aspirin

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synonym Acetylsalicylic acid (acetylsalicylic acid) generally refers to aspirin (drug)

Aspirin, also known as acetylsalicylic acid, is a Organic compound , chemical formula is C nine H eight O four , white Crystallinity Powder, soluble in ethanol 、 Ether , slightly soluble in water, mainly used for antipyretic analgesia NSAIDs , anti platelet aggregation Drugs, which have been clinically used for nearly 100 years, have proved to be effective in relieving mild or moderate pain, such as toothache 、 headache 、 neuralgia 、 Muscle soreness and dysmenorrhea Good effect, also used for cold 、 influenza etc. fever Antipyretic of disease, treatment rheumatic fever Wait, can stop Thrombosis , clinically used for prevention Transient ischemic attack 、 miocardial infarction 、 Artificial heart valve And venous fistula or other thrombosis after surgery.

Drug name: aspirin
Foreign name: aspirin^[90]^[92-93]
Alias: Acetylsalicylic acid
Prescription medicine or not: yes
Main indications: For fever, pain and rheumatoid arthritis
Main drug contraindications: Non steroidal anti-inflammatory drug allergy is prohibited
Dosage form: Oral regular release dosage form (excluding dispersible tablets), sustained and controlled release dosage form, enteric coated sustained release tablets^[91-93]
Careful use by athletes: no
Whether included in medical insurance: yes
Drug type: Platelet aggregation inhibitor, antithrombotic drug, blood and hematopoietic organ drug^[91]

chemical formula: C nine H eight O four
molecular weight: one hundred and eighty point one five seven
CAS login number: 50-78-2
EINECS login number: 200-064-1
Melting point: 134 to 136 ℃
Boiling point: 321.4 ℃
Water solubility: Slightly soluble
Density: 1.35 g/cm³
Appearance: White crystalline powder
Flash point: 131.2 ℃
Security description: S26；S36/37/39
Hazard symbol: Xn
Hazard description: R22；R36/37/38

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Antipyretic and analgesic, non steroidal anti-inflammatory drugs, anti platelet aggregation drugs.

Analgesia and antipyretic

Aspirin can relieve headache in a short time through vasodilation Drug pair Dull pain Is better than Sharp pain Role of. Therefore, the drug can relieve mild or moderate dull pain, such as headache, toothache, neuralgia, muscle pain and menstrual pain; At the same time, it can make bacteria Pyrogen Elevated hypothalamus Thermoregulatory center Set point Restore (reduce) to normal level, so it is also used for cold , flu, etc. This product can only relieve symptoms, and cannot cure the causes of pain and fever, so other drugs should be used at the same time.

Anti inflammation and anti rheumatism

Aspirin is used to treat rheumatic fever be the first choice Drugs can relieve fever, reduce inflammation, improve joint symptoms and reduce ESR, but can not remove the basic pathological changes of rheumatism, nor prevent heart damage and other complication 。 If obvious myocarditis , which is generally advocated to use first Adrenocortical hormone After the rheumatism symptom is controlled and before the hormone is stopped, the drug is added to reduce the Rebound phenomenon 。

Treat arthritis

except arthritis In addition, it is also used to treat rheumatoid arthritis, which can improve symptoms and create conditions for further treatment. In addition, this product is used for Osteoarthritis 、 Ankylosing spondylitis Juvenile arthritis and other bone and muscle pain caused by non rheumatic inflammation can also relieve symptoms.

antithrombosis

The product can inhibit platelet aggregation and prevent Thrombosis It can be used clinically to prevent transient ischemic attack (TIA), myocardial infarction Atrial fibrillation 、 Artificial heart valve 、 Arteriovenous fistula Or other thrombosis after surgery. It can also be used for treatment Unstable angina pectoris 。

Inhibition of platelet aggregation

Aspirin can inhibit the release of platelets and inhibit platelet aggregation when climbing at high altitude.

ease Mucocutaneous lymphnode syndrome (Kawasaki disease)

Children with Kawasaki disease are treated with aspirin to reduce inflammatory reaction And prevent the formation of intravascular thrombosis.

resistance cancer

On August 6, 2014, britain After evaluating and analyzing all available evidence, scientists concluded that taking aspirin every day can reduce the risk of suffering or dying gastric cancer 、 Intestinal cancer The probability of waiting. If people over 50 years old in the UK insist on taking aspirin every day for ten years, it may save about 122000 people from cancer in 20 years.

But scientists also warn that aspirin can cause Internal hemorrhage Therefore, the doctor must be consulted before taking aspirin for a long time. In the medical field, whether aspirin can be taken for a long time has been a controversial issue.

Scientists at Queen Mary College found that aspirin reduced intestinal cancer, stomach cancer and Esophageal cancer Patient mortality.

On the decrease mammary cancer 、 prostatic cancer and lung cancer In terms of mortality, aspirin also played a role, but the effect was not so obvious.

The study also found that only after taking aspirin for at least 5 years can we see positive effects.

The biggest side effects of long-term aspirin use include stomach bleeding and brain bleeding. The older you are, the greater the possibility of internal bleeding. Do this Research After taking internal bleeding and other side effects into account, scientists recommended that the long-term use of aspirin should be set at 10 years, but scientists also warned that doctors should consent before taking aspirin.

Prevent digestive tract tumour

Long term regular use of aspirin can greatly reduce the incidence of gastrointestinal tumors.

Netherlands A new study shows that taking small doses of aspirin may help Colon cancer Patients improve their survival expectations.

Netherlands Leiden University Medical center researchers analyzed 999 colon cancer patients who underwent surgery between 2002 and 2008, and found that 182 of them took aspirin Patient mortality The mortality rate of 817 patients without aspirin was 48.5%. This one data display Aspirin is beneficial to patients with colon cancer.

Further analysis shows that if there is a special antigen called HLA-I in the cancer tissue of colon cancer patients Adjuvant therapy "Most effective". Otherwise, it may have no effect. Therefore, for patients diagnosed with colon cancer and whose tumors express HLA-I antigen, aspirin can improve their life expectancy.

This research result was published in the new issue of JAMA Internal Medicine.

In the review article distributed by the magazine Columbia University Dr. Alfred Neugt pointed out that newly diagnosed colon cancer patients or their families often ask what they should do in addition to the normal medical plan. He had never recommended aspirin before, but was ready to do so.

indication

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1. Aspirin Yes platelet Aggregations of are inhibition , so Aspirin enteric-coated tablets Indications are as follows:

(1) Lower acute myocardial infarction Incidence risk of suspected patients

(2) Prevent recurrence of myocardial infarction

（3） apoplexy Of Secondary prevention

(4) Lower Transient ischemic attack (TIA) and its secondary cerebral apoplexy Risk of

(5) Reduced stability and Unstable angina pectoris Patients' risk of disease

(6) Arteries surgical operation or Interventional surgery After, such as percutaneous coronary angioplasty（ PTCA ）, Coronary artery bypass（ CABG ）, Carotid endarterectomy, arteriovenous bypass

(7) Prevention Major operation after Deep vein thrombosis and pulmonary embolism

(8) Lower cardiovascular Risk factors（ coronary heart disease family history 、 diabetes 、 Dyslipidemia 、 hypertension , obesity, smoking history, people over 50 years old).

