CN105566436A - Tea seed flavonoid aglycone and tea sapogenin zinc coordination complex, method for preparing same and application of tea seed flavonoid aglycone and tea sapogenin zinc coordination complex - Google Patents
Tea seed flavonoid aglycone and tea sapogenin zinc coordination complex, method for preparing same and application of tea seed flavonoid aglycone and tea sapogenin zinc coordination complex Download PDFInfo
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- CN105566436A CN105566436A CN201510962057.4A CN201510962057A CN105566436A CN 105566436 A CN105566436 A CN 105566436A CN 201510962057 A CN201510962057 A CN 201510962057A CN 105566436 A CN105566436 A CN 105566436A
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- China
- Prior art keywords
- tea
- theasapogenol
- tea seed
- flavone aglycone
- sapogenin
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- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 title claims abstract description 55
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 title claims abstract description 55
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 title claims abstract description 55
- 239000011701 zinc Substances 0.000 title claims abstract description 53
- 241001122767 Theaceae Species 0.000 title claims abstract description 45
- -1 zinc coordination complex Chemical class 0.000 title abstract description 11
- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 title abstract description 10
- NWMIYTWHUDFRPL-UHFFFAOYSA-N sapogenin Natural products COC(=O)C1(CO)C(O)CCC2(C)C1CCC3(C)C2CC=C4C5C(C)(O)C(C)CCC5(CCC34C)C(=O)O NWMIYTWHUDFRPL-UHFFFAOYSA-N 0.000 title abstract description 10
- 229930003935 flavonoid Natural products 0.000 title abstract description 9
- 150000002215 flavonoids Chemical class 0.000 title abstract description 9
- 235000017173 flavonoids Nutrition 0.000 title abstract description 9
- 238000000034 method Methods 0.000 title abstract description 9
- 229910052725 zinc Inorganic materials 0.000 title abstract description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 27
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- 238000006243 chemical reaction Methods 0.000 claims abstract description 12
- 238000005406 washing Methods 0.000 claims abstract description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 11
- 239000002244 precipitate Substances 0.000 claims abstract description 9
- 150000003751 zinc Chemical class 0.000 claims abstract description 7
- 235000012054 meals Nutrition 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims abstract description 4
- 229940079593 drug Drugs 0.000 claims abstract description 3
- 229930003944 flavone Natural products 0.000 claims description 55
- 235000011949 flavones Nutrition 0.000 claims description 55
- 229930192129 Theasapogenol Natural products 0.000 claims description 49
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 claims description 47
- 150000002212 flavone derivatives Chemical class 0.000 claims description 47
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- 238000005238 degreasing Methods 0.000 claims description 21
- 239000000706 filtrate Substances 0.000 claims description 18
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- 238000002360 preparation method Methods 0.000 claims description 18
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- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical group [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 8
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- 239000004246 zinc acetate Substances 0.000 claims description 8
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
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- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 8
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 7
- 150000007949 saponins Chemical class 0.000 description 7
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- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 description 5
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- IYRMWMYZSQPJKC-UHFFFAOYSA-N kaempferol Chemical group C1=CC(O)=CC=C1C1=C(O)C(=O)C2=C(O)C=C(O)C=C2O1 IYRMWMYZSQPJKC-UHFFFAOYSA-N 0.000 description 4
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- 206010010904 Convulsion Diseases 0.000 description 1
- UBSCDKPKWHYZNX-UHFFFAOYSA-N Demethoxycapillarisin Natural products C1=CC(O)=CC=C1OC1=CC(=O)C2=C(O)C=C(O)C=C2O1 UBSCDKPKWHYZNX-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
