CN116173103B - Application of radix salviae miltiorrhizae in improving safety of medicines containing radix stephaniae tetrandrae - Google Patents
Application of radix salviae miltiorrhizae in improving safety of medicines containing radix stephaniae tetrandrae Download PDFInfo
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- CN116173103B CN116173103B CN202210979688.7A CN202210979688A CN116173103B CN 116173103 B CN116173103 B CN 116173103B CN 202210979688 A CN202210979688 A CN 202210979688A CN 116173103 B CN116173103 B CN 116173103B
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- tetrandrine
- salviae miltiorrhizae
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- stephaniae tetrandrae
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- 239000003814 drug Substances 0.000 title claims abstract description 30
- 229940079593 drug Drugs 0.000 title description 11
- 241001369613 Stephania tetrandra Species 0.000 claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 238000012546 transfer Methods 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- WVTKBKWTSCPRNU-KYJUHHDHSA-N (+)-Tetrandrine Chemical compound C([C@H]1C=2C=C(C(=CC=2CCN1C)OC)O1)C(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2C[C@@H]2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-KYJUHHDHSA-N 0.000 claims description 148
- WVTKBKWTSCPRNU-UHFFFAOYSA-N rac-Tetrandrin Natural products O1C(C(=CC=2CCN3C)OC)=CC=2C3CC(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2CC2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-UHFFFAOYSA-N 0.000 claims description 74
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- 235000006533 astragalus Nutrition 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 241000132012 Atractylodes Species 0.000 claims description 3
- 244000303040 Glycyrrhiza glabra Species 0.000 claims description 3
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims description 3
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims description 3
- 235000011477 liquorice Nutrition 0.000 claims description 3
- 241001061264 Astragalus Species 0.000 claims description 2
- 210000004233 talus Anatomy 0.000 claims description 2
- 238000003809 water extraction Methods 0.000 claims description 2
- 240000007164 Salvia officinalis Species 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 6
- 229940126680 traditional chinese medicines Drugs 0.000 abstract description 5
- 231100000419 toxicity Toxicity 0.000 abstract description 4
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- 239000000284 extract Substances 0.000 description 12
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- 241000252212 Danio rerio Species 0.000 description 7
- 235000005412 red sage Nutrition 0.000 description 7
- 239000009636 Huang Qi Substances 0.000 description 5
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- 238000005259 measurement Methods 0.000 description 5
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
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- 239000013558 reference substance Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 241000758795 Aristolochiaceae Species 0.000 description 2
- 241000045403 Astragalus propinquus Species 0.000 description 2
- 206010029155 Nephropathy toxic Diseases 0.000 description 2
- 240000007267 Stephania hernandifolia Species 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
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- 238000001291 vacuum drying Methods 0.000 description 2
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 description 1
- 229910000020 calcium bicarbonate Inorganic materials 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 244000132619 red sage Species 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
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- 239000006228 supernatant Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
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- 231100000331 toxic Toxicity 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/59—Menispermaceae (Moonseed family), e.g. hyperbaena or coralbead
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
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- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Toxicology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention belongs to the field of traditional Chinese medicines, and in particular relates to an application of radix salviae miltiorrhizae in reducing toxicity of a radix stephaniae tetrandrae-containing medicine, wherein the radix stephaniae tetrandrae-containing medicine is a radix stephaniae tetrandrae single medicine or a traditional Chinese medicine compound preparation containing radix stephaniae tetrandrae raw materials, and the mass ratio of radix stephaniae tetrandrae to radix salviae miltiorrhizae is 1:0.2-8. The invention discovers that the addition of the root of red-rooted salvia in the prescription containing the stephania tetrandra can greatly reduce the transfer rate of stephania tetrandra, the stephania tetrandra, and the stephania tetrandra has a great attenuation effect on the stephania.
Description
Technical Field
The invention belongs to the field of traditional Chinese medicines, and particularly relates to application of radix salviae miltiorrhizae in improving safety of medicines containing radix stephaniae tetrandrae.
Background
The Chinese pharmacopoeia specifies that the source of the stephania tetrandra is stephania tetrandra, the stephania japonica of Aristolochiaceae is also used as stephania tetrandra in the past, but the Aristolochiaceae has definite nephrotoxicity, and the medicinal standard of the stephania japonica is cancelled due to the clinical medication safety. The stephania tetrandra which is allowed to be used at present is stephania tetrandra.
In recent years, as the studies on the stephania tetrandra are continued, research discoveries and literature reports show that the stephania tetrandra also has obvious hepatorenal toxicity, and even though the stephania tetrandrae is dosed in pharmacopoeia, certain liver and kidney functions are changed for a long time. The hepatotoxicity and nephrotoxicity of tetrandrine are mainly related to alkaloid components, wherein the highest content is tetrandrine and tetrandrine, and the two components have analgesic and anti-inflammatory effects, but also have certain toxicity.
