Drug for killing acid-fast (red) bacillus

Abstract

Disclosed is a drug for killing acid-fast (red) bacillus and use thereof. The drug, using fuchsin as active ingredient, can effectively kill acid-fast bacillus and remove mycobacterium tuberculosis and leprosy bacillus in human body.

Claims

1. An oral drug preparation for killing acid-fast bacillus having a drug composition by percentage weight of basic fuchsine 55-66% and ground rice 35-45%, wherein the basic fuchsine is an active ingredient to kill the acid-fast bacillus and the ground rice is an excipient or an auxiliary ingredient.

2. The oral drug preparation for killing acid-fast bacillus according to claim 1, characterized in that: the oral drug preparation is a tablet, capsule, powder, granule, or dietary supplement.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is the curve showing the changes of urine pH of patients with time after taking drug.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

(2) In this embodiment, the basic fuchsine is purchased from Tianjin Ju Hua Chemical Company Limited.

Embodiment 1

(3) Toxicity Test of Basic Fuchsine

(4) Materials: 24 white guinea pigs, purchased from Shenyang Pharmaceutical University, regular feeding; Basic fuchsine, from Tianjin Ju Hua Chemical Company Limited.

(5) Matching and grouping of experimental animals: randomly divided into 4 groups (each group includes 6 counts, equal number of male and female), namely, control, high, medium, low fuchsine dosage group.

(6) Method of administration: For each guinea pig, administered one time per day at a fixed time in the morning, the dosage for high, medium, low fuchsine dosage group are 8 mg/kg body weight/d, 6 mg/kg body weight/d, and 4 mg/kg body weight/d respectively; the drug administration period is 21 days, observe 3˜4 times per day, observe the guinea pig by spirit condition, appetite, gloss level of skin and hairs, physical condition, alertness and ability to escape. No changes is observed after 21 days.

Embodiment 2

(7) According to the principle of in vitro staining to M. tuberculosis and M. leprae (see acid-fast bacilli staining principle), it is learned that basic fuchsine has a special affinity to M. tuberculosis and M. leprae and is easily stained.

(8) After taking basic fuchsine, the basic fuchsine activity over time can be observed through the blood phenomenon at different times. The fuchsine is absorbed into the bloodstream in a dissolved state, then through the process of blood cells, coloring or combination opportunity is provided to the M. tuberculosis and M. leprae inside the phagocytes, while the pH of body fluid is increased and the growing environment of the bacteria is destroyed, the bacteria is stained and the immune recognition ability is increased, then the activity of immune system is promoted to fully utilized. Accordingly, the basicity and the staining effect on bacteria of fuchsine are the key to remove or kill the bacteria.

(9) Blood Observation

(10) I. Observation object

(11) 1. Healthy individual as normal subject for observation

(12) 2. Patient recovered from the disease who volunteer to testing subject as volunteer subject

(13) II. Instrument:

(14) Binocular microscope xsp-12G model

(15) Manufacturer: Jiang Optical Instrument Main Factory

(16) III. Reagents

(17) Wright-Giemsa stain solution (available in the market)

(18) Phosphate buffer (available in the market)

(19) IV. Method of Operation

(20) 1. Obtain peripheral blood smear from normal subject and volunteer subject (normal control blood film, standby use)

(21) 2. Obtain peripheral blood smear from volunteer subject at different time after taking fuchsine (oral fuchsine blood film, standby use)

(22) 3. After the last blood sampling is complete, carrying staining together with the blood film before taking fuchsine orally of volunteer subject and the peripheral blood film of normal subject

(23) V. observe oral fuchsine blood film under microscope with 100× objective lens (oil immersion) and 12.5× eyepiece, real object is viewed under magnification at 1250 times and the results are shown in Table 3.

