CN110169971A - It is a kind of comprising 3 acetyl-α, the drug of β masticinic acid and its in the application prevented, treated in pancreatitis - Google Patents
It is a kind of comprising 3 acetyl-α, the drug of β masticinic acid and its in the application prevented, treated in pancreatitis Download PDFInfo
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- CN110169971A CN110169971A CN201910313859.0A CN201910313859A CN110169971A CN 110169971 A CN110169971 A CN 110169971A CN 201910313859 A CN201910313859 A CN 201910313859A CN 110169971 A CN110169971 A CN 110169971A
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
The present invention provides the drugs of 3 acetyl-α of one kind, the application of β masticinic acid and treatment pancreatitis, are related to pharmaceutical technology field, the present invention experiments prove that, 3 acetyl-α, β masticinic acid are inhibited to inflammation, and have certain therapeutic effect to pancreatitis.The present invention prevents in preparation and/or treats in the drug of pancreatitis by applying 3 acetyl-α, β masticinic acid, pancreas inflammatory can effectively be inhibited, to greatly improve the therapeutic effect of pancreatitis, foundation is provided for clinical trial, also provides new way for the research and development of new drug.Active constituent provided by the present invention for preventing and/or treating the drug of pancreatitis is 3 acetyl-α, β masticinic acid, therefore can effectively inhibit pancreas inflammatory, plays apparent prevention and/or therapeutic effect to pancreatitis, while safe without toxic side effect is small.
Description
Technical field
The present invention relates to pharmaceutical technology fields, more particularly, to 3 acetyl-α of one kind, the application of β masticinic acid and treatment pancreas
Scorching drug.
Background technique
On the one hand the important function of pancreas organ shows as exocrine function, digestion needed for secretion food digestion and absorption
On the other hand enzyme shows as endocrine function, the hormone secretion being metabolized in vivo is adjusted, such as insulin and glucagon.Pancreatic juice
In contain digestive ferment, such as amylase (hydrolysis carbohydrate), trypsase (aminosal) and lipase (hydrolyze rouge
Fat), pancreatic juice unsmooth flowing is led to due to excessive drinking, gall stone etc., the possible self-dissolving of pancreas develops under above-mentioned enzyme induction
Pancreatitis.Pancreatitis is divided to two kinds: light-duty pancreatitis, with the pancreas week adiponecrosis around interstitial edema and pancreas；Heavy pancreas
Adenositis, with adiponecrosis, pancreatic parenchmal necrosis and bleeding in large area pancreas week and pancreas.
Recognize from pancreatitis early stage pathology, physiological mechanism, macrophage enters pancreas after pancreatic acinar cell is impaired
It will lead to tissue damage when inside gland, (tumour is bad for meeting secretion inducing cell factor IL-1 β (Interleukin -1β), IL-6 and TNF-α
Necrosis factor-α) significant raising is expressed, the cell factor rises in terms of inflammatory cell circulation, pancreas oedema and practical pancreas destruction
Important function.In the serum of patients with acute pancreatitis, it can be observed that the cell factor increases, with complication.It is all
In the case where such as necrosis of pancreas, systemic inflammatory response, multiple organ failure.The effective means for preventing and treating pancreatitis is to try
The cytokine-expressing is reduced, pancreatic acinar cell is reduced and is damaged, restore pancreas function and reduces complication.
Have at present several by experiment in vivo and experiment in vitro, it was demonstrated that some drugs have the reduction cell factor
Expression reaches the effect of mitigating the pancreatitis extent of damage.However when these experimental therapy methods are applied to clinical patients, effect
It is unable to reach desired effect, leading to the drug for treating pancreatitis at present is not very much, to take effect not significant yet.
Therefore, develop a kind of effective drug or monomer to carry out pancreatitis treatment particularly important.
In view of this, the present invention is specifically proposed.
Summary of the invention
The first purpose of this invention is to provide 3 acetyl-α, β masticinic acid in preparation prevention and/or treats pancreatitis
Application in drug.
Second object of the present invention be to provide it is a kind of for preventing and/or treating the drug of pancreatitis, it is existing to alleviate
There is the drug for treating pancreatitis present in technology deficient, and the technical problem that therapeutic effect is poor.
The present invention provides the application of 3 acetyl-α, β masticinic acid in the drug of preparation prevention and/or treatment pancreatitis.
The present invention also provides a kind of for preventing and/or treating the drug of pancreatitis, and the drug includes 3 acetyl-α, β
Masticinic acid.
Further, the drug further includes pharmaceutically acceptable auxiliary material.
Further, the dosage form of the drug includes oral preparation or ejection preparation.
Further, the oral preparation includes tablet, capsule, granule, pill, syrup, oral solution, mouth
Take suspension or Orally taken emulsion.
Further, the ejection preparation includes injection or powder-injection.
Further, the proportion of the drug is 1:1-10:1.
Further, the proportion of the drug is 1:1-1:10.
Further, effective dosage of the drug is 50-500mg/kg/ days.
Further, the pancreatitis includes acute pancreatitis and/or chronic pancreatitis.
The present invention is by a large amount of inside and outside it is experimentally confirmed that 3 acetyl-α, β masticinic acid can be significantly reduced because of pancreas inflammatory
Raised amylase activity, cell factor IL-6, TNF-α expression illustrate that 3 acetyl-α, β masticinic acid have inflammation and inhibit to make
With.Also, 3 acetyl-α, β masticinic acid can also reduce or inhibit pancreatic tissue inflammation, oedema and necrosis, illustrate 3 acetyl-α, β
Masticinic acid has certain therapeutic effect to pancreatitis.The present invention by by 3 acetyl-α, β masticinic acid apply preparation prevention and/
Or in the drug for the treatment of pancreatitis, can effectively inhibit pancreas inflammatory, so that the therapeutic effect of pancreatitis is greatly improved, for clinic
Experiment provides foundation, also provides new way for the research and development of new drug.
Provided by the present invention for preventing and/or treating the drug of pancreatitis, the active constituent of the drug is 3 acetyl-α, β
Therefore masticinic acid can effectively inhibit pancreas inflammatory, play apparent prevention and/or therapeutic effect, while safety to pancreatitis
It is nontoxic, Small side effects.
