LU500644B1 - Drug combination, preparation and application for treating coronary heart disease - Google Patents

Drug combination, preparation and application for treating coronary heart disease Download PDF

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LU500644B1
LU500644B1 LU500644A LU500644A LU500644B1 LU 500644 B1 LU500644 B1 LU 500644B1 LU 500644 A LU500644 A LU 500644A LU 500644 A LU500644 A LU 500644A LU 500644 B1 LU500644 B1 LU 500644B1
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heart disease
coronary artery
parts
weight
pharmaceutical composition
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Peter ping LEE
Jian Li
Shan Xiong
Chenxi Li
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Zibo Weikexun Pharmaceutical Tech Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
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    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
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    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135Compounds containing heavy metals
    • A61K31/714Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/06Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/08Oxides; Hydroxides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate

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Abstract

The invention involves a pharmaceutical composition for treating coronary artery stenosis of coronary heart disease, its preparation method and application. The pharmaceutical composition for treating coronary artery stenosis of coronary heart disease is composed of L- methyl folate salt, coenzyme Q10, methyl vitamin B12, arginine and magnesium oxide as raw materials and supplemented with appropriate dose ratio. The pharmaceutical composition for the treatment of coronary artery stenosis of coronary heart disease is finally prepared. Various raw material components play a synergistic role in improving the function of vascular endothelial cells, eliminating myocardial cell inflammatory factors, and improving myocardial activity. It can effectively metabolize the formed atherosclerosis, dissolve thrombus by thrombolysis, and directly act on the lesion, so as to achieve the purpose of reversing coronary artery stenosis of coronary heart disease. The invention overcomes the defect that the existing technology cannot obtain the imaging improvement effect, and can well achieve lesion reversal and good prognosis.

Description

DRUG COMBINATION, PREPARATION AND APPLICATION FOR TREATING CORONARY HEART DISEASE 0500644
TECHNICAL FIELD
[0001] The invention belongs to the technical field of medicine, specifically relates to the pharmaceutical composition, preparation method and application for treating coronary artery stenosis of coronary heart disease.
BACKGROUND TECHNIQUE
[0002] Coronary heart disease is a heart disease, also known as ischemic heart disease, which is caused by myocardial ischemia, hypoxia (angina) or myocardial necrosis (myocardial infarction) caused by stenosis or obstruction of organic coronary artery (atherosclerosis or dynamic vasospasm). Coronary artery stenosis is caused by thrombus deposition blockage, and the stenosis to a certain extent leads to myocardial infarction, which is myocardial infarction or myocardial infarction.
[0003] Studies have shown that coronary heart disease, myocardial infarction and myocardial infarction are all vascular diseases, which are caused by endothelial cell dysfunction. It is due to the tortuous parts of the physiological structure including cardiovascular and cerebrovascular diseases under the influence of hemodynamics, endothelial cell dysfunction is characterized by lesions. Endothelial cell dysfunction is an important pathological source of many diseases, especially vascular diseases. Coronary heart disease (atherosclerosis) is a vascular disease, a disease of endothelial dysfunction.
[0004] Under physiological conditions, endothelial cells prevent thrombosis by means of different anticoagulant and antiplatelet mechanisms. These cells take part in all major hemostasis pathways triggered during vascular injury and limit blood clot formation to areas requiring hemostasis to restore vascular integrity. As a result of genetic or acquired disorders, this complex breakdown of balance between coagulants and anticoagulant systems can result in bleeding or thrombosis. Endothelial dysfunction not only occurs before the occurrence of atherosclerosis, but also may occur during arterial thrombosis. The above-mentioned conditions are shown in endothelial cells endogenous synthesis and release of NO function. Studies have confirmed that endothelial-derived NO reduction is caused by the endothelial phenotype changes. Based on the above-mentioned theory, NO thrombolysis and thrombosis models were established. In these models, inhibiting endothelial NO production would exacerbate coronary artery lesions, and L- arginine treatment retained vascular morphology.
