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WO2017156648A1 - Composé à effet anti-inflammatoire - Google Patents

Composé à effet anti-inflammatoire Download PDF

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Publication number
WO2017156648A1
WO2017156648A1 PCT/CN2016/000142 CN2016000142W WO2017156648A1 WO 2017156648 A1 WO2017156648 A1 WO 2017156648A1 CN 2016000142 W CN2016000142 W CN 2016000142W WO 2017156648 A1 WO2017156648 A1 WO 2017156648A1
Authority
WO
WIPO (PCT)
Prior art keywords
toe
szy1406
administration
volume
rat
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2016/000142
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English (en)
Chinese (zh)
Inventor
陈秀兰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guangzhou Nuowei Biotechnology Co Ltd
Original Assignee
Guangzhou Nuowei Biotechnology Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Guangzhou Nuowei Biotechnology Co Ltd filed Critical Guangzhou Nuowei Biotechnology Co Ltd
Priority to PCT/CN2016/000142 priority Critical patent/WO2017156648A1/fr
Publication of WO2017156648A1 publication Critical patent/WO2017156648A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
    • C07C57/38—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings polycyclic

Definitions

  • the present invention relates to a novel compound having an anti-inflammatory action.
  • Antipyretic analgesic and anti-inflammatory drugs are a class of drugs that have antipyretic and analgesic effects, and most have anti-inflammatory and anti-rheumatic effects. Because of its different chemical structure and anti-inflammatory mechanism than glucocorticoid steroidal anti-inflammatory drugs (SAIDS), different types of NSAIDs, also known as non-steroidal anti-inflammatory drugs (NSAIDS), have the same mechanism of action. They inhibit the final production of prostacyclin (PGI1), prostaglandins (PGE1, PGE2) and thromboxane A2 (TXA2) by inhibiting the activity of cyclooxygenase.
  • PKI1 prostacyclin
  • PGE1, PGE2 prostaglandins
  • TXA2 thromboxane A2
  • Prostaglandins have many functions: increased vascular permeability; various tissue arterial dilatation; regulation of renal blood flow, increased renal filtration rate; promotion of sodium excretion, lowering blood pressure; inhibition of gastric acid secretion; contraction of uterine muscle fibers, dissolution of the corpus luteum; Relaxation of tracheal smooth muscle; vasoconstriction of nasal mucosa; inhibition of platelet aggregation; promotion of bone resorption; inhibition of glycerolipid decomposition.
  • NSAID also inhibits the release of bradykinin during inflammation, alters lymphocyte responses, and reduces the migration and phagocytosis of granulocytes and monocytes.
  • NSAID inhibits the synthesis of prostaglandins, in addition to the analgesic and anti-inflammatory effects, there are also corresponding side effects. Mainly in the gastrointestinal tract and kidneys. To evaluate the efficacy of NSAIDs, most NSAIDs were compared to ibuprofen or aspirin.
  • the present invention relates to a novel compound SZY1406 (formula I), as shown in the following figure:
  • Non-steroidal anti-inflammatory drugs have anti-inflammatory, analgesic and antipyretic effects; the experimental injection of carrageenan replicates the inflammatory model, and the multi-dose group is established to observe the effect of oral administration of SZY1406 and ibuprofen on paw swelling in rats. The strength of SZY1406 and ibuprofen.
  • ibuprofen 2mg/kg showed a significant increase in the toe volume at each time point after administration, suggesting that ibuprofen 2mg/kg has no anti-inflammatory effect on carrageenan-induced inflammation, and cloth
  • SZY1406 2 mg/kg increased the volume of rat toe after administration, 2 h, 3 h after administration. The increase was more obvious.
  • SZY1406 4, 8 mg/kg showed no increase in rat toe volume at each time point after administration.
  • the swelling rate of the toes in the rats with ibuprofen at 8, 12, and 16 mg/kg was significantly decreased.
  • the swelling rate of the toes in SZY14062, 4, 8, 12, and 16 mg/kg rats decreased to varying degrees.
  • the toe swelling rate of the rats in the dose group was significantly reduced 5 h after administration.
  • ibuprofen and SZY1406 have obvious anti-inflammatory effects, and ibuprofen can obtain stable anti-inflammatory effect at 8mg/kg.
  • SZY1406 2mg/kg can obtain strong anti-inflammatory effect 5h after administration.
  • SZY1406 is an anti-inflammatory and analgesic non-steroidal anti-inflammatory drug.
  • the carrageenan inflammation model used in the experiment is to induce the inflammation of the carrageenan in the animal to cause inflammation or a certain stage of cellular tissue reaction. It can be seen from the experiment that the injection of carrageenan can cause obvious inflammatory reaction in the rat toe. After the intervention of the test substance, the ibuprofen suspension can obtain stable anti-inflammatory effect at 8 mg/kg, SZY1406
  • the swelling rate of the toe in the dose group was reduced at different levels at 1h, 2h, 3h and 4h after administration. 2mg/kg could exert a good anti-inflammatory effect, and the toe swelling of the rat was 5h after administration. The rate is significantly reduced, showing a strong anti-inflammatory effect, suggesting that the anti-inflammatory effect of SZY1406 takes a long time, and the anti-inflammatory effect is stronger than that of ibuprofen.
  • mice Female Kunming mice weighing 20-22 g were used. First, the pain sensitivity screening was performed. The mice were placed on a hot plate at 55.0 °C ⁇ 0.5 °C. The time experienced by the hind paws of the mice was used as the threshold of pain response, and the jumpers were removed and less than 5 s or more than 30 s. None of the responders were screened for 60 pain-sensitive mice, which were randomly divided into five groups according to body weight, with 12 rats in each group. Experiments were performed using SZY1406.
  • SZY1406 low, medium and high dose groups SZY1406 doses of 4, 12, 36mg / kg body weight
  • positive control group ibuprofen, dose of 240mg / kg body weight
  • the solution is prepared as a suspension.
  • the mice in each test group were intragastrically administered with the corresponding drugs, and the blank control group was given an equal volume of physiological saline.
  • the hairs of the mice were removed from the ankle joints of the hind paws with a depilatory agent and dried.
  • the pre-dose pain response threshold was determined in the same manner for each mouse, and then the pain response threshold after each rat administration was measured 1 h after each test group, and the mouse was immediately removed from the hot plate after the hind paw.
  • the threshold of the pain response was measured again 2 h and 3 h after the administration, and the threshold of the pain response between the groups was subjected to t test to evaluate the analgesic effect.
  • the results of the test are shown in Table 1 and Figure 1. The results show that the thresholds of the pain response of the hot plate method before the administration of the mice in each test group are similar. After the administration, the mice in each dose group of SZY1406 are licked at 1h, 2h, 3h.
  • the low, medium, and high dose groups represent the SZY1406 low, medium, and high dose groups, respectively.
  • Self-made rat toe volume measuring instrument Take 2 ml, 20 ml syringes, 1 three-way piston, 1 pipette, 1 infusion tube, and install according to Figure 2. At the top of the 20ml syringe housing, use a black line to circumscribe the horizontal mark as a horizontal line. Rotate the tee to make the pipette communicate with the 2ml syringe. Push the syringe to make the liquid level of the pipette at 0 mark. Rotate the tee to make the 2ml syringe and 20ml. The syringe is connected, the liquid in the 2ml syringe is pushed out, and the liquid level in the syringe of 20ml is adjusted to the horizontal line with a straw. Rat toe volume measurement can be performed.
  • mice 50 rats weighing 220-250g were used, and after 12 hours of fasting, the right hind foot toe volume of all animals was measured as the base volume using a self-made rat toe volume tester. After the measurement, the animals were placed according to the toe volume. They were randomly divided into 5 groups, SZY1406 low, medium and high dose groups (SZY1406 doses were 3.2, 9.6, 28.8 mg/kg body weight, respectively), and another vehicle control group and positive control group (ibuprofen, dose 192 mg/kg). Body weight), 10 rats in each group, the test substance was prepared by using 0.5% sodium carboxymethyl cellulose as a suspension.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne un composé ayant un effet anti-inflammatoire. Le composé a une structure de formule (I), et a un effet anti-inflammatoire et analgésique plus puissant que l'ibuprofène.
PCT/CN2016/000142 2016-03-18 2016-03-18 Composé à effet anti-inflammatoire Ceased WO2017156648A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2016/000142 WO2017156648A1 (fr) 2016-03-18 2016-03-18 Composé à effet anti-inflammatoire

