CN115707461B - Use of DCPIB in preparing analgesic - Google Patents
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- CN115707461B CN115707461B CN202110955333.XA CN202110955333A CN115707461B CN 115707461 B CN115707461 B CN 115707461B CN 202110955333 A CN202110955333 A CN 202110955333A CN 115707461 B CN115707461 B CN 115707461B
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- KHKGTPJPBOQECW-UHFFFAOYSA-N 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-1-oxo-3H-inden-5-yl)oxy]butanoic acid Chemical compound C1C2=CC(OCCCC(O)=O)=C(Cl)C(Cl)=C2C(=O)C1(CCCC)C1CCCC1 KHKGTPJPBOQECW-UHFFFAOYSA-N 0.000 title claims abstract description 55
- 230000000202 analgesic effect Effects 0.000 title claims abstract description 22
- 208000002193 Pain Diseases 0.000 claims abstract description 52
- 230000036407 pain Effects 0.000 claims abstract description 52
- 206010065390 Inflammatory pain Diseases 0.000 claims abstract description 19
- 208000004296 neuralgia Diseases 0.000 claims abstract description 15
- 208000021722 neuropathic pain Diseases 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims description 5
- 229940035676 analgesics Drugs 0.000 claims description 3
- 239000000730 antalgic agent Substances 0.000 claims description 3
- 239000007924 injection Substances 0.000 abstract description 19
- 238000002347 injection Methods 0.000 abstract description 19
- 238000007913 intrathecal administration Methods 0.000 abstract description 13
- 239000003814 drug Substances 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 8
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- 230000003285 pharmacodynamic effect Effects 0.000 abstract description 2
- 238000012360 testing method Methods 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 40
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
- 231100000673 dose–response relationship Toxicity 0.000 description 16
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 16
- 210000002683 foot Anatomy 0.000 description 14
- 239000000243 solution Substances 0.000 description 13
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 10
- 229960002725 isoflurane Drugs 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 230000001684 chronic effect Effects 0.000 description 9
- 102000004877 Insulin Human genes 0.000 description 8
- 108090001061 Insulin Proteins 0.000 description 8
- 229940125396 insulin Drugs 0.000 description 8
- 238000010172 mouse model Methods 0.000 description 8
- 239000002504 physiological saline solution Substances 0.000 description 8
- 210000003497 sciatic nerve Anatomy 0.000 description 8
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 239000007928 intraperitoneal injection Substances 0.000 description 6
- 238000011740 C57BL/6 mouse Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 210000000548 hind-foot Anatomy 0.000 description 5
- 210000000683 abdominal cavity Anatomy 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 210000001015 abdomen Anatomy 0.000 description 3
- 230000003187 abdominal effect Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000036592 analgesia Effects 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 108091006515 Anion channels Proteins 0.000 description 2
- 102000037829 Anion channels Human genes 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 102000004257 Potassium Channel Human genes 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 108020001213 potassium channel Proteins 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 210000000115 thoracic cavity Anatomy 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 101000974733 Homo sapiens Potassium channel subfamily K member 18 Proteins 0.000 description 1
- 101001049835 Homo sapiens Potassium channel subfamily K member 3 Proteins 0.000 description 1
- 101001050878 Homo sapiens Potassium channel subfamily K member 9 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100022756 Potassium channel subfamily K member 18 Human genes 0.000 description 1
- 102100023204 Potassium channel subfamily K member 2 Human genes 0.000 description 1
- 102100023207 Potassium channel subfamily K member 3 Human genes 0.000 description 1
- 102100023205 Potassium channel subfamily K member 4 Human genes 0.000 description 1
- 101710185483 Potassium channel subfamily K member 4 Proteins 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
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- 210000001130 astrocyte Anatomy 0.000 description 1
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- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
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- 239000012876 carrier material Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- JRONPIZRZBBOBR-UHFFFAOYSA-N dichlorine tetroxide Inorganic materials ClOCl(=O)(=O)=O JRONPIZRZBBOBR-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
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- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 108010083945 potassium channel protein TREK-1 Proteins 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a new application of DCPIB in medicines. The novel application of DCPIB in preparing analgesic is provided. The analgesic can reduce thermal pain and/or mechanical pain caused by inflammatory pain; can also relieve thermal pain and/or mechanical pain caused by neuropathic pain. Pharmacodynamic tests prove that the intraperitoneal and intrathecal injection DCPIB can relieve the thermal pain and mechanical pain of inflammatory pain and neuropathic pain models, thereby playing an analgesic role.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to an application of DCPIB in preparing analgesic medicines.