[0005] In an inflammatory state, due to the increase of C-reactive protein level, atherosclerosis is promoted and endothelial dysfunction occurs. By reducing the stability of eNOS mRNA (endothelial nitric oxide synthase messenger ribonucleic acid), to reduce the production of NO mediated by eNOS (endothelial nitric oxide synthase). What's more, the two mediators of 1 atherosclerosis, oxidized lipoproteins and lysophospholipid choline, inhibit the release of NO and EDHF (endothelial-dependent hyperpolarization factor, an important active substance wit! 200644 vasodilator effect). Oxidized low density lipoprotein can also reduce the expression or function of eNOS, which can be reversed by antioxidants. Lipids and oxidants can also reduce the bioavailability of NO by damaging cytoplasmic membrane microcapsules and activating NFxB (nuclear factor)-mediated pro-inflammatory pathway. At present, the consistent content in the research is that: the above physiological processes mainly lead to a kind of amino acid metabolite called “homocysteine”. The accumulation of homocysteine forms high homocysteine and then forms “hyperhomocysteinemia”. Therefore, it is believed that high homocysteine is an independent risk factor for vascular diseases such as stroke and myocardial infarction.
[0006] Based on the above theory, the most important dysfunction of endothelial cells is the synthesis and release of NO. The inventor further realizes in clinical practice that the complex enzymatic reaction process activates three kinds of NO synthases to play the role of NO synthesis. The inhibition of asymmetric dimethylarginine (ADMS) on three NO synthases (NOS: neuronal nitric oxide synthase, nNOS, NOS-1; inducible nitric oxide synthase, INOS, NOS-2; endothelial nitric oxide synthase, eNOS, NOS-3) can be reversed by high concentration of L arginine and catalyzed to NO. NOS can produce superoxide anion and uncoupling when the activity of L arginine substrate or other auxiliary factors is deficient. ADMS can also decompose NOS and lead to the production of superoxide (biological characteristics of ADMS). Therefore, endothelial cell function not only has the effect of thrombolysis, thrombolysis and vasodilation, but more importantly, it can also metabolize the formed vascular plague and the physiological garbage deposited in the vascular wall, so as to improve imaging or eliminate vascular occlusion. This is particularly prominent during reversal treatment of coronary stenosis stents.
[0007] NO is the main substance that maintains and ensures the normal work of endothelial cells. NO not only has the effect of dilating blood vessels, but also is an important neurotransmitter with thrombolytic and thrombolytic effects. Arginine is a direct precursor for NO synthesis, a natural maintenance agent and stabilizer for endothelial NO synthase cofactor, and a maintenance substance for endothelial cells. Studies have shown that increasing arginine supply contributes to increase NO production and improve endothelial cell function. That is: it's helpful to cardiovascular and cerebrovascular diseases. Arginine is a semi-essential amino acid, which is prone to deficiency in a certain population and becomes more obvious with age. Endothelial cell NO synthesis is accomplished by endothelial cell NO synthase. Endothelial cell NO synthase activity is closely related to the cofactors of the enzyme, and patients with cardiovascular and cerebrovascular diseases have different degrees of defects in the cofactors of the synthase.
[0008] At present, therapeutic drugs include lowering plasma cholesterol drugs, inhibiting cholesterol absorption, conversion drugs, and anti-hyperlipidemia drugs. The pharmacology of these drugs is to reduce the formation of atherosclerosis by lowering cholesterol or blood lipids without metabolizing the formed atherosclerosis. Clinically, the treatment of coronary heart 2 disease with cholesterol and blood lipids has been proved to be unable to fundamentally eliminate the formation of atherosclerosis at the root of coronary heart disease, let alone to treat myocardiar 200044 ischemia and hypoxia or myocardial necrosis caused by stenosis or obstruction. Therefore, interventional therapy “stent placement” and coronary artery bypass graft treatment methods have emerged. “Stent placement” is a temporary treatment for dredging blood vessels by clinical physical methods, which cannot prolong the life of patients, and may cause other coronary arteries to accelerate the development of atherosclerosis, and must be treated with antithrombotic drugs for a long time, which has huge side effects.