Detailed description of the invention
It, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution in the prior art
Embodiment or attached drawing needed to be used in the description of the prior art be briefly described, it should be apparent that, it is described below
Attached drawing is some embodiments of the present invention, for those of ordinary skill in the art, before not making the creative labor
It puts, is also possible to obtain other drawings based on these drawings.
Fig. 1 is that the control group pancreatic tissue HE stained slice that the embodiment of the present invention 1 provides amplifies 100 times of images；Fig. 2 is
The control group pancreatic tissue HE stained slice that the embodiment of the present invention 1 provides amplifies 400 times of images；
Fig. 3 is that the experimental group pancreatic tissue HE stained slice that the embodiment of the present invention 1 provides amplifies 100 times of images；
Fig. 4 is that the experimental group pancreatic tissue HE stained slice that the embodiment of the present invention 1 provides amplifies 400 times of images；
Fig. 5 be the embodiment of the present invention 1 provide 3 acetyl-α, β masticinic acid low dose therapy group pancreatic tissue HE stained slice amplification
100 times of images；
Fig. 6 be the embodiment of the present invention 1 provide 3 acetyl-α, β masticinic acid low dose therapy group pancreatic tissue HE stained slice amplification
400 times of images；
Fig. 7 be the embodiment of the present invention 1 provide 3 acetyl-α, β masticinic acid middle dosage treatment group pancreatic tissue HE stained slice amplification
100 times of images；
Fig. 8 be the embodiment of the present invention 1 provide 3 acetyl-α, β masticinic acid middle dosage treatment group pancreatic tissue HE stained slice amplification
400 times of images；
Fig. 9 be the embodiment of the present invention 1 provide 3 acetyl-α, β masticinic acid high-dose therapy group pancreatic tissue HE stained slice amplification
100 times of images；
Figure 10 is the 3 acetyl-α that provide of the embodiment of the present invention 1, β masticinic acid high-dose therapy group pancreatic tissue HE stained slice is put
Big 400 times of images；
Figure 11 is that 3 acetyl-α of use, the β masticinic acid that the embodiment of the present invention 1 provides comment the pathological section of pancreatitis experiment in vivo
Component；
Figure 12 be the embodiment of the present invention 2 provide 3 acetyl-α of use, β masticinic acid is to the Acarbose concentrations of pancreatitis experiment in vivo
Analysis chart；
Figure 13 be the embodiment of the present invention 3 provide 3 acetyl-α of use, β masticinic acid is to the serum interleukin-of pancreatitis experiment in vivo
6 analysis charts；
Figure 14 be the embodiment of the present invention 3 provide 3 acetyl-α of use, β masticinic acid is to the homogenate of pancreatitis experiment in vivo
TNF-α analysis chart；
Figure 15 be the embodiment of the present invention 5 provide 3 acetyl-α of use, β masticinic acid is to mouse macrophage RAW264.7 vigor
Impact analysis figure；
Figure 16 is the use 3 acetyl-α, β masticinic acid, lipopolysaccharides Stimulated Macrophages that the embodiment of the present invention 6 provides
Content of nitric oxide impact analysis figure in inflammatory environment caused by RAW264.7；
Figure 17 is the use 3 acetyl-α, β masticinic acid, lipopolysaccharides Stimulated Macrophages that the embodiment of the present invention 7 provides
Interleukin-6 content impact analysis figure in inflammatory environment caused by RAW264.7；
Figure 18 is the use 3 acetyl-α, β masticinic acid, lipopolysaccharides Stimulated Macrophages that the embodiment of the present invention 7 provides
TNF-α content impact analysis figure in inflammatory environment caused by RAW264.7.
Specific embodiment
Technical solution of the present invention is clearly and completely described below in conjunction with embodiment, it is clear that described reality
Applying example is a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, the common skill in this field
Art personnel every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
The present invention provides the application of 3 acetyl-α, β masticinic acid in the drug of preparation prevention and/or treatment pancreatitis.
Wherein, shown in the chemical structural formula such as formula (I, II) of 3 acetyl-α, β masticinic acid:
The present invention by caerulin inducing mouse pancreatitis illness, treated by 3 acetyl-α, the β masticinic acid for being aided with various dose
Experiment is measured by pancreatic tissue slice, serum amylase, TNF-α, interleukin-6, shows 3 acetyl-α, β masticinic acid to pancreas
Inflammation has inhibiting effect.There is repeatability by many experiments.Cells in vitro experiment uses lipopolysaccharide-induced RAW264.7 cell
The inflammatory model of foundation, by NO, the measurement of TNF-α, interleukin-6 content, is tested using 3 acetyl-α, β masticinic acid as therapeutic agent
3 acetyl-α, β masticinic acid are demonstrate,proved to the inhibiting effect of inflammation.The present invention is prevented by applying 3 acetyl-α, β masticinic acid in preparation
And/or in the drug for the treatment of pancreatitis, it can effectively inhibit pancreas inflammatory, to greatly improve the therapeutic effect of pancreatitis, be
Clinical trial provides foundation, also provides new way for the research and development of new drug.
It should be noted that 3 acetyl-α of the present invention, β masticinic acid, can both be prepared for laboratory,
Can be it is commercially available directly buy, as long as meet the chemical structural formula of formula (I, II).
The present invention also provides a kind of for preventing and/or treating the drug of pancreatitis, including 3 acetyl-α, β masticinic acid.
The active constituent of drug provided by the invention is 3 acetyl-α, β masticinic acid, since 3 acetyl-α, β masticinic acid are to inflammation
Inhibiting effect, which can effectively inhibit pancreas inflammatory, play apparent prevention and/or therapeutic effect to pancreatitis, together
When safe and non-toxic, Small side effects.
In one preferred embodiment, drug further includes pharmaceutically acceptable auxiliary material.
When pharmaceutically acceptable auxiliary material refers to production drug and prescription being dispensed, the excipient and additives used is
Refer in addition to the active ingredient (s, reasonable assessment is had been carried out in terms of safety, and include the substance in pharmaceutical preparation.It is same
Pharmaceutic adjuvant can be used for the pharmaceutical preparation of different way of administration, and play the role of different and purposes.In drug provided by the invention
The pharmaceutically acceptable auxiliary material of middle addition can play the role of excipient, serve as carrier or improve stability, in addition, also having
There are the critical functions such as solubilising, hydrotropy or slow controlled release.
