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CN111000862B - Pharmaceutical composition for targeting mitochondria in early stage cancer and its application - Google Patents

Pharmaceutical composition for targeting mitochondria in early stage cancer and its application Download PDF

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CN111000862B
CN111000862B CN202010085646.XA CN202010085646A CN111000862B CN 111000862 B CN111000862 B CN 111000862B CN 202010085646 A CN202010085646 A CN 202010085646A CN 111000862 B CN111000862 B CN 111000862B
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范理宏
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Abstract

本发明公开了一种靶向线粒体治疗早期癌症的药物组合物,由活性成分孕烯醇酮、褪黑素和硒,以及药学上可以接受的载体组成。本发明的药物组合物作为一种线粒体能量药物,通过对机体线粒体的全面建设,保证线粒体功能的多靶点修复,从而全面有效地调节基体免疫系统功能,发挥其抗癌作用,治疗早期癌症。

Figure 202010085646

The invention discloses a pharmaceutical composition for targeting mitochondria to treat early stage cancer, which is composed of active ingredients pregnenolone, melatonin and selenium, and a pharmaceutically acceptable carrier. As a kind of mitochondrial energy drug, the pharmaceutical composition of the present invention ensures the multi-target repair of mitochondrial function by comprehensively constructing the mitochondria of the body, thereby comprehensively and effectively regulating the function of the matrix immune system, exerting its anti-cancer effect, and treating early cancer.

Figure 202010085646

Description

Medicine composition for treating early cancer by targeting mitochondria and application thereof
Technical Field
The invention relates to a pharmaceutical composition, which can improve the mitochondrial function of an organism and reverse early cancer and is suitable for treating the early cancer.
Background
Mitochondria, one of the organelles essential to the body, are ancient and important, complex and delicate organelles in eukaryotic cells. The ancient symbiotic origin, the unique double-layer membrane ridge structure and the semi-autonomous self-replication capacity of mitochondria endow the mitochondria with important and diverse functions. For the body, mitochondria are the ultimate site for biological oxidation and energy synthesis of eukaryotic cells, and are the fundamental source of energy consumption for human activities.
With further intensive research on mitochondria, it was found that mitochondria are not only "energy-driven factories" of cells, but also involved in many pathophysiological processes such as cell signal transduction, redox balance, calcium level regulation, cell differentiation aging and death. Thus, the development of a variety of body diseases, including neuromuscular diseases, cardiovascular diseases, diabetes, cancer, etc., involves impairment of mitochondrial function.
The modern society develops rapidly, brings convenience and brings a plurality of problems. Natural environment pollution, various stress events, bad work and rest modes, unhealthy diet and no regularity, various external and self factors such as excessive living and working pressure and the like cause various system functional disorders to be damaged, mitochondria in human cells can not be prevented from being damaged, and the nervous system, the cardiovascular system, the immune system and the like which need energy supply most for an organism are most remarkable, so various system symptoms such as insomnia and dreaminess, hypomnesis, chest distress and shortness of breath, arrhythmia, hypodynamia, physical decline, cold and the like of the organism are often caused, and further the occurrence and development of cancers are further caused. Therefore, restoration of impaired mitochondrial function is an important research topic.
The human body is a complete systemic individual, the transformation of medical concepts is imperative, and the proposal of the overall medical view is a necessary and necessary fact. Based on the overall medical view and the wide and important functions of mitochondria, focus on the reconstruction and recovery of the functions of the mitochondria, can recover the whole homeostasis of a human body, improve the immune function and the whole endocrine regulation of the body, and treat, prevent and even reverse the occurrence and development of diseases.
Many reports on related drugs for repairing mitochondrial functions currently exist, and studies show that drugs such as Pregnenolone (PRE), Dehydroepiandrosterone (DHEA), Thyroid Hormone (TH), Melatonin (MLT), selenium (Se), Lipoic Acid (LA), reduced Glutathione (GSH), coenzyme Q10, tyrosine (Tyr), cortisol (cortisol), epinephrine (a) and the like are closely related to mitochondrial functions and play an important role in recovering mitochondrial functions. However, the specific effects reported for these drugs are also mainly limited to antioxidant effects or to compensate for mitochondrial respiratory chain function, and their deeper mechanisms of action are not yet clear. Meanwhile, the research on the synergistic effect among the medicines is less, and no evidence proves that the medicines can be used in combination, and whether the combination of the medicines can improve the fusion efficiency of mitochondria, improve the anti-mutation capability of the mitochondria and improve the activity of the mitochondria is needed to be further researched.
