CN103351307A - 2-(butyryloxy)-5-amino benzoic acid, and preparation method and application thereof - Google Patents
2-(butyryloxy)-5-amino benzoic acid, and preparation method and application thereof Download PDFInfo
- Publication number
- CN103351307A CN103351307A CN2013102324602A CN201310232460A CN103351307A CN 103351307 A CN103351307 A CN 103351307A CN 2013102324602 A CN2013102324602 A CN 2013102324602A CN 201310232460 A CN201310232460 A CN 201310232460A CN 103351307 A CN103351307 A CN 103351307A
- Authority
- CN
- China
- Prior art keywords
- acid
- butyryl acyloxy
- benzaminic
- preparation
- butyryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses 2-(butyryloxy)-5-amino benzoic acid, and a preparation method and an application thereof. According to the invention, 5-nitro salicylic acid and butyric acid are subjected to an esterification reaction; and nitro groups are reduced into amino groups, such that 2-(butyryloxy)-5-amino benzoic acid is obtained. When 2-(butyryloxy)-5-amino benzoic acid is orally taken and enters colon, 2-(butyryloxy)-5-amino benzoic acid can be degraded and 5-aminosalicylic acid and butyric acid can be released. The two acts upon a colonic lesion site together, and provide treatment effects.
Description
Technical field
The invention belongs to the medicament for resisting ulcerative colitis technical field, relate to 2-(butyryl acyloxy)-5-benzaminic acid and its preparation method and application.
Background technology
Ulcerative colitis (ulcerative colitis, UC) at first was described as being different from the independently colonic inflammation disease of bacillary dysentery by Wilks in 1859.It is a kind of chronic nonspecific inflammation of mainly involving rectum, mucous membrane of colon, and clinical manifestation is mainly diarrhoea, stomachache, mucosanguineous feces etc.; Its pathological change is the tissue reaction of filling the air, and comprises that the non-opposite sex of holding such as ulceration, crypt abscess, polyangitis disease, goblet cell minimizing and all kinds cell infiltration show.Can occur with the various autoimmune disease, such as erythema nodosum, sacroiliitis, ankylosing spondylitis, sclerosing cholangitis, autoimmune hemolytic anemia etc.Course of disease protracted course of disease reaches the more than ten years, even decades and the possibility of canceration is arranged.Its sickness rate is about 3～14.3/10 ten thousand in American-European countries, China over nearly 10 years case surpass 20,000.The epidemiologic data prompting, the sickness rate of UC has the trend that increases year by year at home and abroad.This disease cause and onset of disease mechanism is still not very clear; Be difficult to cure, very easily recur; The course of disease is tediously long, has a strong impact on patient body Health and Living quality, is classified as one of modern difficult treatment by the World Health Organization.
Summary of the invention
The problem that the present invention solves is to provide a kind of 2-(butyryl acyloxy)-5-benzaminic acid and preparation method thereof and for the preparation of the pharmaceutical use for the treatment of ulcerative colitis.
The present invention is achieved through the following technical solutions:
A kind of compound, this compound are 2-(butyryl acyloxy)-5-benzaminic acid, and its structural formula is:
The preparation method of compound 2-(butyryl acyloxy)-5-benzaminic acid comprises following operation:
5-NITROSALICYLIC ACID and butanic acid are carried out esterification, and then be amino with nitroreduction, obtain 2-(butyryl acyloxy)-5-benzaminic acid.
The preparation method of compound 2-(butyryl acyloxy)-5-benzaminic acid may further comprise the steps:
1) hydroxyl with 5-NITROSALICYLIC ACID becomes ester with the carboxyl of butanic acid, preparation 2-(butyryl acyloxy)-5-nitrobenzoic acid;
2) hydrogenating reduction is amino with the nitroreduction in 2-(butyryl acyloxy)-5-nitrobenzoic acid, obtains 2-(butyryl acyloxy)-5-benzaminic acid.
