CN115581713A - Chinese buckeye seed extract colon-specific sustained-release pellet and preparation method thereof - Google Patents
Chinese buckeye seed extract colon-specific sustained-release pellet and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a buckeye extract colon-specific sustained-release pellet which comprises a drug-loaded pill core, an isolation layer and an enteric layer, wherein the drug-loaded pill core comprises a blank pill core, a buckeye extract coated on the surface of the blank pill core and an adhesive for coating a drug; the isolating layer comprises a film forming agent, a lubricating agent and a targeting accelerator; the enteric layer comprises Ewing S100, ewing L100-55, plasticizer and antisticking agent. The pellet prepared by the invention can be released in a targeted manner in the colon, has the characteristic of slow release, can make the blood concentration more stable, reduce the peak-valley fluctuation and the administration frequency, improve the compliance of patients, and is expected to play a better role in the treatment of diseases with pathological changes in the colon.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a buckeye extract colon-specific sustained-release pellet and a preparation method thereof.
Background
Horse chestnut (Aesculus Chinensis bge.), zhejiang horse chestnut (Aesculus Chinensis bge.) or muskmelon (Aesculus Chinensis bge. Var. Chekiangensis (Hu et Fang)) dry mature seed, the main active ingredient of the horse chestnut is aescin, which is divided into beta configuration and alpha configuration, and the horse chestnut has multiple functions of anti-inflammation, anti-exudation, anti-encephaledema, venous tension increase and the like. At present, the sodium salt of beta-aescine is mainly applied to clinic, and the sodium salt of aescine, sodium salt of aescine liniment, compound sodium gel of aescine, sodium tablet of aescine and other preparation forms have been developed. Buckeye extract is a primary extract for preparing aescine, contains saponin components, polysaccharides, alkaloids and other components, and can be further purified to obtain high-purity aescine and used for preparing aescine sodium.
Because the oral escin has short half-life period, lower bioavailability and larger gastrointestinal side effects, the applicant develops an enteric sustained-release pellet (CN 106924222A) by using an escin active ingredient in the early period, and the pellet is prepared by using an extrusion rolling method and subjected to enteric coating in the early period of research, so that the medicine can be released in the intestinal tract to reduce the irritation of the stomach and improve the bioavailability. Because the extrusion and spheronization method has high requirements on equipment and the quality of the pellets is not easy to control, the applicant intends to utilize mature and commercialized blank pellet cores and combine with a common coating method to prepare semen aesculi extract enteric-coated pellets, but results show that the pellets prepared by the method have low release degree in the gastrointestinal tract and have high release degree in the colon. On the basis, the applicant further improves and explores the preparation process, and finally realizes the preparation of the buckeye extract colon-specific sustained-release pellet.
Considering that an oral colon specific delivery system (ocdds) can also reduce the side effects of the drug on the gastrointestinal tract, and can also improve the bioavailability of the drug absorbed at the colon part, the ocdds is particularly suitable for treating colonic lesions (such as ulcerative colitis, colon cancer, and the like), the pharmacological activity of the aescin may also be related to the treatment of the colonic lesions, and the application of the aescin in the treatment of the ulcerative colitis is reported in the literature in the prior art, for example, CN 111939166A. Therefore, the colon-specific sustained-release pellet prepared by the invention is expected to play a better role in treating diseases of colonic lesions.
Disclosure of Invention
The invention aims to provide a buckeye extract colon-specific sustained-release pellet and a preparation method thereof. To solve the problems of the background art described above.
The above purpose is realized by the following technical scheme:
a semen Aesculi extract colon-specific sustained-release pellet comprises drug-loaded pellet core, isolation layer, and enteric layer,
medicine carrying pill core: comprises a blank pill core, buckeye extract coated on the surface of the blank pill core and an adhesive for coating a medicament;
isolation layer: the drug-loaded pill core consists of a film-forming agent, a lubricant and a targeting accelerator, wherein the film-forming agent accounts for 10-30% of the mass of the drug-loaded pill core; the lubricant accounts for 0.5-1.5% of the mass of the drug-loaded pill core; the targeted accelerant accounts for 5-12% of the mass of the drug-loaded pill core;
enteric layer: consists of Eudragit S100, eudragit L100-55, plasticizer and antisticking agent, the enteric layer accounts for 40-60% of the total mass of the pellet core and the isolating layer,
the targeting promoter is amylose and/or glucan; the buckeye seed extract contains 60-80% of total saponin.
