Compound retinoic acid gel

Pharmacological Action Retinoic acid is a derivative of vitamin A, and its exact mechanism of action is still unclear. Available evidence suggests that the effect of topical retinoic acid in treating acne (i.e., comedones) is due to its regulation of abnormal follicular keratinization. Follicular comedones are accompanied by hyperkeratinization of epithelial cells. Retinoic acid promotes keratinocyte separation, causing keratinocytes to fall off from the hair follicles. By enhancing the mitotic activity of the follicular epithelium, retinoic acid also increases the turnover rate of thin, loosely adherent keratinocytes. As a result of these actions, comedonal contents are expelled and the formation of microcomedones and acne vulgaris precursor lesions is reduced. In addition, retinoic acid acts by regulating the proliferation and differentiation of epidermal cells. This action is mediated by nuclear retinoic acid receptors that bind to retinoic acid. Activation of these nuclear receptors causes changes in gene expression. The exact mechanism by which retinoic acid causes changes in gene expression to regulate skin function is still unclear. Retinoic acid can also act on melanocytes and dermal fibroblasts, helping to improve excessive pigmentation caused by photodamage, and correct or prevent abnormalities in the biochemical composition and morphological structure of dermal connective tissue caused by physiological aging, light radiation, etc. Erythromycin is a macrolide antibiotic, and its exact mechanism of action in treating acne is still unclear. Erythromycin reversibly binds to the 50S subunit of the ribosome of susceptible bacteria, inhibiting bacterial protein synthesis. Erythromycin is an antibacterial agent, but it also has a bactericidal effect on certain bacteria at high concentrations. Toxicological studies (1) Acute toxicity: The LD50 of erythromycin for intravenous administration in mice is 425 mg/kg, the LD50 for subcutaneous administration in mice is 1849 mg/kg, and the LD50 for oral administration in mice is 2927 mg/kg. The product introduction of ERYGEL (2% erythromycin gel) states that the LD50 value of oral administration in rats, including its alcohol solute, is between 7.06 and 10.6 g/kg. The LD50 of retinoic acid for subcutaneous administration in mice is 790 mg/kg, and the LD50 for oral administration in mice is 2200 mg/kg; the LD50 for subcutaneous administration in rats is 790 mg/kg, and the LD50 for oral administration in rats is 2000 mg/kg. (2) Long-term toxicity, mutagenicity, and reproductive toxicity Compound erythromycin gel is a topical drug for skin application and acts locally. Oral erythromycin preparations are widely used in clinical practice, and their safety has been clinically verified. Both the Ames test and the in vivo micronucleus test in mice show that retinoic acid gel is non-mutagenic. The reproductive toxicity tests of stage I and stage III for retinoic acid skin application have not been conducted. The results of stage I and stage III tests of oral retinoic acid in rats showed that when the dose was greater than 2 mg/kg/day (>400 times the average recommended clinical dose for topical use in humans), the survival rate of newborns decreased and growth was retarded. Oral retinoic acid has teratogenic effects on rats, mice, rabbits, hamsters, and human primates. Oral administration of retinoic acid to rats at doses 1000 times the average recommended human clinical dose for topical use has been reported to cause teratogenic effects and fetotoxicity. Teratogenic doses have been reported to be different in different species of rats. Rhesus monkeys metabolize retinoic acid closer to humans than other species, and fetal abnormalities occurred at doses of 10 mg/kg/day or higher, but this phenomenon was not observed at doses of 5 mg/kg/day (1000 times the average recommended human clinical dose for topical use), although increased skeletal variations were observed in all dose groups. Embryonic mortality and resorptions were reported to increase in a dose-dependent manner. Similar results have been reported in pig-tailed monkeys. The results of teratogenic studies on topical retinoic acid in animals are unclear. Topical administration of retinoic acid to Wistar rats at doses greater than 1 mg/kg/day (200 times the average recommended human clinical dose for topical use) has been reported to cause teratogenic effects (short or curly tail). There have also been reports of fetal abnormalities at a dermal dose of 10 mg/kg/day (humerus: 13% short, 6% curved, 14% incomplete ossification at both ends). In New Zealand white rabbits, increased rates of domes and hydrocephalus have been reported at doses approximately 80 times the recommended human clinical dose, typical of fetal abnormalities caused by retinoic acid in this species. In contrast, several well-controlled animal studies have shown no teratogenic effects when retinoic acid is applied topically to rats and rabbits at doses of 100 and 200 times the recommended human clinical dose, respectively. Retinoic acid was fetogenically toxic when applied topically to the skin of rabbits at doses of 100 times the recommended human clinical dose. Retinoic acid was fetogenically toxic when applied orally to rats at doses of 500 times the recommended human clinical dose. In a lifelong skin study in CD-1 mice, where animals were given doses of 100 or 200 times the average recommended human clinical dose, small skin tumors were observed in females and liver tumors in males. The biological significance of these results is unclear because they occurred at doses exceeding the maximum tolerated skin dose (MTD) of retinoic acid and are within the natural incidence of tumors in this species of mouse. When the topical dose of this product is 5 times the average recommended human topical clinical dose, no potential carcinogenicity is found (the recommended human topical clinical dose is 500 mg of 0.05% retinoic acid cream per day for a 50 kg person). In a chronic, 2-year study measuring vitamin A in mice, diffuse starch deposits were found in the basal layer of the skin in all vitamin A treatment groups. Similar studies conducted on CD-1 mice showed that local transparent changes were found in the treated skin. The incidence of these changes in the vehicle control group, 0.25, 0.5 and 1 mg/kg groups was 0/50, 3/50, 3/50 and 2/50 in male mice, and 1/50, 0/50, 4/50 and 2/50 in female mice, respectively. The results of the hairless albino mouse study showed that retinoic acid may increase the carcinogenic potential of ultraviolet light as an irritant at carcinogenic doses. In another study, the incidence and rate of development of skin tumors in hypopigmented hairless mice treated with retinoic acid were either reduced or unaffected when exposed to ultraviolet light at carcinogenic doses. Due to the different experimental conditions, these data cannot be strictly compared. (2) Skin irritation and allergy test Retinoic acid is irritating to the skin. The skin reactions of experimental animals are significantly more severe than those of humans. Depending on the drug concentration and the number of times the drug is administered, it can cause varying degrees of skin irritation, inflammation, redness, swelling, and erosion, weaken the stratum corneum barrier, increase drug absorption, and cause systemic toxicity. Although it is irritating when applied topically to human skin, it does not have the above-mentioned severe reactions. This may be due to the differences in skin structure between animals and humans and the different sensitivities to retinoic acid stimulation. Therefore, the safety data on topical administration of retinoic acid in animals and its predictive significance for clinical drug safety should be carefully evaluated.

