阅读说明：本技术 青霉素g钠盐的新用途 (New application of penicillin G sodium salt ) 是由 司正仕 于 2020-06-03 设计创作，主要内容包括：本发明涉及药物化学领域,具体的说是一种将青霉素G钠盐用于制备治疗类风湿关节炎的药物组合物或制剂的应用,其特征在于,将青霉素G钠盐或其衍生物用于制备治疗类风湿关节炎的药物组合物或制剂,本发明所述治疗类风湿关节炎的药物组合物或制剂中还含有维生素C,本发明所述药物组合物或制剂中含1600万～2000万单位/日的青霉素G钠盐或其衍生物,本发明具有治疗速度快,有效率特高,治愈率较高(与患者坚持到底的数量、所占比例有关,部分病人只要达到病情被控制就已经很满意而停止继续治疗,无形中影响了治愈率),毒副作用小,安全可靠等显著的优点。(The invention relates to the field of medicinal chemistry, in particular to an application of penicillin G sodium salt in preparing a medicinal composition or a preparation for treating rheumatoid arthritis, the invention is characterized in that penicillin G sodium salt or derivatives thereof are used for preparing a pharmaceutical composition or preparation for treating rheumatoid arthritis, the pharmaceutical composition or preparation for treating rheumatoid arthritis also contains vitamin C, and the pharmaceutical composition or preparation contains 1600-2000 million units/day of penicillin G sodium salt or derivatives thereof.)

1. The new application of penicillin G sodium salt is characterized in that penicillin G sodium salt or derivatives thereof are used for preparing a pharmaceutical composition or a preparation for treating rheumatoid arthritis.

2. The new use of penicillin G sodium salt as claimed in claim 1, wherein said pharmaceutical composition or formulation for treating rheumatoid arthritis further comprises vitamin C.

3. The new use of penicillin G sodium salt as claimed in claim 1, wherein said pharmaceutical composition or formulation comprises 1600 to 2000 ten thousand units/day of penicillin G sodium salt or its derivatives.

4. The new use of penicillin G sodium salt as claimed in claim 1, wherein said pharmaceutical composition or formulation comprises vitamin C in an amount of 25-33.3% by weight of the pharmaceutical composition or formulation.

5. The novel use of penicillin G sodium salt as claimed in claim 1, wherein said pharmaceutical composition or formulation for the treatment of rheumatoid arthritis comprises penicillin G sodium salt and vitamin C, wherein in the first treatment period, 480 ten thousand units of penicillin G sodium salt is added into 250ml of physiological saline for intravenous drip once every 8 hours for 20 days, 250mg of vitamin C injection is added into 500ml of 5% glucose injection for intravenous drip once a day for 10 days; the second course of treatment, penicillin G sodium salt 80 ten thousand units, intramuscular injection, once every 12 hours for 20 days, vitamin C tablet 0.05G, three times a day, oral administration, take 5 days.

6. The novel use of penicillin G sodium salt as claimed in claim 1, wherein said pharmaceutical composition or formulation for the manufacture of a medicament for the treatment of rheumatoid arthritis comprises penicillin G sodium salt and vitamin C, wherein the first treatment period, penicillin G sodium salt is added in 250ml of physiological saline in 800 ten thousand units, and the solution is administered by intravenous drip once every 12 hours for 20 days, and vitamin C is administered in 0.05G tablets three times a day for 10 days; the second course of treatment, penicillin G sodium salt 80 ten thousand units, intramuscular injection, once every 12 hours, 20 days totally, vitamin C injection 250mg, dissolved in 5% glucose injection 500ml, intravenous drip, once a day, 10 days.

7. The novel use of penicillin G sodium salt as claimed in claim 1, wherein said pharmaceutical composition or formulation for the treatment of rheumatoid arthritis comprises penicillin G sodium salt and vitamin C, wherein in the first treatment period, 800 ten thousand units of penicillin G sodium salt is added to 250ml of physiological saline and intravenously administered once every 12 hours for 20 days; vitamin C tablet 0.05g, three times a day, orally taken for 10 days; the second course of treatment, penicillin G sodium salt 80 ten thousand units, intramuscular injection, once every 12 hours, 20 days, vitamin C injection 250mg, dissolved in 5% glucose injection 500ml, intravenous drip, once daily, 10 days.

8. The new use of penicillin G sodium salt as claimed in claim 1, wherein said pharmaceutical composition or formulation for the treatment of rheumatoid arthritis comprises penicillin G sodium salt and vitamin C, wherein when the patient has dyspnea, breath holding, and profuse sputum, and requires nebulization, 2ml of solution is prepared from 20 ten thousand units of penicillin G sodium salt and water for injection, and nebulization is performed twice a day.

The technical field is as follows:

the invention relates to the field of medicinal chemistry, in particular to application of penicillin G sodium salt in preparing a medicinal composition or preparation for treating rheumatoid arthritis.

Background art:

rheumatoid arthritis is a common disease at home and abroad, almost all races and nationalities occur, the incidence rate of the rheumatoid arthritis is about 0.5-1.5% in most people, but the incidence rate of the rheumatoid arthritis is 3.5-5.3% in some Indian tribes in the United states (Pizhong in Jiangling, Meishawu-the fourth chapter of 11 th edition of Utility internal science, rheumatoid arthritis). The disease has a long course of disease and can not be cured for a long time, which not only causes poverty, but also can cause complications of organ injury, seriously threatens the health and life safety of patients, and is one of the diseases which are mainly researched in the department of rheumatism in the world. Rheumatoid arthritis mainly attacks the small joints of hands and feet, and a few of them usually involve one or more large joints and often occur in the knee, shoulder and other parts. The main pathological changes of the disease are: the infiltration of synovial cells of joints, the formation of pannus and the erosion of cartilage and bone tissues can cause the damage and deformity of joint structures and the loss of joint functions; severe cardioinflammation, etc.; ③ rheumatoid pneumonia, pneumoconiosis and the like; extensive damage to the nervous system; impairment of blood cells and hematopoietic function; damage to digestive system; seventhly, kidney damage; the pathological changes of the ② (the fourthly) cause the injury, which becomes the three most serious complications.

