Topical application composition containing sucralfate wet gel

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a composition for topical application containing sucralfate wet gel. The invention relates to a local application composition containing sucralfate wet gel, which is prepared from the following components in percentage by mass: 15 to 25 percent of sucralfate wet gel, 10 to 18 percent of polyethylene glycol, 0.2 to 0.5 percent of polyethylene glycol stearate, 0.1 to 0.21 percent of sodium methyl p-hydroxybenzoate, 0.01 to 0.023 percent of sodium propyl p-hydroxybenzoate and the balance of purified water. The sucralfate wet gel dressing is smeared on a non-infected and carefully disinfected skin wound surface and dried, a solid barrier is formed on the part, the wound surface can be covered, damaged tissues below the wound surface can be protected against external stimulation, and the sucralfate wet gel dressing is used for treating non-infectious wound surfaces and ulcers, especially vascular ulcers, diabetic ulcers, bedsores and radiodermatitis, and has a good application prospect. A layer of protective barrier is formed on the broken or damaged surface, so that physiological healing is promoted.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a topical application composition of a sulforaphane-containing wet gel. Background Technology

[0002] Sucralfate is a basic aluminum salt of sucrose sulfate. As an antacid, it is commonly used to treat digestive system diseases such as gastric ulcers, duodenal ulcers, esophageal ulcers, and acute and symptomatic chronic gastritis. It works by binding to exudative proteins at the ulcer site, forming a complex that adheres to the ulcer surface, thereby protecting the ulcer from damage by gastric acid, pepsin, and bile salts, thus exerting anti-ulcer and gastric mucosal protective effects. However, when sucralfate is applied to wounds, a strongly acidic environment is not present. Sucralfate does not dissociate into negatively charged octasulfate sucrose and remains in its original form, making it unsuitable for use on non-infectious wounds and ulcers.

[0003] In existing technologies, sucralfate is formulated into a wet gel to improve its water solubility. This requires the addition of biomaterials such as tocotrienols and tocopherols to promote epithelial regeneration and increase skin elasticity. However, these biomaterials are prone to oxidation and degradation. Simultaneously, adjuvants such as polyvinyl alcohol and disodium hydrogen phosphate are added to improve stability, but these tend to reduce overall viscosity, preventing the drug from remaining on vertical surfaces. This shortens the effective drug contact time and prevents the formation of a protective barrier on broken or damaged surfaces, thus hindering the promotion of physiological healing of broken or damaged surfaces. Summary of the Invention

[0004] The purpose of this invention is to provide a topical application composition of a sulforaphane-containing wet gel, thereby overcoming the shortcomings of the prior art. This pharmaceutical composition is used to treat non-infectious wounds and ulcers, especially vascular ulcers, diabetic ulcers, pressure sores, and radiation dermatitis, forming a protective barrier on the ruptured or damaged surface, thereby promoting physiological healing.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows: In a first aspect, the present invention provides a topical application composition for a sulforaphane-containing wet gel, comprising, by weight percentage, the following components: The composition consists of 15-25% sucralfate wet gel, 10-18% polyethylene glycol, 0.2-0.5% polyethylene glycol stearate, 0.1-0.21% sodium methylparaben, 0.01-0.023% sodium propylparaben, and the balance being purified water.

[0006] The sucralfate in the wet gel is pre-hydrated, which greatly improves its dispersion uniformity and stability in the final formulation, avoiding problems such as clumping and difficulty in dispersion that may occur with dry powder. The wet gel comes into direct contact with the damaged surface, forming a barrier and increasing adhesion, relieving pain, forming a protective layer on the wound surface, and providing a physical barrier for the wound.