(24) TABLE-US-00003 TABLE 3 Results of observation Drug taking time (h) The status of Stain absorption by blood 0.5 Stain is cluster outside the cell in dissolved form, occasionally inside the cell, uneven distribution 1 Stain existed inside and outside the cell in dissolved form, such as in thick cloudy state, occurrence is more inside the cell than outside the cell 2 Uniform stain overflowed from the cell to outside is commonly seen, such as cloud mist state 4 Traces of stain is seen occasionally from the inside edge of cell 6 Just like the control normal blood film, no stain is observed

(25) Results of Observation:

(26) 1. After taking fuchsine, the fuchsine is absorbed through the body into the blood, then entered into the cell through the cell membrane, then remained inside the cell for about 2-4 hours.

(27) 2. The Mycobacterium tuberculosis and the Mycobacterium Leprae inside the phagocytes have the opportunities to combine to fuchsine, which is then stained or eliminated.

Embodiment 3

(28) Drug Susceptibility Testing

(29) (I) Drug: Basic Fuchsine

(30) (II) Culture Method: Lowenstein-Jensen medium (Improved method)

(31) (III) Composition of Lowenstein-Jensen medium:

(32) KH2PO4: 2.4 g; MgSO4.7H2O 0.24 g; magnesium citrate: 0.6 g; asparagine: 3.6 g; glycerin: 12 ml; distilled water: 600 ml; potato starch: 30 g; fresh whole egg liquid: 1000 ml; 2% malachite green solution: 20 ml

(33) (IV) Instrument

(34) 1. Digital Biochemical Incubator (Huangshi City Hengfeng Medical Devices Company Limited): 36° C. (special setting)

(35) 2. Biological safety cabinet: Biobase Bioteoh

(36) Model specifications: BSC-1500IZB2-X

(37) Manufacturer: Jinan Xinjiuxi Biotechnology Company Limited

(38) 3. Steam Incubator: 85° C.

(39) Manufacturer: Beijing Xinzhongdaye Daibiao Company Limited

(40) 4. Drug: 2% basic fuchsine aqueous solution: 100 ml

(41) (V) Preparation of culture medium

(42) Add water to KH2PO4, MgSO4.7H2O, magnesium citrate, asparagine and glycerin, dissolve through heating in a boiling water bath, then add potato starch and continue heating in water bath for 30 minutes, stir continuously to form a uniform paste. After cooling to about 60° C., add 1000 ml fresh whole egg liquid and 20 ml 2% malachite green solution, mix thoroughly and then filter by double-layered gauze, then dispensed into test tube with screw cap. 7 ml of the prepared solution is added to each test tube, then add the 2% basic fuchsine solution according to a specific proportion into the test tube (see Table 3 for the adding amount), then place the test tube into the 85% steam incubator for 90 minutes, cooling to 60° C. or below and then place the test tube inclinedly into the biological safety cabinet (also called purification station), thereby the culture medium is cooled to solidify and form an incline surface. Put 10.sup.−2/ml living bacilli solution of Mycobacterium tuberculosis to the incline surface of the culture medium. The living bacilli solution for each tube is 0.1 ml. The concentration of bacilli solution in the culture medium is 10.sup.−3 mg/ml. Place in Digital Biochemical Incubator to culture. After culture for 5 weeks, no bacteria growth refers to drug susceptibility, continue bacteria growth refers to drug non-susceptibility (See Table 4 for testing results).

(43) TABLE-US-00004 TABLE 4 Testing results Adding amount of Drug final Tube 2% basic fuchsine dilution Time in 36 C. Testing number solution factor incubator results 1  0.7 ml 500 5 weeks Grow 2 0.525 ml 750 5 weeks Grow 3  0.35 ml 1000 5 weeks Grow

(44) Explanation of Drug Susceptibility Testing of Bacteria Growth:

(45) Since basic fuchsine is non-toxic, in drug susceptibility testing, place basic fuchsine into the Lowenstein-Jensen medium will only cause the changes in color but no toxicity will be caused by the culture medium, and no nutrients content of the Lowenstein-Jensen medium will be affected. Also, since the medium does not provide a somatic environment, the bacteria should grow normally in this medium. This further proves that basic fuchsine is non-toxic, and that the fuchsine itself does not have a killing effect on the acid-fast bacilli killing effect. Instead, the basic fuchsine increases the pH of body fluid and stain the bacteria to become the target, thus the immunity system is activated to remove the bacteria thoroughly. This is the greatest advantage of this drug.

