CN100546573C - A kind of anti-infective medicament composition and preparation method thereof - Google Patents
A kind of anti-infective medicament composition and preparation method thereof Download PDFInfo
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- CN100546573C CN100546573C CNB2006100267982A CN200610026798A CN100546573C CN 100546573 C CN100546573 C CN 100546573C CN B2006100267982 A CNB2006100267982 A CN B2006100267982A CN 200610026798 A CN200610026798 A CN 200610026798A CN 100546573 C CN100546573 C CN 100546573C
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- sodium
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- chlorogenic acid
- mixture
- houttuyfonate
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Abstract
The present invention relates to a kind of anti-infective medicament composition, it is characterized in that, its active component is made up of houttuynine sodium bisulfite or Sodium Houttuyfonate and chlorogenic acid, and the weight ratio of houttuynine sodium bisulfite or Sodium Houttuyfonate and chlorogenic acid is 1: 0.1-1: 3, make drop pill, tablet, freeze-dried powder, nasal drop and capsule.Advantage of the present invention is to have antiviral and antibacterial action, strong drug action.
Description
Technical field
The present invention relates to a kind of anti-infective medicament composition and preparation method thereof, belong to technical field of Chinese medicines.
Background technology
Houttuynine sodium bisulfite (molecular formula C
12H
22O
2, molecular weight 198.30), also claim decanoylacetaldehyde, English Houttuynin by name has multiple pharmacologically active, and is especially more with the antibacterial and anti-inflammation functions report.Many clinically at present sodium sulfite addition products with houttuynine sodium bisulfite claim Sodium Houttuyfonate (molecular formula C
12H
23NaO
5S, molecular weight 302.36 also claims decanoylacetaldehyde sodium hydrosulfite, English Sodium Houttuyfonate by name).Sodium Houttuyfonate has antibacterial and anti-inflammation functions equally, and physicochemical property is more stable.Houttuynine sodium bisulfite both can extract from the Herba Houttuyniae plant, but also synthetic.Sodium Houttuyfonate both can be by the houttuynine sodium bisulfite and the sodium sulfite prepared in reaction of extracted form natural plant, also can be manually complete synthesis.
Chlorogenic acid (molecular formula C
18H
18O
9, molecular weight 354.30), also claim chlorogenic acid, English Chlorogenicacid by name can extract from various plants such as Folium Eucommiae, Flos Lonicerae, Herba Arctii leaf.Bibliographical information, chlorogenic acid has antibiotic, antiviral, hepatic cholagogic, pharmacological actions such as blood pressure lowering.
The houttuynine sodium bisulfite quasi drugs of Xiao Shouing mainly is Sodium Houttuyfonate single component tablet and the plain sodium single component of fish raw meat injection in the market, is used for the treatment of respiratory tract infection, chronic bronchitis, pneumonia, female pelvic inflammation, adnexitis, cervicitis etc.The chlorogenic acid medicine mainly is to contain Chinese patent medicines such as Flos Lonicerae, the Cortex Eucommiae, though these listing medicines have certain curative effect, is subjected to single component limitation itself, and its anti-bacteria and anti-virus spectrum is wide inadequately, and drug effect is strong inadequately, and clinical comprehensive therapeutic effect is not ideal enough.
Summary of the invention
The purpose of this invention is to provide anti-infective medicament composition of a kind of strong drug action and preparation method thereof.
For realizing above purpose, technical scheme of the present invention provides a kind of anti-infective medicament composition, it is characterized in that, its active component is made up of houttuynine sodium bisulfite or Sodium Houttuyfonate and chlorogenic acid, the weight ratio of houttuynine sodium bisulfite or Sodium Houttuyfonate and chlorogenic acid is 1: 0.1-1: 3, make drop pill, tablet, freeze-dried powder, nasal drop and capsule.