Restoration of mitochondrial function is also known as mitochondrial construction, and includes the construction of the intracellular and extracellular environments. The extracellular environment construction includes large internal environment of the body, heavy metal removal and environmental pollution, namely the elimination of evil factors for strengthening body resistance and eliminating evil in the theory of traditional Chinese medicine; the construction of the intracellular environment is based on the construction of the external environment, and various nutrients required by the energy production of mitochondria are provided, so that the functions of the mitochondria are recovered, and the self-healing of cells and human bodies is promoted, namely the strengthening of body resistance and elimination of pathogenic factors in the theory of traditional Chinese medicine.
The overall construction of mitochondria is never achieved by a single nutrient, nor is it simple to restore mitochondrial function with any combination of several nutrients. Just like the monarch, minister, assistant and guide in traditional Chinese medicine, proper mitochondrial function repairing drugs are correctly screened out for combination, and the synergic action and complementary action between the drugs are fully utilized, so that the drugs are combined and matched with each other, and the effect of restoring the mitochondrial function can be better realized.
Disclosure of Invention
The invention aims to provide a medicine composition for treating early cancer by targeting mitochondria, which has good effects of recovering and improving mitochondrial functions as a mitochondrial energy medicine, is safe and reliable and is convenient to apply and popularize.
The invention also provides the application of the pharmaceutical composition in improving the body immunity, reversing cancer cells and treating early cancer.
The present inventors have found that even the same mitochondrial function repairing drug may cause different results when used in the pre-, mid-and post-tumorigenic stages of cancer cells, thereby revealing that the mitochondrial function repairing drug exerts different effects in different stages of cancer. Based on the above findings, the inventors finally screened a pharmaceutical composition suitable for early cancer, capable of significantly reversing cancer cells through mitochondrial construction of the body, and treating early cancer through a large number of studies and experiments.
The invention firstly provides a medicine composition for treating early cancer by targeting mitochondria, which comprises active ingredients of Pregnenolone (PRE), Melatonin (MLT) and selenium (Se) and a pharmaceutically acceptable carrier.
In the present invention, the "pharmaceutically acceptable carrier" refers to a substance suitable for use in humans and mammals without adverse side effects such as toxicity, irritation and allergy, and includes, but is not limited to, various common excipients, diluents, binders, dissolution aids, antioxidants, disintegrants, lubricants, stabilizers, absorption enhancers, colorants and the like.
Furthermore, the pharmaceutical composition of the present invention may be at least one of any pharmaceutically acceptable dosage forms, including but not limited to tablets, capsules, powders, granules, syrups, and the like.
In the pharmaceutical composition of the present invention, there is no particular limitation on the weight ratio of the various active ingredients.
Preferably, however, the pharmaceutical composition may be obtained, for example, in parts by weight of the following active ingredients: 25-50 parts of pregnenolone, 3-8 parts of melatonin and 0.2-0.4 part of selenium.
More preferably, in the pharmaceutical composition of the present invention, the weight parts of each active ingredient are: 25 parts of pregnenolone, 5 parts of melatonin and 0.2 part of selenium.
The pharmaceutical composition can improve the immunity of the organism by recovering the function of mitochondria and improving the energy of mitochondria, and is used for treating low physiological function caused by the injury of mitochondria and various diseases caused by abnormal function of mitochondria.
Furthermore, the pharmaceutical composition can inhibit and reverse early non-gonadal solid tumor cells by improving mitochondrial energy, thereby reversely treating early cancers such as lung cancer, thyroid cancer, bladder cancer, gastric cancer, renal cancer, intestinal cancer and the like.
Furthermore, the pharmaceutical composition provided by the invention has a better and remarkable effect in the aspect of treating early lung cancer.