The preparation of the traditional Chinese medicine compound preparation generally adopts the traditional water extraction and decocting process, the synergistic effect and toxicity reduction effect can be generated by the decoction of the traditional Chinese medicine, and the content of certain effective components can be obviously increased or the content of certain toxic and side effect components can be obviously reduced after the decoction of the traditional Chinese medicine compound preparation generally compared with the single decoction of a certain medicine. Although more experts in the industry recognize the mode of decocting the traditional Chinese medicines in a combined way at present, the research is less, the traditional Chinese medicines have no commonality, and the traditional Chinese medicines do not have the synergistic and toxicity-reducing effects after all the components are decocted in a combined way.
The drug safety of tetrandrine is a study which is paid more attention to, in particular to tetrandrine and tetrandrine components. We found in the study that the transfer rates of tetrandrine and tetrandrine after the tetrandrine was decocted alone varied between 25% -30%.
Disclosure of Invention
Aiming at the defects existing in the prior art, the invention provides a compatibility composition for improving the safety of a medicament containing stephania tetrandra. The transfer rate of tetrandrine and tetrandrine in the stephania tetrandrae can be greatly reduced, and the medication safety of stephania tetrandra is improved.
In order to achieve the purpose of the invention, the technical scheme adopted is as follows:
the invention provides application of radix salviae miltiorrhizae in improving the safety of medicines containing radix stephaniae tetrandrae.
Preferably, the tetrandra-containing medicine is a tetrandra single medicine or a Chinese herbal compound preparation containing tetrandra raw materials.
Preferably, the mass ratio of the stephania tetrandra root to the red sage root is 1:0.2-8.
Preferably, the mass ratio of the stephania tetrandra root to the red sage root is 1:1-5.
Preferably, the radix salviae miltiorrhizae is applied to reducing the content or the transfer rate of tetrandrine and/or tetrandrine in the tetrandrine-containing medicine.
Preferably, the compatible composition comprises a stephania tetrandra medicine and a red sage root, wherein the mass ratio of stephania tetrandra medicine to the red sage root is 1:0.2-8.
Preferably, the mass ratio of the stephania tetrandra root to the red sage root is 1:1-5.
Preferably, the compatible composition further comprises a pharmaceutical auxiliary material, wherein the pharmaceutical auxiliary material is selected from one or more of dextrin, starch, calcium sulfate, calcium bicarbonate, crospovidone, croscarmellose sodium, silicon dioxide, magnesium stearate and talcum powder.
The invention also aims to provide a preparation method of the compatible composition, which comprises the steps of mixing the radix stephaniae tetrandrae and the radix salviae miltiorrhizae, adding water for extraction and concentrating.
Preferably, the mass of water: the total mass of the radix stephaniae tetrandrae-containing medicines is 6-12:1, the extraction temperature is 90-100 ℃, the extraction time is 1-2h, and the extraction times are 1-3.
Compared with the prior art, the invention has the beneficial effects that:
(1) The transfer rate of the tetrandrine and the tetrandrine after the tetrandrine is decocted alone or combined with other medicinal ingredients is between 25 and 30 percent, and the transfer rate of the tetrandrine and the tetrandrine after the radix salviae miltiorrhizae is added and decocted together is reduced to about 5 percent, which is reduced by about 5 times, and the effect is very remarkable.
(2) The toxicity test of zebra fish shows that the invention has MNLC (maximum non-lethal concentration) and LC after the tetrandra root and the red sage root are decocted by hydration 10 The total content of radix Stephaniae Tetrandrae (10% lethal concentration) is greatly improved compared with the single water decoction of radix Stephaniae Tetrandrae, and the Chinese medicinal composition containing radix Stephaniae Tetrandrae (radix Stephaniae Tetrandrae Shang Chufang: radix Stephaniae, radix astragali, atractylodis rhizoma, glycyrrhrizae radix) has MNLC (maximum non-lethal concentration) and LC after Saviae Miltiorrhizae radix is added 10 Compared with the prescription of the radix stephaniae tetrandrae and astragalus decoction, the (10% lethal concentration) is greatly improved, which indicates that the medication safety of the radix stephaniae tetrandrae can be greatly improved after the radix salviae miltiorrhizae is added.
Drawings
FIG. 1 is a chromatogram of a tetrandrine and tetrandrine mixed control solution, peak a is tetrandrine and peak b is tetrandrine.
