CN109704955B - Deuterated rhein and preparation method and application thereof - Google Patents
Deuterated rhein and preparation method and application thereof Download PDFInfo
- Publication number
- CN109704955B CN109704955B CN201910058616.7A CN201910058616A CN109704955B CN 109704955 B CN109704955 B CN 109704955B CN 201910058616 A CN201910058616 A CN 201910058616A CN 109704955 B CN109704955 B CN 109704955B
- Authority
- CN
- China
- Prior art keywords
- rhein
- deuterated
- temperature
- reaction
- preparation
- 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
Abstract
The invention relates to a deuterated rhein and a preparation method and application thereof, wherein the preparation method comprises the following steps: providing reaction raw materials, wherein the reaction raw materials comprise rhein, a platinum-carbon catalyst and heavy water; mixing the reaction raw materials, reacting at a first temperature for 0.5-3 h, and then heating to a second temperature for reacting for 8-20 h to obtain the deuterated rhein; wherein the first temperature is 40-60 ℃ and the second temperature is 100-200 ℃. The invention provides an effective preparation method of deuterated rhein for the first time, the preparation method has mild conditions, low production cost, more deuterated sites and higher yield, can be used for large-scale industrial production, and provides a new way for research and development and application of rhein drugs.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a deuterated rhein and a preparation method and application thereof.
Background
Rhein is coffee needle crystal, and is yellow needle crystal after sublimation. Its chemical name is 1, 8-Dihydroxy-3-carboxyl anthraquinone (1, 8-Dihydroxy-3-carboxyl-anthraquinone), molecular weight is 284.21, and molecular formula is C15H8O6The CAS:478-43-3 has the structural formula shown in the specification. Rhein can be dissolved in pyridine and sodium bicarbonate water solution, is slightly soluble in ethanol, benzene, chloroform, ether and petroleum ether, and is insoluble in water. It is mainly found in the dried roots and rhizomes of Rheum officinale (Rheum officinale Baif.) of Polygonaceae, Rheum palmatum L., and Rheum tanguticum Maxim. Ex Balf.). Rhein has main functional characteristics including antitumor activity, antibacterial activity, immunosuppressive action, diuretic action, purgative action, anti-inflammatory action, and treatment of diabetic nephropathy, and can be used for preparing health products for reducing blood lipid, reducing weight, relaxing bowels, removing toxic substances, cleaning internal environment, preventing gastric cancer, delaying aging, reducing cerebrovascular resistance, improving cerebral blood circulation, increasing cerebral blood flow, and resisting platelet aggregation, and can be used for treating paralysis after cerebrovascular diseases. However, the metabolic stability of rhein still needs to be further improved so as to improve the curative effect of the medicine.
Disclosure of Invention
Accordingly, there is a need for a method for preparing deuterated rhein.
A preparation method of deuterated rhein comprises the following steps:
providing reaction raw materials, wherein the reaction raw materials comprise rhein, a platinum-carbon catalyst and heavy water;
mixing the reaction raw materials, reacting at a first temperature for 0.5-3 h, and then heating to a second temperature for reacting for 8-20 h to obtain the deuterated rhein; wherein the first temperature is 40-60 ℃ and the second temperature is 100-200 ℃.
The preparation method of the deuterated rhein uses heavy water as a deuterium source, and rhein and the heavy water are reacted for 0.5-3 h at a first temperature under the catalysis of a platinum carbon catalyst to carry out pre-reaction, then the temperature is raised to a second temperature to carry out reaction for substitution, so that a deuterated rhein solution is obtained, then solid is removed by filtration, the pH value is adjusted to acidity, organic solvent extraction is carried out, and the deuterated rhein solid is obtained after drying, wherein deuterium is used for substituting hydrogen on a benzene ring. The invention provides an effective preparation method of deuterated rhein for the first time, the preparation method has mild conditions, low production cost, more deuterated sites and higher yield, can be used for large-scale industrial production, and provides a new way for research and development and application of rhein drugs.
In one embodiment, the mass ratio of the platinum carbon catalyst to the rhein is 1 (2-5), and the volume mass ratio of the heavy water to the rhein is (25-35) muL: 1 mg.
