A naked flower of purple gem extract composition and its application

Abstract

The application belongs to the technical field of traditional Chinese medicines, and particularly discloses a naked flower purple perilla extract composition and application thereof.The naked flower purple perilla extract composition comprises, in terms of weight fractions, 1-10 parts of forsythoside B, 15-40 parts of isoviolanthin and 20-35 parts of luteoloside.The forsythoside B, isoviolanthin and luteoloside in the naked flower purple perilla extract composition play a synergistic effect, can treat oral ulcers caused by chemotherapy of tumor patients, can reduce the occurrence of ulcer complications of the tumor patients after chemotherapy and improve the life quality of the tumor patients, and the curative effect is remarkable.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a composition of extract of Callicarpa nudiflora and its application. Background Technology

[0002] Chemotherapy refers to chemical drug therapy, which uses chemotherapeutic drugs to kill cancer cells to achieve therapeutic goals. With the continuous research and development of new chemotherapy drugs, the use of chemotherapy drugs to treat malignant tumors has become a routine treatment method for cancer. However, due to the toxic effects of chemotherapy drugs, cancer patients have a high incidence of mucositis during chemotherapy, resulting in damage to the digestive mucosa such as the oral mucosa, gastric mucosa, and intestinal mucosa, which seriously affects the patient's nutritional intake. Damage to the oral mucosa can lead to oral ulcers, which easily cause oral bacterial infections, thus aggravating the ulcers and creating a vicious cycle. Ulcer symptoms after chemotherapy not only directly affect the patient's quality of life, but can also lead to the interruption or even failure of chemotherapy due to severe mucosal reactions. Therefore, the treatment and care of ulcers after chemotherapy in cancer patients are increasingly attracting attention.

[0003] Currently, traditional Chinese medicine methods for treating chemotherapy-related mucosal damage are used clinically. However, the efficacy of these methods varies greatly, and the overall treatment effect is not ideal. There is still a lack of specific treatment methods and drugs in clinical practice. Chemotherapy-induced mucosal damage seriously affects the quality of life and prognosis of cancer patients, making its prevention and treatment an important clinical issue. Researching and developing a drug with significant preventive and therapeutic effects against chemotherapy-induced mucosal damage is an urgent clinical problem to be solved.

[0004] The roots, stems, and leaves of *Callicarpa nudiflora*, a plant in the Verbenaceae family, contain condensed tannins, flavonoid glycosides, neutral resins, phenols, polysaccharides, hydroxyl compounds, and magnesium, calcium, and iron salts. They possess various functions including anti-inflammatory, detoxifying, astringent, hemostatic, and analgesic effects. *Callicarpa nudiflora* can reduce capillary permeability, exhibiting a significant vasoconstrictive effect. It can inhibit the growth of various bacteria such as *Staphylococcus aureus*, *Streptococcus*, *Salmonella typhi*, and *Pseudomonas aeruginosa*, preventing secondary infections and providing anti-infection benefits. It also has a significant anti-inflammatory response to early inflammatory exudation and swelling, accelerating the absorption of wound exudate and promoting epithelial growth and wound healing. Furthermore, *Callicarpa nudiflora* dispersible tablets also have antiviral effects. Due to its broad pharmacological effects, it is used in the treatment of various skin diseases, such as acne vulgaris, herpes zoster, eczema, contact dermatitis, allergic dermatitis, allergic purpura, cutaneous vasculitis, and post-liquid nitrogen cryotherapy. Chinese patent application CN111671827A discloses the application of *Callicarpa nudiflora* extract in the preparation of drugs for relieving ulcerative colitis. The *Callicarpa nudiflora* extract, by weight, comprises 20-50 parts total flavonoids of *Callicarpa nudiflora*, 15-25 parts total phenylethanol glycosides of *Callicarpa nudiflora*, and 1-5 parts polysaccharides of *Callicarpa nudiflora*. The *Callicarpa nudiflora* extract provided by this invention can effectively treat ulcerative colitis, with good therapeutic effect and safety. However, no research has yet found its use in the preparation of drugs for treating ulcers caused by chemotherapy in cancer patients. Summary of the Invention

[0005] Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “described” as used herein include both singular and plural indicators. Numerical ranges expressed by endpoints include all numerical values ​​and fractions within the corresponding range, along with the expressed endpoints.

[0006] This invention addresses the problems existing in the prior art by providing a composition of Callicarpa nudiflora extract and its application. In this composition, forsythoside B, isorhizonoside, and luteolin have a synergistic effect. By controlling the dosage of forsythoside B, isorhizonoside, and luteolin, oral ulcers caused by chemotherapy in cancer patients can be treated.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] On one hand, the present invention provides a composition of extract of Callicarpa nudiflora, comprising, by weight, 1-10 parts of forsythoside B, 15-40 parts of isorhamnetin and 20-35 parts of luteolin.

[0009] Preferably, the weight ratio of forsythoside B, isorhizonoside and luteolin is 1-3:15-20:25-30.