The human society still has no definition on the etiology and treatment method of rheumatoid arthritis so far, most experts consider that the diseases can be related to heredity, infection and hormone, and are not yet determined, but the fact that the rheumatoid arthritis is cured while various severe infectious diseases are treated for many times in clinic is more prone to the infectious theory. The understanding of rheumatoid arthritis has been deepened in many years, and both famous medical books and textbooks are revised year by year. First, the disease is considered to be "immotile cancer", meaning that the disease is not well treated, but suffers from extreme pain like cancer, but does not affect life like cancer. Second, the disease is called rheumatoid arthritis in the 6 th edition of "practical internal science" which is one of medical books with the highest authority and the highest prize winning: "this disease does not cause direct death, but severe advanced cases can die from secondary infections. ". ③ 11 th edition, this disease is called rheumatoid arthritis instead, and it is considered that: the direct death caused by the wind-like customs (short for) is rare, mainly causes disability, leads the life to be incapable of self-care, reduces the working capacity, influences the life quality and causes serious economic burden to families and society. ". The new prognosis concept has been proposed explicitly starting from the 12 th edition: namely, the patient has three major systemic complications of heart, lung and nervous system at the same time, and the five-year survival rate is less than 50 percent. Fifth, the 13 th edition and later editions and textbooks are successively more clearly written, once complications of the nervous system occur, the five-year survival rate of the patients is less than 50%. Sixthly, once any one of three complications occurs to the patient, the survival rate of the patient in five years is less than 50 percent. Seventhly, once any one of a plurality of complications occurs to the patient, the survival rate of the patient is less than 50 percent in five years. The 15 th edition is then written more clearly: "in the natural course of disease of RA (first letter abbreviation of English word of rheumatoid arthritis), 5-10 years of disability rate is 60%, 30 years of disease rate is 90%, the life is shortened by 10-15 years, and the 5-year survival rate of the patients with the appearance of the joint is only 50%. ". It is proved that people's understanding of rheumatoid arthritis is more and more clear, and it is not only painful, but also fatal. At present, no specific therapy for the disease is available at home and abroad. In the past several years, domestic experts have invited more than thirty experts, scholars and colleagues in countries and regions to study the disease rheumatoid arthritis in China, and the disease is also considered to be difficult to cure. Medical practitioners in the united states describe the disease as 5 "D", namely pain (discofort), death (death), disability (disability), economic loss (villar loss), and drug intoxication (drug toxicity). As Zhang Zhengzhong mr. written in the book of rheumatoid arthritis, rheumatoid arthritis is listed as a disease which is very difficult to cure, and he teaches a process that twin brothers of himself are not recovered. And patients and families in whom rheumatoid arthritis was considered to belong to "5D" were changed from the original "5D". Medical practitioners in the united states describe the disease as 5 "D", namely pain (discofort), death (death), disability (disability), economic loss (villar loss), and drug intoxication (drug toxicity). In addition, on the basis that the initial letters of 5 english words and sentences describing rheumatoid arthritis are all 'D', the disease which is difficult to treat (rheumatoid arthritis is a disease) is added, besides 1 'D', 1 'D' is also a disease which is difficult to see (diffcult to seek) and is 7 'D' in total, so the disease is also called as '7D'. At present, the same way in China still uses conventional non-steroidal anti-inflammatory drugs (salicylic acids, ibuprofen and the like which only have the temporary analgesic effect and have the reduced or eliminated analgesic property after long-term use and serious toxic and side effects); glucocorticoids (prednisone, dexamethasone and the like which can cause severe toxic and side effects such as multiple organ injury, femoral head necrosis, systemic water-salt metabolism disorder and the like after long-term use); the medicines for improving the disease condition (antimalarial drugs, penicillamine and the like which can not avoid serious toxic and side effects after long-term use), immunosuppressant (methotrexate, cyclophosphamide, colchicine, blumea and the like which can kill blood cells and even have serious toxic and side effects such as hematopoietic disorder and the like), tripterygium wilfordii, transfer factor and other various medicines are used together or singly, and the treatment is carried out by adopting a pyramid scheme, a lower step scheme, an upper step scheme and a zigzag scheme, so the effect is not very ideal.

Penicillin is a common antibacterial drug, and the pharmacological characteristic of penicillin G sodium salt is that it has a bactericidal effect during the bacterial reproduction phase. The indications are as follows: for acute infections caused by sensitive bacteria, such as: bacteremia, septicemia, scarlet fever, erysipelas, pneumonia, empyema, tonsillitis, otitis media, cellulitis, furuncle, carbuncle, acute mastitis, endocarditis, osteomyelitis, epidemic meningitis (epidemic meningitis), leptospirosis (good early treatment effect on the disease), pezosene pharyngolaris, wound infection, recurrent fever, gas gangrene, anthrax, gonorrhea, actinomycosis, etc. Tetanus and diphtheria are preferably treated in combination with the corresponding antitoxins. Adverse reactions: (1) common allergic reactions include severe anaphylactic shock and seropathic reactions, leukopenia, drug eruptions, contact dermatitis, asthma attacks, etc. The low dose of penicillin does not cause toxic reactions. When applied in large dose, the medicine can cause neuro-mental symptoms, such as hyperreflexia, sensory disturbance, hallucination, convulsion, lethargy, etc., and also can cause transient mental disorder, drug withdrawal or dose reduction and recovery. For a small number of patients with a deficiency in clotting function, large doses of penicillin can disrupt the clotting mechanism, leading to bleeding tendencies. Procaine penicillin can cause a specific reaction. When the medicine is injected or within 1-2 minutes after the medicine is injected, the patient feels discomfort in mind, endangered fear, dizziness, palpitation, pseudoscopic vision and other symptoms. Generally, there is no respiratory or circulatory disturbance, and in most cases, elevated blood pressure (as distinguished from anaphylactic shock) can occur. Generally, special treatment is not needed, and the symptoms can be recovered to be normal by self after being maintained for 12 hours. Recovery was aided by either sedatives (diazepam) or antihistamines (20 mg diphenhydramine intramuscular injection).

