CN105232506A - Application of butyric acid and salts thereof in preparation of medicine for treating or preventing gastric ulcer - Google Patents
Application of butyric acid and salts thereof in preparation of medicine for treating or preventing gastric ulcer Download PDFInfo
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- CN105232506A CN105232506A CN201510742100.6A CN201510742100A CN105232506A CN 105232506 A CN105232506 A CN 105232506A CN 201510742100 A CN201510742100 A CN 201510742100A CN 105232506 A CN105232506 A CN 105232506A
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Abstract
The invention discloses an application of butyric acid and salts thereof in the preparation of medicines for treating or preventing gastric ulcer, and belongs to the field of medicine. According to the above application, the butyric acid and salts thereof, through anti-inflammation and antioxidation, promote the secretion of gastric mucus, upregulate the apoptin BCL2, downregulate the pro-apoptotic protein Bax, have positive curative and preventive effects on gastric ulcer injury, effectively reduce falling, defect, atrophy and bleeding of the gastric mucous membrane, and have important significance to the prevention or treatment of gastric ulcer.
Description
Technical field
The present invention relates to field of medicaments, particularly a kind of butanoic acid and the application of salt in preparation treatment or preventing gastric ulcer medicine thereof.
Background technology
Gastric ulcer is a kind of Peptic Ulcers betided between cardia to pylorus, is a kind of clinical common gastric mucosal lesion class disease.If gastric ulcer can not be got timely medical treatment, be easy to bore a hole, hemorrhage, block and malignant change of benign gastric ulcer, bring considerable distress to patient's body and mind.Research shows, active oxygen directly can not only destroy cellularity, can also impel inflammatory cytokine, such as the generation of IL-1 β, TNF-α and IL-6, and this is the principal element causing gastric ulcer.And at present for clinical treatment many employings conventional medicine of gastric ulcer, such as proton pump inhibitor, histamine H2 receptor antagonist etc., its clinical efficacy is limited, therefore, provide a kind of newly, the medicine being used for treating gastric ulcer is very necessary.
Butanoic acid (butyricacid, BA) is by a kind of short-chain fatty acid of Microbe synthesis, and its main uses is the energy source as colon, in existing report, butanoic acid is used to treat inflammatory bowel disease, comprises acute radioactive rectitis, colitis and Crohn disease etc.And inventor studies discovery, butanoic acid, by antiinflammatory antioxidation, promotes stomach mucilage secretion, raises anti-apoptotic proteins BCL2, lowers pro apoptotic protein BAX, has positive treatment and preventive effect to gastric ulcer damage.Based on this, a kind of butanoic acid and the application of salt in preparation treatment or preventing gastric ulcer medicine thereof is provided to have great importance for prevention or treatment gastric ulcer.
Summary of the invention
Embodiment of the present invention technical problem to be solved is, provides a kind of butanoic acid and the application of salt in preparation treatment or preventing gastric ulcer medicine thereof.Concrete technical scheme is as follows:
Embodiments provide butanoic acid and the application of pharmaceutically acceptable salt in preparation prevention or treatment Gastric Ulcer Treatment thereof.
Particularly, described medicine comprises butanoic acid and/or its pharmaceutically acceptable salt for the treatment of effective dose.
Particularly, described salt is sodium butyrate.
Further, described medicine also comprises and described butanoic acid or compatible other medicine classes of its pharmaceutically acceptable salt and pharmaceutically acceptable carrier and/or adjuvant.
Particularly, described medicine is pharmaceutically acceptable dosage form.
Particularly, described dosage form is powder, injection, capsule, tablet or oral liquid.
Particularly, described gastric ulcer is ethanol injury gastric ulcer.
The beneficial effect that the technical scheme that the embodiment of the present invention provides is brought is:
Embodiments provide butanoic acid and the application of pharmaceutically acceptable salt in preparation prevention or treatment Gastric Ulcer Treatment thereof, inventor studies discovery, butanoic acid and salt thereof, by antiinflammatory antioxidation, promote stomach mucilage secretion, raise anti-apoptotic proteins BCL2, lower pro apoptotic protein BAX, to gastric ulcer damage, there is positive treatment and preventive effect, effectively alleviate gastric mucosa and come off, defect, atrophy and bleeding, have great importance for prevention or treatment gastric ulcer.