The preparation method of described compound 2-(butyryl acyloxy)-5-benzaminic acid specifically may further comprise the steps:
1) with 5-NITROSALICYLIC ACID and butyryl oxide after the mixed in molar ratio according to 1:1～1.5, under sulphuric acid catalysis, heating reflux reaction 2～5h; Then adding benzene solubilizing reaction product after reaction is finished washes with water, collects organic phase, drying, and solvent evaporated obtains 2-(butyryl acyloxy)-5-nitrobenzoic acid;
2) 2-(butyryl acyloxy)-5-nitrobenzoic acid is dissolved in the methyl alcohol, under Pd/C catalysis, passes into H
2, hydrogenation 10～12h; Filtration after reaction is finished, with residue dissolving and be splined on silicagel column, carry out wash-out as elutriant, the collection product with the mixed solution of sherwood oil and ethyl acetate behind the filtrate evaporated under reduced pressure methyl alcohol, after steaming desolventizes, obtain 2-(butyryl acyloxy)-5-benzaminic acid.
Described sherwood oil and ethyl acetate are that the volume ratio according to 2:1～1.5 is mixed to get elutriant;
When collecting product, also 2-(butyryl acyloxy)-5-benzaminic acid is carried out following qualitative identification:
On the silica GF254 fluorescent plate, at sherwood oil: the volume ratio of ethyl acetate: acetic acid=2:1:0.02～0.05 is mixed as development system, and product shows a spot under the 365nm wavelength, and fluorescence is arranged, and the Rf value is 0.45.
The application of 2-(butyryl acyloxy)-5-benzaminic acid in the preparation medicament for resisting ulcerative colitis.
Described medicament for resisting ulcerative colitis is for lowering the medicine of mucosa injury exponential sum disease activity index.
Described medicament for resisting ulcerative colitis is for reducing the medicine of intestinal tissue MPO level.
Compared with prior art, the present invention has following useful technique effect:
2-provided by the invention (butyryl acyloxy)-5-benzaminic acid, to make up collaborative prodrug with treatment UC with 5-aminosalicylic acid and butyric acid, when it is oral enter colon after, be decomposed into 5-aminosalicylic acid and butyric acid, then the two acting in conjunction is in colon lesions position performance therapeutic action.
The preparation method of 2-provided by the invention (butyryl acyloxy)-5-benzaminic acid carries out esterification with 5-NITROSALICYLIC ACID and butyric acid, and then nitroreduction is obtained for amino; Determine the target compound structure by Fourier's infrared analysis, nucleus magnetic hydrogen spectrum analysis and mass spectroscopy.
2-provided by the invention (butyryl acyloxy)-5-benzaminic acid, should be in the preparation of medicament for resisting ulcerative colitis, 2-(butyryl acyloxy)-5-benzaminic acid can effectively lower mouse mucosa injury exponential sum and improve the DAI degree, reduces intestinal tissue MPO level; Compare with Sodium propanecarboxylate mixture control group with using 5-aminosalicylic acid, all be better than 5-aminosalicylic acid and Sodium propanecarboxylate mixture control group in a plurality of detection indexs and DAI index.
Description of drawings
Fig. 1 is that 2-(butyryl acyloxy)-5-benzaminic acid (5-A-B) is on the figure that affects of Mouse Weight variation;
Fig. 2 is that 2-(butyryl acyloxy)-5-benzaminic acid (5-A-B) is on the figure that affects of mouse DAI index variation;
Fig. 3 is that 2-(butyryl acyloxy)-5-benzaminic acid (5-A-B) is on the figure that affects of mouse weight index of the colon;
Fig. 4 is that 2-(butyryl acyloxy)-5-benzaminic acid (5-A-B) is on the figure that affects of mouse colonic mucosal injury index;
Fig. 5 is that 2-(butyryl acyloxy)-5-benzaminic acid (5-A-B) is on the figure that affects of the MPO of mouse colon activity.
Embodiment
The present invention is described in further detail below in conjunction with specific embodiment, and the explanation of the invention is not limited.
