali and a chelating agent into a beaker, adding pure water, and stirring for dissolving; adding new crocetin into the solution, heating and stirring, filtering, and cooling to obtain solution A;
(2) weighing a surfactant and a macromolecular compound, heating and dissolving the surfactant and the macromolecular compound by using pure water, and cooling to obtain a solution B;
(3) weighing acid, and dissolving with pure water to obtain a solution C;
(4) pouring the B into the A, and quickly and uniformly mixing; and pouring the C into the A together, and quickly and uniformly mixing to obtain a dark red transparent solution D, namely the crocetin microemulsion solution.
Further, the alkaline solution comprises an alkali, a chelating agent and water; base refers to the chemical category of basic compounds, including sodium hydroxide or potassium hydroxide; chelating agents refer to complexes of the chemical category, including EDTA or sodium citrate; the acid is an acidic compound in the chemical category and comprises hydrochloric acid or citric acid; the surfactant is water-soluble surfactant with HLB value of 10-18, and comprises Tween-80 or hydrogenated castor oil polyoxyethylene ether; the macromolecular compound is a water-soluble macromolecular thickener and comprises sodium carboxymethylcellulose or xanthan gum.
Further, the crocetin microemulsion solution comprises the following steps:
(1) putting 1.0g of sodium hydroxide and 0.05g of disodium EDTA into a beaker, adding 500ml of pure water, and stirring for dissolving; then adding 10.0g of crocetin into the solution, heating and stirring, filtering, and cooling to 10 ℃ to obtain a solution A;
(2) weighing 6.0g of hydrogenated castor oil polyoxyethylene ether EL-40 and 1.5g of CMC, and dispersing and dissolving with 50ml of pure water to obtain a solution B;
(3) weighing 5.3g of citric acid, and dissolving with 50ml of pure water to obtain a solution C;
(4) pouring the B into the A, and quickly and uniformly mixing; pouring the C into the mixture, and quickly mixing the mixture uniformly to obtain a dark red transparent solution D, namely the crocetin microemulsion solution.
A lyophilized powder prepared from a crocetin microemulsion, which is prepared from the crocetin microemulsion of claim 1, and comprises the following specific steps (5) added after the step (4): adding a certain amount of filler into D, and freeze-drying under vacuum to obtain spongy crocetin nano freeze-dried powder.
A lyophilized powder prepared from a crocetin microemulsion, which is prepared from the crocetin microemulsion of claim 3, and comprises the following specific steps (5) added after the step (4): taking the crocetin microemulsion, adding mannitol which accounts for 5-20% of the weight of the crocetin microemulsion, uniformly mixing the obtained solution, and carrying out vacuum freeze drying on the obtained solution to obtain the spongy crocetin nano freeze-dried powder.
A lyophilized powder prepared from a crocetin microemulsion, which is prepared from the crocetin microemulsion of claim 3, and comprises the following specific steps (5) added after the step (4): mixing and dissolving the D solution 100ml and 8.0g D-mannitol, and vacuum freeze-drying to obtain sponge-shaped lyophilized powder.
As can be seen from the above description of the present invention, compared to the prior art, prepares crocetin as microemulsion, which can increase its water solubility, and lays the foundation for the subsequent application research and clinical trials.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
FIG. 1 is a schematic diagram showing a comparison of a crocetin microemulsion with a conventional emulsion;
FIG. 2 is a schematic diagram of a crocetin microemulsion lyophilized powder;
FIG. 3 is an enlarged view of lyophilized crocetin under a microscope.
Detailed Description
The first embodiment is as follows: preparation of crocetin microemulsion
(1) Putting 1.4g of potassium hydroxide and 0.05g of potassium citrate into a beaker, adding 500ml of pure water, and stirring for dissolving; then adding 10g of crocetin into the solution, heating and stirring, filtering, and cooling to 5 ℃ to obtain a solution A;
(2) weighing 5.0g of tween-80 and 1.0g of PEG1000, and dispersing and dissolving with 50ml of pure water to obtain a solution B;
(3) weighing 5.3g of citric acid, and dissolving with 50ml of pure water to obtain a solution C;
(4) pouring the B into the A, and quickly and uniformly mixing; and pouring the C into the A together, and quickly and uniformly mixing to obtain a dark red transparent solution D, namely the crocetin microemulsion.