(46) If standard drug is placed inside the Lowenstein-Jensen medium, this equals to giving toxic substances to the food of the bacteria, therefore the bacteria cannot grow because of food poisoning, therefore causing to the culture result as bacteria cannot grow (drug susceptibility). In other words, standard drugs can only have inhibition effect and fail to remove the bacteria thoroughly. Also, serious side effect may be resulted and damage to human detoxification is caused.

(47) Important characteristics of using basic fuchsine to treat Mycobacterium tuberculosis and Mycobacterium leprae are summarized as follows:

(48) 1. Because basic fuchsine can increase pH of the body, causing the bacteria to lose its pH regulation effect, that unable to suppress phagocytes to secret plasmin, thus the fusion of lysosomes and phagosome will lead to the removal of bacteria.

(49) 2. Since basic fuchsine can stain the bacteria, while causing an increase in body pH, therefore the bacteria is tagged while the immunity is increased. Accordingly, the phagocytes is capable of identifying the target and has an increased engulfing ability to eliminate the bacteria.

(50) 3. Since basic fuchsine is intoxic, that its function mechanism is different from existing drug and it cannot inhibit or kill bacteria by toxicity effect, therefore during in vitro drug susceptibility, the bacteria cannot be killed and can growth normally in the culture medium due to the lack of somatic environment.

Embodiment 4

(51) Basic Fuchsine for treatment of Tuberculosis

(52) Dosage for patient: Capsule, 500 mg/capsule, where the weight ratio of basic fuchsine to ground rice is 3:2, each patient takes 1˜2 capsule/day.

(53) Method of administration: Every morning, before breakfast, take the capsule, three month as one treatment course, see Table 5 for patients' records, see Table 6 for treatment results.

(54) Explanation for Patients' Records:

(55) 1. All patients were diagnosis and confirmed by standard TB hospital or TB prevention and treatment center, and all patients encountered disease recurrence after conventional standard drug treatment.

(56) 2. The patients, after conventional standard drug treatment, experienced liver and kidney damages of different level, and can no longer accept conventional standard drug.

(57) 3. Before drug treatment with basic fuchsine drug, all patients have obvious symptoms: body weakness, discomfort, fever, cough, night sweat, ascites, blood spitting, blood vomiting, etc. (skeletal TB patient experience pain, some experience amenorrhea).

(58) 4. Symptoms are significantly reduces after taking basic fuchsine for one month for majority of patients, TB symptoms are eliminated after taking basic fuchsine for three months, recovery are confirmed through X-ray after taking basic fuchsine for six months

(59) 5. Patients' blood test for liver and kidney after taking basic fuchsine shows that the blood test results are normal.

(60) 6. After taking basic fuchsine for one month, no M. tuberculosis is found in sputum (no acid-fast bacilli is found). After taking basic fuchsine for six month, the course of treatment is complete. Normal lives can be resumed physical labor activities can be done.