2、 Antipyretic analgesics , for fever , pain and Rheumatoid arthritis Etc.

3. It is the earliest, most widely used and most common antipyretic analgesic rheumatism Drugs. It has antipyretic, analgesic, anti-inflammatory, anti rheumatism and anti platelet aggregation And so on pharmacological action , the effect is rapid and definite, Overdose Easy to diagnose and handle, rarely occurs Anaphylactic reaction 。 It is often used for colds and fever, headache 、 neuralgia Joint pain, muscle pain Rheumatic fever , Acute Internal humidity nature arthritis 、 Rheumatoid arthritis and toothache Etc. Yes《 National Essential Drug Catalogue 》Listed varieties. Acetylsalicylic acid is also used in other drugs intermediate 。

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Children under 12 years old may cause Ruiyi syndrome （Reye's syndrome） hyperuricemia Long term use may cause liver damage. Avoid use during pregnancy. Drinkers who take aspirin of therapeutic amount will cause spontaneity Anterior chamber hemorrhage Therefore, patients with traumatic hyphema should not use aspirin. caesarean birth Or aspirin is forbidden for abortion patients; Aspirin 6-phosphate glucose dehydrogenase Defective Hemolytic anemia Patient's hemolysis Deterioration; Newborns, children and the elderly seem to be particularly sensitive to the effects of aspirin on bleeding. The therapeutic dose can make children under 2 years old Metabolic acidosis , heating Hyperventilation And brain symptoms.

Gastrointestinal bleeding or cerebral hemorrhage The risk of 50% may offset the benefits of taking a small amount of aspirin.

Research Personnel analysis Lives in Australia The health database of 20000 elderly men and women aged 70 to 74 in Victoria runs the data base And then input the clinical trial results of the advantages and disadvantages of taking aspirin every day into the computer.

adopt computer simulation The study found that taking a small amount of aspirin could prevent 710 elderly people from suffering from heart disease, 54 elderly people avoided stroke, but 1071 elderly people suffered from gastrointestinal bleeding and 129 elderly people suffered from cerebral hemorrhage. However, whether they take aspirin or not has no effect on their life span.

A number of studies have confirmed that aspirin can help prevent the formation of thrombus that can lead to infarction or stroke, but one of the side effects of aspirin is that long-term use will lead to bleeding, and the bleeding site varies according to individual conditions.

American health guidelines recommend that people at high risk of cardiovascular disease and coronary heart disease should take 75 to 150 mg of low-dose aspirin every day. The study believes that, so far, for the elderly, "we should resist the temptation of blindly taking aspirin.

Disabled

1. Ulceration or other activity with bleeding symptoms When bleeding ；

2、 hemophilia or Thrombocytopenia 。

3. Ulcer disease or Corrosive gastritis ；

4、 glucose six phosphoric acid dehydrogenase Defects (hemolytic anemia is occasionally caused by the product);

5、 gout (This product can affect the effect of other acid excretion drugs, and may cause uric acid retention in small doses);

6、 Hypofunction of liver Can aggravate the liver when Toxic reaction , aggravated Bleeding tendency ， Hepatic insufficiency and cirrhosis Patients are prone to kidney adverse reactions;

7、 Cardiac insufficiency Or hypertension, which may cause heart failure or pulmonary edema ；

8、 Renal failure It may increase the risk of nephrotoxicity.

Cautious use

1. Asthma and others Anaphylaxis Reaction time Use with caution.

2. For Hyperthyroid crisis Caused by High fever Patients should use it with caution.

Restricted or prohibited

1. For aspirin, ibuprofen, naphthol, etc Drug allergy The.

2、 favism Patients, because aspirin can cause hemolysis.

3. Yes nephropathy , gastric ulcer, diabetes gout Patients with symptoms, etc. must obtain the doctor's permission before taking it.

4. Children and adolescents should not use aspirin to treat colds.

5. It should not be taken by hemophiliacs or those with other bleeding tendencies.

6. Pregnant women.

In addition, it should be noted that if aspirin is taken with alcohol, it will increase the risk of gastric bleeding. It is better to take aspirin with food or water to reduce gastrointestinal irritation.

Aspirin is generally used for antipyretic and analgesic purposes in small doses, which will not cause adverse reactions. However, long-term use of aspirin in large quantities is prone to side effects, and most pain relievers have aspirin. Common side effects include nausea, vomiting, epigastric discomfort or pain, and rarely gastrointestinal bleeding or induction ulcer 、 Bronchospasm Allergic reactions skin sensibility And liver and kidney damage.

character

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This product is white crystal or Crystallinity Powder, odorless or slightly acetic acid odor, slowly hydrolyzed in case of moisture.

This product is in ethanol Soluble , on Trichloromethane or Ether Soluble in water or anhydrous ether, slightly soluble in sodium hydroxide Solution or sodium carbonate Dissolve in solution, but decompose at the same time.

Specifications

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Tablets: 0.3g, 0.5g;

Enteric coated tablets: 0.3g;^[92]

Enteric coated tablets: 25mg, 50mg, 0.1g, 0.3g.^[93]

Usage and dosage

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Children's oral dose

The study found that if children took aspirin when suffering from viral infectious diseases Reye's syndrome (A serious Adverse drug reactions ， mortality High). Therefore, it is not recommended to give aspirin to children or any children under 19 years old. Always prepare Acetaminophen or ibuprofen To relieve pain and have a fever 。

1. Antipyretic, analgesic, daily press Body surface area 1.5g/m2, taken orally in 4~6 times, or 5~10mg/kg of body weight each time, or 60mg per year, once every 4~6 hours if necessary.

2. Anti rheumatism, daily press weight 80~100mg/kg, divided into 3~4 times. If no curative effect is obtained in 1~2 weeks, it can be determined according to Blood concentration Adjust the dosage. Some cases need to be increased to 130 mg/kg per day.

3. Children for Mucocutaneous lymph node syndrome （ Kawasaki disease ）At the beginning, take it three to four times a day according to the weight of 80~100mg/kg, and change it to 30mg/kg a day after 2-3 days of heat recovery, take it two to four times a day for two months or more, Thrombocytosis Blood High solidification state During this period, 5-10mg/kg/day, once a day.

4. Prevention of thrombus atherosclerosis and myocardial infarction : 0.3g/time, once a day; Prevention temporary cerebral ischemia 0.6g each time, twice a day.