Vitamin C (vitamin C) is contained in fresh vegetables and fruits such as tomato, spinach, orange, jujube, etc. The clinical application is synthetic products. It forms a reversible redox system in humans with ascorbic acid and deoxyascorbic acid, which plays an important role in biological oxidation and reduction and in cellular respiration. Vitamin C is involved in amino acid metabolism, synthesis of neurotransmitters, synthesis of collagen and interstitial tissue. Has effects in reducing capillary permeability, accelerating blood coagulation, stimulating blood coagulation, promoting iron absorption in intestine, reducing blood lipid, enhancing resistance to infection, removing toxic substances, resisting histamine, and preventing carcinogen (nitrosamine) formation. The daily requirement of normal people from fresh vegetables and fruits can generally meet the requirement, but special conditions (such as infectious diseases) can cause deficiency diseases and scurvy diseases. The method is mainly used for: preventing and treating scurvy. ② when acute and chronic infectious diseases are caused, the consumption is increased, and proper supplement is needed. In the recovery period after illness, patients with poor wound healing should be supplemented properly. ③ when the patient with keshan disease is in cardiogenic shock, the patient can be treated with large dose. Fourthly, the medicine is used for treating liver cirrhosis, acute hepatitis, and liver damage caused by chronic poisoning such as arsenic, mercury, lead, benzene and the like. Fifthly, other: can be used for treating anemia, allergic dermatoses, aphtha, and wound healing. It is reported that it has a certain action for cold, some cancers and hyperlipemia, but its clinical therapeutic effect is not yet certain.

The invention content is as follows:

the invention aims to provide an application of penicillin G sodium salt in preparing a pharmaceutical composition or a preparation for treating rheumatoid arthritis, wherein the penicillin G sodium salt is combined with Penicillin Binding Protein (PBP) on a bacterial cell membrane to prevent synthesis of bacterial cell wall mucopeptide from being crosslinked to cause cell wall defect, so that bacterial cell walls are ruptured to die due to rupture of the bacterial cell walls.

The invention is achieved by the following measures:

the new application of penicillin G sodium salt is characterized in that penicillin G sodium salt or derivatives thereof are used for preparing a pharmaceutical composition or a preparation for treating rheumatoid arthritis.

The pharmaceutical composition or preparation for treating rheumatoid arthritis also contains vitamin C.

The pharmaceutical composition or preparation of the invention contains 1600-2000 million units/day of penicillin G sodium salt or derivatives thereof.

The pharmaceutical composition or preparation of the invention contains 25-33.3% of vitamin C in the total weight of the pharmaceutical composition or preparation.

The pharmaceutical composition or preparation for treating rheumatoid arthritis comprises penicillin G sodium salt and vitamin C, wherein in the first treatment course, 480 ten thousand units of penicillin G sodium salt are added into 250ml of normal saline for intravenous drip, the solution is once every 8 hours for 20 days, 250mg of vitamin C injection is added into 500ml of 5% glucose injection, and iydrip is added once a day for 10 days; the second course of treatment, penicillin G sodium salt 80 ten thousand units, intramuscular injection, once every 12 hours for 20 days, vitamin C tablet 0.05G, three times a day, oral administration, take 5 days.

The pharmaceutical composition or preparation for treating rheumatoid arthritis comprises penicillin G sodium salt and vitamin C, wherein in the first treatment course, 800 ten thousand units of penicillin G sodium salt are added into 250ml of normal saline, intravenous drip is carried out once every 12 hours for 20 days, and vitamin C tablets are 0.05G and taken orally for 10 days; the second course of treatment, penicillin G sodium salt 80 ten thousand units, intramuscular injection, once every 12 hours, 20 days totally, vitamin C injection 250mg, dissolved in 5% glucose injection 500ml, intravenous drip, once a day, 10 days.

The pharmaceutical composition or preparation for treating rheumatoid arthritis comprises penicillin G sodium salt and vitamin C, wherein in the first treatment course, 800 ten thousand units of penicillin G sodium salt are added into 250ml of normal saline, and intravenous drip is carried out once every 12 hours for 20 days; vitamin C tablet 0.05g, three times a day, orally taken for 10 days; the second course of treatment, penicillin G sodium salt 80 ten thousand units, intramuscular injection, once every 12 hours, 20 days, vitamin C injection 250mg, dissolved in 5% glucose injection 500ml, intravenous drip, once daily, 10 days.

The pharmaceutical composition or preparation for treating rheumatoid arthritis contains penicillin G sodium salt and vitamin C, wherein when the patients suffer from dyspnea, breath holding, excessive phlegm and the like and need atomization inhalation, 20 thousands of units of penicillin G sodium salt and water for injection are prepared into 2ml of solution, and the solution is atomized and inhaled twice a day.

The penicillin G sodium salt in the pharmaceutical composition or preparation for treating rheumatoid arthritis can be used up to 2000 ten thousand units per day, and is added into physiological saline for intravenous drip in parts, wherein the concentration is 1-4 thousand units/ml.

According to the invention, penicillin G sodium salt is used for preparing a pharmaceutical composition or preparation for treating rheumatoid arthritis, according to the mechanism that penicillin G sodium salt can treat by taking the destruction of bacterial cell walls as a target, pathogenic bacteria in infection factors which are one of main causes of rheumatoid arthritis are killed in a targeted manner, so that the condition of rheumatoid arthritis is effectively controlled, and the aim of curing is finally achieved; the pharmaceutical composition or preparation of the invention also comprises vitamin C, and the vitamin C can reduce the permeability and fragility of capillary vessels to relieve edema, inhibit platelet aggregation and prevent thrombosis, improve the blood supply, oxygen supply and energy supply of tissues and organs by improving the microcirculation of the tissues and organs, promote the repair of damaged tissues and organs, and play a vital role in the later-stage rehabilitation of patients; meanwhile, the vitamin C has anti-inflammatory and anti-allergic effects and has direct inhibition effect on the pathogenesis and/or induction cause of the rheumatoid arthritis; the clinical treatment effect shows that the penicillin G sodium salt is effective on more than 90 percent of pathogenic (or induced) bacteria of the rheumatoid arthritis, and the vitamin C can effectively relieve clinical symptoms and promote the accelerated rehabilitation of patients. The invention has the remarkable advantages of high treatment speed, extremely high effective rate, high cure rate (related to the number and the proportion of patients insisted on the end, partial patients stop continuing treatment as long as the condition of the patient is controlled, and the cure rate is invisibly influenced), small toxic and side effects, safety, reliability and the like.

Description of the drawings:

FIG. 1 is a schematic view showing a comparison of affected parts before and after administration to a patient in example 1 of the present invention, wherein FIG. 1(a) is a picture before treatment and FIG. 1(b) is a picture after the end of the treatment course.