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- 241000700157 Rattus norvegicus Species 0.000 description 1
- 241001074085 Scophthalmus aquosus Species 0.000 description 1
- BWPGKXYWPBQBPV-MWQJAWBESA-N Theasaponin Chemical compound O([C@H]1[C@H](O)[C@H](O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@@H](O)CO1)O[C@H]1[C@@H]([C@@H](O)[C@H](O)CO1)O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(CO)C)C)(C)C[C@@H](O)[C@@]1(CO)[C@@H](OC(C)=O)[C@@H](C(C[C@H]14)(C)C)OC(=O)C(\C)=C/C)C(O)=O)[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BWPGKXYWPBQBPV-MWQJAWBESA-N 0.000 description 1
- BWPGKXYWPBQBPV-ZOADXXHESA-N Theasaponin Natural products O=C(O[C@@H]1[C@@H](OC(=O)C)[C@]2(CO)[C@@H](O)C[C@@]3(C)[C@@]4(C)[C@@H]([C@]5(C)[C@H]([C@@](CO)(C)[C@@H](O[C@@H]6[C@@H](O[C@@H]7[C@H](O[C@@H]8[C@@H](O)[C@H](O)[C@H](O)CO8)[C@H](O)[C@@H](O)CO7)[C@@H](O[C@H]7[C@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O7)[C@H](O)[C@@H](C(=O)O)O6)CC5)CC4)CC=C3[C@@H]2CC1(C)C)/C(=C/C)/C BWPGKXYWPBQBPV-ZOADXXHESA-N 0.000 description 1
- IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
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- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/003—Compounds containing elements of Groups 2 or 12 of the Periodic Table without C-Metal linkages
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of medicines, and discloses a tea seed flavonoid aglycone and tea sapogenin zinc coordination complex, a method for preparing the same and application of the tea seed flavonoid aglycone and tea sapogenin zinc coordination complex. The method particularly includes steps of extracting degreased tea seed meal by the aid of ethyl alcohol aqueous solution to obtain extract liquid; filtering the extract liquid to obtain filter liquid; hydrolyzing the filter liquid by the aid of acid; concentrating the filter liquid to obtain concentrated liquid; precipitating the concentrated liquid to obtain precipitates; redissolving the precipitates by the aid of ethyl alcohol; adding anhydrous sodium carbonate and zinc salt into the precipitates; carrying out reflux reaction to obtain a product; regulating the pH (potential of hydrogen) of the product until the pH of the product reaches 8-10; allowing the product to stand still and precipitating the product; washing the product; drying the product under vacuum conditions to obtain the tea seed flavonoid aglycone and tea sapogenin zinc coordination complex. The tea seed flavonoid aglycone and tea sapogenin zinc coordination complex, the method and the application have the advantages that obvious effects of protecting nerve cells and preventing neurodegeneration can be realized by the tea seed flavonoid aglycone and tea sapogenin zinc coordination complex, and the tea seed flavonoid aglycone and tea sapogenin zinc coordination complex can be applied and developed as a novel medicine for resisting neurodegeneration diseases.
Description
Technical field
The invention belongs to field of medicaments, particularly one has neuroprotective tea seed Flavone aglycone and theasapogenol Zn complex and preparation method thereof, and it is as the application of anti-neurodegenerative disorders medicine.
Background technology
The many compositions of Chinese medicine have neuroprotective, typically have flavonoid, saponins compound.The anti-aging effects of Chinese medicine is exactly the synergy of Multiple components, but under study for action usually by their respectively in addition separation and purification, certainly will reduce action effect like this.
Containing 2 ~ 3% flavones and 12 ~ 14% saponins compounds in tea seed.Conventional flavones and the separation method of saponin(e have extraction process, resin method, chromatography etc., can obtain chromocor compound and theasaponin respectively through separation and purification.But the Neuroprotective effect of separated product is not given prominence to.
Flavones and saponin(e exist mainly with the form of glucosides in plant materials, because molecular weight is comparatively large and water-soluble comparatively strong, are unfavorable for that it plays neuroprotective through hemato encephalic barrier.
Do not added with sapogenin by tea seed flavones and be separated and extracting directly, prepare Flavone aglycone and theasapogenol Zn complex, the research as novel anti-nerve degeneration medicine has no report.
Summary of the invention
In order to overcome shortcoming and defect of the prior art, the object of the present invention is to provide a kind of tea seed Flavone aglycone and theasapogenol Zn complex.