Further, the blank pellet core is a sucrose pellet core, a microcrystalline cellulose pellet core, a starch pellet core or a lactose pellet core. In tests, compared with sucrose, starch and lactose, the microcrystalline cellulose is less prone to degradation in the gastrointestinal tract, has stable properties, and can reduce the release of the medicine in the gastrointestinal tract to enable the medicine to enter the colon more, so the microcrystalline cellulose pill core is further preferred in the invention.
Further, the binder is cellulose ether derivative or polyvinylpyrrolidone, and occupies 1-5% of the mass of the pellet core. The cellulose ether derivatives include, but are not limited to, methyl cellulose, carboxymethyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, and the like.
Further, the film forming agent is selected from one or more of carrageenan, guar gum, gelatin, arabic gum, chitosan and trehalose. These materials have good stability in the gastrointestinal tract and degrade well under the digestive conditions of the colon, thereby facilitating colonic release of the drug.
Further, the plasticizer is triethyl citrate and/or tween 80.
Further, the lubricant is talcum powder or micropowder silica gel.
The invention further provides a method for preparing the buckeye extract colon-specific sustained-release pellet, which comprises the following steps:
s1: placing the blank pill core in a fluidized bed bottom spraying coating device, dissolving the adhesive and the buckeye extract by using a solvent, and spraying to apply medicine to prepare a medicine-carrying pill core;
s2: placing the drug-loaded pill core in a fluidized bed bottom spray coating device, dissolving and uniformly mixing a film forming agent, a lubricant and a targeting accelerant by using a solvent, and then spraying and coating to prepare an isolation layer drug-loaded pill core;
s3: the drug-loaded pill core of the isolating layer is placed in a fluidized bed bottom spray coating device, and the Eudragit S100, the Eudragit L100-55, the plasticizer and the anti-sticking agent are dissolved by a solvent and then spray coated.
Preferably, the spraying parameters are that the atomizing pressure is 1.5-2.0bar, the material temperature is 30-60 ℃, and the air volume is 25-35m 3 /h。
The beneficial effects of the invention are:
according to the invention, the pellet is prepared by using the material which is stable in property in the gastrointestinal tract and can be fully degraded in the colon, the targeting promoter is used, and the dosage of each raw material is groped and optimized, so that the colon-specific administration of the buckeye extract is finally realized, wherein amylose and glucan can resist the degradation of digestive enzymes and bacteria in the gastrointestinal tract, and can be digested and absorbed by the colonic enzymes and bacteria, and a certain colon targeting promoting effect is achieved.
The pellet prepared by the invention can be released in a targeted manner in the colon, has the characteristic of slow release because the colon release conforms to a first-order equation, can make the blood concentration more stable, reduce the peak-valley fluctuation and the administration frequency, and improve the compliance of patients. The invention also has the advantages of long drug release period, high cumulative release degree and the like.
The invention utilizes commercial pellet cores to finish the preparation of the pellets in a set of equipment, and has the advantages of stable property, controllable quality, high yield (more than 95 percent), short production period, low cost and the like compared with the existing extrusion and rolling method.
The pellet prepared by the invention is expected to play a better role in treating diseases with colon lesions (such as ulcerative colitis).
Drawings
FIG. 1: particle size distribution curve chart of the pellet.
FIG. 2: micrographs of pellet surface and cross section.
FIG. 3: in vitro release profile of the pellet (example 1).
FIG. 4 is a schematic view of: in vitro release profile of the pellets (example 2).
FIG. 5: in vitro release profile of the pellets (example 3).
FIG. 6: in vitro release profile of the pellet (example 4).
FIG. 7 is a schematic view of: in vitro release profile of pellets (comparative).
Detailed Description
The present invention will be described in detail with reference to specific examples.
Key raw materials and instruments: semen aesculi extract (lot No. 211001, total saponin purity 76%, wuhan lovers pharmaceutical products limited); aescine sodium reference substance (batch number 100376-2017.3, purity 96.9%, china food and drug testing institute); blank pellet core (Anhui mountain river pharmaceutic adjuvant, inc.).