Typical but non-limiting pharmaceutically acceptable auxiliary material includes: solvent, propellant, solubilizer, cosolvent, emulsification
Agent, colorant, binder, disintegrating agent, filler, lubricant, wetting agent, osmotic pressure regulator, stabilizer, glidant, flavoring
Agent, preservative, suspending agent, coating material, aromatic, anti stickness agent, antioxidant, chelating agent, penetration enhancer, pH adjusting agent,
Buffer, plasticizer, surfactant, foaming agent, defoaming agent, thickener, inclusion agents, moisturizer, absorbent, diluent, wadding
One of solidifying agent and deflocculant, filter aid or release retarding agent are a variety of.
In one preferred embodiment, the dosage form of drug includes oral preparation or ejection preparation.
When oral medication, said medicine can be made into and arbitrarily take orally acceptable dosage form, such as can be, but unlimited
In tablet, capsule, granule, pill, syrup, oral solution, oral suspensions or Orally taken emulsion.
Wherein, the carrier that tablet uses generally comprises lactose and cornstarch, and lubricant such as stearic acid in addition can also be added
Magnesium.The diluent that capsule uses generally comprises lactose and dried corn starch.Oral suspensions are then usually by active constituent
It is used in mixed way with suitable emulsifier and suspending agent.
Optionally, some sweeteners, aromatic or colorant can also be added in the above oral dosage form.
When being administered in the form of injection, said medicine can be made into the acceptable dosage form of any injection, such as can be with
For, but it is not limited to injection or powder-injection.
Wherein, workable carrier and solvent include water, Ringer's solution and isotonic sodium chlorrde solution.In addition, sterilizing
Fixed oil also is used as solvent or suspension media, such as monoglyceride or two glyceride.
In one preferred embodiment, effective dosage of drug is 50-500mg/kg/ days, such as can be,
But it is not limited to 50mg/kg/ days, 100mg/kg/ days, 150mg/kg/ days, 200mg/kg/ days, 250mg/kg/ days, 300mg/kg/
It, 350mg/kg/ days, 400mg/kg/ days, 450mg/kg/ days or 500mg/kg/ days.
In one preferred embodiment, drug ratio ratio can be, but be not limited to 1:1,1:2,1:5,1:10 or
2:1,5:1,10:1.
In one preferred embodiment, administration frequency for example can be, but be not limited to twice daily, once a day,
Once every two days, once-weekly or once-monthly administration.Alternatively, medicine provided by the invention can be given in the form of sustained release preparation
Object, in this case it is necessary to less administration frequency.
Dosage and frequency are different in drug user's intracorporal half-life period according to preparation, in addition it is also possible to according to being pre-
The processing of anti-property or therapeutic treatment and it is different.In prophylactic use, given for a long time with the interval of rather low-frequency rate relatively low
Dosage.In therapeutic application, it is sometimes desirable to relatively high dosage is given with relatively short interval, until the progress quilt of disease
Delay or stop, and is preferably up to the individual partially or completely improvement for showing disease symptoms to give and suffer from after this
Person's prevention scheme.
When the effective dose of administration is in preferred scope, the prevention and/or therapeutic effect of pancreatitis are become apparent from, taken effect
Faster.
In one preferred embodiment, pancreatitis includes acute pancreatitis and/or chronic pancreatitis.
In order to facilitate it is clearer understand the contents of the present invention, be described in detail as follows now in conjunction with specific embodiment.
Unless otherwise instructed, cell, drug used in the embodiment of the present invention and the equal source of reagent are regular and easily purchase canal
Road: cell: RAW264.7 provides for Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences's preclinical medicine cell centre.
Drug and reagent:
3 acetyl-α, β masticinic acid provide for Tianjin University Of Traditional Chinese Medicine laboratory, white crystal.
Preparation method specifically:
(a) 3 kilograms of olibanum medicinal materials are weighed, are crushed, are extracted 3 times with 95% alcohol reflux of solid-liquid ratio 1:8, reflux 2 is small every time
When.Combined extract is concentrated under reduced pressure, and recycling design obtains 95% ethanol extract, therefore medicinal extract is merged, total 2034.8g.
Medicinal extract is first dissolved in petroleum ether, is extracted with water, and petroleum ether layer medicinal extract (983g) is obtained.
(b) by after 600g petroleum ether layer medicinal extract petroleum ether dissolution, sample is mixed with silica gel (100~200 mesh), weighs 1200g
Column chromatography silica gel (100~200 mesh) wet method dress post, with petroleum ether-ethyl acetate (100:0,80:1,60:1,40:1,20:1,
15:1,10:1,8:1,6:1,4:1,2:1,1:1,0:100) it is that eluant, eluent carries out gradient elution.
(c) every 400ml eluent is a fraction, collects 15 parts of fraction altogether, is dissolved using methylene chloride；With petroleum ether-second
Acetoacetic ester (4:1) is solvent, is developed the color in UV (254nm, 365nm) and 10% sulfuric acid, the case where colour developing according to TLC, merging evaporates
Point.As a result: Fr.110；Fr.111, Fr.112 merge, and crystallization are precipitated, through 3 acetyl-α of Spectral Identification, β masticinic acid (3.6g)
DMEM basal medium (high sugar, containing phenol red), Corning company, article No.: R10-017-CV；Superfine fetal calf serum (Fetal
Bovine Serum Sterile), Ausbian company, article No.: VS500T；Dual anti-(the Penicillin- of penicillin streptomycin
Streptomycin Solution), Corning company, article No.: 30-002-CI；Lipopolysaccharides (Lipopolysaccharide,
LPS), sigma company, article No.: L6529；Thiazole basket (MTT), Suo Laibao company, article No.: M1025；PBS buffer solution, the green skies
Biology, article No.: C0021A；Mouse TNF-α kit, eBioscience biotech firm, article No.: 88-7324-77；Mouse IL-6
Kit, eBioscience biotech firm, article No. 88-7064-77；Nitric oxide detection kit, green skies biology, article No.:
S0021。
Instrument: microscope, Lai Ka company, model: DM4000；Centrifuge, Thermo Fisher Scientific, type
Number: Micro 17；Multi-functional plate reading machine, U.S. PerkinElmer, model: Enspire；Cell incubation case, Thermo
Fisher Scientific, model: 3111.Cabinet type shaking table, Shanghai Shiping Experiment Equipment Co., Ltd., model: SPH-2102C.
