CN114939116B - Application of protosappan wood element B in preparation of antipyretic medicine - Google Patents
Application of protosappan wood element B in preparation of antipyretic medicine Download PDFInfo
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- CN114939116B CN114939116B CN202210778514.4A CN202210778514A CN114939116B CN 114939116 B CN114939116 B CN 114939116B CN 202210778514 A CN202210778514 A CN 202210778514A CN 114939116 B CN114939116 B CN 114939116B
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- 239000002023 wood Substances 0.000 title claims abstract description 16
- 230000001754 anti-pyretic effect Effects 0.000 title claims abstract description 13
- 239000002221 antipyretic Substances 0.000 title claims abstract description 12
- 239000003814 drug Substances 0.000 title claims abstract description 9
- 238000002360 preparation method Methods 0.000 title abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 14
- 238000000034 method Methods 0.000 abstract description 10
- 235000007627 Caesalpinia Nutrition 0.000 abstract description 7
- 241000522234 Caesalpinia Species 0.000 abstract description 7
- 238000002474 experimental method Methods 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 229920006122 polyamide resin Polymers 0.000 abstract description 5
- 238000010992 reflux Methods 0.000 abstract description 5
- 238000010898 silica gel chromatography Methods 0.000 abstract description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 4
- 238000000605 extraction Methods 0.000 abstract description 4
- 239000000741 silica gel Substances 0.000 abstract description 4
- 229910002027 silica gel Inorganic materials 0.000 abstract description 4
- 241000196324 Embryophyta Species 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 15
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 10
- 235000014145 Caesalpinia bonduc Nutrition 0.000 description 7
- 244000036978 Caesalpinia bonduc Species 0.000 description 7
- 235000016513 Caesalpinia crista Nutrition 0.000 description 7
- 230000036760 body temperature Effects 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 206010037660 Pyrexia Diseases 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229960005489 paracetamol Drugs 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000000465 moulding Methods 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 235000014138 Caesalpinia decapetala Nutrition 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000220485 Fabaceae Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000031662 Noncommunicable disease Diseases 0.000 description 1
- 241001424341 Tara spinosa Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 238000009529 body temperature measurement Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229930186193 protosappanin Natural products 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- 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]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/16—Eight-membered rings
- C07D313/20—Eight-membered rings condensed with carbocyclic rings or ring systems
-
- 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- 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)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Rheumatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses application of protosappan wood B in preparation of antipyretic drugs, and relates to the technical field of plant medicines. The invention claims the application of protosappan wood element B in preparing antipyretic medicine. The invention also discloses an antipyretic, and the effective component of the antipyretic comprises protosappan wood element B. The method comprises the steps of extracting dried branches of Caesalpinia nux with ethanol under reflux, concentrating under reduced pressure to obtain total extract, rapidly dividing the total extract into four crude fractions by reduced pressure silica gel column chromatography, and separating and purifying the fractions by using silica gel, polyamide resin and reverse phase ODS method to obtain the compound protohematoxylin B with the extraction rate of more than 0.02%. The mouse experiment proves that the extracted protosappan wood element B has obvious antipyretic effect.
Description
Technical Field
The invention relates to the technical field of plant medicines, in particular to application of protohematoxylin B in preparation of antipyretic medicines.
Background
Fever is a symptom that the body temperature exceeds the normal range caused by infectious diseases and non-infectious diseases, and is one of the most common clinical symptoms. Researches report that the folk-custom medicinal material Caesalpinia crista has a certain antipyretic effect. The Caesalpinia [ Caesalpinia decapetala (Roth) Alston ] is a plant of the genus Caesalpinia (Caesalpinia L.) of the family Leguminosae, and has effects of clearing heat and removing dampness. The Caesalpinia crista has rich and diverse chemical components, and mainly contains flavonoid, terpenoid, phenylpropionic acid, steroid and phenolic chemical components. At present, it is not clear what compound in Caesalpinia crista mainly plays a role in relieving fever. The method has important significance in improving the effective application of the Caesalpinia crista by separating and identifying the active compounds in the Caesalpinia crista and researching the pharmacological activity.
Disclosure of Invention
The invention aims to provide an application of protosappan-wood B in preparing antipyretic drugs, so as to solve the problems in the prior art.
In order to achieve the above object, the present invention provides the following solutions:
the invention provides an application of protosappan wood element B in preparing antipyretic drugs.
The invention also provides a method for extracting the protohematoxylin B from the Caesalpinia cristata, which comprises the following steps: and (3) carrying out ethanol reflux extraction on the Caesalpinia spinosa, concentrating to obtain a total extract, separating the total extract by a reduced pressure silica gel column chromatography to obtain a first crude product, separating the first crude product by polyamide resin to obtain a second crude product, separating the second crude product by a reversed-phase ODS column chromatography, and extracting to obtain a finished product of the protosappan wood element B.
