CN115177662A - Application of paliurus ramosissimus or extract thereof in preparation of gout drugs - Google Patents
Application of paliurus ramosissimus or extract thereof in preparation of gout drugs Download PDFInfo
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- CN115177662A CN115177662A CN202210983262.9A CN202210983262A CN115177662A CN 115177662 A CN115177662 A CN 115177662A CN 202210983262 A CN202210983262 A CN 202210983262A CN 115177662 A CN115177662 A CN 115177662A
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- gout
- paliurus ramosissimus
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- 201000005569 Gout Diseases 0.000 title claims abstract description 46
- 239000003814 drug Substances 0.000 title claims abstract description 43
- 239000000284 extract Substances 0.000 title claims abstract description 31
- 241000724119 Paliurus ramosissimus Species 0.000 title claims description 28
- 238000002360 preparation method Methods 0.000 title claims description 10
- 229940079593 drug Drugs 0.000 title abstract description 14
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims abstract description 22
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229940116269 uric acid Drugs 0.000 claims abstract description 14
- 239000008280 blood Substances 0.000 claims abstract description 11
- 210000004369 blood Anatomy 0.000 claims abstract description 11
- 239000000469 ethanolic extract Substances 0.000 claims abstract description 11
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 10
- 241000907663 Siproeta stelenes Species 0.000 claims abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- ADFCQWZHKCXPAJ-GFCCVEGCSA-N equol Chemical group C1=CC(O)=CC=C1[C@@H]1CC2=CC=C(O)C=C2OC1 ADFCQWZHKCXPAJ-GFCCVEGCSA-N 0.000 claims description 10
- 235000019126 equol Nutrition 0.000 claims description 10
- ADFCQWZHKCXPAJ-UHFFFAOYSA-N indofine Natural products C1=CC(O)=CC=C1C1CC2=CC=C(O)C=C2OC1 ADFCQWZHKCXPAJ-UHFFFAOYSA-N 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 7
- 238000002347 injection Methods 0.000 claims description 6
- 239000007924 injection Substances 0.000 claims description 6
- 241000219100 Rhamnaceae Species 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 4
- 125000003158 alcohol group Chemical group 0.000 claims description 3
- 230000000155 isotopic effect Effects 0.000 claims description 3
- 208000018937 joint inflammation Diseases 0.000 claims description 3
- 229940002612 prodrug Drugs 0.000 claims description 3
- 239000000651 prodrug Substances 0.000 claims description 3
- UFLHIIWVXFIJGU-ARJAWSKDSA-N (Z)-hex-3-en-1-ol Chemical compound CC\C=C/CCO UFLHIIWVXFIJGU-ARJAWSKDSA-N 0.000 claims description 2
- 229930184510 Mallotus Natural products 0.000 claims description 2
- 241001060384 Mallotus <angiosperm> Species 0.000 claims description 2
- 241001528187 Paliurus Species 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 230000001684 chronic effect Effects 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 32
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 abstract description 20
- 241000700159 Rattus Species 0.000 abstract description 10
- 230000008961 swelling Effects 0.000 abstract description 10
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- GCKZANITAMOIAR-XWVCPFKXSA-N dsstox_cid_14566 Chemical compound [O-]C(=O)C1=CC=CC=C1.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H]([NH2+]C)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 GCKZANITAMOIAR-XWVCPFKXSA-N 0.000 description 8
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- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- 201000001431 Hyperuricemia Diseases 0.000 description 4
- 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 4
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- 208000002193 Pain Diseases 0.000 description 3
- 229960001338 colchicine Drugs 0.000 description 3
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- XBZYWSMVVKYHQN-MYPRUECHSA-N (4as,6as,6br,8ar,9r,10s,12ar,12br,14bs)-10-hydroxy-2,2,6a,6b,9,12a-hexamethyl-9-[(sulfooxy)methyl]-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid Chemical compound C1C[C@H](O)[C@@](C)(COS(O)(=O)=O)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C XBZYWSMVVKYHQN-MYPRUECHSA-N 0.000 description 2
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- 206010030113 Oedema Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 241001090408 Strobilanthes Species 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
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- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 2
- 238000011047 acute toxicity test Methods 0.000 description 2
- 229960003459 allopurinol Drugs 0.000 description 2
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 2
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- TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 description 1
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- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229960002529 benzbromarone Drugs 0.000 description 1
- WHQCHUCQKNIQEC-UHFFFAOYSA-N benzbromarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(Br)=C(O)C(Br)=C1 WHQCHUCQKNIQEC-UHFFFAOYSA-N 0.000 description 1
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- 229960005101 febuxostat Drugs 0.000 description 1
- BQSJTQLCZDPROO-UHFFFAOYSA-N febuxostat Chemical compound C1=C(C#N)C(OCC(C)C)=CC=C1C1=NC(C)=C(C(O)=O)S1 BQSJTQLCZDPROO-UHFFFAOYSA-N 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
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- 229930003935 flavonoid Natural products 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
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- 150000004677 hydrates Chemical class 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
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- 150000007522 mineralic acids Chemical class 0.000 description 1
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- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
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- 229960004380 tramadol Drugs 0.000 description 1
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Classifications
-
- 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)
- A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Abstract
The invention provides application of malachite seed or an extract thereof in preparing a medicament for treating gout. The invention is proved by experiments that the compound of the equus verniciflua L.f. ethanol extract has the function of inhibiting the plantar swelling of experimental gout rats, and the function of inhibiting the rise of blood uric acid of mice caused by xanthine, and the action strength of the equus verniciflua L.is similar to that of a reference chemical drug, which shows that the compound has better inhibitory activity on the symptoms and main pathological causes of gout.
