CN101480383A - Application of disodium sulfodehydroabietate for treating gastroxia type peptic ulcer and gastrointestinal tract inflammation - Google Patents
Application of disodium sulfodehydroabietate for treating gastroxia type peptic ulcer and gastrointestinal tract inflammation Download PDFInfo
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Abstract
The invention discloses an application of sulfonating dehydrogenated disodium abietic acid on medicine, and relates to the medicine field of preventing from gastrointestinal tract diseases, in particular to medicine for preventing gastrointestinal tract inflammation and ulceration caused by acid stomach. The patent disclosed in CN00818150.0 shows that sulfogroup dehydrogenated rosin mono-sodium salt is better than disodium salt, but the patent does not further disclose the experimental condition and the data result, thus the pharmacological action and the clinical application condition are worthy to further research. Through comparing acid preparation in vitro effect of the mono-sodium salt with the disodium salt, the dissolution rate and the pharmacodynamic test of the mono-sodium salt with the disodium salt in simulated gastric fluid and simulated intestinal fluid, the invention has the result as follows: the sulfonating dehydrogenated disodium abietic acid has stronger acid making property when curing stomach ulcer, acute gastritis, acute attack of chronic gastritis, faster entogastric and intestinal dissolution speed, higher healing effect and quicker deserted effect.
Description
Technical field
The present invention relates to known prevention and treatment digestibility inflammation and medicine for ulcer, i.e. disodium salt in sulfonated dehydro rosin acid and the salt thereof, sulfonated dehydro rosin acid disodium salt is used for the treatment of the gastrointestinal tract inflammation and the new treatment of peptic ulcer of hyperchlorhydria type and uses.
Background technology
Peptic ulcer is one of common frdquently encountered disease, and is wherein common with stomach, duodenal ulcer disease.The peptic ulcer main diseases because of being because harmonization of the stomach duodenum mucosa has unbalanced result between the invasion and attack factor of detrimental effect and the mucosa self-defense factor.Gastric acid and pepsin are the main components of gastric juice, are the principal elements that harmonization of the stomach duodenum mucosa is had the invasion and attack effect.I.e. so-called " anacidity does not have ulcer ".Peptic ulcer patient's average basic gastric acid output and post-stimulatory acid output such as food, pentagastrin are often greater than the normal person, and the gastric acid secretion at night of duodenal ulcer patients is significantly higher than the normal person.Gastric acid secretion existence undesired and gastric acid is the Fundamentals that cause peptic ulcer.
Just often gastric acid does not damage mucosa, has mainly stoped H because of the mucosa defensive barrier
+Back diffusion, just at mucosa sick the damage under the situation that back mucosa self-defense ability weakens taken place because of certain situation, this enzyme of gastric acid/pepsin just plays the autodigestion effect.Gastric acid secretion is the peptic ulcer patient of normal range, and aggressivity also can produce ulcer when tangible increase mucosa defence power weakens.And the principal element that mucosa defence power is weakened is a Helicobacter pylori infection.Because Helicobacter pylori infection causes that duodenal bulbar inflammation can destroy the mucosa barrier, promote H
+Back diffusion, and further strengthen inflammatory reaction, the lyase of inflammatory cell and the oxygen-derived free radicals that is produced can increase the weight of damage.Simultaneously helicobacter pylori is the parasitic of gastric antrum and to cause antral gastritis be the key factor that gastric ulcer patient mucosa resistance weakens, and is normal simultaneously with the anti-stream of duodenum content, increased the weight of ulcer.
Therefore, treatment of peptic ulcer mainly is antiacid treatment and eliminating pylorus.
Antiacid treatment mainly is to reduce gastric acid, and the medicine that reduces gastric acid is mainly antacid.Antacid is a class weak base drug, can react with gastric acid after oral, forms salt and water, thereby Gastric pH is raise, and Gastric pH is generally 1.5-2.5, uses antacid and makes gastric acid keep pH more than 4, could alleviate peptic ulcer patient Upper abdominal pain effectively, and promote ulcer healing.Traditional antacid such as solubility antacid, sodium bicarbonate can very fast dissolving, and reacts rapidly with gastric acid, thus pain relieving rapidly, but they are easy to intestinal absorption from childhood, can cause the storage of alkalosis and sodium to be stayed; Another kind of is insoluble antacid such as calcium carbonate, and oral back is long at gastric transit time, in and gastric acid also longer action time, after the gastric acid reaction, formation water and calcium chloride, but can cause hypercalcemia, acid rebound rising and constipation etc.Antacid used and easily caused the very few of gastric acid at most, thereby it is active obviously to influence pepsic digestion, causes dyspepsia; And pH value is too high can to cause the Secondary cases gastroxia again: ulcer surface protective agent such as carbenoxolone have adrenocorticomimetic effect, stay so can cause the storage of water sodium, diseases such as edema, hypertension, hypokalemia occur.Though various antibiotic all have stronger inhibitory action external to helicobacter pylori, even also not very good with the medication combined result of use of proton pump class clinically.This is because most antibiotics is unstable in gastric acid environment on the one hand, is difficult to reach effective treatment concentration in gastric mucosa surface; Easily produce drug resistance on the other hand.Therefore, extensively the bigeminy of recommending, triple therapy also are difficult to the infection of eliminating pylorus, and easily recurrence.And in case recurrence then more can be quickened the generation of other disease such as digestive tract canceration.Therefore, continue that research and development are novel existingly to be pressed down sour effect and have the prevention of good eliminating pylorus and treatment hyperchlorhydria type digestive ulcer medicament very necessary again by force.
Nineteen eighty-two, USPO disclosed the patent application document US4529602A of Tanade Seiyaku Co., Ltd, wherein disclose sulfonated dehydro rosin acid list sodium salt and had the effect of identical prevention and treatment peptic ulcer with disodium salt, and single sodium salt of further pointing out the sulfo group dehydroabietic acid more has superiority than disodium salt, because of the former more is difficult for moisture absorption and more stable.It is sulfonated dehydro sodium abietate granule (lid is refreshing) listing that sulfonated dehydro rosin acid list sodium salt medicine is arranged in succession, be used for prevention and treatment peptic ulcer, yet spelling out the gastric ulcer active stage in its operation instructions should suppress share with gastric acid, because sulfonated dehydro rosin acid list sodium salt is faintly acid in water, when treatment hyperchlorhydria type peptic ulcer must with acid inhibitor such as famotidine, drug combinations such as ranitidine just can play effective therapeutical effect.Therefore be not medicine most preferably at present to hyperchlorhydria type peptic ulcer.