In one embodiment, the reaction raw material further comprises sodium borohydride, and the preparation method further comprises the following steps: and after the temperature is raised to the second temperature and the reaction is carried out for 8-20 hours, adjusting the pH value to be acidic.
In one embodiment, the mass ratio of the sodium borohydride to the rhein is 1 (11.8-40).
In one embodiment, the mass ratio of the platinum-carbon catalyst to the rhein is 1 (3-4), the volume mass ratio of the heavy water to the rhein is (28-32) muL: 1mg, and the mass ratio of the sodium borohydride to the rhein is 1 (20-24).
In one embodiment, the first temperature is 48-52 ℃ and the second temperature is 140-160 ℃.
In one embodiment, the reaction time at the first temperature is 0.8-1.2 hours, and the reaction time at the second temperature is 12-14 hours.
In one embodiment, the method further comprises the following steps: the prepared product is filtered to obtain filtrate, and then the filtrate is extracted by an organic solvent and dried.
The invention also provides deuterated rhein which has a structure represented by the following general formula I:
in formula I, each R is independently selected from protium or deuterium, and at least one R is deuterium.
The invention also provides an application of the deuterated rhein in preparation of medicines or health-care products.
Detailed Description
In order that the invention may be more fully understood, a more particular description of the invention will now be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
The preparation method of the deuterated rhein provided by the embodiment of the invention comprises the following steps:
providing reaction raw materials, wherein the reaction raw materials comprise rhein, a platinum-carbon catalyst and heavy water;
mixing the reaction raw materials, reacting at a first temperature for 0.5-3 h, and then heating to a second temperature for reacting for 8-20 h to obtain deuterated rhein; wherein the first temperature is 40-60 ℃, and the second temperature is 100-200 ℃.
Deuterium (D) is a stable nonradioactive isotope with the weight of 2.0144, and the content of deuterium in the deuterated compound generated by the synthetic method is far higher than the content of 0.015 percent in nature, so the deuterated compound can be regarded as a novel compound. The C-D bond is more stable than the C-H (protium) bond, so that the metabolism of the medicine can be changed, and the curative effect of the medicine can be improved. The preparation method of the deuterated rhein uses heavy water as a deuterium source, and rhein and the heavy water are reacted for 0.5-3 h at a first temperature under the catalysis of a platinum carbon catalyst to carry out pre-reaction, then the temperature is raised to a second temperature to carry out reaction for substitution, so that the deuterated rhein is obtained, then solid is removed by filtration, the pH value is adjusted to acidity, organic solvent extraction is carried out, and the deuterium is used for substituting hydrogen on a benzene ring after drying, so that the deuterated rhein solid is obtained. The invention provides an effective preparation method of deuterated rhein for the first time, the preparation method has mild conditions, low production cost, more deuterated sites and higher yield, can be used for large-scale industrial production, and provides a new way for research and development and application of rhein drugs.
In a specific example, the mass ratio of the platinum-carbon catalyst to the rhein is 1 (2-5), and the volume mass ratio of the heavy water to the rhein is (25-35) muL: 1 mg.
In a specific example, the reaction raw material further comprises sodium borohydride, and the preparation method further comprises the following steps: after the temperature is raised to the second temperature and the reaction is carried out for 8-20 hours, the pH value is adjusted to be acidic. The sodium borohydride is used as an activator of the platinum-carbon catalyst, the platinum-carbon catalyst can be pre-activated at a first temperature through the synergistic effect of the sodium borohydride and the platinum-carbon catalyst, and then the reaction is carried out at a second temperature, so that deuterated sites can be effectively increased, the deuterated rate is improved, and the penta-deuterated rhein can be obtained at most, and the specific process is shown as follows. The use of other components such as isopropanol, hydrogen, etc. as activators is far less effective than sodium borohydride and the process is more complicated.
In a specific example, the mass ratio of the sodium borohydride to the rhein is 1 (11.8-40).
In a specific example, the mass ratio of the platinum-carbon catalyst to the rhein is 1 (3-4), the volume mass ratio of the heavy water to the rhein is (28-32) muL: 1mg, and the mass ratio of the sodium borohydride to the rhein is 1 (20-24).
In one specific example, the first temperature is 48-52 ℃ and the second temperature is 140-160 ℃.