Accompanying drawing explanation
In order to be illustrated more clearly in the technical scheme in the embodiment of the present invention, below the accompanying drawing used required in describing embodiment is briefly described, apparently, accompanying drawing in the following describes is only some embodiments of the present invention, for those of ordinary skill in the art, under the prerequisite not paying creative work, other accompanying drawing can also be obtained according to these accompanying drawings.
Fig. 1-1 is each experimental mice gastric mucosa general form of providing of the embodiment of the present invention 1 and ulcer area form schematic diagram;
Fig. 1-2 is the ulcer index distribution schematic diagram in each experimental mice gastric ulcer region that the embodiment of the present invention 1 provides;
Fig. 2-1 is that the embodiment of the present invention 2 provides, and each experimental mice carries out the gastric tissue morphosis schematic diagram after HE dyeing;
Fig. 2-2 is the gastric tissue morphosis schematic diagrams after each experimental mice that the embodiment of the present invention 2 provides carries out PAS dyeing;
Fig. 3-1 is that the embodiment of the present invention 3 provides, mda content schematic diagram in normal group, ethanol group and the 4th sodium butyrate group Mouse Stomach tissue;
Fig. 3-2 is that the embodiment of the present invention 3 provides, content of protein carbonyl group schematic diagram in normal group, ethanol group and the 4th sodium butyrate group Mouse Stomach tissue;
Fig. 4-1 is that the embodiment of the present invention 4 provides, the expression schematic diagram of IL-1 β in normal group, ethanol group and the 4th sodium butyrate group Mouse Stomach tissue;
Fig. 4-2 is that the embodiment of the present invention 4 provides, the expression schematic diagram of TNF-α in normal group, ethanol group and the 4th sodium butyrate group Mouse Stomach tissue;
Fig. 4-3 is that the embodiment of the present invention 4 provides, the expression schematic diagram of IL-6 in normal group, ethanol group and the 4th sodium butyrate group Mouse Stomach tissue;
Fig. 5 is that the embodiment of the present invention 5 provides, normal group, ethanol group and the 4th sodium butyrate group mice coat of the stomach mucus changes of contents schematic diagram;
Fig. 6-1 is that the embodiment of the present invention is carried 6 and provided, BAX expression schematic diagram in normal group, ethanol group, the 4th sodium butyrate group Mouse Gastric Mucous Membrane;
Fig. 6-2 is that the embodiment of the present invention 6 provides, expression schematic diagram in normal group, ethanol group, the 4th sodium butyrate group Mouse Gastric Mucous Membrane.
Reference numeral represents respectively:
S normal group,
M ethanol group,
Bt1 first sodium butyrate group,
Bt2 second sodium butyrate group,
Bt3 the 3rd sodium butyrate group,
Bt4 the 4th sodium butyrate group,
Bt5 the 5th sodium butyrate group,
O omeprazole group.
Detailed description of the invention
Unless otherwise defined, all technical terms that the embodiment of the present invention is used all have the identical implication usually understood with those skilled in the art.Wherein, term used herein " treatment effective dose " is for needing the consumption of the medicine producing useful effect, " treatment effective dose " should can adjust and change according to practical situation, and finally determined by medical worker, its factor considered comprises the character and the order of severity etc. of the character of route of administration and preparation, the ordinary circumstance such as body weight, age of receiver and institute's disease therapy.
Embodiments provide butanoic acid and the application of pharmaceutically acceptable salt in preparation prevention or treatment Gastric Ulcer Treatment thereof.
Embodiments provide butanoic acid and the application of pharmaceutically acceptable salt in preparation prevention or treatment Gastric Ulcer Treatment thereof, inventor studies discovery, butanoic acid and salt thereof, by antiinflammatory antioxidation, promote stomach mucilage secretion, raise anti-apoptotic proteins BCL2, lower pro apoptotic protein BAX, to gastric ulcer damage, there is positive treatment and preventive effect, effectively alleviate gastric mucosa and come off, defect, atrophy and bleeding, have great importance for prevention or treatment gastric ulcer.
Particularly, this medicine comprises butanoic acid and/or its pharmaceutically acceptable salt for the treatment of effective dose.For example, this pharmaceutically acceptable butyrate can be sodium butyrate, calcium butyrate etc.
