What Is Loratadine?

Loratadine is a second-generation antihistamine drug that is commonly used to treat allergic symptoms. Compared with the first generation of antihistamines, one of its major characteristics is no sleepiness ^[1] . For allergic rhinitis, acute or chronic urticaria, allergic conjunctivitis, hay fever and other allergic skin diseases.

Drug type: Essential medicines
Drug name: Loratadine

English name: Loratadine
Chinese alias: Clodadidine; noranodine; loratadine
English alias: Claritine; Lisino; Fristamin;

Introduction to loratadine compounds

Loratadine Basic Information

Chinese name: loratadine

Chinese aliases: Keminn; lorastatin; Keminn; Noratidine; Clodadidine; 4- (8-chloro-5,6-dihydro-11H-benzo [5,6] -cycloheptazone [1,2-b] pyridine-11-alkenyl) -1-piperidinecarboxylic acid ethyl ester

English name: Loratadine

English alias: Claritine; Loranox; CLARATYNE; CLARITIN; Tadine; Clarityne; Claritine

CAS number: 79794-75-5

Molecular formula: C ₂₂ H ₂₃ ClN ₂ O ₂

Molecular weight: 382.88300

Exact mass: 382.14500

PSA: 42.43000

LogP: 4.82570

Physical properties of loratadine

Appearance and properties: white or off-white crystalline powder, odorless; easily soluble in methanol, ethanol or acetone; slightly soluble in 0.1mol / L hydrochloric acid solution; almost insoluble in water.

Melting point: 133 137

Density: 1.261 g / cm ³

Melting point: 134-136 ° C

Boiling point: 531.3ºCat 760 mmHg

Flash point: 275.1ºC

Stability: Stable, but possibly heat sensitive-refrigerated. Incompatible with strong oxidants.

Storage conditions: 2-8ºC

Loratadine Safety Information

Customs code: 2933990090

WGK Germany: 2

Danger category code: R36 / 37/38

Safety instructions: S22-S24 / 25

Dangerous goods mark: Xi ^[1]

Loratadine production method

Dissolve 4- (8-chloro-5,6-diamino-11H-benzocycloheptopyridine-11-ylidene) -1-methylpiperidine in toluene and add ethyl chloroformate dropwise.The reaction is complete. After adding water, the benzene layer was separated, washed with water, dried, and concentrated under reduced pressure to obtain an oil. After impregnating with ether, it was recrystallized to obtain loratadine.

Loratadine uses

Antihistamines are highly selective for the peripheral nerve H1 receptors, with strong effects and long duration. It is a long-acting tricyclic antihistamine, which competitively inhibits the histamine H1 receptor and allergic symptoms caused by histamine. No significant anticholinergic and central inhibitory effects. It is used to alleviate the symptoms related to allergic rhinitis, and alleviate the symptoms of chronic urticaria and other allergic skin diseases ^[1] .

Loratadine Pharmacopoeia Standard

[Source (name), content (potency)]

This product is 4- (80chloro-5,6-dihydro-11H benzo [5,6] -cyclohepta [1,2-b] pyridine-11-alkenyl) -1-piperidinecarboxylic acid ethyl ester. Calculated on dry basis, containing C ₂₂ H ₂₃ ClN ₂ O ₂ shall not be less than 99.0%.

[Character]

This product is white or off-white crystalline powder; odorless.

This product is easily soluble in methanol, ethanol or acetone; slightly soluble in 0.1mol / L hydrochloric acid solution; almost insoluble in water.

Melting point

The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 133 to 137 ° C.

[Identification] (1) Take about 10mg of this product, add 2ml of dilute hydrochloric acid solution to dissolve, and add 2 ~ 3 drops of bismuth potassium iodide test solution to produce orange yellow precipitate. (2) Take an appropriate amount of this product and add ethanol to make a solution containing about 10 g per 1 ml. According to ultraviolet-visible spectrophotometry (Appendix IV A), it has the maximum absorption at a wavelength of 247 nm, Minimal absorption. (3) The infrared light absorption spectrum of this product should be consistent with the control spectrum (spectrum set 865).