The animal level verification proves that the pharmaceutical composition has the effects of restoring the functions of mitochondria, improving the energy of mitochondria and treating early cancers.
Mitochondria are used as important organelles for providing energy in eukaryotic cells, are related to the occurrence and development of various chronic diseases, regulate and control the whole mitochondrial network, ensure the health of the mitochondrial network, improve the metabolic capacity of cells, and can promote health, prevent and treat diseases.
According to the experimental result of the invention aiming at the mouse, the pharmaceutical composition can better inhibit the growth of the cancer cells of the mouse when the mouse is tumorigenic and is administered at the same time, which is obviously higher than the administration after tumorigenic administration. The importance of the administration time node on the disease development is illustrated, and the mitochondrial energy pharmaceutical composition is administered in the early stage of cancer cell generation, so that the mitochondrial overall network can be better built, and the disease can be defended, healthily and prevented.
The construction of mitochondria involves the construction of the intracellular and extracellular environment (the internal environment of the body). Life as an organic whole, homeostasis of the intracellular environment is also important as that of the extracellular environment. Multiple systems and multiple organs are needed for coordination and coordination of the health of the organism, and the pharmaceutical composition with improved mitochondrial energy also needs multiple combinations to exert the optimal benefit.
According to the experimental result, the medicinal composition obtained by combining the screened mitochondrial function repairing medicaments has the optimal effect of inhibiting the growth of the cancer cells, which is superior to other combination schemes. Like traditional Chinese medicine wisdom accumulated in thousands of years, the monarch, minister, assistant and guide matched formula can exert the characteristics of all medicines, and the improvement of mitochondrial energy also needs combined medicines (monarch, minister, assistant and guide). The mitochondrial energy-improving pharmaceutical composition obtained by combining the appropriate mitochondrial function repairing drugs can best ensure the multi-target repairing of the mitochondrial function and realize the effect of inhibiting the growth of cancer cells.
Se is an indispensable trace element for human bodies. Se can synthesize thyroxine, thereby regulating metabolism and maintaining relatively stable internal environment. Se can also prevent the formation of peroxides and free radicals, block the metabolism of cancer cells, and inhibit the division and growth of cancer cells. The trace element Se has obvious prevention and treatment effects on various cancers such as liver cancer, breast cancer, ovarian cancer, gastric cancer, colon cancer, rectal cancer, prostate cancer, lung cancer and the like, and the occurrence and development of the cancers are related to the insufficient intake of Se. On one hand, Se has antioxidant activity, and the Se compound can relieve ROS-mediated mitochondrial dysfunction through an Nrf2 signal channel, improve the mitochondrial function of normal cells and has certain effect of preventing cancers. Se can also limit the effects of hypoxia on mitochondrial complexes by normalizing I and IV complex levels and significantly increasing the activity of II and III complexes. These effects may be associated with the modulation of binding of Akt and cAMP response elements. It is also found that Se compound can induce the MGC-803 cell of gastric cancer cell to stop in the cell cycle of G2/M phase, so as to show obvious inhibition effect on the proliferation of cancer cell. On the other hand, Se has a direct killing effect on cancer cells, and recent researches show that Se gradually destroys the mitochondrial membrane potential of liver cancer HepG2 cells, and finally leads to cancer cell apoptosis by triggering Bax-and Bcl-2-mediated mitochondrial apoptosis pathways.
MLT is an amine hormone mainly secreted by pineal body, and has multiple physiological functions of regulating day and night regularity, resisting aging, resisting oxidation, resisting inflammation, regulating immunity and the like. MLT is also an effective natural antioxidant and anti-inflammatory agent that can protect against the toxic side effects of radiation and chemotherapy. MLT increases mitochondrial function and autophagy by increasing the expression of SIRT1 and LC3 and ATP content, reduces ROS levels and TAC increases in damaged cells, can rescue mitochondria from oxidative stress-induced mitochondrial dysfunction, and prevents subsequent cell death, thereby ensuring normal cell function. Meanwhile, MLT increases the membrane potential and membrane fluidity of mitochondria, reduces the permeability of mitochondria and maintains the stability of mitochondrial membranes by increasing the generation activity of an electron transfer system and ATP. In cancer cells, MLT promotes cancer cell apoptosis by modulating several apoptotic mediators, such as Bax, Bcl-2, endogenous ROS, and apoptotic receptors. By increasing the activity of mitochondrial complex I, the generation of ROS and the expression of cyt-c in cell nucleus are increased, and cancer cell apoptosis is caused by triggering Bax and Bcl-2 mediated mitochondrial apoptosis pathways.