The preparation method of described a kind of anti-infective medicament composition the steps include:
A) take by weighing get Sodium Houttuyfonate or houttuynine sodium bisulfite and chlorogenic acid at by weight ratio 1: 0.1-1: 3, merges and pulverize;
B) in the mixture of step a) by weight 1: 1-1: 5 mix with polyethylene glycol 6000, heating and melting, temperature is 85-95 ℃, stirs, and moves to the drop pill machine, is that coolant drips system with the simethicone, promptly gets drop pill;
C) in the mixture of step a), add weight ratio 1: 1-1: 4 medical starch and 1: 0.1-1: 0.8 sodium carboxymethyl cellulose, mix homogeneously is granulated, and tabletting promptly gets tablet;
D) in the mixture of step a) by weight: volume 1: 20-1: 50 add the waters for injection dissolving, regulate PH to 7.0-8.0 with the 35-45% sodium hydroxide solution, the mannitol that adds preparation amount 1%-5%v/g, stirring makes abundant dissolving, add the injection water to preparation amount, use filtering with microporous membrane, packing, lyophilization promptly gets the injection freeze-dried powder;
E) it is standby to get the mixture of 1 part of step a), get the Tween 80 of 0.03-0.3 part volume, 0.05-0.5 part fabaceous lecithin, 75-80 ℃ of hot distilled water of the glycerol of 0.3-0.6 part volume and 1-3 part mixes, and puts homogenize in the high-speed homogenization machine, add the mixture of step a) and the Oleum Glycines of 0.2-0.6 part volume, stir homogenize, add 75-80 ℃ of hot distilled water, continue the high-speed stirred homogenize to 3-5 part volume, divide to be filled to plastic soft bottle, promptly get nasal drop;
F) in the mixture of step a), add weight ratio 1: 0.5-1: 3 carboxymethyl starch sodium, mix homogeneously is granulated, and filled capsules promptly gets capsule;
The invention provides a kind of pharmaceutical composition, have effects such as broad-spectrum antibacterial antiviral, the active constituent content height by Sodium Houttuyfonate or houttuynine sodium bisulfite and chlorogenic acid compatibility, strong drug action, determined curative effect, taking dose is little, be easy to develop various modern formulations, quality is controlled easily.On this basis, this pharmaceutical composition can be mixed with oral formulations, injection, nasal drop and spray etc. with acceptable auxiliary in the medicament and adding ingredient.
In pharmaceutical composition of the present invention, Sodium Houttuyfonate both can be by the houttuynine sodium bisulfite and the sodium sulfite prepared in reaction of extracted form natural plant, also can be manually complete synthesis; Houttuynine sodium bisulfite can be with the houttuynine sodium bisulfite that extracted form natural plant goes out pure product, also available synthetic product also can be substituted by the plant extract of houttuynine sodium bisulfite content 〉=70%.Chlorogenic acid can be with the chlorogenic acid that plant extract goes out pure product, the plant extract of also available chlorogenic acid content 〉=70% substitutes.
Advantage of the present invention is to have antiviral and antibacterial action, strong drug action.
The specific embodiment
The invention will be further described below in conjunction with embodiment.
Embodiment 1:
Get Sodium Houttuyfonate 10g, chlorogenic acid 5g merges and pulverizes, and added polyethylene glycol 6000 by weight 1: 2 and mix in the mixture that merges after pulverizing, heating and melting, temperature is 85 ℃, stirs, moving to the drop pill machine, is 1000 of the coolant systems of dripping with the simethicone, promptly gets drop pill.
Embodiment 2:
Get Sodium Houttuyfonate 10g, chlorogenic acid 20g merges and pulverizes, and adds the 90g medical starch, the 15g sodium carboxymethyl cellulose, and mix homogeneously is granulated, and presses 1000, promptly gets the tablet of pharmaceutical composition of the present invention.
Embodiment 3:
Get Sodium Houttuyfonate 8g, chlorogenic acid 8g merges and pulverizes, and dissolves with 800ml water for injection, regulate PH to 7.0-8.0 with 40% sodium hydroxide solution, add 20g mannitol, stir and make abundant dissolving, add the injection water to 1000ml, with filtering with microporous membrane, 1000 bottles of packing, lyophilization promptly gets the injection freeze-dried powder of pharmaceutical composition of the present invention.
Embodiment 4:
Get Sodium Houttuyfonate 30g, chlorogenic acid 90g merges and pulverizes, and is standby.With 5ml Tween 80,10g fabaceous lecithin, 50ml glycerol and 200ml temperature is that 75-80 ℃ hot distilled water mixes, and puts homogenize in the high-speed homogenization machine.Add Herba Houttuyniae sodium and chlorogenic acid fine powder and 40g Oleum Glycines, stir homogenize, add 75-80 ℃ of hot distilled water, continue the high-speed stirred homogenize, divide to be filled to plastic soft bottle (10ml/ bottle), promptly get pharmaceutical composition nasal drop of the present invention to 1000ml.