Another object of the present invention is to the preparation method that above-mentioned tea seed Flavone aglycone theasapogenol Zn complex are provided.
Another object of the present invention is to provide a kind of above-mentioned tea seed Flavone aglycone and the pharmaceutical preparation with neuroprotective that is namely made into of the application of theasapogenol Zn complex.
Object of the present invention is achieved through the following technical solutions:
A kind of tea seed Flavone aglycone theasapogenol Zn complex, its structural formula is shown below:
Described tea seed Flavone aglycone the preparation method of theasapogenol Zn complex, specifically comprise the following steps:
Degreasing leached tea oil slag aqueous ethanolic solution is extracted, filters, acid hydrolysis in filtrate, concentrated, obtain concentrated solution; In concentrated solution, add precipitation agent precipitate, be precipitated thing; By precipitate dissolves, add anhydrous sodium carbonate and zinc salt, back flow reaction, regulate pH to 8 ~ 10, staticly settle, washing, dry, obtain tea seed Flavone aglycone and theasapogenol Zn complex.
Described concentrated condition is concentrating under reduced pressure under 50 ~ 80 DEG C and 0.01 ~ 0.1 normal atmosphere, and the volume of described concentrated solution is 1/3 of filtrate volume.
Described precipitation agent is water, and the consumption of described precipitation agent is 3 ~ 5 times of concentrated solution volume.
Described precipitate dissolves adds dehydrated alcohol in sensing throw out to dissolve, and consumption and the throw out of described dehydrated alcohol are identical in quality.
The material of described adjustment pH is ammoniacal liquor; Described washing refers to employing washing with alcohol.
Describedly staticly settle 8 ~ 24 hours, the condition of described drying is in 50 ~ 80 DEG C of dryings 3 ~ 6 hours.
The volume fraction of described aqueous ethanolic solution is 70 ~ 85%.
The add-on of described aqueous ethanolic solution and the liquid-solid ratio of degreasing leached tea oil slag raw material are (10 ~ 20) mL:1g; Extracting temperature is 60 ~ 80 DEG C, 1 ~ 3 hour extraction time.
Described acid is hydrochloric acid, in filtrate after acid adding, and the final concentration 2 ~ 5mol/L of HCl; Described hydrolysis temperature is 70 ~ 80 DEG C, and hydrolysis time is 5 ~ 8 hours.
Described anhydrous sodium carbonate add-on is 0.5 ~ 2% of degreasing tea dregs of rice quality, and described zinc salt add-on is 0.5 ~ 2% of degreasing tea dregs of rice quality; Described back flow reaction temperature is 70 ~ 80 DEG C, and the reaction times is 5 ~ 10 hours.
Described zinc salt is zinc acetate.
Described degreasing leached tea oil slag is the wherein one of the degreasing tea-seed dregs of rice or degreasing camellia seed meal.
Described tea seed Flavone aglycone theasapogenol Zn complex for the preparation of having neuroprotective medicine preparation, the preparation of the various pharmaceutical dosage forms that Flavone aglycone theasapogenol Zn complex can be made with any legal Synergist S-421 95 and vehicle.
Of the present invention have in neuroprotective medicine preparation, and formulation can be any one that is oral or injecting drug use formulation.
This theasapogenol derivative is combined to make with acceptable pharmaceutical carrier as activeconstituents and can be used as the oral of the various anti-neurodegenerative disease of prevention and therapy or inject folk prescription and compound preparation.
The present invention compared with prior art tool has the following advantages and effect:
(1) the present invention has Flavone aglycone, theasapogenol and zine ion concurrently simultaneously, and three's synergy significantly improves maincenter neuroprotective activity;
(2) Flavone aglycone of the present invention theasapogenol Zn complex preparation method, adopt degreasing leached tea oil slag after alcohol extracting hydrolysis, Flavone aglycone, the theasapogenol structure of acquisition are little, are conducive to them through hemato encephalic barrier, play central action;
(3) technique is simple, does not need, by flavones and saponin(e separation and purification respectively, to be convenient to suitability for industrialized production.