Background
DCPIB, chemical formula C 22H28Cl2O4, molecular weight 427.37, CAS number: 82749-70-0, which is a white solid with a solubility of 100mM in ethanol, has the following structural formula.
DCPIB are volume-regulating anion channel (VRAC) blockers that block volume-regulating chloride current in various cardiovascular tissues. Glucose-stimulated insulin secretion can be inhibited by inhibiting volume-sensitive anion channels and indirectly activating potassium channels on beta cells. Reversal of swelling in atrial myocytes results in reduced duration of action potential and inhibition of astrocyte swelling in vitro. Simultaneously DCPIB can activate TREK1 and TRAAK potassium ion channels and inhibit TRESK, TASK1 and TASK3 potassium ion channels.
There is no report on the analgesic effect of DCPIB.
Disclosure of Invention
The invention aims to provide a new application of DCPIB in medicines.
The novel application of DCPIB in preparing analgesic is provided.
Further, the analgesic can reduce thermal and/or mechanical pain caused by inflammatory pain.
The analgesic can also relieve thermal pain and/or mechanical pain caused by neuropathic pain.
DCPIB, its CAS number: 82749-70-0 has the following structural formula:
it is a further object of the present invention to provide the use of DCPIB4 in analgesia.
Further, the analgesia may refer to the alleviation of thermal and/or mechanical pain caused by inflammatory pain.
The analgesia may also refer to relief of thermal and/or mechanical pain from neuropathic pain.
The invention also provides an analgesic.
The active ingredients of the analgesic comprise DCPIB.
DCPIB in the analgesic can be used as one of the active ingredients or the only active ingredient.
Carrier materials may also be added in the preparation of the medicament.
Such carriers include, but are not limited to: diluents, suspending agents, buffers, granules, emulsions, excipients, encapsulating agents, sprays, binders, fillers, disintegrants, wetting agents, transdermal absorbents, absorption enhancers, surfactants, flavoring agents, colorants, or adsorption carriers.
The above-mentioned medicines can be made into injection, tablet, capsule, solution and other dosage forms according to conventional methods known to those skilled in the art.
The pharmacodynamic test proves that the abdominal cavity and intrathecal injection DCPIB can relieve the thermal pain and mechanical pain of inflammatory pain and neuropathic pain models, thereby playing an analgesic role. The DCPIB can be used for preparing analgesic drugs.
Drawings
FIG. 1 is a dose-dependent pain relief model of pain due to inflammation in mice injected DCPIB into the abdominal cavity in example 1;
FIG. 2 is a dose-dependent pain relief model of abdominal cavity injection DCPIB in example 2 mechanical pain in mice;
FIG. 3 shows dose-dependent pain relief in mice models of inflammatory pain (A) and mechanical pain (B) for intrathecal injection DCPIB of example 3;
FIG. 4 shows dose-dependent relief of neuropathic pain model mice thermal pain (A) and mechanical pain (B) by abdominal cavity injection DCPIB in example 4;
Fig. 5 shows dose-dependent relief of neuropathic pain model mice with intrathecal injection DCPIB of example 5 for thermal pain (a) and mechanical pain (B).
Detailed Description
The invention will be further illustrated with reference to the following specific examples, but the invention is not limited to the following examples. The methods are conventional methods unless otherwise specified. The starting materials are available from published commercial sources unless otherwise specified.
Example 1, intraperitoneal injection DCPIB dose-dependent pain reduction model mice with inflammatory pain reduction
The experimental method comprises the following steps: a total of 48C 57BL/6 mice of 6-8 weeks of age were used, randomly divided into 6 groups of 8 mice each.