[Inspection] Take this product and use mobile phase to make a solution containing 0.2mg per 1ml as the test solution; take 1ml precisely, place it in a 100ml measuring bottle, dilute to the mark with mobile phase, shake well, As a control solution. Measured according to high performance liquid chromatography (Appendix VD), using octadecylsilane bonded silica as a filler, phosphate buffer solution (take 2.28 g of dipotassium hydrogen phosphate, 800 ml of water to dissolve, adjust the pH value with phosphoric acid to 6.0, then add water to 1000ml) -methanol (20:80) as the mobile phase, the detection wavelength is 247nm, and the theoretical number of plates calculated from the peak of loratadine is not less than 2000. Take 20l of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 25% of the full range, and then accurately measure 20l each of the test solution and the control solution, and inject them into the liquid chromatograph Record the retention time of the chromatogram to the principal component peak 2.5 times. If there are impurity peaks in the chromatogram of the test solution, the area of a single impurity peak must not be greater than 0.5 times (0.5%) the area of the main peak of the control solution, and the sum of the area of each impurity peak must not be greater than the area of the main peak of the control solution (1.0%). Take the appropriate amount of the residual solvent, add the internal standard solution (accurately weigh the appropriate amount of methanol, and add N, N-dimethylformamide to make a solution containing about 0.1mg per 1ml) to make a solution containing 0.1g in 1ml. As a test solution; accurately measure the appropriate amount of n-hexane, acetone, tetrahydrofuran, isopropanol, dichloromethane, acetonitrile, chloroform, and toluene, and add the above-mentioned internal standard solution to make the above components per 1ml 0.029. A mixed solution of mg, 0.5mg, 0.072mg, 0.5mg, 0.06mg, 0.041mg, 0.006mg, 0.089mg was used as a reference solution. According to the residual solvent measurement method (Appendix P third method), using polyethylene glycol as a stationary phase capillary column, the program temperature was increased, the initial temperature was 40 ° C, and the temperature was maintained for 10 minutes. Hold for 3 minutes; inlet temperature 220 ; detector temperature 240 ; nitrogen flow rate is 3ml per minute, split ratio is 10: 1, precisely measure 1l of reference solution, and inject it into the gas chromatograph. The resolution between the standard peaks should meet the requirements. Accurately measure 1 l of the test solution and the reference solution, and inject them into the gas chromatograph, record the chromatogram, and calculate the peak area according to the internal standard method. The content of n-hexane should not exceed 0.029%, the amount of acetone should not exceed 0.5%, and the amount of tetrahydrofuran 0.072%, isopropyl alcohol must not exceed 0.5%, methylene chloride must not exceed 0.06%, acetonitrile must not exceed 0.041%, chloroform must not exceed 0.006%, and toluene must not exceed 0.089%. Take cyanide 1.0g of this product, check it according to law (Appendix F first method), should meet the requirements. Loss on drying: Take this product and dry to constant weight at 105 ° C. Lose weight should not exceed 0.5% (Appendix L). Take 1.0g of this product and check it according to law (Appendix N). The remaining residue should not exceed 0.1%. The heavy metal shall be taken as the residue left under the burning residue, and shall be inspected in accordance with the law (Appendix H, the second method). The content of heavy metal shall not exceed 20 parts per million ^[2] .

[Content determination] Take about 0.3g of this product, accurately weigh, add 40ml glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, titrate with chlorochloric acid titration solution (0.1mol / L) until the solution becomes blue, and The results of the titration were corrected with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 38.29mg of C ₂₂ H ₂₃ ClN ₂ O _{2 ^[2]} .

[Category] Antihistamine.

[Storage] shading and sealed.

