(antipyretic and analgesic)
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Aspirin, also known as acetylsalicylic acid, is a kind of antipyretic and analgesic with a long history, which was born in/kloc-0 on March 6, 899. It can be used to treat common cold, fever, headache, toothache, joint pain and rheumatism, inhibit platelet aggregation, prevent and treat ischemic heart disease, angina pectoris, cardiorespiratory infarction and cerebral thrombosis, and improve the germination rate of plants [1]. It is also effective in angiogenesis and bypass grafting.
Drug name
Aspirin
Foreign name
Aspirin or acetylsalicylic acid
Is it a prescription drug?
Over-the-counter drugs/medicines
Main indications
Used for fever, pain and rheumatoid arthritis.
Major drug contraindications
Non-steroidal anti-inflammatory drugs allergic persons are prohibited.
form of a drug
Tablets enteric-coated tablets enteric-coated capsules effervescent tablets suppository
Athletes use it with caution
Use carefully.
Is it included in the medical insurance?
Bring into a certain state
Registration authentication number
J20080078
Drug type
Analgesic and antipyretic agent
catalogue
Physical and chemical properties of 1
2 R&D history
3 adaptation symptoms
4 Usage and dosage
5 Adverse reactions
6 drug efficacy
Basic efficacy
Other influences
7 preparation method
8 pharmacological action
9 drug toxicity
10 taboo
1 1 Notes
Xiangke medicine
Drug effect improvement
12 cultivation method
13 Pharmacopoeia Revision
Edit physical and chemical properties
Description: White crystalline powder. Tasteless, slightly acidic.
The molecular chemical formula is C9H8O4.
The molecular structural formula is CH3COOC6H4COOH.
Molecular relative mass: 180. 16
Aspirin
Melting point: 136- 140℃
Boiling point: 32 1.4℃ at 760mmhg.
Flash point: 13 1. 1℃
Water solubility: 3.3g/L (20℃)
Steam pressure: 0.000 124 mm Hg at 25℃.
Solubility: slightly soluble in water, soluble in ethanol, ether, chloroform, alkali metal hydroxide solution or carbonic acid solution, and decomposed at the same time.
Safety instructions: S26: In case of contact with eyes, immediately rinse with plenty of water and send to a doctor for treatment; S36/37/39: Wear appropriate protective clothing, gloves and use protective glasses or masks.
Dangerous goods sign: Xn: dangerous substances.
Hazard category code: R22: Harmful if swallowed; R36/37/38: Irritating to eyes, respiratory tract and skin.
Dangerous goods transport number: UN 185 1
InChI code:1/c9H8O4/c1-6 (10)13-8-5-3-2-4-7 (8) 9 (1/kloc-)
R&D history editor
As early as Charles' 1853, Gerhardt synthesized acetylsalicylic acid from salicylic acid and acetic anhydride, but it failed to attract people's attention. From 65438 to 0897, German chemist felix hoffman synthesized it again, and treated rheumatoid arthritis for his father, with excellent curative effect. 1897, felix hoffman did synthesize the main substance of aspirin for the first time, but he succeeded under the guidance of his boss and famous chemist Artur eichengreen, and completely adopted the technical route proposed by eichengreen. [2]
Aspirin was listed in 1898, and it was found that it also has the effect of anti-platelet aggregation, which once again aroused great interest. Aspirin and other salicylic acid derivatives are melt esterified with hydroxyl-containing polymers such as polyvinyl alcohol and cellulose acetate to make them into macromolecules. The anti-inflammatory, antipyretic and analgesic effects of the obtained product are longer than those of free aspirin.
1899 was introduced into clinic by Dreiser and named aspirin. According to documents, the inventor of aspirin was felix hoffman, but in this invention, the Jewish chemist Artur Eichengreen played a very important role. Artur eichengreen's bitter story happened between 1934 and 1949.
1934, Felix Hoffman claimed to have invented aspirin.
At that time, Germany was in the dark period of Nazi rule, and the persecution of Jews intensified. In this case, the arrogant Nazi rulers were even more reluctant to admit that the inventor of aspirin was a Jew, so they mistakenly put the inventor's crown on Felix Hoffman's head and gilded their "German national superiority theory". Nazi rulers shut Artur eichengreen up and put him in a concentration camp.
After World War II, around 1949, Artur Eichengreen raised this question again, but he died soon. Since then, this matter has sunk into the sea. Walter Snead, a British medical doctor and historian, obtained the permission of Bayer Company after many twists and turns, consulted all the files of Bayer Company's laboratory, and finally restored the historical features of this invention with conclusive facts. He pointed out: Artur eichengreen played an important role in the invention of aspirin.
