CN113679751A - Application of extract in preparation of medicines for reducing morphine-induced hepatotoxicity - Google Patents

Application of extract in preparation of medicines for reducing morphine-induced hepatotoxicity Download PDF

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CN113679751A
CN113679751A CN202110991802.3A CN202110991802A CN113679751A CN 113679751 A CN113679751 A CN 113679751A CN 202110991802 A CN202110991802 A CN 202110991802A CN 113679751 A CN113679751 A CN 113679751A
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morphine
extract
group
days
medicament
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汪丽
余员龙
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Zhejiang Baiyue Biotechnology Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/35Caprifoliaceae (Honeysuckle family)
    • A61K36/355Lonicera (honeysuckle)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00General protective or antinoxious agents
    • A61P39/02Antidotes
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5014Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing toxicity
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5082Supracellular entities, e.g. tissue, organisms
    • G01N33/5088Supracellular entities, e.g. tissue, organisms of vertebrates

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Abstract

The invention discloses application of an extract in preparing a medicament for reducing morphine-induced hepatotoxicity, wherein the extract is a honeysuckle extract, and the invention develops new clinical application of the traditional Chinese herbal medicine honeysuckle extract. The honeysuckle extract can obviously inhibit morphine-induced liver injury, does not influence the sedative effect of morphine, and is a powerful adjuvant for improving morphine hepatotoxicity. The honeysuckle extract is easy to obtain from plants, has good safety and can be widely produced and applied.