FIG. 2 shows the content measurement and superposition chromatograms of tetrandrine and tetrandrine in dry extracts obtained by decocting radix Stephaniae Tetrandrae and Saviae Miltiorrhizae radix in different mass ratios in examples 1-5, wherein peak a is tetrandrine and peak b is tetrandrine. The bottom-up chromatograms were example 1, example 2, example 3, example 4, example 5 in this order.
FIG. 3 is a chromatogram of the content measurement of tetrandrine and tetrandrine in the dry extract obtained by decocting radix stephaniae tetrandrae and radix astragali Shang Chufang with radix Salviae Miltiorrhizae in example 7, wherein peak a is tetrandrine and peak b is tetrandrine.
FIG. 4 is a chromatogram of the content measurement of tetrandrine and tetrandrine in the dry extract obtained by decocting the tetrandrine in comparative example 1, wherein peak a is tetrandrine and peak b is tetrandrine.
FIG. 5 is a chromatogram of the content measurement of tetrandrine and tetrandrine in the dry extract of radix astragali Shang Chufang of comparative example 2, wherein peak a is tetrandrine and peak b is tetrandrine.
Note that: the unclear abscissa does not affect the disclosure and understanding of the technical scheme of the invention.
Detailed Description
The invention is further described in connection with the following detailed description.
Examples 1-6 the amounts of the ingredients of the compatible compositions are shown in Table 1.
Table 1 formulation table
| Examples | Radix stephaniae tetrandrae (parts by weight) | Radix salviae miltiorrhizae (weight portions) |
| Example 1 | 1 | 0.2 |
| Example 2 | 1 | 0.5 |
| Example 3 | 1 | 1 |
| Example 4 | 1 | 2 |
| Example 5 | 1 | 5 |
| Example 6 | 1 | 8 |
Examples 1-6 the preparation method of the composition comprising radix stephaniae tetrandrae and radix salviae miltiorrhizae is as follows:
decocting radix Stephaniae Tetrandrae decoction pieces and Saviae Miltiorrhizae radix decoction pieces with water for 2 times, decocting with 8 times of water for 1.5 hr for the first time, decocting with 6 times of water for 1 hr for the second time, filtering, concentrating under reduced pressure at 60deg.C to dry, and vacuum drying at 60deg.C to obtain dry extract. The content of tetrandrine and tetrandrine in the dry extract was measured and the transfer rate was calculated, and the results are shown in table 2 below.
Example 7
Taking 2 parts of stephania tetrandra decoction pieces, 2.5 parts of astragalus membranaceus decoction pieces, 1.5 parts of bighead atractylodes rhizome decoction pieces and 1 part of liquorice decoction pieces, namely stephania tetrandra Shang Chufang (from the 'golden-kukukukui's province), adding 4 parts of salvia miltiorrhiza decoction pieces, decocting with water for 3 times, adding 8 times of water for 1 hour in the first time, adding 6 times of water for 1 hour in the second time, adding 6 times of water for 1 hour in the third time, filtering the water decoction, concentrating to dryness under reduced pressure at 60 ℃, and then spray drying to obtain dry paste.
Comparative example 1
Decocting radix Stephaniae Tetrandrae decoction pieces with water for 2 times, decocting with 8 times of water for 1.5 hr for the first time, decocting with 6 times of water for 1 hr for the second time, filtering, concentrating under reduced pressure at 60deg.C to dry, and vacuum drying at 60deg.C to obtain dry extract.
Comparative example 2
Taking 2 parts of stephania tetrandra decoction pieces, 2.5 parts of astragalus membranaceus decoction pieces, 1.5 parts of bighead atractylodes rhizome decoction pieces and 1 part of liquorice decoction pieces, namely stephania tetrandra Shang Chufang (from the 'golden-kukukukukui's province), adding water for decocting for 2 times, adding 8 times of water for decocting for 1.5 hours for the first time, adding 6 times of water for decocting for 1 hour for the second time, filtering the water decoction, concentrating to dryness under reduced pressure at 60 ℃, and drying under reduced pressure at 60 ℃ to obtain dry paste.
Test 1
The content of tetrandrine and tetrandrine in the dry extract powders of examples 1 to 7 and comparative examples 1 to 2 was measured by HPLC method.
The method for measuring the content of tetrandrine and tetrandrine by high performance liquid chromatography comprises the following steps:
high performance liquid chromatography conditions:
instrument name: agilent 1260 high performance liquid chromatograph
Chromatographic column: ZORBAX Eclipse Plus C18 (column length 150mm, inner diameter 4.6mm, particle size 5 μm)
Flow rate: 1.0ml/min
Column temperature: 25 DEG C
Detection wavelength: 237nm
Mobile phase: acetonitrile-methanol-water-glacial acetic acid (40:30:30:1) (0.41 g sodium dodecyl sulfate per 100 ml)
Preparation of a control solution: the preparation method comprises precisely weighing the proper amounts of tetrandrine reference substance (110793-201807, content is 98.3% of Chinese food and drug detecting institute) and tetrandrine reference substance (110711-201810, content is 99.6% of Chinese food and drug detecting institute), and adding methanol solution to prepare into mixed reference substance solution containing tetrandrine 51.07 μg and tetrandrine 103.70 μg per 1 ml.