[0010] Preferably, the composition of the naked flower purple artichoke extract comprises, by weight, 2 parts forsythoside B, 18 parts isopropanol and 25 parts luteolin.

[0011] Preferably, the preparation method of the Naked Flower Purple Callicarpa extract composition includes: mixing the prescribed amounts of isorhamnetin, forsythoside B and luteolin to obtain the Naked Flower Purple Callicarpa extract composition.

[0012] The present invention also provides a method for preparing the above-mentioned Naked Flower Callicarpa extract composition, comprising mixing isopropanol, forsythoside B and luteolin in the prescribed amounts to obtain the Naked Flower Callicarpa extract composition.

[0013] The present invention also provides the application of the above-mentioned Callicarpa nudiflora extract composition or the above-mentioned method for preparing Callicarpa nudiflora extract composition in the preparation of a drug for treating chemotherapy-induced ulcers.

[0014] Preferably, the ulcer includes at least one of oral ulcer, gastric ulcer, and duodenal ulcer.

[0015] Preferably, the drug comprises pharmaceutically acceptable excipients.

[0016] On the other hand, the present invention provides a medicine comprising the above-described composition of *Callicarpa nudiflora* extract and pharmaceutically acceptable excipients.

[0017] Preferably, the excipients include fillers, binders, disintegrants, lubricants, flow aids, colorants, and sweeteners.

[0018] Preferably, the dosage form of the drug includes capsules, granules, or tablets.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] This invention discovers that forsythoside B, isorhizonol, and luteolin can exert a synergistic effect, and the resulting composition of *Callicarpa nudiflora* extract can treat oral ulcers caused by chemotherapy in cancer patients. It can significantly reduce the number and diameter of oral ulcers, significantly increase serum IL-2 levels, and has a significant therapeutic effect on the phenomenon of oral ulcers caused by immune dysfunction due to decreased IL-2 levels. It can reduce the occurrence of ulcer complications after chemotherapy in cancer patients and improve their quality of life, with significant efficacy. Detailed Implementation

[0021] The present invention will be described below through specific embodiments to make the technical solution of the present invention easier to understand and master. However, the present invention is not limited thereto. The described embodiments are only some embodiments of the present invention, and not all embodiments.

[0022] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0023] Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without inventive effort should fall within the scope of protection of this invention. Unless otherwise specified, the experimental methods described in the following embodiments are conventional methods; the reagents and materials described, unless otherwise specified, are commercially available.

[0024] Luteolin glycoside (CAS: 5373-11-5); Verbascoside (CAS: 61303-13-7); Forsythoside B (CAS: 81525-13-5); Verbascoside (CAS: 61276-17-3); Forsythoside E (CAS: 93675-88-8); Rat IL-2 ELISA kit (purchased from Shanghai Enzyme-Link Biotechnology Co., Ltd., catalog number mlsw_E2138).

[0025] Example 1: A composition of extract from the naked flower Callicarpa purpurea

[0026] By weight, it includes 2 parts forsythoside B, 18 parts isopropanol, and 25 parts luteolin.

[0027] The preparation method is as follows: take isopropanol, forsythoside B and luteolin to mix and obtain the Naked Flower Purple Artemisia extract composition.

[0028] Example 2: A composition of extract from the naked flower Callicarpa purpurea

[0029] By weight, it includes 3 parts forsythoside B, 20 parts isopropanol, and 30 parts luteolin.

[0030] The preparation method is as follows: take isopropanol, forsythoside B and luteolin to mix and obtain the Naked Flower Purple Artemisia extract composition.

[0031] Example 3: A composition of extract from the naked flower Callicarpa purpurea

[0032] By weight, it includes 1 part forsythoside B, 15 parts isopropanol and 25 parts luteolin.

[0033] The preparation method is as follows: take isopropanol, forsythoside B and luteolin to mix and obtain the Naked Flower Purple Artemisia extract composition.

[0034] Example 4: A composition of extract from Callicarpa nudiflora

[0035] By weight, it includes 8 parts forsythoside B, 15 parts isopropanol, and 35 parts luteolin.

[0036] The preparation method is as follows: take isopropanol, forsythoside B and luteolin to mix and obtain the Naked Flower Purple Artemisia extract composition.

[0037] Comparative Example 1: A composition of extract from Callicarpa nudiflora

[0038] By weight, it includes 18 parts verbascoside, 2 parts forsythoside E and 25 parts luteolin.

[0039] The preparation method is as follows: verbascoside, forsythoside E and luteolin are mixed to obtain the Naked Flower Purple Artemisia extract composition.

[0040] Comparative Example 2: A composition of extract from Callicarpa nudiflora

[0041] By weight, it includes 22 parts of isopropanol, 1 part of forsythoside B and 30 parts of luteolin.

[0042] The preparation method is as follows: take isopropanol, forsythoside B and luteolin to mix and obtain the Naked Flower Purple Artemisia extract composition.