INVENTION CONTENT
[0009] In order to solve the above-mentioned problems in the existing technology, the invention offers a drug composition with good safety, good curative effect and basically no side effect, and its preparation method and application. The drug composition can effectively metabolize the atherosclerosis formed in coronary artery stenosis of coronary heart disease, and can obtain imaging improvement.
[0010] The technical scheme of the present invention is:
[0011] The raw material components of the drug composition for the treatment of coronary artery stenosis of coronary heart disease include:
[0012] L-methyl folate salt7.5-15 parts by weight, coenzyme Q10 150-300 parts by weight, methyl vitamin B122-4 parts by weight, arginine 100-200 parts by weight, magnesium oxide 100-200 parts by weight share.
[0013] The raw material components of the further optimized the pharmaceutical composition for the treatment of coronary artery stenosis in coronary heart disease include:
[0014] 8-10 parts by weight of L-methyl folate salt, 180-260 parts by weight of coenzyme Q10,
122.5-3.5 parts by weight of methyl vitamin B, 120-180 parts by weight of arginine, 120-180 parts by weight of magnesium oxide 180 parts by weight.
[0015] The raw material components of the further optimized the pharmaceutical composition for the treatment of coronary artery stenosis in coronary heart disease include:
[0016] 8 parts by weight of L-methyl folate salt, 200 parts by weight of coenzyme Q10, 3 parts by weight of methyl vitamin B12, 150 parts by weight of arginine, and 150 parts by weight of magnesium oxide.
[0017] The formulation of the pharmaceutical composition is powder, pill, tablet or capsule.
[0018] A method for preparing the pharmaceutical composition for the treatment of coronary artery stenosis of coronary heart disease includes the following steps:
[0019] (1) Weigh L-methyl folate salt, coenzyme Q10, and methyl vitamin B12 respectively, and mix under stirring conditions to obtain a mixture A;
[0020] (2) Weigh arginine and magnesium oxide, and mix them under stirring conditions to obtain a mixture B; 3
[0021] (3) Mix mixture A and mixture B uniformly to obtain the pharmaceutical composition for treating coronary artery stenosis of coronary heart disease. LUS00644
[0022] In step (1), the stirring speed is 1000-2000 rpm, and the stirring time is 10-20 min
[0023] In step (2), the stirring speed is 1000-2000 rpm, and the stirring time is 10-20 min.
[0024] In step (3), the particle size of the pharmaceutical composition is 300-500 mesh.
[0025] In step (3), the particle size of the pharmaceutical composition is 400 mesh.
[0026] The application of any of the pharmaceutical composition in preparation of drugs for coronary artery stenosis of coronary heart disease.
[0027] In order to facilitate the understanding of the invention, the bulk drug and drug effect of the invention are further elaborated.
[0028] L-methyl folate salt can enter the human body to obtain L-methyl folate, which is the only active form of folic acid that can pass through the blood-brain barrier. On the one hand, L-methyl folate is a NO synthase cofactor, which controls the synthesis of NO by affecting the activity of NO synthase, and then affects the function of vascular endothelial cells. On the other hand, L- methyl folate takes parts in the mutual conversion of amino acids, converting homocysteine to methionine to eliminate the accumulation of homocysteine to form homocysteine, thus eliminating the damaging effect of high homocysteine on vascular endothelial cells to eliminate obstacles of NO synthesis and release.