In one embodiment, the reaction time at the first temperature is 0.8 to 1.2 hours, and the reaction time at the second temperature is 12 to 14 hours. Thus being beneficial to improving the yield of the deuterated rhein and increasing the deuterated sites.
Optionally, the preparation method further comprises the following steps: the prepared product is filtered to obtain filtrate, and then the filtrate is extracted by an organic solvent and dried.
Alternatively, the organic solvent is at least one of diethyl ether and ethyl acetate, more preferably diethyl ether.
Alternatively, the method of adjusting the pH is by addition of a mineral acid. It is understood that the mineral acid may be hydrochloric acid, sulfuric acid, or the like.
The following are specific examples in which heavy water (99.6% concentration) was used from Beijing Yinaoka technology, Inc., rhein refers to a monomeric compound of rhein obtained from rhubarb having a purity of greater than 90% (HPLC) and was obtained from Dorkoma Biotechnology, Inc., a platinum-carbon catalyst (10% metal content) was obtained from Bailingwei technology, Inc., sodium borohydride was 96% pure, ether was used for analytical purification, and heating was performed using an oven heater. Performing LC-MS separation analysis on the obtained pentadeuterorhein, wherein the mobile phase is methanol: 0.1% formic acid water (volume ratio 85:15), the liquid phase peaks at 4.97min, and the mass spectrum molecular weight is 288.15. The nuclear magnetic hydrogen spectrum of the raw material rhein is as follows: c7-H,7.4；C4,6-H,7.77；C5-H,7.78；C2-H, 8.1; after reaction C7-H,7.4；C4,6-H,7.77；C5-H,7.78；C2Disappearance of the peak at-H, 8.1, indicating that it has been substituted with deuterium, the structure of the penta-deuterated rhein being:
example 1
Respectively adding 10.0mg rhein, 1.0mg Pt/C and 300 mu L of heavy water into a reaction vessel, reacting for 1h at 50 ℃, then heating to 100 ℃ for reacting for 10h to obtain a deuterated rhein product, filtering the reaction solution to obtain a filtrate, extracting with diethyl ether, and drying with nitrogen to obtain a deuterated rhein solid. The starting material rhein (D) was found by mass spectrometry using methanol dilution0) Is a main peak and a small amount of oneRhein D1) Peak of (2).
Example 2
10.0mg rhein, 1.0mg Pt/C, 300. mu.L heavy water and 0.3mg sodium borohydride (NaBH) were added to the reaction vessel, respectively4) Reacting at 50 ℃ for 1h, then heating to 100 ℃ for 10h, adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain a deuterated rhein product, then filtering to obtain a filtrate, extracting by using ether, and drying by using nitrogen to obtain the deuterated rhein solid. Dilute with methanol and detect by mass spectrometry to find emodic acid mononeutral (D)1) Is a main peak, and rhein (D) as raw material0) Peak of (2).
Example 3
10.0mg rhein, 2.0mg Pt/C, 300. mu.L heavy water and 0.3mg sodium borohydride (NaBH) were added to the reaction vessel, respectively4) Reacting at 50 ℃ for 1h, then heating to 100 ℃ for 10h, adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain a deuterated rhein product, then filtering to obtain a filtrate, extracting by using ether, and drying by using nitrogen to obtain the deuterated rhein solid. Dideuterorhein (D) was detected by mass spectrometry using methanol dilution2) Is a main peak and also has high Pseudorhein Trideutero (D)3) And tetradeuterium rhein (D)4) Peak of (2).
Example 4
10.0mg rhein, 3.0mg Pt/C, 300. mu.L heavy water and 0.3mg sodium borohydride (NaBH) were added to the reaction vessel, respectively4) Reacting at 50 ℃ for 1h, then heating to 100 ℃ for 10h, adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain a deuterated rhein product, then filtering to obtain a filtrate, extracting by using ether, and drying by using nitrogen to obtain the deuterated rhein solid. Dideuterorhein (D) was detected by mass spectrometry using methanol dilution2) Is a main peak and also has high Pseudorhein Trideutero (D)3) Peak of (2).
