CN-122005645-A - Application of lupin or lupin extract in preparation of medicines for relieving reproduction toxicity of chemotherapeutic medicines

Abstract

The invention relates to the technical field of medicines, and discloses application of lupin or extract thereof in preparing medicines for relieving reproductive toxicity of chemotherapeutics, wherein the lupin is selected from lupin plants, preferably sweet lupin varieties Jenabillup, and the chemotherapeutics comprise busulfan, cyclophosphamide or cisplatin. The lupin or the extract thereof is administered at a dosage of 0.1-100 mg/kg body weight, the administration period is at least 5 weeks of continuous administration, and experiments show that the lupin can remarkably improve the sperm concentration and sperm motility of a chemotherapy model animal and improve pathological damage of testis tissues, and the mechanism of the lupin relates to the functions of antioxidation, anti-inflammation and anti-apoptosis.

Inventors

• HAO YANAN
• JIA CONGCONG
• WANG XIN
• YANG ZHENG
• SONG ZHIJIE
• CAO YUQING

Assignees

• 山东第一医科大学(山东省医学科学院)

Dates

Publication Date

20260512

Application Date

20260224

Claims (10)

1. 1. Use of lupin or an extract thereof for the manufacture of a medicament for reducing the reproductive toxicity of a chemotherapeutic agent, wherein the lupin is selected from lupin genus plants.
2. 2. Use according to claim 1, characterized in that the lupin is selected from one or more of sweet lupin, lupin angustifolia, lupin white or lupin, preferably sweet lupin variety Jenabillup.
3. 3. The use according to claim 1, wherein the chemotherapeutic agent is one or more of busulfan, cyclophosphamide or cisplatin.
4. 4. The use according to claim 1, wherein the extract is an aqueous extract, an alcoholic extract, an enzymatic extract or a supercritical CO 2 extract.
5. 5. The use of claim 1, wherein the reproductive toxicity comprises one or more of reduced sperm concentration, reduced sperm motility, damaged testis tissue, or apoptosis of spermatogenic epithelial cells.
6. 6. Use according to any one of claims 1 to 5, wherein the lupin or extract thereof is administered in a dose of 0.1-100 mg/kg body weight, preferably 50-100 mg/kg body weight.
7. 7. The use according to claim 6, wherein the administration period is at least 5 weeks of continuous administration and the frequency of administration is once daily.
8. 8. The use according to any one of claims 1 to 5, wherein the pharmaceutical is in the form of an oral liquid, capsule, tablet, granule, powder or functional food.
9. 9. The use according to any one of claims 1 to 5, wherein the medicament further comprises a pharmaceutically acceptable carrier or adjuvant.
10. 10. The use according to any one of claims 1 to 5, wherein the medicament is administered in synchronization with the chemotherapeutic agent or is administered prior to the onset of chemotherapy.

Description

Application of lupin or lupin extract in preparation of medicines for relieving reproduction toxicity of chemotherapeutic medicines Technical Field The invention relates to the technical field of medicines, in particular to application of lupin or an extract thereof in preparing medicines for relieving reproduction toxicity of chemotherapeutic medicines. Background Malignant tumors seriously threaten human health, and chemotherapy is one of the important means for clinically treating malignant tumors at present. Busulfan (Busulfan) is a difunctional alkylating agent, is widely used for treating chronic granulocytic leukemia, bone marrow transplantation pretreatment and the like clinically, and particularly plays an important role in treating children cancers. However, busulfan exerts an antitumor effect and simultaneously produces serious toxic and side effects on normal tissue cells. Researches show that busulfan has remarkable toxic effects on male reproductive systems, and is characterized by reduced sperm concentration, reduced sperm motility and damaged testis tissues, and the serious person can cause permanent infertility. The mechanism of busulfan-induced reproductive toxicity is involved in several aspects. First, busulfan can trigger oxidative stress damage of testis tissue by generating large amounts of Reactive Oxygen Species (ROS), resulting in increased levels of the lipid peroxidation product Malondialdehyde (MDA) with reduced antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) activity. Secondly, busulfan can directly damage testis supporting cells and spermatogenic cells, damage the integrity of spermatogenic epithelium, and inhibit the spermatogenic process. In addition, busulfan can exacerbate reproductive injury by inducing apoptosis, interfering with endocrine regulation, and the like. Other common chemotherapeutics such as cyclophosphamide, cisplatin and the like have obvious reproduction toxicity. Cyclophosphamide as nitrogen mustard alkylating agent can cause testicular atrophy and sperm malformation rate rise, and cisplatin as platinum compound can cause sperm cell DNA damage and apoptosis. The reproductive toxicity of these chemotherapeutics presents a great nuisance to young tumor patients, especially children and adolescent patients in need of fertility. At present, protective measures against the reproductive toxicity of chemotherapeutic drugs are very limited. The fertility preservation is mainly carried out in the clinic by adopting the modes of sperm cryopreservation, testis tissue cryopreservation and the like, but the methods have the advantages of complex operation, high cost and limited applicability to children patients. In the aspect of pharmaceutical intervention, although researches report that certain antioxidants such as vitamin E, N-acetylcysteine (NAC) and the like have a certain protection effect on the reproduction toxicity of chemotherapeutic drugs, the clinical effect and safety of the antioxidants still need to be further verified. Therefore, the development of safe and effective auxiliary drugs for relieving the reproductive toxicity of chemotherapeutic drugs has important clinical value and social significance. Natural products are widely focused in the field of chemotherapy toxic and side effect protection due to the characteristics of multiple targets and low toxicity. In recent years, various plant extracts have been found to have protective effects on chemotherapy-induced reproductive lesions. For example, trogopterus dung extract can reverse busulfan-induced testis damage by activating arginine biosynthetic pathway, alleviating oxidative stress and inflammatory response. However, these studies have focused on compound or single compound of traditional Chinese medicine, and relatively few studies have been conducted on edible plant materials with rich nutrition and high safety. Lupinus (Lupinus) is a collective term for leguminous lupin plants, more than 400 species worldwide, and is mainly distributed in Mediterranean regions, america and africa. As an important edible bean, lupin has the nutrition characteristics of high protein content, low fat content, rich dietary fiber and the like. Lupin (Lupinus angustifolius), also known as blue lupin, is one of the biggest cultivated species of lupin in the world at present. Sweet lupin varieties obtained by breeding improvement, such as Jenabillup cultivated in australia, have the advantages of low alkaloid content (less than 500 mg/kg), good palatability, high safety and the like, and have been widely used in the food and feed industries. Modern research has shown that lupins are rich in a variety of bioactive components. The protein content can reach 35-45%, contains all amino acids essential to human body, and is especially rich in leucine and lysine. Lupin also contains rich polyphenol compounds including flavonoids (luteolin, apigenin, isoflavone), phenolic acids (protocatechuic acid, p