Traditional Chinese medicine compound xanthium sibiricum composition as well as preparation method and application thereof

Abstract

The invention discloses a traditional Chinese medicine compound xanthium sibiricum composition as well as a preparation method and application thereof. The traditional Chinese medicine compound xanthium sibiricum composition comprises xanthium sibiricum, radix angelicae, magnolia flower and mint. The preparation method comprises the following steps: S1, taking 6-10 parts by mass of fructus xanthii, 6-10 parts by mass of radix angelicae, 6-10 parts by mass of flos magnoliae and 6-10 parts by mass of mint, drying, and mixing to obtain a mixed raw material; and S2, adding 7-16 times of distilled water into the mixed raw material, soaking in cold water, decocting with big fire until boiling, decocting with small fire for half an hour, filtering, collecting liquid medicine, adding 5-14 times of distilled water into medicine residues, and decocting with the same method. Combining the two liquid medicines, concentrating under reduced pressure, and drying in an air dry oven to obtain a water-extracted dry extract of the four medicinal materials; according to the preparation method of the traditional Chinese medicine composition granules, research is carried out around the preparation process and the quality standard, a medicine which is reasonable in process, reliable in quality, stable and effective is provided for clinical treatment of allergic rhinitis, effective components in the medicinal materials are fully extracted, and the curative effect of the traditional Chinese medicine composition granules for resisting allergic rhinitis is definite.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine compositions, in particular to a traditional Chinese medicine compound Xanthium sibiricum composition and a preparation method and application thereof. Background Art

[0002] Allergic rhinitis is an inflammatory disease of the nasal mucosa mediated by IgE after the body contacts allergens. It is the main chronic inflammatory disease of the respiratory tract in clinical practice and one of the most common allergic diseases. The main symptoms are repeated sneezing, runny nose, nasal congestion and itching, which may be accompanied by red eyes and tears. It is also a high-risk factor for complications such as bronchial asthma, sinusitis, nasal polyps, and otitis media. Due to the complex pathogenesis of AR, it is difficult to completely cure it clinically. The main drugs used in the clinical treatment of AR in modern medicine, such as glucocorticoids, antihistamines, leukotriene receptor antagonists, decongestants, mast cell membrane stabilizers, anticholinergic drugs, etc., can effectively improve the symptoms of patients, but the clinical treatment effect is still not ideal, there are many adverse reactions, the effect is poor in improving the accompanying symptoms, it is easy to relapse, the long-term effect is poor, it is dependent, and it may even cause adverse consequences such as drug-induced rhinitis, and the price is high. Therefore, it is necessary to develop long-acting and low-toxic therapeutic drugs.

[0003] Therefore, a Chinese medicinal compound Xanthium sibiricum composition and a preparation method and application thereof are proposed. Summary of the invention

[0004] The purpose of the present invention is to provide a traditional Chinese medicine compound Xanthium sibiricum composition and a preparation method and application thereof.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] The invention discloses a traditional Chinese medicine compound Xanthium sibiricum composition, which comprises Xanthium sibiricum fruit, Angelica dahurica, Magnolia officinalis and mint.

[0007] The second object of the present invention is to provide a method for preparing a Chinese medicine compound Xanthium sibiricum composition, comprising the following steps:

[0008] S1, taking 6-10 parts by weight of Xanthium sibiricum, 6-10 parts by weight of Angelica dahurica, 6-10 parts by weight of Magnolia officinalis, and 6-10 parts by weight of Menthus officinalis, drying them and mixing them to obtain a mixed raw material;

[0009] S2, add 7-16 times of distilled water to the mixed raw materials, soak in cold water, boil over high heat, then simmer for half an hour over low heat, filter, collect the liquid, add 5-14 times of distilled water to the residue, and boil in the same way. Combine the two liquids, concentrate under reduced pressure, and dry in a blast drying oven to obtain the water-extracted dry extract of the four medicinal materials;

[0010] S3, crushing the dry extract, sieving, mixing with auxiliary materials, preparing soft material, granulating, drying, and granulating to obtain the Chinese medicine compound Xanthium sibiricum composition

[0011] Preferably, in step S1, the mass ratio of Xanthium sibiricum, Angelica dahurica, Flos Magnoliae, and Mentha is 1:1:1:1.