Embodiment 5:
Get houttuynine sodium bisulfite content and be 70% Herba Houttuyniae extract 150g, chlorogenic acid content is 70% Flos Lonicerae extract 150g, carboxymethyl starch sodium 80g, and mix homogeneously is granulated, and 1000 of filled capsules promptly get the capsule of pharmaceutical composition of the present invention.
With Sodium Houttuyfonate and chlorogenic acid weight ratio is test specimen at 1: 1, carries out toxicity test and pharmacological testing, with the safety and the effectiveness of check pharmaceutical composition of the present invention.
One, acute toxicity test
Get 20 of Kunming mouses, male and female half and half, fasting is 16 hours before the test, and disposable filling stomach 1.5g/kg is equivalent to 341 times of clinical recommended dose.Promptly observe reaction of animals after the administration, comprise outward appearance, the extremity activity is ingested, is drunk water, drainage etc., continuous 7 days.As a result, except that individual animal loose stool, asthenia, the movable minimizing, all the other no abnormality seens are not found animal dead, and body weight all increases to some extent.Animal is dissected in off-test, and naked eyes do not see that each internal organs has obvious pathological change.Show that pharmaceutical composition of the present invention does not have overt toxicity.
Two, pharmacological testing
(1) antibacterial tests
1, extracorporeal bacteria inhibitor test
Pharmaceutical composition of the present invention is made serial dilution with the agar culture medium that has melted, pour into the plating medium that becomes to contain different pharmaceutical concentration.Establish each one of the plating medium that do not add medicinal liquid and contain penicillin, streptomycin simultaneously, make antibacterial normal growth contrast and positive drug respectively and contrast.The flat board of inoculation test bacterium liquid put in 37 ℃ of incubators cultivated 24 hours, each bacterial strain of observed and recorded is at the growing state of different pharmaceutical concentration culture medium.The least concentration of pharmaceutical composition bacteria growing inhibiting of the present invention is minimal inhibitory concentration (MIC), represents the external antibacterial intensity of medicine with it.The results are shown in Table 1.
Table 1 pharmaceutical composition extracorporeal bacteria inhibitor test of the present invention result
| Strain name | The bacterial strain number | Pharmaceutical composition minimal inhibitory concentration MIC of the present invention (ug/ml) | Sodium Houttuyfonate minimal inhibitory concentration MIC (ug/ml) | Chlorogenic acid minimal inhibitory concentration MIC (ug/ml) | Positive control drug streptomycin 1000u/ml | The antibacterial contrast |
| Staphylococcus aureus | 4 | 70.8±10.7 | 72.5±11.8 | 121.3±13.7 | - | + |
| B family streptococcus | 4 | 99.5±9.3 | 93.7±13.5 | 105.8±9.7 | - | + |
| Klebsiella pneumoniae | 4 | 58.1±11.6 | 115.6±9.8 | 96.3±15.1 | - | + |
| Streptococcus pneumoniae | 4 | 51.5±10.1 | 86.9±16.7 | 135.6±16.7 | - | + |
| Escherichia coli | 2 | 112.3±15.8 | 125.3±10.2 | 113.5±11.6 | - | + |
| Bacillus pyocyaneus | 4 | 62.7±8.9 | 110.2±12.8 | 117.3±8.6 | - | + |
Annotate: "-" is no bacterial growth, and "+" is for there being bacterial growth
The result shows, pharmaceutical composition of the present invention all has obvious inhibitory action to the examination antibacterial, especially the minimal inhibitory concentration (MIC) to klebsiella pneumoniae, streptococcus pneumoniae and three kinds of antibacterials of bacillus pyocyaneus is significantly less than single component Sodium Houttuyfonate and single component chlorogenic acid, shows that antibacterial intensity behind two kinds of components compatibilities of Sodium Houttuyfonate and chlorogenic acid is apparently higher than single component.