Embodiment
Below in conjunction with embodiment, further detailed description is done to the present invention, but embodiments of the present invention are not limited thereto.
Embodiment 1
By degreasing tea-seed dregs of rice 1kg, add the aqueous ethanolic solution of the volume fraction 80% of 10L, 70 DEG C of refluxing extraction 3 hours, filter, it is 2mol/L that filtrate adds hydrochloric acid to the final concentration of HCl, 80 DEG C of hydrolysis times 5 hours, 1/3 of filtrate volume is evaporated under 80 DEG C and 0.1 normal atmosphere, add the 3 times of water precipitations of concentrated solution volume, after throw out redissolves with the dehydrated alcohol of its equimultiple quality, add anhydrous sodium carbonate 20g, zinc acetate 10g, 70 DEG C of reaction 10h, pH to 8 is regulated with ammoniacal liquor, staticly settle 24 hours, after collecting precipitation washing with alcohol, 50 DEG C of vacuum-drying 6 hours, the Flavone aglycone of obtained 48g theasapogenol Zn complex.
Product take DMSO as the sample liquid that solvent is made into 0.2mg/mL, and UV scanning shows, and the charateristic avsorption band of flavones and sapogenin all there occurs red shift 10 ~ 15nm; Infrared display, flavones carbonyl peak (1650cm
-1) move 40 ~ 50cm to low frequency direction, and at 500cm
-1place adds a new broad peak, and this place is the stretching vibration peak of metal and oxygen Cheng Jian, illustrates that flavones carbonyl, saponin(e hydroxyl and zine ion there occurs coordination reaction.Results of elemental analyses shows, and the proportioning of Flavone aglycone, theasapogenol and zinc atom is 1:1:1.
Embodiment 2
By degreasing camellia seed meal 1kg, add the aqueous ethanolic solution of the volume fraction 70% of 15L, 60 DEG C of refluxing extraction 2 hours, filter, filtrate adds the final concentration 5mol/L of hydrochloric acid to HCl, 70 DEG C of hydrolysis times 8 hours, 1/3 of filtrate volume is evaporated under 50 DEG C and 0.01 normal atmosphere, add the 5 times of water precipitations of concentrated solution volume, after throw out redissolves with the dehydrated alcohol of its equimultiple quality, add anhydrous sodium carbonate 10g, zinc acetate 5g, 80 DEG C of reaction 5h, pH to 9 is regulated with ammoniacal liquor, staticly settle 8 hours, after collecting precipitation washing with alcohol, 80 DEG C of vacuum-drying 3 hours, the Flavone aglycone of obtained 36g theasapogenol Zn complex.
Product detects equally with embodiment 1, and result is consistent with embodiment 1.
Embodiment 3
By degreasing camellia seed meal 1kg, add the aqueous ethanolic solution of the volume fraction 85% of 12L, 65 DEG C of refluxing extraction 1 hour, filter, filtrate adds the final concentration 3mol/L of hydrochloric acid to HCl, 80 DEG C of hydrolysis times 5 hours, are evaporated to 1/3 of filtrate volume under 60 DEG C and 0.05 normal atmosphere, add the 4 times of water precipitations of concentrated solution volume, after throw out redissolves with the dehydrated alcohol of its equimultiple quality, add anhydrous sodium carbonate 20g, zinc acetate 15g, 70 DEG C of reaction 10h; Regulate pH to 10 with ammoniacal liquor, staticly settle 10 hours, after collecting precipitation washing with alcohol, 60 DEG C of vacuum-drying 4 hours, the Flavone aglycone of obtained 52g theasapogenol Zn complex.
Product detects equally with embodiment 1, and result is consistent with embodiment 1.