Agilent model 1260 high performance liquid chromatograph (Agilent, USA); XSE 205DU electronic balance [ mettler-toledo instruments (shanghai) ltd ]; easy Diss-T X8 model dissolution apparatus (RIG GTEK); FE28-standard type pH meter (Towa measurement and detection technologies, inc., sichuan); FLZB-1.5 type bottom jet fluidized bed (Shanghai Limited, chuanzhi electromechanical science and technology development); an electric stirrer model MYP2011-100 (Shanghai Meiying Xiang instruments manufacturing Co., ltd.).
Example 1 preparation of colon-specific sustained-release pellet with buckeye seed extract
1. Preparation of drug-loaded pill core
| Raw and auxiliary materials | Function of | Dosage of | |
| Microcrystalline cellulose pellet core | Blank pill core | 100g | |
| HPC-EF | Adhesive agent | 2.5g | |
| Semen Aesculi extract | | 12g | |
| 60% ethanol | Solvent(s) | 200ml |
Placing microcrystalline cellulose pill core in fluidized bed bottom spray coating device, dissolving HPC-EF and semen Aesculi extract in 60% ethanol for clarification, and spraying. The spraying parameters are as follows: the atomization pressure is 1.5bar, the material temperature is 40-45 ℃, and the air volume is 25m 3 H is the ratio of the total weight of the catalyst to the total weight of the catalyst. Drying after spraying, discharging, and sieving the pellet with 40-60 mesh sieve to obtain the drug-loaded pellet core.
2. Pellet coating process
(1) Isolating layer coating
| Raw and auxiliary materials | Function of | Dosage of |
| Medicine-carrying pill core | —— | 100g |
| Guar gum | Film forming agent | 15g |
| Talcum powder | Lubricant agent | 0.7g |
| Amylose starch | Targeted promoters | 8g |
| Dextran | Targeted promoters | 2.5g |
| Purified water | Solvent(s) | 300ml |
Placing the pill core in a fluidized bed bottom spray coating device, dissolving guar gum, pulvis Talci, amylose and dextran in purified water, and spray coating. The coating parameters are atomizing pressure of 1.8bar, material temperature of 55-60 deg.C, and air volume of 28m 3 H is the ratio of the total weight of the catalyst to the total weight of the catalyst. Discharging after spraying, and sieving the pellet with 40-60 mesh sieve to obtain the isolating layer drug-loaded pellet core.
(2) Enteric layer coating
| Raw and auxiliary materials | Action | Dosage of |
| Isolating layer medicine-carrying pill core | —— | 100g |
| Youti S100 | Coating agent | 35g |
| Youteqi L100-55 | Coating agent | 6.5g |
| Citric acid triethyl ester | Plasticizer | 3.3 |
| Tween | ||
| 80 | Plasticizer | 0.3g |
| Glycerol monostearate | Anti-sticking agent | 0.6g |
| Water (W) | Solvent(s) | 70ml |
Placing the drug-loaded pellet core in fluidized bed bottom spray coating device, and spraying Yttrium S100, yttrium L100-55, triethyl citrate, tween 80, glycerolDissolving monostearate in water to obtain coating solution, and spray coating. The coating parameters are atomizing pressure of 1.8bar, material temperature of 30-35 deg.C, and air volume of 35m 3 H is the ratio of the total weight of the catalyst to the total weight of the catalyst. Drying and discharging after the liquid spraying is finished, and sieving the pellets by a 20-40 mesh sieve.
Test examples
1. Particle size
Detecting the particle size by using a laser particle size analyzer, wherein the set parameters are as follows: the light shading degree is 0.26%, the particle refractive index is 1.500, the absorptivity is 0.1, the obtained particle size distribution curve is in normal distribution (figure 1), and d (0.1), d (0.5) and d (0.9) are 539.34um, 664.749 and 921.826 respectively.
2. Scanning Electron Microscopy (SEM) topography analysis
The surface and cross-section of the pellet were observed using a Scanning Electron Microscope (SEM). The results show that: the microspheres are solid spheres, the surfaces are compact and smooth, and the drug-loaded layer, the isolating layer and the enteric-coated layer can be distinguished on the fault surface (figure 2).
