Topical cream or patch for scar treatment and preparation method therefor
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
- Filing Date
- 2026-02-27
- Publication Date
- 2026-07-02
Abstract
Description
A topical scar treatment cream or patch and its preparation method Technical Field
[0001] This invention relates to the field of medical materials technology, specifically to a topical preparation for scar treatment that integrates hormones, antibiotics, and chemotherapy drugs, and its preparation method. Background Technology
[0002] Scars are mainly classified into two types: hypertrophic scars and keloids. Hypertrophic scars are caused by tissue proliferation resulting from injuries such as burns and trauma, and the extent of scar proliferation is usually limited to the site of injury. Keloids, on the other hand, are usually caused by tissue proliferation from acne, insect bites, or surgery, and typically extend beyond the area of injury, spreading outwards like a tumor. Both hypertrophic scars and keloids not only cause disfigurement but also bring pain and itching, severely impacting quality of life.
[0003] Currently, there are many methods for treating scars, commonly including drug therapy, pressure therapy, and laser therapy. Drug therapy includes silicone gel, centella asiatica cream, and contractubex, applied topically, but their efficacy is limited, especially for rapidly proliferating scars and keloids. Clinically, the combined injection of hormones (such as dexamethasone or triamcinolone) and chemotherapy drugs (such as 5-fluorouracil, bleomycin, or mitomycin C) shows better results, especially for keloids, and is a commonly used treatment method. The main function of hormones is to inhibit inflammation within the scar and suppress fibroblast and angiogenesis; 5-fluorouracil works by destroying fibroblasts and blood vessels, promoting scar regression. However, both are currently mainly administered via injection, which causes severe pain for patients, so most patients are unwilling to undergo this procedure. Using patches or creams might be more universally applicable.
[0004] Furthermore, we have recently discovered a phenomenon of "bacterial overload" in hypertrophic scars and keloids. The presence of Staphylococcus aureus, predominantly, in hypertrophic scars may be one of the root causes of chronic inflammation and hyperplasia in these conditions. Therefore, designing a topical patch or cream that simultaneously possesses anti-inflammatory, antibacterial, and scar-reducing properties would significantly improve patient acceptance. Summary of the Invention
[0005] This invention addresses the aforementioned needs by designing a topical ointment or patch primarily containing antibiotics, hormones, and chemotherapy drugs. Through the synergistic effect of these multiple components, it produces bactericidal, anti-inflammatory, and fibroblast and angiogenesis-inhibiting effects, thereby achieving multiple benefits such as inhibiting scar hyperplasia, promoting scar softening, and preventing infection, thus improving the treatment outcome of scars. This preparation eliminates the need for injection treatment; it can be applied topically or as a patch, greatly facilitating patient use and achieving the goal of scar prevention and treatment.
[0006] This invention studies the formulation and preparation process of topical ointments and patches, and prepares creams and long-acting sustained-release transdermal patches for scarring. Then, an animal model of rabbit ear hypertrophic scars was established to verify its efficacy. The results showed that the three-drug mixture group was significantly superior to the control group (P<0.01), the hydrocortisone butyrate group (P<0.01), the 5-fluorouracil group (P<0.01), and the fusidic acid group (P<0.05), and there were significant differences compared with these groups.
[0007] Based on the above research, the technical solution to be protected by this invention is as follows:
[0008] The main objective of this invention is to provide a topical preparation for the treatment of scars, and also to provide a corresponding preparation method. The topical preparation is preferably a cream or patch.
[0009] The active ingredients in creams or patches are the same, consisting of hormones, antibiotics, and chemotherapy drugs in a mass ratio of 1:1:1, with the sum accounting for 1% to 10% of the total.
[0010] Preferably, the hormones are selected from Dexamethasone, Triamcinolone, Dexamethasone, etc., with a content of 0.1%-2%; the antibiotics are selected from Fusidic acid, Bactroban, Erythromycin, etc., with a content of 0.1%-2%; and the chemotherapy drugs are selected from Bleomycin or 5-fluorouracil, etc., with a content of 0.1%-2%.
[0011] The first aspect of this invention discloses a cream for topical treatment of scars and a method for preparing the same.
[0012] (I) Formulation
[0013] This cream contains a pharmaceutical ingredient and a base component. The pharmaceutical ingredient is composed as described above; the base component includes an oil phase, emulsifiers, moisturizers, transdermal absorption agents, and bactericides and preservatives.
