Lithospermum ointment and preparation method thereof

Abstract

The invention relates to the technical field of pharmacy, and discloses lithospermum ointment which is prepared from the following raw materials in parts by weight: 10 parts of notopterygium root, 10 parts of divaricate saposhnikovia root, 10 parts of schizonepeta, 10 parts of radix angelicae pubescentis, 10 parts of bupleurum chinense, 10 parts of ligusticum wallichii, 10 parts of honeysuckle, 15 parts of radix sophorae flavescentis, 10 parts of angelica sinensis, 15 parts of radix paeoniae alba, 15 parts of rhizoma atractylodis, 15 parts of frankincense, 15 parts of myrrh, 15 parts of astragalus membranaceus, 15 parts of fructus kochiae, 15 parts of fructus cnidii and 15 parts of lithospermum. The preparation method of the radix arnebiae seu lithospermi ointment comprises the following steps: S1, grinding the traditional Chinese medicines into powder: grinding each medicinal material in the raw material medicines into fine powder; s2, soaking the medicinal powder: uniformly mixing the ground powder, and pouring the mixed powder into tea oil for soaking; s3, filtering medicine liquid: after soaking, separating medicine residues from oil liquid by using filtering equipment to obtain soaked medicine oil; s4, mixing beeswax: mixing the filtered medicinal oil with the beeswax; s5, heating and dissolving; and S6, bottling and cooling. The lithospermum ointment has the effects of diminishing inflammation, relieving pain, repairing wounds, resisting bacteria, diminishing inflammation, clearing away heat and toxic materials and protecting skin.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceuticals, and in particular to lithospermum officinale ointment and a preparation method thereof. Background Art

[0002] Ulcers are a common disease in TCM surgery. They are usually caused by pathogenic bacteria such as Staphylococcus aureus invading the human body, leading to local suppurative infection. In TCM theory, the occurrence of ulcers is often related to factors such as the six exogenous evil toxins, the seven internal injuries, improper diet, and chamber and ventricular injuries. These factors lead to stagnation of qi and blood, disharmony between the Ying and Wei, and obstruction of the meridians, thus causing ulcers.

[0003] The treatment of ulcers usually takes a long time, especially for some deep infections or chronic ulcers, the treatment cycle may be several months or even longer. With the widespread use of antibiotics, some ulcer-causing bacteria have developed drug resistance, making traditional antibiotic treatments less effective. During the treatment of ulcers, if they are not handled properly or the patient's own immunity is low, a series of complications such as sepsis and septicemia may occur. After some ulcer patients are cured, the ulcers may recur due to lifestyle habits, environmental factors or internal diseases. Summary of the invention

[0004] In view of the above-mentioned deficiencies in the prior art, the present invention provides a lithospermum officinale ointment and a preparation method thereof, which solves the problems of long treatment period, easy generation of drug resistance and complications of ulcers in the prior art.

[0005] In order to achieve the above-mentioned purpose of the invention, the technical scheme adopted by the present invention is: a lithospermum officinale paste is made of the following raw materials in weight ratio: 10 parts of Notopterygium wilfordii, 10 parts of Saposhnikovia divaricata, 10 parts of Schizonepeta tenuifolia, 10 parts of Angelica dahurica, 10 parts of Ligusticum chuanxiong, 10 parts of Honeysuckle, 15 parts of Sophora flavescens, 10 parts of Angelica sinensis, 15 parts of White Peony Root, 15 parts of Atractylodes macrocephala, 15 parts of frankincense, 15 parts of Myrrh, 15 parts of Astragalus membranaceus, 15 parts of Kochia scoparia, 15 parts of Cnidium monnieri and 15 parts of lithospermum officinale.

[0006] The invention has the beneficial effects of: honeysuckle clearing away heat and detoxifying, and sophora flavescens drying dampness and killing insects. The combination of the two can not only remove heat and toxins in the body, but also dry dampness and relieve itching, and has a good effect on treating skin diseases, itching and other symptoms caused by damp heat. At the same time, these drugs can also enhance the resistance of the skin and prevent skin infection.

