CN1052472C - Acetyl-salicylic derivate combined with niacinamide and zinc - Google Patents
Acetyl-salicylic derivate combined with niacinamide and zinc Download PDFInfo
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- CN1052472C CN1052472C CN94111976A CN94111976A CN1052472C CN 1052472 C CN1052472 C CN 1052472C CN 94111976 A CN94111976 A CN 94111976A CN 94111976 A CN94111976 A CN 94111976A CN 1052472 C CN1052472 C CN 1052472C
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- zinc
- asprin
- niacinamide
- acetyl
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- 239000011701 zinc Substances 0.000 title claims abstract description 17
- 229910052725 zinc Inorganic materials 0.000 title claims abstract description 17
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 title claims abstract description 14
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 235000005152 nicotinamide Nutrition 0.000 title claims abstract description 13
- 239000011570 nicotinamide Substances 0.000 title claims abstract description 13
- 229960003966 nicotinamide Drugs 0.000 title claims abstract description 13
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 8
- 229960003512 nicotinic acid Drugs 0.000 claims description 4
- 235000001968 nicotinic acid Nutrition 0.000 claims description 4
- 239000011664 nicotinic acid Substances 0.000 claims description 4
- 239000004615 ingredient Substances 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 229960001138 acetylsalicylic acid Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000000202 analgesic effect Effects 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- -1 Asprin aluminum compound Chemical class 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010070840 Gastrointestinal tract irritation Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 201000005917 gastric ulcer Diseases 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 1
- 241000219000 Populus Species 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- CANRESZKMUPMAE-UHFFFAOYSA-L Zinc lactate Chemical compound [Zn+2].CC(O)C([O-])=O.CC(O)C([O-])=O CANRESZKMUPMAE-UHFFFAOYSA-L 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- FTAQWORYXALIGF-UHFFFAOYSA-K dizinc;chloride;sulfate Chemical compound [Cl-].[Zn+2].[Zn+2].[O-]S([O-])(=O)=O FTAQWORYXALIGF-UHFFFAOYSA-K 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229950006238 nadide Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical class C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- GAAKLDANOSASAM-UHFFFAOYSA-N undec-10-enoic acid;zinc Chemical compound [Zn].OC(=O)CCCCCCCCC=C GAAKLDANOSASAM-UHFFFAOYSA-N 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 239000004246 zinc acetate Substances 0.000 description 1
- 229960000314 zinc acetate Drugs 0.000 description 1
- 239000011576 zinc lactate Substances 0.000 description 1
- 229940050168 zinc lactate Drugs 0.000 description 1
- 235000000193 zinc lactate Nutrition 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 229940118257 zinc undecylenate Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Abstract
The present invention relates to an acetyl-salicylic derivative combined with niacinamide and zinc. The structure is shown in the formula above.
Description
But what the present invention relates to is a kind of acetyl-salicylic derivate of hyoscine, specifically is a kind of acetyl-salicylic derivate that is combined with nicotinic acid derivates and metal ingredient.
Acetylsalicylic acid (Asprin) is as classical and unspent so far antipyretic-antalgic anti-inflammatory agent thing was used more than 100 year, and finds constantly again that in the recent period it also has treatment cardiovascular disorder and some anticancer therapeutic, has more enlarged its range of application.But because it is acid strong, the gastrorrhagia that GI irritation is easily caused, even side effect such as ulcerate disease also is the puzzlement people and the problem of managing to solve always.For reducing its acidity, except that making prodrugs such as ester class and acid amides, form double salt also is approach that report is arranged more at present.As J55141438, documents such as DT2909829 have all been reported the Asprin aluminum compound; What DT2925718 introduced is the compound that Asprin is become with zinc; What US4294819 introduced is the salt that Asprin is become with calcium, magnesium; US3284489 has introduced the salt of calcium and amino acid and Asprin combining form; J56022748 has introduced the salt that Asprin is become with basic aminoacids; US3318892 has introduced the form that Asprin combines with nicotinic acid and aluminium; EP200628A, EP233459A, documents such as FR2492368 and FR2638742A have introduced the form that Asprin combines with urea, calcium and/or magnesium respectively.Can understand from the content that these documents are introduced, the derivative of above-mentioned Asprin all can reduce acidity, and increase water-soluble, but on pharmacology the more or new valuable active effect of generation.
At the problems referred to above, the present invention's purpose at first provides a kind of acetyl-salicylic derivate that is combined with the new texture of zinc and niacinamide.A further object of the present invention provides a kind of acidity that not only can reduce in the clinical use, increases water-solublely, and can produce the acetyl-salicylic derivate that is combined with zinc and niacinamide of valuable active effect to acetylsalicylic acid on pharmacology.
