WO2018148930A1

WO2018148930A1 - Use of nadh or fadh2 in nutritional intervention for cancer patient

Info

Publication number: WO2018148930A1
Application number: PCT/CN2017/073917
Authority: WO
Inventors: 傅荣昭
Original assignee: 纯菁生物科技（美国）有限公司; 纯菁生物科技（上海）有限公司
Priority date: 2017-02-17
Filing date: 2017-02-17
Publication date: 2018-08-23

Abstract

Provided are the use of NADH or FADH2 in the preparation of a nutritional agent for cancer patients and the nutritional agent. The nutritional agent is used for improving the physical function of cancer patients and for resisting reductions in body weight and body weight loss.

Description

Application field of NADH or FADH ₂ in nutritional intervention of cancer patients

[0001] The present invention relates to the technical field of application of NADH and FADH ₂ , and specifically relates to a new application of NADH and FADH ₂ in nutritional intervention of cancer patients.

Background technique

[0002] Cancer, also known as malignant tumor, is a local mass formed by abnormal proliferation of local tissues under the action of various tumorigenic factors. Because of its extremely high mortality, it has become an important killer of serious threats to human health. one. For many years, human beings have been working hard to explore effective ways to cure cancer, but they have never been able to get what they want. Nowadays, human attitudes toward cancer can be said to be cancerous, and everyone is at risk.

[0003] Researchers have found that moderate to high concentrations of reactive oxygen species (ROS) induce cellular cell degeneration, apoptosis, and necrosis through cellular oxidative stress, especially in proliferating cells. Because when the cells are highly proliferating, their DNA is completely exposed and replicated in an unprotected state. If this sputum senses a high level of ROS, the process is aborted and the cells are driven into decline. Based on this theoretical study, most traditional anti-cancer methods use physical or chemical means to stimulate the production of ROS and then increase the ability of apoptosis to achieve the purpose of killing tumor cells, such as radiation, etoposide, arsenate, and Changchun. Alkaloids, cisplatin, mitomycin. , doxorubicin, camptothecin, oxytetracycline and new carotenoids. These typical stimuli cause all cells in the body (both cancer cells and healthy cells) to produce R OS and then destroy them. Although tumor cells are more affected, tumor cells have a higher rate of proliferation than normal cells and are less tolerant to ROS, but normal cells are inevitably damaged. The terrible side effects are obvious. .

[0004] In addition, the basic unit of cancer lesions is cancer cells, and the proliferation of cancer cells is endless, which causes a large amount of nutrients in the patient's body to be consumed. At the same time, cancer cells can release a variety of toxins, causing a series of symptoms. If found and treated less than sputum, it can also be transferred to all parts of the body to grow and eventually lead to human body suffocation, weakness, anemia, loss of appetite, fever and impaired organ function. Many cancer patients suffer from severe weight loss, physical loss and weakness in their peers who are suffering from cancer cells. This kind of physical condition makes cancer patients feel very uneasy, both physically and mentally affected, which is even It is also the cause of death.

[0005] The occurrence of physical energy loss, most likely due to the inefficiency of cancer metabolism and the need for glucose circulation to obtain lactate from the liver. Each lactate molecule requires six ATPs (Cori cycle), whereas in cancer cells, the molecular conversion of glucose to lactate produces only two ATPs. Based on this, a new method for treating cancer, namely the introduction of ATP into cancer patients, has been born, and it has achieved some clinical success. However, this method relies on intravenous injection and must be injected for a long time. Inconvenient peers can also cause more or less harm to the patient's body and mind.

[0006] NADH is an abbreviation of reduced nicotinamide Adenine Dinucleotide, a physiology of nicotinamide dinucleotide present in all living cells including human cells. A substance, which is produced in the citric acid cycle of glycolysis and respiration in living organisms, is a substrate substance for oxidative phosphorylation and induces the production of ROS. NADH acts as a hydrogen donor in the enzymatic reaction. It is involved in many physiological activities such as cellular material metabolism, energy synthesis, and cellular DNA repair. It is a control marker in the energy production chain of mitochondria. The most important role of NADH is its driving force for cellular respiration. The glucose metabolism is very little directly produced by the metabolism of ATP. The metabolically produced N ADH can produce a large amount of ATP via an electron-transfer oxidative phosphoric acid reaction. Meet the energy needs of the organism.

[0007] FADH ₂ is an abbreviated form of reduced flavin dinucleotide, and is a substance essential for anaerobic glycolysis and aerobic oxidation of sugars (glucose, fructose, etc.) in the human body. Like NADH, FADH ₂ is also involved in intracellular electron transport and oxidative phosphorylation pathways to produce ATP and induces ROS during oxidative phosphorylation.

[0008] If the natural substances existing in the body of NADH and FADH ₂ can be applied to the field of anti-cancer, it is undoubtedly a great boon for human beings.

technical problem

[0009] In view of the drawbacks of the conventional anticancer method mentioned in the above background art, and the problem that the cancer patient suffers from physical exhaustion and physical weakness for a long time, the object of the present invention is to overcome the deficiencies of the prior art and provide a No/slight side effects against tumor cells and help to improve the physical weakness of cancer patients.