Description
Technical Field
The invention relates to application of malachite seed or an extract thereof in preparing a medicine for treating gout.
Background
Gout (Gout) is a common and complex type of arthritis, and can be suffered from the Gout in all age groups, the average age of onset is 48 years, and the incidence rate of men is higher than that of women, and the ratio is 15. Patients with gout often have sudden joint pain at night, the joint is in urgent attack, severe pain, edema, red swelling and inflammation appear at the joint, and the pain is slowly relieved until the pain disappears for days or weeks. Gout attack is related to the concentration of uric acid in a body, and gout can form urate deposition in joint cavities and other places to activate the immune system of the body, so that acute joint pain is caused. And the human body is in a relative water shortage state at night, so that uric acid is more easily deposited and gathered at joints and other parts, and gout is caused. Diet control is a relatively common and healthy treatment method, such as drinking restriction, alcohol consumes a large amount of water and produces a large amount of purine in the fermentation process, the more purine content in the human body, the more uric acid is produced by metabolism, and the uric acid is produced by stimulating the liver by alcohol, so that the incidence rate of gout and the harm of gout to the human body are increased. Recurrent gout attacks can lead to malformation of the affected joint and to progressive limitation of joint motion due to deposition of urate crystals.
Gout can be divided into three basic types of primary, secondary and idiopathic, the etiology and pathogenesis are unknown, but the gout is related to hyperuricemia and has similar pathological manifestations. The current treatment for gout comprises two main parts: 1) Non-steroidal anti-inflammatory drugs, hormones and colchicine are generally used to control and relieve acute episodes as early as possible, mainly to inhibit inflammation. 2) The blood uric acid reducing agent comprises allopurin, febuxostat, benzbromarone, probenecid and the like. The medicines have obvious toxic and side effects and are difficult to be used for a long time, and gout is a long-term chronic disease with continuous acute attack, so that patients can only select continuously between the toxic and side effects and the treatment effect, and finally, the gout is difficult to be controlled and even cured.
The traditional Chinese medicine also has a treatment effect on gout: the marketed medicines such as gout easing tablets, gout fixing tablets and the like which are marketed at present are all Chinese herbal compounds, and the varieties are few; some Chinese medicinal components, such as cyathula root polysaccharide, ash bark total coumarin and the like, are patented, but are not medicines. The components with definite structure, definite action and low toxic and side effects are searched in the traditional Chinese medicine or natural products to have positive effects on the treatment of gout.
Fructus seu radix Strychni (Paliurus ramosissimus (lour.) Poir) is a plant of genus Strychnos of family Rhamnaceae, and mainly contains chemical components such as triterpenes, flavonoids, and coumarins, and has effects of treating sore, carbuncle, and ulcer, and removing toxic substance. Researches find that the triterpenoid in the paliurus ramosissimus has good in-vitro anti-tumor activity, wherein the anti-tumor activity of the pentacyclic triterpenoid paliurum is stronger than that of other triterpenoid, but no report of application of the paliurum to treatment of gout exists at present.
Disclosure of Invention
In order to solve the problems, the invention provides application of malachite or an extract thereof in preparing a medicament for treating gout.
Further, the Paliurus ramosissimus (Lour.) leaf of Paliurus ramosissimus (Lour.) of the genus Thamnus of the family Rhamnaceae; the extract is a paliurus ramosissimus leaf alcohol extract.
Further, the alcohol extract of the paliurus ramosissimus leaves is an alcohol extract of the paliurus ramosissimus leaves.