Embodiment 1
Normally pancreatic tissue stained slice should be clear in structure under light microscopic, and acinus leaflet is complete, and medium is disease-free without exudation
Neo-Confucianism changes.When pancreatitis occurs, acinar cells will form vacuole, oedema, iuntercellular occur away from becoming larger in pancreatic tissue, scorching
Cell starts to infiltrate, and the necrosis of accidental acinar cells.By this be damaged feature may determine that pancreatitis development and treatment
Degree.This experimental example passes through control group C, model group M, 3 acetyl-α, β masticinic acid low dose therapy group D, 3 acetyl-α, β masticinic acid
Middle dosage treatment group Z, 3 acetyl-α, β masticinic acid high-dose therapy group H carry out animal experiment in vivo, every group 10, pass through dyeing
The light microscopic of slice show compare with pancreatic tissue pathological score, with this come study 3 acetyl-α, β masticinic acid to pancreatitis treatment make
With.
Specifically, carrying out the preparation of pancreatitis animal model and 3 acetyl-α, β using the C57BL/6 mouse of weight about 20 ± 2g
Masticinic acid Experiment on therapy, experiment mice constant temperature (22-26 DEG C), humidity (55-60%) germ-free animal lab in raise,
Mouse is raised with normal solid feed and water, is adapted it to 1 week, all experiment in vivo are according to the animal care of regulation and use
Guide carries out, using the fabulous caerulin inducing mouse pancreatitis illness of reproducibility.
Experiment stops supplying feed to all mouse for first 16 hours, and since experiment, control group is with 1 hour interval through abdomen
5 physiological saline of intracavitary application, each 0.2mL.Except for the control, remaining mouse is with 1 hour interval through 5 rain of intraperitoneal application
Frog peptide, 70 μ g/kg every time, with inducing pancreatic inflammation illness.Behind end 1 hour for applying caerulin, treatment group is taken orally low
(100mg/kg), in (200mg/kg), high (400mg/kg) dosage 3 acetyl-α, β masticinic acid, to study 3 acetyl-α, β cream
Fragrant acid is so carried out continuously the therapeutic effect of pancreatitis 3 days.
It draws materials after allowing mouse survival 24 hours after experiment to pancreatic tissue, is put into formalin solution and is consolidated
It is fixed.Microsection manufacture, the dyeing of HE slice and pathological section scoring are carried out after 3 days.
As shown in figs. 1-11, wherein Fig. 1-10 is the mice pancreatic tissue HE dye obtained by above-mentioned experiment to experimental result
The slice picture of color 100*, 400* under light microscopic.Fig. 1-2 is 100*, 400* photo of control group C, as can be seen from the figure right
Clear in structure according to group pancreatic tissue, acinus leaflet is complete, and medium has no pathological change without exudation；Fig. 3-4 is model group M's
100*, 400* photo, as can be seen from the figure acinar cells has large stretch of vacuolization, oedema and cell in model group pancreatic tissue
Spacing becomes larger, and cell infiltration is obvious, accidental acinar cells necrosis；Fig. 5-10 is (basic, normal, high) treatment group 100*, 400* photograph
Piece, as can be seen from the figure 3 acetyl-α, pancreatic tissue is visible in β masticinic acid treatment group few vacuolization, with model group phase
Than oedema, relatively light, iuntercellular is away from being obviously reduced, and is showed no cell infiltration and necrosis phenomena；Pancreatic tissue damage obviously changes
Kind, injury of pancreas is apparently higher than control group and 3 acetyl-α, β masticinic acid treatment group in the HE stained slice of model group.
It shows and compares from there through slice light microscopic, judge that 3 acetyl-α, β masticinic acid have certain suppression to pancreatitis illness
Production is used.
In addition histological scores, every slice are carried out to mice pancreatic tissue under double blind state using Rongione method
4 visuals field of random detection, average mark are exactly the pathology damage scoring of this slice.By being carried out to each experimental group pathological section
It observes, summarize, the pathological score histogram of Figure 11 has been made using 1 pathological score standard of table.
1 Rongione pancreatic tissue pathological score standard of table
In Figure 11, the Pancreas pathology (scoring is below 3) of model group M is apparently higher than control group C (scoring is 0), by calculating p
< 0.01, there is significant difference.Model group M and 3 acetyl-α, β masticinic acid treatment group D, Z (scoring 2 or less), by calculate p <
0.1, it may have difference.
3 acetyl-α, β masticinic acid is disclosed thus according to pancreatic tissue pathological score to make pancreatitis with good treatment
With.
Embodiment 2
This experimental example passes through control group C, model group M, 3 acetyl-α, β masticinic acid low dose therapy group D, 3 acetyl-α, β masticinic acid
Middle dosage treatment group Z, 3 acetyl-α, β masticinic acid high-dose therapy group H carry out animal experiment in vivo, form sediment in serum after test experience
The active situation of powder enzyme studies 3 acetyl-α, therapeutic effect of the β masticinic acid to pancreatitis with this.
In this experimental example, the preparation of pancreatitis animal model and 3 are carried out using the C57BL/6 mouse of weight about 20 ± 2g
Acetyl-α, β masticinic acid Experiment on therapy, experiment mice are tested in the germfree animal of constant temperature (22-26 DEG C), humidity (55-60%)
It is raised in room, raises mouse with normal solid feed and water, adapt it to 1 week, all experiment in vivo are according to the animal of regulation
Nursing and guide for use carry out, using the fabulous caerulin inducing mouse pancreatitis illness of reproducibility.
Experiment stops supplying feed to all mouse for first 16 hours, and since experiment, control group is with 1 hour interval through abdomen
5 physiological saline of intracavitary application, each 0.2mL.Except for the control, remaining mouse is with 1 hour interval through 5 rain of intraperitoneal application
Frog peptide, 70 μ g/kg every time, with inducing pancreatic inflammation illness.After 1 hour for applying caerulin, treatment group is taken orally low
(100mg/kg), in (200mg/kg), high (400mg/kg) dosage 3 acetyl-α, β masticinic acid, to study 3 acetyl-α, β cream
Fragrant acid is so carried out continuously the therapeutic effect of pancreatitis 3 days.
It allows the mouse survival to win the eyeball of mouse after 24 hours after experiment, serum is taken to each experimental group respectively
It is stored in spare in -80 DEG C of refrigerators.