5. Treatment of biliary tract Ascaris lumbricoides : 1g each time, 2-3 times a day, 2-3 consecutive days.

6. Treatment X-ray Exposure or radiotherapy Caused by diarrhea , 0.6-0.9 g each time, 4 times a day.

7. Governance Tinea pedis , use first warm water Or 1:5000 potassium permanganate Wash with solution, and then spread the powder to the affected part, which can be cured 2~4 times generally. Salicylates morning Administration Long peak time, half life Long, opposite at night. The dosage should be slightly increased in the morning for reasonable administration. One extra night.

Adult oral dose

1. Antipyretic and analgesic, 0.3-0.6g once, three times a day, and once every 4 hours if necessary.

2. Anti rheumatism, 3-5 g a day（ Acute rheumatic fever 7~8g), four times orally.

3. To inhibit platelet aggregation, there is no clear dosage. Most people advocate using small dosage, such as 50-150mg, once every 24 hours.

4. Treatment Biliary ascariasis , 1g once, 2-3 times a day, for 2-3 consecutive days; Discontinue use 24 hours after the paroxysmal colic stops, and then conduct anthelmintic treatment.

Optimum dosage

1. In the prevention of valvular disease heart disease Occur systemic Arterial embolism In terms of, aspirin alone is ineffective, but Dipyridamole When used together, it can enhance the effect of small dose dipyridamole.

2. Avoid and Glucocorticoid share; Avoid and coumarin Class A anticoagulant Hypoglycemic drugs Methotrexate 、 Barbiturates 、 aniline Class, etc.

3、 After dinner 。 According to the evidence-based guidelines of the American College of Chest Physicians Association for Antithrombotic and Thrombolytic Therapy (ACCP), aspirin should be used to prevent myocardial infarction, stroke and vascular death. Patients should use the best dose according to their condition.

A large number of clinical trials show that for most patients, including chronic stability or instability angina pectoris In patients, aspirin 75 mg/day can effectively reduce the risk of acute myocardial infarction and death. This dose can also be reduced Transient ischemic attack Patients with stroke and dead incidence rate 。 A European stroke prevention study shows that there have been transient ischemic attacks and strokes in the past medical history Aspirin 25mg twice a day (50mg/day) can reduce the risk of stroke or death in 30% of patients. clinical Practical proof Even if patients take aspirin with a higher dose than that in the table, the efficacy will not further increase, but the occurrence of side effects will greatly increase. Therefore, in the treatment of various Thrombotic diseases The patient should use the smallest Effective dose , that is, 50~160mg/day for long-term application to achieve the maximum efficacy, while toxic side effect This is the best dose for patients to take aspirin.

matters needing attention

Note: It should be taken with food or with water to reduce gastrointestinal irritation.

Aspirin and alcohol cannot be taken together. The main component of alcohol is alcohol in the liver Alcohol dehydrogenase Under the action of acetaldehyde , and then Acetaldehyde dehydrogenase Under the action of acetic acid , and then generate carbon dioxide And water. Aspirin will reduce the activity of aldehyde dehydrogenase and prevent Acetaldehyde oxidation It is acetic acid, which causes the accumulation of acetaldehyde in the body, aggravates the pain symptoms of the whole body, and causes Liver injury 。

Adverse reactions

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Aspirin is an antipyretic and analgesic with a long history. Aspirin is widely used in clinic for fever, headache, neuralgia, muscle pain, rheumatic fever Acute rheumatic arthritis And so on. With the wide application of aspirin Adverse reactions Therefore, when using aspirin to treat various diseases, its adverse reactions should be closely monitored.

Gastrointestinal symptoms

Gastrointestinal symptoms are the most common adverse reactions of aspirin, and the more common symptoms are nausea, vomiting Epigastrium Discomfort or pain, etc.

Oral aspirin can stimulate directly gastric mucosa Causes upper abdominal discomfort and nausea and vomiting. Long term use may cause damage to gastric mucosa gastric ulcer and Gastric bleeding 。 Blood picture Fecal occult blood test And necessary gastroscope Inspection.

Aspirin is best taken after meals or with Antacid Same service, ulcer Patients should use it with caution or not. enhance Gastric mucosal barrier Functional drugs, such as misoprostol Etc., for aspirin, etc NSAIDs Caused by Peptic ulcer It has special effects.

Anaphylactic reaction

Specificity People with physical constitution can be caused by taking aspirin rash 、 Angioneurotic edema and asthma Allergic reactions such as allergic reactions, mostly seen in middle-aged people or rhinitis 、 nasal polyp patient. Aspirin inhibition prostaglandin And its influence immune system of Asthma is mostly severe and persistent, usually used Antiasthmatic drug Most of them are ineffective, only hormone is effective. Typical aspirin triad (Aspirin intolerance, asthma and nasal polyps).

central nervous system

Nerve symptoms are generally in the dosage Large time Appearance Salicylic acid reaction , the symptoms are headache vertigo 、 tinnitus , Visual Hearing loss When the dosage is too large Insanity 、 convulsions Even coma, the symptoms can be completely recovered 2 to 3 days after drug withdrawal. It can also cause central Nausea and vomiting 。

Liver damage

Aspirin induced liver injury usually occurs at high doses. This kind of damage is not acute. It is characterized by that it occurs several months after treatment, usually without symptoms. Some patients have discomfort and tenderness in the upper right part of the abdomen. serum Hepatocyte The enzyme level is increased, but the jaundice Not very common. This damage is reversible after stopping aspirin, and serum after stopping aspirin transaminase Most of them return to normal within 1 month, systemic type rheumatism Compared with the other two types of rheumatism, children are more prone to liver damage.

After aspirin induced liver damage, clinical processing method It's drug withdrawal, give amino acid fluid infusion , VitC and Inosine And other drugs, oral prednisone The symptoms usually disappear after 1 week.

Renal damage

Long term use of aspirin may occur Interstitial nephritis 、 Renal papilla necrosis 、 renal function Decline. Long term and large dosage of this product may cause oxidative phosphorylation decoupling Union, potassium from Renal tubule Cell exocytosis, leading to Potassium deficiency Uric acid excretion is too high, and the major damage is that protein, cells Tubular type Etc. Some people believe that Carcinoma of renal pelvis Abuse of aspirin, etc anodyne Of secondary complication.

Impact on blood

Aspirin usually does not change white blood cell And the number of platelets and hematocrit hemoglobin Content of. But long-term use of aspirin may lead to iron-deficiency anemia 。

cardiotoxicity

Therapeutic dose of aspirin is not important for cardiovascular Direct action 。 High dose can directly act on blood vessels smooth muscle , leading to peripheral Vasodilation 。 Poisoning dose Through direct and central blood vessels Motor paralysis And inhibit the circulation function.

Reye's syndrome

Aspirin for children influenza or Chicken pox Reye's syndrome may be caused during treatment. Reye's syndrome It is an acute encephalopathy and liver fat infiltration syndrome, often occurring after some acute viral infectious diseases. The etiology is not yet clear, but it is generally believed to be related to the following factors: such as virus（ influenza virus and Varicella virus ）、 salicylate 、 Exogenous Viruses such as（ Aflatoxin ）, internal metabolic defects, and other factors can exist together or affect each other. Clinically Viral cold Aspirin is not recommended.