2, bacteriostatic test in the body
Get 120 of 16-18g mices, be divided into 6 groups at random by body weight.Test group is in bacterial infection preceding 1 day difference lumbar injection pharmaceutical composition of the present invention, single component Sodium Houttuyfonate and single component chlorogenic acid, and matched group is injected with the volume normal saline, positive controls injection penicillin.Infect the same day, staphylococcus aureus has been increased bacterium be diluted to 0.6 hundred million/ml with normal saline after 24 hours, the bacteria suspension of lumbar injection 0.5ml/20g mice, animal dead number in observation is added up 48 hours calculates survival rate.The results are shown in Table 2.
Bacteriostatic test result in the table 2 drug regimen object of the present invention
| Group | Dosage | Mus number (only) | Death toll (only) | Protective rate (%) |
| Matched group | 20 | 18 | 10 | |
| Penicillin | 30u/kg | 20 | 2 | 90 ** |
| Sodium Houttuyfonate | 3.0mg/kg | 20 | 11 | 45 * |
| Chlorogenic acid | 3.0mg/kg | 20 | 14 | 30 |
| Pharmaceutical composition high dose of the present invention | 3.0mg/kg | 20 | 3 | 85 ** |
| Pharmaceutical composition low dosage of the present invention | 1.5mg/kg | 20 | 7 | 65 ** |
Annotate:
*P＜0.05,
*P＜0.01
Above result shows that pharmaceutical composition of the present invention can make infection staphylococcus aureus mortality of mice obviously reduce, and survival rate obviously improves, and is significantly higher than single component Sodium Houttuyfonate and single component chlorogenic acid.
(2) antivirus test
1, extracorporeal antivirus effect test
Get the culture plate that grows up to cell monolayer, outwell culture fluid, the different virus liquid 100 μ l of inoculation 100TCID50 are in cell hole, cell plates of each virus inoculation, stay delegation not virus inoculation do normal cell contrast.Put in 37 ℃ of 5%CO2 incubators and adsorbed 1 hour, outwell viral liquid, after keeping liquid and wash cell face 3 times with the Eagl é s that does not contain calf serum, add each medicinal liquid (comprising the contrast medicine) 100 μ l/ holes (begin dilution from TC0, each concentration adds 3 holes) of 6 concentration of doubling dilution.Establish virus control, normal cell contrast simultaneously, the medicine contrast, fluid infusion is to 200 μ l/ holes.Put in 37 ℃ of 5%CO2 incubators and cultivated 3 days, every day is microscopy cytopathy progress under inverted microscope., calculating therapeutic index (TI) according to TC50 and EC50, therapeutic index is big more, shows that antivirus action is strong more.The results are shown in Table 3.
Table 3 pharmaceutical composition extracorporeal antivirus effect of the present invention result of the test
Annotate: EC
50Be medium effective concentration; TC
50Be the half toxic concentration; TI is therapeutic index=TC
50/ EC
50"+" is for there being inhibitory action; "-" is the unrestraint effect
The result shows, pharmaceutical composition of the present invention is to respiratory syncytial virus (RSV), parainfluenza virus (HVJ) and adenovirus type III etc. have obvious inhibitory action, and its efficacy strength (therapeutic index TI) is significantly higher than single component Sodium Houttuyfonate and single component chlorogenic acid.
2, interior resisting virus test
Get the 14-16g mice, be divided into 7 groups at random, except that normal group, each group mice is slightly anaesthetized with ether, with 15 LD by body weight
50Influenza virus drop nose infects, every 0.05ml.Infect each test group the previous day intraperitoneal injection respectively, every day 2 times, continuous 5 days, took by weighing blood-letting after the mice body weight on the 6th day, dissect, win full lung and weigh, calculate lung exponential quantity and lung index suppression ratio.The lung exponential quantity is big, shows that pneumonopathy range degree is serious.