PRE is an important intermediate for the synthesis of progesterone, finasteride, DHEA, and the like, as a precursor hormone of Dehydroepiandrosterone (DHEA). Mitochondria are important sites of steroid hormone biosynthesis. Cholesterol is metabolized into steroid steroids such as PRE and the like which are necessary for human bodies in mitochondria, the stability of membranes is maintained, and a material basis is provided for the growth and development of organisms. Likewise, mitochondrial cholesterol levels can affect mitochondrial function. Decreased mitochondrial PRE synthesis in cancer cells leads to physiological upregulation of steroidogenic enzymes, resulting in decreased mitochondrial cholesterol levels and a concomitant decrease in mitochondrial membrane stability.
There is literature emphasizing that a variety of nutrients are critical to mitochondrial function, including Se, MLT, and optimizing their availability is expected to improve clinical outcome in critically ill diseases. These nutrients together with mitochondria form a complex network. The bioenergetic function of the mitochondria will be optimal when the substrates and cofactors in the network are present in the optimal combination. Due to the synergistic effect of many nutrients in the metabolic pathway, supplementation of only one nutrient may not improve downstream effects in the absence of another micronutrient. Therefore, the invention combines Se, MLT and PRE to effectively improve the whole mitochondrial network, increase the antioxidant effect from different ways, increase the stability of mitochondrial membranes and inhibit the generation of cancer cells. These active ingredients are important nutrients for the mitochondria to support and protect against oxidative stress.
However, not any combination will produce an effect, for example, an interesting finding of the present invention is that when Se alone is combined with MLT, although it can also inhibit the growth of cancer cells, its ATP level is reduced, suggesting that it is not effective in improving the mitochondrial energy recovery effect, and that any combination of non-mitochondrial energy recovery drugs is effective for modulation of immune system function.
Drawings
Figure 1 is the results of the effect of each single drug group on tumor volume.
Fig. 2 is a result of the influence of each drug composition group on tumor volume.
Figure 3 is the effect of different dosing times of a single drug on tumor volume.
Figure 4 is the results of the effect of each single drug group on ATP levels in tumor tissues.
Fig. 5 shows the effect of each drug composition group on ATP levels in tumor tissues.
Figure 6 is the results of the effect of each single drug group on mitochondrial complex activity in tumor tissues.
Fig. 7 is a result of the effect of each pharmaceutical composition group on the activity of mitochondrial complexes in tumor tissues.
FIG. 8 is a graph of the variation of immune cells in tumor tissue for each single drug group.
FIG. 9 shows the variation of immune cells in tumor tissues for each of the pharmaceutical composition groups.
Detailed Description
The following examples further describe embodiments of the present invention. The following examples are only for illustrating the technical solutions of the present invention more clearly, and do not limit the scope of the present invention. Various changes, modifications, substitutions and alterations to these embodiments will be apparent to those skilled in the art without departing from the principles and spirit of this invention.
Example 1.
Weighing 25g of raw material medicine PRE, 3g of MLT and 0.1g of Se according to 1000 capsules, adding the balance of carrier corn starch, crystalline cellulose, lactose, magnesium stearate and polyvinylpyrrolidone according to the conventional capsule production process, mixing and granulating, and filling into hard gelatin capsules to prepare 1000 capsules, wherein the content of each capsule is 0.5 g.
Example 2.
According to the production of 2000 tablets, raw material drugs of PRE 25g, MLT 5g and Se 0.2g are taken, mixed with the balance of corn starch, crystalline cellulose, lactose, carboxymethyl cellulose and magnesium stearate according to the conventional tablet production process, added with polyvinylpyrrolidone aqueous solution as an adhesive for granulation, finally added with talcum powder as a lubricant, and tabletted to obtain 2000 tablets, wherein each tablet is 0.25 g.