[0007] Angelica sinensis nourishes blood, white peony nourishes blood and softens the liver, and the two complement each other. These medicines can also promote blood circulation, accelerate skin metabolism, and help repair and regenerate the skin.

[0008] Frankincense and myrrh can promote blood circulation, remove blood stasis, reduce swelling and relieve pain. They can also promote the disappearance of inflammation and relieve the pain caused by inflammatory reactions.

[0009] Astragalus can replenish qi and strengthen the exterior, improve the body's immunity and enhance resistance. It can also promote wound healing and accelerate tissue repair.

[0010] Qianghuo, Fangfeng, Jingjie and Duhuo can work synergistically to enhance the overall effect of dispelling wind and relieving exterior symptoms.

[0011] Lithospermum officinale can cool blood and stop bleeding, and can also detoxify and cure rashes. It has a good effect on treating symptoms such as heat toxic sores and measles. With the synergistic effect of other drugs, the efficacy of Lithospermum officinale has been further exerted and improved.

[0012] Furthermore, the preparation method of the above-mentioned Lithospermum officinale paste comprises the following steps:

[0013] S1, Chinese medicine powdering: grind each medicinal material in the raw material into fine powder;

[0014] S2, soaking the powder: mixing the ground powder evenly and pouring it into tea oil to soak;

[0015] S3, filtering the drug liquid: after soaking, use filtering equipment to separate the drug residue and the oil liquid to obtain the soaked drug oil;

[0016] S4, mixing beeswax: mixing the filtered medicinal oil with beeswax;

[0017] S5, heating and dissolving: heat the mixed medicinal oil and beeswax over a low fire, and stir continuously until the beeswax is completely dissolved to obtain lithospermum officinale paste;

[0018] S6, Bottling and cooling: Pour the comfrey paste into a pre-prepared container while it is still hot, and place the container in a cool and ventilated place to cool naturally.

[0019] The beneficial effect of adopting the above further scheme is: grinding the medicinal materials finely can increase the contact area between the medicinal materials and tea oil, thereby improving the dissolution rate of the effective ingredients during the soaking process. Tea oil, as a natural plant oil, has good permeability and moisturizing properties. By soaking the powder in tea oil, the fat-soluble components in the medicinal materials can be effectively extracted, and the moisturizing and maintenance effects of tea oil itself can be used to enhance the protective effect of lithospermum officinale paste on the skin. Filtering the liquid medicine can ensure the purity of the final product. Beeswax, as a natural ingredient, has excellent formability and stability, which can keep the lithospermum officinale paste in a solid state at room temperature, which is easy to carry and use. At the same time, beeswax can also form a protective film on the surface of the paste to prevent the paste from deteriorating due to water evaporation. The process of heating and dissolving ensures the full fusion of beeswax and medicinal oil to form a uniform paste. Using low heat heating and continuous stirring not only avoids the destruction of the medicinal ingredients by high temperature, but also ensures the fineness and uniformity of the paste. By pouring the paste into a pre-prepared container while it is still hot and placing it in a cool and ventilated place to cool naturally, it can be ensured that the paste will not have an uneven internal structure due to temperature gradient during the cooling process.

[0020] Furthermore, in the preparation method of the above-mentioned lithospermum officinale ointment, the mass ratio of S4 traditional Chinese medicine oil to beeswax is 1:2.5.

[0021] The beneficial effect of adopting the above further scheme is that the ratio of medicated oil to beeswax of 1:2.5 helps to form a more solid and stable paste.

[0022] Furthermore, in the preparation method of the above-mentioned lithospermum officinale paste, the ground powder in S2 is immersed in tea oil for two months.

[0023] The beneficial effect of adopting the above further solution is that during the long soaking process, the components in the medicinal materials will be fully integrated with the tea oil to form a stable mixture. This mixture can remain uniform during the subsequent heating and boiling process to avoid component separation or precipitation.

