CN115804752B - Preparation method of digitalis glycoside-containing eye drops - Google Patents
Preparation method of digitalis glycoside-containing eye drops Download PDFInfo
- Publication number
- CN115804752B CN115804752B CN202310071088.5A CN202310071088A CN115804752B CN 115804752 B CN115804752 B CN 115804752B CN 202310071088 A CN202310071088 A CN 202310071088A CN 115804752 B CN115804752 B CN 115804752B
- Authority
- CN
- China
- Prior art keywords
- digitalis
- water
- solution
- layer
- glycoside
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation method of an eye drop containing digitalis glycoside, which comprises the following steps: adding 20g of boric acid and 0.1g of esculin into 500ml of water for injection, stirring at room temperature for 5 minutes to dissolve, then adding the liquid digitalis leaf extract, stirring at room temperature for 5 minutes to dissolve, adjusting the pH value of the solution to 5.5-6.5 by using sodium hydroxide, stirring for 5 minutes, and adding purified water to 1000ml; step two, sterile filtration and filling; the eye drop containing digitonin has the packaging specification of 0.4ml, namely 0.006mg digitonin and 0.040mg esculin.
Description
Technical Field
The invention relates to a preparation method of a pharmaceutical preparation, in particular to a preparation method of a novel digitalis glycoside-containing eye drop.
Background
The eye drops containing digitalis glycoside are a drug which is already marketed and have the general name: the esculin and digitalis double-glycoside eye drops comprise the following components: each 10ml contains digitonin 0.15mg, hepta She Tinggan 1.0.0 mg, boric acid and purified water as auxiliary materials, and has the advantages of fundus macular degeneration and asthenopia as indication, 0.4ml digitonin 0.006mg and esculin 0.040mg.
The digitalis glycoside (English name: digitalis glycosides) is extract of digitalis leaf, contains 20 or more kinds of cardiac glycoside, is mainly prepared by condensing 3 kinds of cardiac glycoside-digitalis aglycone, hydroxy digitalis aglycone and different sugar, and is used as extract of digitalis leaf for eye medicine, and is dissolved in water.
The digitalis leaf extract which is currently marketed comprises an aqueous extract and an alcoholic extract, the content of which is 20-60% (weight percent) calculated as digitalis glycoside.
Esculin is a coumarin compound extracted from dried branch bark or dry bark of Carpinus chinensis belonging to Oleaceae, and is white crystalline powder at normal temperature, and can be prepared by synthetic method, chemical name: 6- (. Beta. -D-glucopyranosyloxy) -7-hydroxy-2H-1-benzofuran-2-one, english chemical name: 6- (. Beta. -D-glucopyranosyloxy) -7-hydroxy-2H-1-benzopyran-2-one. Other names for esculetin include: horse chestnut bark glycoside, escin, aesculin, escin, bicolorin, crataegin, enalachrome, escosyl, esculetin 6-beta-D-glucoside, esculeline.
Solubility of esculin: can be dissolved in hot water, hot ethanol, acetic acid, methanol, pyridine and chloroform, and slightly dissolved in cold water and ethanol. Very slightly soluble in diethyl ether.
Methods for preparing eye drops from digitalis extract and esculin have been reported in the prior art, such as: chinese patent CN200510030723.7 example 3, chinese patent CN200610147972.9 example 19, both dosed as digitalis leaf dry extract, wherein the extract is derived from organic layers such as chloroform, ethyl acetate, etc.
Chinese patent CN200910242110.8, example 2, discloses the preparation and use of digitalis extract, wherein the extract is derived from the aqueous layer, and the digitalis extract prepared in CN200910090337.5, comparative example 2, is derived from the aqueous layer.
In the prior art, all the components of the extract contain digitalis glycoside, but the content and the components are different due to different extraction methods, and the digitalis leaf extract contains components with lower water solubility, so that the digitalis dry extract is difficult to dissolve in water, the operation difficulty of the eye drop preparation process is increased, the stability of the obtained eye drop aqueous solution preparation is poor, the storage time is short, and the precipitation or color change of a long-time or low-temperature storage solution occurs, so that the production of the medicine is difficult.
Disclosure of Invention
Compared with the prior art, the invention uses the characteristic that digitalis leaf extract is slightly soluble in water, and uses liquid digitalis leaf extract for feeding, so that the dissolution speed is greatly improved, the preparation efficiency of the preparation is improved, and in addition, the unexpected discovery is that the stability of the obtained eye drops is also greatly improved, and the medicine quality is improved.