Cross anaphylaxis

When allergic to this product, it may also be allergic to another kind of salicylic acid allergy 。 But people who are allergic to this product may not be right Acetylation Allergic to salicylic acid.

Pharmacology and toxicology

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pharmacology

Pharmacokinetics

Aspirin is the first antiplatelet drug used in antithrombotic therapy and has been established as a treatment acute myocardial infarction （ AMI ）It is a classic drug for the secondary prevention of unstable angina pectoris and myocardial infarction (MI). The principle of action is that aspirin Cyclooxygenase （cyclooxygenase， COX ）COX-1 in Active site Polypeptide chain 530 bits serine Residue Irreversible acetylation of hydroxyl group of, leading to COX Inactivation And then blocked the pathway from AA to thromboxane A2 (TXA2), and inhibited the aggregation of PLT.

COXs are key to the production of TXA2 and prostaglandin I2 (PGI2) from AA Rate limiting enzyme There are two forms of COX-1 and COX-2 in human body, COX-1 is inherent in PLT. clinical research It shows that for various ischemia nature Cardiovascular and cerebrovascular diseases Patients and others High risk group Short term or long-term aspirin treatment for prevention Possible There are clear benefits in myocardial infarction, stroke and vascular death of Aspirin resistance There is still controversy on the issue. With the development of research on antiplatelet aggregation drugs, the main clinical problem is to determine the laboratory monitoring indicators of the efficacy and side effects of antiplatelet aggregation drugs.

1. Analgesic effect: mainly by inhibiting prostaglandins and others sense of pain For mechanical or chemical Sexual stimulation Sensitive substances (such as bradykinin 、 histamine ）Synthesis of, belonging to peripheral Analgesics 。 However, the possibility of central analgesia (possibly acting on the hypothalamus) cannot be ruled out;

2、 Antiphlogistic effect; The exact mechanism is still unclear, which may be due to the effect of the product on inflammatory tissue, which can be caused by inhibiting prostaglandins or other Inflammatory reaction The synthesis of substances (such as histamine) Lysosomal enzyme Release and white blood cell Vitality may also be related to it;

3. Antipyretic effect: possibly by acting on the hypothalamus Thermoregulatory center It can cause peripheral blood vessel expansion, increase skin blood flow, sweat, and increase heat dissipation, which has antipyretic effect. This central effect may be related to the inhibition of prostaglandin synthesis in the hypothalamus;

4. Anti rheumatism effect: The anti rheumatism mechanism of this product, in addition to its antipyretic and analgesic effects, mainly lies in its anti-inflammatory effect;

5. Inhibition of platelet aggregation: by inhibiting prostaglandins in platelets Cyclooxygenase (prostaglandin cyclooxygenase) to prevent the formation of thromboxane A2 TXA2 (TXA2 can promote platelet aggregation). This function is Irreversibility 。

Pharmacokinetics

The absorption is rapid and complete after oral administration. It has begun to be absorbed in the stomach, and most of it can be absorbed in the upper part of the small intestine. absorptivity And solubility And gastrointestinal pH. Food can be reduced Absorption rate , but does not affect the absorption. Enteric coated tablets absorb slowly. This product and sodium bicarbonate It can be absorbed quickly with the same service. After absorption, it is distributed in various tissues and can also penetrate Articular cavity 、 cerebrospinal fluid Medium. Aspirin has low protein binding rate, but after hydrolysis Salicyl The acid salt protein binding rate was 65~90%. When the blood concentration is high, the binding rate decreases accordingly. Poor renal function and low feeding rate during pregnancy. The half-life is 15-20 hours; salicylic acid The half-life of salt depends on the dosage and urine pH, and it is about 2-3 hours when taking small doses at a time; It can last for more than 20 hours at large doses and 5~18 hours at repeated doses. The half-life of salicylate in milk is 3.8-12.5 hours after 0.65g aspirin is taken orally once. Most of the product is quickly hydrolyzed into salicylate in gastrointestinal tract, liver and blood, and then Liver metabolism 。 metabolite Mainly salicyl uric acid (salicyluric acid) and Glucuronic acid Conjugates , a small part is oxidized to gentianic acid （gentisic acid）。 The blood drug peak value was reached 1~2 hours after a single administration. During analgesia and antipyretic, the blood concentration was 25-50 μ g/ml; 150 ～ 300 μ g/mL for anti internal dampness and anti inflammation. Blood concentration reaches stable state The time required increases with the increase of daily dose and blood concentration, and can be as long as 7 days in large doses (such as anti rheumatism). For patients with long-term high-dose medication, as the main metabolic pathway of the drug has been saturated, a slight increase in the dose can lead to a large change in the blood concentration. Most of the product is mixed with metabolites, and a small part is free salicylic acid Renal excretion 。 The excretion of unmetabolized salicylic acid increases when the dosage is large. There can be great differences between individuals. The pH of urine has an impact on the excretion rate. The excretion rate is accelerated in alkaline urine, and the amount of free salicylic acid is increased, but the opposite is true in acidic urine.

The product can be excreted in milk ， Lactating women After oral administration of 650mg, the drug concentration in the milk can reach 173-483 μ g/ml after 5-8 hours, so infants may have adverse reactions when taking large doses of drugs for a long time.

Toxicology

Compound Aspirin It is a compound antipyretic and analgesic drug, in which aspirin and Phenacetin All of them have antipyretic and analgesic effects. Aspirin can inhibit hypothalamus The synthesis and release of prostaglandins can restore the central sensation of temperature regulation neuron Normal of Reactivity It has antipyretic and analgesic effect; Aspirin also has analgesic, anti-inflammatory and anti rheumatic effects by inhibiting the synthesis of peripheral prostaglandins, etc. Aspirin also inhibits platelets Aggregation 。 Coffee can excite because of central nerve stimulants Cerebral cortex , improve the external Inductivity , with shrinkage Cerebrovascular To strengthen the effect of the first two drugs on relieving headache. acute toxicity test result: Rat Oral LD fifty 1500mg/kg; Oral LD in mice fifty 1100mg/kg.

In animal tests, application of this product in the first three months may cause Teratology , such as Spina bifida , cranial fissure, facial fissure, leg deformity, and central nervous system Visceral and skeletal Hypoplasia 。 There are also reports of fetal defects after the use of this product in humans. In addition, long-term and large application of this product in the third month of pregnancy can make Pregnancy Prolonged, increased delayed labor syndrome and Prenatal bleeding Risk of. Application in the last 2 weeks of pregnancy can increase the risk of fetal hemorrhage or neonatal hemorrhage. stay Late pregnancy Long term medication may also make the fetus Ductus arteriosus Shrinkage or early locking, resulting in Persistent pulmonary hypertension in neonates and heart failure 。 Overuse or abuse in the third trimester of pregnancy has been reported to increase the incidence of stillbirth or neonatal death (possibly due to ductus arteriosus atresia, prenatal bleeding or low weight), but the use of General treatment The above side effects have not been found in the dose.

