CN110038017A - The new application of 5-aminosalicylic acid - Google Patents
The new application of 5-aminosalicylic acid Download PDFInfo
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- CN110038017A CN110038017A CN201810040512.9A CN201810040512A CN110038017A CN 110038017 A CN110038017 A CN 110038017A CN 201810040512 A CN201810040512 A CN 201810040512A CN 110038017 A CN110038017 A CN 110038017A
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- drug
- depression
- mouse
- aminosalicylic acid
- anxiety
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/606—Salicylic acid; Derivatives thereof having amino groups
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- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses 5-aminosalicylic acids to treat the purposes in drug of the depression with anxiety state in preparation.5-aminosalicylic acid of the present invention can well alleviate depression with anxiety state, and reduce its hippocampus level of inflammation, help to improve anti depressant medication effect, reduce drug side-effect.
Description
Technical field
The present invention relates to the new applications of 5-aminosalicylic acid, specifically in preparation treatment depression with anxiety state
Drug in purposes.
Background technique
Depression is a kind of common mood disorder, and core symptom is depressed, retardation of thinking, bulesis subtracts
It moves back, moreover it is possible to sleep disturbance, repeatedly suicidal thought etc. occur.It is counted according to WHO, there are about 1.21 hundred million patients with depression in the whole world at present, often
There is the death of 850.000 people related to depression in year.
For depression there are many simultaneous phenomenon, anxiety symptom is one of the main concomitant symptoms of depression, and incidence can be high
Up to 75%.The anxiety state pathogenesis of depression is complicated, and mechanism is still not known at present.Clinical depression treatment generallys use
SSRI or SNRI class drug, but it is poor to the anxiety symptom curative effect of patients with depression.Therefore, finding one kind can effectively improve suppression
The drug of strongly fragrant disease anxiety symptom, for improving the therapeutic effect of depression, dosage is reduced to reduce its side effect and have its reality
Meaning.
5-aminosalicylic acid (mesalazine, 5-ASA), structural formula isFor a kind of use
In treatment ulcerative colitis and the drug of Crohn disease.Have no that it has effects that treat the anxiety symptom of depression at present
Report.
Summary of the invention
The purpose of the present invention is to provide the new applications of 5-aminosalicylic acid.
The present invention provides purposes of the 5-aminosalicylic acid in the drug of preparation treatment antianxiety symptom.
Wherein, the drug is the drug for treating the anxiety symptom of depression.
Wherein, the drug is depression caused by treating enteric microorganism disorder with the drug of anxiety state.
Wherein, the drug is the drug for inhibiting hippocampus inflammation.
The present invention provides purposes of the 5-aminosalicylic acid in the drug of preparation treatment hippocampus inflammation.
The present invention also provides a kind of depression for the treatment of with the drug of anxiety state, it is with 5-aminosalicylic acid for work
Property ingredient, in addition the preparation that pharmaceutically acceptable auxiliary material or complementary ingredient are prepared.
Wherein, the preparation is oral preparation.
The present invention, which tests, to be confirmed, can be significantly improved small with anxiety-depression with antianxiety by oral 5-aminosalicylic acid
The hippocampus inflammatory conditions of mouse simultaneously improve mouse anxiety state, illustrate that 5-aminosalicylic acid can be used for treating depression with anxiety
State provides a kind of new selection with anxiety state for clinical treatment depression.
Obviously, above content according to the present invention is not being departed from according to the ordinary technical knowledge and customary means of this field
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification, replacement or change of other diversified forms can also be made.
The specific embodiment of form by the following examples remakes further specifically above content of the invention
It is bright.But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to example below.It is all to be based on above content of the present invention
The technology realized all belongs to the scope of the present invention.
Detailed description of the invention
Mice behavior shows situation after the transplanting of Fig. 1 excrement.Depressive patient excrement is transplanted mouse and is transplanted compared with normal person's excrement
Mouse shows as higher levels of anxiety and depressive state.
Fig. 2 shows situation using 5-aminosalicylic acid retarded depression patient's excrement transplanting mice behavior.Give 5- amino water
Poplar acid retarded depression patient's excrement transplanting mouse shows as anxiety level reduction.
Fig. 3 uses the obtained Fig. 1 and Fig. 2 hippocampus of mice inflammatory factor of qRT-PCR and its associated receptor expression.5- ammonia
Base salicylic acid can reverse the expression of hippocampus of mice inflammation associated receptor TLR4 caused by depressive patient enteric microorganism completely, and make
Anti-inflammatory factors IL6 returns back to normal level.