By 20 15, aspirin has been used for one hundred years and has become one of the three classic drugs in medical history. It is still the most widely used antipyretic, analgesic and anti-inflammatory drug in the world, and it is also the standard preparation for comparing and evaluating other drugs. It has antithrombotic effect in vivo, and can inhibit platelet release reaction and platelet aggregation, which is related to reducing TXA2 production. Clinically, it is used to prevent the attack of cardiovascular and cerebrovascular diseases.
Adaptive disease editor
Uses 1: acetylsalicylic acid is the raw material for preparing 4-hydroxycoumarin, an intermediate of rodenticide.
Use 2: Salicylic acid and acetic acid. Commonly used antipyretic and analgesic drugs. It is used for relieving pain, relieving fever, resisting rheumatism, promoting uric acid excretion of gout patients, resisting platelet aggregation and treating biliary ascaris.
Usage 3: Used for manufacturing outdoor and strong light irradiated structural parts and instrument parts, such as automobile body, agricultural machinery parts, electric meters and lampshades, road markings, etc. [3]
Usage 4: antipyretic and analgesic, for fever, pain and rheumatoid arthritis.
Usage 5: It is the earliest, most widely used and most common antipyretic, analgesic and antirheumatic drug. It has many pharmacological effects such as antipyretic, analgesic, anti-inflammatory, anti-rheumatic and anti-platelet aggregation. The curative effect is rapid and accurate, overdose is easy to diagnose and treat, and allergic reaction is less. Commonly used for common cold, fever, headache, neuralgia, arthralgia, myalgia, rheumatic fever, acute internal wet arthritis, rheumatoid arthritis and toothache. It is a variety listed in the national essential drug list. Acetylsalicylic acid is also an intermediate of other drugs.
Usage and dosage editing
Oral dose for children
Studies have found that if children take aspirin when they are infected with the virus, they are more likely to have Derrida syndrome [a serious adverse drug reaction with high mortality, see Baidu Encyclopedia for details]. Therefore, it is not recommended to give aspirin to children or people under 19. Always keep acetaminophen or ibuprofen to relieve pain and fever.
(1) antipyretic and analgesic drugs shall be taken orally according to body surface area 1.5g/m2, 4-6 times a day, or 5- 10mg/kg each time, or 60mg every year, and every 4-6 hours 1 time if necessary.
② Anti-rheumatism: Take it at a weight of 80- 100 mg/kg, 3-4 times a day. If there is no curative effect after 1-2 weeks, the dosage can be adjusted according to the blood concentration. Some cases need to be increased to 130mg/kg/ day.
③ Children were used for cutaneous mucosal lymph node syndrome (Kawasaki disease), starting with 80- 100 mg/kg daily, divided into 3-4 times, and after 2-3 days of fever, it was changed to 30mg/kg daily, divided into 2-4 times, taking it continuously for more than 2 months, and 5- 10 daily during thrombocytosis and hypercoagulability.
④ Prevention of thrombosis, atherosclerosis and myocardial infarction: 0.3g/ time, daily 1 time; To prevent transient cerebral ischemia, 0.6g each time, twice a day.
⑤ Treatment of biliary ascaris: once 1g, 2-3 times a day for 2-3 days.
⑥ Treat diarrhea caused by X-ray irradiation or radiotherapy, 0.6-0.9g each time, 4 times a day.
⑦ To treat tinea pedis, first rinse with warm water or 1: 5000 potassium permanganate solution, and then apply the powder to the affected area, which can be cured for 2-4 times. Salicylic acid has a long peak time in the morning and a long half-life, but it is the opposite at night. The reasonable dosage should be increased slightly in the morning. Eat it again at night. [4]
Adult oral dose
(1) antipyretic and analgesic, 0.3—0.6g once, three times a day, and every 4 hours/kloc-0 once if necessary.
② Anti-rheumatism, 3-5g per day (7-8g for acute rheumatic fever), taken orally for 4 times.
③ There is no exact dose to inhibit platelet aggregation, and it is recommended to use a small dose, such as 50- 150mg,/kloc-0 once every 24 hours.
④ Treatment of biliary ascariasis, 1g once, 2-3 times a day for 2-3 days; Paroxysmal strangulation was stopped after 24 hours, and then treated with insect repellent. [4]
Optimum dose
① Aspirin alone is ineffective in preventing systemic arterial embolism in valvular heart disease, but it can strengthen the effect of low dose dipyridamole when combined with dipyridamole.