The detection of amylase in serum: serum takes out from -80 DEG C of refrigerators, and room temperature is melted, and illustrates to be grasped according to kit
Make: 1. control group serum samples dilute 50 times, and model group serum sample dilutes 100 times, 3 acetyl-α, β masticinic acid treatment group blood
Clear 300 times of Sample Dilution.
2. taking pipe 16,600 μ L shell, the substrate buffer solution (using preceding 37 DEG C of pre-temperature 5min) of 50 μ L is added, by each group blood
10 μ L of final proof sheet is added in corresponding shell pipe, and blank tube not react 7.5 minutes in 37 DEG C of constant temperature incubators by reagent adding, mixing.
3. 50 μ L iodine application liquid are added into each shell pipe after incubator takes out.
4. control group, model group and elemi eleostearic acid treatment group are separately added into 300 μ L distilled waters, 310 μ L are added in blank tube
Distilled water.
5. each shell pipe mixes, and respectively takes 100 μ L to be added in 96 orifice plates, wavelength 660nm reads absorbance value.
6. drawing amylase activity box figure according to each experimental group absorbance value.
Figure 12 shows the box figure of amylase activity in this experimental example serum, shows the starch that different experiments group detects
Enzymatic activity expresses degree.It can be seen from the figure that control group C has statistical significance #, p < 0.5, explanation compared with model group M
Amylase activity in caerulin model group dramatically increases, and meaning induces pancreatitis；3 acetyl-α, β masticinic acid low dose therapy
Group D, 3 acetyl-α, β masticinic acid middle dosage treatment group Z, 3 acetyl-α, β masticinic acid high-dose therapy group H have compared with the control group
Amylase activity significantly reduces in the significant difference * * acetyl of *, p < 0.01,3-α, β masticinic acid treatment group.
Degree comparison is expressed by amylase activity, illustrates that 3 acetyl-α, β masticinic acid are inhibited to pancreatitis.
3 pancreatitis of embodiment induces activated immune cell, aggravates injury of pancreas, and then by including inflammatory cytokine
Various humoral factor inducing systemic organ damages.Immune cell activated causes most to represent involved in inflammatory reaction in pancreas
The factor of property is TNF-α, Interleukin -1β (IL-1 β) and interleukin-6 (IL-6).In the case where pancreatitis occurs, serum IL-
6 and TNF-α raised.This experimental example passes through control group C, model group M, 3 acetyl-α, β masticinic acid low dose therapy group D, 3
Acetyl-α, β masticinic acid middle dosage treatment group Z, 3 acetyl-α, β masticinic acid high-dose therapy group H carry out animal experiment in vivo, detection
TNF-α, the content of interleukin-6 (IL-6) in pancreatic tissue study 3 acetyl-α with this, β masticinic acid makees the treatment of pancreatitis
With.
In this experimental example, the preparation of pancreatitis animal model and 3 are carried out using the C57BL/6 mouse of weight about 20 ± 2g
Acetyl-α, β masticinic acid Experiment on therapy, experiment mice are tested in the germfree animal of constant temperature (22-26 DEG C), humidity (55-60%)
It is raised in room, raises mouse with normal solid feed and water, adapt it to 1 week, all experiment in vivo are according to the animal of regulation
Nursing and guide for use carry out, using the fabulous caerulin inducing mouse pancreatitis illness of reproducibility.
Experiment stops supplying feed to all mouse for first 16 hours, and since experiment, control group is with 1 hour interval through abdomen
5 physiological saline of intracavitary application, each 0.2mL.Except for the control, remaining mouse is with 1 hour interval through 5 rain of intraperitoneal application
Frog peptide, 70 μ g/kg every time, with inducing pancreatic inflammation illness.1 hour after application caerulin, treatment group is taken orally low
(100mg/kg), in (200mg/kg), high (400mg/kg) dosage 3 acetyl-α, β masticinic acid, to study 3 acetyl-α, β cream
Fragrant acid is so carried out continuously the therapeutic effect of pancreatitis 3 days.
It allows the mouse survival to be drawn materials after 24 hours to pancreatic tissue after experiment, is stored in standby in -80 DEG C of refrigerators
With.
Pancreatic tissue is crushed with liquid nitrogen grinding, adds protein lysate in placing 30min, 4 DEG C of 12000rpm/min on ice
15min takes supernatant.Protein quantification is carried out using BCA method, keeps its Tissue protein concentration consistent, it is spare to be placed in 4 DEG C of refrigerators.
TNF-α, IL-6 content concrete operation step in pancreatic tissue homogenate: 1, Preparatory work of experiment work are measured by ELISA method
Make: in advance taking out coated antibody, coated antibody dilution and the standard items in kit from refrigerator, balance to room temperature
(18-25 DEG C) cannot directly be dissolved at 37 DEG C.
(1) prepare coated antibody: take out coated antibody (250 ×), with coated antibody diluted to 1 ×, current phase
Match.
(2) it prepares cleaning solution: 25mL, 20 × PBS being diluted to 500mL with 475mL pure water, and 20% Tween is added
1.25mL matching while using.
(3) prepare detection antibody: take out detection antibody (250 ×), with ELISA diluted to 1 ×, current matching.
(4) prepare Avidin-HRP enzyme: taking out Avidin-HRP enzyme (250 ×), with ELISA diluted to 1 ×, it is existing
With matching.
(5) standard items are prepared: taking out 1 standard items freeze-dried powder, 1mL deionized water is added with 1mL syringe in room temperature, slightly
It rocks, room temperature 15min, mixes.Matching while using.
(6) standard solution is prepared:
1. TNF-α standard items: successively multiple proportions with ELISA dilution dilution is respectively obtained 1000,500,250,125,62.5,
31.2, eight 15.6,0pg/mL concentration.
2. IL-6 standard items: successively multiple proportions with ELISA dilution dilution is respectively obtained 500,250,125,62.5,
31.2,15.6, eight 8.3,0pg/mL concentration.
2, concrete operation step:
(1) add coated antibody: 100 μ L being added in 96 hole elisa Plates, ELISA Plate adds overlay film, and 4 DEG C overnight.
(2) board-washing: abandoning liquid, and 300 hole μ L/ cleaning solutions impregnate 1min, discard liquid in hole, dries.
(3) add ELISA dilution: 200 holes μ L/, overlay film is added on ELISA Plate, 1 hour (4) board-washing: room temperature abandons liquid, 300 μ
The hole L/ cleaning solution impregnates 1min, discards liquid in hole, dries, is repeated 2 times.
