Application of periplaneta americana extract in preparation of medicine for treating radiodermatitis
By preparing topical formulations using extracts from American cockroaches, the problems of lack of precise intervention and side effects in existing radiation dermatitis treatments have been solved, achieving efficient and low-cost improvement of dermatitis symptoms and wound healing.
Patent Information
- Application Number
- CN202511506995.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-21
- Publication Date
- 2025-12-23
AI Technical Summary
Existing drugs for treating radiation dermatitis lack precise intervention targeting the pathogenesis, have side effects, and are expensive, making them difficult to use widely, leading to increased patient suffering, treatment costs, and reduced treatment effectiveness.
Topical preparations are made from extracts of the American cockroach, including ethanol soaking and reflux extraction, and formulated into solutions, ointments, emulsions, gels, films or aerosols with suitable carriers for the treatment of radiation dermatitis.
American cockroach extract significantly promotes wound healing, improves symptoms of radiation dermatitis, and is more effective than existing drugs. It reduces wound area, increases wound healing rate, and reduces dermatitis scores, demonstrating a significant skin damage repair effect.
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Figure CN121177342A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of new application technology of American cockroach extract, specifically, it relates to the application of American cockroach extract in the preparation of drugs for treating radiation dermatitis. Background Technology
[0002] Radiation dermatitis is a common side effect in over 90% of cases during radiotherapy for malignant tumors. It is classified into four grades based on severity: erythema, dry desquamation, wet desquamation, and ulcerative necrosis. Mild radiation dermatitis causes itching and burning, while severe radiation dermatitis leads to skin damage and infection. This not only significantly reduces the patient's quality of life but may also force a reduction in radiotherapy dose or interrupt treatment, affecting the effectiveness of cancer treatment.
[0003] Currently, there are many treatment methods commonly used in clinical practice for radiation dermatitis, including: pausing or adjusting the radiation dose, basic skin care, drug therapy, physical therapy, and nutritional supplementation and psychological counseling.
[0004] Drug therapy is frequently used in many treatment options due to its convenience and wide applicability. However, existing drugs have many limitations. For example, glucocorticoids are used to relieve inflammation, antibiotics are used to prevent infection, and antihistamines are used to relieve itching. However, these drugs lack precise intervention on the pathogenesis of radiation dermatitis and fail to solve the problem at its root.
[0005] Furthermore, some medications have side effects. For example, long-term or high-dose use of glucocorticoids may lead to adverse reactions such as skin atrophy, telangiectasia, and pigmentation; certain antibiotics may trigger allergic reactions or lead to bacterial resistance. Moreover, while some imported or newer drugs may have advantages in treatment efficacy, they are often expensive and require high qualification thresholds, making them unaffordable for many patients and limiting their widespread use. In actual treatment, patients often experience prolonged illness due to poor drug response, which not only increases patient suffering but also adds to the complexity and cost of treatment.
[0006] Therefore, developing a drug that can effectively treat radiation dermatitis, has few side effects, is affordable, and targets the pathogenesis is of great clinical significance and market demand. Summary of the Invention
[0007] In view of the above-mentioned shortcomings in the prior art, the purpose of this invention is to provide an application of American cockroach extract in the preparation of a drug for treating radiation dermatitis.
[0008] To achieve the above objectives, the solution adopted by the present invention is as follows:
[0009] An application of an American cockroach extract in the preparation of a drug for treating radiation dermatitis. The preparation of the American cockroach extract includes: (1) taking fresh American cockroaches and soaking them in ethanol with a concentration of 20% to 45% at 1.5 to 3.5 times the weight of the fresh American cockroaches for 10 to 60 days at a temperature of 30°C to 50°C; (2) adding ethanol with a concentration of 50% to 80% at 1.5 to 3.5 times the weight of the fresh American cockroaches and refluxing for 1 to 3 times for 1 to 2 hours, then filtering and combining the filtrates; (3) concentrating the filtrate under reduced pressure at a temperature of 60°C to 90°C to obtain an extract with a relative density of 1.04 to 1.08 at 60°C.
[0010] Furthermore, in a preferred embodiment of the invention, the drug consists of an American cockroach extract and a drug-acceptable carrier.
[0011] Furthermore, in a preferred embodiment of the present invention, the drug is a topical preparation.
[0012] Furthermore, in a preferred embodiment of the present invention, the dosage form of the topical preparation includes solutions, ointments, emulsions, gels, films, and aerosols.