(61) TABLE-US-00005 TABLE 5 Patients' records of TB Patients Patent Sputum Side Effect of Sex Place of Name of Acid-Fast Convention Age diagnosis disease Bacilli treatment Disease Condition Li XX Shenyang Pulmonary TB(+) Dizziness, Cough, sputum F Chest TB nausea, cannot with blood, whole 65 Hospital eat, vomiting, body weakness, very high uric low-grade fever acid test result, with increased high seriousness in the transaminase test afternoon, night result sweat Zhao XX Jilin TB Cavitary TB TB(+) Liver and kidney Whole body F Hospital damage weakness, fatigue, 38 cough, low-grade fever, face flushing, night sweat, amenorrhea Yu XX Jilin TB Secondary TB(+) Nausea, Year round hands M Prevention TB vomiting, and foot fever, 48 and dizziness, liver weakness, cough, Treatment and kidney night sweat, Center damage, elevated weight loss transaminase and uric acid Zhang XX Liaoyuan Thoracic CT Scan Dizziness, Relied on F City TB vertebrae TB(+) nausea, liver and painkiller, cannot 62 Hospital TB kidney damage, lie up and down high by herself, sharp transaminase pain when coughing Dong XX Jilin TB Infiltrate TB(+) Nausea, vomit, fever with F Hospital Pulmonary dizziness, increased 60 TB fatigue, whole seriousness in the body weakness, afternoon, night high sweat, cough, transaminase whole body weakness, fatigue Yu XX Jilin TB Pulmonary TB(+) Serious drug Cough, fever, M Hospital TB reaction, cannot night sweat, 43 eat, high weakness, fatigue, transaminase and whole body uric acid discomfort, weight loss Jiang XX Shenyang Pulmonary TB(+) Nausea, vomit, Cough, fever, M Dongling TB cannot eat, high night sweat, 26 Hospital transaminase and weakness, fatigue, uric acid whole body discomfort Wu XX Jilin TB Miliary TB TB(+) Nausea, vomit, Cough, low-grade M Hospital dizziness, weight fever with 21 loss, high increased transaminase and seriousness in the uric acid afternoon, fact rash, night sweat, weakness Yan XX Shenyang Cavitary TB TB(+) No improvement Cough, night F Chest after treatment sweat, body 22 Hospital (many times), weakness, liver and kidney aggregated flu, damage, liver and kidney hydrothorax, damage, significant lower weakness, back pain menstruation amenorrhea Wu XX Heilongjiang Neck and TB(+) Insignificant Serious cough, F Military armpit treatment result weakness, fatigue, 63 Hospital lymph nodes with relief only, enlarged neck and TB recurrence armpit lymph repeatedly, nodes, with dizziness, vomit, hardening and nausea, weakness pain is aggravate Yu XX Siping TB Pulmonary TB(+) Nausea, Cough, sputum F Hospital TB vomiting, production, 69 dizziness, liver occasional low- and kidney grade fever, damage weakness, fatigue Sun XX Siping TB Cavitary TB TB(+) dizziness Nausea, Cough, low-grade M Hospital liver and kidney fever, weakness, 32 damage, fatigue, weight weakness, night loss sweat Hou XX Siping TB Pulmonary TB(+) Nausea, anorexia, Low-grade fever, M Hospital TB increased night sweat, 60 heartbeat, whole body weakness, high weakness, cough transaminase Qi XX Shenyang Pulmonary TB(+) Nausea, Cough, low-grade F No. 2 TB TB dizziness, liver fever, weakness, 62 Hospital and kidney fatigue damage Meng XX Shenyang Pulmonary TB(+) Nausea, anorexia, Cough, easy to get M Dongling TB liver and kidney a flu, night sweat, 51 TB Hospital damage, elevated fatigue, weakness transaminase Zhou XX Fushun TB Pulmonary TB(+) Nausea, Cough, weakness, F Hospital TB increased fatigue, 77 heartbeat, liver drowsiness, easy and kidney to catch a cold damage Li XX Fushun TB Pulmonary TB(+) Headache, Cough, sputum F Hospital TB anorexia, liver production, 49 and lung weakness, night damage, high sweat, fatigue, transaminase whole body discomfort Li XX Fushun TB Tuberculosis TB(+) Nausea, Weak, fatigue, M Hospital Pleurisy headache, discomfort, low- 48 anorexia, liver grade fever, night and kidney sweat, chest pain, damage, cough terminated treatment, thoracentesis 4 times Zhang XX Zhangchun Double TB(+) Whole body Cough, low fever, F TB Hospital Miliary TB weakness, more serious in 26 nausea, anorexia, the afternoon, dizziness, liver night sweat and kidney damage Wamg XX Jilin Jiutai Double TB(+) Nausea, anorexia, Cough, blooding M TB Hospital Miliary TB, headache, liver spitting, whole 40 3 cavity in and kidney body weakness, the lung damage low-grade fever, night sweat, bedrest, weight loss

