What Is Sucralfate?

Sucralfate, tasteless and hygroscopic. This product is an effective anti-peptic ulcer, which has the effect of protecting the ulcer surface and promoting ulcer healing. Its mechanism of action is that under acidic conditions, this product dissociates sucrose sulfate complex ions, and the complex ions polymerize into insoluble negatively charged colloids, which can combine with positively charged protein exudates on the ulcer surface to form a layer of protection. The membrane covers the ulcer surface and promotes healing of the ulcer. It also has the effect of adsorbing pepsin and bile acid; it promotes the synthesis of endogenous prostaglandins and adsorbs epidermal growth factor (EGF), so that it can be concentrated in the ulcer area to facilitate mucosal regeneration.

Sucralfate, tasteless and hygroscopic. This product is an effective anti-peptic ulcer, which has the effect of protecting the ulcer surface and promoting ulcer healing. Its mechanism of action is that under acidic conditions, this product dissociates sucrose sulfate complex ions, and the complex ions polymerize into insoluble negatively charged colloids, which can combine with positively charged protein exudates on the ulcer surface to form a layer of protection. The membrane covers the ulcer surface and promotes healing of the ulcer. It also has the effect of adsorbing pepsin and bile acid; it promotes the synthesis of endogenous prostaglandins and adsorbs epidermal growth factor (EGF), so that it can be concentrated in the ulcer area to facilitate mucosal regeneration.

Chinese name

Sucralfate

English name

Sucralfate

nickname

Wei Weining, Di Xian, Wei Xiao, Shu Kefei

Water soluble

not soluble in water

Exterior

White or off-white powder

Application

Antipeptic ulcer

Ingredients

This product is a basic aluminum salt of sucrose sulfate.

Sucralfate compounds

Sucralfate Basic Information

Chinese name: sulfur sugar aluminum

Chinese alias: Wei Kui Ning; Shu Kejie; Shu Kefei; Wei Kui Ning; Weixiao; Aluminum Sucrose Sulfate; Diso; Soder; Dixian

English name: Sucralfate

English alias: Venter; Urba; Sucrate; Succosa; Antepsin; Surcalfatum; Urban; Ulcerlmin

CAS number: 54182-58-0

Molecular formula: C ₁₁ H ₆₀ Al ₁₆ O ₇₅ S ₈

Structural formula:

Molecular weight: 2080.77000

Exact mass: 2079.57000

PSA: 1435.37000

Physicochemical properties of sucralfate

Storage conditions: 2-8ºC ^[1]

Traits: odorless, almost odorless; hygroscopic. It is almost insoluble in water, ethanol or chloroform, easily soluble in dilute hydrochloric acid or dilute sulfuric acid, and slightly soluble in dilute nitric acid.

Sucralfate drug analysis

Method name: Sucralfate-Determination of Aluminum-Complex Titration

Application range: This method uses complex titration to determine the aluminum content in sucralfate.

This method is applicable to the determination of aluminum in sucralfate.

Method principle:

Take an appropriate amount of the test product, after dissolving, diluting and neutralizing it, add acetic acid-ammonium acetate buffer solution, precisely add ethylenediamine tetraacetic acid disodium titration solution (0.05mol / L), boil for 3 to 5 minutes, and let cool to room temperature Add xylenol orange indicator solution, titrate with zinc titration solution (0.05mol / L) until the solution changes from yellow to red, and correct with blank test. Each 1mL of ethylenediamine tetraacetic acid sodium titration solution (0.05mol / L) is equivalent to 1.349mg of aluminum, which is calculated.

Reagent: ^[2]

1. Water (newly boiled to room temperature)

2. Acetic acid-ammonium acetate buffer (pH6.0)

3 Xylenol orange indicator liquid

4 Zinc titration solution (0.05mol / L)

5. Ethylenediamine tetraacetic acid disodium titration solution (0.05mol / L)

6. Reference zinc oxide

7. Dilute hydrochloric acid

8. Methyl red in ethanol (0.025%)

9. Ammonia test solution

10 Chrome black T indicator

11. Ammonia-ammonium chloride buffer (pH 10.0)

Sample preparation:

1. Acetic acid-ammonium acetate buffer (pH6.0)

Take 100 g of ammonium acetate, add 300 mL of water to dissolve, add 7 mL of glacial acetic acid, and shake to obtain.

2. Xylenol orange indicator liquid

Take 0.2 g of xylenol orange and add 100 mL of water to dissolve.