[0012] Preferably, step S2 is specifically as follows: adding distilled water with a volume 10 times that of the mixed raw materials to the mixed raw materials, soaking for 1 hour, decocting over high heat until boiling, then decocting over low heat for half an hour, filtering, collecting the medicinal liquid, adding 8 times the distilled water to the residue, decocting in the same way, combining the two medicinal liquids, and concentrating under reduced pressure to obtain a dry extract.

[0013] Preferably, the step S3 is specifically as follows: crushing the dry extract, passing through an 80-mesh sieve, adding 20% ​​lactose and mixing evenly, then adding 0.4 times of 90% ethanol to make a soft material, granulating with a 14-mesh sieve, drying at 60° C., passing through a 12-mesh sieve to obtain granules.

[0014] The third object of the present invention is to provide a Chinese medicinal compound Xanthium sibiricum composition prepared by the above method for use in treating allergic rhinitis.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] The present invention provides a preparation method of the above-mentioned Chinese medicine composition granules, and studies are conducted around its preparation process and quality standards, so as to provide a drug with reasonable process, reliable quality, stable and effective for the clinical treatment of allergic rhinitis. The effective ingredients in the medicinal materials are fully extracted, and the curative effect of the anti-allergic rhinitis is clear. The compound granules obtained thereafter have uniform particle size, stable quality and controllable quality. Xanthium sibiricum, Angelica dahurica, Flos magnoliae and Mentha are all classical prescriptions commonly used in the clinical treatment of allergic rhinitis. Experimental studies are conducted on the extraction process and efficacy thereof, and the effect of the treatment of allergic rhinitis is clarified. And through prescription analysis and molding process optimization, a reasonable and feasible method for preparing granules is provided, and the granules obtained by the method have qualified quality, are easy to carry, and have little side effects, are safe and inexpensive, so as to meet market demand; the present invention can affect the Th1 / Th2 cell balance by regulating the release of IgE and IL-4 in the body, reduce the release of histamine and improve the clinical symptoms of allergic rhinitis, and then play the role of treating allergic rhinitis. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is the mouse behavioral index result provided by the embodiment of the present invention;

[0018] Figure 2 This is the microscopic observation result of HE staining of mouse nasal mucosa provided in the embodiment of the present invention;

[0019] Figure 3It is the mouse thymus organ index result provided in the embodiment of the present invention;

[0020] Figure 4 It is the mouse spleen organ index result provided in the embodiment of the present invention;

[0021] Figure 5 The results of IgE content in mouse serum provided in the embodiments of the present invention;

[0022] Figure 6 The results of IL-4 content in mouse serum provided in the examples of the present invention;

[0023] Figure 7 The results of IFN-γ content in mouse serum provided in the examples of the present invention;

[0024] Figure 8 The results of histamine content in mouse serum provided by the embodiments of the present invention;

[0025] Fig. 9 is the comprehensive weighted scoring formula using the L9 (34) orthogonal test method in Example 2 of the present invention;

[0026] Fig.10 is the factor level table in Example 2 of the present invention;

[0027] Fig.11 It is the evaluation index formula of ethanol usage in Example 2 of the present invention. DETAILED DESCRIPTION

[0028] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] The invention discloses a traditional Chinese medicine compound Xanthium sibiricum composition and a preparation method and application thereof.

