What Is Adapalene?

Adapalene, also known as Daphne gel, is a white or off-white chemical. Chemical name 6- [3- (1-adamantyl) -4-methoxyphenyl] -2-naphthoic acid, molecular formula is C ₂₈ H ₂₈ O ₃ , molecular weight is 412.52000, insoluble in water or ethanol, slightly soluble In tetrahydrofuran. Adapalene is a dermatological drug, which is clinically applicable to the skin treatment of acne vulgaris, which is mainly manifested by acne, pimples and pustules. It can also be used to treat acne on the face, chest and back.

Chinese name: Adapalin
Foreign name: Adapalene

CAS number: 106685-40-9
Molecular formula: C28H28O3
Molecular weight: 412.52000

Adapalin Basic Information

Chinese name

English name: adapalene

English alias: 6- [3- (1-Adamantyl) -4-methoxyphenyl] -2-naphthoic Acid; Adapaleno; Adaferin; Adapalene; Differine;

CAS number: 106685-40-9

Molecular formula: C ₂₈ H ₂₈ O ₃

Chemical structure:

Molecular weight: 412.52000

Exact mass: 412.20400

PSA: 46.53000

LogP: 6.68140

Adapalene physical and chemical properties

Appearance and properties: white to off-white crystalline powder

Density: 1.233 g / cm ³

Melting point: 319-322ºC

Boiling point: 606.3ºC at 760 mmHg

Flash point: 205.9ºC

Refractive index: 1.654

Storage conditions: Store in original container in a cool dark place.

Vapor pressure: 1.49E-15mmHg at 25 ° C ^[1]

Adapalin drug related information

Adapalin Classification

Chemicals & Biological Products >> Dermatology Drugs >> Antikeratinizing Drugs

English name of adapalene

Adapalene

Adapalin drug alias

Duffin, Differin Gel

Adapalene dosage form

Gel: 0.1%.

Adapalene pharmacological effects

Adapalin mainly binds to RAR and RAR, and the binding force to RAR is very weak. It can inhibit glutamine converting enzyme of keratinocytes in vitro, inhibit the keratinization process, and regulate cell differentiation. Animal experiments found that adapalene has acne lysis and local anti-inflammatory effects, and its anti-inflammatory activity may be related to its interference with the function of polymorphonuclear leukocytes and the metabolism of arachidonic acid ^[2] .

Adapalene pharmacokinetics

Adapalene is stable in chemical and photochemical properties, and has no degradation reaction during percutaneous penetration. In vivo experiments in rats showed that the epidermal concentration of adapalene was 5 × 10 mol / L, and the dermis was 10 times lower. This product is highly lipophilic, mostly concentrated in hair follicles, and easily soluble in sebum. Humans have less percutaneous penetration and cannot be detected in blood during treatment ^[2] .

Adapalene indication

Mild to moderate acne vulgaris ^[2] .

Adapalin contraindications

1. Allergic to this medicine. 2. Large area of severe acne. 3. Pregnant women. 4. Breastfeeding women ^[2] .

Adapalin notes

1. Effects of the drug on children: The safety and efficacy of this drug in children under 12 years of age (not yet clear). 2. The impact of drugs on pregnancy: The US Food and Drug Administration (FDA) classifies this drug as a pregnancy risk class C. 3. The effect of the drug on breastfeeding: It is unclear whether the drug is secreted by milk. It is recommended that breastfeeding women do not apply the drug to the breast. 4. Animal experiments show that the exposure to ultraviolet rays or sunlight at the same time increases the risk of carcinogenesis. Patients are advised to avoid or minimize exposure to sunlight and artificial ultraviolet radiation sources when taking medication. 5. This medicine is for external use only. Care should be taken to avoid contact with the mucous membranes of the eyes, mouth, nose, etc. If it is accidentally contacted, it should be washed immediately with warm water. 6. This medicine should not be used on damaged skin (cuts, friction injuries, etc.) or on skin with eczema. 7. This medicine can increase photosensitivity. Avoid excessive sunlight and ultraviolet radiation during the medication. 8. Acne can be significantly exacerbated in the first few weeks of treatment. It should not be regarded as an indication of drug withdrawal, and the effect should be observed after 8-12 weeks. 9. If allergy or severe irritation occurs, the drug should be discontinued ^[2] .

Adapalene adverse reactions

There may be erythema, dryness, desquamation and burning sensation locally, but it is lighter than 0.025% all-trans vitamin A acid cream ^[2] .

Adapalene dosage

Apply it once a night ^[2] .

Adapalene drug interactions

1. It is not advisable to use other drugs (such as retinoids) at the same time. 2. Should not be combined with preparations containing sulfur, resorcinol or salicylic acid, and the application of this drug should be started after the effects of these drugs have subsided. Other interactions: It can increase the local area when combined with other external preparations that can dry or irritate the skin (such as medicinal soaps, cleansers, soaps or cosmetics with drying effects, high-concentration ethanol preparations, astringents, perfumes or lime preparations, etc.) Stimulation ^[2] .