(5) it is loaded: sequentially adding 100 each concentration standards of μ L, remaining hole is added 100 μ L samples to be tested, adds on ELISA Plate and cover
Film, room temperature, 2 hours.
(6) board-washing: abandoning liquid, and 300 hole μ L/ cleaning solutions impregnate 1min, discard liquid in hole, dries, is repeated 3 times.
(7) plus detection antibody: it is added 100 μ L in 96 hole elisa Plates, ELISA Plate adds overlay film, room temperature, and 1 hour.
(8) board-washing: abandoning liquid, and 300 hole μ L/ cleaning solutions impregnate 1min, discard liquid in hole, dries, is repeated 5 times.
(9) add Avidin-HRP enzyme: 100 μ L being added in 96 hole elisa Plates, ELISA Plate adds overlay film, room temperature, 30min.
(10) board-washing: abandoning liquid, and 300 hole μ L/ cleaning solutions impregnate 1min, discard liquid in hole, dries, is repeated 7 times.
(11) add color developing agent and terminate liquid: 100 holes μ L/, room temperature, 5-10min.When standard items first four gradient blue,
At once plus 50 hole μ L/ of terminate liquid, blue switch to yellow by blue.
(12) microplate reader detects the optical density (O.D value) in every hole at 450nm wavelength.
3, result judgement
Standard curve is drawn according to standard items, using standard concentration as abscissa, O.D value is ordinate, with the connection of smooth line
Each coordinate points.Its concentration is calculated on standard curve by the O.D value of sample.
Figure 13 shows the expression of this experimental example serum IL-6 content, and abscissa is respectively control group C, model group M, 3 second
Acyl-α, β masticinic acid treatment group low dose group D, 3 acetyl-α, β masticinic acid treatment group middle dose group Z, 3 acetyl-α, β masticinic acid are controlled
Treatment group high dose group H, ordinate are interleukin-6 concentration value.
It can be seen that 3 acetyl-α, β masticinic acid have inhibiting effect to the expression of inflammatory mediator interleukin-6.
Figure 14 shows the expression of this experimental example TNF-α content, and abscissa is respectively control group C, model group M, 3 acetyl-α, β
Masticinic acid treatment group low dose group D, 3 acetyl-α, β masticinic acid treatment group middle dose group Z, 3 acetyl-α, β masticinic acid treatment group are high
Dosage group H, ordinate are TNF-α concentration value.#, which represents normal group and model group ratio, has statistical significance, p < 0.5.* * generation
Table, which is normally organized, has statistical significance, p < 0.01 with 3 acetyl-α, β masticinic acid treatment group ratio.
It can be seen that 3 acetyl-α, β masticinic acid have inhibiting effect to the expression of inflammatory mediator TNF-α.
Embodiment 4
Mtt assay is a kind of method for detecting cell survival and growth.Its testing principle is that the succinic acid in living cells mitochondria is de-
Hydrogen enzyme can make exogenous MTT be reduced to bluish violet crystallization first a ceremonial jade-ladle, used in libation (Formazan) of water-insoluble and be deposited in cell, and
Dead cell is without this function.Dimethyl sulfoxide (DMSO) can dissolve the first a ceremonial jade-ladle, used in libation in cell, with enzyme-linked immunosorbent assay instrument in 490nm wavelength
Place measures its absorbance value, can reflect living cells quantity indirectly.Within the scope of certain cell number, MTT crystallizes the amount to be formed and thin
Born of the same parents' number is directly proportional.This method be widely used in the Activity determinations of some bioactie agents, large-scale screening anti-tumor medicine,
Cell toxicity test and tumor radiosensitivity measurement etc..Its feature is high sensitivity, economy.
By RAW264.7 cell, secondary culture, collection logarithmic growth phase cell adjust the close of cell suspension according to a conventional method
Degree is 1 × 105/mL or so, and cell is placed in loading slot, using eight channel liquid-transfering guns, by cell inoculation in 96 orifice plates,
Every 100 μ L of hole, is placed in 37 DEG C, 5%CO2, cultivates in the cell incubator of saturated humidity.
After culture for 24 hours, cell adherent growth to 80%-90% is discarded supernatant, and the medicine of DMEM basal medium dissolution is added
Object: 3 acetyl-α, β masticinic acid (320 μM, 160 μM, 80 μM, 40 μM, 20 μM, 10 μM, 5 μM, 1 μM), every group sets 5 in parallel again
Hole, and 100 hole μ L/ DMEM high glycosyl basal culture medium of blank group is set to return to zero.It is placed in incubator after continuing culture for 24 hours, discards
The DMEM high glycosyl basal culture medium of 100 μ L 0.5mg/mLMTT is added in supernatant, every hole.
It after cultivating 4h in incubator, discards supernatant, bottom hole first a ceremonial jade-ladle, used in libation is avoided to lose as far as possible.Every hole is added 150 μ LDMSO, and 37
DEG C shaking table 55rpm shakes 10min, dissolves first a ceremonial jade-ladle, used in libation in hole.Absorbance is detected at wavelength 490nm, and is recorded result and (MTT is added
Operating process later should all be protected from light), box figure is made using record.
Figure 15 shows the relationship of 3 acetyl-α of this experimental example, β masticinic acid each concentration and absorbance value, * * * represent control group with
Give 3 acetyl-α, β masticinic acid ratio has significant difference, p < 0.01.
As can be seen from Figure 15,3 acetyl-α, β masticinic acid significantly affect cell viability generation when being greater than 20 μM, small
Cell viability is not influenced when 20 μM, provides experiment basis for next step experiment.
Embodiment 5
Lipopolysaccharides can induce the inflammatory model of RAW264.7 cell foundation, and NO content can rise in inflammation, this experimental example attempts
Use 3 acetyl-α, β masticinic acid as treatment anti-inflammatory drugs, 3 acetyl-α of detection, β masticinic acid make the inhibition of NO in inflammatory model
With.
By RAW264.7 cell, secondary culture, collection logarithmic growth phase cell adjust density to 3 × 105 according to a conventional method
A/mL, by cell inoculation in 24 orifice plates, every hole 1mL is placed in 37 DEG C, 5%CO2, trains in the cell incubator of saturated humidity
It supports.After cultivating 48h, cell adherent growth to 90% or more is discarded supernatant.