[0013] The beneficial effects of the American cockroach extract provided by this invention in the preparation of drugs for treating radiation dermatitis are as follows:
[0014] (1) In the study of the efficacy of promoting skin wound healing, it was found that the American cockroach extract provided by the present invention has a significant effect on promoting repair in the rat model of full-thickness skin defects established by surgery. It can promote the growth of new epidermis in the wound, improve the coverage of granulation tissue at the defect by the new epidermis, thereby accelerating wound recovery, effectively reducing the wound area, and improving the wound healing rate. Its effect is significantly better than that of Kangfuxin liquid.
[0015] (2) In the efficacy study of preventing and treating X-ray-induced radiation dermatitis in rats, it was found that the American cockroach extract provided by the present invention can significantly improve the clinical symptoms of radiation dermatitis model of Wistar rats induced by X-ray irradiation and accelerate the healing of dermatitis. Its efficacy is significantly better than that of the positive drug triethanolamine cream.
[0016] (3) In the study of the efficacy of topical application on electron beam-induced dorsal dermatitis in rats, it was found that the American cockroach extract provided by the present invention can improve the clinical symptoms of the radiation dermatitis model of SD rats induced by electron beam irradiation, effectively reduce the dermatitis score, and show a significant skin damage repair effect. Attached Figure Description
[0017] Figure 1 These are photographs of the epidermal percentage and exposed granulation area of rats in each group on day 19, provided in Experimental Example 2 of this invention.
[0018] Figure 2 This is a comparison chart of dermatitis scores of different groups of X-ray-induced rat back dermatitis models provided in Experiment Example 3 of this invention;
[0019] Figure 3 This is a comparison chart of AUC scores for the dermatitis of rat back dermatitis models induced by electron beams during the drug administration period (D10-D69) provided in Experimental Example 4 of this invention. Detailed Implementation
[0020] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased commercially.
[0021] The following is a detailed description of the application of an American cockroach extract provided in the embodiments of the present invention in the preparation of a drug for treating radiation dermatitis.
[0022] The features and performance of the present invention will be further described in detail below with reference to embodiments.
[0023] Example 1
[0024] This embodiment provides a method for preparing an extract of American cockroaches, comprising: weighing 1000g of fresh American cockroaches, placing them in a glass bottle, adding 1500ml of 25% ethanol, sealing, and placing at 40℃ for 20 days, then removing them and extracting them three times with 80% ethanol, each time for 1 hour. The first extraction is done with 1.5 times the volume of ethanol, and the second and third extractions are done with 3 times the volume of ethanol each. The mixture is filtered, the filtrates are combined, and the ethanol is recovered under reduced pressure at 65℃ and concentrated to 60℃, where the relative density is measured to be 1.04.
[0025] Cool, add water to 3000ml, mix well, heat to boiling for 10 minutes, and when the temperature drops to 70℃, slowly add 600ml of clarifying agent, stir for 10 minutes, cool, refrigerate overnight, and filter to obtain the American cockroach extract. The clarifying agent used was a 1% chitosan solution and a 1% gelatin solution in a 1:3 ratio.
[0026] Example 2
[0027] 1. Experimental animals: 30 male SD rats, weighing 250±20g.
[0028] 2. Experimental Methods:
[0029] 2.1 Model Establishment: A 5×5cm area on the back of the rats was shaved with a razor, then depilated with hair removal cream for skin preparation. The prepared area was wiped with saline-soaked cotton balls, disinfected with iodine, and then deiodized with 75% alcohol. Using the spine as the midline and the junction of the cervical and thoracic vertebrae as the center, a hole was marked with a diameter of 3cm (area = 7.07cm²). 2 The circular skin is cut with scissors, removing the full thickness of the skin down to the deep fascia layer in the marked area. Ophthalmic scissors are used to cut away the fascia. Sterile gauze or cotton balls are used to compress intraoperative bleeding, ultimately forming a full-thickness skin defect wound.
[0030] 2.2 Grouping and Dosing:
[0031] Grouping: Based on the wound area and skin thickness, the animals were randomly divided into 3 groups: the model group, the Kangfuxin Liquid group (Sichuan Good Doctor Panxi Pharmaceutical Co., Ltd., National Drug Approval Number Z51021834), and the American cockroach extract group provided in Example 1 (concentration of 10 mg / mL after adding water), with 10 animals in each group.
