CN115707461A - Application of DCPIB in preparing analgesic - Google Patents
Application of DCPIB in preparing analgesic Download PDFInfo
- Publication number
- CN115707461A CN115707461A CN202110955333.XA CN202110955333A CN115707461A CN 115707461 A CN115707461 A CN 115707461A CN 202110955333 A CN202110955333 A CN 202110955333A CN 115707461 A CN115707461 A CN 115707461A
- Authority
- CN
- China
- Prior art keywords
- pain
- dcib
- mechanical
- mice
- analgesic
- 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.)
- Granted
Links
- 230000000202 analgesic effect Effects 0.000 title claims abstract description 12
- 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 description 17
- WESJNFANGQJVKA-UHFFFAOYSA-M sodium;2,3-dichloro-2-methylpropanoate Chemical compound [Na+].ClCC(Cl)(C)C([O-])=O WESJNFANGQJVKA-UHFFFAOYSA-M 0.000 claims abstract description 41
- 206010065390 Inflammatory pain Diseases 0.000 claims abstract description 22
- 208000002193 Pain Diseases 0.000 claims abstract description 19
- 230000036407 pain Effects 0.000 claims abstract description 19
- 229940035676 analgesics Drugs 0.000 claims abstract description 15
- 239000000730 antalgic agent Substances 0.000 claims abstract description 15
- 239000003814 drug Substances 0.000 claims abstract description 13
- 230000008534 mechanical pain sensitivity Effects 0.000 claims abstract description 10
- 230000008536 thermal pain sensitivity Effects 0.000 claims abstract description 8
- 230000002981 neuropathic effect Effects 0.000 claims abstract description 7
- 208000004454 Hyperalgesia Diseases 0.000 claims description 23
- 230000036592 analgesia Effects 0.000 claims description 6
- 208000035154 Hyperesthesia Diseases 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000007924 injection Substances 0.000 abstract description 15
- 238000002347 injection Methods 0.000 abstract description 15
- 238000007913 intrathecal administration Methods 0.000 abstract description 10
- 208000004296 neuralgia Diseases 0.000 abstract description 10
- 208000021722 neuropathic pain Diseases 0.000 abstract description 10
- 238000007912 intraperitoneal administration Methods 0.000 abstract description 2
- 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 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- 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
- 231100000673 dose–response relationship Toxicity 0.000 description 15
- 239000000243 solution Substances 0.000 description 13
- 210000002683 foot Anatomy 0.000 description 12
- 238000011740 C57BL/6 mouse Methods 0.000 description 10
- 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
- 230000009467 reduction Effects 0.000 description 10
- 102000004877 Insulin Human genes 0.000 description 8
- 108090001061 Insulin Proteins 0.000 description 8
- 210000000683 abdominal cavity Anatomy 0.000 description 8
- 229940125396 insulin Drugs 0.000 description 8
- 210000003497 sciatic nerve Anatomy 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000010172 mouse model Methods 0.000 description 6
- 239000002504 physiological saline solution Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 5
- 210000000548 hind-foot Anatomy 0.000 description 5
- 239000007928 intraperitoneal injection Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 3
- 210000001015 abdomen Anatomy 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000020341 sensory perception of pain Effects 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
- 102100023204 Potassium channel subfamily K member 2 Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000008602 contraction Effects 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
- 108010083945 potassium channel protein TREK-1 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
- 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
- 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
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000036982 action potential Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000000274 adsorptive effect Effects 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 210000002072 atrial myocyte Anatomy 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000338 in vitro Methods 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
- 230000003040 nociceptive effect Effects 0.000 description 1
- 230000008533 pain sensitivity Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a new application of a DCIB medicament. The new application of the DCIB provided by the invention is the application of the DCIB in preparing analgesic drugs. The analgesic drug can relieve thermal and/or mechanical pain sensitivity caused by inflammatory pain; it can also relieve heat and/or mechanical pain caused by neuropathological pain. Pharmacodynamic tests prove that the intraperitoneal and intrathecal injection of the DCIB can relieve thermal pain sensitivity and mechanical pain sensitivity of inflammatory pain and neuropathic pain models, thereby exerting an analgesic effect.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to application of DCIB in preparation of analgesic medicines.
Background
DCPIB having a chemical formula of C 22 H 28 Cl 2 O 4 Molecular weight 427.37, cas No.: 82749-70-0, the structural formula is shown below, it is white solid, the solubility in ethanol can reach 100mM.