On April 30th, 2003, Chinese Patent Office disclosed the patent application document of Tanade Seiyaku Co., Ltd, denomination of invention is " medicine of prevention or treatment inflammatory bowel disease " (application number 00818150.0), has proposed this medicine and contain structural formula of compound as effective ingredient in claim 1:
Or its pharmaceutically acceptable salt.In claim 2 claim 1 has been done qualification: at pharmaceutically acceptable salt is TA-2711.Point out that in description preferred salt is sodium salt in the pharmaceutically acceptable salt, especially single sodium salt, and point out that further single sodium salt of sulfo group dehydroabietic acid more has superiority than disodium salt, because of the former more is difficult for moisture absorption and more stable.
Hence one can see that; above-mentioned application protection domain is very wide; when treatment inflammation class intestinal tract disease; every salt with sulfonated dehydro rosin acid all is to belong to its protection domain; but in the so broad protection domain, what can obtain the description support only is TA-2711, does not obtain the support of description as for other salt of sulfo group dehydroabietic acid; their pharmacological action, clinical practice what state also are worth further research.
Summary of the invention
Purpose of the present invention is for providing a kind of curative effect height, instant effect, safe control hyperchlorhydria type alimentary canal inflammation and the medicine sulfonated dehydro rosin acid disodium of peptic ulcer.
The technical scheme that realizes foregoing invention is as follows: sulfonated dehydro rosin acid disodium is the medicine that is used to prevent and treat hyperchlorhydria type gastric ulcer, acute gastritis, chronic gastritis acute attack, enteritis, duodenal ulcer etc. in application pharmaceutically.Adopt oral or non-oral medicine during administration, the dosage form of oral administration has dosage forms such as tablet, capsule, powder, granule, Emulsion, solution, syrup, adds pharmaceutically acceptable corresponding auxiliary material and adjuvant in each dosage form.The molecular structural formula of sulfonated dehydro rosin acid disodium is:
Wherein, R=2Na n=0
Study of pharmacy, pharmacodynamic study, toxicologic study, embodiment.
The outer antacid effect comparative study of medicine sulfonated dehydro rosin acid disodium granule of the present invention and sulfonated dehydro rosin acid list sodium granule
One, purpose:
Relatively sulfonated dehydro rosin acid disodium granule and the particulate acid-base value of sulfonated dehydro rosin acid list sodium and the amount that consumes simulated gastric fluid (0.1mol/L hydrochloric acid), the antacid ability when determining that with this two is used for gastric ulcer due to the hyperchlorhydria.
Two, method:
Measure sulfonated dehydro rosin acid disodium granule and the particulate original pH value of sulfonated dehydro rosin acid list sodium, measure pH value after adding the hydrochloric acid mixing of equivalent 0.1mol/L more one by one.
1, sample
Sulfonated dehydro rosin acid disodium granule: the 2.0g/ of Aisheng Pharmaceutical Co., Ltd., Zhejiang bag (containing sulfonated dehydro rosin acid disodium 1.0g), one time one bag, twice on the one;
Sulfonated dehydro rosin acid list sodium granule: limit, the field pharmacy Zhu Shi 1.5g/ of commercial firm bag (containing sulfonated dehydro rosin acid list sodium 1.0g), one time one bag, twice on the one.
2, preparation
Sulfonated dehydro rosin acid disodium granule add for 2 bags the cold distilled water 40ml dissolving of newly boiling (1#3.9934g, 2#4.0777g);
Sulfonated dehydro rosin acid list sodium granule add for 2 bags the cold distilled water 40ml dissolving of newly boiling (3#3.0009g, 4#3.0252g);
0.1mol/L hydrochloric acid: get concentrated hydrochloric acid 9ml adding distil water and be diluted to 1000ml promptly.
3, instrumental correction
Instrument model: pHS-3C type acidometer
Ambient temperature: 26 ℃
Standard buffer solution: Potassium Hydrogen Phthalate standard buffer solution (pH4.00)
Phosphate standard buffer solution (pH6.86)
Three, result's (seeing Table 1)
Table 1 sulfonated dehydro rosin acid list sodium and sulfonated dehydro rosin acid disodium are to the influence (preliminary test) of simulated gastric fluid acidity
Sulfonated dehydro rosin acid disodium granule in 0.1mol/L hydrochloric acid addition is between the 31ml to 41ml, sulfonated dehydro rosin acid list sodium is that pH value has a sudden change between the 2ml to 4ml in 0.1mol/L hydrochloric acid addition, and the terminal point that there is a neutralization reaction in it is described.So test once more, measure relation between 0.1mol/L hydrochloric acid addition and the pH value with a small amount of method that repeatedly drips, finally determine its accurate reaction end.
With sulfonated dehydro rosin acid disodium and single sodium salt carry out respectively to simulated gastric fluid acidity to influence test method the same.
Sample:
Sulfonated dehydro rosin acid disodium granule 1#4.0838g 2#3.9987g
Sulfonated dehydro rosin acid list sodium granule 3#3.0099g 4#3.0131g
The results are shown in Table 2, table 3.
Table 2 sulfonated dehydro rosin acid disodium is to the influence of simulated gastric fluid acidity
Table 3 sulfonated dehydro rosin acid list sodium is to the influence of simulated gastric fluid acidity
Analyze from table 3, for sulfonated dehydro rosin acid list sodium particle solution, when the hydrochloric acid content of accumulative total adding reaches 3.00～4.25ml, pH value begins to take place rapid decline, and maximum pH value descends and reaches 0.53, when reaching 4.75ml, pH value descends and tends towards stability, therefore, can judge that terminal point should be about 4.25ml, this moment, the solution pH value was 2.73～2.80.Alleviate peptic ulcer patient Upper abdominal pain effectively for making, and promote ulcer more, gastric acid PH must remain on more than 4, as seen from Table 3, makes gastric acid keep PH more than 4, and accumulative total adds hydrochloric acid content and only is 3.00ml, promptly single sodium salt can only in and 3.00ml gastric acid.
Analyze from table 2, to sulfonated dehydro rosin acid disodium particle solution, in the whole process that adds hydrochloric acid, the rapid drop point that pH value do not occur, the maximum drop-out value of the pH value that each point records is no more than 0.15, therefore, proves that sulfonated dehydro rosin acid disodium particle solution has stronger buffer capacity.When pH value reach sulfonated dehydro rosin acid list sodium particle solution terminal point 2.73～2.80 the time, the simulated gastric fluid that is consumed reaches 40.70ml, is equivalent to 9.57 times (about 10 times) of single sodium.For making gastric acid keep PH more than 4, it is 34.20ml that accumulative total adds hydrochloric acid content, is equivalent to 11 times of single sodium.