The preparation method comprises the following steps:
adding 20g of boric acid and 0.1g of esculin into 500ml of water for injection, stirring at room temperature for 5 minutes to dissolve, then adding 0.015g of liquid digitalis leaf extract, stirring at room temperature for 5 minutes to dissolve, adjusting the pH value of the solution to 5.5-6.5 by using sodium hydroxide, stirring for 5 minutes, and adding purified water to 1000ml;
filtering the liquid medicine into a sterile storage tank, then canning into a unit dose container made of polyethylene particles under the protection of nitrogen, and sealing and packaging to obtain the medicine; the package size of the eye drop containing digitonin is 0.4ml, the package size of the eye drop containing digitonin is 0.006mg, and the package size of the eye drop containing esculin is 0.04mg.
Wherein the unit dose container made of polyethylene particles is a disposable container of 0.4ml capacity.
According to the invention, boric acid and esculin which can be dissolved usually by heating are put into water and stirred, the esculin can be quickly dissolved without heating (boric acid has a dissolution assisting effect), and the liquid digitalis leaf extract prepared by the method can be quickly dissolved under the condition of not heating after the esculin is dissolved, so that the operation is quickened, the efficiency is improved, and the product is more stable.
The invention further discovers that nitrogen is introduced in the filling process, so that oxidation reaction can be prevented, the formula composition of the invention is simplified and safer, and no other additives are needed.
The key point of the invention is that the liquid digitalis leaf extract is prepared by the following method,
1) Adding 100g digitalis leaf coarse powder into 300ml of 90% (V/V) ethanol solution, reflux-extracting at 80deg.C for 60 min, extracting for three times, mixing extractive solutions, recovering ethanol from extractive solution, concentrating, and centrifuging to obtain solid containing digitalis glycoside;
2) Dispersing the solid with 150ml of water, extracting with equal volume of chloroform for three times, mixing chloroform layers, washing chloroform solution with 1L of 2% (W/W) NaOH solution, separating chloroform layer, washing chloroform layer with water until water layer is neutral, separating chloroform layer, collecting all water layer and NaOH solution layer, mixing, and concentrating to obtain concentrate containing digitonin 100ml;
3) The digitalis glycoside-containing concentrate was dissolved in 100ml of 50% aqueous acetone solution, extracted twice with an equal volume of ethyl acetate, and separated to give a digitalis glycoside-containing aqueous layer, which was examined by HPLC, wherein digitalis glycoside was 1.36mg/10ml.
The invention utilizes the characteristic that part of digitalis glycoside is dissolved in water and part of digitalis glycoside is slightly dissolved in water to prepare the liquid digitalis leaf extract, and the liquid digitalis leaf extract is used for feeding, so that the dissolution speed is greatly improved, the preparation efficiency of the preparation is improved, and in addition, the unexpected discovery is that the stability of the obtained eye drops is also greatly improved, and the medicine quality is improved.
The invention discovers that the solubility of glycosides depends on the molecular structure, and the more polar the glycosides are, the more water-soluble the glycosides are; whereas aglycone is poorly water-soluble if it is macromolecular or of low polarity and has few glycosyl groups. The present invention takes advantage of this property and provides a digitalis leaf extract which is soluble in water and suitable for preparation into eye drops by modification of the extraction process.
The digitalis leaf extract obtained by the method is a compound digitalis glycoside extract, contains various components, and the main component is water-soluble, but some of the digitalis leaf extract is amphiphilic and can be dissolved in water or an organic solvent, so that the extract is a component which can be dissolved in water. In the process of the present invention, step 1) is to remove ethanol after 90% ethanol extraction to obtain a product which is dissolved in water and dried to obtain a solid which comprises water-soluble and amphiphilic components but is mainly water-soluble. Step 2) using chloroform extraction, wherein the purpose is to remove fat-soluble components in the solid in the previous step, washing the chloroform layer by using an alkaline aqueous solution, so as to keep the effective components to the maximum extent, avoiding taking away a small amount of amphiphilic components by chloroform to remove the components cleanly, and finally, collecting and concentrating all water layers in the step, wherein the main components are water-soluble, but some of the water layers are amphiphilic components. Step 3) dissolving the concentrate of the previous step with an aqueous acetone solution is not problematic because the ingredients therein are both water-soluble and amphiphilic, and extraction with ethyl acetate is intended to remove the amphiphilic portion thereof which is more prone to lipid solubility, making the product more soluble in water, and finally obtaining an aqueous layer which is the product of the present invention, wherein digitonin content is 1.36mg/10ml.