[0029] Coenzyme Q10 is a kind of fat-soluble quinone compound which exists in nature and its structure is similar to vitamin K, vitamin E and quinone. It is involved in energy production and activation in human body cells and is the most effective antioxidant component to prevent the formation of atherosclerosis. At the age of 20, the ability of self-synthesized coenzyme Q10 reaches the peak and maintains at about 50 years old. Then it will decrease year by year, because the mitochondrial DNA material stored in coenzyme Q10 is destroyed by oxygen free radicals, resulting in the reduction of independent synthesis of coenzyme Q10. As a result, the metabolic function of human cells, especially heart cells, decreases. The physiological process of coenzyme Q10 is similar to that of NO synthesis by endothelial cells. At the age of 20, the synthesis of NO in endothelial cells reaches the peak, and then the vascular function reaches the best state. After that, the synthesis of NO in endothelial cells decreases gradually. At the age of 60, the function of endothelial cells is only about 15 % of the peak. Coenzyme Q10 helps to provide sufficient oxygen for myocardium and prevent sudden heart disease, and it especially plays a vital role during myocardial hypoxia. Since most patients with cardiovascular and cerebrovascular diseases take statins in large quantities, statins inhibit cholesterol synthesis and lipid-lowering, and also inhibit the production of coenzyme Q10 in the body. Middle-aged and elderly patients are more likely to have insufficient coenzyme Q10 in the body. Therefore, the patients must supplement coenzyme Q10 at the same time when using statins.
[0030] Methyl vitamin B12 is one of two bioactive vitamin B12. Methyl vitamin B12 is the main form of circulating vitamin B12, which is transported to peripheral tissues in this form. Vitamin B12 4 plays a vital role in maintaining the normal function of the nervous system and it is also involved in the physiological process related to B12. Vitamin B12 deficiency can cause anemia, mental 200644 retardation, nervous system dysfunction and other diseases. Aging and many diseases can lead to vitamin B12 activation disorders, causing cardiovascular and cerebrovascular diseases.
[0031] Arginine, a semi-essential amino acid, is the direct precursor for NO synthesis. It is a biologically active substance necessary to maintain the normal function of the nervous system and blood circulation, and it will be increasingly scarce with age.
[0032] Magnesium oxide enhances the activity of various enzymes in heart organs, helps blood circulation and relieves nerves, maintains normal muscle (including myocardium) and nerve activity and reduces calcification in soft tissues (including myocardium).
[0033] The beneficial effect of the invention is:
[0034] The pharmaceutical composition for the treatment of coronary artery stenosis of coronary heart disease described in the present invention adopts L- methyl folate salt, coenzyme Q10, methyl vitamin B12, arginine, and magnesium oxide as raw materials for formulation and supplemented by appropriate dose ratio. Among them, L- methyl folate salt and arginine correct and improve the function of vascular endothelial cells by regulating the synthesis and release of NO in vascular endothelial cells. Magnesium ion provided by magnesium oxide is an activator of NO synthase in a variety of vascular endothelial cells, which regulates the synthesis of NO in vascular endothelial cells by activating neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS ) induced by injury. In addition, magnesium ions have the effect of blocking the outward current of potassium ion channels, and regulating the balance of myocardial potassium by preventing the outflow of potassium ions to avoid heart failure caused by low potassium. Meanwhile, magnesium ion, as a calcium blocker, can have the effect of inhibiting calcium channels and avoid excessive “calcium repair’ caused by inflammatory factors leading to vascular blockage and vascular calcification. Coenzyme Q10 has the effect of activating inducible nitric oxide synthase (iNOS), acting on cardiac atherosclerosis or directly reacting with peroxide free radicals through anti-lipid peroxidation, while regulating cardiac energy metabolism to maintain myocardial activity. The final prepared pharmaceutical composition for the treatment of coronary artery stenosis of coronary heart disease, with the synergistic effect of various raw material components, plays a joint role in improving the function of vascular endothelial cells, eliminating the inflammatory factors of myocardial cells, and improving myocardial viability. It effectively metabolizes the formed atherosclerosis, dissolves thrombus by thrombolysis, and directly acts on the lesion, thus achieving the purpose of reversing coronary artery stenosis of coronary heart disease. The invention overcomes the defect that the prior technique cannot obtain the imaging improvement effect, thus well achieving the lesion reversal and a good prognosis.
DESCRIPTION FOR THE FIGURES
[0035] FIG. 1 shows the CTA scan of a patient before treatment in a typical case 1 of the clinical 900644 trial of the invention;
[0036] FIG. 2 shows the CTA scan of a patient after treatment in a typical case 1 of the clinical trial of the invention;
[0037] 1-Calcification point; 2-right coronary artery.
