Flavored shuangbai gel plaster, preparation method and application thereof

Abstract

The application provides a flavored double-cypress gel plaster and a preparation method thereof, which is composed of raw materials and excipients, and the raw materials are composed of the following components in percentage by mass: 2.33-2.85% of rhubarb, 2.33-2.85% of golden bark, 5.16-6.30% of Chinese arborvitae leaves, 2.33-2.85% of privet, 2.33-2.85% of mint, 0.71-0.87% of menthol, 0.71-0.87% of mint essential oil, 0.71-0.87% of borneol, and 0.71-0.87% of pine oil; and the excipients are composed of the following components: 5.38-6.58% of partially neutralized sodium polyacrylate NP700, 0.23-0.29% of glycyrrhizic acid, 0.17-0.21% of L (+) -tartaric acid, 0.06-0.08% of disodium edetate, 3.47-4.25% of povidone K90, 4.34-5.30% of kaolin, 13.30-16.26% of glycerol, and 45.70-55.86% of purified water. The plaster has good air permeability, stable adhesion and good absorbability.

Description

Technical Field

[0001] This invention relates to the field of plasters and their preparation, and more particularly to a flavored double cypress gel plaster and its preparation method. Background Technology

[0002] The latest prior art of this invention is a modified Shuangbai Ointment (ointment) prepared in-house, derived from Professor Huang Yaoshen's empirical formula. It possesses the effects of promoting blood circulation, removing blood stasis, reducing swelling, and relieving pain, and is widely used clinically to treat sprains, contusions, and other traumatic injuries. This formula has been used clinically for nearly 30 years with definite efficacy. However, the existing modified Shuangbai Ointment dosage form is a traditional ointment, made by adding finely powdered medicinal materials to petroleum jelly. This traditional dosage form has the following significant drawbacks: 1. Poor breathability, easily causing skin allergies: The petroleum jelly base has strong hydrophobicity. When applied externally, it forms a closed physical barrier on the skin surface, resulting in poor breathability and interfering with the normal physiological functions of the skin. It can easily induce allergic reactions such as itching and rashes in patients with allergies, thus limiting the clinically applicable population.

[0003] 2. Poor adhesion, easy softening and leakage, staining clothes: The melting point of petrolatum base is about 45-60℃. Under the influence of summer environment or human body temperature, it is easy to soften and melt, causing the ointment to leak out and migrate. This not only reduces the efficacy of the medicine, but also seriously stains clothes, affecting the patient's daily life and compliance.

[0004] 3. Poor transdermal drug absorption: The hydrophobic matrix clogs pores, hindering the release and transdermal penetration of active drug components, reducing bioavailability, and directly affecting the clinical efficacy of reducing swelling and pain, and promoting blood circulation.

[0005] 4. Inconvenient to use and unable to accurately administer medication: Traditional ointments require medical staff to add water and heat them on the spot, and patients need to come to the hospital every day to change the dressing, which is a cumbersome process; moreover, the dosage relies on manual experience and cannot be accurately controlled, affecting the stability of the therapeutic effect. Summary of the Invention

[0006] The main objective of this invention is to provide a flavored Shuangbai gel patch and its preparation method to solve the above-mentioned technical problems.

[0007] To achieve the above objectives, the technical solution adopted by this invention is as follows: a flavored Shuangbai gel plaster, composed of raw materials and excipients, wherein the raw materials, by mass percentage, consist of the following components: rhubarb 2.33%–2.85%, phellodendron bark 2.33%–2.85%, arborvitae leaf 5.16%–6.30%, eupatorium 2.33%–2.85%, peppermint 2.33%–2.85%, menthol 0.71%–0.87%, peppermint oil 0.71%–0.87%, borneol 0.71%–0.87%, and turpentine oil 0.71%–0.87%; The excipients consist of the following components: partially neutralized sodium polyacrylate NP700 5.38%–6.58%, aluminum hydroxyacetate 0.23%–0.29%, L(+)-tartaric acid 0.17%–0.21%, disodium edetate 0.06%–0.08%, povidone K90 3.47%–4.25%, kaolin 4.34%–5.30%, glycerol 13.30%–16.26%, and purified water 45.70%–55.86%.

