CN110841075A - Preparation method of paeonol inclusion compound - Google Patents
Preparation method of paeonol inclusion compound Download PDFInfo
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- CN110841075A CN110841075A CN201911124856.9A CN201911124856A CN110841075A CN 110841075 A CN110841075 A CN 110841075A CN 201911124856 A CN201911124856 A CN 201911124856A CN 110841075 A CN110841075 A CN 110841075A
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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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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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
- A61K31/12—Ketones
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- 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]
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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Abstract
The invention belongs to the field of medicine, and mainly relates to a preparation method of a paeonol inclusion compound, which comprises the steps of extracting paeonol solution from a tree peony bark medicinal material by a steam distillation method, directly adding a certain amount of β -cyclodextrin into the paeonol solution, stirring to form saturated solution of- β cyclodextrin, stirring for inclusion for a period of time, refrigerating the inclusion solution at low temperature, filtering and drying to obtain the inclusion compound.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a preparation method of a paeonol clathrate compound.
Technical Field
Paeonol is one of the main active ingredients in traditional Chinese medicinal materials of tree peony bark, and has various pharmacological activities, such as antipyretic analgesia, anti-inflammation antibacterial, antianaphylaxis, cardiovascular protection, anti-tumor, blood sugar reduction and the like, the paeonol has obvious pharmacological activity, less adverse reaction and short half life, and has wide application prospect, the paeonol is a small molecular phenol compound, is white or yellowish needle-shaped crystals with luster, has low melting point, is unstable to light and heat, has special smell and poor water solubility, and has a certain stimulation effect on gastrointestinal mucosa, and β -cyclodextrin is mostly adopted to perform inclusion on the paeonol at present so as to reduce the volatility, increase the water solubility, improve the stability and the bioavailability.
The common paeonol inclusion process is that a paeonol solution is extracted from tree peony bark by a steam distillation method, the solution is refrigerated overnight to obtain paeonol crystals, the crystals are dissolved by a proper amount of ethanol and then included by a saturated aqueous solution of β -cyclodextrin.
Disclosure of Invention
In order to solve the defects of complicated steps and long time consumption of the paeonol inclusion compound preparation method in the prior art, the invention provides a novel paeonol inclusion compound preparation method.
The purpose of the invention is realized by the following technical scheme:
the preparation method of the paeonol inclusion compound is characterized by comprising the following steps of:
(1) soaking cortex moutan in water.
(2) Heating, and distilling with steam to keep boiling to obtain paeonol solution.
(3) Collecting paeonol solution, stirring in 40-70 deg.C water bath, directly adding β -cyclodextrin to the solution to make β -cyclodextrin form saturated solution, and stirring at constant temperature to clathrate.
(4) And (4) refrigerating the inclusion solution at low temperature, carrying out suction filtration on the suspension, and drying the filter cake to obtain the paeonol inclusion compound.
Wherein, the water adding amount in the step (1) is 5-10 times of the weight of the tree peony bark, the soaking time is 1-3h, preferably, the water adding amount is 10 times of the weight of the tree peony bark, and the soaking time is 1 h.
The water vapor distillation micro-boiling time in the step (2) is 2-6h, and preferably 3 h.
In the step (3), the inclusion temperature is 40-60 ℃, the inclusion time is 1-2h, preferably, the inclusion temperature is 50 ℃, and the inclusion time is 2 h.
The refrigeration time of the step (4) is 15-44h, and the drying temperature of the inclusion compound is 40-50 ℃.
Compared with the prior art, the preparation method of the paeonol inclusion compound provided by the invention has the advantages of simple operation, time saving, efficiency improvement, stable quality of the inclusion compound and high inclusion efficiency.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The present invention is further illustrated below by specific examples in order to provide those skilled in the art with a full understanding of the present invention, but it should be understood by those skilled in the art that the examples of the present invention are not to be construed as limiting the present invention in any way.