Example 3: effect of pharmaceutical composition on tumor volume.
The experimental animals were C57BL/6J mice, 4 week old males, randomized into tumor-bearing control, DDP and several drug groups, 3 per group. The experimental period was 3 weeks.
The drug groups are further specifically divided into single drug groups and drug composition groups.
Wherein, the single medicine components are divided into PRE group, MLT group and Q10 group 3.
The medicinal composition group comprises 4 groups of Se + PRE group, Se + MLT group, PRE + MLT group and the medicinal composition group.
Taking tumor-bearing control group, DDP group and mice of each drug group, using LLC cell (mouse lung cancer cell) to make Lewis lung cancer model,3×105cells/mouse, injected subcutaneously.
After modeling, each drug group mixes the single drug or the drug composition in the feed to feed the mice, the administration dosage is calculated according to the conversion formula of the administration dosage of the mice and the human, the PRE is 7.6mg/kg, the MLT is 0.76mg/kg, the Se is 30.3 mug/kg, and the Q10 is 45.5 mg/kg. The dosage of each pharmaceutical composition group is the cumulative amount of each single dosage.
DDP group was treated with DDP (cisplatin) for drug intervention, 1mg/ml, i.p., 3 times for 1 week, until the end of the experiment.
After the experiment is finished, mice in each experimental group are killed by dislocation of spinal cords, subcutaneous tumor tissues of the mice are peeled, the tumor volume is measured, and the data are sorted and analyzed.
The comparison of tumor volumes for each group is shown in FIGS. 1 and 2. In the figure, x:p<0.001;****:p<0.0001。ns:p> 0.05, no statistical difference.
As can be seen from fig. 1, in the single-drug group, the tumor volume of the PRE group is significantly smaller than that of the tumor-bearing control group and that of the DDP group, and the tumor volume of the MLT group is slightly larger than that of the DDP group, although smaller than that of the tumor-bearing control group, indicating that the inhibition effect of each single drug on cancer cells is different. As can also be seen from fig. 1, the tumor volume of the Q10 group, although not statistically different from that of the tumor-bearing control group, showed a tendency to exceed that of the tumor-bearing control group, thereby demonstrating that not all of the mitochondrial function-restoring drugs had inhibitory effects on the growth of cancer cells.
As can be seen from fig. 2, the Se + MLT group, PRE + MLT group and the pharmaceutical composition group of the present invention were all able to significantly suppress tumor volume and were superior to the DDP group. However, there was no statistical difference between the tumor volume of Se + PRE group and the tumor-bearing control group, and there was almost no inhibition, indicating that the effect of reversing tumor volume could be achieved without any superimposed combination of the mitochondrial function-restoring drugs. Since mitochondria are an indispensable link for various vital activities, mitochondria have different targets in terms of oxidative stress resistance, hormone application, and biosynthetic metabolism. Mitochondrial repair at a single or very distinct target may not be able to reverse mitochondrial damage and may even be antagonistic. The treatment aiming at mitochondria needs to be comprehensive and integrated treatment, simultaneously meets the energy production requirement, the anti-oxidation requirement, the positive hormone output and the biosynthesis requirement, reconstructs the energy metabolism environment of the organism, and improves the micro-ecology of the whole body, thereby playing the role of achieving twice the result with half the effort.
Example 4: effect of different administration times of a single drug on tumor volume.
The experimental animals were C57BL/6J mice, 4-week-old males, randomly divided into tumor-bearing control group, PRE group, MLT group and Q10 group 3 single drug groups, 3 of each group. The experimental period was 3 weeks.
The experiment adopts a drug administration mode after tumor formation. The LLC cells (mouse lung cancer cells) are used for producing Lewis lung cancer models of mice of each experimental group, namely 3 multiplied by 105cells/mouse, injected subcutaneously.
One week after molding, the single drug groups were fed to mice with each single drug in the feed until the end of the experiment. The dose of each single drug group was the same as in example 3.
After the experiment is finished, mice in each experimental group are killed by dislocation of spinal cords, subcutaneous tumor tissues of the mice are peeled, the tumor volume is measured, and the data are sorted and analyzed.