1, makes up collaborative prodrug: 2-(butyryl acyloxy)-5-benzaminic acid with 5-aminosalicylic acid and butanic acid
5-NITROSALICYLIC ACID and butanic acid are carried out esterification, and then be amino with nitroreduction, obtain 2-(butyryl acyloxy)-5-benzaminic acid, its structural formula is as follows:
2, the preparation of 2-(butyryl acyloxy)-5-benzaminic acid
May further comprise the steps:
1) hydroxyl with 5-NITROSALICYLIC ACID becomes ester with the carboxyl of butanic acid, preparation 2-(butyryl acyloxy)-5-nitrobenzoic acid;
2) hydrogenating reduction is amino with the nitroreduction in 2-(butyryl acyloxy)-5-nitrobenzoic acid, obtains 2-(butyryl acyloxy)-5-benzaminic acid.
Its synthetic route is as follows:
2.12-(butyryl acyloxy)-5-nitrobenzoic acid is synthetic
4.6g(26mmol) 5-NITROSALICYLIC ACID 6.17g(39mmol) butyryl oxide is heated to 189 ℃, add three vitriol oils, 189 ℃ of backflow 4h, add the benzene dissolving, wash with water 2 times, collect organic phase, drying, solvent evaporated gets 2-(butyryl acyloxy)-5-nitrobenzoic acid brown color oily matter.
Qualitative identification: at sherwood oil: under the development system that ethyl acetate: acetic acid=2mL:1mL:1 drips, show a spot on the silica GF254 fluorescent plate, the Rf value is 0.52.
2.22-(butyryl acyloxy)-5-benzaminic acid is synthetic
2.0g(7.9mmol) mixture of 2-(butyryl acyloxy)-5-nitrobenzoic acid is dissolved in the B30mL methyl alcohol, adds 100mg10%Pd/C, fills with H
2Balloon be connected in reaction flask by T-valve, hydrogenation, the reaction 12h.Filtering reacting liquid, reduction vaporization methyl alcohol are with silicagel column on the residue, and sherwood oil: ethyl acetate (2:1) is as eluent.Collect product, solvent evaporated under reduced pressure gets 2-(butyryl acyloxy)-5-benzaminic acid 1.11g.White powder; Productive rate is 63.3%.Its fusing point is 214.0 ℃.
Qualitative identification: at sherwood oil: under the development system that ethyl acetate: acetic acid=2mL:1mL:1 drips, the silica GF254 fluorescent plate shows a spot under the 365nm ultraviolet wavelength, and fluorescence is arranged, and the Rf value is 0.45.
The structure elucidation of 2-(butyryl acyloxy)-5-benzaminic acid:
1) Fourier's infrared spectra of 2-(butyryl acyloxy)-5-benzaminic acid
2962.46cm
-1, 2929.67cm
-1, 2875.67cm
-1Be respectively ν CH3-on 2-(butyryl acyloxy)-5-benzaminic acid butyryl radicals, ν-CH2-, the absorption peak of ν-CH2-; 1650.95cm
-1Be the stretching vibration peak of ester bond C=O key, 1189.10cm
-1The asymmetrical stretching vibration peak of ester bond C-O-C.
2) proton nmr spectra of 2-(butyryl acyloxy)-5-benzaminic acid
Proton nmr spectra (DMSO) ownership is as follows:
δ 0.9064 (t, 3H) is three hydrogen on the butyryl radicals α C, δ 1.6110 (m; 2H) be two hydrogen on the butyryl radicals β C, δ 2.2183 (t, 2H) is two hydrogen on the butyryl radicals γ C; δ 6.9083 (d; 1H), δ 7.6717 (d, 1H); δ 8.1065 (s; 1H) be respectively the chemical shift of benzene ring hydrogen, δ 9.8044 (s, 1H) is chemical shift hydrogeneous in the carboxyl.
3) 2-(butyryl acyloxy)-5-benzaminic acid mass spectrum:
MS(ESI)m/z223[M+H]
+。
In sum, this compound is 2-(butyryl acyloxy)-5-benzaminic acid.
