CN113620953A - Matrine crystal, pharmaceutical composition, therapeutic agent for soil-borne diseases and application - Google Patents
Matrine crystal, pharmaceutical composition, therapeutic agent for soil-borne diseases and application Download PDFInfo
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- CN113620953A CN113620953A CN202111037315.XA CN202111037315A CN113620953A CN 113620953 A CN113620953 A CN 113620953A CN 202111037315 A CN202111037315 A CN 202111037315A CN 113620953 A CN113620953 A CN 113620953A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The embodiment of the invention provides matrine crystals, a pharmaceutical composition, a therapeutic agent for soil-borne diseases and an application, which are used for reducing the solubility of matrine and a medicament taking matrine as an active ingredient and playing a role in slow release, wherein the matrine crystals show diffraction peaks at the following diffraction angles 2 theta in an X-ray powder diffraction pattern detected by Cu Ka radiation: a diffraction peak at 17.951 ° ± 0.2 °; diffraction peaks at 12.146 ° ± 0.2 ° and 14.858 ° ± 0.2 °; diffraction peaks at 20.333 ° ± 0.2 ° and 26.414 ° ± 0.2 °; diffraction peaks at 10.754 ° ± 0.2 ° and 13.794 ° ± 0.2 °, 18.369 ° ± 0.2 °, 21.054 ° ± 0.2 °, 21.348 ° ± 0.2 °. Through the characteristic of small solubility of the matrine crystal, the matrine crystal has lower solubility in water and slower diffusion, can prolong the lasting period of the matrine crystal when being used for soil-borne diseases, can effectively reduce the action speed of the matrine and prolong the action time, thereby generating the drug action in a longer time and meeting the drug requirement of long-acting release.
Description
Technical Field
The invention relates to a new crystal of matrine.
Background
Matrine is a common variety of plant-derived pesticides. At present, the research on matrine mainly focuses on the field of pest control, and no one can research the crystal form of the original drug. The matrine has short lasting time due to fast dissolution in the control process of common soil-borne diseases such as damping off, blight, root rot, epidemic disease, root-knot nematode and the like.
The XRPD spectrogram of the conventional matrine crystal form shows that 2 theta (+ -0.2 ℃) of the crystal form I (anhydrous matrine) has diffraction peaks at 11.678 degrees, 14.090 degrees and 23.006 degrees, and the relative abundance exceeds 50 percent; diffraction peaks at 7.024 ° and 11.453 ° with relative abundances between 50% and 30%; there is a diffraction peak at 16.676 ° and the relative abundance is between 20% and 10%.
Disclosure of Invention
The embodiment of the invention provides matrine crystals, a pharmaceutical composition, a therapeutic agent for soil-borne diseases and application thereof, which are used for reducing the solubility of matrine and a medicament taking matrine as an active ingredient and playing a role in slow release.
The embodiment of the invention is realized by the following technical scheme:
in a first aspect, embodiments of the present invention provide a matrine crystal that exhibits diffraction peaks at the following diffraction angles 2 θ in an X-ray powder diffraction pattern detected using Cu ka radiation:
a diffraction peak at 17.951 ° ± 0.2 °;
diffraction peaks at 12.146 ° ± 0.2 ° and 14.858 ° ± 0.2 °;
diffraction peaks at 20.333 ° ± 0.2 ° and 26.414 ° ± 0.2 °;
diffraction peaks at 10.754 ° ± 0.2 ° and 13.794 ° ± 0.2 °, 18.369 ° ± 0.2 °, 21.054 ° ± 0.2 °, 21.348 ° ± 0.2 °.
In a second aspect, the embodiment of the present invention provides a matrine crystal, wherein the preparation method of the matrine crystal is a suspension crystal transformation method; the suspension crystal transformation method comprises the following steps:
maintaining matrine and solvent in suspension state under stirring, and filtering to obtain matrine crystal;
the solvent is n-heptane.
Further, the stirring temperature of the suspension crystal transformation method is 50 ℃.
Further, the stirring time is 5 days.
Further, the ratio of the matrine to the solvent is 50.53mg to 0.2 mL.
In a third aspect, the embodiments of the present invention provide a pharmaceutical composition, which contains the matrine crystal as an active ingredient.
In a fourth aspect, the present invention provides a therapeutic agent for a soil-borne disease, which comprises the matrine crystal according to claim 1 as an active ingredient.
Further, the therapeutic agent for soil-borne diseases includes a therapeutic agent for damping-off, wilt, root rot, epidemic disease or symptoms accompanied by root-knot nematodes.
In a fifth aspect, the embodiment of the present invention provides a use of the matrine crystal as an active ingredient of a sustained-release drug.
Compared with the prior art, the embodiment of the invention has the following advantages and beneficial effects:
according to the matrine crystal, the pharmaceutical composition, the soil-borne disease therapeutic agent and the application, the matrine crystal has the characteristics of low solubility, lower solubility in water and slower diffusion, and can prolong the lasting period of soil-borne diseases, effectively reduce the action speed of matrine and prolong the action time, so that the pharmaceutical effect is generated in a longer time, and the requirement of long-acting release of the pharmaceutical is met.