Mice were anesthetized with isoflurane, and 20 μl of Complete Freund's Adjuvant (CFA) was injected subcutaneously into the left plantar side of the mice with an insulin syringe, to prepare a chronic inflammatory pain model (CFA group), and a control group (Sham group) was injected with the same volume of physiological saline in the same manner.
DCPIB solutions of three concentrations of 0.3mg/ml, 1mg/ml and 3mg/ml were prepared, and the solvents were 4% dimethyl sulfoxide (Dimethylsulfoxide, DMSO) and 96% physiological saline. 0.01ml was withdrawn from DCPIB solutions at different concentrations for intraperitoneal administration to meet DCPIB at a final dose of 3, 10 or 30 mg/kg. Mice were anesthetized with isoflurane and then a drug or solvent control was injected into the lower abdomen of the mice with an insulin syringe. The foot withdrawal latency (PAW WITHDRAWING LATENCY, PWL) of 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, 24h after administration was measured with a plantar thermal pain meter (Hargreaves method) and indicated thermal pain. The shorter the incubation period for the foot contraction, the more severe the thermal pain sensitization.
Experimental results:
Abdominal injection DCPIB can reduce the thermal pain of mice with inflammatory pain models in a dose-dependent manner. The inflammatory pain model was constructed using 6-8 week C57BL/6 mice left plantar subcutaneous injection of Complete Freund's Adjuvant (CFA). On day 3 of the CFA model, DCPIB doses of 3, 10 and 30mg/kg were administered by intraperitoneal injection, and it was found that relief of hind paw thermal pain occurred in the left hand paw of the mice 1.5 hours after the administration, and the analgesic effect reached a peak at 6 hours after the administration, and the response threshold was returned to the pre-administration level at 12 hours after the administration, and the results are shown in fig. 1.
Example 2, intraperitoneal injection DCPIB dose-dependent pain reduction model mice with mechanical pain
The experimental method comprises the following steps: a total of 48C 57BL/6 mice of 6-8 weeks of age were used, randomly divided into 6 groups of 8 mice each.
Mice were anesthetized with isoflurane, and 20 μl of Complete Freund's Adjuvant (CFA) was injected subcutaneously into the left plantar side of the mice with an insulin syringe, to prepare a chronic inflammatory pain model (CFA group), and a control group (Sham group) was injected with the same volume of physiological saline in the same manner.
DCPIB solutions of three concentrations of 0.3mg/ml, 1mg/ml and 3mg/ml were prepared, and the solvents were 4% dimethyl sulfoxide (Dimethylsulfoxide, DMSO) and 96% physiological saline. 0.01ml was withdrawn from DCPIB solutions at different concentrations for intraperitoneal administration to meet DCPIB at a final dose of 3, 10 or 30 mg/kg. Mice were anesthetized with isoflurane and then a drug or solvent control was injected into the lower abdomen of the mice with an insulin syringe. Mechanical foot-constrictive thresholds (PAW WITHDRAWAL thresholds, PWTs) at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, 24h post-administration were determined using Von Frey filaments. The lower the mechanical pinch threshold, the more sensitive the mechanical touch induced pain.
Experimental results:
abdominal injection DCPIB can reduce mechanical pain of mice with inflammatory pain model in a dose-dependent manner. The inflammatory pain model was constructed using 6-8 week C57BL/6 mice left plantar subcutaneous injection of Complete Freund's Adjuvant (CFA). On day 3 of the CFA model, DCPIB at doses of 3, 10 and 30mg/kg were administered by intraperitoneal injection, and it was found that the left hind paw mechanociception in the mice was relieved 1.5 hours after administration, and the analgesic effect reached a peak at 6 hours after administration, and the response threshold at 12 hours after administration was returned to the pre-administration level, and the results are shown in fig. 2.
Example 3 dose-dependent reduction of inflammatory pain model mice thermal and mechanical pain by intrathecal injection DCPIB
The experimental method comprises the following steps: a total of 32C 57BL/6 mice of 6-8 weeks of age were used, randomly divided into 4 groups of 8 mice each.