Further, the extract is equol, a pharmaceutically acceptable salt, stereoisomer, isotopic label, solvate, polymorph or prodrug thereof; the structural formula of the equol is as follows:
further, the medicament is a medicament for treating acute gout attack.
Further, the medicament is a medicament for inhibiting joint inflammation during acute gout attack.
Further, the medicament is a medicament for treating chronic gout.
Further, the drug is a drug that lowers blood uric acid.
The invention also provides a medicament for treating gout, which is a preparation prepared by taking the malachite seed or the extract thereof as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients; said Paliurus is the leaf of Paliurus ramosissimus (Lour.) Poir of the genus Mallotus of the family Rhamnaceae; the extract is an alcohol extract of the leaf of the paliurus ramosissimus, preferably an alcohol extract of the leaf of the paliurus ramosissimus or paliurus ramosissimus; the structural formula of the equol is as follows:
further, the preparation is an oral preparation, an external preparation or an injection.
As used herein, "ethanol" refers to ethanol at a concentration ranging from 40% to 90%.
The term "pharmaceutically acceptable salt" as used herein refers to salts that retain the biological effectiveness of the free acid and free base of the specified compound and that are biologically or otherwise not otherwise undesirable.
Salts in this application refer to acid salts formed with organic/inorganic acids, as well as basic salts formed with organic/inorganic bases.
As used herein, "solvate" refers to a combination of a compound of the present application and a solvent molecule formed by solvation. Such as hydrates, ethanol solvates, methanol solvates, and the like.
The term "polymorph" or "polymorph" as used herein refers to a compound of the present application in the form of a distinct crystal lattice.
The term "isotopic label" as used herein refers to a compound of the present invention which is labeled with an isotope. For example, isotopes in the compounds of the present application include various isotopes of H, C, O, such as 2 H， 3 H， 13 C， 14 C， 18 O， 17 O。
As used herein, "pharmaceutically acceptable prodrug" refers to any pharmaceutically acceptable salt, ester, salt of an ester, or other derivative of a compound of the present application that, upon administration to a receptor, is capable of providing, directly or indirectly, a compound of the present application or a pharmaceutically active metabolite or residue thereof.
"stereoisomers" as used herein refers to isomers resulting from the different spatial arrangement of atoms in a molecule.
Pharmacodynamic studies show that the equol extract and the compound equol have the effect of inhibiting plantar edema of rats with experimental gout, the compound equol has the effect of inhibiting blood uric acid rise of mice caused by xanthine, the action strength is similar to that of a reference chemical, and the compound has good inhibitory activity on symptoms and main pathological causes of gout.
Toxicology studies showed that the ethanol extract of the leaf of the paliurus ramosissimus (40% ethanol extract of the leaf of the paliurus ramosissimus combined with 90% extract of the residue, 7.1g crude drug/g) was administered to the mice by gavage at the maximum dose (12 g/kg) without any toxic reaction; the compound emamectin is used for treating gout, and the dosage of the compound emamectin is 100 times of the dosage of the drug for treating gout, and the compound emamectin is administrated to mice by intragastric administration, so that no obvious toxic reaction is seen, and the compound emamectin has good safety.
It will be apparent that various other modifications, substitutions and alterations can be made in the present invention without departing from the basic technical concept of the invention as described above, according to the common technical knowledge and common practice in the field.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Detailed Description
Example 1 Effect of ethanol extract of Strobilanthes and Compound Strobilanthes on swelling of the foot of rats with Experimental gout
1. Experimental animal SD rat, male, 200-240g, provided by Experimental animal center of Chinese medicine academy of sciences of Sichuan province, the experimental animal produces license number SCXK (Chuan) 2018-19, and license number SYXK (Chuan) 2018-100 is used.
2. Reference and main reagent equipment and instrument
PV-200 plantar volume measurement, duntai Union; 0.5mg of colchicine tablets, kunming pharmaceutical group GmbH, chinese medicine Standard H53021389; uric acid, sigma.
3. Test method
All the test and control samples were made up of 0.5% sodium carboxymethylcellulose (CMC) as a suspension. The microcrystalline sodium urate is prepared by recrystallization, and the concentration is 100g/l by using normal saline injection. The above 48 rats were divided into 6 groups by weight, and each group consisted of 8 rats, a model control group (0.5% CMC), a 400mg/kg group of the ethanol extract of hippophae seeds (7.1 g crude drug per g extract), 5, 20, 50mg/kg groups of compound hippophae seeds, and 0.5mg/kg group of colchicine. The aforementioned sodium urate suspension was injected at 0.1 ml/sole in all animals at the foot sole, while the test or control, solvent was administered by gavage, and the swelling rate (swelling degree/basal volume x 100%, where swelling degree = toe volume-basal volume at each detection time point after sodium urate injection) was calculated by measuring the foot sole volume with a foot sole plethysmometer at 0.5, 1, 2, 4, 6h after administration, respectively. Results are expressed as mean and standard deviation
Description is given; if the distribution accords with normal distribution, performing single-factor variance analysis, otherwise performing K-W nonparametric test; during one-way anova, LSD test is adopted for the homogeneity of variance, and Tamhane's T2 test is adopted for the heterogeneity of variance. Significance level α =0.05.