[0014] Preferably, in this scar cream, the weight of the active ingredient and the oil phase matrix, emulsifier, moisturizer, transdermal absorbent, and bactericide / preservative is 1-10%, 50%-80%, 10%-30%, 0.5-5%, 0.5-5%, and 0.5-5%, respectively.
[0015] Further preferred formulations include: ① an oil phase matrix selected from one or more of stearic acid and white petrolatum; ② an emulsifier selected from one or more of glyceryl monostearate, sodium lauryl sulfate, and polysorbate 80; ③ a humectant selected from one or more of propylene glycol, glycerin, sorbitol, and / or polyethylene glycol; ④ a transdermal absorbent selected from one or more of azone, urea, peppermint oil, borneol, and / or eucalyptus oil; and ⑤ a bactericidal preservative selected from ethylparaben.
[0016] (II) Preparation method:
[0017] (1) Preparation of oil phase: The oil phase matrix, oily emulsifier and transdermal absorbent are placed in a container and melted by water bath heating to form the oil phase.
[0018] (2) Preparation of aqueous phase: Add water-based emulsifier, humectant and bactericide and preservative to distilled water and heat in a water bath to dissolve them as aqueous phase.
[0019] (3) Preparation of the main drug phase: Add hormones, antibiotics and 5-fluorouracil to distilled water as the main drug phase.
[0020] (4) Preparation of scar cream: Add the oil phase obtained in step (1) to the aqueous phase obtained in step (2). During this process, the temperature is controlled at 55°C. While heating and stirring, the mixture is kept warm and stirred for 30 minutes at a stirring speed of 1300 r / min. Then add the main drug phase, stop heating, and continue stirring until room temperature at a stirring speed of 1300 r / min to obtain the cream.
[0021] The second aspect of this invention discloses a long-acting sustained-release transdermal patch for local treatment of scars and a method for preparing the same.
[0022] (I) Structural Composition
[0023] This long-acting, sustained-release transdermal patch for scar treatment consists of three layers: a backing layer, a drug-containing matrix layer, and a protective layer. The drug-containing layer comprises hormones, antibiotics, 5-fluorouracil, pressure-sensitive adhesive, a penetration enhancer, and a thickener. The specific content of each component in the drug-containing layer, by weight, is as follows: 20 parts drug (in a 1:1:1 ratio), 200 parts pressure-sensitive adhesive, 1 part penetration enhancer, and 50 parts thickener.
[0024] Preferably, ① the backing layer is selected from polyethylene film, polyvinyl chloride film, polypropylene film, polyester film, aluminum foil, and the protective layer is selected from polyethylene film, polystyrene film, polypropylene film and release paper treated with paraffin or dimethyl silicone oil release agent.
[0025] ②The drug is composed of hormones, antibiotics and 5-fluorouracil.
[0026] ③ The pressure-sensitive adhesive is selected from any one or any combination of several of the following: polyvinyl alcohol, cellulose acetate, acrylates containing carboxyl groups, acrylates containing hydroxyl groups, acrylates without functional groups, polybutene, polysiloxane, and natural rubber.
[0027] ④ The penetration enhancer is composed of one or more of levulinic acid, glyceryl triacetate, and propylene glycol. ⑤ The adhesive is preferably any one or a combination of any of polybutadiene, diene isoprene-styrene star polymer, and poly(butyl methacrylate-methyl methacrylate) copolymer.
[0028] (II) Preparation Method
[0029] Step 1: Place the pressure-sensitive adhesive and the binder in the same container, add the solvent, and shake to evenly disperse the binder in the base pressure-sensitive adhesive;
[0030] Step 2: Add the hormone, antibiotic, 5-fluorouracil, and penetration enhancer to the solvent and dissolve them into a clear solution;
[0031] Step 3: Transfer all the obtained clear solution to the pre-dispersed matrix, protect it from light, continue shaking, stir evenly, and let it stand to obtain the drug-loaded matrix;
[0032] Step 4: Coat the obtained drug-loaded matrix onto the protective layer to obtain a drug-containing layer, and then dry it in an oven at 60°C for a period of time before naturally cooling it to room temperature;
[0033] Step 5: Cover the medicated layer with a backing layer, and cut it to obtain the transdermal patch.