[0008] This invention also provides a method for preparing a flavored Shuangbai gel patch, which specifically includes the following steps: Step 1: Preparation of sterilized medicinal powder: Clean and dry rhubarb, phellodendron bark, arborvitae leaves, eupatorium, and mint, then grind them into fine powder. All of the powder should pass through a No. 5 sieve, and more than 95% should pass through a No. 6 sieve. After sterilization, the powder is ready for use. Step 2: Prepare the mixed medicinal oil: Weigh out menthol, peppermint oil, borneol, and turpentine oil, mix and heat until melted, stir until homogeneous and transparent, and seal for later use; Step 3: Prepare the oil phase, which includes the following steps: Step 31: Add part of the neutralized sodium polyacrylate NP700, aluminum hydroxyl, disodium edetate, and kaolin to glycerin and stir thoroughly until there is no dry powder or particles. Step 32: Add the mixed medicinal oil to the product from step 31 and continue stirring until it becomes a uniform semi-fluid. Set aside for later use. Step 4: Prepare the aqueous phase, which includes the following steps: Step 41: Add L (+)-tartaric acid and povidone K90 to purified water and stir until completely dissolved and fully swollen; Step 42: Add sterilized medicinal powder to the product of step 41 and stir continuously until it becomes a smooth, lump-free paste. Set aside. Step 5: Preparation of viscous colloid: Slowly add the oil phase prepared in step 3 to the aqueous phase prepared in step 4, and continue stirring for 6 minutes to form a uniform, fine, and coating-friendly viscous colloid. Step 6: Preparation of plaster semi-finished product: The viscous colloid prepared in step 5 is evenly coated on the medical non-woven fabric backing layer, covered with polyethylene anti-adhesive film, cut and pressed into shape according to specifications to obtain plaster semi-finished product. Step 7: Preparation of the finished product of Jiawei Shuangbai gel plaster: Place the semi-finished plaster prepared in Step 6 in a clean environment for curing. The ambient temperature is 20℃~30℃ and the relative humidity is 50%~70%. After curing for a period of time, the matrix forms a stable three-dimensional network gel structure. After curing, seal the plaster in a pharmaceutical aluminum foil bag to obtain the finished product of Jiawei Shuangbai gel plaster.

[0009] Compared with the prior art, the present invention has the following beneficial effects: 1. Excellent breathability, reducing the risk of skin allergies: This invention abandons the traditional hydrophobic matrix of petrolatum and adopts a hydrophilic cross-linked gel matrix such as purified water, glycerin, sodium polyacrylate (hydrophilic skeleton), aluminum hydroxyl (cross-linking agent), and tartaric acid (cross-linking regulator). This avoids the formation of a closed physical barrier on the skin surface, significantly improves breathability, does not interfere with the normal physiological function of the skin, is gentle on the skin and has low irritation, and can greatly reduce allergic phenomena such as itching and rashes, thus expanding the clinically applicable population.

[0010] 2. Stable adhesion, no leakage or staining of clothing: This invention uses a three-dimensional network cross-linking structure and room temperature precise curing process to make the ointment stable and cohesive, overcoming the defects of traditional ointments that are easy to soften and melt at high temperatures. After application, it does not shift, leak, or stain clothing, and does not affect the patient's daily life, thus improving user compliance.

[0011] 3. Improves transdermal absorption and enhances clinical efficacy: This invention utilizes a hydrophilic gel matrix with synergistic effects of penetration-enhancing components such as menthol, peppermint oil, borneol, and turpentine oil to avoid clogging pores with the hydrophobic matrix. This facilitates the full release and transdermal penetration of the drug's active ingredients, improves bioavailability, and enhances the clinical effects of promoting blood circulation, removing blood stasis, reducing swelling, and relieving pain.