Four, conclusion:
Terminal point with simulated gastric fluid in the sulfonated dehydro rosin acid disodium particle solution is a pH value 2.73～2.80, the consumption simulated gastric fluid is 4.25ml, but sulfonated dehydro rosin acid disodium particle solution in and in the process of simulated gastric fluid, tangible terminal point does not appear, when its pH value reaches the molten endpoint pH of sulfonated dehydro rosin acid list sodium, the simulated gastric fluid that is consumed reaches 40.70ml, about 10 times of simulated gastric fluid amounts that consumed to sulfonated dehydro rosin acid list sodium particle solution.For keeping gastric acid PH more than 4, the simulated gastric fluid that two sodium consumed reaches 34.20ml, and single sodium only is 3.00ml, 11 times of the single approximately sodium of two sodium.
Therefore, sulfonated dehydro rosin acid disodium granule has more significantly antacid ability than sulfonated dehydro rosin acid list sodium granule.
Five, discuss:
A) when the preparation sample solution, sulfonated dehydro rosin acid disodium granule more easily is dissolved in water, and sulfonated dehydro rosin acid list sodium granule is insoluble in water; Sulfonated dehydro rosin acid disodium particle solution is transparence liquid, the sulfonated dehydro rosin acid list sodium particle solution suspension that is creamy white.
B) sulfonated dehydro rosin acid disodium particle solution pH value 6.2, sulfonated dehydro rosin acid list sodium particle solution pH value 5.0, the former is high more about 1.2 than latter pH value, and the former is nearly neutrality, and the latter is faintly acid.Therefore, aspect antacid power, sulfonated dehydro rosin acid disodium granule has inborn advantage than sulfonated dehydro rosin acid list sodium granule, when pH value reaches the pH value of sulfonated dehydro rosin acid list sodium particle solution itself, sulfonated dehydro rosin acid disodium particle solution can consume about simulated gastric fluid 30ml, is equivalent in the sulfonated dehydro rosin acid list sodium granule and 7 times of simulated gastric fluid amount that gastric acid consumes when reaching terminal point.
C) sulfonated dehydro rosin acid disodium granule pH value variation tendency in antacid whole process is mild, and is gentle to the stomach effect; And sulfonated dehydro rosin acid list sodium granule in and in the gastric acid process, wherein with gastric acid amount only about 4ml, solution is strong acidic environment very soon.
D) normal gastric juice pH is 1.5～2.5, when pH value is 4.0 when above, could effectively alleviate peptic ulcer patient Upper abdominal pain, and promote ulcer healing, normal empty stomach after 12 hours the gastric juice amount be 30～50ml.The each dose of sulfonated dehydro rosin acid disodium granule can in and the about 30ml of simulated gastric fluid about, its pH is remained on more than 4, can effectively alleviate peptic ulcer patient Upper abdominal pain, and the promotion ulcer healing.And single sodium keeps PH more than 4, only can in and 3ml gastric acid.In treatment during peptic ulcer, single sodium must with the effective reduction of patient Upper abdominal pain of acid inhibitor drug combination, and need not add any antacid with pair sodium, himself just has very strong capacity antacid.
To sum up experimentation is described, sulfonated dehydro rosin acid disodium granule can be better than sulfonated dehydro rosin acid list sodium granule in and gastric acid, thereby the protection gastric tissue is used for gastritis, gastric ulcer that hyperchlorhydria causes, will bring into play excellent more clinical efficacy.
Medicine sulfonated dehydro rosin acid disodium of the present invention and the comparative study of sulfonated dehydro rosin acid list sodium dissolution
One, sulfonated dehydro rosin acid list sodium salt and the disodium salt dissolution determination in simulated gastric fluid
1. dissolution medium: (dilute hydrochloric acid 16.4ml adds the about 800ml of water to simulated gastric fluid, and after pepsin 10g shook up, thin up became 1000ml, promptly.)
2. other conditions: 900ml, the oar method, 50 rev/mins, 37.0 ℃, the 751GW spectrophotometer detects wavelength 270nm.
3. contrast: it is fixed molten to 10ml that sulfonated dehydro rosin acid disodium 11.5mg adds simulated gastric fluid, adds the NaOH to 50ml of 0.1mol/L again.
4. sample:
A: sulfonated dehydro rosin acid list sodium granule (the 1.5g/ bag contains sulfonated dehydro rosin acid list sodium 1.0g).
Get 20ml and cross leaching subsequent filtrate 5ml, the NaOH that adds 0.1mol/L is fixed molten to 25ml.
B: sulfonated dehydro rosin acid disodium granule (the 2.0g/ bag contains sulfonated dehydro rosin acid disodium 1.0g).
Get 20ml and cross leaching subsequent filtrate 5ml, the NaOH that adds 0.1mol/L is fixed molten to 25ml.
5, result of the test: see the following form 4, table 5
Table 4 sulfonated dehydro rosin acid list sodium granule is at simulated gastric fluid dissolution (%)
| Numbering | 1# | 2# | 3# | 4# | 5# | 6# | Meansigma methods | Standard deviation | Adjust number | Accumulative total dissolution % |
| Sample size g | 1.5349 | 1.5297 | 1.5248 | 1.535 | 1.5331 | 1.5373 | 1.5325 | 0.0045 | ||
| 5min | 57.5 | 58.3 | 55.3 | 53.1 | 58 | 53 | 55.867 | 2.4221 | 55.87 | |
| 10min | 74.1 | 74.2 | 67.5 | 68.2 | 74.7 | 68.7 | 71.233 | 3.4233 | 1.242 | 72.47 |
| 20min | 93.9 | 95.6 | 87.4 | 90.2 | 934 | 88 | 91.417 | 3.3731 | 2.824 | 94.24 |
| 30min | 95.7 | 95.5 | 92.5 | 93.3 | 95.3 | 90.7 | 93.833 | 2.0146 | 4.856 | 98.69 |
| 45min | 95.3 | 95 | 95.3 | 95.2 | 94.9 | 91.7 | 94.567 | 1.4137 | 6.941 | 101.51 |
| 60min | 95.3 | 94.9 | 95.7 | 93.9 | 94.9 | 91.3 | 94.333 | 1.6021 | 9.043 | 103.38 |
Table 5 sulfonated dehydro rosin acid disodium granule is at simulated gastric fluid dissolution (%)
| Numbering | 1# | 2# | 3# | 4# | 5# | 6# | Meansigma methods | Standard deviation | Adjust number | The accumulative total dissolution |
| Sample size g | 2.0252 | 2.0164 | 2.0335 | 2.0366 | 2.0093 | 1.9794 | 2.0167 | 0.021 | ||
| 5min | 94.2 | 96.4 | 93 | 94 | 95 | 98.4 | 95.167 | 1.949 | 95.17 | |
| 10min | 96.2 | 97.8 | 97.2 | 95.2 | 96 | 95 | 96.233 | 1.0985 | 2.115 | 98.35 |
| 20min | 95.4 | 95.6 | 95.4 | 94.4 | 96.2 | 94.6 | 95.267 | 0.6653 | 4.253 | 99.52 |
| 30min | 93.4 | 94.8 | 95 | 93.2 | 94.6 | 94.2 | 94.2 | 0.7483 | 6.37 | 100.57 |
| 45min | 92.8 | 92.4 | 95.4 | 92.4 | 93.6 | 92 | 93.1 | 1.2506 | 8.464 | 101.56 |
| 60min | 92.4 | 92.2 | 99 | 91 | 91.4 | 91.4 | 92.9 | 3.0351 | 10.53 | 103.43 |
As can be seen from the above table, the 5mins stripping 55.8% in simulated gastric fluid of sulfonated dehydro rosin acid list sodium granule, 10mins stripping 72.5%, 20mins stripping 94.2%, 30mins stripping 98.7%, the complete stripping of 45mins, its process in leaching is slower.And 5mins is stripping 95.2% in the sulfonated dehydro rosin acid disodium granule simulated gastric fluid, 10mins stripping 98.3%, the complete stripping of 20mins, its process in leaching is very fast, most solute strippings are promptly arranged in the 5mins, and dissolution velocity makes it react rapidly with gastric acid soon, thus pain relieving rapidly.Therefore it is very fast in gastric performance curative effect.
