CN112516125A - Application of tyrosine in preparing medicine for preventing and treating intravascular hemolysis induced by puerarin injection - Google Patents
Application of tyrosine in preparing medicine for preventing and treating intravascular hemolysis induced by puerarin injection Download PDFInfo
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- CN112516125A CN112516125A CN202011545842.7A CN202011545842A CN112516125A CN 112516125 A CN112516125 A CN 112516125A CN 202011545842 A CN202011545842 A CN 202011545842A CN 112516125 A CN112516125 A CN 112516125A
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- injection
- puerarin
- tyrosine
- hemolysis
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- 238000002347 injection Methods 0.000 title claims abstract description 123
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- HKEAFJYKMMKDOR-VPRICQMDSA-N puerarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=C(O)C=CC(C2=O)=C1OC=C2C1=CC=C(O)C=C1 HKEAFJYKMMKDOR-VPRICQMDSA-N 0.000 title claims abstract description 122
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 title claims abstract description 66
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic 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
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
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- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a compatible application method of tyrosine and puerarin, which is characterized in that the tyrosine and the puerarin are compatible to prepare an injection containing the puerarin, or the tyrosine is firstly used and then the puerarin is used, thereby effectively overcoming the accidental hemolytic adverse reaction of the puerarin injection and improving the safety of the puerarin injection administration.
Description
Technical Field
The invention relates to medical application of tyrosine, in particular to application in puerarin injection.
Background
L-tyrosine (L-Tyr) is one of the essential amino acids, is a nutrient substance necessary for establishing and maintaining positive nitrogen balance, and plays an important role in metabolism, growth and development of human and animals. It is an integral part of proteins and also a key precursor of hormones and neurotransmitters and is present in foods such as fish, soy, egg, milk and bananas. Too low a tyrosine content will cause albinism and brown yellow. The content of tyrosine will also affect the nutrition and hair color of animals.
Puerarin is an isoflavone compound extracted from dried root of Pueraria lobata Ohwi of Leguminosae, 4', 7-dihydroxy-8-beta-D-glucosyl isoflavone. Is widely used for treating cardiovascular diseases clinically. The prior clinical medicine preparation containing puerarin is mainly injection. With the wide use of puerarin, more and more reports about adverse reactions of puerarin are provided in recent years, and the wide attention of the medical field is attracted. By analyzing the adverse reaction of the traditional Chinese medicine in the last 20 years, the puerarin injection is ranked at the 18 th position. The national adverse drug reaction monitoring center reported adverse reactions of puerarin injection in adverse drug reaction information report 3 of 1 month in 2003. Most researchers think that the puerarin injection is prepared by using 50% propylene glycol as a solvent, so that the purity is not enough due to the difference of extraction processes, technologies and the like, and various reactions caused by introducing impurities cannot be avoided (see the analysis of adverse reactions in clinical puerarin injection in xu daohui, Shanghai J.Med., 2006, 40 (8): 71-72; and the clinical application and adverse reactions of puerarin in Xu Shi Guo, Shizhen Chinese medicine, 2005, 16 (12): 1307-1308). After 63 adverse reactions of puerarin reported in main medical journal in 2004 in 2000-year, 40 men and 23 women were discovered; the age is 34-81 (57.5 +/-23.5). In all cases intravenous drip was administered. The administration dosage is 0.4-0.6 g, and the drug diluent is 5% glucose solution, normal saline, 5% glucose saline and the like. The fastest reaction time is 3 min, the slowest reaction time is 13 d, and the reaction time is in the administration process. 47 responders appeared with the first dose and 16 responders appeared with repeated doses. Statistics show that the common adverse reactions include allergy (fever, tremor and the like, 24 cases), anaphylactic shock (4 cases), hemolytic anemia (13 cases), liver damage, kidney damage (7 cases), drug fever (10 cases) and death (5 cases). All cases had no history of allergy, and the patients who stopped taking the drug after the reaction were recovered by symptomatic treatment (except dead cases). The dosage and the used diluent are within the prompting range of the medicine instruction, and all reactions are definitely caused by puerarin. The adverse reaction is independent of the disease, age and sex, and is not related to the drug diluent. It is related to the difference in constitutions of patients, especially the elderly and infirm. The length of the reaction time is related to the slow onset of action of the Chinese medicinal preparation (see the general Rongrong written analysis of 63 cases of adverse reactions of puerarin documents, journal of the modern Chinese and Western medicine combination, 2005, 14 (1): 140). A patient with intravenous injection of puerarin shows acute renal insufficiency and hemolytic anemia after about 10min (see Kunming written "puerarin induced hemolytic anemia", journal of adverse drug reactions, 2003, 5: 291). Therefore, the hemolytic anemia caused by puerarin is caused by puerarin itself.