[0034] The beneficial protections and effects of this invention are as follows:
[0035] This invention provides a topical scar treatment cream or patch and its preparation method. It mainly contains antibiotics, hormones, and chemotherapy drugs. Through the synergistic effect of these three components, it produces bactericidal, anti-inflammatory, and fibroblast and angiogenesis-inhibiting effects, achieving multiple benefits such as inhibiting scar hyperplasia, promoting scar softening, and preventing infection, thus improving the scar treatment effect. This preparation does not require injection treatment; it can be applied topically or as a patch, greatly facilitating patient use and achieving the goal of scar prevention and treatment. It provides a multi-functional, safe, and effective scar treatment method. Attached Figure Description
[0036] The present disclosure will be further described below with reference to the accompanying drawings, which are shown only for illustrating the embodiments of the present disclosure and are not intended to limit the scope of the present disclosure.
[0037] Figure 1 shows a visual comparison of different treatment groups for hypertrophic scarring of rabbit ears.
[0038] Figure 2 shows the Vancouver Scar Score for different treatment groups. Detailed Implementation
[0039] The following examples and experimental cases further illustrate the present invention and should not be construed as limiting the invention. The examples do not include detailed descriptions of conventional methods, such as methods for constructing vectors and plasmids, methods for inserting genes encoding proteins into vectors and plasmids, or methods for introducing plasmids into host cells. Such methods are well known to those skilled in the art and have been described in numerous publications.
[0040] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as are familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention, and the preferred embodiments and materials described herein are for illustrative purposes only.
[0041] Example 1 Cream
[0042] (I) Formulation
[0043] This cream contains both pharmaceutical ingredients and a base component.
[0044] The drug composition includes a hormone selected from dexamethasone, with a content of 1%; an antibiotic selected from fusidic acid, with a content of 1%; and a chemotherapy drug selected from 5-fluorouracil, with a content of 1%.
[0045] The matrix components include an oil phase matrix, emulsifiers, humectants, transdermal absorption agents, and bactericides and preservatives. The weight percentages of the active pharmaceutical ingredient and the oil phase matrix, emulsifiers, humectants, transdermal absorption agents, and bactericides and preservatives are 3%, 70%, 20%, 3%, 3%, and 1%, respectively.
[0046] The oil phase matrix is selected from white petrolatum, the emulsifier is selected from glyceryl monostearate and sodium lauryl sulfate, the humectant is propylene glycol, the transdermal absorbent is azone, and the bactericidal preservative is selected from ethylparaben.
[0047] (II) Preparation method:
[0048] (1) Preparation of oil phase: Glyceryl monostearate, white petrolatum and azone were placed in a container and melted by water bath to form the oil phase.
[0049] (2) Preparation of aqueous phase: Sodium dodecyl sulfate, propylene glycol and ethylparaben were added to distilled water and dissolved by water bath heating to form the aqueous phase.
[0050] (3) Preparation of the main drug phase: Add hormones, antibiotics and 5-fluorouracil to distilled water as the main drug phase.
[0051] (4) Preparation of scar cream: Add the oil phase obtained in step (1) to the aqueous phase obtained in step (2). During this process, the temperature is controlled at 55°C. While heating and stirring, the mixture is kept warm and stirred for 30 minutes at a stirring speed of 1300 r / min. Then add the main drug phase, stop heating, and continue stirring until room temperature at a stirring speed of 1300 r / min to obtain the cream.
[0052] Example 2 Cream
[0053] (I) Formulation
[0054] This cream contains both pharmaceutical ingredients and a base component.
[0055] The drug composition includes a hormone selected from Depo-Medrol (2%), an antibiotic selected from Bactroban (2%), and a chemotherapy drug selected from Bleomycin (2%).
[0056] The matrix components include an oil phase matrix, emulsifiers, humectants, transdermal absorption agents, and bactericides and preservatives. The weight percentages of the active pharmaceutical ingredient, oil phase matrix, emulsifiers, humectants, transdermal absorption agents, and bactericides and preservatives are 6%, 62%, 20%, 5%, 5%, and 2%, respectively.
[0057] The oil phase matrix is selected from white petrolatum, the emulsifier is selected from glyceryl monostearate and sodium lauryl sulfate, the moisturizer is glycerin, the transdermal absorbent is borneol, and the bactericidal preservative is selected from ethylparaben.
[0058] (II) Preparation method:
[0059] (1) Preparation of oil phase: Glyceryl monostearate, white petrolatum and borneol were placed in a container and melted by water bath heating to form the oil phase.
[0060] (2) Preparation of aqueous phase: Sodium dodecyl sulfate, glycerol and ethylparaben were added to distilled water and dissolved by water bath heating to form the aqueous phase.