[0030] Example 1 Extraction process

[0031] Take 10 parts by weight of each of the four medicinal materials of stir-fried Xanthium sibiricum, Angelica dahurica, Flos Magnoliae, and Mentha, and mix them to obtain a mixed raw material. Add distilled water 10 times the volume of the mixed raw material to the mixed raw material, soak for 1 hour, boil over high heat, turn to low heat and boil for half an hour, filter, collect the liquid medicine, add 8 times the distilled water to the residue, boil in the same way, and combine the two liquid medicines. Put the liquid medicine into a round-bottom flask, install the round-bottom flask on a rotary evaporator, start the rotary evaporator to evaporate the filtrate in the round-bottom flask, evaporate the filtrate to a thick extract, and obtain a preparatory paste. Put the preparatory paste into a 50°C oven for drying and take it out to obtain a dry extract.

[0032] Example 2 Pharmacodynamic Verification

[0033] (1) Experimental groups

[0034] SPF healthy male ICR mice were adaptively fed for 3 days and randomly divided into 6 groups, 15 mice in each group, namely: normal group, model group, loratadine positive drug group, and Cang Er San low-, medium-, and high-dose drug groups.

[0035] (2) Establishment of AR mouse model and drug administration

[0036] A. Basic sensitization: Except for the normal group, each mouse was intraperitoneally injected with aluminum hydroxide OVA suspension on days 0, 7, and 14 to sensitize the experimental mice. The normal group mice were intraperitoneally injected with equal amounts of normal saline.

[0037] B. Local stimulation and administration: One week after the completion of basic sensitization, the nasal enhancement stimulation phase was entered. Except for the mice in the normal group, the OVA solution was dripped into the bilateral nasal cavities of the mice, 20 μL on each side, and the normal group mice were dripped into each nostril with equal amounts of saline for 7 days. The drug was administered by gavage 30 minutes before each nasal enhancement for 7 days. The mice were killed by cervical dislocation on the last day and the samples were collected.

[0038] C. Modeling evaluation: The local stimulation stage was carried out 7 times in total. In order to preliminarily understand whether the modeling was successful, the last local stimulation in this experiment was recorded, and then the mice were scored based on the number of nose scratching, sneezing, and runny nose.

[0039] (3) Pharmacodynamic evaluation

[0040] A. Behavioral Observation

[0041] Record the number of nasal scratching, sneezing and runny nose within 15 minutes after nasal drip.

[0042] Results Figure 1 It can be seen that compared with the blank group, the nasal symptom score of the model group was significantly increased, which was statistically significant; compared with the model group, the nasal symptom score of the Cangli Powder drug group and the loratadine positive drug group was reduced, which was statistically significant.

[0043] B. After the behavioral observation of pathological changes in the nasal mucosa of mice, the mice were killed by cervical dislocation, and the palatine bones of the nose were quickly separated. The nose was incised along the midline, and the nasal bones and frontal bones were removed to expose the nasal septum and bilateral nasal mucosa. The nasal septum with bilateral nasal mucosa was clamped and fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned for H&E staining. The integrity of the nasal mucosa and the infiltration of inflammatory cells were observed under an optical microscope.

[0044] Results Figure 2In the model group, the basement membrane of the nasal mucosa was partially peeled off, the columnar cell layer was significantly peeled off, and most of the ciliary structure was significantly peeled off. The surrounding glands and small blood vessels proliferated, the tissue was edematous, and there was infiltration of inflammatory cells such as eosinophils and lymphocytes, showing the remodeling characteristics of the nasal mucosal tissue of the mice in the model group; the basement membrane peeling of the Cang Er San group and the loratadine positive drug group was significantly less than that of the model group, the shedding of the columnar cell layer was not as obvious as that of the model group, the ciliary shedding phenomenon was greatly reduced, there was still a little glandular hyperplasia, the blood vessels were slightly dilated, the tissue was edematous, and the tissue remodeling phenomenon was alleviated; the basement membrane of the normal control group was intact, the columnar cell layer was intact, the ciliary structure was also intact, the epithelial cells were neatly arranged, there was no obvious glandular hyperplasia and vascular dilation, and no nasal mucosal tissue remodeling was observed.