The results of comparing the tumor volumes of the mice in the experimental groups are shown in FIG. 3. In the figure, x:p<0.05;ns:p> 0.05, no statistical difference.
As can be seen from fig. 3, in each drug group administered with a single drug 1 week after tumorigenesis, MLT and PRE contributed to the inhibition of cancer cell growth and decreased tumor volume, compared to the tumor-bearing control group, but the tumor volume was significantly increased after Q10 administration. The above experimental results show that the same drug used in different stages of tumorigenesis leads to different results, and it is clear that the mitochondrial function-restoring drug exerts different effects in different stages of cancer cells.
Example 5: effect of pharmaceutical composition on ATP level of tumor tissue.
The specific experimental procedure was the same as in example 3.
After the experiment is finished, the subcutaneous tumor tissue of the mouse is stripped, necrotic tissue is removed, and the tumor tissue is homogenized to prepare single cell suspension of cancer cells. And respectively using an ATP detection kit and mitochondrial complex I, II, III and IV activity detection kits to detect the mitochondrial productivity and 4 mitochondrial complex activities in the mouse cancer cells, and sorting and analyzing the collected data.
The results of comparison of ATP levels in tumor tissues of mice in each experimental group are shown in FIGS. 4 and 5. In the figure, x:p<0.05;***:p<0.001;****:p<0.0001。ns:p> 0.05, no statistical difference.
As can be seen from fig. 4, the ATP level of the tumor tissue in the MLT group was significantly higher than that of the tumor-bearing control group, the PRE group and the Q10 group were not statistically different compared to the tumor-bearing control group, and the ATP level of the tumor tissue in the DDP group was lower than that of the tumor-bearing control group. The above conclusion shows that the single mitochondrial function recovery drug has a different mechanism of inhibiting tumor volume from DDP, which can inhibit tumor volume but kill virtually all rapidly proliferating cells (including mucosa, sperm cells) destructively, so that the body immunity level is also reduced; the single mitochondrial function recovery drug achieves the purposes of inhibiting the generation and development of cancer cells by repairing the mitochondrial function, and simultaneously rebuilds the internal environment of an organism to eliminate the microenvironment suitable for the growth of the cancer cells, thereby achieving the purpose of reversing the cancer.
As can be seen from fig. 5, the ATP level of each pharmaceutical composition group was higher than that of the tumor-bearing control group and DDP group, which was substantially consistent with its tumor volume-inhibiting effect, demonstrating that its tumor volume-inhibiting mechanism is different from that of DDP, and its mitochondrial repair effect.
In fig. 4, the effect of MLT on ATP level was most pronounced, but when combined with Se, the effect was significantly reduced. It was demonstrated that not random combinations have a synergistic effect on mitochondrial recovery.
Furthermore, this example also examined the activity of mitochondrial complexes in tumor tissues.
The results in fig. 6 show that a single drug acts on different complexes of mitochondria. For example, MLT can increase the activity of complexes I and II, but PRE and Q10 decrease the activity of complexes I and II instead. None of the single agents had a significant effect on the effect of complex III. Meanwhile, all single drugs have the function of improving the activity of the compound IV. According to the results of fig. 7, the present inventors found that the effect of the combined use of the drugs on the complex was not a simple superposition of the effects of the individual drugs. Comparing the effect of Se + Pre and the pharmaceutical composition of the invention on mitochondria I, II and IV complexes, the pharmaceutical composition of the invention can comprehensively improve the activity of each complex. Comparing Pre + MLT with the pharmaceutical composition of the invention, the former is found to promote the activity of the compound I obviously, but promote the activity of the compound II weakly, even reduce the activity of the compound IV, and play an antagonistic role, while the latter has a more comprehensive role in the activity of the compound. The influence results of tumor volume and tumor tissue ATP level are combined, so that the pharmaceutical composition has balanced effects on various mitochondrial complexes, and has optimal effects of comprehensively repairing mitochondrial functions and inhibiting cancer cell growth compared with other drug groups.
The results further verify that the treatment of mitochondrial function repair is not simple superposition of various mitochondrial function repair drugs, the random combination of single drugs is not enough to comprehensively repair mitochondrial functions, and a comprehensive mitochondrial energy drug composition with a synergistic effect needs to be screened out.