[0007] Polyethylene glycol 400 is a clear, viscous, and colorless liquid, miscible with water due to its hydrophilicity. It is used as a solubilizer, viscosity modifier, and emulsion stabilizer, and is also used in the manufacture of gels, ointments, and suppositories. Polyethylene glycol is not absorbed by the human body and has been included in the pharmacopoeia as a pharmaceutical excipient. In this composition, polyethylene glycol acts as a diluent, constructs a gel network to provide viscosity, suspends and stabilizes the sucralfate wet gel, prevents particle aggregation and sedimentation, maintains the physical stability and uniformity of the gel, and ensures accurate dosage for each administration. It also gives the gel suitable flowability and spreadability, facilitating extrusion from the tube and allowing for good adhesion to mucosal surfaces after application.

[0008] Polyethylene glycol stearate, also known as polyethylene glycol stearate, is a pharmaceutical excipient widely used in pharmaceutical formulations and manufacturing processes. It is commonly used as an emulsifier in oil-in-water creams and lotions. Its hydrophilicity or lipophilicity depends on the number of ethoxylated units; the higher the number, the stronger the hydrophilicity. Polyethylene glycol stearate is primarily used as an emulsifier in topical formulations and has also been used in intravenous and oral formulations. Having passed extensive animal toxicity tests, it is widely used in pharmaceuticals and cosmetics and is generally considered non-toxic and non-irritating. In this composition, polyethylene glycol stearate acts as an emulsifier, wetting agent, and stabilizer, strongly wetting and dispersing sucralfate wet gel, achieving micronization and long-term physical stability, potentially enhancing drug efficacy, and avoiding the problems of potentially coarse, grainy, and easily separated gel textures.

[0009] Parabens are commonly used preservatives widely applied in the pharmaceutical, food, and textile industries. In the food industry, they prevent food spoilage and extend shelf life. In the pharmaceutical field, they can be used as preservatives in certain drugs, ensuring their quality and stability. Furthermore, sodium methylparaben can be used for the preservation of textiles and as a preservative in some cosmetics and personal care products. In this composition, sodium methylparaben and sodium propylparaben act as preservatives, working synergistically to provide broad-spectrum and highly effective preservative protection, ensuring the microbial stability of the entire formulation during storage and use, ensuring product safety, and preventing the gel from quickly deteriorating, moldy, losing its efficacy, and becoming dangerous.

[0010] Specifically, the topical application composition of the sucralfate wet gel consists of the following components by weight percentage: Sucralfate wet gel 15, 17, 20, 23 or 25%, polyethylene glycol 10, 12, 14, 16 or 18%, polyethylene glycol stearate 0.2, 0.3, 0, 4 or 0.5%, sodium methylparaben 0.1, 0.15, 0.2 or 0.21%, sodium propylparaben 0.01, 0.015, 0.02 or 0.023%, balance being purified water.

[0011] In some other embodiments, the topical application composition of the sucralfate wet gel consists of the following components by weight percentage: The formula comprises 25% sucralfate wet gel, 18% polyethylene glycol 400, 0.5% polyethylene glycol stearate, 0.206% sodium methylparaben, 0.022% sodium propylparaben, and the balance being purified water. This formulation produces a sucralfate wet gel composition with better stability and efficacy.

[0012] In some other embodiments, the polyethylene glycol is polyethylene glycol 400. PEG 400, when dissolved in water, forms a hydrophilic network structure, imparting a suitable viscosity to the formulation.

[0013] In some other embodiments, the water content of the sucralfate wet gel is 50-79 wt%. Specifically, the water content of the sucralfate wet gel is 50, 60, 65, 70, 75 or 79 wt%, and the sucralfate wet gel with this water content has good stability.

[0014] In some other embodiments, the purified water is either deionized water or distilled water. This purified water does not contain metal ions or other impurities, ensuring product stability.

[0015] In some other embodiments, the dosage form of the pharmaceutical composition is one or more of the following: gel, ointment, suppository, and spray.

[0016] In a second aspect, the present invention provides a method for preparing an application composition for the sulfur-containing sucralfate wet gel described in the first aspect, comprising the following steps: The sucralfate gel, polyethylene glycol, polyethylene glycol stearate, sodium methylparaben, sodium propylparaben, and water were homogenized to obtain an application composition containing sucralfate wet gel. The application composition of the sulfur-containing sucralfate wet gel is sterilized by ionizing radiation to obtain the application composition of the sulfur-containing sucralfate wet gel.