Mice were anesthetized with isoflurane, and 20 μl of Complete Freund's Adjuvant (CFA) was injected subcutaneously into the left plantar side of the mice with an insulin syringe, to prepare a chronic inflammatory pain model (CFA group), and a control group (Sham group) was injected with the same volume of physiological saline in the same manner.
DCPIB solutions at 50. Mu.M and 100. Mu.M were prepared in a solvent of 0.07% dimethyl sulfoxide (Dimethylsulfoxide, DMSO) and 99.93% physiological saline. Mice were anesthetized with isoflurane, 10 μl of various concentrations DCPIB solution or solvent control was withdrawn using an insulin syringe, and the syringe was inserted into the thoracic 13-lumbar 1 segment vertebrae of the mice for intrathecal injection. Foot withdrawal latency (PAW WITHDRAWING LATENCY, PWL) was measured with a plantar thermal pain detector (Hargreaves method) at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, 24h post-dose; mechanical foot-constrictive thresholds (PAW WITHDRAWAL thresholds, PWTs) at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, 24h post-administration were determined using Von Frey filaments.
Experimental results:
intrathecal injection DCPIB can reduce thermal and mechanical pain in mice with inflammatory pain models in a dose-dependent manner. The inflammatory pain model was constructed using 6-8 week C57BL/6 mice left plantar subcutaneous injection of Complete Freund's Adjuvant (CFA). On day 3 of the CFA model, DCPIB was administered at 50 and 100 μm doses by intrathecal injection, and it was found that relief of hind paw thermal pain (a) and mechanical pain (B) occurred in mice 0.5 hours post-dose, and analgesic effect reached a peak at 3 hours post-dose, with the 24 hour response threshold returning to pre-dose level, results shown in fig. 3.
EXAMPLE 4 Abdominal injection DCPIB dose-dependent relief of neuropathic pain model mice thermal and mechanical pain
The experimental method comprises the following steps: a total of 48C 57BL/6 mice of 6-8 weeks of age were used, randomly divided into 6 groups of 8 mice each.
In the preparation of a model of chronic ligature injury (Chronic constriction injury, CCI) to sciatic nerve, mice were anesthetized with isoflurane and left sciatic nerve trunks were exposed. 4 loose ligatures are sequentially carried out on the sciatic nerve trunk from the proximal end to the distal end by using a No. 6 surgical silk thread, each ligature is 1mm apart, and the incision is sutured by using a No. 4 surgical silk thread after completion.
DCPIB solutions of three concentrations of 0.3mg/ml, 1mg/ml and 3mg/ml were prepared, and the solvents were 4% dimethyl sulfoxide (Dimethylsulfoxide, DMSO) and 96% physiological saline. 0.01ml was withdrawn from DCPIB solutions at different concentrations for intraperitoneal administration to meet DCPIB at a final dose of 3, 10 or 30 mg/kg. Mice were anesthetized with isoflurane and then a drug or solvent control was injected into the lower abdomen of the mice with an insulin syringe. Foot withdrawal latency (PAW WITHDRAWING LATENCY, PWL) was measured with a plantar thermal pain detector (Hargreaves method) at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, 24h post-dose; mechanical foot-constrictive thresholds (PAW WITHDRAWAL thresholds, PWTs) at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, 24h post-administration were determined using Von Frey filaments.
Experimental results:
The intraperitoneal injection DCPIB can relieve the thermal pain and mechanical pain of the mice with the model of neuropathic pain in a dose-dependent manner. A neuropathic pain model was constructed using chronic ligature injury (CCI) of the left sciatic nerve in 6-8 weeks C57BL/6 mice. The CCI model was given DCPIB at doses of 3, 10 and 30mg/kg by intraperitoneal injection on day 14, and it was found that relief of hind paw thermal and mechanical pain occurred in mice 1.5 hours post-dose, and analgesic effect peaked 3-6 hours post-dose, with 24 hour post-dose response threshold back to pre-dose level, and the results are shown in fig. 4.