Example two: preparation of crocetin microemulsion
(1) Putting 1.0g of sodium hydroxide and 0.05g of disodium EDTA into a beaker, adding 500ml of pure water, and stirring for dissolving; then adding 10.0g of crocetin into the solution, heating and stirring, filtering, and cooling to 10 ℃ to obtain a solution A;
(2) weighing 6.0g of hydrogenated castor oil polyoxyethylene ether EL-40 and 1.5g of CMC, and dispersing and dissolving with 50ml of pure water to obtain a solution B;
(3) weighing 5.3g of citric acid, and dissolving with 50ml of pure water to obtain a solution C;
(4) pouring the B into the A, and quickly and uniformly mixing; and pouring the C into the A together, and quickly and uniformly mixing to obtain a dark red transparent solution D, namely the crocetin microemulsion.
Example three: preparation of crocetin freeze-dried powder
Taking 100mL of the crocetin microemulsion solution in the first example, adding 15.0g of D-mannitol, stirring to completely dissolve, subpackaging the solution in 10mL penicillin bottles with 2mL of each bottle, and freeze-drying according to the following parameters to obtain spongy crocetin freeze-dried powder.
TABLE 1 Freeze drying Process
Example four: preparation of crocetin essence
(1) Phase A: heating and uniformly mixing 10.9mL of 1, 3-butanediol, 0.1mL of caprylic/capric triglyceride and 4mL of 1, 2-pentanediol in a beaker;
(2) phase B: mixing 50mL of 0.2% hyaluronic acid stock solution, 10mL of crocetin microemulsion, 5.0mL of VB5 aqueous solution and 20mL of 5% collagen aqueous solution in a beaker;
(3) mixing the phase A and phase B, and stirring with high speed stirrer for 30min to obtain crocetin essence.
To demonstrate the effectiveness of the present invention, the following experiments were performed:
solubility test of (mono) crocetin
1. Crocetin solubility as a function of pH
20mL of each of buffers (measured by a pH meter) having different pH values were prepared using phosphoric acid-sodium hydroxide and sodium bicarbonate-sodium carbonate, 0.50g of crocetin solid powder was added, the mixture was equilibrated for 4 hours in a 30 ℃ water bath, the solution was filtered through a 0.45 μm microporous membrane, the filtrate was diluted with methanol, and the content of crocetin, i.e., the solubility of crocetin in aqueous solutions having different pH values, was measured by HPLC.
TABLE 2 crocetin solubility as a function of pH
And (4) conclusion: crocetin is insoluble in acidic aqueous solutions and soluble in moderately strong alkaline solutions.
2. Solubility of crocetin in common organic solvents
Taking several Erlenmeyer flasks, adding 0.50g crocetin and 5.0g organic solvent, respectively, covering with a stopper, and balancing in a 30 deg.C water bath for 4 h. After equilibration, 1mL of the above filtrate was diluted with methanol and the content of crocetin, i.e., the solubility of crocetin in various organic solutions, was determined by HPLC.