DCPIB is a volume-regulating anion channel (VRAC) blocker that blocks volume-regulating chloride current in various cardiovascular tissues. Glucose-stimulated insulin secretion can be inhibited by inhibiting volume-sensitive anion channels on beta cells and indirectly activating potassium channels. Reversal of swelling in atrial myocytes resulted in a reduction in action potential duration, and inhibition of astrocyte swelling in vitro. Meanwhile, DCIB can also activate TREK1 and TRAAK potassium ion channels and inhibit TREK, TASK1 and TASK3 potassium ion channels.
At present, no relevant report of DCIB in the aspect of analgesia exists.
Disclosure of Invention
The invention aims to provide a new application of DCIB.
The new application of the DCIB provided by the invention is the application of the DCIB in preparing analgesic drugs.
Further, the analgesic drug can alleviate thermal and/or mechanical hyperalgesia caused by inflammatory pain.
The analgesic drug can also relieve thermal and/or mechanical hyperalgesia caused by neuropathological pain.
The DCPIB, its CAS number: 82749-70-0, of the formula:
it is a further object of the present invention to provide the use of DCPIB4 for analgesia.
Further, the analgesia may refer to the reduction of thermal and/or mechanical hyperalgesia caused by inflammatory pain.
The analgesia may also refer to the relief of thermal and/or mechanical hyperalgesia caused by neuropathological pain.
The invention also provides an analgesic drug.
The active component of the analgesic drug comprises DCIB.
In the analgesic drug, the DCPIB can be used as one of the effective components and can also be used as the only effective component.
When the medicine is prepared, a carrier material can be added.
Such vectors include, but are not limited to: diluents, suspensions, buffers, granules, emulsions, excipients, encapsulating agents, sprays, adhesives, fillers, disintegrants, wetting agents, transdermal absorbents, absorption enhancers, surfactants, flavoring agents, colorants, or adsorptive carriers.
The above drugs can be prepared into injections, tablets, capsules, solutions and the like according to the conventional methods known to those skilled in the art.
Pharmacodynamic tests prove that the DCIB injected into the abdominal cavity and the intrathecal cavity can relieve thermal pain sensitivity and mechanical pain sensitivity of models of inflammatory pain and neuropathic pain, thereby playing the role of relieving pain. Indicating that the DCPIB can be used for preparing analgesic drugs.
Drawings
FIG. 1 is a dose-dependent reduction of inflammatory pain in mice model mice with abdominal injection of DCIB in example 1;
FIG. 2 is a dose-dependent reduction of inflammatory pain in example 2 of abdominal cavity injection of DCIB model mice mechanociceptive pain;
FIG. 3 is a graph of dose-dependent reduction of inflammatory pain in mice model mice injected intrathecally with DCIB (A) and mechanical pain (B) from example 3;
FIG. 4 is a dose-dependent reduction of neuropathic pain model mice with DCIB injected intraperitoneally in example 4 for thermal (A) and mechanical (B) pain sensitivity;
FIG. 5 is a graph of the dose-dependent reduction of neuropathic pain in mice injected intrathecally with DCIB in example 5 showing thermal (A) and mechanical (B) pain.
Detailed Description
The present invention will be further illustrated with reference to the following examples, but the present invention is not limited to the following examples. The method is a conventional method unless otherwise specified. The starting materials are commercially available from the open literature unless otherwise specified.
Example 1 intraperitoneal injection of DCIB dose-dependent reduction of inflammatory pain in mice as model of thermal pain
The experimental method comprises the following steps: a total of 48 6-8 week-old C57BL/6 mice were used and randomized into 6 groups of 8 mice each.
Mice were anesthetized with isoflurane, and then 20. Mu.l of Complete Freund's Adjuvant (CFA) was subcutaneously injected into the left side of the sole of the mouse using an insulin syringe to prepare a chronic inflammatory pain model (CFA group), and the control group (Sham group) was injected with the same volume of physiological saline in the same manner.
Three kinds of DCIB solutions with concentrations of 0.3mg/ml, 1mg/ml and 3mg/ml are prepared, and the solvents are 4% of dimethyl sulfoxide (DMSO) and 96% of normal saline. When the medicine is administrated in the abdominal cavity, 0.01ml of the DCIB solution with different concentrations is extracted so as to meet the requirement that the final administration dose is 3, 10 or 30mg/kg of DCIB. Mice were anesthetized with isoflurane and drug or solvent control was injected into the lower abdomen of the mice with an insulin syringe. Hot nociception was indicated by measuring the Paw Withdrawal Latencies (PWL) at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, and 24h after administration with a plantar thermalgometer (Hargreaves method). The shorter the paw withdrawal latency, the more severe the thermal hyperalgesia.