3,5-A-B is to the therapeutic action of mouse TNBS colitis
3.1 the foundation of mouse TNBS colitis model
The mouse experiment chamber is conventional raises, and 48 mouse are divided into 4 groups immediately, 12 every group., weigh and record successively each group mouse label respectively with picric acid.Fasting 12h before the modeling freely drinks water.With the mouse of fasting 12h with the slight little anesthesia of ether, insert the mouse colonic with blunt nosed gavage pin per anum, head end is apart from anus approximately about 4cm, slowly inject volume fraction and be the 50% ethanolic soln 0.1ml of 2.5% TNBS, after keeping mouse to be inverted a downward posture 30s, put back to normal raising the in the cage; The Normal group mouse gives normal saline enema.Begin administration behind the modeling 24h.
3.2 experiment grouping and observation index
Normal group, model control group, 5-aminosalicylic acid and Sodium propanecarboxylate mixture (5-ASA+BA) control group and 2-(butyryl acyloxy)-5-benzaminic acid (5-A-B) group are established in experiment, gastric infusion, and be administered once every day, successive administration 5 days.Normal and model control group all gives 0.5% the CMC-Na aqueous solution of equivalent.5-aminosalicylic acid and Sodium propanecarboxylate mixture control group dosage are [100mg (5-ASA)+40mg (Sodium propanecarboxylate)] kg
-15-A-B dosage 146mgkg
-1After modeling the 6th day, the mouse anesthesia of fasting 12h to be put to death, back of the body position is fixing.Mouse is cut belly open, takes out total colectomy.Vertically cut off colon along mesentery, rinse out intestinal contents with cold saline, the situation of visual inspection colonic mucosal injury.
Colonic mucosal injury index standards of grading: 0 minute: not damaged; 1 minute: without ulcer, contrafluxion; 2 minutes: ulcer is arranged; 3 minutes: only a position existed ulcer and inflammation; 4 minutes: two a plurality of positions existed ulcer and inflammation; 5 minutes: ulcer surpassed 2cm.
Measure total colectomy length and weigh calculating weight index of the colon (total colectomy weight/total colectomy length).Get one in colonic pathological change position tissue ,-20 ℃ of preservations are measured MPO active.
Other observation index: 1) statistics is respectively organized the dead mouse situation; 2) observing Mouse Weight changes; 3) observe mouse disease activity index (Disease activity index, DAI), the DAI standards of grading see Table 1; Wherein stool in mice is occulted blood to measure and is adopted adjacent first benzidine method, and criterion sees Table 2.
Table 1 mouse DAI standards of grading
The adjacent first benzidine method of table 2 is measured fecal occult blood criterion
| The result | Phenomenon |
| Normally | Still do not develop the color after adding reagent 2min |
| Occult blood+ | After adding reagent 10s, just aobvious light blue, become gradually blue |
| Occult blood ++ | After adding reagent, just aobvious light blue, turn gradually blue brown |
| Occult blood +++ | Show immediately blue brown after adding reagent |
MPO determination of activity: adopt the dianisidine method.Get mouse colon and weigh, add the pH7.0PBS of 9 times of volumes, 4 ℃ of homogenate 30s, the centrifugal 30min of 12000rpm abandons supernatant liquor, takes off the HTAB solution of layer tissue 50mg adding 0.5%, 4 ℃ of homogenate 30s, the centrifugal 15min of 12000rpm condition.Get supernatant liquor 0.1m, add ODD solution 2.9ml, mixing in 460nm METHOD FOR CONTINUOUS DETERMINATION 3min, calculates per minute absorbancy changing value fast.Being defined in the amount that per minute under 25 ℃ of conditions decomposes 1 micromole's superoxide is a unit of enzyme activity.
The enzymic activity of 100 μ l sample tissue units is:
Annotate: 1molL
-1H
2O
2Absorbancy to change be 1.13 * 10
4So according to definition, 1 MPO of unit is 1 μ molL
-1H
2O
2Absorbance, be 1.13 * 10
-2
3.3 statistical analysis
Experimental data is with means standard deviation
Expression, statistical method adopts the t check analysis.There is statistical significance P＜0.05 for difference.
3.4 experimental result
1) on the impact of mouse survival situation: 12 of Normal group survivals, 7 of TNBS group survivals, 6 of 5-aminosalicylic acid and the survivals of Sodium propanecarboxylate mixture control group, 7 of 5-A-B group survivals.