3. Detection of drug Release Properties
Taking 0.1mol/L hydrochloric acid solution, pH6.8 phosphate buffer solution, pH7.6 phosphate buffer solution as dissolution medium and simulating in vivo digestive tract conditions, and examining the dissolution performance of the medicine by detecting the content of total saponins. Referring to the second method, XD in appendix of the second part of Chinese pharmacopoeia, hydrochloric acid solution is used as a dissolution medium, pH6.8 phosphate buffer is replaced after 2h, and pH7.6 phosphate buffer is replaced after 6 h. The rotation speed is 100r/min, the temperature is 37 +/-0.5 ℃, 5mL of solution is taken at regular time, 0.45 mu m of solution is filtered, 5mL of dissolution medium is added, the content of total saponin is measured by an HPLC method, the measurement is carried out once every 1h, and the cumulative release degree is calculated according to the measurement result.
Chromatographic conditions are as follows: agilent ZORBAX SB-C18 column (250 mm. Times.4.6 mm,5 μm); the mobile phase was acetonitrile-0.2% phosphoric acid (40,v/v); the flow rate is 1.0mL/min; the column temperature is 30 ℃; the detection wavelength is 220nm; the sample volume was 20. Mu.l. And (4) expressing the peak areas of the total saponins by using the peak areas of aescin A, aescin B, aescin C and aescin D, and calculating the content of the total saponins by an external standard method.
The cumulative release of the prepared pellets in simulated gastric fluid (2 h) and intestinal fluid (4 h) was 0.85% and 1.73%, respectively, the cumulative release at 6h in simulated colonic fluid was 91.50%, and the drug release after 5h was close to peak (fig. 3), indicating that most of the drug was released in the colon.
Fitting analysis is carried out on the release curve in the simulated colon, the fitting effect of the zero-order equation and the Higuchi equation is poor, the first-order equation R2 is 0.99911, and the fitting effect is good. Therefore, the in-vitro release rule of the pellet prepared by the invention accords with a first-order equation, and the result shows that the pellet has the sustained-release characteristic in colon.
Example 2 preparation of colon-specific sustained-release pellet with buckeye seed extract
1. Preparation of drug-loaded pellet core
| Raw and auxiliary materials | Function of | Dosage of |
| Sucrose pill core | Blank pill core | 100g |
| HPC-EF | Adhesive agent | 3g |
| Semen Aesculi extract | Active ingredient | 12g |
| 60% ethanol | Solvent(s) | 300ml |
Placing the sucrose pill core in a fluidized bed bottom spraying coating device, dissolving HPC-EF and semen Aesculi extract into 60% ethanol for clarification, and spraying.
2. Pellet coating process
(1) Insulating layer
| Raw and auxiliary materials | Action | Amount of the composition |
| Medicine-carrying pill core | —— | 100g |
| Gelatin | Film forming agent | 25g |
| Silica gel micropowder | Lubricant agent | 0.5g |
| Amylose starch | Targeted promoters | 8g |
| Purified water | Solvent(s) | 450ml |
Placing the drug-loaded pill core in a fluidized bed bottom spray coating device, dissolving gelatin, micro-powder silica gel and amylose in purified water, and performing spray coating.
(2) Enteric layer
Placing the drug-loaded core in fluidized bed bottom spray coating device, dissolving Ewing S100, ewing L100-55, triethyl citrate, and glyceryl monostearate with water to obtain coating solution, and spray coating.
The cumulative release of the prepared pellets in simulated gastric fluid (2 h), intestinal fluid (4 h) was 1.17%, 3.55%, respectively, and the cumulative release at 6h in simulated colon was 85.65% and approached peak after 3h (fig. 4).
Example 3 preparation of colon-specific sustained-release pellet with buckeye seed extract
1. Preparation of drug-loaded pill core
| Raw and auxiliary materials | Action | Amount of the composition |
| Starch pellet core | Blank pill core | 100g |
| PVP K90 | Adhesive agent | 1.5g |
| Semen Aesculi extract | Active ingredient | 12g |
| 60% ethanol | Solvent(s) | 200ml |
And (3) placing the starch pill core in a fluidized bed bottom spraying coating device, dissolving PVP K90 and semen Aesculi extract into 60% ethanol for clarification, and spraying the medicine.
2. Pellet coating process
(1) Insulating layer
| Raw and auxiliary materials | Function of | Dosage of |
| Medicine-carrying pill core | —— | 100g |
| Trehalose | Film forming agent | 20g |
| Talcum powder | Lubricant agent | 1.1g |
| Glucan | Targeted promoters | 5g |
| Purified water | Solvent(s) | 300ml |
Placing the drug-loaded pill core in a fluidized bed bottom spray coating device, dissolving trehalose, talcum powder and glucan in purified water, and spray coating.
