Application of Pien Tze Huang in preparation of medicine for promoting healing of deep second-degree burn and research method of Pien Tze Huang

Abstract

The invention discloses application of Pien Tze Huang in preparation of drugs for promoting healing of deep II-degree burns and a research method, and relates to the technical field of burns, the deep II-degree burns are common acute skin injuries in daily life, and in addition to complications such as severe pain and infection, abnormal healing, scar formation and discoloration are possibly caused. Therefore, intervention on deep second-degree burn wounds as early as possible, inhibition of inflammatory response, pain relief, healing promotion, further shortening of wound healing time and inhibition of scar generation are always a hot spot of clinical burn research. The invention provides application of Pien Tze Huang in preparation of a deep II-degree burn healing promoting medicine and a research method. Pien Tze Huang improves deep II-degree wound healing by inhibiting inflammatory response. The action molecular mechanism of the Pien Tze Huang is to relieve the oxidative stress pressure of the wound surface and promote the vascularization of the wound surface. The single dosage of the Pien Tze Huang is 0.6 g.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of burn, in particular to the application of Piancailuon in preparing deep II degree burn healing-promoting drugs and a research method. BACKGROUND

[0002] Deep II degree burn is a common acute skin injury in daily life, which can cause severe pain, infection and other complications, and can also cause abnormal healing, scar formation and disfigurement. Therefore, early intervention of deep II degree burn wound, inhibition of inflammatory response, pain relief and promotion of healing, further shortening of wound healing time and inhibition of scar formation, has always been a hot spot in clinical research of burn.

[0003] As a national first-class protected Chinese medicine, Piancailuon mainly contains precious Chinese herbal medicines such as cow-bezoar, snake gall, musk, etc., which has the effects of clearing heat and resolving toxin, cooling blood and removing blood stasis, and relieving swelling and pain, and is used for acute and chronic viral hepatitis caused by heat toxin and blood stasis, carbuncle, furuncle, unknown swelling and toxin, sprains and injuries, and various inflammations. Piancailuon is widely used in clinic, mainly focusing on liver protection, anti-inflammatory, anti-tumor and other aspects, and has good effects of liver protection, enzyme reduction, immune regulation and inflammation inhibition. In recent years, oral or external use of Piancailuon has been confirmed in rat and mouse models to promote wound healing by anti-inflammatory, oxidative stress inhibition and inhibition of fibroblast apoptosis. SUMMARY

[0004] In view of the above problems, the present application aims to provide the application of Piancailuon in preparing deep II degree burn healing-promoting drugs and a research method, which can observe the curative effect of oral Piancailuon on deep II degree burn wound, evaluate its effect on improving wound healing and safety, and provide a reference for the application of Piancailuon in the repair of soft tissue defects such as burn wound.

[0005] The main idea of the technical solution adopted in the present application is that Piancailuon can inhibit inflammatory response, which is conducive to its effect of improving deep II degree wound healing. Red heat and pain are specific symptoms of inflammatory response after burn, and high level of inflammatory response can lead to deepening of burn wound and prolongation of healing time. Studies have shown that Piancailuon can significantly relieve inflammatory response caused by endotoxin, and inhibit the concentration of tumor necrosis factor-α, IL-6, IL-8 and the level of white blood cells in the serum of New Zealand rabbits injected with E. coli endotoxin. Piancailuon has a positive effect on the healing of diabetic wounds, which can promote wound healing by inhibiting abnormal apoptosis and aging of epidermal fibroblasts, activating Nrf2 / ARE pathway to regulate the level of oxidative stress in the body and increasing the expression of growth factors to improve angiogenesis, which is indirectly related to its function of inhibiting inflammatory response.

[0006] In order to achieve the above purpose, the technical solution adopted in the present application is as follows:

[0007] The application of Pianzaihu in preparation of a deep II degree burn healing promoting medicine, Pianzaihu can improve deep II degree wound healing by inhibiting inflammatory response.

[0008] Through the above technical scheme, further: the molecular mechanism of the action of Pianzaihu is to relieve wound oxidative stress and promote wound vascularization.

[0009] The research method of Pianzaihu in deep II degree burn healing promotion is as follows:

[0010] S1, according to the inclusion criteria and exclusion criteria, patients meeting the diagnostic criteria of deep II degree burn are selected as research objects, and are divided into a control group and a treatment group;

[0011] S2, all patients are treated with Pianzaihu.

[0012] S3, wound healing is observed at 7, 14 and 21 days of treatment, wound healing rate is calculated, and wound healing time is recorded, and then the research data is analyzed and processed.

[0013] Through the above technical scheme, further: in step S2, the single dose of Pianzaihu is 0.6g, three times a day.

[0014] Through the above technical scheme, further: in step S3,

[0015]

[0016] The beneficial effects of the present application are:

[0017] 1, Pianzaihu is composed of ox gall, musk, Sanqi and snake gall, Sanqi is warm, sweet and slightly bitter, and is good at removing blood stasis, swelling, stopping bleeding and relieving pain; snake gall is cool, slightly bitter and sweet, and has the functions of clearing heat and detoxifying, clearing liver and benefiting gallbladder, and is the monarch drug. Ox gall is cool and sweet, and is a good medicine for clearing heat and detoxifying, resolving phlegm and relieving cough, and removing wind and dampness, which can enhance the functions of the monarch drug in clearing heat and detoxifying, and swelling, and can also resolve phlegm caused by heat evil and decoction, so it is a minister drug. Musk is warm and can be used to promote blood circulation, remove blood stasis, and disperse swelling and toxic substances, which can help the monarch and minister drugs to promote blood circulation, remove blood stasis, and relieve swelling and pain, and is a minister drug. The combination of the above drugs can achieve the effects of clearing heat and detoxifying, promoting blood circulation and removing blood stasis, and relieving swelling and pain. The idea of using traditional Chinese medicine to treat deep II degree wound is to achieve the purposes of promoting blood circulation and removing blood stasis, relieving swelling and pain, enhancing immunity, anti-inflammatory and bactericidal effects. The molecular mechanism of Pianzaihu in relieving wound oxidative stress and promoting wound vascularization is verified in a rat wound healing model. According to traditional Chinese medicine theory, burn is caused by external injury of fire and heat evil, and should be treated by clearing heat and detoxifying, promoting blood circulation and removing blood stasis, and bitter cold astringent method. The efficacy of Pianzaihu is consistent with this.

[0018] 2. Pien Tze Huang inhibits inflammatory responses, which is beneficial for its role in improving the healing of deep second-degree burns. Redness, heat, swelling, and pain are specific symptoms of inflammatory responses after burns. Elevated inflammatory levels can lead to deeper burn wounds and prolonged healing time. Studies have shown that Pien Tze Huang can significantly alleviate inflammatory responses caused by endotoxins and inhibit the concentrations of tumor necrosis factor-α, IL-6, and IL-8, as well as leukocyte levels, in the serum of New Zealand rabbits injected with E. coli endotoxin. Pien Tze Huang has a positive effect on the healing of diabetic wounds. It promotes wound healing by inhibiting abnormal apoptosis and senescence of epidermal fibroblasts, activating the Nrf2 / ARE pathway to regulate oxidative stress levels in the body, and increasing the expression of growth factors, thereby improving angiogenesis. This is indirectly related to its function of inhibiting inflammatory responses.

[0019] 3. In summary, oral administration of Pien Tze Huang can improve the healing of deep second-degree burn wounds. This effect is achieved through its heat-clearing, detoxifying, anti-inflammatory, blood-cooling, and blood-stasis-removing properties, and the oral administration of Pien Tze Huang has a good safety profile. This study provides a reference for the application of Pien Tze Huang in burn wound healing and also provides a basis for further research on the use of Pien Tze Huang in soft tissue defects and repair. Attached Figure Description

[0020] Figure 1 Diagrams showing the burn sites of patients during the initial stage of the experiment;

[0021] Figure 2 Images showing the burn sites of patients during the middle of the experiment;

[0022] Figure 3 Images showing the burn sites on patients during the later stages of the experiment;

[0023] Figure 4 This is a diagram showing the burn sites on patients during the later stages of the experiment. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. The components of the embodiments of this application described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0025] The inventors' research revealed that deep second-degree burns are common acute skin injuries in daily life. Besides causing severe pain and infections, they can also lead to abnormal healing, scarring, and disfigurement. Therefore, early intervention in deep second-degree burn wounds to suppress inflammatory responses, relieve pain, and promote healing, thereby shortening wound healing time and inhibiting scar formation, has always been a hot topic in clinical burn research.

[0026] Based on the above findings, the present application proposes the application and research method of Pianzhihuang in the preparation of deep II degree burn healing promoting drugs. Pianzhihuang can inhibit inflammatory response and is beneficial to its role in improving deep II degree wound healing. Red hot pain is a specific symptom of inflammatory response after burn, and the increase of inflammatory response level can lead to deepening of burn wound and prolongation of healing time. Studies have shown that Pianzhihuang can significantly alleviate inflammatory response caused by endotoxin, and inhibit the concentration of tumor necrosis factor-α, IL-6, IL-8 and the level of white blood cells in the serum of New Zealand rabbits injected with E. coli endotoxin. Pianzhihuang has a positive effect on the healing of diabetic wounds, which can promote wound healing by inhibiting the abnormal apoptosis and aging of epidermal fibroblasts, activating the Nrf2 / ARE pathway to regulate the oxidative stress level in the body and increasing the expression of growth factors to improve angiogenesis, which is indirectly related to its function of inhibiting inflammatory response.

[0027] Example 1

[0028] The present application discloses the application and research method of Pianzhihuang in the preparation of deep II degree burn healing promoting drugs. Pianzhihuang is composed of cow-bezoar, musk, Sanqi and snake gall, etc. Sanqi is warm in nature, sweet and slightly bitter in taste, and is good at dissipating blood stasis, swelling, stopping bleeding and pain. Snake gall is cool in nature, slightly bitter and sweet in taste, and has the functions of clearing heat and detoxifying, clearing liver and benefiting gallbladder. The two drugs are the monarch drugs. Cow-bezoar is cool in nature and sweet in taste, and is a good drug for clearing heat and detoxifying, resolving phlegm and relieving cough, and removing wind and dampness, which can enhance the functions of the monarch drugs in clearing heat and reducing fire, and heat-toxin reducing swelling. It can also resolve phlegm caused by heat evil and decoction of body fluid. Therefore, it is the minister drug. Musk is warm and can be used to dredge channels, and is pungent and can be used to dissipate and move, so it is good at promoting blood circulation to remove blood stasis and dissipating swelling and toxic materials, and can help the monarch and minister drugs to promote blood circulation to remove blood stasis and dissipate swelling and pain, and is the auxiliary drug. The combination of the above drugs can achieve the functions of clearing heat and detoxifying, promoting blood circulation to remove blood stasis, and dissipating swelling and pain.

[0029] The idea of using traditional Chinese medicine to treat deep II degree wounds is to use traditional Chinese medicine to achieve the purposes of promoting blood circulation to remove blood stasis, dissipating swelling and pain, enhancing immunity, anti-inflammatory, and bactericidal. The molecular mechanism of Pianzhihuang in relieving oxidative stress and promoting vascularization of wounds in rats has been verified in the wound healing model of rats. According to traditional Chinese medicine theory, burn is caused by external injury of fire heat and toxic evil, and should be treated by clearing heat and detoxifying, promoting blood circulation to remove blood stasis, and bitter cold astringent. The efficacy of Pianzhihuang is consistent with this.

[0030] Pianzhihuang can inhibit inflammatory response and is beneficial to its role in improving deep II degree wound healing.

[0031] Example 2

[0032] Specifically, by observing the efficacy of oral Pianzhihuang for deep II degree burn wounds, the effect of improving wound healing and safety is evaluated, which provides a reference for the application of Pianzhihuang in the repair of soft tissue defects such as burn wounds.

[0033] 1.1 Selection of experimental patients

[0034] The study was approved by the hospital ethics committee with the approval number 2020LL018-02. 50 patients who met the diagnostic criteria for deep II degree burns were selected from December 2020 to November 2021 in the emergency department of the Burn Department of Jiangnan University Affiliated Hospital. 50 patients were randomly divided into treatment group and control group, 25 cases in each group. In the control group, 20 males and 5 females, aged 22-64 years, with an average age of (43.4±12.0) years; burn site: 19 cases of extremities, 4 cases of trunk, 2 cases of face; the ratio of observed wound area to total body surface area was (0.10±0.09)%; in the treatment group, 16 males and 9 females, aged 22-65 years, with an average age of (43.5±14.0) years; burn site: 18 cases of extremities, 3 cases of trunk, 4 cases of face; the ratio of observed wound area to total body surface area was (0.11±0.07)%. The age, gender, and ratio of observed wound area to total body surface area of the treatment group and the control group were comparable, and the difference was not statistically significant (P>0.05).

[0035] Inclusion criteria: ① meet the diagnostic criteria for acute wound of II degree burn; ② the total area of the wound accounts for ≤30% of the total body surface area; ③ at least one wound with an area of 0.075%-0.15% of the total body surface area; ④ age 18-70 years old, gender unrestricted; ⑤ agree to participate in this clinical study and sign the informed consent form.

[0036] Exclusion criteria: ① patients with a history of malignant tumors or other serious diseases; ② patients with serious systemic diseases (determined by the investigator); ③ patients with skin diseases that affect the study; ④ patients with mental illness and no self-awareness, who cannot express clearly; ⑤ patients with known ingredients of the drugs used in this trial; ⑥ pregnant or lactating women; ⑦ other reasons, the investigator considers that the subjects cannot be selected.

[0037] 1.2 Treatment method

[0038] The selected patients were timely cleaned, debrided, iodophor disinfected, vaseline gauze covered, and multi-layer gauze bandaged upon admission, as well as routine treatment such as fluid replacement and analgesia. At 7, 14 and 21 days after the start of treatment, the wound condition was observed, and for patients with more exudation, vaseline gauze and external application were replaced according to the situation to avoid infection caused by excessive accumulation of exudate. Patients in the treatment group used Pianzhiwu (Zhangzhou Pianzhiwu Pharmaceutical Co., Ltd., National Drug Code Z35020243), 0.6g each time, 3 times a day. Patients in the control group were treated with human epidermal growth factor gel, antibiotics, analgesics, etc. according to the clinical actual situation.

[0039] 1.3 Observation index

[0040] Wound healing: Wound healing was observed at 7, 14, and 21 days after treatment, and the wound healing rate was calculated using the following formula: The wound healing time was recorded, with a wound healing rate exceeding 95% defined as the clinical cure standard. Adverse events occurring in both groups of patients during the treatment period were also observed.

[0041] Severity of wound inflammation: Four specific inflammatory indicators were observed, namely redness, swelling, heat and exudation. The indicators were judged according to four levels: none, mild, moderate and severe, and scored as 0, 1, 2 and 3 points respectively. The total score of the four indicators represents the overall degree of inflammation.

[0042] 1.4 Statistical Processing

[0043] Data were statistically analyzed using SPSS v17.0 software. Quantitative data were expressed as mean ± standard deviation. Or the median, analyzed using a t-test or Wilcoxon rank-sum test, and the χ² value. 2 Qualitative data analysis was performed using the test, with P < 0.05 indicating statistical significance.

[0044] 2 Results

[0045] Two patients dropped out in both the treatment and control groups, with a total of 23 patients completing the study in each group. Both groups also had 23 patients who met the perprotocol set (PPS). Therefore, the relevant clinical observation indicators and statistical analysis were limited to PPS patients. Figures one to four visible, Figure one The condition of the burn sites on the patients during the initial stage of the experiment. Figures two to four The image shows the recovery of the burn site during the treatment process. It can be seen that the effect after use is significant. From May 20 to June 11, the patient's wound gradually healed after the epidermis peeled off and the base was red and white.

[0046] 2.1 Comparison of wound healing rates between the two groups of patients

[0047] As shown in Table 1, after 7 days of treatment, the median wound healing rate in the treatment group was significantly higher than that in the control group (P > 0.05). After 21 days of treatment, the median wound healing rates in the two groups were comparable (P > 0.05). After 14 days of treatment, the median wound healing rate in the treatment group was significantly higher than that in the control group (P < 0.05).

[0048] Table 1. Wound healing rates of the two groups of patients at 7, 14, and 21 days after treatment.

[0049]

[0050]

[0051] 2.2 Analysis of wound healing rate in each treatment interval

[0052] Table 2 shows the changes of wound healing rate in different healing time intervals of the two groups. The results of chi-square test analysis showed that in the three treatment time intervals, the healing rate of the treatment group was better than that of the control group, and the difference was statistically significant (P<0.05), indicating that the time and group factors affecting the healing rate existed interaction, among which, the wound healing rate of the two groups in the treatment interval of 14 days was significantly different, which was the main reason for the interaction of time and group, suggesting that in the three time intervals, the best treatment course of Pien Tze Huang for deep II degree burn was 14 days.

[0053] Table 2 Wound healing rate of the two groups

[0054]

[0055] 2.3 Degree of wound inflammatory reaction

[0056] Table 3 shows the degree of wound inflammatory reaction score reduction of the two groups at different treatment times. The results showed that after treatment for 7, 14 and 21 days, there was no significant difference in the reduction of wound inflammatory reaction between the two groups (P>0.05).

[0057] Table 3 Reduction of inflammatory reaction degree of the two groups after treatment for 7, 14 and 21 days

[0058]

[0059] *: Compared with baseline

[0060] 2.4 Safety

[0061] Adverse events of the treatment group included fever, constipation, and allergy; adverse events of the control group included fever, constipation, insomnia, and abnormal liver function. The number of times of mild adverse events in the treatment group was 15 times; in the control group, it was 17 times. Among them, 1 case of adverse reaction related to the drug occurred in the treatment group, and the adverse reaction name was allergy. The subject was significantly relieved after anti-allergy treatment, and did not stop taking the drug during the trial. No serious adverse events occurred in the two groups.

[0062] 3 Discussion

[0063] Deep II degree burn wound is a common skin injury, which not only causes severe pain, but also leads to infection and scar formation. Early intervention in the wound healing process can not only alleviate symptoms such as redness, swelling, heat and pain, but also accelerate wound healing, thereby inhibiting the occurrence of serious consequences such as infection, scar formation and hyperplasia. Traditional Chinese medicine has a long history of treating burns, and its method of treating acute burns with early intervention is of great significance. The results of this study show that oral Pianzaihu can improve the healing of deep II degree wounds and has good safety.

[0064] The results of this study show that oral Pianzaihu significantly improves the healing rate of deep II degree wounds after 14 days of treatment, indicating that oral Pianzaihu has a positive effect on the healing of deep II degree wounds. No serious adverse events occurred in either group, and one case of allergic reaction occurred in the treatment group, which was relieved after anti-allergic treatment; neither group had wound allergic reactions, indicating that oral Pianzaihu is safe. This prescription is composed of cow-bezoar, musk, Sanqi and snake gall. Sanqi is warm in nature, sweet and slightly bitter in taste, and is good at dissipating blood stasis, swelling, stopping bleeding and relieving pain; snake gall is cool in nature, slightly bitter and sweet in taste, and has the functions of clearing heat and detoxifying, clearing the liver and benefiting the gallbladder, and is the monarch drug. Cow-bezoar is cool in nature and sweet in taste, and is a good drug for clearing heat and detoxifying, resolving phlegm and relieving cough, and removing wind and dampness, which can enhance the monarch's function of clearing heat and reducing swelling, and also can resolve phlegm caused by heat evil and decoction of body fluid, so it is the ministerial drug. Musk is warm and can be used to promote blood circulation, dispel stasis and dissipate swelling, and can help the monarch and ministerial drugs to promote blood circulation and remove blood stasis, and is the auxiliary drug. The combination of these drugs can clear heat and detoxify, promote blood circulation and remove blood stasis, and relieve pain. The idea of using traditional Chinese medicine to treat deep II degree wounds is to use traditional Chinese medicine to promote blood circulation and remove blood stasis, relieve pain, enhance immunity, and kill bacteria. The molecular mechanism of Pianzaihu in relieving oxidative stress and promoting wound vascularization has been verified in a rat wound healing model. Traditional Chinese medicine theory believes that burns are caused by external injury of fire and heat evil, and should be treated with clearing heat and detoxifying, promoting blood circulation and removing blood stasis, and bitter cold astringent method. The efficacy of Pianzaihu is consistent with this.

[0065] Pianzaihu can inhibit inflammatory response, which is conducive to its role in improving the healing of deep II degree wounds. Red heat and pain are specific symptoms of inflammatory response after burns, and elevated inflammatory response can lead to deeper burns and prolonged healing time. Studies have shown that Pianzaihu can significantly alleviate inflammatory response caused by endotoxin, and inhibit the concentration of tumor necrosis factor-α, IL-6, IL-8 and white blood cell level in serum of New Zealand rabbits injected with Escherichia coli endotoxin. Pianzaihu has a positive effect on the healing of diabetic wounds, which can promote wound healing by inhibiting abnormal apoptosis and aging of epidermal fibroblasts, activating Nrf2 / ARE pathway to regulate oxidative stress level and increase expression of growth factors, and there is an indirect connection between its function of inhibiting inflammatory response.

[0066] In summary, oral PQA has the effect of improving the healing of deep II degree burn wounds, which is achieved through the effects of clearing heat and resolving toxins, anti-inflammatory, cooling blood and removing blood stasis, and the safety of oral PQA is good. This study provides a reference for the application of PQA in burn wound healing and provides a basis for further research on the use of PQA for soft tissue defects and repair.

[0067] The above shows and describes the basic principles, main features and advantages of the present application. Those skilled in the art should understand that the present application is not limited to the above examples, and the above examples and descriptions in the specification are only to illustrate the principles of the present application. Without departing from the spirit and scope of the present application, various changes and improvements can be made to the present application, and these changes and improvements all fall within the scope of the claimed present application. The scope of protection of the present application is defined by the appended claims and their equivalents.

Claims

1. The use of Pianzaihuan in the preparation of a drug for promoting healing of deep II degree burns, characterized in that: Piancayue can improve the healing of deep II degree wound by inhibiting inflammatory response.

2. Use according to claim 1, characterized in that: The molecular mechanism of Piancayue is to relieve the oxidative stress of wound and promote the vascularization of wound.

3. The method for studying the promotion of healing in deep II degree burns by Pien Tze Huang is characterized in that: The specific steps are as follows: S1, according to the inclusion criteria and exclusion criteria, patients who meet the diagnostic criteria of deep II degree burn are selected as research objects, and are divided into control group and treatment group; S2, all patients are treated with Piancayue. S3, the healing of wound is observed, the healing rate is calculated and the healing time of wound is recorded on the 7th, 14th and 21st day of treatment, and the research data is analyzed and processed.

4. The method of study of claim 3, wherein: In step S2, the single dose of Piancayue is 0.6g, three times a day.

5. The method of claim 3, wherein: In step S3,

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