[0012] 4. Convenient to use and accurate dosage: This invention is a ready-to-use gel patch that does not require medical staff to add water or heat it for preparation. Patients can use the medication themselves without having to go to the hospital every day to change the dressing. 5. In the preparation method of the present invention, the feeding and mixing method of first dispersing the fine powder of traditional Chinese medicine in an aqueous phase containing povidone and tartaric acid, and then mixing it with an oil phase containing a cross-linked skeleton, solves the problems of uneven mixing and clumping when the drug loading is high. Detailed Implementation

[0013] The following description is intended to disclose the invention and enable those skilled in the art to implement it. The preferred embodiments described below are merely examples, and other obvious variations will occur to those skilled in the art.

[0014] Example 1 A flavored double-cypress gel plaster, composed of raw materials and excipients, wherein the raw materials, by mass percentage, consist of the following components: rhubarb 2.33%–2.85%, phellodendron bark 2.33%–2.85%, arborvitae leaf 5.16%–6.30%, eupatorium 2.33%–2.85%, peppermint 2.33%–2.85%, menthol 0.71%–0.87%, peppermint oil 0.71%–0.87%, borneol 0.71%–0.87%, and turpentine oil 0.71%–0.87%; The excipients consist of the following components: partially neutralized sodium polyacrylate NP700 5.38%–6.58%, aluminum hydroxyacetate 0.23%–0.29%, L(+)-tartaric acid 0.17%–0.21%, disodium edetate 0.06%–0.08%, povidone K90 3.47%–4.25%, kaolin 4.34%–5.30%, glycerol 13.30%–16.26%, and purified water 45.70%–55.86%.

[0015] Example 2 This embodiment describes the preparation method of the plaster in Example 1, specifically including the following steps: Step 1: Preparation of sterilized medicinal powder: Clean and dry rhubarb, phellodendron bark, arborvitae leaves, eupatorium, and mint, then grind them into fine powder. All of the powder should pass through a No. 5 sieve, and more than 95% should pass through a No. 6 sieve. After sterilization, the powder is ready for use. Step 2: Prepare the mixed medicinal oil: Weigh out menthol, peppermint oil, borneol, and turpentine oil, mix and heat until melted, stir until homogeneous and transparent, and seal for later use; Step 3: Prepare the oil phase, which includes the following steps: Step 31: Add part of the neutralized sodium polyacrylate NP700, aluminum hydroxyl, disodium edetate, and kaolin to glycerin and stir thoroughly until there is no dry powder or particles. Step 32: Add the mixed medicinal oil to the product from step 31 and continue stirring until it becomes a uniform semi-fluid. Set aside for later use. Step 4: Prepare the aqueous phase, which includes the following steps: Step 41: Add L (+)-tartaric acid and povidone K90 to purified water and stir until completely dissolved and fully swollen; Step 42: Add sterilized medicinal powder to the product of step 41 and stir continuously until it becomes a smooth, lump-free paste. Set aside. Step 5: Preparation of viscous colloid: Slowly add the oil phase prepared in step 3 to the aqueous phase prepared in step 4, and continue stirring for 6 minutes to form a uniform, fine, and coating-friendly viscous colloid. Step 6: Preparation of plaster semi-finished product: The viscous colloid prepared in step 5 is evenly coated on the medical non-woven fabric backing layer, covered with polyethylene anti-adhesive film, cut and pressed into shape according to specifications to obtain plaster semi-finished product. Step 7: Preparation of the finished product of Jiawei Shuangbai gel plaster: Place the semi-finished plaster prepared in Step 6 in a clean environment for curing, control the temperature at 20℃~30℃ and the relative humidity at 50%~70%, and cure for 48 hours to allow the matrix to form a stable three-dimensional network gel structure; after curing, seal and package it in a pharmaceutical aluminum foil bag to obtain the finished product of Jiawei Shuangbai gel plaster.

[0016] Experimental Example Materials needed: 26g rhubarb, 26g phellodendron bark, 57g arborvitae leaves, 26g eupatorium, 26g peppermint, 8g menthol, 8g peppermint oil, 8g borneol, 8g turpentine oil; partially neutralized sodium polyacrylate NP700 60g, aluminum hydroxyacetate 3g, L (+)-tartaric acid 2g, disodium edetate 1g, povidone K90 39g, kaolin 48g, glycerin 148g, purified water 506g.