[0017] In some other embodiments, the sucralfate gel is prepared as follows: sucralfate is dissolved in hydrochloric acid, and sodium hydroxide solution is added to adjust the pH to obtain sucralfate gel; The concentration of the hydrochloric acid is 1-3 mol / L, and the pH is 4-4.5.

[0018] The product of this invention is provided in a sterile form, with a sterilization shelf life of 36 months.

[0019] Thirdly, the present invention provides the use of the topical application composition of the sucralfate wet gel described in the first aspect in the preparation of a medicament for treating non-infectious wounds and ulcers.

[0020] Sucralfate wet gel applied to skin wounds is not absorbed by the wound surface; it only forms a physical barrier, and its effect is physical. Sucralfate wet gel dressings have good adhesion and can maintain barrier function for a relatively long time.

[0021] In some other embodiments, the non-infectious wounds and ulcers are one or more of vascular ulcers, diabetic ulcers, bedsores, and radiation dermatitis.

[0022] The beneficial effects of this invention are: (1) The topical application composition of sucralfate wet gel provided by the present invention consists of sucralfate wet gel, polyethylene glycol 400, polyethylene glycol stearate, sodium methylparaben (E219), sodium propylparaben (E217), and purified water. Each component is in direct contact with the damaged surface; the product does not contain any biological materials or derivatives, drugs, or active ingredients. This product remains stable over a long period, ensuring stable spraying and providing good coverage of the damaged area.

[0023] (2) Sucralfate wet gel dressing is applied to a non-infected and carefully disinfected skin wound. After drying, it forms a solid barrier on the wound, which can cover the wound and protect the damaged tissue below from external stimulation. Therefore, the product achieves its intended use through physical action, not through pharmacological, immunological or metabolic means. Attached Figure Description

[0024] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0025] Figure 1 This is a morphological image of L929 cells in Example 1 of the present invention (contact sample extract for 24 hours). Detailed Implementation

[0026] It should be noted that the following detailed descriptions are exemplary and intended to provide further explanation of the invention. Unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0027] This invention does not impose specific limitations on the raw materials used, but the following sources may be selected: sucralfate wet gel (CAS number 54182-58-0), polyethylene glycol 400 (CAS number 25322-68-3), polyethylene glycol stearate (CAS number 9004-99-3), sodium methylparaben (CAS number 5026-62-0), and sodium propylparaben (CAS number 35285-69-9). Purified water is either deionized water or distilled water.

[0028] As mentioned earlier, existing sucralfate wet gel dressings / spray formulations contain biomaterials or derivatives, drugs or active ingredients such as tocotrienols and tocopherols. When applied to the skin surface, the added biomaterials are easily oxidized and deactivated. The added polyvinyl alcohol and disodium hydrogen phosphate can easily reduce the overall viscosity, making it impossible to stay on vertical surfaces, shortening the effective contact time of the drug, and failing to form a protective barrier on broken or damaged surfaces.

[0029] This invention provides a topical application composition for a sucralfate wet gel that can be applied to a non-infected and carefully disinfected skin wound. After drying, it forms a solid barrier at the site, which can both cover the wound and protect the underlying damaged tissue from external stimuli. It has good adhesion and can maintain the barrier function for a long time.

[0030] The solution of the present invention will be described below with reference to specific embodiments: Example 1 This embodiment provides a topical application composition for a sucralfate wet gel, which comprises the following components by weight percentage: The composition consists of 25% sucralfate wet gel, 18% polyethylene glycol 400, 0.5% polyethylene glycol stearate, 0.206% sodium methylparaben, 0.022% sodium propylparaben, and the remainder is purified water.