Two, sulfonated dehydro rosin acid list sodium salt and the disodium salt dissolution determination in simulated intestinal fluid
1, dissolution medium: (potassium dihydrogen phosphate 6.8g adds water 500ml and makes dissolving simulated intestinal fluid, and the NaOH with 0.4% transfers pH to 6.8; Other gets pancreatin 10g, adds water and makes dissolving in right amount; After the mixing of two liquid, thin up becomes 1000ml, promptly.)
2, other conditions: 900ml, the oar method, 50 rev/mins, 37.0 ℃, the 751GW spectrophotometer detects wavelength 270nm.
3, contrast: it is fixed molten to 10ml that sulfonated dehydro rosin acid disodium 11.3mg adds simulated intestinal fluid, adds the NaOH to 50ml of 0.1mol/L again.
4, sample:
A: sulfonated dehydro rosin acid list sodium granule (the 1.5g/ bag contains sulfonated dehydro rosin acid list sodium 1.0g).
Get 20ml and cross leaching subsequent filtrate 5ml, the NaOH that adds 0.1mol/L is fixed molten to 25ml.
B: sulfonated dehydro rosin acid disodium granule (the 2.0g/ bag contains sulfonated dehydro rosin acid disodium 1.0g).
Get 20ml and cross leaching subsequent filtrate 5ml, the NaOH that adds 0.1mol/L is fixed molten to 25ml.
5, result of the test: the results are shown in following table 6, table 7
Table 6 sulfonated dehydro rosin acid list sodium granule dissolution (%) in simulated intestinal fluid
Table 7 sulfonated dehydro rosin acid disodium granule dissolution (%) in simulated intestinal fluid
As can be seen from the above table, the 5mins stripping 77.8% in simulated intestinal fluid of sulfonated dehydro rosin acid list sodium granule, 10mins stripping 90.8%, 20mins stripping 95.1%, the complete stripping of 30mins, its process in leaching is slower.And 5mins is stripping 90.9% in the sulfonated dehydro rosin acid disodium granule simulated gastric fluid, 10mins stripping 94.2%, and the complete stripping of 45mins, its process in leaching is very fast, and most solute strippings are promptly arranged in the 5mins, so it is rapid in enteral performance curative effect.
Three, conclusion and discussion:
1, the dissolution test in simulated gastric fluid of sulfonated dehydro rosin acid list sodium granule and sulfonated dehydro rosin acid disodium granule shows, the former stripping is slower, 5mins stripping 55.8%, stripping needs 45mins fully, latter's stripping is very fast, 5mins stripping 95.2%, the promptly basic stripping fully of 10mins, the whole strippings of 20mins.Therefore, the more single sodium salt of sulfonated dehydro rosin acid disodium salt is faster at the dissolution rate of gastric, and reacts rapidly with gastric acid, thereby pain relieving rapidly plays a role rapider to gastritis, gastric ulcer.
2, the dissolution test in simulated intestinal fluid of sulfonated dehydro rosin acid list sodium granule and sulfonated dehydro rosin acid disodium granule shows, the former stripping is slower, 5mins stripping 77.8%, stripping needs 30mins fully, latter's stripping is very fast, 5mins stripping 90.9%, the whole strippings of 45mins, and the former dissolution (about 91%) will reach the latter 5mins time needs the double time (10mins).Therefore, the more single sodium salt of sulfonated dehydro rosin acid disodium salt is faster at the dissolution rate of enteral, plays a role rapider to enteritis, intestinal ulcer.
The pharmacological toxicology research of medicine of the present invention
(1) medicine sulfonated dehydro rosin acid disodium of the present invention and the comparative study of sulfonated dehydro rosin acid list sodium main pharmacodynamics
One, content of the test:
For investigating prevention and the therapeutical effect of sulfonated dehydro rosin acid disodium (sulfonated dehydro rosin acid disodium) to peptic ulcer, and to the influence of gastric secretion, animal is adopted rat, select gastric ulcer models such as dehydrated alcohol, pylorus ligation, acetic acid, with the sulfonated dehydro rosin acid list sodium (sulfonated dehydro sodium abietate) of reagent as positive control, design a series of dosage, observation and comparison reagent are estimated its pharmacodynamics to the influence of acute injury, gastric ulcer, pepsin activity and the gastric acidity etc. of gastric mucosa.
Two, test material
2.1 experiment purpose
Antiulcer activity to reagent carries out thoroughly evaluating and comparison, and decision content validity response relation is also tried to achieve median effective dose.
2.2 test material
Medicine: sulfonated dehydro rosin acid disodium, be white powder, soluble in water, send out center Chinese medicine one Room by Chinese Medicine research Ji lot number is provided: 20000706G1 (NIPWNN48066), 20000713G1 (NIPWNN48068) face the time spent and are mixed with desired concn with 0.5% sodium carboxymethylcellulose pyce; The sulfonated dehydro sodium abietate provides lot number by Traditional Chinese Medicine Research ﹠ Development Center's Chinese medicine one Room: 20000630E1 (NIPWN 12441), 20000705EI (NIPWN12641) face the time spent and are mixed with desired concn with 0.5% sodium carboxymethylcellulose pyce.