SPECIFIC IMPLEMENTATION MODE
[0038] The invention is further illustrated below by specific embodiments.
[0039] Example 1
[0040] This embodiment provides a pharmaceutical composition for treating coronary artery of coronary heart disease, and the raw material components include:
[0041] L-Calcium methyl folate 7.5mg Coenzyme Q10 150mg Methyl vitamins B12 2mg Arginine 100mg Magnesium Oxide 100mg
[0042] Further, provide a method for preparing the drug for coronary stenosis of coronary heart disease, including the following steps:
[0043] (1) Weigh L-methyl folate calcium, coenzyme Q10, and methyl vitamin B12 respectively, and stir them at a stirring speed of 1000 rpm for 20 min to obtain mixture A;
[0044] (2) Weigh arginine and magnesium oxide, and stir them at a stirring speed of 1000 rpm for min to obtain mixture B;
[0045] (3) Mix the mixture A and the mixture B uniformly to obtain a pharmaceutical composition for the treatment of coronary artery stenosis with a particle diameter of 300 nm.
[0046] (4) Add conventional adjuvants to the pharmaceutical composition for treating coronary artery stenosis of coronary heart disease described in step (3), and prepare a capsule according to a conventional process.
[0047] Example 2
[0048] The embodiment provides a pharmaceutical composition for the treatment of coronary artery stenosis of coronary heart disease. The raw materials include:
[0049] L-Magnesium Methyl folate 8mg Coenzyme Q10 180mg Methyl vitamins B12 2.5mg Arginine 120mg Magnesium Oxide 120mg 6
[0050] Further, provide a method for preparing the drug for coronary stenosis of coronary heart disease, including the following steps: LUS00644
[0051] (1) Weigh L-methyl magnesium folate, coenzyme Q10, and methyl vitamin B12 respectively, and stir them at a stirring speed of 1000 rpm for 20 min to obtain mixture A;
[0052] (2) Weigh arginine and magnesium oxide, and stir them at a stirring speed of 2000 rpm for min to obtain mixture B;
[0053] (3) Mix the mixture A and the mixture B uniformly to obtain a pharmaceutical composition for the treatment of coronary artery stenosis of coronary heart disease with a particle diameter of 300 nm.
[0054] (4) Add conventional adjuvants to the pharmaceutical composition for treating coronary artery stenosis of coronary heart disease described in step (3), and prepare powders according to conventional techniques.
[0055] Example 3
[0056] This embodiment provides a pharmaceutical composition for the treatment of coronary artery stenosis of coronary heart disease; the raw material components include:
[0057] L- Calcium methyl folate 15mg Coenzyme Q10 300mg Methyl vitamins B12 4mg Arginine 200mg Magnesium Oxide 200mg
[0058] Further, it provides a method for preparing the drug for coronary stenosis of coronary heart disease, including the following steps:
[0059] (1) Weigh L-methyl folate calcium, coenzyme Q10, and methyl vitamin B12 respectively, and stir them at a stirring speed of 1000 rpm for 20 min to prepare a mixture A;
[0060] (2) Weigh arginine and magnesium oxide, and stir them at a stirring speed of 2000 rpm for 10 min to obtain a mixture B;
[0061] (3) Mix the mixture A and the mixture B uniformly to obtain a pharmaceutical composition for treating coronary artery stenosis of coronary heart disease with a particle diameter of 500 nm.
[0062] (4) Add conventional adjuvants to the pharmaceutical composition for treating coronary artery stenosis of coronary heart disease described in step (3), and prepare a pill according to a conventional process.