(2) Enteric layer
| Raw and auxiliary materials | Action | Dosage of |
| Isolating layer medicine-carrying pill core | —— | 100g |
| Youteqi S100 | Coating agent | 26g |
| Youteqi L100-55 | Coating agent | 12.5g |
| Citric acid triethyl ester | Plasticizer | 3.5 |
| Tween | ||
| 80 | Plasticizer | 0.6g |
| Glycerol monostearate | Anti-sticking agent | 0.9g |
| Water (W) | Solvent(s) | 50ml |
Placing the drug-loaded pellet core in fluidized bed bottom spray coating device, dissolving Ewing S100, ewing L100-55, triethyl citrate, tween 80 and glyceryl monostearate with water to obtain coating solution, and spray coating.
The cumulative release of the prepared pellets in simulated gastric fluid (2 h), intestinal fluid (4 h) was 3.37%, 5.13%, respectively, the cumulative release at 6h in simulated colon was 95.15% and approached peak after 4h (fig. 5).
Example 4 preparation of Colon-specific sustained-release pellet with buckeye extract
1. Preparation of drug-loaded pill core
| Raw and auxiliary materials | Action | Dosage of |
| Lactose pill core | Blank pill core | 100g |
| CMC | Adhesive agent | 5g |
| Semen Aesculi extract | Active ingredient | 12g |
| 60% ethanol | Solvent(s) | 350ml |
Placing the lactose pill core in a fluidized bed bottom spray coating device, dissolving CMC and semen Aesculi extract in 60% ethanol to obtain clear solution, and spraying.
2. Pellet coating process
(1) Insulating layer
Placing the drug-loaded pill core in a fluidized bed bottom spray coating device, dissolving chitosan, talcum powder, amylose and glucan in purified water, and spray coating.
(2) Enteric layer
| Raw and auxiliary materials | Function of | Dosage of |
| Isolating layer medicine-carrying pill core | —— | 100g |
| Youteqi S100 | Coating agent | 30g |
| Youteqi L100-55 | Coating agent | 6g |
| Citric acid triethyl ester | Plasticizer | 3.3 |
| Tween | ||
| 80 | Plasticizer | 0.5g |
| Glycerol monostearate | Anti-sticking agent | 1.2g |
| Water (W) | Solvent(s) | 50ml |
Placing the drug-loaded pellet core in fluidized bed bottom spray coating device, dissolving Ewing S100, ewing L100-55, triethyl citrate, tween 80 and glyceryl monostearate with water to obtain coating solution, and spray coating.
The prepared pellets had a cumulative release of 0.57% and 6.81% in simulated gastric fluid (2 h) and intestinal fluid (4 h), respectively, and a cumulative release of 89.23% in simulated colon for 6h (fig. 6).
Comparative example enteric-coated pellets prepared by conventional method
1. Preparation of drug-loaded pellet core
Placing the sucrose pill core in a fluidized bed bottom spraying coating device, dissolving CMC and semen Aesculi extract in 60% ethanol to obtain clear solution, and spraying.
2. Pellet coating process
(1) Insulating layer
| Raw and auxiliary materials | Function of | Dosage of |
| Medicine-carrying pill core | —— | 100g |
| HPLC | Film forming agent | 25g |
| Purified water | Solvent(s) | 400ml |
And (3) placing the drug-loaded pill core in a fluidized bed bottom spraying coating device, dissolving HPLC into purified water, and spraying a liquid coating.
(2) Enteric layer
| Raw and auxiliary materials | Function of | Dosage of |
| Isolating layer medicine-carrying pill core | —— | 100g |
| Youteqi L100-55 | Coating agent | 45g |
| Citric acid triethyl ester | Plasticizer | 3.3g |
| Glycerol monostearate | Anti-sticking agent | 0.6g |
| Purified water | Solvent(s) | 50ml |
Placing the drug-loaded core in a fluidized bed bottom spray coating device, dissolving Ewing L100-55, triethyl citrate, and glyceryl monostearate with water to obtain coating solution, and spray coating.