The invention is treated by the above method, especially the concentrate in step 3) is dissolved by 100ml of 50% acetone aqueous solution, and extracted by equal volume of ethyl acetate for two times, and the ethyl acetate layer is separated to obtain the water layer containing digitalis leaf extract, so that the product is easier to dissolve in water, the water layer can be directly taken as a raw material for feeding after detecting and adjusting the concentration, and for liquid preparation, the feeding method can solve all problems caused by indissolvable digitalis glycoside in the preparation process, overcomes the defects of the prior art, and achieves unexpected technical effects. The method of the invention is superior to the prior art in both material dissolution rate and product stability.
Drawings
FIG. 1, HPLC chromatogram of liquid digitalis leaf extract of the present invention.
Detailed Description
The invention is further illustrated by the following examples.
Example 1
An eye drop formulation containing digitalis glycoside:
seven She Tinggan 0.1.1 g
Adding liquid digitalis leaf extract (calculated as digitalis glycoside) 15mg
Boric acid 20g
Proper amount of sodium hydroxide
Purified water was added to 1000ml.
The preparation method comprises the following steps:
adding 20g of boric acid and 0.1g of esculin into 500ml of water for injection, stirring at room temperature for 5 minutes to dissolve, then adding liquid digitalis leaf extract (the added amount is 0.015g according to digitalis), stirring at room temperature for 5 minutes to dissolve, adjusting the pH value of the solution to 5.5-6.5 by using sodium hydroxide, stirring for 5 minutes, and adding purified water to 1000ml;
filtering the liquid medicine into a sterile storage tank, then canning into a unit dose container made of polyethylene particles under the protection of nitrogen, and sealing and packaging to obtain the medicine;
the package size of the eye drop containing digitonin is 0.4ml, contains digitonin 0.006mg and esculin 0.04mg.
Wherein the unit dose container made of polyethylene particles is a disposable container of 0.5ml capacity.
The preparation method of the liquid digitalis leaf extract comprises the following steps:
1) Adding 100g digitalis leaf coarse powder into 300ml of 90% (V/V) ethanol solution, reflux-extracting at 80deg.C for 60 min, extracting for three times, mixing extractive solutions, recovering ethanol from extractive solution, concentrating, and centrifuging to obtain solid containing digitalis glycoside;
2) Dispersing the solid with 150ml of water, extracting with equal volume of chloroform for three times, mixing chloroform layers, washing chloroform solution with 1L of 2% (W/W) NaOH solution, separating chloroform layer, washing chloroform layer with water until water layer is neutral, separating chloroform layer, collecting all water layer and NaOH solution layer, mixing, and concentrating to obtain concentrate containing digitonin 100ml;
3) The digitalis glycoside-containing concentrate was dissolved in 100ml of 50% aqueous acetone solution, extracted twice with an equal volume of ethyl acetate, and separated to give a digitalis glycoside-containing aqueous layer, which was examined by HPLC, wherein digitalis glycoside was 1.36mg/10ml.
The content determination of digitonin in the liquid digitalis leaf extract of the invention belongs to the prior art, and can be detected by a method in Chinese patent CN 200610147972.9.
Example 2
HPLC chromatogram of liquid digitalis leaf extract of the invention adopts octadecylsilane chemically bonded silica gel as filler (200 mm×4.6mm,5 μm); water-acetonitrile is taken as a mobile phase (the volume ratio of water to acetonitrile is 1:1); the flow rate is 1ml/min; the detection wavelength is 220nm. 20 μl of the liquid digitalis leaf extract of the present invention was taken and tested under the above chromatographic conditions, and the obtained chromatogram was shown in FIG. 1.
Comparative example:
preparation of dried digitalis leaf extract:
1) Adding 300ml of 90% ethanol solution into 100g of digitalis leaf coarse powder, reflux-extracting at 80 ℃ for 60 minutes, extracting three times, mixing the extracting solutions, recovering ethanol from the obtained extracting solutions, and centrifuging and filtering the concentrated solution to obtain a solid.
2) Dispersing the solid with 150ml of water, extracting with equal volume of chloroform for three times, mixing chloroform layers, washing chloroform solution with 1L of 2% (W/W) NaOH solution, separating chloroform layer, washing chloroform layer with water until water layer is neutral, separating chloroform layer, mixing water layer with NaOH solution, and concentrating to obtain concentrate 100ml;
3) The concentrate is dried to obtain dried digitalis leaf extract 51.2mg, and the content of digitalis glycoside in the dried digitalis leaf extract is 20.4mg.
