CN101757016A - Medicine composition for treating flu and preparation method thereof - Google Patents
Medicine composition for treating flu and preparation method thereof Download PDFInfo
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- CN101757016A CN101757016A CN201010039528A CN201010039528A CN101757016A CN 101757016 A CN101757016 A CN 101757016A CN 201010039528 A CN201010039528 A CN 201010039528A CN 201010039528 A CN201010039528 A CN 201010039528A CN 101757016 A CN101757016 A CN 101757016A
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Abstract
The invention discloses a medicine composition for treating flu and a preparation method thereof. The medicine composition is mainly prepared from glycyrrhizic acid, baicalin, pseudoephedrine, taurine and other compounds. The invention has the advantages of simple medicine composition and exact curative effect; and animal experiments indicate that the medicine composition has strong inhibiting effect on influenza A virus and influenza B virus, and has the effects of killing various respiratory tract pathogenic bacteria to different degrees. The medicine composition has obvious and long-lasting antipyretic action and obviously relieves various cold symptoms, such as rhinorrhoea, snuffle, pains, cough and the like. The medicine composition has the action of synergy, can address both the symptoms and root causes against the causes and the symptoms of cold, and can obviously shorten the course of cold. The medicine composition can be made into any acceptable excipient in pharmaceutics.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of pharmaceutical composition for the treatment of flu and preparation method thereof, the compound preparation that this pharmaceutical composition is made up of middle pharmaceutically active ingredient.
Background technology
Flu be by multiple virus or (with) bacterial infection, and the low dual function of immunity of human body itself and the upper respiratory tract infection disease that causes.Especially influenza, infectiousness is strong, and the sickness rate height is produced people ' s health and work and to be brought very big influence, and flu prevention and treatment are the important research objectives of field of medicaments.Aspect treatment owing to lack to viral infection effective chemical medicine, clinical can only anti symptom treatment, the curative effect instability, often repeatedly.The Chinese patent medicine and the Chinese and Western bound drug of treatment flu are various in style on the market, but curative effect is all not satisfactory.Especially in recent years influenza virus variant (bird flu, swine flue etc.), large-scale outbreak lacks active drug more, the novel coldrex of urgent clinical needs determined curative effect.
To the treatment of flu, except that giving antiviral, antibacterials, also should carry out symptomatic treatment at the symptom of influenza.Symptoms such as heating, headache, whole body pain, tired weakness, chest discomfort, cough, it is bigger that the present compound recipe coldrex composition that uses clinically mostly is such drug side effectes such as acetaminophen, caffeine, chlorphenamine maleate.The antiviral drugs of Ying Yonging mainly contains amantadine clinically, and amantadine is only effective to influenza A virus, and is invalid to Influenza B virus, and in clinical practice, is prone to the multidrug resistant disease strain, and toleration is poor, and untoward reaction is many.Therefore being badly in need of clinically can anti-virus sterilizing, can improve cold symptoms again, and the low novel anti coldrex of toxic and side effects.
Baicalin is one of main effective ingredient of baikal skullcap root, deepens continuously attested pharmacological action along with what baicalin was studied in recent years: remove oxygen-derived free radicals, the ischemia that alleviates tissue, reperfusion injury, regulate the effect of immunity, antitumor, anti-HIV.Existing bibliographical information baicalin has very wide antiviral spectrum, to influenza virus also have very strong inhibitory action (just positive cloud, first bright, Teng Yu. resisiting influenza virus effect CHINA JOURNAL OF CHINESE MATERIA MEDICA 2007,32 (22) in the baicalin body: 2413-2415).Because the influence of factors such as bioavailability is used baicalin to treat grippal effect clinically separately and is still failed clearly.
Glycyrrhizic acid is one of main effective ingredient of Chinese medicine Radix Glycyrrhizae, and the effect of significant adrenocortical hormone sample is arranged, and can be used for flight against senium of human body, antiinflammatory, blood pressure lowering, enhancing human body immunity power, improves physiological function, anticancer growth etc.; In recent years the new discovery glycyrrhizic acid has the effect of broad-spectrum antiviral, comprises influenza virus, hepatitis virus, HIV (human immunodeficiency virus) (Human Immunodeficiency Virus) etc., and is main at present as the treating hepatitis medicine.We find in experimentation recently, and glycyrrhizic acid can stop proliferation of influenza virus, also can human body immunity improving power, intend adrenocortical hormone sample antiinflammatory action in addition, with other several in the pharmaceutically active ingredient compatibilities, Synergistic, treatment flu curative effect brilliance.
Herba Ephedrae is one of representative drugs of treatment by Chinese herbs flu, pseudoephedrine is one of effective ingredient of purification in the drug anesthesia Huang therefrom, pseudoephedrine belongs to the beta 2 receptor agonist, major function is to shrink the upper respiratory tract blood vessel, eliminate the inflammation of nasopharynx throat, clinical extensively as the compatibility composition of Coritab, be used to eliminate sneeze, stream is sneezed and the symptom of shedding tears.
