CN1445220A - Lactone category compound of sweetsop as well as new usage in medicines and its preparing method - Google Patents

Lactone category compound of sweetsop as well as new usage in medicines and its preparing method Download PDF

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CN1445220A
CN1445220A CN 03111501 CN03111501A CN1445220A CN 1445220 A CN1445220 A CN 1445220A CN 03111501 CN03111501 CN 03111501 CN 03111501 A CN03111501 A CN 03111501A CN 1445220 A CN1445220 A CN 1445220A
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annonaceousacetogenicompounds compounds
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CN1255397C (en
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姚新生
王保平
胡昌奇
邱峰
苏京
王晶
曲戈霞
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SHENZHEN RESEARCH CENTER OF TRADIONAL CHINESE MEDICINE AND NATURAL MEDICINE
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SHENZHEN RESEARCH CENTER OF TRADIONAL CHINESE MEDICINE AND NATURAL MEDICINE
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Abstract

An anonacelactone compound used for preparing medicines to treat diabetes is prepared through extracting from natural plant, chemical synthesising, concentrating, extracting, eluting, and chromatographic separation. It can promote the differential myogenic cells to have the power of capturing glucose and to generate lactic acid.

Description

Annonaceousacetogenicompounds compounds and new medical use and preparation method
Technical field:
The present invention relates to medical technical field, exactly it is a kind of Annonaceousacetogenicompounds compounds and new medical use and preparation method.
Background technology:
Annonaceae (Annona Linn.) plant, ingredient mainly contains type compounds such as Annona lactone (actogenins), vinylbenzene lactone, polyoxy tetrahydrobenzene, alkaloid, flavones and terpene.The focus of research is the anticancer and insecticidal activity of the contained Annonaceousacetogenicompounds compounds of this section plant at present.Since nineteen eighty-two first Annona lactone report, found more than 300 of this compounds so far, be considered to the natural compounds that another class behind the taxol has strong antitumour activity.To be index with the C2C12 sarcoplast of differentiation to the capture functions of glucose and the ability that produces lactic acid carry out the anti-diabetic activity screening to the extract of one over thousands of kind of natural medicinal plant for we, find the stronger extract of several activity, wherein comprised the extract of multiple annonaceae plant.And utilize active method of following the trail of from extracts such as corossol, Jin Pinggena perfume (or spice), to separate to obtain several and have stronger active Annonaceousacetogenicompounds compounds.
Summary of the invention:
The purpose of this invention is to provide Annonaceousacetogenicompounds compounds and new medical use and preparation method, above-claimed cpd is expected to be developed to a kind of novel natural ofhypoglycemic medicine, is used for treatment of diabetes.It is characterized in that: containing at least one saturated or unsaturated five Yuans lactonic ring structures and a long polysubstituted fat chain structure in the Annonaceousacetogenicompounds compounds molecule, can be one of following structure:
Structure I:
Figure A0311150100051
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R2 or R3 can be a kind of (as when the O, should form carbonyl with the carbon that is connected) among H, O, OH, the OCOCH3; X, m or n can be 0～10.
Structure I I:
Figure A0311150100061
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; M or n can be 0～10.
Structure III:
Figure A0311150100062
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2～R 7, can be O, OH, OCH 3, a kind of (when being O, should form carbonyl) among the OCOCH3 with the carbon that is connected; M or n can be 0～10.
Structure I V:
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R2～R9 can be a kind of (as when the O, should form carbonyl with the carbon that is connected) among H, O, OH, OCH3, the OCOCH3; M, n, x, y, z can be 0～10.
Structure V:
Figure A0311150100064
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2～R 7, can be H, O, OH, OCH 3, OCOCH 3
In a kind of (when being O, forming carbonyl) with the carbon that is connected; M, n, x, y can be 0～10.
Structure VI:
Figure A0311150100071
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2Or R 3, can be H, O, OH, OCH 3, OCOCH 3In a kind of (when being O, forming carbonyl) with the carbon that is connected; M or n can be 0～10.
Structure VII:
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2～R 4, can be H, O, OH, OCH 3, OCOCH 3
In a kind of (when being O, forming carbonyl) with the carbon that is connected; M or n can be 0～10.
Structure VIII:
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2Or R 3, can be H, O, OH, OCH 3, OCOCH 3
In a kind of (when being O, forming carbonyl) with the carbon that is connected; M or n can be 0～10.
Structure I X:
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2Or R 3, can be H, O, OH, OCH 3, OCOCH 3
In a kind of (when being O, forming carbonyl) with the carbon that is connected; M or n can be 0～10.
The present invention is not limited only to above-mentioned nine kinds of structure types, also should comprise other Annonaceousacetogenicompounds compounds (acetogenins).