FIG. 2 is a schematic diagram showing a comparison of the same affected part before and after administration to a patient in example 2 of the present invention, wherein FIG. 2(a) is a picture before treatment and FIG. 2(b) is a picture after the end of treatment.

FIG. 3 is a schematic diagram showing a comparison of the same affected part before and after administration to a patient in example 3 of the present invention, wherein FIG. 3(a) is a picture before treatment and FIG. 3(b) is a picture after the end of treatment.

The specific implementation mode is as follows:

the present invention will be further described with reference to the following examples.

The invention provides a new application of penicillin G sodium salt, which is to use the penicillin G sodium salt or derivatives thereof to prepare a pharmaceutical composition or preparation for treating rheumatoid arthritis; the pharmaceutical composition or preparation for treating rheumatoid arthritis also contains vitamin C.

The penicillin G sodium salt can be administered by intravenous route, intramuscular injection route and aerosol inhalation route; the vitamin C can be administered by intravenous route, intramuscular route, or oral route.

Example 1

Patients who are aged 61 years old or women who have a certain age will be treated with more than 1 month aggravated due to swelling and pain of the fingers, toes and joints of the limbs. The current medical history indicates that the patient suddenly becomes cold once in 1 day before 1 year, the afternoon fever reaches 39.6 ℃, the patient feels uncomfortable with acid swelling of fingers and toes after sweating, the patient becomes stiff with two hands the next day, the stiffness of the fingers moving slightly at the beginning disappears, the fingers and the toes become more severe after 2 months until the time exceeds 1 hour each day, and the swelling and pain of the fingers and the toes gradually become more severe, particularly the swelling and pain of the metacarpophalangeal joints and the proximal interphalangeal joints of the two hands are more obvious and last for more than half a year. In the last 1 month, the disease condition is aggravated, the swelling and pain are obviously aggravated, and a lump grows out on the left toe, which is not painful when pressed. Physical examination: the old women are clear in spirit, painful in expression, limping, normal in heart sound, free of noise, regular in heart rhythm, 88 times/minute in heart rate, clear in breathing sound of the two lungs, smellless dry and wet rale, slightly swollen in the two wrists, swollen and deformed in the second, third and fourth metacarpophalangeal joints of the two hands, part of proximal interphalangeal joints are in a fusiform, all toes are swollen, and part of interphalangeal joints are in a subluxation state. The lateral aspect of the dorsum of the second toe of the left foot is seen to be a tumor with a diameter of about 5mm and obviously higher than the skin surface, and the pressure is not painful. According to the following steps: patients have morning stiffness of over 60 minutes per day and have been on for more than half a year; ② metacarpophalangeal joint swelling and spindle fingers of more than 4 groups; thirdly, the disease is in the good hair position of the wrist joint, the metacarpophalangeal joint and the proximal interphalangeal joint; fourthly, symmetrically attacking left and right hand joints and foot joints; rheumatoid subcutaneous nodules appear on the left foot, and the diagnosis of rheumatoid arthritis can be established.

After the hospital is admitted, 480 ten thousand units of penicillin G sodium salt are added into 250ml of normal saline for intravenous drip, and the solution is once every 8 hours for 20 days; the vitamin C injection is 250mg and is infused intravenously, once a day, for 10 days. The second treatment course, 80 ten thousand units of penicillin G sodium salt and intramuscular injection are carried out once every 12 hours for 20 days; vitamin C tablet 0.05g, three times daily, oral, total 10 days.

Thereafter, the swelling and pain of the hands and feet and joints of the patient were reduced, and morning stiffness was significantly reduced. Now the rheumatoid subcutaneous nodules have disappeared. After 4 weeks of discharge, the examination shows that most of the swelling of the fingers and toes of the patient has subsided, the spindle fingers still exist, but the pain of the hands and feet is reduced. After one year of reexamination, the patient has completely recovered, the fusiform fingers of both hands completely disappear, the joint of the subluxation has been reset, the patient has no discomfort on the whole body, the hands and the feet move freely, and the patient can be engaged in various jobs in housework and fields. After 10 years, the patient is followed and visited, and the patient is healthy and painless. The hands and feet have no deformity, the old aged 70 years old can still be competent for housework and partial field work, and is full and comfortable in mood, and never like a person suffering from rheumatoid arthritis.

According to the clinical treatment and research, the effective embodiment 1 of the present invention is that the pharmaceutical composition or preparation comprises: in the first course of treatment, 480 ten thousand units of penicillin G sodium salt is dissolved in 250ml of normal saline (prepared by 1 to 4 thousand units/ml), and intravenous drip is carried out, G8h, and the treatment lasts for 20 days; dissolving 250mg of vitamin C injection in 500ml of 5% glucose injection, and performing intravenous drip once a day for 10 days; the second course of treatment, penicillin G sodium salt 80 ten thousand units, intramuscular injection, once every 12 hours, use 20 days; vitamin C tablet 0.05g, three times daily, orally administered for 10 days. Then the general articular edema of the patient is obviously relieved, the rheumatoid subcutaneous nodules are reduced, the pain of the joints of the hands and the feet is relieved, the morning stiffness is relieved, and no obvious toxic or side effect exists.

Example 2

Some Yi, woman, 61 years old, is marked by general pain, especially in the knee joints. Admission to the examinee: listlessness, 5 mung bean-size nodules, hard texture, no pain in pressing and complete deformity of small joints of hands are found on the dorsal side of the hands: the proximal interphalangeal joints are fusiform swelling, the wrists of the hands rotate and deviate to the radial side, the fingers and the palmar ulnar side deviate, the proximal interphalangeal joints are seriously bent, the hyperextension of the distal interphalangeal joints is deformed like buttonhole flowers and is more than 4 groups, the proximal interphalangeal joints of a plurality of fingers are changed like fusiform, the joints of a plurality of toes are dislocated or subluxation, the toes are basically irregularly arranged in an up-and-down overlapping mode, particularly, the joints of the two knees are highly swollen, the skin of the knees is almost cracked and transparent, the bent deformity is formed, the lower limbs are extremely thin like firewood, the feet cannot stand, the feet cannot walk, the feet are completely bedridden, the life cannot be managed by oneself, and the only hope for treatment when the family members and the patients come for diagnosis is that the feet can stand up.