② Avoid combination with glucocorticoid; Avoid using coumarin anticoagulants, methotrexate, barbiturates and aniline and other hypoglycemic agents.
③ Take it after meals. The evidence-based guidelines of the American College of Chest Physicians (ACCP) point out that patients should use aspirin to prevent myocardial infarction, stroke and vascular death, and the optimal dosage should be used according to the condition.
A large number of clinical trials show that aspirin 75mg/ day can effectively reduce the risk of acute myocardial infarction and death in most patients, including patients with chronic stable or unstable angina pectoris. This dose can also reduce the incidence of stroke and death in patients with transient ischemic attack. A stroke prevention study in Europe shows that patients with a history of transient ischemic attack and stroke can reduce the risk of stroke or death by taking 25mg of aspirin twice a day, that is, 50mg/ day. Clinical practice has proved that even if patients take aspirin at a dose higher than that in the table, the curative effect will not be further improved, but the occurrence of side effects will be greatly increased. Therefore, in the treatment of various thrombotic diseases, patients should use the minimum effective dose, that is, long-term application of 50- 160mg/ day, in order to achieve the maximum curative effect and minimize the side effects, which is the best dose for patients to take aspirin. [4]
Matters needing attention
Note: Take with food or water to reduce gastrointestinal irritation. [4]
Aspirin and alcohol cannot be eaten at the same time. Alcohol, the main component of wine, becomes acetaldehyde under the action of liver alcohol dehydrogenase, and then becomes acetic acid under the action of acetaldehyde dehydrogenase, thus generating carbon dioxide and water. Aspirin can reduce the activity of acetaldehyde dehydrogenase, prevent acetaldehyde from oxidation to acetic acid, lead to acetaldehyde accumulation in the body, aggravate systemic pain symptoms, and lead to liver injury.
Adverse reaction editor
Aspirin is a antipyretic and analgesic drug with a long history. Aspirin is widely used to treat fever, headache, neuralgia, myalgia, rheumatic fever and acute rheumatoid arthritis because of its easy absorption after oral administration. With the wide application of aspirin, its adverse reactions are gradually increasing. Therefore, when aspirin is used to treat various diseases, its adverse reactions should be closely monitored.
1 gastrointestinal symptoms
Gastrointestinal symptoms are the most common adverse reactions of aspirin, and the more common symptoms are nausea, vomiting, epigastric discomfort or pain.
Oral aspirin can directly stimulate gastric mucosa, causing epigastric discomfort and nausea and vomiting. Long-term use is easy to cause gastric mucosal damage, causing gastric ulcer and gastric bleeding. Long-term use should always monitor blood picture, fecal occult blood test and necessary gastroscopy.
When using aspirin, it is best to take it after meals or with antacids, and patients with ulcers should use it with caution or not. Drugs that enhance the barrier function of gastric mucosa, such as misoprostol, have special effects on peptic ulcer caused by non-steroidal anti-inflammatory drugs such as aspirin.
2 allergic reaction
People with specific physique can cause allergic reactions such as rash, angioneurotic edema and asthma after taking aspirin, which is more common in middle-aged people or patients with rhinitis and nasal polyps. It is caused by aspirin inhibiting prostaglandin production, and it is also related to its influence on immune system. Asthma is mostly severe and persistent. General antiasthmatic drugs are ineffective, and only hormones have better effects. Typical aspirin triad (aspirin intolerance, asthma and nasal polyps) can also occur.
3 Central nervous system
Taking large doses will generally lead to neurological symptoms, so-called salicylic acid reaction. Symptoms are headache, dizziness, tinnitus and hearing loss. Mental disorders, convulsions and even coma may occur when taking large doses, and symptoms can be completely recovered 2-3 days after stopping taking drugs. Large doses can also cause central nausea and vomiting.
4 liver injury
Aspirin-induced liver injury usually occurs in large doses. This kind of damage is not an acute effect, which is usually asymptomatic for several months after treatment, and some patients have discomfort and tenderness in the right upper abdomen. The level of serum liver enzymes increased, but obvious jaundice was not common. This damage is reversible after stopping taking aspirin. After stopping aspirin, serum transaminase mostly returned to normal within 1 month. Children with systemic rheumatoid diseases are more prone to liver damage than the other two kinds of rheumatism.