The chemical name of taurine is a 2-aminoethyl sulfonic acid, is one of important component of rare Chinese medicine Calculus Bovis.Very pharmacological actions widely such as that taurine has is analgesic, antiinflammatory, analgesia and film are stable.Its antiinflammatory, refrigeration function, the stimulation pain that can diminish inflammation and cause; Cooling effect is quick and durable, does not have knock-on; Can also improve the specificity and the non-specific immunity of body, viral infection is had good antagonism, the inflammation that also can the antagonism various bacteria causes.Take by therapeutic dose and can alleviate the cold, fever symptom rapidly, good especially to moderate heating and low caloric effect, without any toxic and side effects.
We find in drug screening and pharmacological experiment; with baicalin, glycyrrhizic acid, taurine, pseudoephedrine compatibility, treatment all kinds flu can produce good synergistic function; antiviral and bactericidal action are not only arranged; and can human body immunity improving power, alleviate the heating paresthesia of flu or influenza, obviously improve curative effect; shorten the flu course of disease; side effect is low, and better tolerance is applicable to adult, children.
Summary of the invention
The present invention has provided a kind of pharmaceutical composition for the treatment of flu, and this preparation of drug combination method.
Medicine compositions of the present invention, make by the crude drug that following weight is formed:
Baicalin 100-500 part, glycyrrhizic acid 50-300 part, taurine 100-200 part, pseudoephedrine 10-50 part.
Also can be following composition:
Baicalin 20-200 part, glycyrrhizic acid 10-100 part, taurine 10-150 part, pseudoephedrine 1-20 part.
Glycyrrhizic acid of the present invention, pseudoephedrine, taurine can be free forms, also can be glycyrrhizic acid, pseudoephedrine, the pharmaceutically acceptable various salt of taurine.
Chemical compound combination of the present invention can be any two, three chemical compounds or four combination of compounds in glycyrrhizic acid, baicalin, pseudoephedrine, the taurine.
Glycyrrhizic acid of the present invention, baicalin, pseudoephedrine, taurine are the herbal function composition; part can chemosynthesis, and therefore above-mentioned four kinds of chemical compounds both can extract purification from Chinese medicine; also available chemosynthesis or bionic method obtain, but all should meet the national drug standard.
Said medicine of the present invention can be according to pharmaceutical preparation, add adjuvants such as corresponding correctives, excipient, make any dosage form of using clinically that is applicable to, as tablet, granule, capsule, suspensoid, oral liquid, buccal tablet, effervescent tablet etc.
The present invention relates to the application of aforementioned pharmaceutical compositions in the medicine of preparation prevention or treatment flu.
The invention still further relates to aforementioned pharmaceutical compositions, the application in the various diseases medicine that preparation treatment upper respiratory tract infection causes.
The invention still further relates to aforementioned pharmaceutical compositions, the application in the medicine of preparation treatment influenza, pharyngitis, acute/chronic bronchitis, tonsillitis or pneumonia.
The invention still further relates to aforementioned pharmaceutical compositions, have application in antiviral, the antibacterial medicines in preparation.
The present invention confirms that simultaneously glycyrrhizic acid, baicalin, pseudoephedrine, taurine compatibility use, and can obviously improve the blood drug level of baicalin, glycyrrhizic acid, improve bioavailability greatly, therefore produces synergistic function.
The present invention illustrates glycyrrhizic acid, baicalin, pseudoephedrine, taurine composition compound preparation from multi-angles such as toxicology, pharmacodynamics, pharmacokineticss, and treatment flu effect obviously is better than using separately wherein a kind of composition, has the good one-tenth property of medicine.
The instantiation mode
The following examples can illustrate in greater detail the present invention, but do not limit the present invention in any form.
Following experimentation can further specify the beneficial effect that the present invention treats various flu, and used sweet pornographic movie is the medicine by the present invention's preparation in the experiment.
Embodiment 1: sweet yellow compositions vitro antibacterial activity
Experiment medicine: glycyrrhizic acid standard substance (content is greater than 97%), baicalin standard substance (content is greater than 97%), sweet pornographic movie (by optimal proportion of the present invention).
Strain: staphylococcus aureus, escherichia coli, bacillus pyocyaneus, first Salmonella paratyphi, Diplococcus pneumoniae, hemophilus influenza, Hemolytic streptococcus.
Experimental technique: the preparation culture medium, autoclaving is standby.Get 10 of clean tube, with the medicine of 10 concentration of continuous coubling dilution preparation, maximum concentration is 10mg/mL.Each concentration repeats 3 times, a kind of bacterium of each series inoculation, 0.1 milliliter of bacterium liquid of every test tube inoculation.Detect MIC (minimal inhibitory concentration): the test tube that will inoculate bacterium liquid places 37 ℃ to hatch 24 h, if the matched group bacterial growth is good, takes place muddy; Muddiness also takes place in drug liquid tube, the expression bacterial growth, and this concentration is subjected to the reagent thing not have bacteriostasis; If the experimental group drug liquid tube is limpid, the expression bacterial growth is suppressed, and it is the medicinal liquid of greatest dilution that can bacteria growing inhibiting, be this medicine minimal inhibitory concentration (minimal inhibiting concentration, MIC).