[0032] Administration:
[0033] Model group: Wet dressings were applied using fabric containing 3400 μL of physiological saline and fixed with 3M transparent dressings to create a moist healing environment, once every 2 days, for 19 consecutive days;
[0034] Kangfuxin Liquid Group: Wet dressings were applied using a fabric containing 3400μL of the drug solution, and fixed with 3M transparent dressings to create a moist healing environment. The treatment was performed once every two days, and the patients were observed for 19 consecutive days.
[0035] Example 1: The American cockroach extract group was wet-dressed with a fabric containing 3400 μL of drug solution and fixed with a 3M transparent dressing to create a moist healing environment. The treatment was performed once every 2 days and observed for 19 consecutive days.
[0036] 2.3 Observation indicators: During the period, animal weight was monitored, wound images were collected, wound area and granulation area were measured, and the proportion of newly formed epidermis and the proportion of exposed granulation area were calculated to assess the wound healing speed.
[0037] 3. Experimental Results:
[0038] (1) Figure 1 The figures show the percentage of epidermis and the area of exposed granulation tissue in each group of rats on day 19. In the model group, one of the ten rats died during the experiment, leaving nine rats. Figure 1 It is evident that the wound recovery in rats in the American cockroach extract group was significantly better than that in the Kangfuxin liquid group and the model group.
[0039] (2) The coverage rate of new epidermis is shown in Table 1:
[0040] Table 1. New epidermal coverage rate of wounds in rats of each group (%) (mean ± SD)
[0041]
[0042] Note: Compared to the model group, * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001; compared with the Kangfuxin liquid group, ## P<0.01.
[0043] The data in Table 1 show that, by the end of the experiment, compared with the model group, the animals in the American cockroach extract group showed increased epidermal coverage and improved new epidermal coverage on Day 7, and continued to show increased new epidermal coverage at subsequent time points, effectively promoting wound healing (P < 0.01–0.0001). In addition, the epidermal regeneration rate of the animals in the American cockroach extract group was significantly faster than that in the Kangfuxin solution group, and the epidermal coverage rate was significantly increased from Day 17 to Day 19 (P < 0.01).
[0044] (3) The exposed area of granulation tissue is shown in Table 2:
[0045] Table 2. Percentage of exposed granulation tissue area in the wounds of rats in each group (%) (mean ± SD)
[0046] Note: Compared to the model group, * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001; compared with the Kangfuxin liquid group, # P<0.05.
[0047] The data in Table 2 show that, by the end of the experiment, compared with the model group, the granulation area of animals in the American cockroach extract group and the Kangfuxin liquid group was significantly reduced on Day 7, and the proportion of exposed granulation area was significantly lower (P < 0.01). This effect was also significant at subsequent time points (P < 0.01 to 0.0001). In addition, the proportion of exposed granulation area in the wound of animals in the American cockroach extract group was significantly lower than that in the Kangfuxin liquid group, and the proportion of exposed granulation area in the wound was significantly lower on Day 19 (P < 0.05).
[0048] Combining Table 1, Table 2 and Figure 1Data shows that the American cockroach extract group provided in this application has a significant promoting effect on the repair of full-thickness skin defect rat model established by surgery. It can significantly promote the growth of new epidermal tissue in the wound, improve the coverage of new epidermal tissue on granulation tissue at the defect site, thereby accelerating wound recovery, effectively reducing wound area, and improving wound healing rate. Moreover, the effect is significantly better than that of Kangfuxin liquid.
[0049] Example 3
[0050] 1. Experimental animals: 40 male Wister rats aged 6-8 weeks, weighing 300±20g.
[0051] 2. Experimental Methods:
[0052] 2.1 Model establishment: On Day 0, the skin of the right hind leg thigh lateral 3cm×3cm of all rats was shaved. Except for the normal group, the other animals were modeled by irradiating the shaved area with a dose of 38Gy using a biological X-ray irradiator.
[0053] 2.2 Grouping and Dosing:
[0054] Grouping: The animals were randomly divided into 4 groups, including: normal group, model group, positive control group (triethanolamine cream (content specification of 0.67%), JANSSEN CILAG), and American cockroach extract group provided in Example 1 (concentration of 10 mg / mL after adding water), with 10 animals in each group.
