Application of nicotinamide mononucleotide in preparation of medicine for preventing or treating NT-proBNP abnormity

Abstract

The invention relates to the field of medicines, in particular to application of nicotinamide mononucleotide in preparation of a medicine for preventing or treating NT-proBNP abnormality. By orally taking NMN to treat abnormal dogs, the level of NT-proBNP can be effectively reduced, so that heart failure is found earlier, heart function classification is reflected, heart functions are improved, and the early diagnosis and treatment effects on heart diseases are improved.

Description

Technical Field

[0001] The present invention relates to the field of medicines, and in particular to the use of nicotinamide mononucleotide in preparing medicines for preventing or treating abnormal NT-proBNP. Background Art

[0002] Under normal circumstances, myocardial cells will secrete probrain natriuretic peptide (proBNP) into the blood circulation when they are under stress or ischemia. This hormone plays an important role in regulating blood pressure and maintaining water and salt balance. However, when myocardial cells are under excessive stress or ischemia, proBNP will break down into BNP and N-terminal probrain natriuretic peptide (NT-proBNP), both of which will enter the blood circulation. Among them, NT-proBNP has a longer half-life than BNP and a higher concentration in the body than BNP, so it can better reflect the condition, detect heart failure earlier, and reflect the grade of heart function.

[0003] As for the treatment of abnormally elevated NT-proBNP, there is no clear solution yet. The existing technology for dealing with abnormal NT-proBNP has the following main problems: First, for the treatment of abnormally elevated NT-proBNP, the current methods are mainly to improve heart function, control primary diseases, etc., but these methods often cannot effectively reduce the level of NT-proBNP. Secondly, although some studies have shown that nicotinamide mononucleotide (NMN) may improve heart function by improving the energy metabolism of cardiomyocytes, there is currently no research on the effect of NMN on abnormal NT-proBNP.

[0004] On the other hand, elevated BNP / NT-proBNP levels do not necessarily indicate decompensated heart failure or impending decompensation, because patients with clinically stable heart failure are often accompanied by elevated BNP / NT-proBNP levels. BNP / NT-proBNP levels may also be elevated in patients with acute coronary syndrome, various hyperdynamic states (sepsis, hyperthyroidism, cirrhosis, etc.), and severe lung diseases (pulmonary embolism, pulmonary hypertension). Similarly, normal BNP / NT-proBNP cannot completely rule out heart failure, such as patients with constrictive pericarditis even if they have heart failure. Therefore, in dealing with the problem of abnormal NT-proBNP, the existing technology for improving cardiac function does not necessarily effectively reduce NT-proBNP levels. Summary of the invention

[0005] The purpose of the present invention is to provide the use of nicotinamide mononucleotide in preparing a drug for preventing or treating abnormal NT-proBNP.

[0006] The beneficial effects of the present invention are:

[0007] Oral NMN treatment of abnormal dogs can effectively reduce the level of NT-proBNP, thereby detecting heart failure earlier and reflecting the grade of heart function, improving heart function, and enhancing the early diagnosis and treatment of heart disease. DETAILED DESCRIPTION

[0008] In order to make the technical scheme of the present invention more clearly understood by those skilled in the art, the following embodiments are listed for illustration. It should be pointed out that the following embodiments do not limit the protection scope of the present invention.

[0009] Unless otherwise specified, the raw materials, reagents or devices used in the following examples and comparative examples can be obtained from conventional commercial sources or by existing known methods.

[0010] The NMN active ingredient used in the examples (the purity of NMN is over 99%).

[0011] Study subjects: The 6 experimental animals in the following examples are dogs with abnormally elevated NT-proBNP during physical examination or clinical examination, some of which have no clinical symptoms, and some have obvious heart disease and other underlying diseases. The basic information is shown in Table 1. Dogs No. 1, No. 2 and No. 3 were all found to have elevated NT-proBNP during physical examination: NT-proBNP was re-examined about 2 weeks later, and it was found that both were elevated compared to the first examination. Both dogs had no other clinical symptoms and no abnormalities in physical examination. Dogs No. 2 and No. 3 were found to have elevated NT-proBNP during routine follow-up examinations. Except for the underlying disease, no other physical examinations were abnormal, and there were no organic changes in the heart. Dog No. 6 is a chronic kidney disease patient who has been receiving subcutaneous fluid infusion and oral kidney disease medication for a long time. During routine follow-up examinations, abnormally elevated NT-proBNP was found, but there were no organic changes in the heart.

[0012] Research methods: Examine the dogs that come to the clinic, and conduct different examinations according to different clinical symptoms. For dogs with abnormal NT-proBNP found during physical examination and examination, if there are no other underlying diseases, only take NMN orally. If there are other clinical symptoms, take NMN orally at the same time during treatment. Take NMN orally at a dose of 10-30 mg / time, twice a day, according to the weight of the animal, check NT-proBNP every 2-3 weeks, and continue to use the medicine for 3 months (stop the medicine when the index returns to normal). Record the changes in NT-proBNP before and after medication.

[0013] Table 1 Basic information of experimental dogs

[0014] Serial number age gender weight Clinical symptoms 1 9 years old female 2.8kg Intermittent diarrhea, dental calculus, elevated NT-proBNP in preoperative physical examination 2 6 years old female 28kg Physical examination revealed elevated NT-proBNP, but no other abnormalities were found 3 12 years old female 14.7kg Physical examination revealed abnormal NT-proBNP 4 12 years old female 6.3kg Polycythemia, allergic dermatitis 5 13 years old female 4.4kg Cough, fainting 6 15 years old male 14.5kg Chronic kidney disease .