[0043] Comparative Example 3: A composition of extract from Callicarpa nudiflora

[0044] By weight, it includes 18 parts of isopropanol and 27 parts of luteolin.

[0045] The preparation method is as follows: take isopropanol and luteolin to mix and obtain the Naked Flower Purple Artemisia extract composition.

[0046] Effect of a combination of extracts of Callicarpa nudiflora on oral ulcers in rats after chemotherapy

[0047] 1. Laboratory animals: SPF-grade Wistar rats (provided by the Experimental Animal Science and Technology Center of Jiangxi University of Traditional Chinese Medicine), weighing 200±20g. Husbandry conditions: temperature 23±2℃, humidity 50-70%, light intensity 150-200Lx, 12-hour light-dark cycle (6:00 AM - 6:00 PM); drinking water was filtered and sterilized tap water, placed in autoclaved water bottles for free access; feed was standard feed for free consumption. Throughout the experiment, humane care was provided according to the 3R principle for laboratory animals.

[0048] 2. Modeling and Grouping: After adaptive feeding, rats were randomly divided into a normal group, a model group, Examples 1-4, and Comparative Examples 1-3, with 6 rats in each group. Except for the normal group, the remaining rats were injected intramuscularly with the chemotherapy drug paclitaxel 3 mg / L, with an injection volume of 50 μL per rat. The normal group received an equal volume of physiological saline. Injections were given once daily for 2 days. Observation revealed that, except for the rats in the normal group, all other rats showed obvious ulcers at the oral model site. Specifically, the ulcers were characterized by central depression, red and swollen edges, and signs of suppuration on the surface, indicating successful modeling.

[0049] After successful modeling, the extract composition of *Callicarpa nudiflora* was prepared into a suspension with an appropriate amount of distilled water and administered to rats in Examples 1-4 and Comparative Examples 1-3 by gavage at a dose of 25 mg / kg, once daily for 5 consecutive days. The model group and the normal group were administered an equal volume of physiological saline by gavage. Five hours after the last administration, the rats were sacrificed, and tissue from the right buccal mucosa of the rats was cut and fixed in 10% neutral buffered formalin solution. The tissue was then dehydrated, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (HE). The histopathological changes and number of ulcers in the oral mucosa were observed under a microscope. The average ulcer diameter of the largest ulcer was measured using a graduated periodontal probe. The specific results are shown in Table 1. The serum IL-2 level was measured using a rat IL-2 ELISA kit before administration and 5 days after administration, with fasting blood samples collected. The specific results are shown in Table 2.

[0050] Table 1. Effects of the extract composition of Callicarpa nudiflora on oral ulcers after chemotherapy.

[0051]

[0052]

[0053] Note: Compared with the normal group, *** indicates P<0.001; compared with the model group, # indicates P<0.05, ## indicates P<0.01, and ### indicates P<0.001.

[0054] The results show that the composition provided in this embodiment of the invention, compared with the model group, can significantly reduce the number of oral ulcers after chemotherapy and can significantly reduce the diameter of oral ulcers. This indicates that the composition provided in this embodiment of the invention has excellent therapeutic effect on oral ulcers after chemotherapy.

[0055] Table 2. Effects of the composition of extracts from *Callicarpa nudiflora* on serum IL-2 levels after chemotherapy.

[0056]

[0057]

[0058] Note: Compared with the normal group, *** indicates P<0.001; compared with the model group, # indicates P<0.05; ## indicates P<0.01.

[0059] As shown in Table 2, the composition provided in this embodiment of the invention can significantly increase serum IL-2 levels compared to the model group, and has a significant effect on treating oral ulcers caused by immune dysfunction due to decreased IL-2 levels.

[0060] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. The use of a composition of extract of *Callicarpa nudiflora* in the preparation of a drug for treating oral ulcers after chemotherapy, characterized in that, The composition of the extract of Callicarpa nudiflora comprises, by weight, 1-10 parts forsythoside B, 15-40 parts isobarbiturin, and 20-35 parts luteolin. The weight ratio of forsythoside B, isorhizonol and luteolin is 1-3:15-20:25-30.

2. The application according to claim 1, characterized in that, The aforementioned Naked Flower Purple Callicarpa extract composition, by weight, comprises: 2 parts forsythoside B, 18 parts isopropanol, and 25 parts luteolin.

3. The application according to claim 1, characterized in that, The preparation method of the Naked Flower Purple Callicarpa extract composition includes: mixing the prescribed amounts of verbascoside, forsythoside B and luteolin to obtain the Naked Flower Purple Callicarpa extract composition.

4. The application according to claim 1, characterized in that, The drug includes pharmaceutically acceptable excipients.

5. The application according to claim 1, characterized in that, The drug is made from the aforementioned Naked Flower Artemisia extract composition and pharmaceutically acceptable excipients.

6. The application according to claim 1, characterized in that, The dosage form of the drug includes capsules, granules, or tablets.

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