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2016/000142 WO2017156648A1 (fr) 2016-03-18 2016-03-18 Composé à effet anti-inflammatoire

Publications (1)

Publication Number Publication Date
WO2017156648A1 true WO2017156648A1 (fr) 2017-09-21

Family

ID=59850057

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2016/000142 Ceased WO2017156648A1 (fr) 2016-03-18 2016-03-18 Composé à effet anti-inflammatoire

Country Status (1)

Country Link
WO (1) WO2017156648A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106279353A (zh) * 2016-03-18 2017-01-04 广州诺威生物技术有限公司 一种用于抗炎的化合物

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007012838A2 (fr) * 2005-07-27 2007-02-01 The University Of Manchester Systeme d'administration de medicament
CN1944378A (zh) * 2006-10-23 2007-04-11 广东中科药物研究有限公司 一种联苯乙酸氨丁三醇盐及其制备方法
CN1962614A (zh) * 2006-11-30 2007-05-16 广东中科药物研究有限公司 联苯乙酸对乙酰氨基酚酯及其制备方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007012838A2 (fr) * 2005-07-27 2007-02-01 The University Of Manchester Systeme d'administration de medicament
CN1944378A (zh) * 2006-10-23 2007-04-11 广东中科药物研究有限公司 一种联苯乙酸氨丁三醇盐及其制备方法
CN1962614A (zh) * 2006-11-30 2007-05-16 广东中科药物研究有限公司 联苯乙酸对乙酰氨基酚酯及其制备方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106279353A (zh) * 2016-03-18 2017-01-04 广州诺威生物技术有限公司 一种用于抗炎的化合物

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