Example 5
10.0mg rhein, 3.0mg Pt/C, 300. mu.L heavy water and 0.3mg sodium borohydride (NaBH) were added to the reaction vessel, respectively4) Firstly reacting at 50 ℃ for 1h, then heating to 130 ℃ for reaction for 10h, and adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain the deuterated rhubarbAnd (3) filtering the acid product to obtain filtrate, extracting the filtrate by using ether, and drying the filtrate by using nitrogen to obtain the deuterated rhein solid. Dilute with methanol and detect by mass spectrometry to find the Rhein Trideuteroate (D)3) The yield was 72% with the main peak.
Example 6
10.0mg rhein, 3.0mg Pt/C, 300. mu.L heavy water and 0.3mg sodium borohydride (NaBH) were added to the reaction vessel, respectively4) Reacting at 50 ℃ for 1h, then heating to 150 ℃ for 10h, adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain a deuterated rhein product, then filtering to obtain a filtrate, extracting by using ether, and drying by using nitrogen to obtain the deuterated rhein solid. Dilute with methanol and detect by mass spectrometry to find the Rhein tetradeuterium (D)4) The yield was 70% with a main peak.
Example 7
10.0mg rhein, 3.0mg Pt/C, 300. mu.L heavy water and 0.25mg sodium borohydride (NaBH) were added to the reaction vessel, respectively4) Reacting at 50 ℃ for 1h, then heating to 150 ℃ for 10h, adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain a deuterated rhein product, then filtering to obtain a filtrate, extracting by using ether, and drying by using nitrogen to obtain the deuterated rhein solid. Dilute with methanol and detect by mass spectrometry to find the Rhein tetradeuterium (D)4) Is a main peak, and also has higher rhein pentadeuterium (D)5) Peak of (2).
Example 8
10.0mg rhein, 3.0mg Pt/C, 300. mu.L heavy water and 0.35mg sodium borohydride (NaBH) were added to the reaction vessel, respectively4) Reacting at 50 ℃ for 1h, then heating to 150 ℃ for 10h, adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain a deuterated rhein product, then filtering to obtain a filtrate, extracting by using ether, and drying by using nitrogen to obtain the deuterated rhein solid. Dilute with methanol and detect by mass spectrometry to find the Rhein tetradeuterium (D)4) Is a main peak and also has high pentadeuterium rhein (D)5) Peak of (2).
Example 9
10.0mg rhein, 3.0mg Pt/C, 300. mu.L heavy water and 0.45mg sodium borohydride (NaBH) were added to the reaction vessel, respectively4)，Firstly reacting at 50 ℃ for 1h, then heating to 150 ℃ for reaction for 10h, adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain a deuterated rhein product, then filtering to obtain a filtrate, extracting by using ether, and drying by using nitrogen to obtain a deuterated rhein solid. Dilute with methanol and detect by mass spectrometry to find Rhein pentadeuterium (D)5) Is a main peak and also has very high tetradeuterium rhein (D)4) Peak of (2).
Example 10
10.0mg rhein, 3.0mg Pt/C, 300. mu.L heavy water and 0.55mg sodium borohydride (NaBH) were added to the reaction vessel, respectively4) Reacting at 50 ℃ for 1h, then heating to 150 ℃ for 10h, adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain a deuterated rhein product, then filtering to obtain a filtrate, extracting by using ether, and drying by using nitrogen to obtain the deuterated rhein solid. Dilute with methanol and detect by mass spectrometry to find the Rhein tetradeuterium (D)4) Is a main peak and also has high pentadeuterium rhein (D)5) Peak of (2).
Example 11
10.0mg rhein, 3.0mg Pt/C, 300. mu.L heavy water and 0.85mg sodium borohydride (NaBH) were added to the reaction vessel, respectively4) Reacting at 50 ℃ for 1h, then heating to 150 ℃ for 10h, adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain a deuterated rhein product, then filtering to obtain a filtrate, extracting by using ether, and drying by using nitrogen to obtain the deuterated rhein solid. Dilute with methanol and detect by mass spectrometry to find the tetradeuterated rhein (D)4) Is a main peak and also has high trideuterorhein (D)3) Peak of (2).
Example 12
10.0mg rhein, 3.0mg Pt/C, 300. mu.L heavy water and 0.45mg sodium borohydride (NaBH) were added to the reaction vessel, respectively4) Reacting at 50 ℃ for 1h, then heating to 150 ℃ for 13h, adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain a deuterated rhein product, then filtering to obtain a filtrate, extracting by using ether, and drying by using nitrogen to obtain the deuterated rhein solid. Using methanol dilution and mass spectrometric detection, pentadeuterated rhein (D) was found5) The yield was 70% with a main peak.
