阅读说明：本技术 一种生物碱在制备骨相关疾病药物中的用途 (Application of alkaloid in preparation of medicine for treating bone related diseases ) 是由 夏连科 孙建波 郭方圆 郭江 张伟 扬子来 李清洋 郑春山 胡明涛 黄靖 于 2019-10-13 设计创作，主要内容包括：本发明属于生物医药领域,具体公开了一种生物碱在制备骨相关疾病药物中的用途。其中生物碱选自苦木酮碱、甲基苦木酮碱或四氢鸭脚木碱中的一种。其中苦木酮碱、甲基苦木酮碱对骨关节炎症和骨质疏松显示出改善效果；四氢鸭脚木碱对骨质疏松和外伤骨折愈合中骨痂重建显示出改善效果。所述骨相关疾病药物可以是口服药物、外用药物或静脉注射、皮下注射药物中的一种。(The invention belongs to the field of biological medicines, and particularly discloses application of alkaloid in preparation of a medicine for treating bone related diseases. Wherein the alkaloid is selected from one of picrasma quassioides alkali, methyl picrasma quassioides alkali or tetrahydropicrasma quassioides alkali. Wherein the limonine and the methyllimonine show improvement effect on osteoarthritis and osteoporosis; tetrahydropicatine has been shown to improve callus remodeling in osteoporosis and traumatic fracture healing. The bone-related disease drug can be one of oral drugs, external drugs or intravenous injection drugs and subcutaneous injection drugs.)

1. An application of alkaloid in preparing medicine for treating bone related diseases is disclosed, wherein the alkaloid is one of picrasma quassioides alkali, methyl picrasma quassioides alkali or tetrahydropicrasma picrinine.

2. Use according to claim 1, characterized in that: the medicament for treating the bone related diseases is a medicament for improving osteoporosis, and the alkaloid is one of picrasma quassioides alkali, methyl picrasma quassioides alkali or tetrahydropicrasma picrinine.

3. use according to claim 1, characterized in that: the medicament for treating the bone related diseases is a medicament for promoting callus reconstruction in fracture healing, and the alkaloid is tetrahydropiceidine.

4. Use according to claim 3, characterized in that: the medicine for promoting callus reconstruction in fracture healing is a medicine for promoting callus reconstruction in trauma fracture healing.

5. Use according to claim 1, characterized in that: the bone-related disease medicament is a medicament for relieving osteoarthritis, and the alkaloid is picrasidone alkali or methyl picrasidone alkali.

6. use according to claim 5, characterized in that: the osteoarthritis is one of rheumatoid arthritis, knee osteoarthritis and ankylosing spondylitis.

7. The use according to claims 1-7, characterized in that: the medicament for treating the bone related diseases is one of oral medicaments, external medicaments and intravenous injection medicaments.

8. Use according to claim 7, characterized in that: the medicament for treating the bone related diseases is an intravenous injection medicament or a subcutaneous injection medicament.

9. Use according to claim 7, characterized in that: the medicament for treating the bone related diseases is an oral medicament.

10. Use according to claim 7, characterized in that: the medicament for treating the bone-related diseases is an external medicament.

Technical Field

The invention belongs to the field of biological medicines, and particularly relates to application of alkaloid in preparation of a medicine for treating bone related diseases.

Background

Bone-related diseases including osteoporosis, bone fractures, osteoarthritis, and the like, are a large group of diseases that are common in real life and in clinical practice. With the aging process, the absolute number of patients with osteoporosis and osteoarthritis tends to increase. With the popularization of motor vehicles and the expansion of human living space, fracture accidents caused by traffic accidents, field activities, sports and the like also tend to increase.

Among them, osteoporosis is associated with abnormalities of hormones such as estrogen and thyroxine, and endocrine dysregulation and bone metabolic abnormalities caused by estrogen deficiency and hyperthyroidism in postmenopausal women are common causes of osteoporosis. Some drugs, such as glucocorticoids, also cause osteoporosis with prolonged use. Osteoporosis is also a disease associated with bone calcium and cytokines. Cytokines are involved in the regulation of bone metabolism. In addition, vascular calcium deposition has this inverse relationship with bone calcium deposition. Common anti-osteoporosis drugs include drugs for supplementing or mimicking estrogen, drugs for inhibiting osteoclastic bone resorption, drugs for promoting bone formation, dual-acting drugs, and the like.