The preparation method for preparing the digitalis glucoside-containing eye drops by adopting the dried digitalis leaf extract comprises the following steps:
1) Step one, adding 20g of boric acid and 0.1g of esculin into 500ml of water for injection, then adding 15mg of dried digitalis leaf extract, heating to 40 ℃, stirring for 30 minutes to dissolve, adjusting the pH value of the solution to 5.5-6.5 by using sodium hydroxide, stirring, and adding purified water to 1000ml.
2) Filtering the liquid medicine into a sterile storage tank, then canning into a unit dose container made of polyethylene particles under the protection of nitrogen, and sealing and packaging to obtain the medicine;
the package size of the eye drop containing digitonin is 0.4ml, contains digitonin 0.006mg and esculin 0.04mg.
Experimental example
The beneficial effects of the invention are further illustrated by experimental data below.
1. Solubility experiment
The experiment adopts the following method to feed, 20g of boric acid and 0.1g of esculin are put into 500ml of water for injection, and then 0.015g of digitalis leaf extract is added;
the feeding method is carried out by adopting the same method, wherein the digitalis glycoside is prepared by adopting the following different methods:
1) Preparation of digitalis leaf extract batch by the method of example 1 of the present invention
2) Preparation of digitalis leaf extract batch by method of preparation example 1 of Chinese patent CN2005100307237 example
3) Preparation of digitalis leaf extract batch by method of example 15 of Chinese patent CN200610147972.9
4) Preparation of digitalis leaf extract batch by comparative example method of the present invention
After observing the material feeding prepared by different methods, the material dissolution time is observed under the condition of stirring at room temperature, and the results are shown in the following table:
TABLE 1 dissolution schedule
2. Stability investigation
The eye drops containing digitonin are prepared according to the packaging specification of 0.4ml, 0.006mg containing digitonin and 0.04mg containing esculin, and are prepared by the following four methods:
1) Preparation of digitalis leaf extract and preparation of eye drops by the method of example 1 of the present invention
2) Chinese patent CN2005100307237, example 1, digitalis leaf extract and example 3, eye drops
3) Chinese patent CN200610147972.9, example 15, preparation of digitalis leaf extract, example 19, preparation of eye drops
4) Comparative example method of the invention preparation of digitalis leaf extract and preparation of eye drops
The method of example 2 of the present invention was used for content measurement.
Experiment 1, accelerated stability experiment at 45 ℃ for 90 days, the results are shown in the following table:
TABLE 2 high temperature acceleration stability Meter
Experiment 2, test 4500LX, 90 days irradiation accelerated stability test, results are shown in the following table:
TABLE 3 light acceleration stability Meter
3. Animal experiment:
effect of digitalis-containing eye drops prepared in example 1 of the present invention on Experimental macular degeneration in rats
The experimental method is to establish a macular degeneration rat model by a sodium iodate tail intravenous injection method, randomly divide the rats after modeling into 2 groups of 10 rats each, and respectively obtain a physiological saline group and an eye drop group containing digitalis glycoside. Normal group 10 animals are normally fed, normal saline and digitalis-containing eye drops are respectively added on day 1 after molding, the administration time is 9:00, 12:00 and 15:00 for 3 times/day, the administration is carried out for 10 days, animals are treated after 10 days, and the pathological tissues of retina are observed and detected.
The pathological tissue fixing, dehydrating, embedding and slicing methods are as follows:
(1) Drawing materials: after the rats are anesthetized, the eyeballs are quickly picked up, and redundant muscles and conjunctival tissues are carefully removed;
(2) Fixing:
1) Placing the anterior chamber puncture in 4% PFA solution for pre-fixation for 20min;
2) Cutting cornea along limbus, removing anterior segment and part of vitreous body, placing the rest tissue in 4% PFA solution again, fixing at 4deg.C for 24 hr;
(3) Dehydrating: discarding the PFA solution, placing the tissue in an EP tube filled with 30% sucrose solution for dehydration, and ending the dehydration when the tissue is immersed into the bottom of the tube;
(4) Embedding: discarding the sucrose solution, placing the tissue in an embedding box filled with an O.C.T embedding agent, placing the long axis direction of the optic nerve in parallel with the long side of the embedding box, and slowly freezing the tissue by liquid nitrogen after placing the optic nerve in position; after the tissue is completely frozen, the tissue is placed in a refrigerator at the temperature of minus 80 ℃ for preservation.