Animal: secondary Wistar rat, male and female half and half, body weight 180-240g is provided credit number: SCXK11-00-0006 by Institute of Experimental Animals, Chinese Academy of Medical Sciences's breeding field.Water is can't help in preceding fasting 24-48 hour of experiment.
Reagent: 37-40% formalin, Beijing chemical reagents corporation product, lot number 00408 is mixed with 1% solution and uses; Dehydrated alcohol, the Beijing Chemical Plant produces, lot number 991016; Sodium hydroxide: the Beijing Chemical Plant produces, lot number: 20000127, and be mixed with 0.01N NaOH solution and use; Concentrated hydrochloric acid: the Beijing Chemical Plant produces, lot number: 980709, and be mixed with 0.05N HCI solution and use; The Mett pipe is some, adopts the pure system of fresh egg.
Instrument: PJS-4 type acidometer, Shanghai thunder magnetic instrument plant produces.The CytopermHeraeus CO2 gas incubator, German product.
Three, test method
1. to the influence of pylorus ligation gastric secretion
1.1 the list of references method is got the adult healthy rat, body weight 180-220g is respectively by sex, body weight random packet.Animal fasting 48h freely drinks water.During experiment with ether with Animal Anesthesia, open the abdominal cavity, the ligation pylorus.Postoperative i.g administration immediately, each is organized dosage and is respectively: blank group (i.g0.5%MC), sulfonated dehydro rosin acid disodium (4 each dosage group: 12.5mg/kg, 25.0mg/kg, 50.0mg/kg, 100.0mg/kg), positive control drug sulfonated dehydro sodium abietate (100.0mg/kg), dosage is 2.0ml/kg.Behind the administration 4h, put to death animal, dissect and get stomach (ligation pylorus, cardia), collect gastric juice (cutting off) along greater gastric curvature, the record cumulative volume, and at the centrifugal 10min of 2500rpm, record residue volume (ml) calculates gastric juice volume (ml).Get supernatant gastric juice and carry out gastric acid and pepsic mensuration.
(1) mensuration of gastric juice amount and gastric acidity
Gastric juice amount (ml)=gastric juice cumulative volume (ml)-residue volume (ml)
Gastric acidity=pH (measuring) with acidometer
(2) acid concentration of gastric juice, the mensuration of total acid content
Get supernatant gastric juice 0.5ml, adding distil water 20ml shakes up, and uses the acidometer titration, and volumetric solution is the 0.01N caustic lye of soda, and titration is during to pH=7.0, record sodium hydroxide volume.
The acid concentration MEL=TAC ÷ 2 * 1000 of gastric juice
TAC is equivalent to drip periodic volume with the 0.1N sodium hydroxide.0.01N sodium hydroxide titration 0.5ml gastric juice is converted into the volume of the required sodium hydroxide of the whole gastric juice of 0.1N sodium hydroxide titration, i.e. TAC, and computational methods:
(V0.5ml refers to the volume with 0.01N sodium hydroxide titration 0.5ml gastric juice)
Gastric juice total acid content MEAH=MEL * gastric juice amount ÷ 1000
(3) mensuration of pepsin activity (the special capillary tube method of wheat)
The glass capillary of internal diameter 1.0mm even thickness is cut into 10.0cm length, cleans and dry.Get an amount of Ovum Gallus domesticus album and fully beat even back and use filtered through gauze, above-mentioned capillary tube is utilized siphonage, fill Ovum Gallus domesticus album (manage planted agent do not have bubble sneak into).Be positioned over then in 85 ℃ of vapourss and make protein coagulation.After cooling, taking-up with the sealing of protein pipe two ends, is store in the refrigerator standby with paraffin.Get gastric juice 1.0ml during experiment and put into the 50ml triangular flask, add 0.05N hydrochloric acid solution 15.0ml, shake up, put two of long approximately 2.0cm protein pipe into.Filled in bottleneck, be put in 37 ℃ of calorstats temperature and incubate 24h.Measure the length (mm) of protein pipe two ends transparent part with chi and ask its meansigma methods with the value of four ends.
Pepsic unit=meansigma methods
2* 16
And calculating pepsin activity suppression ratio (%).
Statistical method: each is organized index and gets average and organize t check, compares to determine significant difference with the blank group.According to the dose-effect relationship of pepsin activity suppression ratio judgement reagent,, calculate its ED if dose-effect is remarkable
50Value.Utilize professor Sun Ruiyuan chief editor's NDST software to carry out statistical computation.
1.2 the results are shown in Table 8-1,8-2.
Table 8-1 sulfonated dehydro rosin acid disodium etc. to the influence of gastric juice acid-base value (χ ± S, n=10)
Annotate: compare with the blank group
*Expression P＜0.05
*Expression P＜0.01
Represent that with positive control drug sulfonated dehydro sodium abietate comparison # P＜0.05 ## represents P＜0.01
Table 8-2 sulfonated dehydro rosin acid etc. are to the influence of pepsin activity and suppression ratio
1.3 conclusion: sulfonated dehydro rosin acid disodium is to the effect of gastric secretion
1.3.1 influence to acid concentration, total acid content, acidity
Sulfonated dehydro rosin acid disodium 12.5,100.0mg/kg all significantly reduce the acidity of gastric juice acid concentration, gastric juice total acid content, gastric juice, and the effect of high dose is more remarkable, illustrate that reagent can significantly change the Acidity of Aikalinity of gastric juice, and acid reduction, total acid content are descended.Under the same experiment condition, contrast medicine sulfonated dehydro rosin acid 100.0mg/kg also can suppress the acidity of gastric juice acid concentration, gastric juice total acid content, gastric juice, but its suppression ratio is close with sulfonated dehydro rosin acid disodium 12.5mg/kg effect, shows that sulfonated dehydro rosin acid disodium is more than 8 times of single sodium to the influence of gastric juice acid-base value.The results are shown in Table 8-1.
1.3.2 effect to pepsin activity
Sulfonated dehydro rosin acid disodium 12.5,25.0,50.0,100.0mg/kg all have significant inhibitory effect (P＜0.01) to pepsin activity, 100.0mg/kg dosage pepsin activity suppression ratio reaches maximum 92.0%, and there is significant dose-effect reaction relation, ED
50Value is 20.8mg/kg.Under the same experiment condition, positive control drug sulfonated dehydro sodium abietate (100.0mg/kg), also inhibitory action, pepsin activity suppression ratio to be arranged be 70.9%.