Further, the specific operation of ethanol reflux comprises the following steps: soaking in ethanol for 12 hr, reflux-extracting at 60deg.C for 3 hr, and repeating the extraction for 3 times.
Further, the concentration is reduced pressure concentration.
Further, the gradient elution conditions of the reduced pressure silica gel column chromatography are as follows: CH (CH) 2 Cl 2 And MeOH in the volume ratios of 100:1, 50:1, 10:1, and 0:1 in this order.
Further, the gradient elution conditions for the polyamide resin separation are: etOH and H 2 The volume ratio of O is 30:70, 60:40 and 90:10 in sequence.
Further, the gradient elution conditions of the reversed-phase ODS column chromatography are as follows: meOH and H 2 The volume ratio of O is 30:70, 60:40 and 90:10 in sequence.
The invention also provides an antipyretic, and the effective component comprises protosappan wood element B.
Further, the antipyretic also comprises a pharmaceutically acceptable carrier or excipient.
The invention discloses the following technical effects:
according to the invention, the component protohematoxylin B in the medicinal material Caesalpinia cristata has an antipyretic effect on a mouse fever model for the first time, and can reduce the body temperature of a fever mouse to a normal range.
The method comprises the steps of extracting dried branches of the Caesalpinia crista with ethanol under reflux, concentrating under reduced pressure to obtain total extract, rapidly dividing the total extract into four crude fractions by using a reduced pressure silica gel column chromatography, and separating and purifying the fractions by using a silica gel, polyamide resin and reverse-phase ODS method to obtain the compound protohematoxylin B.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 shows the results of anal temperature detection in the mouse experiment of example 2.
Detailed Description
Various exemplary embodiments of the invention will now be described in detail, which should not be considered as limiting the invention, but rather as more detailed descriptions of certain aspects, features and embodiments of the invention.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. In addition, for numerical ranges in this disclosure, it is understood that each intermediate value between the upper and lower limits of the ranges is also specifically disclosed. Every smaller range between any stated value or stated range, and any other stated value or intermediate value within the stated range, is also encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the invention described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from consideration of the specification of the present invention. The specification and examples of the present invention are exemplary only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are intended to be inclusive and mean an inclusion, but not limited to.
EXAMPLE 1 preparation of Prosappan-in B
Soaking 10.0kg of dry branch of Caesalpinia crista in 50L of 95% (80-100% with the same effect) ethanol for 12 hr, heating to 60deg.C, refluxing for 3 hr, extracting for 3 times, concentrating under reduced pressure at 60deg.C (55-65deg.C with the same effect) to obtain total extract 400g, dissolving the total extract with 2L of methanol, mixing with 500g of silica gel (200-300 mesh), volatilizing methanol at normal temperature to obtain total extract silica gel adsorption mixture, and adsorbing with CH 2 Cl 2 MeOH (volume ratio 100:1, 50:1, 15:1, 0:1) in 8L of each solvent, and separating by vacuum silica gel column chromatography to quickly and sequentially divide the solvent into four crude fractions fr.1-fr.4; fr.1 (80 g) was treated with EtOH: H 2 O (volume ratio of 30:70, 60:40, 90:10) gradient elution, each elution volume of 4L, polyamide resin separation, fr.1-1 to Fr.1-3 fractions Fr.1-1 (40 g) were obtained sequentially with MeOH: H 2 O (volume ratio of 30:70, 60:40, 90:10) gradient elution, separating by reversed phase ODS column chromatography, and sequentially obtaining fractions Fr.1-1-1 to Fr.1-1-3; fr.1-1-2 was tested by nuclear magnetic resonance spectroscopy (results are shown in Table 1) and proved to be protohematoxylin B (2.5 g) with a purity of 95%.
The compounds of Table 1 1 H (600 MHz) and 13 C NMR(150MHz)
note that: the solvent is CD 3 OD, hydrogen spectrum test (600 MHz), carbon spectrum test (150 MHz).
The extraction rate of the protosappan wood B in the Caesalpinia cristata prepared by the method is 0.025 percent.
EXAMPLE 2 test of the antipyretic effect of Prosappan-in B
1 Experimental materials
1.1 test article: the protosappan wood element B prepared in example 1
1.2 instrument: FT3400 type animal thermometer (Nanjing Karl biological technology Co., ltd.)
1.3 reagent: yeast powder (Dalian Mei Lun Biotechnology Co., ltd.), acetaminophen (Dalian Mei Lun Biotechnology Co., ltd.), physiological saline (Shandong Chen Xin pharmaceutical Co., ltd.), and the rest of the reagents were all of domestic analytical purity.
1.4 animals: the experimental animals were SPF-grade C57BL/6J mice, 50 males, 6 weeks old, and 18-20 g in weight, purchased from Liaoning long life biotechnology Co.
2 Experimental methods
2.1 preparation method of test solution
Taking 100mg of protosappan wood B and acetaminophen powder as positive drugs respectively, and preparing a 10mg/mL administration test solution by pure water; the total amount and volume required for each administration was calculated based on the body weight of the mice and the amount of the administered agent (100 mg/kg), and pure water was administered in the same volume to the blank group and the model group. 5g of yeast powder was taken and mixed with 25mL of physiological saline to prepare a yeast injection.