[0024] The beneficial effects of the invention are as follows: the lithospermum ointment has a strong anti-inflammatory effect, can be used to treat symptoms such as skin inflammation, eczema, burns, scalds, etc., and relieve pain and itching; can accelerate the repair and regeneration of wounds, reduce scar formation, and is suitable for treating skin injuries such as trauma and ulcers; the active ingredients in the lithospermum ointment have a certain antibacterial effect, can be used to treat symptoms such as skin infection, furuncle, carbuncle, etc., and effectively kill pathogenic microorganisms; has the effect of clearing away heat and detoxifying, can be used to treat inflammatory skin diseases such as acne, furuncle, etc., and promotes the healing and detoxification of lesions; can form a protective film to prevent further damage to the skin by irritants, and is suitable for solving problems such as skin allergies and itching. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1The present invention is a flow chart of the preparation method of Lithospermum officinale paste;

[0026] Figure 2 The Venn diagram of effective ingredient targets of Lithospermum officinale-Fructus Cnidium-Notopterygium wilfordii-Sophora flavescens-Olibanum-Myrrha and inflammation-related targets;

[0027] Figure 3 It is a network diagram of "traditional Chinese medicine - active ingredients - targets - diseases";

[0028] Figure 4 It is a key core target map;

[0029] Figure 5 This is a GO enrichment analysis diagram;

[0030] Figure 6 This is the KEGG enrichment analysis result diagram;

[0031] Figure 7 This is the docking diagram of PIK3CA and propionylshikonin;

[0032] Figure 8 This is the docking diagram of PIK3CB and propionylshikonin;

[0033] Fig. 9 This is the docking diagram of EGFR and propionylshikonin. DETAILED DESCRIPTION

[0034] The specific implementation modes of the present invention are described below so that those skilled in the art can understand the present invention. However, it should be clear that the present invention is not limited to the scope of the specific implementation modes. For those of ordinary skill in the art, as long as various changes are within the spirit and scope of the present invention as defined and determined by the attached claims, these changes are obvious, and all inventions and creations utilizing the concept of the present invention are protected.

[0035] The present embodiment provides a lithospermum officinale paste, which is prepared from the following raw materials in weight proportion: 10 parts of Notopterygium wilfordii, 10 parts of Saposhnikovia divaricata, 10 parts of Schizonepeta tenuifolia, 10 parts of Angelica dahurica, 10 parts of Ligusticum chuanxiong, 10 parts of Honeysuckle, 15 parts of Sophora flavescens, 10 parts of Angelica sinensis, 15 parts of White Peony Root, 15 parts of Atractylodes macrocephala, 15 parts of frankincense, 15 parts of Myrrh, 15 parts of Astragalus membranaceus, 15 parts of Kochia scoparia, 15 parts of Cnidium monnieri and 15 parts of Lithospermum officinale. Qianghuo, Fangfeng, Jingjie, Duhuo, etc. have the effects of dispelling wind and dampness, as well as relieving pain, and can effectively relieve the itching and pain of the skin caused by rheumatism; honeysuckle and Sophora flavescens have the effects of clearing away heat and detoxifying, and drying dampness, and have a significant effect on alleviating symptoms such as skin inflammation and redness and swelling; Angelica sinensis, white peony, etc. can promote blood circulation and replenish blood, nourish yin and blood, help improve the nutritional status of the skin, and promote skin repair; Astragalus, frankincense, myrrh, etc. have the effects of replenishing qi and blood, promoting blood circulation and removing blood stasis, and can enhance the tissue-regenerating effect of Lithospermum officinale ointment.

[0036] like Figure 1 As shown, the preparation method of Lithospermum officinale paste comprises the following steps:

[0037] S1, Chinese medicine powdering: Grind each medicinal material in the raw material into fine powder.

[0038] S2, soaking medicinal powder: mix the ground powder evenly and pour it into tea oil for soaking. Tea oil, as a natural plant oil, has good permeability and stability, and can effectively promote the dissolution and release of the active ingredients in the medicinal materials. The ground powder is soaked in tea oil for two months, and stirred regularly during this period to ensure that the medicinal powder is in full contact with the tea oil, so as to maximize the extraction of the active ingredients in the medicinal materials. A cool and dry environment should be selected for soaking, and the temperature and humidity should be checked regularly to prevent excessive temperature and humidity from causing the ingredients in the medicinal materials to deteriorate or degrade.