3 Zinc titration solution (0.05mol / L)

Preparation: Take 15g of zinc sulfate (equivalent to about 3.3g of zinc), add 10mL of dilute hydrochloric acid and water to dissolve into 1000mL, and shake well.

Calibration: Take a precise amount of 25mL of this solution, add 1 drop of 0.025% methyl red in ethanol solution, add the ammonia test solution to the solution slightly yellow, add 25mL of water, ammonia-ammonium chloride buffer (pH10.0) and chrome black A small amount of T indicator was titrated with ethylenediamine tetraacetic acid disodium titration solution (0.05mol / L) until the solution changed from purple to pure blue, and the result of the titration was corrected by a blank test. According to the consumption of ethylenediamine tetraacetic acid disodium titrant titration solution, calculate the concentration of this solution, and get it.

4 Ethylenediamine tetraacetic acid disodium titration solution (0.05mol / L)

Preparation: Take 19 g of disodium ethylenediamine tetraacetate, add freshly boiled cold water to 1000 mL, and shake well.

Calibration: Take 0.12g of reference zinc oxide which is burned to constant weight at 800 , accurately weigh, add 3mL of dilute hydrochloric acid to dissolve, add 25mL of water, add 1 drop of 0.025% methyl red ethanol solution, and dropwise add ammonia test solution to The solution is yellowish, add 25mL of water and 10mL of ammonia-ammonium chloride buffer (pH10.0), add a small amount of chrome black T indicator, titrate with this solution until the solution changes from purple to pure blue, and use the titration result with Blank test correction. Each 1mL of ethylenediaminetetraacetic acid disodium titration (0.05mol / L) is equivalent to 4.069mg of zinc oxide. Calculate the concentration of the solution based on the consumption of the solution and the amount of zinc oxide taken.

Storage: Keep in glass stopper bottle, avoid contact with rubber stopper, rubber tube, etc.

5. Dilute hydrochloric acid

Take 234mL of hydrochloric acid and dilute to 1000mL with water to obtain. This solution should contain HCl at 9.5-10.5%.

6. Ammonia test solution

Take 400mL of concentrated ammonia solution and add water to make it into 1000mL.

7. Chrome black T indicator

Take 0.1 g of chrome black T, add 10 g of sodium chloride, and grind evenly to obtain.

8. Ammonia-ammonium chloride buffer (pH 10.0)

Take 5.4g of ammonium chloride, add 20mL of water to dissolve, add 35mL of concentrated ammonia solution, and then add water to dilute to 100mL.

Steps:

Take about 1.0g of this product, accurately weigh it, place it in a 200mL volumetric flask, add 10mL of dilute hydrochloric acid to dissolve it, add water to dilute to the mark, shake well, take 20mL with precision measurement, neutralize with ammonia test solution to just precipitate, and then drip Add dilute hydrochloric acid until the precipitate just dissolves, add 20mL of acetic acid-ammonium acetate buffer (pH6.0), and then add 25mL of ethylenediaminetetraacetic acid disodium titration solution (0.05mol / L). Boil for 3 ~ 5 minutes. Cool to room temperature, add 1 mL of xylenol orange indicator solution, titrate with zinc titration solution (0.05 mol / L) until the solution changes from yellow to red, and correct the titration result with a blank test.

Note 1: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weight. Precision requirements.

Note 2: "Determination of moisture" uses the drying method, taking 2 to 5 g of the test sample, and spreading it in a flat weighing bottle that is dry to constant weight, the thickness does not exceed 5 mm, and the loose test sample does not exceed 10 mm. Open the bottle cap and dry at 100 ~ 105 ° C for 5 hours. Place the cap on the dryer, cool it for 30 minutes, and weigh it precisely. Then dry it at the above temperature for 1 hour, cool, and weigh until two times in a row. The difference in weighing does not exceed 5 mg. Calculate the moisture content (%) in the test product based on the lost weight ^[3] .

Sucralfate Pharmacopoeia Standard

Sucralfate source (name), content (potency)

This product is a basic aluminum salt of sucrose sulfate. Calculated based on dry products, aluminum (Al) should be 18.0% to 22.0%, and sulfur (S) should be 8.5% to 12.5%.

Sucralfate

This product is white or off-white powder; odorless, almost odorless; hygroscopic.

This product is almost insoluble in water, ethanol or chloroform; easily soluble in dilute hydrochloric acid or sulfuric acid, and slightly soluble in dilute nitric acid.