Compare with positive drug, sulfonated dehydro rosin acid disodium 100.0mg/kg is significantly higher than sulfonated dehydro rosin acid 100.0mg/kg (P＜0.01) to the pepsin activity suppression ratio, and action intensity is respectively 1.3 times of single sodium.Sulfonated dehydro rosin acid disodium 50.0mg/kg dosage to pepsin activity inhibitory action and sulfonated dehydro rosin acid 100.0mg/kg effect near there not being significant difference (P〉0.05) between group.The effect comparable situation of each medicine sees Table 8-2.
2. the effect on the gastric mucosa injury model that dehydrated alcohol causes
2.1 get 80 of adult healthy rat, body weight 200-240g, male and female half and half, respectively by the body weight random packet, fasting (can't help water) 48h.12.5,25.0,50.0 each is organized dosage and is respectively: blank (gives 0.5% methylcellulose, 0.5%MC), reagent sulfonated dehydro rosin acid (4 dosage groups:, 100.0mg/kg), positive control drug sulfonated dehydro rosin acid (100.0mg/kg).All adopt gastric infusion (i.g), dosage is 2.0ml/kg, and behind the administration 40min, 1.0ml/ Mus of i.g dehydrated alcohol put to death behind the 1h.Get stomach (ligation cardia and pylorus), inject 1% formalin 8ml in gastral cavity, stomach is immersed in 1% formalin, 2h tailing edge greater gastric curvature is cut off, and observes the gastric ulcer situation.
The evaluation methodology of gastric ulcer degree: streak damage, length are measured its length greater than 1.0mm person, and every 1.0mm meter 1 minute is if its length greater than 1, doubles its score; What point-like was damaged counts 1 fen with 5 points, and score adds up to the ulcer index of this animal, and the significance that carries out group difference compares, and calculates damage suppression ratio (%), and computational methods are as follows:
Statistical method: each is organized ulcer index and gets average and organize f check, compares to determine significant difference with the blank group.According to the dose-effect reaction relation of ulcerative lesions suppression ratio judgement reagent,, calculate its ED if dose-effect is remarkable
50Value.Utilize professor Sun Ruiyuan chief editor's NDST software to carry out statistical computation.
2.2 the results are shown in Table 9-1.
Table 9-1. sulfonated dehydro rosin acid disodiums etc. cause the influence of gastric mucosa injury and suppression ratio to ethanol
2.3 conclusion: sulfonated dehydro rosin acid disodium causes the preventive effect of gastric mucosa injury to dehydrated alcohol
Sulfonated dehydro rosin acid disodium 12.5,25.0,50.0,100.0mg/kg group and the relatively ulcer index significance reduction of blank group, show that reagent has significant preventive effect to acute gastric mucosal lesion, 100.0mg/kg the mucosa injury suppression ratio reaches and is 98.8% (P＜0.01) to the maximum during dosage, in the 12.5-100.0mg/kg dosage range, there are significant dose-effect relationship, ED
50Value is 11.7mg/kg.Under the same experiment condition, contrast medicine sulfonated dehydro sodium abietate (100.0mg/kg) group also has inhibitory action to ulcer.
Compare with the positive drug group, sulfonated dehydro rosin acid disodium 100.0mg/kg ulcer index significantly reduces than sulfonated dehydro sodium abietate 100.0mg/kg dosage, and action intensity is its 4 times; Sulfonated dehydro rosin acid disodium 50.0mg/kg is approaching to ulcer inhibition rate and sulfonated dehydro sodium abietate 100.0mg/kg effect, does not have significant difference (P〉0.05) between group.The effect comparable situation of each medicine sees Table 9-1.
3. the effect of the gastric ulcer that pylorus ligation is caused
3.1 select the adult healthy rat for use, male and female half and half, body weight 180-220g, random packet, animal fasting 48h freely drinks water, and with Animal Anesthesia, opens the abdominal cavity with ether, the ligation pylorus.The i.g administration, each is organized dosage and is respectively: sulfonated dehydro rosin acid disodium (4 each dosage group 12.5,25.0,50.0,100.0mg/kg), sulfonated dehydro sodium abietate (100.0mg/kg), blank group (0.5%MC), with the 2.0ml/kg administration, 18h dissects and gets stomach (ligation cardia) after the administration, injects 1% formalin 8ml in gastral cavity.Stomach is immersed in 1% formalin, behind the 10min, cut off stomach along greater gastric curvature, a situation arises to observe gastric ulcer.The evaluation of ulcer level, the counting gastric ulcer area, with its summation as ulcer index.And calculate ulcer and suppress percentage rate (%).
Statistical method: each is organized ulcer index and gets average and organize t check, compares to determine significant difference with the blank group.Suppress the dose-effect relationship that percentage rate is judged reagent according to ulcer,, calculate its ED if dose-effect is remarkable
50Value.Utilize professor Sun Ruiyuan chief editor's NDST software to carry out statistical computation.
3.2 the results are shown in Table 10-1.
Table 10-1 sulfonated dehydro rosin acid disodiums etc. are to the influence of pylorus ligation rat gastric ulcer
3.3 conclusion: sulfonated dehydro rosin acid disodium is to the preventive effect of pylorus ligation gastric ulcer
Sulfonated dehydro rosin acid disodium 25.0,50.0,100.0mg/kg all has significance inhibitory action (P＜0.05, P＜0.01) to the pylorus ligation gastric ulcer, 100.0mg/kg act on significance the most, ulcer inhibition rate is 89.3% to the maximum, and highly significant dose-effect relationship, ED are arranged at 12.5-100.0mg/kg
50Value is 19.3mg/kg.Sulfonated dehydro sodium abietate 100.0mg/kg also has significant difference (P＜0.01, P＜0.05) under the similarity condition.
With the comparison of positive drug effect, sulfonated dehydro rosin acid disodium 100.0mg/kg is higher than sulfonated dehydro sodium abietate 100.0mg/kg group (P＜0.05) (P＜0.05) to the inhibitory action significance of ulcer.The action intensity of positive drug sulfonated dehydro sodium abietate 100.0mg/kg is between sulfonated dehydro rosin acid disodium 25.0mg/kg and 50.0mg/kg dosage: the results are shown in Table 10-1.
4. to the influence of external pepsin activity
4.1 with reference to pylorus ligation gastric secretion experimental technique, collect a certain amount of gastric juice and centrifugal, get supernatant and be used for this experiment.Get the clean conical flask of 50ml, add 0.9ml gastric juice respectively, add the medicinal liquid 0.1ml of respective concentration then in each bottle, blank adds 0.1ml0.05N HCl, after temperature is incubated 20min in 37 ℃ of constant temperature, add 0.05N HCl 15.0ml again in every bottle, two of the long Mett pipes of 3-4cm.Reference literature carries out determination of peptic activity.
Determination of peptic activity and computational methods are tested with above-mentioned pylorus ligation gastric secretion.