Table 4 pharmaceutical composition interior resisting virus of the present invention result of the test (X ± SD)
| Group | Number of animals (only) | Dosage (mg/kg) | Body weight (g) | Lung exponential quantity (g/100g) | Suppression ratio (%) |
| Infect contrast | 10 | 14.79±1.13 | 1.71±0.15 | ||
| Normal control | 10 | 19.15±1.54 ** | 0.91±0.11 ** | ||
| The compositions high dose | 10 | 6.0 | 17.54±1.48 ** | 1.32±0.09 ** | 57.39 |
| The compositions low dosage | 10 | 3.0 | 16.35±1.15 * | 1.48±0.13 * | 48.16 |
| Sodium Houttuyfonate | 10 | 6.0 | 15.21±1.58 | 1.59±0.09 | 31.37 |
| Chlorogenic acid | 10 | 6.0 | 15.02±1.65 | 1.61±0.08 | 29.45 |
| Virazole | 10 | 1.5 | 18.0±1.72 ** | 1.09±0.12 ** | 68.33 |
The result shows, infection group and viral infection group mice body weight obviously descends, the lung exponential quantity obviously increases, each administration group body weight all increases in various degree, the lung exponential quantity descends in various degree, pharmaceutical composition of the present invention can make the virus infected mice body weight significantly increase, and the lung index significantly descends, and drug effect obviously is better than single component Sodium Houttuyfonate and single component chlorogenic acid.
Above pharmacological toxicology result of the test shows that pharmaceutical composition of the present invention has significant antibiosis and antiviral functions, and security is good.
Claims (2)
1. anti-infective medicament composition, it is characterized in that, its active component is made up of houttuynine sodium bisulfite or Sodium Houttuyfonate and chlorogenic acid, and the weight ratio of houttuynine sodium bisulfite or Sodium Houttuyfonate and chlorogenic acid is 1: 0.1-1: 3, make drop pill, tablet, freeze-dried powder, nasal drop and capsule.
2. the preparation method of an anti-infective medicament composition, it comprises the following steps:
A) by weight ratio 1: 0.1-1: 3 take by weighing Sodium Houttuyfonate or houttuynine sodium bisulfite and chlorogenic acid respectively, merge to pulverize;
B) by weight 1: 1-1: 5 add polyethylene glycol 6000 mixes, heating and melting, and temperature is 85-95 ℃, stirs, and moves to the drop pill machine, is that coolant drips system with the simethicone, promptly gets drop pill;
C) in the mixture of step a), add weight ratio 1: 1-1: 4 medical starch and 1: 0.1-1: 0.8 sodium carboxymethyl cellulose, mix homogeneously is granulated, and tabletting promptly gets tablet;
D) in the mixture of step a) by weight: volume 1: 20-1: 50 add the waters for injection dissolving, regulate PH to 7.0-8.0 with the 35-45% sodium hydroxide solution, the mannitol that adds preparation amount 1%-5% (v/g), stirring makes abundant dissolving, add the injection water to preparation amount, use filtering with microporous membrane, packing, lyophilization promptly gets the injection freeze-dried powder;
E) it is standby to get the mixture of 1 part of step a), get the Tween 80 of 0.03-0.3 part volume, 0.05-0.5 part fabaceous lecithin, 75-80 ℃ of hot distilled water of the glycerol of 0.3-0.6 part volume and 1-3 part mixes, and puts homogenize in the high-speed homogenization machine, add the mixture of step a) and the Oleum Glycines of 0.2-0.6 part volume, stir homogenize, add 75-80 ℃ of hot distilled water, continue the high-speed stirred homogenize to 3-5 part volume, divide to be filled to plastic soft bottle, promptly get nasal drop;
F) in the mixture of step a), add weight ratio 1: 0.5-1: 3 carboxymethyl starch sodium, mix homogeneously is granulated, and filled capsules promptly gets capsule.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100267982A CN100546573C (en) | 2006-05-23 | 2006-05-23 | A kind of anti-infective medicament composition and preparation method thereof |
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|---|---|---|---|
| CNB2006100267982A CN100546573C (en) | 2006-05-23 | 2006-05-23 | A kind of anti-infective medicament composition and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN1850060A CN1850060A (en) | 2006-10-25 |
| CN100546573C true CN100546573C (en) | 2009-10-07 |
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|---|---|---|---|
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100425229C (en) * | 2006-12-20 | 2008-10-15 | 上海慈瑞医药科技有限公司 | Local medicine preparation containing antiinfective medicine composition and its preparing method |
| CN113648299A (en) * | 2020-12-07 | 2021-11-16 | 山东第一医科大学(山东省医学科学院) | Application of chlorogenic acid in preparation of anti-A6 Coxsackie virus medicine |
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