Disclosure of Invention
The invention aims to provide a new medical application of tyrosine, namely the application of tyrosine in puerarin injection, wherein tyrosine can effectively prevent and treat intravascular hemolysis adverse reaction induced by puerarin.
Actually, the invention relates to the application of tyrosine in preparing puerarin injection compound preparation, and can also be temporarily matched with puerarin injection in the injection and transfusion modes, or tyrosine is applied in the injection and transfusion modes and then the puerarin injection is applied.
In order to achieve the purpose, the invention adopts the technical scheme that: new use of tyrosine in preparing puerarin injection is provided. The injection of tyrosine and puerarin is used in combination temporarily in injection and transfusion modes. The injection is prepared by applying tyrosine in injection and infusion modes and then applying puerarin injection.
The relevant content in the above technical solution is explained as follows:
1. in the scheme, the injection comprises the following medicines in parts by weight: l-50 parts of tyrosine and l-50000 parts of puerarin.
2. In the scheme, the injection also comprises 1-50 parts by weight of auxiliary materials and l-10000 parts by weight of water for injection. The auxiliary materials are sodium bicarbonate solution, glucose solution, propylene glycol solution, glucose saline, sodium chloride injection or normal saline.
3. In the scheme, the injection can be clinically acceptable injection, powder injection or infusion.
4. In the above scheme, the preparation method of the injection is as follows:
the powder injection is prepared by mixing tyrosine and puerarin and sterilizing; or mixing tyrosine, puerarin and sodium chloride, dissolving in water for injection, adjusting pH to 5.0-8.5 with hydrochloric acid or sodium bicarbonate solution, filtering, sterilizing the filtrate, packaging in powder ampoule, and sterilizing.
The injection is prepared by the following steps. Mixing tyrosine, puerarin and sodium chloride, adding injectable water for dissolving, adjusting pH to 5.0-8.5 with hydrochloric acid or sodium bicarbonate solution, filtering, bottling the filtrate, and sterilizing. Or tyrosine is prepared from 5% glucose solution, 5% glucose saline, propylene glycol solution (prepared from propylene glycol and normal saline at volume ratio of 1:1, and containing propylene glycol 0.5 ml/ml), sodium chloride injection or normal saline by dissolving, mixing with puerarin injection, filtering, packaging the filtrate in ampoule, and sterilizing.
The infusion is prepared by mixing tyrosine, puerarin and sodium chloride, dissolving with injectable water, adjusting pH to 5.0-8.5 with hydrochloric acid or sodium bicarbonate solution, dissolving, filtering, bottling the filtrate in saline glass bottle, and sterilizing. Or tyrosine is prepared from 5% glucose solution, 5% glucose saline, propylene glycol solution (prepared from propylene glycol and normal saline at volume ratio of 1:1, and containing propylene glycol 0.5 ml/ml), sodium chloride injection or normal saline by dissolving, mixing with puerarin injection, filtering, packaging the filtrate in ampoule, and sterilizing.
5. In the scheme, the temporary matching application refers to that the puerarin injection is mixed with tyrosine to be infused or injected together when being applied in a hospital.
6. In the above scheme, the application of the tyrosine followed by the puerarin injection in the injection and infusion modes means that the tyrosine is applied in the injection and infusion modes and then the puerarin injection is applied in the injection and infusion modes in hospitals.