Experimental result: sweet pornographic movie is to each minimum inhibitory concentration for the examination strain; compare with the minimum inhibitory concentration of normal saline group, baicalin group, glycyrrhizic acid group respectively; sweet pornographic movie all is lower than baicalin and glycyrrhizic acid to the Mlc of Diplococcus pneumoniae, hemophilus influenza, Hemolytic streptococcus; Mlc is at 0.078mg/mL; oral sweet pornographic movie; human body blood drug level promptly can reach this concentration; glycyrrhizic acid, baicalin, pseudoephedrine, four kinds of compatibility of drugss of taurine, external have certain collaborative bacteriostasis.
The minimum inhibitory concentration of the sweet pornographic movie of table 1, MIC (mg/mL)
Embodiment 2: sweet yellow compositions vivo bacteria corrosion action
1, medicine and material
Grouping: negative control group, 0.9% sodium chloride injection; The baicalin group, the preparation of baicalin standard substance; The glycyrrhizic acid group, the preparation of glycyrrhizic acid standard substance; Sweet yellow compositions group is established the high and low dose group; Positive controls: SHUANGHUANGLIAN KOUFUYE (Sanjing Pharmaceutical Co., Ltd., Hayao Group, lot number: 06011832), gentamycin sulfate (Jiaozhuo first pharmaceutical factory), and each three groups, 10 every group.
Animal: ICR mice, 20 ± 2g, Zhejiang Province's medical research institute Experimental Animal Center, the quality certification number: SCXK (Zhejiang) 2003-0001.
Bacterial strain: with 5% gastric Mucin dilution staphylococcus aureus, escherichia coli, Diplococcus pneumoniae suspension, bacteria containing amount is 1010/ml.
2, method and result:
Mice is pressed 0.25ml/10g lumbar injection bacterium liquid, begins to irritate stomach in 1 hour behind the injection bacterium liquid to give Drug therapy, once a day for three days on end.Write down the metainfective reaction of each treated animal, death toll and surviving animals situation.Occur phenomenons such as lethargy, enophthalmos,enophthalmus, inappetence, loose stool behind the zoogenetic infection antibacterial, death generally occurs in infected the back 24-72 hour.The results are shown in Table 2.
The result: in each treatment group of infection of staphylococcus aureus mice, sweet yellow compositions group various dose obviously is better than baicalin group, glycyrrhizic acid group to the protective effect of infecting mouse, and is close with the gentamycin effect; Sweet yellow compositions is also used separately significantly better than baicalin, glycyrrhizic acid the protective effect of escherichia coli and Diplococcus pneumoniae infecting mouse.
The sweet yellow compositions of table 2 is to the protective effect (n=10) of infecting mouse
Embodiment 3: the resisiting influenza virus effect of sweet yellow compositions
1, experiment material
Strain: influenza first 3, B-mode, available from Virology Inst., China Academy of Preventive Medicine Sciences, TCID50 (making the half cell culture tube viral dilution degree logarithm of pathological changes occur) is respectively 10-3.8,10-4.5, during test with 100 TCID50/0.1mL; Influenza virus Mus lung adapted strain (FM1) is available from Virology Inst., China Academy of Preventive Medicine Sciences.
Passage cell: Testis et Pentis Canis mdck cell China TCM Academy of Sciences Xiyuan Hospital basic research chamber provides.
Animal: SPF mice, 13～15g, Zhejiang Province's medical research institute Experimental Animal Center, the quality certification number: SCXK (Zhejiang) 2003-0001.
Experiment medicine and reagent: ribavirin injection (Shandong XinHua Pharmacy stock Co., Ltd, lot number: 0504005); SHUANGHUANGLIAN KOUFUYE (Sanjing Pharmaceutical Co., Ltd., Hayao Group, lot number: 06011832); Baicalin, glycyrrhizic acid, sweet yellow compositions (all preparing) with standard substance; DMEM culture medium (U.S. GIBCO product, lot number: 12100203); Hyclone (HyClone, lot number: AJM11171).
2, extracorporeal antivirus effect experimental technique:
(1) drug toxicity concentration determination: the medicine doubling dilution is become a plurality of Concentraton gradient with cell culture fluid, the medicine that dilution is good inserts 96 cultivations that grow up to cell monolayer, in the hole, 0.1 mL/ hole, 37 ℃ of incubators of 5%CO2 are cultivated, every day, observation of cell changed, and calculated poisonous concentration of half and maximal non-toxic concentration.(2) medicine is to the inhibitory action of influenza first 3 types in the mdck cell, B virus breeding: will dilute in the good virus access cell hole, every hole 0.1 mL puts 37 ℃ of absorption 1 h, wash after 2 times and to add the liquid of keeping that contains different pharmaceutical concentration respectively with keeping liquid, 96 orifice plates, 0.1 mL/ hole, 37 ℃ of incubators of 5%CO2 are cultivated, and observation of cell pathological changes every day (CPE) is after the cultivation 48, with mtt assay dyeing, survey the OD value at 490 nm.Be calculated as follows the suppression ratio of sample to CPE due to the influenza cell.CPE (%)=(experimental port OD value-virus control hole OD value)/(normal cell control wells value-virus control hole OD value) * 100%.Poisonous concentration/the medium effective concentration of therapeutic index=half.