After the liver damage caused by aspirin, the clinical treatment is to stop taking medicine, give amino acid rehydration, VitC, inosine and oral prednisone. Symptoms usually disappear after 1 week.
5 renal damage
Long-term use of aspirin can lead to interstitial nephritis, renal nipple necrosis and renal insufficiency. Long-term and large-scale use of this product can lead to oxidative phosphorylation decoupling, potassium escaping from renal tubular cells, resulting in potassium deficiency and high uric acid excretion in urine. The greater harm is that protein, cells and casts can appear in lower urine. Some people think that partial renal pelvis cancer is a secondary complication of the abuse of painkillers such as aspirin.
6 Effect on blood
Aspirin usually does not change the number of white blood cells and platelets, hematocrit and hemoglobin content. But taking aspirin for a long time can lead to iron deficiency anemia.
7 cardiotoxicity
The therapeutic dose of aspirin has no important direct effect on cardiovascular system. High dose can directly act on vascular smooth muscle, leading to peripheral vascular dilatation. Toxic dose can inhibit circulatory function through direct and central vascular contraction and pulsation.
Wright's syndrome
When aspirin is used to treat influenza or chickenpox in children, it may cause Wright syndrome. Wright syndrome is an acute encephalopathy and fatty infiltration syndrome of liver, which often occurs after some acute viral infections. The etiology is not clear, but it is generally believed to be related to the following factors: viruses (influenza virus and varicella virus), salicylates, exogenous viruses such as aflatoxin, inherent metabolic defects and so on. Can be caused by the coexistence or interaction of many factors. Aspirin is not recommended for viral cold in clinic.
9. Cross allergic reaction
When you are allergic to this product, you may also be allergic to another salicylic acid drug. However, people who are allergic to this product may not be allergic to non-acetylsalicylic acid drugs.
Drug efficacy editing
Basic efficacy
Analgesia and antipyretic
Aspirin can relieve headache in a short time by dilating blood vessels, and its curative effect on dull pain is better than that of acute pain. Therefore, the medicine can relieve mild or moderate dull pain, such as headache, toothache, neuralgia, muscle pain and menstrual pain; At the same time, it can restore (reduce) the set point of hypothalamic thermoregulation center raised by bacterial pyrogen to normal level, so it is also used to reduce fever such as cold and flu. This product can only relieve symptoms, but cannot treat the causes of pain and fever, so other drugs should be used at the same time to participate in the treatment.
Anti-inflammatory and anti-rheumatism
Aspirin is the first choice to treat rheumatic fever, which can relieve fever, anti-inflammation, improve joint symptoms and reduce ESR, but it can't eliminate the basic pathological changes of rheumatism and prevent complications such as heart damage. If there is obvious myocarditis, it is generally advocated to use adrenocortical hormone first, and then add it before stopping the hormone after the rheumatism symptoms are controlled, so as to reduce the rebound caused by stopping the hormone.
Treat arthritis
Besides rheumatoid arthritis, the product can also be used to treat rheumatoid arthritis, which can improve symptoms and create conditions for further treatment. In addition, this product can also be used for skeletal muscle pain with non-rheumatic inflammation such as osteoarthritis, ankylosing spondylitis and juvenile arthritis, and can relieve symptoms.
Anti-thrombotic
The product has the effects of inhibiting platelet aggregation and preventing thrombosis, and can be used for preventing transient ischemic attack (TIA), myocardial infarction, atrial fibrillation, artificial heart valve, arteriovenous fistula or other postoperative thrombosis. It can also be used to treat unstable angina pectoris.
Inhibit platelet aggregation
Aspirin can inhibit platelet release and platelet aggregation when climbing at high altitude. [5]
Other influences
Relieve cutaneous mucosal lymph node syndrome (Kawasaki disease)
Aspirin is used in children with Kawasaki disease to reduce inflammatory reaction and prevent intravascular thrombosis.
Face cancer bravely
On August 6th, 20 14, British scientists evaluated and analyzed all available evidence, and concluded that taking aspirin every day can reduce the chances of suffering from gastric cancer, intestinal cancer and other diseases or death. If people over the age of 50 in Britain insist on taking aspirin every day for ten years, about 65.438+0.22 million people may be free from cancer after 20 years. [6]
However, scientists also warned that aspirin can cause internal bleeding, so you should consult your doctor before taking aspirin for a long time. Whether aspirin can be taken for a long time has always been a controversial issue in the medical field. [6]
Scientists at Queen Mary College found that aspirin reduced the mortality rate of patients with intestinal cancer, gastric cancer and esophageal cancer by 30% to 40%.