Problem solution Technical solution

[0010] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0011] The use of NADH or FADH ₂ in the preparation of a nutrient for cancer patients, characterized in that NADH or FADH _{2 is} used as a main component of the nutrient.

[0012] Further, the nutrient is used to improve the body function of cancer patients and to resist weight loss and physical loss.

[0013] NADH can be delivered on the surface of eukaryotes and prokaryotes, and extracellular NADH can communicate to oxidative phosphorylation and increase intracellular ATP. External uptake of NADH helps to improve the functioning of tumor-bearing organisms, especially for people who suffer from severe weight loss, physical loss and weakness. Currently NADH can be obtained by oral or intravenous/intraperitoneal input.

[0014] Further, the nutrient is suitable for cancer patients carrying tumor cells capable of oxidative phosphorylation

[0015] There are two types of tumor cells. The first type of tumor cells will perform aerobic respiration under non-proliferative conditions. This process produces ROS, but the DNA is not exposed and is not stimulated by ROS; the cells are proliferating ( In the case where the tumor cells are ready to spread, only the aerobic glycolysis reaction is carried out. Although the DNA of this cockroach is unprotected, it does not produce or rarely produces ROS because it does not perform aerobic respiration. No irritation to DNA. The second type of tumor cells will only undergo glycolysis regardless of proliferation or non-proliferation, because its oxidative phosphorylation is defective, and such tumor cells never undergo a process of producing ROS via oxidative phosphorylation.

[0016] For the first type of tumor cells, in the case of supplementation of NADH or FADH ₂ , oxidative phosphorylation reaction can be induced and ROS can be produced, and an opportunistic (critical engraving) destroys its proliferation in cell proliferation and division. And the second type of tumor cells by the presence of defects in oxidative phosphorylation, of OXPHOS --- --- NADH can not be achieved the mechanism of ROS, it is impossible to use NADH or FADH _2, it is added NADH or FADH ₂ destruction of such tumors invalid.

[0017] Further, the nutrient is suitable for an adult cancer patient.

[0018] ROS stimulates not only the DNA of proliferating tumor cells, but also the DN of highly dividing cells.

A has a stimulating effect. Tumor cells are only one type of highly dividing cells. Therefore, the adolescent population is not suitable for this mechanism of action. In theory, it also prevents the division of normal cells and causes normal cells to also apoptosis. . However, in adults, the proportion of healthy cells that proliferate at a high rate is very small. If there are tumor cells, the frequency of tumor cell division is faster than other normal cells. Therefore, R

OS stimulation of tumor cells is more intense and concentrated. Therefore, for adult cancer patients, supplement NAD

The side effects of H or FADH ₂ are minimal.

[0019] A nutrient for cancer patients, which is used for improving the body function of cancer patients and resisting weight loss and physical loss, and the nutrient is mainly composed of NADH or FADH ₂ .

[0020] Further, the nutrient is suitable for cancer patients carrying tumor cells capable of oxidative phosphorylation

[0021] Further, the nutrient is suitable for an adult cancer patient.

[0022] A nutritional intervention method for a cancer patient, which provides a physiologically acceptable dose of a nutritional supplement containing NADH or FADH ₂ as a main component to a cancer patient in a medically acceptable manner.

[0023] Further, the nutrient is administered together with a ketogenic diet.

[0024] The so-called ketogenic diet refers to a formula with a high proportion of fat, a low proportion of carbohydrates, protein and other nutrients, and its English name is ketogenic-diet, abbreviated as KD.

[0025] Further, the intervention method is applicable to an adult cancer patient.

Advantageous effects of the invention

Beneficial effect

Compared with the prior art, the beneficial effects of the present invention are as follows: Applying NADH or FADH ₂ to the nutritional intervention of cancer patients can not only inhibit the function of tumor cells, but also enhance the physical quality of cancer patients. Improving the level of health has the dual effect of killing two birds. In addition, NADH or FADH ₂ has a better targeted therapeutic effect on cancer, overcoming the drawbacks of traditional anti-cancer methods that cause great damage to normal cells. In addition, NADH and FADH ₂ are natural substances that exist in the body itself. They are not harmful to most normal cells, or have very low side effects. They only provide extra energy, so they can be taken for a long time, and NADH and FADH ₂ can be administered orally, overcoming the drawbacks of the ATP input method that must rely on intravenous administration. NADH and FAD H _{2 are} natural metabolites that can be used in banned communities and religions.

Embodiments of the invention The present invention will be further described in detail with reference to the preferred embodiments thereof. The following examples are illustrative of the invention, and the invention is not limited to the following examples.