After hospitalization, 800 ten thousand units of penicillin G sodium salt are added into 250ml of normal saline, and intravenous drip is carried out once every 12 hours for 20 days, and vitamin C tablets are 0.05G and taken orally three times a day for 10 days. In the second course, 80 ten thousand units of penicillin G sodium salt is administered for intramuscular injection once every 12 hours for 20 days, and 250mg of vitamin C injection is added into 500ml of 5% glucose injection for intravenous drip once a day for 10 days.

After the above combination treatment, all 5 nodules disappeared. The disease condition is greatly improved, edema begins to subside, the double knee joints are particularly obvious, the fusiform of the small joints of the two fingers still exists, the two fingers move more flexibly, the pain of the two feet is relieved, and the patient can not walk in a standing mode. The patient has increased appetite and seems to have strength, and starts to exercise the muscle strength of the upper limbs, prepare to stand by holding up the crutch and walk in head-on.

During the treatment process of the patient, 20 ten thousand units of penicillin G sodium salt is immediately given to the patient with asthma attack, wheezing, cough, suffocating and dyspnea, dissolved and diluted by water for injection to prepare 2ml solution, and the solution is atomized and inhaled twice a day for 1 week, so that the respiratory system symptoms disappear, and the atomized inhalation stops. At present, the general condition of a patient is improved, the spirit is more vigorous, and certain confidence is provided. On the right palmar side, 5 high-skinned, soft nodules with a diameter of about 1.5cm were found, which were not painful to press. The treatment cycle is about the same as the previous treatment cycle except that the patient is treated for the stomach illness. When treated by day five, all subcutaneous nodules were suddenly found to disappear altogether. With the continuous advancing of time, the disease condition of the patient is further improved, the swelling degree of the fusiform fingers and the deformed fingers of the two hands is reduced, the joint of the individual finger is recovered quickly, and the phenomenon of the upper and lower overlapping of the toes caused by the dislocation of the joints of the two toes due to the transverse displacement is reduced. The individual toe joints gradually begin to return to their original positions. At this time, the patient can stand by leaning on the bed, but can not walk because the knee joint pain is still serious, and the patient is not allowed to walk by himself according to the medical advice, and the patient has no adverse reaction in the period, and is discharged after a month.

The patient goes home for about half a month, is suddenly sent back to the hospital by family, and is cared for the medical history, the patient carelessly walks by self-training to hold up the crutch, slips carelessly, sits on the ground, feels lumbago, dizziness and giddiness immediately, is held up by other people, and gets out of the hospital again because of unstable standing. The 2 nd lumbar vertebra moderate compression fracture is found by shooting, the hospitalization is cured in one month, and the penicillin G sodium salt intravenous drip treatment is also added in the period. The patient is discharged about ten days after the patient is discharged, and the patient is re-admitted to the hospital to treat the rheumatoid arthritis by using penicillin G sodium salt and vitamin C. After 1 month, the deformity of the joints of both hands is found to be gradually recovered to be normal, particularly, the swelling of all the minor joints of the left hand is completely removed without swelling and slight pain, all the fingers move flexibly, the swelling of the joints of both knees is obviously relieved, the pain still exists slightly, and the patient mistakenly thinks that the disease is cured. The patient is not treated for nine months continuously, the self-induced disease has a recurrence phenomenon, the finger pain is aggravated, the finger deformity seems to reappear, and the patient is in a hospital urgently. After half a month of treatment, the disease condition is recovered quickly and the treatment is continued.

According to clinical treatment and research, in this example, the pharmaceutical composition or formulation comprises: the first course of treatment is 800 ten thousand units of penicillin G sodium salt, added into 250ml of normal saline, and subjected to intravenous drip once every 12 hours for 20 days; vitamin C tablet 0.05g, three times a day, orally taken for 10 days; the second course of treatment, penicillin G sodium salt 80 ten thousand units, intramuscular injection, once every 12 hours, use 20 days; 250mg of vitamin C injection is dissolved in 500ml of 5 percent glucose injection and is infused intravenously, and the vitamin C injection is taken once a day for 10 days. The joint swelling degree is obviously improved, the pain of a patient is relieved, the appetite, the food intake and the weight are increased, and no obvious toxic or side effect exists.

Example 3

The patient king a certain person, woman, age 41 is afraid of activities for two years due to multiple joints of both hands, morning stiffness, swelling and pain, multiple joint deformation of fingers, dare for activities, incapability of moving due to severe pain of both wrists and weakness of both hands, no ability of holding a rice bowl even, frequent bowl dropping, chopstick dropping, and requirement of helping patients and friends to eat rice when in hospital. The psychological stress of patients is very large, the appetite is very poor, the food intake is less and less, only half two meals are eaten per meal, the dishes are not eaten, and the patients are successively diagnosed as rheumatoid arthritis in local hospitals for many times before being admitted into the hospital.

The physical examination shows that: middle-aged women, thin, the nutrition is poor, the proximal finger joints of the index finger, the middle finger and the ring finger with two hands symmetry are all in a fusiform shape, the flat plate display is carried out, all metacarpal bones of the two hands are seriously eroded, the joint gaps are blurred, the patient has standard morning stiffness (the morning stiffness lasts for more than 60 minutes every day, the lasting date reaches 2 months), more than 3 groups of symmetric joint swelling of typical good-occurring parts and bone erosion displayed by a hand X-ray plate, and the diagnosis of rheumatoid arthritis is met.

In the first treatment course after admission, adding 800 ten thousand units of penicillin G sodium salt into 250ml of normal saline for intravenous drip once every 12 hours for 20 days; 0.05g of vitamin C tablets are taken orally three times a day for 10 days. The second course of treatment, penicillin G sodium salt 80 ten thousand units, intramuscular injection, once every 12 hours, 20 days, vitamin C injection 250mg, add into 5% glucose injection 500ml, intravenous drip, once a day, 10 days.

After that, the disease condition is gradually improved, the swelling and pain of the hands are relieved, the appetite and the food intake are gradually increased, and each meal can reach four or two meals and one dish. Discharging the patient in hospital for one month. Hospitalization continued with the same treatment as the first one month later. By about the tenth day of the second course, the patient has to control diet to lose weight because the weight of the patient is increased by more than twenty jin, and each meal is limited to two meals and one dish. The mental state of the patient is good, the gall disappears after two months, the hands move flexibly, strength is gradually exerted, and no obvious toxic or side effect appears. Until six years, the condition is not repeated in 2019, the health is recovered 4 years ago before the disease is not affected, and a consumer becomes a social wealth creator.