Example 5 dose-dependent alleviation of neuropathic pain model mice thermal and mechanical pain by intrathecal injection DCPIB
The experimental method comprises the following steps: a total of 40C 57BL/6 mice of 6-8 weeks of age were used, randomly divided into 5 groups of 8 mice each.
In the preparation of a model of chronic ligature injury (Chronic constriction injury, CCI) to sciatic nerve, mice were anesthetized with isoflurane and left sciatic nerve trunks were exposed. 4 loose ligatures are sequentially carried out on the sciatic nerve trunk from the proximal end to the distal end by using a No. 6 surgical silk thread, each ligature is 1mm apart, and the incision is sutured by using a No. 4 surgical silk thread after completion.
DCPIB solutions at 50. Mu.M and 100. Mu.M were prepared in a solvent of 0.07% dimethyl sulfoxide (Dimethylsulfoxide, DMSO) and 99.93% physiological saline. Mice were anesthetized with isoflurane, 10 μl of various concentrations DCPIB solution or solvent control was withdrawn using an insulin syringe, and the syringe was inserted into the thoracic 13-lumbar 1 segment vertebrae of the mice for intrathecal injection. Foot withdrawal latency (PAW WITHDRAWING LATENCY, PWL) was measured with a hotplate apparatus at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, 24h post-administration; mechanical foot-constrictive thresholds (PAW WITHDRAWAL thresholds, PWTs) at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, 24h post-administration were determined using Von Frey filaments.
Experimental results:
Intrathecal injection DCPIB can reduce the thermal and mechanical pain of mice with neuropathic pain models in a dose-dependent manner. A neuropathic pain model was constructed using chronic ligature injury (CCI) of the left sciatic nerve in 6-8 weeks C57BL/6 mice. On day 14 of CCI model, DCPIB was administered at 50 and 100 μm doses by intrathecal injection, and it was found that relief occurred in the left hind paw thermal pain (a) and mechanical pain (B) in mice 0.5-1.5 hours post-dose, and the analgesic effect peaked at 3 hours post-dose, with the response threshold returning to pre-dose levels at 12-24 hours post-dose, as seen in fig. 5.
In summary, intraperitoneal and intrathecal injection DCPIB can alleviate thermal and mechanical pain in inflammatory and neuropathic pain models, thereby exerting analgesic effects.
The above examples are intended to be illustrative of the technical solution of the present invention and not limiting, and although the present invention has been described in detail with reference to specific embodiments, it will be apparent to those skilled in the art that modifications and improvements can be made to the technical solution of the present invention. Accordingly, all such modifications and improvements as do not depart from the scope of the invention are intended to be within the scope of the invention.
Claims (2)
1. The DCPIB shown in the formula I is applied to the preparation of analgesic drugs;
the analgesic can reduce thermal pain and/or mechanical pain caused by inflammatory pain.
2. The DCPIB shown in the formula I is applied to the preparation of analgesic drugs;
The analgesic can relieve thermal pain and/or mechanical pain caused by neuropathic pain.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4465850A (en) * | 1980-09-02 | 1984-08-14 | Merck & Co., Inc. | Treatment of brain injury due to gray matter edema with (indanyloxy) butanoic acids |
| CN113143900A (en) * | 2021-04-19 | 2021-07-23 | 南方医科大学 | Application of ML365 in preparation of medicine for preventing and/or treating NLRP3 inflammasome-related diseases |
-
2021
- 2021-08-19 CN CN202110955333.XA patent/CN115707461B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4465850A (en) * | 1980-09-02 | 1984-08-14 | Merck & Co., Inc. | Treatment of brain injury due to gray matter edema with (indanyloxy) butanoic acids |
| CN113143900A (en) * | 2021-04-19 | 2021-07-23 | 南方医科大学 | Application of ML365 in preparation of medicine for preventing and/or treating NLRP3 inflammasome-related diseases |
Non-Patent Citations (1)
| Title |
|---|
| TREK-1通道分子动力学行为研究及其配体的发现;罗启超等;CNKI博士学位论文全文库(第第1期期);9-11 * |
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