Embodiment 4
By degreasing Camellia Leaves seed dregs of rice 1kg, add the aqueous ethanolic solution of the volume fraction 80% of 20L, 65 DEG C of refluxing extraction 2 hours, filter, filtrate adds the final concentration 2.5mol/L of hydrochloric acid to HCl, 75 DEG C of hydrolysis times 6 hours; Be evaporated to 1/3 of filtrate volume under 70 DEG C and 0.1 normal atmosphere, add the 3.5 times of water precipitations of concentrated solution volume, throw out adds anhydrous sodium carbonate 5g, zinc acetate 5g after redissolving with the dehydrated alcohol of its equimultiple quality, 80 DEG C of reaction 7h; Regulate pH to 8.5 with ammoniacal liquor, staticly settle 16 hours, after collecting precipitation washing with alcohol, 70 DEG C of vacuum-drying 4 hours, the Flavone aglycone of obtained 40g theasapogenol Zn complex.
Product detects equally with embodiment 1, and result is consistent with embodiment 1.
Embodiment 5
By degreasing tea-seed dregs of rice 1kg, add the aqueous ethanolic solution of the volume fraction 75% of 16L, 75 DEG C of refluxing extraction 1.5 hours, filter, filtrate adds the final concentration 4mol/L of hydrochloric acid to HCl, 80 DEG C of hydrolysis times 7 hours; Be evaporated to 1/3 of filtrate volume under 70 DEG C and 0.05 normal atmosphere, add the 4.5 times of water precipitations of concentrated solution volume, throw out adds anhydrous sodium carbonate 15g, zinc acetate 10g after redissolving with the dehydrated alcohol of its equimultiple quality, 75 DEG C of reaction 8h; Regulate pH to 9 with ammoniacal liquor, staticly settle 20 hours, after collecting precipitation washing with alcohol, 60 DEG C of vacuum-drying 5 hours, the Flavone aglycone of obtained 45g theasapogenol Zn complex.
Product detects equally with embodiment 1, and result is consistent with embodiment 1.
Embodiment 6
By degreasing camellia seed meal 1kg, add the aqueous ethanolic solution of the volume fraction 70% of 18L, 80 DEG C of refluxing extraction 2.5 hours, filter, filtrate adds the final concentration 4.5mol/L of hydrochloric acid to HCl, 75 DEG C of hydrolysis times 8 hours; 1/3 of filtrate volume is evaporated under 65 DEG C and 0.03 normal atmosphere, add the 5 times of water precipitations of concentrated solution volume, throw out adds anhydrous sodium carbonate 17g, zinc acetate 14g after redissolving with the dehydrated alcohol of its equimultiple quality, 80 DEG C of reaction 9h, regulate pH to 9 with ammoniacal liquor, staticly settle 12 hours, after collecting precipitation washing with alcohol, 80 DEG C of vacuum-drying 3.5 hours, the Flavone aglycone of obtained 34g theasapogenol Zn complex.
Product detects equally with embodiment 1, and result is consistent with embodiment 1.
Embodiment 7
The Flavone aglycone of Example 1 ~ 6 theasapogenol Zn complex 10g, mix by 3:7 mixture 30g, 1% Magnesium Stearate with lactose, crystalline cellulose, make the tablet of every sheet 200mg through tabletting machine.
Embodiment 8
Take the obtained Flavone aglycone of embodiment 1 ~ 6 and theasapogenol Zn complex 10g, add medicinal Microcrystalline Cellulose 30g, mix, wet granulation, regulate with ethanol, obtained loose particles crosses 20 mesh sieves, dries.Filled capsules after dry, obtains Flavone aglycone and the capsule of theasapogenol Zn complex.
Embodiment 9
The Flavone aglycone of Example 1 ~ 6 theasapogenol Zn complex 10g, after dissolving, pour into bottle, make injection with Spheron MD 30/70 1000mL.
Embodiment 10
Take the obtained Flavone aglycone of embodiment 1 ~ 6 and theasapogenol Zn complex 10g, add 50gPEG6000, mix after being heated to 60 DEG C of fusings, be placed in pill dripping machine, use whiteruss refrigeration, dripping pill.Cool and obtain Flavone aglycone and the pill of theasapogenol Zn complex.
Flavone aglycone of the present invention theasapogenol Zn complex has remarkable neuroprotective, is confirmed by following experiment.