2) impact that Mouse Weight is changed: each organizes the Mouse Weight result of variations as shown in Figure 1.Mouse Weight descends after the modeling, and body weight is gone up gradually after the pharmacological agent.5-A-B group Mouse Weight recovers the most obvious.
3) on the impact of mouse DAI index: mouse all bloody stool, just rare can occur after the TNBS modeling behind 24h, and movable, feed reduces the situations such as weight loss.Each DAI index variation of organizing mouse as shown in Figure 2, TNBS group mouse DAI index obviously raises, modeling is basicly stable after 3 days, the DAI index significantly reduces behind the drug treatment, 5-A-B is better than 5-aminosalicylic acid and Sodium propanecarboxylate mixture control group to the impact of DAI index.
4) on the impact of mouse weight index of the colon and colonic mucosal injury index
The mouse colon mucous hyperemia oedema occurs after the TNBS bowel lavage is processed, the intestines wall thickening, and there are necrosis and ulceration in the surface, compares with normal group, and the mucosa injury index of TNBS group significantly increases (P＜0.01) and shows that Mouse Ulcerative Colitis Model foundation is good; Compare the mucosa injury index of 5-A-B group significantly descend (P＜0.01) with TNBS group.It is downright bad that the saturating wall damage of colon appears in the part mouse, and there be hardening, distortion or narrow in various degree in enteron aisle.Colon contraction in length, its weight index of the colon significantly increase (P＜0.01), compare with the TNBS group, and the mouse weight index of the colon of administration group is to some extent decline (P＜0.05) all.The above results is referring to Fig. 3, Fig. 4.
Among Fig. 3, compare ##P＜0.01 with Normal group; Compare * * P＜0.01 with the modeling group;
Among Fig. 4, compare ##P＜0.01 with Normal group; Compare * P＜0.05 with the modeling group.
5) on the impact of MPO activity in the mouse colon
The mouse colon obviously raises because MPO in the colons such as inflammation, oedema, ulceration is active after the TNBS bowel lavage is processed.Compare active significantly increase (P＜0.01) of MPO in the TNBS group mouse colon with normal group; Compare active significantly descend (P＜0.01) of MPO in the 5-A-B group mouse colon with the TNBS group.Experimental result as shown in Figure 5.
Among Fig. 5, compare ##P＜0.01 with Normal group; Compare * * P＜0.01 with the modeling group; Compare Δ P＜0.05 with 5-ASA with BA mixing group.
To sum up, the synthetic route of the 2-that provides (butyryl acyloxy)-5-benzaminic acid simple, productive rate is high.In 2-(butyryl acyloxy)-5-benzaminic acid building-up process, meet light system meeting variable color, affect the result, therefore when filtering Pd/C, all operations must guarantee the lucifuge operation.
Synthetic product has carried out the research of preliminary anti-ulcerative colitis effect after determining structure by analysis.Select the mouse TNBS colitis model similar to acute human and active ulcerativ e colitis, and analyzed the therapeutic action of 2-(butyryl acyloxy)-5-benzaminic acid for ulcerative colitis.
Experimental result shows that 2-(butyryl acyloxy)-5-benzaminic acid can effectively lower mouse mucosa injury exponential sum and improve the DAI degree, reduces intestinal tissue MPO level.
The 2-(butyryl acyloxy) that the present invention will make up with 5-aminosalicylic acid and butyric acid-5-benzaminic acid, as collaborative prodrug with treatment UC, when it is oral enter colon after, the two acting in conjunction is brought into play therapeutic action in the colon lesions position; Compare with using simultaneously respectively 5-ASA, Sodium propanecarboxylate, all be better than ammonia fourth control group in a plurality of detection indexs and DAI index.