[0063] Example 4
[0064] This embodiment provides a pharmaceutical composition for the treatment of coronary artery stenosis of coronary heart disease; the raw material components include:
[0065] L- Magnesium Methyl folate 10mg Coenzyme Q10 260mg 7
Methyl vitamins B12 3.5mg Arginine 180mg LUS00644 Magnesium Oxide 180mg
[0066] Further, provide a method for preparing the drug for coronary stenosis of coronary heart disease, including the following steps:
[0067] (1) Weigh L-methyl magnesium folate, coenzyme Q10, and methyl vitamin B12 respectively, and stir them at a stirring speed of 1000 rpm for 18 min to obtain a mixture A;
[0068] (2) Weigh arginine and magnesium oxide, and stir them at a stirring speed of 1000 rpm for 18 minutes to obtain a mixture B;
[0069] (3) Mix the mixture A and the mixture B uniformly to obtain a pharmaceutical composition for the treatment of coronary artery stenosis with a particle size of 400 nm.
[0070] (4) Add conventional excipients to the pharmaceutical composition for treating coronary artery stenosis of coronary heart disease described in step (3), and prepare tablets according to conventional techniques.
[0071] Example 5
[0072] This embodiment provides a pharmaceutical composition for the treatment of coronary artery stenosis of coronary heart disease, and the raw material components include:
[0073] L- Calcium Methyl folate 8mg Coenzyme Q10 200mg Methyl vitamins B12 3mg Arginine 150mg Magnesium Oxide 150mg
[0074] Further, provide a method for preparing the drug for coronary stenosis of coronary heart disease, including the following steps:
[0075] (1) Weigh L-methyl folate calcium, coenzyme Q10, and methyl vitamin B12 respectively, and stir them at a stirring speed of 2000 rpm for 15 min to prepare a mixture A;
[0076] (2) Weigh arginine and magnesium oxide, and stir them at a stirring speed of 2000 rpm for mins to obtain a mixture B;
[0077] (3) Mix the mixture A and the mixture B uniformly to obtain a pharmaceutical composition for the treatment of coronary artery stenosis with a particle diameter of 400 nm.
[0078] (4) Add conventional adjuvants to the pharmaceutical composition for treating coronary artery stenosis of coronary heart disease described in step (3), and prepare a capsule according to a conventional process.
[0079] Clinical trial example
[0080] I. Clinical data: From June 2012 to now, 68 patients with coronary artery stenosis and 18 patients with carotid artery plaque were clinically screened for efficacy study. Among the patients with coronary artery stenosis, 35 cases with severe stenosis and 15 cases with moderate stenosis. 8
[0081] Il. Judgment of curative effect:
[0082] Significantly effective: coronary stenosis is reversed more than one level (20 %). LUS00644
[0083] Effective: stenosis is improved, symptoms are relieved.
[0084] The effect is not obvious or ineffective: the symptoms are not relieved or improved.
[0085] Ill. Clinical trial results: 50 cases of coronary artery stenosis are significantly effective in the treatment of coronary heart disease, accounting for 73.5%; 5 cases are effective, accounting for 7.4%; 13 cases are ineffective, accounting for 19.1%, and the total effective rate is 80 .9%. In the treatment of carotid plaque, 12 cases are significantly effective, 66.7%; 3 cases are effective, accounting for 16.6%, and 3 cases are ineffective, accounting for 16.7%; the total effective rate is 83.3%.
[0086] IV. Typical cases
[0087] Typical Case 1:
[0088] Li, male, 42 years old. On November 17, 2016, due to a sudden cardiac discomfort, he went to a third-class hospital in a central hospital, the hospital's CTA scan showed that there were more shadows around the calcification point of the right coronary artery (see Figure 1), and the vascular lumen was narrowed by about 90%, which was a severe stenosis. The hospital recommended doing radiograph and putting the stent for him. Li considered that he was still young and the stent might cause permanent damage to the heart. He disagreed with the hospital's recommendation and was discharged. After consultation, he agreed to take the capsules of the drug composition of the present invention, and stop taking any other drugs. After taking the drug composition for 16 days, the heart discomfort symptoms were basically relieved. One month later, he felt quite good. He went to the same hospital for a follow-up visit after 5 months. The CTA scan showed that the shadowed part around the calcification point of the right coronary artery was metabolized and disappeared (see Figure 2). The stenosis was about 50%, belonging to moderate stenosis, which was better than before.