Drawings
In order to more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the drawings that are required to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and that for those skilled in the art, other related drawings can be obtained from these drawings without inventive effort.
Fig. 1 is an XRPD pattern of conventional matrine crystals (form I).
Figure 2 is an XRPD pattern of matrine crystals (form III).
Figure 3 is a TGA diagram of matrine crystals (form III).
Fig. 4 is the resulting data analysis data of fig. 3.
FIG. 5 is HNMR picture of matrine crystal (form III).
Fig. 6 is the detection condition data of fig. 5.
FIG. 7 is a DSC of matrine crystal (form III).
Fig. 8 is the detection parameter data of fig. 7.
FIG. 9 is a PLM diagram of matrine crystal (form III). Wherein (a) in fig. 9 is a detection diagram of 90 ° off-normal light; fig. 9 (b) is a detection diagram of 0 ° off-normal light.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to examples and accompanying drawings, and the exemplary embodiments and descriptions thereof are only used for explaining the present invention and are not meant to limit the present invention.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be apparent to one of ordinary skill in the art that: it is not necessary to employ these specific details to practice the present invention.
Examples
Referring to fig. 2, an embodiment of the present invention provides a matrine crystal (hereinafter referred to as crystal III) detected by Cu ka radiation
Shows diffraction peaks at the following diffraction angles 2 θ in the X-ray powder diffraction pattern of (a):
a diffraction peak at 17.951 ° ± 0.2 °;
diffraction peaks at 12.146 ° ± 0.2 ° and 14.858 ° ± 0.2 °;
diffraction peaks at 20.333 ° ± 0.2 ° and 26.414 ° ± 0.2 °;
diffraction peaks at 10.754 ° ± 0.2 ° and 13.794 ° ± 0.2 °, 18.369 ° ± 0.2 °, 21.054 ° ± 0.2 °, 21.348 ° ± 0.2 °.
Referring to FIG. 3, the TGA analysis of form III was performed in NETZSCH TG 209F3 TGA209F3A-0652-L using a crucible of AL2O3Material quality; referring to FIG. 4, the initial decomposition temperature is in the range of 40.9 ℃ to 50 ℃ and the temperature range of 7% mass reduction is 50 ℃ to 150 ℃; the temperature range for a 92.5% mass reduction is 150-344.8 ℃.
Referring to fig. 5, form III identifies the structure of matrine in the form under HNMR. The detection conditions are shown with reference to fig. 6.
Referring to fig. 7 and fig. 8, fig. 7 is a DSC analysis of form III.
Referring to fig. 9, fig. 9 is a PLM diagram of matrine crystal of form III (form III).
In a second aspect, the embodiment of the present invention provides a matrine crystal, wherein the preparation method of the matrine crystal is a suspension crystal transformation method; the suspension crystal transformation method comprises the following steps:
maintaining matrine and solvent in suspension state under stirring, and filtering to obtain matrine crystal;
the solvent is n-heptane.
Further, the stirring temperature of the suspension crystal transformation method is 50 ℃.
Further, the stirring time is 5 days.
Further, the ratio of the matrine to the solvent is 50.53mg to 0.2 mL.
Suspension crystal transformation is adopted to study the matrine crystal form II. About 50mg of the raw material was weighed into a sample bottle, a certain amount of solvent was added, the system was maintained in a suspended and stirred state at a certain temperature, and filtered for five days, and the obtained solid was analyzed, and the results are shown in table 1 below.
TABLE 1
In a third aspect, the embodiments of the present invention provide a pharmaceutical composition, which contains the matrine crystal as an active ingredient.
In a fourth aspect, the present invention provides a therapeutic agent for a soil-borne disease, which comprises the matrine crystal according to claim 1 as an active ingredient.
Further, the therapeutic agent for soil-borne diseases includes a therapeutic agent for damping-off, wilt, root rot, epidemic disease or symptoms accompanied by root-knot nematodes.
In a fifth aspect, the embodiment of the present invention provides a use of the matrine crystal as an active ingredient of a sustained-release drug.
The solubility data for each form is shown in table 2 below.
TABLE 2
Test conditions: the temperature is 25 ℃, and the pH value of the water is 5.8-7.4
As can be seen from table 2 above, the solubility of the crystal form III is much lower than the solubilities of the matrines of the crystal forms I and II, so that when the matrine needs to be slowly released for treatment, the crystal form III can slowly release the drug to have a delayed effect, and can be used for the preparation and use of a sustained-release drug which needs to use the matrine as an active ingredient. For example, the crystal form III can be used as a slow-release medicament in a therapeutic agent for soil-borne diseases such as damping-off, blight, root rot, epidemic diseases or symptoms accompanied by root-knot nematodes.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are merely exemplary embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (9)
1. Matrine crystal characterized in that it shows diffraction peaks at the following diffraction angles 2 θ in an X-ray powder diffraction pattern detected using Cu ka radiation:
a diffraction peak at 17.951 ° ± 0.2 °;
diffraction peaks at 12.146 ° ± 0.2 ° and 14.858 ° ± 0.2 °;
diffraction peaks at 20.333 ° ± 0.2 ° and 26.414 ° ± 0.2 °;
diffraction peaks at 10.754 ° ± 0.2 ° and 13.794 ° ± 0.2 °, 18.369 ° ± 0.2 °, 21.054 ° ± 0.2 °, 21.348 ° ± 0.2 °.