[0031] A method for preparing a topical application composition of a sulfur-containing sucralfate wet gel includes the following steps: (1) Sucralfate was dissolved in 2 mol / L hydrochloric acid and sodium hydroxide solution was added to adjust the pH to 4.5 to obtain sucralfate gel; (2) Sucralfate gel, polyethylene glycol 400, polyethylene glycol stearate, sodium methylparaben, sodium propylparaben and purified water were placed in a high pressure homogenizer for homogenization to obtain an application composition containing sucralfate wet gel. (3) The application composition of the sulfur-containing sucralfate wet gel is sterilized by ionizing radiation.

[0032] Example 2 This embodiment provides a topical application composition for a sucralfate wet gel, which comprises the following components by weight percentage: The composition consists of 15% sucralfate wet gel, 10% polyethylene glycol 400, 0.2% polyethylene glycol stearate, 0.1% sodium methylparaben, 0.01% sodium propylparaben, and the remainder is purified water.

[0033] The preparation method is the same as in Example 1.

[0034] Example 3 This embodiment provides a topical application composition for a sucralfate wet gel, which comprises the following components by weight percentage: The composition consists of 20% sucralfate wet gel, 5% polyethylene glycol 400, 0.4% polyethylene glycol stearate, 0.15% sodium methylparaben, 0.015% sodium propylparaben, and the remainder is purified water.

[0035] The preparation method is the same as in Example 1.

[0036] Comparative Example 1 Unlike Example 1, the topical application composition of the sucralfate wet gel consists of the following components by weight percentage: The composition consists of 25% sucralfate wet gel, 0.1% polyvinyl alcohol 2200, 0.5% polyethylene glycol stearate, 0.206% sodium methylparaben, 0.022% sodium propylparaben, and the remainder is purified water.

[0037] The preparation method is the same as in Example 1.

[0038] Comparative Example 2 Unlike Example 1, the topical application composition of the sucralfate wet gel consists of the following components by weight percentage: The composition consists of 25% sucralfate wet gel, 18% polyethylene glycol 400, 1% disodium hydrogen phosphate, 0.206% sodium methylparaben, 0.022% sodium propylparaben, and the remainder is purified water.

[0039] The preparation method is the same as in Example 1.

[0040] Comparative Example 3 Unlike Example 1, the topical application composition of the sucralfate wet gel consists of the following components by weight percentage: The composition consists of 25% sucralfate wet gel, 18% polyethylene glycol 400, 0.206% sodium methylparaben, 0.022% sodium propylparaben, and the remainder is purified water.

[0041] The preparation method is the same as in Example 1.

[0042] Application examples This application example provides a method of using a topical composition of a sucralfate wet gel, comprising the following steps: (1) Thoroughly clean and disinfect the wound with a disinfectant solution (such as hydrogen peroxide or iodine-based disinfectant); (2) Spray or apply the application composition of sulforaphane wet gel to clean and disinfected wounds; if necessary, cover the wound with sterile gauze after spraying or applying. (3) After use, clean the open end of the test tube containing the application composition of sucralfate wet gel with sterile gauze and tighten the screw to close it.

[0043] Performance Characterization 1. Performance: Appearance (observed under normal or corrected visual acuity) 2. Viscosity: Tested using a rotational viscometer at 25℃±1℃.

[0044] 3. Barrier maintenance time: Spread 1g of sample evenly on the silica gel sheet, invert it, and observe the time when the sample begins to fall off.

[0045] 4. Cytotoxicity: Extract at a ratio of 0.2 g / mL, using serum-containing culture medium, at a temperature of 37 ± 1°C, for a time of 24 ± 2 h. Use the extract as the test solution and perform the test according to the extract test method specified in GB / T16886.5-2017.

[0046] 5. Skin irritation: Extract at a ratio of 0.2 g / mL, using 0.9% sodium chloride injection and cottonseed oil as the extraction medium, at a temperature of 37 ± 1°C, for a time of 72 ± 2 h. Use the extract as the test solution and proceed according to the method specified in GB / T16886.23-2023.