2.2 building of heating model
Mice are normally kept under SPF environment for 5 days, so that the mice are adapted to laboratory environment, the anus temperature of the mice is monitored every 3 hours at intervals of 3 days before the experiment, the basal body temperature of the mice is recorded, and the mice with abnormal body temperature are adapted to temperature measurement operation. The basal body temperature of the mice was measured at 0 hour from the beginning of the experiment, and 38 mice of the experimental group were subcutaneously injected with the yeast injection prepared by 0.2ml of 2.1 at the back to heat them, and 10 mice of the blank group were injected with the same volume of physiological saline.
2.3 random grouping and administration
Taking 30 mice of an experimental group with body temperature raised by more than 1 ℃ and randomly dividing the mice into 3 groups, namely a model group, a acetaminophen group and an protosappan wood element B group, wherein the acetaminophen groups are respectively used for lavage administration of 2.1 prepared acetaminophen solutions 1 hour, 5 hours and 9 hours after molding; the raw hematoxylin B solution prepared by 2.1 is respectively injected into the stomach 1 hour, 5 hours and 9 hours after molding; the model group was given the same volume of pure water at the same time.
2.4 observation of subcutaneous graft tumor and measurement of each index
The temperature of the mice was measured once per hour within 13 hours of the experiment, and the anal temperature of the mice was measured 24 hours after molding.
2.5 experimental results
Compared with a blank control group, the anal temperature of the mice in the model group is obviously increased, and the heating state lasts for 13 hours; both acetaminophen and protosappanin B-dosed groups were able to significantly lower the anal temperature in mice, with statistical differences compared to the model group (fig. 1). Therefore, the protosappan wood B has the prospect of preparing the clinical medicine for treating fever.
The above embodiments are only illustrative of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention, and various modifications and improvements made by those skilled in the art to the technical solutions of the present invention should fall within the protection scope defined by the claims of the present invention without departing from the design spirit of the present invention.
Claims (1)
1. The application of protosappan-wood B as the only active component in preparing antipyretic medicine.
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CN202210778514.4A CN114939116B (en) | 2022-07-04 | 2022-07-04 | Application of protosappan wood element B in preparation of antipyretic medicine |
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4014645A1 (en) * | 1990-05-08 | 1991-11-14 | Univ Magdeburg Tech | Extinguishing agent for non-self-igniting chloro-silane(s) - comprises inert gas contg. at least 1 per cent alkane, up to a limit determined by flammability of mixt. |
JPH06135842A (en) * | 1992-10-22 | 1994-05-17 | Toyama Pref Gov | Antipyretic and its production |
CN108329292A (en) * | 2018-04-16 | 2018-07-27 | 黄榜昇 | A method of preparing former haematoxylin B |
CN110530990A (en) * | 2019-08-07 | 2019-12-03 | 贵州良济药业有限公司 | A kind of detection method of mysorethorn flu mixture |
CN114295753A (en) * | 2021-12-30 | 2022-04-08 | 贵州医科大学 | Animal model construction method for corium versicolor drug pharmacokinetics and tissue distribution |
-
2022
- 2022-07-04 CN CN202210778514.4A patent/CN114939116B/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4014645A1 (en) * | 1990-05-08 | 1991-11-14 | Univ Magdeburg Tech | Extinguishing agent for non-self-igniting chloro-silane(s) - comprises inert gas contg. at least 1 per cent alkane, up to a limit determined by flammability of mixt. |
JPH06135842A (en) * | 1992-10-22 | 1994-05-17 | Toyama Pref Gov | Antipyretic and its production |
CN108329292A (en) * | 2018-04-16 | 2018-07-27 | 黄榜昇 | A method of preparing former haematoxylin B |
CN110530990A (en) * | 2019-08-07 | 2019-12-03 | 贵州良济药业有限公司 | A kind of detection method of mysorethorn flu mixture |
CN114295753A (en) * | 2021-12-30 | 2022-04-08 | 贵州医科大学 | Animal model construction method for corium versicolor drug pharmacokinetics and tissue distribution |
Non-Patent Citations (4)
Title |
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Anti-inflammatory Constituents of Sappan Lignum;Makiko W ASHIYAMA et al.;《Biol. Pharm. Bull.》;第32卷(第5期);第942页表1;第943页右栏部分 * |
刘俊宏等.UPLC 测定云实皮中二氢红花菜豆酸苷和原苏木素 B 的含量.《中国实验方剂学杂志》.2013,第19卷(第20期),第77-80页. * |
樊代明主编.《肿瘤研究前沿》.西安交通大学出版社,2002,第2卷第250页. * |
郭鹏举等主编.《中国非处方药完全手册》.陕西科学技术出版社,2005,第191页. * |
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