This product is a compound preparation, its components are retinoic acid 0.025% and erythromycin 4%.

This product is a colorless to slightly yellow gel.

For inflammatory acne.

Usage: Wash the medication area thoroughly with neutral soap and water and dry it, then apply this product lightly to the area with your fingertips, once a day, preferably before going to bed, do not rub it, and be careful not to use it near the mucous membranes such as the eyes, mouth, and nose to avoid irritation. Start with a small dose and gradually increase the dose. If too much is applied, it will not only fail to accelerate the efficacy, but will cause erythema, peeling or other discomfort. When using it, it may be accompanied by a short-term local fever or irritation. If a severe inflammatory reaction occurs locally, the drug should be discontinued. Once an adverse reaction occurs, consider discontinuing the drug or reducing the frequency of use. After the adverse reaction disappears, you can reconsider using this product. Some patients may experience a worsening of the appearance of common acne in the early stage of using this product. The therapeutic effect may appear after 2 to 3 weeks of using this product. However, the ideal therapeutic effect appears after 8 to 10 weeks of using this product. Once the common acne is improved with the use of this product, the symptoms may also be relieved by reducing the frequency of use. Patients using this product can use cosmetic agents at the same time. However, the combined use of astringents may worsen the symptoms.

Individuals with sensitive skin, especially those with fair complexion, may experience redness, edema, blisters or crusting when using this product. Adverse reactions such as pain, burning, tenderness, irritation and itching have been reported occasionally. If the above adverse reactions occur, the drug should be discontinued until the integrity of the skin is restored, or the medication plan should be adjusted appropriately to the patient's tolerance. There have been reports of transient hyperpigmentation or hypopigmentation with repeated use of retinoic acid. To date, all adverse reactions that have occurred clinically with the use of retinoic acid have been reversible after discontinuation of the drug. Topical use of erythromycin may cause desquamation and excessive dryness. Many patients also experience mild to moderate irritation reactions. However, cases of severe irritation are rare. Urticaria, greasiness, and toughening of the skin around the mouth may also occur.

It is contraindicated for women in the first 3 months of pregnancy. It is contraindicated for patients with acute or subacute dermatitis, eczema, and those who are allergic to retinoic acid and/or erythromycin and/or any of their ingredients.

Precautions for children: Not yet clear. Precautions for pregnancy and lactation: Women of childbearing age can only apply retinoic acid topically after contraceptive counseling. It is recommended that pregnant women do not use compound erythromycin gel. There are rare reports of women who use retinoic acid topically during pregnancy giving birth to children with birth defects. However, there is a lack of rigorous case-control studies on the topical use of retinoic acid by pregnant women. Studies on the safety of erythromycin for pregnant women are unclear, and erythromycin can cross the placental barrier. It is not clear whether retinoic acid is secreted in human milk, but erythromycin is secreted in human milk. Therefore, when using this product for breastfeeding women, it is necessary to comprehensively consider whether to stop the drug or stop breastfeeding. Precautions for the elderly: Not yet clear.

Before using this product, it is recommended to stop using other topical acne treatments. Be cautious when using other topical medications while using this product as this may cause a more intense reaction. Be especially cautious when using medications containing peeling ingredients (such as sulfur, resorcinol, benzoyl peroxide, or salicylic acid). If you are using medications containing peeling ingredients, it is best to let the skin rest for a period of time before starting this product to allow the peeling effect to clear. The simultaneous use of abrasives, medicated soaps, cosmetics containing alcohol, or the application of astringents after using shaving lotion may aggravate the dryness and irritation of the topical medication area.

Keep away from light and store in a cool dark place (not exceeding 20℃).

Retinoic acid 0.025% and erythromycin 4%

Tentative 24 months

Shanghai Shyndec Pharmaceutical Co., Ltd.

• Founded in:

  1996-11-27

• Address:

  No. 378, Jianlu Road, Pudong New Area, Shanghai

• Tax NO.:

  91310000630459924R

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  1,341,172,692 yuan

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