[0047] 6. pH value: Extract at a ratio of 0.2 g / mL, using purified water as the extraction medium, at a temperature of 37 ± 1°C, for a time of 24 ± 2 h. Take the extract and test the pH value with a pH meter.

[0048] 7. Stability maintenance time: Place the product in a constant temperature and humidity chamber at 50℃ and 70% humidity. Observe the morphology of the sample every month. If oil and water separation occurs, it means that the product is no longer stable. The above observation point is taken as the stability time of the product.

[0049] The performance characterization results of the application compositions of the sulfur-containing sucralfate wet gel prepared in the examples and comparative examples are shown in Table 1.

[0050] Table 1 Performance Characterization

[0051] As shown in Table 1, Example 1 exhibits the best performance. Compared to Example 1, Example 2 significantly reduces the content of each component, especially the sucralfate wet gel, resulting in a decrease in viscosity and barrier maintenance time, but still meeting the usage requirements. Compared to Example 1, Example 3 has a lower content of polyethylene glycol 400, leading to a decrease in barrier maintenance time. Although Comparative Example 1 has a better viscosity than Examples 2 and 3, it exhibits higher cytotoxicity and mild irritation. Comparative Examples 2-3 show higher cytotoxicity than Examples 1-3, accompanied by mild irritation, indicating that the sucralfate wet gel plays an important role in the product viscosity, and that the components work synergistically.

[0052] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. An application composition for a sulfur-containing sucralfate wet gel, characterized in that, It consists of the following components by mass percentage: The composition consists of 15-25% sucralfate wet gel, 10-18% polyethylene glycol, 0.2-0.5% polyethylene glycol stearate, 0.1-0.21% sodium methylparaben, 0.01-0.023% sodium propylparaben, and the balance being purified water.

2. The application composition of the sulfur-containing sucralfate wet gel according to claim 1, characterized in that, It consists of the following components by mass percentage: The composition consists of 25% sucralfate wet gel, 18% polyethylene glycol 400, 0.5% polyethylene glycol stearate, 0.206% sodium methylparaben, 0.022% sodium propylparaben, and the remainder is purified water.

3. The application composition of the sulfur-containing sucralfate wet gel according to claim 1, characterized in that, The polyethylene glycol is polyethylene glycol 400.

4. The application composition of the sulfur-containing sucralfate wet gel according to claim 1, characterized in that, The water content of the sucralfate wet gel is 50-79 wt%.

5. The application composition of the sulfur-containing sucralfate wet gel according to claim 1, characterized in that, The purified water is either deionized water or distilled water.

6. The application composition of the sulfur-containing sucralfate wet gel according to claim 1, characterized in that, The dosage form of the pharmaceutical composition is one or more of the following: gel, ointment, suppository, and spray.

7. A method for preparing an application composition of the sulfur-containing sucralfate wet gel according to any one of claims 1-6, characterized in that, Includes the following steps: The sucralfate gel, polyethylene glycol, polyethylene glycol stearate, sodium methylparaben, sodium propylparaben, and purified water were homogenized to obtain an application composition containing sucralfate wet gel. The application composition of sulfur-containing sucralfate wet gel is obtained by sterilizing it with ionizing radiation.

8. The method for preparing the application composition of the sulfur-containing sucralfate wet gel according to claim 7, characterized in that, The preparation method of sucralfate gel is as follows: Sucralfate is dissolved in hydrochloric acid, and sodium hydroxide solution is added to adjust the pH to obtain sucralfate gel; The concentration of the hydrochloric acid is 1-3 mol / L, and the pH is 4-4.

5.

9. The use of an application composition of the sulforaphane-containing wet gel according to any one of claims 1-6 in the preparation of a medicament for treating non-infectious wounds and ulcers.

10. The application according to claim 9, characterized in that, The non-infectious wounds and ulcers are one or more of the following: vascular ulcers, diabetic ulcers, bedsores, and radiation dermatitis.

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