Many active oxygen metabolic products that studies confirm that are relevant with UC, and oxyradical mainly is present in neutrophil leucocyte, and inflammation can be induced Observation of Polymorphonuclear Leukocyte Oxidizing, produce a large amount of free radicals, cause cell membrane damage.TNBS induces colitis mucous membrane of colon neutrophil infiltration to increase, and produces a large amount of oxyradicals.Experimental result shows that TNBS induces colitis to have significant mucous membrane of colon oxidative damage, and through 2-(butyryl acyloxy)-5-benzaminic acid treatment, MDA content is than the obvious decline of model group in the colon, and GSH, SOD and GSH-Px level obviously raise.Prompting 2-(butyryl acyloxy)-5-benzaminic acid treatment ulcerative colitis may be relevant with its antioxygenation.
Claims (8)
1. a compound is characterized in that, this compound is 2-(butyryl acyloxy)-5-benzaminic acid, and its structural formula is:
2. the preparation method of compound 2-(butyryl acyloxy)-5-benzaminic acid is characterized in that, comprises following operation:
5-NITROSALICYLIC ACID and butanic acid are carried out esterification, and then be amino with nitroreduction, obtain 2-(butyryl acyloxy)-5-benzaminic acid.
3. the preparation method of compound 2-as claimed in claim 2 (butyryl acyloxy)-5-benzaminic acid is characterized in that, may further comprise the steps:
1) hydroxyl with 5-NITROSALICYLIC ACID becomes ester with the carboxyl of butanic acid, preparation 2-(butyryl acyloxy)-5-nitrobenzoic acid;
2) hydrogenating reduction is amino with the nitroreduction in 2-(butyryl acyloxy)-5-nitrobenzoic acid, obtains 2-(butyryl acyloxy)-5-benzaminic acid.
4. the preparation method of compound 2-as claimed in claim 3 (butyryl acyloxy)-5-benzaminic acid is characterized in that, specifically may further comprise the steps:
1) with 5-NITROSALICYLIC ACID and butyryl oxide after the mixed in molar ratio according to 1:1～1.5, under sulphuric acid catalysis, heating reflux reaction 2～5h; Then adding benzene solubilizing reaction product after reaction is finished washes with water, collects organic phase, drying, and solvent evaporated obtains 2-(butyryl acyloxy)-5-nitrobenzoic acid;
2) 2-(butyryl acyloxy)-5-nitrobenzoic acid is dissolved in the methyl alcohol, under Pd/C catalysis, passes into H
2, hydrogenation 10～12h; Filtration after reaction is finished with silicagel column on the residue, is carried out wash-out with the mixed solution of sherwood oil and ethyl acetate as elutriant behind the filtrate evaporated under reduced pressure methyl alcohol, collects product, after steaming desolventizes, obtains 2-(butyryl acyloxy)-5-benzaminic acid.
5. the preparation method of compound 2-as claimed in claim 4 (butyryl acyloxy)-5-benzaminic acid is characterized in that, described sherwood oil and ethyl acetate are that the volume ratio according to 2:1～1.5 is mixed to get elutriant;
When collecting product, also 2-(butyryl acyloxy)-5-benzaminic acid is carried out following qualitative identification:
On the silica GF254 fluorescent plate, at sherwood oil: the volume ratio of ethyl acetate: acetic acid=2:1:0.02～0.05 is mixed as development system, and product shows a spot under the 365nm wavelength, and fluorescence is arranged, and the Rf value is 0.45.
The application of (6.2-butyryl acyloxy)-5-benzaminic acid in the preparation medicament for resisting ulcerative colitis.
7. use as claimed in claim 6, it is characterized in that, described medicament for resisting ulcerative colitis is for lowering the medicine of mucosa injury exponential sum disease activity index.