Annotate: medicine contrast, virus control, cell contrast, every test group 4 porocytes, repeated trials 2 times are established in above test simultaneously.
3, interior resisting virus experimental technique:
(1) to the protective effect of influenza virus induced mice death: body weight 13～15 g SPF level mice random packet; every group 10, establish normal control group, virus control group, ribavirin (200 mg/kg) group, SHUANGHUANLIAN group (400mg/kg), glycyrrhizic acid (200 mg/kg) group, baicalin group (400mg/kg), sweet yellow compositions high and low dose group (400mg/kg, 200mg/kg).Each treated animal is in infection beginning in preceding 1 day gastric infusion, and every day 1 time, 5d after infecting is total to administration 7d, the normal saline of the 1st, 2 group of capacity such as filling stomach, and other each group filling stomach gives relative medicine and treats.After the administration the 2nd day, with influenza virus 0.1 mL/ of mice (except the 1st group) 15 times of LD50 of inoculation under the slight anesthesia of ether only, collunarium infected, and the 1st group with method inoculation normal saline 0.1mL.From infecting, observe 14 d continuously, record dead mouse number calculates mortality rate, dead protective rate, mean survival time.
(2) to the influence of influenza virus Lung Index of mice infected by Influenza virus: body weight 13～15 g SPF level mice random packet, every group 10, establish normal control group, virus control group, ribavirin (200 mg/kg) group, SHUANGHUANLIAN group (400mg/kg), glycyrrhizic acid (200 mg/kg) group, baicalin group (400mg/kg), sweet yellow compositions high and low dose group (400mg/kg, 200mg/kg).With influenza virus 0.1 mL/ of mice (except the 1st group) 8 times of LD50 of inoculation under the slight anesthesia of ether only, collunarium infects, and the 1st group with method inoculation normal saline 0.1 mL.Begin administration in infecting back 24 h, irritate stomach for the 1st, 2 group and the capacity normal saline such as give, other group gives corresponding medicine, successive administration 4 d, water 8 h are prohibited in fasting in the 5th day, and mice is weighed, and cut off the carotid artery blood-letting and cause death, take out full lung, clean with normal saline, and sop up residual brine, weigh with clean filter paper, calculate lung index and lung index suppression ratio, and the Mus lung is done histopathologic examination.
4, experimental result:
The experiment of external resisiting influenza virus shows: glycyrrhizic acid and baicalin all can suppress the cytopathy that influenza virus causes, but the thin compound performance of sweet Huang that contains the two better presses down the toxic effect fruit.The interior resisting virus experimental result shows that normal group does not have dead mouse, and all the other each groups all have dead mouse, and the model group mice is all dead, with other 5 groups of comparing differences remarkable (P＜0.05); 2 dosage groups of sweet yellow compositions mouse death rate is starkly lower than model group (P＜0.05); The mean survival time of model group mice is the shortest, and more all there were significant differences (table 4) with other each groups.Administration group and normal group and virus model group relatively the lung index there were significant differences (P＜0.05), the effect that pneumonopathy becomes due to the better inhibition influenza virus is arranged; It is obviously poor that sweet yellow compositions high low dose group lung index and ribavirin group do not have, and curative effect obviously is better than single with glycyrrhizic acid and baicalin treatment (table 5).More than experiment shows, sweet yellow compositions antivirus action not only can significantly suppress and delay cytopathy and occur on cellular level, and can suppress developing of animal influenza virus property pneumonia, curative effect obviously is better than the curative effect of single component glycyrrhizic acid, baicalin in the compositions, these chemical compound compatibilities use, and can reduce the consumption of single medicine.
The medium effective concentration and the therapeutic index of external influenza first 3 types of sweet yellow compositions of table 3 and component, B virus
Annotate: ND represents that the half toxic concentration of baicalin and sweet yellow compositions can't measure, so do not calculate therapeutic index.
The sweet yellow compositions of table 4 is to the protective effect of influenza virus FM1 infecting mouse
The protective effect of viral pneumonia due to the sweet yellow compositions of table 5 infects FM1
Annotate: * represents to compare P＜0.05 with the virus control group
Embodiment 4: the analgesic activity of sweet yellow compositions
1, material and method
Medicine: sweet yellow compositions, glycyrrhizic acid, baicalin are the standard substance preparation; The positive control drug aspirin, 25mg/ sheet, Beijing doube bridge drugmaker, lot number: 20090902.The experiment dosage is 300mg/kg.Put into mortar with 6 and grind adding 5ml distilled water.
