About benzocaine

 

【Background and overview】

Benzocaine (Benzocaine), is a white needle-like crystal, the chemical name is 4-aminobenzoic acid ethyl ester or p-aminobenzoic acid ethyl ester (CAS number: 94-09-7, molecular formula: C9H11NO2, molecular mass: 165), the melting point is 90-92 °C, slightly soluble in water, and easily soluble in organic solvents. Such as: ethanol, chloroform, ether, soluble in almond oil, olive oil. As a water-insoluble local anesthetic, benzocaine has analgesic and antipruritic effects. It is clinically used for wound anesthesia, ulcer surface anesthesia, mucosal surface anesthesia and hemorrhoid anesthesia. Its pharmacological effect is mainly to block nerve endings to relieve Pain and itching. The distinctive feature of benzocaine is that it is easy to combine with the lipid layer on the mucosa or skin surface, and it is not easy to enter the human body to produce toxicity. There are more than 100 kinds of benzocaine preparations abroad, including 27 kinds of tablets, 17 kinds of ointments, 6 kinds of creams, 3 kinds of capsule bases, and other preparations such as: suppositories, lotions, Gels, aerosols, etc., are mainly used for oral sterilization, oral ulcers, and sore throats. Compared with foreign countries, domestic use of benzocaine is only used in ointment to relieve itching, and the variety of preparations needs to be further developed. In addition, benzocaine is an important organic synthesis intermediate. Mainly used in the production of medicine, plastics and coatings. Benzocaine has anesthesia, and based on this, anesthetics such as oxoform, oxocaine and new oxoform can be synthesized. Since then, many excellent local anesthetics of para-aminobenzoate have been synthesized. Like procaine and many procaine analogs. Such anesthetics have the advantages of good stability, fast onset of action, long maintenance time and small side effects, so they are widely used.

 

 

【Indications】

Temporary relief for painful and itchy skin, minor burns, sunburns, wounds and bites. Auricular preparations are used to relieve pain and itching in acute congestive, congestive otitis externa, swimmer’s otitis, and external use. It is also effective for toothache, sore throat, mouth ulcers, various hemorrhoids, anal fissures, genital itching, and as a male genital desensitizer to slow ejaculation. Or as an anesthetic lubricant for catheters and endoscopic tubes.

 

 

【Pharmacological action and mechanism of action】

The local anesthetic effect of benzocaine is weaker than that of procaine, it cannot be used for infiltration, and the local absorption is slow and durable. It is hydrolyzed to p-aminobenzoic acid, which is non-irritating and toxic at a normal concentration of 2% to 10%. The toxicity is only 5% or 10% of cocaine. The maximum safe amount for topical use is 5g or 25 mL of a 20% solution. Inhibits the conduction of nerve impulses from sensory nerve endings, dulls the sense of taste, and has a structure similar to procaine, so it is absorbed slowly and has a long-lasting anesthetic effect.

 

 

【Pharmacokinetics】

Benzocaine profile and formulation development is rarely absorbed through the normal skin, but more rapidly absorbed through the mucous membranes. Metabolized by plasma cholinesterase and to a lesser extent by hepatic cholinesterase. This product has small absorption when used locally, and takes effect within 15 to 30 minutes of topical anesthesia. Topical application of 7.5% gel takes effect in 7 minutes, and the effect lasts for 12 to 15 minutes, and topical application of 10% or 20% gel lasts for 3 to 5 hours. This product is metabolized by the liver after absorption, and a small amount is excreted by the kidney as the original drug.

 

 

【Adverse reactions】

Benzocaine can cause allergic reactions. The positive response rate of patients undergoing benzocaine patch test was 3.3% to 5.9%. Occasionally dizziness, nausea, local or systemic allergic reactions, such as rash, urticaria, edema, etc.

 

 

【Notes】

Have a history of drug allergy. Skin exfoliation or severe trauma to mucous membranes, use with caution in children < 6 years old. Benzocaine neutralizes the effects of sulfonamide antibacterials. Avoid eye contact with all formulations, when using spray, be careful not to inhale mist, keep spray away from open flames or soldering irons and do not expose to heat, spray at least 30 cm away from affected area; benzocaine application Before treatment, chemical burns should be washed; before using hemorrhoid preparations, the rectal area should be thoroughly cleaned or dried, and used frequently in the morning, evening or after each bowel movement; preparations should be stored in a closed container at 15°C to 30°C.

 

 

【Synthesis】

Method 1: Using p-nitrobenzoic acid as a raw material, under the alkaline action of ammonia water, ferrous sulfate reduces the nitro group into an amino group to obtain p-aminobenzoic acid, and p-aminobenzoic acid undergoes esterification under the acidic condition of ethanol to form p-aminobenzoic acid Ethyl aminobenzoate (benzocaine).

方法1
Method 2: Using p-nitrobenzoic acid as a raw material, under the catalysis of concentrated sulfuric acid, firstly carry out an esterification reaction with ethanol to generate ethyl p-nitrobenzoate, and under the action of iron powder, ethyl p-nitrobenzoate, Reduction to obtain ethyl p-aminobenzoate (benzocaine), the product yield is about 30%. The method has simple steps, readily available and inexpensive raw materials, and is widely used by domestic manufacturers.

方法2

Method 3: take p-nitrobenzoic acid as raw material, use hydrochloric acid as solvent, Sn as catalyst for reduction, and then neutralize with ammonia water and acetic acid to obtain the product p-aminobenzoic acid with a yield of 45, 64%, p-aminobenzoic acid and ethanol. The esterification reaction was carried out under the action of concentrated sulfuric acid, and then neutralized with sodium carbonate to obtain ethyl p-aminobenzoate with a yield of 92.88%. In the ammoniation stage, referring to a large number of literatures, it is found that the use of Sn as a catalyst can produce a product with high yield and purity.

方法3

Method 4: Using p-nitrotoluene as raw material, p-nitrobenzoic acid is prepared under the oxidation of KMnO4, and p-nitrobenzoic acid is esterified with ethanol in SnCl4 5H2O solution to generate ethyl p-nitrobenzoate , p-nitro: ethyl benzoate is reduced with hydrogen using PtO as a catalyst to finally generate ethyl p-aminobenzoate. The synthetic route is: oxidation-reduction-esterification to synthesize benzocaine. In the esterification reaction stage, high tin chloride is used as a catalyst, so that the esterification yield is as high as 92.6% or more, and the total product yield is more than 80.2%.

方法4

 

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Post time: Jun-13-2022