(5) Slicing: taking out the tissue block from the refrigerator at-80deg.C, and balancing in the refrigerator at-20deg.C for 30min. Slicing 8 μm along the long axis direction of the eyeball optic nerve by using a frozen microtome, collecting 2-3 samples from each slice by using a clean anti-drop glass slide when the tissue passing the optic nerve is observed, airing at room temperature, adding O.C.T, placing the slice into a glass staining jar filled with acetone after the O.C.T is dried, and fixing for 15min; drying and storing at-20deg.C.
Dyeing the slices by TUNEL method, air drying, and storing in a refrigerator at-20deg.C in dark place; the following day is observed by a fluorescent inverted microscope, ultraviolet light and green light are adopted for excitation respectively, 3 slices are randomly selected from each group, 5 fields are randomly selected from each slice for shooting, the number of apoptosis positive cells and the total number of cells in each field are counted respectively, and the apoptosis rate (%) = the number of apoptosis positive cells/the total number of cells in the same field x 100%.
TUNEL assay detects retinal apoptosis results:
at 10 days, the retinal pigment epithelium and outer nuclear layer of the model control group showed a large number of apoptotic cells in a uniformly contracted or crescent shape, and the difference was statistically significant (P < 0.05) compared with the normal group. The eye drops containing digitalis have reduced apoptosis of retinal pigment epithelium and exocarpium (P < 0.05) compared with the model control group.
Table 4 comparison of% apoptosis rate of retinal cells in each group of rats 10 days after administration
Note, ×: compared with the normal group, the differences were statistically significant (P<0.05)。 & : compared with the model group, the difference is statistically significant (P<0.05)。
It is concluded that the eye drop containing digitalis glycoside has protecting effect on retina of experimental dry AMD rat, can improve retina cell function and pathological tissue damage, and can inhibit apoptosis of macular degeneration retina cell of experimental rat.
Claims (2)
1. A method for preparing an eye drop containing digitalis glycoside, which is characterized by comprising the following steps:
adding 20g of boric acid and 0.1g of esculin into 500ml of water for injection, stirring at room temperature for 5 minutes to dissolve, then adding 0.015g of liquid digitalis leaf extract, stirring at room temperature for 5 minutes to dissolve, adjusting the pH value of the solution to 5.5-6.5 by using sodium hydroxide, stirring for 5 minutes, and adding purified water to 1000ml;
filtering the liquid medicine into a sterile storage tank, then canning into a unit dose container made of polyethylene particles under the protection of nitrogen, and sealing and packaging to obtain the medicine; wherein, the liquid digitalis leaf extract is prepared by the following steps:
1) Extracting digitalis leaf coarse powder 100g with 90% ethanol solution 300ml at 80deg.C under reflux for 60 min for three times, mixing extractive solutions, recovering ethanol, concentrating, and centrifuging to obtain digitalis glycoside-containing solid;
2) Dispersing the solid with 150ml of water, extracting with equal volume of chloroform for three times, mixing chloroform layers, washing chloroform solution with 1L of 2% NaOH solution, separating chloroform layer, washing chloroform layer with water until water layer is neutral, separating chloroform layer, collecting all water layer and NaOH solution layer, mixing, and concentrating to obtain concentrate containing digitalis glycoside 100ml;
3) The digitalis glycoside-containing concentrate was dissolved in 100ml of 50% aqueous acetone solution, extracted twice with an equal volume of ethyl acetate, and separated to give a digitalis glycoside-containing aqueous layer, which was examined by HPLC, wherein digitalis glycoside was 1.36mg/10ml.