8. use as claimed in claim 6, it is characterized in that, described medicament for resisting ulcerative colitis is for reducing the medicine of intestinal tissue MPO level.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102324602A CN103351307A (en) | 2013-06-09 | 2013-06-09 | 2-(butyryloxy)-5-amino benzoic acid, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102324602A CN103351307A (en) | 2013-06-09 | 2013-06-09 | 2-(butyryloxy)-5-amino benzoic acid, and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103351307A true CN103351307A (en) | 2013-10-16 |
Family
ID=49307745
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2013102324602A Pending CN103351307A (en) | 2013-06-09 | 2013-06-09 | 2-(butyryloxy)-5-amino benzoic acid, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103351307A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113398112A (en) * | 2021-06-17 | 2021-09-17 | 西南医科大学 | FA-mediated BBA/CM-beta-CD targeted drug delivery system, preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011148297A1 (en) * | 2010-05-24 | 2011-12-01 | Sofar Spa | Novel derivatives of mesalazine, process of their preparation and their use in the treatment of intestinal inflammatory diseases |
| WO2013007694A1 (en) * | 2011-07-11 | 2013-01-17 | Chemi S.P.A. | Prodrug of an anti-inflammatory active ingredient |
-
2013
- 2013-06-09 CN CN2013102324602A patent/CN103351307A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011148297A1 (en) * | 2010-05-24 | 2011-12-01 | Sofar Spa | Novel derivatives of mesalazine, process of their preparation and their use in the treatment of intestinal inflammatory diseases |
| WO2013007694A1 (en) * | 2011-07-11 | 2013-01-17 | Chemi S.P.A. | Prodrug of an anti-inflammatory active ingredient |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113398112A (en) * | 2021-06-17 | 2021-09-17 | 西南医科大学 | FA-mediated BBA/CM-beta-CD targeted drug delivery system, preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106916161B (en) | A kind of isoamylene radical chromocor and its purposes in preparing treatment diseases associated with inflammation drug | |
| CN107721959A (en) | Myricetin derivative and preparation method, and its application in treatment colitis, the conversion of preventing and treating colitis cancer and treatment colorectal cancer | |
| CN103417556A (en) | Applications of stilbene compounds | |
| CN109912600A (en) | It is a kind of prevent and treat pulmonary fibrosis imidazopyrimidine analog derivative and its application | |
| CN106749089A (en) | The preparation of new fluoro thiazole hydrazone compounds and its application in antineoplastic | |
| CN101703588A (en) | Shuanghuanglian in situ gel preparation and preparation method thereof | |
| CN103351307A (en) | 2-(butyryloxy)-5-amino benzoic acid, and preparation method and application thereof | |
| CN106008446A (en) | Xanthone derivatives, and preparation methods and use of xanthone and derivatives thereof | |
| CN105777685A (en) | Pharmaceutical composition of felodipine and pharmaceutical application of pharmaceutical composition | |
| CN101570528B (en) | Glycyrrhizin derivatives and preparation and use thereof | |
| CN103483220B (en) | Compound, preparation method thereof and applications of compound in prevention of ulcerative colitis | |
| CN103333084B (en) | 3,3'-azobis[6-(butanoyloxy)benzoic acid] and preparation method and application thereof | |
| JP2022089845A (en) | Medicament having action on anti-inflammatory bowel diseases, and preparation method therefor and applications thereof | |
| CN103664568B (en) | Dendrobium loddigesii Rolfe dimerization stilbene compound and its preparation method and application | |
| CN103483214B (en) | Compound, preparation method thereof and applications of compound in prevention of ulcerative colitis | |
| CN105198714B (en) | Red bayberry 01 derivatives and its preparation method and application | |
| CN109516903A (en) | One kind is for treating the stilbenes compound, preparation method and its application of hepatic injury | |
| CN103083289A (en) | Application of curcumin in preparation of medicine for treating psoriasis | |
| CN101313901B (en) | Medicine uses of herpetone | |
| CN106309442A (en) | Application of dehydrocorydaline in preparation of anti-inflammatory and analgesic drugs | |
| CN105294799B (en) | The class dipeptide compound of 3 β hydroxy-androstanes, 5 alkene 17 and its preparation and application | |
| CN100368413C (en) | Composition stable blood porphrin derivative, its preparation method and injection agent | |
| CN114948977B (en) | Application of dihydroflavonoid glycoside derivative in preparation of medicines for preventing and treating colonitis | |
| CN103922927B (en) | α-terpinenol derivant and its preparation method and application | |
| CN104277046B (en) | Metal complex of chlorophyll degradation product chlorin e 6 derivant and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20131016 |