Specific embodiment
The 5-aminosalicylic acid of the present invention of embodiment 1 treats depression with the experiment of anxiety state
1, depression is prepared with the model of anxiety state
The stool sample containing enteric microorganism for transplanting is selected from clinical male's Serious depression patient and male at random
Normal healthy controls.Night soil-treatment carries out in an aseptic environment, each stool sample 0.1g is outstanding to be mixed in the sterile PBS of 1.5ml, and 5
The outstanding mixed liquid of the excrement of a equal portions mixes together.Outstanding mixed liquid is poured into (stomach-filling 0.2ml, stomach-filling 1 time) adult hero by gastric perfusion needle
Property kunming mice (15-30 mouse) (6-8 weeks) is colonized.The excrement of the Serious depression or normal healthy controls that are mixed is outstanding mixed
Liquid passes through sterile transferring window respectively and is passed to different isolators, and all field planting operations carry out in isolator, rigorous aseptic.
Behavior test second week after excrement field planting carries out.Pass through tail-suspention test, forced swim test, wilderness experiment point
It analyses depressive patient excrement transplanting mouse and normal human faecal mass transplants mouse, it is determined whether modeling success:
Wilderness experiment:
Wilderness experiment is to judge locomitivity and the relevant behaviouristics of anxiety.Behavior test instrument is one rectangular
Uncovered black resin glass made of box, having a size of 45cm × 45cm × 30cm (length × width × height).Each mouse
It is individually put into a fixed corner of box, mouse is allowed freely to explore 6 minutes in box.The behavior whole process quilt of mouse
Camera recordings are got off, and finally utilize last 5 points of video track analysis software (SMART, Spain/Panlab) analysis video
Clock.Move the locomitivity of total distance reaction mouse.When in cartridge bottom middle, the time Zhan of a quarter regional movement is total
Between percentage, referred to as center movement time.Judgment criteria as anxiety-like behavior.
Tail-suspention test:
The experimental apparatus of tail-suspention test is the black resin glass chest of top buckle.When experiment starts, in mouse distance
The place of tail portion tip 2cm, which is wrapped with adhesive tape and hangs by the feet, is hung on case top.Experiment whole process is made video recording using video camera, is tested
Journey is 6min, and the analysis of dead time is carried out to rear 5min.If experiment mice climbs up hook, which arranges from the experiment
It removes.When mouse body is motionless and passive suspension, then it is considered as the dead time.
Forced swimming:
The utensil of forced swimming is a cylindrical non-covered container, it is made of transparent resin glass having a size of diameter 15cm,
High 30cm.Deep about 20cm is packed into container, temperature is the warm water of 23-25 degree.Mouse is put into utensil one by one, and video camera level is right
Quasi- container, record mouse enter the behavior in water in 6 minutes.Using video track analysis software (SMART, Spain/
Panlab last 5 minutes for) analyzing video, record its dead time (resting time).The suppression of dead time reaction mouse
Strongly fragrant sample behavior.
Experimental result as shown in Figure 1, the dead time of depressive patient excrement transplanting mouse be significantly higher than normal human faecal mass and move
Mouse is planted, center movement distance is substantially less than normal human faecal mass and transplants mouse, and depressive patient excrement transplanting mouse shows coke
Consider symptom and depressive state, illustrates depression anxiety symptom model modeling success, can be used for screening corresponding therapeutic agent.
2,5-aminosalicylic acid of the present invention alleviates depression anxiety symptom
Firstly, on the basis of the depression anxiety symptom model of aforementioned foundation, by sterile centrifugation tube by 5- amino water
Poplar acid is passed to different Sterilized isolators by sterile transferring window, presses 5-aminosalicylic acid and sterilising drinking water in isolator
The proportional arrangement of 5mg/ml allows aforementioned depression anxiety symptom model mice freely to absorb, and dressing is primary every other day, and all experiments are equal
It is carried out in isolator, rigorous aseptic, control group is to give sterilising drinking water.
Second week carries out Behavior test upon administration.Inhibition test, detection are fed by Elevated plus-maze, new environment
The effect of 5-aminosalicylic acid:
New environment feeds Inhibition test (Novelty suppressed feeding test)
24 hours before experiment starts, mouse is fasted, while guaranteeing the supply that mouse drinks water enough.30 points before experiment
Mouse is transferred to clean cage and adapted it to by clock.Experimental facilities is one (long × wide having a size of 45cm × 45cm × 30cm
× it is high) black wilderness case, put the filter paper that a diameter is 12cm in the middle in wilderness bottom portion, filter paper center puts one
The short and small rat chow of grain.When experiment starts, mouse is put off from one fixed angles of spacious field into recording before mouse is put into mouse
Limb takes the time (latency time) of food meal in one's arms.The long short reaction of the time of the feed of the mouse anxiety-depression of mouse
Degree.Then mouse is put back in cage, the food meal amount in record mouse 5 minutes, to exclude appetite difference to eating time
Influence.
Elevated plus-maze
Elevated plus-maze by the opposite closed arm of two opposite open arms (30cm × 5cm) and two (30cm ×
5cm) right-angled intersection forms.Mouse is put in infall center, faces open arms, and 1 minute postscript is adapted in labyrinth in mouse
The motion profile of record activity 5 minutes thereafter.Time conduct of the record mouse in time and closure arm exploration that open arms are explored is commented
The index of valence mouse anxiety.After every mouse is tested, labyrinth is cleaned using 10% alcohol to avoid smell and mouse residue
Influence to follow-up test.