Further, this medicine also can comprise and butanoic acid or compatible other medicine classes of its pharmaceutically acceptable salt and pharmaceutically acceptable carrier and/or adjuvant.For example, " other medicine classes " herein refer to butanoic acid or its pharmaceutically acceptable butyrate compatible, butanoic acid or butyrate can not be made to occur neutralization, hydrolysis, the physical and chemical reactions such as damage inactivation, and with butanoic acid or butyrate synergism after, the medicine class of effect of butanoic acid or butyrate treatment gastric ulcer can be improved.And the pharmaceutical carrier that above-mentioned carrier can be commonly used for this area, such as chitosan, liposome, alginic acid, agar, fibrin, collagen protein and synthesis type high molecular polymerization carrier etc.Above-mentioned adjuvant is without physiologically active, do not affect pharmaceutical preparation active medicine curative effect, assay and stability, and main purpose facilitates the preparation of preparation and the material of clinical practice, for example, its starch, pregelatinized Starch, dextrin, sucrose, lactose, mannitol, microcrystalline Cellulose, calcium sulfate, calcium hydrogen phosphate, light magnesium oxide, calcium carbonate, dried starch, Sodium Hydroxymethyl Stalcs, low-substituted hydroxypropyl cellulose, gas-producing disintegrant, polyvinylpolypyrrolidone etc. can commonly used for this area.
Particularly, this medicine can be pharmaceutically acceptable dosage form, such as, be powder, injection, capsule, tablet or oral liquid etc.Correspondingly, according to the pharmaceutical dosage form of reality, the administering mode of this medicine is optional from suction, mouth blown, nasal administration, transbuccally administration, parenteral or rectally, local canalis spinalis administration etc.
Particularly, the receptor of the gastric ulcer described in the embodiment of the present invention is not only for the mankind, also can for animal, such as rat etc.
Particularly, the ethanol injury gastric ulcer that the embodiment of the present invention is caused by ethanol for mice has carried out butyrate treatment experiment, for making the object, technical solutions and advantages of the present invention clearly, below in conjunction with accompanying drawing, in the mode of specific embodiment, embodiment of the present invention is described further in detail.In following specific embodiment, the unreceipted condition person of involved operation, the condition of all conveniently condition or manufacturer's suggestion is carried out.Raw materials used unreceipted production firm and specification person are can by the conventional products of commercial acquisition.
Embodiment 1
1, by 32 BALB/c mouse random packet, obtain 8 groups of experimental grouies of mean allocation, and as followsly carry out modeling process:
Normal group: refer to the Normal group not carrying out any process;
Ethanol group: refer to and adopt ethanol modeling, but the matched group of intervening is carried out without any medicine;
First sodium butyrate group: refer to and gavage dosage with 50mg sodium butyrate/kg mice, after mouse gavaging sodium butyrate, then use ethanol modeling;
Second sodium butyrate group: refer to and gavage dosage with 100mg sodium butyrate/kg mice, after mouse gavaging sodium butyrate, then use ethanol modeling;
3rd sodium butyrate group: refer to and gavage dosage with 200mg sodium butyrate/kg mice, after mouse gavaging sodium butyrate, then use ethanol modeling;
4th sodium butyrate group: refer to and gavage dosage with 400mg sodium butyrate/kg mice, after mouse gavaging sodium butyrate, then use ethanol modeling;
5th sodium butyrate group: refer to and gavage dosage with 600mg sodium butyrate/kg mice, after mouse gavaging sodium butyrate, then use ethanol modeling;
Omeprazole group: refer to and gavage dosage with 20mg omeprazole/kg mice, after mouse gavaging omeprazole, then use ethanol modeling.
It will be appreciated by persons skilled in the art that above-mentioned employing ethanol modeling refers to adopts ethanol to cause mouse gastric ulcer, even if mice forms ethanol injury gastric ulcer.For each experimental mice above-mentioned, adopt the operating process of ethanol modeling and operation dosage to be consistent, with guarantee test result, there is comparability.Because the active component playing prevention or the effect for the treatment of gastric ulcer is butanoic acid root, so select sodium butyrate to carry out above-mentioned each modeling experiment at this.
