A vitamin E cream and a method for preparing the same

Abstract

The application belongs to the technical field of pharmaceutical preparations and relates to a vitamin A palmitate vitamin E cream and a preparation method thereof.The vitamin A palmitate vitamin E cream comprises vitamin A palmitate, vitamin E, glycerol monostearate, stearic acid, lanolin, white vaseline, glycerol, a surfactant, a transdermal enhancer, a preservative and the balance of water, the surfactant is Span-85, the transdermal enhancer is laurocapram and eucalyptus oil, and the weight ratio of laurocapram to eucalyptus oil is 1:2-3.The application solves the problem of low transdermal absorption efficiency of drugs in the vitamin A palmitate vitamin E cream by screening the types of the surfactant and the transdermal enhancer and optimizing the composition of the transdermal enhancer, and the preparation process is simple and can be scaled up.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a tretinoin vitamin E cream and its preparation method. Background Technology

[0002] Acne and follicular keratosis are common chronic inflammatory skin diseases, prevalent among adolescents and those with high sebum production. They are characterized by clogged hair follicles, abnormal sebum secretion, keratinization, and inflammatory skin damage. These conditions not only affect the skin's appearance but also easily lead to itching, redness, swelling, acne scars, and pigmentation. Long-term, recurrent flare-ups can severely impact a patient's physical and mental health and quality of life. Currently, topical retinoids are commonly used to treat these conditions, possessing the core functions of regulating epithelial cell proliferation and differentiation, unblocking follicular sebaceous gland ducts, and inhibiting abnormal keratinization.

[0003] Retinoic acid esters, as a low-toxicity retinoic acid derivative, significantly reduce skin irritation compared to traditional retinoic acid drugs. They also possess anti-inflammatory, keratin metabolism-regulating, and follicular keratosis-improving effects, making them a preferred raw material for treating acne and keratotic skin diseases. Vitamin E is a classic skin antioxidant, moisturizing, and repairing ingredient. It can scavenge free radicals, repair damaged skin barriers, and alleviate dryness and irritation caused by anti-inflammatory drugs. The combination of retinoic acid esters and vitamin E achieves complementary efficacy, exhibiting a significant synergistic effect in acne treatment, skin repair, and reducing adverse reactions. Therefore, retinoic acid ester and vitamin E compound cream has become a commonly used topical dermatological preparation in clinical practice.

[0004] Current formulations of tretinoin and vitamin E creams typically use an oil / water-based cream base, supplemented with emulsifiers, emollients, preservatives, and other excipients. However, tretinoin has a large molecular weight and high lipid solubility, resulting in poor solubility in the cream base and extremely low transdermal absorption efficiency. The cumulative transdermal absorption rate after 24 hours is less than 5%, with most of the drug remaining only on the skin surface and failing to penetrate to hair follicles and inflamed areas of the dermis. This leads to slow efficacy and a long treatment cycle. Therefore, developing a tretinoin and vitamin E cream with good quality stability and high transdermal absorption efficiency has significant clinical application value and market demand. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a tretinoin vitamin E cream and its preparation method. By screening the types of surfactants and transdermal absorption enhancers and optimizing the composition of the transdermal absorption enhancers, the problem of low transdermal absorption efficiency of drugs in tretinoin vitamin E cream is solved.

[0006] This invention provides a tretinoin and vitamin E cream, comprising tretinoin, vitamin E, glyceryl monostearate, stearic acid, lanolin, white petrolatum, glycerin, surfactant, transdermal penetration enhancer, preservative, and water.

[0007] Preferably, the tretinoin and vitamin E cream comprises, by weight, 0.5 parts tretinoin, 0.3 parts vitamin E, 8-12 parts glyceryl monostearate, 8-12 parts stearic acid, 2-5 parts lanolin, 0.5-2 parts white petrolatum, 15-30 parts glycerin, 2.5-4 parts surfactant, 0.5-1.5 parts transdermal penetration enhancer, 0.01-0.1 parts preservative, and the balance being water.

[0008] Preferably, the tretinoin and vitamin E cream comprises, by weight, 0.5 parts tretinoin, 0.3 parts vitamin E, 10 parts glyceryl monostearate, 10 parts stearic acid, 3.5 parts lanolin, 1.5 parts white petrolatum, 20 parts glycerin, 3 parts surfactant, 1 part transdermal penetration enhancer, 0.05 parts preservative, and the balance being water.