4.2 the results are shown in Table 11-1.
Table 11-1 sulfonated dehydro rosin acid disodiums etc. are to the influence of external pepsin activity
4.3 conclusion: sulfonated dehydro rosin acid disodium is to the influence of external pepsin activity
Sulfonated dehydro rosin acid disodium is in external 9.4-3.8 * 10
-5Under the g/ml concentration pepsin activity there is significant inhibitory effect, under high concentration 9.4 * 10
-5The highest suppression ratio of g/ml is 75.8%, medium effective concentration 6.5 * 10
-5(g/ml), medium effective concentration 6.5 * 10
-5(g/ml) the sulfonated dehydro rosin acid disodium (43.6%) under the concentration is higher than contrast medicine sulfonated dehydro sodium abietate 7.5 * 10 to the inhibitory action of pepsin activity
-5(g/ml) (41.4%).The results are shown in Table 11-1.
(2) drug toxicology experiment of the present invention
After sulfonated dehydro rosin acid disodium salt is given gastric infusion of mice, none death of animal in the 7d, its maximum dosage-feeding is 8000mg/kg, is equivalent to about 240 times (in 60kg people 2000mg every day) of clinical plan consumption approximately.
After sulfonated dehydro rosin acid disodium is given intraperitoneal administration of mice, according to the big toy of dosage show as movablely reduce, hind leg is stiff, easily frightened, twitch and dead, the gross anatomy perusal shows no obvious abnormalities.Death time in 20min～12h, lumbar injection LD
50=378.0mg/kg is equivalent to 114 times of clinical plan consumption approximately.
(3) medicine general pharmacology of the present invention is learned research
Adopt mice and domesticated dog that the general pharmacological action of sulfonated dehydro rosin acid disodium is observed, comprise spiritual nervous system, respiratory system and cardiovascular system, its result is as follows:
By the oral sulfonated dehydro rosin acid of mice disodium series dosage, observe reagent to the neural influence of animal spirit.When adopting the oral 35mg/kg of mice, 70mg/kg, 140mg/kg sulfonated dehydro rosin acid disodium, in the regular hour, observe the mice general behavior.Observed result does not have phenomenons such as sialorrhea, amyostasia and pupil variation and occurs, no abnormality seen posture, gait etc. yet; Each dosage group and blank group compare, and significance does not appear in autonomic activities to be changed.
Adopt the oral sulfonated dehydro rosin acid of anesthesia domesticated dog disodium series dosage, observe the influence of reagent animal breath system and cardiovascular system.When the oral sulfonated dehydro rosin acid of domesticated dog disodium 7.5mg/kg, each dosage of 15.0mg/kg, 30.0mg/kg, breathing, blood pressure, electrocardio were observed 3 hours continuously, adopt contrast before and after self, the result show sulfonated dehydro rosin acid disodium oral to animal breath frequency and the degree of depth, systolic arterial pressure and diastolic pressure, electrocardio (ECG II) schemes each ripple and heart rate does not have the significance influence.
Conclusion: above result can think, sulfonated dehydro rosin acid disodium oral dose 35mg/kg, 70mg/kg, 140mg/kg do not have significance influence (P〉0.05) to mice spirit, nervous system.Sulfonated dehydro rosin acid disodium oral dose 7.5mg/kg, 15.0mg/kg, 30.0mg/kg do not have significance influence (P〉0.05) to anesthesia domesticated dog respiratory system and cardiovascular system.
(4), pharmacological toxicology research summary opinion:
Sulfonated dehydro rosin acid disodium 12.5mg/kg to gastric juice acid concentration, gastric juice total acid content, gastric juice acid with sulfonated dehydro sodium abietate 100.0mg/kg effect quite, show that disodium is 8 times of single sodium to the influence of gastric juice acid-base value.Disodium has very strong capacity antacid.
Sulfonated dehydro rosin acid disodium 50.0mg/kg is suitable with single sodium 100.0mg/kg to the pepsin activity inhibitory action of pylorus ligation.
It is suitable with single sodium 100.0mg/kg that sulfonated dehydro rosin acid disodium 50.0mg/kg causes acute mucosal lesion ulcer inhibitory action to dehydrated alcohol.
Suitable with single sodium 100.0mg/kg between sulfonated dehydro rosin acid disodium 12.5mg/kg and 50.0mg/kg dosage to pyloric ligation ulcers gastric ulcer inhibitory action.
Sulfonated dehydro rosin acid disodium 6.5 * 10
-5(g/ml) external pepsin activity inhibitory action is higher than single sodium 7.5 * 10
-5(g/ml).
Show by above results of pharmacodynamic test, sulfonated dehydro rosin acid disodium is higher than single sodium far away to the regulating power of gastric acid, and disodium does not need any other the antiacid medicine of use in conjunction can play good adjusting gastric juice acid-base value when treatment hyperchlorhydria type peptic ulcer.Other is at each index observing of the prevention of peptic ulcer and therapeutical effect, interaction in vitro, and disodium is the curative effect of single sodium more than two times, or is higher than single sodium salt.To show that double sodium salt is used for the treatment of hyperchlorhydria type peptic ulcer faster than single sodium salt onset for results of pharmacodynamic test thus, and effect is more obvious, and safety is higher.
The present invention has following beneficial effect:
(1) sulfonated dehydro rosin acid disodium independent medication good effect when treatment hyperchlorhydria type peptic ulcer and gastrointestinal tract inflammation, instant effect, safe.
(2) with sulfonated dehydro rosin acid list sodium relatively, the antacid ability of sulfonated dehydro rosin acid disodium is stronger, do not need drug combination just can be better in and gastric acid, protection stomach intestinal tissue; Dissolution rate at gastric and enteral is faster, and the ulcer of stomach, intestinal and the treatment performance of inflammation are acted on faster; All be better than single sodium salt aspect peptic ulcer prevention and the treatment, effect is higher.
The specific embodiment
Now technical scheme of the present invention is described further by following examples.
Embodiment is the model case with medicine treatment hyperchlorhydria type peptic ulcer of the present invention
1. Wang Weiguo, man, 44 years old
The regular pain of patient's epigastrium 13 years, the feed back is alleviated, heartburn acid regurgitation, loss of appetite, gastroscopy: gastric ulcer 0.3 X 0.45cm, diagnosis: hyperchlorhydria type gastric ulcer.Through repeatedly taking Chinese and western drugs DeGrains such as famotidine, aluminium hydroxide.The patient seeks medical advice in many ways, all inefficacy.After change clothes medicine sulfonated dehydro rosin acid disodium of the present invention, do not add any sour medicine that presses down, take medicine a course of treatment, the above-mentioned symptom complete obiteration is fully recovered.Phone is followed up a case by regular visits to, so far not recurrence again.