Puerarin has effects in dilating coronary artery and cerebral vessels, reducing oxygen consumption of myocardium, improving microcirculation, and resisting blood platelet aggregation. Clinically, the traditional Chinese medicine composition is used for auxiliary treatment of coronary heart disease, angina, myocardial infarction, retinal artery and vein occlusion, sudden deafness, ischemic cerebrovascular disease, infantile viral myocarditis, diabetes and the like. Puerarin can be mixed with tyrosine to make compound puerarin injection for preventing and treating various diseases, such as diabetic peripheral neuropathy, hypertension complicated with diabetes, diabetic nephropathy, acute cerebral infarction, stable angina pectoris, lower limb deep venous thrombosis and vertebrobasilar artery ischemia giddiness. However, puerarin in the puerarin-containing injection is very easy to cause intravascular hemolysis. The tyrosine not only has a plurality of physiological activities of protecting liver, strengthening brain and the like, but also has the function of antagonizing intravascular hemolysis adverse reaction induced by puerarin and improves the safety of puerarin injection administration.
The purpose and the achieved effect of the present invention will be further described below with reference to some tests.
The experiment refers to the technical guidance principle of research on the irritation and hemolysis of traditional Chinese medicines and natural medicines to carry out a preliminary test on the hemolysis test, and the result shows that 4-6mM puerarin can cause 10% hemolysis of rabbit red blood cells of 1%, the occurrence probability of the in vitro hemolysis test is 100%, the hemolysis test results are all reproduced, and the method can be repeated. The method can be used for finding potential accidental hemolysis of the injection, is a feasible test method for carrying out new drug development of the injection and judging whether accidental hemolysis exists, is beneficial to reducing adverse reactions and improving the safety of the injection. The invention takes rabbits as an experimental animal model to research the action and the effect of tyrosine on the hemolytic adverse reaction of puerarin solution.
Action and effect of tyrosine antagonism of hemolytic adverse reaction of puerarin-containing solution
Hemolysis test of puerarin injection
The influence of the combination of tyrosine and puerarin on rabbit erythrocytes was studied. The administration method of rabbit comprises dividing the group treated with puerarin and the group (puerarin injection + tyrosine) into 2 groups, each group containing 5 rabbits. The puerarin injection and tyrosine are administered by ear vein at a dose of 15 mg/kg per day according to body mass－1Dosing. The puerarin-treated rabbits were administered with puerarin at 15 mg/kg per day according to body mass－1Dosing. 1 administration cycle, 10 d per cycle. Blood was collected before dosing and 24 h after dosing on day 6 of the week.
Taking red blood cells of puerarin injection group rabbits, respectively adding a certain dosageTyrosine and puerarin, observing erythrocyte state and hemolysis incidence after 10min, and using X2And (4) testing, counting and analyzing the experimental result, and searching the antagonistic effect of tyrosine on accidental hemolysis of the puerarin injection. The results are now reported as follows:
1 materials of the experiment
1.1 test drugs
Tyrosine injection (I), wherein tyrosine is purchased from Beijing Solebao scientific and technological Limited, 7.25mg of tyrosine is accurately weighed by an electronic balance, dissolved in a normal saline solution, and the tyrosine solution is metered to 10mL by a 10mL volumetric flask, thus the injection (I) has the concentration of 4mmol-1. Filtering with microporous membrane (0.22 μm) for sterilization, and storing at 4 deg.C.
Injection agent 2: the injection (r) is diluted to 2 mmol.L with sterilized normal saline-110mL, stored at 4 ℃ until use.
Injection (c): the injection (r) is diluted to 1 mmol.L with sterilized normal saline-110mL, stored at 4 ℃ until use.
And 4, puerarin injection IV: 2mL of the puerarin powder is provided by Zhejiang Connbei pharmaceutical products GmbH, and the product batch number is 090501, and each mL of the injection contains 50mg of puerarin.