Toxicity test data
number	Toxicity type	test method	Test object	Dosage	Toxic effect
one	acute toxicity	Oral	Adult male	13036mg/kg/5Y-I	Gastrointestinal toxicity - other changes Skeletal muscle toxicity - affects joints Skin and accessory toxicity - dermatitis (after systemic exposure)
two	acute toxicity	Oral	children	10mg/kg/1D-I	Lung, chest or respiratory toxicity - acute pulmonary edema Kidney, ureter and bladder toxicity: changes in renal tubules (including acute renal failure and acute tubular necrosis) Kidney, ureter and bladder toxicity - decreased urine output
three	acute toxicity	Oral	Adult male	857mg/kg	Behavioral toxicity - coma Lung, chest or respiratory toxicity - respiratory tract irritation
four	acute toxicity	Oral	adult female	525mg/kg/5D-I	Hepatotoxicity - hepatitis (hepatocyte necrosis), diffusion
five	acute toxicity	Oral	adult female	480mg/kg/5D-I	Kidney, ureter and bladder toxicity: changes in renal tubules (including acute renal failure and acute tubular necrosis) Biochemical toxicity - other changes in metabolism
six	acute toxicity	Oral	Adult male	1625mg/kg	Behavioral toxicity - coma Nutritional and metabolic toxicity - elevated body temperature
seven	acute toxicity	Oral	baby	120mg/kg	Lung, chest or respiratory toxicity - respiratory tract irritation Kidney, ureter and bladder toxicity - hematuria Nutritional and metabolic system toxicity - dehydration occurs
eight	acute toxicity	Oral	children	104mg/kg	Lung, chest or respiratory toxicity - acute pulmonary edema Gastrointestinal toxicity - nausea and vomiting Hemotoxicity - bleeding
nine	acute toxicity	Oral	children	39mg/kg/13D-I	Hepatotoxicity - hepatitis (hepatocyte necrosis), diffusion
ten	acute toxicity	Oral	human beings	669mg/kg/11D	Hepatotoxicity - decreased liver function
eleven	acute toxicity	Oral	human beings	2880mg/kg/8W	Ototoxicity - Tinnitus Gastrointestinal toxicity - nausea and vomiting Gastrointestinal toxicity - decreased intestinal motility or constipation
twelve	acute toxicity	Oral	adult female	800mg/kg	Kidney, ureter and bladder toxicity: changes in renal tubules (including acute renal failure and acute tubular necrosis) Skeletal muscle toxicity - other changes
thirteen	acute toxicity	Oral	human beings	480mg/kg/7D-I	Ototoxicity - Tinnitus Behavioral toxicity - sleepiness Gastrointestinal toxicity - other changes
fourteen	acute toxicity	Oral	human beings	1050mg/kg/14D-I	Vascular toxicity - other changes
fifteen	acute toxicity	Not reported	Adult male	294mg/kg	No values other than lethal dose were reported for detailed effects
sixteen	acute toxicity	Rectal injection	adult female	4550mg/kg	Brain toxicity - encephalitis Behavioral toxicity - coma Cardiotoxicity - arrhythmia
seventeen	acute toxicity	Oral	Rat	200mg/kg	No values other than lethal dose were reported for detailed effects
eighteen	acute toxicity	intraperitoneal injection	Rat	340mg/kg	No values other than lethal dose were reported for detailed effects
nineteen	acute toxicity	Rectal injection	Rat	790mg/kg	No values other than lethal dose were reported for detailed effects
twenty	acute toxicity	Oral	mice	250mg/kg	No values other than lethal dose were reported for detailed effects
twenty-one	acute toxicity	intraperitoneal injection	mice	167mg/kg	No values other than lethal dose were reported for detailed effects
twenty-two	acute toxicity	subcutaneous injection	mice	1020mg/kg	No values other than lethal dose were reported for detailed effects
twenty-three	acute toxicity	Not reported	mice	1350mg/kg	No values other than lethal dose were reported for detailed effects
twenty-four	acute toxicity	Oral	dog	700mg/kg	Behavioral toxicity - changes in sleep time (including righting reflection change) Respiratory toxicity of lung and chest patients - respiratory depression
twenty-five	acute toxicity	intravenous injection	dog	681mg/kg	Behavioral toxicity - analgesia
twenty-six	acute toxicity	Oral	rabbit	1010mg/kg	Behavioral toxicity - sports behavior changes (Specific analysis of specific conditions)
twenty-seven	acute toxicity	Oral	guinea pig	1075mg/kg	Behavioral toxicity - changes in sleep time (including righting reflection change) Behavioral toxicity - sleepiness Behavioral toxicity - tremor
twenty-eight	acute toxicity	Oral	Hamster	3500mg/kg	No values other than lethal dose were reported for detailed effects
twenty-nine	acute toxicity	Oral	mammal	1750mg/kg	No values other than lethal dose were reported for detailed effects
thirty	Chronic toxicity	Oral	Rat	200mg/kg/4D-I	Gastrointestinal toxicity - gastrointestinal ulcer or bleeding
thirty-one	Chronic toxicity	Oral	Rat	8127mg/kg/43W-C	Kidney, ureter and bladder toxicity - changes in urine components
thirty-two	Chronic toxicity	inhalation	Rat	25mg/m three /4H/17W-I	Brain toxicity - affects the central nervous system in specific regions Blood toxicity - coagulation factor changes Hemotoxicity - changes in serum composition (such as TP, bilirubin, cholesterol)
thirty-three	Chronic toxicity	Oral	Rat	9500mg/kg/3W-I	Chronic disease related toxicity - death
thirty-four	Chronic toxicity	intraperitoneal injection	Rat	8750mg/kg/21D-I	Kidney, ureter and bladder toxicity: changes in renal tubules and glomeruli
thirty-five	Mutagenic toxicity		Bacillus subtilis	5mg/disc
thirty-six	Mutagenic toxicity		Human lymphocytes	100μmol/L
thirty-seven	Mutagenic toxicity		Human lymphocytes	75mg/L
thirty-eight	Mutagenic toxicity		Human fibroblast	100mg/L
thirty-nine	Mutagenic toxicity		Human leukocytes	100μg/L
forty	Mutagenic toxicity		Human lymphocytes	10 mg/L
forty-one	Mutagenic toxicity		Rat fetus	108μg/plate
forty-two	Mutagenic toxicity	intraperitoneal injection	mice	100mg/kg
forty-three	Mutagenic toxicity		Hamster lung	1660mg/L
forty-four	Reproductive toxicity	Oral	adult female	7500mg/kg, female pregnancy 34-37 week(s) after conception	Reproductive toxicity - affecting the mother Reproductive toxicity - stillbirth of newborn
forty-five	Reproductive toxicity	Oral	adult female	700mg/kg, female pregnancy 35-36 week(s) after conception	Reproductive toxicity - central nervous system dysplasia Reproductive toxicity - abnormal development of cardiovascular circulatory system Reproductive toxicity - affecting biochemistry and metabolism of newborns
forty-six	Reproductive toxicity	Oral	adult female	546mg/kg, female pregnancy 37-39 week(s) after conception	Reproductive toxicity - other effects on newborns
forty-seven	Reproductive toxicity	Oral	adult female	546mg/kg, female pregnancy 37-39 week(s) after conception	Reproductive toxicity - central nervous system dysplasia Reproductive toxicity - cranial and facial dysplasia (including nose/tongue) Reproductive toxicity - other developmental abnormalities
forty-eight	Reproductive toxicity	Oral	adult female	17550mg/kg, female pregnancy 12-39 week(s) after conception	Reproductive toxicity - affecting delivery