[0061] (3) Preparation of the main drug phase: Add hormones, antibiotics and bleomycin to distilled water as the main drug phase.
[0062] (4) Preparation of scar cream: Add the oil phase obtained in step (1) to the aqueous phase obtained in step (2). During this process, the temperature is controlled at 55°C. While heating and stirring, the mixture is kept warm and stirred for 30 minutes at a stirring speed of 1300 r / min. Then add the main drug phase, stop heating, and continue stirring until room temperature at a stirring speed of 1300 r / min to obtain the cream.
[0063] Example 3: Long-acting sustained-release transdermal patch
[0064] (I) Structural Composition
[0065] This long-acting, sustained-release transdermal patch for scar treatment consists of three layers: a backing layer, a drug-containing matrix layer, and a protective layer. The drug-containing matrix layer comprises hormones, antibiotics, 5-fluorouracil, pressure-sensitive adhesive, a penetration enhancer, and a thickener. The specific content of each component in the drug-containing layer, by weight, is as follows: 20 parts drug (in a 1:1:1 ratio), 200 parts pressure-sensitive adhesive, 1 part penetration enhancer, and 50 parts thickener.
[0066] The backing layer is made of polyethylene film;
[0067] The drug consists of dexamethasone, fusidic acid, and 5-fluorouracil, each comprising 1% of the drug.
[0068] The pressure-sensitive adhesive is made of polyvinyl alcohol;
[0069] The penetration enhancer used is levulinic acid;
[0070] The adhesive selected is polybutadiene.
[0071] (II) Preparation Method
[0072] Step 1: Place the pressure-sensitive adhesive and the binder in the same container, add the solvent, and shake to evenly disperse the binder in the base pressure-sensitive adhesive;
[0073] Step 2: Add the hormone, antibiotic, 5-fluorouracil, and penetration enhancer to the solvent and dissolve them into a clear solution;
[0074] Step 3: Transfer all the obtained clear solution to the well dispersed matrix pressure-sensitive adhesive, protect it from light, continue shaking, stir evenly, and let it stand to obtain the drug-loaded matrix;
[0075] Step 4: Coat the obtained drug-loaded matrix onto the protective layer to obtain a drug-containing layer, and then dry it in an oven at 60°C for a period of time before naturally cooling it to room temperature;
[0076] Step 5: Cover the medicated layer with a backing layer, and cut it to obtain the transdermal patch.
[0077] Example of technical effect in Example 4:
[0078] Modeling: An animal model of hypertrophic scarring in rabbit ears was established using 6 rabbit ear models, with 4 wounds per ear, totaling 48 wounds. Hypertrophic scars formed on the wounds within 25 days. The scars were red, raised above the skin, and had a firm texture.
[0079] Grouping and Experimental Methods: Scars were divided into 5 groups: a control group (no medication applied), a hydrocortisone butyrate cream group, a fusidic acid cream group, a 5-fluorouracil cream group, and a mixed cream group (Example 1). Each group contained 8 scars. Medication was applied every other day, followed by massage for absorption. The experiment ended on day 50. Photos were taken before each application, and scar scores were calculated using the Vancouver Scar Assessment Method.
[0080] The experimental results are shown in Figures 1 and 2: All scars showed significant reduction after treatment (50 days); compared with the beginning of the experiment (25 days), there were significant differences. However, comparing the differences before and after treatment, the three-drug combination group was significantly better than the control group (P<0.01), the hydrocortisone butyrate group (P<0.01), the 5-fluorouracil group (P<0.01), and the fusidic acid group (P<0.05), showing significant differences compared to these groups.
[0081] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the embodiments described. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention, and these equivalent modifications or substitutions are all included within the scope defined by the claims of this application.
Claims
1. A topical therapeutic external preparation for cicatricial treatment, characterized by, Its active ingredients consist of hormones, antibiotics and chemotherapy drugs, with a mass ratio of 1:1:1, and the sum accounts for 1% to 10% of the total.
2. The topical therapeutic external preparation for keloid according to claim 1, characterized by, The hormone is selected from any one of Dexamethasone, Triamcinolone Acetonide, and Dexamethasone, with a content of 0.1%-2%; the antibiotic is selected from any one of Fusidic Acid, Bactroban, and Erythromycin, with a content of 0.1%-2%; the chemotherapy drug is selected from Bleomycin or 5-fluorouracil, with a content of 0.1%-2%.
3. The topical therapeutic external preparation for keloid according to claim 1, characterized by, The topical preparation is a cream or patch.