Description

Application of extract in preparation of medicines for reducing morphine-induced hepatotoxicity
Technical Field
The invention relates to the technical field of biomedicine, in particular to application of a honeysuckle extract, and particularly relates to application of the honeysuckle extract in preparation of a medicament for reducing morphine-induced hepatotoxicity.
Background
Abuse of opioids has become a serious social problem of concern at home and abroad. Morphine, a potent analgesic, is commonly used in the treatment of acute and chronic pain and is one of the opioids. However, the clinical use of morphine, which causes cell death and apoptosis in various systems and organs, has been very limited (NestlerEJ, AghajanianGK. molecular and cellular basis analysis. science.1997; 278: 58-63.Yin D, MufsonRA, WangR, ShiY. Fas-mediatedcell and protein book. Nature.1999; 397-218.HuS, ShengWS, Lokensgard JR, Peterson PK. Morphiloneindus dispensing of human tissue and neurones. neuropharmacology.2002; 42: 829-836.). Among them, morphine damage to the liver is significant and severe, which is a fact confirmed by the medical community. The search for drugs that protect liver damage caused by morphine is of great significance in reducing the side effects of morphine and in applying morphine more widely.
Morphine is a classical opioid drug, is a clinical common anesthetic, has a strong analgesic effect, and is used for severe pain caused by trauma, surgery, burns and the like. However, prolonged use of morphine can be toxic to the liver and kidneys. A large number of animal experiments show that the liver injury and oxidative stress reaction of mice can be caused by long-term injection of small dose morphine, so that the liver cells are subjected to apoptosis. Morphine, as a pair of double-edged sword, is both an effective analgesic and may also cause serious side effects. In order to achieve the clinical curative effect of morphine and solve the adverse reaction, the key point is to find the drug for reducing the liver toxicity of morphine.
The flos Lonicerae extract is the active ingredient of flos Lonicerae, and has various pharmacological effects including antiinflammatory and antibacterial, antioxidant, immunoregulatory, hepatoprotective and antitumor effects. The honeysuckle extract can obviously inhibit liver fibrosis and liver cell apoptosis, and reports show that the honeysuckle extract can reduce the hepatotoxicity caused by morphine, so the honeysuckle extract has important research significance in the clinical and scientific fields.
Disclosure of Invention
The invention provides application of an extract in preparing a medicament for reducing morphine-induced hepatotoxicity, and solves the problems in the prior art.
In order to solve the technical problems, the invention is realized by the following technical scheme:
an application of an extract in preparing a medicament for reducing morphine-induced hepatotoxicity, wherein the extract is a honeysuckle extract.
The flos Lonicerae extract has therapeutic application of inhibiting liver toxicity.
The dosage of flos Lonicerae extract is 0-10 g/kg.
Use of an extract in the preparation of a medicament for reducing morphine-induced hepatotoxicity, comprising the following analytical steps:
the method comprises the following steps: selecting male mice of 4 weeks old;
step two: dissolving flos Lonicerae extract in physiological saline, and preparing neutral formalin fixing solution, neutral resin, hematoxylin and eosin staining solution;
step three: dividing male mice into four groups, and performing four experiments including control group, morphine group, flos Lonicerae extract group and flos Lonicerae extract + morphine group, each group containing 8 mice;
step four: according to four groups of experiments, the influence of the honeysuckle extract on the morphine sedation effect, the influence of the honeysuckle extract on the AST and ALP levels in the serum of mice and the protective effect of the honeysuckle extract on the morphine-induced liver tissue injury of the mice are obtained.
The control group is prepared by injecting 1ml of normal saline into the abdominal cavity of the mouse every day on days 1-20; the morphine group is prepared by injecting 20mg/kg morphine into the abdominal cavity of the mouse every day on the 1 st to 5 th days, injecting 20mg/kg morphine every two days on the 6 th to 10 th days, and injecting 30mg/kg morphine every two days on the 11 th to 20 th days; the honeysuckle extract group is prepared by feeding 45g/kg of honeysuckle extract to the mice by intragastric administration every day on the 1 st to 20 th days; the honeysuckle extract + morphine group was continued for 20 days, and the mice received the same treatment as the morphine group and the honeysuckle extract group.
A medicament prepared from an extract in the application of preparing a medicament for reducing morphine-induced hepatotoxicity comprises a pharmaceutically effective amount of honeysuckle extract and a pharmaceutically acceptable carrier.
The pharmaceutical dosage forms comprise suspensions, emulsions, tablets, capsules, granules, oral liquids and injections.
The invention discloses a new clinical application of the traditional Chinese herbal medicine honeysuckle extract. The honeysuckle extract can obviously inhibit morphine-induced liver injury, does not influence the sedative effect of morphine, and is a powerful adjuvant for improving morphine hepatotoxicity. The honeysuckle extract is easy to obtain from plants, has good safety and can be widely produced and applied.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.
Figure 1 is a graph of the effect of honeysuckle extract on morphine sedation;
FIG. 2 is a graph of the effect of honeysuckle extract on levels of AST and ALP in serum of morphine-induced mice;
figure 3 is a graph of the effect of honeysuckle extract on morphine-induced liver tissue damage in mice.
Detailed Description
The following further describes the embodiments of the present invention. It should be noted that the description of the embodiments is provided to help understanding of the present invention, but the present invention is not limited thereto. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
An application of an extract in preparing a medicament for reducing morphine-induced hepatotoxicity, wherein the extract is a honeysuckle extract.
The flos Lonicerae extract has therapeutic application of inhibiting liver toxicity.
The dosage of flos Lonicerae extract is 0-10 g/kg.
Use of an extract in the preparation of a medicament for reducing morphine-induced hepatotoxicity, comprising the following analytical steps:
the method comprises the following steps: selecting male mice of 4 weeks old;
step two: dissolving flos Lonicerae extract in physiological saline, and preparing neutral formalin fixing solution, neutral resin, hematoxylin and eosin staining solution;
step three: dividing male mice into four groups, and performing four experiments including control group, morphine group, flos Lonicerae extract group and flos Lonicerae extract + morphine group, each group containing 8 mice;
step four: according to four groups of experiments, the influence of the honeysuckle extract on the morphine sedation effect, the influence of the honeysuckle extract on the AST and ALP levels in the serum of mice and the protective effect of the honeysuckle extract on the morphine-induced liver tissue injury of the mice are obtained.
The control group is prepared by injecting 1ml of normal saline into the abdominal cavity of the mouse every day on days 1-20; the morphine group is prepared by injecting 20mg/kg morphine into the abdominal cavity of the mouse every day on the 1 st to 5 th days, injecting 20mg/kg morphine every two days on the 6 th to 10 th days, and injecting 30mg/kg morphine every two days on the 11 th to 20 th days; the honeysuckle extract group is prepared by feeding 45g/kg of honeysuckle extract to the mice by intragastric administration every day on the 1 st to 20 th days; the honeysuckle extract + morphine group was continued for 20 days, and the mice received the same treatment as the morphine group and the honeysuckle extract group.
A medicament prepared from an extract in the application of preparing a medicament for reducing morphine-induced hepatotoxicity comprises a pharmaceutically effective amount of honeysuckle extract and a pharmaceutically acceptable carrier.
The pharmaceutical dosage forms comprise suspensions, emulsions, tablets, capsules, granules, oral liquids and injections.
The invention discloses a new clinical application of the traditional Chinese herbal medicine honeysuckle extract. The honeysuckle extract can obviously inhibit morphine-induced liver injury, does not influence the sedative effect of morphine, and is a powerful adjuvant for improving morphine hepatotoxicity. The honeysuckle extract is easy to obtain from plants, has good safety, and can be widely produced and applied in example 1: effect of honeysuckle extract on the sedative Effect of morphine
The sedative effects of morphine were evaluated by recording the time of the mice during the induction, anesthesia and recovery phases. The anaesthesia phase is as follows: induction phase (although mice fall, there are still various responses, breathing is mainly chest breathing); an anesthesia period: (mice are stable in breathing, even muscle is relaxed, limbs are not active, corneal reflex is weak, skin pain reaction, toe reaction disappears); the convalescent phase (various reflexes and reactions begin to recover, limbs begin to wobble). The results are shown in FIG. 1.
Example 2: effect of honeysuckle extract on AST and ALP levels in mouse serum
After sacrifice, midline laparotomy was performed. The liver was removed and blood was drawn by cardiac puncture. After centrifugation of the blood by density gradient centrifugation, the serum was separated for liver function testing. The AST and ALP contents in serum were measured by an automated biochemical analyzer. The results are shown in FIG. 2.
Example 3: protection effect of honeysuckle extract on morphine-induced mouse liver tissue injury
In the experiment, the protective effect of the honeysuckle extract on the morphine-induced liver tissue injury of the mouse is detected by H & E staining. Liver samples were fixed in 10% neutral formalin fixative. The fixed tissue was then dehydrated, cleared and embedded in paraffin. Paraffin embedded tissues were cut to 4 μm, then dried and deparaffinized. Tissue sections were stained with hematoxylin and eosin in sequence. The tissue sections were then sequentially dehydrated, deparaffinized and blocked with neutral resin. The results are shown in FIG. 3.
And (3) detection results:
1. the flos Lonicerae extract has no influence on the sedative effect of morphine
As shown in fig. 1, the time of the induction period, the sedation period and the recovery period of the honeysuckle extract + morphine group did not significantly affect the morphine group, indicating that the honeysuckle extract did not affect the sedation effect of morphine.
2. Flos Lonicerae extract can significantly reduce morphine-induced AST and ALP level increase
As shown in fig. 2, the levels of AST and ALP of the morphine group were significantly higher than those of the control group, while the levels of AST and ALP of the honeysuckle extract + morphine group were lower than those of the morphine group, indicating that the honeysuckle extract was effective in inhibiting the increase of ASR and ALP levels caused by morphine.
3. Flos Lonicerae extract can relieve morphine-induced liver injury
As shown in FIG. 3, the liver tissue of the control group was normal, while the liver tissue of the morphine group was significantly damaged, Copffer cytosis increased, and the central hepatic vein is enlarged. Morphine-induced liver tissue damage is alleviated after treatment with honeysuckle extract.
The embodiments of the present invention have been described in detail, but the present invention is not limited to the described embodiments. It will be apparent to those skilled in the art that various changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, and the scope of protection is still within the scope of the invention.