2. Matrine crystal, characterized in that the preparation method of matrine crystal is suspension crystal transformation method; the suspension crystal transformation method comprises the following steps:
maintaining matrine and solvent in suspension state under stirring, and filtering to obtain matrine crystal;
the solvent is n-heptane.
3. The matrine crystal of claim 2, wherein the stirring temperature of the suspension crystallization method is 50 ℃.
4. The matrine crystal of claim 2, wherein the stirring time is 5 days.
5. The matrine crystal of claim 2, wherein the ratio of matrine to solvent is 50.53mg:0.2 mL.
6. A pharmaceutical composition comprising the matrine crystal according to claim 1 as an active ingredient.
7. A therapeutic agent for soil-borne diseases, which comprises the matrine crystal according to claim 1 as an active ingredient.
8. The agent for treating a soil-borne disease according to claim 3, wherein the agent for treating a soil-borne disease comprises an agent for treating a disease accompanied by damping-off, wilt, root rot, epidemic disease or root-knot nematode.
9. Use of the matrine crystal of claim 1 as an active ingredient of a sustained-release drug.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111037315.XA CN113620953A (en) | 2021-09-06 | 2021-09-06 | Matrine crystal, pharmaceutical composition, therapeutic agent for soil-borne diseases and application |
| PCT/CN2022/107823 WO2023029814A1 (en) | 2021-09-06 | 2022-07-26 | Matrine crystal, pharmaceutical composition, therapeutic agent for soil-borne diseases, pesticide and uses thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111037315.XA CN113620953A (en) | 2021-09-06 | 2021-09-06 | Matrine crystal, pharmaceutical composition, therapeutic agent for soil-borne diseases and application |
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| CN113620953A true CN113620953A (en) | 2021-11-09 |
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| CN202111037315.XA Pending CN113620953A (en) | 2021-09-06 | 2021-09-06 | Matrine crystal, pharmaceutical composition, therapeutic agent for soil-borne diseases and application |
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| WO (1) | WO2023029814A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023029814A1 (en) * | 2021-09-06 | 2023-03-09 | 成都新朝阳作物科学股份有限公司 | Matrine crystal, pharmaceutical composition, therapeutic agent for soil-borne diseases, pesticide and uses thereof |
| WO2023029812A1 (en) * | 2021-09-06 | 2023-03-09 | 成都新朝阳作物科学股份有限公司 | Matrine crystal, pharmaceutical composition, pesticide and uses thereof |
Citations (2)
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| US20060083798A1 (en) * | 2004-10-14 | 2006-04-20 | Jeffrey Young | Composition of natural herb extract for treating cardiovascular disease and its method of preparation thereof |
| CN107400133A (en) * | 2017-08-24 | 2017-11-28 | 广西大学 | A kind of method that high-purity matrine is prepared from subprostrate sophora |
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| CN101058580B (en) * | 2007-03-28 | 2010-05-26 | 东北农业大学 | Method of extracting matrine by ultrasound wave method |
| CN102633798A (en) * | 2012-04-26 | 2012-08-15 | 宁夏紫荆花制药有限公司 | Method for preparing high-purity matrine from sophora alopecuroides |
| CN110256431A (en) * | 2019-07-16 | 2019-09-20 | 山东花物堂生物科技有限公司 | The extraction of biology total alkali and separation purifying technique in a kind of kuh-seng |
| CN113620953A (en) * | 2021-09-06 | 2021-11-09 | 成都新朝阳作物科学股份有限公司 | Matrine crystal, pharmaceutical composition, therapeutic agent for soil-borne diseases and application |
| CN113620954A (en) * | 2021-09-06 | 2021-11-09 | 成都新朝阳作物科学股份有限公司 | Matrine crystal, pharmaceutical composition and application |
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2021
- 2021-09-06 CN CN202111037315.XA patent/CN113620953A/en active Pending
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2022
- 2022-07-26 WO PCT/CN2022/107823 patent/WO2023029814A1/en unknown
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| US20060083798A1 (en) * | 2004-10-14 | 2006-04-20 | Jeffrey Young | Composition of natural herb extract for treating cardiovascular disease and its method of preparation thereof |
| CN107400133A (en) * | 2017-08-24 | 2017-11-28 | 广西大学 | A kind of method that high-purity matrine is prepared from subprostrate sophora |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023029814A1 (en) * | 2021-09-06 | 2023-03-09 | 成都新朝阳作物科学股份有限公司 | Matrine crystal, pharmaceutical composition, therapeutic agent for soil-borne diseases, pesticide and uses thereof |
| WO2023029812A1 (en) * | 2021-09-06 | 2023-03-09 | 成都新朝阳作物科学股份有限公司 | Matrine crystal, pharmaceutical composition, pesticide and uses thereof |
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| WO2023029814A1 (en) | 2023-03-09 |
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