4. The topical treatment preparation for scars according to claim 3, characterized in that: wherein The cream comprises a pharmaceutical ingredient and a base component; the pharmaceutical ingredient comprises as described in claim 1 or 2; the base component comprises an oil phase matrix, an emulsifier, a moisturizer, a transdermal absorption agent, and a bactericide and preservative. The weight ratio of the drug component as the main drug to the oil phase matrix, emulsifier, moisturizer, transdermal absorbent, bactericide and preservative is 1-10:50-80:10-30:0.5-5:0.5-5:0.5-5.
5. The topical treatment preparation for scar treatment according to claim 4, characterized in that: wherein The oil phase matrix is selected from one or more of stearic acid and white petrolatum; the emulsifier is selected from one or more of glyceryl monostearate, sodium lauryl sulfate, and polysorbate 80; the humectant is one or more of propylene glycol, glycerin, sorbitol, and / or polyethylene glycol; the transdermal absorbent is selected from one or more of azone, urea, peppermint oil, borneol, and / or eucalyptus oil; and the bactericidal preservative is selected from ethylparaben.
6. The topical therapeutic external preparation for keloid according to claim 5, characterized by, The preparation method of the cream is as follows: (1) Preparation of oil phase: The oil phase matrix, oily emulsifier and transdermal absorbent were placed in a container and melted by water bath heating to form the oil phase; (2) Preparation of aqueous phase: Add aqueous emulsifier, humectant and bactericide and preservative to distilled water and heat in a water bath to dissolve them to form the aqueous phase; (3) Preparation of the main drug phase: Hormones, antibiotics and 5-fluorouracil were added to distilled water as the main drug phase; (4) Preparation of scar cream: Add the oil phase obtained in step (1) to the aqueous phase obtained in step (2). During this process, the temperature is controlled at 55°C. While heating and stirring, the mixture is kept warm and stirred for 30 minutes at a stirring speed of 1300 r / min. Then add the main drug phase, stop heating, and continue stirring until room temperature at a stirring speed of 1300 r / min to obtain the cream.
7. The topical treatment preparation for scars according to claim 3, characterized in that: wherein The patch is a long-acting sustained-release transdermal patch, consisting of three layers: a backing layer, a drug-containing matrix layer, and a protective layer. The drug-containing matrix layer is composed of the active ingredient, pressure-sensitive adhesive, penetration enhancer, and tackifier. The specific contents of each component of the drug-containing layer by weight are as follows: active ingredient 20 parts, pressure-sensitive adhesive 200 parts, penetration enhancer 1 part, and tackifier 50 parts. The active pharmaceutical ingredient is the active pharmaceutical ingredient as described in claim 1 or 2.
8. The topical treatment preparation for scars according to claim 7, characterized in that: wherein The backing layer is made of polyethylene film, polyvinyl chloride film, polypropylene film, polyester film, or aluminum foil; the protective layer is made of one of the following: polyethylene film, polystyrene film, polypropylene film, or release paper, which has been treated with paraffin or dimethyl silicone oil release agent. The pressure-sensitive adhesive is selected from any one or any combination of several of the following: polyvinyl alcohol, cellulose acetate, acrylates containing carboxyl groups, acrylates containing hydroxyl groups, acrylates without functional groups, polybutene, polysiloxane, and natural rubber. The penetration enhancer is composed of one or more of levulinic acid, glyceryl triacetate, and propylene glycol; The adhesive is selected as any one or any combination of several of the following: polybutadiene, diene isoprene styrene star polymer, and poly(butyl methacrylate-methyl methacrylate) copolymer.
9. The topical therapeutic external preparation for keloid according to claim 7, characterized by, The preparation method of the patch is as follows: Step 1: Place the pressure-sensitive adhesive and the binder in the same container, add the solvent, and shake to evenly disperse the binder in the base pressure-sensitive adhesive; Step 2: Add the hormone, antibiotic, 5-fluorouracil, and penetration enhancer to the solvent and dissolve them into a clear solution; Step 3: Transfer all the obtained clear solution to the pre-dispersed matrix, protect it from light, continue shaking, stir evenly, and let it stand to obtain the drug-loaded matrix; Step 4: Coat the obtained drug-loaded matrix onto the protective layer to obtain a drug-containing layer, and then dry it in an oven at 60°C for a period of time before naturally cooling it to room temperature; Step 5: Cover the medicated layer with a backing layer, and cut it to obtain the transdermal patch.