forty-nine	Reproductive toxicity	Oral	adult female	100 mg/kg, female pregnancy 37 week(s) after conception	Reproductive Toxicity Effects on Newborn - other negative measures or effects
fifty	Reproductive toxicity	Oral	adult female	17280mg/kg, female pregnancy 1-39 week(s) after conception	Reproductive toxicity - abnormal development of cardiovascular circulatory system Reproductive toxicity - dysplasia of respiratory system Reproductive Toxicity Effects on Newborn - Apgar score (human only)
fifty-one	Reproductive toxicity	Oral	adult female	189mg/kg, female pregnancy 12-39 week(s) after conception	Reproductive toxicity - affecting delivery Reproductive toxicity - fetal toxicity (such as fetal dysplasia, but not death) Reproductive toxicity - abnormal development of blood and lymphatic system (including spleen and bone marrow)
fifty-two	Reproductive toxicity	Not reported	adult female	1200mg/kg, 20 days before female pregnancy	Reproductive toxicity - impact on newborns
fifty-three	Reproductive toxicity	Oral	Rat	1mg/kg, 12 days after female pregnancy	Reproductive toxicity - increased mortality after implantation Reproductive toxicity - death of embryos or fetuses
fifty-four	Reproductive toxicity	Oral	Rat	2100mg/kg, 14 days before male breeding	Reproductive toxicity - changes in testis, epididymis and vas deferens
fifty-five	Reproductive toxicity	Oral	Rat	500mg/kg, 9 days after female pregnancy	Reproductive toxicity - death of embryos or fetuses
fifty-six	Reproductive toxicity	Oral	Rat	200mg/kg, 9 days after female pregnancy	Reproductive toxicity - fetal toxicity (such as fetal dysplasia, but not death)
fifty-seven	Reproductive toxicity	Oral	Rat	10mg/kg, 22 days after female pregnancy	Reproductive toxicity - affecting delivery Reproductive toxicity - stillbirth of newborn Reproductive toxicity - affecting live birth index of newborn
fifty-eight	Reproductive toxicity	Oral	Rat	500mg/kg, 9 days after female pregnancy	Reproductive toxicity - central nervous system dysplasia Reproductive toxicity - abnormal ear/eye development Reproductive Toxicity - Musculoskeletal Dysplasia
fifty-nine	Reproductive toxicity	Oral	Rat	125mg/kg, 12 days after female pregnancy	Reproductive Toxicity - Musculoskeletal Dysplasia
sixty	Reproductive toxicity	Oral	Rat	1mg/kg, 3 days after female pregnancy	Reproductive toxicity - increased mortality after implantation
sixty-one	Reproductive toxicity	subcutaneous injection	Rat	1800mg/kg, 12 days before male breeding	Reproductive toxicity - abnormal male spermatogenesis (including genetic material, sperm morphology, sperm vitality and count) Reproductive toxicity - changes in testis, epididymis and vas deferens
sixty-two	Reproductive toxicity	subcutaneous injection	Rat	380mg/kg, 9 days after female pregnancy	Reproductive toxicity - increased mortality after implantation Reproductive toxicity - fetal toxicity (such as fetal dysplasia, but not death) Reproductive toxicity - other developmental abnormalities
sixty-three	Reproductive toxicity	subcutaneous injection	Rat	500mg/kg, female after 11 days of pregnancy	Reproductive toxicity - increased mortality after implantation Reproductive toxicity - death of embryos or fetuses Reproductive toxicity - cranial and facial dysplasia (including nose/tongue)
sixty-four	Reproductive toxicity	subcutaneous injection	Rat	500mg/kg, female after 11 days of pregnancy	Reproductive Toxicity - Musculoskeletal Dysplasia
sixty-five	Reproductive toxicity	subcutaneous injection	Rat	500mg/kg, female after 11 days of pregnancy	Reproductive toxicity - producing additional embryonic structures (e.g. placenta, umbilical cord) Reproductive toxicity - fetal toxicity (such as fetal dysplasia, but not death) Reproductive toxicity - cranial and facial dysplasia (including nose/tongue)
sixty-six	Reproductive toxicity	subcutaneous injection	Rat	300mg/kg, 1 day before female pregnancy	Reproductive toxicity - affecting fertility
sixty-seven	Reproductive toxicity	Not reported	Rat	350mg/kg, 6-15 days after female pregnancy	Reproductive Toxicity - Musculoskeletal Dysplasia Reproductive toxicity - other developmental abnormalities
sixty-eight	Reproductive toxicity	Intrauterine	Rat	2mg/kg, 4 days after female pregnancy	Reproductive toxicity - increased mortality before embryo implantation
sixty-nine	Reproductive toxicity	Oral	mice	1200mg/kg, 8-9 days after female pregnancy	Reproductive toxicity - increased mortality after implantation Reproductive toxicity - cranial and facial dysplasia (including nose/tongue)
seventy	Reproductive toxicity	Oral	mice	800mg/kg, 17 days after female pregnancy	Reproductive toxicity - death of embryos or fetuses Reproductive toxicity - affects the fetus Reproductive toxicity - other developmental abnormalities
seventy-one	Reproductive toxicity	Oral	mice	19200mg/kg, 6-21 days after female pregnancy	Reproductive toxicity - stillbirth of newborn Reproductive Toxicity - Effects on Newborn - other negative measures or effects
seventy-two	Reproductive toxicity	Oral	mice	2500mg/kg, 6-15 days after female pregnancy	Reproductive toxicity - fetal toxicity (such as fetal dysplasia, but not death) Reproductive Toxicity - Musculoskeletal Dysplasia
seventy-three	Reproductive toxicity	subcutaneous injection	mice	500mg/kg, female after 11 days of pregnancy	Reproductive toxicity - increased mortality after implantation
seventy-four	Reproductive toxicity	Oral	dog	3200mg/kg, 23-30 days after female pregnancy	Reproductive Toxicity - Musculoskeletal Dysplasia Reproductive toxicity - abnormal development of cardiovascular circulatory system Reproductive toxicity - dysplasia of respiratory system
seventy-five	Reproductive toxicity	Not reported	dog	3mg/kg, 20-34 days after female pregnancy	Reproductive toxicity - death of embryos or fetuses
seventy-six	Reproductive toxicity	Oral	cat	300mg/kg, 10-15 days after female pregnancy	Reproductive toxicity - fetal toxicity (such as fetal dysplasia, but not death) Reproductive Toxicity - Musculoskeletal Dysplasia
seventy-seven	Reproductive toxicity	Oral	rabbit	800mg/kg, 8-15 days after female pregnancy	Reproductive toxicity - impact on newborns Reproductive toxicity - cranial and facial dysplasia (including nose/tongue) Reproductive Toxicity - Musculoskeletal Dysplasia
seventy-eight	Reproductive toxicity	Oral	rabbit	1800mg/kg, 8-16 days after female pregnancy	Reproductive Toxicity - Musculoskeletal Dysplasia Reproductive toxicity - abnormal development of cardiovascular circulatory system Reproductive toxicity - death of embryos or fetuses
seventy-nine	Reproductive toxicity	Oral	rabbit	1750mg/kg, 6-12 days after female pregnancy	Reproductive toxicity - fetal toxicity (such as fetal dysplasia, but not death)
eighty	Reproductive toxicity	Oral	rabbit	600mg/kg, 2 days before female pregnancy	Reproductive toxicity - affecting fertility
eighty-one	Reproductive toxicity	Not reported	rabbit	11250mg/kg, 16-30 days after female pregnancy	Reproductive toxicity - death of embryos or fetuses