TABLE 3 solubility of crocetin in organic solvent (30 ℃ C.)
| Solvent(s) | Concentration at equilibrium (mg/mL, 30 ℃ C.) |
| Methanol | 1.8 |
| Ethanol | 2.2 |
| 50% ethanol | 3.4×10-3 |
| N-hexane | 6.1×10-4 |
| Ethyl acetate | 4.2 |
| DMSO | 24.0 |
And (4) conclusion: crocetin is soluble in DMSO, slightly soluble in methanol, ethanol, ethyl acetate, insoluble in n-hexane, 50% ethanol. It follows that the solubility of crocetin in common non-toxic organic solvents is very low. Evaluation of microemulsion Effect of crocetin (II)
1. Appearance contrast
Preparation of a common emulsified sample: a sample of emulsified crocetin was prepared by emulsifying 10.0g of crocetin, 5.1g of Tween-80, 1.0g of Peg-1000, 0.5g of citric acid and 600ml of purified water in a beaker with a high speed emulsifier for 30 minutes. The emulsified samples are diluted according to the dilution times of 1, 10, 100, 1000 and 10000, and the diluted solution is poured into a test tube, and the appearance of the test tube is as shown in the left four tubes of the figure 1 (the concentration increases from left to right).
Preparing a micro-emulsified sample: the sample prepared in example 1 is diluted according to the dilution ratio multiples of 1, 10, 100, 1000 and 10000, and the dilution liquid is poured into a test tube, and the appearance of the test tube is as shown in the right four tubes (from left to right, the concentration is reduced in sequence) of the figure 1.
And (4) conclusion: as can be seen from FIG. 1, with the process of the present invention, crocetin can form a clear and homogeneous solution with water, which is difficult to achieve with conventional emulsification techniques.
2. Comparison of solubilization Effect
TABLE 4 comparison of Water solubility before and after emulsification of crocetin (30 deg.C)
3. Turbidity measurement
Turbidity is an important parameter for measuring the amount of particles in a solution, and the measurement method comprises a transmission method and a scattering method. The transmission method is that near infrared light passes through a sample solution with a certain thickness, and particulate matters with the diameter similar to or larger than the wavelength of incident light in the solution can generate scattering or reflection action on the incident light, so that the transmitted light intensity is attenuated. Therefore, 880nm near infrared light is used as detection wavelength in the experiment, the amount of particles above 140nm in the reaction solution can be approximated, and the micro-emulsification effect can be further represented. Samples of examples 1 to 3 were each placed in a beaker, and diluted with purified water to a concentration of 0.25% of crocetin, and the absorbance was measured at 880 nm.
TABLE 5 turbidity assay (30 ℃ C.)
4. Observation of freeze-dried powder
And (3) carrying out sensory observation and redissolution test on the prepared freeze-dried powder.
And (4) conclusion: FIG. 2 is a lyophilized powder of crocetin, which is porous sponge-like; FIG. 3 is a micrograph (. times.400) showing that red complexes of crocetin and D-mannitol (dark in the figure) are partially radial with a large number of holes (light portions) distributed therebetween.
In the redissolution test, 0.3g of crocetin freeze-dried powder and 5mL of water are added into a test tube, and the crocetin freeze-dried powder is completely dissolved within 10 seconds by shaking for 3-5 minutes to form a transparent and uniform solution.
The alkali used in the embodiment of the present invention is sodium hydroxide and potassium hydroxide, and many related alkaline chemicals are not listed here.
The chelating agents used in the embodiment of the invention are sodium citrate and disodium EDTA, and many related chemical chelating agents are used, which are not listed here.
The surfactants used in the embodiment of the invention are tween-80 and hydrogenated castor oil polyoxyethylene ether EL-40, and many related surfactants are not listed.
The polymer compound used in the embodiment of the invention plays roles in dissolving aid and stabilizing, and is PEG1000 and sodium carboxymethyl cellulose (CMC), and related polymer thickeners are various in types, which are not listed.
The acid used in the embodiment of the present invention is citric acid, and the related acidic substances are various, such as acetic acid, lactic acid, hydrochloric acid, and the like, which are not listed here.
The description of the above specification and examples is intended to be illustrative of the scope of the present invention and is not intended to be limiting. Modifications, equivalents and other improvements which may occur to those skilled in the art and which may be made to the embodiments of the invention or portions thereof through a reasonable analysis, inference or limited experimentation, in light of the common general knowledge, the common general knowledge in the art and/or the prior art, are intended to be within the scope of the invention.