[0017] Prepare according to the following steps: Step 1: Preparation of sterilized medicinal herb powder: 26g of rhubarb, 26g of phellodendron bark, 57g of arborvitae leaves, 26g of eupatorium, and 26g of mint were selected to remove impurities. After rapid washing with purified water, they were placed in a 60℃ forced-air drying oven and dried for 4 hours until the moisture content was ≤8%. After removal, the powder was pulverized using a universal pulverizer. The pulverized powder was then passed through a No. 5 sieve and a No. 6 sieve. Any remaining coarse powder on the sieves was returned to the pulverizer for further pulverization until all the powder passed through the No. 5 sieve. 100g of the powder passing through the No. 5 sieve was taken and its particle size was determined according to Method 1 of General Chapter 0982 in the 2025 edition of the Chinese Pharmacopoeia. The passing rate through the No. 6 sieve was 96.8%, which met the requirements. The qualified powder was placed in a moist heat sterilizer and sterilized at approximately 120℃ for 18 minutes. After cooling to room temperature, the sterilized medicinal herb powder was obtained and sealed for later use.

[0018] Step 2: Preparation of mixed medicinal oil: Weigh 8g of menthol, 8g of peppermint oil, 8g of borneol, and 8g of turpentine oil, place them in a 250mL beaker, and heat them in a 45℃ constant temperature water bath. While heating, stir at a speed of 40r / min. After about 8 minutes, they will all melt. Continue stirring for 5 minutes until the solution is uniform and transparent, with no visible insoluble matter. The mixed medicinal oil is obtained. Seal and keep warm at 40℃ for later use.

[0019] Step 3: Preparation of the oil phase: Add 60g of neutralized sodium polyacrylate NP700, 3g of aluminum hydroxyl, 1g of disodium edetate, and 48g of kaolin to a 1000mL beaker containing 148g of glycerol. Stir at 70r / min for 18 minutes until the system is free of dry powder and particles and forms a uniform paste. Then slowly add the mixed medicinal oil obtained in Step 2 and continue stirring at 50r / min for 12 minutes to obtain a uniform semi-fluid oil phase for later use.

[0020] Step 4: Preparation of the aqueous phase: Add 2g of L(+)-tartaric acid and 39g of povidone K90 to a 2000mL beaker containing 506g of purified water. Stir until completely dissolved, and let stand for 35 minutes to allow the povidone K90 to fully swell. Then add the sterilized medicinal powder from Step 1 and stir continuously at 90r / min for 25 minutes until the system is uniform, smooth, and free of lumps, forming a paste-like consistency. This is the aqueous phase, which is then ready for use.

[0021] Step 5: Preparation of viscous colloid: Slowly add the oil phase to the aqueous phase at a rate of 75 mL / min, while continuously stirring at a speed of 110 r / min. After the addition is complete, continue stirring for 6 minutes to obtain a uniform, fine, bubble-free viscous colloid with good extensibility.

[0022] Step Six: Preparation of the semi-finished plaster: Transfer the viscous colloid obtained in Step Five to the hopper of an automatic coating machine, adjust the coating thickness to 1.0 mm, and evenly coat it onto the medical non-woven fabric backing layer. Immediately cover it with a polyethylene anti-adhesive film. Then, use a slitting machine to cut it to a size of 10 cm × 7 cm, and use an edge pressing machine to press and shape the edges to obtain the semi-finished plaster. Approximately 140 plasters were produced in total.

[0023] Step 7: Prepare and cure the finished product: Transfer the semi-finished plaster to a constant temperature and humidity curing chamber, set the temperature to 25℃ and the relative humidity to 60%, and let it cure for 48 hours. After curing, remove the plaster, seal it individually in a pharmaceutical aluminum foil bag, and you will get the finished flavored Shuangbai gel plaster.