Adapalene drug evaluation

Adapalene gel has a good effect on mild to moderate acne vulgaris. Clinical studies have found that it can reduce non-inflammatory skin lesions by 69.6% -73.2%, reduce inflammatory skin lesions by 68% -72.1%, and cure rate of 17.5%. 22.2%; the total effective rate is 75% 95%. One study found that adapalene gel was as effective for acne as retinoic acid, but better for inflammatory pimples and pustules than the latter. ^[2-3]

A Safety comparison of adapalene and other topical retinoids

Traditional topical retinoids (RA) are indeed effective in treating acne vulgaris, but their side effects such as irritation limit its use. RA has local irritation due to a series of fragile divalent bond chains in its molecular structure that make the molecule unstable and poor receptor selectivity. Experiments show that RA can be degraded by many factors: within 24 h of exposure to sunlight, 60.0% to 80.0% of the baseline RA concentration is degraded; if RA is used and an oxidant such as benzoyl peroxide is used, 80.0% of RA is degraded within 4 h, 24 h all disappeared. In order to find a more stable molecule, which has the effect of RA and reduce its side effects, people have developed naphthoic acid derivative, adapalene. The reason why adapalene is less irritating is because of: molecular stability: the unstable bivalent bond chain of RA is replaced by the naphthoic acid aromatic ring, so that the molecule remains stable under the action of light and oxidant, and it will not degrade in 72 hours. Receptor binding is highly selective: After RA enters the cell, it must first bind to cytosolic retinoic acid binding protein (CRABP), and it has no selective binding to nuclear receptors RAR, , and . Adapalene does not bind to CRABP, but selectively binds to specific amino acids at the nuclear receptor RAR- and RAR- receptor binding sites, and then binds to RXR to further bind to DNA specific sites and regulate the transcription mechanism. It affects protein synthesis and regulates cell proliferation and differentiation, so it has high specificity and small side effects. Low cytotoxicity: Studies have found that different retinoids have different degrees of cytotoxicity on keratinocytes, and adapalene molecules are neutral. Compared with long-chain organic acids of retinoids, they are more effective on keratinocytes The cytotoxic effect is small. Adapalene has a clear anti-inflammatory effect, but this effect of other vitamin A acids is not clear.

In short, adapalene, as the third generation of vitamin A acid drugs, has stronger regulation of epidermal cell differentiation, inhibition of hair follicle keratinocyte proliferation and keratinization, and inhibition than all-retinoic acid drugs such as vitamin A acids. In addition to the role of sebaceous gland cell proliferation, lytic horn plugs and acne, it also has a strong anti-inflammatory effect. Because of its unique stability, it has significantly improved efficacy and tolerability compared with other vitamin A acids.

Adapalene preparation method

Using 1-adamantyl alcohol and 4-bromophenol as raw materials, 2 ((1-adamantyl) -4-bromo) is prepared by Fuke alkylation reaction under the catalyst of concentrated sulfuric acid

Synthetic roadmap Phenol; methyl 2- (1-adamantyl) -4-bromophenol was then methylated with dimethyl sulfate to obtain 2- (1-adamantyl) -4-bromoanisole; and then 2 Magnesium Grignarding Reagent of Mono (1-adamantyl) -4-bromoanisole, converts the magnesium Grignard Reagent of 2- (1-adamantyl) -4-bromoanisole to its corresponding zinc Reagent, the obtained product is then reacted with methyl 6-bromo-2-naphthoate to obtain methyl 6- [3-a (1-adamantyl) -4 4-methoxyphenyl] -2 methyl naphthalate; 6 Saponification and hydrolysis of mono- [3-mono (1-adamantyl) -4-methoxymethoxyphenyl] 2-naphthoate to adapalene under the catalysis of sodium hydroxide.

Adapalene toxicology data

Adapalene is an retinoic acid compound that has been shown to have anti-inflammatory properties in in vivo and in vitro inflammation models. Adapalene has a stable chemical structure and is not easily decomposed in air and light. In terms of mechanism of action, adapalene binds to a specific retinoic acid nuclear receptor like retinoic acid. Unlike retinoic acid, adapalene does not bind to cytoplasmic receptors that bind to proteins.

Adapalene has been shown to treat acne in skin medication tests in animal models established in mice, and also has an effect on acne vulgaris and the differentiation process. The mechanism of action of adapalene is thought to reduce the formation of tiny acne by normalizing hair follicle epithelial cells.

Adapalene is superior to retinoic acid in standard anti-inflammatory analysis in vivo and in vitro. It can inhibit the chemotactic response of human polynuclear leukocytes, and can inhibit the metabolism of polymorphonuclear leukocytes by inhibiting the transformation of arachidonic acid into an inflammatory mediator through a lipid oxidation reaction. This shows that adapalene applied to acne affected areas can alleviate the inflammatory response mediated by cellular responses. Human clinical trials have shown that adapalene can relieve the inflammatory reactions of acne (such as pustules and pimples).

The oral LD50 of this product in mice and rats is greater than 10ml / . Long-term intake of this drug may cause some side effects related to excessive oral vitamin A.

Animal tests have shown that this product has a carcinogenic effect. When exposed to sunlight, there is a risk of an increased incidence of skin cancer. In vivo and in vitro studies in animals have shown that this product is not mutagenic or genotoxic. Rats took adapalene 20 mg / / day orally without reproductive toxicity. Teratogenic effects occurred when rats and rabbits took oral adapalene up to the maximum recommended human dose of 24 and 48 times, respectively.

The acute poisoning dose of this drug in mice was 10 g / kg. If this medicine is inadvertently taken, measures should be taken to empty the gastrointestinal tract unless the dose is small.

If there is a strong allergic reaction, stop using this product immediately.

In some patients, irritant reactions such as erythema and burning sensation are related to the onset of drugs. When the number of medications is reduced or the medications are stopped, the side effects will disappear ^[3] .