[0045] C. Mouse spleen and thymus index After the mice were killed, their spleen and thymus were taken out, weighed and then their spleen and thymus indexes were calculated to evaluate the impact on their immune function.

[0046] Results Figure 3 , 4 It can be seen that compared with the blank group, the organ indexes of thymus and spleen in the model group were significantly increased, which was statistically significant; compared with the model group, the organ indexes of thymus and spleen in the Cangli Powder drug group and the loratadine positive drug group were decreased, which was statistically significant.

[0047] D. Detection of related factors in serum: Eyeballs of anesthetized mice were removed and blood was collected in sodium heparin anticoagulant tubes. The blood was allowed to stand at room temperature for a period of time and then centrifuged at 3000 r / min-1 at 4°C for 10 min. The upper serum was collected and frozen at -80°C. The serum was collected and the levels of IgE, IL-4 and IFN-γ in the serum were detected according to the instructions of the ELISA kit.

[0048] Results Figure 5 , 6 , 7. In the serum of mice, the levels of IgE and IL-4 changed significantly, while the changes of IFN-γ were not obvious. Among them, the levels of IgE and IL-4 in the model group increased, while those in the Cangli Powder group and the loratadine positive drug group showed a downward trend, which was statistically significant.

[0049] E. Determination of histamine content in blood Take the treated serum, prepare the reagent with the relevant number according to the method instructions in the ELISA kit and determine its content.

[0050] Results Figure 8 Compared with the blank group, the histamine content in the model group increased, which was statistically significant; compared with the model group, the histamine content in the Cangli Powder drug group and the loratadine positive drug group decreased, which was statistically significant.

[0051] F. Data Statistical Processing

[0052] SPSS26.0 and Prism 9 software were used for statistical analysis and visualization analysis. The data were expressed as mean ± standard deviation (X ± S). One-way ANOVA was used to analyze the data differences among multiple groups. P < 0.05 indicated statistically significant differences.

[0053] Example 3 Particle Forming Process

[0054] The dry extract of Xanthium sibiricum water extract is crushed to obtain medicinal powder, which is sieved, mixed evenly with auxiliary materials to prepare soft material, granulated, dried, and granulated to obtain the traditional Chinese medicine compound Xanthium sibiricum granules.

[0055] The technical solution of the present invention is further described below in conjunction with the technical route.

[0056] (1) Extraction process research In the extraction process research, the selection of Angelica dahurica and Magnolia officinalis components should be the main criterion. Therefore, the content of imperatorin in Angelica dahurica and magnolia officinalis and the solid yield were used as evaluation indicators, respectively, and a comprehensive weighted score was used.

[0057] A. Detection method of evaluation index: Take the extract of Xanthium sibiricum powder to prepare the test solution, select the index components magnolin and imperatorin in the prescription medicinal materials to prepare the corresponding reference solution, and explore the chromatographic conditions to finally determine the optimal conditions such as wavelength, column temperature, flow rate, mobile phase, etc. Methodological validation is carried out, including: specificity test, linear relationship investigation, precision investigation, repeatability investigation, stability investigation, sample recovery rate determination and sample content determination, etc.

[0058] As shown in Figure 9, the L9 (34) orthogonal test method was used to investigate the water addition multiple, soaking time and extraction times. Through the unified analysis of the data of magnolia linalool, imperatorin and extract yield, the best extraction process was selected based on the comprehensive weighted score, and the process was verified. The factor level table is shown in Figure 10.

[0059] (2) Research on particle forming process

[0060] A. Selection of auxiliary materials

[0061] Take dry extract powder, add soluble starch, microcrystalline cellulose, lactose and dextrin respectively, mix well with the extract powder, add 95% ethanol as a wetting agent to prepare granules, and examine the excipients with molding rate, hygroscopicity, angle of repose and solubility as evaluation indicators.