[0039] S3, filtering the medicinal liquid: after soaking, use filtering equipment to separate the medicinal residue and the oil liquid to obtain the soaked medicinal oil.

[0040] S4, mixed with beeswax: the filtered medicinal oil is mixed with beeswax, and the mass ratio of medicinal oil to beeswax is 1:2.5. Beeswax, as a natural wax, has good stability and moisturizing properties, and can effectively enhance the texture and stability of lithospermum ointment.

[0041] S5, heating and dissolving: Heat the mixed medicinal oil and beeswax on a low fire and stir continuously until the beeswax is completely dissolved to form a uniform lithospermum paste. In this process, the temperature must be kept stable and the stirring speed must be uniform to ensure the quality and stability of the lithospermum paste.

[0042] S6, Bottling and cooling: Pour the lithospermum paste into the pre-prepared container while it is still hot, and quickly place the container in a cool and ventilated place for natural cooling. After the lithospermum paste is completely cooled and solidified, it can be sealed for storage and use.

[0043] When used, the lithospermum officinale ointment of the present invention is evenly applied to the patient's sores. In order to evaluate the actual effect of lithospermum officinale ointment, four clinical trial subjects were selected for trial and observation. By observing the symptom changes of the trial subjects in three aspects of skin itching, pain and sores before and after treatment, the itching changes according to the symptom score, and the 4-point distinction standard of skin itching in "Modern Dermatology" and the 3-point scoring method of "Guidelines for Clinical Research of New Chinese Medicines (Trial)" are scored, among which: 0 points for symptom disappearance; 1 point for mild; 2 points for moderate; 3 points for severe. The improvement of skin itching in this embodiment is shown in Table 1:

[0044] Table 1:

[0045] patient Before treatment (minutes) After treatment (minutes) Change (points) Efficacy evaluation Patient one 3 1 -2 Significant improvement Patient two 2 0 -2 Complete remission Patient 3 3 1 -2 Significant improvement Patient 4 2 0 -2 Complete remission

[0046] Pain was assessed using a numerical rating scale that determined the degree of pain on a scale of 0 to 10, with 0 representing no pain and 10 representing severe pain. The numerical rating system can better distinguish the subtle differences in pain intensity. The pain improvement of this example is shown in Table 2:

[0047] Table 2:

[0048] patient Before treatment (level) After treatment (level) Change (level) Efficacy evaluation Patient one 7 3 -4 Significant improvement Patient two 5 2 -3 Significant improvement Patient 3 6 3 -3 Significant improvement Patient 4 5 0 -5 Complete remission

[0049] Ulcers Symptoms The efficacy of Lithospermum officinale paste on ulcers was evaluated by measuring the change in the area of ​​ulcers. A decrease in the area indicated a significant therapeutic effect. The change in the area of ​​ulcers in this example is shown in Table 3:

[0050] Table 3:

[0051] patient <![CDATA[Before treatment (cm 2 )]]> <![CDATA[After treatment (cm 2 )]]> <![CDATA[Change (cm 2 )]]> Efficacy evaluation Patient one 8 4 -4 Significant improvement Patient two 6 2 -4 Significant improvement Patient 3 10 4 -6 Significant improvement Patient 4 5 0 -5 Complete remission

[0052] By comparing the changes before and after treatment, it can be seen that the lithospermum ointment performs well in relieving itching, alleviating pain, and reducing the area of ​​ulcers. It can quickly relieve skin inflammation and itching symptoms and promote the healing and repair of damaged skin. At the same time, the lithospermum ointment does not cause any adverse reactions such as stinging or allergies during use, and has high safety and comfort.