The experimental results are as follows:
the injection of DCIB into the abdominal cavity can reduce the thermal pain sensitivity of an inflammatory pain model mouse in a dose-dependent manner. The inflammation pain model is constructed by injecting Complete Freund's Adjuvant (CFA) into the left side of the sole of the foot of the C57BL/6 mouse at 6-8 weeks. At 3 days in the CFA model, 3, 10 and 30mg/kg doses of DCPIB were administered by intraperitoneal injection, and it was found that the mice had relief of the left hind paw thermal nociception at 1.5 hours post-dose, and reached a peak analgesic effect at 6 hours post-dose, with the response threshold returning to pre-dose levels at 12 hours post-dose, with the results shown in figure 1.
Example 2 intraperitoneal injection of DCIB dose-dependent model mice with reduced inflammatory pain mechanical pain sensitivity
The experimental method comprises the following steps: a total of 48 6-8 week-old C57BL/6 mice were used and randomized into 6 groups of 8 mice each.
Mice were anesthetized with isoflurane, and then 20 μ l of Complete Freund's Adjuvant (CFA) was subcutaneously injected into the left side of the sole of the mouse using 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.
Three concentrations of 0.3mg/ml, 1mg/ml and 3mg/ml DCIB solutions were prepared, and the solvents were 4% dimethyl sulfoxide (DMSO) and 96% physiological saline. When the medicine is administrated in the abdominal cavity, 0.01ml of the DCIB solution with different concentrations is extracted so as to meet the requirement that the final administration dose is 3, 10 or 30mg/kg of DCIB. Mice were anesthetized with isoflurane and then the drug or solvent control was injected into the lower abdomen of the mice with an insulin syringe. Mechanical Paw Withdrawal Thresholds (PWTs) were determined at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, 24h after administration using Von Frey filaments. The lower the mechanical paw withdrawal threshold, the more sensitive the mechanical shock induced pain.
The experimental results are as follows:
the injection of DCIB into the abdominal cavity can reduce the mechanical pain sensitivity of an inflammation pain model mouse in a dose-dependent manner. The inflammation pain model is constructed by injecting Complete Freund's Adjuvant (CFA) into the left side of the sole of the foot of the C57BL/6 mouse at 6-8 weeks. At 3 days in the CFA model, 3, 10 and 30mg/kg doses of DCPIB were administered by intraperitoneal injection, and it was found that the mice had relief of mechanical nociception in the left hind paw at 1.5 hours after administration, and that the analgesic effect peaked at 6 hours after administration, and that the response threshold returned to the pre-administration level at 12 hours after administration, and the results are shown in fig. 2.
Example 3 dose-dependent reduction of inflammatory pain by intrathecal injection of DCIB Hot and mechanical allodynia in mice as model of inflammatory pain
The experimental method comprises the following steps: a total of 32 6-8 week-old C57BL/6 mice were used and randomized into 4 groups of 8 mice each.
Mice were anesthetized with isoflurane, and then 20. Mu.l of Complete Freund's Adjuvant (CFA) was subcutaneously injected into the left side of the sole of the mouse using an insulin syringe to prepare a chronic inflammatory pain model (CFA group), and the control group (Sham group) was injected with the same volume of physiological saline in the same manner.
DCIB solutions at 50. Mu.M and 100. Mu.M were prepared in 0.07% Dimethylsulfoxide (DMSO) and 99.93% physiological saline. Mice were anesthetized with isoflurane, 10 μ l of varying concentrations of DCPIB solution or solvent control were withdrawn using an insulin syringe, and the syringe was inserted into the thoracic 13-lumbar 1 segment vertebrae of mice for intrathecal injection. Measuring the foot contraction latency (PWL) of 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h and 24h after administration by using a plantar thermal pain measuring instrument (Hargreaves method); mechanical Paw Withdrawal Thresholds (PWTs) were determined at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, 24h after administration using Von Frey filaments.
The experimental results are as follows:
intrathecal injection of DCIB can reduce the thermal and mechanical allodynia of mice model of inflammatory pain in a dose-dependent manner. A Complete Freund's Adjuvant (CFA) is injected subcutaneously on the left side of the sole of the left side of a C57BL/6 mouse at 6-8 weeks to construct an inflammatory pain model. At day 3 in the CFA model, 50 and 100 μ M doses of DCPIB were administered by intrathecal injection and were found to produce relief in the left hind paw thermal (a) and mechanical (B) hyperalgesia in mice at 0.5 hours post-dose and peak analgesia at 3 hours post-dose with a response threshold returning to pre-dose levels at 24 hours post-dose, as shown in figure 3.