Control group C, model group (LPS) M, pharmaceutical intervention low concentration group D, concentration group Z, drug in pharmaceutical intervention is respectively set
Intervene high concentration group H and individually gives medicine group DD, every group of 4 holes (n=4).
DMEM high glycosyl basal culture medium is only added in control group C；Model group M is added in DMEM high glycosyl basal culture medium
0.5μg/mLLPS；3 acetyl-α, β masticinic acid and 0.5 that configuration concentration is 2 μM is added in pharmaceutical intervention low concentration group D in training base
3 acetyl-α, β masticinic acid and 0.5 μ that configuration concentration is 4 μM is added in μ g/mLLPS, concentration group Z in pharmaceutical intervention in training base
3 acetyl-α, β masticinic acid and 0.5 μ that configuration concentration is 8 μM is added in g/mL LPS, pharmaceutical intervention high concentration group H in training base
G/mLLPS individually gives medicine group DD 3 acetyl-α, β masticinic acid that 8 μM of DMEM high glycosyl basal culture medium is only added.
Group of cells supernatant is collected in culture afterwards for 24 hours.NO concentration is measured with Griess method.
Take Griess reagent standard (1mol) with DMEM high glycosyl basal culture medium dilute be configured to final concentration of 100 μM,
80μM,60μM,40μM,20μM,10μM,5μM,2μM,1μM.Various concentration standard items and cell conditioned medium are added by 50 holes μ L/
Then 96 orifice plates are being separately added into GriessI, GriessII, every hole 50Ul detects absorbance at microplate reader wavelength 540nm,
And calculate NO concentration in sample.
Figure 16 shows in this experimental example NO Concentration Testing in each experimental group, it can be seen from the figure that control group C and model group
(LPS) M is compared, and has significant difference；p<0.01.Pharmaceutical intervention low concentration group D compared with model group M, have difference, p <
0.05；Concentration group Z, pharmaceutical intervention high concentration group H have significant difference compared with model group M in pharmaceutical intervention；p<0.01；It is single
Solely give medicine group DD no difference compared with control group C.
Thus illustrate, lipopolysaccharides can promote cell NO content to significantly rise, 3 acetyl-α, β masticinic acid is administered alone will not
Cell NO content is influenced, in lipopolysaccharides and 3 acetyl-α, the mixing administration of β masticinic acid, 3 acetyl-α, β masticinic acid can significantly press down
The rising of cell NO content processed.Also 3 acetyl-α be can be regarded as, β masticinic acid can inhibit the development of inflammation, the suppression including pancreatitis
System.
Embodiment 6
Lipopolysaccharides can induce the inflammatory model of RAW264.7 cell foundation, IL-6 in inflammation, and TNF-α content can rise, this reality
It tests example to attempt to use 3 acetyl-α, β masticinic acid as treatment anti-inflammatory drugs, 3 acetyl-α of detection, β masticinic acid are in inflammatory model
IL-6, the inhibiting effect of TNF-α.
By RAW264.7 cell, secondary culture, collection logarithmic growth phase cell adjust density to 3 × 105 according to a conventional method
A/mL, by cell inoculation in 24 orifice plates, every hole 1mL is placed in 37 DEG C, 5%CO2, trains in the cell incubator of saturated humidity
It supports.After cultivating 48h, cell adherent growth to 90% or more is discarded supernatant.
Control group C, model group (LPS) M, pharmaceutical intervention low concentration group D, concentration group Z, drug in pharmaceutical intervention is respectively set
Intervene high concentration group H and individually gives medicine group DD, every group of 4 holes (n=4).
DMEM high glycosyl basal culture medium is only added in control group C；Model group M is added in DMEM high glycosyl basal culture medium
0.5μg/mLLPS；3 acetyl-α, β masticinic acid and 0.5 that configuration concentration is 2 μM is added in pharmaceutical intervention low concentration group D in training base
3 acetyl-α, β masticinic acid and 0.5 μ that configuration concentration is 4 μM is added in μ g/mLLPS, concentration group Z in pharmaceutical intervention in training base
3 acetyl-α, β masticinic acid and 0.5 μ that configuration concentration is 8 μM is added in g/mL LPS, pharmaceutical intervention high concentration group H in training base
G/mLLPS individually gives medicine group DD 3 acetyl-α, β masticinic acid that 8 μM of DMEM high glycosyl basal culture medium is only added.
Group of cells supernatant is collected in culture afterwards for 24 hours.IL-6, TNF-α concentration are measured with Elisa method.
1, Preparatory work of experiment works: in advance by coated antibody, coated antibody dilution and the standard items in kit from refrigerator
Middle taking-up, balance to room temperature (18-25 DEG C) cannot directly be dissolved at 37 DEG C.
(1) prepare coated antibody: take out coated antibody (250 ×), with coated antibody diluted to 1 ×, current phase
Match.
(2) it prepares cleaning solution: 25mL, 20 × PBS being diluted to 500mL with 475mL pure water, and 20% Tween is added
1.25mL matching while using.
(3) prepare detection antibody: take out detection antibody (250 ×), with ELISA diluted to 1 ×, current matching.
(4) prepare Avidin-HRP enzyme: taking out Avidin-HRP enzyme (250 ×), with ELISA diluted to 1 ×, it is existing
With matching.
(5) standard items are prepared: taking out 1 standard items freeze-dried powder, 1mL deionized water is added with 1mL syringe in room temperature, slightly
It rocks, room temperature 15min, mixes.Matching while using.
(6) standard solution is prepared:
1. TNF-α standard items: successively multiple proportions with ELISA dilution dilution is respectively obtained 1000,500,250,125,62.5,
31.2, eight 15.6,0pg/mL concentration.
2. IL-6 standard items: successively multiple proportions with ELISA dilution dilution is respectively obtained 500,250,125,62.5,
31.2,15.6, eight 8.3,0pg/mL concentration.
2, concrete operation step:
(1) add coated antibody: 100 μ L being added in 96 hole elisa Plates, ELISA Plate adds overlay film, and 4 DEG C overnight.
(2) board-washing: abandoning liquid, and 300 hole μ L/ cleaning solutions impregnate 1min, discard liquid in hole, dries.
(3) add ELISA dilution: 200 holes μ L/, add overlay film, room temperature, 1h on ELISA Plate.