According to the clinical treatment and research, the effective embodiment 3 of the present invention is that the pharmaceutical composition or preparation comprises: the first course of treatment is 800 ten thousand units of penicillin G sodium salt, added into 250ml of normal saline, and subjected to intravenous drip once every 12 hours for 20 days; vitamin C tablet 0.05g, three times a day, orally taken for 10 days; the second course of treatment is intramuscular injection of 80 ten thousand units of penicillin G sodium salt, once every 12 hours and lasting for 20 days; 250mg of vitamin C injection is added into 500ml of 5 percent glucose injection and is instilled intravenously once a day for 10 days. For example, the patient has symptoms of cough, spitting and breath holding, the penicillin G sodium salt is 20 ten thousand units (diluted with water for injection to prepare 2ml solution), and the solution is atomized and inhaled twice a day, and after 2 weeks, the cough and breath holding of the patient are relieved. The general articular edema is obviously relieved after 4 weeks, rheumatoid subcutaneous nodules are obviously reduced, nodules with the diameter of less than 5mm completely disappear, the pain of hand-foot joints is relieved, morning stiffness disappears, hands can move freely, and no obvious toxic or side effect exists.

Example 4

If a patient is cold and a woman is 47 years old, the joints of the proximal fingers of the two fingers are changed in a spindle shape due to morning stiffness more than one hour every day, the pain cannot be diagnosed for more than two years, and the patient has suffered from cerebral infarction (nervous system complications) before one year.

The physical examination shows that the dorsal sides of the two hands have 7 nodules, the diameter is about 0.2cm, the two knee joints are swollen, the knee joints are pressed and painful at multiple points, the plain film shows that the distal interphalangeal joints of the ring finger of the right hand are in a half-dislocation state, the finger bones are corroded, the blood tests show that the rheumatoid factors, the blood sedimentation and the like are in a normal range, and the diagnosis of the rheumatoid arthritis of the patient can be established according to morning stiffness, spindle fingers, the swelling of a plurality of proximal finger joints and metacarpophalangeal joints with bilateral symmetry and the bone corrosion displayed by a hand X-ray film.

In the first treatment course after hospitalization, 800 ten thousand units of penicillin G sodium salt are added into 250ml of normal saline for intravenous drip, and the solution is once every 12 hours for 20 days; vitamin C tablet 0.05g is taken orally three times a day for 10 days. The second course of treatment, penicillin G sodium salt 80 ten thousand units, intramuscular injection, once every 12 hours, 20 days, vitamin C injection 250mg, add into 5% glucose injection 500ml, intravenous drip, once a day, 10 days.

After the medicine is comprehensively treated for dozens of days, the swelling of the double knee joints is completely removed, the swelling of the double fingers is basically disappeared, the morning stiffness time is obviously shortened to reach about half an hour every day, and 7 small nodules are completely removed; however, both hands are painful and well tolerated, and the "spindle" shape of the interphalangeal joints is still present (normally, after proper treatment, it will recover after months or a year), with a large increase in finger activity. The existing patients have good mental state, the confidence is doubled, the patients are firmly required to cure the disease, the appetite is increased, the whole body is relaxed, and the patients are treated discontinuously without obvious toxic and side effects.

Example 5

The patient Zhao somewhat, a woman, 60 years old, has been diagnosed with morning stiffness of 2 hours each day, general pain, swelling and pain of the small joints of both hands, deformation for more than three years, bedridden patients, odynuria, urgent micturition, frequent micturition and edema of both eyelids for three months.

Physical examination: the female in middle-aged and elderly patients suffer from chronic consumptive disease, poor nutrition and double-eyelid swelling, the double-eyelid of the patients is found to be swollen, all proximal interphalangeal joints of the hands are fusiform swelling, the middle and little toes of the feet are in a half dislocation state, T37.2 ℃, P88 times/minute, R26 times/minute, Bp160/80mmHg, blood assay: 12.93mmol/L of blood sugar, more than 20IU/ml of rheumatoid factors, 101mm/h of blood sedimentation, routine test of urine: protein + +, white blood cells + +, glucose + +, were discharged after a month of hospitalization, were discharged again after a half month interval for a month, and through comprehensive treatment with penicillin G sodium salt and vitamin C drugs, the pain in urination, urgency of urination, frequency of urination and eyelid edema disappeared, the general pain and hand and foot facet joint swelling were significantly relieved earlier, rheumatoid factors decreased to 39IU/h, blood sedimentation 18mm/h, urinalysis: protein (-), wbc (-), glucose (-). After being discharged from hospital for more than ten years, the patient is not hospitalized for reasons, and only treated by oral administration of the tripterygium wilfordii, although the disease is not cured, the disease is not greatly developed, and the patient is not bedridden and can be in the homework and the labor of the patient.

Example 6

The patient is around a certain male, aged 58 years, suffered from rheumatoid arthritis for more than 10 years, paralyzed for six years in bed, and can not work for many years, and the life of the inside, the outside and the inside is born by the lovers. Physical examination finds that the whole body of a patient is edema, fusiform fingers, double-foot polydactyly, the little fingers of both hands are shortened, a plurality of metacarpophalangeal joints are malformed, blood test rheumatoid factors are positive, the blood sedimentation is 56mm/h, one menstruation is subjected to comprehensive treatment by penicillin G sodium salt and vitamin C in hospital, the edema is resolved, the general cachexia condition is greatly improved, the patient can walk away from a crutch, after being discharged for one month, fruits can be sold out by oneself to replace the family to conduct farm work in the field, but the treatment is not thorough, the true healing is not achieved, and the life is not influenced.

Example 7

When a patient pays for a certain woman in the age of 59 years, the patient feels a diagnosis because the swelling and pain of the left wrist are more than two years, then the morning stiffness of the hands appears, the period is more than two hours every day and lasts for more than half a year, and the proximal interphalangeal joints of a plurality of (more than four groups of) fingers with bilateral symmetry are changed in a fusiform manner, so that the disease condition gradually worsens.