Example 1
Taking 300g of tree peony bark medicinal material, adding 5 times of drinking water, soaking for 1h, heating to slightly boil, extracting for 2h by a steam distillation method, collecting 420mL of paeonol aromatic aqueous solution, taking a small amount of paeonol concentration detected according to a pharmacopeia method, placing in a three-mouth round-bottom flask, heating in a water bath at 40 ℃, starting stirring, keeping constant temperature, weighing 58.7g of β -cyclodextrin, adding into the aromatic aqueous solution, stirring, gradually clarifying the solution, starting stirring for inclusion for 1h, then placing the inclusion solution into a container, carrying out low-temperature cold precipitation for 15h, then carrying out cold precipitation to precipitate white solid at the bottom of the inclusion solution, carrying out suction filtration on the inclusion solution, carrying out hot air drying on a filter cake at 40 ℃, weighing after drying is finished, obtaining 45.7g of the paeonol inclusion compound, weighing an appropriate amount of the paeonol inclusion compound, carrying out content measurement on the inclusion compound according to the method for detecting paeonol according to.
The inclusion rate of paeonol is (weight of the inclusion compound is multiplied by the content of paeonol in the inclusion compound) divided by the input amount of paeonol multiplied by 100 percent
The yield of the inclusion compound is the weight of the inclusion compound ÷ (β cyclodextrin addition amount + paeonol addition amount)
Through calculation, the content of paeonol in the clathrate is 12.24%, the inclusion rate of paeonol is 81.82%, and the yield of the clathrate is 70.31%.
Example 2
Adding 1000g of moutan bark medicinal material into 8 times of drinking water, soaking for 1.5h, heating to slightly boil, extracting for 4h by a steam distillation method, collecting 1960mL of paeonol aromatic aqueous solution, standby, adding 80mL of 95% alcohol into the aromatic aqueous solution, uniformly stirring, placing in a three-mouth round-bottom flask, heating in a water bath at 50 ℃, starting stirring, keeping constant temperature, weighing 122.5g of β -cyclodextrin into the aromatic aqueous solution, stirring, gradually clarifying the solution, starting stirring for inclusion for 1.5h, then placing the inclusion solution into a container, carrying out low-temperature cold precipitation for 24h, then separating out obvious white solid at the bottom of the inclusion solution, carrying out suction filtration on the inclusion solution, carrying out hot air drying on a filter cake at 50 ℃, weighing after drying is finished, weighing a proper amount of paeonol inclusion compound, carrying out content determination on the paeonol inclusion compound according to a paeonol detection method in Chinese pharmacopoeia, calculating the inclusion rate of paeonol and the inclusion yield of the paeonol in the same method as in embodiment 1.
Through calculation, the content of paeonol in the clathrate is 13.17%, the inclusion rate of paeonol is 82.07%, and the yield of the clathrate is 75.72%.
Example 3
3000g of moutan bark medicinal material is taken, 10 times of drinking water is added, the moutan bark medicinal material is soaked for 1h, the mixture is heated to slight boiling, the extraction is carried out for 3h by a steam distillation method, 4470mL of paeonol aromatic aqueous solution is collected for standby, 150mL of 95% alcohol is added into the aromatic aqueous solution, the mixture is uniformly stirred, the mixture is placed in a three-mouth round-bottom flask, water bath heating at 50 ℃ is carried out, stirring is started, constant temperature is kept, 172.2g of β cyclodextrin is weighed and added into the aromatic aqueous solution, stirring is carried out, the solution is gradually clarified, stirring and inclusion are started for 2h, the inclusion solution is placed in a container after stirring, cold precipitation is carried out for 30h at low temperature, obvious white solid is separated out at the bottom of the inclusion solution, suction filtration is carried out on the inclusion solution, hot air drying is carried out on a filter cake at 50 ℃, weighing is carried out after drying is finished, 133.4g of the paeonol inclusion compound, a proper amount of the paeonol is weighed, the inclusion compound is measured.
The inclusion rate of paeonol is 85.43 percent and the content of paeonol in the inclusion compound is 12.69 percent. The clathrate yield was 77.47%.
