A drug composition for promoting tissue regeneration, preparation and application thereof

Abstract

The application discloses a drug composition for promoting tissue regeneration and preparation and application thereof. The drug composition for promoting tissue regeneration is composed of rhizoma paridis, radix lithospermi, dragon's blood, radix angelicae dahuricae, eustegia macrantha, goldthread, corydalis, rhizoma phellodendri, radix et rhizoma rhei, radix sophorae flavescentis, radix paeoniae alba and cortex mali. The drug composition for promoting tissue regeneration is added with pharmaceutically acceptable adjuvants to prepare a preparation. The drug composition for promoting tissue regeneration and the preparation can be used for preparing a medicine for treating hemorrhoids, anal fissure, anal fistula, swelling and pain or itching around anus, hemorrhoids and anal fistula, anal abscess, postoperative pain, constipation, anal distension, edema of anal margin and urinary retention.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceuticals, specifically relating to a tissue-regenerating pharmaceutical composition, its formulation, and its application. Background Technology

[0002] Anorectal diseases are common in clinical practice. With the improvement of living standards and changes in lifestyle, their incidence and recurrence rate are increasing year by year. A study on the prevalence of anorectal diseases among urban residents in my country showed that the overall prevalence rate reached 51.14%. Examples include hemorrhoids, anal fissures, anal fistulas, perianal swelling and pain or itching, and anal abscesses. Currently, most anorectal diseases are treated surgically, but the surgical results vary from person to person and recurrence is very common. Postoperative complications often include pain, constipation, anal tenesmus, perianal edema, urinary retention, and chronic healing. These complications not only impose a physical and psychological burden on patients and affect their quality of life, but also pose a difficult and unavoidable challenge for clinicians. Currently, postoperative treatment typically involves adjunctive therapies such as fluid replacement, pain relief, and correction of electrolyte imbalances. However, conventional methods can only improve the patient's symptoms and signs to a certain extent and cannot fundamentally solve the problem. Therefore, it is essential to develop a drug that can effectively treat anorectal diseases such as hemorrhoids, anal fissures, anal fistulas, perianal swelling and pain or itching, and anal abscesses, and can fundamentally solve problems such as postoperative pain, constipation, anal tenesmus, perianal edema, urinary retention, and slow healing in anorectal diseases. Summary of the Invention

[0003] To address the shortcomings of existing technologies, the present invention aims to provide a tissue-regenerating pharmaceutical composition, its formulation, and its application. The aforementioned tissue-regenerating pharmaceutical composition possesses the effects of clearing heat and detoxifying, drying dampness and relieving itching, removing necrotic tissue and promoting tissue regeneration, and is safe with no side effects.

[0004] The objective of this invention is achieved through the following technical solution:

[0005] A tissue-regenerating pharmaceutical composition, by weight, comprises the following components: 10-20 parts of Paris polyphylla, 30-40 parts of Lithospermum erythrorhizon, 20-30 parts of Dragon's Blood, 30-40 parts of Angelica dahurica, 30-50 parts of Euphorbia fischeriana, 30-50 parts of Cyperus rotundus, 10-20 parts of Coptis chinensis, 10-20 parts of Phellodendron chinense, 10-20 parts of Rheum palmatum, 30-40 parts of Sophora flavescens, 30-50 parts of Astragalus membranaceus, and 20-40 parts of Dictamnus dasycarpus.

[0006] Preferably, the tissue-regenerating pharmaceutical composition comprises, by weight, the following components: 12-20 parts of Paris polyphylla, 31-38 parts of Lithospermum erythrorhizon, 20-28 parts of Dragon's Blood, 32-38 parts of Angelica dahurica, 35-45 parts of Euphorbia fischeriana, 35-45 parts of Cyperus rotundus, 12-18 parts of Coptis chinensis, 10-15 parts of Phellodendron chinense, 10-15 parts of Rheum palmatum, 30-35 parts of Sophora flavescens, 35-45 parts of Astragalus membranaceus, and 25-35 parts of Dictamnus dasycarpus.

[0007] More preferably, the tissue-regenerating pharmaceutical composition comprises, by weight, the following components: 14-18 parts of Paris polyphylla, 32-36 parts of Lithospermum erythrorhizon, 22-27 parts of Dragon's Blood, 32-36 parts of Angelica dahurica, 36-44 parts of Euphorbia fischeriana, 38-44 parts of Cyperus rotundus, 13-17 parts of Coptis chinensis, 12-14 parts of Phellodendron chinense, 12-14 parts of Rheum palmatum, 30-33 parts of Sophora flavescens, 36-42 parts of Astragalus membranaceus, and 26-32 parts of Dictamnus dasycarpus.

[0008] In this formula, Paris polyphylla is a bitter and purgative herb with detoxifying properties. It has the effects of clearing heat and detoxifying, reducing swelling, relieving pain, and stopping bleeding. It can treat various sores and carbuncles. Since anorectal diseases are mostly caused by damp-heat accumulation, Paris polyphylla can eliminate both damp-heat and blood stasis, preventing damp-heat from damaging the blood and causing toxicity. Therefore, it is the principal herb.

[0009] Lithospermum erythrorhizon clears heat, invigorates blood, detoxifies, and relieves constipation, thus reducing heat. Dragon's blood invigorates blood, relieves pain, removes blood stasis, stops bleeding, promotes tissue regeneration, and astringes sores. It invigorates blood and removes blood stasis to alleviate the harm caused by knife wounds. With the addition of Angelica dahurica, the three herbs promote tissue regeneration and astringe sores, promoting the growth of new flesh. Eupatorium fortunei and Cyperus rotundus have the functions of clearing heat and detoxifying. Eupatorium fortunei can promote diuresis and relieve itching, while Cyperus rotundus can reduce swelling and relieve pain. They clear damp heat and relieve pain and itching. The combination of the two herbs can help Paris polyphylla clear heat and detoxify, and eliminate damp heat. When combined with Lithospermum erythrorhizon, Dragon's blood, and Angelica dahurica, they can clear internal evils and promote tissue regeneration. They are all assistant herbs.

[0010] Coptis chinensis and Phellodendron chinense, being bitter and cold, have a purgative effect; both can clear heat, detoxify, heal sores, and dry dampness. Rhubarb can purge heat toxins and promote blood circulation. The combination of these three herbs can dry dampness, detoxify heat toxins, and promote blood circulation, directly addressing the pathogenesis. Sophora flavescens primarily enters the large intestine meridian, while Phellodendron chinense mainly treats damp-heat in the lower burner. Since the disease location is in the lower part of the body, the combination of the two can guide the medicinal power to the affected area. The fourth herb can enhance the heat-clearing and detoxifying effects of Paris polyphylla. Astragalus membranaceus, while containing tonifying properties, can harmonize qi and blood, remove necrotic tissue to promote new tissue growth; Dictamnus dasycarpus clears heat and dries dampness, and can also treat the rectal mucosa with the skin. The above six herbs serve as adjuvant herbs.

[0011] The formula treats damp-heat to eliminate pathogenic factors, removes necrotic tissue and promotes the formation of new tissue, thus achieving the effects of clearing heat and detoxifying, drying dampness and relieving itching, and removing necrotic tissue and promoting tissue regeneration.

[0012] The tissue-regenerating pharmaceutical composition may also be formulated with pharmaceutically acceptable excipients, such as liquid formulations.

[0013] The aforementioned tissue-regenerating pharmaceutical composition and its preparations have the effects of clearing heat and detoxifying, drying dampness and relieving itching, removing necrotic tissue and promoting tissue regeneration. They can be used to prepare drugs for treating hemorrhoids, anal fissures, anal fistulas, perianal swelling and pain or itching, as well as hemorrhoid fistulas and anal abscesses. They can also effectively relieve postoperative pain, constipation, anal distension, perianal edema, urinary retention and other symptoms of anorectal diseases, and promote wound healing.

[0014] Compared with the prior art, the present invention has the following beneficial effects:

[0015] 1. The tissue-regenerating pharmaceutical composition and its preparations of the present invention have excellent efficacy for anorectal diseases such as hemorrhoids, anal fissures, anal fistulas, perianal swelling and pain or itching, and anal abscesses. Common perianal diseases are mainly caused by wind, dampness, heat, dryness, blood stasis, qi deficiency, and blood deficiency. These pathogenic factors can cause disease individually or in combination, but damp-heat accumulation in the lower abdomen is the most common. In the tissue-regenerating pharmaceutical composition, Sophora flavescens primarily enters the large intestine meridian, and Phellodendron amurense primarily treats damp-heat in the lower abdomen, where the disease location is in the lower part of the body; Dictamnus dasycarpus, using the plant bark, can treat the skin with the bark and also acts as a guiding herb; the combination of these three can guide the medicinal power to the affected area. The composition also contains Paris polyphylla, Coptis chinensis, Phellodendron amurense, Rheum palmatum, Sophora flavescens, Euphorbia lathyris, and Cyperus rotundus, all of which have heat-clearing and dampness-drying effects. Therefore, the tissue-regenerating pharmaceutical composition and its preparations of the present invention are particularly effective for the above-mentioned anorectal diseases caused by damp-heat accumulation in the lower abdomen.

[0016] 2. The tissue-regenerating pharmaceutical composition and its preparations described in this invention, combined with the pathogenesis characteristics of anorectal diseases where although the lesions are removed during surgery, pathogenic factors remain, and postoperative blood stasis is common, follow the principle that "new tissue cannot grow without removing necrotic tissue." They are used in the form of decoction fumigation and sitz baths to treat postoperative complications of anorectal diseases such as anal canal mucosal edema, incision pain, and slow wound healing, and have good therapeutic effects.

[0017] 3. The tissue-regenerating pharmaceutical composition and its preparations of the present invention apply the drug directly to the lesion site, concentrating the medicinal power and delivering it directly to the lesion to exert a therapeutic effect.

[0018] 4. The tissue-regenerating pharmaceutical composition and its preparations described in this invention are applied locally using a fumigation and washing method. While exerting the therapeutic effect of the drug, it also has a cleaning effect on the anal area. The efficacy of the drug is not limited by the specific location and can maximize the therapeutic effect. Attached Figure Description

[0019] Figure 1 Line graph showing the general condition scores of the three groups of rats in Application Example 1. Detailed Implementation

[0020] The present invention will be further described below with reference to the embodiments, but the present invention is not limited to the embodiments. Example 1

[0021] A tissue-regenerating pharmaceutical composition comprising the following components: 20g of Paris polyphylla, 40g of Lithospermum erythrorhizon, 30g of Dragon's Blood, 40g of Angelica dahurica, 50g of Euphorbia fischeriana, 50g of Cyperus rotundus, 20g of Coptis chinensis, 20g of Phellodendron chinense, 20g of Rheum palmatum, 40g of Sophora flavescens, 50g of Astragalus membranaceus, and 40g of Dictamnus dasycarpus. Example 2

[0022] A tissue-regenerating pharmaceutical composition comprising the following components: 15g of Paris polyphylla, 35g of Lithospermum erythrorhizon, 25g of Dragon's Blood, 35g of Angelica dahurica, 40g of Euphorbia fischeriana, 40g of Cyperus rotundus, 15g of Coptis chinensis, 15g of Phellodendron chinense, 15g of Rheum palmatum, 35g of Sophora flavescens, 40g of Astragalus membranaceus, and 30g of Dictamnus dasycarpus. Example 3

[0023] A tissue-regenerating pharmaceutical composition comprising the following components: 10g of Paris polyphylla, 30g of Lithospermum erythrorhizon, 20g of Dragon's Blood, 30g of Angelica dahurica, 30g of Euphorbia fischeriana, 30g of Cyperus rotundus, 10g of Coptis chinensis, 10g of Phellodendron chinense, 10g of Rheum palmatum, 30g of Sophora flavescens, 30g of Astragalus membranaceus, and 20g of Dictamnus dasycarpus. Example 4

[0024] A tissue-regenerating pharmaceutical composition comprising the following components: 15g of Paris polyphylla, 31g of Lithospermum erythrorhizon, 25g of Dragon's Blood, 36g of Angelica dahurica, 45g of Euphorbia fischeriana, 50g of Cyperus rotundus, 10g of Coptis chinensis, 12g of Phellodendron chinense, 14g of Rheum palmatum, 40g of Sophora flavescens, 30g of Astragalus membranaceus, and 20g of Dictamnus dasycarpus. Example 5

[0025] A tissue-regenerating pharmaceutical composition comprising the following components: 18g of Paris polyphylla, 32g of Lithospermum erythrorhizon, 27g of Dragon's Blood, 38g of Angelica dahurica, 50g of Euphorbia fischeriana, 30g of Cyperus rotundus, 12g of Coptis chinensis, 14g of Phellodendron chinense, 15g of Rheum palmatum, 30g of Sophora flavescens, 35g of Astragalus membranaceus, and 25g of Dictamnus dasycarpus. Example 6

[0026] A tissue-regenerating pharmaceutical composition comprising the following components: 20g of Paris polyphylla, 35g of Lithospermum erythrorhizon, 28g of Dragon's Blood, 40g of Angelica dahurica, 30g of Euphorbia fischeriana, 35g of Cyperus rotundus, 13g of Coptis chinensis, 15g of Phellodendron chinense, 20g of Rheum palmatum, 33g of Sophora flavescens, 36g of Astragalus membranaceus, and 26g of Dictamnus dasycarpus. Example 7

[0027] A tissue-regenerating pharmaceutical composition comprising the following components: 12g of Paris polyphylla, 36g of Lithospermum erythrorhizon, 30g of Dragon's Blood, 30g of Angelica dahurica, 35g of Euphorbia fischeriana, 38g of Cyperus rotundus, 15g of Coptis chinensis, 20g of Phellodendron chinense, 10g of Rheum palmatum, 35g of Sophora flavescens, 40g of Astragalus membranaceus, and 30g of Dictamnus dasycarpus. Example 8

[0028] A tissue-regenerating pharmaceutical composition comprising the following components: 14g of Paris polyphylla, 38g of Lithospermum erythrorhizon, 20g of Dragon's Blood, 32g of Angelica dahurica, 36g of Euphorbia fischeriana, 40g of Cyperus rotundus, 17g of Coptis chinensis, 10g of Phellodendron chinense, 12g of Rheum palmatum, 40g of Sophora flavescens, 42g of Astragalus membranaceus, and 32g of Dictamnus dasycarpus. Example 9

[0029] A tissue-regenerating pharmaceutical composition comprising the following components: 15g of Paris polyphylla, 40g of Lithospermum erythrorhizon, 22g of Dragon's Blood, 35g of Angelica dahurica, 40g of Euphorbia fischeriana, 44g of Cyperus rotundus, 18g of Coptis chinensis, 12g of Phellodendron chinense, 14g of Rheum palmatum, 30g of Sophora flavescens, 45g of Astragalus membranaceus, and 35g of Dictamnus dasycarpus. Example 10

[0030] A tissue-regenerating pharmaceutical composition comprising the following components: 18g of Paris polyphylla, 30g of Lithospermum erythrorhizon, 25g of Dragon's Blood, 36g of Angelica dahurica, 44g of Euphorbia fischeriana, 45g of Cyperus rotundus, 20g of Coptis chinensis, 14g of Phellodendron chinense, 15g of Rheum palmatum, 33g of Sophora flavescens, 50g of Astragalus membranaceus, and 40g of Dictamnus dasycarpus. Example 11

[0031] A preparation of a tissue-regenerating pharmaceutical composition, wherein the medicinal materials are weighed according to the weight of the pharmaceutical composition described in any one of Examples 1-10, all the medicinal materials are soaked in warm water for 30 minutes, decocted for 20 minutes, and after the temperature drops to 30-45℃, the decoction is used to fumigate and wash the affected area for 5-10 minutes each time.

[0032] Application Example 1 – The therapeutic effect of the tissue-regenerating pharmaceutical composition of the present invention on hemorrhoids caused by damp-heat accumulation.

[0033] 1 Materials and Instruments

[0034] 1.1 Source and feeding of laboratory animals

[0035] Thirty-six male SPF-grade SD rats were housed at the Experimental Animal Center of Pu'er Traditional Chinese Medicine Hospital. The rats were kept under the following conditions: room temperature 22-26℃, relative humidity 50%-60%, and good ventilation. They were allowed to acclimatize in a quiet and clean environment for one week, with free access to food and water, and a diurnal light-dark cycle. This experiment was approved by the Animal Ethics Committee of Pu'er Traditional Chinese Medicine Hospital (Approval No.: 2022018).

[0036] 1.2 Experimental Drugs

[0037] The drug used in this application example is a formulation prepared according to the method described in Example 11, based on the tissue-regenerating pharmaceutical composition described in Example 1.

[0038] 1.3 Preparation of drugs for experimental modeling

[0039] Prepare a 1% solution of carrageenan powder with physiological saline. Prepare a 0.5% solution of lipopolysaccharide powder with physiological saline and store at 4°C. Prepare a 10 mg / mL solution of bromhexine raw material with physiological saline. -1 The solution to be used.

[0040] 1.4 Main Instruments and Reagents for the Experiment

[0041] PCR amplification instrument, three-channel real-time quantitative PCR instrument, enzyme reader, homogenizer, 4℃ medical refrigerator, handheld centrifuge, ELISA kits for IL-1β, IL-6, and TNF-α, DNA extraction kit, RNA extraction kit, PromegaGoScipt reverse transcription kit, 4% paraformaldehyde.

[0042] 2 methods

[0043] 2.1 Animal grouping, model establishment, and drug administration

[0044] 2.1.1 Grouping

[0045] After one week of acclimatization, the animals were randomly divided into three groups according to their weight. Twelve rats were randomly selected as the control group, and the remaining rats were used to create the wound model. The rats that successfully developed the wound model were randomly divided into the model group and the drug treatment group, with 12 rats in each group.

[0046] 2.1.2 Modeling Method

[0047] Twenty-four hours prior to modeling, all 36 rats were fasted and dehydrated. Their anus was stimulated with cotton swabs to empty their bowels, and they were anesthetized with ether (0.3 mL / 100g per rat). After successful anesthesia, the rats were fixed in a prone position, and hair removal cream was applied to a skin area approximately 7cm × 4cm above the midline of the lumbar spine. The area was disinfected with 75% alcohol and placed on a sterile operating table. The surgical area was routinely disinfected and draped with sterile sheets. Appropriate doses of the combined drug were administered via subcutaneous injection into the rectum. The wound was rinsed with physiological saline and covered with clean gauze. Except for the control group, the model group and the drug administration group underwent intrarectal injection of a combination of carrageenan, lipopolysaccharide, bromhexine, and ethamsylate to simulate clinical pathological conditions. Clinical pathological features and processes were simulated by observing corresponding indicators such as severe constipation, perianal swelling, rectal deformation and prolapse, significant inflammatory infiltration, and thrombus formation. This model can simulate the pathological symptoms of hemorrhoids and has the advantages of simple operation, stable trauma, and easy observation.

[0048] Screening indicators and symptom scores for modeling: ① such as perianal redness and swelling, difficulty in defecation, etc., and significantly increased the perianal diameter of the model animals. ② In the observation of pathological sections of rat anorectal tissue, it was found that the anorectal tissue of the model animals had obvious pathological changes such as vascular proliferation, thrombosis, hemorrhoid formation, inflammation, and granuloma, which can better reflect the pathological symptoms of hemorrhoids (Zhou Jun, Lü Xiaohui, Dang Liyun, et al. Research on the method of establishing a new animal model of hemorrhoids [J]. Chinese Journal of Modern Applied Pharmacy, 2019, 36(5): 526-531).

[0049] 2.1.2 Administration method

[0050] Through a two-week modeling experiment and observation, it was found that this modeling method can produce clinical symptoms similar to those of human hemorrhoids, such as perianal redness and swelling, and difficulty in defecation, and significantly increase the perianal diameter of the model animals.

[0051] Rats that successfully developed the model were randomly divided into two groups: the model group and the drug administration group (0.5 mL / kg). The injection site for the modeling reagent in the drug administration group was 0.2 cm inside the anus, at 4 points in the submucosal seromuscular layer. The experimental drug was applied once a day at 21:00. The control group and the model group were treated with the corresponding volume of physiological saline once a day for 2 consecutive weeks.

[0052] 2.2 Experimental Procedure

[0053] Sample collection: Twelve rats from each of the three groups were observed for 14 days. After the observation period, the rats were injected with ether intraperitoneally. After anesthesia, the wound tissue was taken and placed in a test tube containing 4% paraformaldehyde for subsequent testing.

[0054] RNA Extraction: After obtaining the tissue as described above, follow the instructions to flash-freeze the tissue in liquid nitrogen, cut it into small pieces, and homogenize it using a homogenizer. Add 1 mL of Trizol reagent to every 30-50 mg of tissue, homogenize, and aspirate the homogenate. Let it stand at room temperature for 5 min. Centrifuge at 12000 rpm for 10 min, and transfer the supernatant to a new 1.5 mL centrifuge tube. Extract total RNA using Trizol reagent. Using an RNA reverse transcription kit, take 1 μg of RNA for reverse transcription to prepare cDNA. Finally, perform real-time quantitative polymerase chain reaction (RT-QPCR) to detect the expression levels of IL-1β, IL-6, and TNF-α inflammatory factors.

[0055] ELISA assay: After obtaining the tissue according to the above procedure, the tissue was homogenized and centrifuged at 13000 rpm for 5 min. The supernatant was then collected into a centrifuge tube. The expression of IL-1β, IL-6, and TNF-α in the skin tissue was detected by ELISA.

[0056] 2.3 Specimen Collection and Index Testing

[0057] 2.3.1 General Observation

[0058] The presence, size, presence and degree of redness and swelling, anal moisture, ulcer healing time, and behavioral patterns of rats were observed daily and statistically analyzed. The observation period was 60 minutes, starting 1 hour before drug administration. The rats' activity level was primarily reflected by reduced normal activity levels, generalized or partial muscle tension, and abnormal licking behaviors. The scoring rules are shown in Table 1, with scores ranging from 5 to 0, indicating a gradual increase in severity.

[0059]

[0060] 2.3.2 Degree of perianal swelling

[0061] The perianal diameter of each rat was measured after each general observation and before drug administration. Three precise measurements were taken for each rat using vernier calipers, and the average value was recorded.

[0062] 2.3.3 Molecular biological detection

[0063] The expression of inflammation-related genes or proteins, such as inflammatory factors (IL-1β, IL-6, TNF-α, etc.), in skin tissue is detected using techniques such as PCR and ELISA to assess the degree and type of skin inflammation.

[0064] 2.3.4 Statistical Methods

[0065] Statistical analysis of the data was performed using GraphPad Prism 8.0 data analysis software. For measurement data, the average value at each time point of each group was used, expressed as mean ± standard error. Repeated measures ANOVA was used to compare the means between groups. For data that conformed to a normal distribution and had homogeneous variances, independent samples t-tests were used for comparisons between two groups, and one-way ANOVA was used for comparisons among multiple groups. P <0.05 indicates a significant difference.

[0066] 3 Results and Analysis

[0067] 3.1 General Case

[0068] The symptom observations during this study mainly included the degree of perianal redness and swelling, and the degree of difficulty in defecation, which can indirectly reflect the behavioral manifestations of hemorrhoid pain symptoms. We statistically analyzed the changes in the three groups of rats according to the scoring rules. The results showed that compared with the model group, there was no significant difference in the drug treatment group in the first 3 days ( P >0.05), after day 9, the indicator scores of the treated rats began to show an upward trend, indicating that the drug group could effectively alleviate the perianal redness and swelling and defecation difficulties in the rats. However, as time went on, the indicator scores of the model group rats began to decline continuously, their condition worsened, and some even died (e.g., Figure 1 (As shown).

[0069] 3.2 Changes in the degree of perianal swelling

[0070] Compared with the control group, there were significant differences in the degree of perianal swelling between the model group and the drug administration group on the 3rd day after modeling. P<0.05 indicates successful model establishment. Compared with the model group, the diameter of perianal swelling in the treatment group began to shrink and recover from day 6.

[0071] P <0.05). In the model group, the swelling gradually worsened on days 3, 6, 9, and 14, as shown in Table 2.

[0072]

[0073] 3.3 Comparison of serum IL-1β, IL-6, and TNF-α levels in different groups of rats

[0074] On day 14, perianal skin tissue samples were collected from the three groups of rats, and PCR and enzyme-linked immunosorbent assay (ELISA) were used to detect inflammation-related genes (IL-1β, IL-6, TNF-α, etc.) in the skin tissue to assess the degree and type of skin inflammation. The results showed that, compared with the model group, the levels of inflammatory factors IL-1β, IL-6, and TNF-α in the drug-treated rats were reduced, as shown in Tables 3 and 4.

[0075]

[0076] 4. Conclusion

[0077] This application example utilizes a drug reagent with local irritant effects, administered locally to the submucosal seromuscular layer of the rectum, to verify the efficacy of the pharmaceutical composition described in this invention, from the overall condition to local inflammatory expression. The experimental results show that the formulation of the tissue-regenerating pharmaceutical composition of this invention significantly improves the size, redness, and degree of swelling in animal models, and can significantly inhibit the inflammatory response caused by perianal swelling and pain. This indicates that the formulation of the tissue-regenerating pharmaceutical composition of this invention can effectively alleviate perianal swelling and inflammatory expression in rats, and promote the recovery of perianal ulcers.

[0078] Application Example 2 – Clinical observation of the therapeutic effect of the formulation of the tissue-regenerating pharmaceutical composition of the present invention on patients after anal abscess surgery.

[0079] 1. General Information

[0080] Sixty patients with perianal abscesses admitted to the Department of Anorectal Surgery at Pu'er Traditional Chinese Medicine Hospital from January 1, 2020 to December 22, 2023 were collected. They were randomly divided into a treatment group and a control group using a random number table. The treatment group consisted of 26 male patients and 4 female patients, while the control group consisted of 25 male patients and 5 female patients. There were no statistically significant differences in gender or age between the two groups. P The difference was >0.05, indicating comparability. In the treatment group, 27 patients had low-lying abscesses and 3 had high-lying abscesses; in the control group, 27 patients had low-lying abscesses and 3 had high-lying abscesses. There was no statistically significant difference, indicating comparability.

[0081] 2 Observation Indicators

[0082] 2.1 Therapeutic Indicators

[0083] 2.1.1 Postoperative wound pain score

[0084] Postoperative wound pain was assessed using the visual analogue scale (VAS). A 10cm straight line was selected, with the leftmost side representing no pain and the rightmost side representing extreme pain. Patients were assessed on wound pain levels on postoperative days 3, 7, and 14, with a score ranging from 0 to 3. The specific scoring criteria were as follows:

[0085] 0 points: No pain (VAS=0cm);

[0086] 1 point: Mild pain, occasional pain, but does not affect normal independent activities (1cm≤VAS≤3cm).

[0087] 2 points: Moderate pain, persistent pain that affects activity, requiring oral analgesia for relief (4cm≤VAS≤6cm).

[0088] 3 points: Severe pain, persistent and intense pain, affecting sitting and lying down, requiring local injection of analgesics to relieve pain (7cm≤VAS≤10cm).

[0089] 2.1.2 Postoperative granulation tissue growth score

[0090] The growth of granulation tissue on the wound was observed and scored on days 7 and 14 post-surgery, with a score of 0-3. A lower score indicated better granulation tissue growth, and vice versa. The specific scoring criteria were as follows:

[0091] 0 points: The granulation tissue is firm, red and granular, and there is no edema.

[0092] 1 point: The granulation tissue is growing well, with a relatively firm texture, and is light red and granular. There is a small area of ​​granulation edema, which does not exceed 1 / 3 of the wound surface.

[0093] 2 points: Granulation tissue growth is average, the texture is relatively soft, the color is pale, and nearly half of the area is edematous;

[0094] 3 points: The granulation tissue grows slowly, is soft in texture, and is dark in color, with a large area of ​​edema on the wound surface.

[0095] 2.1.3 Relative area of ​​wound

[0096] The wound area was observed on postoperative days 3, 7, and 14. The longitudinal and transverse diameters of the wound were measured in the patient's knee-chest position. The relative wound area = longitudinal diameter of the wound × transverse diameter of the wound.

[0097] 2.1.4 Healing time

[0098] According to the "Standards for Diagnosis and Treatment of Diseases in Traditional Chinese Medicine Proctology": the wound was completely covered by newly formed epithelial tissue. Patients who had been discharged were informed that they needed to undergo outpatient visits or telephone follow-ups before participating in the study to record wound healing time.

[0099] 2.2 Use of medication

[0100] The drug used in this application example is a formulation prepared according to the method described in Example 11 based on the tissue-regenerating pharmaceutical composition described in Example 2.

[0101] 3 Experimental Results

[0102] 3.1 Analysis of postoperative wound pain scores in the two groups

[0103] The pain scores of the wound were compared between the treatment group and the control group on the 3rd, 7th and 14th days after surgery. The results are shown in Table 5.

[0104]

[0105] 3.2 Analysis of the scoring of granulation tissue growth in the two groups after surgery

[0106] The scores of granulation tissue growth in the wound were compared between the treatment group and the control group on the 7th and 14th postoperative days. The results are shown in Table 6.

[0107]

[0108] 3.3 Analysis of wound secretion scores in the two groups

[0109] The wound secretion scores of the treatment group and the control group were compared on the 3rd, 7th and 14th days after surgery. The results are shown in Table 7.

[0110]

[0111] 3.4 Analysis of the relative area of ​​the two groups of wounds

[0112] The relative wound area on postoperative day 1 in the treatment group was 9.13±2.20, while that in the control group was 10.07±1.71. The comparison of relative wound areas on postoperative days 3, 7, and 14 between the treatment and control groups is shown in Table 8.

[0113]

[0114] 3.5 Analysis of complete wound healing time in the two groups

[0115] The shortest healing time in the treatment group was 15 days, and the longest was 22 days; the shortest healing time in the control group was 21 days, and the longest was 28 days. The results of the comparison of the complete healing time of the wound are shown in Table 9.

[0116]

[0117] 4. Conclusion

[0118] Based on the above results, the formulation of the tissue-regenerating pharmaceutical composition of the present invention can effectively reduce wound pain, promote the growth of granulation tissue, reduce wound secretions, promote wound healing, and shorten wound healing time. This indicates that the formulation of the tissue-regenerating pharmaceutical composition of the present invention, when used in postoperative patients with anorectal diseases, can effectively relieve postoperative pain and promote wound healing.

Claims

1. A pharmaceutical composition for promoting tissue regeneration, characterized in that, By weight, it consists of the following components: 10-20 parts of Paris polyphylla, 30-40 parts of Lithospermum erythrorhizon, 20-30 parts of Dragon's Blood, 30-40 parts of Angelica dahurica, 30-50 parts of Euphorbia fischeriana, 30-50 parts of Cyperus rotundus, 10-20 parts of Coptis chinensis, 10-20 parts of Phellodendron chinense, 10-20 parts of Rheum palmatum, 30-40 parts of Sophora flavescens, 30-50 parts of Astragalus membranaceus, and 20-40 parts of Dictamnus dasycarpus.

2. The tissue-regenerating pharmaceutical composition according to claim 1, characterized in that, By weight, it consists of the following components Composition: 12-20 parts of Paris polyphylla, 31-38 parts of Lithospermum erythrorhizon, 20-28 parts of Dragon's Blood, 32-38 parts of Angelica dahurica, 35-45 parts of Euphorbia fischeriana, 35-45 parts of Cyperus rotundus, 12-18 parts of Coptis chinensis, 10-15 parts of Phellodendron chinense, 10-15 parts of Rheum palmatum, 30-35 parts of Sophora flavescens, 35-45 parts of Astragalus membranaceus, and 25-35 parts of Dictamnus dasycarpus.

3. The tissue-regenerating pharmaceutical composition according to claim 2, characterized in that, By weight, it consists of the following components: Paris polyphylla 14-18 parts, Lithospermum erythrorhizon 32-36 parts, Dragon's blood 22-27 parts, Angelica dahurica 32-36 parts, Euphorbia fischeriana 36-44 parts, Cyperus rotundus 38-44 parts, Coptis chinensis 13-17 parts, Phellodendron chinense 12-14 parts, Rheum palmatum 12-14 parts, Sophora flavescens 30-33 parts, Astragalus membranaceus 36-42 parts, and Dictamnus dasycarpus 26-32 parts.

4. A formulation of the tissue-regenerating pharmaceutical composition according to any one of claims 1 to 3, characterized in that, The formulation is made by adding pharmaceutically acceptable excipients to the tissue-regenerating pharmaceutical composition.

5. The formulation of the tissue-regenerating pharmaceutical composition according to claim 4, characterized in that, The preparation is a topical sitz bath solution.

6. A method for preparing a formulation of the tissue-regenerating pharmaceutical composition according to claim 5, characterized in that, The process includes the following steps: soaking all the medicinal materials in warm water, decocting them, and then waiting for the temperature to drop to 30-45℃ to obtain the final product.

7. Use of the tissue-regenerating pharmaceutical composition according to any one of claims 1 to 3 in the preparation of a medicament for treating hemorrhoids or perianal abscesses.

8. The use of the formulation of the tissue-regenerating pharmaceutical composition of claim 4 in the preparation of a medicament for treating hemorrhoids or perianal abscess.

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