The patients were examined to have 5 nodules with a diameter of about 5mm on the extending side of the limbs, hard mass, no pain when pressed, swelling and deformation of multiple small joints of the two hands, and the proximal interphalangeal joints of the middle finger and ring finger are in the shape of "shuttle", and the fingers of the two hands are not bent or extended. The provincial hospital has been left to test 11.10IU/mL of rheumatoid factor, 12mm/60min of blood sedimentation, 0.93G/L of immunoglobulin M (nephelometry, the same below), 1.5/L of immunoglobulin A, 14.40/L of immunoglobulin G, E162.30IU/mL of immunoglobulin (electrochemiluminescence), positive antinuclear antibody, (immunofluorescence) and nuclear type 1 particle type.

The patients are only treated in hospital intermittently at the time of leisure, 800 million units of penicillin G sodium salt are added into 250ml of normal saline for seven times without giving up field labor, intravenous drip is carried out once every 12 hours for 5-20 days, and vitamin C tablets, 0.05G, are taken orally three times a day.

Through comprehensive treatment, the disease condition is improved in different degrees each time, the swelling of the whole body is relieved, the morning stiffness is relieved, the spindle-shaped fingers of all joints are gradually relieved, the fingers move flexibly, all the nodules disappear, particularly the swelling and pain of the left wrist disappear, the movement is flexible, the disease is controlled for more than one year, but the disease is not completely cured, the confidence of the patient is high, and the patient needs to be consolidated for treatment in the hospital for radical treatment.

Example 8

A patient Liu is a certain woman, is 42 years old, is highly swollen (possibly accompanied by hormone reaction) due to the whole body height, the high swelling of joints of four limbs and small joints, "fusiform" fingers, proximal interphalangeal joints hyperextension, distal interphalangeal joints are bent to form "goose neck-like" deformity, metacarpophalangeal joints are dislocated, elbows, knees and ankle joints are all in ankylosis deformity, the functions of the joints are severely limited, one of ten fingers and ten toes cannot move and bounce independently, the activities such as flexion and extension of the elbows, the knees and the ankles are extremely difficult, and the movement of the upper limbs is completed by the movement of the shoulders.

The patient was hospitalized for one month, given: adding 800 thousands of penicillin G sodium salt into 250ml of normal saline, carrying out intravenous drip once every 8 hours for 20 days, and orally taking 0.05G of vitamin C tablets three times a day for 10 days; the second course of treatment is changed into 80 ten thousand units of penicillin G sodium salt, intramuscular injection is carried out once every 12 hours, the administration lasts 20 days, 250mg of vitamin C injection is added into 500ml of 5% glucose injection, intravenous drip is carried out, and the administration lasts 10 days once a day. After discharge, the treatment with penicillin G sodium salt and vitamin C is continued according to the requirements of the medical advice.

After five and a half months of reexamination, the body of a patient is recovered, joints have no swelling and pain, the original deformed joints are all recovered to be normal, each facet joint and each major joint have no disability, the movement is flexible, the walking is free, the patient can be completely regarded as two persons with the cachexia state just before hospitalization, the child special journey returns home from thousands of miles, the child returns home with the mother, small grapes are brought from home, and as a result, people can not find the situation, the fingers of the patient can flexibly pick and clamp each grape grain, medical staff forget that the patient is a patient who has been treated in the home and can not flick both hands and feet, the patient can recover to the perfect ground step, and the patient feels too large wonderful mark.

Example 9

For some patients in Liu, men and 51 years old, because of general pain, especially pain of both lower limbs, ischemic necrosis of both femoral heads and necrosis of femoral shaft are diagnosed in three hospitals in many local places, and bilateral femoral head replacement is recommended.

The self-contained plain film clearly shows that the double femoral bones and the femoral shaft of a patient are eroded in multiple places, the bone has multiple serious osteoporosis phenomena, spontaneous fracture can occur at any time, if femoral head replacement is carried out, no matter whether femoral head replacement is carried out singly or hip replacement is carried out, a metal connecting piece is required to be inserted into a bone tube at the lower end of the femoral shaft, the femoral shaft with the bone seriously eroded in such a way can not support the metal support to be worn, the bone can be broken and split quickly, the replaced femoral head loses support and fails, and the rheumatoid arthritis aggravates more and more, so that the patient can lose double lower limbs due to the pathological changes of the femoral shaft possibly.

After admission, the first course of treatment: adding 480 ten thousand units of penicillin G sodium salt into 250ml of normal saline, carrying out intravenous drip once every 8 hours for 20 days, adding 250mg of vitamin C injection into 500ml of 5% glucose injection, carrying out intravenous drip once a day for 10 days.

The second course of treatment comprises 80 ten thousand units of penicillin G sodium salt, intramuscular injection, administration for 20 days every 12 hours, and administration for 10 days with 0.05G vitamin C tablet three times a day.

After two months of intermittent treatment, the pain completely disappears like a normal person, an X-ray film is taken to show that all bone erosion shadows disappear, the femoral head does not have the bone erosion shadows, black spots and deformation, but the disease is not completely cured, the femoral head cannot fall off with light mind, the femoral head is required to be continuously treated for 2-3 (or more) treatment courses to be consolidated, and if the femoral head necrosis signs are found, the femoral head ischemic necrosis is immediately treated. The patients in this example were treated just a few months ago, no toxic side effects appeared, all the cases were good, and the observation period was strict.

Example 10

The patient is old for a certain time, women, and patients of 48 years old, morning stiffness, swelling, deformation and partial dislocation of small joints of hands and feet, general pain, completely bedridden for 2 years, nearly 1 month, cold and fever due to self-induction, gradually aggravated illness, cough, yellow purulent sputum, physical examination: chronic face-beautifying, forced right lateral decubitus, very listened spirit, spindle-shaped proximal interphalangeal joints of a plurality of fingers and fingers, left-right symmetry onset, patient body temperature of 39 ℃, heart rate of 119/min, regular heart rate, X-ray visualization, weight gain and disorder of double lung texture, scattered in cloud flocculent density increase shadow, suggestion: the method comprises the steps of firstly, intrapulmonary infection, osteoporosis and bone erosion of phalanges of both hands, secondly, the fuzzy gap of double wrist joints, and finally, the method conforms to the pathological changes of rheumatoid arthritis, and fourthly, the half dislocation of the far-end finger of the unknown finger of the right hand. Blood normal WBC11000/mm3, neutral 76%, lymph 22%, low anti-O content, rheumatoid factor positivity and blood sedimentation 45mm/h, and the patient is considered to have rheumatoid arthritis and lung infection.