Puerarin injection (250 mM): accurately weighing 1.041g of puerarin powder (purchased from Jiangsu Tiancheng drug Co., Ltd.) by using an electronic balance, dissolving by using 40% dimethyl sulfoxide (DMSO, DZ0231 and AMRESCO), assisting in dissolving by using ultrasound, diluting the physiological saline solution to 9mL, fixing the volume of a volumetric flask to 10mL, and enabling the color of the solution to be colorless (in a configuration environment: carried out in an ultra-clean workbench). The solvent was 40% DMSO solution. Filtering with microporous membrane (0.22 μm) for sterilization, and storing at 4 deg.C.
Compound puerarin injection (sixty percent): 0.04mL of injection and 0.20 mL of injection are uniformly mixed to form 0.24mL of injection. Each mL of the injection contains 41.67mg of puerarin and 120.8 mug of tyrosine.
Compound puerarin injection (c): 0.04mL of injection and 0.20 mL of injection are uniformly mixed to form the injection (c), wherein the total volume is 0.24 mL. Each mL of the injection contains 41.67mg of puerarin and 60.4 mug of tyrosine.
Compound puerarin injection (b): 0.04mL of injection and 0.20 mL of injection are uniformly mixed and totally 0.24mL is prepared to form the injection. Each mL of the injection contains 41.67mg of puerarin and 30.2 mug of tyrosine.
Ninthly, the compound puerarin injection: 0.04mL of injection and 0.099 mL of injection are uniformly mixed to form 0.14mL of injection. Each mL of the injection contains 73.61mg of puerarin and 207.1 μ g of tyrosine.
Compound puerarin injection r: 0.04mL injection and 0.099 mL injection are mixed to total 0.14mL to form injection in the form of injection in the amount of R. Each mL of the injection contains 73.61mg of puerarin and 103.6 μ g of tyrosine.
Compound puerarin injection ≈ 11: 0.04mL of injection and 0.099 mL of injection are mixed uniformly to obtain 0.14mL of injection. Each mL of the injection contains 73.61mg of puerarin and 51.8 μ g of tyrosine.
1.2 Experimental animals
10 rabbits (about 2.5 Kg) are provided by the animal experiment center of northwest agriculture and forestry science and technology university. Feeding the chicken at the room temperature of 15-25 ℃ and the relative humidity of 50%.
1.3 reagents, instruments
Sodium chloride injection, Shiyao silver lake pharmaceutical Co Ltd; water for injection is prepared by self; TGL-16B high speed centrifuge, Hunan Star science instruments, Inc.; HPY-01B Biochemical incubator, Huangshi Hengfeng medical appliances Co., Ltd; BIO-RAD680 enzyme-linked immunosorbent assay device; the enzyme label is purchased from Jiangsu Haimen III and Xinya medical instrument factories and is purchased from Yanglinbao Xin equipment Co., Ltd. of Shaanxi province.
2 method
2.1 preparation of erythrocyte suspensions
10 rabbits are divided into puerarin injection group and puerarin injection + tyrosine treatment group, and blood is collected 24 h after 6 days of ear marginal vein injection. The hemolysis experiments were performed separately. 10mL of blood is collected from the heart of each rabbit, 160IU of heparin sodium (Jiangsu Wanbang Biochemical medicine, Inc.) is anticoagulated, then the rabbit is placed in a graduated centrifugal tube, the rabbit is centrifuged at 2000 r/min for 10min, the blood plasma is discarded, a proper amount of sodium chloride injection is added for washing, and the rabbit is centrifuged to discard the supernatant and the leucocyte layer. Adding appropriate amount of normal saline, shaking, centrifuging, and repeatedly washing for 3 times until the supernatant is colorless and transparent after centrifuging. The packed red blood cells were diluted with physiological saline to form an 11% (by volume) red blood cell suspension. This completes the preparation of the red blood cell suspension.
2.2 Puerarin solution in vitro hemolysis experiment design
Let the concentration of puerarin solution on erythrocytes be 6mM (0.00259 g.mL)-1). Setting a negative control group, a solvent control group (DMSO is used for replacing puerarin solution to act on erythrocytes), a drug treatment group and a positive control group. The puerarin solution was measured to have a pH of 7.16 using a METTLER TOLEDO benchtop pH meter.