^[1-87]

matters needing attention

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1. It should be stopped one week before operation to avoid Coagulation dysfunction , causing continuous bleeding.

2. It should not be used after drinking, because it can aggravate gastric mucosa The barrier is damaged, resulting in gastric bleeding.

3. Not suitable for use after deliquescence. Aspirin decomposes into salicylic acid and acetic acid , which may cause adverse reactions.

4. People with coagulation dysfunction should avoid using it, such as severe liver damage Hypoprothrombinemia 、 vitamin K Lack of.

5. Not suitable for ulcer patients. Suffering from stomach and duodenal ulcer Aspirin can lead to bleeding or perforation in 30% of patients.

6. Asthma patients should avoid using it. Some asthma patients may have allergic reactions after taking aspirin, such as Urticaria 、 Laryngeal edema , Asthma Grand mal 。

7. Not for pregnant women. Taking within three months after pregnancy can cause fetal abnormalities; If taken regularly, it may delay delivery, and there is a great risk of bleeding. It should be forbidden 2-3 weeks before delivery.

8. It should not be taken in large quantities for a long time, or it may cause poisoning, headache, dizziness, nausea, vomiting, tinnitus, hearing and vision loss, and serious cases Acid-base imbalance , mental disorder, coma, or even life-threatening.

9、 Viral infection Febrile Not suitable for children It is reported that children and adolescents under 16 years old who suffer from influenza, chickenpox or other viral infections, and then take aspirin, will have severe liver dysfunction and encephalopathy symptoms, although rare, they can die.

Cannot take medicine with aspirin

Aspirin is a commonly used drug for prevention and treatment of thrombus, but it should not be taken together with the following drugs:

Oral Hypoglycemic drugs ： Jiangtangling 、 Euglycemic and Chlorosulfonylpropionylurea Drugs such as aspirin should not be used together, because aspirin has a hypoglycemic effect, which can ease the metabolism and excretion of hypoglycemic drugs, and enhance the hypoglycemic effect. The combination of the two will cause Hypoglycemic coma 。

hypnotic ： Phenobarbital (Rumina) and Jiannao Tablets Can promote Pharmaceutical enzyme The activity is enhanced, the metabolism of aspirin is accelerated, and the therapeutic effect is reduced.

Lipid-lowering drugs ： Cholagogue It should not be used together with aspirin, otherwise it will form complex obstruction Drug absorption 。

Diuretic : Diuretics combined with aspirin will cause Drug accumulation In vivo, aggravating toxic reaction; Acetazolamide Combined with aspirin, it can increase the blood concentration and cause toxic reactions.

Antiinflammatory and analgesic drugs: Indomethacin 、 Yantongjing Combination with aspirin is easy to cause gastric bleeding; Drugs such as non steroidal analgesic ibuprofen and aspirin may cause gastrointestinal bleeding.

Anti gout drug ： Probenecid 、 Baotaisong and Benzazolone Of Therapeutic effect , may be antagonized by aspirin, resulting in gout It should not be used in combination with the onset of disease.

vitamin: Aspirin can reduce vitamin C In the intestine Internal absorption , promote its excretion and reduce the curative effect; Vitamin B1 It can promote the decomposition of aspirin and aggravate the irritation to gastric mucosa.

Hormones: Long term use of prednisone dexamethasone 、 Prednisolone Can cause stomach duodenum , even esophagus And large intestine Peptic ulcer Aspirin can aggravate this adverse reaction, so it should not be taken together.

Improved efficacy

As the effect of single aspirin on human body is not very lasting Pharmaceutical industry People combine aspirin and other salicylic acid derivatives with polyvinyl alcohol, cellulose acetate and other hydroxyl groups polymer Melt esterification to make polyvinyl alcohol, cellulose acetate and other polymers carry acetylsalicylic acid Acid anhydride 。 When the polymer enters the human body gastric acid Under the action of Process rate Slow, so the effect of aspirin is more sustainable.

Aspirin carboxyl Polyvinyl alcohol Alcohol hydroxyl happen esterification The polymer can be obtained by removing one molecule of water, and polyvinyl alcohol is a polymer Long chain There are multiple alcohol hydroxyl groups on it, so it can carry multiple anhydrides of acetylsalicylic acid to improve the Pharmacodynamics 。

Obtained by this method Macromolecular compound The anti-inflammatory, antipyretic and analgesic effects are longer than those of free aspirin. This has a great role in promoting medicine.

R&D history

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As early as the summer of 1853, Frederick· Gerar (Gerhardt) salicylic acid And acetic anhydride Acetylsalicylic acid (acetylated salicylic acid) was synthesized, but it did not attract people's attention. In 1897, German chemist Felix Hoffman It was synthesized and used to treat rheumatoid arthritis for his father, with excellent effect. In 1897, Bayer, Germany, synthesized the main substance of aspirin for the first time.

Aspirin was marketed in 1898, and it was found that it also has anti platelet The role of cohesion has aroused great interest again. Aspirin and other salicylic acid derivatives are mixed with Polyvinyl alcohol 、 Cellulose acetate Such hydroxyl containing polymer is melt esterified to make it polymer, and the anti-inflammatory, antipyretic and analgesic properties of the obtained product are longer than that of free aspirin.

By 1899, Bayer had sold the drug to the world under the trademark Aspirin.

By 2015, aspirin has been used for a hundred years, becoming one of the three classic drugs in the history of medicine. So far, it is still the most widely used antipyretic, analgesic and Anti inflammatory drugs It is also a standard preparation for comparison and evaluation of other drugs. In vivo antithrombosis It can inhibit the release of platelets and inhibit platelet aggregation, which is related to the reduction of TXA2 production. clinical It is used to prevent the attack of cardiovascular and cerebrovascular diseases.