Aspirin has also played a role in reducing the mortality of breast cancer, prostate cancer and lung cancer, but the effect is not so obvious. [6]
The study also found that you must take aspirin for at least five years to see positive effects.
The biggest side effects of taking aspirin for a long time include gastric bleeding and cerebral hemorrhage, and the older you get, the greater the possibility of internal bleeding. After considering the side effects such as internal bleeding, the scientists who conducted this survey suggested that the long-term use time of aspirin should be 10 year, but they also warned that the doctor's consent should be obtained before taking it. [6]
Prevention of digestive tract tumors
Long-term regular use of aspirin can greatly reduce the incidence of gastrointestinal tumors.
A new study in the Netherlands shows that taking low-dose aspirin may help some colon cancer patients improve their life expectancy. [7]
Researchers at Leiden University Medical Center in the Netherlands analyzed 999 colon cancer patients who underwent surgery from 2002 to 2008, and found that the mortality rate of patients who took aspirin 182 was 37.9%, while that of patients who did not take aspirin17 was 48.5%. This data shows that aspirin is beneficial to patients with colon cancer. [7]
Further analysis shows that if there is a special antigen called HLA-I in the cancer tissue of colon cancer patients, then the adjuvant therapy of aspirin is "the most effective". On the other hand, it may not work. Therefore, for patients diagnosed with colon cancer and whose tumors express HLA-I antigen, aspirin can improve their life expectancy. [7]
The research results are published in the new issue of Journal of Internal Medicine of American Medical Association. [7]
In a commentary distributed by the magazine, Dr. Alfred Neuger of Columbia University pointed out that newly diagnosed patients with colon cancer or their families often ask patients what they should do outside the normal medical plan. He has never recommended aspirin before, but now he intends to do so. [7]
Preparation method editing
Acetylation of salicylic acid to obtain aspirin: add acetic anhydride (0.7889 times of the total amount of salicylic acid) into the reaction tank, then add two thirds of salicylic acid, stir and raise the temperature, and react at 8 1-82℃ for 40-60 minutes. Cool to 8 1-82℃ and react for 2 hours. After checking that the free salicylic acid is qualified, cooling to 65438 03℃, separating out crystals, filtering, washing, washing and drying with water, and airflow drying at 65-70℃ to obtain acetylsalicylic acid. [8]
The main laboratory methods of aspirin therapy monitoring include platelet aggregation detection, platelet index, urine 1 1- dehydrogenation -TXB2 detection, flow cytometry and so on.
Pharmacological action editor
Pharmacokinetics of pharmacodynamics
Aspirin is the earliest antiplatelet drug used in antithrombotic therapy, and has been established as a classic drug for the treatment of acute myocardial infarction, unstable angina pectoris and secondary prevention of myocardial infarction. The principle of action is that aspirin is irreversibly acetylated with the hydroxyl group of serine residue at position 530 of COX- 1 polypeptide chain in cyclooxygenase (COX), which leads to the inactivation of COX, thus blocking the pathway of AA transforming into thromboxane A2(TXA2) and inhibiting PLT aggregation.
Cox is the key rate-limiting enzyme in the process of AA producing TXA2 and prostaglandin I2(PGI2). There are two forms of COX- 1 and COX-2 in human body, and COX- 1 is inherent in PLT. Clinical research shows that short-term or long-term aspirin therapy for high-risk groups such as patients with ischemic cardiovascular and cerebrovascular diseases has clear benefits in preventing myocardial infarction, stroke and vascular death that may occur in the later stage, but there are still disputes about the optimal dose and aspirin resistance. With the deepening of the 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: It mainly exerts peripheral analgesic effect by inhibiting the synthesis of prostaglandin and other substances that can make pain sensitive to mechanical or chemical stimuli (such as bradykinin and histamine). However, the possibility of central analgesia (which may act on hypothalamus) cannot be ruled out. ② Anti-inflammatory effect. The exact mechanism is not clear, which may be due to the anti-inflammatory effect of this product by inhibiting the synthesis of prostaglandin or other substances that can cause inflammatory reaction (such as histamine), inhibiting the release of lysosomal enzymes and the activity of white blood cells.