The preparation method of Annonaceousacetogenicompounds compounds separates from natural goods, also can be chemosynthesis, also can be to carry out structural modification or bio-transformation etc. on the basis of certain annonaceous acetogenins.Below be the working method when from natural phant, separating Annonaceousacetogenicompounds compounds:
Branches and leaves, trunk, root, pericarp or seed with the annonaceae plant are raw material, adopt solvent-extraction process, and one or both technologies in the technologies such as resin adsorption method are made concentrated extract, use organic solvent extractions such as chloroform, ether then.Extract separates through silica gel column chromatography.The silica gel granularity of filling in the silicagel column can be 60～300 orders (optimum size is 100～200 orders), with hexanaphthene, chloroform, acetone, methyl alcohol etc. form by the eluting solvent wash-out of little polarity to high polarity, the annonaceous acetogenins that contains that obtains is partly utilized high performance liquid chromatography (normal phase silica gel chromatography post or anti-phase ODS chromatographic column) to separate to prepare Annona lactone.
In the solvent-extraction process that is adopted, organic solvents such as optional water or methyl alcohol, ethanol, propyl alcohol, butanols, amylalcohol, acetone, ethyl acetate, ethyl formate, chloroform, methylene dichloride, ether, or two or more mixed solvents that dissolve each other, at room temperature dipping extracts or with the refluxing extraction under supersound extraction or the heated condition.Extraction time can be once, also can be repeatedly.
In the solvent extration that is adopted, the above-mentioned extract that obtains can be suspended in water directly extracts with suitable solvent (butanols, amylalcohol, ethyl acetate, ethyl formate, chloroform, methylene dichloride, ether etc.).Extraction times can be once, also can be repeatedly.
The resin method that is adopted, macroporous adsorbent resin etc.As, water, alcohol or pure water extract can be handled with macroporous adsorbent resin, discard the water elution part, collect pure wash-out part.
The separation method of Annonaceousacetogenicompounds compounds of the present invention comprises that also carbon dioxide upercritical fluid extraction separates.
With the preparation Annonaceousacetogenicompounds compounds as anti-diabetic effective constituent, can use separately or share, or combine with suitable vehicle etc., make oral dosage form or non-oral dosage form (injection, sprays, patch etc.) is applied to treatment of diabetes according to ordinary method.
Advantage of the present invention is: the present invention utilizes Annonaceousacetogenicompounds compounds as the anti-diabetic effective ingredient, has the natural drug characteristics, is expected to be developed to the new type natural ofhypoglycemic medicine, is used for the treatment of II pattern type i diabetes.In addition, technology of the present invention is simple, is easy to amplify, and is convenient to suitability for industrialized production.
Description of drawings:
Fig. 1 is cis-Annonacin of the present invention and arianacin promoter action (n=4) table with test results to the C2C12 cellular uptake glucose that breaks up
Fig. 2 for Leiogenin of the present invention and Gigantriocin to the C2C12 cellular uptake glucose of differentiation and generate promoter action (n=4) table with test results of lactic acid
Embodiment:
Embodiment 1: corossol seed 1kg, pulverize, and with 95% alcohol reflux of 10 times of amounts 2 hours, filtration was concentrated into the semi-solid extract.With water suspendible, chloroform extraction.The silica gel (100～140 order) of gained chloroform extract and triplication is mixed sample, silica gel (100～200 order) with 50 times of amounts carries out column chromatography, to contain Annonaceousacetogenicompounds compounds and partly carry out high performance liquid chromatography preparation (positive SiO2 filler chromatographic column: anti-phase ODS filler chromatographic column) obtain cis-annonacin (32mg), arianacin (14mg) annonacin-10-one (11mg), gigantetronein (6mg), gigantetrocinA (4mg), goniothalamicin (23mg).The gained part of compounds has promoter action to the ability of the C2C12 sarcoplast ingestion of glucose of differentiation, and test result is as shown in table 1.The plane chemical structure of cis-Annonacin: The plane chemical structure of Arianacin:
Embodiment 2: the dry root 2kg of Jin Pinggena perfume (or spice) (Goniothalamus Leiocarpus), pulverize, and with the chloroform refluxing extraction of 10 times of amounts 2 hours, filtration was concentrated into the semi-solid extract.Gained is got the silica gel (100～140 order) of thing and triplication and mixed sample, silica gel (100～200 order) with 50 times of amounts carries out column chromatography, will contain Annonaceousacetogenicompounds compounds and partly carry out high performance liquid chromatography preparation (positive SiO2 filler chromatographic column or anti-phase ODS filler chromatographic column) and obtain Leiogenin and Gigantriocin.They are to the C2C12 sarcoplast ingestion of glucose of differentiation and to generate the promoter action of lactic acid ability as shown in table 2.The chemical structure of Leiogenin:
Figure A0311150100093
The chemical structure of Gigantriocin:

Claims (8)

1, the new medicine use of Annonaceousacetogenicompounds compounds, it is characterized in that: with the effective ingredient of lipoid substance in the sweetsop as the preparation antidiabetic medicine, can use separately or share or combine, make the antidiabetic medicine of oral dosage form or non-oral dosage form according to ordinary method with suitable vehicle etc.
2, the new medicine use of Annonaceousacetogenicompounds compounds according to claim 1, it is characterized in that: Annonaceousacetogenicompounds compounds can be isolating from natural goods, also can be chemosynthesis, can also be on the basis of certain annonaceous acetogenins, carry out structural modification or bio-transformation etc.
3, a kind of Annonaceousacetogenicompounds compounds as claimed in claim 1 is characterized in that: containing at least one saturated or unsaturated five Yuans lactonic ring structures and a long polysubstituted fat chain structure in the molecule, can be following structure:
Structure I:
Figure A0311150100021
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R2 or R3 can be a kind of (as when the O, should form carbonyl with the carbon that is connected) among H, O, OH, the OCOCH3; X, m or n can be 0～10.
Structure I I:
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; M or n can be 0～10.
Structure III:
Figure A0311150100023
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2～R 7, can be O, OH, OCH 3, a kind of (when being O, should form carbonyl) among the OCOCH3 with the carbon that is connected; M or n can be 0～10.
Structure I V:
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R2～R9 can be a kind of (as when the O, should form carbonyl with the carbon that is connected) among H, O, OH, OCH3, the OCOCH3; M, n, x, y, z can be 0～10.
Structure V:
Figure A0311150100032
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2～R 7, can be H, O, OH, OCH 3, OCOCH 3In a kind of (when being O, forming carbonyl) with the carbon that is connected; M, n, x, y can be 0～10.
Structure VI:
Figure A0311150100033
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2Or R 3, can be H, O, OH, OCH 3, OCOCH 3In a kind of (when being O, forming carbonyl) with the carbon that is connected; M or n can be 0～10.
Structure VII:
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2～R 4, can be H, O, OH, OCH 3, OCOCH 3In a kind of (when being O, forming carbonyl) with the carbon that is connected; M or n can be 0～10.
Structure VIII:
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2Or R 3, can be H, O, OH, OCH 3, OCOCH 3In a kind of (when being O, forming carbonyl) with the carbon that is connected; M or n can be 0～10.
Structure I X:
Figure A0311150100041
R 1Can be CH 3, CH 2OH, CH 2COCH 3In a kind of; R 2Or R 3, can be H, O, OH, OCH 3, OCOCH 3In a kind of (when being O, forming carbonyl) with the carbon that is connected; M or n can be 0～10.
4, a kind of preparation method of Annonaceousacetogenicompounds compounds as claimed in claim 3, it is characterized in that: with the branches and leaves of annonaceae plant, trunk, root, pericarp or seed are raw material, adopt solvent-extraction process, one or both technologies in the technologies such as resin adsorption method are made concentrated extract, use chloroform then, organic solvent extractions such as ether, extract separates through silica gel column chromatography, the silica gel granularity of filling in the silicagel column can be 60～300 orders, use hexanaphthene, chloroform, acetone, methyl alcohol etc. form by the eluting solvent wash-out of little polarity to high polarity, the annonaceous acetogenins that contains that obtains is partly utilized high performance liquid chromatography to separate to prepare Annona lactone.
5, the preparation method of Annonaceousacetogenicompounds compounds according to claim 4, it is characterized in that: in the solvent-extraction process that is adopted, organic solvents such as optional water or methyl alcohol, ethanol, propyl alcohol, butanols, amylalcohol, acetone, ethyl acetate, ethyl formate, chloroform, methylene dichloride, ether, or two or more mixed solvents that dissolve each other, at room temperature dipping extracts or with the refluxing extraction under supersound extraction or the heated condition, extraction time can be once, also can be repeatedly.
6, the preparation method of Annonaceousacetogenicompounds compounds according to claim 4, it is characterized in that: in the solvent extration that is adopted, the above-mentioned extract that obtains can be suspended in water directly extracts with suitable solvent, and extraction times can be once, also can be repeatedly.
7, the preparation method of Annonaceousacetogenicompounds compounds according to claim 4, it is characterized in that: the resin method that is adopted, macroporous adsorbent resins etc. can be handled with macroporous adsorbent resin as water, alcohol or pure water extract, discard the water elution part, collect pure wash-out part.
8, the preparation method of Annonaceousacetogenicompounds compounds according to claim 4 is characterized in that: the separation method of Annonaceousacetogenicompounds compounds comprises that also carbon dioxide upercritical fluid extraction separates.
CN 03111501 2003-04-21 2003-04-21 Lactone category compound of sweetsop as well as new usage in medicines and its preparing method Expired - Fee Related CN1255397C (en)