(62) TABLE-US-00006 TABLE 6 Treatment results of TB Patients Patent Dosage Sex (capsule/ Drug treatment after Drug treatment after Drug treatment after Age day) 1 month 3 month 6 month Li XX 1 TB Improved (−) Resume physical TB (−) confirmed by F strength, TB symptoms X-ray, liver and 65 such as fatigue are kidney function eliminated normal Zhao XX 1 TB Improved (−) Symptoms of night TB (−) confirmed by F normal sweat, cough, weakness X-ray, liver and 38 menstruation low-grade fever are kidney function eliminated normal Yu XX 1 TB Improved (−) Resume physical TB (−) confirmed by M strength, symptoms of X-ray, liver and 48 cough night sweat and kidney function low-grade fever are normal eliminated Zhang XX 2 Pain reduced Resume physical liver and kidney F strength, pain is function normal, no 62 relieved, stop use of significant changes in painkiller X-ray Dong XX 1 Reduced symptoms Resume physical TB (−) confirmed by F of cough and others strength, TB symptoms X-ray, liver and 60 are eliminated kidney function normal Yu XX 1 Cough and night Resume physical TB (−) confirmed by M sweat disappeared, strength, symptoms of X-ray, liver and 43 Improved cough, weakness and kidney function night sweat are normal eliminated Jiang XX 1 Normal All TB symptoms are TB (−) confirmed by M transaminase eliminated X-ray, liver and 26 TB (−) kidney function normal Wu XX 1 Normal All TB symptoms are TB (−) confirmed by M transaminase eliminated, physical X-ray, liver and 21 TB (−) strength is improved kidney function normal Yan XX 1 No lower back All TB symptoms are TB (−) confirmed by F pain, normal eliminated, physical X-ray, liver and 22 menstruation, TB (−) strength is improved, kidney function ascites dissappeared normal Wu XX 1 Improved, Resume physical TB (−), neck and F softening of hard strength, all TB armpit tubercles 63 tissue symptoms are disappeared eliminated Yu XX 1 Improved TB (−) Feel body strength, TB (−) confirmed by F cough is gone, not X-ray, liver and 69 fatigue anymore, low- kidney function grade fever normal disappaeared Sun XX 1 Significantly Resume physical TB (−) confirmed by M improved TB (−) strength, weight gain, X-ray, liver and 32 all TB symptoms are kidney function eliminated normal Hou XX 1 Improved TB (−) Fatigue is gone, feel to TB (−) confirmed by M have strength, all all X-ray, liver and 60 TB symptoms are kidney function eliminated normal Qi XX 1 Improved TB (−) Resume physical TB (−) confirmed by F strength, not fatigue X-ray, liver and 62 anymore, all TB kidney function symptoms are normal eliminated Meng XX 1 Improved TB (−) Cough disappeared, TB (−) confirmed by M whole body with X-ray, liver and 51 strength again, all TB kidney function symptoms are normal eliminated Zhou XX 1 Improved TB (−) fatigue disappeared, TB (−) confirmed by F cough is gone, all TB X-ray, liver and 77 symptoms are kidney function eliminated normal Li XX 1 Improved TB (−) Feel improved physical TB (−) confirmed by F strength, fatigue and all X-ray, liver and 49 TB symptoms are kidney function eliminated normal Li XX 1 Significantly improved physical TB (−) confirmed by M improved TB (−) strength, all TB X-ray, liver and 48 symptoms are kidney function eliminated, ascites normal disappeared Zhang XX 1 Improved TB (−) Cough and all TB TB (−) confirmed by F symptoms are X-ray, liver and 26 eliminated kidney function normal Wang XX 1 Improved TB (−) all TB symptoms are TB (−) confirmed by M eliminated, feel X-ray, liver and 40 improved physical kidney function strength, weight gain normal