Embodiment 1

[0029] Anti-tumor mouse experiment of NADH and FADH ₂

[0030] 1. Experimental materials:

[0031] 36 healthy adult mice, SPF grade, male or female, body weight (20 ± 1) g, purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.; NADH dry powder and FADH ₂ dry powder, purchased from Bangtai Bioengineering (Shenzhen

) Ltd.

[0032] 2. Experimental method:

The selected tumor cells which were normally subjected to oxidative phosphorylation were diluted with physiological saline to a tumor cell number of 1 x 10 7 /ml, and seeded on the back of all the experimental mice, 0.2 ml per mouse. The experimental mice inoculated with the tumor cells are kept in a suitable environment of light, temperature and humidity, and are free to move and give sufficient drinking water and basic food.

[0034] After 7 days, all experimental mice were randomly divided into three groups, a control group, a NADH group, and a FADH ₂ group, with 12 rats in each group. From the 8th day, NADH was administered to NADH mice on the basis of adequate drinking water and basic food, intraperitoneal administration, once daily, 1 mg/g body weight per day; FADH ₂ mice were administered FADH ₂ , intraperitoneal input, once daily, 1 mg/g body weight each time.

[0035] After 28 days, after observing the mental state of each experimental mouse, all the mice were sacrificed, the dorsal tumor was peeled off and the recording was weighed.

[0036] 3, the experimental results:

[0037] All the mice in the control group were apathetic, not euphoric, and the body was eliminated; 2 of the 12 mice died before the end of the experiment, and the average tumor weight of the remaining 10 mice and the tumor The average body weight is shown in Table 1.

[0038] All the mice in the NADH group and the FADH ₂ group were significantly better than the control group, the behavior was slightly more active, the body type was stronger than the control group, and no abnormal changes were observed in the vital organs such as the heart, liver, lungs, and stomach. 24 mice did not die before the end of the experiment. The mean tumor weight and mean tumor weight of the NADH and FADH ₂ mice are shown in Table 1.

Table 1 [] [Table i]

[0040] 4, the results of the discussion

[0041] The above test results show that: NADH and FADH are resistant to weight loss, increase physical strength and improve body function in adult cancer-bearing mice, and can effectively inhibit tumor growth and have no toxic side effects on the body.

Embodiment 2

[0043] Clinical laboratory data

[0044] 1, case selection

[0045] In all adult cancer patients who voluntarily participate in clinical trials, screening cancer patients suffering from cancer, physical debilitation, weakness, and carrying tumor cells that can normally undergo oxidative phosphorylation, male or female, young Not limited to, signed informed consent, all patients, 36 males, 54 females, aged 23 to 72 years old.

[0046] 2. Administration method

[0047] All cancer patients screened were randomly divided into three groups, the control group, the NADH group, and the FADH ₂ group, with 30 persons in each group. NADH group was given NADH 50mg/kg body weight per day, orally, once or in multiple doses; FADH ₂ was given FADH ₂ 50mg/kg body weight per day, orally, once or in multiple doses; Each place was given a placebo 50 mg/kg body weight per day, orally, once or in multiple doses.

[0048] 3, efficacy evaluation criteria

[0049] The patient self-evaluates his or her physical condition, and the person who feels energy or physical strength or a significant increase in weight is considered effective, otherwise it is considered invalid.

[0050] 4, clinical trial results One month after administration, the effective rate was 6% in the control group, 20% in the NADH group, and 93.3% in the NADH group; 27 in the FADH ₂ group, the effective rate was 90<3⁄4.

Claims

Claim

[Application 1] The use of NADH or FADH ₂ in the preparation of a nutrient for cancer patients, characterized in that

: NADH or FADH ^ is the main component of the nutrient.

[Claim 2] The use according to claim 1, wherein the nutrient is used to improve the body function of a cancer patient and to resist weight loss and physical loss.

[Clave 3] The use according to claim 1, wherein the nutrient is suitable for a cancer patient carrying a tumor cell capable of oxidative phosphorylation.

[Claim 4] The use according to claim 3, wherein: the nutrient is suitable for an adult cancer patient.

[Claim 5] A nutrient for cancer patients, which is used for improving the body function of a cancer patient and resisting weight loss and physical loss, wherein the nutrient is mainly composed of NADH or 011 ₂ .

[Claim 6] The nutrient for cancer patients according to claim 5, wherein the nutrient is applied to a cancer patient carrying a tumor cell capable of oxidative phosphorylation.

[Claim 7] The nutrient for cancer patients according to claim 6, wherein the nutrient is suitable for an adult cancer patient.

[Claim 8] A nutritional intervention method for a cancer patient, characterized in that a physiologically acceptable dose of a nutrient containing NADH or FADH ₂ as a main component is administered to a cancer patient in a medically acceptable manner.

[Claim 9] The nutritional intervention method for a cancer patient according to claim 8, wherein the nutrient is administered together with a ketogenic diet.

[Claim 10] The nutritional intervention method for a cancer patient according to claim 8, wherein the intervention method is suitable for an adult cancer patient.