Preparation of test solution: mixing the above materials, decocting, adding 50% ethanol 25ml, weighing, ultrasonic treating (power 200W, frequency 40 kHz) for 30 min, taking out, cooling, weighing, supplementing the weight with 50% ethanol, centrifuging (8000 rpm) for 10 min, and collecting supernatant.
The chromatogram of the tetrandrine and tetrandrine mixed reference substance solution is shown in figure 1; the content measurement superposition chromatograms of the tetrandrine and the tetrandrine in the dry paste obtained by the combined decoction of the tetrandrine and the red sage root in different mass ratios in examples 1-5 are shown in figure 2; example 7A chromatogram for determining the content of tetrandrine and tetrandrine in a dry extract obtained by decocting radix astragali Shang Chufang and Saviae Miltiorrhizae radix is shown in figure 3; comparative example 1 content determination chromatogram of tetrandrine and tetrandrine in dry extract obtained by decocting radix Stephaniae Tetrandrae is shown in figure 4; comparative example 2A chromatogram of the content determination of tetrandrine and tetrandrine in the dry extract obtained by decocting radix astragali Shang Chufang is shown in figure 5. And calculate the transfer rate, the results are shown in Table 2 below
The content of tetrandrine and tetrandrine in each of the examples and comparative examples was measured by the above chromatographic conditions, and the transfer rate was calculated, and the results are shown in table 2 below.
TABLE 2
Test 2
Zebra fish toxicity tests were performed on the dry extracts prepared in examples 3-5, example 7 and comparative examples 1-2, and the MNLC (maximum non-lethal concentration) and LC of each sample on zebra fish were calculated 10 (10% lethal concentration).
The test method comprises the following steps:
2dbf wild type AB strain zebra fish were randomly selected in 6-well plates, 30 zebra fish were treated in each well (experimental group), and a normal control group was set with a capacity of 3mL per well. The treatment is carried out at 28 ℃ for 72 hours, the death quantity of the zebra fish of each experimental group is counted every day and removed in time, and the acute toxicity incidence rate of each experimental group is counted after 72 hours. The optimal "concentration-mortality" effect curve was plotted using Origin 8.0 statistical software and the MNLC and LC of the samples on zebra fish were calculated 10 。
MNLC (maximum non-lethal concentration) and LC 10 The (10% lethal concentration) results are shown in Table 3 and the concentration-mortality results are shown in Table 4.
TABLE 3 MNLC (maximum non-lethal concentration) and LC 10 (10% lethal concentration) results
| Group of | MNLC(μg/mL) | LC 10 (μg/mL) |
| Example 3 | 3379 | 3500 |
| Example 4 | 3427 | 3474 |
| Example 5 | 2938 | 2982 |
| Example 7 | 2923 | 2967 |
| Comparative example 1 | 359 | 367 |
| Comparative example 2 | 1945 | 1989 |
TABLE 4 concentration-mortality results
The foregoing detailed description is directed to one of the possible embodiments of the present invention, which is not intended to limit the scope of the invention, but is to be accorded the full scope of all such equivalents and modifications so as not to depart from the scope of the invention.
Claims (2)
1. The application of the radix salviae miltiorrhizae in reducing the content or the transfer rate of the tetrandrine and/or the tetrandrine in the tetrandrine medicine is characterized in that the tetrandrine medicine is a tetrandrine single medicine or a Chinese herbal compound preparation, the mass ratio of the tetrandrine to the radix salviae miltiorrhizae is 1:0.2-8, the Chinese herbal compound preparation is prepared from 2 parts of tetrandrine decoction pieces, 2.5 parts of astragalus decoction pieces, 1.5 parts of bighead atractylodes rhizome decoction pieces, 1 part of liquorice decoction pieces and 4 parts of radix salviae miltiorrhizae decoction pieces, and the specific method for reducing the content or the water extraction transfer rate of the tetrandrine and/or the tetrandrine in the tetrandrine medicine is that the radix salviae miltiorrhizae and the tetrandrine medicine are mixed according to the weight ratio, extracted by adding water and concentrated.
2. The use according to claim 1, wherein the mass ratio of stephania tetrandra and salviae miltiorrhizae is 1:1-5.
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