Sucralfate identification

(1) Take about 0.1g of this product, add 1ml of dilute hydrochloric acid, boil and dissolve, let cool, neutralize with sodium hydroxide test solution, and slowly add the lukewarm alkaline copper tartrate test solution to produce cuprous oxide. Red precipitate.

(2) Take about 0.1g of this product, add 1ml of dilute hydrochloric acid to dissolve it, and add barium chloride test solution. If precipitation occurs, filter and heat the filtrate to boil, which will generate a large amount of white precipitate.

(3) Take about 0.1g of this product, add 1ml of dilute hydrochloric acid to dissolve it, add ammonia test solution to make it alkaline, boil, filter, precipitate, add dilute hydrochloric acid to dissolve, and identify the aluminum salt of the solution. Appendix III) ^[4] .

Sucralfate inspection

Acid power

Take about 0.5g of this product, weigh it accurately, place it in a 250ml conical flask with a stopper, add 100ml of hydrochloric acid titration solution (0.1mol / L), tightly stopper, shake at 37 ° C for 1 hour, and let cool to room temperature. After filtration, 50 ml of the filtrate was accurately measured, a few drops of bromophenol blue indicator liquid was added, and titration was performed with a sodium hydroxide titration solution (0.1 mol / L). Calculated on dry basis, the consumption of hydrochloric acid titrant (0.1mol / L) per 1g shall not be less than 130ml.

acidity

Take 0.20g of this product, add 20ml of water, heat it in a water bath for 2 ~ 3 minutes, then let it cool to room temperature, and measure it according to law (Appendix VIH of Pharmacopoeia Part II of 2010 Edition), the pH value should be 3.5 ~ 5.5.

Clarity of acid solution

Take 1.0g of this product, add 10ml of dilute hydrochloric acid, shake and dissolve, the solution should be clarified; if it is turbid, compare with No. 3 turbidity standard solution (Appendix B of Part II of the Pharmacopoeia of 2010 Edition), it must not be more concentrated.

chloride

Take 0.10g of this product, place it in a 100ml measuring bottle, add 2ml / L nitric acid solution 30ml and water, and dilute to the mark with water. Shake well; measure 10.0ml, and check according to law (Appendix A of Part II of the Pharmacopoeia of the 2010 edition), Compared with the control solution made from 5.0ml of standard sodium chloride solution, it must not be more concentrated (0.50%).

-methylpyridine

Take an appropriate amount of this product, grind it carefully, weigh 2.0g, place it in a 10ml stoppered test tube, add 5.0ml of water, heat it in a water bath at 80-90 ° C for 30 minutes, and shake it from time to time. After cooling, transfer it to a centrifuge tube. Centrifuge and take the supernatant as the test solution; take an appropriate amount of -methylpyridine reference substance, weigh it accurately, and make a solution containing about 20 g per 1 ml of water as the reference solution. Precisely measure 2 l each of the test solution and the reference solution, and check them by gas chromatography (Appendix VE of Part Two of the 2010 Pharmacopoeia), using divinylbenzene-ethylvinylbenzene polymer porous beads with a diameter of 0.25 to 0.18mm. The stationary phase was measured at a column temperature of 200 to 225 ° C. The peak height of the -methylpyridine in the test solution should not be greater than the peak height of the reference solution (0.005%).

Loss on drying

Take this product and dry it at 105 ° C for 3 hours, and the weight loss shall not exceed 14.0% (Appendix L of Pharmacopoeia Part II of 2010 Edition).

Heavy metal

Take 1.0g of this product, add 20ml of hydrochloric acid solution (9 100), stir to dissolve, add ammonia test solution to alkalinity, then add another 2ml, leave it for a while, filter, and wash the precipitate with water. Combine the washing liquid and filtrate Add water to make 25ml, and take a certain amount of standard lead solution. After the same treatment, check according to law (Appendix H of the 2010 edition of the Pharmacopoeia, the third method), the content of heavy metals must not exceed 10 parts per million.

Arsenic salt

Take 1.0g of this product, add 10ml of dilute sulfuric acid and 5ml of bromine test solution, boil, let cool, add a few drops of acidic stannous chloride test solution to fade, add 3ml of hydrochloric acid and water to 28ml, check according to law (2010 Pharmacopoeia (Appendix 2 to Part I, Law 1), shall comply with the regulations (0.0002%) ^[4] .