Animal: ICR mice, 20 ± 2g, Zhejiang Province's medical research institute Experimental Animal Center, the quality certification number: SCXK (Zhejiang) 2003-0001.
Algogen: glacial acetic acid, AR. Chemical Reagent Co., Ltd., Sinopharm Group, lot number: T20090910.Face with preceding and be made into 0.7% solution with distilled water.
Method: test divides 6 groups, that is: model control group (giving normal saline), glycyrrhizic acid group, baicalin group, aspirin group, sweet yellow compositions high and low dose group.Every group of 10 mices, by above-mentioned dosage with the volume gastric infusion of 0.1ml/10g after 1 hour, every mouse peritoneal is injected 0.7% acetum 0.1ml/10g body weight.Occur turning round in time and 20 minutes of body each Mus after the observed and recorded injection algogen for the 1st time and turn round the body number of times,, calculate pain with following formula and react suppression ratio through the difference that the t check relatively causes the threshold of pain and turns round the body number of times between each group.
2, experimental result
This experimental observation the influence of sweet yellow compositions to 0.7% acetic acid induced mice writhing response, the result shows that this medicine reduces very significantly and turns round body number (P＜0.001) that the pain suppression ratio is more than 50%, and can prolong the pain time (P＜0.01～0.001) that causes.Said composition but has better analgesic effect.See Table 6
The sweet yellow compositions of table 6 is to the influence of pain reaction due to 0.7% acetic acid: (n=10 X ± SD)
Annotate: *, * *, * * * compare P＜0.05,0.01,0.001 with model group respectively.
Embodiment 5: the refrigeration function of sweet yellow compositions
1, experiment material and method
Laboratory animal; Healthy Wistar kind rat, body weight 120～150g, male, Zhejiang Province's medical research institute Experimental Animal Center, the quality certification number: SCXK (Zhejiang) 2003-0001.
The experiment medicine: sweet yellow compositions, glycyrrhizic acid, baicalin are the standard substance preparation; The positive control drug aspirin, 25mg/ sheet, Beijing doube bridge drugmaker, lot number: 20070902.The experiment dosage is 300mg/kg.Put into mortar with 6 and grind adding 5ml distilled water
Pyrogen: yeast tablet, Gannan Pharmaceutic Factory produces, and every contains dry yeast 0.5g, lot number: 20070105.Be mixed with the suspension of 15% concentration during test with physiological saline solution.
Experimental technique: all laboratory animals were surveyed body temperature two days in advance, 1 day 1 time.Select 70 of the normal rats of body temperature to be divided into six groups at random, model control group (giving normal saline), glycyrrhizic acid group, baicalin group, aspirin group, sweet yellow compositions high and low dose group.Every rat back subcutaneous injection 15% yeast suspension 2ml, then once by above-mentioned dosage difference gastric infusion.After pyrogenicity, measure each Mus body temperature once in 3,4,5,7 and 9 hours, represent the variation of body temperature with the difference of normal body temperature before body temperature that records and the pyrogenicity.The result learns by statistics and handles the difference that compares between administration group and the blank group.
2, result of the test
3,4,5,7 hours have suppressed rat temperature to sweet yellow compositions very significantly after pyrogenicity increases, with blank group comparing difference highly significant (P＜0.05～0.001), the high dose effect of bringing down a fever is suitable with aspirin, antipyretic persistence and effect obviously are better than glycyrrhizic acid, baicalin, the results are shown in Table 7.
The sweet yellow compositions of table 7 is to the influence of yeast pyrogenicity rat temperature: (X ± SD)
Annotate: *, * *, * * * with respectively with the blank group relatively, p＜0.05,0.01,0.001.
Embodiment 6; The antiinflammatory action of sweet yellow compositions
1, experiment material and method:
Laboratory animal: get 60 of healthy Wistar kind rats, body weight 150～200g, male, Zhejiang Province's medical research institute Experimental Animal Center, the quality certification number: SCXK (Zhejiang) 2003-0001.
The experiment medicine: sweet yellow compositions, glycyrrhizic acid, baicalin are the standard substance preparation; The positive control drug aspirin, 25mg/ sheet, Beijing doube bridge drugmaker, lot number: 20070902.The experiment dosage is 300mg/kg.Put into mortar with 6 and grind adding 5ml distilled water.
Proinflammatory agent: Oleum Tiglii, carry certainly.Olive oil, Beijing fragrant grass medical science chemical institute packing (Spain's import), lot number: 20070428.It is standby to be mixed with 1% Oleum Tiglii with olive oil before the experiment.