Example 13
Respectively adding 10.0mg rhein, 3.0mg Pt/C, 300 mu L of heavy water and 100 mu L of isopropanol into a reaction vessel, firstly reacting for 1h at 50 ℃, then heating to 100 ℃ for reaction for 12h, adjusting the pH value to 6 by using 0.1M hydrochloric acid to obtain a deuterated rhein product, then filtering to obtain a filtrate, extracting by using ether, and drying by using nitrogen to obtain the deuterated rhein solid. The starting material rhein (D) was found by mass spectrometry using methanol dilution0) Is a main peak and also has high dideuteremodic acid (D)2) Rhein tri-deuterium (D)3) And tetradeuterium rhein (D)4) Peak of (2).
Comparative example 1
Respectively adding 10.0mg of rhein, 300 mu L of heavy water and 0.3mg of sodium borohydride into a reaction container, reacting for 1h at 50 ℃, then heating to 100 ℃ for reacting for 10h, filtering the reaction liquid to obtain filtrate, adjusting the pH value to 6 by using 0.1M hydrochloric acid, extracting by using ether, and drying by using nitrogen. The starting material rhein (D) was found by mass spectrometry using methanol dilution0) Is the main peak.
Comparative example 2
Respectively adding 10.0mg rhein, 1.0mg Pt/C and 300 mu L heavy water into a reaction vessel, directly heating to 100 ℃ for reaction for 10h, filtering the reaction liquid to obtain a filtrate, adjusting the pH value to 6 by using 0.1M hydrochloric acid, extracting by using ether, and drying by using nitrogen. The starting material rhein (D) was found by mass spectrometry using methanol dilution0) Is the main peak.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (8)
1. A preparation method of deuterated rhein is characterized by comprising the following steps:
providing reaction raw materials, wherein the reaction raw materials comprise rhein, a platinum-carbon catalyst and heavy water;
mixing the reaction raw materials, reacting at a first temperature for 0.5-3 h, and then heating to a second temperature for reacting for 8-20 h to obtain the deuterated rhein; wherein the first temperature is 40-60 ℃ and the second temperature is 100-200 ℃.
2. The method of claim 1, wherein the mass ratio of the platinum-carbon catalyst to the rhein is 1 (2-5), and the volume-to-mass ratio of the heavy water to the rhein is 25-35 μ L:1 mg.
3. The method of claim 1, wherein the reaction starting material further comprises sodium borohydride, and the method further comprises the following steps: and after the temperature is raised to the second temperature and the reaction is carried out for 8-20 hours, adjusting the pH value to be acidic.
4. The method for preparing deuterated rhein as claimed in claim 3, wherein the mass ratio of the sodium borohydride to the rhein is 1 (11.8-40).
5. The method of claim 3, wherein the mass ratio of the platinum-carbon catalyst to the rhein is 1 (3-4), the volume mass ratio of the heavy water to the rhein is (28-32) μ L:1mg, and the mass ratio of the sodium borohydride to the rhein is 1 (20-24).
6. The method of any one of claims 1-5, wherein the first temperature is 48-52 ℃ and the second temperature is 140-160 ℃.
7. The method of any one of claims 1-5, wherein the reaction time at the first temperature is 0.8-1.2 hours, and the reaction time at the second temperature is 12-14 hours.