Compound Introduction

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essential information

essential information
attribute	information
chemical formula	C9H8O4
molecular weight	one hundred and eighty point one five seven
CAS No	50-78-2
EINECS No	200-064-1

Physical and chemical properties

Physical and chemical properties
attribute	information
density	1.34g/cm three
melting point	136-140 ℃
boiling point	321.4 ℃
flash point	131.1 ℃
Refractive index	one point five five one
appearance	White crystalline powder
Solubility	Soluble in ethanol, ether, slightly soluble in water^[88]

Molecular structure data

Molecular structure data
attribute	information
Molar refractive index	forty-four point five two
Molar volume (cm three /mol）	one hundred and thirty-nine point five
Isotonic specific volume (90.2K)	three hundred and seventy point nine
Surface tension (dyne/cm)	forty-nine point eight
Polarization (10 -24 cm three ）	seventeen point six five^[88]

Calculate chemical data

Calculate chemical data
attribute	information
Drainage parameter calculation reference value (XlogP)	one point two
Number of hydrogen bond donors	one
Number of hydrogen bond receptors	four
Number of rotatable chemical bonds	three
Number of tautomers	zero
Topological molecular polar surface area (TPSA)	sixty-three point six
Number of heavy atoms	thirteen
surface charge	zero
Complexity	two hundred and twelve
Number of isotope atoms	zero
Determine the number of atomic geometric centers	zero
Number of atomic geometric centers in uncertainty	zero
Determine the number of chemical bond stereocenters	zero
Number of uncertain chemical bond stereocenters	zero
Number of covalent bond units	one^[88]

identify

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1. Take about 0.1g of this product, add 10mL of water, boil it, cool it, add three Ferric chloride Test solution 1 drop, immediately visible Corydalis Color.

2. Take about 0.5g of this product, add 10mL of sodium carbonate test solution, boil it for 2 minutes, cool it, and add excessive Dilute sulfuric acid That is, white precipitate is precipitated and the odor of acetic acid is generated.

3. Of this product infrared light The absorption spectrum should be consistent with the control spectrum (Spectral Set 5).

inspect

Solvous Clarity

Take 0.50g of this product, heat it to about 45 ° C and dissolve 10mL of sodium carbonate test solution. The solution should be clear.

Details of operation items
project	detailed information
Determination of free salicylic acid	mirror High performance liquid chromatography Method (General Rule 0512), newly prepared for temporary use
reagent	Methanol solution of 1% glacial acetic acid
Preparation of test solution	Take about 0.1g of this product, weigh it accurately, put it into a 10mL measuring bottle, add some solvent, shake it to dissolve it, dilute it to the scale, and shake it well
Preparation of reference solution	Take about 10mg of salicylic acid reference substance, precisely weigh it, put it into a 100mL measuring flask, add appropriate solvent to dissolve it and dilute it to the scale, shake it up, precisely measure 5mL, put it into a 50mL measuring flask, dilute it to the scale with solvent, shake it up
Chromatographic conditions	Filler: octadecyl silane bonded silica gel; Mobile phase: acetonitrile tetrahydrofuran glacial acetic acid water (20:5:5:70); Detection wavelength: 303nm; Injection volume: 10 µ L
System suitability requirements	The number of theoretical plates shall not be less than 5000 according to the calculation of salicylic acid peak, and the resolution between Aspirin peak and salicylic acid peak shall meet the requirements
Assay	Accurately measure the test solution and the reference solution, respectively inject them into the liquid chromatograph, and record the chromatogram
limit	If there is a chromatographic peak with the same retention time as the salicylic acid peak in the chromatogram of the test solution, the peak area shall not exceed 0.1% according to the external standard method

Carbonizable substance

Take 0.50g of this product, check it according to the law (general rule 0842), and compare it with the control solution (for color comparison Cobalt chloride Liquid 0.25mL, for color comparison potassium dichromate Liquid 0.25mL, for color comparison copper sulphate Liquid 0.40mL, add water to make it 5mL), and it shall not be deeper.

Related substances

Determine according to the method of high performance liquid chromatography (general rule 0512).

Details of operation items
project	detailed information
solvent	Methanol solution of 1% glacial acetic acid
Preparation of test solution	Take about 0.1g of this product, put it into a 10mL measuring bottle, add some solvent, shake it to dissolve it, dilute it to the scale, and shake it well
Preparation of reference solution	Accurately measure 1mL of the test solution, place it in a 200mL volumetric flask, dilute it to the scale with solvent, and shake it well
Salicylic acid reference solution	See reference solution under free salicylic acid
Sensitivity solution preparation	Accurately measure 1mL of the reference solution, place it in a 10mL measuring bottle, dilute it to the scale with solvent, and shake it well
Chromatographic conditions	Filler: octadecyl silane bonded silica gel; Mobile phase A: acetonitrile tetrahydrofuran glacial acetic acid water (20:5:5:70); Mobile phase B: acetonitrile; Gradient elution; Detection wavelength: 276nm; Injection volume: 10 µ L

Time (minutes)	Mobile phase A (%)	Mobile phase B (%)
zero	one hundred	zero
sixty	twenty	eighty

System suitability requirements: the retention time of Aspirin peak is about 8 minutes, and the separation between Aspirin peak and salicylic acid peak should meet the requirements. The peak height of the main component in the sensitivity solution chromatogram Signal-to-noise ratio It should be greater than 10.

Determination method: Precisely measure the test solution, reference solution, sensitivity solution and salicylic acid reference solution, inject them into the liquid chromatograph, and record the chromatogram.

Limit: If there are impurity peaks in the chromatogram of the test solution, the sum of the areas of other impurity peaks, except for the salicylic acid peak, shall not be greater than the main peak area of the reference solution (0.5%), and the chromatographic peaks smaller than the main peak area of the sensitivity solution shall be ignored.

Loss on drying

Take the product and place it Phosphorus pentoxide by desiccant Of dryer Medium, at 60 ° C Vacuum drying To constant weight, the weight loss shall not exceed 0.5% (general rule 0831).

Ignition residue

Not more than 0.1% (general rule 0841).

heavy metal

Take 1.0g of this product, add 23mL ethanol to dissolve it, and then add Acetate buffer (pH 3.5) 2mL, inspected according to the law (General Rule 0821, Method 1), the content of heavy metals shall not exceed 10% per million.

Assay

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Take about 0.4g of this product, weigh it precisely, and add neutral ethanol (right Phenolphthalein Indicator solution appears neutral) After 20mL is dissolved, add 3 drops of phenolphthalein indicator solution, and use sodium hydroxide Titrant （0.1 mol/L ）Titration. Every 1mL of sodium hydroxide titrant (0.1mol/L) is equivalent to 18.02mg of C nine H eight O four 。