[0055] Administration:
[0056] Model group: The drug administration volume was 360 μL / time, and physiological saline was administered daily until the end of the experiment, 4 times a day, for 28 consecutive days;
[0057] Positive drug group: 80mg / time applied topically, twice daily, for 28 consecutive days;
[0058] The American cockroach extract group provided in Example 1: The administration volume was 360 μL / time, administered daily until the end of the experiment, 4 times a day, and observed continuously for 28 days.
[0059] 2.3 Observation indicators: The efficacy of each group was evaluated by the clinical score of the radiotherapy oncology group (RTOG) twice a week.
[0060] 3. Experimental Results:
[0061] (1) The dermatitis scores of the X-ray-induced rat dorsal dermatitis models in each group are shown in Table 3 and Figure 1 (Note: Compared with the model control group,) * P<0.05, ** P<0.01, *** P<0.001, ****P < 0.0001. The corresponding color represents the corresponding group; D = Day):
[0062] Table 3. Dermatitis scores (mean ± SEM) of X-ray induced rat dorsal dermatitis models in each group.
[0063]
[0064] Note: Compared to the model group, ** P<0.01, **** P<0.0001.
[0065] Figure 1 The data results showed that, compared with the normal group, the model group developed dermatitis symptoms on Day 12, and the dermatitis score reached its highest level on Day 15, after which the dermatitis score gradually decreased.
[0066] Table 3 and Figure 1 The data showed that, compared with the model group, the dermatitis scores of the American cockroach extract group were significantly lower at Day 15 and later time points (P < 0.001 to 0.0001); the dermatitis symptoms of the positive drug group appeared earlier than those of the model group, and there was no significant difference in dermatitis scores at Day 15 and later time points.
[0067] Combined with Table 3 and Figure 1 Data shows that the American cockroach extract group provided in this application, when applied topically four times a day, can significantly improve the clinical symptoms of radiation dermatitis model induced by X-ray irradiation in Wistar rats, accelerate the healing of dermatitis, and its efficacy is significantly better than that of the positive control drug triethanolamine cream.
[0068] Example 4
[0069] 1. Experimental animals: 68 male SD rats, weighing 200±20g.
[0070] 2. Experimental Methods:
[0071] 2.1 Model Establishment: On Day 0, the skin of the rats' backs and buttocks was shaved and then treated with Marbella hair removal cream. The prepared skin area was slightly larger than the irradiation field area to facilitate positioning during irradiation. Except for 6 normal rats, the remaining animals were anesthetized by intraperitoneal injection of 10% chloral hydrate (w / v) prepared with 3 mL / kg physiological saline (adjusted slightly according to the rats' condition). Then, a single irradiation of a 3cm × 4cm area on the back of the rats with 45 Gy electron beams from the Elekta Synergy electron beam system (6-MeV) was performed to establish the model.
[0072] 2.2 Grouping and Dosing:
[0073] Grouping: 10 animals were in the normal group. The remaining animals were randomly divided into 3 groups again on Day 10 after modeling, according to the severity of dermatitis: model group, positive drug group (triethanolamine cream (content specification of 0.67%), JANSSEN CILAG), and American cockroach extract group provided in Example 1 (concentration of 10 mg / mL with water), with 10 animals in each group.
[0074] Administration:
[0075] Normal group: No modeling was performed. Sterile saline was administered starting on Day 11 at a rate of 0.04 mL / cm². 2 Administer once, 4 times a day, with each dose retained for 30 minutes;
[0076] Model group: After modeling, sterile saline was administered starting on Day 11 at a rate of 0.04 mL / cm². 2 Administer once, 4 times a day, with each dose retained for 30 minutes;
[0077] Positive drug group: After modeling, the drug was administered on Day 11. A thin layer was evenly applied to the corresponding irradiated area twice a day, and the drug was allowed to be absorbed naturally after each administration.
[0078] The American cockroach extract group provided in Example 1: After modeling, administration began on Day 11 at a dose of 0.04 mL / cm³. 2 Administer once, 4 times a day, with each dose retained for 30 minutes.
[0079] All test samples were evenly applied to the irradiated area.
[0080] 2.3 Observation indicators: Clinical scores of dermatitis symptoms were dynamically collected during the drug administration period to evaluate the dermatitis healing effect of each group.
[0081] 3. Experimental Results:
[0082] (1) The AUC (area under the plasma concentration-time curve) of the electron beam-induced dermatitis model in rats during the drug administration period (D10-D69) is shown in Table 4. Figure 2 (Note: Compared with the model control group, *P<0.05, **P<0.01, ***P<0.001; D=Day):
[0083] Table 4. AUC (mean ± SEM) scores of electron beam-induced dorsal dermatitis models in each group during the drug administration period (D10–D69).