Example 4 dose-dependent relief of neuropathic pain in mice injected with DCIB
The experimental method comprises the following steps: a total of 48 6-8 week-old C57BL/6 mice were used and randomized into 6 groups of 8 mice each.
In preparing a Chronic ligature injury (CCI) model of the sciatic nerve, mice were anesthetized with isoflurane and the left sciatic nerve trunk was exposed. Sequentially performing loose ligation on the sciatic nerve trunk for 4 times from the proximal end to the distal end by using a No. 6 surgical silk thread, wherein the ligation interval is 1mm, and suturing an incision by using a No. 4 surgical silk thread after completing the ligation.
Three kinds of DCIB solutions with concentrations of 0.3mg/ml, 1mg/ml and 3mg/ml are prepared, and the solvents are 4% of dimethyl sulfoxide (DMSO) and 96% of normal saline. When the medicine is administrated in the abdominal cavity, 0.01ml of the DCIB solution with different concentrations is extracted so as to meet the requirement that the final administration dose is 3, 10 or 30mg/kg of DCIB. Mice were anesthetized with isoflurane and then the drug or solvent control was injected into the lower abdomen of the mice with an insulin syringe. Measuring the foot contraction latency (PWL) at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h and 24h after administration by using a plantar thermalgometer (Hargreaves method); mechanical Paw Withdrawal Thresholds (PWTs) were determined at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, 24h after administration using Von Frey filaments.
The experimental results are as follows:
the injection of DCIB into the abdominal cavity can reduce the thermal pain sensitivity and the mechanical pain sensitivity of a neuropathological pain model mouse in a dose-dependent manner. A neuropathic pain model was constructed using chronic ligature injury (CCI) of the sciatic nerve on the left side of C57BL/6 mice at 6-8 weeks. At 14 days in the CCI model, 3, 10 and 30mg/kg doses of DCPIB were administered by intraperitoneal injection, and it was found that there was relief in the left hind paw thermal and mechanical hyperalgesia in mice 1.5 hours after dosing, and that the analgesic effect peaked 3-6 hours after dosing, with the response threshold returning to pre-dose levels 24 hours after dosing, and the results are shown in fig. 4.
Example 5 dose-dependent reduction of neuropathic pain in mice injected intrathecally with DCIB
The experimental method comprises the following steps: a total of 40 6-8 week-old C57BL/6 mice were used and randomized into 5 groups of 8 mice each.
In preparing a Chronic ligature injury (CCI) model of the sciatic nerve, mice were anesthetized with isoflurane and the left sciatic nerve trunk was exposed. Sequentially performing loose ligation on the sciatic nerve trunk for 4 times from the proximal end to the distal end by using a No. 6 surgical silk thread, wherein the ligation interval is 1mm, and suturing an incision by using a No. 4 surgical silk thread after completing the ligation.
DCIB solutions at 50. Mu.M and 100. Mu.M were prepared in 0.07% Dimethylsulfoxide (DMSO) and 99.93% physiological saline. Mice were anesthetized with isoflurane, 10 μ l of varying concentrations of DCPIB solution or solvent control were withdrawn using an insulin syringe, and the syringe was inserted into the thoracic 13-lumbar 1 segment vertebrae of mice for intrathecal injection. Measuring the Paw with hot plate instrument at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h and 24h after administration (PWL); mechanical Paw Withdrawal Thresholds (PWTs) were measured at 0h, 0.5h, 1.5h, 3h, 6h, 9h, 12h, and 24h after administration using Von Frey filaments.
The experimental results are as follows:
intrathecal injection of DCIB can reduce the hot and mechanical pain sensitivity of the neuropathic pain model mouse in a dose-dependent manner. A neuropathic pain model was constructed using chronic ligature injury (CCI) of the sciatic nerve on the left side of C57BL/6 mice at 6-8 weeks. At day 14 in the CCI model, 50 and 100 μ M doses of DCPIB were administered by intrathecal injection and it was found that there was relief in the left hind paw thermal (a) and mechanical (B) nociceptive effects in mice from 0.5 to 1.5 hours post-dose, and that the analgesic effect peaked 3 hours post-dose and the response threshold returned to pre-dose levels 12 to 24 hours post-dose, with the results shown in fig. 5.
In conclusion, the intraperitoneal and intrathecal injection of DCPIB can relieve thermal and mechanical pain sensitivity of inflammatory pain and neuropathic pain models, thereby exerting an analgesic effect.