(4) board-washing: abandoning liquid, and 300 hole μ L/ cleaning solutions impregnate 1min, discard liquid in hole, dries, is repeated 2 times.
(5) it is loaded: sequentially adding 100 each concentration standards of μ L, remaining hole is added 100 μ L samples to be tested, adds on ELISA Plate and cover
Film, room temperature, 2h.
(6) board-washing: abandoning liquid, and 300 hole μ L/ cleaning solutions impregnate 1min, discard liquid in hole, dries, is repeated 3 times.
(7) it plus detects antibody: 100 μ L being added in 96 hole elisa Plates, ELISA Plate adds overlay film, room temperature, 1h.
(8) board-washing: abandoning liquid, and 300 hole μ L/ cleaning solutions impregnate 1min, discard liquid in hole, dries, is repeated 5 times.
(9) add Avidin-HRP enzyme: 100 μ L being added in 96 hole elisa Plates, ELISA Plate adds overlay film, room temperature, 30min.
(10) board-washing: abandoning liquid, and 300 hole μ L/ cleaning solutions impregnate 1min, discard liquid in hole, dries, is repeated 7 times.
(11) add color developing agent and terminate liquid: 100 holes μ L/, room temperature, 5-10min.When standard items first four gradient blue,
At once plus 50 hole μ L/ of terminate liquid, blue switch to yellow by blue.
(12) microplate reader detects the optical density (O.D value) in every hole at 450nm wavelength.
3, result judgement
Standard curve is drawn according to standard items, using standard concentration as abscissa, O.D value is ordinate, with the connection of smooth line
Each coordinate points.Its concentration is calculated on standard curve by the O.D value of sample.
Figure 17 shows in this experimental example IL-6 Concentration Testing in each experimental group, it can be seen from the figure that control group C and model
Group (LPS) M is compared, and has significant difference；p<0.01.Pharmaceutical intervention low concentration group D is statistically significant compared with model group M；p
<0.5；Concentration group Z has difference compared with model group M in pharmaceutical intervention；p<0.1；, pharmaceutical intervention high concentration group H and model group
M is compared to statistically significant；p<0.5；It is statistically significant compared with blank group C individually to give medicine group DD；p<0.5.
Thus illustrate, lipopolysaccharides can promote cell IL-6 content to significantly rise, and 3 acetyl-α, β masticinic acid are administered alone not
It will affect cell IL-6 content, in lipopolysaccharides and 3 acetyl-α, the mixing administration of β masticinic acid, 3 acetyl-α, β masticinic acid can be shown
Write the rising for inhibiting cell IL-6 content.Also 3 acetyl-α be can be regarded as, β masticinic acid can inhibit the development of inflammation, including pancreas
Scorching inhibition.
Figure 18 shows in this experimental example TNF-α Concentration Testing in each experimental group, it can be seen from the figure that blank group C and mould
Type group (LPS) M is compared, and has significant difference；p<0.01.Concentration group Z, drug are dry in pharmaceutical intervention low concentration group D, pharmaceutical intervention
Pre- high concentration group H has significant difference compared with model group M；p<0.01；Medicine group DD is individually given not have compared with blank group C
It is variant.
Thus illustrate, lipopolysaccharides can promote cell TNF-α content to significantly rise, and 3 acetyl-α, β masticinic acid are administered alone
It will not influence cell TNF-α content, in lipopolysaccharides and 3 acetyl-α, the mixing administration of β masticinic acid, 3 acetyl-α, β masticinic acid can be with
Significantly inhibit the rising of cell TNF-α content.Also 3 acetyl-α be can be regarded as, β masticinic acid can inhibit the development of inflammation, including
The inhibition of pancreatitis.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to
So be possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features into
Row equivalent replacement；And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (10)
- The application of 1.3 acetyl-α, β masticinic acid in the drug of preparation prevention and/or treatment pancreatitis.
- 2. a kind of for preventing and/or treating the drug of pancreatitis, which is characterized in that the drug includes 3 acetyl-α, β olibanum Acid.
- 3. drug according to claim 2, which is characterized in that the drug further includes pharmaceutically acceptable auxiliary material.
- 4. drug according to claim 2, which is characterized in that the dosage form of the drug includes oral preparation or injection system Agent.
- 5. drug according to claim 4, which is characterized in that the oral preparation include tablet, capsule, granule, Pill, syrup, oral solution, oral suspensions or Orally taken emulsion.
- 6. drug according to claim 4, which is characterized in that the ejection preparation includes injection or powder-injection.
- 7. according to the described in any item drugs of claim 2-6, which is characterized in that the proportion of the drug is 1:1-1:10.
- 8. according to the described in any item drugs of claim 2-6, which is characterized in that the proportion of the drug is 1:1-10:1.
- 9. according to the described in any item drugs of claim 2-6, which is characterized in that effective dosage of the drug is 50- 500mg/kg/ days.
- 10. application according to claim 1 or drug as claimed in claim 2, which is characterized in that the pancreatitis includes Acute pancreatitis and/or chronic pancreatitis.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114591447A (en) * | 2022-01-26 | 2022-06-07 | 沈阳药科大学 | Polysaccharide compound separated from frankincense or vinegar frankincense and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013537894A (en) * | 2010-09-22 | 2013-10-07 | フラウンホフェル−ゲゼルシャフト ツ−ル フォルダルング デル アンゲバンドテン フォルシュング エー．ファウ． | Use of boswellic acid for the prevention and / or treatment of damage and / or inflammation of the islets of Langerhans |
| CN108653296A (en) * | 2018-06-25 | 2018-10-16 | 天津中医药大学 | The application of elemi eleostearic acid and the drug for treating pancreatitis |
-
2019
- 2019-04-18 CN CN201910313859.0A patent/CN110169971A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013537894A (en) * | 2010-09-22 | 2013-10-07 | フラウンホフェル−ゲゼルシャフト ツ−ル フォルダルング デル アンゲバンドテン フォルシュング エー．ファウ． | Use of boswellic acid for the prevention and / or treatment of damage and / or inflammation of the islets of Langerhans |
| CN108653296A (en) * | 2018-06-25 | 2018-10-16 | 天津中医药大学 | The application of elemi eleostearic acid and the drug for treating pancreatitis |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114591447A (en) * | 2022-01-26 | 2022-06-07 | 沈阳药科大学 | Polysaccharide compound separated from frankincense or vinegar frankincense and preparation method and application thereof |
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