2. The method according to claim 1, wherein the ophthalmic solution containing digitonin has a package size of 0.4ml, contains 0.006mg digitonin and 0.04mg esculin.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310071088.5A CN115804752B (en) | 2023-02-07 | 2023-02-07 | Preparation method of digitalis glycoside-containing eye drops |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310071088.5A CN115804752B (en) | 2023-02-07 | 2023-02-07 | Preparation method of digitalis glycoside-containing eye drops |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115804752A CN115804752A (en) | 2023-03-17 |
CN115804752B true CN115804752B (en) | 2023-08-11 |
Family
ID=85487535
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310071088.5A Active CN115804752B (en) | 2023-02-07 | 2023-02-07 | Preparation method of digitalis glycoside-containing eye drops |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115804752B (en) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1954855A (en) * | 2005-10-26 | 2007-05-02 | 信谊药厂 | Eye preparation containing sodium hyaluronate for treating fundus macular degeneration and its preparation method |
CN101209312A (en) * | 2006-12-26 | 2008-07-02 | 信谊药厂 | Digitalis extract and preparation thereof |
CN101623377A (en) * | 2009-08-05 | 2010-01-13 | 锦州奥鸿药业有限责任公司 | Digitalis extract as well as preparation method and application thereof |
CN101874848A (en) * | 2009-12-08 | 2010-11-03 | 于洪儒 | Digitalis extract, preparation method and application thereof |
WO2022268048A1 (en) * | 2021-06-22 | 2022-12-29 | Nanjing Nutrabuilding Bio-Tech Co., Ltd | Use of l-ergothioneine for alleviating and preventing age-related visual degeneration |
-
2023
- 2023-02-07 CN CN202310071088.5A patent/CN115804752B/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1954855A (en) * | 2005-10-26 | 2007-05-02 | 信谊药厂 | Eye preparation containing sodium hyaluronate for treating fundus macular degeneration and its preparation method |
CN101209312A (en) * | 2006-12-26 | 2008-07-02 | 信谊药厂 | Digitalis extract and preparation thereof |
CN101623377A (en) * | 2009-08-05 | 2010-01-13 | 锦州奥鸿药业有限责任公司 | Digitalis extract as well as preparation method and application thereof |
CN101874848A (en) * | 2009-12-08 | 2010-11-03 | 于洪儒 | Digitalis extract, preparation method and application thereof |
WO2022268048A1 (en) * | 2021-06-22 | 2022-12-29 | Nanjing Nutrabuilding Bio-Tech Co., Ltd | Use of l-ergothioneine for alleviating and preventing age-related visual degeneration |
Non-Patent Citations (1)
Title |
---|
尹莲主编.天然药物化学.中国中医药出版社,2017,(第第2版版),328. * |
Also Published As
Publication number | Publication date |
---|---|
CN115804752A (en) | 2023-03-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CZ377192A3 (en) | Process of purifying hyaluronic acid and a fraction of a pure hyaluronic acid for ophthalmological use | |
Refojo et al. | Extraction of retinol and cholesterol by intraocular silicone oils | |
US8329232B2 (en) | Process for preparing water extract of cinnamon | |
CN104189043A (en) | Novel milk thistle extract, method for the production, and use | |
CN112457426A (en) | Method for simultaneously extracting different lycium barbarum polysaccharide components | |
US20130150335A1 (en) | Paclitaxel/steroidal complex | |
CN103432066A (en) | Compound mannitol injection and preparation method thereof | |
CN115804752B (en) | Preparation method of digitalis glycoside-containing eye drops | |
Burnstock et al. | Prolonged hypotension and ultrastructural changes in sympathetic neurones following guanacline treatment | |
WO2012065556A1 (en) | Process for preparing water extract of cinnamon | |
CN104257615A (en) | Dezocine freeze-dried pharmaceutical composition and preparation method thereof | |
CN103319409A (en) | Edaravone compound, medicinal composition thereof, and preparation methods of compound and composition | |
CN107365337A (en) | Hesperidine and its extraction process | |
CN114748566B (en) | Anti-alcohol liver-protecting composition and application thereof | |
CN105796486A (en) | Butylphthalide fat emulsion injection and preparation process thereof | |
ES2909313T3 (en) | Diosmin Preparation Method | |
CN113995074A (en) | Molecular essence solid beverage with blood glucose reducing function and preparation method thereof | |
Ginting et al. | In Vivo study of Antidiabetic Activity from Ethanol Extract of Clitoria ternatea L. Flower | |
CN110227062B (en) | Baicalin liposome ointment and preparation method thereof | |
CN111437263B (en) | Corncob total flavone solid dispersion osmotic pump tablet and preparation method thereof | |
CN101623377B (en) | Digitalis extract as well as preparation method and application thereof | |
CN108066315A (en) | Puerarin and scutellarin lipid nano particle eye-drops preparations and preparation method thereof | |
CN108324688B (en) | Rizatriptan benzoate in-situ gel nasal spray | |
CN109985075B (en) | Ginkgo leaf extract injection and preparation method thereof | |
KR0128493B1 (en) | Process for prepating jang won soft capsule |
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 |