4. Test results
The test results are shown in table 1. The results show that: the hippophae rhamnoides ethanol extract is administrated by intragastric administration at a concentration of 400mg/kg, and can inhibit the foot sole swelling of rats caused by sodium urate microcrystal 4h and 6h after administration; the compound emamectin is administrated by gastric lavage, can start to inhibit rat plantar swelling caused by sodium urate microcrystal 1h after administration, and last for 4-6h, and the effective dose is 20mg and 50mg/kg. The vest ethanol extract and the compound vest essence can inhibit joint inflammation in the acute gout attack stage, thereby relieving gout symptoms.
TABLE 1 Malaytea seed ethanolEffect of extracts and Compounds Malamectin on rat foot swelling caused by sodium urate
Note: p <0.01, P <0.05 compared to model control group
Example 2 Effect test on xanthine-induced hyperuricemia in mice
1. Experimental animal KM mouse, male, 18-22g, provided by the experimental animals center of the institute of traditional chinese medicine and science, sichuan province, experimental animal produces license number SCXK (chun) 2018-19, license number SYXK (chun) 2018-100 is used.
2. Reference and main reagent equipment and instrument
Allopurinol tablets, 0.1g, guangzhou Pedi pharmaceutical Co., ltd., national Standard H44021368; xanthine, sigma.
3. Test method
All the test and control samples were made up of 0.5% sodium carboxymethylcellulose (CMC) as a suspension. The xanthine was prepared as a 6% solution in physiological saline. The above-mentioned 60 mice were divided into 6 groups at random by weight, and 10 mice each group were divided into a normal control group (0.5% CMC), a model control group (0.5% CMC), a compound of equol 5, 20, 50mg/kg and an allopurinol tablet of 100 mg/kg. Except for normal control group, the xanthine solution is injected into abdominal cavity at 0.1ml/10g, normal control group is injected into abdominal cavity with normal saline at equal dosage. After injection, the test sample or the reference substance and the solvent are given according to groups. Daily injections of xanthine were given and the drug was given for 3 consecutive days. On the fourth day, no xanthine solution is injected, only the test sample or the reference sample and the solvent are given, blood is collected from the orbit of the mouse 1h, the blood is centrifuged, the serum is separated, and the blood uric acid concentration is detected according to a kit method. Results are in mean and standard deviation
Description is given; such as a fit to a normal distribution,performing single-factor variance analysis, otherwise performing K-W nonparametric inspection; during one-way anova, LSD test is adopted for the homogeneity of variance, and Tamhane's T2 test is adopted for the heterogeneity of variance. Significance level α =0.05.
4. Test results
The test results are shown in table 2. The results show that the concentration of uric acid in blood of an experimental hyperuricemia mouse can be obviously reduced by intragastric administration of the compound equine formin for 4 days, and the effective dose is 20mg and 50mg/kg. The compound of the emamectin can reduce the blood uric acid, thereby treating the gout.
TABLE 2 Effect of the Compound Maramectin on xanthine-induced hyperuricemia in mice
Note: p <0.01 compared to model control group
EXAMPLE 3 Compound Maramectin mouse acute toxicity test
1. The experimental animal KM mouse is male, 18-22g, provided by the experimental animal center of the academy of traditional Chinese medicine and sciences of Sichuan province, and the experimental animal produces the license number SCXK (Chuan) 2018-19 and uses the license number SYXK (Chuan) 2018-100.
2. Test method
The test compound, tramadol, was formulated as a suspension using 0.5% sodium carboxymethylcellulose (CMC). The above 40 animals were divided into 2 groups of 20 animals each, which were a normal control group (0.5% CMC) and a compound-emamectin group (2 g/kg), respectively, by weight division. And (3) intragastrically administering a corresponding solvent and a test sample, recording the reaction and death condition of the animal, taking off the cervical vertebra to kill the animal on 14 days and 15 days continuously, and carrying out general anatomical observation on the main viscera.