(3) Antipyretic effect: It may act on the thermoregulatory center of hypothalamus, causing peripheral blood vessels to dilate, skin blood flow to increase, sweating and heat dissipation, which may be related to hypothalamus inhibiting prostaglandin synthesis;
④ Anti-rheumatic effect: The anti-rheumatic mechanism of this product is mainly anti-inflammatory besides antipyretic and analgesic effects;
⑤ Inhibitory effect on platelet aggregation: It can prevent the formation of thromboxane A2 by inhibiting prostaglandin cyclooxygenase of platelets (TXA2 can promote platelet aggregation). This effect is irreversible. [9]
pharmacokinetics
It is absorbed quickly and completely after oral administration. It has been absorbed in the stomach and most of it can be absorbed in the upper part of the small intestine. The absorption rate is related to solubility and gastrointestinal pH value ... Food can reduce the absorption rate, but it does not affect the absorption amount. The absorption of enteric-coated tablets is slow. This product can be absorbed quickly with sodium bicarbonate. After absorption, it is distributed in various tissues and can also penetrate into joint cavity and cerebrospinal fluid. The protein binding rate of aspirin is low, while the protein binding rate after salicylate hydrolysis is 65 ~ 90%. When the blood concentration is high, the binding rate decreases accordingly. Poor renal function during pregnancy and low mating rate. The half-life is 15 ~ 20 hours; The half-life of salicylate depends on the dose and urine pH value, which is about 2 ~ 3 hours when taking a small dose each time. Large dose can last for more than 20 hours, and repeated use can last for 5 ~ 18 hours. After taking 0.65g aspirin orally, the half-life of salicylate in milk is 3.8 ~12.5h.. Most of this product is rapidly hydrolyzed into salicylate in gastrointestinal tract, liver and blood, and then metabolized in liver. The main metabolites are salicylic acid and glucuronic acid, and a small part of them are oxidized into cholic acid. After one dose, the peak plasma concentration was 1 ~ 2 hours. The blood concentration of analgesic and antipyretic drugs is 25 ~ 50 μ g/ml; The anti-inflammatory rate of internal dampness is 150 ~ 300μ g/ml. The time required for the blood drug concentration to reach a stable state increases with the increase of daily dose and blood drug concentration, which can be as long as 7 days in the case of large dose of drugs (such as anti-rheumatism). For patients who take large doses of drugs for a long time, because the main metabolic pathways of drugs are saturated, the increase of small doses can lead to great changes in blood drug concentration. Most of the products are excreted from the kidney in the form of bound metabolites, and a small part is excreted in the form of free salicylic acid. When the dose is large, the excretion of unmetabolized salicylic acid increases. There will be great differences between individuals. Urine pH has an effect on excretion rate. In alkaline urine, the excretion rate is accelerated and the amount of free salicylic acid is increased, while in acidic urine, the opposite is true.
This product can be excreted in breast milk, and the drug concentration in breast milk can reach 173-483 μ g/ml 5-8 hours after breast-feeding women take 650mg orally, so infants may have adverse reactions after taking it in large doses for a long time.
Drug toxicity editor
Compound aspirin is a compound antipyretic and analgesic drug, in which both aspirin and phenacetin have antipyretic and analgesic effects. Aspirin can inhibit the synthesis and release of prostaglandin in hypothalamus, restore the normal reactivity of sensory neurons in thermoregulation center, and play an antipyretic and analgesic role. Aspirin also has analgesic, anti-inflammatory and anti-rheumatic effects by inhibiting the synthesis of peripheral prostaglandin. Aspirin also inhibits platelet aggregation. Coffee can excite the cerebral cortex, improve the sensitivity to the outside world, contract the cerebral vessels, and strengthen the first two drugs to relieve headaches because of central nervous system stimulants. Results of acute toxicity test: The oral LD50 of rats was1500mg/kg; The oral LD50 of mice was 1 100mg/kg.
Animal experiments show that the product can cause teratomas in the first three months, such as spina bifida, crania, facial fissure, leg deformity, central nervous system, visceral and skeletal hypoplasia. There are also reports of human fetal defects after using this product. In addition, long-term and large-scale application of this product in the third trimester of pregnancy can prolong pregnancy and increase the risk of overdue delivery syndrome and prenatal bleeding. Use in the last 2 weeks of pregnancy will increase the risk of fetal bleeding or neonatal bleeding. Long-term medication in the third trimester may also cause fetal arterial catheter contraction or early atresia, leading to persistent pulmonary hypertension and heart failure in newborns. It has been reported that excessive use or abuse in the third trimester of pregnancy will increase the incidence of stillbirth or neonatal death (possibly due to arterial catheter atresia, prenatal bleeding or low weight), but the above side effects have not been found by using general therapeutic doses.