Experimental technique: all experimental rats at omoplate district subcutaneous injection 20ml air, form air bag with the sterile working, inject 1% Oleum Tiglii 1ml to air bag immediately, immediately down with the Mus back of the body, slowly rotate, Oleum Tiglii is fully contacted in capsule, take out gas in the capsule after 24 hours.Injection Oleum Tiglii divided 6 groups of (the same test) gastric infusions, 1 time on the 1st, successive administration 7 days the same day at random.Cause scorching back and dissected in the 8th day, transudate in the capsule is taken out to the greatest extent, separate the granulation lump, take by weighing weight in wet base, then to take by weighing dry weight behind 90 ℃ of baking box oven dry 24h with syringe.Experimental result is learned by statistics and is handled the difference that compares between administration group and the blank group.Calculate the granuloma suppression ratio with following formula.
2, experimental result
It is as shown in the table for result of experiment, and the aspirin group has significant inhibitory effect to the inflammation due to 1% Oleum Tiglii, and suppression ratio is 29.5%, compares P＜0.01 with the blank group.Glycyrrhizic acid, baicalin, the high low dose group of sweet yellow compositions have all suppressed the hypertrophy of granulation, and with blank group comparing difference remarkable (P＜0.05～0.001), suppression ratio is 26.4～45.1.Result of the test points out sweet yellow compositions that chronic granulation hyperplasia inflammation is had significant inhibitory effect, and the compositions antiinflammatory action obviously strengthens.
The table 8 silver yellow lupus granule that disappears brings out the influence of rat granulation tissue hyperplasia to 1% Oleum Tiglii: (the n=10 of X ± SD)
Annotate: *, * *, * * * compare P＜0.05,0.01,0.001 with blank group.
Embodiment 7: the acute toxicity test of sweet yellow compositions
1, experiment material
Medicine: sweet yellow compositions, prepare at laboratory with standard substance, be made into desired concn with distilled water during test.
Animal: ICR mice, 20 ± 2g, Zhejiang Province's medical research institute Experimental Animal Center, the quality certification number: SCXK (Zhejiang) 2003-0001.
Test method: experiment is divided into matched group and administration group, animal fasting 16 hours, and gastric infusion twice in 24 hours, and medicinal liquid Cmax 39mg/ml, administration maximum volume are 30ml/kg body weight (0.6ml/20g body weight), integral dose 2.34g crude drug/kg; Observe animal hair color, autonomic activities, breathing, diet, body weight and death condition, observed continuously seven.
2, experimental result
Observed seven days continuously after the administration, weigh every day, and 20 mices of administration group do not have obvious adverse reaction and death.Weight increase, week back body weight a 27.60 ± 2.21g (seeing Table 15-1).The mental status is good, and hair color is white and glossy, and is large and small just normal.Sweet yellow compositions integral dose reaches 2.34g/kg and does not see overt toxicity, and said composition toxicity is less, and the good one-tenth property of medicine is arranged.
Table 9 body weight gain table (n=20, X ± SD)
Embodiment 8: the pharmacokinetic of sweet yellow compositions
Medicine and reagent: baicalin reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute); Glycyrrhizic acid reference substance: (Nat'l Pharmaceutical ﹠ Biological Products Control Institute); Sweet yellow compositions (press this patent invention preparation, contain baicalin 50mg/100mg, contain glycyrrhizic acid 17.5mg/100mg), chromatograph acetonitrile (Baker), chromatograph methanol (Beijing chemical reagents corporation), potassium dihydrogen phosphate (analytical pure).
Laboratory animal: male SD rat, body weight 200g ± 10g, Zhejiang Province's medical research institute Experimental Animal Center, the quality certification number: SCXK (Zhejiang) 2003-0001.
Experimental technique: preparation at the bottom of (1) standard reserving solution: precision takes by weighing baicalin, each 2mg of glycyrrhizic acid, and in the 10ml volumetric flask, methanol constant volume promptly is made into the standard solution of 200 μ g/ml to scale.(2) baicalin chromatographic condition: Tianjin, island high performance liquid chromatograph, chromatographic column, 35 ℃ of column temperatures, mobile phase: acetonitrile-012% phosphoric acid (22: 78); Flow velocity: 1ml/min detects wavelength: 276nm; Sampling volume: 20 μ l (3) glycyrrhizic acid chromatographic conditions: analytical column i.d.25 cm * 4 mm, pre-column i.d. are (213 cm * 319 mm), and column packing is C18 (particle diameter is 10 μ m); (87: 12.15: 0.3: 0.55) form, pH value was that 5.4 flow velocitys are 1.0 mLmin to mobile phase by methanol-water-acetic acid-triethylamine
-1, the ultraviolet detection wavelength is 254 nm, column temperature is 20 ℃.(4) administration and sampling: get 15 of male rats, irritate stomach by 400mg/kg and award sweet yellow compositions, then behind medicine the 2nd, 4,6,8,10,12,14,16,24h plucks eyeball blood sampling (3 rats of each point sampling), external anticoagulant heparin, with the centrifugal 15min of 3000r/min, separated plasma is preserved down for-20 ℃.(5) sample pretreatment is got 5 parts of each 0.1ml of blood plasma in the centrifuge tube of 1.5ml, adds the potassium dihydrogen phosphate 50 μ l of 1mol/l and the acetonitrile precipitation albumen of 0.8ml respectively, and the mixed back of whirlpool is with the centrifugal 15min of the speed of 3000r/ml.Supernatant in 5 parts of centrifuge tubes is changed over to separately in the penicillin bottle of 5ml, after 37 ℃ of water-baths volatilize, methanol with 1.5ml is transferred to the residue in each penicillin bottle in the penicillin bottle of a 5ml, after 37 ℃ of water-baths volatilize once more, the methanol whirlpool dissolved residue that quantitatively adds 0.1 ml, behind the centrifugal 15min of the speed of 15000r/ml, sample introduction 20 μ l.Adopt comparison method with standard quantitatively to formulate standard curve in the experiment.The response rate and precision are got blank plasma respectively, are made into 3 groups of concentration of 0.05,0.5,2 μ g/ml, by " sample pretreatment " operation.After drawing measured value with comparison method with standard, calculate in a few days, day to day precision and the response rate.Medicine with the 3P87 software processes, is done statistical test with EXCEL software for parameter, with t＜0.05 for having the significance meaning.