Example 4
Taking 9kg of moutan bark medicinal material, adding 10 times of drinking water, soaking for 3h, heating to slight boiling, extracting for 6h by using a steam distillation method, collecting 13.4L of paeonol solution for later use, adding 300mL of 95% alcohol into the paeonol solution, uniformly stirring, placing in a glass reaction kettle, heating in a circulating water bath at 70 ℃, starting stirring, keeping constant temperature, weighing 515.4g of β cyclodextrin into the aromatic water solution, stirring, gradually clarifying the solution, beginning to stir for inclusion for 2h, placing the inclusion solution into a container after stirring, carrying out low-temperature cold precipitation for 44h, separating out obvious white solid at the bottom of the inclusion solution after cold precipitation, carrying out suction filtration on the inclusion solution, carrying out hot air drying on a filter cake at 50 ℃, weighing after drying, obtaining 395.6g of the paeonol inclusion compound, weighing an appropriate amount of paeonol, carrying out content determination on the inclusion compound according to a method for detecting the paeonol according to Chinese pharmacopoeia, and calculating the inclusion rate and the yield of the paeonol.
Through calculation, the content of paeonol in the clathrate is 13.52 percent, and the inclusion rate of the paeonol is 82.43 percent. The clathrate yield was 76.76%.
Comparative examples
Taking 1kg of tree peony bark, adding drinking water with the volume 5 times of the medicinal material amount, soaking for 1h, heating to slightly boil, extracting for 2h by a steam distillation method, collecting 1540mL of paeonol solution, refrigerating overnight at 4 ℃, performing suction filtration and drying, collecting solid matters, namely 8.93g of paeonol crystals, taking 8g of the crystals, dissolving by a small amount of absolute ethyl alcohol, dropwise adding the crystals into saturated aqueous solution containing 64g of β cyclodextrin, stirring and clathrating for 2h at 40 ℃, performing cold precipitation of clathration solution for 15h at low temperature, performing suction filtration, drying the solid matters by hot air at 40 ℃ to obtain 52.11g of white clathration compound, weighing a proper amount of the clathration compound of the paeonol, performing content measurement according to a method for detecting the paeonol by Chinese pharmacopoeia, and calculating the cla.
Through calculation, the content of paeonol in the clathrate is 11.73%, the inclusion rate of paeonol is 80.42%, and the yield of the clathrate is 70.38%.
Claims (9)
1. The preparation method of the paeonol inclusion compound is characterized by comprising the following steps of:
(1) soaking cortex moutan in water;
(2) heating, maintaining slight boiling by steam distillation, and extracting paeonol solution;
(3) collecting paeonol solution, stirring in 40-70 deg.C water bath under heat preservation, directly adding β -cyclodextrin into the solution to make β -cyclodextrin form saturated solution, and stirring at constant temperature to clathrate;
(4) and (4) refrigerating the inclusion solution at low temperature, carrying out suction filtration on the suspension, and drying the filter cake to obtain the paeonol inclusion compound.
2. The preparation method of the clathrate compound according to claim 1, wherein the water addition amount in the step (1) is 5-10 times of the weight of the cortex moutan medicinal material, and the soaking time is 1-3 h.
3. The preparation method of the clathrate compound according to claim 2, wherein the amount of water added in the step (1) is 10 times of the weight of the tree peony bark, and the soaking time is 1 h.
4. The method for preparing a clathrate compound according to claim 1, wherein the water vapor distillation micro-boiling time in step (2) is 2 to 6 hours.
5. The method for preparing a clathrate compound according to claim 4, wherein the water vapor distillation micro-boiling time in the step (2) is 3 hours.
6. The preparation method of the clathrate compound according to claim 1, wherein the inclusion temperature in the step (3) is 40-70 ℃ and the inclusion time is 1-2 hours.
7. The method for preparing a clathrate compound according to claim 6, wherein the temperature of inclusion in step (3) is 50 ℃ and the time of inclusion is 2 hours.
8. The preparation method of the clathrate compound according to claim 1, wherein the refrigerating time in the step (4) is 15 to 44 hours.
9. The method for preparing a clathrate compound according to claim 1, wherein a drying temperature of the clathrate compound in the step (4) is 40 to 50 ℃.
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| CN201911124856.9A CN110841075A (en) | 2019-11-18 | 2019-11-18 | Preparation method of paeonol inclusion compound |
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| CN201911124856.9A CN110841075A (en) | 2019-11-18 | 2019-11-18 | Preparation method of paeonol inclusion compound |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114028341A (en) * | 2021-11-17 | 2022-02-11 | 北京康仁堂药业有限公司 | Cortex moutan formula particle and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114028341A (en) * | 2021-11-17 | 2022-02-11 | 北京康仁堂药业有限公司 | Cortex moutan formula particle and preparation method thereof |
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