Lipids and lipids compound used as medicines for treating pain and application method of lipids and lipids compound

An application method and compound technology, applied in the direction of drug combination, pharmaceutical formula, antipyretic, etc., can solve problems such as low quality of life, addiction and abuse, social and emotional disorders, etc., to improve efficacy, reduce toxicity, prevent or The effect of drug resistance

Inactive Publication Date: 2019-12-20
崔建国
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Inappropriate pain treatment leads to poor quality of life as well as social and emotional disorders, addiction and abuse

Method used

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  • Lipids and lipids compound used as medicines for treating pain and application method of lipids and lipids compound
  • Lipids and lipids compound used as medicines for treating pain and application method of lipids and lipids compound
  • Lipids and lipids compound used as medicines for treating pain and application method of lipids and lipids compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] Example 1: Electrodes were installed on the eleventh thoracic vertebrae of rats with seltzer neuropathy.

[0082] The cathode (3x2x0.2mm silver sheet) was placed in the dorsal epidural space. The anode (copper sheet with a diameter of 4 mm) is implanted in the subcutaneous tissue of the vertebral body. These wires are threaded subcutaneously to secure the neck skin in microcontact. The SCS electrodes were connected via microcontacts to a GrassS44 stimulator (GrassInstr., Quinsey, MA) with a constant current unit CCU1. The stimulation parameters were set as follows: stimulation frequency 50 Hz, pulse width 0.2 ms, intensity between 0.4 and 1.5 mA, equivalent to 2 / 3 of the intensity required to induce a motor response. In the lower part of the rat's body (these parameters matched as closely as possible those used in clinical practice). Apply SCS for 30 minutes. During SCS, a vonfrey test was performed every 5 minutes to assess the effect of SCS.

[0083] Spinal cord ...

Embodiment 2

[0096] Embodiment 2: Seltzer model and neurobehavioral testing.

[0097] Male Sprague-Dawley rats (250 g) will be subjected to the left sciatic nerve injury procedure as described by Seltzer et al. [Seltzer et al., Pain. 43(2):205-18 (1990)] The 1 / 2-1 / 3 dorsal portion of the nerve will be tightly ligated at the upper mid-thigh level. In a quiet room with daylight-like lighting, animals will acclimatize 3 times for 15 min before data collection. Data will be collected between 9:30 am and 3:30 pm.

[0098] Foot plantar tactile threshold reflex test:

[0099] In terrariums (20 x 20 cm) with a wire mesh bottom, animals were subjected to a test for tactile allodynia, in which innocuous tactile stimuli may induce transient. A series of von-frey filaments ranging from 0.01 g to 30 g (WoodDale, IL) starting at 1 g were applied to the plantar of rats and increased or decreased. If a filament induced a plantar tactile reflex 3 times out of 5 stimuli, this value was recorded as its ...

Embodiment 3

[0110] Example 3: Evaluation of five analgesic lipid molecules (ALMS): eicosapentaenoic acid (EPA), ethyl eicosapentaenoate (EE-EPA), all-cis-7,10,13, 16,19-Docosapentaenoic acid (DPA-7; omega-3 fatty acid), all-cis-4,7,10,13,16-docosapentaenoic acid (DPA-4; omega-6 fatty acids) and 12-hydroxyeicosatetraenoic acid (12-HETE) for the inhibition of neuropathic pain. Administered directly intrathecally in rats with seltzer neuropathy (ligation of the left sciatic nerve in the dorsal 1 / 3 fiber) in one bolus injection. Use 3-6 rats (see Figure 5-9 ) each ALM was tested by assessing the PAW mechano-tactile reflex threshold ((vonFrey fiber test). Thresholds below 8g indicate pain. Pain medications are expected to raise thresholds to normal levels (20g or more in these experiments; 26g is the cutoff value).

[0111] Five ALMs were tested at doses of 3 nM, 30 nM and 300 nM in a volume of 10 μl, which corresponded approximately to 0.01 ng, 0.1 ng and 1 ng, respectively. The time cou...

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Abstract

The invention discloses lipids and lipids compound used as medicines for treating pain and an application method of the lipids and the lipids compound. The lipids and lipids compound comprise the following lipids compositions including eicosapentaenoic acid ethyl ester (EE-EPA), docosapentaenoic acid ethyl ester (EE-DPA), docosahexaenoic acid ethyl ester (EE-DHA), ethyl linoleate (EE-LA), arachidonic acid ethyl ester (EE-AA), 12-hydroxy eicosanoic acid ethyl ester (EE-12-HETE), linoleic acid (LA), docosahexaenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (DPA) and 12-hydroxy eicosanoic acid (12-HETE), wherein the DPA is all-cis type-7,10,13,16,19-docosapentaenoic acid (DPA) and the like as well as combined application of a variety of lipids; medicines are administered in anoptimal dosage amount in intrathecal, epidural or intranasal ways while combined application of the medicines is allowed, and the medicines can be allowed to repeatedly and continuously administered through the ways, and the medicines directly act upon a central nervous system, so that potential side effects of the medicines and side effects of opiates medicines are reduced as much as possible when the pain is suppressed or prevented by adopting the medicines at the same time.

Description

technical field [0001] The invention relates to lipids as medicines, lipid-improved medicines and application methods, in particular to lipids and lipid compounds used as medicines to treat pain and application methods thereof. Background technique [0002] Persistent pain (or chronic pain) affects more than 300 million people each year. Neuropathic pain (NP) caused by trauma, surgery, or other diseases is typically persistent pain. NP is associated with neural pathway mechanisms in multiple lesions. As with many other forms of persistent pain, commonly used therapeutic drugs are often ineffective against NP [Jensen et al., cur.opin.neurol.22(5):467-74 (2009); Vranken et al., Nervous System Medicinal Agents 9 (1): 71-8 (2009)], such as opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, and antidepressants, which often result in multiple side effects, including long-term dependence, addiction, and / or abuse. This pain disorder costs society more tha...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/232A61K31/231A61K31/23A61P29/00A61P25/04
CPCA61K31/232A61K31/231A61K31/23A61P29/00A61P25/04A61K2300/00
Inventor 崔建国袁建华崔建成
Owner 崔建国
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