[0062] B. Selection of auxiliary materials

[0063] The dry paste powder is mixed with different amounts of auxiliary materials. According to the "Technical Requirements for Granules", the ratio of the amount of auxiliary materials used in the formula granules to the dry paste powder generally does not exceed 1:1. Therefore, this study selected auxiliary materials with a proportion of 40%, 30%, 20% and 10% respectively, and the particle forming rate, moisture absorption rate, angle of repose and solubility were used as evaluation indicators to screen the amount of auxiliary materials.

[0064] C. Investigation of ethanol concentration

[0065] Take the auxiliary materials and the dry paste powder and mix them evenly, and use 80%, 85%, 90% and 95% ethanol to granulate them respectively. The concentration of ethanol is screened based on the formation rate, moisture absorption rate and solubility of the granules.

[0066] D. Investigation of ethanol dosage

[0067] like Fig.11 As shown, dry paste powder was added with auxiliary materials, and 0.3 times, 0.4 times, 0.5 times, and 0.6 times of 90% ethanol were added to granulate, and the amount of ethanol was screened based on the granule forming rate, moisture absorption rate, angle of repose and solubility.

[0068] It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above and that the invention can be implemented in other specific forms without departing from the spirit or essential features of the invention. Therefore, the embodiments should be considered exemplary and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description, and it is intended that all variations falling within the meaning and scope of the equivalent elements of the claims be included in the invention. Any reference numeral in a claim should not be considered as limiting the claim to which it relates.

[0069] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A Chinese medicinal compound Xanthium sibiricum composition, characterized in that: Including Xanthium sibiricum, Angelica dahurica, Magnolia officinalis, and mint.

2. A method for preparing the Chinese medicinal compound Xanthium sibiricum composition according to claim 1, characterized in that: The following steps are involved: S1, taking 6-10 parts by weight of Xanthium sibiricum, 6-10 parts by weight of Angelica dahurica, 6-10 parts by weight of Magnolia officinalis, and 6-10 parts by weight of Menthus officinalis, drying them and mixing them to obtain a mixed raw material; S2, add 7-16 times of distilled water to the mixed raw materials, soak in cold water, boil over high heat, then simmer for half an hour over low heat, filter, collect the liquid, add 5-14 times of distilled water to the residue, and boil in the same way. Combine the two liquids, concentrate under reduced pressure, and dry in a blast drying oven to obtain the water-extracted dry extract of the four medicinal materials; S3, the dry extract is crushed, sieved, and evenly mixed with auxiliary materials to make a soft material, which is then granulated, dried, and granulated to obtain a traditional Chinese medicine compound Xanthium sibiricum composition.

3. The method for preparing the Chinese medicinal compound Xanthium sibiricum composition according to claim 2, characterized in that: In the step S1, the mass ratio of Xanthium sibiricum, Angelica dahurica, Flos Magnoliae and Mentha is 1:1:1:

1.

4. The method for preparing the Chinese medicinal compound Xanthium sibiricum composition according to claim 2, characterized in that: The step S2 specifically comprises: adding distilled water with a volume 10 times that of the mixed raw materials to the mixed raw materials, soaking for 1 hour, boiling over high heat, then boiling over low heat for half an hour, filtering, collecting the medicinal liquid, adding 8 times the distilled water to the residue, boiling in the same way, combining the two medicinal liquids, and concentrating under reduced pressure to obtain a dry extract.

5. The method for preparing the Chinese medicinal compound Xanthium sibiricum composition according to claim 2, characterized in that: The step S3 specifically comprises: crushing the dry extract, passing through an 80-mesh sieve, adding 20% ​​lactose and mixing evenly, then adding 0.4 times of 90% ethanol to make a soft material, granulating with a 14-mesh sieve, drying at 60° C., passing through a 12-mesh sieve to obtain granules.

6. A Chinese medicinal compound Xanthium sibiricum composition prepared by the preparation method of the Chinese medicinal compound Xanthium sibiricum composition according to any one of claims 2 to 5, which is used for treating allergic rhinitis.

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