[0089] CTA detection report content:
[0090] On Nov. 17”, 2016, CTA observations and impressions of coronary arteries and heart: calcified plagues are seen in the trunk of left coronary artery, and local lumen is slightly narrow; low-density plaque is observed in the proximal segment of left anterior descending branch, and local lumen is slightly narrow; there is no obvious abnormality in the left circumflex. Mixed density plaques are observed in the proximal segment of the right coronary artery, and local lumen is severely narrow. Diagnosis opinions: 1. Left main coronary artery calcified plaques are formed, and local lumen is slightly narrow. 2. The left anterior descending branch of proximal low-density plaques are formed, and local lumen is slightly narrow. 3. The right coronary artery proximal mixed density plaques are formed, and local lumen is slightly narrow.
[0091] On May. 5, 2017, CTA findings and impressions of coronary artery and cardiac: the main left coronary artery is not abnormal, mixed-density plaque formation is seen on the wall of the beginning of the left anterior descending branch, and the corresponding lumen stenosis is about 9
40%; There are no obvious abnormalities in the remaining segments and main branches; no obvious abnormalities in the left circumflex branch; mixed-density plagues are formed on the wal 200644 of the proximal right coronary artery, and the corresponding lumen stenosis degree is about 50%, compared with the film on November 17, 2016 , which is smaller than before; no obvious abnormalities in the remaining sections. Diagnosis opinions: 1. Mixed plaques are formed on the wall at the beginning of the left anterior descending branch, and the corresponding lumen is slightly narrowed; 2. Mixed-density plaques are formed on the proximal wall of the right coronary artery, and the corresponding lumen is moderately narrowed, which is better than before, please combine with clinical.
[0092] Typical Case 2:
[0093] Wei XX, male, 54 years old. His coronary heart disease was serious. A CTA scan of Dec. 2nd, 2016 in a medical school shows that diffuse calcification and non-calcified plague formation were seen in the proximal left circumflex artery, resulting in severe narrowing of the corresponding lumen, discontinuous filling of local contrast media, and poor distal filing; The hospital recommended to put at least 3 stents for him. Because of his serious condition, it was difficult for him to go upstairs, and he even dare not “tilt the waist”, which would cause dizziness; walking one or two hundred meters makes him feel very uncomfortable. It was suggested to treat him with the pharmaceutical composition of the present invention. After 7 days, the symptoms wer relieved, and drugs such as Plavix and aspirin were stopped. Taking into account the patient's severe hypertension, the drugs cannot be stopped immediately. The hypertension drugs and blood lipid- lowering drugs were slowly reduced. After 2 months, the discomfort was basically eliminated. After months, a CTA scan in a third-class hospital of a central hospital shows that multiple soft plaques and mixed plaque formation were seen in the left circumflex branch; the corresponding lumen had different degrees of narrowing, and the severe stenosis disappeared.
[0094] CTA detection report content:
[0095] On Dec. 2", 2016, Clinical diagnosis: coronary atherosclerotic coronary heart disease. In the proximal segment of the left anterior descending coronary artery, localized mixed plaques are observed, with mainly calcified components, resulting in mild stenosis of the corresponding lumen; In the proximal segment of the second diagonal branch, localized non-calcifying plaques are observed, resulting in slight narrowing of the corresponding lumen; Diffuse calcification and non- calcification plaque formation are seen in the proximal part of the left circumflex branch, resulting in severe narrowing of the corresponding lumen, discontinuous filling of local contrast media, and poor distal filling; The middle branch and pure marginal branch are slender. Diffuse calcification and non-calcification plaque formation are seen in the right coronary artery. Diagnosis opinions:
1. Based on the CTA manifestations of left circumflex plaque formation and subtotal occlusion, DSA testing is recommended; 2. It is consistent with the CTA manifestation of multiple coronary plaque formation and luminal stenosis.