[0053] This example uses network pharmacology and molecular docking technology to explore the potential mechanism of the Chinese medicine combination of Lithospermum officinale, Cnidium monnieri, Notopterygium incisum, Sophora flavescens, Olibanum and Myrrh in the treatment of inflammation. By analyzing the active ingredients of the drugs, predicting targets, building networks, enrichment analysis and performing molecular docking, the molecular action pathways of the multi-component, multi-target combination in the treatment of inflammation are revealed.

[0054] Screening of drug components and targets: Using TCMSP2.3 database and PubChem database, with "lithophane", "Cnidium monnieri", "Notopterygium incisum", "Sophora flavescens", "Frankincense", and "Myrrh" as search keywords, the chemical components and molecular formulas of each drug were obtained. The active ingredients of the drugs were screened out according to oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18, and the simplified molecular input line entry system (SMILES) and 3D structural formula of the isomers corresponding to these ingredients were obtained from the PubChem database. The screened drug component isomer SMILES were imported into the Swiss Target Prediction database to predict human targets related to these drug components, and a total of 457 predicted targets were screened out. As shown in Table 1, they are the effective active ingredients of lithophane-Cnidium monnieri-Notopterygium incisum-Sophora flavescens-Frankincense-Myrrh.

[0055] Table 1:

[0056]

[0057]

[0058] Identification of core inflammation targets and drug-disease common targets: In the seventh version of the disease gene network (DisGeNETv7.0) and the GeneCards database, "inflammation" was used as the keyword to search for inflammation-related genes, and 466 and 13,268 genes were obtained, respectively. By setting the relevance score threshold, the relevance score (relevancescore)>3, 1,306 highly correlated inflammation genes were screened out. The search results of the two databases were merged and deduplicated, and 1,667 inflammation-related targets were finally determined. The Venn diagram was constructed in conjunction with the microbial information platform to identify 267 common targets of drugs and inflammation, such as Figure 2 shown.

[0059] Network construction and analysis: Cytoscape 3.10.2 software was used to construct a "TCM-active ingredient-target-disease" network diagram to intuitively demonstrate the multi-component, multi-target mechanism of action of Lithospermum officinale-Fructus Cnidium-Notopterygium-Sophora flavescens-Olibanum-Myrrh in treating inflammation. Figure 3 As shown in the figure, diamonds represent Chinese medicine, circles represent Chinese medicine ingredients, V-shaped represents common targets, and red hexagons represent diseases. It can be found from the figure that Lithospermum officinale-Cnidium monnieri-Notopterygium incisum-Sophora flavescens-Olibanum-Myrrh can treat inflammation with multiple ingredients and multiple targets. According to the degree of the node, the top five active ingredients in the network are screened out. As shown in Table 2, the information of the top five active ingredients is shown.

[0060] Table 2:

[0061]

[0062] Protein interaction network (PPI) construction: The targets shared by Lithospermum officinale-Cnidium monnieri-Notopterygium incisum-Sophora flavescens-Olibanum-Myrrh and inflammation were recorded and analyzed in the STRING12.0 database. The target corresponding to each gene was selected with the required minimum interaction score and the highest confidence of 0.900 as the selection condition. Each node in the figure represents a protein, and the edge represents the interaction between proteins. The results were saved and imported into Cytoscape3.10.2 software, and the MCODE plug-in was used for calculation. Finally, the top five core target networks with the highest degree values ​​were obtained. The core targets include PIK3CB, PIK3CA, EGFR, IGF1R, PDGFRA, etc. Figure 4 shown.