Claims (6)
1. A crocetin microemulsion characterized by: dissolving crocetin with alkali solution, adding surfactant and macromolecular compound, and acidifying to form microemulsion; the method comprises the following specific steps:
(1) putting alkali and a chelating agent into a beaker, adding pure water, and stirring for dissolving; adding new crocetin into the solution, heating and stirring, filtering, and cooling to obtain solution A;
(2) weighing a surfactant and a macromolecular compound, heating and dissolving the surfactant and the macromolecular compound by using pure water, and cooling to obtain a solution B;
(3) weighing acid, and dissolving with pure water to obtain a solution C;
(4) pouring the B into the A, and quickly and uniformly mixing; and pouring the C into the A together, and quickly and uniformly mixing to obtain a dark red transparent solution D, namely the crocetin microemulsion solution.
2. The microemulsion of crocetin of claim 1, wherein: the alkaline solution comprises alkali, a chelating agent and water; base refers to the chemical category of basic compounds, including sodium hydroxide or potassium hydroxide; chelating agents refer to complexes of the chemical category, including EDTA or sodium citrate; the acid is an acidic compound in the chemical category and comprises hydrochloric acid or citric acid; the surfactant is water-soluble surfactant with HLB value of 10-18, and comprises Tween-80 or hydrogenated castor oil polyoxyethylene ether; the macromolecular compound is a water-soluble macromolecular thickener and comprises sodium carboxymethylcellulose or xanthan gum.
3. A crocetin microemulsion according to claim 1 or 2, wherein: the method comprises the following steps:
(1) putting 1.0g of sodium hydroxide and 0.05g of disodium EDTA into a beaker, adding 500ml of pure water, and stirring for dissolving; then adding 10.0g of crocetin into the solution, heating and stirring, filtering, and cooling to 10 ℃ to obtain a solution A;
(2) weighing 6.0g of hydrogenated castor oil polyoxyethylene ether EL-40 and 1.5g of CMC, and dispersing and dissolving with 50ml of pure water to obtain a solution B;
(3) weighing 5.3g of citric acid, and dissolving with 50ml of pure water to obtain a solution C;
(4) pouring the B into the A, and quickly and uniformly mixing; pouring the C into the mixture, and quickly mixing the mixture uniformly to obtain a dark red transparent solution D, namely the crocetin microemulsion solution.
4. A freeze-dried powder prepared from crocetin microemulsion is characterized in that: the microemulsion of crocetin is prepared by the microemulsion of crocetin as claimed in claim 1, and comprises the following steps (5): adding a certain amount of filler into D, and freeze-drying under vacuum to obtain spongy crocetin nano freeze-dried powder.
5. A freeze-dried powder prepared from crocetin microemulsion is characterized in that: the microemulsion of crocetin is prepared by the microemulsion of crocetin as claimed in claim 3, and comprises the following steps (5): taking the crocetin microemulsion, adding mannitol which accounts for 5-20% of the weight of the crocetin microemulsion, uniformly mixing the obtained solution, and carrying out vacuum freeze drying on the obtained solution to obtain the spongy crocetin nano freeze-dried powder.