Determination of sucralfate

aluminum

Take about 1.0g of this product, weigh it accurately, put it in a 200ml measuring bottle, add 10ml of dilute hydrochloric acid to dissolve it, dilute it with water to the mark, and shake well; take a precise amount of 20ml, add ammonia test solution to neutralize until just precipitated, and then drip Add dilute hydrochloric acid until the precipitate just dissolves, add 20ml of acetic acid-ammonium acetate buffer (pH 6.0), and then add 25ml of ethylenediamine tetraacetic acid disodium titration solution (0.05mol / L), boil for 3 to 5 minutes, and let cool At room temperature, add 1ml of xylenol orange indicator solution, titrate with zinc titration solution (0.05mol / L) until the solution changes from yellow to red, and correct the result of the titration with a blank test. Each 1ml of ethylenediaminetetraacetic acid disodium titration (0.05mol / L) is equivalent to 1.349mg of Al.

sulfur

Take about 1.0g of this product, weigh it accurately, put in a beaker, add 10ml of nitric acid solution (1 2) and 10ml of water, slowly boil for 10 minutes, add ammonia test solution to alkaline and then add 5ml, boil for 1 minute, Let it cool, transfer to a 100ml volumetric flask, dilute to the mark with water, shake well, filter with dry filter paper, take a precise amount of 10ml of the filtrate, add 1mol / L hydrochloric acid solution, and add just 3 drops after it becomes acidic. Add 10ml of barium chloride-magnesium chloride solution (take 6g of barium chloride and 5g of magnesium chloride, add water to dissolve and dilute to 500ml), shake well, let it stand for a while, add 15ml of ammonia-ammonium chloride buffer (pH 10.0), triethanolamine (1 2) A small amount of 5ml and chrome black T indicator was titrated with ethylenediamine tetraacetic acid disodium titrant (0.05mol / L), and the results of the titration were corrected by a blank test. Each 1ml of ethylenediaminetetraacetic acid disodium titration (0.05mol / L) is equivalent to 1.603mg of S ^[4] .

Sucralfate category

Antacids.

Sucralfate storage

Sealed and stored in a dry place.

Sucralfate

(1) Sucralfate oral suspension (2) Sucralfate dispersible tablets (3) Sucralfate chewable tablets (4) Sucralfate capsules

Sucralfate version

Pharmacopoeia of the People's Republic of China 2010

Sucralfate drug description

Classification of sucralfate

Digestive System Drugs> Acid and Gastric Mucosal Protection

Sucralfate

White or almost white powder; odorless, almost odorless; hygroscopic. It is almost insoluble in water, ethanol or chloroform, easily soluble in dilute hydrochloric acid or dilute sulfuric acid, and slightly soluble in dilute nitric acid.

Sucralfate dosage form

1. Tablets: 0.25g, 0.5g each;

2. Capsule: 0.25g;

3. Suspension: 1g (5ml), 20g (10ml).

Sucralfate pharmacological action

Sucralfate is a basic aluminum salt of sucrose sulfate. It is a gastric mucosa protectant, which has the effect of protecting the ulcer surface and promoting ulcer healing. Sucralfate can dissociate into negatively charged sucrose octasulfate in an acidic environment and polymerize insoluble colloids to protect the gastric mucosa; it can bind to positively charged exudate proteins on ulcers or inflammations, and on the ulcers or inflammations Form a thin film to protect the ulcer or inflammatory mucosa from the attack of gastric acid and promote healing of the ulcer. The affinity to ulcer lesions is about 6 to 7 times that of normal mucosa. At the same time, sucralfate can adsorb pepsin and inhibit the enzyme from breaking down proteins. At therapeutic doses, pepsin activity can be reduced by about 30%. Sucralfate can also neutralize gastric acid, but its effect is weak. 1g sucralfate can only neutralize 2.5mmol / L hydrochloric acid. In addition, sucralfate can also absorb epidermal growth factors in saliva and concentrate them on the ulcer to promote ulcer healing; it can also stimulate the synthesis of endogenous prostaglandin E and stimulate the surface epithelium to secrete bicarbonate, thus causing To cell protection. When sucralfate is used in the treatment of peptic ulcer, there is no significant difference between the two compared with H2 receptor antagonists. But sucralfate can reduce the recurrence rate of ulcer disease. At the same time, both sucralfate and H2 receptor antagonists can effectively prevent the occurrence of upper gastrointestinal bleeding with comparable effects. Other scholars have reported that sucralfate also has a protective effect on the esophageal mucosa, so it can also be used for reflux esophagitis ^[5] .