Wherein the healing process after fracture comprises hematoma formation, granulation tissue repair, callus formation, and transformation of woven bone into platy bone. Some anti-osteoporosis drugs, such as bisphosphonates, although they promote callus formation and the formed callus is large, they delay callus remodeling and are not conducive to the transformation of the woven bone into the lamellar bone, resulting in delayed or poor fracture healing and increased fracture risk. The healing speed after fracture is fast and slow, and the local blood supply is also concerned. Therefore, resting is not conducive to fracture recovery. Partial fractures are caused by osteoporosis and are called fragility fractures. Research shows that the healing process and characteristics of osteoporosis fracture and young and strong fracture are different.

Among them, osteoarthritis mostly occurs at the position of a long bone joint, and some diseases also occur at the spinal joint and the finger joint. This bone joint inflammation is associated with an excessive increase in cytokines at the site of onset.

Currently, the clinical application of drugs for osteoporosis, bone fracture and osteoarthritis is limited.

the picropodophylline, methylpicropodophylline or tetrahydropicraline are alkaloids present in medicinal plants. The reported effects of tetrahydropiceide include anti-cerebral ischemia, anti-arteriosclerosis, antibacterial, and blood sugar lowering effects. In addition to antibacterial effects, the picropodophylline and methylpicropodophylline have been found to have new effects. In addition, alkaloids have a wide range of activities and have been widely reported in bone-related diseases including osteoporosis, fracture healing, arthritis, and the like. 97197563.9, 98813791.7, 00811597.4, 201110326731.1 and other Chinese patents disclose the use of some alkaloids in bone related diseases.

Disclosure of Invention

In view of the above problems, the present invention aims to provide an application of alkaloid in preparing a medicament for treating bone related diseases, which provides more options for treating diseases.

The main content of the invention is as follows:

An application of alkaloid in preparing medicine for treating bone related diseases is disclosed, wherein the alkaloid is one of picrasma quassioides alkali, methyl picrasma quassioides alkali or tetrahydropicrasma picrinine.

In a first aspect, the bone-related disease drug is a drug for improving menopausal osteoporosis, and the alkaloid is one of picrasidone, methylpicrasidone or tetrahydropicrinine.

Wherein, in the second aspect, the bone-related disease drug is a drug for promoting callus reconstruction in fracture healing, and the alkaloid is tetrahydropiceide. Further, the medicament for promoting callus reconstruction in fracture healing is a medicament for promoting callus reconstruction in traumatic fracture healing. Herein, traumatic fracture refers to non-osteoporotic fracture or fracture accompanied by osteoporosis.

In the third aspect, the bone-related disease drug is a drug for alleviating osteoarthritis, and the alkaloid is a picrasidone base or a methylpicrasidone base. Further, the osteoarthritis is one of rheumatoid arthritis, knee osteoarthritis and ankylosing spondylitis.

In a specific application aspect, the bone-related disease drug is one of an oral drug, an external drug, an intravenous injection drug and a subcutaneous injection drug.

In the specific application aspect, the dosage of the picrasma quassioides alkali and the methylpicrasma quassioides alkali in treating bone related diseases can be 10-40 mg/kg; the dosage of the tetrahydropiceide for treating bone related diseases can be 3-30 mg/kg.

Wherein the said picrasma quassioides ketone alkali is also called picrasma quassioides alkali; methyl-picrasidone base is a derivative of picrasidone base, which is the product of the replacement of the hydrogen of the hydroxyl group of picrasidone base into a methyl group.

Wherein the tetrahydropiceide is also called tetrahydropiceide.

In animal research, the picropodophylline has an improvement effect on osteoporosis and arthritis, and the tetrahydropiceidine has an improvement effect on osteoporosis and fracture healing. The picropodophylline, tetrahydropiceidine and their derivatives and analogs have potential application value in bone related diseases.

Detailed Description

The technology of the present invention is further shown and described by way of examples below. The examples are not to be construed as limiting the scope of protection. In the demonstration of the embodiment, the simple substitution made should be regarded as the protection scope of the invention.