[0009] Preferably, the surfactant is selected from Tween-20, Tween-80, Span-85, and sodium dodecyl sulfate.

[0010] More preferably, the surfactant is selected from Span-85.

[0011] Preferably, the transdermal penetration enhancer is selected from laurocapram, eucalyptus oil, clove oil, oleic acid, and menthol.

[0012] More preferably, the transdermal penetration enhancer is selected from laurocapram and eucalyptus oil.

[0013] More preferably, the weight ratio of laurocapram to eucalyptus oil is 1:2-3.

[0014] Preferably, the preservatives include benzoic acid, sodium benzoate, potassium sorbate, benzalkonium chloride, benzalkonium bromide, and parabens.

[0015] The present invention also provides a method for preparing tretinoin vitamin E cream, comprising the following steps: (1) preparing an aqueous phase: adding glycerin, surfactant and preservative to water, heating to 70-85℃ and stirring to dissolve; (2) preparing an oil phase: heating glyceryl monostearate, stearic acid, lanolin and white petrolatum to 70-85℃ and stirring to melt; (3) preparing a cream: mixing the aqueous phase and oil phase, homogenizing and emulsifying, cooling to 40-50℃, adding tretinoin, vitamin E and transdermal penetration enhancer, homogenizing and mixing, cooling to room temperature, and filling to obtain the cream.

[0016] This invention solves the problem of low transdermal absorption efficiency of tretinoin vitamin E cream by screening the types of surfactants and transdermal absorption enhancers and optimizing the composition of transdermal absorption enhancers. Moreover, the preparation process is simple and can be scaled up for production. Detailed Implementation

[0017] In view of the deficiencies of the prior art, the inventors, through long-term research and extensive practice, have proposed the technical solution of this invention. The invention is further illustrated below by means of embodiments, but these embodiments do not constitute a limitation of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without inventive effort are within the scope of protection of this invention.

[0018] Example 1: Screening of Surfactant Types Preparation method: (1) Preparation of aqueous phase: Add glycerin, surfactant (not added in prescription 1) and sodium benzoate to water, heat to 80°C and stir to dissolve; (2) Preparation of oil phase: Heat glyceryl monostearate, stearic acid, lanolin and white petrolatum to 80°C and stir to melt; (3) Preparation of cream: Mix the aqueous phase and oil phase, homogenize and emulsify, cool to 45°C, add isotretinoin, vitamin E, laurocapram and eucalyptus oil, homogenize and mix, cool to room temperature, and fill to obtain the cream.

[0019] The ointments prepared according to prescriptions 1-5 were subjected to in vitro transdermal tests. Rat skin was used in the transdermal tests, and a Franz diffusion cell with a diffusion area of ​​4.8 cm² was employed as the permeation device. 2 The receiving cell had a volume of 13.5 mL. Samples were taken at 1 h, 2 h, 3 h, 6 h, 12 h, and 24 h for testing. The cumulative permeation rate of tretinoin at 12 h and 24 h was calculated. The results of the transdermal test are as follows: The results show that Formula 1, without the addition of a surfactant, resulted in a cream with a low cumulative permeation rate of tretinoin at 24 hours. Formulas 2, 3, and 5, using Tween-20, Tween-80, and sodium lauryl sulfate as surfactants, respectively, resulted in creams with relatively low cumulative permeation rates of tretinoin at 12 hours and 24 hours. In contrast, Formula 4, using Span-85 as a surfactant, resulted in a cream with high cumulative permeation rates of tretinoin at 12 hours and 24 hours, with a cumulative permeation rate of 7.5% at 24 hours. Therefore, Span-85 was chosen as the surfactant.

[0020] Example 2: Screening of Transdermal Transdermal Enhancer Types and Compositions Preparation method: Same as in Example 1.