The corresponding components were added to the tubes separately, taking care of the order of addition, as shown in Table 1 below. After each addition of one ingredient, shake gently. After all the components in the system are added into the system, the mixture is gently shaken and uniformly mixed, and then the mixture is placed in a biochemical incubator at 37 ℃ for incubation. After 10min hemolysis and coagulation reactions were observed. The condensation reaction determination method comprises: if the solution has reddish brown or brownish red flocculent precipitate, it will not disperse after shaking, indicating that there is agglutination of red blood cells, if the aggregate can be uniformly dispersed after shaking, it will be false agglutination, if the aggregate is not shaken, it will be true agglutination. The tubes were then centrifuged at 5000rpm/min and the color of the supernatant visually observed. The supernatant was collected and the light absorption (OD value) was measured at a wavelength of 540 nm. According to 2005 technical guidance principle of stimulation and hemolysis research of traditional Chinese medicine and natural medicine, the hemolysis rate (%) of each tube of each group is calculated according to a formula:
hemolysis rate (%) = (drug-treated OD value-negative control OD value)/(positive control OD value-negative control OD value)
Reference evaluation criteria: the hemolysis rate >5% indicates that hemolysis occurred and was statistically processed.
TABLE 1 puerarin solution and tyrosine in vitro hemolysis experiment grouping design
3 results
Puerarin daily rootAccording to the body constitution, 15 mg.kg is adopted－1When the dosage is treated, 15 mg.kg is simultaneously administered－1At the dose of tyrosine, no hemolysis was found in the experimental rabbits. The test also considers the influence of tyrosine of 40 muM, 20 muM and 10 muM on the red blood cells of 5 rabbits injected with puerarin when the puerarin concentration is 6mM, and simultaneously carries out the sporadic hemolysis experimental study of the four and five aspects of the puerarin injection, and the experimental results are all recorded in detail. X2The results of the test statistical analysis are shown in Table 2.
TABLE 210 statistical table of hemolysis test results of rabbits
Note: a P <0.01 compared to saline negative group; b P <0.01 compared with puerarin injection group
The results show that: the saline group showed no hemolysis, and the water for injection showed complete hemolysis: compared with the normal saline group, the puerarin Injection (IV) and (V) are all hemolyzed, and the occurrence rate of hemolysis is very different from that of the normal saline group (P is less than 0.01); the results of the hemolysis test are reproduced, which shows that the hemolysis test method is stable and reliable, and the test results can be repeated. Comparing with the fourth and the fifth groups of puerarin injections, the compound puerarin injections (P <0.01) have no hemolysis in the groups of (VI), (III; compared with the normal saline, the hemolysis incidence of each group of compound puerarin injections (P >0.05) and (b) does not differ from that of the normal saline; the compound puerarin injections (sixty percent, nine, eight, 11) have the same puerarin concentration (6 mM), but the compound puerarin injections (sixty percent, nine, seven, eight, nine, ten, nine, ten, nine, ten, twelve and ten, eight, twelve and twelve tyrosine respectively. The above results suggest: the tyrosine with different concentrations and the puerarin can resist hemolytic adverse reaction induced by the puerarin and reduce the incidence rate to the normal saline level.
The above experimental results show that: the puerarin can induce hemolysis, the injection containing the puerarin can induce hemolysis, and the hemolysis adverse reaction containing the puerarin can be eliminated after tyrosine is added.
The above test results suggest: the puerarin injection and the injection prepared by matching puerarin and tyrosine have no occurrence of hemolytic reaction.
Therefore, when the puerarin-containing injection is prepared or used, the tyrosine is added, so that hemolytic adverse reactions caused by puerarin can be eliminated, and the safety of puerarin injection administration is improved.
The invention has the advantages that: tyrosine is added when the puerarin-containing injection is prepared or used, so that the injection has better antagonism to intravascular hemolysis adverse reaction induced by puerarin, is low in price, has no toxic or side effect, and is safe.