2, operation process: after above-mentioned modeling terminates, cervical dislocation puts to death mice, open the abdominal cavity of mice, the stomach of mice is taken out, cut open along greater gastric curvature, exenterate, launch stomach, use filter paper suck dry moisture, observe the gastric ulcer situation of mice stomach and take pictures, then the whole stomach albumen (hereinafter referred to as pepsin) of technology to each experimental mice commonly used especially by this area has carried out quantitative test, lipid peroxidation detects, protein carbonyl detects, gastric tissue cytokine IL-1 β (interleukin-1 ' beta '), TNF-α (tumor necrosis factor-alpha), the evaluation of IL-6 (interleukin-6) and anti-apoptotic proteins BCL2, the mensuration of pro apoptotic protein BAX expression, and above-mentioned experiment the data obtained is added up to the treatment and preventive effect of evaluating butanoic acid and salt pair mouse gastric ulcer thereof.Wherein, the process of above-mentioned each test experiments can see embodiment 2-6, and due to above-mentioned each Foundation is experiment field common, so the embodiment of the present invention does not do very not concrete restriction to it at this.
The gastric mucosa general form of butanoic acid pretreatment on mice stomach and the impact of ulcer area form, its result as Figure 1-1, visible, the stomach of ethanol group mice is after ethanol modeling, and gastric mucosa presents large-area hemorrhage, and is feature along vascularity, wherein, some coat of the stomach has shrinkage, occurs streak change, and serious bleed site even presents black or kermesinus.And the first sodium butyrate group is to the mice of the 5th sodium butyrate group, after the sodium butyrate of its stomach through raising dosage gradually carries out preventative process, by the first sodium butyrate group to the 5th sodium butyrate group only, the gastric ulcer symptom of mice stomach alleviates gradually, its bleeding lesions obviously alleviates, when sodium butyrate gavage dosage >200mg/kg time, mice stomach gastric ulcer relief of symptoms is even more excellent compared with omeprazole group.
By adopting the stomach cardinal principle picture of IPP6.0 software analysis to each experimental mice to analyze, obtaining the gross area of ulcerative lesions and the area of whole gastric mucosa, and the two is done ratio, drawing ulcer index.About the gastric ulcer region of each experimental mice ulcer index as shown in Figure 1-2, visible, after sodium butyrate dosage is greater than 50mg/kg, the degree of injury of gastric mucosa comparatively ethanol group significantly alleviates, p<0.05 or p<0.01; Sodium butyrate dosage is more than after 200mg/kg, and its gastric mucosa injury comparatively omeprazole group also significantly alleviates, p<0.01.It can thus be appreciated that, by carrying out Prevention Processing to mouse gavaging sodium butyrate, the gastric ulcer symptom of mice obviously alleviates along with the increase gavaging dosage, when sodium butyrate gavage dosage >200mg/kg time, mice stomach gastric ulcer relief of symptoms is even more excellent compared with omeprazole group.
Embodiment 2
The present embodiment passes through each experimental mice gastric tissue pathological section mentioned in embodiment 1 and carries out HE dyeing and PAS dyeing, detect the symptom of mice stomach tissue gastric ulcer damage, wherein, it will be understood by those skilled in the art that, the above-mentioned gastric tissue to mice carries out HE dyeing and carries out PAS dyeing being the conventional technology in this area, and the embodiment of the present invention does not more specifically limit it at this.Fig. 2-1 shows and carries out HE dyeing (hematoxylin-eosinstaining to the gastric tissue of each group of mice, hematoxylin-eosin stains) after result, Fig. 2-2 shows and carries out the result after PAS dyeing (PeriodicAcid-Schiffstain, periodic acid Schiff stain) to the gastric tissue of each group of mice.As shown in Fig. 2-1 and Fig. 2-2, for ethanol group, mice coat of the stomach 4 is secondary roughly clear layer by layer, but there is obvious pathological change, clearly, downright bad mucosa comes off mucosal lesion in a large number, cause part gastric mucosa especially epithelium there is defect, atrophy phenomenon, body of gland is destroyed, having occurred the epithelial cells fragments come off in lumen of gland, also there is exception in the cell of gastric mucosa, and the dyeing of its endochylema shoals, visible transparence sky is dizzy, have also appeared the phenomenon of cell infiltration.For omeprazole group, the mucosal lesion degree of mice comparatively ethanol group obviously reduces, and mucosal epithelium is more complete, and body of gland is less destroyed, and arrangement is comparatively neat, the phenomenon of epithelial cell shedding also comparatively ethanol group obviously alleviate.For the first sodium butyrate group to the 5th sodium butyrate group, mucosal lesion degree comparatively ethanol group obviously reduces, mucosal epithelium is continuously more complete, the arrangement of body of gland is more neat, have no obvious damage, visible, effect and the omeprazole of sodium butyrate treatment gastric ulcer are quite even better, and are dose dependent when adopting sodium butyrate treatment gastric ulcer.