Administration of: the penicillin G sodium salt is 800 ten thousand units, is added into 250ml of normal saline to be intravenously instilled once every 12 hours for 20 days, and is orally taken for 10 days, wherein 0.05G of vitamin C tablets are taken three times a day. In the second course of treatment, 80 ten thousand units of penicillin G sodium salt is used for intramuscular injection once every 12 hours for 20 days, and 250mg of vitamin C injection is added into 500ml of 5% glucose injection for intravenous drip once a day. The above treatments were repeated thereafter. Sometimes the patient has more obvious cough, spitting and breath holding, 20 ten thousand units of penicillin G sodium salt is added with water for injection to prepare 2ml solution, and the solution is atomized and inhaled twice a day, and after 1 week, the symptoms are relieved. After the medicine is repeatedly applied, after comprehensive treatment is carried out for more than 4 months, not only the symptoms of the respiratory system are completely disappeared, but also the arthroncus and deformity are completely recovered to a normal state, the movement of hands and fingers is flexible, and as a result, the rheumatoid arthritis is also cured. After the patient is discharged from the hospital and continues to be consolidated and treated for a period of time, the disease condition does not relapse for decades, and the patient is healthier than before the disease. Now, people in the age of 80 can dance every night and retrieve lost life, which is more than happy.

Example 11

For a certain patient, a woman who is 67 years old, more than one hour per day due to morning stiffness of both hands, swelling and pain of the small joints of the limbs and deformation of a plurality of small joints, the whole body is ill, and the patient is paralyzed in bed for two years and several times and all rescued by the family. The examination finds that the metacarpophalangeal joints of the index finger and the middle finger of both hands are totally swollen and deformed, the back of the hand is obviously raised, the proximal interphalangeal joints are all fusiform, the four metacarpophalangeal joints are in buckling deformity, the proximal interphalangeal joints are over-stretched, the distal interphalangeal joints are in buckling deformity and are in goose-neck-like deformity, and the X-ray film shows that the existing phalangeal bones of the finger are damaged and the phenomenon of obvious decalcification exists, and the joints are in subluxation.

The medicine cost is not required to be reimbursed across administrative regions, and the medicine is self-paid and hospitalized, and the penicillin G sodium salt is added into 250ml of normal saline by 800 ten thousand units, and the mixture is intravenously instilled once every 12 hours for 20 days, 0.05G of vitamin C tablets are taken three times a day, and the vitamin C tablets are orally taken. The second course of treatment, penicillin G sodium salt 80 ten thousand units, intramuscular injection, once every 12 hours, 20 days, vitamin C injection 250mg, add into 5% glucose injection 500ml, intravenous drip, once a day, 10 days.

After the comprehensive treatment, the condition of the disease is improved, the joint edema is relieved, the pain is eliminated, and the joint deformity is improved. When discharged, the family members need to buy all the medicines in the pharmacy of the hospital with the sacks. After returning home, the injection is continued to take 80 ten thousand units of penicillin G sodium salt for intramuscular injection once every 12 hours for 20 days according to the advice of doctors. After the rest for 10 days, the circulating medication is adopted for treatment, and proper Chinese patent medicine for improving the state of an illness is adopted for regulation when the pain is severe, so that the state of the illness is gradually improved.

The later doctors visit the local business trip, the disease is cured, no recurrence occurs, and no obvious toxic and side effect occurs. The family economic condition is good, a patient can visit the park twice a day in the morning and at night, the park can not be ridden all the year round, and the patient can take an umbrella to go to the park in winter, so that the self-wording that the life is really good and I do not live enough is realized.

Example 12

A patient is a certain girl or a woman in the age of 45, because the two hands are morning stiffness and last for more than 1 hour every day, the metacarpophalangeal joints of the left and right middle fingers and the index finger are symmetrically swollen and deformed, the proximal interphalangeal joints are changed in a shuttle shape, the two hands are afraid of being cold and can not be used for cooking housework, the rheumatoid factors 560U are checked through hematopoiesis in a certain three-part hospital (provincial level) in the local area, the blood sedimentation is 100mm/h, the rheumatoid arthritis is confirmed by combining physical examination, 800 ten thousand units of penicillin G sodium salt are applied in hospital, 250ml of normal saline is added, intravenous drip is carried out once every 12 hours, 0.05G of vitamin C tablets are taken orally, ti is taken orally, and the treatment lasts for 20 days. The anti-inflammatory tablet is only intermittently taken for about one month after discharge due to insufficient cost, hospitalization is not continued, the rheumatoid factor is rechecked to be reduced to 110U after three months, the blood sedimentation is reduced to 33mm/h, morning stiffness is relieved, joint swelling is relieved, pain is relieved, and housework can be reluctant.

The inventor has succeeded in anti-inflammatory treatment of rheumatoid arthritis patients for decades, which shows that the mortality of the patients due to the disease or complications of the disease can be greatly reduced and the five-year survival rate can reach more than 90 percent after the anti-inflammatory treatment of the rheumatoid arthritis by penicillin G sodium salt for a plurality of courses of treatment. As for the familial factoriology considered, namely, other patients with the same disease may exist in the patient family, we investigated 271 families of patients with rheumatoid arthritis, 28 patients with relatives, about 10.33% of the total number of patients, 32 patients suffering from cold and dampness, about 11.81% of the total number of patients, 26 patients suffering from overstrain, about 9.59% of the total number of patients, 21 patients in close contact with the patients in life, about 7.75% of the total number of patients, 33 patients suffering from body resistance reduction due to cold, production, abortion, trauma, surgery, etc., about 12.18% of the total number of patients, 41 patients with various factors, about 15, 13%, 90 patients without causes, and about 33.21%. Of the 271 patients studied, about 33.21% except for 90 of unknown causes; the rest of the diseases have certain causal relationship with the infection, wherein 28 cases of 'suffering from cold and dampness' with relatives, '32 cases of' fatigue attack '26 cases of' close contact attack '21 cases of' resistance decline attack '33 cases of' and 41 cases of 'attack by various factors' account for 66.79% together, the factors are related to the occurrence or induction of the infection, and more importantly, factors related to the infection exist in 'unknown reasons'. In the investigation, 91 cases of men accounted for 33.58% and 180 cases of women accounted for 66.42%. The data show that gender differences do exist, family factors have no obvious tendency, and clinical antibiotic treatment effects are obviously inclined to the infectious theory.