The invention is further described below with reference to the following examples:
the specific implementation mode is as follows:
example i: (preparation of Compound puerarin injection)
Taking 15mg of tyrosine and 10 g of puerarin, adding 9g of sodium chloride, adding water to 1000mL, adjusting the pH to 5.0-8.5 by using 1mol/l hydrochloric acid or sodium bicarbonate solution, filtering, encapsulating the filtrate in an ampoule of 2, 5 or 10mL, and sterilizing at 100 ℃ for 30min to obtain the injection. The product can be used for the adjuvant treatment of coronary heart disease, angina pectoris, myocardial infarction, retinal artery and vein occlusion, sudden deafness, ischemic cerebrovascular disease, infantile viral myocarditis, diabetes, etc. The product can be injected intravenously or intramuscularly, each time is l-500 mL, 1-3 times a day, l 0-20 days is a treatment course, and the product can be continuously used for 2-3 treatment courses.
Example 2: (preparation of Compound puerarin powder for injection)
Taking 30mg of tyrosine and 1g of puerarin, encapsulating in a 10mL ampoule of powder for injection, and sterilizing at 100 ℃ for 30min to obtain the powder for injection. The product can be used for the adjuvant treatment of coronary heart disease, angina pectoris, myocardial infarction, retinal artery and vein occlusion, sudden deafness, ischemic cerebrovascular disease, infantile viral myocarditis, diabetes, etc. When in application, the prepared powder injection of l to 5000mg is mixed with sodium chloride injection or normal saline injection evenly, and intravenous injection or intramuscular injection can be carried out, wherein l to 500mL of the powder injection is carried out each time, l to 3 times a day, 10 to 20 days are a treatment course, and the powder injection can be continuously used for 2 to 3 treatment courses.
Example 3: (preparation of Compound puerarin infusion)
Adding water into tyrosine 7.5mg, puerarin 2g and sodium chloride 9g to 1000mL, adjusting pH to 5.0-8.5 with lmol/l hydrochloric acid or sodium bicarbonate solution, filtering, bottling the filtrate in 250mL saline glass bottle, and sterilizing at 100 deg.C for 30min to obtain infusion. The product can be used for the adjuvant treatment of coronary heart disease, angina pectoris, myocardial infarction, retinal artery and vein occlusion, sudden deafness, ischemic cerebrovascular disease, infantile viral myocarditis, diabetes, etc. When the Chinese medicinal composition is applied, intravenous injection or intramuscular injection can be directly carried out, wherein the Chinese medicinal composition is used for 1-3 times per day by l-500 mL each time, and l 0-20 days are a treatment course and can be continuously used for 2-3 treatment courses.
The above embodiments are merely illustrative of the technical ideas and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (7)
1. Application of tyrosine in preparing medicine for preventing and treating intravascular hemolysis induced by puerarin injection is provided.
2. Use according to claim 1, characterized in that: tyrosine is applied by infusion, and then puerarin injection is used.
3. Use according to claim 1, characterized in that: the puerarin injection and the tyrosine injection are mixed evenly before use and then applied in an infusion way.
4. Use according to claim 2, characterized in that: the injection is applied after tyrosine infusion and then puerarin injection.
5. Use according to claim 1, characterized in that: comprises the following medicaments in part by weight: 1-50 parts of tyrosine and 1-50000 parts of puerarin.
6. Use according to claim 1, 2, 3, 4, characterized in that: contains 1-50 parts by weight of auxiliary materials.
7. An adjuvant according to claim 6, characterized in that: the auxiliary materials are sodium bicarbonate solution, glucose solution, propylene glycol solution or sodium chloride injection.
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| CN101920019A (en) * | 2009-06-10 | 2010-12-22 | 浙江中医药大学 | Hydrophilic polymer-puerarin specific conjugated non-hemolytic conjugate |
| CN104042625A (en) * | 2014-05-28 | 2014-09-17 | 西北农林科技大学 | Application of sodium bicarbonate in puerarin injection |
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| CN104042625A (en) * | 2014-05-28 | 2014-09-17 | 西北农林科技大学 | Application of sodium bicarbonate in puerarin injection |
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| 森本泰子等: "Protective Effects of Some Neutral Amino Acids against Hypotonic Hemolysis" * |
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