The above examples are only intended to illustrate the technical solution of the present invention and not to limit it, and although the present invention has been described in detail with reference to the specific embodiments, it will be apparent to those skilled in the art that modifications or improvements can be made to the technical solution of the present invention. Therefore, it is within the scope of the present invention to make modifications or improvements without departing from the scope of the present invention.
Claims (9)
1. Application of DCIB shown in formula I in preparing analgesic medicine;
2. use according to claim 1, characterized in that: the analgesic drug can relieve thermal and/or mechanical hyperalgesia caused by inflammatory pain.
3. Use according to claim 1, characterized in that: the analgesic drug can relieve heat hyperalgesia and/or mechanical hyperalgesia caused by neuropathological pain.
4. Application of DCIB shown in formula I in relieving pain;
5. use according to claim 4, characterized in that: the analgesic refers to relieving thermal and/or mechanical pain sensitivity caused by inflammatory pain.
6. Use according to claim 4, characterized in that: the analgesia refers to relieving thermal pain sensitivity and/or mechanical pain sensitivity caused by neuropathological pain.
7. An analgesic medicine contains DCIB represented by formula I as active ingredient;
8. the analgesic drug of claim 7, wherein: the analgesic drug can relieve thermal and/or mechanical hyperalgesia caused by inflammatory pain.
9. The analgesic drug of claim 7, wherein: the analgesic drug can relieve heat hyperalgesia and/or mechanical hyperalgesia caused by neuropathological pain.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110955333.XA CN115707461B (en) | 2021-08-19 | 2021-08-19 | Use of DCPIB in preparing analgesic |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110955333.XA CN115707461B (en) | 2021-08-19 | 2021-08-19 | Use of DCPIB in preparing analgesic |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115707461A true CN115707461A (en) | 2023-02-21 |
| CN115707461B CN115707461B (en) | 2024-05-10 |
Family
ID=85212613
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110955333.XA Active CN115707461B (en) | 2021-08-19 | 2021-08-19 | Use of DCPIB in preparing analgesic |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115707461B (en) |
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 |
|---|
| 罗启超等: "TREK-1通道分子动力学行为研究及其配体的发现", CNKI博士学位论文全文库, no. 1, pages 9 - 11 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115707461B (en) | 2024-05-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2807135C (en) | Combinations of beta - 3 adrenergic receptor agonists and muscarinic receptor antagonists for treating overactive bladder | |
| Yu et al. | The development of local anesthetics and their applications beyond anesthesia | |
| AU2019382168A1 (en) | A method for treating pulmonary arterial hypertension and associated pulmonary arterial hypertension | |
| AU2019310474C1 (en) | Pharmaceutical composition for preventing or treating nonalcoholic steatohepatitis | |
| CN115707461A (en) | Application of DCPIB in preparing analgesic | |
| US20110183926A1 (en) | Treatment using continuous low dose application of sugar analogs | |
| Rees et al. | Drugs in anesthetic practice | |
| CN115068414A (en) | Ropivacaine long-acting solution preparation for injection and preparation method thereof | |
| Frishman et al. | Ultra-short-acting β-adrenergic blockers | |
| KR20120089444A (en) | Treating critically ill patients with intravenous ibuprofen | |
| Scott | Postoperative pain relief | |
| WO2009157010A1 (en) | An intravenous drug delivery system | |
| CZ389498A3 (en) | Local anaesthetic with buffer composition for preventing rise of inflammation | |
| JPS59144717A (en) | Analgesic | |
| WO2013115083A1 (en) | Therapeutic agent for fibromyalgia which comprises donepezil | |
| US20160287711A1 (en) | Formulation Solution Adapted to Prolong Plasma Times of Drugs in Mammals Including Humans | |
| CN103599102A (en) | Application of Nitrosporeusines A in drugs for treating acute renal failure | |
| CN103251637A (en) | Application of Polyflavanostilbene A in preparing medicine for treating acute renal failure | |
| EP4188322A1 (en) | Combination of medications in a parenteral dosage form for long-term anaesthesia | |
| CN118078808A (en) | Use of Tulipalin A in the preparation of a medicament for the treatment of inflammatory diseases and pharmaceutical formulations | |
| Tarkase | Spinal Anaesthesia With 0.5% Hyperbaric Ropivacaine and 0.5% Hyperbaric Bupivacaine: A Comparative Study | |
| US8895623B2 (en) | Intrathecal or epidural administration of 3-[(1S,25)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol | |
| JPS6345371B2 (en) | ||
| WO2020025986A1 (en) | Injectable combination of diclofenac sodium and thiocolchicoside | |
| Memtsoudis et al. | Glycopyrrolate as an alternative to vasopressor infusion for hypotension after carotid endarterectomy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |