Traditional Chinese medicine navel application agent for activating abdominal immune network and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine navel application agent for activating an abdominal cavity immune network and a preparation method thereof, through specific compatibility of 11 pungent and warm medicines (including five medicines for resolving dampness with aromatics, five medicines for warming the interior and one medicine for astringing the intestine), and in combination with a superfine grinding technology (the particle size is less than or equal to 30 microns) and a beta-cyclodextrin inclusion process, the transdermal absorption rate of the medicines is increased to 3-5 times that of common navel therapy. Animal experiments show that the preparation can increase the phagocytic rate of macrophages in the abdominal cavity of a mouse by 32.7%, the CD4 + / CD8 + ratio of T lymphocytes is recovered from 1.2 to 1.8 + / -0.2, and the slgA concentration of mucous membranes is increased by 2.3 times. Clinical observation shows that the effective rates for diarrhea, stomachache and vomiting symptoms caused by deficiency-cold of spleen and stomach of children within 24 hours respectively reach 90.2%, 85.6% and 80.4%, and liver and kidney dysfunction is not found.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine umbilical application for activating the peritoneal immune network and its preparation method. Background Technology

[0002] Pediatric spleen and stomach deficiency-cold syndrome is a common digestive system disease in pediatric clinical practice, mainly manifested as chronic diarrhea, recurrent abdominal pain, and loss of appetite. Its pathogenesis is closely related to the physiological characteristic of children's "frequent spleen deficiency." Modern medical research shows that the occurrence and development of this syndrome involves multiple pathological links, including gastrointestinal microecological imbalance, impaired intestinal mucosal barrier function, and abnormal immune regulation. Traditional Chinese medicine treatment often uses oral prescriptions that strengthen the spleen and warm the middle jiao, and aromatically resolve dampness, but these have problems such as poor taste, low patient compliance, and significant first-pass effect of the liver. In recent years, umbilical therapy has gradually gained attention as a unique external treatment method. It allows for direct absorption of drug components through the Shenque acupoint, with advantages such as rapid action and few side effects.

[0003] However, existing umbilical therapy formulas often focus on single treatments, lacking systematic combinations targeting the complex pathogenesis of "cold, dampness, and deficiency." Furthermore, research on their mechanisms of action remains at the level of empirical summaries, failing to meet the needs of modern precision medicine. Currently, commonly used umbilical therapy drugs face the following technical bottlenecks: First, the formulation design lacks modern pharmacological support; most formulas rely solely on traditional empirical combinations, and the synergistic effects between drugs remain unclear. Second, the dosage forms are outdated; traditional powders or ointments suffer from low transdermal efficiency and short duration of action, leading to unstable clinical efficacy. Third, quality control standards are lacking; the processing of Chinese medicinal materials is not standardized, resulting in large fluctuations in the content of effective components, severely affecting the reproducibility of treatment effects. More importantly, existing research is mostly limited to single-target effects, failing to systematically reveal the deep mechanisms by which umbilical therapy regulates the body's immune function through multiple pathways. This dual lag in theory and technology severely restricts the application potential of umbilical therapy in the treatment of spleen and stomach deficiency-cold syndrome in children.

[0004] This invention addresses the aforementioned technical challenges by creatively constructing a novel treatment system of "pungent-warm transdermal absorption, immune activation, and bidirectional regulation." By carefully selecting 11 pungent-warm Chinese herbal medicines with synergistic effects and employing modern ultrafine pulverization technology and β-cyclodextrin inclusion processing, the transdermal absorption rate of the active ingredients is significantly improved. Clinical observations show that this preparation can rapidly relieve core symptoms such as diarrhea and abdominal pain within 24 hours. Its mechanism of action is not only reflected in the local antibacterial and anti-inflammatory effects but also in systemic immune regulation through activation of the peritoneal immune network. Compared to traditional therapies, this invention achieves breakthroughs in scientific formulation, advanced dosage form, and significant efficacy, providing a completely new solution for the clinical treatment of pediatric spleen and stomach deficiency syndrome. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine umbilical application for activating the peritoneal immune network and its preparation method.

[0006] To achieve the above objectives, this invention utilizes the following technical solution: a traditional Chinese medicine umbilical application for activating the peritoneal immune network and its preparation method. The application is composed of three types of pungent and warm traditional Chinese medicines, which are combined in specific proportions to achieve synergistic therapeutic effects. The aromatic dampness-resolving group uses five herbs: Amomum villosum, Atractylodes lancea, Pogostemon cablin, Amomum tsao-ko, and Amomum tsao-ko. Amomum villosum promotes qi circulation and warms the middle jiao; Atractylodes lancea dries dampness and strengthens the spleen; Pogostemon cablin resolves dampness and invigorates the spleen; Amomum tsao-ko warms the middle jiao and stops vomiting; and Amomum tsao-ko dispels turbidity. The combination of these five herbs effectively resolves cold-dampness in the spleen and stomach. The warming-interior group uses cloves, Evodia rutaecarpa, cinnamon, Alpinia galanga, and pepper as its core ingredients. Cloves warm the kidneys and assist yang; Evodia rutaecarpa dispels cold and relieves pain; cinnamon tonifies fire and assists yang; Alpinia galanga warms the stomach and stops vomiting; and pepper warms the middle jiao and dries dampness, collectively achieving the effect of warming the middle jiao and dispelling cold. The astringent and antidiarrheal group uses only roasted nutmeg, which, after being stir-fried with wheat bran, has a stronger astringent and antidiarrheal effect, consolidating the large intestine and relieving prolapse. After the three types of drugs were ultra-finely pulverized to a particle size of ≤30μm, the specific surface area of ​​the drugs increased significantly, and the transdermal absorption rate of the active ingredients was improved. They were then delivered directly to the affected area through the Shenque acupoint, achieving a triple therapeutic effect of "aromatic dampness removal, warming the interior and dispelling cold, and astringing the intestines and stopping diarrhea". This formulation design not only conforms to the TCM principle of "treating cold with heat", but also overcomes the limitation of low transdermal efficiency in traditional umbilical therapy through modern ultra-fine pulverization technology.

[0007] Furthermore, the standard for volatile oil content in the aromatic dampness-resolving group of traditional Chinese medicines was set at ≥2.5%, an indicator precisely determined by steam distillation. Volatile oil components are key carriers for the efficacy of these drugs; among them, Amomum villosum contains bornyl acetate, Atractylodes lancea contains atractylodes alcohol, Pogostemon cablin contains patchouli alcohol, and Amomum cardamomum contains eucalyptol. These volatile substances not only directly inhibit the growth of pathogenic bacteria but also improve the digestive tract microecological environment by regulating the balance of intestinal flora. The lower limit for volatile oil content was set based on previous pharmacodynamic studies; below this threshold, the antibacterial effect of the drugs significantly decreases. Using steam distillation for extraction preserves the biological activity of volatile components while avoiding the risk of organic solvent residues, ensuring the safety of the formulation.

[0008] Furthermore, the total alkaloid content standard for the warming-interior group of traditional Chinese medicines was set at ≥1.8%, accurately detected by high-performance liquid chromatography (HPLC). Alkaloids are the main material basis for the warming-interior effects of these medicines. Examples include eugenol in cloves, evodia rutaecarpa, cinnamaldehyde in cinnamon, galangal, and piperine. These alkaloids can generate a warming sensation by activating TRPV1 receptors while inhibiting the release of inflammatory mediators. The total alkaloid content was set based on pharmacological experimental data; below this value, the warming effect and anti-inflammatory activity of the medicine would be weakened. HPLC, with its high resolution and sensitivity, can accurately determine the content of various alkaloid components, providing a reliable basis for quality control.

[0009] Furthermore, the processing of nutmeg employs a bran-frying method, specifically involving frying clean nutmeg and wheat bran together in a 1:0.8 ratio. During frying, the heat must be carefully controlled; the bran should be removed quickly and sifted out when it turns a deep brown color. This process effectively reduces the drying properties of nutmeg through the adsorption effect of the bran, while enhancing its astringent and antidiarrheal effects. After processing, the volatile oil components of nutmeg undergo chemical transformation, increasing the content of active ingredients such as methyl eugenol and acetylborneol, while significantly reducing irritating components such as myristole. Cooling to room temperature in a cool place before pulverizing prevents oxidation and deterioration, ensuring the stability of the finished product. The processing parameters were optimized through multiple orthogonal experiments, ultimately determining a 1:0.8 bran-frying ratio as the optimal proportion.

[0010] Furthermore, the preparation method employs an integrated technology of "supercritical extraction-ultrafine pulverization-β-cyclodextrin inclusion complex". First, cardamom, clove, cinnamon, and pepper are subjected to CO2 supercritical extraction. This method selectively extracts volatile oil components at 35 MPa and 45℃, avoiding the hydrolytic damage of steam distillation. The extract is freeze-dried to obtain high-purity volatile oil with an eugenol content exceeding 35%. The remaining medicinal materials are ultrafine pulverized to a D90 ≤ 30 μm, resulting in a concentrated particle size distribution and a more than 5-fold increase in specific surface area. Subsequently, the volatile oil is converted into a β-cyclodextrin inclusion complex using a saturated aqueous solution method, achieving an inclusion rate of over 82%. Finally, the inclusion complex is uniformly mixed with the ultrafine powder and packaged into breathable medical dressings, with each dressing containing a strictly controlled amount of drug at 0.5 g ± 0.05 g. This process effectively solves the technical challenges of volatile oil's easy volatility and poor absorption, increasing the transdermal drug penetration rate to four times that of ordinary powders.

[0011] Furthermore, this umbilical application activates the peritoneal immune network through multiple pathways: firstly, it significantly increases the macrophage phagocytic index to over 32.7%, enhancing the body's non-specific immune defense capabilities; secondly, it regulates the proportion of T lymphocyte subsets, restoring the CD4+ / CD8+ ratio to the normal range (1.5-2.5), thus rebuilding cellular immune balance; and simultaneously, it promotes a 2.3-fold increase in the secretion of sl gA antibodies in the intestinal mucosa, strengthening the local immune barrier. Experimental data show that after 7 days of continuous administration, the expression of Fc receptors on the surface of mouse peritoneal macrophages increased by 40%, and the secretion of IFN-γ increased by 28%. This immunomodulatory effect is achieved through a mechanism of "acupoint stimulation-meridian conduction-systemic response," which can both rapidly relieve acute symptoms and regulate immune dysregulation in chronic inflammatory states.

[0012] Furthermore, the activation mechanism involves multi-level regulation of the TLR4 / NF-κB signaling pathway: the drug component can downregulate TLR4 receptor expression by 22% and inhibit NF-κB p65 nuclear translocation, thereby blocking inflammatory signal transduction. ELISA detection showed a 45% decrease in the levels of pro-inflammatory factors such as IL-6 and TNF-α, while the concentrations of anti-inflammatory factors such as IL-10 and TGF-β increased threefold. Western blot results showed reduced p-IκBα protein expression, confirming that NF-κB activation was effectively inhibited. This bidirectional regulatory mechanism can both control acute inflammatory responses and prevent secondary infections caused by excessive immunosuppression, reflecting the TCM treatment concept of "strengthening the body's resistance and eliminating pathogenic factors."

[0013] Furthermore, the umbilical application procedure follows a standardized process: after cleaning the navel area, apply 0.5g of the medicinal powder evenly to a sterile dressing, cover with sterile gauze, and secure with breathable adhesive tape. Change the dressing once daily, with 7 days constituting one course of treatment. This is combined with 808nm infrared light irradiation for 20 minutes daily at a power density of 2W / cm². 2 The thermal effect of infrared light can promote local blood circulation and accelerate drug absorption, while gently stimulating the Shenque acupoint to enhance its stimulation effect. Clinical trials have shown that the combined light irradiation group showed a 23% improvement in efficacy compared to the simple umbilical application group, and a 1.5-day reduction in diarrhea time. This treatment achieves a comprehensive therapeutic effect by employing a triple mechanism of action: transdermal drug delivery, physical stimulation, and meridian conduction.

[0014] Furthermore, pharmacodynamic data showed that significant efficacy could be observed 24 hours after application of the umbilical application: the effective rate of stopping diarrhea reached 90.2% (n=60), and the frequency of bowel movements decreased from an average of 5.2 times / day to 1.3 times / day; the VAS score for abdominal pain decreased by 85.6%, and the incidence of nausea and vomiting decreased by 80.4%. Regarding safety, only 3 cases experienced mild skin itching, which resolved spontaneously after discontinuation of the medication. Pharmacokinetic studies showed that the drug remained in the umbilical microenvironment for up to 72 hours, with blood drug concentrations below the detection limit, avoiding metabolic burden on the liver and kidneys. This efficacy data was achieved thanks to the improved transdermal absorption rate and the synergistic effect of immunomodulatory effects.

[0015] Furthermore, the immunomodulatory effect was evaluated using a multi-dimensional detection system: flow cytometry was used to detect macrophage phagocytosis rate, fluorescent labeling was used to analyze T lymphocyte subsets, ELISA was used to quantitatively detect sIgA concentration, and multiplex PCR chips were used to screen the expression levels of 27 inflammatory factors. Results showed that after treatment, the proportion of CD14+ macrophages increased by 35%, the proportion of CD4+ T cells increased from 28% to 42%, and the sIgA concentration increased from 0.8 mg / mL to 2.7 mg / mL. Gene chip analysis revealed a decrease in the expression levels of TLR4, MyD88, and NF-κB mRNA, while the transcription levels of IL-10 and TGF-β were upregulated. This comprehensive evaluation system fully reflects the multi-level regulatory effects of the drug on innate immunity, adaptive immunity, and mucosal immunity, providing a scientific basis for research on the mechanism of efficacy.

[0016] This invention provides a traditional Chinese medicine umbilical application for activating the peritoneal immune network and its preparation method, which has the following beneficial effects:

[0017] Traditional Chinese medicine umbilical application has significant technical advantages and innovative value, mainly reflected in the following aspects: First, the formulation design follows the TCM principle of "principal, assistant, adjuvant, and guide" in drug pairing. The 11 herbs form an organic whole across three functional dimensions: pungent and warming to dispel heat, aromatically resolving dampness, and astringing the intestines to stop diarrhea. Among them, the aromatic dampness-resolving group regulates the intestinal microecology through volatile oil components, the warming group activates immune cells through alkaloids, and the astringent group repairs the mucosal barrier through tannins. The synergistic effect of these three can simultaneously address complex pathogenesis such as "dampness obstructing the middle jiao," "cold stagnation and blood stasis," and "incontinence." This multi-target, multi-level treatment strategy breaks through the limitations of traditional single-treatment methods of umbilical therapy.

[0018] Secondly, this invention innovatively employs a dual transdermal enhancement technology of "ultra-micro pulverization + β-cyclodextrin encapsulation." By using supercritical CO2 extraction to extract volatile medicinal materials such as cardamom and cloves, the bioactivity of effective components such as eugenol and cinnamaldehyde is preserved to the maximum extent. β-cyclodextrin molecular encapsulation technology solves the technical problem of the easy volatility and poor absorption of volatile oil components. Experimental data show that the transdermal transdermal rate of drugs processed by this technology is 3-5 times higher than that of traditional powders, and the cumulative release time of the drug in the umbilical microenvironment is extended to 72 hours, achieving a long-lasting and sustained-release therapeutic effect.

[0019] Third, this invention establishes a scientific and standardized quality control system. Strict processing parameters are set for each medicinal material. For example, when processing nutmeg using the bran-frying process, the ratio of bran to medicinal material is clearly specified as 1:0.8, the frying temperature is controlled at 180-200℃, and the material is removed immediately when the bran turns a dark brown color. Simultaneously, high-performance liquid chromatography and gas chromatography-mass spectrometry are used to quantitatively control key quality indicators such as the volatile oil content, eugenol purity, and cinnamaldehyde content of amomum villosum, ensuring the stability and uniformity of efficacy across different batches of products.

[0020] Fourth, this invention elucidates its unique immunomodulatory mechanism through systematic pharmacodynamic studies. Animal experiments show that this preparation can significantly upregulate the phagocytic index of mouse peritoneal macrophages by 32.7%, promote the restoration of the CD4+ / CD8+ ratio of T lymphocytes to normal levels, and simultaneously induce a 2.3-fold increase in the secretion of sl gA mucosal immunoglobulin. This dual activation effect of "innate immunity-adaptive immunity" can not only rapidly alleviate clinical symptoms but also fundamentally rebuild the body's immune homeostasis, effectively preventing disease recurrence.

[0021] Fifth, this invention demonstrates significant advantages in clinical efficacy. A randomized controlled trial on 60 children with mesenteric lymphadenitis of the spleen and stomach deficiency-cold type showed that the treatment group achieved a 90.2% effective rate in stopping diarrhea within 24 hours, an 85.6% rate in relieving abdominal pain, and an 80.4% rate in stopping vomiting; all indicators were significantly better than those in the control group. Most importantly, no adverse events such as abnormal liver function or allergic reactions occurred in any of the children, fully validating the drug's safety. This "highly effective and low-toxicity" therapeutic characteristic makes it particularly suitable for children, a special patient group.

[0022] Sixth, this invention establishes a complete "diagnosis-treatment-evaluation" technical system. Regarding diagnostic criteria, a comprehensive scoring system combining "number of diarrhea episodes + severity of abdominal pain + tongue appearance score" is adopted, improving the accuracy of disease identification. For treatment plans, a phased therapy of "intensive umbilical application during the acute phase + consolidation treatment during the remission phase" is designed. For efficacy evaluation, multi-dimensional detection indicators including immunoglobulins, inflammatory factors, and gut microbiota have been established. The establishment of this standardized diagnostic and treatment process lays a solid foundation for the standardized promotion of umbilical therapy technology.

[0023] Seventh, this invention represents a significant innovation in formulation technology. By employing ultra-micro pulverization technology to refine the particle size of medicinal materials to below 30μm, the specific surface area of ​​the active pharmaceutical ingredients increases hundreds of times, significantly improving transdermal absorption efficiency. Simultaneously, the use of aseptic dressing encapsulation technology ensures both the sterility of the drug and, through the design of a controlled-release membrane, enables controlled drug release. This modern production process retains the core advantages of traditional umbilical therapy while endowing it with the superior characteristics of modern pharmaceutical formulations.

[0024] Eighth, this invention establishes a comprehensive intellectual property protection system. By patenting key technologies such as the specific compatibility ratios of the 11 traditional Chinese medicines, ultrafine grinding process parameters, and β-cyclodextrin inclusion conditions, a robust technology protection network has been formed. In particular, the precise definition of core technical parameters such as the bran-frying process of nutmeg and the CO2 extraction conditions of clove volatile oil effectively prevents the possibility of technology imitation and product substitution.

[0025] Ninth, this invention has significant socio-economic benefits and promising application prospects. Statistics show that approximately 8 million children in my country suffer from spleen and stomach deficiency syndrome each year. If this technology can be promoted to primary healthcare institutions, it is estimated that each child's family can save approximately 3,000 yuan in medical expenses, resulting in annual savings of 2.4 billion yuan in social medical expenditure. Furthermore, the successful application of this technology will promote the modernization of external treatment methods in traditional Chinese medicine, providing new technical support for traditional Chinese medicine to go global.

[0026] Tenth, this invention has significant theoretical innovation value. Through modern pharmacological research, it reveals for the first time the molecular mechanism by which pungent and warm Chinese medicines regulate immune function through the TLR4 / NF-κB signaling pathway, providing a scientific basis for the TCM theory of "external treatment with internal effect." Simultaneously, the established "medicine-acupoint-meridian" three-in-one treatment model enriches the theoretical connotation of TCM external treatment methods and is of great significance for promoting the modern interpretation of TCM theory. Detailed Implementation

[0027] How to use

[0028] This umbilical application is suitable for children with spleen and stomach deficiency-cold syndrome causing symptoms such as diarrhea, abdominal pain, and vomiting. It achieves both symptomatic and root-cause treatment by activating the peritoneal immune network. The following steps must be strictly followed when using it:

[0029] I. Formulation and Preparation

[0030] 1. Prepare the medicinal materials according to the following weight proportions:

[0031] Aromatic dampness-resolving group: Amomum villosum 10-15 parts, Atractylodes lancea 8-12 parts, Pogostemon cablin 6-10 parts, Amomum cardamomum 5-8 parts, Amomum tsao-ko 4-6 parts

[0032] The warming group consists of: cloves 3-5 parts, evodia rutaecarpa 2-4 parts, cinnamon 1-3 parts, galangal 1-2 parts, and pepper 0.5-1.5 parts.

[0033] Astringent and antidiarrheal group: 6-10 parts of roasted nutmeg. All medicinal materials in each group must meet quality control standards, and the content of volatile oils and alkaloids must reach the specified thresholds.

[0034] II. Drug Preparation

[0035] 1. The aromatic dampness-resolving herbs were treated with steam distillation to extract volatile oils, and the resulting transparent, pale yellow liquid was collected for later use.

[0036] 2. The active ingredients of the Wenli group medicinal materials were obtained by supercritical CO2 extraction, with the extraction pressure controlled at 35 MPa and the temperature at 45℃.

[0037] 3. The remaining medicinal materials are subjected to ultra-fine pulverization to achieve a particle size ≤30μm, then sieved and sealed for storage.

[0038] 4. Mix the volatile oil and ultrafine powder in a certain proportion, and add β-cyclodextrin for inclusion treatment, achieving an inclusion rate of over 82%.

[0039] 5. The final mixture is aseptically dispensed, with each dressing containing 0.5g ± 0.05g of medication.

[0040] III. Umbilical Application Procedure

[0041] 1. Clean the navel area before use, wiping away dirt and oil with saline solution.

[0042] 2. Apply a single dose of umbilical dressing evenly to the center of the sterile dressing, forming a medicated film with a diameter of 3cm.

[0043] 3. Secure the dressing with breathable medical tape, ensuring the edges extend 1cm beyond the umbilicus to prevent slippage.

[0044] 4. Change the dressing every morning upon waking, observing the condition of the skin around the navel during the change.

[0045] IV. Combined Treatment

[0046] 1. Applying the oval dressing to the navel while simultaneously using far-infrared irradiation as an adjunct therapy:

[0047] Using an 808nm infrared light source

[0048] Irradiation power 2W / cm 2

[0049] Twice a day, 20 minutes each time.

[0050] Irradiate at a distance of 30cm from the skin, aiming for a warm sensation.

[0051] 2. Keep the navel area dry during treatment, and avoid contact with water and chemical irritants.

[0052] V. Treatment Course Management

[0053] 1. During an acute attack, it is recommended to treat continuously for 7 days as one course of treatment.

[0054] 2. After symptoms subside, enter the consolidation phase and the application can be adjusted to every other day.

[0055] 3. After the complete course of treatment is completed, a 3-day interval is required before starting the next cycle of treatment.

[0056] 4. During treatment, the frequency, consistency, and changes in accompanying symptoms of bowel movements should be recorded.

[0057] VI. Quality Control

[0058] 1. The processing parameters for medicinal materials must be strictly followed:

[0059] Amomum villosum is dried at a low temperature (≤60℃).

[0060] Cinnamon needs to be sliced ​​and air-dried.

[0061] When stir-frying nutmeg with wheat bran, the ratio of wheat bran to medicinal herbs should be maintained at 1:0.8.

[0062] 2. Finished products must pass the following tests:

[0063] Volatile oil content ≥ 2.5% (steam distillation method)

[0064] Total alkaloid content ≥1.8% (HPLC method)

[0065] Microbial limits meet the standards of the Chinese Pharmacopoeia.

[0066] VII. Precautions

[0067] 1. A skin sensitivity test is required for first-time use. Observe for 2 hours; if no redness or swelling is observed, you can continue.

[0068] 2. If a localized burning sensation occurs, the application time can be shortened to 4 hours.

[0069] 3. Avoid raw, cold, and greasy foods while taking this medication, and avoid getting your abdomen cold.

[0070] 4. If severe skin allergies occur, discontinue use immediately and seek medical attention.

[0071] Example 1: Treatment Case of Diarrhea in Children with Spleen and Stomach Deficiency and Cold

[0072] A 3-year-old boy, surnamed Wang, presented with diarrhea lasting 10 days after consuming raw or cold food. He had 6-8 bowel movements per day, with loose stools containing undigested food, accompanied by a sallow complexion, cold extremities, and a pale tongue with a white, greasy coating. Laboratory tests ruled out bacterial infection, and he was diagnosed with spleen and stomach deficiency-cold syndrome. He was treated with the umbilical application solution of this invention: after cleaning the navel, 0.5g of the solution was evenly applied to a sterile dressing and secured with gauze. The dressing was changed once daily, and the navel was simultaneously irradiated with 808nm infrared light twice daily for 20 minutes each time. After 3 days of treatment, the frequency of bowel movements decreased to twice daily, and the stool became soft; after 7 days, the symptoms completely disappeared, and there was no recurrence during a one-month follow-up. No skin irritation or other adverse reactions occurred during the treatment period.

[0073] Example 2: Comprehensive Intervention for Chronic Mesenteric Lymphadenitis

[0074] The patient, Ms. Zhang, a 5-year-old girl, presented with recurrent periumbilical pain and decreased appetite for 6 months. Ultrasound examination revealed mesenteric lymphadenopathy (maximum diameter 1.2 cm). A phased umbilical application regimen was adopted: during the acute phase, the preparation of this invention was applied daily, combined with infrared light irradiation; after 7 days, the application was changed to every other day, and this was continued for 2 weeks for consolidation. During the treatment, changes in serum inflammatory factors were monitored, and the results showed that IL-6 levels decreased from 45 pg / mL to 18 pg / mL, and TNF-α decreased from 32 pg / mL to 12 pg / mL. After the course of treatment, a follow-up ultrasound showed that the lymphadenopathy had shrunk to 0.5 cm, and the child's appetite and mental state had significantly improved.

[0075] Example 3: Verification of the Processing Technology of Prepared Nutmeg

[0076] Prepared nutmeg according to the process described in claim 4: Take 10 kg of cleaned nutmeg and 8 kg of wheat bran and stir-fry together, controlling the temperature at 180-200℃, until the wheat bran turns brown. High-performance liquid chromatography (HPLC) analysis showed that the myristicin content decreased from 0.8% to 0.3% after processing, while the methyl eugenol content increased from 0.5% to 1.2%. Animal experiments showed that the intestinal propulsion rate of mice in the processed product group was 35% higher than that in the raw product group, confirming that the wheat bran stir-frying process effectively enhances the astringent and antidiarrheal effects.

[0077] Example 4: Quality Control of Ultrafine Grinding Technology

[0078] The medicinal materials, including Amomum villosum and clove, were subjected to ultrafine pulverization, with D90 particle size ≤30μm. In vitro transdermal diffusion experiments showed that the cumulative drug permeation of the ultrafine powder group was 4.2 times higher than that of the ordinary pulverized group, with a 24-hour transdermal rate of 21.6μg / cm³. 2 Stability studies showed that after being stored in a sealed container at 4°C for 6 months, the volatile oil content of the ultrafine powder decreased by less than 5%, meeting the requirements for formulation stability.

[0079] Example 5: Validation of Multi-Target Immune Regulation

[0080] Flow cytometry was used to detect peripheral blood T lymphocyte subsets in children after umbilical cord application treatment. Results showed that the proportion of CD4+ cells increased from 28% to 41%, while the proportion of CD8+ cells decreased from 22% to 16%, and the CD4+ / CD8+ ratio returned to normal (1.8±0.3). ELISA was used to detect mucosal slgA concentration, which increased from 0.9 mg / mL to 2.8 mg / mL after 7 days of treatment, indicating a significant enhancement of the intestinal local immune barrier function. Molecular biology experiments showed that the expression level of p-IκBα, a protein related to the TLR4 / NF-κB pathway, decreased by 42%, confirming that the immune regulation mechanism is related to pathway inhibition.

[0081] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine umbilical application for activating the peritoneal immune network and its preparation method, characterized in that: It is prepared by ultra-fine pulverization of the following pungent and warm Chinese herbal medicines in parts by weight: Aromatic dampness-resolving group: Amomum villosum 10-15 parts, Atractylodes lancea 8-12 parts, Pogostemon cablin 6-10 parts, Amomum cardamomum 5-8 parts, Amomum tsao-ko 4-6 parts; Wenli group: 3-5 parts cloves, 2-4 parts evodia, 1-3 parts cinnamon, 1-2 parts galangal, 0.5-1.5 parts pepper; Astringent and antidiarrheal group: 6-10 parts of roasted nutmeg. The above components are ultra-finely pulverized to a particle size ≤30μm and then mixed evenly.

2. The traditional Chinese medicine umbilical application for activating the peritoneal immune network according to claim 1 and its preparation method, characterized in that: The volatile oil content of the aromatic dampness-resolving herbs was ≥2.5%, determined by steam distillation.

3. The traditional Chinese medicine umbilical application for activating the peritoneal immune network according to claim 1 and its preparation method, characterized in that: The total alkaloid content of the herbs in the Wenli group was ≥1.8%, and was detected by high performance liquid chromatography.

4. The traditional Chinese medicine umbilical application for activating the peritoneal immune network according to claim 1 and its preparation method, characterized in that: The processing method for the prepared nutmeg is as follows: Stir-fry the nutmeg and wheat bran together in a ratio of 1:0.8; Remove from the pan when the bran turns brownish-brown, and sift out the bran. After cooling to room temperature in a cool place, crush it.

5. The traditional Chinese medicine umbilical application for activating the peritoneal immune network according to any one of claims 1-4 and its preparation method, characterized in that: Includes the following steps: a) Weigh out each of the Chinese medicinal herbs according to the proportions; b) The cardamom, cloves, cinnamon, and pepper were subjected to supercritical CO2 extraction to collect the volatile oil components; c) The remaining medicinal materials are ultra-finely pulverized to a particle size ≤30μm; d) Mix the volatile oil obtained in step b) with the powder obtained in step c), and add β-cyclodextrin for inclusion treatment; e) Dispense the medication into breathable medical dressings, with each dressing containing 0.5g ± 0.05g of medication.

6. The application of the traditional Chinese medicine umbilical application preparation for activating the peritoneal immune network according to any one of claims 1-4 and its preparation method in drugs for activating the peritoneal immune network, characterized in that: This can be achieved through the following methods: Increased macrophage phagocytic index by ≥32.7%; Promotes the restoration of the CD4+ / CD8+ ratio of T lymphocytes to normal; Enhances the mucosal immune barrier function of sl gA.

7. The application of the traditional Chinese medicine umbilical application for activating the peritoneal immune network according to claim 6 and its preparation method, characterized in that: The activation mechanism includes: Activate the TLR4 / NF-κB signaling pathway; Upregulates the expression of anti-inflammatory factors such as IL-10 and TGF-β; It inhibits the release of pro-inflammatory factors such as IL-6 and TNF-α.

8. The traditional Chinese medicine umbilical application for activating the peritoneal immune network according to claim 1 and its preparation method, characterized in that: The umbilical application method for treating spleen and stomach deficiency-cold syndrome in children includes the following steps: a) After cleaning the skin around the navel, apply 0.5g of the umbilical application agent as described in claim 1 externally; b) Cover with sterile gauze and secure with medical tape; c) Change the dressing once a day, for a course of treatment lasting 7 days; d) Combined with infrared irradiation (wavelength 808nm, power 2W / cm²) 2 ), 20 minutes daily.

9. The traditional Chinese medicine umbilical application for activating the peritoneal immune network according to claim 8 and its preparation method, characterized in that: The umbilical application solution is applied 24 hours after use: The effectiveness rate in stopping diarrhea is ≥90%. Abdominal pain relief rate ≥85%; Vomiting cessation rate ≥80%.

10. The traditional Chinese medicine umbilical application for activating the peritoneal immune network according to claim 1 and its preparation method, characterized in that: Methods for evaluating the effects of immune regulation include the following detection indicators: Macrophage phagocytosis rate assay (flow cytometry); T lymphocyte subset analysis (fluorescent labeling method); Mucosal slgA concentration detection (ELISA method); Inflammatory factor profiling analysis (multiplex PCR microarray technology).