(1) to the protective effect of L-glutamic acid (Glu) injury rats hippocampal tissue
Method: get 4 ~ 5 monthly age male Wistar rat 40, body weight (200 ± 20) g, is divided into sham operated rats, Glu damage group, Flavone aglycone theasapogenol Zn complex group, kaempferol group, tea saponin group often organize 8 at random.Administration group is gastric infusion 10d in advance, all the other group gavage normal saline.Mouse is after tail vein injection Thiopental Anesthesia, be fixed on stereotaxic apparatus, cut calvarium center skin and periosteum, clear exposure bregma, 0.8mm after bregma, on the right side of sagittal suture, other 1.5mm place brill opens skull, with microsyringe capable intracerebroventricular injection Glu4 μ L (1mg/kg), depth of needle 3.8mm, let the acupuncture needle remain at a certain point 5min.Observe after getting pin rat behavior change, with occur epilepsy seizure show as model success.After injection Glu solution 2h, by rat sacrificed by decapitation, get rapidly full brain, isolate hippocampus, after weighing, add the hippocampal homogenates that normal saline becomes 1:10 (weightmeasurement ratio).Get each group of hippocampal homogenates, in strict accordance with the operation of test kit specification sheets, detect wherein MDA content, SOD and GSH-Px activity by multi-functional microplate reader.The results are shown in Table 1.
Result: intracerebroventricular injection Glu can cause MDA content in Rat hippocampus to raise, and the activity of SOD and GSH-Px reduces (p<0.05); Compare with Glu damage group; medicine group MDA content all reduces; the activity of SOD and GSH-Px all raises; Flavone aglycone and theasapogenol Zn complex group change maximum; reach conspicuous level (P<0.01); show Flavone aglycone and theasapogenol Zn complex can improve the activity of antioxidase in brain and the neurotoxicity of antagonism Glu, have neuroprotective, its effect is better than kaempferol and tea saponin group.
Table 1 Flavone aglycone theasapogenol Zn complex are on activities of antioxidant enzymes impact in hippocampal tissue
(2) to the Protection of MPTP induced mice dopamine neuron damage
Method: get 5 ~ 6 monthly age male mice 50, body weight (20 ± 2) g, is divided into Normal group, MPTP group, Flavone aglycone theasapogenol Zn complex, kaempferol group, tea saponin group at random, often organizes 10.Administration group is intraperitoneal injection 3d in advance, every day 1 time, all the other group abdominal injection normal saline.4d is except normal group, and other all injects MPTP solution 4mg/kg.After 7d, by mouse sacrificed by decapitation, get rapidly full brain, isolate striatum, after weighing, add the tissue homogenate that PE buffer becomes 1:10 (weightmeasurement ratio).After homogenate is centrifugal, measure Dopamine HCL (DA) content through HPLC.The results are shown in Table 2.
Result: MPTP group DA content compared with normal group significantly reduces (p<0.05), shows that MPTP causes the damage of dopamine neuron.Flavone aglycone theasapogenol Zn complex administration group DA content and MPTP, according to organizing than significantly improving (p<0.05), illustrate Flavone aglycone and theasapogenol Zn complex has better protecting effect to the damage of dopamine neuron caused by MPTP.
Table 2 Flavone aglycone theasapogenol Zn complex are on the impact of striatum DA level
Claims (10)
1. tea seed Flavone aglycone a theasapogenol Zn complex, is characterized in that: its structural formula is shown below:
2. tea seed Flavone aglycone the preparation method of theasapogenol Zn complex according to claim 1, is characterized in that: specifically comprise the following steps: extracted by degreasing leached tea oil slag aqueous ethanolic solution, filters, acid hydrolysis in filtrate, concentrated, obtains concentrated solution; In concentrated solution, add precipitation agent precipitate, be precipitated thing; By precipitate dissolves, add anhydrous sodium carbonate and zinc salt, back flow reaction, regulate pH to 8 ~ 10, staticly settle, washing, dry, obtain tea seed Flavone aglycone and theasapogenol Zn complex.