Acetyl-salicylic derivate of the present invention by two acetylsalicylic acid respectively with carboxyl, and the forms that combine with a zinc simultaneously with pyridine ring N respectively of two niacinamide, its structure is
This derivative of the present invention (I) synthetic general and uncomplicated can be with reference to as US3318892, EP233459A, and the similar document of EP200628A or other institute reported method is carried out, and also can carry out with reference to following method.Wherein used solvent can be methyl alcohol, ethanol, Virahol, or the small molecular alcohol of C1-C5 such as acetone, butanone or ketone.Zinc can use mineral acid zinc salts such as zinc chloride zinc sulfate, zinc nitrate, or organic acid zinc salt such as zinc lactate, zinc acetate, Zinc Undecylenate.The consumption of each material composition can be by acetylsalicylic acid during preparation: niacinamide: zinc salt=(1.8～2.4): (1.8～2.4): (0.9～1.2) [mol ratio].For example: acetylsalicylic acid 36 grams under agitation are dissolved in 200 milliliters of acetone.In addition niacinamide 22 grams and zinc sulfate 30 grams are dissolved in 40 ml waters.Under agitation the above-mentioned aqueous solution is splashed in the acetone soln, stirred 5 hours under the room temperature.Filtration gained precipitation is washed with anhydrous propanone.After 60 ℃ of oven dry, must this derivative products (I) 40 grams (yield 60%), mp142～145 ℃, purity detecting content is not less than 98%.Acetylsalicylic acid content ratio in the product (I) is about 54%.This product is easily molten in water, and solubleness is 5～8%, and is molten at ethanol, acetone part omitted, almost insoluble in ether, chloroform, ethyl acetate.Product is made and recorded pH in 5% aqueous solution is 6.4.Except that this method, also can adopt method of fractional steps preparation, for example, be prepared into niacinamide zinc earlier after, again with acetylsalicylic acid synthetic product (I), or be prepared into earlier behind the Zinc acelylsalicylate again and niacinamide synthetic product (I).
The chemical formula of this derived products (I) is C30H26N4O10Zn, and the ultimate analysis theoretical value should be: C:53.95%, H:3.92%, N:8.39%, Zn:9.79%.The ultimate analysis measured value of above-mentioned product (I) is: C:54.19%, H:4.01%, N:8.07%, Zn:9.95%.
The infrared absorpting light spectra of above-mentioned product (I) as shown in drawings.Wherein the ownership of charateristic avsorption band is: 3340 (wave numbers, as follows) (NH), 1750 (C=O), 1625 (C=N), 1600 (C=C), 1370 (C-H), 1220 (C-N).
It is an amount of to get above-mentioned product (I) sample, puts respectively in 50 ℃ of baking ovens 5 days and room temperature was placed after 18 months, and free-water poplar acid content shows that all less than 0.2% the above-mentioned product of the present invention (I) has good stability in the sample for reference.
The above-mentioned product of the present invention (I) is made the acute toxicity animal experiment: get 60 of the mouse of body weight 19～23 gram male and female half and half, be divided into two batches totally six groups at random, test group and control group respectively are a collection of three groups.The Asprin of product (I) and contrast usefulness all is made into oral administration behind the suspensoid with tragakanta, according to animal dead situation gained medium lethal dose (LD50) result in 72 hours: Asprin is 972.7 (literature values 1050), and product (I) is 1456 (milligram/kilograms).
The result of relevant pharmacological experiment is as follows:
Irritation test to stomach: get body weight and be 70 of the SD rats that 210～230 gram male and female have concurrently, random packet.After the fasting 24 hours, above-mentioned product (I) and Asprin reference substance are made into the suspensoid of various dose respectively with tragakanta, make blank with equivalent tragakanta liquid in addition, all put to death after 6 hours, do the inspection of stomach ulcer index with filling stomach form administration.Median ulcerated dose (UD50) result that the result is done after the linear regression processing is: Asprin 215.7, product (I) 631.1 (wherein being equivalent to Asprin 340.8) (milligram/kilogram).