[0015] Example 1

[0016] The use of NMN by Dog No. 1 in Example 1 is shown in Table 2.

[0017] Table 2 Medication and NT-proBNP changes in dog No. 1

[0018]

[0019] Dog No. 1 took 10 mg / time, bid for the first time and was re-examined about one month later. The NT-proBNP level was slightly higher than before, so the NMN dose was doubled. After about one and a half months of continuous oral administration, the NT-proBNP level returned to normal. However, the NT-proBNP level was increased again when re-examined about 10 days after stopping the medication, as shown in Table 2.

[0020] Example 2

[0021] The use of NMN by Dog No. 2 in Example 2 is shown in Table 3.

[0022] Table 32 Medication and NT-proBNP changes in dog No.

[0023]

[0024] After taking NMN orally for 2 weeks, the NT-proBNP of dog No. 2 had returned to normal (see Table 3).

[0025] Example 3

[0026] The use of NMN by Dog No. 3 in Example 3 is shown in Table 4.

[0027] Table 4 Medication and NT-proBNP changes in dog No. 3

[0028]

[0029] After continuous use of NMN, the NT-proBNP level of dog No. 3 returned to normal (see Table 4).

[0030] Example 4

[0031] The use of NMN by dog ​​No. 4 in Example 4 is shown in Table 5.

[0032] Table 5 Medication and NT-proBNP changes in dog No. 4

[0033]

[0034]

[0035] After continuous use of NMN, the NT-proBNP level of dog No. 4 returned to normal (see Table 5).

[0036] Example 5

[0037] The use of NMN by Dog No. 5 in Example 5 is shown in Table 6.

[0038] Table 65 Medication and NT-proBNP changes in dog

[0039]

[0040] Dog No. 5 had a significant decrease in NT-proBNP during the treatment period, as shown in Table 6.

[0041] Example 6

[0042] The use of NMN by dog ​​No. 6 in Example 6 is shown in Table 7

[0043] Table 76 Medication and NT-proBNP changes in dog

[0044]

[0045] The patient took NMN orally at a dose of 30 mg twice a day for more than a month. After 20 days, NT-proBNP returned to normal and was within the normal range until the time of death due to acute gastric dilatation.

[0046] The detection of NT-proBNP is a good auxiliary indicator for the diagnosis of heart disease in clinical practice. It can not only exclude or accurately diagnose whether symptoms such as dyspnea or exercise intolerance in dogs are caused by heart disease, but also interpret the course of heart disease in combination with cardiac ultrasound examination. It is one of the serum markers for early detection of heart disease. When the NT-proBNP concentration in dog plasma is <900pmol / L, it indicates that the current clinical symptoms such as dyspnea, exercise intolerance, and cough are unlikely to be caused by cardiac causes; when the NT-proBNP concentration in dog plasma is between 900-1800pmol / L, it indicates that the current clinical symptoms such as dyspnea, exercise intolerance, and cough may be caused by cardiac causes, or may be caused by other reasons, and further differential diagnosis should be performed: when the NT-proBNP concentration is >1800pmol / L, it is very likely that there is a problem with the heart, and further heart examination is recommended.

[0047] In the above example, a total of 6 dogs with abnormal BNP results were treated and observed. In the first examination, dogs 1 and 2 were found to have a mild to moderate increase in BNP. After a reexamination 2 weeks later, NT-proBNP showed a trend of continuous increase. After continuous oral administration of NMN for a period of time, the NT-proBNP concentrations of the two dogs recovered to below 900pmol / L. Neither of the two dogs had any other clinical symptoms, but the NT-proBNP concentration in the plasma was found to be greater than 900pmol / L during the physical examination. Electrocardiogram and ultrasound examination confirmed that there were no obvious abnormalities in cardiac function and morphological structure. It shows that NMN may have a certain improvement effect on the increase of NT-proBNP in dogs without abnormal cardiac function and abnormal cardiac morphological structure.

[0048] For dogs with abnormal NT-proBNP and other non-cardiovascular diseases, after continuous oral administration of NMN, the NT-proBNP in plasma can also be reduced from a high level to below 900pmol / L, suggesting that NMN may have a certain improvement effect on the elevated NT-proBNP in dogs without abnormal cardiac function and cardiac morphology and structure, but with other systemic diseases. The results of the observation suggest that continuous oral administration of NMN at 20-30mg / time, twice a day, may help improve the plasma NT-proBNP level of dogs without obvious abnormal cardiac morphology and structure, and without obvious decline in cardiac function.

[0049] This application proposes a new method for treating NT-proBNP abnormalities, that is, by taking NMN orally, the level of NT-proBNP can be effectively reduced, which has important clinical significance in the field of veterinary medicine, especially in the field of heart disease treatment. Secondly, this technical solution also provides new ideas for the research in the field of biological preparations, that is, NMN may improve cardiac function by improving the energy metabolism of myocardial cells, which has an important role in promoting the development and application of biological preparations.

[0050] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. Use of nicotinamide mononucleotide in the preparation of a drug for preventing or treating abnormal NT-proBNP.

Images