8. The method of any one of claims 1 to 5, further comprising the steps of: filtering the prepared product to obtain filtrate, extracting with an organic solvent which is at least one of diethyl ether and ethyl acetate, and drying.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910058616.7A CN109704955B (en) | 2019-01-22 | 2019-01-22 | Deuterated rhein and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910058616.7A CN109704955B (en) | 2019-01-22 | 2019-01-22 | Deuterated rhein and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109704955A CN109704955A (en) | 2019-05-03 |
| CN109704955B true CN109704955B (en) | 2020-06-02 |
Family
ID=66261739
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910058616.7A Active CN109704955B (en) | 2019-01-22 | 2019-01-22 | Deuterated rhein and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109704955B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114560763B (en) * | 2022-03-07 | 2024-02-20 | 山东汉峰新材料科技有限公司 | Production process of deuterated acetic acid |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009269825A (en) * | 2008-04-30 | 2009-11-19 | Shinshu Univ | Method for producing deuterated aromatic carboxylic acid |
| CN101973844A (en) * | 2010-10-29 | 2011-02-16 | 天津市佰斯康科技有限公司 | Method for synthesizing 1,2,3,4- tetradeutero-9-bromoanthracene |
| CN102010522A (en) * | 2010-11-15 | 2011-04-13 | 周良文 | Dry-type plastic composite coloring material |
-
2019
- 2019-01-22 CN CN201910058616.7A patent/CN109704955B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009269825A (en) * | 2008-04-30 | 2009-11-19 | Shinshu Univ | Method for producing deuterated aromatic carboxylic acid |
| CN101973844A (en) * | 2010-10-29 | 2011-02-16 | 天津市佰斯康科技有限公司 | Method for synthesizing 1,2,3,4- tetradeutero-9-bromoanthracene |
| CN102010522A (en) * | 2010-11-15 | 2011-04-13 | 周良文 | Dry-type plastic composite coloring material |
Non-Patent Citations (3)
| Title |
|---|
| 201910058616.7;皮本响;《STN检索报告》;20110908;第5-6页 * |
| NADPD isotope effect on activity of emodin deoxygenase;JOHN A. ANDERSON;《Phytochemistry》;20010306;第32卷(第4期);全文 * |
| 大黄酸对药物转运体和代谢酶影响的研究进展;卜天赐;《药物评价研究》;20170930;第40卷(第9期);全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109704955A (en) | 2019-05-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102976909A (en) | Method for extracting and purifying 6-gingerol from ginger | |
| EP2828276B1 (en) | Rutin-rich extract of uncaria elliptica and method of preparation | |
| CN109704955B (en) | Deuterated rhein and preparation method and application thereof | |
| CN102796203A (en) | Method for preparing anti-oxidization active camellia olefera cake polysaccharide | |
| CN107805270A (en) | A kind of ginsenoside Rh2Extracting method | |
| CN109438213B (en) | Isopentenyl chalcone compound and preparation method thereof | |
| CN107793458B (en) | Preparation method of vidarabine monophosphate | |
| CN109400665B (en) | Method for preparing four triterpenoid compound reference substances from pubescent holly root | |
| CN103130817B (en) | Bilobalide B compound and preparation method thereof | |
| CN113754620B (en) | Lignan amide compound in fructus cannabis, and preparation method and application thereof | |
| CN114621224A (en) | Maca alkaloid and preparation method and application thereof | |
| CN103012431A (en) | Method for synthesizing deuterated tazobactam | |
| CN103145729A (en) | Bilobalide B compound and preparation method thereof | |
| CN105968150A (en) | Preparation method for 7-O-ethylmorroniside | |
| CN108997509B (en) | Diaphragma juglandis polysaccharide, preparation method and application thereof | |
| CN109490448A (en) | A kind of preparation method of digoxin standard substance | |
| CN103130818B (en) | Bilobalide B compound and preparation method thereof | |
| CN102485719A (en) | Preparation method of Imatinib amine | |
| CN107235893B (en) | (3,4- dihydroxy phenyl) pyridine of 3,5- bis- and its extracting method and application | |
| CN111285832A (en) | Preparation method and novel medical application of myricetin derivative | |
| CN111018675A (en) | Method for efficiently and incrementally extracting cannabidiol | |
| CN111303071A (en) | Synthesis method of febuxostat impurity | |
| CN110713471A (en) | Synthetic method of trimetazidine hydrochloride | |
| CN101302235B (en) | Purification of picoplatin | |
| CN108084241A (en) | The method that separation prepares fucosterol from sargassum fusifome |
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 | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20190503 Assignee: Hunan Prima Pharmaceutical Research Center Co.,Ltd. Assignor: HUNAN NORMAL University Contract record no.: X2023980035753 Denomination of invention: Deuterinated Rhein and Its Preparation Method and Application Granted publication date: 20200602 License type: Common License Record date: 20230518 |
|
| EE01 | Entry into force of recordation of patent licensing contract |