[0063] GO analysis and KEGG pathway enrichment analysis: Extract genes that intersect drug components and diseases, upload targets in the metascape database, limit species to "human (Homosapiens)", perform GO and KEGG functional enrichment analysis, and screen with P < 0.05 as the value. Each gene has different functions in cellular components and biological pathways. Through GO and KEGG analysis, the 267 genes obtained after the intersection of drugs and diseases are classified by function and the pathways involved. For the GO analysis results, select the top 10 items to draw a bar chart for display, and for the KEGG analysis results, select the top 20 to draw a bubble chart for display, see Figure 5 and Figure 6 . The results of GO analysis showed that Lithospermum officinale-Fructus Cnidium-Notopterygium wilfordii-Sophora flavescens-Olibanum-Complexa oxyphylla can exert anti-inflammatory effects through a variety of biological processes, cellular components and molecular functions. Specifically, the biological processes involved are mainly responses to inflammation. In terms of cellular components, most genes are related to plasma membranes, receptor complexes and membrane rafts. In terms of molecular functions, the functions of most genes are related to the kinase activity of histones H3Y41 and H2AXY142. The results of KEGG analysis showed that pathways such as lipid metabolism, atherosclerosis, and Th17 cell differentiation may be biological pathways through which Lithospermum officinale-Fructus Cnidium-Notopterygium wilfordii-Sophora flavescens-Olibanum-Complexa oxyphylla acts on inflammation and cancer.

[0064] Molecular docking verification: The top five active ingredients screened out were molecularly docked with the core targets propionylshikonin (PIK3CA) (PIK3CB) (EGFR), luteolin (EGFR) (IGF1R), luteolin N (EGFR) (PDGFRA), and norcarbazine (EGFR) (IGF1R). The docking results showed that all of them had good binding activity, among which propionylshikonin was the most stable. Some docking results are as follows Figure 7 to Figure 9 shown.

[0065] This example explores the mechanism of action of Lithospermum officinale-Fructus Cnidium-Notopterygium-Sophora flavescens-Olibanum-Myrrh in treating inflammation through a series of bioinformatics methods. Studies have found that these drug ingredients can regulate inflammation-related pathways in a multi-target manner, thereby exerting anti-inflammatory effects. Among them, core targets such as PIK3CB, PIK3CA, EGFR, IGF1R, and PDGFRA play a key role in the anti-inflammatory process of drugs. In addition, GO analysis and KEGG pathway enrichment analysis reveal that these drug ingredients can exert anti-inflammatory effects by regulating pathways such as lipid metabolism, atherosclerosis, and Th17 cell differentiation. The molecular docking verification results also show that the screened active ingredients have good binding activity with the core targets, which provides strong support for the anti-inflammatory effects of these drug ingredients.

Claims

1. A lithospermum officinale paste, characterized in that: The drug is prepared from the following raw materials in weight ratio: 10 parts of Notopterygium wilfordii, 10 parts of Saposhnikovia divaricata, 10 parts of Schizonepeta tenuifolia, 10 parts of Angelica dahurica, 10 parts of Ligusticum chuanxiong, 10 parts of Honeysuckle, 15 parts of Sophora flavescens, 10 parts of Angelica sinensis, 15 parts of White Peony Root, 15 parts of Atractylodes macrocephala, 15 parts of Frankincense, 15 parts of Myrrh, 15 parts of Astragalus, 15 parts of Kochia scoparia, 15 parts of Cnidium monnieri and 15 parts of Lithospermum officinale.

2. A method for preparing the lithospermum officinale paste according to claim 1, characterized in that: The following steps are involved: S1, Chinese medicine powdering: grind each medicinal material in the raw material into fine powder; S2, soaking the powder: mix the ground powder evenly and pour it into tea oil to soak; S3, filtering the drug liquid: after soaking, use filtering equipment to separate the drug residue and the oil liquid to obtain the soaked drug oil; S4, mixing beeswax: mixing the filtered medicinal oil with beeswax; S5, heating to dissolve: heat the mixed medicinal oil and beeswax over a low fire, and stir continuously until the beeswax is completely dissolved to obtain lithospermum officinale paste; S6, Bottling and cooling: Pour the comfrey paste into a pre-prepared container while it is still hot, and place the container in a cool and ventilated place to cool naturally.

3. The preparation method of Lithospermum officinale paste according to claim 2, characterized in that: The mass ratio of S4 traditional Chinese medicine oil to beeswax is 1:2.

5.

4. The method for preparing Lithospermum officinale paste according to claim 2, characterized in that: The ground powder in S2 was soaked in tea oil for two months.

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