Experimental result: bibliographical information, baicalin and glycyrrhizic acid water solublity are big, and bioavailability is poor, and oral absorption is considerably less, is difficult to reach effective blood drug concentration.The two share when smaller dose just can reach higher blood drug level.Our experiment shows that in sweet yellow compositions, glycyrrhizic acid and baicalin might be collaborative mutually, the absorption of mutually promoting, thus strengthen drug effect greatly.Bibliographical information, alkali condition are unfavorable for that baicalin absorbs, and the weak acid environment that glycyrrhizic acid forms helps the absorption of baicalin at small intestinal.
Table 10 baicalin, glycyrrhizic acid are in the pharmacokinetics in rats parameter
Embodiment 9: sweet yellow composition tablet preparation
1, prescription
Prescription 1:
Baicalin 210.0g
Glycyrrhizic acid 70.0g
Taurine 100.0g
Pseudoephedrine 30.0g
Pregelatinized Starch 120.0g
Microcrystalline Cellulose 60.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4.0g
Carboxymethylstach sodium 8.0g
Prepare 1000 altogether
Prescription 2:
Baicalin 300.0g
Glycyrrhizic acid 100.0g
Taurine 150.0g
Pseudoephedrine 30.0g
Pregelatinized Starch 120.0g
Microcrystalline Cellulose 60.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4.0g
Carboxymethylstach sodium 8.0g
Prepare 1000 altogether
Prescription 3:
Baicalin 250.0g
Glycyrrhizic acid 50.0g
Taurine 150.0g
Pseudoephedrine 20.0g
Pregelatinized Starch 120.0g
Microcrystalline Cellulose 60.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4.0g
Carboxymethylstach sodium 8.0g
Prepare 1000 altogether
Prescription 4:
Baicalin 100.0g
Glycyrrhizic acid 200.0g
Taurine 150.0g
Pseudoephedrine 30.0g
Pregelatinized Starch 120.0g
Microcrystalline Cellulose 60.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4.0g
Carboxymethylstach sodium 8.0g
Prepare 1000 altogether
2, concrete steps
1) glycyrrhizic acid, baicalin, taurine, pseudoephedrine were pulverized 100 mesh sieves, standby.
2) take by weighing raw material and adjuvant by recipe quantity
3) hydroxypropyl methylcellulose 2% the aqueous solution made soluble in water is standby.
4) with glycyrrhizic acid, baicalin, taurine, pseudoephedrine, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is 60 ℃ of oven dry.
7) dry good granule adds magnesium stearate and carboxymethylstach sodium, and mix homogeneously is crossed 18 mesh sieve granulate.
8) sampling, the semi-finished product chemical examination.
9) the sheet weight sheet of determining according to chemical examination.
10) finished product is examined entirely, the packing warehouse-in.
Embodiment 10: the preparation of sweet yellow composition capsule
1, prescription
Prescription 1:
Baicalin 105.0g
Glycyrrhizic acid 35.0g
Taurine 50.0g
Pseudoephedrine 15.0g
Pregelatinized Starch 60.0g
Microcrystalline Cellulose 40.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4.0g
Prepare 1000 altogether
Prescription 2:
Baicalin 200.0g
Glycyrrhizic acid 70.0g
Taurine 100.0g
Pseudoephedrine 20.0g
Pregelatinized Starch 60.0g
Microcrystalline Cellulose 20.0g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4.0g
Prepare 1000 altogether
2, concrete steps
1) glycyrrhizic acid, baicalin, taurine, pseudoephedrine were pulverized 100 mesh sieves, standby.
2) take by weighing raw material and adjuvant by recipe quantity
3) hydroxypropyl methylcellulose 2% the aqueous solution made soluble in water is standby.
4) with glycyrrhizic acid, baicalin, taurine, pseudoephedrine, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
5) cross 20 mesh sieve system granules.
6) granule is 60 ℃ of oven dry.
7) dry good granule adds magnesium stearate, crosses 18 mesh sieve granulate, mix homogeneously.