[0024] The obtained finished products were taken into three batches and labeled as S1, S2 and S3 respectively. Ten patches were randomly selected from each batch of finished products and subjected to the following two tests: 1) Routine testing: One patch is randomly selected from each batch. The test results are shown in Table 1. Table 1. Results of routine testing

[0025] 2) The total anthraquinone content of rhubarb and quercetin content of Platycladus orientalis were determined by HPLC. One sample was randomly selected from each batch, and the results are shown in Table 2. Table 2. Detection results of total anthraquinones from rhubarb and quercetin from arborvitae leaves.

[0026] The above routine tests and content tests show that the active ingredient content of the ointment of the present invention is stable and the batch-to-batch variation is small.

[0027] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the claimed invention. The scope of protection claimed by the appended claims and their equivalents is defined.

Claims

1. A flavored double-cypress gel patch, characterized in that, Composed of active pharmaceutical ingredients (APIs) and excipients, the APIs, by mass percentage, consist of the following components: rhubarb 2.33%–2.85%, phellodendron bark 2.33%–2.85%, arborvitae leaf 5.16%–6.30%, eupatorium 2.33%–2.85%, peppermint 2.33%–2.85%, menthol 0.71%–0.87%, peppermint oil 0.71%–0.87%, borneol 0.71%–0.87%, and turpentine oil 0.71%–0.87%. The excipients consist of the following components: partially neutralized sodium polyacrylate NP700 5.38%–6.58%, aluminum hydroxyacetate 0.23%–0.29%, L(+)-tartaric acid 0.17%–0.21%, disodium edetate 0.06%–0.08%, povidone K90 3.47%–4.25%, kaolin 4.34%–5.30%, glycerol 13.30%–16.26%, and purified water 45.70%–55.86%.

2. The preparation method of the flavored Shuangbai gel patch according to claim 1, characterized in that, Specifically, the steps include the following: Step 1: Preparation of sterilized medicinal powder: Clean and dry rhubarb, phellodendron bark, arborvitae leaves, eupatorium, and mint, then grind them into fine powder. All of the powder should pass through a No. 5 sieve, and more than 95% should pass through a No. 6 sieve. After sterilization, the powder is ready for use. Step 2: Prepare the mixed medicinal oil: Weigh out menthol, peppermint oil, borneol, and turpentine oil, mix and heat until melted, stir until homogeneous and transparent, and seal for later use; Step 3: Prepare the oil phase; Step 4: Prepare the aqueous phase; Step 5: Preparation of viscous colloid: Slowly add the oil phase prepared in step 3 to the aqueous phase prepared in step 4, and continue stirring for 6 minutes to form a uniform, fine, and coating-friendly viscous colloid. Step 6: Preparation of plaster semi-finished product: The viscous colloid prepared in step 5 is evenly coated on the medical non-woven fabric backing layer, covered with polyethylene anti-adhesive film, cut and pressed into shape according to specifications to obtain plaster semi-finished product. Step 7: Preparation of the finished product of Jiawei Shuangbai gel plaster: Place the plaster semi-finished product prepared in step 6 in a clean environment for curing. The ambient temperature is 20℃~30℃ and the relative humidity is 50%~70%. After curing for a period of time, the matrix forms a stable three-dimensional network gel structure. After curing, seal the plaster in a pharmaceutical aluminum foil bag to obtain the finished product of Jiawei Shuangbai gel plaster.

3. The preparation method according to claim 2, characterized in that, Step three specifically includes the following steps: Step 31: Add part of the neutralized sodium polyacrylate NP700, aluminum hydroxyl, disodium edetate, and kaolin to glycerin and stir thoroughly until there is no dry powder or particles. Step 32: Add the mixed medicinal oil to the product from step 31 and continue stirring until it becomes a uniform semi-fluid. Set aside for later use.

4. The preparation method according to claim 2, characterized in that, Step four specifically includes the following steps: Step 41: Add L (+)-tartaric acid and povidone K90 to purified water and stir until completely dissolved and fully swollen; Step 42: Add sterilized medicinal powder to the product from step 41 and stir continuously until it becomes a smooth, lump-free paste. Set aside.

Images