2. oldly enter man, 30 years old
Gastroscope report 1.5 * 1.0cm ulcer had depression when the patient came, the periphery erosion, and stomachache, spirit is poor, through obeying medicine sulfonated dehydro rosin acid disodium of the present invention separately, does not add any sour medicine that presses down, and treats for six weeks, and gastroscope check ulcer disappears, patient's recovery from illness.
3. poplar winter Asia, woman, 47 years old.
The gastroscopy prompting: the visible lesser curvature side mucosal erosion in top hyperemia at the bottom of the stomach, edema, indefinite border, matter is crisp, and that touches is easily hemorrhage.Be diagnosed as hyperchlorhydria type chronic gastric ulcer, the pathologic finding conclusion conforms to.The prescription on individual diagnosis proxima luce (prox. luc) once rejected kermesinus blood and food debris, about 60ml.Examine and see that both hands protect the abdomen curling oneself up, shallow complexion, gastral cavilty portion persistence dull pain, the time and noisy dull pain is alleviated after must eating slightly, but feed is few, retches and feels sick, and tells saliva clearly frequently, black stool (occult blood test +++).In the upper abdomen obvious tenderness of limitation of having taken back, heavily by can be radiated to breast side of body portion, and the sense of desiring belch, vowing gas is arranged.Do not add any sour medicine that presses down, single medicine of the present invention bleeding from anus on the 2nd of using ends, the Fecal Occult Blood Testing feminine gender, and surplus card all has clear improvement.Fully recover after serveing on a course of treatment.
4. Wang Sai English, woman, 36 years old
Patient's gastric abscess, pantothenic acid, belch showed effect existing 5 years repeatedly.Once be interrupted with Chinese medicine and western medicine and failed to respond to any medical treatment.After going to a doctor,, be diagnosed as the big chronic ulcer of hyperchlorhydria gastric antrum portion lesser curvature side Semen Glycines through the X barium meal examination.Be addicted to drink, nearly two weeks comes, often stomachache, inappetence.The patient does not add with any and presses down sour medicine, and single clothes medicine of the present invention is after course of treatment, and pain disappears.Check to hospital after two months, the X barivm meal fluoroscopy (screem), the lesser curvature side niche disappears, the ulcer surface healing.The patient fully recovers so far, and phone is followed up a case by regular visits to, and does not see recurrence.
5. patient: Liu Hui, man, 50 years old.
First visit on November 30 in 2006.Stomachache history 2 years are arranged, control few effect repeatly.Be diagnosed as hyperchlorhydria chronic superficial atrophic gastritis through gastroscopy.Do not add any sour medicine that presses down, through single clothes one week of medicine of the present invention, stomachache alleviates, and appetite takes a turn for the better; After obeying a course of treatment, stomachache ends, and the abdominal distention belch disappears, conscious spirit multiplication, no sense of discomfort.Check gastroscope and biopsy show that chronic superficial gastritis, atrophic gastritis have obtained recovery from illness after leaving hospital.
5. patient: Han Xuejing, woman, 23 years old.
The patient is diagnosed as hyperchlorhydria and causes the small intestinal segmental enteritis, and the state of an illness is alleviated and worsened repeatedly, uses routine medication, but that intestinal bleeding and deterioration are failed is controlled.Recommend it to use medicine of the present invention, one day oral administration secondary, this liquid medicine solution of this external by anus once a day rectally to intestinal.After one course of treatment, sb.'s illness took a favorable turn, and inflammation is obviously improved, administration after 1 year the state of an illness do not see that recurrence worsens.
6. patient: Liu Hongli, man, 45 years old.
The patient is diagnosed as hyperchlorhydria and causes duodenum multiple ulcer pathological changes, uses routine medication, but does not improve.Recommend it to use medicine of the present invention, one day oral administration secondary does not add any sour medicine that presses down.After two courses of treatment, sb.'s illness took a favorable turn, and inflammation is obviously improved, administration after 3 years the state of an illness do not see recurrence.
Claims (2)
1, application sulfonated dehydro rosin acid disodium salt control hyperchlorhydria type peptic ulcer and gastrointestinal tract inflammation is characterized by and be used to prevent and treat hyperchlorhydria type peptic ulcer and gastrointestinal tract inflammation disease, comprise gastric ulcer, duodenal ulcer, acute or chronic gastritis, enteritis, chronic gastritis acute attack.The molecular structural formula of sulfonated dehydro rosin acid disodium is:
Wherein, R=2Na n=0
2. application sulfonated dehydro rosin acid disodium salt control hyperchlorhydria type peptic ulcer according to claim 1 and gastrointestinal tract inflammation, it is characterized by and adopt oral or non-oral administration, the dosage form of oral administration has tablet, capsule, powder, granule, Emulsion, solution, syrup formulation, adds pharmaceutically acceptable corresponding auxiliary material and adjuvant in each dosage form.
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| CNA2008101108944A CN101480383A (en) | 2008-06-17 | 2008-06-17 | Application of disodium sulfodehydroabietate for treating gastroxia type peptic ulcer and gastrointestinal tract inflammation |
| CN2009101477093A CN101590031B (en) | 2008-06-17 | 2009-06-17 | preparation method of disodium sulfodehydroabietate (DSDA) and composition |
| PCT/CN2009/001474 WO2010145066A1 (en) | 2008-06-17 | 2009-12-16 | Compositions of sulfodehydroabietic acid disodium salt for preventing or treating hyperacid gastroenteritis and peptic ulcers and preparation methods thereof |
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| WO2010145066A1 (en) * | 2008-06-17 | 2010-12-23 | 浙江爱生药业有限公司 | Compositions of sulfodehydroabietic acid disodium salt for preventing or treating hyperacid gastroenteritis and peptic ulcers and preparation methods thereof |
| CN102042964A (en) * | 2010-11-12 | 2011-05-04 | 武汉人福药业有限责任公司 | Method for detecting dissolution rates of acetylkitasamycin capsules |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010145066A1 (en) * | 2008-06-17 | 2010-12-23 | 浙江爱生药业有限公司 | Compositions of sulfodehydroabietic acid disodium salt for preventing or treating hyperacid gastroenteritis and peptic ulcers and preparation methods thereof |
| CN102042964A (en) * | 2010-11-12 | 2011-05-04 | 武汉人福药业有限责任公司 | Method for detecting dissolution rates of acetylkitasamycin capsules |
| CN102042964B (en) * | 2010-11-12 | 2012-07-04 | 武汉人福药业有限责任公司 | Method for detecting dissolution rates of acetylkitasamycin capsules |
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