[0084] Group <![CDATA[Dermatitis score AUC (D10～D69) > normal group <![CDATA[0.00±0.00 *** ]]> Model group 352.35±43.73 Positive drug group 315.85±11.07 American cockroach extract group <![CDATA[270.50±14.69 * ]]>
[0085] Note: Compared with the model control group. * P<0.05, **P<0.01, *** P<0.001.
[0086] During the experiment, the skin symptoms of the model animals were mainly erythema and wet desquamation, with occasional dry desquamation. On Day 13, wet desquamation became the main symptom, with occasional ulceration, bleeding and blisters. As the experiment progressed, the dermatitis lesions gradually shrank, accompanied by repeated exudation, crusting and re-exudation. On Day 41, the dermatitis lesions improved and the dermatitis symptoms recovered, until the end of the experiment.
[0087] Table 4 and Figure 2 The results showed that the dermatitis scores of the normal group animals were significantly lower than those of the model control group at all time points (P < 0.001). Compared with the model group, the positive drug triethanolamine showed a decreasing trend in dermatitis scores on Day 23, but the positive drug group animals only showed a decrease in dermatitis scores on Day 34 (P < 0.05), and no statistically significant differences were observed at other time points.
[0088] Table 4 and Figure 2 The data results showed that, compared with the model group, the animals treated with the American cockroach extract provided in Example 1 showed a decrease in dermatitis scores 6 days after administration (Day 16), indicating a trend of dermatitis improvement. By Day 23, the American cockroach extract provided in Example 1 significantly reduced the dermatitis scores of the animals, and continued to reduce the dermatitis scores from Day 23 to Day 37 (P < 0.05 to 0.001). The area under the curve of the score was significantly reduced during the administration period (P < 0.05). The dermatitis symptoms of the animals in the American cockroach extract group provided in Example 1 were significantly improved.
[0089] Combine Table 4 and Figure 2 Data shows that the American cockroach extract group provided in this application, when applied topically four times a day, can improve the clinical symptoms of an electron beam irradiation-induced radiation dermatitis model in SD rats, effectively reduce dermatitis scores, and demonstrate a significant skin damage repair effect.
[0090] In summary, the *Periplaneta americana* extract provided by this invention, in efficacy studies on promoting skin wound healing, showed that it significantly promoted the repair of surgically established full-thickness skin defects in rats, with effects significantly superior to Kangfuxin liquid. In efficacy studies on preventing X-ray-induced radiation dermatitis in rats, the extract significantly improved the clinical symptoms of X-ray irradiation-induced radiation dermatitis in Wistar rats, with efficacy significantly superior to the positive control drug triethanolamine cream. In efficacy studies on topical application to electron beam-induced dorsal dermatitis in rats, the extract significantly improved the clinical symptoms of electron beam irradiation-induced radiation dermatitis in SD rats, demonstrating a significant skin damage repair effect. The *Periplaneta americana* extract provided in this application has certain application prospects in the preparation of drugs for treating radiation dermatitis.
[0091] 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. Use of an extract of Periplaneta americana for the preparation of a medicament for the treatment of radiation dermatitis, characterized in that: The preparation of the Periplaneta americana extract comprises: (1) taking fresh Periplaneta americana, soaking with ethanol with a concentration of 20% to 45% at a concentration of 1.5 to 3.5 times the weight of the fresh Periplaneta americana, the soaking time being 10 to 60 days, and the soaking temperature being 30°C to 50°C; (2) adding ethanol with a concentration of 50% to 80% at a concentration of 1.5 to 3.5 times the weight of the fresh Periplaneta americana, refluxing for 1 to 3 times, the refluxing time being 1 to 2 hours, then filtering and combining the filtrate; (3) concentrating the filtrate at a temperature of 60°C to 90°C under reduced pressure to a relative density of 1.04 to 1.08 at 60°C, and obtaining the extract after clarification.
2. Use according to claim 1, characterized in that: The medicine is composed of the Periplaneta americana extract and a pharmaceutically acceptable carrier.
3. Use according to claim 1, characterized in that: The medicine is an external preparation.
4. Use according to claim 3, characterized in that: The dosage form of the external preparation includes solution, ointment, emulsion, gel, film-coating agent and aerosol.