Quantitative fluorescent PCR (qRT-PCR)
The hippocampal tissue RNA of Fresh Frozen uses Trizol (Invitrogen, CA, USA) milling and extracting in ice face.It adopts
With PrimeScript RT Reagent Kit (Takara, Dalian, China) kit by RNA reverse transcription be cDNA.
QRT-PCR uses LightCycler 96system (Roche, Germany), and reagent uses FastStart Essential
DNA Green Master (Roche), is operated by manufacturer's recommended method.Primer screening is from verified Primerbank
(Harvard) database is synthesized by Sangon Biotech (Shanghai, China).Target mrna expression amount uses β-
Actin is corrected, and is normalized using control group.
Compared with the control group, the food-intake of 5-aminosalicylic acid group significantly improves, and the time that arm is explored significantly shortens, and
Have remarkable result (as shown in Figure 2) to male and female individual, specification 5-aminosalicylic acid has good angst resistance effect.
As shown in figure 3, the animal model hippocampus discovery after 5-aminosalicylic acid treatment, 5-aminosalicylic acid can reverse completely
The expression of hippocampus of mice inflammation associated receptor TLR4 caused by depressive patient enteric microorganism, and return back to anti-inflammatory factors IL6
Normal level illustrates that 5-aminosalicylic acid can send out anti-inflammatory effect in hippocampus.
5-aminosalicylic acid of the present invention can well alleviate depression anxiety symptom, and reduce its hippocampus level of inflammation, help
In improving anti depressant medication effect, drug side-effect is reduced, improves remission rate after treating depression.
Claims (7)
- Purposes of the 1.5- aminosalicylic acid in the drug of preparation treatment antianxiety symptom.
- 2. purposes according to claim 1, it is characterised in that: the drug is the medicine for treating the anxiety symptom of depression Object.
- 3. purposes according to claim 1 or 2, it is characterised in that: the drug is the drug for inhibiting hippocampus inflammation.
- Purposes of the 4.5- aminosalicylic acid in the drug that preparation inhibits hippocampus inflammation.
- 5. purposes according to claim 4, it is characterised in that: the drug is the hippocampus inflammation for treating depression anxiety symptom The drug of disease.
- 6. a kind of depression for the treatment of is with the drug of anxiety state, it is characterised in that: it be with 5-aminosalicylic acid for activity at Point, in addition the preparation that pharmaceutically acceptable auxiliary material or complementary ingredient are prepared.
- 7. drug according to claim 6, it is characterised in that: the preparation is oral preparation.
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CN201810040512.9A CN110038017A (en) | 2018-01-16 | 2018-01-16 | The new application of 5-aminosalicylic acid |
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Cited By (4)
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CN114159563A (en) * | 2021-12-16 | 2022-03-11 | 江西中医药大学 | Anti-depression medicine and screening method thereof |
CN114208770A (en) * | 2021-12-17 | 2022-03-22 | 江苏集萃药康生物科技股份有限公司 | Method for obtaining sterile mice |
CN115137709A (en) * | 2022-06-30 | 2022-10-04 | 重庆医科大学 | Podocyte active targeting reinforced biological homogeneous composite membrane nano-drug delivery system and preparation method and application thereof |
CN115212195A (en) * | 2022-06-17 | 2022-10-21 | 重庆医科大学 | Application of malic acid in preparation of medicine for preventing and/or treating depression |
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US20120040939A1 (en) * | 2009-02-09 | 2012-02-16 | Neurotech Pharmaceuticals Co., Ltd. | Medicinal use of 5-benzylaminosalicylic acid derivative or its salt |
CN104394691A (en) * | 2012-05-19 | 2015-03-04 | 福尔克博士药物有限责任公司 | Compositions and methods for treatment of irritable bowel syndrome with 5-aminosalicylate |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114159563A (en) * | 2021-12-16 | 2022-03-11 | 江西中医药大学 | Anti-depression medicine and screening method thereof |
CN114208770A (en) * | 2021-12-17 | 2022-03-22 | 江苏集萃药康生物科技股份有限公司 | Method for obtaining sterile mice |
CN115212195A (en) * | 2022-06-17 | 2022-10-21 | 重庆医科大学 | Application of malic acid in preparation of medicine for preventing and/or treating depression |
CN115212195B (en) * | 2022-06-17 | 2024-02-27 | 重庆医科大学 | Application of malic acid in preparation of medicines for preventing and/or treating depression |
CN115137709A (en) * | 2022-06-30 | 2022-10-04 | 重庆医科大学 | Podocyte active targeting reinforced biological homogeneous composite membrane nano-drug delivery system and preparation method and application thereof |
CN115137709B (en) * | 2022-06-30 | 2023-05-09 | 重庆医科大学 | Podocyte active targeting reinforced biological homogeneous composite membrane nano drug delivery system and preparation method and application thereof |
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Application publication date: 20190723 |