Embodiment 3
3.1) in each experimental mice pepsin of mentioning embodiment 1 of the present embodiment, malonaldehyde and content of protein carbonyl group measure, wherein, mda content measures and adopts thiobarbituricacidα-(TBA) method, according to malonaldehyde and TBA condensation, the red product formed has absorption maximum at 532nm place, obtains every milligram of albumen mda content (μm ol/gprot).
Specific operation process is as follows: get 10% gastric mucosa tissue homogenate 0.1ml, proceed as follows by malonaldehyde testing cassete description:
1. the preparation of TBA storage liquid: take appropriate TBA, prepares liquid with TBA and is mixed with the TBA storage liquid that mass concentration is 0.37%.
2. the preparation of malonaldehyde testing liquid: according to TBA diluent: TBA storage liquid: the proportions malonaldehyde testing liquid of antioxidant=150:50:3.
3. the dilution of standard substance: standard substance distilled water diluting to 1,2,5,10,20,50 μMs, for follow-up production standard curve.
4. blank tube preparation: add normal saline 0.1ml, malonaldehyde testing liquid 0.2ml; Mensuration control is standby: add tissue homogenate to be measured (10%) 0.1ml, malonaldehyde testing liquid 0.2ml; Standard regulation is standby: add the standard substance 0.1ml being diluted to each concentration respectively, malonaldehyde testing liquid 0.2ml.
5., after mixing, 100 DEG C or boiling water bath heat 15 minutes.Must note during heating avoiding liquid bumping to spill.
6. water-bath is cooled to room temperature, centrifugal 10 minutes of 1000g room temperature.Getting 200 microlitre supernatants joins in 96 orifice plates, measures absorbance subsequently by microplate reader at 532nm.
7. the calculating of mda content: directly calculate the molar concentration obtaining malonaldehyde according to standard curve, μm ol/g gastric tissue.
Experimental result as shown in figure 3-1, known, in 4th sodium butyrate group small mouse pepsin the content of malonaldehyde comparatively ethanol group be provided with significant significant difference (p<0.01), it can thus be appreciated that, after treated with sodium butyrate, in the pepsin of the 4th sodium butyrate group small mouse, the content of malonaldehyde obviously reduces, this shows to utilize butanoic acid to gavage pretreatment to mice, effectively can alleviate the gastric ulcer oxidative damage degree of mice.
3.2) mensuration for content of protein carbonyl group is then carried out as follows according to used kit description:
1. reagent one and gastric tissue are diluted with the volume ratio of 1:9, and homogenate in ice-water bath, the centrifugal 10min of 2500r/min, obtains the first supernatant.
2. get supernatant 450ul and add 50ul reagent two, room temperature places the centrifugal 10min of 10min, 1100r/min, obtains the second supernatant.
3. getting appropriate second supernatant, to be diluted to volumetric concentration be 0.5%, and be BCA with this and measure total protein concentration.
4. get residue supernatant, do content of protein carbonyl group and measure, operating procedure is specific as follows:
Whirlpool mixes, and by whole resolution of precipitate, with the centrifugal 15min of 12000r/min, get supernatant in 370nm place (ultraviolet), reagent six returns to zero, measures absorbance.Calculate Protein carbonyl content to specifications, and do ratio with total protein, draw the concentration of protein carbonyl group, unit is nmol/mg gastric tissue.
Experimental result as shown in figure 3-2, visible, in 4th sodium butyrate group Mouse Stomach albumen the content of protein carbonyl group comparatively ethanol group be provided with significant significant difference (p<0.01), it can thus be appreciated that, after treated with sodium butyrate, in the pepsin of the 4th sodium butyrate group small mouse, the content of protein carbonyl group obviously reduces, this shows to utilize butanoic acid to gavage pretreatment to mice, effectively can alleviate the oxidative damage of the gastric ulcer of mice.