3. tea seed Flavone aglycone the preparation method of theasapogenol Zn complex according to claim 2, is characterized in that: the volume fraction of described aqueous ethanolic solution is 70 ~ 85%; Described Extracting temperature is 60 ~ 80 DEG C, 1 ~ 3 hour extraction time; Described hydrolysis temperature 70 ~ 80 DEG C, hydrolysis time 5 ~ 8 hours; Described back flow reaction temperature 70 ~ 80 DEG C, the reaction times is 5 ~ 10h.
4. tea seed Flavone aglycone the preparation method of theasapogenol Zn complex according to claim 2, is characterized in that: the add-on of described aqueous ethanolic solution and the liquid-solid ratio of degreasing leached tea oil slag raw material are (10 ~ 20) mL:1g; Described acid is hydrochloric acid; After described hydrochloric acid adds filtrate, the final concentration of HCl is 2 ~ 5mol/L.
5. tea seed Flavone aglycone the preparation method of theasapogenol Zn complex according to claim 2, it is characterized in that: described anhydrous sodium carbonate add-on is 0.5 ~ 2% of degreasing tea dregs of rice quality, described zinc salt add-on is 0.5 ~ 2% of degreasing tea dregs of rice quality; Described zinc salt is zinc acetate.
6. tea seed Flavone aglycone the preparation method of theasapogenol Zn complex according to claim 2, is characterized in that: described precipitate dissolves points to add dehydrated alcohol in throw out and dissolve, and consumption and the throw out of ethanol are identical in quality.
7. tea seed Flavone aglycone the preparation method of theasapogenol Zn complex according to claim 2, is characterized in that: described concentrated condition is concentrating under reduced pressure under 50 ~ 80 DEG C and 0.01 ~ 0.1 normal atmosphere, and described concentrated solution volume is 1/3 of filtrate volume; The condition of described drying is 50 ~ 80 DEG C of dryings 3 ~ 6 hours.
8. tea seed Flavone aglycone the preparation method of theasapogenol Zn complex according to claim 2, it is characterized in that: described precipitation agent is water, the consumption of precipitation agent is concentrated solution volume 3 ~ 5 times; The material of described adjustment pH is ammoniacal liquor; Described washing refers to and adopts ethanol to wash; Described degreasing leached tea oil slag is the middle one of the degreasing tea-seed dregs of rice or degreasing camellia seed meal.
9. tea seed Flavone aglycone the application of theasapogenol Zn complex according to claim 1, is characterized in that: described tea seed Flavone aglycone theasapogenol Zn complex are for the preparation of having neuroprotective medicine preparation.
10. the application of theasapogenol Zn complex according to claim 9, is characterized in that: the formulation of described pharmaceutical preparation is the one of external application, oral or injecting drug use formulation.
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| CN107551066A (en) * | 2017-10-10 | 2018-01-09 | 广东省天宝生物制药有限公司 | One kind uses nanometer sapogenin and nanometer flavone aglycone and its preparation method and application made of degreasing tea seed cake |
| CN108383891A (en) * | 2018-03-03 | 2018-08-10 | 广西师范大学 | A method of from the withered middle extraction saponin co-production Kaempferol of oil tea |
| CN115364161A (en) * | 2021-12-29 | 2022-11-22 | 江西环境工程职业学院 | Tea oil glycoprotein saponin nano intestinal probiotic accelerant and preparation method and application thereof |
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| CN107551066A (en) * | 2017-10-10 | 2018-01-09 | 广东省天宝生物制药有限公司 | One kind uses nanometer sapogenin and nanometer flavone aglycone and its preparation method and application made of degreasing tea seed cake |
| CN108383891A (en) * | 2018-03-03 | 2018-08-10 | 广西师范大学 | A method of from the withered middle extraction saponin co-production Kaempferol of oil tea |
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| CN115364161A (en) * | 2021-12-29 | 2022-11-22 | 江西环境工程职业学院 | Tea oil glycoprotein saponin nano intestinal probiotic accelerant and preparation method and application thereof |
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