The pellets prepared had a cumulative release of 2.56% and 30.51% in simulated gastric fluid (2 h) and intestinal fluid (4 h), respectively, and a cumulative release of 75.65% in simulated colon for 6h (fig. 7). The drug is released in the intestinal tract in a small amount, and the release of the drug begins to be large after entering colon fluid.
Claims (8)
1. A colon-specific sustained-release pellet containing semen Aesculi extract is composed of a drug-loaded pellet core, an isolation layer, and an enteric layer,
carrying out drug loading on the pellet core: comprises a blank pill core, buckeye extract coated on the surface of the blank pill core and an adhesive for coating a medicament;
isolation layer: the drug-loaded pill core consists of a film-forming agent, a lubricant and a targeting promoter, wherein the film-forming agent accounts for 10-30% of the mass of the drug-loaded pill core; the lubricant accounts for 0.5-1.5% of the mass of the drug-loaded pill core; the targeted accelerant accounts for 5-12% of the mass of the drug-loaded pill core;
enteric layer: consists of Eudragit S100, eudragit L100-55, plasticizer and antisticking agent, the enteric layer accounts for 40-60% of the sum of the weight of the medicine-carrying pill core and the isolating layer,
the targeting promoter is amylose and/or glucan; the buckeye seed extract contains 60-80% of total saponins.
2. A colon-specific sustained-release pellet as claimed in claim 1, wherein the colon-specific sustained-release pellet comprises: the blank pellet core is a sucrose pellet core, a microcrystalline cellulose pellet core, a starch pellet core or a lactose pellet core.
3. A colon-specific sustained-release pellet as claimed in claim 1, wherein the colon-specific sustained-release pellet comprises: the adhesive is cellulose ether derivative or polyvinylpyrrolidone, and occupies 1-5% of the mass of the white pill core.
4. A colon-specific sustained-release pellet as claimed in claim 1, wherein the colon-specific sustained-release pellet comprises: the film forming agent is selected from one or more of carrageenan, guar gum, gelatin, arabic gum, chitosan and trehalose.
5. A colon-specific sustained-release pellet as claimed in claim 1, wherein the colon-specific sustained-release pellet comprises: the plasticizer is triethyl citrate and/or tween 80.
6. A colon-specific sustained-release pellet as claimed in claim 1, wherein the colon-specific sustained-release pellet comprises: the lubricant is talcum powder or micro silica gel.
7. A method for preparing colon specific sustained release pellets of an extract from buckeye according to any one of claims 1 to 6, characterised in that it comprises the steps of:
s1: placing the blank pill core in a fluidized bed bottom spraying coating device, dissolving the adhesive and the buckeye extract by using a solvent, and spraying to apply medicine to prepare a medicine-carrying pill core;
s2: placing the drug-loaded pill core in a fluidized bed bottom spraying coating device, dissolving and uniformly mixing a film-forming agent, a lubricant and a targeting accelerator by using a solvent, and then spraying and coating to prepare an isolation layer drug-loaded pill core;
s3: the drug-loaded pill core of the isolating layer is placed in a fluidized bed bottom spray coating device, and the Eudragit S100, the Eudragit L100-55, the plasticizer and the anti-sticking agent are dissolved by a solvent and then spray coated.
8. A preparation method of colon-specific sustained-release pellets of buckeye extract as claimed in claim 7, wherein the preparation method comprises the following steps: the spraying parameters are that the atomizing pressure is 1.5-2.0bar, the material temperature is 30-60 ℃, and the air quantity is 25-35m 3 /h。
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| CN202211303070.5A CN115581713B (en) | 2022-10-24 | 2022-10-24 | Chinese buckeye extract colon-specific sustained-release pellets and preparation method thereof |
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| CN202211303070.5A CN115581713B (en) | 2022-10-24 | 2022-10-24 | Chinese buckeye extract colon-specific sustained-release pellets and preparation method thereof |
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| CN113527379A (en) * | 2021-08-19 | 2021-10-22 | 海南师范大学 | Method for extracting, separating and purifying aescine from semen Veronicae |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113527379A (en) * | 2021-08-19 | 2021-10-22 | 海南师范大学 | Method for extracting, separating and purifying aescine from semen Veronicae |
Non-Patent Citations (1)
| Title |
|---|
| 石沁等: "罐组分级逆流提取技术在娑罗子提取工艺中的应用", 世界科学技术-中医药现代化, vol. 12, no. 4, pages 603 - 607 * |
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