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Medicament component of berberine for the use of prevention and treatment of psycological dependence on and analgesic tolerance to morphine

A composition, tolerance technology, applied in the field of pharmaceutical compositions with harmful effects, can solve the problems of application restrictions, reduction of analgesic effect, dosage increase, etc.

Active Publication Date: 2010-05-05
SUNGKYUNKWAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Increased doses of this narcotic analgesic lead to various side effects and are therefore severely toxic to humans
[0007] As a representative example of a narcotic analgesic, morphine is known to have the highest analgesic effect among analgesics developed so far. However, repeated administration of morphine leads to a gradual decrease in its analgesic effect, which eventually leads to loss of the analgesic effect of morphine. Development of tolerance. For these reasons, the use of morphine in the clinical field is limited despite its excellent efficacy. Therefore, in order to utilize morphine as an analgesic, the initial analgesic effect of morphine is maintained without reducing its analgesic effect upon repeated use is very important. This purpose can be achieved by inhibiting the development of tolerance to morphine.

Method used

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  • Medicament component of berberine for the use of prevention and treatment of psycological dependence on and analgesic tolerance to morphine
  • Medicament component of berberine for the use of prevention and treatment of psycological dependence on and analgesic tolerance to morphine
  • Medicament component of berberine for the use of prevention and treatment of psycological dependence on and analgesic tolerance to morphine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1: Evaluation of the inhibitory effect of berberine on psychological dependence on morphine

[0035] The development of psychological dependence on morphine was detected by the conditioned place preference test.

[0036] The conditioned place preference test was performed in two equally sized boxes (15 x 15 x 15 cm), each with a front surface made of a transparent polypropylene sheet. The other three surfaces of each case are made of white or black polypropylene panels. The two boxes are connected by a gray passage (3×3×7.5 cm), and this passage can be blocked with a withdrawable gate.

[0037] To allow the mice to perceive the texture of the box floor, the white box had a rough floor and the black box had a smooth floor. Mice were cultured under a light intensity of 20 Lux.

[0038] Step 1 (preprocessing stage)

[0039] On day 1, the gate of the box was opened and the mice were allowed to freely explore both compartments for 5 min. On day 2, mice were hous...

Embodiment 2

[0044] Example 2: Evaluation of the inhibitory effect of berberine on the increase in spontaneous locomotor activity induced by morphine

[0045] Spontaneous locomotor activity tests were performed in a plastic chamber (26 x 30 x 30 cm) using a video tracking system. First, 10 mg / kg of morphine was administered to mice once a day for 6 days. Immediately after the last dose, mice were placed in a plastic chamber, and spontaneous locomotor activity was recorded for 30 min and analyzed using a computer program. Berberine was orally administered to mice at 1 and 2 mg / kg 1 hour before morphine administration. The results are shown in figure 2 middle. Such as figure 2 As shown, when only morphine was administered, the locomotor activity of the mice increased significantly, with 50,242 forefoot steps. In contrast, when 1 and 2 mg / kg of berberine were pre-administered, the locomotor activity of the mice was 19,744 steps and 20,027 steps, respectively. In other words, compared ...

Embodiment 3

[0046] Example 3: Evaluation of the effect of berberine on the analgesic effect of morphine in a single dose

[0047] Male ICR mice, weighing 18-25 g, were acclimatized to the new environment by culturing in a temperature- and humidity-controlled vivarium for one week. 10 mice were used in each group. Morphine and berberine (berberine hemisulfate) were purchased from Keukdong Pharm Company (Inchon, Korea) and Sigma Company (USA), respectively, and dissolved in distilled water before use.

[0048] The effect of berberine on the analgesic effect of morphine was evaluated by applying heat stimulation to mice by hot plate test. For the hot plate test, each mouse was placed on a hot plate at 52°C and the latency until the mouse first showed signs of discomfort (hind paw flapping or jumping) was observed. To avoid tissue damage, a maximum heat exposure time (cut-off time) was artificially enforced, which was 30 seconds. If no behavioral response was shown for more than 30 seconds...

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Abstract

Disclosed is a pharmaceutical composition for preventing and treating addiction to morphine or preventing and inhibiting the development of tolerance to the analgesic effects of morphine, containing berberine as an effective ingredient, wherein the berberine has an inhibitory effect versus psychological dependence on abused drugs such as morphine and the increase of spontaneous locomotor activityupon administration of the drugs, The pharmaceutical composition and a Coptis japonica plant extract of the present invention, which contain berberine, are highly effective in inhibiting the aforementioned symptoms of morphine addiction, and are thus useful for prevention and treatment of addiction to abused drugs such as morphine. In addition, the pharmaceutical composition additionally containing a pharmaceutical acceptable carrier can be applied to prevent and inhibit morphine tolerance caused by repeated administration of morphine, while not affecting the analgesic effects of morphine upona single administration.

Description

technical field [0001] In general, the present invention relates to a pharmaceutical composition for the prevention and treatment of the deleterious effects of narcotic analgesics. More specifically, the present invention relates to a pharmaceutical composition comprising berberine as an active ingredient, wherein the pharmaceutical composition has an inhibitory effect on psychological dependence on morphine and morphine-induced spontaneous locomotor activity. [0002] Drug abusers often suffer from psychological dependence, which is the compulsion to continue taking drugs because of their euphoric effects, despite the potential adverse effects of the drug, and such drugs include morphine or its derivatives, cocaine, and meth Amphetamine or its derivatives. [0003] Morphine is a narcotic analgesic with psychostimulant effects, the most common symptoms of which are hallucinations and delirium when relatively high doses are used or when low doses are used repeatedly over a lon...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4375A61P25/30
CPCA61P25/36A61K31/4375A61K36/718
Inventor 张春坤李硕镕
Owner SUNGKYUNKWAN UNIVERSITY
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