Loratadine Drug Description

Loratadine classification

Antiallergic Drugs> Antihistamines

Loratadine pharmacology

A piperidine antihistamine is a derivative of azastatin, which has the effect of selectively antagonizing the peripheral histamine H1 receptor. Its antihistamine effect is fast, strong and long lasting. Its effect is stronger than that of astemizole and terfenadine. This product has no sedative effect and no anti-muscarinic choline effect. No strengthening effect on ethanol. Quickly and well absorbed after oral administration. The peak time tmax of the plasma concentration was 1.5 hours. The binding rate to plasma proteins was 98%. Most are metabolized in the liver, and the metabolite decarboxyethoxyloratadine still has antihistamine activity. This product and its metabolites are excreted from urine and feces, and t1 / 2 is about 20 hours. This product and its metabolites are not easy to cross the blood-brain barrier, but can appear in milk.

Loratadine pharmacokinetics

It is well absorbed orally, rapidly and extensively metabolized in the liver, and eliminated by urine and feces. After taking the drug, the effect is fast, and some patients show effects within 30 minutes, the tmax is 1.5 to 2 hours, and the elimination half-life is 8 to 14 hours. The half-life of the active metabolite decarboxymethylethoxyloratadine (DCL) is 17 to 24 hours. The half-life of older people and patients with liver disease may be longer. The ratio of loratadine to plasma proteins was 97% to 99%, and DCL was 73% to 76%. After taking the drug for 24 hours, about 27% of loratadine was excreted from the urine, about 40% was eliminated from the urine after 10 days, and 42% was excreted from the stool. With less milk secretion, medication during lactation is safe ^[3] .

Loratadine indications

For allergic rhinitis, acute or chronic urticaria, allergic conjunctivitis, hay fever and other allergic skin diseases.

Loratadine dosage

Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.

Loratadine adverse reactions

(1) Less. Occasionally dry mouth and headache. (2) Occasionally hepatic dysfunction, jaundice, hepatitis, liver necrosis, and liver function impairment should be reduced. (3) Rare polymorphic erythema and systemic allergic reactions.

Loratadine contraindications

Those who are allergic to this product are prohibited. Not recommended for children under 2 years. Use with caution in pregnant and lactating women.

Loratadine precautions

1. Patients with severe liver or kidney impairment, children under 2 years old, pregnant women, lactating women should be used with caution.

2. If loratadine is continuously used for more than 1 month, the drug type should be changed to prevent drug resistance.

3. Drinkers and those who regularly take antipsychotics should use loratastat regularly to observe whether it has aggravated drowsiness or other central inhibitory effects, and pay attention to adjusting the dosage, or stop drinking alcohol and stop using it during the medication. Zizania drugs.

4. About 48 hours before the skin test, loratadine should be discontinued, because antihistamines can prevent or reduce the skin's positive response to the antigen used.

Loratadine Drug Interactions

Metabolized by the liver CYP450 enzyme, so drugs that inhibit liver enzyme activity, such as macrolide antibiotics and antifungal ketoconazole, can slow down the metabolism of this product and increase the blood concentration of this product, which may cause Adverse reactions increased. Combined with other central inhibitors, tricyclic antidepressants or drinking alcohol can cause severe drowsiness. Monoamine oxidase inhibitors can increase the adverse reactions of this product.

Loratadine poisoning

Loratadine is a long-acting tricyclic antihistamine with strong antihistamine effect, no central nervous system inhibitory effect, and no anticholinergic effect. It is used to treat allergic diseases of various skin and mucous membranes. Effective after 30 minutes, half-life 8 ~ 18 hours, commonly used amount 10mg / d, stun.

Clinical manifestation

1. Adverse reactions are rare, including fatigue, headache, and dry mouth.

2. Central nervous system inhibition or excitement may occur in excess.

treatment

The main points of treatment for loratadine poisoning are:

Symptomatic treatment.

Loratastat

Tablets and capsules: 5mg, 10mg

Loratadine Expert Reviews

Loratadine has no central sedative effect. It only needs to be taken once a day, and the drug effect can be maintained for 1 day. The patient has better obedience and better efficacy for chronic urticaria. Its efficacy is better than that of chlorpheniramine, clomustine, terfenadine, and astemizole. But the price is more expensive. Loratadine is a selective peripheral H1 receptor antagonist without cholinergic and epinephrine antagonistic effects. Ophthalmology is mostly used for skin and mucosal allergies, such as eyelid contact dermatitis and allergic conjunctivitis ^[3] .

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