Embodiment 4
The present embodiment adopts double-antibody sandwich ABC-ELISA method (avidinbiotincomplex-ELISA Avidin-Biotin compound ELISA), in each experimental mice gastric tissue mention embodiment 1, the expression of IL-1 β, TNF-α, IL-6 is tested, and carries out as follows according to the description of used kit:
1. sample diluent (1%BSA-carbonate buffer solution), cleaning mixture (0.02mol/LPH=7.4Tris-HCl-Tween20 solution) preparation.Again standard substance (HBsAg sterling) are diluted to suitable a series of gradient concentrations.
2. application of sample: every hole adds standard substance stomach function regulating tissue homogenate (by homogenate: normal saline=2:3 dilution) 100ul, Sptting plate is fully mixed rearmounted 37 DEG C 40 minutes.
3. wash plate: with cleaning mixture, Sptting plate is fully washed 5 times, on filter paper, print is dry.
4. every hole adds distilled water and first antibody working solution (biotinylated mAb) each 50ul (except blank).Sptting plate is fully mixed rearmounted 37 DEG C 20 minutes.And again carry out washing plate by the step 3. identical with step.
5. every hole adds enzyme labelled antibody working solution 100ul, Sptting plate is put 37 DEG C 10 minutes.And again carry out washing plate by the step 3. identical with step.
6. every hole adds substrate working solution (TMB solution) 100ul, puts 37 DEG C of dark places and reacts 15 minutes.Then every hole adds 100ul stop buffer (0.1mol/LH
2sO
4solution) mixing.
7. absorbance is surveyed by microplate reader at 450nm place.According to the standard substance absorbance production standard curve of a series of concentration, then carry out the calculating of IL-1 β, TNF-α, IL-6.
Experimental result is as shown in Fig. 4-1, Fig. 4-2, Fig. 4-3, gavage after pretreatment through sodium butyrate, TNF-α in 4th sodium butyrate group small mouse gastric tissue, the expression of IL-1 β and IL-6 all significantly reduces (p<0.01), (wherein in Fig. 4-1, Fig. 4-2 and Fig. 4-3, vertical coordinate represents that every mg gastric tissue contains the IL-6 of TNF-α and pg of IL-1 β, pg of specific ng respectively).This shows to utilize butanoic acid to gavage pretreatment to mice, effectively can alleviate the gastric ulcer symptom of mice.
Embodiment 5
The coat of the stomach mucus amount of the present embodiment to each experimental mice that embodiment 3 and embodiment 4 are mentioned detects, and detailed process is as described below:
1. scraping contains the gastric tissue of body of gland part and weighs, as sample.This sample with mass concentration be immediately 1% A Li Xinlan sodium acetate buffer (pH is 5.0) hatch.
2. by sucrose solution rinsing, unconjugated Alcian blue dyes is removed.
3. with MgCl
2the Alcian blue dyes that eluant solution combines.
4., after this eluent fully mixes with ethyl acetate, collected after centrifugation aqueous phase liquid, at 580nm wavelength place, measures absorbance.
5. production standard curve: the standard curve being drawn absorbance and A Li Xinlan concentration by the absorbance measuring the A Li Xinlan solution of the variable concentrations of configured in advance,
6. utilize this standard curve to calculate the amount of coat of the stomach in conjunction with A Li Xinlan (being called for short AB), do ratio with total mucosal protein quality, obtain unit concentration (ngAB/mg gastric tissue).
Experimental result is as shown in Figure 5, visible, and the coat of the stomach mucus amount compared with normal group of ethanol group mice significantly reduces (p < 0.01), and this also causes the mechanism of gastric ulcer to match with ethanol calcination.And through the mice of treated with sodium butyrate coat of the stomach mucus amount comparatively ethanol group significantly improve, even with normal group zero difference, this illustrates and gavages process in advance can improve coat of the stomach mucus protein content by carrying out butanoic acid to mice, alleviate the damage of the gastric mucosa that ethanol causes, effectively the generation of prevention mouse gastric ulcer.
Embodiment 6
The present embodiment carries out SABC test to BAX and BCL2 in the gastric tissue of each experimental mice that embodiment 3 and embodiment 4 are mentioned, primary antibodie concentration, by preliminary experiment, is defined as: BAX is 1:250 respectively; BCL2 is 5 μ g/ml.Concrete operation step is as follows:
1. roasting sheet: slide is put into roasting sheet 1.5h in the baking oven of 65 DEG C.
2. dewax: dimethylbenzene (I): 10min; Dimethylbenzene (II): 10min.