8) sampling, the semi-finished product chemical examination.
9) encapsulated according to the definite amount of chemical examination.
10) finished product is examined entirely, the packing warehouse-in.
Embodiment 11: the preparation of sweet yellow composition granule
1, prescription
Prescription 1:
Baicalin 105.0g
Glycyrrhizic acid 35.0g
Taurine 50.0g
Pseudoephedrine 15.0g
Icing Sugar 2000.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription 2:
Baicalin 250.0g
Glycyrrhizic acid 70.0g
Taurine 150.0g
Pseudoephedrine 30.0g
Icing Sugar 2000.0g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
2, concrete steps
1) glycyrrhizic acid, baicalin, taurine, pseudoephedrine were pulverized 100 mesh sieves, standby.
2) take by weighing raw material and adjuvant by recipe quantity
3) glycyrrhizic acid, baicalin, taurine, pseudoephedrine, Icing Sugar are increased progressively mix homogeneously by equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes suitable soft material.
4) cross 20 mesh sieve system granules.
5) granule is 60 ℃ of oven dry.
6) dry good granule is crossed 18 mesh sieve granulate.
7) sampling, the semi-finished product chemical examination, the amount of determining according to chemical examination packs.Finished product is examined entirely, the packing warehouse-in.
List of references
1, Li Yikui chief editor, herbal pharmacology experimental methodology Shanghai: 353 pages of Science and Technology of Shanghai publishing house 1991 front pages
2, Beijing is learned by Xu Shuyun, Bian Rulian, Chen Xiu chief editor pharmacological evaluation side: People's Health Publisher, 1991: second edition 722～723
3, just positive cloud is first bright, Teng Yu. resisiting influenza virus effect CHINA JOURNAL OF CHINESE MATERIA MEDICA 2007,32 (22): 2413-2415 in the baicalin body.
Claims (9)
1. pharmaceutical composition for the treatment of flu: it is characterized in that, make: baicalin 100-500 part, glycyrrhizic acid 50-300 part, taurine 100-200 part, pseudoephedrine 10-50 part by the following ingredients ratio of weight and number.
2. based on the described compositions of claim 1: it is characterized in that, by baicalin 20-200 part, glycyrrhizic acid 10-100 part, taurine 10-150 part, pseudoephedrine 1-20 part.
3. based on glycyrrhizic acid, pseudoephedrine, the taurine described in the claim 1,2, can be free form, also can be glycyrrhizic acid, pseudoephedrine, the pharmaceutically acceptable various salt of taurine.
4. according to the described chemical compound combination among the claim 1-2, it is characterized in that any two or three combination of compounds in glycyrrhizic acid, baicalin, pseudoephedrine, the taurine.
5. according to each described compositions among the claim 1-2, the application in the medicine of preparation prevention or treatment flu.
6. according to each described compositions among the claim 1-2, the application in the various diseases medicine that preparation treatment upper respiratory tract infection causes.
7. according to each described compositions among the claim 1-2, the application in the medicine of preparation treatment influenza, pharyngitis, acute/chronic bronchitis, tonsillitis or pneumonia.
8. according to each described compositions among the claim 1-2, has application in antiviral, the antibacterial medicines in preparation.
9. according to each described compositions among the claim 1-2, it is characterized in that described compositions is made the dosage form that various pharmacy such as tablet, injection, granule, capsule, oral liquid, suspensoid, buccal tablet, effervescent tablet or chewable tablet allow.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010039528A CN101757016A (en) | 2010-01-06 | 2010-01-06 | Medicine composition for treating flu and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010039528A CN101757016A (en) | 2010-01-06 | 2010-01-06 | Medicine composition for treating flu and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101757016A true CN101757016A (en) | 2010-06-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010039528A Pending CN101757016A (en) | 2010-01-06 | 2010-01-06 | Medicine composition for treating flu and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101757016A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103142709A (en) * | 2013-04-07 | 2013-06-12 | 步新源 | Medicament for treating cold |
| CN103191142A (en) * | 2013-03-15 | 2013-07-10 | 江西青峰药业有限公司 | Baicalin and taurine composition and application thereof in preparation of medicament |
| CN103550236A (en) * | 2013-10-26 | 2014-02-05 | 苏州天南星生物科技有限公司 | Compound taurine preparation |
-
2010
- 2010-01-06 CN CN201010039528A patent/CN101757016A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103191142A (en) * | 2013-03-15 | 2013-07-10 | 江西青峰药业有限公司 | Baicalin and taurine composition and application thereof in preparation of medicament |
| CN103191142B (en) * | 2013-03-15 | 2018-11-06 | 江西青峰药业有限公司 | Scutelloside and taurine composition and its prepare medicinal usage |
| CN103142709A (en) * | 2013-04-07 | 2013-06-12 | 步新源 | Medicament for treating cold |
| CN103550236A (en) * | 2013-10-26 | 2014-02-05 | 苏州天南星生物科技有限公司 | Compound taurine preparation |
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Open date: 20100630 |