Analgesic activities test: 70 random packet of mouse of heavy 18～22 gram male and female half and half of taking a sample.Water is prohibited in fasting before the experiment.Product (I) is made into the aqueous solution, and contrast is made into suspensoid with Asprin with tragakanta, and blank is an equivalent physiological saline.Behind the oral administration 30 minutes,, begin counting animal writhing response number of times in 15 minutes after 5 minutes by amount abdominal injection 0.6% acetate solution of 10 milliliters/kg body weight.Cause pain significant quantity (ED50) result according to causing the half that reacts the linear regression gained of inhibiting rate bitterly: Asprin is 368.2, and product (I) is 216.5 (wherein being equivalent to Asprin 116.9) (milliliter/kilograms).The analgesic activity that shows product (I) is equivalent to 3.2 times of Asprin.
Anti-inflammatory activity test: get 70 random packet of above-mentioned mouse equally.Water is prohibited in fasting before the experiment.Trial drug preparation and blank product are identical with the analgesic activities test.Behind the oral administration 30 minutes, drip 0.03 milliliter of dimethylbenzene with micro sample adding appliance at animal left side ear and cause inflammation after 30 minutes, put to death animal, get auricle with punch tool and weigh, calculate the swelling degree shown in the two auricle weight differences.Reach 15% o'clock anti-inflammatory effective amount (ED15) result according to causing the inhibiting rate that scorching reaction inhibiting rate makes the linear regression gained: Asprin 682.8, product (I) are 138.2 (wherein being equivalent to Asprin 74.6) (milligram/kilograms).The anti-inflammatory action that shows product (I) is equivalent to 9.2 times of Asprin.
These experimental results fully show, the aqueous solution of the above-mentioned product of the present invention (I) is neutral, oral back is little to gastric stimulation, and there have been obviously analgesic activity and anti-inflammatory action the while and increase substantially, and has significantly reduced the actual amount of Asprin under identical curative effect.
In addition, niacinamide is the main component of nadide as water-soluble vitamins, is playing an important role aspect the metabolism of participation body.Zinc element is the trace element of needed by human, and is relevant with the activity of tens of kinds of enzymes in the body, particularly keep the cell integrity and reactive aspect play an important role.Recently entered the clinical experiment stage with zinc as the novel method for the treatment of stomach ulcer, having demonstrated due to antagonism Asprin has remarkable superiority aspect the gastrointestinal irritation side effect.Above-mentioned acetyl-salicylic derivate of the present invention (I) combines with Asprin by niacinamide and zinc element, replenishing human body beneficial's element and composition and when can obviously resist the side effect of Asprin, also significantly improving the pharmacology performance of traditional Asprin medicine.Along with the continuous discovery and the expansion of new purposes of Asprin and suitable application area scope, the shown positive effect that goes out of said derivative of the present invention (I) and be worth also will be day by day obviously and important.
Claims (1)
1, a kind of acetyl-salicylic derivate that is combined with nicotinic acid derivates and metal ingredient is characterized in that nicotinic acid derivates wherein is a niacinamide, and metal ingredient is a zinc, and has following structure
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94111976A CN1052472C (en) | 1994-11-16 | 1994-11-16 | Acetyl-salicylic derivate combined with niacinamide and zinc |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94111976A CN1052472C (en) | 1994-11-16 | 1994-11-16 | Acetyl-salicylic derivate combined with niacinamide and zinc |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1107140A CN1107140A (en) | 1995-08-23 |
| CN1052472C true CN1052472C (en) | 2000-05-17 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN94111976A Expired - Fee Related CN1052472C (en) | 1994-11-16 | 1994-11-16 | Acetyl-salicylic derivate combined with niacinamide and zinc |
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| JP6033041B2 (en) * | 2012-10-31 | 2016-11-30 | 株式会社オハラ | Automatic quality inspection device for optical glass base material and automatic quality inspection method for optical glass base material |
| CN116063356A (en) * | 2023-01-18 | 2023-05-05 | 广东电网有限责任公司 | A heterogeneous metal derivative of alkyl salicylic acid and its preparation method and application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0200628A1 (en) * | 1985-04-19 | 1986-11-05 | Rhone-Poulenc Sante | Derivative of acetylsalicylic acid, its preparation and pharmaceutical compositions containing it |
| EP2333459A2 (en) * | 2009-11-30 | 2011-06-15 | Sanyo Electric Co., Ltd. | Refrigerating apparatus |
-
1994
- 1994-11-16 CN CN94111976A patent/CN1052472C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0200628A1 (en) * | 1985-04-19 | 1986-11-05 | Rhone-Poulenc Sante | Derivative of acetylsalicylic acid, its preparation and pharmaceutical compositions containing it |
| EP2333459A2 (en) * | 2009-11-30 | 2011-06-15 | Sanyo Electric Co., Ltd. | Refrigerating apparatus |
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| Publication number | Publication date |
|---|---|
| CN1107140A (en) | 1995-08-23 |
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