[0096] On May. 12", 2017, CTA findings and impressions of coronary artery and heart: there is no abnormality in the trunk of left coronary artery, localized mixed plaques are observed in the proximal segment of left anterior descending artery, and corresponding lumen has mild [0500644 moderate stenosis. Multiple soft plaques and mixed plaques are seen in the left circumflex branch and the corresponding lumen has different degrees of narrowing; Multiple soft plaques and mixed plaques are observed in the right coronary artery, and the corresponding lumen has different degrees of narrowing. Diagnosis opinions: 1. Mixed plague formation are seen in the proximal segment of left anterior descending branch, and the corresponding lumen has mild to moderate stenosis. 2. Multiple soft plaques and mixed plaques are seen in the left circumflex branch and the corresponding lumen has different degrees of narrowing. 3. Multiple soft plaques and mixed plaques are observed in the right coronary artery, and the corresponding lumen has different degrees of narrowing.
[0097] The contents mentioned above are only the specific embodiments of the invention, but the protection scope of the invention is not limited to this. And any technical person familiar with the technical field who can easily think of changes or replacements within the technical scope disclosed by the invention shall be covered by the protection scope of the invention. Therefore, the protection scope of the invention should be subject to the protection scope of the claims.
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Claims (10)

  1. CLAIMS LU500644
    1. The feature of the pharmaceutical composition for treating coronary artery stenosis of coronary heart disease is that the raw material components include:
    7.5-15 parts by weight of L-methyl folate salt, 150-300 parts by weight coenzyme Q10, 2-4 parts by weight of methyl vitamin B12, 100-200 parts by weight of arginine, and 100-200 parts by weight of magnesium oxide.
    2. According to the drug composition for treating coronary artery stenosis of coronary heart disease described in claim 1, its features are that the raw material components include: 8-10 parts by weight of L-methyl folate salt, 180-260 parts by weight of coenzyme Q10, 122.5-
    3.5 parts by weight of methyl vitamin B, 120-180 parts by weight of arginine, 120-180 parts by weight of magnesium oxide.
    3. According to the drug composition for treating coronary artery stenosis of coronary heart disease described in claim 1, its features are that the raw material composition includes: 8 parts by weight of L-methyl folate salt, 200 parts by weight of coenzyme Q10, 3 parts by weight of methyl vitamin B12, 150 parts by weight of arginine, and 150 parts by weight of magnesium oxide.
    4. According to the claim 1-3 any of the pharmaceutical composition for treating coronary artery stenosis of coronary heart disease, its features are that the dosage form of the pharmaceutical composition is powder, pill, tablet or capsule.
    5. A method for preparing the pharmaceutical composition for treating coronary artery stenosis in coronary heart disease described in any of the requirements 1-4 consists of below steps: (1) Weigh L-methyl folate salt, coenzyme Q10, and methyl vitamin B12 respectively, and mix under stirring conditions to obtain mixture A; 2) Weigh arginine and magnesium oxide, and mix them under stirring conditions to obtain mixture B; 12
    L 44 (3) Mix the mixture A and the mixture B uniformly to obtain the the pharmaceutical 5006 composition for treating coronary artery stenosis of coronary heart disease.
    6. According to the method described in claim 5 for the preparation of the pharmaceutical composition for treating coronary artery stenosis of coronary heart disease, the feature is that in step (1), the stirring speed is 1000 — 2000 rpm, and the stirring time is 10 — 20 min.
    7. According to the method described in claim 5 for the preparation of the pharmaceutical composition for treating coronary artery stenosis of coronary heart disease, the feature is that in step (2), the stirring speed is 1000 — 2000 rpm, and the stirring time is 10 — 20 min.
    8. According to the preparation method of drug composition described in claim 5, its feature is that in step (3), the particle size of the drug composition is 300 — 500 meshes.
    9. According to the method of preparing the pharmaceutical composition described in claim 8, the feature is that the particle size of the pharmaceutical composition is 400 mesh.
    10. Application of any of the pharmaceutical composition described in claim 1-4 in preparation of drugs for treating coronary stenosis of coronary heart disease.
    13
LU500644A 2021-09-10 2021-09-10 Drug combination, preparation and application for treating coronary heart disease LU500644B1 (en)

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