Claims (7)

1. Use of an extract for the preparation of a medicament for reducing morphine-induced hepatotoxicity, characterized in that: the extract is honeysuckle extract.
2. Use of an extract according to claim 1 for the preparation of a medicament for reducing morphine-induced hepatotoxicity, characterized in that: the flos Lonicerae extract has therapeutic application of inhibiting liver toxicity.
3. Use of an extract according to claim 1 or 2 for the preparation of a medicament for reducing morphine-induced hepatotoxicity, characterized in that: the dosage of flos Lonicerae extract is 0-10 g/kg.
4. Use of an extract according to claim 1 for the preparation of a medicament for reducing morphine-induced hepatotoxicity, characterized in that: the method comprises the following analysis steps:
the method comprises the following steps: selecting male mice of 4 weeks old;
step two: dissolving flos Lonicerae extract in physiological saline, and preparing neutral formalin fixing solution, neutral resin, hematoxylin and eosin staining solution;
step three: dividing male mice into four groups, and performing four experiments including control group, morphine group, flos Lonicerae extract group and flos Lonicerae extract + morphine group, each group containing 8 mice;
step four: according to four groups of experiments, the influence of the honeysuckle extract on the morphine sedation effect, the influence of the honeysuckle extract on the AST and ALP levels in the serum of mice and the protective effect of the honeysuckle extract on the morphine-induced liver tissue injury of the mice are obtained.
5. Use of an extract according to claim 4 for the preparation of a medicament for reducing morphine-induced hepatotoxicity, characterized in that: the control group is prepared by injecting 1ml of normal saline into the abdominal cavity of the mouse every day on days 1-20; the morphine group is prepared by injecting 20mg/kg morphine into the abdominal cavity of the mouse every day on the 1 st to 5 th days, injecting 20mg/kg morphine every two days on the 6 th to 10 th days, and injecting 30mg/kg morphine every two days on the 11 th to 20 th days; the honeysuckle extract group is prepared by feeding 45g/kg of honeysuckle extract to the mice by intragastric administration every day on the 1 st to 20 th days; the honeysuckle extract + morphine group was continued for 20 days, and the mice received the same treatment as the morphine group and the honeysuckle extract group.
6. A medicament prepared from the extract of claim 1 for use in the preparation of a medicament for reducing morphine-induced hepatotoxicity, wherein: the medicine contains a pharmaceutically effective amount of honeysuckle extract and a pharmaceutically acceptable carrier.
7. The use of an extract according to claim 6 in the preparation of a medicament for reducing morphine-induced hepatotoxicity, wherein: the pharmaceutical dosage forms comprise suspensions, emulsions, tablets, capsules, granules, oral liquids and injections.
CN202110991802.3A 2021-08-27 2021-08-27 Application of extract in preparation of medicines for reducing morphine-induced hepatotoxicity Pending CN113679751A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106261362A (en) * 2016-08-08 2017-01-04 南昌大学 A kind of honeysuckle composition beverage with the liver protecting effect and preparation method

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106261362A (en) * 2016-08-08 2017-01-04 南昌大学 A kind of honeysuckle composition beverage with the liver protecting effect and preparation method

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
《中华人民共和国药典临床用药须知 2015年版 中药饮片卷》: "《中华人民共和国药典临床用药须知 2015年版 中药饮片卷》", 30 September 2017 *
景恒翠等: "金银花的药用成分及药理分析", 《河南中医》 *

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Application publication date: 20211123