3. rehydration: 100% ethanol: 5min; 95% ethanol: 5min; 80% ethanol: 5min; 70% ethanol: 5min; 50% ethanol: 5min; Pure water is hatched: 5min.
4. antigen retrieval: citrate buffer slide being put into 0.01mol/L, then puts into after pressure cooker is heated to boiling and keeps 10min again, take out the citrate buffer being placed with slide.
5. immunoreation specific as follows shown in:
5.1, slide drips the H that mass concentration is 3%
2o
2, and put into wet box and hatch 15min;
5.2, PBS wash buffer 3 times, each 3min;
5.3, primary antibodie working solution is dripped, incubated at room 1.5h;
5.4, PBS wash buffer 3 times, each 3min;
5.5, dripping two resists in tissue, incubated at room 30min;
5.6, PBS wash buffer 3 times, each 5min;
5.7, drip diaminobenzidine (DAB) working solution of now joining, incubated at room, examines under a microscope, and uses distilled water cessation reaction when there is specific chromogenic;
5.8, haematoxylin redyes about 10S;
5.9, PBS returns indigo plant.
6. dewater: 50% ethanol: 5min; 70% ethanol: 5min; 80% ethanol: 5min; 95% ethanol: 5min; 100% ethanol: 5min.
7. transparent: dimethylbenzene (I): 3min; Dimethylbenzene (II): 3min; Dimethylbenzene (III): 3min.
8. sealing: resinene mounting.
9. result judges: often open section and choose 5 high power lens visuals field (× 200), and observation gastric mucosa Bax, BCL2 express degree.That is, the amplification of image shown in Fig. 6-1 and Fig. 6-2 is 200.
About BAX expression as in Figure 6-1, normal group Bax is expressed as the weak positive, is positioned at endochylema, and main integrated distribution is at mucous layer.The expression of ethanol group BAX is strong positive, apparently higher than normal group.And the expression of the 4th sodium butyrate group gastric mucosa BAX is far below ethanol group.
Represent about BCL2 expression such as 6-2: normal group BCL2 is expressed as the weak positive, is positioned at endochylema, main integrated distribution is at mucous layer.The expression compared with normal group of ethanol group raises a little to some extent, but is not clearly.And the 4th sodium butyrate group BCL2 expression significantly improves.
In sum, butanoic acid and butyrate are by antiinflammatory antioxidation, promote stomach mucilage secretion, upregulation of apoptosis protein B CL2, BAX, have positive treatment and preventive effect to gastric ulcer damage, effectively alleviate gastric mucosa to come off, defect, atrophy and bleeding, have great importance for prevention or treatment gastric ulcer.
The foregoing is only preferred embodiment of the present invention, not in order to limit the scope of the invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (7)
1. butanoic acid and the application of pharmaceutically acceptable salt in preparation prevention or treatment Gastric Ulcer Treatment thereof.
2. application according to claim 1, is characterized in that, described medicine comprises butanoic acid and/or its pharmaceutically acceptable salt for the treatment of effective dose.
3. application according to claim 2, is characterized in that, described salt is sodium butyrate.
4. application according to claim 2, is characterized in that, described medicine also comprises and described butanoic acid or compatible other medicine classes of its pharmaceutically acceptable salt and pharmaceutically acceptable carrier and/or adjuvant.
5. application according to claim 4, is characterized in that, described medicine is pharmaceutically acceptable dosage form.
6. application according to claim 5, is characterized in that, described dosage form is powder, injection, capsule, tablet or oral liquid.
7. the application according to any one of claim 1-6, is characterized in that, described gastric ulcer is ethanol injury gastric ulcer.
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| CN105769840A (en) * | 2016-04-01 | 2016-07-20 | 温州医科大学 | Application of acetic acid and salt thereof |
| CN105769840B (en) * | 2016-04-01 | 2018-06-29 | 温州医科大学 | The application of acetic acid and its salt |
| CN109758444A (en) * | 2019-03-27 | 2019-05-17 | 中国农业科学院特产研究所 | Application of the 2- methyl substituted fatty acid at anti-oxidant aspect |
| CN114796175A (en) * | 2022-06-13 | 2022-07-29 | 杭州市五云山医院(杭州市健康促进研究院) | Application of butyric acid and its salt in preparing medicine for treating cervical cancer |
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Application publication date: 20160113 |