Sucralfate pharmacokinetics

Sucralfate can release aluminum ions and sucrose octasulfate complex ions after oral administration. The gastrointestinal absorption is only 5%, and the effect lasts about 5 hours. It is mainly excreted with feces, and a small amount is excreted with urine as disaccharide sulfate. The serum and urine aluminum concentrations of patients with chronic renal insufficiency were significantly higher than those with normal renal function.

Sucralfate indications

Commonly used for gastric and duodenal ulcers ^[6] .

Sucralfate matters needing attention

1. Chronic renal insufficiency.

2. Must be taken on an empty stomach.

3. Continuous application should not exceed 8 weeks.

Sucralfate usage and dosage

1. Active gastric and duodenal ulcers: 1g each time, 3 to 4 times a day, medication for 4 to 6 weeks.

2. Prevent the recurrence of duodenal ulcer: 1g each time, 2 times a day.

Sulfate is forbidden to use with caution

Patients with renal insufficiency, after taking sucralfate, the aluminum content in plasma increases. Although the accumulation of aluminum in the body after long-term medication cannot be determined, it should be used with caution.

Sucralfate adverse reactions

More common is constipation; rare or occasional back pain, diarrhea, dizziness, lethargy, dry mouth, indigestion, nausea, rash, itching, and stomach cramps.

Individual cases have dry mouth, nausea, constipation, severe stomach pain, and long-term use of large doses may appear aluminum poisoning. Sucralfate causes a decrease in the level of phosphate in the plasma, and osteomalacia may occur during long-term use.

The incidence of adverse reactions was about 4.7%, including constipation (2.2%). Individual patients may have dry mouth, nausea, stomach pain, etc., and can be combined with appropriate anticholinergics.

Should not be combined with multi-enzyme tablets, otherwise the efficacy of both will be reduced. This is because the multi-enzyme tablets contain pepsin, pancreatin, and amylase, and their pharmacological effects are antagonized with this product. The digestive enzymes, especially pepsin, affect the healing of ulcers. When combined with cimetidine, it may reduce the efficacy of this product.

Interaction of sucralfate drugs

1. Sucralfate can interfere with the absorption of fat-soluble vitamins (vitamins A, D, E, and K).

2. Sucralfate can reduce oral anticoagulants (such as warfarin), digoxin, quinolones (such as ciprofloxacin, lomefloxacin, norfloxacin, sparfloxacin), phenytoin, The digestive tract absorption of ibuprofen, indomethacin, aminophylline, thyroxine and other drugs should be separated by sucralfate and these drugs for more than 2 hours if necessary.

3. Sucralfate can affect the gastrointestinal absorption of tetracycline, and its mechanism may be related to the formation of relatively insoluble integrants of tetracycline and aluminum ions. Therefore, simultaneous application should be avoided. If combined, sucralfate should be given at least 2 hours after taking tetracycline, and avoid administration of sucralfate before taking tetracycline.

4. Sucralfate can significantly affect the absorption of amitriptyline, but the exact mechanism is still unclear. If the two drugs are combined, the interval between the two drugs should be extended as much as possible, and the efficacy of amitriptyline should be monitored, and the amitriptyline dose should be increased if necessary.

5. When sucralfate is used in combination with multi-enzyme tablets, the efficacy of both is reduced. This is because multi-enzyme tablets contain pepsin, pancreatin and amylase. Sucralfate can complex with pepsin and reduce the effect of Efficacy; on the other hand, the pharmacological effects of multi-enzyme tablets are antagonized with orthosucralfate. The digestive enzymes, especially pepsin, can affect the healing of ulcers. Therefore, the two should not be used together.

6. Antacids can interfere with the pharmacological effects of sucralfate. Sucralfate can also reduce the absorption of cimetidine. Generally, it is not advisable to combine sucralfate and cimetidine. However, in order to relieve ulcer pain, antacids can be used in combination. The latter must be administered 0.5h before taking sucralfate or 1h after taking it.

7. Sucralfate protects the stomach and duodenal mucosa in acidic environments, so it should not be used in combination with alkaline drugs.

8. Anticholinergic drugs can alleviate adverse reactions such as constipation and stomach upset caused by sucralfate ^[5] .

Sucralfate Expert Reviews

The healing rate of gastric and duodenal ulcer disease is similar to that of H2 receptor antagonist. But symptoms improved significantly. The one-year recurrence rate of sucralfate is about 35%, and there is no significant difference compared with H2 receptor antagonists ^[5] .