Embodiment 5

(63) Basic Fuchsine for Treatment of Leprosy:

(64) I. Type of drug:

(65) 1. Oral capsule: Dosage for patient: Capsule, 500 mg/capsule, where the weight ratio of basic fuchsine to ground rice is 3:2, each patient takes 1˜2 capsule/day;

(66) 2. Topical tincture, apply to ulcer surface.

(67) II. Preparation of Basic Fuchsine Tincture:

(68) Materials: 1. Basic fuchsine, 2. Medical alcohol (75% ethanol solution)

(69) Preparation Process:

(70) 1. Pour 100 g basic fuchsine and 800 ml 75% ethanol into a glass beaker, then stir evenly by a glass rod.

(71) 2. Grip an alcohol cotton with forceps, light up by a lighter and place to the surface of the beaker which contains basic fuchsine and 75% ethanol, ignite the mixture, stir with the glass rod while burning until the flame is out.

(72) 3. Wait till the temperature reached 60° C., then pour the drug solution after burning into a grinding jar through a funnel.

(73) 4. Soaking the prepared tincture solution into cotton ball in an auxiliary tank.

(74) III. Method of Use

(75) External use: wash the ulcer surface of leprosy patients with saline, then apply the cotton ball which is prepared with basic fuchsine tincture solution, apply repeatedly and then wrap by gauze. Repeat the above steps every 3 days until the wound is healed.

(76) Internal use: Every morning before breakfast, take 1 capsule with warm water until recovery. One treatment course is three months. See Table 7 for treatment results.

(77) Explanation for patients' records: The subjects are patients from Shandong Tengzhou City Leprosy Village and patients from Leprosy Rehabilitation Center of Puguang Hospital in Wuchaun City, Guangdong Province.

(78) TABLE-US-00007 TABLE 7 Patient's records of Leprosy Patients Condition Patent Name Years Convention before Sex of of treatment Fuchsine Treatment Treatment Age disease Ulcer method Treatment method results Remarks Du XX Leprosy More Serious Cannot Oral and After oral After M ulcers than 60 drug sleep due external treatment treatment 81 years reaction, to pain, for 7 days, for 1 increased swollen leg's month, ulcer area, and red swelling scab is bone pain calf and redness formed on disappeared, the ulcer ulcer area is area reduced Zhang Leprosy More Palpitation, Swollen Oral and After oral After XX ulcers than 40 nausea, and red external treatment treatment M years anorexia finger, for 10 days, for 1 68 sticky, swelling month, ulcer on and redness scab is feet disappeared, formed on foot ulcer the ulcer area is area, hands reduced are healed Cao XX Leprosy Few Used many Ulcer and External After half Absorbed, M ulcers decades external bleeding month, area continue 76 medication on two of ulcer is treatment but feet reduced, ineffective scab is formed at the edges Liu XX Leprosy Many Used many Ulcer on External scab formed Continuous M ulcers years external one foot use of after half monitoring 70 medication tincture month but ineffective Chen Leprosy 45 Used many Pus and External scab formed Pain XX ulcers years external pain on use of after half disappeared M medication one foot tincture month on the day 66 but of ineffective application

(79) One skilled in the art will understand that the embodiment of the present invention as shown in the drawings and described above is exemplary only and not intended to be limiting. It will thus be seen that the objects of the present invention have been fully and effectively accomplished. It embodiments have been shown and described for the purposes of illustrating the functional and structural principles of the present invention and is subject to change without departure from such principles. Therefore, this invention includes all modifications encompassed within the spirit and scope of the following claims.