4. Test results
All tested animals showed no obvious behavioral abnormalities and death during the observation period. The compound emamectin is administrated by intragastric administration at 100 times (2 g/kg) of pharmacodynamically effective dose of 20mg/kg, has no obvious toxicity, and indicates that the compound emamectin is good in safety.
Example 4 Malaysia ethanol extract mouse acute toxicity test
1. The experimental animal KM mouse is male, 18-22g, provided by the experimental animal center of the academy of traditional Chinese medicine and sciences of Sichuan province, and the experimental animal produces the license number SCXK (Chuan) 2018-19 and uses the license number SYXK (Chuan) 2018-100.
2. Test method
The extract of fructus Artocarpi Heterophylli (40% ethanol, 90% ethanol, and the residue) is mixed to obtain a suspension, and the suspension is prepared from 0.5% sodium carboxymethylcellulose (CMC) and 7.1g crude drug per g extract. The above 40 animals were divided into 2 groups of 20 animals each, which were a normal control group (0.5% CMC) and a vest ethanol extract group (12 g/kg) by weight. And (3) intragastrically administering a corresponding solvent and a test sample, recording the reaction and death condition of the animal, taking off the cervical vertebra to kill the animal on 14 days and 15 days continuously, and carrying out general anatomical observation on the main viscera.
4. Test results
All tested animals showed no obvious behavioral abnormalities and death during the observation period. The vest ethanol extract is administrated by intragastric administration at the maximum dose (12 g/kg), has no obvious toxicity, and indicates that the safety is good.
In conclusion, the invention proves that the compound of the paliurus ramosissimus alcohol extract has the effect of inhibiting experimental gout rat plantar swelling and inhibiting mouse blood uric acid increase caused by xanthine, and the action strength of the paliurus ramosissimus is similar to that of a reference chemical drug, so that the compound of the paliurus ramosissimus alcohol extract has good inhibition activity on gout symptoms and main pathological causes.
Claims (10)
1. Use of paliurus ramosissimus or its extract in preparing medicine for treating gout is provided.
2. Use according to claim 1, characterized in that: the Paliurus ramosissimus (Lour.) leaf of Paliurus ramosissimus (Lour.) Poir of the genus Thamnus of the family Rhamnaceae; the extract is an alcohol extract of the leaf of the paliurus ramosissimus.
3. Use according to claim 2, characterized in that: the paliurus ramosissimus leaf alcohol extract is an ethanol extract of paliurus ramosissimus leaves.
4. Use according to claim 1, characterized in that: the extract is equol, a pharmaceutically acceptable salt, a stereoisomer, an isotopic label, a solvate, a polymorph or a prodrug thereof; the structural formula of the equol is as follows:
5. the use according to claim 4, wherein the medicament is a medicament for the treatment of acute gout flares.
6. The use according to claim 5, wherein the medicament is a medicament for inhibiting joint inflammation during gout flares.
7. The use according to claim 4, wherein the medicament is a medicament for the treatment of chronic gout.
8. Use according to claims 1 to 7, characterized in that the medicament is a medicament for lowering blood uric acid.
9. The medicine for treating gout is characterized in that the medicine is a preparation prepared by taking malachite or an extract thereof as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients; said Paliurus is the leaf of Paliurus ramosissimus (Lour.) Poir of the genus Mallotus of the family Rhamnaceae; the extract is an alcohol extract of the leaf of the paliurus ramosissimus, preferably an alcohol extract of the leaf of the paliurus ramosissimus or paliurus ramosissimus; the structural formula of the equol is as follows:
10. the medicament according to claim 9, wherein the preparation is an oral preparation, a topical preparation or an injection.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103735654A (en) * | 2014-01-23 | 2014-04-23 | 四川省中医药科学院 | Traditional Chinese medicine extractive having bidirectional immunity adjustment effect and application |
| CN106421083A (en) * | 2016-10-27 | 2017-02-22 | 金秀瑶族自治县瑶医医院 | Yao medicine health care bath bag having function of treating rheumatic bone pain and preparation method of health care bath bag |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103735654A (en) * | 2014-01-23 | 2014-04-23 | 四川省中医药科学院 | Traditional Chinese medicine extractive having bidirectional immunity adjustment effect and application |
| CN106421083A (en) * | 2016-10-27 | 2017-02-22 | 金秀瑶族自治县瑶医医院 | Yao medicine health care bath bag having function of treating rheumatic bone pain and preparation method of health care bath bag |
Non-Patent Citations (1)
| Title |
|---|
| 余悦;白筱璐;雷玲;王李晋;李东晓;徐超群;张毅;: "马甲子急性毒性抗肿瘤作用及对免疫功能影响的初步研究", no. 08, pages 53 - 56 * |
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