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101575324B (en) * 2009-05-15 2011-05-25 贵州正鑫药业有限公司 Preparation method for extracting anticancer valid-position medicine SHIKEMOXIN from sweetsop
CN106543117A (en) * 2016-11-10 2017-03-29 南京中医药大学 With double tetrahydrofuran type Annonaceousacetogenicompounds compounds and preparation method and application between anti-tumor activity
CN106543159A (en) * 2016-11-10 2017-03-29 南京中医药大学 Epoxy type Annonaceousacetogenicompounds compounds with anti-tumor activity and preparation method and application
CN107674065A (en) * 2017-10-13 2018-02-09 江苏建康职业学院 Annonaceous acetogenins and its application with antitumor activity
CN107753532A (en) * 2017-11-07 2018-03-06 海南医学院 A kind of soursop root extract and its anti-diabetes use
CN111184032A (en) * 2020-01-10 2020-05-22 云南农业大学 Goniothalamus affinis nematode killing extract as well as preparation method and application thereof
CN111317750A (en) * 2020-02-17 2020-06-23 江苏卫生健康职业学院 Application of sweetsop seed total lactone in preparing medicine for preventing and treating diabetes

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101575324B (en) * 2009-05-15 2011-05-25 贵州正鑫药业有限公司 Preparation method for extracting anticancer valid-position medicine SHIKEMOXIN from sweetsop
CN106543117A (en) * 2016-11-10 2017-03-29 南京中医药大学 With double tetrahydrofuran type Annonaceousacetogenicompounds compounds and preparation method and application between anti-tumor activity
CN106543159A (en) * 2016-11-10 2017-03-29 南京中医药大学 Epoxy type Annonaceousacetogenicompounds compounds with anti-tumor activity and preparation method and application
CN106543159B (en) * 2016-11-10 2019-02-05 南京中医药大学 Epoxy type Annonaceousacetogenicompounds compounds with anti-tumor activity and the preparation method and application thereof
CN107674065A (en) * 2017-10-13 2018-02-09 江苏建康职业学院 Annonaceous acetogenins and its application with antitumor activity
CN107753532A (en) * 2017-11-07 2018-03-06 海南医学院 A kind of soursop root extract and its anti-diabetes use
CN111184032A (en) * 2020-01-10 2020-05-22 云南农业大学 Goniothalamus affinis nematode killing extract as well as preparation method and application thereof
CN111184032B (en) * 2020-01-10 2021-05-07 云南农业大学 Goniothalamus affinis nematode killing extract as well as preparation method and application thereof
CN111317750A (en) * 2020-02-17 2020-06-23 江苏卫生健康职业学院 Application of sweetsop seed total lactone in preparing medicine for preventing and treating diabetes

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