Example 6: effect of pharmaceutical composition on the proportion of tumor tissue immune cells.
The single cell suspensions of the cancer cells prepared in example 5 were analyzed by flow cytometry for changes in the proportions of the immune cells (M, T, B, DC, NK) in the tumor tissues of mice, and the data were sorted and analyzed. The specific results are shown in fig. 8 and fig. 9.
From fig. 8, when PRE and MLT were administered simultaneously with tumorigenesis, the ratio of T cells and the ratio of B cells were increased, compared to the tumor-bearing control group, suggesting that these mitochondrial function-restoring drugs can exert antitumor effects by increasing the ratio of immune cells in the tumor microenvironment.
In the experiment of simultaneous administration of the pharmaceutical composition group shown in fig. 9, from the results of flow cytometry, Se + MLT, Pre + MLT and the pharmaceutical composition of the present invention can increase the ratio of M cells, and the ratio of DC cells and NK cells in tumor tissues of mice can be significantly increased.
The DC cell is an important efficient professional antigen presenting cell for stimulating immune response mediated by B and T lymphocytes, and can actively take a series of different antigen substances; NK cells can recognize and kill target cells and are an important immune factor for resisting cancers and infection of the body. According to the experimental result, the chemotherapeutic drug kills cancer cells by directly acting on the cancer cells, but the regulation immunity effect of the chemotherapeutic drug is weaker, the antigen presenting capability of the immune cells in vivo cannot be improved, and the capability of the body of killing the cancer cells by self is reduced. The medicine composition can simultaneously improve the proportion of DC cells and NK cells in an organism, can up-regulate the antigen presenting capability to resist the immune escape capability of cancer cells, and plays a role in killing the cancer cells depending on the NK cell proportion generated by the organism, thereby showing that the medicine composition can achieve the effect of resisting the cancer cells by regulating autoimmunity.
Hormones are used as messengers in vivo to transmit information, play an important role in regulating physiological processes of organisms and are important substances in life. Recent studies have found that hormones play a crucial role in the development of cancer. Hormone supplementation or reduction is also known as cancer endocrine therapy, and the hormone is used for building the level of mitochondria so as to better play the anticancer role. In the pharmaceutical composition, Se can synthesize thyroxine, so that the metabolism of organisms is regulated, the internal environment is maintained to be relatively stable, the formation of peroxides and free radicals is prevented, the metabolism of cancer cells is blocked, and the division and the growth of the cancer cells are inhibited; PRE is a precursor of androgen synthesis and is very important in the development of lung cancer, the positive rate of androgen receptor in lung cancer tissues is 20%, and androgen deficiency may be a key factor in the onset of lung cancer in men. MLT can enter hypothalamic pituitary axis to regulate human body circadian rhythm, and literature reports show that the MLT can obviously inhibit the invasion and metastasis of lung cancer cell strain A549 and promote apoptosis. The invention combines cancer endocrine therapy, utilizes hormone to build mitochondrial level, comprehensively and effectively regulates the function of immune system and plays a role in resisting cancer.

Claims (5)

1. A medicine composition for treating early cancer by targeting mitochondria comprises pregnenolone, melatonin, selenium as active ingredients and a pharmaceutically acceptable carrier.
2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises the following active ingredients in parts by weight: 25-50 parts of pregnenolone, 3-8 parts of melatonin and 0.2-0.4 part of selenium.
3. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises the following active ingredients in parts by weight: 25 parts of pregnenolone, 5 parts of melatonin and 0.2 part of selenium.
4. The pharmaceutical composition according to claim 1, 2 or 3, wherein the pharmaceutical composition is prepared into any pharmaceutically acceptable dosage form selected from the group consisting of tablets, capsules, powders, granules and syrups.
5. Use of the pharmaceutical composition of any one of claims 1 to 3 for the preparation of a medicament for treating early stage lung cancer by increasing mitochondrial energy.
CN202010085646.XA 2020-02-11 2020-02-11 Pharmaceutical composition for targeting mitochondria in early stage cancer and its application Active CN111000862B (en)

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