6. A freeze-dried powder prepared from crocetin microemulsion is characterized in that: the microemulsion of crocetin is prepared by the microemulsion of crocetin as claimed in claim 4, and comprises the following steps (5): mixing and dissolving the D solution 100ml and 8.0g D-mannitol, and vacuum freeze-drying to obtain sponge-shaped lyophilized powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811028777.3A CN109091458B (en) | 2018-09-05 | 2018-09-05 | Crocetin microemulsion and preparation method of freeze-dried powder thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811028777.3A CN109091458B (en) | 2018-09-05 | 2018-09-05 | Crocetin microemulsion and preparation method of freeze-dried powder thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109091458A CN109091458A (en) | 2018-12-28 |
| CN109091458B true CN109091458B (en) | 2021-02-19 |
Family
ID=64865162
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811028777.3A Active CN109091458B (en) | 2018-09-05 | 2018-09-05 | Crocetin microemulsion and preparation method of freeze-dried powder thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109091458B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021114089A1 (en) * | 2019-12-10 | 2021-06-17 | Hangzhou Menglanruisi Biotechnology Co., Ltd. | Methods of using crocetin in treating solid tumors |
| CN116178308B (en) * | 2021-11-28 | 2024-10-22 | 南京艾德凯腾生物医药有限责任公司 | Crocetin derivative and pharmaceutical application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102293740A (en) * | 2011-08-04 | 2011-12-28 | 广东省中药研究所 | crocetin injection and preparation method thereof |
-
2018
- 2018-09-05 CN CN201811028777.3A patent/CN109091458B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102293740A (en) * | 2011-08-04 | 2011-12-28 | 广东省中药研究所 | crocetin injection and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 藏红花酸固体分散缓释片的研究;钟慧;《江苏大学2014年硕士毕业论文》;20141231;全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109091458A (en) | 2018-12-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Pan-In et al. | Depositing α-mangostin nanoparticles to sebaceous gland area for acne treatment | |
| CN101374534B (en) | Compositions for vaginal use | |
| WO2002022132A2 (en) | Novel topical oestroprogestational compositions with systemic effect | |
| CN108159102B (en) | Preparation method and application of wormwood extract nano-emulsion gel | |
| CN109091458B (en) | Crocetin microemulsion and preparation method of freeze-dried powder thereof | |
| Na et al. | Development and evaluation of a film-forming system hybridized with econazole-loaded nanostructured lipid carriers for enhanced antifungal activity against dermatophytes | |
| CN102614107A (en) | Micro-emulsion thermosensitive gel for skin external use and preparation method thereof | |
| Tang et al. | Fabrication and characterization of multiple herbal extracts-loaded nanofibrous patches for topical treatment of acne vulgaris | |
| CN110522761A (en) | It is a kind of to have effects that prevent and treat the biological polyoses of acne and its application | |
| CA2682250A1 (en) | Ibuprofen, cyclodextrines and ternary agent complexes, and pharmaceutical uses thereof | |
| CN102964468B (en) | Procyanidine-modified carboxymethyl chitosan | |
| CN115177975B (en) | A method for extracting polysaccharides, polyphenols and triterpenes from Phellinus linteus by supermolecular process | |
| CN110179685A (en) | A kind of Essence containing natural astaxanthin | |
| CN112957379A (en) | Method for extracting centella asiatica extract with high biological safety | |
| CN101411686A (en) | Clarithromycin sub-microemulsion injection and preparation method thereof | |
| CN104826129A (en) | Nanometer traditional Chinese medicine quercetin-PLGA (poly lactic acid-glycolic acid) and preparation method thereof | |
| CN109568217A (en) | A kind of preparation method of Salvia root P.E and its application in anti-acne | |
| KR20200060890A (en) | The shampoo composition comprising extract of natural micro organism-fermented black ginseng | |
| CN104027390A (en) | Oil-in-water type compound amphotericin B nano-emulsion | |
| Zhang et al. | A novel natural polysaccharide dissolving microneedle capable of adsorbing pus to load EGCG for the treatment of acne vulgaris | |
| CN111067930A (en) | Lamiophlomis rotate (Benth.) kudo extract nanometer preparation and preparation method thereof | |
| CN104274826A (en) | Oil-in-water type compound colistin nanoemulsion | |
| CN106798333A (en) | A kind of mulberry fruit polyphenol microcapsules, its preparation method and application | |
| CN115154408A (en) | Novel nano drug-loading system of tanshinone extract microemulsion hydrogel as well as preparation method and application of novel nano drug-loading system | |
| CN106923350A (en) | Method for preparing water-soluble dietary fiber from corn stigma |
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 |