[0021] The ointment prepared according to prescription 6-13 was subjected to an in vitro transdermal test. Rat skin was used in the transdermal test, and a Franz diffusion cell with a diffusion area of ​​4.8 cm² was employed. 2The receiving cell had a volume of 13.5 mL. Samples were taken at 1 h, 2 h, 3 h, 6 h, 12 h, and 24 h for testing. The cumulative permeation rate of tretinoin at 12 h and 24 h was calculated. The results of the transdermal test are as follows: The results show that Formula 6, which uses laurocapram as a transdermal penetration enhancer, produced a cream with a high cumulative permeability of isotretinoin at 12 hours, but the rate remained essentially unchanged at 24 hours. Formula 7, which uses eucalyptus oil as a transdermal penetration enhancer, produced a cream with low cumulative permeability of isotretinoin at both 12 and 24 hours. Formulas 8, 9, and 10, which replaced eucalyptus oil with clove oil, oleic acid, and menthol respectively, showed that Formula 8 had a high cumulative permeability at 12 hours, but the increase was slower at 24 hours, while Formulas 9 and 10 had low cumulative permeability at both 12 and 24 hours. In Formulas 11 and 12, when the weight ratio of laurocapram to eucalyptus oil was 1:1 and 1:4 respectively, the increase in cumulative permeability at 24 hours was slower compared to Formulas 4 and 13, both below 7%. Formulas 4 and 13 selected laurocapram and eucalyptus oil as transdermal penetration enhancers, with a weight ratio of laurocapram to eucalyptus oil of 1:2-3. The creams prepared with these formulas had high cumulative permeability of isotretinoin at 12h and 24h, with a cumulative permeability of over 7% at 24h.

[0022] It should be understood that the technical solutions of the present invention are not limited to the specific embodiments described above. Any technical modifications made to the technical solutions of the present invention without departing from the spirit and scope of the claims are within the scope of protection of the present invention.

Claims

1. A tretinoin and vitamin E cream, characterized in that, Based on 100 parts by weight, the product comprises: 0.5 parts tretinoin, 0.3 parts vitamin E, 8-12 parts glyceryl monostearate, 8-12 parts stearic acid, 2-5 parts lanolin, 0.5-2 parts white petrolatum, 15-30 parts glycerin, 2.5-4 parts surfactant, 0.5-1.5 parts transdermal penetration enhancer, 0.01-0.1 parts preservative, and the balance being water. The surfactant is Span-85, and the transdermal penetration enhancer is laurocapram and eucalyptus oil, with a weight ratio of laurocapram to eucalyptus oil of 1:2-3.

2. The tretinoin and vitamin E cream according to claim 1, characterized in that, Based on 100 parts by weight, it includes: 0.5 parts tretinoin, 0.3 parts vitamin E, 10 parts glyceryl monostearate, 10 parts stearic acid, 3.5 parts lanolin, 1.5 parts white petrolatum, 20 parts glycerin, 3 parts surfactant, 1 part transdermal penetration enhancer, 0.05 parts preservative, and the balance being water.

3. The tretinoin and vitamin E cream according to claim 2, characterized in that, The preservatives include benzoic acid, sodium benzoate, potassium sorbate, benzalkonium chloride, benzalkonium bromide, and parabens.

4. The method for preparing the tretinoin vitamin E cream according to any one of claims 1-3, characterized in that, The process includes the following steps: (1) Preparation of the aqueous phase: Glycerin, surfactant, and preservative are added to water, heated to 70-85°C, and stirred to dissolve; (2) Preparation of the oil phase: Glyceryl monostearate, stearic acid, lanolin, and white petrolatum are heated to 70-85°C and stirred to melt; (3) Preparation of the cream: The aqueous phase and oil phase are mixed, homogenized and emulsified, cooled to 40-50°C, tretinoin, vitamin E, and transdermal penetration enhancer are added, homogenized and mixed, cooled to room temperature, and then filled and sealed.

5. The method for preparing the tretinoin vitamin E cream according to claim 4, characterized in that, The water phase temperature is heated to 80℃.

6. The method for preparing the tretinoin vitamin E cream according to claim 5, characterized in that, The oil phase temperature is heated to 80℃.

7. The method for preparing the tretinoin vitamin E cream according to claim 6, characterized in that, After homogenization and emulsification, the temperature is lowered to 45°C.

8. The tretinoin vitamin E cream prepared by the preparation method according to any one of claims 4-7.

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